# Homeostasis

## Overview

The human organism consists of trillions of cells all working together for the maintenance of the entire organism. While cells may perform very different functions, all the cells are quite similar in their metabolic requirements. Maintaining a constant internal environment with all that the cells need to survive (oxygen, glucose, mineral ions, waste removal, and so forth) is necessary for the well-being of individual cells and the well-being of the entire body. The varied processes by which the body regulates its internal environment are collectively referred to as homeostasis.

### What is Homeostasis?

Homeostasis in a general sense refers to stability or balance in a system. It is the body's attempt to maintain a constant internal environment. Maintaining a stable internal environment requires constant monitoring and adjustments as conditions change. This adjusting of physiological systems within the body is called homeostatic regulation.

Homeostatic regulation involves three parts or mechanisms: 1) the receptor, 2) the control center and 3) the effector.

The receptor receives information that something in the environment is changing. The control center or integration center receives and processes information from the receptor. And lastly, the effector responds to the commands of the control center by either opposing or enhancing the stimulus. This is an ongoing process that continually works to restore and maintain homeostasis. For example, in regulating body temperature there are temperature receptors in the skin, which communicate information to the brain, which is the control center, and the effector is our blood vessels and sweat glands in our skin.

Because the internal and external environments of the body are constantly changing and adjustments must be made continuouslyg to stay at or near the set point, homeostasis can be thought of as a synthetic equilibrium.

Since homeostasis is an attempt to maintain the internal conditions of an environment by limiting fluctuations, it must involve a series of negative feedback loops.

### Positive and Negative Feedback

When a change of variable occurs, there are two main types of feedback to which the system reacts:

• Negative feedback: a reaction in which the system responds in such a way as to reverse the direction of change. Since this tends to keep things constant, it allows the maintenance of homeostasis. For instance, when the concentration of carbon dioxide in the human body increases, the lungs are signaled to increase their activity and expel more carbon dioxide. Thermoregulation is another example of negative feedback. When body temperature rises, receptors in the skin and the hypothalamus sense a change, triggering a command from the brain. This command, in turn, effects the correct response, in this case a decrease in body temperature.
Home Heating System Vs. Negative Feedback
When you are at home, you set your thermostat to a desired temperature. Let's say today you set it at 70 degrees. The thermometer in the thermostat waits to sense a temperature change either too high above or too far below the 70 degree set point. When this change happens the thermometer will send a message to to the "Control Center", or thermostat,which in turn will then send a message to the furnace to either shut off if the temperature is too high or kick back on if the temperature is too low. In the home-heating example the air temperature is the "NEGATIVE FEEDBACK." When the Control Center receives negative feedback it triggers a chain reaction in order to maintain room temperature.
• Positive feedback: a response is to amplify the change in the variable. This has a destabilizing effect, so does not result in homeostasis. Positive feedback is less common in naturally occurring systems than negative feedback, but it has its applications. For example, in nerves, a threshold electric potential triggers the generation of a much larger action potential. Blood clotting in which the platelets process mechanisms to transform blood liquid to solidify is an example of positive feedback loop. Another example is the secretion of oxytocin which provides a pathway for the uterus to contract, leading to child birth.
Harmful Positive Feedback
Although Positive Feedback is needed within Homeostasis it also can be harmful at times. When you have a high fever it causes a metabolic change that can push the fever higher and higher. In rare occurrences the body temperature reaches 113 degrees Fahrenheit / 45 degrees Celsius and the cellular proteins stop working and the metabolism stops, resulting in death.

Summary: Sustainable systems require combinations of both kinds of feedback. Generally with the recognition of divergence from the homeostatic condition, positive feedbacks are called into play, whereas once the homeostatic condition is approached, negative feedback is used for "fine tuning" responses. This creates a situation of "metastability," in which homeostatic conditions are maintained within fixed limits, but once these limits are exceeded, the system can shift wildly to a wholly new (and possibly less desirable) situation of homeostasis.

Homeostatic systems have several properties

• They are ultra-stable, meaning the system is capable of testing which way its variables should be adjusted.
• Their whole organization (internal, structural, and functional) contributes to the maintenance of balance.
• Physiology is largely a study of processes related to homeostasis. Some of the functions you will learn about in this book are not specifically about homeostasis (e.g. how muscles contract), but in order for all bodily processes to function there must be a suitable internal environment. Homeostasis is, therefore, a fitting framework for the introductory study of physiology.

Where did the term "Homeostasis" come from?

The concept of homeostasis was first articulated by the French scientist Claude Bernard (1813-1878) in his studies of the maintenance of stability in the "milieu interior." He said, "All the vital mechanisms, varied as they are, have only one object, that of preserving constant the conditions of life in the internal environment" (from Leçons sur les Phénonèmes de la Vie Commune aux Animaux et aux Végétaux, 1879). The term itself was coined by American physiologist Walter Cannon, author of The Wisdom of the Body (1932). The word comes from the Greek homoios (same, like, resembling) and stasis (to stand, posture).

### Cruise Control on a car as a simple metaphor for homeostasis

When a car is put on cruise control it has a set speed limit that it will travel. At times this speed may vary by a few miles per hour but in general the system will maintain the set speed. If the car starts to go up a hill, the systems will automatically increase the amount of fuel given to maintain the set speed. If the car starts to come down a hill, the car will automatically decrease the amount of fuel given in order to maintain the set speed. It is the same with homeostasis- the body has a set limit on each environment. If one of these limits increases or decreases, the body will sense and automatically try to fix the problem in order to maintain the pre-set limits. This is a simple metaphor of how the body operates—constant monitoring of levels, and automatic small adjustments when those levels fall below (or rise above) a set point.

## Pathways That Alter Homeostasis

A variety of homeostatic mechanisms maintain the internal environment within tolerable limits. Either homeostasis is maintained through a series of control mechanisms, or the body suffers various illnesses or disease. When the cells in the body begin to malfunction, the homeostatic balance becomes disrupted. Eventually this leads to disease or cell malfunction. Disease and cellular malfunction can be caused in two basic ways: either, deficiency (cells not getting all they need) or toxicity (cells being poisoned by things they do not need). When homeostasis is interrupted in your cells, there are pathways to correct or worsen the problem. In addition to the internal control mechanisms, there are external influences based primarily on lifestyle choices and environmental exposures that influence our body's ability to maintain cellular health.

• Nutrition: If your diet is lacking in a specific vitamin or mineral your cells will function poorly, possibly resulting in a disease condition. For example, a menstruating woman with inadequate dietary intake of iron will become anemic. Lack of hemoglobin, a molecule that requires iron, will result in reduced oxygen-carrying capacity. In mild cases symptoms may be vague (e.g. fatigue), but if the anemia (British English: anaemia) is severe the body will try to compensate by increasing cardiac output, leading to palpitations and sweatiness, and possibly to heart failure.
• Toxins: Any substance that interferes with cellular function, causing cellular malfunction. This is done through a variety of ways; chemical, plant, insecticides, and/or bites. A commonly seen example of this is drug overdoses. When a person takes too much of a drug their vital signs begin to waver; either increasing or decreasing, these vital signs can cause problems including coma, brain damage and even death.
• Psychological: Your physical health and mental health are inseparable. Our thoughts and emotions cause chemical changes to take place either for better as with meditation, or worse as with stress.
• Physical: Physical maintenance is essential for our cells and bodies. Adequate rest, sunlight, and exercise are examples of physical mechanisms for influencing homeostasis. Lack of sleep is related to a number of ailments such as irregular cardiac rhythms, fatigue, anxiety and headaches.
• Genetic/Reproductive: Inheriting strengths and weaknesses is part of our genetic makeup. Genes are sometimes turned off or on due to external factors which we can have some control over, but at other times little can be done to correct or improve genetic diseases. Beginning at the cellular level a variety of diseases come from mutated genes. For example, cancer can be genetically inherited or can be caused due to a mutation from an external source such as radiation or genes altered in a fetus when the mother uses drugs.
• Medical: Because of genetic differences some bodies need help in gaining or maintaining homeostasis. Through modern medicine our bodies can be given different aids, from anti-bodies to help fight infections, or chemotherapy to kill harmful cancer cells. Traditional and alternative medical practices have many benefits, but like any medical practice the potential for harmful effects is present. Whether by nosocomial infections, or wrong dosage of medication, homeostasis can be altered by that which is trying to fix it. Trial and error with medications can cause potential harmful reactions and possibly death if not caught soon enough.

The factors listed above all have their effects at the cellular level, whether harmful or beneficial. Inadequate beneficial pathways (deficiency) will almost always result in a harmful waver in homeostasis. Too much toxicity also causes homeostatic imbalance, resulting in cellular malfunction. By removing negative health influences, and providing adequate positive health influences, your body is better able to self-regulate and self-repair, thus maintaining homeostasis.

## Homeostasis Throughout the Body

Each body system contributes to the homeostasis of other systems and of the entire organism. No system of the body works in isolation, and the well-being of the person depends upon the well-being of all the interacting body systems. A disruption within one system generally has consequences for several additional body systems. Here are some brief explanations of how various body systems contribute to the maintenance of homeostasis:

### Nervous System

Since the nervous system does not store nutrients, it must receive a continuous supply from blood. Any interruption to the flow of blood may bring brain damage or death. The nervous system maintains homeostasis by controlling and regulating the other parts of the body. A deviation from a normal set point acts as a stimulus to a receptor, which sends nerve impulses to a regulating center in the brain. The brain directs an effector to act in such a way that an adaptive response takes place. If, for example, the deviation was a lowering of body temperature, the effector acts to increase body temperature. The adaptive response returns the body to a state of normalcy and the receptor, the regulating center, and the effector temporarily cease their activities. Since the effector is regulated by the very conditions it produced, this process is called control by negative feedback. This manner of regulating normalcy results in a fluctuation between two extreme levels. Not until body temperature drops below normal do receptors stimulate the regulating center and effectors act to raise body temperature. Regulating centers are located in the central nervous system, consisting of the brain and spinal cord. The hypothalamus is a portion of the brain particularly concerned with homeostasis; it influences the action of the medulla oblongata, a lower part of the brain, the autonomic nervous system, and the pituitary gland.

The nervous system has two major portions: the central nervous system and the peripheral nervous system. The peripheral nervous system consists of the cranial and spinal nerves. The autonomic nervous system is a part of peripheral nervous system and contains motor neurons that control internal organs. It operates at the subconscious level and has two divisions, the sympathetic and parasympathetic systems. In general, the sympathetic system brings about those results we associate with harsh situations, often called fight or flight hormone, and the parasympathetic system produces those effects necessary to our everyday existence.

### Endocrine System

The endocrine system consists of glands which secrete hormones into the bloodstream. Each hormone has an effect on one or more target tissues. In this way the endocrine system regulates the metabolism and development of most body cells and body systems. To be more specific, the Endocrine system has sex hormones that can activate sebaceous glands, development of mammary glands, alter dermal blood flow and release lipids from adipocytes. MSH can stimulate melanocytes on our skin. Our bone growth is regulated by several hormones, and the endocrine system helps with the mobilization of calcitonin and calcium. In the muscular system, hormones adjust muscle metabolism, energy production, and growth. In the nervous system, hormones affect neural metabolism, regulate fluid/electrolyte balance and help with reproductive hormones that influence CNS development and behaviors. In the Cardiovascular system, we need hormones that regulate the production of RBC's (red blood cells), which elevate and lower blood pressure. Hormones also have anti-inflammatory effects and stimulate the lymphatic system. In summary, the endocrine system has a regulatory effect on basically every other body system.

### Integumentary System

The integumentary system (the skin) is involved in protecting the body from invading microbes (mainly by forming a thick impenetrable layer), regulating body temperature through sweating and vasodilation/vasoconstriction, or shivering and piloerection (goose bumps), and regulating ion balances in the blood. Stimulation of mast cells also produce changes in blood flow and capillary permeability which can effect the blood flow in the body and how it is regulated. It also helps synthesize vitamin D which interacts with calcium and phosphorus absorption needed for bone growth, maintenance, and repair. Hair on the skin guards entrance into the nasal cavity or other orifices, preventing invaders from getting further into our bodies. Our skin also helps maintain balance by excretion of water and other solutes (i.e.) the keratinized epidermis limits fluid loss through skin. It also provides mechanical protection against environmental hazards. We need to remember that our skin is integumentary; it is our first line of defense.

### Skeletal System

As the structural framework for the human body, the skeletal system consists mainly of the 206 or so bones of the skeletal system but also includes cartilages, ligaments, and other connective tissues that stabilize and interconnect them. Bones work in conjunction with the muscular system to aid in posture and locomotion. Many bones of the skeleton function as levers, which change the magnitude and direction of forces generated by skeletal muscle. Protection is a pivotal role occupied by the skeletal system, as many vital organs are encased within the skeletal cavities (eg. cranial and spinal), and bones form much of the structural basis for other body cavities (ex: thoracic and pelvic cavities). The skeletal system also serves as an important mineral reserve. For example, if blood levels of calcium or magnesium are low and the minerals are not available in the diet, they will be taken from the bones. Also, the skeletal system provides calcium needed for all muscular contraction. Finally, red blood cells, lymphocytes and other cells relating to the immune response are produced and stored in the bone marrow.

### Muscular System

The muscular system is one of the most versatile systems in the body. The muscular system contains the heart, which constantly pumps blood through the body. The muscular system is also responsible for involuntary (e.g. goose bumps, digestion, breathing) and voluntary (e.g. walking, picking up objects) actions. Muscles also help protect organs in the body's cavities. The muscles in your body contract, which increases your body heat when you're cold. The act of shivering occurs when the internal temperature drops. Muscles around vital organs contract, breaking down ATP and thereby expanding heat, which is then distributed to the rest of the body.

### Cardiovascular System

The cardiovascular system, in addition to needing to maintain itself within certain levels, plays a role in maintenance of other body systems by transporting hormones (heart secretes Atrial Natriuretic Peptide and Brain Natriuretic Peptide, or ANP and BNP, respectively) and nutrients (oxygen, EPO to bones,etc.), taking away waste products, and providing all living body cells with a fresh supply of oxygen and removing carbon dioxide. Homeostasis is disturbed if the cardiovascular or lymphatic systems are not functioning correctly. Our skin, bones, muscles, lungs, digestive tract, and nervous, endocrine, lymphatic, urinary and reproductive systems use the cardiovascular system as its "road" or "highway" as far as distribution of things such as nutrients, oxygen, waste products, hormones, drugs, etc. There are many risk factors for an unhealthy cardiovascular system. Some diseases associated are typically labeled "uncontrollable" or "controllable." The main uncontrollable risk factors are age, gender, and a family history of heart disease, especially at an early age.

The cardiovascular system also contains sensors to monitor blood pressure, called baroreceptors, that work by detecting how stretched a blood vessel is. This information is relayed to the Medulla Oblongata in the brain where action is taken to raise or lower blood pressure via the autonomic nervous system.

### Lymphatic System

The lymphatic system has three principal roles. First is the maintenance of blood and tissue volume. Excess fluid that leaves the capillaries when under pressure would build up and cause edema. Secondly, the lymphatic system absorbs fatty acids and triglycerides from fat digestion so that these components of digestion do not enter directly into the blood stream. Third, the lymphatic system is involved in defending the body against invading microbes, and the immune response. This system assists in maintenance, such as bone and muscle repair after injuries. Another defense is maintaining the acidic pH of urine to fight infections in the urinary system. The tonsils are our bodies "helpers" to defend us against infections and toxins absorbed from the digestive tract. The tonsils also protect against infections entering into our lungs.

### Respiratory System

The respiratory system works in conjunction with the cardiovascular system to provide oxygen to cells within every body system for cellular metabolism. The respiratory system also removes carbon dioxide. Since CO2 is mainly transported in the plasma as bicarbonate ions, which act as a chemical buffer, the respiratory system also helps maintain proper blood pH levels, a fact that is very important for homeostasis. As a result of hyperventilation, CO2 is decreased in blood levels. This causes the pH of body fluids to increase. If acid levels rise above 7.45, the result is respiratory alkalosis. On the other hand, too much CO2 causes pH to fall below 7.35 which results in respiratory acidosis. The respiratory system also helps the lymphatic system by trapping pathogens and protecting deeper tissues within. Note that when you have increased thoracic space it can provide abdominal pressure through the contraction of respiratory muscles. This can assist in defecation.

The organs of the respiratory system include the nose, pharynx, larynx, trachea, bronchi and lungs. Together these organs permit the movement of air into the tiny, thin walled sacs of the lungs called alveoli. It is in the alveoli that oxygen from the air is exchanged for the waste product carbon dioxide, which is carried to lungs by the blood so that it can be eliminated from the body.

### Digestive System

Without a regular supply of energy and nutrients from the digestive system, all body systems would soon suffer. The digestive system absorbs organic substances, vitamins, ions, and water that are needed all over the body. In the skin, the digestive tract provides lipids for storage in the subcutaneous layer. Note that food undergoes three types of processes in the body: digestion, absorption, and elimination. If one of these is not working, you will have problems that will be extremely noticeable. Mechanics of digestion can include chemical digestion, movements, ingestion absorption, and elimination. In order to maintain a healthy and efficient digestive system, we have to remember the components involved. If these are disturbed, digestive health may be compromised.

### Urinary System

Toxic nitrogenous wastes accumulate as proteins and nucleic acids are broken down and used for other purposes. The urinary system rids the body of these wastes. The urinary system is also directly involved in maintaining proper blood volume (and indirectly blood pressure) and ion concentration within the blood. One other contribution is that the kidneys produce a hormone (erythropoietin) that stimulates red blood cell production. The kidneys also play an important role in maintaining the correct water content of the body and the correct salt composition of extracellular fluid. External changes that lead to excess fluid loss trigger feedback mechanisms that act to inhibit fluid loss.

### Reproductive System

The Reproductive System is unique in that it does little to contribute to the homeostasis of the organism. Rather than being tied to the maintenance of the organism, the reproductive system relates to the maintenance of the species. Having said that, the sex hormones do have an effect on other body systems, and an imbalance can lead to various disorders (e.g. a woman whose ovaries are removed early in life is at much higher risk of osteoporosis).

### Excretory System

Excretory System is responsible for removing wastes, excess water and salt in the urine. Regulates the volume and pH of the internal environment. The human excretory system maintains homeostasis by removing metabolic waste such as water, salt and metabolite concentrations in the blood. The kidneys, which are the primary excretory organs, are major organs of homeostasis because they excrete nitrogenous wastes, and regulate water-salt balance and acid base balance. This section will examine the kidney in details.

## Thermoregulation

The living bodies have been characterized with a number of automated processes, which make them self-sustainable in the natural environment. Among these many processes are that of reproduction, adjustment with external environment, and instinct to live, which are gifted by nature to living beings.

The survival of living beings greatly depends on their capability to maintain a stable body temperature irrespective of temperature of surrounding environment. This capability of maintaining body temperature is called thermoregulation. Cold blooded animals, such as reptiles, have somewhat different means of temperature regulation than warm blooded (or homeothermic) animals, such as humans and other mammals. This section is most relevant when considering warm blooded organisms.

Body temperature depends on the heat produced minus the heat lost. Heat is lost by radiation, convection, and conduction, but the net loss by all three processes depends on a gradient between the body and the outside. Thus, when the external temperature is low, radiation is the most important form of heat loss. When there is a high external temperature, evaporation is the most important form of heat loss. The balance of heat produced and heat lost maintains a constant body temperature. However, temperature does vary during the day, and this set point is controlled by the hypothalamus.

Body temperature is usually about 37.4°C, but does vary during the day by about 0.8°C. The lowest daily temperature is when the person is asleep. Temperature receptors are found in the skin, the great veins, the abdominal organs and the hypothalamus. While the ones in the skin provide the sensation of coldness, the hypothalamic (central core) temperature receptors are the most important. The core body temperature is usually about 0.7-1.0°C higher than axillary or oral temperature.

When body temperature drops due to external cold, an important component of protection is vaso-constriction of skin and limb blood vessels. This drops the surface temperature, providing an insulating layer (such as the fat cell layer) between the core temperature and the external environment. Likewise, if the temperature rises, blood flow to the skin increases, maximizing the potential for loss by radiation and evaporation. Thus, if you dilated the skin blood vessels by alcohol ingestion this might give a nice warm glow, but it would increase heat loss (if the external temperature was still low). The major adjustments in cold are to shiver to increase heat production, and constrict blood vessels in the periphery and skin. This helps to minimize heat loss through the skin, and directs blood to the vital internal organs.

Besides the daily variation in body temperature, there are other cyclic variations. In women, body temperature falls prior to ovulation and rises by about 1°C at ovulation, largely due to progesterone increasing the set point. Thyroid hormone and pyrogens also increase the set point. The basal metabolic rate (BMR) is about 30 calories/sq m/h. It is higher in children than in adults, partly as a result of different surface area to body mass ratio. Due to this relationship, young children are more likely to drop their temperature rapidly; there is greater temperature variation in children than in adults. It is increased by thyroid hormone and decreased by thyroid hormone lack. Different foods can affect BMR and the Respiratory Quotient of foods differ. Carbohydrate 1.0; Protein = 1.0; Fats = 0.7

## Body Composition

Extracellular Fluid

Cellular Fluid

Volume

plasma – 3 litres

interstitial – 10 litres

30 litres

Osmolality (mOsm)

290

290

Na + (mmol/l)

140

15

Ca 2+ (mmol/l)

2.2

< 10 -6

Cl - (mmol/l)

110

10

HCO3 - (mmol/l)

30

10

K + (mmol/l)

4

150

Mg 2+ (mmol/l)

1.5

15

PO4 3+ (mmol/l)

2

40

pH

7.4

7.1

Potential Difference (mV)

-70

Blood pressure is expressed as two different numbers. The first number is called the "systolic" blood pressure, and the second is the "diastolic" blood pressure. Systolic blood pressure is the pressure at the time of the cardiac cycle when the heart contracts, forcing blood out(called systole). This is the time of greatest pressure. The Diastolic number comes from the time in the cardiac cycle when pressure is at its lowest, while the heart is refilling with blood. This phase is called Diastole. The blood pressure in large arteries is about 120/80 mmHg. By the time this comes to the capillaries it has partly lost its pulsatile nature and has a pressure of about 35 mmHg. The pressure falls rapidly along the capillary to 15 mmHg at the venous end. This hydrostatic pressure tends to force fluid out of the capillary into the interstitium (the fluid between cells) but balance is maintained by the colloid osmotic pressure (due to protein, principally albumin) of 26 mmHg. Net water movement is small (about 2%) and thus colloid osmotic pressure is the same at the arterial and venous end of the capillary.

At the arterial end of the capillary there is a net outward force of about 11 mmHg while at the venous end the net inward force is about 9 mmHg (ie. -9). There is an imbalance between water movement out and movement back in which leads to an imbalance of about 3 litres/day, which is removed as lymph. There is some albumin in the interstitial tissue and it varies in different organs but the concentration may be up to 10 or 20% of plasma. This gives an interstitial oncotic pressure which causes movement of fluid into the interstitium. However the bulk movement of water is not the way nutrients get to cells. Nutrients diffuse down their concentration gradient as the capillary is very permeable to all small molecules.

The extracellular volume is approximately thirteen litres in a seventy kg person. Ten litres are in the interstitial space and three litres in plasma. The capillaries are the interface between the two compartments and are permeable to most substances with a molecular weight less than 20,000. Thus nutrients can readily diffuse across the wall and go from blood to cell. Despite the high permeability of the capillary water is maintained inside due to the oncotic pressure and only about 2% of the plasma flowing through the capillary moves across the wall.

The blood volume is about 5 litres of which about 3 litres are plasma and about 2 litres red blood cells. The red blood cell volume (haematocrit) is about 43% and the relationship between plasma and blood volume and haematocrit is Blood Volume = Plasma Volume 100/(100 - Ht). Most of the blood is usually in the veins (70%).

Capillaries differ in their permeability throughout the body. Brain capillaries are relatively impermeable due to tight junctions between endothelial cells lining the blood vessels. This is known as the blood brain barrier, or BBB, and helps prevent toxins from entering the brain.

In order of less permeability:

Brain < Muscle < Glomerulus < Liver sinusoids.

The capillaries, while having a large surface area, only contain about 7% of the blood volume. The arteries and arterioles contain about 15%. Most of the blood is in the veins.

## Body Fluid Distribution

The cell membrane is a bilipid layer that is permeable to water and lipid soluble particles. However, it is impermeable to charged particles. It is the osmolality controlling factor. Osmolality in the cell and interstitial fluid are the same but the anionic and cationic compositions differ. Made of albumin, the capillary membrane is permeable to everything except proteins. The membranes in different tissues differ. There are fenestrae (or pores) to promote better flow of fluids. Particles weighing over 40,000 have low permeability. It is the oncotic pressure controlling factor. Capillaries in the brain are relatively impermeable while capillaries in liver sinusoids and glomeruli are extremely permeable.

Water (litres)

Sodium (mmol)

Potassium (mmol)

Total

43

3700

4000

Intracellular

30

400

Bone

-

1500

300

Extracellular

13

1820

52

Plasma

3

420

12

Interstitial

10

1400

40

Usual Intake

1.5

180

70

Range

0.7-5

5-400

50-400

## Dehydration and Volume Depletion

Plasma osmolality is about 290 mosmol/l contributed mainly by sodium (140 mmol/l) and it's accompanying anions. In dehydration water is lost from the body. The rise in osmolality that occurs in the plasma (also sodium rises) causes water to initially move out of the cells along the osmotic gradient. Thus cell volume is initially reduced but cell homeostatic processes subsequently return it towards normal by taking up solute.

In dehydration water is removed from the plasma and thus haematocrit and albumin which have not been lost will have a higher concentration. In volume depletion water and electrolytes are both lost and thus there will be little effect on either sodium concentration or osmolality. As osmolality is not altered there will be no force to pull water out of the cells and cell volume is not affected.

In volume depletion due to blood loss the haematocrit acutely is the same but the resultant fall in blood pressure causes fluid to come out of the interstitium into the vascular compartment and albumin and haematocrit both decrease. When there is volume depletion due to electrolyte and water loss by vomiting or diarrhoea there will be little or no effect on plasma osmolality or sodium concentration. However there will be a small increase in haematocrit and plasma albumin because the volume is lost from the extracellular space and as blood cells and albumin are not lost this increases the concentration.

In volume depletion forces are activated that retain sodium and water in the body. The sodium retention works to a major extent by the renin-angiotensin-aldosterone system which is activated by a fall in blood pressure caused by volume depletion. In dehydration, the high osmolality activates ADH secretion which causes water retention. As there is also volume depletion, this activates the renin-angiotensin-aldosterone system which causes sodium to be retained. This retention would tend to cause a rise in sodium concentration which is already high but the water retention would correct this. There is no effective receptor that monitors and controls Na concentration by altering sodium excretion. Sodium retaining hormones are predominantly regulated by the volume and blood pressure. Initially in blood loss the haematocrit is not altered but falls as fluid comes in from the interstitial space.

## Water Balance

Vasopressin, also called Antidiuretic Hormone (ADH), is the principal compound controlling water balance by decreasing water output by the kidney, and thus decreased urination. It perceives the need by monitoring plasma osmolality and if this is high, vasopressin is secreted. Vasopressin is formed in the hypothalamus and travels down axons to the posterior pituitary where it is stored.

Plasma osmolality is the usual factor regulating vasopressin release but other factors alter the release. Pain and emotion release vasopressin together with the other posterior pituitary hormone oxytocin. Alcohol inhibits the release of vasopressin and thus causes a diuresis. A low plasma volume also releases vasopressin which in high concentration can cause vasoconstriction. These different factors can overcome the usual physiological control of osmolality.

Osmoreceptors in the hypothalamus monitor the plasma osmolality and send a signal down the axon that releases vasopressin from the posterior pituitary gland. Vasopressin travels by the blood to the kidney and binds to a receptor on the basolateral membrane and by a series of cellular events alters the permeability of the luminal membrane to water, thereby increasing the water permeability of the collecting duct and due to osmotic gradients created in the kidney causes water to be retained by the body (ie. an antidiuresis) which provides the other name for vasopressin of antidiuretic hormone.

Vasopressin released by the pituitary binds to a receptor on the basolateral membrane and activates adenyl cyclase which increases cyclic AMP levels in the kidney. This by a series of reactions, some of which involve calcium, cause microfilaments to contract and insert preformed water channels (aquaporins) into the luminal membrane increasing water permeability.

A high plasma osmolality is the important physiological stimulus causing vasopressin release. Urea in plasma in a normal person only has a concentration of 6 mmol/l and thus contributes to only a small part of plasma osmolality. Even if plasma urea is elevated to 30 mmol/l it would not have a significant effect on vasopressin release as membranes (including those of the osmoreceptor cells) are permeable to urea. If there is excessive ADH water is retained and the osmolality and sodium concentration would fall (hyponatraemia). If there is no ADH water is lost and osmolality and sodium concentration would rise (hypernatraemia). While ADH is released if the plasma volume falls the most important factor to restore volume is retention of sodium by the renin-angiotensin-aldosterone and other salt retaining systems.

## Sodium Balance

Amount

Concentration

Amount in body

3700 mmol

Intracellular

400 mmol

15 mmol/l

Extracellular

1800 mmol

140 mmol/l

Plasma

420 mmol

140 mmol/l

Interstitial

1400 mmol

140 mmol/l

Bone

1500 mmol

Amount in diet

Hunter Gatherer

20 mmol/day

Western

180 mmol/day

Japanese

300 mmol/day

Obligatory Need

< 5 mmol/day

Sodium is an important cation distributed primarily outside the cell. The cell sodium concentration is about 15 mmol/l but varies in different organs and with an intracellular volume of 30 litres about 400 mmol are inside the cell. The plasma and interstitial sodium is about 140 mmol/l with an extracellular volume of about 13 litres, 1800 mmol are in the extracellular space. The total body sodium, however, is about 3700 mmol as there is about 1500 mmol stored in bones.

The usual sodium intake of an Australian diet is about 180 mmol/d but varies widely (50-400 mmol/day) depending on habit and cultural influences. The body has potent sodium retaining mechanisms and even if a person is on 5 mmol Na+/day they can maintain sodium balance. Extra sodium is lost from the body by reducing the activity of the renin angiotensin aldosterone system which leads to increased sodium loss from the body. Sodium is lost through the kidney, sweat and faeces. In states of sodium depletion aldosterone levels increase and in states of sodium excess aldosterone levels decrease. The major physiological controller of aldosterone secretion is the plasma angiotensin II level which increases aldosterone secretion. A high plasma potassium also increases aldosterone secretion because besides retaining Na+ high plasma aldosterone causes K+ loss by the kidney. Plasma Na+ levels have little effect on aldosterone secretion.

A low renal perfusion pressure stimulates the release of renin, which forms angiotensin I which is converted to angiotensin II. Angiotensin II will correct the low perfusion pressure by causing constriction of blood vessels and by increasing sodium retention by a direct effect on the proximal renal tubule and by an effect operated through aldosterone. The perfusion pressure to the adrenal gland has little direct effect on aldosterone secretion and the low blood pressure operates to control aldosterone via the renin angiotensin system.

In addition to aldosterone and angiotensin II other factors influence sodium excretion. Thus in high sodium states due either to excess intake or cardiac disease (+ others) atrial peptide is secreted from the heart and by a series of actions causes loss of sodium by the kidney. Elevated blood pressure will also tend to cause Na+ loss and a low blood pressure usually leads to sodium retention. Aldosterone also acts on the sweat ducts and colonic epithelium to conserve sodium. When aldosterone has been activated to retain sodium the plasma sodium tends to rise. This immediately causes release of ADH which causes water to be retained, thus retaining Na+ and H2O in the right proportion to restore plasma volume.

## Potassium Balance

Amount

Concentration

Amount in body

4000 mmol

Intracellular

3000 + mmol

110 mmol/l

Extracellular

53 mmol

4 mmol/l

Plasma

12 mmol

4 mmol/l

Interstitial

40 mmol

4 mmol/l

Bone

300 mmol

Amount in diet

Hunter Gatherer

200 – 400 mmol/day

Western

50 – 100 mmol/day

Obligatory Need

30 – 50 mmol/day

Potassium is predominantly an intracellular ion and most of the total body potassium of about 4000 mmol is inside the cells and the next largest proportion (300-500 mmol) is in the bones. Cell K+ concentration is about 150 mmol/l but varies in different organs. Extracellular potassium is about 4.0 mmol/l and with an extracellular value of about 13 litres, 52 mmol (ie. less than 1.5%) is present here and only 12 mmol in the plasma.

In an unprocessed diet potassium is much more plentiful than sodium and is present as an organic salt while sodium is added as NaCl. In a hunter gatherer K+ intake may be as much as 400 mmol/d while in the Western diet it is 70 mmol/d or less if a person has a minimal amount of fresh fruit and vegetables. Processing of foods replaces K+ with NaCl. While the body can excrete a large K+ load it is unable to conserve K+. On a zero K+ intake or in a person with K+ depletion there will still be a loss of K+ of 30-50 mmol/d in the urine and faeces.

If there is a high potassium intake, eg. 100 mmol, this would potentially increase the extracellular K+ level 2 times before the kidney could excrete the extra potassium. The body buffers the extra potassium by equilibrating it within the cells. The acid base status controls the distribution between plasma and cells. A high pH (ie. alkalosis >7.4) favours movement of K+ into the cells whilst a low pH (ie. acidosis) causes movement out of the cell. A high plasma potassium increases aldosterone secretion and this increases the potassium loss from the body, restoring balance. This change of distribution with the acid base status means that the plasma K+ may not reflect the total body content. Thus a person with an acidosis (pH 7.1) and a plasma K+ of 6.5 mmol/l could be depleted of total body potassium. This occurs in diabetic acidosis. Conversely a person who is alkalotic with a plasma K+ of 3.4 mmol/l may have normal total body potassium.

## Calcium and Phosphate Balance

Amount

Concentration

Amount in body

Interstitial (0.9%)

270 mmol

9 mmol/l

Cytoplasm

<1 mmol

10-6 mmol/l

Cell organelles

270 mmol

9 mmol/l

Extracellular (0.1%)

30 mmol

2.2 mmol/l

Plasma

7 mmol

2.2 mmol/l

Interstitial

23 mmol

2.2 mmol/l

Bone (99%)

27.5 mol (1.1 kg)

Amount in diet

1200 mg/day

40 mmol/day

Amount absorbed

300 mg/day

10 mmol/day

Amount excreted

300 mg/day

10 mmol/day

Obligatory Need

100 mg/day

3 mmol/day

Bone => Plasma

500 mmol/day

Calcium is a very important electrolyte. 99% or more is deposited in bone but the remainder is importantly associated with nerve conduction, muscle contraction, hormone release and cell signalling. The plasma concentration of Ca++ is 2.2 mmol/l and phosphate 1.0 mmol/l. The solubility product of Ca and P is close to saturation in plasma. The concentration of Ca++ in the cytoplasm is < 10-6 mmol/l but the concentration of Ca++ in the cell is much higher as calcium is taken up (and is able to be released from) cell organelles.

In the Australian diet there is about 1200 mg/d of calcium. Even if it was all soluble it is not all absorbed as it combines with phosphates in the intestinal secretions. In addition absorption is regulated by active Vitamin D and increased amounts increase Ca++ absorption. Absorption is controlled by Vitamin D while excretion is controlled by parathyroid hormones. However, the distribution from bone to plasma is controlled by both the parathyroid hormones and vitamin D. There is a constant loss of calcium by the kidney even if there was none in the diet. The excretion of calcium by the kidney and its distribution between bone and the rest of the body is primarily controlled by parathyroid hormone.

Calcium in plasma exists in 3 forms. Ionized, non ionized and protein bound. It is the ionized calcium concentration that is monitored by the parathyroid gland and if low, parathyroid hormone secretion is increased. This acts to increase ionized calcium levels by increasing bone re-absorption, decreasing renal excretion and acting on the kidney to increase the rate of formation of active Vitamin D, and thereby increase gut absorption of calcium.

The usual amount of phosphate in the diet is about 1 g/d but not all is absorbed. Any excess is excreted by the kidney and this excretion is increased by parathyroid hormone. Parathyroid hormone also causes phosphate to come out of bone. Plasma phosphate has no direct effect on parathyroid hormone secretion. However if it is elevated it combines with Ca++ decreasing the ionized Ca++ in plasma, thereby increasing parathyroid hormone secretion.

## Case Study

Heat stroke and Heat exhaustion

If you have ever performed heavy manual labor or competed in an athletic event on a very hot day, you may have experienced symptoms of heat exhaustion. Typically these include an elevated core body temperature (above 104F or 40C), profuse sweating, pale color, muscle cramps, dizziness, and in some extreme circumstances, fainting or loss of consciousness.

Heat exhaustion occurs as a consequence of disruption of the body's own system of thermoregulation, the means by which it adjusts temperature. Sweating is the principal means through which the body cools itself down, but diverting blood from other regions toward the skin also serves this purpose. Although sweat allows excess heat to dissipate as the moisture reaches the skin surface, it can also have dangerous implications for blood pressure and volume. As sweating increases, blood volume can drop precipitously, meaning that the brain and other body systems are at risk for insufficient oxygen and nutrient supplies. Furthermore, diverting blood away from other systems and towards the skin compounds the changes in blood volume and blood pressure induced through sweating.

Heat stroke is a far more serious condition. This happens when the body's temperature rises out of control due to the failure of the thermoregulating system. If the body is unable to reduce its temperature due to outside or physical influences, the brain will start to malfunction. Delirium and loss of consciousness set in. The center of the brain controlling the sweat glands will stop functioning, halting the production of sweat. This causes the body's temperature to rise even faster. Furthermore, with the increase of the body's temperature, the metabolic process will speed up causing even more heat in the body. If left untreated this will result in death. One of the easiest ways to spot heat stroke is the skin. If it is flushed due to the increase of blood flow but dry because the sweat glands have stopped secreting, the individual will need prompt medical attention.

## Other Examples

• Thermoregulation
• The skeletal muscles can shiver to produce heat if the body temperature is too low.
• Non-shivering thermogenesis involves the decomposition of fat to produce heat.
• Sweating cools the body with the use of evaporation.
• Chemical regulation
• The pancreas produces insulin and glucagon to control blood-sugar concentration.
• The lungs take in oxygen and give off carbon dioxide, which regulates pH in the blood.
• The kidneys remove urea, and adjust the concentrations of water and a wide variety of ions.

Main examples of homeostasis in mammals are as follows:

• The regulation of the amounts of water and minerals in the body. This is known as osmoregulation. This happens primarily in the kidneys.
• The removal of metabolic waste. This is known as excretion. This is done by the excretory organs such as the kidneys and lungs.
• The regulation of body temperature. This is mainly done by the skin.
• The regulation of blood glucose level. This is mainly done by the liver and the insulin and glucagon secreted by the pancreas in the body.

Most of these organs are controlled by hormones secreted from the pituitary gland, which in turn is directed by the hypothalamus.

## Review Questions I

Answers for these questions can be found here

1. Meaning of Homeostasis:

A) contributor and provider

B) expand

C) same or constant

2. What is the normal pH value for body fluid?

A) 7.15-7.25

B) 7.35-7.45

C) 7.55- 7.65

D) 7.00-7.35

E) 6.5-7.5

3. An example of the urinary system working with the respiratory system to regulate blood pH would be

A) When you hold your breath the kidneys will remove CO2 from your blood

B) If you exercise a lot your urine will become more acidic

C) If you have emphysema the kidneys will remove fewer bicarbonate ions from circulation

D) If you hyperventilate the kidneys will counteract the alkalinity by adding hydrogen ions into the blood stream

E) None of the above-the urinary system never works with the respiratory system

4. The urge to breathe comes in direct response to:

A) How long it has been since you last took a breath

B) The oxygen concentration of your surrounding environment

C) The build-up of nitrogen within your blood stream

D) The pH of your blood

E) The build-up of blood pressure that occurs when you don't breathe

5. In response to a bacterial infection my body's thermostat is raised. I start to shiver and produce more body heat. When my body temperature reaches 101 degrees, I stop shivering and my body temperature stops going up. This is an example of:

A) Negative feedback

B) A malfunctioning control system

C) Positive feedback

D) A negative impact

6. Which of the following is an example of a positive feedback?

A) Shivering to warm up in a cold winter storm

B) A cruise control set on your car applies more gas when going up a hill

C) You sweat on a hot summer's day and the blood vessels in your skin vasodilate

D) You get cut and platelets form a clot. This in turn activates the fibrin clotting system and more blood forms clots

7. Where is the body's "thermostat" found?

A) Within the nervous system, in the Hypothalamus

B) Within the integumentary system, in the skin

C) Within the brain, in the corpus callosum

D) Within the Urinary system, in the kidneys

8. What system has little to contribute to the homeostasis of the organism?

A) Urinary System

B) Reproductive System

C) Respiratory System

D) Nervous System

9. Select the phrase(s) below that best describe(s) homeostasis.

A) Fluctuating within a homeostatic range

B) Maintaining a constant internal environment

C) Dynamic equilibrium

D) Deviating

10.In which part of the nephron does ADH act?

A)PCT

B)DCT

C)Loop of Henle

D)None

• 1=C
• 2=B
• 3=C
• 4=D
• 5=A
• 6=D
• 7=A
• 8=B
• 9=B
• 10=B

## Glossary

• Control Center or Integration Center: receives and processes information from the receptor
• Effector: responds to the commands of the control center by either opposing or enhancing the stimulus
• Homeostasis: refers to stability, balance or equilibrium
• Negative Feedback: a reaction in which the system responds in such a way as to reverse the direction of change
• Positive Feedback: a response is to amplify the change in the variable
• Receptor: receives information that something in the environment is changing

# Cell Physiology

## Cell Structure and Function

### What is a Cell?

A cell is a structure as well as a functional unit of life. Every living thing has cells: bacteria, protozoans, fungi, plants, and animals are the main group of living things. Some organisms are made up of just one cell are called unicellular. (e.g. bacteria and protozoans), but animals, including human beings, are multi-cellular. An adult human body is composed of about 100,000,000,000,000 cells! Each cell has basic requirements to sustain it, and the body's organ systems are largely built around providing the many trillions of cells with those basic needs (such as oxygen, food, and waste removal).

Hi cells are awesome. Cell are made of many different things called organelles.

There are about 200 different kinds of specialized cells in the human body. When many identical cells are organized together it is called a tissue (such as muscle tissue, nervous tissue, etc). Various tissues organized together for a common purpose are called organs (e.g. the stomach is an organ, and so is the skin, the brain, and the uterus).

Ideas about cell structure have changed considerably over the years. Early biologists saw cells as simple membranous sacs containing fluid and a few floating particles. Today's biologists know that cells are inconceivably more complex than this. Therefore, a strong knowledge of the various cellular organelles and their functions is important to any physiologist. If a person's cells are healthy, then that person is healthy. All physiological processes, disease, growth and development can be described at the cellular level.

### Specialized Cells of the Human Body

Although there are specialized cells - both in structure and function - within the body, all cells have similarities in their structural organization and metabolic needs (such as maintaining energy levels via conversion of carbohydrate to ATP and using genes to create and maintain proteins).

Here are some of the different types of specialized cells within the human body.

• Nerve Cells: Also called neurons, these cells are in the nervous system and function to process and transmit information (it is hypothesized). They are the core components of the brain, spinal cord and peripheral nerves. They use chemical synapses that can evoke electrical signals, called action potentials, to relay signals throughout the body.
• Epithelial cells: Functions of epithelial cells include secretion, absorption, protection, transcellular transport, sensation detection, and selective permeability. Epithelium lines both the outside (skin) and the inside cavities and lumen of bodies.
• Exocrine cells: These cells secrete products through ducts, such as mucus, sweat, or digestive enzymes. The products of these cells go directly to the target organ through the ducts. For example, the bile from the gall bladder is carried directly into the duodenum via the bile duct.
• Endocrine cells: These cells are similar to exocrine cells, but secrete their products directly into the bloodstream instead of through a duct. Endocrine cells are found throughout the body but are concentrated in hormone-secreting glands such as the pituitary. The products of the endocrine cells go throughout the body in the blood stream but act on specific organs by receptors on the cells of the target organs. For example, the hormone estrogen acts specifically on the uterus and breasts of females because there are estrogen receptors in the cells of these target organs.
• Blood Cells: The most common types of blood cells are:
• red blood cells (erythrocytes). The main function of red blood cells is to collect oxygen in the lungs and deliver it through the blood to the body tissues. Gas exchange is carried out by simple diffusion.
• various types of white blood cells (leukocytes). They are produced in the bone marrow and help the body to fight infectious disease and foreign objects in the immune system. White cells are found in the circulatory system, lymphatic system, spleen, and other body tissues.

### Cell Size

Cells are the smallest structural & functional living units within our body, but play a big role in making our body function properly. Many cells never have a large increase in size like eggs, after they are first formed from a parental cell. Typical stem cells reproduce, double in size, then reproduce again. Most Cytosolic contents such as the endomembrane system and the cytoplasm easily scale to larger sizes in larger cells. If a cell becomes too large, the normal cellular amount of DNA may not be adequate to keep the cell supplied with RNA. Large cells often replicate their chromosomes to an abnormally high amount or become multinucleated. Large cells that are primarily for nutrient storage can have a smooth surface membrane, but metabolically active large cells often have some sort of folding of the cell surface membrane in order to increase the surface area available for transport functions.

### Cellular Organization

Several different molecules interact to form organelles within our body. Each type of organelle has a specific function. Organelles perform the vital functions that keep our cells alive.

#### Cell Membranes

The boundary of the cell, sometimes called the plasma membrane, separates internal metabolic events from the external environment and controls the movement of materials into and out of the cell. This membrane is very selective about what it allows to pass through; this characteristic is referred to as "selective permeability." For example, it allows oxygen and nutrients to enter the cell while keeping toxins and waste products out. The plasma membrane is a double phospholipid membrane, or a lipid bilayer, with the nonpolar hydrophobic tails pointing toward the inside of the membrane and the polar hydrophilic heads forming the inner and outer surfaces of the membrane.

The molecular structure of the cell membrane.

22

#### Protein and Cholesterol

Proteins and cholesterol molecules are scattered throughout the flexible phospholipid membrane. Peripheral proteins attach loosely to the inner or outer surface of the plasma membrane. Integral proteins lie across the membrane, extending from inside to outside. A variety of proteins are scattered throughout the flexible matrix of phospholipid molecules, somewhat like icebergs floating in the ocean, and this is termed the fluid mosaic model of the cell membrane.

The phospholipid bilayer is selectively permeable. Only small, uncharged polar molecules can pass freely across the membrane. Some of these molecules are H2O and CO2, hydrophobic (nonpolar) molecules like O2, and lipid soluble molecules such as hydrocarbons. Other molecules need the help of a membrane protein to get across. There are a variety of membrane proteins that serve various functions:

• Channel proteins: Proteins that provide passageways through the membranes for certain hydrophilic or water-soluble substances such as polar and charged molecules. No energy is used during transport, hence this type of movement is called facilitated diffusion.
• Transport proteins: Proteins that spend energy (ATP) to transfer materials across the membrane. When energy is used to provide passageway for materials, the process is called active transport.
• Recognition proteins: Proteins that distinguish the identity of neighboring cells. These proteins have oligosaccharide or short polysaccharide chains extending out from their cell surface.
• Adhesion proteins: Proteins that attach cells to neighboring cells or provide anchors for the internal filaments and tubules that give stability to the cell.
• Receptor proteins: Proteins that initiate specific cell responses once hormones or other trigger molecules bind to them.
• Electron transfer proteins: Proteins that are involved in moving electrons from one molecule to another during chemical reactions.

#### Passive Transport Across the Cell Membrane

Passive transport describes the movement of substances down a concentration gradient and does not require energy use.

• Bulk flow is the collective movement of substances in the same direction in response to a force, such as pressure. Blood moving through a vessel is an example of bulk flow.
• Simple diffusion, or diffusion, is the net movement of substances from an area of higher concentration to an area of lower concentration. This movement occurs as a result of the random and constant motion characteristic of all molecules, (atoms or ions) and is independent from the motion of other molecules. Since, at any one time, some molecules may be moving against the gradient and some molecules may be moving down the gradient, although the motion is random, the word "net" is used to indicate the overall, eventual end result of the movement.
• Facilitated diffusion is the diffusion of solutes through channel proteins in the plasma membrane. Water can pass freely through the plasma membrane without the aid of specialized proteins (though facilitated by aquaporins).
• Osmosis is the diffusion of water molecules across a selectively permeable membrane. When water moves into a body by osmosis, hydrostatic pressure or osmotic pressure may build up inside the body.
• Dialysis is the diffusion of solutes across a selectively permeable membrane.

#### Active Transport Across the Cell Membrane

Active transport is the movement of solutes against a gradient and requires the expenditure of energy, usually in the form of ATP. Active transport is achieved through one of these two mechanisms:

##### Protein Pumps
• Transport proteins in the plasma membrane transfer solutes such as small ions (Na+, K+, Cl-, H+), amino acids, and monosaccharides.
• The proteins involved with active transport are also known as ion pumps.
• The protein binds to a molecule of the substance to be transported on one side of the membrane, then it uses the released energy (ATP) to change its shape, and releases it on the other side.
• The protein pumps are specific, there is a different pump for each molecule to be transported.
• Protein pumps are catalysts in the splitting of ATP → ADP + phosphate, so they are called ATPase enzymes.
• The sodium-potassium pump (also called the Na+/K+-ATPase enzyme) actively moves sodium out of the cell and potassium into the cell. These pumps are found in the membrane of virtually every cell, and are essential in transmission of nerve impulses and in muscular contractions.

Cystic fibrosis is a genetic disorder that results in a mutated chloride ion channel. By not regulating chloride secretion properly, water flow across the airway surface is reduced and the mucus becomes dehydrated and thick.

##### Vesicular Transport
• Vesicles or other bodies in the cytoplasm move macromolecules or large particles across the plasma membrane. Types of vesicular transport include:
1. Exocytosis, which describes the process of vesicles fusing with the plasma membrane and releasing their contents to the outside of the cell. This process is common when a cell produces substances for export.
2. Endocytosis, which describes the capture of a substance outside the cell when the plasma membrane merges to engulf it. The substance subsequently enters the cytoplasm enclosed in a vesicle.
There are three kinds of endocytosis:
• Phagocytosis or cellular eating, occurs when the dissolved materials enter the cell. The plasma membrane engulfs the solid material, forming a phagocytic vesicle.
• Pinocytosis or cellular drinking occurs when the plasma membrane folds inward to form a channel allowing dissolved substances to enter the cell. When the channel is closed, the liquid is encircled within a pinocytic vesicle.
• Receptor-mediated endocytosis occurs when specific molecules in the fluid surrounding the cell bind to specialized receptors in the plasma membrane. As in pinocytosis, the plasma membrane folds inward and the formation of a vesicle follows.
Note: Certain hormones are able to target specific cells by receptor-mediated endocytosis.

## Parts of the Cell

### Cytoplasm

The gel-like material within the cell membrane is referred to as the cytoplasm. It is a fluid matrix, the cytosol, which consists of 80% to 90% water, salts, organic molecules and many enzymes that catalyze reactions, along with dissolved substances such as proteins and nutrients. The cytoplasm plays an important role in a cell, serving as a "molecular soup" in which organelles are suspended and held together by a fatty membrane.

Within the plasma membrane of a cell, the cytoplasm surrounds the nuclear envelope and the cytoplasmic organelles. It plays a mechanical role by moving around inside the membrane and pushing against the cell membrane helping to maintain the shape and consistency of the cell and again, to provide suspension to the organelles. It is also a storage space for chemical substances indispensable to life, which are involved in vital metabolic reactions, such as anaerobic glycolysis and protein synthesis.

The cell membrane keeps the cytoplasm from leaking out. It contains many different organelles which are considered the insoluble constituents of the cytoplasm, such as the mitochondria, lysosomes, peroxysomes, ribosomes, several vacuoles and cytoskeletons, as well as complex cell membrane structures such as the endoplasmic reticulum and the Golgi apparatus that each have specific functions within the cell.

• Cytoskeleton

Threadlike proteins that make up the cytoskeleton continually reconstruct to adapt to the cell's constantly changing needs. It helps cells maintain their shape and allows cells and their contents to move. The cytoskeleton allows certain cells such as neutrophils and macrophages to make amoeboid movements.

The network is composed of three elements: microtubules, actin filaments, and intermediate fibers.

• Microtubules

Microtubules function as the framework along which organelles and vesicles move within a cell. They are the thickest of the cytoskeleton structures. They are long hollow cylinders, composed of protein subunits, called tubulin. Microtubules form mitotic spindles, the machinery that partitions chromosomes between two cells in the process of cell division. Without mitotic spindles cells could not reproduce.

Microtubules, intermediate filaments, and microfilaments are three protein fibers of decreasing diameter, respectively. All are involved in establishing the shape or movements of the cytoskeleton, the internal structure of the cell.

A photograph of microfilaments.
• Microfilaments

Microfilaments provide mechanical support for the cell, determine the cell shape, and in some cases enable cell movements. They have an arrow-like appearance, with a fast growing plus or barbed end and a slow growing minus or pointed end. They are made of the protein actin and are involved in cell motility. They are found in almost every cell, but are predominant in muscle cells and in the cells that move by changing shape, such as phagocytes (white blood cells that scour the body for bacteria and other foreign invaders).

### Organelles

Organelles are bodies embedded in the cytoplasm that serve to physically separate the various metabolic activities that occur within cells. The organelles are each like separate little factories, each organelle is responsible for producing a certain product that is used elsewhere in the cell or body.

Cells of all living things are divided into two broad categories: prokaryotes and eukaryotes. Bacteria (and archea) are prokaryotes, which means they lack a nucleus or other membrane-bound organelles. Eukaryotes include all protozoans, fungi, plants, and animals (including humans), and these cells are characterized by a nucleus (which houses the chromosomes) as well as a variety of other organelles. Human cells vary considerably (consider the differences between a bone cell, a blood cell, and a nerve cell), but most cells have the features described below.

A comparison of Eukaryote and Prokaryote cells.

#### Nucleus

Controls the cell; houses the genetic material (DNA). The nucleus is the largest of the cells organelles. Cells can have more than one nucleus or lack a nucleus all together. Skeletal muscle cells contain more than one nucleus whereas red blood cells do not contain a nucleus at all. The nucleus is bounded by the nuclear envelope, a phospholipid bilayer similar to the plasma membrane. The space between these two layers is the nucleolemma Cisterna.

The nucleus contains the DNA, as mentioned above, the hereditary information in the cell. Normally the DNA is spread out within the nucleus as a threadlike matrix called chromatin. When the cell begins to divide, the chromatin condenses into rod-shaped bodies called chromosomes, each of which, before dividing, is made up of two long DNA molecules and various histone molecules. The histones serve to organize the lengthy DNA, coiling it into bundles called nucleosomes. Also visible within the nucleus are one or more nucleoli, each consisting of DNA in the process of manufacturing the components of ribosomes. Ribosomes are shipped to the cytoplasm where they assemble amino acids into proteins. The nucleus also serves as the site for the separation of the chromosomes during cell division.

A cross-sectional diagram of a nucleus.
• Chromosomes
A rough sketch of a chromosome.

Inside each cell nucleus are chromosomes. Chromosomes are made up of chromatin, which is made up of protein and deoxyribonucleic acid strands. Deoxyribonucleic acid is DNA, the genetic material that is in the shape of a twisted ladder, also called the double helix. Humans have 23 pairs of chromosomes. Down Syndrome and Cri du Chat Syndrome result from having an abnormal number of chromosomes.

#### Centrioles

Centrioles are rod like structures composed of 9 bundles which contain three microtubules each. Two perpendicularly placed centrioles surrounded by proteins make up the centrosome. Centrioles are very important in cellular division, where they arrange the mitotic spindles that pull the chromosome apart.

Centrioles and basal bodies act as microtubule organizing centers. A pair of centrioles (enclosed in a centrosome) located outside the nuclear envelope gives rise to the microtubules that make up the spindle apparatus used during cell division. Basal bodies are at the base of each flagellum and cilium and appear to organize their development.

#### Ribosomes

Ribosomes play an active role in the complex process of protein synthesis, where they serve as the structures that facilitate the joining of amino acids. Each ribosome is composed of a large and small subunit which are made up of ribosomal proteins and ribosomal RNAs. They can either be found in groups called polyribosomes within the cytoplasm or found alone. Occasionally they are attached to the endoplasmic reticulum.

A cutaway view inside a mitochondria.

#### Mitochondria

Mitochondria are the organelles that function as the cell "powerhouse", generating ATP, the universal form of energy used by all cells. It converts food nutrients such as glucose, to a fuel (ATP) that the cells of the body can use. Mitochondria are tiny sac-like structures found near the nucleus. Little shelves called cristae are formed from folds in the inner membrane. Cells that are metabolically active such as muscle, liver and kidney cells have high energy requirements and therefore have more mitochondria.

Mitochondria are unique in that they have their own mitochondrial DNA (separate from the DNA that is in the nucleus). It is believed that eukaryotes evolved from one cell living inside another cell, and mitochondria share many traits with free-living bacteria (similar chromosome, similar ribosomes, etc).

#### Endoplasmic Reticulum

Endoplasmic means "within the plasm" and reticulum means "network".

A complex three dimensional internal membrane system of flattened sheets, sacs and tubes, that play an important role in making proteins and shuttling cellular products; also involved in metabolisms of fats, and the production of various materials. In cross-section, they appear as a series of maze-like channels, often closely associated with the nucleus. When ribosomes are present, the rough ER connects polysaccharide groups to the polypeptides as they are assembled by the ribosomes. Smooth ER, without ribosomes, is responsible for various activities, including the synthesis of lipids and hormones, especially in cells that produce these substances for export from the cell.

Rough endoplasmic reticulum has characteristic bumpy appearance due to the multitude of ribosomes coating it. It is the site where proteins not destined for the cytoplasm are synthesized.

Smooth endoplasmic reticulum provides a variety of functions, including lipid synthesis and degradation, and calcium ion storage. In liver cells, the smooth ER is involved in the breakdown of toxins, drugs, and toxic byproducts from cellular reactions.

#### Golgi Apparatus

"Packages" cellular products in sacs called vesicles so that the products can cross the cell membrane and exit the cell. The Golgi apparatus is the central delivery system for the cell. It is a group of flattened sacs arranged much like a stack of bowls. They function to modify and package proteins and lipids into vesicles, small spherically shaped sacs that bud from the ends of a Golgi apparatus. Vesicles often migrate to and merge with the plasma membrane, releasing their contents outside the cell. The Golgi apparatus also transports lipids and creates lysosomes and organelles involved in digestion.

#### Vacuoles

Spaces in the cytoplasm that sometimes serve to carry materials to the cell membrane for discharge to the outside of the cell. Vacuoles are formed during endocytosis when portions of the cell membrane are pinched off.

#### Lysosomes

Lysosomes are sac-like compartments that contain a number of powerful degradative enzymes. They are built in the Golgi apparatus. They break down harmful cell products and waste materials, cellular debris, and foreign invaders such as bacteria, and then force them out of the cell. Tay-Sachs disease and Pompe's disease are just two of the malfunctions of lysosomes or their digestive proteins.

#### Peroxisomes

Organelles in which oxygen is used to oxidize substances, breaking down lipids and detoxifying certain chemicals. Peroxisomes self replicate by enlarging and then dividing. They are common in liver and kidney cells that break down potentially harmful substances. Peroxisomes can convert hydrogen peroxide, a toxin made of H2O2 to H2O.

### Extracellular structures

• Extracellular matrix

Human cells, like other animal cells, do not have a rigid cell wall. Human cells do have an important and variable structure outside of their cell membrane called the extracellular matrix. Sometimes this matrix can be extensive and solid (examples = calcified bone matrix, cartilage matrix), while other times it consists of a layer of extracellular proteins and carbohydrates. This matrix is responsible for cells binding to each other and is incredibly important in how cells physically and physiologically interact with each other.

• Flagella

Many prokaryotes have flagella, allowing, for example, an E. coli bacteria to propel its way up the urethra to cause a UTI (Urinary Tract Infection). Human cells, however (and in fact most eukaryotic cells) lack flagella. This makes sense since humans are multicellular, and individual cells do not need to swim around. The obvious exception to this is with sperm, and indeed each sperm is propelled by a single flagellum. The flagellum of sperm is composed of microtubules.

• Cilia

Cilia are especially notable on the single-celled protozoans, where they beat in synchrony to move the cells nimbly through the water. They are composed of extensions of the cell membrane that contain microtubules. When present in humans they are typically found in large numbers on a single surface of the cells, where rather than moving cells, they move materials. The mucociliary escalator of the respiratory system consists of mucus-secreting cells lining the trachea and bronchi, and ciliated epithelial cells that move the mucus ever-upward. In this manner mold spores, bacteria, and debris are caught in the mucus, removed from the trachea, and pushed into the esophagus (to be swallowed into a pit of acid). In the oviducts cilia move the ovum from the ovary to the uterus, a journey which takes a few days.

A magnified view of several cells, with visible cilia.

## Cell Junctions

The plasma membranes of adjacent cells are usually separated by extracellular fluids that allow transport of nutrients and wastes to and from the bloodstream. In certain tissues, however, the membranes of adjacent cells may join and form a junction. Three kinds of cell junctions are recognized:

• Desmosomes are protein attachments between adjacent cells. Inside the plasma membrane, a desmosome bears a disk shaped structure from which protein fibers extend into the cytoplasm. Desmosomes act like spot welds to hold together tissues that undergo considerable stress, such as our skin or heart muscle.
• Tight junctions are tightly stitched seams between cells. The junction completely encircles each cell, preventing the movement of material between the cell. Tight junctions are characteristic of cells lining the digestive tract, where materials are required to pass through cells,rather than intercellular spaces, to penetrate the bloodstream.
• Gap junctions are narrow tunnels that directly connect the cytoplasm of two neighbouring cells, consisting of proteins called connexons. These proteins allow only the passage of ions and small molecules. In this manner, gap junctions allow communication between cells through the exchange of materials or the transmission of electrical impulses.

## Cell Metabolism

Cell metabolism is the total energy released and consumed by a cell. Metabolism describes all of the chemical reactions that are happening in the body. Some reactions, called anabolic reactions, create needed products. Other reactions, called catabolic reactions, break down products. Your body is performing both anabolic and catabolic reactions at the same time and around the clock, twenty four hours a day, to keep your body alive and functioning. Even while you sleep, your cells are busy metabolizing.

• Catabolism: The energy releasing process in which a chemical or food is used (broken down) by degradation or decomposition, into smaller pieces.
• Anabolism: Anabolism is just the opposite of catabolism. In this portion of metabolism, the cell consumes energy to produce larger molecules via smaller ones.

### Energy Rich Molecules

Chemical diagram of an ATP molecule.

ATP is the currency of the cell. When the cell needs to use energy such as when it needs to move substances across the cell membrane via the active transport system, it "pays" with molecules of ATP. The total quantity of ATP in the human body at any one time is about 0.1 Mole. The energy used by human cells requires the hydrolysis of 200 to 300 moles of ATP daily. This means that each ATP molecule is recycled 2000 to 3000 times during a single day. ATP cannot be stored, hence its consumption must closely follow its synthesis. On a per-hour basis, 1 kilogram of ATP is created, processed and then recycled in the body. Looking at it another way, a single cell uses about 10 million ATP molecules per second to meet its metabolic needs, and recycles all of its ATP molecules about every 20-30 seconds.

When two hydrogen atoms are bonded, FAD is reduced to FADH2 and is turned into an energy-carrying molecule. FAD accommodates two equivalents of Hydrogen; both the hydride and the proton ions. This is used by organisms to carry out energy requiring processes. FAD is reduced in the citric acid cycle during aerobic respiration

NAD is used extensively in glycolysis and the citric acid cycle of cellular respiration. The reducing potential stored in NADH can be converted to ATP through the electron transport chain or used for anabolic metabolism. ATP "energy" is necessary for an organism to live. Green plants obtain ATP through photosynthesis, while other organisms obtain it by cellular respiration.

NADP is used in anabolic reactions, such as fat acid and nucleic acid synthesis, that require NADPH as a reducing agent. In chloroplasts, NADP is an oxidising agent important in the preliminary reactions of photosynthesis. The NADPH produced by photosynthesis is then used as reducing power for the biosynthetic reactions in the Calvin cycle of photosynthesis.

Chemical diagram of an NADH molecule.

MH2 + NAD+ → NADH + H+ + M: + energy, where M is a metabolite. Two hydrogen ions (a hydride ion and an H+ ion) are transferred from the metabolite. One electron is transferred to the positively-charged nitrogen, and one hydrogen attaches to the carbon atom opposite to the nitrogen.

The human body synthesizes NAD from the vitamin niacin in the form of nicotinic acid or nicotinamide.

#### Cellular Respiration

Cellular respiration is the energy releasing process by which sugar molecules are broken down by a series of reactions and the chemical energy gets converted to energy stored in ATP molecules. The reactions that convert the fuel (glucose) to usable cellular energy (ATP) are glycolysis, the Krebs cycle (sometimes called the citric acid cycle), and the electron transport chain. Altogether these reactions are referred to as "cellular respiration" or "aerobic respiration." Oxygen is needed as the final electron acceptor, and carrying out cellular respiration is the very reason we breathe and the reason we eat.

Flowchart of cellular respiration.

### Glycolysis

The glycolytic pathway (glycolysis) is where glucose, the smallest molecule that a carbohydrate can be broken into during digestion, gets oxidized and broken into two 3-carbon molecules (pyruvates), which are then fed into the Kreb's Cycle. Glycolysis is the beginning of cellular respiration and takes place in the cytoplasm. Two molecules of ATP are required for glycolysis, but four are produced so there is a net gain of two ATP per glucose molecule. Two NADH molecules transfer electrons (in the form of hydrogen ions) to the electron transport chain in the mitochondria, where they will be used to generate additional ATP. During physical exertion when the mitochondria are already producing the maximum ATP possible with the amount of oxygen available, glycolysis can continue to produce an additional 2 ATP per glucose molecule without sending the electrons to the mitochondria. However, during this anaerobic respiration lactic acid is produced, which may accumulate and lead to temporary muscle cramping.

### Krebs Cycle

The Krebs cycle was named after Sir Hans Krebs (1900-1981), who proposed the key elements of this pathway in 1937 and was awarded the Nobel Prize in Medicine for its discovery in 1953.

Two molecules of pyruvate enter the Krebs cycle, which is called the aerobic pathway because it requires the presence of oxygen in order to occur. This cycle is a major biological pathway that occurs in humans and every plant and animal.

After glycolysis takes place in the cell's cytoplasm, the pyruvic acid molecules travel into the interior of the mitochondrion. Once the pyruvic acid is inside, carbon dioxide is enzymatically removed from each three-carbon pyruvic acid molecule to form acetic acid. The enzyme then combines the acetic acid with an enzyme, coenzyme A, to produce acetyl coenzyme A, also known as acetyl CoA.

Once acetyl CoA is formed, the Krebs cycle begins. The cycle is split into eight steps, each of which will be explained below.

• Step 1: The acetic acid subunit of acetyl CoA is combined with oxaloacetate to form a molecule of citrate. The acetyl coenzyme A acts only as a transporter of acetic acid from one enzyme to another. After Step 1, the coenzyme is released by hydrolysis so that it may combine with another acetic acid molecule to begin the Krebs cycle again.
• Step 2: The citric acid molecule undergoes an isomerization. A hydroxyl group and a hydrogen molecule are removed from the citrate structure in the form of water. The two carbons form a double bond until the water molecule is added back. Only now, the hydroxyl group and hydrogen molecule are reversed with respect to the original structure of the citrate molecule. Thus, isocitrate is formed.
• Step 3: In this step, the isocitrate molecule is oxidized by a NAD molecule. The NAD molecule is reduced by the hydrogen atom and the hydroxyl group. The NAD binds with a hydrogen atom and carries off the other hydrogen atom leaving a carbonyl group. This structure is very unstable, so a molecule of CO2 is released creating alpha-ketoglutarate.
• Step 4: In this step, our friend, coenzyme A, returns to oxidize the alpha-ketoglutarate molecule. A molecule of NAD is reduced again to form NADH and leaves with another hydrogen. This instability causes a carbonyl group to be released as carbon dioxide and a thioester bond is formed in its place between the former alpha-ketoglutarate and coenzyme A to create a molecule of succinyl-coenzyme A complex.
• Step 5: A water molecule sheds its hydrogen atoms to coenzyme A. Then, a free-floating phosphate group displaces coenzyme A and forms a bond with the succinyl complex. The phosphate is then transferred to a molecule of GDP to produce an energy molecule of GTP. It leaves behind a molecule of succinate.
• Step 6: In this step, succinate is oxidized by a molecule of FAD (Flavin adenine dinucleotide). The FAD removes two hydrogen atoms from the succinate and forces a double bond to form between the two carbon atoms, thus creating fumarate.
• Step 7: An enzyme adds water to the fumarate molecule to form malate. The malate is created by adding one hydrogen atom to a carbon atom and then adding a hydroxyl group to a carbon next to a terminal carbonyl group.
• Step 8: In this final step, the malate molecule is oxidized by a NAD molecule. The carbon that carried the hydroxyl group is now converted into a carbonyl group. The end product is oxaloacetate which can then combine with acetyl-coenzyme A and begin the Krebs cycle all over again.
• Summary: In summary, three major events occur during the Krebs cycle. One GTP (guanosine triphosphate) is produced which eventually donates a phosphate group to ADP to form one ATP; three molecules of NAD are reduced; and one molecule of FAD is reduced. Although one molecule of GTP leads to the production of one ATP, the production of the reduced NAD and FAD are far more significant in the cell's energy-generating process. This is because NADH and FADH2 donate their electrons to an electron transport system that generates large amounts of energy by forming many molecules of ATP.

### Electron Transport System

The most complicated system of all. In the respiration chain, oxidation and reduction reactions occur repeatedly as a way of transporting energy. The respiratory chain is also called the electron transport chain. At the end of the chain, oxygen accepts the electron and water is produced.

#### Redox Reaction

This is a simultaneous oxidation-reduction process whereby cellular metabolism occurs, such as the oxidation of sugar in the human body, through a series of very complex electron transfer processes.

The chemical way to look at redox processes is that the substance being oxidized transfers electrons to the substance being reduced. Thus, in the reaction, the substance being oxidized (aka. the reducing agent) loses electrons, while the substance being reduced (aka. the oxidizing agent) gains electrons. Remember: LEO (Losing Electrons is Oxidation) the lion says GER (Gaining Electrons is Reduction); or alternatively: OIL (Oxidation is Loss) RIG (Reduction is Gain).

The term redox state is often used to describe the balance of NAD+/NADH and NADP+/NADPH in a biological system such as a cell or organ. The redox state is reflected in the balance of several sets of metabolites (e.g., lactate and pyruvate, β-hydroxybutyrate and acetoacetate) whose interconversion is dependent on these ratios. An abnormal redox state can develop in a variety of deleterious situations, such as hypoxia, shock, and sepsis.

## Cell Building Blocks

What major classes of molecules are found within cells?

### Lipids

The term is more-specifically used to refer to fatty-acids and their derivatives (including tri-, di-, and mono-glycerides and phospholipids) as well as other fat-soluble sterol-containing metabolites such as cholesterol. Lipids serve many functions in living organisms including energy storage, serve as structural components of cell membranes, and constitute important signaling molecules. Although the term lipid is sometimes used as a synonym for fat, the latter is in fact a subgroup of lipids called triglycerides and should not be confused with the term fatty acid.

### Carbohydrates

Carbohydrate molecules consist of carbon, hydrogen, and oxygen. They have a general formula Cn(H2O)n. There are several sub-families based on molecular size.

Carbohydrates are chemical compounds that contain oxygen, hydrogen, and carbon atoms, and no other elements. They consist of monosaccharide sugars of varying chain lengths.

Certain carbohydrates are an important storage and transport form of energy in most organisms, including plants and animals. Carbohydrates are classified by their number of sugar units: monosaccharides (such as glucose and fructose), disaccharides (such as sucrose and lactose), oligosaccharides, and polysaccharides (such as starch, glycogen, and cellulose).

The simplest carbohydrates are monosaccharides, which are small straight-chain aldehydes and ketones with many hydroxyl groups added, usually one on each carbon except the functional group. Other carbohydrates are composed of monosaccharide units and break down under hydrolysis. These may be classified as disaccharides, oligosaccharides, or polysaccharides, depending on whether they have two, several, or many monosaccharide units.

### Proteins

All proteins contain carbon, hydrogen, oxygen and nitrogen. Some also contain phosphorus and sulfur. The building blocks of proteins are amino acids. There are 20 different kinds of amino acids used by the human body. They unite by peptide bonds to form long molecules called polypeptides. Polypeptides are assembled into proteins. Proteins have four levels of structure

• Primary

Primary structure is the sequence of amino acids bonded in the polypeptide.

• Secondary

The secondary structure is formed by hydrogen bonds between amino acids. The polypeptide can coil into a helix or form a pleated sheet.

• Tertiary

The tertiary structure refers to the three-dimensional folding of the helix or pleated sheet.

• Quaternary

The quaternary structure refers to the spatial relationship among the polypeptide in the protein.

• Hexagonary

The hexagonary structure refers to the carpal relationship among the bipeptide in the person.

### Enzymes

A biological molecule that catalyzes a chemical reaction. Enzymes are essential for life because most chemical reactions in living cells would occur too slowly or would lead to different products without enzymes. Most enzymes are proteins and the word "enzyme" is often used to mean a protein enzyme. Some RNA molecules also have a catalytic activity, and to differentiate them from protein enzymes, they are referred to as RNA enzymes or ribozymes.

## Review Questions

Answers for these questions can be found here

1. List 2 functions of the cell membrane:

Questions 2 - 6 Match the following organelles with their function: 2. Mitochondria 3. Vacuoles 4. Cilia 5. Smooth ER 6. Golgi Apparatus

A. Movement of the cell
B. Lipid synthesis and transport
C. "Powerhouse" of the cell, makes ATP
D. Storage areas, mainly found in plant cells
E. Packages and distributes cellular products

7. The diffusion of H2O across a semi permeable or selectively permeable membrane is termed

A. Active transport
B. Diffusion
C. Osmosis
D. Endocytosis

8. Oxygen enters a cell via?

a. Diffusion
b. Filtration
c. Osmosis
d. Active transport

9. The term used to describe, "cell eating" is?

a. Exocytosis
b. Phagocytosis
c. Pinocytosis
d. Diffusion

10. Which of the following requires energy?

a. Diffusion
b. Osmosis
c. Active transport
d. Facilitated diffusion

11. Protein synthesis occurs at the

a. Mitochondria
b. Lysosomes
c. Within the nucleus
d. Ribosomes

12. Which of the following is not found in the cell membrane?

a. Cholesterol
b. Phospholipids
c. Proteins
d. Galactose
e. Nucleic acids

13. What is a cell?

a. The largest living units within our bodies.
b. Enzymes that "eat" bacteria
c. Microscopic fundamental units of all living things.
d. All of the above.

## Glossary

Active Transport: the movement of solutes against a gradient and requires the expenditure of energy

Adenosine Triphosphate (ATP): a cell’s source of energy

Bulk Flow: the collective movement of substances in the same direction in response to a force

Cells: the microscopic fundamental unit that makes up all living things

Cell Membrane: boundary of the cell, sometimes called the plasma membrane

Cytoplasm: a water-like substance that fills cells. The cytoplasm consists of cytosol and the cellular organelles, except the cell nucleus. The cytosol is made up of water, salts, organic molecules and many enzymes that catalyze reactions. The cytoplasm holds all of the cellular organelles outside of the nucleus, maintains the shape and consistency of the cell, and serves as a storage place for chemical substances.

Cytoskeleton: made of threadlike proteins, helps cells maintain their shape and allows cells and their contents to move

Dialysis: the diffusion of solutes across a selectively permeable membrane. Most commonly heard of when a patient has had renal failure. In medicine, dialysis is a type of renal replacement therapy which is used to provide an artificial replacement for lost kidney function due to renal failure. It is a life support treatment and does not treat any kidney diseases.

Endocrine cells: similar to exocrine cells, but secrete their products directly into the bloodstream instead of through a duct

Endocytosis: the capture of a substance outside the cell when the plasma membrane merges to engulf it

Endoplasmic Reticulum: organelle that play an important role in making proteins and shuttling cellular products; also involved in metabolisms of fats, and the production of various materials

Epithelial Cells: cells that aid in secretion, absorption, protection, trans-cellular transport, sensation detection, and selective permeability

Exocrine Cells: cells that secrete products through ducts, such as mucus, sweat, or digestive enzymes

Exocytosis: the process of vesicles fusing with the plasma membrane and releasing their contents to the outside of the cell

Facilitated Diffusion: the diffusion of solutes through channel proteins in the plasma membrane

Golgi Apparatus: "packages" cellular products in sacs called vesicles so that the products can cross the cell membrane and exit the cell

Glycolysis: process in which sugars (glucose) are converted to acid

Lysosomes: sac-like compartments that contain a number of powerful degradative enzymes

Microfilaments: provide mechanical support for the cell, determine the cell shape, and in some cases enable cell movements

Microtubules: function as the framework along which organelles and vesicles move within a cell

Mitochondria: the organelles that function as the cell "powerhouse", generating ATP

Nucleus: controls the cell; houses the genetic material

Organelles: bodies embedded in the cytoplasm that serve to physically separate the various metabolic activities that occur within cells

Osmosis: the diffusion of water molecules across a selectively permeable membrane from an area of high solute concentration to an area of low solute concentration.

Passive Transport: the movement of substances down a concentration gradient and does not require energy use

Peroxisomes: organelles in which oxygen is used to oxidize substances, breaking down lipids and detoxifying certain chemicals

Phagocytosis: a form of endocytosis wherein large particles are enveloped by the cell membrane of a (usually larger) cell and internalized to form a phagosome, or "food vacuole." In animals, phagocytosis is performed by specialized cells called phagocytes, which serve to remove foreign bodies and thus fight infection. In vertebrates, these include larger macrophages and smaller granulocytes, types of blood cells. Bacteria, dead tissue cells, and small mineral particles are all examples of objects that may be phagocytosed.

Pinocytosis: also called cellular drinking, is a form of endocytosis, a process in which small particles are taken in by a cell by splitting into smaller particles. The particles then form small vesicles which subsequently fuse with lysosomes to hydrolyze, or to break down, the particles. This process requires adenosine triphosphate (ATP).

Receptor-mediated Endocytosis: occurs when specific molecules in the fluid surrounding the cell bind to specialized receptors in the plasma membrane

Red Blood Cells (erythrocytes): cells that collect oxygen in the lungs and deliver it through the blood to the body tissues

Ribosomes: play an active role in the complex process of protein synthesis, where they serve as the structures that facilitate the joining of amino acids

Simple Diffusion: the net movement of substances from an area of higher concentration to an area of lower concentration

Vacuoles: spaces in the cytoplasm that sometimes serve to carry materials to the cell membrane for discharge to the outside of the cell

White Blood Cells (leukocytes): produced in the bone marrow and help the body to fight infectious disease and foreign objects in the immune system

# The Integumentary System

## Introduction

The integumentary system consists of the skin, hair, nails, the subcutaneous tissue below the skin,and assorted glands.The most obvious function of the integumentary system is the protection that the skin gives to underlying tissues. The skin not only keeps most harmful substances out, but also prevents the loss of fluids.

A major function of the subcutaneous tissue is to connect the skin to underlying tissues such as muscles. Hair on the scalp provides insulation from cold for the head. The hair of eyelashes and eyebrows helps keep dust and perspiration out of the eyes, and the hair in our nostrils helps keep dust out of the nasal cavities. Any other hair on our bodies no longer serves a function, but is an evolutionary remnant. Nails protect the tips of fingers and toes from mechanical injury. Fingernails give the fingers greater ability to pick up small objects.

There are four types of glands in the integumentary system: Sudoriferous glands, Sebaceous glands, Ceruminous glands, and Mammary glands. Sudoriferous glands are sweat producing glands. These are important to help maintain body temperature. Sebaceous glands are oil producing glands which help inhibit bacteria, keep us waterproof and prevent our hair and skin from drying out. Ceruminous glands produce earwax which keeps the outer surface of the eardrum pliable and prevents drying. Mammary glands produce milk.

## Skin

In zoology and dermatology, skin is an organ of the integumentary system made up of a layer of tissues that guard underlying muscles and organs. As the interface with the surroundings, it plays the most important role in protecting against pathogens. Its other main functions are insulation and temperature regulation, sensation and vitamin D and B synthesis. Skin is considered one of the most important parts of the body.

Skin has pigmentation, melanin, provided by melanocytes, which absorbs some of the potentially dangerous radiation in sunlight. It also contains DNA repair enzymes which reverse UV damage, and people who lack the genes for these enzymes suffer high rates of skin cancer. One form predominantly produced by UV light, malignant melanoma, is particularly invasive, causing it to spread quickly, and can often be deadly. Human skin pigmentation varies among populations in a striking manner. This has sometimes led to the classification of people(s) on the basis of skin color.

Damaged skin will try to heal by forming scar tissue, often giving rise to discoloration and depigmentation of the skin.

The skin is often known as "the largest organ in the human body". This applies to exterior surface, as it covers the body, appearing to have the largest surface area of all the organs. Moreover, it applies to weight, as it weighs more than any single internal organ, accounting for about 15 percent of body weight. For the average adult human, the skin has a surface area of between 1.5-2.0 square meters, most of it is between 2-3 mm thick. The average square inch of skin holds 650 sweat glands, 20 blood vessels, 60,000 melanocytes, and more than a thousand nerve endings.

The use of natural or synthetic cosmetics to treat the appearance of the face and condition of the skin (such as pore control and black head cleansing) is common among many cultures.

### Layers

The skin has two major layers which are made of different tissues and have very different functions.

Diagram of the layers of human skin

Skin is composed of the epidermis and the dermis. Below these layers lies the hypodermis or subcutaneous adipose layer, which is not usually classified as a layer of skin.

The outermost epidermis consists of stratified squamous keratinizing epithelium with an underlying basement membrane. It contains no blood vessels, and is nourished by diffusion from the dermis. The main type of cells which make up the epidermis are keratinocytes, with melanocytes and Langerhans cells also present. The epidermis can be further subdivided into the following strata (beginning with the outermost layer): corneum, lucidum, granulosum, spinosum, basale. Cells are formed through mitosis at the innermost layers. They move up the strata changing shape and composition as they differentiate, inducing expression of new types of keratin genes. They eventually reach the corneum and become sloughed off (desquamation). This process is called keratinization and takes place within about 30 days. This layer of skin is responsible for keeping water in the body and keeping other harmful chemicals and pathogens out.

Blood capillaries are found beneath the dermis, and are linked to an arteriole and a venule. Arterial shunt vessels may bypass the network in ears, the nose and fingertips.

The dermis lies below the epidermis and contains a number of structures including blood vessels, nerves, hair follicles, smooth muscle, glands and lymphatic tissue. It consists of loose connective tissue otherwise called areolar connective tissue—collagen, elastin and reticular fibers are present. Erector muscles, attached between the hair papilla and epidermis, can contract, resulting in the hair fiber pulled upright and consequentially goose bumps. The main cell types are fibroblasts, adipocytes (fat storage) and macrophages. Sebaceous glands are exocrine glands which produce a mixture of lipids and waxy substances known as sebum. Sebum serves many functions, including lubrication, water-proofing, softening, and also provides antimicrobial properties. Sweat glands open up via a duct onto the skin by a pore.

The dermis is made of an irregular type of fibrous connective tissue consisting of collagen and elastin fibers. It can be split into the papillary and reticular layers. The papillary layer is outermost and extends into the epidermis to supply it with vessels. It is composed of loosely arranged fibers. Papillary ridges make up the lines of the hands giving us fingerprints. The reticular layer is more dense and is continuous with the hypodermis. It contains the bulk of the structures (such as sweat glands). The reticular layer is composed of irregularly arranged fibers and resists stretching.

The hypodermis is not part of the skin, and lies below the dermis. Its purpose is to attach the skin to underlying bone and muscle as well as supplying it with blood vessels and nerves. It consists of loose connective tissue and elastin. The main cell types are fibroblasts, macrophages and adipocytes (the hypodermis contains 95% of body fat). Fat serves as padding and insulation for the body.

Clinical Application:
The patch drug delivery system. The transdermal patch is an increasingly popular drug delivery system. These patches are designed so that the drug molecules diffuse through the epidermis to the blood vessels in the dermis layer. A typical patch works well for small lipid-soluble molecules (for example, estrogen, nitroglycerin, and nicotine) that can make their way between epidermal cells.

### Functions

1. Protection: Skin gives an anatomical barrier between the internal and external environment in bodily defense; Langerhans cells in the skin are part of the immune system
2. Sensation: Skin contains a variety of nerve endings that react to heat, cold, touch, pressure, vibration, and tissue injury; see somatosensory system and touch.
3. Heat regulation: The skin contains a blood supply far greater than its requirements which allows precise control of energy loss by radiation, convection and conduction. Dilated blood vessels increase perfusion and heat loss while constricted vessels greatly reduce cutaneous blood flow and conserve heat. Erector pili muscles are significant in animals.

## Hair

### Types of hair

Humans have three different types of hair:

• Lanugo, the fine, unpigmented hair that covers nearly the entire body of a fetus, although most has been replaced with vellus by the time of the baby's birth
• Vellus hair, the short, downy, "peach fuzz" body hair (also unpigmented) that grows in most places on the human body. While it occurs in both sexes, and makes up much of the hair in children, men have a much smaller percentage (around 10%) vellus whereas 2/3 of a female's hair is vellus.
• Terminal hair, the fully developed hair, which is generally longer, coarser, thicker, and darker than vellus hair, and often is found in regions such as the axillary, male beard, and pubic.

### Pathological impacts on hair

Drugs used in cancer chemotherapy frequently cause a temporary loss of hair, noticeable on the head and eyebrows, because they kill all rapidly dividing cells, not just the cancerous ones. Other diseases and traumas can cause temporary or permanent loss of hair, either generally or in patches.

The hair shafts may also store certain poisons for years, even decades, after death. In the case of Col. Lafayette Baker, who died July 3, 1868, use of an atomic absorption spectrophotometer showed the man was killed by white arsenic. The prime suspect was Wallace Pollock, Baker's brother-in-law. According to Dr. Ray A. Neff, Pollack had laced Baker's beer with it over a period of months, and a century or so later minute traces of arsenic showed up in the dead man's hair. Mrs. Baker's diary seems to confirm that it was indeed arsenic, as she writes of how she found some vials of it inside her brother's suit coat one day.

## Nails

### Parts of the fingernail

The parts of a finger nail

The fingernail is an important structure made of keratin. The fingernail generally serve two purposes. It serves as a protective plate and enhances sensation of the fingertip. The protection function of the fingernail is commonly known, but the sensation function is equally important. The fingertip has many nerve endings in it allowing us to receive volumes of information about objects we touch. The nail acts as a counterforce to the fingertip providing even more sensory input when an object is touched.

### Nail Structure

The structure we know of as the nail is divided into six specific parts - the root, nail bed, nail plate, eponychium (cuticle), perionychium, and hyponychium.

Root The root of the fingernail is also known as the germinal matrix. This portion of the nail is actually beneath the skin behind the fingernail and extends several millimeters into the finger. The fingernail root produces most of the volume of the nail and the nail bed. This portion of the nail does not have any melanocytes, or melanin producing cells. The edge of the germinal matrix is seen as a white, crescent shaped structure called the lunula.

Nail Bed The nail bed is part of the nail matrix called the sterile matrix. It extends from the edge of the germinal matrix, or lunula, to the hyponychium. The nail bed contains the blood vessels, nerves, and melanocytes, or melanin-producing cells. As the nail is produced by the root, it streams down along the nail bed, which adds material to the undersurface of the nail making it thicker. It is important for normal nail growth that the nail bed be smooth. If it is not, the nail may split or develop grooves that can be cosmetically unappealing.

Nail Plate The nail plate is the actual fingernail, made of translucent keratin. The pink appearance of the nail comes from the blood vessels underneath the nail. The underneath surface of the nail plate has grooves along the length of the nail that help anchor it to the nail bed.

eponychium The cuticle of the fingernail is also called the eponychium. The cuticle is situated between the skin of the finger and the nail plate fusing these structures together and providing a waterproof barrier.

Perionychium The perioncyhium is the skin that overlies the nail plate on its sides. It is also known as the paronychial edge. The perionychium is the site of hangnails, ingrown nails, and an infection of the skin called paronychia.

Hyponychium The hyponychium is the area between the nail plate and the fingertip. It is the junction between the free edge of the nail and the skin of the fingertip, also providing a waterproof barrier.

Nails: left hand, adult human male

### Nail Diseases

Nail diseases are in a separate category from diseases of the skin. Although nails are a skin appendage, they have their own signs and symptoms which may relate to other medical conditions. Nail conditions that show signs of infection or inflammation require medical assistance and cannot be treated at a beauty parlor. Deformity or disease of the nails may be referred to as onychosis.

There are many disease that can occur with the fingernails and toenails. The most common of these diseases are ingrown nails and fungal infections.

#### Ingrown Nails

Onychocryptosis, commonly known as "ingrown nails" (unguis incarnatus), can affect either the fingers or the toes. In this condition, the nail cuts into one or both sides of the nail bed, resulting in inflammation and possibly infection. The relative rarity of this condition in the fingers suggests that pressure from the ground or shoe against the toe is a prime factor. The movements involved in walking or other physical disturbances can contribute to the problem. Mild onychocryptosis, particularly in the absence of infection, can be treated by trimming and rounding the nail. More advanced cases, which usually include infection, are treated by surgically excising the ingrowing portion of the nail down to its bony origin and cauterizing the matrix, or 'root', to prevent recurrence. This surgery is called matricectomy. The best results are achieved by cauterizing the matrix with phenol. Another method, which is much less effective, is excision of the matrix, sometimes called a 'cold steel procedure'

#### Nail Fungus

An infection of nail fungus (onychomycosis) occurs when fungi infect one or more of your nails. Onychomycosis generally begins as a white or yellow spot under the tip of the fingernail or toenail. As the nail fungus spreads deeper into the nail, it may cause the nail to discolor, thicken and develop crumbling edges — an unsightly and potentially painful problem.

Infections of nail fungus account for about half of all nail disorders. These infections usually develop on nails continually exposed to warm, moist environments, such as sweaty shoes or shower floors. Nail fungus isn't the same as athlete's foot, which primarily affects the skin of the feet, but at times the two may coexist and can be caused by the same type of fungus.

An infection with nail fungus may be difficult to treat, and infections may recur. But medications are available to help clear up nail fungus permanently.

### Clinical Application

Nail inspection can give a great deal of information about the internal working of the body as well, and like tongue or iris inspection, has a long history of diagnostic use in cantraditional medical practices such as Chinese medicine.

Pliability:

Brittleness is associated with iron deficiency, thyroid problems, impaired kidney function, circulation problems[2], and biotin deficiency[3] Splitting and fraying are associated with psoriasis, folic acid, protein and/or Vitamin C deficiency. Unusual thickness is associated with circulation problems. Thinning nails and itchy skin are associated with lichen planus[4].

Shape and texture:

Clubbing, or nails that curve down around the fingertips with nail beds that bulge is associated with oxygen deprivation and lung, heart, or liver disease. Spooning, or nails that grow upwards is associated with iron or B12 deficiency. Flatness can indicate a B12 vitamin deficiency[5] or Raynaud's disease[6] Pitting of the nails is associated with Psoriasis. Horizontal ridges indicate stress, and Beau's lines are associated with many serious conditions. Vertical ridges are associated with arthritis[7]. Vertical grooves are associated with kidney disorders, aging, and iron deficiency[8]. Beading is associated with rheumatoid arthritis[9]. Nails that resemble hammered brass are associated with (or portend) hair loss[10]. Short small beds are associated with heart disease[11].

Coloration of the nail bed:

Mee's lines are associated with arsenic or thallium poisoning, and renal failure. White lines across the nail are associated with heart disease, liver disease, or a history of a recent high fever[12]. Opaque white nails with a dark band at the fingertip are associated with cancer, cirrhosis, congestive heart failure, diabetes and aging[13]. Paleness or whitening is associated with liver or kidney disease and anemia[14]. Yellowing of the nail bed is associated with chronic bronchitis, lymphatic problems, diabetes, and liver disorders. Brown or copper nail beds are associated with arsenic or copper poisoning, and local fungal infection. Grey nail beds are associated with arthritis, edema, malnutrition, post-operative effects, glaucoma and cardio-pulmonary disease[15]. redness is associated with heart conditions. dark nails are associated with B12 deficiency. Stains of the nail plate (not the nail bed) are associated with nail polish[16], smoking, and henna use.

Markings:

Pink and white nails are associated with kidney disease[17]. Parallel white lines in the nails are associated with hypoalbuminemia. red skin at the base of the nail is associated with connective tissue disorders[18]. blue lunulae are associated with silver poisoning or lung disorder[19]. blue nail beds are (much like blue skin) associated with poor oxygenation of the blood (asthma, emphysema, etc)[20]. small white patches are associated with zinc or calcium deficiency or malabsorption, parasites, or local injury[21]. receded lunulae (fewer than 8) are associated with poor circulation[22], shallow breathing habits or thyroid mysfunction[23]. large lunulae (more than 25% of the thumb nail) is associated with high blood pressure.

## Glands

### Sweat Glands

A diagrammatic sectional view of the skin (magnified). Sweat gland labeled as "sudoriferous gland" at center right.

In humans, there are two kinds of sweat glands which differ greatly in both the composition of the sweat and its purpose: Also "click" here"How our body Sweats" to see a short movie on sweat glands.

#### Eccrine (a.k.a. merocrine)

Eccrine sweat glands are exocrine glands distributed over the entire body surface but are particularly abundant on the palms of hands, soles of feet, and on the forehead. These produce sweat that is composed chiefly of water (99%) with various salts. The primary function is body temperature regulation.

Eccrine sweat glands are coiled tubular glands derived leading directly to the most superficial layer of the epidermis (out layer of skin) but extending into the inner layer of the skin (dermis layer). They are distributed over almost the entire surface of the body in humans and many other species, but are lacking in some marine and fur-bearing species. The sweat glands are controlled by sympathetic cholinergic nerves which are controlled by a center in the hypothalamus. The hypothalamus senses core temperature directly, and also has input from temperature receptors in the skin and modifies the sweat output, along with other thermoregulatory processes.

Human eccrine sweat is composed chiefly of water with various salts and organic compounds in solution. It contains minute amounts of fatty materials, urea, and other wastes. The concentration of sodium varies from 35–65 mmol/l and is lower in people acclimatised to a hot environment. The sweat of other species generally differ in composition.

#### Apocrine

Apocrine sweat glands only develop during early- to mid-puberty (approximately age 15) and release more than normal amounts of sweat for approximately a month and subsequently regulate and release normal amounts of sweat after a certain period of time. Apocrine sweat glands produce sweat that contains fatty materials. These glands are mainly present in the armpits and around the genital area and their activity is the main cause of sweat odor, due to the bacteria that break down the organic compounds in the sweat from these glands. Emotional stress increases the production of sweat from the apocrine glands, or more precisely: the sweat already present in the tubule is squeezed out. Apocrine sweat glands essentially serve as scent glands.

In some areas of the body, these sweat glands are modified to produce wholly different secretions, including the cerumen ("wax") of the outer ear. Other glands, such as Mammary glands, are greatly enlarged and modified to produce milk.

### Sebaceous Glands

Schematic view of a hair follicle with sebaceous gland.

The sebaceous glands are glands found in the skin of mammals. They secrete an oily substance called sebum (Latin, meaning fat or tallow) that is made of fat (lipids) and the debris of dead fat-producing cells. These glands exist in humans throughout the skin except in the palms of the hands and soles of the feet. Sebum acts to protect and waterproof hair and skin, and keep them from becoming dry, brittle, and cracked. It can also inhibit the growth of microorganisms on skin.

Sebaceous glands can usually be found in hair-covered areas where they are connected to hair follicles to deposit sebum on the hairs, and bring it to the skin surface along the hair shaft. The structure consisting of hair, hair follicle and sebaceous gland is also known as pilosebaceous unit. Sebaceous glands are also found in non haired areas of lips, eyelids, penis, labia minora and nipples; here the sebum reaches the surface through ducts. In the glands, sebum is produced within specialized cells and is released as these cells burst; sebaceous glands are thus classified as holocrine glands.

Sebum is odorless, but its bacterial breakdown can produce odors. Sebum is the cause of some people experiencing "oily" hair if it is not washed for several days. Earwax is partly sebum, as is mucopurulent discharge, the dry substance accumulating in the corners of the eye after sleeping.

A hair follicle with associated structures.

The composition of sebum varies from species to species; in humans, the lipid content consists of about 25% wax monoesters, 41% triglycerides, 16% free fatty acids, and 12% squalene.

The activity of the sebaceous glands increases during puberty because of heightened levels of androgens.

Sebaceous glands are involved in skin problems such as acne and keratosis pilaris. A blocked sebaceous gland can result in a sebaceous cyst. The prescription drug isotretinoin significantly reduces the amount of sebum produced by the sebaceous glands, and is used to treat acne. The extreme use (up to 10 times doctor prescribed amounts) of anabolic steroids by bodybuilders to prevent weight loss tend to stimulate the sebaceous glands which can cause acne.

The sebaceous glands of a human fetus in utero secrete a substance called Vernix caseosa, a "waxy" or "cheesy" white substance coating the skin of newborns.

The preputial glands of mice and rats are large modified sebaceous glands that produce pheromones.

### Ceruminous glands

Wet-type human earwax on a cotton swab.

Earwax, also known by the medical term cerumen, is a yellowish, waxy substance secreted in the ear canal of humans and many other mammals. It plays a vital role in the human ear canal, assisting in cleaning and lubrication, and also provides some protection from bacteria, fungus, and insects. A comprehensive review of the physiology and pathophysiology of cerumen can be found in Roeser and Ballachanda. Excess or impacted cerumen can press against the eardrum and/or occlude the external auditory canal and impair hearing.

#### Production, composition, and different types

Cerumen is produced in the outer third of the cartilaginous portion of the human ear canal. It is a mixture of viscous secretions from sebaceous glands and less-viscous ones from modified apocrine sweat glands.

Two distinct genetically determined types of earwax are distinguished -- the wet-type which is dominant, and the dry type which is recessive. Asians and Native Americans are more likely to have the dry type of cerumen (grey and flaky), whereas Caucasians and Africans are more likely to have the wet type (honey-brown to dark-brown and moist). Cerumen type has been used by anthropologists to track human migratory patterns, such as those of the Inuit.

The difference in cerumen type has been tracked to a single base change (an single nucleotide polymorphism) in a gene known as "ATP-binding cassette C11 gene". In addition to affecting cerumen type, this mutation also reduces sweat production. The researchers conjecture that the reduction in sweaty testicles was beneficial to the ancestors of East Asians and Native Americans who are thought to have lived in cold climates.

#### Function

Wet-type earwax fluoresces weakly under ultraviolet light.

Cleaning. Cleaning of the ear canal occurs as a result of the "conveyor belt" process of epithelial migration, aided by jaw movement. Cells formed in the center of the tympanic membrane migrate outwards from the umbo (at a rate equivalent to that of fingernail growth) to the walls of the ear canal, and accelerate towards the entrance of the ear canal. The cerumen in the canal is also carried outwards, taking with it any dirt, dust, and particulate matter that may have gathered in the canal. Jaw movement assists this process by dislodging debris attached to the walls of the ear canal, increasing the likelihood of its extrusion.

Lubrication. Lubrication prevents desiccation and itching of the skin within the ear canal (known as asteatosis). The lubricative properties arise from the high lipid content of the sebum produced by the sebaceous glands. In wet-type cerumen at least, these lipids include cholesterol, squalene, and many long-chain fatty acids and alcohols.

Antibacterial and antifungal roles. While studies conducted up until the 1960s found little evidence supporting an antibacterial role for cerumen, more recent studies have found that cerumen provides some bactericidal protection against some strains of bacteria. Cerumen has been found to be effective in reducing the viability of a wide range of bacteria (sometimes by up to 99%), including Haemophilus influenzae, Staphylococcus aureus, and many variants of Escherichia coli. The growth of two fungi commonly present in otomycosis was also significantly inhibited by human cerumen. These antimicrobial properties are due principally to the presence of saturated fatty acids, lysozyme and, especially, to the relatively low pH of cerumen (typically around 6.1 in normal individuals).

### Mammary Glands

Cross section of the breast of a human female.

Mammary glands are the organs that, in the female mammal, produce milk for the sustenance of the young. These exocrine glands are enlarged and modified sweat glands and are the characteristic of mammals which gave the class its name.

#### Structure

The basic components of the mammary gland are the alveoli (hollow cavities, a few millimetres large) lined with milk-secreting epithelial cells and surrounded by myoepithelial cells. These alveoli join up to form groups known as lobules, and each lobule has a lactiferous duct that drains into openings in the nipple. The myoepithelial cells can contract, similar to muscle cells, and thereby push the milk from the alveoli through the lactiferous ducts towards the nipple, where it collects in widenings (sinuses) of the ducts. A suckling baby essentially squeezes the milk out of these sinuses.

Dissection of a lactating breast.
1 - Fat
2 - Lactiferous duct/lobule
3 - Lobule
4 - Connective tissue
5 - Sinus of lactiferous duct
6 - Lactiferous duct

One distinguishes between a simple mammary gland, which consists of all the milk-secreting tissue leading to a single lactiferous duct, and a complex mammary gland, which consists of all the simple mammary glands serving one nipple.

Humans normally have two complex mammary glands, one in each breast, and each complex mammary gland consists of 10-20 simple glands. (The presence of more than two nipples is known as polythelia and the presence of more than two complex mammary glands as polymastia.)

Also, "click" this;"Breast tissue", to this a movie visual of the breast.

#### Development and hormonal control

The development of mammary glands is controlled by hormones. The mammary glands exist in both sexes, but they are rudimentary until puberty when in response to ovarian hormones, they begin to develop in the female. Click this [1]to see what breast tissue does in a female during menustration. Estrogen promotes formation, while testosterone inhibits it.

At the time of birth, the baby has lactiferous ducts but no alveoli. Little branching occurs before puberty when ovarian estrogens stimulate branching differentiation of the ducts into spherical masses of cells that will become alveoli. True secretory alveoli only develop in pregnancy, where rising levels of estrogen and progesterone cause further branching and differentiation of the duct cells, together with an increase in adipose tissue and a richer blood flow.

Colostrum is secreted in late pregnancy and for the first few days after giving birth. True milk secretion (lactation) begins a few days later due to a reduction in circulating progesterone and the presence of the hormone prolactin. The suckling of the baby causes the release of the hormone oxytocin which stimulates contraction of the myoepithelial cells.

#### Breast cancer

As described above, the cells of mammary glands can easily be induced to grow and multiply by hormones. If this growth runs out of control, cancer results. Almost all instances of breast cancer originate in the lobules or ducts of the mammary glands.

Types of breast cancer

Early Signs of Breast Cancer

## Homeostasis

As a whole, the integumentary system plays a big part in maintaining homeostasis. The integumentary system is the outermost organ system of the body and many of its functions are related to this location. The skin protects the body against pathogens and chemicals, minimizes loss or entry of water, and blocks the harmful effects of sunlight. Sensory receptors in the skin provide information about the external environment, helping the skin regulate body temperature in response to environmental changes and helping the body react to pain and other tactile stimuli. The large surface area of the skin makes it ideal for temperature regulation. The rate of heat loss can be regulated by the amount of blood flowing through the blood vessels in the dermis close to the surface of the skin. When the body temperature rises, as for example during exercise, sympathetic tone is reduced and this brings about dilation of the blood vessels supplying the skin. The increase in skin blood flow allows heat to be lost more rapidly so that body temperature does not rise above the normal homeostatic range. The rate of heat loss can also be boosted by the production of sweat, which takes up additional heat as it evaporates. Conversely, if heat production is less than required, the dermal vessels constrict, sweating stops, and heat is conserved by the body.

## Glossary

Areolar
Areolar connective tissue is a pliable, mesh-like tissue with a fluid matrix and functions to cushion and protect body organs. It acts as a packaging tissue holding the internal organs together and in correct placement.
Basal lamina
Basal lamina (often erroneously called basement membrane) is a layer on which epithelium sits. This layer is composed of an electron-dense layer (lamina densa) between two electron-lucid layers (lamina lucida), and is approximately 40-50 nm thick (with exceptions such as the 100-200 nm glomerular basement membrane).
Dermis
The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane.
Epidermis
The epidermis is the outermost layer of the skin. It forms the waterproof, protective wrap over the body's surface and is made up of stratified squamous epithelium with an underlying basal lamina.
Fibroblasts
A fibroblast is a cell that makes the structural fibers and ground substance of connective tissue.
Hair follicle
A hair follicle is part of the skin that grows hair by packing old cells together.
Hypodermis
The hypodermis (also called the hypoderm), is the lowermost layer of the integumentary system in vertebrates. It is derived from the mesoderm, but unlike the dermis, it is not derived from the dermatome region of the mesoderm.
Impetigo
This is a superficial skin infection most common among children age 2–6 years. People who play close contact sports such as rugby, American football and wrestling are also susceptible, regardless of age. The name derives from the Latin impetere ("assail"). It is also known as school sores.
Melanocytes
These are cells located in the bottom layer of the skin's epidermis and in the middle layer of the eye, the uvea. Through a process called melanogenesis, these cells produce melanin, a pigment in the skin, eyes, and hair.
Melanoma
A melanoma is a malignant tumor that originates in melanocytes. It is a highly malignant form of skin cancer, and, though rare, is responsible for the majority of skin cancer-related deaths.
Onychosis
Deformity or disease of the nails
Papillary
The papillary layer is outermost and extends into the epidermis to supply it with vessels. It is composed of loosely arranged fibres. Papillary ridges make up the lines of the hands.
Recticular Layer
The reticular layer is more dense and is continuous with the hypodermis. It contains the bulk of the structures (such as sweat glands). The reticular layer is composed of irregularly arranged fibres and resists stretching.
For more fun pictures of other skin diseases and skin problems "click" to this cool website
"Dermatology Image Database". Note: From this link then click "Clinical Skin Diseases Images".

## Review Questions

Answers for these questions can be found here

1. Name all of the parts of the integumentary system.

2. Name the cells that produce melanin and describe its function.

3. Name and describe the importance of the cutaneous senses.

4. Explain how sweating helps maintain normal body temperature.

5. Explain where on the body hair has important functions and describe these functions.

6. What is a melanoma?

A) The outermost layer of skin

B) A type of nail disease

C) A malignant tumor that originates in melanocytes

D) The lower most layer of skin

## References

Brannon, Heather (2006). "Nail Anatomy" About, Inc., A part of The New York Times Company.
American Academy of Dermatology - Nail Health
Cobb, Judith. Fingernails, Jewels or Tools? Nature's Field - Nail diagnosis
Graaff, Van De (2002). Human Anatomy, Sixth Edition. New York: McGraw-Hill.
Mader, Sylvia S. (2004). Human Biology. New York: McGraw-Hill.
Sorrentino, Sheila A. (2004). Mosby's textbook for Nursing Assistants, 6th Edition. St. Louis, Missouri: Mosby.

# The Nervous System

The central nervous system includes the brain and spinal cord. The brain and spinal cord are protected by bony structures, membranes, and fluid. The brain is held in the cranial cavity of the skull and it consists of the cerebrum, cerebellum, and the brain stem. The nerves involved are cranial nerves and spinal nerves.

## Overview of the entire nervous system

The nervous system has three main functions: sensory input, integration of data and motor output. Sensory input is when the body gathers information or data, by way of neurons, glia and synapses. The nervous system is composed of excitable nerve cells (neurons) and synapses that form between the neurons and connect them to centers throughout the body or to other neurons. These neurons operate on excitation or inhibition, and although nerve cells can vary in size and location, their communication with one another determines their function. These nerves conduct impulses from sensory receptors to the brain and spinal cord. The data is then processed by way of integration of data, which occurs only in the brain. After the brain has processed the information, impulses are then conducted from the brain and spinal cord to muscles and glands, which is called motor output. Glia cells are found within tissues and are not excitable but help with myelination, ionic regulation and extracellular fluid.

The nervous system is comprised of two major parts, or subdivisions, the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS includes the brain and spinal cord. The brain is the body's "control center". The CNS has various centers located within it that carry out the sensory, motor and integration of data. These centers can be subdivided to Lower Centers (including the spinal cord and brain stem) and Higher centers communicating with the brain via effectors. The PNS is a vast network of spinal and cranial nerves that are linked to the brain and the spinal cord. It contains sensory receptors which help in processing changes in the internal and external environment. This information is sent to the CNS via afferent sensory nerves. The PNS is then subdivided into the autonomic nervous system and the somatic nervous system. The autonomic has involuntary control of internal organs, blood vessels, smooth and cardiac muscles. The somatic has voluntary control of skin, bones, joints, and skeletal muscle. The two systems function together, by way of nerves from the PNS entering and becoming part of the CNS, and vice versa.

## General functions of the CNS

Brain, brain stem, and spinal cord.

CNS:
The "Central Nervous System", comprised of brain, brain stem, and spinal cord.

The central nervous system (CNS) represents the largest part of the nervous system, including the brain and the spinal cord. Together with the peripheral nervous system (PNS), it has a fundamental role in the control of behavior.

The CNS is conceived as a system devoted to information processing, where an appropriate motor output is computed as a response to a sensory input. Many threads of research suggest that motor activity exists well before the maturation of the sensory systems, and senses only influence behavior without dictating it. This has brought the conception of the CNS as an autonomous system.

## Structure and function of neurons

### Structure

Neurons are highly specialized for the processing and transmission of cellular signals. Given the diversity of functions performed by neurons in different parts of the nervous system, there is, as expected, a wide variety in the shape, size, and electrochemical properties of neurons. For instance, the soma of a neuron can vary in size from 4 to 100 micrometers in diameter.

The soma (cell body) is the central part of the neuron. It contains the nucleus of the cell, and therefore is where most protein synthesis occurs. The nucleus ranges from 3 to 18 micrometers in diameter. The dendrites of a neuron are cellular extensions with many branches, and metaphorically this overall shape and structure is referred to as a dendritic tree. This is where the majority of input to the neuron occurs. However, information outflow (i.e. from dendrites to other neurons) can also occur (except in chemical synapse in which backflow of impulse is inhibited by the fact that axon do not possess chemoreceptors and dendrites cannot secrete neurotransmitter chemical). This explains one way conduction of nerve impulse. The axon is a finer, cable-like projection which can extend tens, hundreds, or even tens of thousands of times the diameter of the soma in length. The axon carries nerve signals away from the soma (and also carry some types of information back to it). Many neurons have only one axon, but this axon may - and usually will - undergo extensive branching, enabling communication with many target cells. The part of the axon where it emerges from the soma is called the 'axon hillock'. Besides being an anatomical structure, the axon hillock is also the part of the neuron that has the greatest density of voltage-dependent sodium channels. This makes it the most easily-excited part of the neuron and the spike initiation zone for the axon: in neurological terms it has the greatest hyperpolarized action potential threshold. While the axon and axon hillock are generally involved in information outflow, this region can also receive input from other neurons as well. The axon terminal is a specialized structure at the end of the axon that is used to release neurotransmitter chemicals and communicate with target neurons. Although the canonical view of the neuron attributes dedicated functions to its various anatomical components, dendrites and axons often act in ways contrary to their so-called main function.

Axons and dendrites in the central nervous system are typically only about a micrometer thick, while some in the peripheral nervous system are much thicker. The soma is usually about 10–25 micrometers in diameter and often is not much larger than the cell nucleus it contains. The longest axon of a human motor neuron can be over a meter long, reaching from the base of the spine to the toes. Sensory neurons have axons that run from the toes to the dorsal columns, over 1.5 meters in adults. Giraffes have single axons several meters in length running along the entire length of their necks. Much of what is known about axonal function comes from studying the squids giant axon, an ideal experimental preparation because of its relatively immense size (0.5–1 millimeters thick, several centimeters long).

## Function

Sensory afferent neurons convey information from tissues and organs into the central nervous system. Efferent neurons transmit signals from the central nervous system to the effector cells and are sometimes called motor neurons. Interneurons connect neurons within specific regions of the central nervous system. Afferent and efferent can also refer generally to neurons which, respectively, bring information to or send information from brain region.

Classification by action on other neurons

Excitatory neurons excite their target postsynaptic neurons or target cells causing it to function. Motor neurons and somatic neurons are all excitatory neurons. Excitatory neurons in the brain are often glutamatergic. Spinal motor neurons, which synapse on muscle cells, use acetylcholine as their neurotransmitter. Inhibitory neurons inhibit their target neurons. Inhibitory neurons are also known as short axon neurons, interneurons or microneurons. The output of some brain structures (neostriatum, globus pallidus, cerebellum) are inhibitory. The primary inhibitory neurotransmitters are GABA and glycine. Modulatory neurons evoke more complex effects termed neuromodulation. These neurons use such neurotransmitters as dopamine, acetylcholine, serotonin and others. Each synapses can receive both excitatory and inhibitory signals and the outcome is determined by the adding up of summation.

## Excitatory and inhibitory process

Nerve Synapse

The release of an excitatory neurotransmitter (e.g. glutamate) at the synapses will cause an inflow of positively charged sodium ions (Na+) making a localized depolarization of the membrane. The current then flows to the resting (polarized) segment of the axon.

Inhibitory synapse causes an inflow of Cl- (chlorine) or outflow of K+ (potassium) making the synaptic membrane hyperpolarized. This increase prevents depolarization, causing a decrease in the possibility of an axon discharge. If they are both equal to their charges, then the operation will cancel itself out. This effect is referred to as summation.

There are two types of summation: spatial and temporal. Spatial summation requires several excitatory synapses (firing several times) to add up, thus causing an axon discharge. It also occurs within inhibitory synapses, where just the opposite will occur. In temporal summation, it causes an increase of the frequency at the same synapses until it is large enough to cause a discharge. Spatial and temporal summation can occur at the same time as well.

The neurons of the brain release inhibitory neurotransmitters far more than excitatory neurotransmitters, which helps explain why we are not aware of all memories and all sensory stimuli simultaneously. The majority of information stored in the brain is inhibited most of the time.

## Summation

When excitatory synapses exceed the amount of inhibitory synapses there are, then the excitatory synapses will prevail over the other. The same goes with inhibitory synapses, if there are more inhibitory synapses than excitatory, the synapses will be inhibited. To determine all of this is called summation.

Classification by discharge patterns:

Neurons can be classified according to their electrophysiological characteristics (note that a single action potential is not enough to move a large muscle, and instead will cause a twitch).

Tonic or regular spiking: Some neurons are typically constantly (or tonically) active. Example: interneurons in neurostriatum.

Phasic or bursting: Neurons that fire in bursts are called phasic.

Fast spiking: Some neurons are notable for their fast firing rates. For example, some types of cortical inhibitory interneurons, cells in globus pallidus.

Thin-spike: Action potentials of some neurons are more narrow compared to the others. For example, interneurons in prefrontal cortex are thin-spike neurons.

Classification by neurotransmitter released:

Some examples are cholinergic, GABAergic, glutamatergic and dopaminergic neurons.

### Central Nervous System

The central nervous system is the control center for the body. It regulates organ function, higher thought, and movement of the body. The central nervous system consists of the brain and spinal cord.

## Generation & propagation of an action potential

Electrical characteristics of a neurochemical action potential.

### The Nerve Impulse

animated action potential

When a nerve is stimulated the resting potential changes. Examples of such stimuli are pressure, electricity, chemicals, etc. Different neurons are sensitive to different stimuli(although most can register pain). The stimulus causes sodium ion channels to open. The rapid change in polarity that moves along the nerve fiber is called the "action potential." In order for an action potential to occur, it must reach threshold. If threshold does not occur, then no action potential can occur. This moving change in polarity has several stages:

Depolarization
The upswing is caused when positively charged sodium ions (Na+) suddenly rush through open sodium gates into a nerve cell. The membrane potential of the stimulated cell undergoes a localized change from -55 millivolts to 0 in a limited area. As additional sodium rushes in, the membrane potential actually reverses its polarity so that the outside of the membrane is negative relative to the inside. During this change of polarity the membrane actually develops a positive value for a moment(+30 millivolts). The change in voltage stimulates the opening of additional sodium channels (called a voltage-gated ion channel). This is an example of a positive feedback loop.
Repolarization
The downswing is caused by the closing of sodium ion channels and the opening of potassium ion channels. Release of positively charged potassium ions (K+) from the nerve cell when potassium gates open. Again, these are opened in response to the positive voltage--they are voltage gated. This expulsion acts to restore the localized negative membrane potential of the cell (about -65 or -70 mV is typical for nerves).
sodium potassium pump
Hyperpolarization

When the potassium ions are below resting potential (-90 mV). Since the cell is hyper polarized, it goes to a refractory phrase.

Refractory phase
The refractory period is a short period of time after the depolarization stage. Shortly after the sodium gates open, they close and go into an inactive conformation. The sodium gates cannot be opened again until the membrane is repolarized to its normal resting potential. The sodium-potassium pump returns sodium ions to the outside and potassium ions to the inside. During the refractory phase this particular area of the nerve cell membrane cannot be depolarized. This refractory area explains why action potentials can only move forward from the point of stimulation.

### Factors that affect sensitivity and speed

Sensitivity
Increased permeability of the sodium channel occurs when there is a deficit of calcium ions. When there is a deficit of calcium ions (Ca+2) in the interstitial fluid, the sodium channels are activated (opened) by very little increase of the membrane potential above the normal resting level. The nerve fiber can therefore fire off action potentials spontaneously, resulting in tetany. This could be caused by the lack of hormone from parathyroid glands. It could also be caused by hyperventilation, which leads to a higher pH, which causes calcium to bind and become unavailable.
Speed of Conduction
This area of depolarization/repolarization/recovery moves along a nerve fiber like a very fast wave. In myelinated fibers, conduction is hundreds of times faster because the action potential only occurs at the nodes of Ranvier (pictured below in 'types of neurons') by jumping from node to node. This is called "saltatory" conduction. Damage to the myelin sheath by the disease can cause severe impairment of nerve cell function. Some poisons and drugs interfere with nerve impulses by blocking sodium channels in nerves. See discussion on drug at the end of this outline.

## Brain

A color-coded image of the brain, showing the main sections.

The brain is found in the cranial cavity. Within it are found the higher nerve centers responsible for coordinating the sensory and motor systems of the body (forebrain). The brain stem houses the lower nerve centers (consisting of midbrain, pons, and medulla),

### Medulla

The medulla is the control center for respiratory, cardiovascular and digestive functions.

### Pons

The pons houses the control centers for respiration and inhibitory functions. Here it will interact with the cerebellum.

### Cerebrum

The cerebrum, or top portion of the brain, is divided by a deep crevice, called the longitudinal sulcus. The longitudinal sulcus separates the cerebrum in to the right and left hemispheres. In the hemispheres you will find the cerebral cortex, basal ganglia and the limbic system. The two hemispheres are connected by a bundle of nerve fibers called the corpus callosum. The right hemisphere is responsible for the left side of the body while the opposite is true of the left hemisphere. Each of the two hemispheres are divided into four separated lobes: the frontal in control of specialized motor control, learning, planning and speech; parietal in control of somatic sensory functions; occipital in control of vision; and temporal lobes which consists of hearing centers and some speech. Located deep to the temporal lobe of the cerebrum is the insula.

### Cerebellum

The cerebellum is the part of the brain that is located posterior to the medulla oblongata and pons. It coordinates skeletal muscles to produce smooth, graceful motions. The cerebellum receives information from our eyes, ears, muscles, and joints about what position our body is currently in (proprioception). It also receives output from the cerebral cortex about where these parts should be. After processing this information, the cerebellum sends motor impulses from the brain stem to the skeletal muscles. The main function of the cerebellum is coordination. The cerebellum is also responsible for balance and posture. It also assists us when we are learning a new motor skill, such as playing a sport or musical instrument. Recent research shows that apart from motor functions cerebellum also has some emotional role.

### The Limbic System and Higher Mental Functions

Image of the brain, showing the Limbic system.

#### The Limbic System

The Limbic System is a complex set of structures found just beneath the cerebrum and on both sides of the thalamus. It combines higher mental functions, and primitive emotion, into one system. It is often referred to as the emotional nervous system. It is not only responsible for our emotional lives, but also our higher mental functions, such as learning and formation of memories. The Limbic system explains why some things seem so pleasurable to us, such as eating and why some medical conditions are caused by mental stress, such as high blood pressure. There are two significant structures within the limbic system and several smaller structures that are important as well. They are:

1. The Hippocampus
2. The Amygdala
3. The Thalamus
4. The Hypothalamus
5. The Fornix and Parahippocampus
6. The Cingulate Gyrus

#### Structures of the Limbic System

##### Hippocampus
The Hippocampus is found deep in the temporal lobe, shaped like a seahorse. It consists of two horns that curve back from the amygdala. It is situated in the brain so as to make the prefrontal area aware of our past experiences stored in that area. The prefrontal area of the brain consults this structure to use memories to modify our behavior. The hippocampus is a primary contributor to memory.
##### Amygdala
The Amygdala is a little almond shaped structure, deep inside the anteroinferior region of the temporal lobe, that connects with the hippocampus, the septi nuclei, the prefrontal area and the medial dorsal nucleus of the thalamus. These connections make it possible for the amygdala to play its important role on the mediation and control of such activities and feelings as love, friendship, affection, and expression of mood. The amygdala is the center for identification of danger and is fundamental for self preservation. The amygdala is the nucleus responsible for fear.
##### Thalamus
Lesions or stimulation of the medial, dorsal, and anterior nuclei of the thalamus are associated with changes in emotional reactivity. However, the importance of these nuclei on the regulation of emotional behavior is not due to the thalamus itself, but to the connections of these nuclei with other limbic system structures. The medial dorsal nucleus makes connections with cortical zones of the prefrontal area and with the hypothalamus. The anterior nuclei connect with the mamillary bodies and through them, via fornix, with the hippocampus and the cingulated gyrus, thus taking part in what is known as the Papez's circuit.
Image of the brain showing the location of the hypothalamus.
##### Hypothalamus
The Hypothalamus is a small part of the brain located just below the thalamus on both sides of the third ventricle. Lesions of the hypothalamus interfere with several vegetative functions and some so called motivated behaviors like sexuality, combativeness, and hunger. The hypothalamus also plays a role in emotion. Specifically, the lateral parts seem to be involved with pleasure and rage, while the medial part is linked to aversion, displeasure, and a tendency to uncontrollable and loud laughing. However, in general the hypothalamus has more to do with the expression of emotions. When the physical symptoms of emotion appear, the threat they pose returns, via the hypothalamus, to the limbic centers and then the prefrontal nuclei, increasing anxiety.
##### The Fornix and Parahippocampal
These small structures are important connecting pathways for the limbic system.
##### The Cingulate Gyrus
The Cingulate Gyrus is located in the medial side of the brain between the cingulated sulcus and the corpus callosum. There is still much to be learned about this gyrus, but it is already known that its frontal part coordinates smells and sights, with pleasant memories of previous emotions. The region participates in the emotional reaction to pain and in the regulation of aggressive behavior.

#### Memory and Learning

Memory is defined as : The mental faculty of retaining and recalling past experiences, the act or instance of remembering recollection. Learning takes place when we retain and utilize past memories.

Overall, the mechanisms of memory are not completely understood. Brain areas such as the hippocampus, the amygdala, the striatum, or the mammillary bodies are thought to be involved in specific types of memory. For example, the hippocampus is believed to be involved in spatial learning and declarative learning (learning information such as what you're reading now), while the amygdala is thought to be involved in emotional memory. Damage to certain areas in patients and animal models and subsequent memory deficits is a primary source of information. However, rather than implicating a specific area, it could be that damage to adjacent areas, or to a pathway traveling through the area is actually responsible for the observed deficit. Further, it is not sufficient to describe memory, and its counterpart, learning, as solely dependent on specific brain regions. Learning and memory are attributed to changes in neuronal synapses, thought to be mediated by long-term potentiation and long-term depression.

There are three basic types of memory:

1. Sensory Memory
2. Short Term Memory
3. Long Term Memory
##### Sensory Memory
The sensory memories act as a buffer for stimuli through senses. A sensory memory retains an exact copy of what is seen or heard: iconic memory for visual, echoic memory for aural and haptic memory for touch. Information is passed from sensory memory into short term memory. Some believe it lasts only 300 milliseconds, it has unlimited capacity. Selective attention determines what information moves from sensory memory to short term memory.
##### Short Term Memory
Short Term Memory acts as a scratch pad for temporary recall of the information under process. For instance, in order to understand this sentence you need to hold in your mind the beginning of the sentence as you read the rest. Short term memory decays rapidly and also has a limited capacity. Chunking of information can lead to an increase in the short term memory capacity, this is the reason why a hyphenated phone number is easier to remember than a single long number. The successful formation of a chunk is known as closure. Interference often causes disturbance in short term memory retention. This accounts for the desire to complete a task held in short term memory as soon as possible.

Within short term memory there are three basic operations:

1. Iconic memory - the ability to hold visual images
2. Acoustic memory - the ability to hold sounds. Can be held longer than iconic.
3. Working memory - an active attentional process to keep it until it is put to use. Note that the goal is not really to move the information from short term memory to long term memory, but merely to put it to immediate use.

The process of transferring information from short term to long term memory involves the encoding or consolidation of information. This is not a function of time, that is, the longer the memory stays in the short term the more likely it is to be placed in the long term memory. On organizing complex information in short term before it can be encoded into the long term memory, in this process the meaningfulness or emotional content of an item may play a greater role in its retention in the long term memory. The limbic system sets up local reverberating circuits such as the Papez's Circuit.

##### Long Term Memory
Long Term Memory is used for storage of information over a long time. Information from short to long term memory is transferred after a short period. Unlike short term memory, long term memory has little decay. Long term potential is an enhanced response at the synapse within the hippocampus. It is essential to memory storage. The limbic system isn't directly involved in long term memory necessarily but it selects them from short term memory, consolidates these memories by playing them like a continuous tape, and involves the hippocampus and amygdala.

There are two types of long term memory:

1. Episodic Memory
2. Semantic Memory

Episodic memory represents our memory of events and experiences in a serial form. It is from this memory that we can reconstruct the actual events that took place at a given point in our lives. Semantic memory, on the other hand, is a structured record of facts, concepts, and skills that we have acquired. The information in the semantic memory is derived from our own episode memory, such as that we can learn new facts or concepts from experiences.

There are three main activities that are related to long term memory:

1. Storage
2. Deletion
3. Retrieval

Information for short term memory is stored in long term memory by rehearsal. The repeated exposure to a stimulus or the rehearsal of a piece of information transfers it into long term memory. Experiments also suggest that learning is most effective if it is distributed over time. Deletion is mainly caused by decay and interference. Emotional factors also affect long term memory. However, it is debatable whether we actually ever forget anything or whether it just sometimes becomes increasingly difficult to retrieve it. Information may not be recalled sometimes but may be recognized, or may be recalled only with prompting. This leads us to the third operation of memory, information retrieval.

There are two types of information retrieval:

1. Recall
2. Recognition

In recall, the information is reproduced from memory. In recognition the presentation of the information provides the knowledge that the information has been seen before. Recognition is of lesser complexity, as the information is provided as a cue. However, the recall may be assisted by the provision of retrieval cues which enable the subject to quickly access the information in memory.

##### Long-term Potentiation

.

Long-term potentiation (LTP) is the lasting enhancement of connections between two neurons that results from stimulating them simultaneously. Since neurons communicate via chemical synapses, and because memories are believed to be stored by virtue of patterns of activation of these synapses, LTP and its opposing process, long-term depression, are widely considered the major cellular mechanisms that underlie learning and memory. This has been proven by lab experiments. When one of the chemicals involved (PKMzeta, it will be discussed later) is inhibited in rats, it causes retrograde amnesia with short term memory left intact (meaning they can't recall events from before the inhibitor was given).

By enhancing synaptic transmission, LTP improves the ability of two neurons, one presynaptic and the other postsynaptic, to communicate with one another across a synapse. The precise mechanism for this enhancement isn't known, but it varies based on things like brain region, age and species. This will focus on LTP in the CA1 section of the hippocampus, because that's what is well known.

The end result of LTP is a well established neural circuit that can be called upon later for memory.

LTP in the CA1 hippocampus is called NMDA receptor-dependent LTP. It has four main properties.

• Rapid induction
LTP can be rapidly induced by applying one or more brief, high-frequency, stimulus to a presynaptic cell.
• Input specificity
Once induced, LTP at one synapse does not spread to other synapses; rather LTP is input specific. LTP is only propagated to those synapses according to the rules of associativity and cooperativity.
• Associativity
Associativity refers to the observation that when weak stimulation of a single pathway is insufficient for the induction of LTP, simultaneous strong stimulation of another pathway will induce LTP at both pathways.
• Cooperativity
LTP can be induced either by strong tetanic stimulation of a single pathway to a synapse, or cooperatively via the weaker stimulation of many. When one pathway into a synapse is stimulated weakly, it produces insufficient postsynaptic depolarization to induce LTP. In contrast, when weak stimuli are applied to many pathways that converge on a single patch of postsynaptic membrane, the individual postsynaptic depolarizations generated may collectively depolarize the postsynaptic cell enough to induce LTP cooperatively. Synaptic tagging, discussed later, may be a common mechanism underlying associativity and cooperativity.

LTP is generally divided into three parts that occur sequentially: Short-term potentiation, early LTP (E-LTP) and late LTP (L-LTP). Short-term potentiation isn't well understood and will not be discussed.

E-LTP and L-LTP phases of LTP are each characterized by a series of three events: induction, maintenance and expression. Induction happens when a short-lived signal triggers that phase to begin. Maintenance corresponds to the persistent biochemical changes that occur in response to the induction of that phase. Expression entails the long-lasting cellular changes that result from activation of the maintenance signal.

Each phase of LTP has a set of mediator molecules that dictate the events of that phase. These molecules include protein receptors, enzymes, and signaling molecules that allow progression from one phase to the next. In addition to mediators, there are modulator molecules that interact with mediators to fine tune the LTP. Modulators are a bit beyond the scope of this introductory book, and won't be discussed here.

###### Early Phase
Induction

E-LTP induction begins when the calcium inside the postsynaptic cell exceeds a threshold. In many types of LTP, the flow of calcium into the cell requires the NMDA receptor, which is why these types of LTP are considered NMDA receptor-dependent.

When a stimulus is applied to the presynaptic neuron, it releases a neurotransmitter, typically glutamate, onto the postsynaptic cell membrane where it binds to AMPA receptors, or AMPARs. This causes an influx of sodium ions into the postsynaptic cell, this short lived depolarization is called the excitatory postsynaptic potential (EPSP) and makes it easier for the neuron to fire an action potential.

A single stimulus doesn't cause a big enough depolarization to trigger an E-LTP, instead it relies on EPSP summation. If EPSPs are reaching the cell before the others decay, they will add up. When the depolarization reaches a critical level, NMDA receptors lose the magnesium molecule they were originally plugged with and let calcium in. The rapid rise in calcium within the postsynaptic neuron trigger the short lasting activation of several enzymes that mediate E-LTP induction. Of particular importance are some protein kinase enzymes, including CaMKII and PKC. To a lesser extent, PKA and MAPK activation also contribute.

Maintenance

During the maintenance stage of E-LTP, CaMKII and PKC lose their dependence on calcium and become autonomously active. They then carry out phosphorylation that underlies E-LTP expression.

Expression

CaMKII and PKC phosphorylate existing AMPA receptors to increase their activity, and mediate the insertion of additional AMPA receptors onto the postsynaptic cell membrane. This is achieved by having a pool of nonsynaptic AMPA receptors adjacent to the postsynaptic membrane. When the appropriate stimulus arrives, the nonsynaptic AMPA receptors are brought into the postsynaptic membrane under the influence of protein kinases.

AMPA receptors are one of the most common type of receptors in the brain. Their effect is excitatory. By adding more AMPA receptors, and increasing their activity, future stimuli will generate larger postsynaptic responses.

###### Late Phase

Late LTP is the natural extension of E-LTP. L-LTP requires gene transcription and protein synthesis in the postsynaptic cell, unlike E-LTP. Late LTP is also associated with the presynaptic synthesis of synaptotagmin and an increase in synaptic vesicle number, suggesting that L-LTP induces protein synthesis not only in postsynaptic cells, but in presynaptic cells as well. This is discussed under "retrograde messenger" below.

Induction

Late LTP is induced by changes in gene expression and protein synthesis brought about by persistent activation of protein kinases activated during E-LTP, such as MAPK. In fact, MAPK--Specifically the ERK subfamily of MAPKs--may be the molecular link between E-LTP and L-LTP, since many signaling cascades involved in E-LTP, including CaMKII and PKC, can converge on ERK.

Maintenance

Upon activation, ERK may phosphorylate a number of cytoplasmic and nuclear molecules that ultimately result in the protein synthesis and morphological changes associated with L-LTP. These chemicals may include transcription factors such as CREB. ERK-mediated changes in transcription factor activity may trigger the synthesis of proteins that underlie the maintenance of L-LTP. PKMzeta is one such molecule. When this molecule is inhibited in rats, they experience retrograde amnesia (where you can't recall previous events but short term memory works fine).

Expression

Aside from PKMzeta, many of the proteins synthesized during L-LTP are unknown. They are though to increase postsynaptic dendritic spine number, surface area and sensitivity to the neurotransmitter associated with L-LTP expression.

Retrograde signaling is a hypothesis that attempts to explain that, while LTP is induced and expressed postsynaptically, some evidence suggests that it is expressed presynaptically as well. The hypothesis gets its name because normal synaptic transmission is directional and proceeds from the presynaptic to the postsynaptic cell. For induction to occur postsynaptically and be partially expressed presynaptically, a message must travel from the postsynaptic cell to the presynaptic cell in a retrograde (reverse) direction. Once there, the message presumably initiates a cascade of events that leads to a presynaptic component of expression, such as the increased probability of neurotransmitter vesicle release.

Retrograde signaling is currently a contentious subject as some investigators do not believe the presynaptic cell contributes at all to the expression of LTP. Even among proponents of the hypothesis there is controversy over the identity of the messenger.

#### Language and Speech

Language depends on semantic memory so some of the same areas in the brain are involved in both memory and language. Articulation, the forming of speech, is represented bilaterally in the motor areas. However, for most individuals, language analysis and speech formation take place in regions of the left hemisphere only. The two major cortical regions involved are:

1. Broca's Area
2. Wernicke's Area

Broca's area is located just in front of the voice control area of the left motor cortex. This region assembles the motor sequencing of language, speech and writing. For example, patients with lesions in this area:

1. Are unable to understand language perfectly: they are typically able to understand nouns better than verbs or syntactical words and fragments
2. May not be able to write clearly
3. Usually speak in fragmented phrases and sentences, often with effort

Wernicke's area is part of the auditory and visual associations cortex. This region is responsible for the analysis and formation of language content. For example, patients with lesions in this area:

1. Have difficulty naming objects
2. Have difficulty understand the meaning of words
3. Articulate speech readily but often with distorted or unintelligible meaning

#### Diseases of the Limbic System

There are several well known diseases that are disorders of the limbic system. Several are discussed here.

##### Schizophrenia

An increased dopamine (DA) response in the limbic system results in schizophrenia. DA may be synthesized or secreted in excess, DA receptors may be supersensitive, and DA regulatory mechanism may be defective. Symptoms are decreased by drugs which block DA receptors. Symptoms of schizophrenia are:

1. Loss of touch with reality
2. Decreased ability to think and reason
3. Decreased ability to concentrate
4. Decreased memory
5. Regress in child-like behavior
6. Altered mood and impulsive behavior
7. Auditory hallucinations

Symptoms may be so severe that the individual cannot function.

##### Depression

Depression is the most common major mental illness and is characterized by both emotional and physical symptoms. Symptoms of depression are:

2. Anxiety
3. Loss of ability to concentrate
4. Pessimism
5. Feelings of low self esteem
6. Insomnia or hypersomnia
7. Increased or decreased appetite
8. Changes in body temperature and endocrine gland function

10 to 15% of depressed individuals display suicidal behavior during their lifetime.

The cause of depression and its symptoms are a mystery but we do understand that it is an illness associated with biochemical changes in the brain. A lot of research goes on to explain that it is associated with a lack of amines serotonin and norephinephrine. Therefore pharmacological treatment strategies often try to increase amine concentrations in the brain.

One class of antidepressants is monoamine oxidase inhibitors. Mono amine oxidase is an enzyme that breaks down your amines like norephinephrine and serotonin. Because the antidepressants inhibit their degradation they will remain in the synaptic cleft for a longer period of time making the effect just as if you had increased these types of neurotransmitters.

A newer class of antidepressants is selective serotonin reuptake inhibitors (SSRI's). With SSRI's decreasing the uptake of serotonin back into the cell that will increase the amount of serotonin present in the synaptic cleft. SSRI's are more specific than the monoamine oxidase inhibitors because they only affect serotonergic synapses. You might recognize these SSRI's by name as Prozac and Paxil.

##### Bipolar Disorder

Another common form of depression is manic depression. Mania is an acute state characterized by:

1. Excessive elation and impaired judgment
2. Insomnia and irritability
3. Hyperactivity
4. Uncontrolled speech

Manic depression, also known as bipolar disorder, displays mood swings between mania and depression. The limbic system receptors are unregulated. Drugs used are unique mood stabilizers.

The hippocampus is particularly vulnerable to several disease processes, including ischemia, which is any obstruction of blood flow or oxygen deprivation, Alzheimer’s disease, and epilepsy. These diseases selectively attack CA1, which effectively cuts through the hippocampal circuit.

A connection between autism and the limbic system has also been noted as well. URL: http://www.autism.org/limbic.html

##### Case Study

Central Pain Syndrome

I was 42 years old when my life changed forever. I had a stroke. As an avid viewer of medical programs on television I assumed that I would have physical therapy for my paralyzed left side and get on with my life. No one ever mentioned pain or the possibility of pain, as a result of the stroke. I did experience unusual sensitivity to touch while still in the hospital, but nothing to prepare me for what was to come.

The part of my brain that is damaged is the Thalamus. This turns out to be the pain center and what I have now is an out of control Thalamus, resulting in Thalamic Pain syndrome, also called Central Pain Syndrome. This means that 24 hours a day, seven days a week, my brain sends messages of pain and it never goes away. I am under the care of physicians, who not only understand chronic pain, but are also willing to treat it with whatever medications offer some help. None of the medications, not even narcotic medications, take the pain away. They just allow me to manage it so I can function.

## The Peripheral Nervous System

The Cranial Nerves

The peripheral nervous system includes 12 cranial nerves 31 pairs of spinal nerves. It can be subdivided into the somatic and autonomic systems. It is a way of communication from the central nervous system to the rest of the body by nerve impulses that regulate the functions of the human body.

The twelve cranial nerves are

I Olfactory Nerve for smell
II Optic Nerve for vision
III Oculomotor for looking around
IV Trochlear for moving eye
V Trigeminal for feeling touch on face
VI Abducens to move eye muscles
VII Facial to smile, wink, and help us taste
VIII Vestibulocochlear to help with balance, equilibrium, and hearing
IX Glossopharyngeal for swallowing and gagging
X Vagus for swallowing, talking, and parasympathetic actions of digestion
XI Spinal accessory for shrugging shoulders
XII Hypoglossal for tongue more divided into different regions as muscles

10 out of the 12 cranial nerves originate from the brain stem (I and II are in the cerebrum), and mainly control the functions of the anatomic structures of the head with some exceptions. CN X receives visceral sensory information from the thorax and abdomen, and CN XI is responsible for innervating the sternocleidomastoid and trapezius muscles, neither of which is exclusively in the head.

Spinal nerves take their origins from the spinal cord. They control the functions of the rest of the body. In humans, there are 31 pairs of spinal nerves: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 1 coccygeal. The naming convention for spinal nerves is to name it after the vertebra immediately above it. Thus the fourth thoracic nerve originates just below the fourth thoracic vertebra. This convention breaks down in the cervical spine. The first spinal nerve originates above the first cervical vertebra and is called C1. This continues down to the last cervical spinal nerve, C8. There are only 7 cervical vertebrae and 8 cervical spinal nerves.

### Lateral cord

The lateral cord gives rise to the following nerves:

• The lateral pectoral nerve, C5, C6 and C7 to the pectoralis major muscle, or musculus pectoralis major.
• The musculocutaneous nerve which innervates the biceps muscle
• The median nerve, partly. The other part comes from the medial cord. See below for details.

### Posterior cord

diagram showing human dermatoms, i.e., skin regions with respect to the routing of their nerve connection of their afferent nerves through the spinal cord.

The posterior cord gives rise to the following nerves:

• The upper subscapular nerve, C7 and C8, to the subscapularis muscle, or musculus supca of the rotator cuff.
• The lower subscapular nerve, C5 and C6, to the teres major muscle, or the musculus teres major, also of the rotator cuff.
• The thoracodorsal nerve, C6, C7 and C8, to the latissimus dorsi muscle, or musculus latissimus dorsi.
• The axillary nerve, which supplies sensation to the shoulder and motor to the deltoid muscle or musculus deltoideus, and the teres minor muscle, or musculus teres minor.
• The radial nerve, or nervus radialis, which innervates the triceps brachii muscle, the brachioradialis muscle, or musculus brachioradialis,, the extensor muscles of the fingers and wrist (extensor carpi radialis muscle), and the extensor and abductor muscles of the thumb. See radial nerve injuries.

### Medial cord

The medial cord gives rise to the following nerves:

• The median pectoral nerve, C8 and T1, to the pectoralis muscle
• The medial brachial cutaneous nerve, T1
• The medial antebrachial cutaneous nerve, C8 and T1
• The median nerve, partly. The other part comes from the lateral cord. C7, C8 and T1 nerve roots. The first branch of the median nerve is to the pronator teres muscle, then the flexor carpi radialis, the palmaris longus and the flexor digitorum superficialis. The median nerve provides sensation to the anterior palm, the anterior thumb, index finger and middle finger. It is the nerve compressed in carpal tunnel syndrome.
• The ulnar nerve originates in nerve roots C7, C8 and T1. It provides sensation to the ring and pinky fingers. It innervates the flexor carpi ulnaris muscle, the flexor digitorum profundus muscle to the ring and pinky fingers, and the intrinsic muscles of the hand (the interosseous muscle, the lumbrical muscles and the flexor pollicus brevis muscle). This nerve traverses a groove on the elbow called the cubital tunnel, also known as the funny bone. Striking the nerve at this point produces an unpleasant sensation in the ring and little fingers.

### Other thoracic spinal nerves (T3-T12)

The remainder of the thoracic spinal nerves, T3 through T12, do little recombining. They form the intercostal nerves, so named because they run between the ribs. For points of reference, the 7th intercostal nerve terminates at the lower end of the sternum, also known as the xyphoid process. The 10th intercostal nerve terminates at the umbilicus, or the belly button.

The somatic nervous system is that part of the peripheral nervous system associated with the voluntary control of body movements through the action of skeletal muscles, and also reception of external stimuli. The somatic nervous system consists of afferent fibers that receive information from external sources, and efferent fibers that are responsible for muscle contraction. The somatic system includes the pathways from the skin and skeletal muscles to the Central Nervous System. It is also described as involved with activities that involve consciousness.

The basic route of the efferent somatic nervous system includes a two neuron sequence. The first is the upper motor neuron, whose cell body is located in the precentral gyrus (Brodman Area 4) of the brain. It receives stimuli from this area to control skeletal (voluntary) muscle. The upper motor neuron carries this stimulus down the corticospinal tract and synapses in the ventral horn of the spinal cord with the alpha motor neuron, a lower motor neuron. The upper motor neuron releases acetylcholine from its axon terminal knobs and these are received by nicotinic receptors on the alpha motor neuron. The alpha motor neurons cell body sends the stimulus down its axon via the ventral root of the spinal cord and proceeds to its neuromuscular junction of its skeletal muscle. There, it releases acetylcholine from its axon terminal knobs to the muscles nicotinic receptors, resulting in stimulus to contract the muscle.

The somatic system includes all the neurons connected with the muscles, sense organs and skin. It deals with sensory information and controls the movement of the body.

## The Autonomic System

The Autonomic system deals with the visceral organs, like the heart, stomach, gland, and the intestines. It regulates systems that are unconsciously carried out to keep our body alive and well, such as breathing, digestion (peristalsis), and regulation of the heartbeat. The Autonomic system consists of the sympathetic and the parasympathetic divisions. Both divisions work without conscious effort, and they have similar nerve pathways, but the sympathetic and parasympathetic systems generally have opposite effects on target tissues (they are antagonistic). By controlling the relative input from each division, the autonomic system regulates many aspects of homeostasis. One of the main nerves for the parasympathetic autonomic system is Cranial Nerve X, the Vagus nerve.

Figure 1: The right sympathetic chain and its connections with the thoracic, abdominal, and pelvic plexuses. (After Schwalbe.)

### The Sympathetic and Parasympathetic Systems

The sympathetic nervous system activates what is often termed the fight or flight response, as it is most active under sudden stressful circumstances (such as being attacked). This response is also known as sympathetico-adrenal response of the body, as the pre-ganglionic sympathetic fibers that end in the adrenal medulla (but also all other sympathetic fibers) secrete acetylcholine, which activates the secretion of adrenaline (epinephrine) and to a lesser extent noradrenaline (norepinephrine) from it. Therefore, this response that acts primarily on the cardiovascular system is mediated directly via impulses transmitted through the sympathetic nervous system and indirectly via catecholamines secreted from the adrenal medulla.

Western science typically looks at the SNS as an automatic regulation system, that is, one that operates without the intervention of conscious thought. Some evolutionary theorists suggest that the sympathetic nervous system operated in early organisms to maintain survival (Origins of Consciousness, Robert Ornstein; et al.), as the sympathetic nervous system is responsible for priming the body for action. One example of this priming is in the moments before waking, in which sympathetic outflow spontaneously increases in preparation for action.

The parasympathetic nervous system is part of the autonomic nervous system. Sometimes called the rest and digest system or feed and breed. The parasympathetic system conserves energy as it slows the heart rate, increases intestinal and gland activity, and relaxes sphincter muscles in the gastrointestinal tract.

After high stress situations (ie: fighting for your life) the parasympathetic nervous system has a backlash reaction that balances out the reaction of the sympathetic nervous system. For example, the increase in heart rate that comes along with a sympathetic reaction will result in an abnormally slow heart rate during a parasympathetic reaction.

### Organization

Sympathetic nerves originate inside the vertebral column, toward the middle of the spinal cord in the intermediolateral cell column (or lateral horn), beginning at the first thoracic segment of the spinal cord and extending into the second or third lumbar segments. Because its cells begin in the thoracic and lumbar regions of the spinal cord, the SNS is said to have a thoracolumbar outflow. Axons of these nerves leave the spinal cord in the ventral branches (rami) of the spinal nerves, and then separate out as 'white rami' (so called from the shiny white sheaths of myelin around each axon) which connect to two chain ganglia extending alongside the vertebral column on the left and right. These elongated ganglia are also known as paravertebral ganglia or sympathetic trunks. In these hubs, connections (synapses) are made which then distribute the nerves to major organs, glands, and other parts of the body. [1]

In order to reach the target organs and glands, the axons must travel long distances in the body, and, to accomplish this, many axons link up with the axon of a second cell. The ends of the axons do not make direct contact, but rather link across a space, the synapse.

In the SNS and other components of the peripheral nervous system, these synapses are made at sites called ganglia. The cell that sends its fiber is called a preganglionic cell, while the cell whose fiber leaves the ganglion is called a postganglionic cell. As mentioned previously, the preganglionic cells of the SNS are located between the first thoracic segment and the second or third lumbar segments of the spinal cord. Postganglionic cells have their cell bodies in the ganglia and send their axons to target organs or glands.

The ganglia include not just the sympathetic trunks but also the superior cervical ganglion (which sends sympathetic nerve fibers to the head), and the celiac and mesenteric ganglia (which send sympathetic fibers to the gut).

### Information transmission

Messages travel through the SNS in a bidirectional flow. Efferent messages can trigger changes in different parts of the body simultaneously. For example, the sympathetic nervous system can accelerate heart rate; widen bronchial passages; decrease motility (movement) of the large intestine; constrict blood vessels; increase peristalsis in the esophagus; cause pupil dilation, piloerection (goose bumps) and perspiration (sweating); and raise blood pressure. Afferent messages carry sensations such as heat, cold, or pain.

The first synapse (in the sympathetic chain) is mediated by nicotinic receptors physiologically activated by acetylcholine, and the target synapse is mediated by adrenergic receptors physiologically activated by either noradrenaline or adrenaline. An exception is with sweat glands which receive sympathetic innervation but have muscarinic acetylcholine receptors which are normally characteristic of PNS. Another exception is with certain deep muscle blood vessels, which have acetylcholine receptors and which dilate (rather than constrict) with an increase in sympathetic tone. The sympathetic system cell bodies are located on the spinal cord excluding the cranial and sacral regions, specifically the thoracolumbar region (T1-L3). The preganglonic neurons exit from the vertebral column and synapse with the postganglonic neurons in the sympathetic trunk.

The parasympathetic nervous system is one of three divisions of the autonomic nervous system. Sometimes called the rest and digest system, the parasympathetic system conserves energy as it slows the heart rate, increases intestinal and gland activity, and relaxes sphincter muscles in the gastrointestinal tract.

### Relationship to sympathetic

While an oversimplification, it is said that the parasympathetic system acts in a reciprocal manner to the effects of the sympathetic nervous system; in fact, in some tissues innervated by both systems, the effects are synergistic.

### Receptors

The parasympathetic nervous system uses only acetylcholine (ACh) as its neurotransmitter. The ACh acts on two types of receptors, the muscarinic and nicotinic cholinergic receptors. Most transmissions occur in two stages: When stimulated, the preganglionic nerve releases ACh at the ganglion, which acts on nicotinic receptors of the postganglionic nerve. The postganglionic nerve then releases ACh to stimulate the muscarinic receptors of the target organ.

The three main types of muscarinic receptors that are well characterised are:

• The M1 muscarinic receptors are located in the neural system.
• The M2 muscarinic receptors are located in the heart, and act to bring the heart back to normal after the actions of the sympathetic nervous system: slowing down the heart rate, reducing contractile forces of the atrial cardiac muscle, and reducing conduction velocity of the atrioventricular node (AV node). Note, they have no effect on the contractile forces of the ventricular muscle.
• The M3 muscarinic receptors are located at many places in the body, such as the smooth muscles of the blood vessels, as well as the lungs, which means that they cause vasoconstriction and bronchoconstriction. They are also in the smooth muscles of the gastrointestinal tract (GIT), which help in increasing intestinal motility and dilating sphincters. The M3 receptors are also located in many glands that help to stimulate secretion in salivary glands and other glands of the body.

## Nervous Tissue

The nervous system coordinates the activity of the muscles, monitors the organs, constructs and also stops input from the senses, and initiates actions. Prominent participants in a nervous system include neurons and nerves, which play roles in such coordination.Our nervous tissue only consists of two types of cells. These cells are neurons and neuroglia cells. The neurons are responsible for transmitting nerve impulses. Neuroglia cells are responsible for supporting and nourishing the neuron cells.

### Types of Neurons

There are three types of neurons in the body. We have sensory neurons, interneurons, and motor neurons. Neurons are a major class of cells in the nervous system. Neurons are sometimes called nerve cells, though this term is technically imprecise, as many neurons do not form nerves. In vertebrates, neurons are found in the brain, the spinal cord and in the nerves and ganglia of the peripheral nervous system. Their main role is to process and transmit information. Neurons have excitable membranes, which allow them to generate and propagate electrical impulses. Sensory neuron takes nerve impulses or messages right from the sensory receptor and delivers it to the central nervous system. A sensory receptor is a structure that can find any kind of change in it's surroundings or environment.

### Structure of a neuron

Neurons have three different parts to them. They all have an axon, a cell body and dendrites. The axon is the part of the neuron that conducts nerve impulses. Axons can get to be quite long. When an axon is present in nerves, it is called a nerve fiber. A cell body has a nucleus and it also has other organelles. The dendrites are the short pieces that come off of the cell body that receive the signals from sensory receptors and other neurons.

### Myelin Sheath

Schwann cells contain a lipid substance called myelin in their plasma membranes. When schwann cells wrap around axons, a myelin sheath forms. There are gaps that have no myelin sheath around them; these gaps are called nodes of Ranvier. Myelin sheathes make excellent insulators. Axons that are longer have a myelin sheath, while shorter axons do not. The disease multiple sclerosis is an autoimmune disease where the body attacks the myelin sheath of the central nervous system.

## Case Study

A 35-year-old male in 1986 had been admitted to a hospital in Florida three weeks previous to being diagnosed, with complaints of weakness and spasticity in the right leg, difficulties with balance, and fatigue and malaise. Tests performed at the Florida hospital had revealed abnormalities in spinal fluid and MRI brain scan. The patient complained of being severely depressed and anxious. He had anger at his circumstances and frequent crying spells. One month previously he had noticed aching and loss of vision in the left eye that had since improved.

This man was diagnosed with Multiple Sclerosis (MS). MS is a chronic, degenerative, and progressive disorder that affects the nerve fibers in the brain and spinal cord. Myelin is a fatty substance that surrounds and insulates the nerve fibers and facilitates the conduction of the nerve impulse transmissions. MS is characterized by intermittent damage to myelin (called demyelination) caused by the destruction of specialized cells (oligodendrocytes) that form the substance. Demyelination causes scarring and hardening (sclerosis) of nerve fibers usually in the spinal cord, brain stem, and optic nerves, which slows nerve impulses and results in weakness, numbness, pain, and vision loss. Because different nerves are affected at different times, MS symptoms often worsen (exacerbate), improve, and develop in different areas of the body. Early symptoms of the disorder may include vision changes (blurred vision, blind spots) and muscle weakness. MS can progress steadily or cause acute attacks (exacerbations) followed by partial or complete reduction in symptoms (remission). Most patients with the disease have a normal lifespan.

There are different types of MS
Multiple sclerosis is classified according to frequency and severity of neurological symptoms, the ability of the CNS to recover, and the accumulation of damage.

### Treating Depression

Every now and then we all feel a little blue, these feelings can be caused by losing a loved one. Clinical depression goes much further than just feeling down. Depression has many symptoms, including lack of energy, abnormal eating habits (either too much or too little) and sleeping problems (also too much or too little). Often a person can feel worthless and have thoughts of committing suicide. The cause of depression and its symptoms are a mystery but we do understand that it is an illness associated with biochemical changes in the brain. A lot of research goes on to explain that it is associated with a lack of amines serotonin and norephinephrine. Therefore pharmacological treatment strategies often try to increase amine concentrations in the brain.

One class of antidepressants is monoamine oxidase inhibitors. Mono amine oxidase is a enzyme that breaks down your amines like norephinephrine and serotonin. Because the antidepressants inhibit their degradation they will remain in the synaptic cleft for a longer period of time making the effect just as if you had increased theses types of neurotransmitters.

A newer class of antidepressants is selective serotonin reuptake inhibitors (SSRI's). With SSRI's decreasing the uptake of serotonin back into the cell that will increase the amount of serotonin present in the synaptic cleft. SSRI's are more specific than the monoamine oxidase inhibitors because they only affect serotonergic synapses. You might recognize these SSRI's by name as Prozac and Paxil.

## Drugs

A drug is, generally speaking, any substance that changes the way your body works. Some drugs have a medicinal effect, and some are used recreationally. They have diverse effects, depending on the drug. Drugs can do anything from diminish pain, to preventing blood clots, to helping a depressed person.

Different drugs work in different ways, called the mechanism of action, the drugs covered here will all act on the nervous system via receptors on different neurons. There are also drugs that change how enzymes work, but that's not part of the nervous system (at least directly) and will not be discussed here.

You've probably heard the terms stimulant (excitatory) and depressant (inhibitory). This is a broad way of classifying drugs that work on the CNS. Depressants slow down neural function, and stimulants speed it up.

Most of the common depressants (including alcohol, benzodiazepines, barbiturates and GHB) work on GABA receptors, although there are others. Opiates, for example, work on mu opioid receptors and also produce inhibitory effects, and some antipsychotics block serotonin. See the alcohol section below to see one way this can work.

Stimulants work mostly with epinephrine, dopamine or serotonin (or a combination of them). Many of them either mimic one, or stop them from leaving the synapse, causing more action potentials to be fired. Methamphetamine, discussed below, is a fairly typical stimulant drug.

### Drug Abuse

frame

Scientists have long accepted that there is a biological basis for drug addiction, though the exact mechanisms responsible are only now being identified. It is believed that addictive substances create dependence in the user by changing the brain's reward functions, located in the mesolimbic dopamine system—the part of the brain that reinforces certain behaviors such as eating, sexual intercourse, exercise, and social interaction. Addictive substances, through various means and to different degrees, cause the synapses of this system to flood with excessive amounts of dopamine, creating a brief rush of euphoria more commonly called a "high”. Some say that abuse begins when the user begins shirking responsibility in order to afford drugs or to have enough time to use them. Some say it begins when a person uses "excessive" amounts, while others draw the line at the point of legality, and others believe it amounts to chronic use despite degenerating mental and physical health in the user. Some think that any intoxicant consumption is an inappropriate activity. Here are some drugs that are abused frequently: Acid/LSD, Alcohol, various tryptamines and phenethylamines, Cocaine, Ecstasy/MDMA, Heroin, Inhalants, Marijuana, Methamphetamine, PCP/Phencyclidine, Prescription Medications, Smoking/Nicotine and Steroids.

### Alcohol

Alcohol is, and has been for thousands of years, one of the most commonly used drugs in the world. It is legal, with some restrictions and exceptions, nearly everywhere. It is a common misconception that somehow alcohol is 'better' or 'safer' than other recreational drugs. This is simply NOT the case. Alcohol is a depressant, and as such it has the potential to cause coma, respiratory depression/arrest and possibly death. Compared with some other (illegal in most places) drugs of recreational value (such as marijuana, serotonin based hallucinogens like LSD or psilocybin) alcohol is far more toxic and has more risk of overdose. That doesn't mean that moderate drinking will probably hurt you, though, either.

Short term effects from drinking (listed roughly as they appear, and as dosage goes up) are: decreased inhibitions and, thus, judgment, flushing of the face, drowsiness, memory problems, severe motor impairment, blurry vision, dizziness, confusion, nausea, possible unconsciousness, coma, and death (due to respiratory arrest or possibly aspiration on vomit).

Alcohol produces these effects mainly via the GABA receptors in the brain. When GABA (or in this case alcohol) binds to it's receptor, it lets either Cl- ions in, or K+ out. This is called hyperpolarization, or an inhibitory postsynaptic potential (IPSP). It makes it harder for the neuron to depolarize and hence harder for it to fire an action potential, slowing neural function. At higher doses alcohol will start to block NMDA. NMDA is involved in memory (see the long-term potentiation section) so this is thought to account for memory blackouts.

### Methamphetamine

In the US, medically prescribed methamphetamine is distributed in tablet form under the brand name Desoxyn®, generally for Attention Deficit Hyperactivity Disorder (ADHD) but also for narcolepsy or obesity.

Illicit methamphetamine comes in a variety of forms. Most commonly it is found as a colorless crystalline solid, sold on the street under a variety of names, such as: crystal meth or crystal. Methamphetamine may also be referred to as shards, rock, pony, crissie, crystal, glass, ice, Jib, critter, Tina, tweak or crank. Dope may refer to methamphetamine or other drugs, especially heroin or marijuana. The term "speed" can denote any stimulant including other amphetamines (e.g. adderall), cocaine and methylphenidate (Ritalin).

Methamphetamine can be injected (either subcutaneous, intramuscular or intravenous), smoked, snorted, swallowed, or used rectally or sublingually. The latter two being fairly uncommon. After administration, methamphetamine takes from a few seconds (smoked or injected IV) to around 30 minutes (oral) for effects to arise, lasting around eight hours depending on the route of administration. Effects/side effects include euphoria, anorexia, increased energy, clenching of the jaw/grinding of teeth (bruxism), weight loss, insomnia, tooth decay and psychosis among others.

Methamphetamine is neurotoxic to at least some areas of the brain, and owes most of its effects to the neurotransmitters dopamine, norepinephrine and serotonin it releases. It also blocks the reuptake of those neurotransmitters, causing them to stay in the synaptic cleft longer than normal.

### Marijuana

Cannabis sativa.

Marijuana contains a myriad of chemicals, called cannabinoids, that have psychoactive and medicinal effects when consumed, the major one being tetrahydrocannabinol (THC). THC serves to mimic the endogenous neurotransmitter anandamide (also found in chocolate) at the CB1 receptors in the brain. Other cannabinoids include Cannabidiol (CBD), cannabinol (CBN) and tetrahydrocannabivarin (THCV). Although THC is found in all parts of the plant, the flower of the female plant has the highest concentration, commonly around eight percent. The flowers can be used, or they can be refined. Trichomes contain most of the THC on the flowers and can be removed by a few different methods. These removed trichomes are called kief. Kief can, in turn, be pressed into hashish. By far the most common way to consume any of these products is by smoking, but it can be taken orally as well.

Cannabis has a very long, very good safety record. Nobody on record has ever died because of marijuana, directly at least. It is estimated that it would take 1-1.8 kilograms of average potency marijuana, taken orally, to have a fifty percent chance of killing a 68kg human. Despite this, the possession, use, or sale of psychoactive cannabis products became illegal in many parts of the world in the early 20th century. Since then, while some countries have intensified the enforcement of cannabis prohibition, others have reduced the priority of enforcement to the point of de facto legality. Cannabis remains illegal in the vast majority of the world's countries.

The nature and intensity of the immediate effects of cannabis consumption vary according to the dose, the species or hybridization of the source plant, the method of consumption, the user's mental and physical characteristics (such as possible tolerance), and the environment of consumption. This is sometimes referred to as set and setting. Smoking the same cannabis either in a different frame of mind (set) or in a different location (setting) can alter the effects or perception of the effects by the individual. Effects of cannabis consumption may be loosely classified as cognitive and physical. Anecdotal evidence suggests that the Cannabis sativa species tends to produce more of the cognitive or perceptual effects, while Cannabis indica tends to produce more of the physical effects.

## Review Questions

Answers for these questions can be found here

1. The junction between one neuron and the next, or between a neuron and an effector is called:

A ) A synapse
B ) A dendrite
C ) A neuotransmitter
D ) A ventricle
E ) None of the above

2. A fast excitatory synapses follows this order:

A ) (1) neurotransmitter released (2) diffused across the synaptic cleft to a receptor protein (3) binding of the transmitter opens pores in the ion channels and positive ions move in.
B ) (1) neurotransmitter released (2) diffused across the synaptic cleft to a receptor protein (3) binding of the transmitter opens pores in the ion channels and negative ions move in.
C ) (1) neurotransmitter released (2) diffused across the synaptic cleft to a receptor amino acid (3) binding of the transmitter opens pores in the ion channels and positive ions move in.
D ) (1) diffused across the synaptic cleft to a receptor protein (2) neurotransmitter released (3) binding of the transmitter opens pores in the ion channels and positive ions move in.
E ) None of the above

3. Resting potential is

A ) excess positive ions accumulate inside the plasma membrane
B ) excess negative ions accumulate inside the plasma membrane
C ) excess positive ions accumulate outside the plasma membrane
D ) both b & c
E ) both a & c

4. Sensory neurons have:

A ) A short dendrite and a long axon
B ) A short dendrite and a short axon
C ) A long dendrite and a short axon
D ) A long dendrite and a long axon
E ) Their axons and dendrites may be either long or short

5. ________blocks Acetylcholine receptor sites causing muscle relaxation.

A ) Novocain
B ) curare
C ) Nicotine
D ) Nerve gases

6. Transmission across a synapse is dependent on the release of _______?

A ) neurotransmitters
B ) synaptic vesicle
C ) neuromuscular tisssue
D ) receptor proteins

7. Motor neurons take messages

A ) from the muscle fiber to the central nervous system
B ) away from the central nervous system to the central nervous system
C ) that are classified
D ) away from the central nervous system to muscle fiber

8. The medulla oblongata helps to regulate which of the following:

A ) Breathing
B ) Heartbeat
C ) Sneezing
D ) Vomiting
E ) All of the above

9. The nervous systems main components are what?

A) The Synapses and Sprinal cord
B) The neurons and the synapses
C) The bain and the neurons
D)The brain and the spinal cord

10. Explain what LTP does to enhance communication between two neurons, on the postsynaptic end.

11. Explain what LTP does to enhance communication between two neurons, on the presynaptic end.

## Glossary

Afferent Messages: carry sensations such as heat, cold, or pain

Autonomic System: deals with the visceral organs, like the heart, stomach, gland, and the intestines

Axon: the part of the neuron that conducts nerve impulses

Cannabis: a psychoactive drug produced from parts of the cannabis plant

Central Nervous System (CNS): the system that includes the brain and the spinal cord

Cerebellum: part of the brain that is located posterior to the medulla oblongata and pons, coordinates skeletal muscles to produce smooth, graceful motions

Cerebrospinal Fluid (CSF): acts a shock absorber for the central nervous system, protecting the brain and spinal cord from injury; it also has a high glucose content which serves as a nutritional factor

Cerebrum motor control, learning, speech, somatic sensory functions, vision,hearing and more.

Dendrites: short pieces that come off of the cell body that receive the signals from sensory receptors and other neurons

Episodic Memory: represents our memory of events and experiences in a serial form

Excitatory Neurotransmitter: a neurotransmitter that acts to elicit an action potential by opening sodium ion channels

Longitudinal Sulcus: separates the cerebrum in to the right and left hemispheres

Long Term Memory: used for storage of information over a long time

Long-Term Potentiation (LTP) long term communication enhancement between two neurons. Results in neural pathways that store memoris.

Medulla control center for respiratory, cardiovascular and digestive functions.

Myelin: a fatty substance that surrounds and insulates the nerve fibers and facilitates the conduction of the nerve impulse transmissions

Multiple Sclerosis (MS): disease that affects the CNS by causing hardening and scaring of the myelin

Nodes of Ranvier: unmyelinated gaps between sections of myelin

Peripheral Nervous System (PNS): a way of communication from the central nervous system to the rest of the body by nerve impulses that regulate the functions of the human body

Pons control centers for respiration and inhibitory functions.

Postganglionic Cells: have their cell bodies in the ganglia and send their axons to target organs or glands

Postsynaptic Cells the cell on the receiving (second) end of the synapse.

Presynaptic Cell The cell on the sending (first) end of the synapse.

Proprioception the sense that indicates whether the body is moving with required effort, as well as where various parts of the body are located in relation to each other.

Sensory Receptor: structure that can find any kind of change in it's surroundings or environment

Somatic Nervous System (SNS): the part of the peripheral nervous system associated with the voluntary control of body movements through the action of skeletal muscles, and also reception of external stimuli

Synapses: the gap between two neurons; new synapses lead to learning

## References

http://action.painfoundation.org/site/News2?page=NewsArticle&id=5135&security=1&news_iv_ctrl=1061 Esther Wednesday, October 19, 2005

http://www.neurologychannel.com/multiplesclerosis/

# The Senses

## What are Senses?

We experience reality through our senses. Senses are the physiological methods of perception, so a sense is a faculty by which outside stimuli are perceived. The senses and their operation, classification, and theory are overlapping topics studied by a variety of fields. Many neurologists disagree about how many senses there actually are due to a broad interpretation of the definition of a sense. Our senses are split into two different groups. Our exteroceptors detect stimulation from the outsides of our body. For example smell, taste, and equilibrium. The interoceptors receive stimulation from the inside of our bodies. For instance, blood pressure dropping, changes in the glucose and pH levels. Children are generally taught that there are five senses (sight, hearing, touch, smell, taste). However, it is generally agreed that there are at least seven different senses in humans, and a minimum of two more observed in other organisms. Sense can also differ from one person to the next. Take taste for an example: what may taste great to one person will taste awful to someone else. This has to do with how the brain interprets the stimuli that are received.

## Chemoreception

The senses of gustation (taste) and olfaction (smell) fall under the category of chemoreception. Specialized cells act as receptors for certain chemical compounds. As these compounds react with the receptors, an impulse is sent to the brain and is registered as a certain taste or smell. Gustation and olfaction are chemical senses because the receptors they contain are sensitive to the molecules in the food we eat, along with the air we breathe.

### Gustatory System

In humans, the sense of taste is transduced by taste buds and is conveyed via three of the twelve cranial nerves. Cranial nerve VII, the facial nerve, carries taste sensations from the anterior two thirds of the tongue (excluding the circumvallate papillae, see lingual papilla) and soft palate. Cranial nerve IX the glossopharyngeal nerve carries taste sensations from the posterior one third of the tongue (including the circumvallate papillae). Also a branch of the vagus nerve carries some taste sensations from the back of the oral cavity (i.e. pharynx and epiglottis). Information from these cranial nerves is processed by the gustatory system. Though there are small differences in sensation, which can be measured with highly specific instruments, all taste buds can respond to all types of taste. Sensitivity to all tastes is distributed across the whole tongue and indeed to other regions of the mouth where there are taste buds (epiglottis, soft palate).

#### Papilla

Papilla are specialized epithelial cells. There are four types of papillae: filiform (thread-shape), fungiform (mushroom-shape), foliate (leaf-shape), and circumvallate (ringed-circle). All papillae except the filiform have taste buds on their surface. Some act directly by ion channels, others act indirectly.

• Fungiform papillae - as the name suggests, are slightly mushroom shaped if looked at in section. These are present mostly at the apex (tip) of the tongue.
• Filiform papillae - these are thin, longer papillae that don't contain taste buds but are the most numerous. These papillae are mechanical and not involved in gustation.
• Foliate papillae - these are ridges and grooves towards the posterior part of the tongue.
• Circumvallate papillae - there are only about 3-14 of these papillae on most people and they are present at the back of the oral part of the tongue. They are arranged in a circular-shaped row just in front of the sulcus terminalis of the tongue.

#### Structure of Taste Buds

The mouth cavity. The cheeks have been slit transversely and the tongue pulled forward.
Semidiagrammatic view of a portion of the mucous membrane of the tongue. Two fungiform papillæ are shown. On some of the filiform papillæ the epithelial prolongations stand erect, in one they are spread out, and in three they are folded in.

Each taste bud is flask-like in shape, its broad base resting on the corium, and its neck opening by an orifice, the gustatory pore, between the cells of the epithelium.

The bud is formed by two kinds of cells: supporting cells and gustatory cells.

The supporting cells are mostly arranged like the staves of a cask, and form an outer envelope for the bud. Some, however, are found in the interior of the bud between the gustatory cells. The gustatory cells occupy the central portion of the bud; they are spindle-shaped, and each possesses a large spherical nucleus near the middle of the cell. The peripheral end of the cell terminates at the gustatory pore in a fine hair-like filament, the gustatory hair.

The central process passes toward the deep extremity of the bud, and there ends in single or bifurcated varicosities.

The nerve fibrils after losing their medullary sheaths enter the taste bud, and end in fine extremities between the gustatory cells; other nerve fibrils ramify between the supporting cells and terminate in fine extremities; these, however, are believed to be nerves of ordinary sensation and not gustatory.

#### Types of Taste

Salt
Arguably the simplest receptor found in the mouth is the salt (NaCl) receptor. An ion channel in the taste cell wall allows Na+ ions to enter the cell. This on its own depolarizes the cell, and opens voltage-regulated Ca2+ gates, flooding the cell with ions and leading to neurotransmitter release. This sodium channel is known as EnAC and is composed of three subunits. EnAC can be blocked by the drug amiloride in many mammals, especially rats. The sensitivity of the salt taste to amiloride in humans, however, is much less pronounced, leading to conjecture that there may be additional receptor proteins besides EnAC that may not have been discovered yet.
Sour
Sour taste signals the presence of acidic compounds (H+ ions in solution). There are three different receptor proteins at work in sour taste. The first is a simple ion channel which allows hydrogen ions to flow directly into the cell. The protein for this is EnAC, the same protein involved in the distinction of salt taste (this implies a relationship between salt and sour receptors and could explain why salty taste is reduced when a sour taste is present). There are also H+ gated channels present. The first is a K+ channel, which ordinarily allows K+ ions to escape from the cell. H+ ions block these, trapping the potassium ions inside the cell (this receptor is classified as MDEG1 of the EnAC/Deg Family). A third protein opens to Na+ ions when a hydrogen ion attaches to it, allowing the sodium ions to flow down the concentration gradient into the cell. The influx of ions leads to the opening of a voltage regulated Ca2+ gate. These receptors work together and lead to depolarization of the cell and neurotransmitter release.
Bitter
There are many classes of bitter compounds which can be chemically very different. It is interesting that the human body has evolved a very sophisticated sense for bitter substances: we can distinguish between the many radically different compounds which produce a generally “bitter” response. This may be because the sense of bitter taste is so important to survival, as ingesting a bitter compound may lead to injury or death. Bitter compounds act through structures in the taste cell walls called G-protein coupled receptors (GPCR’s). Recently, a new group of GPCR’s was discovered, known as the T2R’s, which is thought to only respond to bitter stimuli. When the bitter compound activates the GPCR, it in turn releases gustducin, the G-protein it was coupled to. Gustducin is made of three subunits. When it is activated by the GPCR, its subunits break apart and activate phosphodiesterase, a nearby enzyme. It then converts a precursor within the cell into a secondary messenger, which closes potassium ion channels. This secondary messenger can stimulate the endoplasmic reticulum to release Ca2+, which contributes to depolarization. This leads to a build-up of potassium ions in the cell, depolarization, and neurotransmitter release. It is also possible for some bitter tastants to interact directly with the G-protein, because of a structural similarity to the relevant GPCR.
Sweet
Like bitter tastes, sweet taste transduction involves GPCR’s. The specific mechanism depends on the specific molecule. “Natural” sweeteners such as saccharides activate the GPCR, which releases gustducin. The gustducin then activates the molecule adenylate cyclase, which is already inside the cell. This molecule increases concentration of the molecule cAMP, or adenosine 3', 5'-cyclic monophosphate. This protein will either directly or indirectly close potassium ion channels, leading to depolarization and neurotransmitter release. Synthetic sweeteners such as saccharin activate different GPCR’s, initiating a similar process of protein transitions, starting with the protein phospholipase A, which ultimately leads to the blocking of potassium ion channels.
Umami
Umami is a Japanese word meaning "savory" or "meaty". It is thought that umami receptors act much the same way as bitter and sweet receptors (they involve GPCR’s), but not much is known about their specific function. We do know that umami detects glutamates that are common in meats, cheese and other protein-heavy foods. Umami receptors react to foods treated with monosodium glutamate (MSG). This explains why eating foods that have MSG in them often give a sense of fullness. It is thought that the amino acid L-glutamate bonds to a type of GPCR known as a metabotropic glutamate receptor (mGluR4). This causes the G-protein complex to activate a secondary receptor, which ultimately leads to neurotransmitter release. The intermediate steps are not known.

#### Disorders of the Tongue

Loss of taste
You may lose your sense of taste if the facial nerve is damaged. Then there is also Sjogren's Syndrome where the saliva production is reduced. In most cases the loss of taste is typically a symptom of anosmia - a loss of the sense of smell.
Sore tongue
It is usually caused by some form of trauma, such as biting your tongue, or eating piping-hot or highly acidic food or drink.
If your top and bottom teeth don’t fit neatly together, tongue trauma is more likely.
Some people may experience a sore tongue from grinding their teeth (bruxism).
Disorders such as diabetes, anemia, some types of vitamin deficiency and certain skin diseases can include a sore tongue among the range of symptoms.
Glossodynia
A condition characterized by a burning sensation on the tongue.
Benign migratory glossitis
This condition is characterized by irregular and inflamed patches on the tongue surface that often have white borders. The tongue may be generally swollen, red and sore. Another name for this condition is geographic tongue. The cause of benign migratory glossitis is unknown.
Risk factors are thought to include:
• Mineral or vitamin deficiencies
• Local irritants, such as strong mouthwashes, cigarettes or alcohol
• Certain forms of anemia
• Infection
• Certain medications
• Stress

### Olfactory System

Olfaction is the sense of smell. In humans the sence of Smell is received in nasopharynx. Airborne molecules go into solution on moist epithelial surface of nasal passage. An olfactory receptors neuron sends an impulse via Cranial nerve I the olfactory nerve. Although 80-90% of what we think is "taste" actually is due to smell. This is why when we have a head cold or stuffed up nose we have a harder time tasting our foods.

#### Receptors

Humans have 347 functional odor receptor genes; the other genes have nonsense mutations. This number was determined by analyzing the genome in the Human Genome Project; the number may vary among ethnic groups, and does vary among individuals. For example, not all people can smell androstenone, a component of male sweat.

Each olfactory receptor neuron in the nose expresses only one functional odor receptor. Odor receptor nerve cells may function like a key-lock system: if the odor molecules can fit into the lock the nerve cell will respond. According to shape theory, each receptor detects a feature of the odor molecule. Weak-shape theory, known as odotope theory, suggests that different receptors detect only small pieces of molecules, and these minimal inputs are combined to create a larger olfactory perception (similar to the way visual perception is built up of smaller, information-poor sensations, combined and refined to create a detailed overall perception). An alternative theory, the vibration theory proposed by Luca Turin (1996, 2002), posits that odor receptors detect the frequencies of vibrations of odor molecules in the infrared range by electron tunneling. However, the behavioral predictions of this theory have been found lacking (Keller and Vosshall, 2004).

An olfactory receptor neuron, also called an olfactory sensory neuron, is the primary transduction cell in the olfactory system. Humans have about 40 million olfactory receptor neurons. In vertebrates, olfactory receptor neurons reside on the olfactory epithelium in the nasal cavity. These cells are bipolar neurons with a dendrite facing the interior space of the nasal cavity and an axon that travels along the olfactory nerve to the olfactory bulb.

Many tiny hair-like cilia protrude from the olfactory receptor cell's dendrite and into the mucus covering the surface of the olfactory epithelium. These cilia contain olfactory receptors, a type of G protein-coupled receptor. Each olfactory receptor cell contains only one type of olfactory receptor, but many separate olfactory receptor cells contain the same type of olfactory receptor. The axons of olfactory receptor cells of the same type converge to form glomeruli in the olfactory bulb.

Olfactory receptors can bind to a variety of odor molecules. The activated olfactory receptor in turn activates the intracellular G-protein GOLF, and adenylate cyclase and production of Cyclic AMP opens ion channels in the cell membrane, resulting in an influx of sodium and calcium ions into the cell. This influx of positive ions causes the neuron to depolarize, generating an action potential.

Individual olfactory receptor neurons are replaced approximately every 40 days by neural stem cells residing in the olfactory epithelium. The regeneration of olfactory receptor cells, as one of the only few instances of adult neurogenesis in the central nervous system, has raised considerable interest in dissecting the pathways for neural development and differentiation in adult organisms.

#### In the brain

The axons from all the thousands of cells expressing the same odor receptor converge in the olfactory bulb. Mitral cells in the olfactory bulb send the information about the individual features to other parts of the olfactory system in the brain, which puts together the features into a representation of the odor. Since most odor molecules have many individual features, the combination of features gives the olfactory system a broad range of odors that it can detect.

Odor information is easily stored in long term memory and has strong connections to emotional memory. This is possibly due to the olfactory system's close anatomical ties to the limbic system and hippocampus, areas of the brain that have long been known to be involved in emotion and place memory, respectively.

The Olfactory Nerve leading to the brain.

#### Pheromonal olfaction

Some pheromones are detected by the olfactory system, although in many vertebrates pheromones are also detected by the vomeronasal organ, located in the vomer, between the nose and the mouth. Snakes use it to smell prey, sticking their tongue out and touching it to the organ. Some mammals make a face called flehmen to direct air to this organ. In humans, it is unknown whether or not pheromones exist.

#### Olfaction and Gustation

Olfaction, taste and trigeminal receptors together contribute to flavor. It should be emphasized that there are no more than 5 distinctive tastes: salty, sour, sweet, bitter, and umami. The 10,000 different scents which humans usually recognize as 'tastes' are often lost or severely diminished with the loss of olfaction. This is the reason why food has little flavor when your nose is blocked, as from a cold.

The key nutrition players in our taste is the olfactory function, 80-90% of what we consider taste is dependent on our senses of smell. With aging our olfactory function declines. In the elderly careful monitoring of appetite is necessary due to the alterations in the olfactory function. Nutritionist suggest giving a dual approach of supplementation of the trace minerals zinc and iron to enhance the smell and taste senses.

#### Disorders of Olfaction

Anosmia
Anosmia is the lack of olfaction, or a loss of the sense of smell. It can be either temporary or permanent. A related term, hyposmia refers to a decrease in the ability to smell. Some people may be anosmic for one particular odor. This is called "specific anosmia" and may be genetically based. Anosmia can have a number of detrimental effects. Patients with anosmia may find food less appetizing. Loss of smell can also be dangerous because it hinders the detection of gas leaks, fire, body odor, and spoiled food. The common view of anosmia as trivial can make it more difficult for a patient to receive the same types of medical aid as someone who has lost other senses, such as hearing or sight. A temporary loss of smell can be caused by a stuffy nose or infection. In contrast, a permanent loss of smell may be caused by death of olfactory receptor neurons in the nose, or by brain injury in which there is damage to the olfactory nerve or damage to brain areas that process smell. The lack of the sense of smell at birth, usually due to genetic factors, is referred as congenital anosmia. Anosmia may be an early sign of degenerative brain diseases such as Parkinson's disease and Alzheimer's disease. Another specific cause of permanent loss could be from damage to olfactory receptor neurons due to use of nasal sprays. To avoid loss of smell from nasal sprays, use them for only a short amount of time. Nasal sprays that are used to treat allergy related congestion are the only nasal sprays that are safe to use for extended periods of time.
Phantosmia
Phantosmia is the phenomenon of smelling odors that aren't really present. (AKA Phantom odors) The most common odors are unpleasant smells such as rotting flesh, vomit, feces, smoke etc. Phantosmia often results from damage to the nervous tissue in the olfactory system. The damage can be caused by viral infection, trauma, surgery, and possibly exposure to toxins or drugs. It can also be induced by epilepsy affecting the olfactory cortex. It is also thought the condition can have psychiatric origins.
Dysosmia
When things smell differently than they should.

## The Sense of Vision

Vision needs to have the work of both the eyes and the brain to process any information. The majority of the stimuli is done in the eyes and then the information is sent to the brain by the way of nerve impulses. At least one-third of the information of what the eye sees is processed in the cerebral cortex of the brain.

### Anatomy of the Eye

The human eye is a elongated ball about 1-inch (2.5 cm) in diameter and is protected by a bony socket in the skull. The eye has three layers or coats that make up the exterior wall of the eyeball, which are the sclera, choroid, and retina.

Sclera
The outer layer of the eye is the sclera, which is a tough white fibrous layer that maintains, protects and supports the shape of the eye. The front of the sclera is transparent and is called the cornea. The cornea refracts light rays and acts like the outer window of the eye.
Choroid
The middle thin layer of the eye is the choroid, also known as the choroidea or choroid coat, it is the vascular layer of the eye lying between the retina and the sclera. The choroid provides oxygen and nourishment to the outer layers of the retina. It also contains a nonreflective pigment that acts as a light shield and prevents light from scattering. Light enters the front of the eye through a hole in the choroid coat called the pupil. The iris contracts and dilates to compensate for the changes in light intensity. If the light is bright the iris then contracts making the pupil smaller, and if the light is dim, the iris dilates making the pupil bigger. Just posterior to the iris is the lens, which is composed mainly of proteins called crystallins. The lens is attached by the zonules to the ciliary body that contains the ciliary muscles that control the shape of the lens for accommodation. Along with the ciliary body and iris, the choroid forms the uveal tract. The uvea is the middle of the three concentric layers that make up an eye. The name is possibly a reference to its almost black color, wrinkled appearance and grape-like size and shape when stripped intact from a cadaveric eye.
Retina
Illustration of the "blind spot." Situate your head about one foot from the monitor. Close your right eye and look at the dot on the right with your left eye. Move your head slowly closer. When you get to the correct spot, the dot on the left will disappear.
The third or the innermost layer of the eye is call the retina. In adult humans the entire retina is 72% of a sphere about 22 mm in diameter. The retina lays over the back two thirds of the choroid coat, which is located in the posterior compartment. The compartment is filled with vitreous humor which is a clear, gelatinous material. Within the retina there are cells called rod cells and cone cells also known as photoreceptors. The rod cells are very sensitive to light and do not see color, that is why when we are in a darkened room we see only shades of gray. The cone cells are sensitive to different wavelengths of light, and that is how we are able to tell different colors. It is a lack of cones sensitive to red, blue, or green light that causes individuals to have deficiencies in color vision or various kinds of color blindness. At the center of the retina is the optic disc, sometimes known as "the blind spot" because it lacks photoreceptors. It is where the optic nerve leaves the eye and takes the nerve impulses to the brain. The cornea and the lens of the eye focuses the light onto a small area of the retina called the fovea centralis where the cone cells are densely packed. The fovea is a pit that has the highest visual acuity and is responsible for our sharp central vision - there are no rods in the fovea.

Retina's simplified axial organization. The retina is a stack of several neuronal layers. Light is concentrated from the eye and passes across these layers (from left to right) to hit the photoreceptors (right layer). This elicits chemical transformation mediating a propagation of signal to the bipolar and horizontal cells (middle yellow layer). The signal is then propagated to the amacrine and ganglion cells. These neurons ultimately may produce action potentials on their axons. This spatiotemporal pattern of spikes determines the raw input from the eyes to the brain.

Photoreceptors
A photoreceptor, or photoreceptor cell, is a specialized type of neuron found in the eye's retina that is capable of phototransduction. More specifically, the photoreceptor sends signals to other neurons by a change in its membrane potential when it absorbs photons. Eventually, this information will be used by the visual system to form a complete representation of the visual world. There are 2 types of photoreceptors: rods are responsible for scotopic, or night vision, whereas cones are responsible for photopic, or daytime vision as well as color perception.
Extraocular muscles
Each eye has six muscles that control its movements: the lateral rectus, the medial rectus, the inferior rectus, the superior rectus, the inferior oblique, and the superior oblique. When the muscles exert different tensions, a torque is exerted on the globe that causes it to turn. This is an almost pure rotation, with only about one millimeter of translation, thus, the eye can be considered as undergoing rotations about a single point in the center of the eye. Five of the extraocular muscles have their origin in the back of the orbit in a fibrous ring called the annulus of Zinn. Four of these then course forward through the orbit and insert onto the globe on its anterior half (i.e., in front of the eye's equator). These muscles are named after their straight paths, and are called the four rectus muscles, or four recti. They insert on the globe at 12, 3, 6, and 9 o'clock, and are called the superior, lateral, inferior and medial rectus muscles. (Note that lateral and medial are relative to the subject, with lateral toward the side and medial toward the midline, thus the medial rectus is the muscle closest to the nose).

### Eye Movement

The visual system in the brain is too slow to process that information if the images are slipping across the retina at more than a few degrees per second, thus, for humans to be able to see while moving, the brain must compensate for the motion of the head by turning the eyes. To get a clear view of the world, the brain must turn the eyes so that the image of the object of regard falls on the fovea. Eye movements are thus very important for visual perception, and any failure to make them correctly can lead to serious visual disabilities. Having two eyes is an added complication, because the brain must point both of them accurately enough that the object of regard falls on corresponding points of the two retinas; otherwise, double vision would occur. The movements of different body parts are controlled by striated muscles acting around joints. The movements of the eye are no exception, but they have special advantages not shared by skeletal muscles and joints, and so are considerably different.

Try This Experiment

### How we see an object

• The light rays enter the eye through the cornea (transparent front portion of eye to focus the light rays).
• Then, light rays move through the pupil, which is surrounded by Iris to keep out extra light
• Then, light rays move through the crystalline lens (Clear lens to further focus the light rays )
• Then, light rays move through the vitreous humor (clear jelly like substance)
• Then, light rays fall on the retina, which processes and converts incident light to neuron signals using special pigments in rod and cone cells.
• These neuron signals are transmitted through the optic nerve,
• Then, the neuron signals move through the visual pathway - Optic nerve > Optic Chiasm > Optic Tract > Optic Radiations > Cortex
• Then, the neuron signals reach the occipital (visual) cortex and its radiations for the brain's processing.
• The visual cortex interprets the signals as images and along with other parts of the brain, interpret the images to extract form, meaning, memory and context of the images.

### Depth Perception

Depth perception is the visual ability to perceive the world in three dimensions. It is a trait common to many higher animals. Depth perception allows the beholder to accurately gauge the distance to an object.

Depth perception is often confused with binocular vision, also known as Stereopsis. Depth perception does rely on binocular vision, but it also uses many other monocular cues.

### Diseases, disorders, and age-related changes

There are many diseases, disorders, and age-related changes that may affect the eyes and surrounding structures. As the eye ages certain changes occur that can be attributed solely to the aging process. Most of these anatomic and physiologic processes follow a gradual decline. With aging, the quality of vision worsens due to reasons independent of aging eye diseases. While there are many changes of significance in the non-diseased eye, the most functionally important changes seem to be a reduction in pupil size and the loss of accommodation or focusing capability (presbyopia). The area of the pupil governs the amount of light that can reach the retina. The extent to which the pupil dilates also decreases with age. Because of the smaller pupil size, older eyes receive much less light at the retina. In comparison to younger people, it is as though older persons wear medium-density sunglasses in bright light and extremely dark glasses in dim light. Therefore, for any detailed visually guided tasks on which performance varies with illumination, older persons require extra lighting.

File:Colorblind3.png
This image contains a two digit number similar to the sample above. Someone who is protanopic might not see this number.
Color Blindness
Color Blindness or color vision deficiency, in humans is the inability to perceive differences between some or all colors that other people can distinguish. It is most often of genetic nature, but may also occur because of eye, nerve, or brain damage, or due to exposure to certain chemicals. There are many types of color blindness. The most common variety are hereditary (genetic) photoreceptor disorders, but it is also possible to acquire color blindness through damage to the retina, optic nerve, or higher brain areas. There is generally no treatment to cure color deficiencies, however, certain types of tinted filters and contact lenses may help an individual to distinguish different colors better.
Night Blindness
Also known as Nyctalopia, is a condition making it difficult or impossible to see in the dark. It is a symptom of several eye diseases. Night blindness may exist from birth, or be caused by injury or malnutrition (for example, a lack of vitamin A). The most common cause of nyctalopia is retinitis pigmentosa, a disorder in which the rod cells in the retina gradually lose their ability to respond to the light. Patients suffering from this genetic condition have progressive nyctalopia and eventually their day-time vision may also be affected. In congenital stationary night blindness the rods do not work from birth, but as the name implies, sufferers do not get worse. Another cause of night blindness is a deficiency of retinol, or vitamin A, found in fish oils, liver and dairy products.
Day Blindness
Also known as Hemeralopia is the inability to see clearly in bright light. The daytime vision gets worse and worse. Nighttime vision remains unchanged due to the use of rods as opposed to cones (during the day), which get affected by hemeralopia and in turn degrade the daytime optical response.
Impression of floaters, as seen against a blue sky.
Floater
Also known as "Muscae Volitantes" are deposits of various size, shape, consistency, refractive index, and motility within the eye's normally transparent vitreous humour. Floaters are suspended in the vitreous humour, the thick fluid or gel that fills the eye. Thus, they generally follow the rapid motions of the eye, while drifting slowly within the fluid. Floaters are visible only because they do not remain perfectly fixed within the eye. The shapes are shadows projected onto the retina by tiny structures of protein or other cell debris discarded over the years and trapped in the vitreous humour. They are also common after cataract operations or after trauma. In some cases, floaters are congenital.
Picture of children holding a ball as seen by someone with glaucoma.
Glaucoma
A group of diseases of the optic nerve involving loss of retinal ganglion cells in a characteristic pattern of optic neuropathy. Although raised intraocular pressure is a significant risk factor for developing glaucoma, there is no set threshold for intraocular pressure that causes glaucoma. One person may develop nerve damage at a relatively low pressure, while another person may have high eye pressures for years and yet never develop damage. Untreated glaucoma leads to permanent damage of the optic nerve and resultant visual field loss, which can progress to blindness.
Visual Agnosia
Visual agnosia is the inability of the brain to make sense of or make use of some part of otherwise normal visual stimulus, and is typified by the inability to recognize familiar objects or faces. This is distinct from blindness, which is a lack of sensory input to the brain due to damage to the eye or optic nerve. Visual agnosia is often due to damage, such as stroke, in posterior parietal lobe in the right hemisphere of the brain. Careful analysis of the nature of visual agnosia has led to improved understanding of the brain's role in normal vision.
Deadly Nightshade is a plant oil that can potentially kill you. Atrophine taken from this plant causes your eyes to dilate. This was used in the middle ages by women who wanted to look more attractive for men. To this day, it is still used by opthamologists. How this works is that the atrophine is a competitor with acetylcholine. The Nightshadow goes into your receptors on the postsynaptic membrane of an action potential. This makes it so that the acetylcholine doesn’t have any receptor site so the Na ion is not able to be released.

### Critical Thinking

The answers for these critical thinking questions is right here

1. Explain why you are normally unaware of your blind spot.
2. Stare at a bright light for 10 seconds and then stare at a white sheet of paper. What do you observe and why?
3. What is it that makes things "disappear" when you are staring at them at night, and how do you make them reappear?
4. Name what rods are sensitive to and also what cones are sensitive to.

## The Senses Of Hearing

The ear is the sense organ that collects and detects sound waves and plays a major role in the sense of balance and body position. The sensory receptors for both hearing and equilibrium are mechanoreceptors found in the inner ear; these receptors are hair cells that have stereocilia (long microvilli) that are extremely sensitive to mechanical stimulations.

### Anatomy of the Ear

The ear has three divisions: the outer ear, the middle ear, and the inner ear.

Anatomy of the human ear.
Outer Ear (Auricle, Ear Canal, Surface of Ear Drum)
The outer ear is the most external portion of the ear. The outer ear includes the pinna (also called auricle), the ear canal, and the very most superficial layer of the ear drum (also called the tympanic membrane). Although the word "ear" may properly refer to the pinna (the flesh covered cartilage appendage on either side of the head), this portion of the ear is not vital for hearing. The complicated design of the human outer ear does help capture sound, but the most important functional aspect of the human outer ear is the ear canal itself. This outer ear canal skin is applied to cartilage; the thinner skin of the deep canal lies on the bone of the skull. If the ear canal is not open, hearing will be dampened. Ear wax (medical name - cerumen) is produced by glands in the skin of the outer portion of the ear canal. Only the thicker cerumen-producing ear canal skin has hairs. The outer ear ends at the most superficial layer of the tympanic membrane. The tympanic membrane is commonly called the ear drum.
Middle Ear (Air Filled Cavity behind the Ear Drum, includes most of the Ear Drum, and Ear Bones)
The middle ear includes most of the ear drum (tympanic membrane) and the 3 ear bones ossicles: malleus (or hammer), incus (or anvil), and stapes (or stirrup). The opening of the Eustachian tube is also within the middle ear. The malleus has a long process (the handle) that is attached to the mobile portion of the ear drum. The incus is the bridge between the malleus and stapes. The stapes is the smallest named bone in the human body. The stapes transfers the vibrations of the incus to the oval window, a portion of the inner ear to which it is connected. It is the final bone in the chain to transfer vibrations from the eardrum to the inner ear. The arrangement of these 3 bones is a sort of Rube Goldberg device: movement of the tympanic membrane causes movement of the first bone, which causes movement of the second, which causes movement of the third. When this third bone pushes down, it causes movement of fluid within the cochlea (a portion of the inner ear). This particular fluid only moves when the stapes footplate is depressed into the inner ear. Unlike the open ear canal, however, the air of the middle ear is not in direct contact with the atmosphere outside the body. The Eustachian tube connects from the chamber of the middle ear to the back of the pharynx. The middle ear in humans is very much like a specialized paranasal sinus, called the tympanic cavity, it, like the paranasal sinuses, is a hollow mucosa lined cavity in the skull that is ventilated through the nose. The mastoid portion of the temporal bone, which can be felt as a bump in the skull behind the pinna, also contains air, which ventilates through the middle ear.
Inner Ear (Cochlea, Vestibule, and Semi-Circular Canals)
The inner ear includes both the organ of hearing (the cochlea) and a sense organ (the labyrinth or vestibular apparatus) that is attuned to the effects of both gravity and motion. The balance portion of the inner ear consists of three semi-circular canals and the vestibule. The inner ear is encased in the hardest bone of the body. Within this ivory hard bone, there are fluid-filled hollows. Within the cochlea are three fluid filled spaces: the tympanic canal, the vestibular canal, and the middle canal. The eighth cranial nerve comes from the brain stem to enter the inner ear. When sound strikes the ear drum, the movement is transferred to the footplate of the stapes, which attaches to the oval window and presses into one of the fluid-filled ducts of the cochlea. The hair cells in the organ of Corti are stimulated by particular frequencies of sound, based on their location within the cochlea. High pitch sounds are at a higher frequency and, due to the shorter wavelength they "hit" the membrane "faster" (ie. close to the oval window). In contrast, low frequency sounds have large wavelengths, and will travel further through the scala vestibuli before "hitting" the tectorial membrane near the apex of the cochlea. The fluid inside the cochlea is moved, flowing against the receptor (hair) cells of the organ of Corti, which fire in a graded response based on the volume of the sound. The hair cells then stimulate the nerve cells in the Spiral Ganglion, which sends information through the auditory portion of the eighth cranial nerve to the brain. Humans are able to hear sounds between about 20 Hz and 20,000 Hz. Mammals that can hear lower frequency sounds, such as whales and elephants, have a longer cochlea. Humans tend to lose high-frequency hearing first, which has led some teenagers to using high-frequency ring tones (above 17,000 Hz) that may go undetected by their middle-aged teachers.
Cross section of the cochlea
Hair Cell
Hair cells are columnar cells, each with a bundle of 100-200 specialized cilia at the top, for which they are named. These cilia are the mechanosensors for hearing. Lightly resting atop the longest cilia is the tectorial membrane, which moves back and forth with each cycle of sound, tilting the cilia and allowing electric current into the hair cell. Hair cells, like the photoreceptors of the eye, show a graded response, instead of the spikes typical of other neurons. Immediately over the hair cells of the organ of Corti is an overhanging “tectorial membrane.” When the Bones of the Middle Ear vibrate the oval window, these vibrations are transmitted to the fluid within the cochlea and eventually cause the round window on the cochlea to bulge outward. These vibrations deflect the membrane on which the Organ of Corti is located, causing the three rows of outer hair cells to “rub” against the overhanging tectorial membrane. By their muscle-like activity they ampify the weakest vibrations for the inner hair cells. The louder sounds are not amplified. The disturbed inner hair cells will then activate the cochlear nerve fibers. The current model is that cilia are attached to one another by “tip links”, structures which link the tips of one cilium to another. Stretching and compressing the tip links may open an ion channel and produce the receptor potential in the hair cell. These graded potentials are not bound by the “all or none” properties of an action potential. There are far fewer hair cells than afferent (leading to the brain) nerve fibers in the cochlea. The nerve that innervates the cochlea is the cochlear nerve, and forms cranial nerve number VIII with the vestibular nerve from the balance organ. Neuronal dendrites innervate cochlear hair cells. The neurotransmitter itself is thought to be glutamate. At the presynaptic juncture, there is a distinct “presynaptic dense body” or ribbon. This dense body is surrounded by synaptic vesicles and is thought to aid in the fast release of neurotransmitter. Efferent projections from the brain to the cochlea also play a role in the perception of sound. Efferent synapses occur on outer hair cells and on afferent dendrites under inner hair cells.

### Process of Hearing

Detection of sound motion is associated with the right posterior superior temporal gyrus. The superior temporal gyrus contains several important structures of the brain, including: (1)marking the location of the primary auditory cortex, the cortical region responsible for the sensation of sound. Sections 41 and 42 are called the primary auditory area of the cerebrum, and processes the basic characteristics of sound such as pitch and rhythm. The auditory association area is located within the temporal lobe of the brain, in an area called the Wernicke's area, or area 22. This area, near the lateral cerebral sulcus, is an important region for the processing of acoustic energy so that it can be distinguished as speech, music, or noise. It also interprets words that are heard into an associated thought pattern of understanding. The gnostic area of the cerebrum, (areas 5, 7, 39 and 40) helps to integrate all incoming sense patterns so that a common thought can be formed (correlated) using all arriving sensory information.

### Hearing Under Water

Hearing threshold and the ability to localize sound sources are reduced underwater. in which the speed of sound is faster than in air. Underwater, hearing is by bone conduction and localization of sound appears to depend on differences in amplitude detected by bone conduction.

### Localization of Sound by Humans

Humans are normally able to hear a variety of sound frequencies, from about 20Hz to 20kHz. Our ability to estimate just where the sound is coming from, sound localization, is dependent on both hearing ability of each of the two ears, and the exact quality of the sound. Since each ear lies on an opposite side of the head, a sound will reach the closest ear first, and its amplitide will be loudest in that ear. Much of the brain's ability to localize sound depends on interaural (between ears) intensity differences and interaural temporal or phase differences.

Two mechanisms are known to be used.

Bushy neurons can resolve time differences as small as the time it takes sound to pass one ear and reach the other (10 milliseconds). For high frequencies, frequencies with a wavelength shorter than the listener's head, more sound reaches the nearer ear. Human echolocation is a technique involving echolocation used by some blind humans to navigate within their environment.

### Process of Equilibrium

Equilibrioception or sense of balance is one of the physiological senses. It allows humans and animals to walk without falling. Some animals are better in this than humans, for example allowing a cat (as a quadruped using its inner ear and tail) to walk on a thin fence. All forms of equilibrioception can be described as the detection of acceleration.

It is determined by the level of fluid properly called endolymph in the labyrinth - a complex set of tubing in the inner ear.

When the sense of balance is interrupted it causes dizziness, disorientation and nausea.

You can temporarily disturb your sense of balance by closing your eyes and turning rapidly in circles five or six times. This starts the fluid swirling in circles inside your ear canal. When you stop turning it takes a few seconds for the fluid to lose momentum, and until then the sense from your inner ear conflicts with the information coming from your vision, causing dizziness and disorientation. Most astronauts find that their sense of balance is impaired when in orbit, because there is not enough gravity to keep the ear's fluid in balance. This causes a form of motion sickness called space sickness.

### Disorders with the Ear

Case Study A 45-year-old woman wakes up not feeling well. She believes that she may be coming down with the flu due to nausea that she is feeling, so she continues with her day. As the day progresses so does the feeling of nausea. While watching a movie with members of her family, the sick feeling seems to intensify and so they leave the movie. In the lobby of the movie theater she becomes very unbalanced and collapses. The fear is that she is experiencing a stroke. After being taken to the hospital via ambulance, the ER doctors also feel that it may be a stroke and do CAT scans to verify. Nothing shows up on the scans but the feeling of nausea and vertigo are intense. The woman is later diagnosed with an inner ear infection. The next 6-9 months of her life are filled with antibiotics, balance therapy and continued nausea and vertigo. Nothing seems to help so the doctors go into her inner ear surgically through her skull. They cut the vestibular nerve that is linked to the balance center on the left side. The right inner ear will eventually compensate for this loss of balance however it will take months of balance therapy. After a year from the onset on the inner ear infection, the woman has had three inner ear surgeries, loss of hearing in the left ear and problems with her balance. Doctors have told her they have done everything that they can and that she will now have to live with these conditions on a daily basis.

Deafness
The word deaf can have at least two different meanings. The first term is used to indicate the presence of enough hearing loss such that an individual is not sensitive to sound. Someone with a partial loss of hearing is more likely to be referred to as hearing impaired or the qualified partially deaf by professionals. The second term is used to indicate someone who considers themselves 'culturally deaf', and they often use a capital D to distinguish this. Deaf people often are signers and consider that their Deafness is not something that needs to be medically fixed.

Cochlear Implants A cochlear implant is a device which has been used to restore hearing function to some deaf and hearing impaired people. It consists of an internal device; which extends electrodes into the cochlea and indirectly stimulates the auditory nerve, and an external device; which works much like a hearing aid, except it transmits information to the internal device rather than to the ear. The cochlear implant basically bypasses the middle ear and the cochlea hair cells, and allows some people with damage to these structures to hear 'electronically'.

Otitis Media
An inflammation of the middle ear segment. It is usually associated with a buildup of fluid and frequently causes an earache. The fluid may or may not be infected. The typical progress of otitis media is: the tissues surrounding the Eustachian tube swell due to an infection and/or severe congestion. The Eustachian tube remains blocked most of the time. The air present in the middle ear is slowly absorbed into the surrounding tissues. A strong negative pressure creates a vacuum in the middle ear. The vacuum reaches a point where fluid from the surrounding tissues accumulates in the middle ear. Streptococcus pneumoniae and Haemophilus influenzae are the most common bacterial causes of otitis media. As well as being caused by Streptococcus pneumoniae and Haemophilus influenzae it can also be caused by the common cold.
Vertigo (dizziness)
Vertigo, sometimes called a headrush, is a major symptom of a balance disorder. It is the sensation of spinning while the body is stationary with respect to the earth or surroundings. With the eyes shut, there will be a sensation that the body is in movement, called subjective vertigo; if the eyes are open, the surroundings will appear to move past the field of vision, called objective vertigo. The effects may be slight. It may cause nausea or, if severe, may give rise to difficulty with standing and walking. Vertigo is usually associated with a problem in the inner ear balance mechanisms (vestibular system), in the brain, or with the nerve connections between these two organs. The most common cause is benign paroxysmal positional vertigo, or BPPV. Vertigo can be a symptom of an underlying harmless cause, such as in BPPV or it can suggest more serious problems. These include drug toxicities, strokes or tumors (though these are much less common than BPPV).
Motion sickness
Motion sickness is a condition in which the endolymph (the fluid found in the semicircular canals of the inner ears) becomes 'stirred up', causing confusion between the difference between apparent perceived movement (none or very little), and actual movement. Depending on the cause, it is also referred to as seasickness, carsickness, airsickness, or spacesickness. Nausea is the most common symptom of motion sickness. If the motion causing nausea is not resolved, the sufferer will frequently vomit within twenty minutes. Unlike ordinary sickness, vomiting in motion sickness tends not to relieve the nausea. If you don't want to consult a doctor, one common form of relief is to eat mints.
Dysacusis
Dysacusis is a hearing impairment characterized by difficulty in processing details of sound, but not primarily a loss of the ability to perceive sound. May also refer to pain or discomfort due to sound.

### Critical Thinking

The answers for these critical thinking questions can be found here.

1. Explain how the pitch of sound is coded. How is the loudness of sound coded?
2. What do the three semicircular canals in the inner ear enable us to do? How do they accomplish this?
3. What does the eustachian tube do? What does the eustachian tube have to do with a middle ear infection?
4. What is the advantage of having a oval window?

## Touch

Touch is the first sense developed in the womb and the last sense used before death. With 50 touch receptors for every square centimeter and about 5 million sensory cells overall, the skin is very sensitive and is the largest and one of the most complex organs in our bodies. These touch receptors are grouped by type and include Mechanoreceptors (sensitive to pressure, vibration and slip), Thermoreceptors (sensitive to changes in temperature), and Nocioreceptors (responsible for pain).

### Pacinian Corpuscles

Pacinian corpuscles detect gross pressure changes and vibrations. They are the largest of the receptors. Any deformation in the corpuscle causes action potentials to be generated, by opening pressure-sensitive sodium ion channels in the axon membrane. This allows sodium ions to influx in, creating a receptor potential. Pacinian corpuscles cause action potentials when the skin is rapidly indented but not when the pressure is steady, due to the layers of connective tissue that cover the nerve ending (Kandel et al., 2000). It is thought that they respond to high velocity changes in joint position.

### Meissner's Corpuscle

Meissner's corpuscles are distributed throughout the skin, but concentrated in areas especially sensitive to light touch, such as the fingertips, palms, soles, lips, tongue, face, nipples and the external skin of the male and female genitals. They are primarily located just beneath the epidermis within the dermal papillae. Any physical deformation in the Meissner’s corpuscle will cause an action potential in the nerve. Since they are rapidly adapting or phasic, the action potentials generated quickly decrease and eventually cease. If the stimulus is removed, the corpuscle regains its shape and while doing so (ie: while physically reforming) causes another volley of action potentials to be generated. (This is the reason one stops "feeling" one's clothes.) This process is called sensory adaption. Because of their superficial location in the dermis, these corpuscles are particularly sensitive to touch and vibrations, but for the same reasons, they are limited in their detection because they can only signal that something is touching the skin. Meissner's corpuscles do not detect pain; this is signaled exclusively by free nerve endings.

Layers of the skin, showing the Merkel's Cell.

### Merkel’s Discs

Merkel’s Discs are Mechanoreceptors, making them sensitive to pressure and vibration. In humans, Merkel cells occur in the superficial skin layers, and are found clustered beneath the ridges of the fingertips that make up fingerprints. They’re somewhat rigid in structure, and the fact that they are not encapsulated, causes them to have a sustained response (in the form of action potentials or spikes) to mechanical deflection of the tissue. Merkel nerve endings are extremely sensitive to tissue displacement, and may respond to displacements of less than 1 um. Several studies indicate that they mediate high-resolution tactile discrimination, and are responsible for the ability of our fingertips to feel fine detailed surface patterns (e.g. for reading Braille).

### Ruffini corpuscles

Ruffini corpuscles are Thermoreceptors, aiding in the detection of temperature changes. Named after Angelo Ruffini, the Ruffini ending is a class of slowly adapting mechanoreceptor thought to exist only in the glabrous dermis and subcutaneous tissue of humans. This spindle-shaped receptor is sensitive to skin stretch, and contributes to the kinesthetic sense of and control of finger position and movement.

### Disorders of Touch

Sensory Processing Disorder
In most people sensory integration occurs naturally without a thought process. But in some people the sensory integration does not develop properly and becomes distorted. In these people, the brain and central nervous system misinterprets everyday sensory information such as touch, sound and movement. Research is still being done on this disorder but they are finding direct links to SPD with other disorders like ADD/ADHD, premature birth, Autism, Down’s Syndrome and Fragile X.
Tactile defensiveness
Considered a category of SPD, tactile defensiveness is an overreaction to the sense of touch. Identified by Dr. Jean Ayers in the 1960’s. A person with tactile defensiveness will react with a “flight or fight” reaction to touch stimuli that a normal person would interpret as harmless. Most cases are noticed in children or babies due to the fact that they do not want to be touched or cuddled as a normal child would. A child with this disorder will probably have these sign or symptoms:
• Does not like to go barefoot or have feet touched
• Does not enjoy baths, haircuts, nail clipping
• Requires tags to be removed from all clothing
• Does not want their face touched
• Hard time eating because of textures, temperatures of the food
• Does not want to touch anything that is messy or has a sticky texture
Congenital insensitivity to pain with anhidrosis or CIPA
Exceedingly rare disease. There are only about 35 known cases in the United States. CIPA is a severe autosomal recessive condition in which the peripheral nerves demonstrate a loss of unmyelinated and small myelinated fibers. The actual physiopathological mechanism is still unknown and being studied- this is an extremely hard disease to study due to the rarity of cases. Most people with the disease will not live long due to injuries received that go untreated because they are unknown and severe

### Case Study

Insensitivity to pain

Wouldn't it wonderful if you could no longer feel pain. Is that not something we all would like to have? Or do we have pain for a good reason? Although it is rare there is a disease known as congenital insensitivity to pain. This genetic abnormality cause some people to lack certain components of the sensory system to receive pain. The exact reason for the problem is unknown and varies between people. Sadly people who have the disease often die in childhood. Injuries are very common with people who have congenital insensitivity to pain. They often will lose digits, may suffer from burns and their knees often have sores from kneeling to long. Clearly pain has a purpose, it is our warning signal when things are awry.

## The newborn's senses

Newborns can feel all different sensations, but respond most enthusiastically to soft stroking, cuddling and caressing. Gentle rocking back and forth will oftentimes calm a crying infant, as will massages and warm baths. Newborns may comfort themselves by sucking their thumbs, or a pacifier. The need to suckle is instinctive and allows newborns to feed.

Vision
Newborn infants have unremarkable vision, being able to focus on objects only about 18 inches (45 cm) directly in front of their face. While this may not be much, it is all that is needed for the infant to look at the mother’s face when breastfeeding. When a newborn is not sleeping, or feeding, or crying, he or she may spend a lot of time staring at random objects. Usually anything that is shiny, has sharp contrasting colors, or has complex patterns will catch an infant's eye. However, the newborn has a preference for looking at other human faces above all else.
Hearing
While still inside the mother, the infant can hear many internal noises, such as the mother's heartbeat, as well as many external noises including human voices, music and most other sounds. Therefore, although a newborn's ears may have some fluid present, he or she can hear sound from birth. Newborns usually respond to a female's voice over a male's. This may explain why people will unknowingly raise the pitch of their voice when talking to newborns. The sound of other human voices, especially the mother's, can have a calming or soothing effect on the newborn. Conversely, loud or sudden noises will startle and scare a newborn.
Taste
Newborns can respond to different tastes, including sweet, sour, bitter, and salty substances, with preference toward sweets.
Smell
A newborn has a developed sense of smell at birth, and within the first week of life can already distinguish the differences between the mother's own breast milk and the breast milk of another female.
Reflex Stimulation Response Age of disappearance Function
Eye blink Bright light shinning in eyes or clap hands by eyes. Closes eyelids quickly. Permanent This reflex protects the infant from an excessive amount of stimulation.
Withdrawal Stick sole of foot with a stimulus like a pin. This causes the foot to withdraw. Flexing of the knee to hip occurs. Decreases after the 10th day of birth This protects the infant from excessive unpleasant tactile stimulation.
Rooting Touch cheek near the corner of the mouth. The infant's head will turn towards the site of stimulation. 3 weeks (due to the voluntary response that is now capable for infant to do at this time) This reflex helps baby to find the mothers' nipple.
Sucking Place fingers in infant's mouth. The infant will suck finger rhythmically. 4 months (voluntary sucking will come about) This helps with feeding.
Swimming Place the baby in pool of water face down. The baby paddles and kicks in swimming movements. 4 to 6 month This helps baby to survive if dropped into the water.
Moro Hold infant in a cradling horizontal position and slightly lower the baby in a fast motion toward the ground while making a loud sound. The baby will make a embracing motion and arch its back extending it's legs and throwing it's arms outward. Finally it will bring the arms in toward its body 6 months In the evolutionary past this may have helped the baby cling to the mother.
Palmar grasp Place the finger in baby's palm and press against the palm. The baby will immediately grasp the finger. 3 to 4 months This prepares infant for voluntary grasping.
Tonic neck Turn the baby's head to one side while the baby is awake. This will cause the baby to extend one arm in front of its eye or to the side to which the head has been turned. 4 months This may prepare for voluntary reaching.
Stepping Hold the baby under the arm and permit the bare feet of the baby to touch a flat surface. The baby will lift one foot after the other in a stepping fashion. 2 months (this applies to a baby who has gained weight. For baby who is not as heavy, this reflex may be submissive.) This prepares the baby for voluntary walking.
Babinski Touch the foot in a stroking manner form the toe toward the heel. The baby's toes will fan out and curl as the foot twists inward. 8 to 12 months Unknown

## Review Questions

Answers for these questions can be found here

1. Located under the hardest bone in the body, these control not only hearing but also a sense of gravity and motion:

A) The incus and the stapes

B) The pinna and the ear drum

C) the vestibular nerve and the semi circular canals

D) The eustachian tube and the stapes

2. The retina does the following;

A) allows vision in light and dark, using cones and rods

B) Gives depth perception using binocular vision

C) Contains the ciliary muscles that control the shape of the lens

D) Protects and supports the shape of the eye

3. This is the reason that we stop feeling the clothes that we are wearing

A) Merkel’s Discs are somewhat rigid in structure, and the fact that they are not encapsulated, causes them to have a sustained response

B) Meissner’s corpuscle are rapidly adapting or phasic, the action potentials generated quickly decrease and eventually cease

C) Ruffini corpuscles is a class of slowly adapting mechanoreceptor

D) Pacinian corpuscles allow sodium ions to influx in, creating a receptor potential

4. When eating a piece of candy, I will use the following to sense that it is sweet

A) Fungiform papillae

B) Filiform papillae

C) Foliate papillae

D) Circumvallate papillae

E) All of the above

5. If I have a cold, food may not taste as good to me because

A) The nerve fibrils are not functioning properly

B) My food will taste the same; taste and smell have nothing in common

C) Papilla become blocked by mucus and are unable to function

D) Olfaction, taste and trigeminal receptors together contribute to the flavor of my food

6. Walking from a well lit room into a dark room would cause the following to occur

A) The sclera in the eye to open and eventually allow me to see in the dark

B) The extraocular muscles in the eye to open and eventually allow me to see in the dark

C) The cones in the eye to open and eventually allow me to see in the dark

D) the rods in the eye to open and eventually allow me to see in the dark

7. Hair cells in the ear

A) Are the actual sensory receptors that will fire off action potentials when they are disturbed

B) Show a graded response, instead of the spikes typical of other neurons

C) “Rub” against the overhanging tectorial membrane

D) All of the above

8. Eyesight decreases with age because

A) Older eyes receive much less light at the retina

B) There are numerous eye diseases that can affect an older eye

C) The extent to which the pupil dilates decreases with age

D) all of the above

9. Teens walking off of a roller coaster in Magic Mountain seem to have vertigo because

A) The fluid in the auricle has not stopped moving causing conflicts with the information coming from your vision

B) the fluid in the cochlea has not stopped moving causing conflicts with the information coming from your vision

C) The fluid in the tympanic membrane has not stopped moving causing conflicts with the information coming from your vision

D) The fluid in the stirrup has not stopped moving causing conflicts with the information coming from your vision

10. These receptors react to foods treated with monosodium glutamate

A) Salt

B) Sour

C) Bitter

D) Sweet

E) Umami

11. What senses fall under the catagory of chemoreception?

A) Hearing and smell

B) Touch and hearing

C) Vision and taste

D) Taste and smell

## Glossary

Anosmia: Lack of olfaction, or a loss of the sense of smell

Auditory Canal: Tube from the auditory meatus or opening of the ear to the tympanic membrane

Auditory Tube: Either of the paired tubes connecting the middle ears to the nasopharynx; equalizes air pressure on the two sides of the eardrum

Chemoreception: Physiological response of a sense organ to a chemical stimulus

Choroid: Vascular layer of the eye lying between the retina and the sclera

Circumvallate papillae: Papillae that are present on the back of the oral part of the tongue

Cochlea: Is concerned with hearing, resembling a shell of a snail

Dysosmia: When things smell differently than they should

Equilibrium: Sense of balance

Extraocular muscles: Six muscles that control eye movements: lateral rectus, medial rectus, inferior rectus, superior rectus, inferior oblique and superior oblique

Filiform papillae: Thin, longer papillae that don't contain taste buds but are the most numerous

Foliate papillae: Ridges and grooves towards the posterior part of the tongue

Fungiform papillae: These are present mostly at the apex (tip) of the tongue- slightly mushroom shaped

Gustation: The sense of taste

Hair Cell: Mechanosensors for hearing, columnar cells each with a bundle of 100-200 specialized cilia at the top

Haptic: From the Greek Haphe, means pertaining to the sense of touch

Hyposmia: Decreased ability to smell

Inner Ear: Innermost part of the ear, contains the cochlea, westibule and semi-circular canals

Mechanoreceptor: Sensory receptor that responds to mechanical pressure or distortion

Meissner's Corpuscle: Encapsulated unmyelinated nerve endings, usually found in areas sensitive to light touch

Middle Ear: Air Filled Cavity behind the Ear Drum, includes most of the ear Drum and ear Bones

Nasopharynx: Nasal part of the pharynx that lies behind the nose and above the level of the soft palate

Nociception: The perception of pain

Olfaction: The sense of smell

Otitis Media: An inflammation of the middle ear

Outer Ear: External portion of the ear, includes the auricle, ear canal and surface of the ear drum

Oval Window: Fenestra that has the base of the stapes attached to it

Pacinian Corpuscles; Detect gross pressure changes and vibrations

Papilla: Specialized epithelial cells that are small projections on the top of the tongue

Perception: The brain’s interpretation of a sensation

Phantosmia: Phenomenon of smelling odors that aren't really present (AKA Phantom odors)

Photoreceptors: Specialized type of neuron found in the eye's retina that is capable of phototransduction

Pinna: Auricle of the ear

Retina: Thin layer of neural cells that lines the back of the eyeball of vertebrates and some cephalopods

Round Window: Fenestra leading into the cochlea

Sclera: White outer coating of the eye- gives the eye its shape and helps to protect the delicate inner parts

Semicircular Canals: Certain canals of the inner ear

Sensation: Occurs when nerve impulses arrive in the brain

Sensory adaptation: A decrease in response to stimuli

Stapes: One of the small bones in the tympanum of the ear; the stirrups bone

Tactition: The sense of pressure perception, generally in the skin

Tympanic Membrane: The membrane in the ear that vibrates to produce sound

Umami: Japanese word meaning savory or meaty- type of taste signal

## References

• Hänig, D.P., 1901. Zur Psychophysik des Geschmackssinnes. Philosophische Studien, 17: 576-623.
• Collings, V.B., 1974. Human Taste Response as a Function of Locus of Stimulation on the Tongue and Soft Palate. Perception & Psychophysics, 16: 169-174.
• Buck, Linda and Richard Axel. (1991). A Novel Multigene Family May Encode Odorant Receptors: A Molecular Basis for Odor Recognition. Cell 65:175-183.

# The Muscular System

The muscular system is the biological system of humans that produces movement. The muscular system, in vertebrates, is controlled through the nervous system, although some muscles, like cardiac muscle, can be completely autonomous. Muscle is contractile tissue and is derived from the mesodermal layer of embryonic germ cells. Its function is to produce force and cause motion, either locomotion or movement within internal organs. Much of muscle contraction occurs without conscious thought and is necessary for survival, like the contraction of the heart or peristalsis, which pushes food through the digestive system. Voluntary muscle contraction is used to move the body and can be finely controlled, such as movements of the finger or gross movements that of the biceps and triceps.

Muscle structure

Muscle is composed of muscle cells (sometimes known as "muscle fibers"). Within the cells are myofibrils; myofibrils contain sarcomeres which are composed of actin and myosin. Individual muscle cells are lined with endomysium. Muscle cells are bound together by perimysium into bundles called fascicles. These bundles are then grouped together to form muscle, and is lined by epimysium. Muscle spindles are distributed throughout the muscles, and provide sensory feedback information to the central nervous system. Skeletal muscle, which involves muscles from the skeletal tissue, is arranged in discrete groups. An example is the biceps brachii. It is connected by tendons to processes of the skeleton. In contrast, smooth muscle occurs at various scales in almost every organ, from the skin (in which it controls erection of body hair) to the blood vessels and digestive tract (in which it controls the caliber of a lumen and peristalsis, respectively).

A top-down view of skeletal muscle

There are approximately 640 skeletal muscles in the human body (see list of muscles of the human body). Contrary to popular belief, the number of muscle fibers cannot be increased through exercise; instead the muscle cells simply get bigger. It is however believed that myofibrils have a limited capacity for growth through hypertrophy and will split if subject to increased demand. There are three basic types of muscles in the body (smooth, cardiac, and skeletal). While they differ in many regards, they all use actin sliding against myosin to create muscle contraction and relaxation. In skeletal muscle, contraction is stimulated at each cell by nervous impulses that releases acetylcholine at the neuromuscular junction, creating action potentials along the cell membrane. All skeletal muscle and many smooth muscle contractions are stimulated by the binding of the neurotransmitter acetylcholine. Muscular activity accounts for most of the body's energy consumption. Muscles store energy for their own use in the form of glycogen, which represents about 1% of their mass. Glycogen can be rapidly converted to glucose when more energy is necessary.

## Types

There are three types of muscles:

• Smooth muscle or "involuntary muscle" consists of spindle shaped muscle cells found within the walls of organs and structures such as the esophagus, stomach, intestines, bronchi, uterus, ureters, bladder, and blood vessels. Smooth muscle cells contain only one nucleus and no striations.
• Cardiac muscle is also an "involuntary muscle" but it is striated in structure and appearance. Like smooth muscle, cardiac muscle cells contain only one nucleus. Cardiac muscle is found only within the heart.
• Skeletal muscle or "voluntary muscle" is anchored by tendons to the bone and is used to effect skeletal movement such as locomotion. Skeletal muscle cells are multinucleated with the nuclei peripherally located. Skeletal muscle is called 'striated' because of the longitudinally striped appearance under light microscopy. Functions of the skeletal muscle include:
• Support of the body
• Aids in bone movement
• Helps maintain a constant temperature throughout the body
• Assists with the movement of cardiovascular and lymphatic vessels through contractions
• Protection of internal organs and contributing to joint stability

Cardiac and skeletal muscle are striated in that they contain sarcomere and are packed into highly-regular arrangements of bundles; smooth muscle has neither. Striated muscle is often used in short, intense bursts, whereas smooth muscle sustains longer or even near-permanent contractions.

Skeletal muscle is further divided into several subtypes:

• Type I, slow oxidative, slow twitch, or "red" muscle is dense with capillaries and is rich in mitochondria and myoglobin, giving the muscle tissue its characteristic red color. It can carry more oxygen and sustain aerobic activity.
• Type II, fast twitch, muscle has three major kinds that are, in order of increasing contractile speed:
• a) Type IIa, which, like slow muscle, is aerobic, rich in mitochondria and capillaries and appears red.
• b) Type IIx (also known as type IId), which is less dense in mitochondria and myoglobin. This is the fastest muscle type in humans. It can contract more quickly and with a greater amount of force than oxidative muscle, but can sustain only short, anaerobic bursts of activity before muscle contraction becomes painful (often attributed to a build-up of lactic acid). N.B. in some books and articles this muscle in humans was, confusingly, called type IIB
• c) Type IIb, which is anaerobic, glycolytic, "white" muscle that is even less dense in mitochondria and myoglobin. In small animals like rodents or rabbits this is the major fast muscle type, explaining the pale color of their meat.

For most muscles, contraction occurs as a result of conscious effort originating in the brain. The brain sends signals, in the form of action potentials, through the nervous system to the motor neuron that innervates the muscle fiber. However, some muscles (such as the heart) do not contract as a result of conscious effort. These are said to be autonomic. Also, it is not always necessary for the signals to originate from the brain. Reflexes are fast, unconscious muscular reactions that occur due to unexpected physical stimuli. The action potentials for reflexes originate in the spinal cord instead of the brain.

There are three general types of muscle contractions, skeletal muscle contractions, heart muscle contractions, and smooth muscle contractions.

## Muscular System Working With Other Body Systems

• 1. Homeostasis
• 2. Protection
• 3. Calcium Metabolism
• 4. Maintaining Body Temperature

## Skeletal Muscle Contractions

Steps of a skeletal muscle contraction:

• An action potential reaches the axon of the motor neuron.
• The action potential activates voltage gated calcium ion channels on the axon, and calcium rushes in.
• The calcium causes acetylcholine vesicles in the axon to fuse with the membrane, releasing the acetylcholine into the cleft between the axon and the motor end plate of the muscle fiber.
• The skeletal muscle fiber is excited by large myelinated nerve fibers which attach to the neuromuscular junction. There is one neuromuscular junction for each fiber.
• The acetylcholine diffuses across the cleft and binds to nicotinic receptors on the motor end plate, opening channels in the membrane for sodium and potassium. Sodium rushes in, and potassium rushes out. However, because sodium is more permeable, the muscle fiber membrane becomes more positively charged, triggering an action potential.
• The action potential on the muscle fiber causes the sarcoplasmic reticulum to release calcium ions(Ca++).
• The calcium binds to the troponin present on the thin filaments of the myofibrils. The troponin then allosterically modulates the tropomyosin. Normally the tropomyosin physically obstructs binding sites for cross-bridge; once calcium binds to the troponin, the troponin forces the tropomyosin to move out of the way, unblocking the binding sites.
• The cross-bridge (which is already in a ready-state) binds to the newly uncovered binding sites. It then delivers a power stroke.
• ATP binds the cross-bridge, forcing it to conform in such a way as to break the actin-myosin bond. Another ATP is split to energize the cross bridge again.
• Steps 7 and 8 repeat as long as calcium is present on thin filament.
• Throughout this process, the calcium is actively pumped back into the sarcoplasmic reticulum. When no longer present on the thin filament, the tropomyosin changes back to its previous state, so as to block the binding sites again. The cross-bridge then ceases binding to the thin filament, and the contractions cease as well.
• Muscle contraction remains as long as Ca++ is abundant in sarcoplasm.

Types of Contractions:

• Isometric contraction--muscle does not shorten during contraction and does not require the sliding of myofibrils but muscles are stiff.
• Isotonic contraction--inertia is used to move or work. More energy is used by the muscle and contraction lasts longer than isometric contraction. Isotonic muscle contraction is divided into two categories: concentric, where the muscle fibers shorten as the muscle contracts (ie. biceps brachialis on the up phase of a biceps curl); and eccentric, where the muscle fibers lengthen as they contract (ie. biceps brachialis on the down phase of a biceps curl).
• Twitch--exciting the nerve to a muscle or by passing electrical stimulus through muscle itself. Some fibers contract quickly while others contract slowly.
• Tonic -maintaining postural tone against the force of gravity.

The Efficiency of Muscle Contraction:

• Only about 20% of input energy converts into muscular work. The rest of the energy is heat.
• 50% of energy from food is used in ATP formation.
• If a muscle contraction is slow or without movement, energy is lost as maintenance heat.
• If muscle contraction is rapid, energy is used to overcome friction.

Summation of Muscle Contraction: It is the adding together of individual muscle twitches to make strong muscle movements.

• Multiple motor unit summation--increasing number of motor units contracting simultaneously.
• Wave summation--increasing rapidity of contraction of individual motor units.
• Tetanization--higher frequency successive contractions fuse together and cannot be distinguished from one another.

## Sliding Filament theory

When a muscle contracts, the actin is pulled along myosin toward the center of the sarcomere until the actin and myosin filaments are completely overlapped. The H zone becomes smaller and smaller due to the increasing overlap of actin and myosin filaments, and the muscle shortens. Thus when the muscle is fully contracted, the H zone is no longer visible (as in the bottom diagram, left). Note that the actin and myosin filaments themselves do not change length, but instead slide past each other.

### Cellular Action of Skeletal Muscles

During cellular respiration the mitochondria, within skeletal muscle cells, convert glucose from the blood to carbon dioxide and water in the process of producing ATP (see cell physiology). ATP is needed for all muscular movement. When the need of ATP in the muscle is higher than the cells can produce with aerobic respiration, the cells will produce extra ATP in a process called anaerobic respiration. The first step of aerobic respiration(glycolysis) produces two ATP per glucose molecule. When the rest of the aerobic respiration pathway is occupied the pyruvate molecule can be converted to lactic acid. This method produces much less ATP than the aerobic method, but it does it faster and allows the muscles to do a bit more than if they relied solely on ATP production from aerobic respiration. The drawback to this method is that lactic acid accumulates and causes the muscles to fatigue. They will eventually stop contracting until the breakdown of lactic acid is sufficient to allow for movement once again. People experience this most noticeably when they repeatedly lift heavy things such as weights or sprint for a long distance. Muscle soreness sometimes occurs after vigorous activity, and is often misunderstood by the general public to be the result of lactic acid buildup. This is a misconception because the muscle does fatigue from lactic acid buildup, but it does not stay in the muscle tissue long enough to cause tissue breakdown or soreness. During heavy breathing, following exercise, the cells are converting the lactic acid either back into glucose or converting it to pyruvate and sending it through the additional steps of aerobic respiration. By the time a person is breathing normally again the lactic acid has been removed. The soreness is actually from small tears in the fibers themselves. After the fibers heal they will increase in size. The number of mitochondria will also increase if there is continued demand for additional ATP. Hence, through exercise the muscles can increase in both strength and endurance.

Another misconception is that as the muscle increases in size it also gains more fibers. This is not true. The fibers themselves increase in size rather than in quantity. The same holds true for adipose tissue--fat cells do not increase in number, but rather the amount of lipids (oil) in the cells increase.

Muscle fibers are also genetically programmed to reach a certain size and stop growing from there, so after awhile even the hardest working weightlifter will only reach a certain level of strength and endurance. Some people will get around this by taking steroids. The artificial steroids cause all sorts of trouble for the person. They can cause the adrenal glands to stop producing corticosteroids and glucosteroids. This leads to the atrophy of the gland's medulla and causes permanent loss of the production of these hormones. The testicles may also atrophy in response to steroids. Eventually the testes will stop making testosterone and sperm, rendering the male infertile.

One of the more serious problems associated with abnormal gain of muscle mass is heart failure. While for most people gaining muscle and losing fat is desirable, a body builder is at risk of producing more muscle mass than the heart can handle. One pound of fat contains about 3.5 miles of blood vessels, but one pound of muscle has about 6.5 miles. Hence, additional muscle causes the heart to pump more blood. Some people that have too much muscle will be very strong but will not have a healthy aerobic endurance, in part because of the difficulty of providing oxygenated blood to so much tissue.

Sliding filament theory
This link shows the animation of the sliding filament theory.
explanation and image of sliding filament theory
this link gives a better demonstration of the theory with the explanation.

## Involuntary Muscle Movement

Spasms

When Smooth and skeletal muscles go through multiple spasms it is referred either as seizure or convulsion.

Cramps

Strenuous activities can cause painful spasms that are long, this is referred to as cramps.

## Injury

Sprain

An injury to a joint that involves a stretched or torn ligament.

Muscle Strain

A strain occurs when a muscle or the tendon that attaches it to the bone is overstretched or torn. Muscle strains are also called pulled muscles. Who gets it?

Anyone can strain a muscle. However, people involved in sports or other forms of strenuous exercise are more likely to strain a muscle. What causes it?

Muscles are bunches of fibers that can contract. Muscle strains usually occur during activities that require the muscle to tighten forcefully. The muscle is strained either because it is not properly stretched, or warmed up, before the activity; it is too weak; or because the muscle is already injured and not allowed time to recover. So, many muscle strains occur during exercise or sports activities. They can also occur when lifting heavy objects. What are the symptoms?

When a muscle is strained, it hurts and is difficult to move. You may also feel a burning sensation in the area of the injured muscle, or feel as though something has "popped." Sometimes the area of the strained muscle looks bruised or swells. A strained muscle might spasm, which means it contracts suddenly and involuntarily, causing severe pain. How is it diagnosed?

To diagnose a muscle strain, your doctor will examine the painful area, and ask how and when the injury happened. He or she may order other diagnostic tests, such as x-rays, to rule out any injury to the bone.

What is the treatment?

Muscle strains are treated with rest, ice, compression, and elevation, or RICE. You will be told to rest the injured area to reduce pain and swelling. If the strain is in the leg or foot area, you may need to use crutches. Ice packs are recommended at regular intervals (as recommended by your doctor) over the first few days after the injury. Ice causes the blood vessels to constrict, which reduces inflammation and pain. Anti-inflammatory medications might also be used to relieve pain. Compression and elevation help to reduce swelling. Your doctor may also recommend physical therapy to speed your recovery. You should avoid the type of activity that caused the injury until the muscle is completely healed. Self-care tips

You can prevent muscle strains by warming up for at least 10 minutes before participating in any strenuous exercise or heavy lifting. When you warm up, you increase the blood circulation to the muscle and prepare it for exercise. When starting any new exercise program or sport, it's important to begin gradually so your muscles are conditioned for the activity.

### Steroids

Anabolic steroids, which are synthetic versions of the primary male sex hormone testosterone, can be injected, taken orally, or used transdermally. These drugs are Controlled Substances that can be prescribed to treat conditions such as body wasting in patients with AIDS, and other diseases that occur when the body produces abnormally low amounts of testosterone. However, the doses prescribed to treat these medical conditions are 10 to 100 times lower than the doses that are used for performance enhancement.

Let me be clear:- while anabolic steroids can enhance certain types of performance or appearance,they are dangerous drugs, and when used inappropriately, they can cause a host of severe, long-lasting, and often irreversible negative health consequences. These drugs can stunt the height of growing adolescents, masculinize women, and alter sex characteristics of men. Anabolic steroids can lead to premature heart attacks, strokes, liver tumors, kidney failure and serious psychiatric problems. In addition, because steroids are often injected, users risk contracting or transmitting HIV or hepatitis.

Abuse of anabolic steroids differs from the abuse of other illicit substances because the initial use of anabolic steroids is not driven by the immediate euphoria that accompanies most drugs of abuse, such as cocaine, heroin, and marijuana, but by the desire of the user to change their appearance and performance, characteristics of great importance to adolescents. These effects of steroids can boost confidence and strength leading the user to overlook the potential serious long-term damage that these substances can cause.

Government agencies such as NIDA support research that increases our understanding of the impact of steroid use and improves our ability to prevent abuse of these drugs. For example, NIDA funding led to the development of two highly effective programs that not only prevent anabolic steroid abuse among male and female high school athletes, but also promote other healthy behaviors and attitudes. The ATLAS (targeting male athletes) and ATHENA (targeting female athletes) programs have been adopted by schools in 29 states and Puerto Rico. Both Congress and the Substance Abuse and Mental Health Services Administration have endorsed ATLAS and ATHENA as model prevention programs, which could and should be implemented in more communities throughout the country.

In addition to these prevention programs and other research efforts, also has invested in public education efforts to increase awareness about the dangers of steroid abuse. We have material on our website about steroid abuse at www.steroidabuse.gov and in April 2005 we again will distribute a "Game Plan" public service announcement designed to bring attention to abuse of anabolic steroids.

Research has shown that the inappropriate use of anabolic steroids can have catastrophic medical, psychiatric and behavioral consequences.

I hope that students, parents, teachers, coaches and others will take advantage of the information on our website about anabolic steroids abuse and join us in our prevention and education efforts. Participating in sports offers many benefits, but young people and adults shouldn't take unnecessary health risks in an effort to win.(Nora D. Volkow, M.D.)

-Human-made substances related to male sex hormones. Some athletes abuse anabolic steroids to enhance performance. Abuse of anabolic steroids can lead to serious health problems, some of which are irreversible.

Major side effects can include liver tumors and cancer, jaundice, high blood pressure, kidney tumors, severe acne, and trembling. In males, side effects may include shrinking of the testicles and breast development. In females, side effects may include growth of facial hair, menstrual changes, and deepened voice. In teenagers, growth may be halted prematurely and permanently.

The therapeutic use of steroids can be realized by patients and their doctors by using them in a manner that is beneficial to the person.

### MyoD and other muscular factors

MyoD is a protein and a transcription factor that activates muscle cell differentiation by turning on transcription of specific regulatory genes. It turns stem cells into myoblasts, a cell that can turn into many muscle cell, also called "muscle stem cell". MyoD belongs to a family of proteins knowns as myogenic regulatory factor(MRFs). MyoD can also turn on transcription of it's own regulatory genes (MyoD protein coding genes), and this means that it can produce more of itself. The positive feedback turns on transcription of other muscle proteins, cell cycle blockers, and microRNA-206. One of the main actions of MyoD is to remove cells from the cell cycle by enhancing the transcription of p21The function of MyoD is to commit mesoderm cells to a skeletal lineage. MyoD can also regulate muscle repair. One of the main actions of MyoD is to remove cells from the cell cycle by enhancing the transcription of p21. Bidirectional Signalling- muscle cells and nerves cells send signals back and forth to each other. Amyotrophic Lateral Sclerosis(ALS) is a loss of motor neuron and this blocks the formation of neuromuscular junctions. Therefore, no muscle growth which means a potential of leading to paralysis. Stephen Hawking suffers from this disease.

### Muscle Homeostasis

MicroRNA-206 indirectly forms neuromuscular junctions with motor neurons. Neuromuscular junction sends synaptic signals to MyoD and this blcoks MyoD and stops or limits muscle development. Myostatin is a protein that also blocks MyoD. Without myostatin, muscle development increases.

Myostatin Mutations In Sheep: they can have a mutant myostatin that causes microRNA-206 to block myostatin translation

Myostatin Mutations In Humans: humans with mutant myostatin will develop lots of muscle (like a body builder) is possible to create a drug that blocks myostatin production.

## Smooth Muscle Contraction

• Contractions are initiated by an influx of calcium which binds to calmodulin.
• The calcium-calmodulin complex binds to and activates myosin light-chain kinase.
• Myosin light-chain kinase phosphorylates myosin light-chains using ATP, causing them to interact with actin filaments.
• Powerstroke.
• Calcium is actively pumped out of the cell by receptor regulated channels. A second messanger, IP3, causes the release.
• As calcium is removed the calcium-calmodulin complex breaks away from the myosin light-chain kinase, stopping phosphorylation.
• Myosin phophatase dephosphorylates the myosin. If the myosin was bound to an actin molecule, the release is slow, this is called a latch state. In this manner, smooth muscle is able to stay contracted for some time without the use of much ATP. If the myosin was not bound to an actin chain it loses its affinity for actin.

It should be noted that ATP is still needed for crossbridge cycling, and that there is no reserve, such as creatine phosphate, available. Most ATP is created from aerobic metabolism, however anaerobic production may take place in times of low oxygen concentrations.

## Cardiac Muscle

Cardiac muscle is found in the heart and lungs of humans.

## ATP in the Human Body

Muscles cells, like all cells, use ATP as an energy source. The total quantity of ATP in the human body at any one time is about 0.1 Mole. The energy used by human cells requires the hydrolysis of 200 to 300 moles of ATP daily. This means that each ATP molecule is recycled 2000 to 3000 times during a single day. ATP cannot be stored, hence its consumption must closely follow its synthesis. On a per-hour basis, 1 kilogram of ATP is created, processed and then recycled in the body. Looking at it another way, a single cell uses about 10 million ATP molecules per second to meet its metabolic needs, and recycles all of its ATP molecules about every 20-30 seconds.

## Lactic Acid

Catabolized carbohydrates is known as glycolysis. The end product of glycolysis, pyruvate can go into different directions depending on aerobic or anaerobic conditions. In aerobic it goes through the Krebs cycle and in anaerobic it goes through the Cori cycle. In the Cori cycle pyruvate is converted to lactate, this forms lactic acid, lactic acid causes muscle fatigue. In the aerobic conditions pyruvate goes through the Krebs cycle. For more about Krebs cycle refer to chapter 2 Cell Physiology.

## Muscle Disorders

### Dermatomyositis and Polymyositis

Dermatomyositis and polymyositis cause inflammation of the muscles. They are rare disorders, affecting only about one in 100,000 people per year. More women than men are affected. Although the peak age of onset is in the 50s, the disorders can occur at any age.

Signs and symptoms — Patients complain of muscle weakness that usually worsens over several months, though in some cases symptoms come on suddenly. The affected muscles are close to the trunk (as opposed to in the wrists or feet), involving for example the hip, shoulder, or neck muscles. Muscles on both sides of the body are equally affected. In some cases, muscles are sore or tender. Some patients have involvement of the muscles of the pharynx (throat) or the esophagus (the tube leading from the throat to the stomach), causing problems with swallowing. In some cases, this leads to food being misdirected from the esophagus to the lungs, causing severe pneumonia.

In dermatomyositis, there is a rash, though sometimes the rash resolves before muscle problems occur. A number of different types of rash can occur, including rashes on the fingers, the chest and shoulders, or on the upper eyelids (show picture 1-3). In rare cases, the rash of dermatomyositis appears but myopathy never develops.

Other problems sometimes associated with these diseases include fever, weight loss, arthritis, cold-induced color changes in the fingers or toes (Raynaud phenomenon), and heart or lung problems.

### Muscle Atrophy

Alternative names : Atrophy of the muscles, Muscle wasting, Wasting

The majority of muscle atrophy in the general population results from disuse. People with sedentary jobs and senior citizens with decreased activity can lose muscle tone and develop significant atrophy. This type of atrophy is reversible with vigorous exercise. Bed-ridden people can undergo significant muscle wasting. Astronauts, free of the gravitational pull of Earth, can develop decreased muscle tone and loss of calcium from their bones following just a few days of weightlessness.

Muscle atrophy resulting from disease rather than disuse is generally one of two types, that resulting from damage to the nerves that supply the muscles, and disease of the muscle itself. Examples of diseases affecting the nerves that control muscles would be poliomyelitis, amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), and Guillain-Barre syndrome. Examples of diseases affecting primarily the muscles would include muscular dystrophy, myotonia congenita, and myotonic dystrophy as well as other congenital, inflammatory or metabolic myopathies.

Even minor muscle atrophy usually results in some loss of mobility or power.

Common Causes

• some atrophy that occurs normally with ageing
• cerebrovascular accident (stroke)
• spinal cord injury
• peripheral nerve injury (peripheral neuropathy)
• other injury
• prolonged immobilization
• osteoarthritis
• rheumatoid arthritis
• prolonged corticosteroid therapy
• diabetes (diabetic neuropathy)
• burns
• poliomyelitis
• amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease)
• Guillain-Barre syndrome
• muscular dystrophy
• myotonia congenita
• myotonic dystrophy
• myopathy

### Muscular Dystrophy

Muscular dystrophy (MD) is a group of rare inherited muscle diseases in which muscle fibers are unusually susceptible to damage. Muscles, primarily voluntary muscles, become progressively weaker. In the late stages of muscular dystrophy, muscle fibers are often replaced by fat and connective tissue. In some types of muscular dystrophy, heart muscles, other involuntary muscles and other organs are affected.

The most common types of muscular dystrophy appear to be due to a genetic deficiency of the muscle protein dystrophin. There's no cure for muscular dystrophy, but medications and therapy can slow the course of the disease.

## Medical Mysteries

#### Sleep Twitches

The twitching phenomenon that happens in the early stage of sleep is called a hypnagogic massive jerk, or simply a hypnic jerk. It has also been referred to as a sleep start. There has been little research on this topic, but there have been some theories put forth. When the body drifts off into sleep, it undergoes physiological changes related to body temperature, breathing rate and muscular tone. Hypnic jerks may be the result of muscle changes. Another theory suggests that the transition from the waking to the sleeping state signals the body to relax. But the brain may interpret the relaxation as a sign of falling and then signal the arms and legs to wake up. Electroencephalogram studies have shown sleep starts affect almost 10 percent of the population regularly, 80 percent occasionally, and another 10 percent rarely.

Muscle movement or twitching also may take place during the Rapid Eye Movement, or REM, phase of sleep. This also is the time when dreams occur. During the REM phase, all voluntary muscular activity stops with a drop in muscle tone, but some individuals may experience slight eyelid or ear twitching or slight jerks. Some people with REM behavioral disorder, or RBD, may experience more violent muscular twitching and full-fledged activity during sleep. This is because they do not achieve muscle paralysis, and as a result, act out their dreams. Researchers think that people with RBD lack neurological barriers that define the different stages of sleep. New research done by the Mayo Clinic and published in the July 2003 issue of Sleep Medicine shows that melatonin can help lessen RBD symptoms.

Resources:

Sleep twitches, or myoclonic jerks, as they are sometimes called, are explained in easily understood language on this website.
View information about various sleep disorders such as insomnia, apnea, and narcolepsy.

## Microbiology

Clostridium tetani
Tetanus
Normally a nerve impulse initiates contraction of a muscle. At the same time, an opposing muscle receives the signal to relax so as not to oppose the contraction. Tetanus toxin blocks the relaxation, so both sets of muscle contract. The usual cause of tetany is lack of calcium, but excess of phosphate (high phosphate-to-calcium ratio) can also trigger the spasms.
Clostridium botulinum
Infant botulism (floppy baby syndrome) the most common form of botulism in the U.S. of the four forms of botulism.
If ingested, the toxin is absorbed in the intestine, goes to the blood, and on to the nervous system. It acts on the peripheral nervous system by blocking the impulse that is normally passes along to the nervous system. By clocking the impulse that is normally passed along to motor end plates so the muscle contraction can be released, resulting in paralysis.

## Glossary

Actin
A protein that forms a long polymer rods called microfilaments; Interacts with myosin to cause movement in muscles.
ATP
"Adenosine Triphosphate" is a nucleotide that comes from adenosine that takes place in muscle tissue: This provides a large source of energy for cellular reactions.
Cardiac muscle
is also an "involuntary muscle" but it's a specialized kind of muscle found only within the heart.
Clostridium botulinum
A pathogen that causes botulism, gram stain positive, morphology is rod shaped, grows in anaerobic conditions, and produces spores.
Clostridium tetani
A pathogen that causes lock jaw, gram stain positive, morphology is tennis racket shaped rod, grows in anaerobic conditions, and produces spores.
Cori cycle
In anaerobic conditions produces lactic acid.
Cramp
A localized muscle spasm that happens after strenuous activity.
Glycogen
Glucose that has been converted for energy storage. Muscles store energy for their own use in this form.
Lactic acid
Causes muscle fatigue.
Muscle
Contractile tissue that is derived from the mesodermal layer of embryonic germ cells.
Muscular Dystrophy
A hereditary disease characterized by progressive atrophy of muscle fibers
Myosin
The fibrous motor protein that uses ATP to drive movements along actin filaments.
Sarcoplasmic Reticulum
Smooth-surfaced tubules forming a plexus around each myofibril that function as a storage and release area for calcium ions (CA+2).
Skeletal muscle
this "voluntary muscle" is anchored by tendons to the bone and is used to affect skeletal movement such as locomotion.
Smooth muscle
this "involuntary muscle" is found within the walls of organs and structures such as the esophagus, stomach, intestines, bronchi, uterus, ureters, bladder, and blood vessels.
Sprain
Injuries that involves a stretched or torn ligament.
Strain
A injury to the muscle or tendon attachment

charitin; a form of drug use to ensure muscle growth.

## References

• Van De Graaff (2002) Human Anatomy 6th ed. McGraw-Hill Higher Education
• Windmaier, P.W. Raff, H. Strang, T.S. (2004) Vander, Sherman, & Luciano's Human Physiology, the Mechanisms of Body Function 9th ed. Mcgraw-Hill

Neil A. Campbell , Jane B. Reece "Biology 8th edition"

# Blood Physiology

## Overview of Blood

The primary function of blood is to supply oxygen and nutrients as well as constitutional elements to tissues and to remove waste products. Blood also enables hormones and other substances to be transported between tissues and organs. Problems with blood composition or circulation can lead to downstream tissue malfunction. Blood is also involved in maintaining homeostasis by acting as a medium for transferring heat to the skin and by acting as a buffer system for bodily pH.

The blood is circulated through the lungs and body by the pumping action of the heart. The right ventricle pressurizes the blood to send it through the capillaries of the lungs, while the left ventricle re-pressurizes the blood to send it throughout the body. Pressure is essentially lost in the capillaries, hence gravity and especially the actions of skeletal muscles are needed to return the blood to the heart.

Blood circulation from the heart to the lungs.

### Gaseous Exchange

Oxygen (O2) is the most immediate need of every cell and is carried throughout the body by the blood circulation. Oxygen is used at the cellular level as the final electron acceptor in the electron transport chain (the primary method of generating ATP for cellular reactions). Oxygen is carried in the blood bound to hemoglobin molecules within red blood cells. Hemoglobin binds oxygen when passing through the alveoli of the lungs and releases oxygen in the warmer, more acidic environment of bodily tissues, via simple diffusion.

Carbon dioxide (CO2) is removed from tissues by blood and released into the air via the lungs. Carbon dioxide is produced by cells as they undergo the processes of cellular respiration (particularly the Kreb's Cycle). The molecules are produced from carbons that were originally part of glucose. Most of the carbon dioxide combines with water and is carried in the plasma as bicarbonate ions. An excess of carbon dioxide (through exercise, or from holding ones breath) quickly shifts the blood pH to being more acidic (acidosis). Chemoreceptors in the brain and major blood vessels detect this shift and stimulate the breathing center of the brain (the medulla oblongata). Hence, as CO2 levels build up and the blood becomes more acidic, we involuntarily breathe faster, thus lowering CO2 levels and stabilizing blood pH. In contrast, a person who is hyperventilating (such as during a panic attack) will expire more CO2 than being produced in the body and the blood will become too alkaline (alkalosis).

## Blood Composition

Blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). Anatomically, blood is considered a connective tissue, due to its origin in the bones and its function. Blood is the means and transport system of the body used in carrying elements (e.g. nutrition, waste, heat) from one location in the body to another, by way of blood vessels.

Blood is made of two parts:

1. Plasma which makes up 55% of blood volume.
2. Formed cellular elements (red and white blood cells, and platelets) which combine to make the remaining 45% of blood volume.

### Plasma makeup

Plasma is made up of 90% water, 7-8% soluble proteins (albumin maintains bloods osmotic integrity, others clot, etc), 1% carbon-dioxide, and 1% elements in transit. One percent of the plasma is salt, which helps with the pH of the blood. The largest group of solutes in plasma contains three important proteins to be discussed. There are: albumins, globulins, and clotting proteins.

Albumins are the most common group of proteins in plasma and consist of nearly two-thirds of them (60-80%). They are produced in the liver. The main function of albumins is to maintain the osmotic balance between the blood and tissue fluids and is called colloid osmotic pressure. In addition, albumins assist in transport of different materials, such as vitamins and certain molecules and drugs (e.g. bilirubin, fatty acids, and penicillin).

Globulins are a diverse group of proteins, designated into three groups: gamma, alpha, and beta. Their main function is to transport various substances in the blood. Gamma globulins assist the body's immune system in defense against infections and illness.

Clotting proteins are mainly produced in the liver as well. There are at least 12 substances, known as "clotting factors" that participate in the clotting process. One important clotting protein that is part of this group is fibrinogen, one of the main components in the formation of blood clots. In response to tissue damage, fibrinogen makes fibrin threads, which serve as adhesive in binding platelets, red blood cells, and other molecules together, to stop the blood flow. (This will be discussed in more detail later on in the chapter.)

Plasma also carries Respiratory gases; CO2 in large amounts(about 97%) and O2 in small amounts(about 3%), various nutrients(glucose, fats), wastes of metabolic exchange(urea, ammonia), hormones, and vitamins.

Picture of red blood cells.

### Red Blood Cells

#### Overview

Red blood cell (erythrocyte) also known as "RBCs". RBCs are formed in the myeloid tissue or most commonly known as red bone marrow, although when the body is under severe conditions the yellow bone marrow, which is also in the fatty places of the marrow in the body will also make RBCs. The formation of RBCs is called erythropoiesis ( erythro / red; poiesis / formation). Red blood cells lose nuclei upon maturation, and take on a biconcave, dimpled, shape. They are about 7-8 micrometers in diameter. There are about 1000x more red blood cells than white blood cells. RBCs live about 120 days and do not self repair. RBCs contain hemoglobin which transports oxygen from the lungs to the rest of the body, such as to the muscles, where it releases the oxygen load.The hemoglobin gets its red color from their respiratory pigments.

Shape

RBCS have a shape of a disk that appears to be “caved in” or almost flattened in the middle; this is called bi-concave. This bi-concave shape allows the RBC to carry oxygen and pass through even the smallest capillaries in the lungs. This shape also allows RBCs to stack like dinner plates and bend as they flow smoothly through the narrow blood vessels in the body. RBCs lack a nucleus (no DNA) and no organelles, meaning that these cells cannot divide or replicate themselves like the cells in our skin and muscles. RBCs have a short life span of about 120 days, however, as long as our myeloid tissue is working correctly, we will produce about 2-3 million RBCs per second. That is about 200 billion a day! This allows us to have more to replace the ones we lose.

Main Component

The main component of the RBC is hemoglobin protein, of which there are about 250 million per cell. The word hemoglobin comes from "hemo" meaning blood and "globin" meaning protein. Hemoglobin is composed of four protein subunits: polypeptide globin chains that contain anywhere from 141 to 146 amino acids. Hemoglobin is responsible for the cell’s ability to transport oxygen and carbon dioxide. Hemoglobin, iron, and oxygen interact with each other, forming the RBCs' bright red color. You can call this interaction by product oxyhemoglobin. Carbon Monoxide binds with hemoglobin faster than oxygen, and stays bound for several hours, making hemoglobin temporarily unavailable for oxygen transport. One red blood cell contains about 200 million hemoglobin molecules. If all this hemoglobin was in the plasma rather than inside the cells, blood would be so "thick" that the heart would have a difficult time pumping it through. The thickness of blood is called viscosity. The greater the viscosity of blood, the more friction there is, and more pressure is needed to force blood through.

#### Functions

The main function is the transportation of oxygen throughout the body and the ability of the blood to carry out carbon dioxide which is called carbamino – hemoglobin. Maintaining the balance of blood is important. The balance can be measured by the acid and base levels in the blood. This is called pH. Normal pH of blood ranges between 7.35-7.45; this normal blood is called Alkaline (less acidic then water). A drop in pH is called Acidic. This condition is also called Acidosis. A jump in pH higher then 7.45 is called "Alkalosis". To maintain the homeostasis (or balance,) the blood has tiny molecules within the RBC that help prevent drops or increases from happening.

From left to right diagram of Erythrocyte, Thrombocyte, and Leukocyte

Destruction

Red blood cells are broken down and hemoglobin is released. The globin part of the hemoglobin is broken down into amino acid components, which in turn are recycled by the body. The iron is recovered and returned to the bone marrow to be reused. The heme portion of the molecule experiences a chemical change and then gets excreted as bile pigment (bilirubin) by the liver. Heme portion after being broken down contributes to the color of feces and your skin color changing after being bruised.

### White Blood Cells

Shape

White blood cells are different from red cells in the fact that they are usually larger in size 10-14 micrometers in diameter. White blood cells do not contain hemoglobin which in turn makes them translucent. Many times in diagrams or pictures white blood cells are represented in a blue color, mainly because blue is the color of the stain used to see the cells. White blood cells also have nucleii, that are some what segmented and are surrounded by electrons inside the membrane.

#### Functions

White blood cells (leukocytes) are also known as "WBC's". White blood cells are made in the bone marrow but they also divide in the blood and lymphatic systems. They are commonly amoeboid (cells that move or feed by means of temporary projections, called pseudopods (false feet), and escape the circulatory system through the capillary beds. The different types of WBC's are Basophils, Eosinophils, Neutrophils, Monocytes, B- and T-cell lymphocytes. Neutrophils, Eosinophils, and Basophils are all granular leukocytes. Lymphocytes and Monocytes are agranular leukocytes. Basophils store and synthesize histamine which is important in allergic reactions. They enter the tissues and become "mast cells" which help blood flow to injured tissues by the release of histamine. Eosinophils are chemotoxic and kill parasites. Neutrophils are the first to act when there is an infection and are also the most abundant white blood cells. Neutrophils fight bacteria and viruses by phagocytosis which mean they engulf pathogens that may cause infection. The life span of a of Neutrophil is only about 12-48 hours. Monocytes are the biggest of the white blood cells and are responsible for rallying the cells to defend the body. Monocytes carry out phagocytosis and are also called macrophages. Lymphocytes help with our immune response. There are two Lymphocytes: the B- and T- cell. B-Lymphocytes produce antibodies that find and mark pathogens for destruction. T-Lymphocytes kill anything that they deem abnormal to the body.

WBCs are classified by phenotype which can be identified by looking at the WBCs under a microscope. The Granular phenotype are able to stain blue. The Agranular phenotype are able to stain red. Neutrophils make up 50-70% of Granular cells Eosinophils make up 2-4%, and Basophils 0-1%. Monocytes make up 2-8% of Agranular cells. B and T Lymphocytes make up 20-30%. As you can see, there is a great deal of differentiation between WBCs. These special cells help our bodies defend themselves against pathogens. Not only do they help our immune system but they remove toxins, wastes, and abnormal or damaged cells. Thus, we can say that WBCs' main function is being Phagocytic which means to engulf or swallow cells.

### Platelets

A 250 ml bag of newly collected platelets.

Platelets, also called thrombocytes, are membrane-bound cell fragments. Platelets have no nucleus, they are between one to two micrometers in diameter, and are about 1/10th to 1/20th as abundant as white blood cells. Less than 1% of whole blood consists of platelets. They result from fragmentation of large cells called Megakaryocytes - which are cells derived from stem cells in the bone marrow. Platelets are produced at a rate of 200 billion per day. Their production is regulated by the hormone called Thrombopoietin. The circulating life of a platelet is 8–10 days. The sticky surface of the platelets allow them to accumulate at the site of broken blood vessels to form a clot. This aids in the process of hemostasis ("blood stopping"). Platelets secrete factors that increase local platelet aggregation (e.g., Thromboxane A), enhance vasoconstriction (e.g., Serotonin), and promote blood coagulation (e.g., Thromboplastin).

## Hemostasis (Coagulation or Clotting)

Hemostasis is the natural process of stopping blood flow or loss of blood following an injury. (hemo = blood; stasis = standing). It has three stages: (1) vascular spasm, vasoconstriction, or intense contraction of blood vessels, (2) formation of a platelet plug and (3) blood clotting or coagulation. Once the flow of blood has been stopped, tissue repair can begin.

Vascular spasm or Vasoconsriction: In a normal individual, immediately after a blood vessel has been cut and endothelial cells are damaged, vasoconstriction occurs, thus slowing blood flow to the area. Smooth muscle in the vessel wall goes through spasms or intense contractions that constrict the vessel. If the vessels are small, spasms compress the inner walls together and may be able to stop the bleeding completely. If the vessels are medium to large-sized, the spasms slow down immediate outflow of blood, lessening the damage but still preparing the vessel for the later steps of hemostasis. These vascular spasms usually last for about 30 minutes, long enough for the next two stages of hemostasis to take place.

Formation of a Platelet Plug: Within 20 seconds of an injury, coagulation is initiated. Contrary to popular belief, clotting of a cut on the skin is not initiated by air or drying out, but by platelets adhering to and activated by collagen in the blood vessels endothelium. The activated platelets then release the contents of their granules, which contain a variety of substances that stimulate further platelet activation and enhance the hemostatic process.

When the lining of a blood vessel breaks and endothelial cells are damaged, revealing collagen proteins in the vessel wall, platelets swell, grow spiky extensions, and start clumping together. They start to stick to each other and the walls of the vessel. This continues as more platelets congregate and undergo these same transformations. This process results in a platelet plug that seals the injured area. If the injury is small, a platelet plug may be able to form and close it within several seconds. If the damage is more serious, the next step of blood clotting will take place. Platelets contain secretory granules. When they stick to the proteins in the vessel walls, they degranulate, thus releasing their products, which include ADP (adenosine diphosphate), serotonin, and thromboxane A2.

A Blood Clot Forms: If the platelet plug is not enough to stop the bleeding, the third stage of hemostasis begins: the formation of a blood clot. First, blood changes from a liquid to a gel. At least 12 substances called clotting factors take part in a series of chemical reactions that eventually create a mesh of protein fibers within the blood. Each of the clotting factors has a very specific function. We will discuss just three of the substances here: prothrombin, thrombin, and fibrin. Prothrombin and fibrinogen are proteins that are produced and deposited in the blood by the liver.

• Prothrombin: When blood vessels are damaged, vessels and nearby platelets are stimulated to release a substance called prothrombin activator, which in turn activates the conversion of prothrombin, a plasma protein, into an enzyme called thrombin. This reaction requires calcium ions.
• Thrombin: Thrombin facilitates the conversion of a soluble plasma protein called fibrinogen into long insoluble fibers or threads of the protein fibrin.
• Fibrin: Fibrinogen is cleaved by thrombin to form its active form, "fibrin." Fibrin threads wind around the platelet plug at the damaged area of the blood vessel, forming an interlocking network of fibers and a framework for the clot. This net of fibers traps and helps hold platelets, blood cells and other molecules tight to the site of injury, functioning as the initial clot. This temporary fibrin clot can form in less than a minute, and usually does a good job of reducing the blood flow. Next, platelets in the clot begin to shrink, tightening the clot and drawing together the vessel walls. Usually, this whole process of clot formation and tightening takes less than a half hour.

The use of adsorbent chemicals, such as zeolites, and other hemostatic agents, are also being explored for use in sealing severe injuries quickly.

## ABO Group System

The ABO blood group is represented by substances on the surface of red blood cells (RBCs). These substances are important because they contain specific sequences of amino acid and carbohydrates which are antigenic. As well as being on the surface of RBCs, some of these antigens are also present on the cells of other tissues. A complete blood type describes the set of 29 substances on the surface of RBCs, and an individual's blood type is one of the many possible combinations of blood group antigens. Usually only the ABO blood group system and the presence or absence of the Rhesus D antigen (also known as the Rhesus factor or RH factor) are determined and used to describe the blood type. Over 400 different blood group antigens have been found, many of these being very rare. If an individual is exposed to a blood group antigen that is not recognized as self, the individual can become sensitized to that antigen; the immune system makes specific antibodies which binds specifically to a particular blood group antigen and an immunological memory against that particular antigen is formed. These antibodies can bind to antigens on the surface of transfused red blood cells (or other tissue cells) often leading to destruction of the cells by recruitment of other components of the immune system. Knowledge of a individual's blood type is important to identify appropriate blood for transfusion or tissue for organ transplantation.

### Surface Antigens

Several different RBC surface antigens stemming from one allele (or very closely linked genes) are collectively labeled as a blood group system (or blood group). The two most important blood group systems were discovered during early experiments with blood transfusion, the ABO group in 1901 and the Rhesus group in 1937 . These two blood groups are reflected in the common nomenclature A positive, O negative, etc. with letters referring to the ABO group and positive/negative to the presence/absence of the RhD antigen of the Rhesus group. Development of the Coombs test in 1945 and the advent of transfusion medicine led to discovery of more blood groups.

Compatibility of blood types

Blood group AB individuals have both A and B antigens on the surface of their RBCs, and their blood serum does not contain any antibodies against either A or B antigen. Therefore, a individual with type AB blood can receive blood from any group (with AB being preferable), but can only donate blood to another group AB individual. AB blood is also known as "universal receiver".

Blood group A individuals have the A antigen on the surface of their RBCs, and blood serum containing IgM antibodies against the B antigen. Therefore, a group A individual can only receive blood from individuals of groups A or O (with A being preferable), and can donate blood to individuals of groups A or AB.

Blood group B individuals have the B antigen on their surface of their RBCs, and blood serum containing IgM antibodies against the A antigen. Therefore, a group B individual can only receive blood from individuals of groups B or O (with B being preferable), and can donate blood to individuals of groups B or AB.

Blood group O individuals do not have either A or B antigens on the surface of their RBCs, but their blood serum contains IgM antibodies against both A and B antigens. Therefore, a group O individual can only receive blood from a group O individual, but they can donate blood to individuals of any ABO blood group (ie A, B, O or AB). O blood is also known as "universal donor".

### Inheritance

Blood types are inherited and represent contributions from both parents. The ABO blood type is controlled by a single gene with three alleles: i, IA, and IB. The gene encodes an enzyme that modifies the carbohydrate content of the red blood cell antigens.

IA gives type A, IB gives type B, i give types O

Mother/Father O A B AB Blood group inheritance O O O, A O, B A, B A O, A O, A O, A, B, AB A, B, AB B O, B O, A, B, AB O, B A, B, AB AB A, B A, B, AB A, B, AB A, B, AB

IA and IB are dominant over i, so ii people have type O, IAIA or IAi have A, and IBIB or IBi have type B. IAIB people have both phenotypes because A and B are codominant, which means that type A and B parents can have an AB child. Thus, it is extremely unlikely for a type AB parent to have a type O child (it is not, however, direct proof of illegitimacy): the cis-AB phenotype has a single enzyme that creates both A and B antigens. The resulting red blood cells do not usually express A or B antigen at the same level that would be expected on common group A or B red blood cells, which can help solve the problem of an apparently genetically impossible blood group.

Rh Factor

Many people have the Rh Factor on the red blood cell. Rh carriers do not have the antibodies for the Rh Factor, but can make them if exposed to Rh. Most commonly Rh is seen when anti-Rh antibodies cross from the mothers placenta into the child before birth. The Rh Factor enters the child destroying the child's red blood cells. This is called Hemolytic Disease.

### Compatibility in Blood/Plasma Transfusions

Blood transfusions between donor and recipient of incompatible blood types can cause severe acute immunological reactions, hemolysis (RBCT destruction), renal failure, shock, and sometimes death. Antibodies can be highly active and can attack RBCs and bind components of the complement system to cause massive hemolysis of the transfused blood.

A patient should ideally receive their own blood or type-specific blood products to minimize the chance of a transfusion reaction. If time allows, the risk will further be reduced by cross-matching blood, in addition to blood typing both recipient and donor. Cross-matching involves mixing a sample of the recipient's blood with a sample of the donor's blood and checking to see if the mixture agglutinates, or forms clumps. Blood bank technicians usually check for agglutination with a microscope, and if it occurs, that particular donor's blood cannot be transfused to that particular recipient. Blood transfusion is a potentially risky medical procedure and it is vital that all blood specimens are correctly identified, so in cross-matching labeling is standardized using a barcode system known as ISBT 128.

Plasma compatibility table
Donor Recipient
O A B AB
O OK OK OK OK
A OK OK
B OK OK
AB OK

When considering a plasma transfusion, keep in mind that plasma carries antibodies and no antigens. For example you can't give type O plasma to a type A, B or AB, because a person with type O blood has A and B antibodies and the recipient would have an immune response. On the other hand an AB donor could give plasma to anyone, since they have no antibodies.

The table to the right is for plasma transfusions, and it's just the opposite for RBC transfusions. It doesn't take the Rh factor into effect, though, because most people don't have antibodies for the Rhesus factor (it only happens upon exposure).

#### Hemolytic Disease of the Newborn

Often a pregnant woman carries a fetus with a different blood type to herself, and sometimes the mother forms antibodies against the red blood cells of the fetus, leading to low fetal blood counts, a condition known as hemolytic disease of the newborn.

Hemolytic disease of the newborn, (also known as HDN) is an alloimmune condition that develops in a fetus when the IgG antibodies produced by the mother and passing through the placenta include ones which attack the red blood cells in the fetal circulation. The red cells are broken down and the fetus can develop reticulocytosis and anemia. The fetal disease ranges from mild to very severe and fetal death from heart failure - hydrops fetalis - can occur. When the disease is moderate or severe many erythroblasts are present in the fetal blood and so these forms of the disease can be called erythroblastosis fetalis.

Before birth, options for treatment include intrauterine transfusion or early induction of labor when pulmonary maturity has been attained, fetal distress is present, or 35 to 37 weeks of gestation have passed. The mother may also undergo plasma exchange to reduce the circulating levels of antibody by as much as 75%.

After birth, treatment depends on the severity of the condition, but could include temperature stabilization and monitoring, phototherapy, transfusion with compatible packed red blood, exchange transfusion with a blood type compatible with both the infant and the mother, sodium bicarbonate for correction of acidosis and/or assisted ventilation.

Rh negative mothers who have had a pregnancy with or are pregnant with a Rh positive infant, are given Rh immune globulin (RhIG) also known as Rhogam, during pregnancy and after delivery to prevent sensitization to the D antigen. It works by binding any fetal red cells with the D antigen before the mother is able to produce an immune response and form anti-D IgG. A drawback to pre-partum administration of RhIG is that it causes a positive antibody screen when the mother is tested which is indistinguishable from immune reasons for antibody production.

## Diseases of the Blood

### Von Willebrand Disease

The most common inherited bleeding disorder, von Willebrand disease affects both men and women equally. Von Willebrand disease is similar to hemophilia in that it involves a definciency in the ability of blood to clot properly. Those affect by von Willebrand disease will have one or more of the following- low levels of von Willebrand factor (a protein that helps the blood to clot), and/or their von Willebrand factor doesn't work properly. While it is mostly an inherited disease (with factors contributed by both parents), von Willebrand disease may be an aquired syndrome in rare cases.

There are three types of von Willebrand disease: Type 1, which is the mildest and most common form of the disease; Type 2, which has four subtypes (2A, 2B, 2M, and 2N) and ranges from mild to moderate in severity; and finally, Type 3, which is very rare and is the most severe form.

Type 1

In type 1 von Willebrand disease, there is a low level of von Willebrand factor. The level of factor VIII may also be lower than normal. This is the mildest and most common form of the disease. About 3 out of 4 people diagnosed with von Willebrand disease have type 1.

Type 2

In type 2 von Willebrand disease, a defect in von Willebrand factor causes it to not work properly. Type 2 is divided into 2A, 2B, 2M, and 2N. Each is treated differently, so knowing the exact type is important.

People with type 1 and type 2 von Willebrand disease may have the following mild-to-moderate bleeding symptoms: easy bruising, nosebleeds, bleeding from the gums after a dental procedure, heavy menstrual bleeding in women, blood in their stools or urine (from bleeding in the intestines, stomach, kidneys or bladder), excessive bleeding after a cut or other accident or surgery.

Type 3

People with type 3 von Willebrand disease usually have no von Willebrand factor and very low factor VIII. Type 3 is severe and very rare.

Symptoms of type 3 von Willebrand disease might include any of the symptoms of types 1 and 2, and also include severe bleeding episodes for no reason, which can be life threatening if not treated immediately. Bleeding into soft tissues or joints (hemarthrosis), causing severe pain and swelling, is another symptom.

Treatment

Many people with von Willebrand disease do not require treatment to manage the disease. However, if treatment is ncessary, it may include a range of different interventions depending on the severity. These involve medicine to increase the level of von Willebrand factor in the blood (DDAVP), medicine to prevent the breakdown of clots (called antifibrinolytic drugs), medicine to control heavy menstrual bleeding in women (often birth control pills), or injection of clotting factor concentrates (containing von Willebrand factor and factor VIII).

### Disseminated Intravascular Coagulation

Disseminated intravascular coagulation (DIC), also called consumptive coagulopathy, is a pathological process in the body where the blood starts to coagulate throughout the whole body. This depletes the body of its platelets and coagulation factors, and there is a paradoxically increased risk of hemorrhage. It occurs in critically ill patients, especially those with Gram-negative sepsis (particularly meningococcal sepsis) and acute promyelocytic leukemia.

### Hemophilia

Hemophilia is a disease where there is low or no blood protein, causing an inability to produce blood clots. There are two types of Hemophilia: Type A, which is a deficiency in factor VIII and Type B, (Christmas disease) a deficiency on factor IX. Because people with hemophilia have an impaired ability to make blood clots, even a little cut may take hours or days to fully clot, and a small bump or jar to the body could cause severe bruising that doesn't heal for months. Internal muscle bleeds are the most common symptom though, causing swelling and varying degrees of pain.

Hemophilia is passed down from mothers to their sons. Hemophilia is sometimes known as the "Royal Disease". This is because Queen Victoria, Queen of England (1837-1901), was a carrier of hemophilia. The hemophilia disease was passed down to her son Leopold who ended up dying at age 31. Queen Victoria also had two daughters who were carriers. These daughters passed hemophilia into the Spanish, German, and Russian royal families. One of the most famous stories is that of the Russian royal family. Alexandra, granddaughter to Queen Victoria, married Nicholas (Tsar of Russia in the 1900s). Alexandra was a carrier of the disease and passed the disease to their first son, Tsarevich Alexi, who was heir to the throne of Russia. The family tried to keep their son's secret from the people, but Alexi suffered with serious bruises and extreme pain. The family found help from a monk named Rasputin. He kept their secret and gained a great deal of power over the family, making them think he was their only hope. During this time of great turmoil in Russia, Nicholas and Alexandra spent most of their attentions on their son, and not on the people. It wasn't long before the Bolshevik Revolution of 1917 began.

### Factor V Leiden

The opposite of Hemophilia, Factor V Leiden is the name given to a variant of human factor V that causes a hypercoagulability disorder. In this disorder the Leiden variant of factor V, cannot be inactivated by activated protein C. Factor V Leiden is the most common hereditary hypercoagulability disorder amongst Eurasians. It is named after the city Leiden (The Netherlands), where it was first identified in 1994 by Prof R. Bertina et al. Those that have it are at a slightly higher risk of developing blood clots than those without. Those that test positive for factor V should avoid (oral contraceptives, obesity, smoking, and high blood pressure.)

### Anemia

Anemia (AmE) or anaemia (BrE), from the Greek (Ἀναιμία) meaning "without blood", refers to a deficiency of red blood cells (RBCs) and/or hemoglobin. This results in a reduced ability of blood to transfer oxygen to the tissues, causing hypoxia. Since all human cells depend on oxygen for survival, varying degrees of anemia can have a wide range of clinical consequences. Hemoglobin (the oxygen-carrying protein in the red blood cells) has to be present to ensure adequate oxygenation of all body tissues and organs.

The three main classes of anemia include excessive blood loss (acutely such as a hemorrhage or chronically through low-volume loss), excessive blood cell destruction (hemolysis) or deficient red blood cell production (ineffective hematopoiesis). In menstruating women, dietary iron deficiency is a common cause of deficient red blood cell production.

### Sickle cell

Image of RBC's with Sickle Cell mutations.

Sickle-cell disease is a general term for a group of genetic disorders caused by sickle hemoglobin (Hgb S or Hb S). In many forms of the disease, the red blood cells change shape upon deoxygenation because of polymerization of the abnormal sickle hemoglobin. This process damages the red blood cell membrane, and can cause the cells to become stuck in blood vessels. This deprives the downstream tissues of oxygen and causes ischemia and infarction. The disease is chronic and lifelong. Individuals are most often well, but their lives are punctuated by periodic painful attacks. In addition to periodic pain, there may be damage of internal organs, and/or stroke. Lifespan is often shortened with sufferers living to an average of 40 years. It is common in people from parts of the world where malaria is or was common, especially in sub-Saharan Africa or in descendants of those peoples.

Genetics: Sickle-cell disease is inherited in the autosomal recessive pattern, depicted above. The allele responsible for sickle cell anemia is autosomal recessive. A person who receives the defective gene from both father and mother develops the disease; a person who receives one defective and one healthy allele remains healthy, but can pass on the disease and is known as a carrier. If two parents who are carriers have a child, there is a 1-in-4 chance of their child developing the illness and a 1-in-2 chance of their child just being a carrier.

### Polycythemia

Polycythemia is a condition in which there is a net increase in the total circulating erythrocyte (red blood cell) mass of the body. There are several types of polycythemia.

Primary Polycythemia

In primary polycythemia, there may be 8 to 9 million and occasionally 11 million erythrocytes per cubic millimeter of blood (a normal range for adults is 4-5 million), and the hematocrit may be as high as 70 to 80%. In addition, the total blood volume can increase to as much as twice as normal. The entire vascular system can become markedly engorged with blood, and circulation times for blood throughout the body can increase up to twice the normal value. The increased numbers of erythrocytes can increase of the viscosity of the blood to as much as five times normal. Capillaries can become plugged by the very viscous blood, and the flow of blood through the vessels tends to be extremely sluggish.

As a consequence of the above, people with untreated Polycythemia are at a risk of various thrombotic events (deep venous thrombosis, pulmonary embolism), heart attack and stroke, and have a substantial risk of Budd-Chiari syndrome (hepatic vein thrombosis). The condition is considered chronic; no cure exists. Symptomatic treatment (see below) can normalize the blood count and most patients can live a normal life for years.

Secondary polycythemia

Secondary polycythemia is caused by either appropriate or inappropriate increases in the production of erythropoietin that result in an increased production of erythrocytes. In secondary polycythemia, there may be 6 to 8 million and occasionally 9 million erythrocytes per cubic millimeter of blood. A type of secondary polycythemia in which the production of erythropoietin increases appropriately is called physiologic polycythemia. Physiologic polycythemia occurs in individuals living at high altitudes (4275 to 5200 meters), where oxygen availability is less than at sea level. Many athletes train at higher altitudes to take advantage of this effect — a legal form of blood doping. Actual polychthemia sufferers have been known to use their condition as an athletic advantage for greater stamina.

Other causes of secondary polycythemia include smoking, renal or liver tumors, or heart or lung diseases that result in hypoxia. Endocrine abnormalities, prominently including pheochromocytoma and adrenal adenoma with Cushing's Syndrome, are also secondary causes. Athletes and bodybuilders who abuse anabolic steroids or erythropoietin may develop secondary polycythemia.

Relative polycythemia

Relative polycythemia is an apparent rise of the erythrocyte level in the blood; however, the underlying cause is reduced blood plasma. Relative polycythemia is often caused by fluid loss i.e. burns, dehydration and stress polycythemia.

### Leukemia

Leukemia is a cancer of the blood or bone marrow characterized by an abnormal proliferation of blood cells, usually white blood cells (leukocytes). It is part of the broad group of diseases called hematological neoplasms. Damage to the bone marrow, by way of displacing the normal marrow cells with increasing numbers of malignant cells, results in a lack of blood platelets, which are important in the blood clotting process. This means people with leukemia may become bruised, bleed excessively, or develop pin-prick bleeds (petechiae).

White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional, putting the patient at the risk of developing infections. The red blood cell deficiency leads to anaemia, which may cause dyspnea. All symptoms may also be attributable to other diseases; for diagnosis, blood tests and a bone marrow biopsy are required.

## Glossary

Albumin: a major blood protein responsible for the maintenance of osmotic (water) pressure in the blood

Anemia: a deficiency of red blood cells or hemoglobin caused by lack of iron, folic acid or vitamin B12 in the diet, or by red blood cell destruction; associated with decreased ability of blood to carry oxygen

B-Cell: cell responsible for the distribution of antibodies

Basophil: this white blood cell enters damaged tissues and releases a histamine and other chemicals that promote inflammation in the body to fight pathogens

Blood: the means and transport system of the body used in carrying elements - nutrition, waste, heat - from one location in the body to another by way of blood vessels

Eosinophil: white blood cell that is involved in the immune response against parasitic worms (such as tapeworms and roundworms). Named because it stains with the red dye "eosin."

Factor V Leiden most common genetic hypercoagulability disorder.

Formed Elements: the red blood cells, white blood cells and platelets found in blood

Hematocrit: measurement of the % of red blood cells found in blood

Hemoglobin (Hb): iron-containing pigment in red blood cells that combines with and transports oxygen

Hemophilia: genetic disorder in which the affected individual may have uncontrollable bleeding; blood does not clot

Hemostasis: the process by which blood flow is stopped; also describes the clotting of blood

Lymphocytes: cells of the Lymphatic system, provide defense against specific pathogen or toxins

Monocytes: The largest white blood cell. Becomes a macrophage when activated. Engulfs pathogens and debris through phagocytosis, also involved in presenting antigens to B and T lymphocytes.

Neutrophils: the most common white blood cell; they are phagocytic and engulf pathogens or debris in the tissues; also release cytotoxic enzymes and chemicals to kill pathogens

NK-Cells: also known as "Natural Killer Cells", these T lymphocytes are responsible for surveillance and detection of abnormal tissue cells; important in preventing cancer

Phagocytosis: process by which amoeboid-like cells engulf and ingest, and thereby destroy, foreign matter or material

T-Cell: cells that mediate by coordinating the immune system and enter the peripheral tissues. They can attack foreign cells directly and control the activities of other lymphocytes ,

## Review Questions

Answers for these questions can be found here

1.Taking aspirin every day can reduce the risk of heart disease because:

A) it is a powerful vasodilator
B) it blocks pain receptors in heart tissue
C) it stops ventricular fibrillation
D) it loosens plaque on arterial walls
E) it prevents platelet clumping

2. A hematocrit measures percentage of:

A) White blood cells
B) Plasma
C) Platelets
D) Red blood cells

3. Fred's blood type is O- and Ginger's is B+. Fred and Ginger have a son who is AB+. What do you conclude?

A) If they have a second child Ginger needs to have RhoGam shot
B) There is no risk to a second child, unless it has a negative blood type
C) If the child needs a blood transfusion Fred could provide it safely, but not Ginger
D) Fred is not the boy’s father

4. Which blood component plays the largest role in maintaining the osmotic pressure of blood?

A) albumin
B) carbon dioxide
C) white blood cells
D) fibrinogen
E) globulins

5. If you hold your breath for one minute

A) The kidneys will increase sodium ion reabsorption
B) Hydrogen-ion concentration in the blood will increase
C) Your heart rate will greatly slow
D) Hemoglobin will bind to oxygen more strongly

6. Most of the carbon dioxide produced by tissues is transported to the lungs as:

A) Small gas bubbles in the plasma
B) Gas bound to hemoglobin in the red blood cells
C) Bicarbonate ions in the plasma
D) Gas bound to white blood cells and albumin
E) Gas transported through the lymphatic system

7. To prevent blood loss after a tissue injury, blood vessels first

A) Form a platelet plug
B) Form a clot
D) Constrict and form barriers

8. You take a blood sample from a male cyclist at the end of a long race. The hematocrit is 60%. The most likely conclusion is:

A) This is within normal range for most adult males
B) This cyclist is anemic
C) This low of a hematocrit could indicate liver damage or leukemia
D) The cyclist is dehydrated
E) The cyclist has been taking pharmaceutical erythropoietin

9. In a normal blood sample, which of the following cells will be the most abundant?

A) Neutrophils
B) Basophils
C) Eosinophils
D) Monocytes
E) Lymphocytes

10. A bag of donated blood does not clot because

A) There is not enough oxygen
B) It cannot dry out
C) It is kept refrigerated
D) There is no free calcium
E) All of the above

11. What is the primary function of bood?

A) Supply nutrients to tissues
B) Remove waste products
C) To keep your body at one consistent temperature
D) A and B
E) B and C

12. What is the main component of the Red blood cell?

A) Albumin
B) Globulins
C) Hemoglobin
D) Nucleus

# The Cardiovascular System

Model of a human heart

## Introduction

The heart is the life-giving, ever-beating muscle in your chest. From inside the womb until death, the thump goes on. The heart for the average human will contract about 3 billion times; never resting, never stopping to take a break except for a fraction of a second between beats. At 80 years of age, a person's heart will continue to beat an average of 100,000 times a day. Many believe that the heart is the first organ to become functional. Within weeks of conception the heart starts its mission of supplying the body with nutrients even though the embryo is no bigger than a capital letter on this page. The primary function of the heart is to pump blood through the arteries, capillaries, and veins. There are an estimated 60,000 miles of vessels throughout an adult body. Blood transports oxygen, nutrients, disease causing viruses, bacteria, hormones and has other important functions as well. The heart is the pump that keeps blood circulating properly. Americans today have many options to take care of their heart and circulatory system. Expanding medical technology has made it much easier to do so. This chapter is dedicated to the heart and its many parts.

## The Heart

The heart is a hollow, muscular organ about the size of a fist. It is responsible for pumping blood through the blood vessels by repeated, rhythmic contractions. The heart is composed of cardiac muscle, an involuntary muscle tissue that is found only within this organ. The term "cardiac" (as in cardiology) means "related to the heart” and comes from the Greek word kardia, for "heart." It has a four-chambered, double pump and is located in the thoracic cavity between the lungs. The cardiac muscle is self-exciting, meaning it has its own conduction system. This is in contrast with skeletal muscle, which requires either conscious or reflex nervous stimuli. The heart's rhythmic contractions occur spontaneously, although the frequency or heart rate can be changed by nervous or hormonal influence such as exercise or the perception of danger.

### Endocardium

The endocardium is the innermost lining of the heart which consists of the endothelial cells forming a smooth membrane in places, and a pocked and tribeculated surface in others (mainly the ventricles, or lower pumping chambers).

### Myocardium

The myocardium is the muscular tissue of the heart. The myocardium is composed of specialized cardiac muscle cells with an ability not possessed by muscle tissue elsewhere in the body. Cardiac muscle, like other muscles, can contract, but it can also conduct electricity, like nerves. The blood to the myocardium is supplied by the coronary arteries. If these arteries are occluded by atherosclerosis and/or thrombosis, this can lead to angina pectoris or myocardial infarction due to ischemia (lack of oxygen). Failure of the heart to contract properly (for various reasons) is termed heart failure, generally leading to fluid retention, edema, pulmonary edema, renal insufficiency, hepatomegaly, a shortened life expectancy and decreased quality of life.

### Epicardium

The outer most layer next to the myocardium is known as the Epicardium. This is the outer layer after endocardium and myocardium that consists of a thin layer of connective tissue and fat.

### Pericardium

The pericardium is the thick, membranous sac that surrounds the heart. It protects and lubricates the heart. There are two layers to the pericardium: the fibrous pericardium and the serous pericardium. The serous pericardium is divided into two layers; in between these two layers there is a space called the pericardial cavity.

### Heart Chambers

The heart has four chambers, two atria and two ventricles. The atria are smaller with thin walls, while the ventricles are larger and much stronger.

#### Atrium

There are two atria on either side of the heart. On the right side is the atrium that contains blood which is poor in oxygen. The left atrium contains blood which has been oxygenated and is ready to be sent to the body. The right atrium receives de-oxygenated blood from the superior vena cava and inferior vena cava. The left atrium receives oxygenated blood from the left and right pulmonary veins. Atria facilitate circulation primarily by allowing uninterrupted venous flow to the heart, preventing the inertia of interrupted venous flow that would otherwise occur at each ventricular systole.

#### Ventricles

The ventricle is a heart chamber which collects blood from an atrium and pumps it out of the heart. There are two ventricles: the right ventricle pumps blood into the pulmonary artery which takes the blood through the pulmonary circuit, and the left ventricle pumps blood into the aorta for systemic circulation to the rest of the body. Ventricles have thicker walls than the atria, and thus can create the higher blood pressure. Comparing the left and right ventricle, the left ventricle has thicker walls because it needs to pump blood to the whole body. This leads to the common misconception that the heart lies on the left side of the body.

### Septum

The inter ventricular septum (ventricular septum, or during development septum inferius) is the thick wall separating the lower chambers (the ventricles) of the heart from one another. The ventricular septum is directed backward and to the right, and is curved toward the right ventricle. The greater portion of it is thick and muscular and constitutes the muscular ventricular septum. Its upper and posterior part, which separates the aortic vestibule from the lower part of the right atrium and upper part of the right ventricle, is thin and fibrous, and is termed the membranous ventricular septum.

### Valves

The two atrioventricular (AV) valves are one-way valves that ensure that blood flows from the atria to the ventricles, and not the other way. The two semilunar (SL) valves are present in the arteries leaving the heart; they prevent blood from flowing back into the ventricles. The sound heard in a heart beat is the heart valves shutting. The right AV valve is also called the tricuspid valve because it has three flaps. It is located between the right atrium and the right ventricle. The tricuspid valve allows blood to flow from the right atrium into the right ventricle when the heart is relaxed during diastole. When the heart begins to contract, the heart enters a phase called systole, and the atrium pushes blood into the ventricle. Then, the ventricle begins to contract and blood pressure inside the heart rises. When the ventricular pressure exceeds the pressure in the atrium, the tricuspid valve snaps shut. The left AV valve is also called the bicuspid valve because it has two flaps. It is also known as the mitral valve due to the resemblance to a bishop's mitre (liturgical headdress). This valve prevents blood in the left ventricle from flowing into the left atrium. As it is on the left side of the heart, it must withstand a great deal of strain and pressure; this is why it is made of only two cusps, as a simpler mechanism entails a reduced risk of malfunction. There are two remaining valves called the Semilunar Valves. They have flaps that resemble half moons. The pulmonary semilunar valve lies between the right ventricle and the pulmonary trunk. The aortic semilunar valve is located between the ventricle and the aorta.

### Subvalvular Apparatus

The chordae tendinae are attached to papillary muscles that cause tension to better hold the valve. Together, the papillary muscles and the chordae tendinae are known as the subvalvular apparatus. The function of the subvalvular apparatus is to keep the valves from prolapsing into the atria when they close. The subvalvular apparatus have no effect on the opening and closing of the valves. This is caused entirely by the pressure gradient across the valve.

### Complications with the Heart

The most common congenital abnormality of the heart is the bicuspid aortic valve. In this condition, instead of three cusps, the aortic valve has two cusps. This condition is often undiagnosed until the person develops calcific aortic stenosis. Aortic stenosis occurs in this condition usually in patients in their 40s or 50s, an average of 10 years earlier than in people with normal aortic valves. Another common complication of rheumatic fever is thickening and stenosis (partial blocking) of the mitral valve. For patients who have had rheumatic fever dentists are advised to prophylactically administer antibiotics prior to dental work to prevent bacterial endocarditis that occurs when bacteria from the teeth enter the circulation and attach to damaged heart valves.

The aortic valve is a semilunar valve, but it´s called bicuspid because of it´s regular three "cusps" or "semilunar" valves, and is not to be confused with the left atrioventricular valve, which is more commonly called the mitral valve, and is one of the two cuspidal valves.

## Passage of Blood Through the Heart

Diagram of the human heart

While it is convenient to describe the flow of the blood through the right side of the heart and then through the left side, it is important to realize that both atria contract at the same time and that both ventricles contract at the same time. The heart works as two pumps, one on the right and one on the left that works simultaneously. The right pump pumps the blood to the lungs or the pulmonary circulation at the same time that the left pump pumps blood to the rest of the body or the systemic circulation. Venous blood from systemic circulation (deoxygenated) enters the right atrium through the superior and inferior vena cava. The right atrium contracts and forces the blood through the tricuspid valve (right atrioventricular valve) and into the right ventricles. The right ventricles contract and force the blood through the pulmonary semilunar valve into the pulmonary trunk and out the pulmonary artery. This takes the blood to the lungs where the blood releases carbon dioxide and receives a new supply of oxygen. The new blood is carried in the pulmonary veins that take it to the left atrium. The left atrium then contracts and forces blood through the left atrioventricular, bicuspid, or mitral, valve into the left ventricle. The left ventricle contracts forcing blood through the aortic semilunar valve into the ascending aorta. It then branches to arteries carrying oxygen rich blood to all parts of the body.

### Blood Flow After the Heart

Aorta-Arteries-Arterioles-Capillaries-Venules-Veins-Vena Cava

### Blood Flow Through Capillaries

From the arterioles, the blood then enters one or more capillaries. The walls of capillaries are so thin and fragile that blood cells can only pass in single file. Inside the capillaries, exchange of oxygen and carbon dioxide takes place. Red blood cells inside the capillary releases their oxygen which passes through the wall and into the surrounding tissue. The tissue then releases waste, such as carbon dioxide, which then passes through the wall and into the red blood cells.

## The Circulatory System

The circulatory system is extremely important in sustaining life. It’s proper functioning is responsible for the delivery of oxygen and nutrients to all cells, as well as the removal of carbon dioxide, waste products, maintenance of optimum pH, and the mobility of the elements, proteins and cells, of the immune system. In developed countries, the two leading causes of death, myocardial infarction and stroke are each direct results of an arterial system that has been slowly and progressively compromised by years of deterioration.

### Arteries

Arteries are muscular blood vessels that carry blood away from the heart, oxygenated and deoxygenated blood . The pulmonary arteries will carry deoxygenated blood to the lungs and the sytemic arteries will carry oxygenated blood to the rest of the body. Arteries have a thick wall that consists of three layers. The inside layer is called the endothelium, the middle layer is mostly smooth muscle and the outside layer is connective tissue. The artery walls are thick so that when blood enters under pressure the walls can expand.

#### Arterioles

An arteriole is a small artery that extends and leads to capillaries. Arterioles have thick smooth muscular walls. These smooth muscles are able to contract (causing vessel constriction) and relax (causing vessel dilation). This contracting and relaxing affects blood pressure; the higher number of vessels dilated, the lower blood pressure will be. Arterioles are just visible to the naked eye.

### Capillaries

Capillaries are the smallest of a body’s vessels; they connect arteries and veins, and most closely interact with tissues. They are very prevalent in the body; total surface area is about 6,300 square meters. Because of this, no cell is very far from a capillary, no more than 50 micrometers away. The walls of capillaries are composed of a single layer of cells, the endothelium, which is the inner lining of all the vessels. This layer is so thin that molecules such as oxygen, water and lipids can pass through them by diffusion and enter the tissues. Waste products such as carbon dioxide and urea can diffuse back into the blood to be carried away for removal from the body.

The "capillary bed" is the network of capillaries present throughout the body. These beds are able to be “opened” and “closed” at any given time, according to need. This process is called autoregulation and capillary beds usually carry no more than 25% of the amount of blood it could hold at any time. The more metabolically active the cells, the more capillaries it will require to supply nutrients.

### Veins

Veins carry blood to the heart. The pulmonary veins will carry oxygenated blood to the heart awhile the systemic veins will carry deoxygenated to the heart. Most of the blood volume is found in the venous system; about 70% at any given time. The veins outer walls have the same three layers as the arteries, differing only because there is a lack of smooth muscle in the inner layer and less connective tissue on the outer layer. Veins have low blood pressure compared to arteries and need the help of skeletal muscles to bring blood back to the heart. Most veins have one-way valves called venous valves to prevent backflow caused by gravity. They also have a thick collagen outer layer, which helps maintain blood pressure and stop blood pooling. If a person is standing still for long periods or is bedridden, blood can accumulate in veins and can cause varicose veins. The hollow internal cavity in which the blood flows is called the lumen. A muscular layer allows veins to contract, which puts more blood into circulation. Veins are used medically as points of access to the blood stream, permitting the withdrawal of blood specimens (venipuncture) for testing purposes, and enabling the infusion of fluid, electrolytes, nutrition, and medications (intravenous delivery).

### Venules

A venule is a small vein that allows deoxygenated blood to return from the capillary beds to the larger blood veins, except in the pulmonary circuit were the blood is oxygenated. Venules have three layers; they have the same makeup as arteries with less smooth muscle, making them thinner.

## The Cardiovascular Pathways

Human circulatory system. Arteries are shown in red, veins blue.

The double circulatory system of blood flow refers to the separate systems of pulmonary circulation and the systemic circulation in amphibians, birds and mammals (including humans.) In contrast, fishes have a single circulation system. For instance, the adult human heart consists of two separated pumps, the right side with the right atrium and ventricle (which pumps deoxygenated blood into the pulmonary circulation), and the left side with the left atrium and ventricle (which pumps oxygenated blood into the systemic circulation). Blood in one circuit has to go through the heart to enter the other circuit. Blood circulates through the body two to three times every minute. In one day, the blood travels a total of 19,000 km (12,000 miles), or four times the distance across the U.S. from coast to coast.

### The Pulmonary Circuit

In the pulmonary circuit, blood is pumped to the lungs from the right ventricle of the heart. It is carried to the lungs via pulmonary arteries. At lungs, oxygen in the alveolae diffuses to the capillaries surrounding the alveolae and carbon dioxide inside the blood diffuses to the alveolae. As a result, blood is oxygenated which is then carried to the heart's left half -to the left atrium via pulmonary veins. Oxygen rich blood is prepared for the whole organs and tissues of the body. This is important because mitochondria inside the cells should use oxygen to produce energy from the organic compounds.

### The Systemic Circuit

The systemic circuit supplies oxygenated blood to the organ system. Oxygenated blood from the lungs is returned to the left atrium, then the ventricle contracts and pumps blood into the aorta. Systemic arteries split from the aorta and direct blood into the capillaries. Cells consume the oxygen and nutrients and add carbon dioxide, wastes, enzymes and hormones. The veins drain the deoxygenated blood from the capillaries and return the blood to the right atrium.

### Aorta

The aorta is the largest of the arteries in the systemic circuit. The blood is pumped from the left ventricle into the aorta and from there it branches to all parts of the body. The aorta is an elastic artery, and as such is able to distend. When the left ventricle contracts to force blood into the aorta, the aorta expands. This stretching gives the potential energy that will help maintain blood pressure during diastole, as during this time the aorta contracts passively.

### Superior Venae Cavae

The superior vena cava (SVC) is a large but short vein that carries de-oxygenated blood from the upper half of the body to the heart's right atrium. It is formed by the left and right brachiocephalic veins (also referred to as the innominate veins) which receive blood from the upper limbs and the head and neck. The azygous vein (which receives blood from the ribcage) joins it just before it enters the right atrium.

### Inferior Venae Cavae

The inferior vena cava (or IVC) is a large vein that carries de-oxygenated blood from the lower half of the body into the heart. It is formed by the left and right common iliac veins and transports blood to the right atrium of the heart. It is posterior to the abdominal cavity, and runs along side of the vertebral column on its right side.

### Coronary Arteries

Heart showing the Coronary Arteries

Heart showing the Coronary Arteries The coronary circulation consists of the blood vessels that supply blood to, and remove blood from, the heart muscle itself. Although blood fills the chambers of the heart, the muscle tissue of the heart, or myocardium, is so thick that it requires coronary blood vessels to deliver blood deep into the myocardium. The vessels that supply blood high in oxygen to the myocardium are known as coronary arteries. The vessels that remove the deoxygenated blood from the heart muscle are known as cardiac veins. The coronary arteries that run on the surface of the heart are called epicardial coronary arteries. These arteries, when healthy, are capable of auto regulation to maintain coronary blood flow at levels appropriate to the needs of the heart muscle. These relatively narrow vessels are commonly affected by atherosclerosis and can become blocked, causing angina or a heart attack. The coronary arteries are classified as "end circulation", since they represent the only source of blood supply to the myocardium: there is very little redundant blood supply, which is why blockage of these vessels can be so critical. In general there are two main coronary arteries, the left and right. • Right coronary artery • Left coronary artery Both of these arteries originate from the beginning (root) of the aorta, immediately above the aortic valve. As discussed below, the left coronary artery originates from the left aortic sinus, while the right coronary artery originates from the right aortic sinus. Four percent of people have a third, the posterior coronary artery. In rare cases, a patient will have one coronary artery that runs around the root of the aorta.

### Hepatic Veins

In human anatomy, the hepatic veins are the blood vessels that drain de-oxygenated blood from the liver and blood cleaned by the liver (from the stomach, pancreas, small intestine and colon) into the inferior vena cava. They arise from the substance of the liver, more specifically the central vein of the liver lobule. They can be differentiated into two groups, the upper group and lower group. The upper group of three typically arises from the posterior aspect of the liver and drain the quadrate lobe and left lobe. The lower group rise from the right lobe and caudate lobe, are variable in number, and are typically smaller than those in the upper group. None of the hepatic veins have valves.

## Cardiac Cycle

Cardiac cycle is the term used to describe the relaxation and contraction that occur, as a heart works to pump blood through the body. Heart rate is a term used to describe the frequency of the cardiac cycle. It is considered one of the four vital signs. Usually it is calculated as the number of contractions (heart beats) of the heart in one minute and expressed as "beats per minute" (bpm). When resting, the adult human heart beats at about 70 bpm (males) and 75 bpm (females), but this rate varies between people. However, the reference range is nominally between 60 bpm (if less termed bradycardia) and 100 bpm (if greater, termed tachycardia). Resting heart rates can be significantly lower in athletes, and significantly higher in the obese. The body can increase the heart rate in response to a wide variety of conditions in order to increase the cardiac output (the amount of blood ejected by the heart per unit time). Exercise, environmental stressors or psychological stress can cause the heart rate to increase above the resting rate. The pulse is the most straightforward way of measuring the heart rate, but it can be deceptive when some strokes do not lead to much cardiac output. In these cases (as happens in some arrhythmias), the heart rate may be considerably higher than the pulse. Every single 'beat' of the heart involves three major stages: atrial systole, ventricular systole and complete cardiac diastole. Throughout the cardiac cycle, the blood pressure increases and decreases. As ventricles contract the pressure rise, causing the AV valves to slam shut.

### Systole

The heart in the systole phase.

### Diastole

The heart in the diastole phase.

The heart in the diastole phase. Cardiac Diastole is the period of time when the heart relaxes after contraction in preparation for refilling with circulating blood. Ventricular diastole is when the ventricles are relaxing, while atrial diastole is when the atria are relaxing. Together they are known as complete cardiac diastole. It should be noted that even this relaxation is an active, energy-spending process. During ventricular diastole, the pressure in the (left and right) ventricles drops from the peak that it reaches in systole. When the pressure in the left ventricle drops to below the pressure in the left atrium, the mitral valve opens, and the left ventricle fills with blood that was accumulating in the left atrium. Likewise, when the pressure in the right ventricle drops below that in the right atrium, the tricuspid valve opens and the right ventricle fills with blood that was in the right atrium

### "Lub-Dub"

The first heart tone, or S1, "Lub" is caused by the closure of the atrioventricular valves, mitral and tricuspid, at the beginning of ventricular contraction, or systole. When the pressure in the ventricles rises above the pressure in the atria, these valves close to prevent regurgitation of blood from the ventricles into the atria. The second heart tone, or S2 (A2 and P2), "Dub" is caused by the closure of the aortic valve and pulmonic valve at the end of ventricular systole. As the left ventricle empties, its pressure falls below the pressure in the aorta, and the aortic valve closes. Similarly, as the pressure in the right ventricle falls below the pressure in the pulmonary artery, the pulmonic valve closes. During inspiration, negative intrathoracic pressure causes increased blood return into the right side of the heart. The increased blood volume in the right ventricle causes the pulmonic valve to stay open longer during ventricular systole. This causes an increased delay in the P2 component of S2. During expiration, the positive intrathoracic pressure causes decreased blood return to the right side of the heart. The reduced volume in the right ventricle allows the pulmonic valve to close earlier at the end of ventricular systole, causing P2 to occur earlier, and "closer" to A2. It is physiological to hear the splitting of the second heart tone by younger people and during inspiration. During expiration normally the interval between the two components shortens and the tone becomes merged.

## The Heart's Electrical Conduction System

The heart is primarily made up of muscle tissue. A network of nerve fibers coordinates the contraction and relaxation of the cardiac muscle tissue to obtain an efficient, wave-like pumping action of the heart

How Stuff Works (The Heart)

#### Control of Heartbeat

The heart contains two cardiac pacemakers that spontaneously cause the heart to beat. These can be controlled by the autonomic nervous system and circulating adrenaline. If the cardiac muscles just contracted and relaxed randomly at a natural rhythm the cycle would become disordered and the heart would become unable to carry on its function of being a pump. Sometimes when the heart undergoes great damage to one part of the cardiac muscle or the person incurs an electric shock, the cardiac cycle can become uncoordinated and chaotic. Some parts of the heart will contract whilst others will relax so that instead of contracting and relaxing as a whole, the heart will flutter abnormally. This is called fibrillation and can be fatal if not treated within 60 seconds.

Schematic representation of the sinoatrial node and the atrioventricular bundle of His. The location of the SA node is shown in blue. The bundle, represented in red, originates near the orifice of the coronary sinus, undergoes slight enlargement to form the AV node. The AV node tapers down into the bundle of HIS, which passes into the ventricular septum and divides into two bundle branches, the left and right bundles. The ultimate distribution cannot be completely shown in this diagram.

SA Node
The sinoatrial node (abbreviated SA node or SAN, also called the sinus node) is the impulse generating (pacemaker) tissue located in the right atrium of the heart. Although all of the heart's cells possess the ability to generate the electrical impulses (or action potentials) that trigger cardiac contraction, the sinoatrial node is what normally initiates it, simply because it generates impulses slightly faster than the other areas with pacemaker potential. Because cardiac myocytes, like all nerve cells, have refractory periods following contraction during which additional contractions cannot be triggered, their pacemaker potential is overridden by the sinoatrial node. The SA node emits a new impulse before either the AV or purkinje fibers reach threshold. The sinoatrial node (SA node) is a group of cells positioned on the wall of the right atrium, near the entrance of the superior vena cava. These cells are modified cardiac myocytes. They possess some contractile filaments, though they do not contract. Cells in the SA node will naturally discharge (create action potentials) at about 70-80 times/minute. Because the sinoatrial node is responsible for the rest of the heart's electrical activity, it is sometimes called the primary pacemaker. If the SA node doesn't function, or the impulse generated in the SA node is blocked before it travels down the electrical conduction system, a group of cells further down the heart will become the heart's pacemaker. These cells form the atrioventricular node (AV node), which is an area between the right atrium and ventricle, within the atrial septum. The impulses from the AV node will maintain a slower heart rate (about 40-60 beats per a minute). When there is a pathology in the AV node or purkinje fibers, an ectopic pacemaker can occur in different parts of the heart. The ectopic pacemaker typically discharges faster than the SA node and causes an abnormal sequence of contraction. The SA node is richly innervated by vagal and sympathetic fibers. This makes the SA node susceptible to autonomic influences. Stimulation of the vagus nerve causes decrease in the SA node rate (thereby causing decrease in the heart rate). Stimulation via sympathetic fibers causes increase in the SA node rate (thereby increasing the heart rate). The sympathetic nerves are distributed to all parts of the heart, especially in ventricular muscles. The parasympathetic nerves mainly control SA and AV nodes, some atrial muscle and ventricular muscle. Parasympathetic stimulation from the vagal nerves decreases the rate of the AV node by causing the release of acetylcholine at vagal endings which in turn increases the K+ permeability of the cardiac muscle fiber. Vagal stimulation can block transmission through AV junction or stop SA node contraction which is called "ventricular escape." When this happens, the purkinje fibers in the AV bundle develops a rhythm of their own. In the majority of patients, the SA node receives blood from the right coronary artery, meaning that a myocardial infarction occluding it will cause ischemia in the SA node unless there is a sufficiently good anastomosis from the left coronary artery. If not, death of the affected cells will stop the SA node from triggering the heartbeat

#### AV Node

The atrioventricular node (abbreviated AV node) is the tissue between the atria and the ventricles of the heart, which conducts the normal electrical impulse from the atria to the ventricles. The AV node receives two inputs from the atria: posteriorly via the crista terminalis, and anteriorly via the interatrial septum. [1] An important property that is unique to the AV node is decremental conduction. This is the property of the AV node that prevents rapid conduction to the ventricle in cases of rapid atrial rhythms, such as atrial fibrillation or atrial flutter. The atrioventricular node delays impulses for 0.1 second before spreading to the ventricle walls. The reason it is so important to delay the cardiac impulse is to ensure that the atria are empty completely before the ventricles contract (Campbell et al., 2002). The blood supply of the AV node is from a branch of the right coronary artery in 85% to 90% of individuals, and from a branch of the left circumflex artery in 10% to 15% of individuals. In certain types of supraventricular tachycardia, a person could have two AV Nodes; this will cause a loop in electrical current and uncontrollably-rapid heart beat. When this electricity catches up with itself, it will dissipate and return to normal heart-beat speed.

#### AV Bundle

The bundle of HIS is a collection of heart muscle cells specialized for electrical conduction that transmits the electrical impulses from the AV node (located between the atria and the ventricles) to the point of the apex of the fascicular branches. The fascicular branches then lead to the Purkinje fibers which innervate the ventricles, causing the cardiac muscle of the ventricles to contract at a paced interval. These specialized muscle fibers in the heart were named after the Swiss cardiologist Wilhelm His, Jr., who discovered them in 1893. Cardiac muscle is very specialized, as it is the only type of muscle that has an internal rhythm; i.e., it is myogenic which means that it can naturally contract and relax without receiving electrical impulses from nerves. When a cell of cardiac muscle is placed next to another, they will beat in unison. The fibers of the Bundle of HIS allow electrical conduction to occur more easily and quickly than typical cardiac muscle. They are an important part of the electrical conduction system of the heart as they transmit the impulse from the AV node (the ventricular pacemaker) to the rest of the heart. The bundle of HIS branches into the three bundle branches: the right left anterior and left posterior bundle branches that run along the intraventricular septum. The bundles give rise to thin filaments known as Purkinje fibers. These fibers distribute the impulse to the ventricular muscle. Together, the bundle branches and purkinje network comprise the ventricular conduction system. It takes about 0.03-0.04s for the impulse to travel from the bundle of HIS to the ventricular muscle. It is extremely important for these nodes to exist as they ensure the correct control and co-ordination of the heart and cardiac cycle and make sure all the contractions remain within the correct sequence and in sync.

#### Purkinje Fibers

Purkinje fibers (or Purkyne tissue) are located in the inner ventricular walls of the heart, just beneath the endocardium. These fibers are specialized myocardial fibers that conduct an electrical stimulus or impulse that enables the heart to contract in a coordinated fashion. Purkinje fibers work with the sinoatrial node (SA node) and the atrioventricular node (AV node) to control the heart rate. During the ventricular contraction portion of the cardiac cycle, the Purkinje fibers carry the contraction impulse from the left and right bundle branches to the myocardium of the ventricles. This causes the muscle tissue of the ventricles to contract and force blood out of the heart — either to the pulmonary circulation (from the right ventricle) or to the systemic circulation (from the left ventricle). They were discovered in 1839 by Jan Evangelista Purkinje, who gave them his name.

#### Pacemaker

The contractions of the heart are controlled by electrical impulses, these fire at a rate which controls the beat of the heart. The cells that create these rhythmical impulses are called pacemaker cells, and they directly control the heart rate. Artificial devices also called pacemakers can be used after damage to the body's intrinsic conduction system to produce these impulses synthetically.

#### Fibrillation

Fibrillation is when the heart flutters abnormally. This can be detected by an electrocardiogram which measures the waves of excitation passing through the heart and plotting a graph of potential difference (voltage) against time. If the heart and cardiac cycle is functioning properly the electrocardiogram shows a regular, repeating pattern. However if there is fibrillation there will be no apparent pattern, either in the much more common 'Atrial Fibrillation', or the less likely but much more dangerous 'Ventricular Fibrillation'. In a hospital during VF the monitor would make a sound and alert the doctors to treat the fibrillation by passing a huge current through the chest wall and shocking the heart out of its fibrillation. This causes the cardiac muscle to stop completely for 5 seconds and when it begins to beat again the cardiac cycle would have resumed to normal and the heart will be beating in a controlled manner again. Fibrillation is an example of "circus movement" of impulses through the heart muscle.

Circus movement occurs when an impulse begins in one part of the heart muscle and spreads in a circuitous pathway through the heart then returns to the originally excited muscle and "re-enters" it to stimulate it once more. The signal never stops. A cause of circus movement is long length pathway in which the muscle is no longer in a refractory state when the stimulus returns to it. A "flutter" is a circus movement in coordinated, low frequency waves that cause rapid heart rate. If the Bundle of HIS is blocked, it will result in dissociation between the activity of the atria and that of the ventricles, otherwise called a third degree heart block. The other cause of a third degree block would be a block of the right, left anterior, and left posterior bundle branches. A third degree block is very serious medical condition that will most likely require an artificial pacemaker.

## The ECG

E.C.G stands for Electrocardiogram and represents the electrophysiology of the heart. Cardiac electrophysiology is the science of the mechanisms, functions, and performance of the electrical activities of specific regions of the heart. The ECG is the recording of the heart's electrical activity as a graph. The graph can show the heart's rate and rhythm, it can detect enlargement of the heart, decreased blood flow, or the presence of current or past heart attacks. ECG's are inexpensive, Non-invasive, quick, and painless. Depending on the results, the patient’s medical history, and a physical exam; further tests or a combination of medications and lifestyle changes may be ordered.

#### How To Read An ECG

ECG Waveform

P
P wave- indicates that the atria are electrically stimulated (depolarized) to pump blood into the ventricles.
QRS
QRS complex- indicates that the ventricles are electrically stimulated (depolarized) to pump blood out.
ST
ST segment- indicates the amount of time from the end of the contraction of the ventricles to the beginning of the T wave.
T
T wave- indicates the recovery period (repolarization) of the ventricles.
U
U wave- rarely seen, and thought to possibly be the repolarization of the papillary muscles

### Cardiac Muscle Contraction

After an action potential excites the plasma membrane of the cardiac muscle cell the contraction is due to an increase in the cytoplasmic concentration of Calcium ions. Similar to skeletal muscle, the release of Ca+ ions from the sarcoplasmic reticulum binds to troponin which allows actin to bind with myosin. The difference between skeletal muscle and cardiac muscle is that when the action potential opens voltage gated calcium ion channels in the T-tubules. The increase in cytosolic calcium causes calcium ions to bind to receptors on the surface of the sarcoplasmic reticulum. The binding of calcium ions to these receptors causes the opening of more calcium ion channels in the SR membrane. Calcium ions then rush out of the SR and bind to troponin and allow the myosin and actin to bind together which causes contraction. This sequence is called calcium-induced calcium release. Contraction ends when the level of cytosolic calcium returns to normal resting levels.

### Blood Pressure

Blood pressure is the pressure exerted by the blood on the walls of the blood vessels. Unless indicated otherwise, blood pressure refers to systemic arterial blood pressure, i.e., the pressure in the large arteries delivering blood to body parts other than the lungs, such as the brachial artery (in the arm). The pressure of the blood in other vessels is lower than the arterial pressure. Blood pressure values are universally stated in millimeters of mercury (mmHg). The systolic pressure is defined as the peak pressure in the arteries during the cardiac cycle; the diastolic pressure is the lowest pressure (at the resting phase of the cardiac cycle). The mean arterial pressure and pulse pressure are other important quantities. Typical values for a resting, healthy adult are approximately 120 mmHg systolic and 80mm Hg diastolic (written as 120/80 mmHg), with individual variations. These measures of blood pressure are not static, but undergo natural variations from one heartbeat to another, and throughout the day (in a circadian rhythm); they also change in response to stress, nutritional factors, drugs, or disease.

#### Systolic Pressure

Systolic Pressure is the highest when the blood is being pumped out of the left ventricle into the aorta during ventricular systole. The average high during systole is 120 mmHg.

#### Diastolic Pressure

Diastolic blood pressure lowers steadily to an average low of 80 mmHg during ventricular diastole.

## Cardiovascular Disease

Cardiovascular disease refers to the class of diseases that involve the heart and/or blood vessels (arteries and veins). While the term technically refers to any disease that affects the cardiovascular system, it is usually used to refer to those related to atherosclerosis (arterial disease). These conditions have similar causes, mechanisms, and treatments. Over 50 million Americans have cardiovascular problems, and most other Western countries face high and increasing rates of cardiovascular disease. It is the number 1 cause of death and disability in the United States and most European countries. By the time that heart problems are detected, the underlying cause (atherosclerosis) is usually quite advanced, having progressed for decades. There is therefore increased emphasis on preventing atherosclerosis by modifying risk factors, such as healthy eating, exercise and avoidance of smoking.

#### Hypertension

Hypertension or high blood pressure is a medical condition wherein the blood pressure is chronically elevated. Hypertension is defined by some authors as systolic pressure over 130 and diastolic over 85 mmHg. [1] Hypertension often has an insidious or un-noticed onset and is sometimes called the silent killer because stretching of the arteries causes microscopic tears in the arterial wall and accelerates degenerative changes. Persistent hypertension is one of the risk factors for strokes, heart attacks, heart failure and arterial aneurysm, and is a leading cause of chronic renal failure

#### Atherosclerosis

Severe atherosclerosis of the aorta. Autopsy specimen.

Atherosclerosis is a disease affecting the arterial blood vessel. It is commonly referred to as a "hardening" or "furring" of the arteries. It is caused by the formation of multiple plaques within the arteries. Arteriosclerosis ("hardening of the artery") results from a deposition of tough, rigid collagen inside the vessel wall and around the atheroma. This increases the stiffness, decreases the elasticity of the artery wall. Atherosclerosis typically begins in early adolescence, is usually found in most major arteries, and yet is asymptomatic and not detected by most diagnostic methods during life. It most commonly becomes seriously symptomatic when interfering with the coronary circulation supplying the heart or cerebral circulation supplying the brain, and is considered the most important underlying cause of strokes, heart attacks, various heart diseases including congestive heart failure and most cardiovascular diseases in general.

#### Plaque

Plaque Atheroma or commonly known as plaque is an abnormal inflammatory accumulation of macrophage white blood cells within the walls of arteries.

#### Circulatory Shock

Circulatory Shock is a severe condition that results from reduced blood circulation.

#### Thrombus

A thrombus, or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e. clotting factors). A thrombus is physiologic in cases of injury, but pathologic in case of thrombosis.

Preventing blood clots reduces the risk of stroke, heart attack and pulmonary embolism. Heparin and warfarin are often used to inhibit the formation and growth of existing blood clots, thereby allowing the body to shrink and dissolve the blood clots through normal methods.

#### Embolism

An embolism occurs when an object (the embolus) migrates from one part of the body (through circulation) and causes a blockage (occlusion) of a blood vessel in another part of the body. Blood clots form the most common embolic material by far: other possible embolic materials include fat globules (a fat embolism), air bubbles (an air embolism), septic emboli (containing pus and bacteria), or amniotic fluid.

#### Stroke

A stroke, also known as cerebrovascular accident (CVA), is an acute neurological injury whereby the blood supply to a part of the brain is interrupted. Strokes can be classified into two major categories: ischemic and hemorrhagic. ~80% of strokes are due to ischemia.

• Ischemic Stroke: In ischemic stroke, which occurs in approximately 85-90% of strokes, a blood vessel becomes occluded and the blood supply to part of the brain is totally or partially blocked. Ischemic stroke is commonly divided into thrombotic stroke, embolic stroke, systemic hypoperfusion (Watershed or Border Zone stroke), or venous thrombosis
• Hemorrhagic Stroke: A hemorrhagic stroke, or cerebral hemorrhage, is a form of stroke that occurs when a blood vessel in the brain ruptures or bleeds. Like ischemic strokes, hemorrhagic strokes interrupt the brain's blood supply because the bleeding vessel can no longer carry the blood to its target tissue. In addition, blood irritates brain tissue, disrupting the delicate chemical balance, and, if the bleeding continues, it can cause increased intracranial pressure which physically impinges on brain tissue and restricts blood flow into the brain. In this respect, hemorrhagic strokes are more dangerous than their more common counterpart, ischemic strokes. There are two types of hemorrhagic stroke: intracerebral hemorrhage, and subarachnoid hemorrhage.

The term "brain attack" is starting to come into use in the United States for stroke, just as the term "heart attack" is used for myocardial infarction, where a cutoff of blood causes necrosis to the tissue of the heart. Many hospitals have "brain attack" teams within their neurology departments specifically for swift treatment of stroke. If symptoms of stroke are detected at early on-set, special "clot busting" drugs may be administered. These clot busters will dissolve clots before they can cause tissue death and restore normal circulation. One of the initial drugs used to dissolve clots was streptokinase, although its use creates a possibility of clot destruction throughout the entire body, leading to serious hemorrhage. There are newer, third generation thrombolytics that are safer.

#### Heart Attack

Acute myocardial infarction (AMI or MI), commonly known as a heart attack, A heart attack occurs when the supply of blood and oxygen to an area of heart muscle is blocked, usually by a clot in a coronary artery. Often, this blockage leads to arrhythmias (irregular heartbeat or rhythm) that cause a severe decrease in the pumping function of the heart and may bring about sudden death. If the blockage is not treated within a few hours, the affected heart muscle will die and be replaced by scar tissue. It is the leading cause of death for both men and women all over the world

#### Angina Pectoris

Angina Pectoris is chest pain due to ischemia (a lack of blood and hence oxygen supply) of the heart muscle, generally due to obstruction or spasm of the coronary arteries (the heart's blood vessels).

#### Coronary Bypass

Coronary artery bypass surgery, coronary artery bypass graft surgery and heart bypass are surgical procedures performed on patients with coronary artery disease for the relief of angina and possible improved heart muscle function. Veins or arteries from elsewhere in the patient's body are grafted from the aorta to the coronary arteries, bypassing coronary artery narrowing caused by atherosclerosis and improves the blood supply to the myocardium (heart muscle).

#### Congestive Heart Failure

Congestive heart failure (CHF), also called congestive cardiac failure (CCF) or just heart failure, is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. It is not to be confused with "cessation of heartbeat", which is known as asystole, or with cardiac arrest, which is the cessation of normal cardiac function in the face of heart disease. Because not all patients have volume overload at the time of initial or subsequent evaluation, the term "heart failure" is preferred over the older term "congestive heart failure". Congestive heart failure is often undiagnosed due to a lack of a universally agreed definition and difficulties in diagnosis, particularly when the condition is considered "mild". Right sided heart failure commonly causes peripheral edema, or swelling of the extremities. Left sided heart failure commonly causes pulmonary edema, or fluid buildup in the lungs.

#### Aneurysm

An aneurysm (or aneurism) is a localized dilation or ballooning of a blood vessel by more than 50% of the diameter of the vessel and can lead to instant death at anytime. Aneurysms most commonly occur in arteries at the base of the brain (the circle of Willis) and in the aorta (the main artery coming out of the heart) - this is an aortic aneurysm. This bulge in a blood vessel, much like a bulge on an over-inflated inner tube, can lead to death at anytime. The larger an aneurysm becomes, the more likely it is to burst. Aneurysms are also described according to their shape: Saccular or fusiform. A saccular aneurysm resembles a small sack; a fusiform aneurysm is shaped like a spindle.

#### Dissolving Blood Clots

To dissolve blood clots you would use a drug that converts plasminogen (molecule found in blood), to plasmin, (enzyme that dissolves blood clots).

#### Clearing Clogged Arteries

One way to unblock a coronary artery (or other blood vessel) is percutaneous transluminal coronary angioplasty (PTCA), which was first performed in 1977. A wire is passed from the femoral artery in the leg or the radial artery in the arm up to the diseased coronary artery, to beyond the area of the coronary artery that is being worked upon. Over this wire, a balloon catheter is passed into the segment that is to be opened up. The end of the catheter contains a small folded balloon. When the balloon is hydraulically inflated, it compresses the atheromatous plaque and stretches the artery wall to expand. At the same time, if an expandable wire mesh tube (stent) was on the balloon, then the stent will be implanted (left behind) to support the new stretched open position of the artery from the inside.

### Dilated and Inflamed Veins

#### Varicose Veins

Varicose veins are veins on the leg which are large, twisted, and ropelike, and can cause pain, swelling, or itching. They are an extreme form of telangiectasia, or spider veins. Varicose veins result due to insufficiency of the valves in the communicating veins. These are veins which link the superficial and deep veins of the lower limb. Normally, blood flows from the superficial to the deep veins, facilitating return of blood to the heart. However, when the valve becomes defective, blood is forced into the superficial veins by the action of the muscle pump (which normally aids return of blood to the heart by compressing the deep veins). People who have varicose veins are more at risk of getting a Deep Vein Thrombosis (DVT) and pulmonary embolisms.

#### Phlebitis

Phlebitis is an inflammation of a vein, usually in the legs. This is usually the most serious if found in a deep vein. However, most people with the condition, perhaps 80 to 90 percent, are women. The disease may also have a genetic component, as it is known to run in families.

### Congenital Heart Defects

Illustration of VSD

Heart defects present at birth are called congenital heart defects. Slightly less than 1% of all newborn infants have congenital heart disease. Eight defects are more common than all others and make up 80% of all congenital heart diseases, whereas the remaining 20% consist of many independently infrequent conditions or combinations of several defects.

#### Acyanotic Defects

Acyanotic heart defects are those in which there is a normal amount of oxygen in the bloodstream. The most common congenital heart defect is a ventral septal defect, which occurs in about 20% of all children with congenital heart disease. In VSD blood from the left ventricle is shunted to the right ventricle, resulting in oxygenated blood returning into pulmonic circulation. One of the potential problems of VSD is pulmonary hypertension.

#### Cyanotic Defects

Cyanotic heart defects refer to defects that result in decreased amounts of oxygen in the blood. In cyanotic heart defects deoxygenated blood from the right ventricle flows into the systemic circulation. Cyanotic defects include tetrogy of Fallot and transposition of the great arteries.

## Homeostasis

Homeostasis in the body is only possible if the cardiovascular system is working properly. This means that the system needs to deliver oxygen and nutrients to the tissue fluid that surrounds the cells and also take away the metabolic waste. The heart is composed of arteries that take blood from the heart, and vessels that return blood to the heart. Blood is pumped by the heart into two circuits: the pulmonary and systemic circuits. The pulmonary circuit carries blood through the lungs where gas exchange occurs and the systemic system transports blood to all parts of the body where exchange with tissue fluid takes place. The cardiovascular system works together with all other systems to maintain homeostasis.

### The Lymphatic System

The lymphatic system is closely related to the cardiovascular system. There are three main ways that they work together to maintain homeostasis: the lymphatic system receives the excess tissue fluid and returns it to the bloodstream, lacteal take fat molecules from the intestinal villi and transport them to the bloodstream and both systems work together to defend the body against disease.The lymphatic system can create white blood cells that fight off disease and infections.

## Interesting Facts

• Heart Disease is the number one killer in American women.
• 16.7 million deaths are result forms of cardiovascular disease, heart disease and stroke.
• Stress, eating high fat foods, obesity, tobacco and alcohol use are just some risk factors of developing heart disease.
• Recent research suggests that taking a small dose of aspirin daily may help prevent a heart attack (because aspirin inhibits platelet clumping).
• The length of all your blood vessels lined up is about 60,000 miles long! To put this in perspective, the Earth's circumference is 40,075.02 kilometres and 60,000 miles is around 96,000 km - so your blood vessels would go twice around the world and still have some to spare!

## Ways to a Healthy Heart

• Eating healthy, good nutrition.

• Fitness and Exercise.

• Having a healthy lifestyle; don't drink, smoke, or do drugs.

• Lowering LDL cholesterol and high blood pressure.

• Reduce the fat, sodium, and calories in your diet.

## Aging

The heart muscle becomes less efficient with age, and there is a decrease in both maximum cardiac output and heart rate, although resting levels may be more than adequate. The health of the myocardium depends on its blood supply, and with age there is greater likelihood that atherosclerosis will narrow the coronary arteries. Atherosclerosis is the deposition of cholesterol on and in the walls of the arteries, which decreases blood flow and forms rough surfaces that may cause intravascular clot formation High blood pressure (hypertension) causes the left ventricle to work harder. It may enlarge and outgrow its blood supply, thus becoming weaker. A weak ventricle is not an efficient pump, and may progress to congestive heart failure. This process may be slow or rapid. The heart valves may become thickened by fibrosis, leading to heart murmurs and less efficient pumping. Arrhythmias are also more common with age, as the cells of the conduction pathway become less efficient.

## Shock

Physiological Stress

Physiological stress can be any kind of injury from burns, to broken bones; the body's response to stress is categorized in two phases the ebb phase (early phase) begins immediately after the injury. And the second phase is about 36 to 48 hours after injury is called the flow phase. In the ebb (shock) phase there is Inadequate circulation, decreased insulin level, decreased oxygen consumption, hypothermia (low body temperature), hypovolemia (low blood volume), and hypotension (low blood pressure). In the flow phase there is increased levels of catecholamine, glucocorticoids, and glucagons, normal or elevated insulin levels, catabolic (breakdown), hyperglycemic (high blood sugar), increased oxygen consumption/respiratory rate, hyperthermia (high body temperature) fever sets in, hypermetabolism, increased insulin resistance, increased cardiac output.

## Premature ventricular contractions (PVC's)

Excitation occurs through the SA node to the AV node if there are abnormalities or drug interference that malfunctions the AV node the ventricles will not receive the initiating stimuli and the autorhythmic cells in the bundle branches begin to initiate actions on their own rate becoming the pacemakers for the ventricles. This in turn will cause conduction disorder. With conduction that causes problems with the bundle branches there is the right and the left premature ventricular contractions. Right is most common and may go untreated. Left is always a serious problem and must be treated.

## Intrinsic Control of heartbeat

• SA node (located in the right atrium near the entrance of the superior vena cava)
• AV node (located at the base of right atrium)

• AV bundle (located in the intraventricular septum between the two ventricles that go in two directions right and left bundle branches that leave the septum to enter the walls of both ventricle)
• Bundle Branches (the branching off the septum to the walls of the ventricles that run into the purkinje fibers that then make contact with ventricular myocardial cells to spread the impulse to the rest of the ventricles)

Animation of a normal ECG wave.

## Electrocardiogram

• The P is the atrial depolarization
• QRS is the ventricular depolarization, as well as atrial repolarization.
• T is the ventricular repolarization

Schematic representation of normal ECG

## Extrinsic Control of Heartbeat

Autonomic system with two subdivisions: the sympathetic division and the parasympathetic division. Hormonal control of blood pressure

• Epinephrine
• Norepinephrine
• ANP : Atrial natriuretic peptide
• Renin-Angiotension system

## Case Study

#### Stroke

Cerebrovascular disease are those that affect blood vessels in the brain and happen to be the third cause of death in the United States only behind heart disease and cancer. Stroke (also called cerebrovascular accident or CVR) is a cerebrovascular disorder caused by a sudden decrease or stoppage of blood flow to a part of the brain. Decreased blood flow also known as ischemia is dangerous to any tissue but brain tissue is even more vulnerable, mainly due to the high rate of its metabolic reactions. In fact if you stopped blood flow for no more than three minutes it may be sufficient enough to cause death of most brain cells. For this reason a stroke can kill people within minutes or leave them with severe brain damage.

Strokes may be classified as either occlusive or hemorrhagic and may happen either in the interior of the brain or on its surface. In a occlusive stroke blood flow through a vessel is blocked. In a hemorrhagic stroke a blood vessel ruptures causing a hemorrhage.

## Summary

As with all of the body systems, the cardiovascular system plays a part in maintaining homeostasis. The nervous system regulates the functioning of the heart based on what the heart is supposed to do. The pumping of the heart maintains normal blood pressure and proper oxygenation of tissues. The vascular system forms passageways for the blood, but they aren't simply just a pipeline system. The vessels are not passive tubes, but rather active contributors to homeostasis. The arteries and veins help maintain blood pressure, and the capillaries provide sites for the necessary exchanges of materials between the blood and the tissues.

## Review Questions

Answers for these questions can be found here

1. This conducts electricity like nerves

A) Epicardium
B) Pericardium
C) Myocardium
D) Subvalaular Apparatus
E) None of these, only nerves conduct electricity

2. This carries the most blood at any given time in the body

A) Veins
B) Capillary Beds
C) Veins
D) Aorta
E) Vena Cava

3. The following contract together to pump blood

A) Right atrium with the right ventricle and left atrium with the left ventricle
B) Right atrium with left atrium and right ventricles with left ventricle
C) Tricuspid valve and mitral valve
D) Aorta and pulmonary artery
E) Aorta, pulmonary artery and pulmonary vein

4. This is the pacemaker of the heart

A) AV node
B) Purkinje fibers
C) AV Bundle
D) SA node
E) None of these, a pacemaker is surgically inserted

5. When reading an EKG, this letter shows the depolarization from the AV node down to the AV bundle

A) S
B) P
C) U
D) T
E) Q

6. The T wave in an EKG shows

A) Resting potential
B) Atrial depolarization
C) SA node excitation
D) Ventricle repolarization
E) Purkinje Excitation

7. Blood pressure is the measure of

A) Pressure exerted by the blood on the walls of the blood vessels
B) Pressure exerted by the blood on the arteries
C) Pressure exerted by the blood on the veins
D) Pressure exerted by the blood on the aorta
E) Pressure exerted by the blood on the capillaries

8. Systolic Pressure is

A) An average of 120 mm Hg
B) Lowers steadily during ventricle systole
C) The highest when blood is being pumped out of the left ventricle into the aorta
D) An average of 80 mm Hg
E) Both A and C
F) Both B and D

9. The heart has how many chambers?

A) One
B) Two
C) Three
D) Four
E) Five

## Glossary

Acute myocardial infarction (AMI or MI) commonly known as a heart attack, is a disease state that occurs when the blood supply to a part of the heart is interrupted. The resulting ischemia or oxygen shortage causes damage and potential death of heart tissue. Aorta: the largest of the arteries in the systemic circuit
Aortic Valve: lies between the left ventricle and the aorta
Antidiuretic hormone: Produced in the posterior pituitary ADH (vasopressin), major function is to regulate blood pressure by water retention by the kidneys.
Arteriole: a small diameter blood vessel that extends and branches out from an artery and leads to capillaries
Atrial natriuretic peptide: Produced in the atria of the heart, it increases urinary excretion of sodium which causes water loss which in turn the viscosity of the blood is lowered and in turn lowers the blood pressure.
Atrioventricular Node (abbreviated AV node): the tissue between the atria and the ventricles of the heart, which conducts the normal electrical impulse from the atria to the ventricles
Atrioventricular valves: large, multi-cusped valves that prevent backflow from the ventricles into the atria during systole
AV Bundle: collection of heart muscle cells specialized for electrical conduction that transmits the electrical impulses from the AV node
Barbiturates: CNS depressants, sedative-hypnotics
Blood Pressure: the pressure exerted by the blood on the walls of the blood vessels
Capillaries: the smallest of a body’s vessels, they connect arteries and veins
Cardiac Cycle: term used to describe the sequence of events that occur as a heart works to pump blood through the body
Cerebral Vascular Accident (CVA): Also known as a stroke, is a rapidly developing loss of a part of brain function or loss of consciousness due to an interruption in the blood supply to all or part of the brain. That is, a stroke involves the sudden loss of neuronal function due to a disturbance in cerebral perfusion. There are many different causes for the interruption of blood supply, and different parts of the brain can be affected. Because of this, a stroke can be quite heterogeneous. Patients with the same cause of stroke can have widely differing handicaps. Similarly, patients with the same clinical handicap can in fact have different causes of their stroke.
Chordae Tendinae: cord-like tendons that connect the papillary muscles to the tricuspid valve and the mitral valve in the heart
Coronary Arteries: blood vessels that supply blood to, and remove blood from, the heart muscle itself
Continuous Capillaries: have a sealed epithelium and only allow small molecules, water and ions to diffuse
Deep-vein thrombosis (DVT): is the formation of a blood clot ("thrombus") in a deep vein. It commonly affects the leg veins, such as the femoral vein or the popliteal vein or the deep veins of the pelvis. Occasionally the veins of the arm are affected
Diastole: period of time when the heart relaxes after contraction in preparation for refilling with circulating blood
Diastolic Pressure: lowest point in blood pressure where the heart relaxes
Edema: The swelling that forms when too much tissue fluid forms or not enough taken away
Electrocardiogram: the recording of the heart's electrical activity as a graph
Epinephrine: Produced in the adrenal medulla of the adrenal glands, major function is vasoconstriction that will in turn increase respiratory rate and increase cardiac out put.
Fenestrated Capillaries: have openings that allow larger molecules to diffuse
Fibrous Pericardium: a dense connective tissue that protects the heart, anchoring it to the surrounding walls, and preventing it from overfilling with blood
Heart Rate: term used to describe the frequency of the cardiac cycle
Hepatic Veins: blood vessels that drain de-oxygenated blood from the liver and blood cleaned by the liver (from the stomach, pancreas, small intestine and colon) into the inferior vena cava
Hypertension or High Blood Pressure: medical condition wherein the blood pressure is chronically elevated
Inferior Vena Cava (or IVC): a large vein that carries de-oxygenated blood from the lower half of the body into the heart
Intraventricular Septum: the stout wall separating the lower chambers (the ventricles) of the heart from one another
Left Atrium:receives oxygenated blood from the left and right pulmonary veins
Lub: first heart tone, or S1; caused by the closure of the atrioventricular valves, mitral and tricuspid, at the beginning of ventricular contraction, or systole
Lumen: hollow internal cavity in which the blood flows
Lymph: originates as blood plasma that leaks from the capillaries of the circulatory system, becoming interstitial fluid, filling the space between individual cells of tissue
Mitral valve: also known as the bicuspid valve; prevents blood flowing from the left ventricle into the left atrium
Myocardium: the muscular tissue of the heart.
Norepinephrine: Produced in the adrenal medulla of the adrenal glands, major function is a strong vasoconstrictor that will in turn increase respiratory rate.
Pacemaker Cells: cells that create these rhythmical impulses of the heart
Plaque: an abnormal inflammatory accumulation of macrophage white blood cells within the walls of arteries
Pulmonary Valve: lies between the right ventricle and the pulmonary artery; prevents back-flow of blood into the ventricle
Pulse: the number of heartbeats per minute
Purkinje Fibers (or Purkinje tissue): located in the inner ventricular walls of the heart, just beneath the endocardium; specialized myocardial fibers that conduct an electrical stimulus or impulse that enables the heart to contract in a coordinated fashion
Renin-Angiotension system:
Right Atrium: receives de-oxygenated blood from the superior vena cava and inferior vena cava
Serous Pericardium: functions in lubricating the heart to prevent friction from occurring during heart activity
Semilunar Valves: positioned on the pulmonary artery and the aorta
Sinoatrial Node: (abbreviated SA node or SAN, also called the sinus node): the impulse generating (pacemaker) tissue located in the right atrium of the heart
Sinusoidal Capillaries: special forms of fenestrated capillaries that have larger opening allowing RBCs and serum proteins to enter
Systole: contraction of the heart
Systolic Pressure:' the highest point in blood pressure when the blood is being pumped out of the left ventricle into the aorta during ventricular systole
Superior Vena Cava (SVC): a large but short vein that carries de-oxygenated blood from the upper half of the body to the heart's right atrium
Thrombus: a blood clot in an intact blood vessel
Tricuspid Valve: on the right side of the heart, between the right atrium and the right ventricle; allows blood to flow from the right atrium into the right ventricle when the heart is relaxed during diastole
Vasoconstriction: the constriction of blood vessels
Vasodilation: the dilation of blood vessels
Veins:carry de-oxygenated blood from the capillary blood vessels to the right part of the heart
Ventricle: a heart chamber which collects blood from an atrium
Venule: a small blood vessel that allows deoxygenated blood to return from the capillary beds to the larger blood vessels called veins

## References

1. Van De Graaff, Kent M. Human Anatomy. McGraw Hill Publishing, Burr Ridge, IL. 2002.
2. Essentials of Anatomy and Physiology, Valerie C. Scanlon and Tina Sanders
3. Tortora, G. & Grabowski, S. (2000) Principles of Anatomy & Physiology. Wiley & Sons. Brisbane, Singapore & Chichester.
4. Anderson, RM. The Gross Physiology of the Cardiovascular System (1993) <http://cardiac-output.info>.
1. Tortora, G. & Grabowski, S. (2000)Principles of anatomy and physiology. Ninth Edition. Wiley page 733.

# The Urinary System

## Introduction

The Urinary System is a group of organs in the body concerned with filtering out excess fluid and other substances from the bloodstream. The substances are filtered out from the body in the form of urine. Urine is a liquid produced by the kidneys, collected in the bladder and excreted through the urethra. Urine is used to extract excess minerals or vitamins as well as blood corpuscles from the body. The Urinary organs include the kidneys, ureters, bladder, and urethra. The Urinary system works with the other systems of the body to help maintain homeostasis. The kidneys are the main organs of homeostasis because they maintain the acid base balance and the water salt balance of the blood.

## Functions of the Urinary System

One of the major functions of the Urinary system is the process of excretion. Excretion is the process of eliminating, from an organism, waste products of metabolism and other materials that are of no use. The urinary system maintains an appropriate fluid volume by regulating the amount of water that is excreted in the urine. Other aspects of its function include regulating the concentrations of various electrolytes in the body fluids and maintaining normal pH of the blood. Several body organs carry out excretion, but the kidneys are the most important excretory organ. The primary function of the kidneys is to maintain a stable internal environment (homeostasis) for optimal cell and tissue metabolism. They do this by separating urea, mineral salts, toxins, and other waste products from the blood. They also do the job of conserving water, salts, and electrolytes. At least one kidney must function properly for life to be maintained. Six important roles of the kidneys are:

Regulation of plasma ionic composition. Ions such as sodium, potassium, calcium, magnesium, chloride, bicarbonate, and phosphates are regulated by the amount that the kidney excretes.

Regulation of plasma osmolarity. The kidneys regulate osmolarity because they have direct control over how many ions and how much water a person excretes.

Regulation of plasma volume. Your kidneys are so important they even have an effect on your blood pressure. The kidneys control plasma volume by controlling how much water a person excretes. The plasma volume has a direct effect on the total blood volume, which has a direct effect on your blood pressure. Salt(NaCl)will cause osmosis to happen; the diffusion of water into the blood.

Regulation of plasma hydrogen ion concentration (pH). The kidneys partner up with the lungs and they together control the pH. The kidneys have a major role because they control the amount of bicarbonate excreted or held onto. The kidneys help maintain the blood Ph mainly by excreting hydrogen ions and reabsorbing bicarbonate ions as needed.

Removal of metabolic waste products and foreign substances from the plasma. One of the most important things the kidneys excrete is nitrogenous waste. As the liver breaks down amino acids it also releases ammonia. The liver then quickly combines that ammonia with carbon dioxide, creating urea which is the primary nitrogenous end product of metabolism in humans. The liver turns the ammonia into urea because it is much less toxic. We can also excrete some ammonia, creatinine and uric acid. The creatinine comes from the metabolic breakdown of creatine phospate (a high-energy phosphate in muscles). Uric acid comes from the break down of nucleotides. Uric acid is insoluble and too much uric acid in the blood will build up and form crystals that can collect in the joints and cause gout.

Secretion of Hormones The endocrine system has assistance from the kidney's when releasing hormones. Renin is released by the kidneys. Renin leads to the secretion of aldosterone which is released from the adrenal cortex. Aldosterone promotes the kidneys to reabsorb the sodium (Na+) ions. The kidneys also secrete erythropoietin when the blood doesn't have the capacity to carry oxygen. Erythropoietin stimulates red blood cell production. The Vitamin D from the skin is also activated with help from the kidneys. Calcium (Ca+) absorption from the digestive tract is promoted by vitamin D.

CC: Chapter Check: Name the role of the kidneys and how they work?

## Organs in the Urinary System

### Kidneys And Their Structure

Kidney Diagram: 1. Renal pyramid 2. Interlobar artery 3. Renal artery 4. Renal vein 5. Renal hylum 6. Renal pelvis 7. Ureter 8. Minor calyx 9. Renal capsule 10. Inferior renal capsule 11. Superior renal capsule 12. Interlobar vein 13. Nephron 14. Minor calyx 15. Major calyx 16. Renal papilla 17. Renal column

The kidneys are a pair of bean shaped, brown organs about the size of your fist.It measures 10-12 cm long. They are covered by the renal capsule, which is a tough capsule of fibrous connective tissue. Adhering to the surface of each kidney is two layers of fat to help cushion them. There is a concaved side of the kidney that has a depression where a renal artery enters, and a renal vein and a ureter exit the kidney. The kidneys are located at the rear wall of the abdominal cavity just above the waistline, and are protected by the ribcage. They are considered retroperitoneal, which means they lie behind the peritoneum. There are three major regions of the kidney, renal cortex, renal medulla and the renal pelvis. The outer, granulated layer is the renal cortex. The cortex stretches down in between a radially striated inner layer. The inner radially striated layer is the renal medulla. This contains pyramid shaped tissue called the renal pyramids, separated by renal columns. The ureters are continuous with the renal pelvis and is the very center of the kidney.

#### Renal Vein

The renal veins are veins that drain the kidney. They connect the kidney to the inferior vena cava. Because the inferior vena cava is on the right half of the body, the left renal vein is generally the longer of the two. Unlike the right renal vein, the left renal vein often receives the left gonadal vein (left testicular vein in males, left ovarian vein in females). It frequently receives the left suprarenal vein as well.

#### Renal Artery

The renal arteries normally arise off the abdominal aorta and supply the kidneys with blood. The arterial supply of the kidneys are variable and there may be one or more renal arteries supplying each kidney. Due to the position of the aorta, the inferior vena cava and the kidneys in the body, the right renal artery is normally longer than the left renal artery. The right renal artery normally crosses posteriorly to the inferior vena cava. The renal arteries carry a large portion of the total blood flow to the kidneys. Up to a third of the total cardiac output can pass through the renal arteries to be filtered by the kidneys.

### Ureters

The ureters are two tubes that drain urine from the kidneys to the bladder. Each ureter is a muscular tube about 10 inches (25 cm) long. Muscles in the walls of the ureters send the urine in small spurts into the bladder, (a collapsible sac found on the forward part of the cavity of the bony pelvis that allows temporary storage of urine). After the urine enters the bladder from the ureters, small folds in the bladder mucosa act like valves preventing backward flow of the urine. The outlet of the bladder is controlled by a sphincter muscle. A full bladder stimulates sensory nerves in the bladder wall that relax the sphincter and allow release of the urine. However, relaxation of the sphincter is also in part a learned response under voluntary control. The released urine enters the urethra.

The urinary bladder is a hollow, muscular and distendible or elastic organ that sits on the pelvic floor (superior to the prostate in males). On its anterior border lies the pubic symphysis and, on its posterior border, the vagina (in females) and rectum (in males). The urinary bladder can hold approximately 17 to 18 ounces (500 to 530 ml) of urine, however the desire to micturate is usually experienced when it contains about 150 to 200 ml. When the bladder fills with urine (about half full), stretch receptors send nerve impulses to the spinal cord, which then sends a reflex nerve impulse back to the sphincter (muscular valve) at the neck of the bladder, causing it to relax and allow the flow of urine into the urethra. The Internal urethral sphincter is involuntary. The ureters enter the bladder diagonally from its dorsolateral floor in an area called the trigone. The trigone is a triangular shaped area on the postero-inferior wall of the bladder. The urethra exits at the lowest point of the triangle of the trigone. The urine in the bladder also helps regulate body temperature. A bladder when operating normally empties completely upon a complete discharge, otherwise it is a sign that its elasticity is compromised, when it becomes completely void of fluid, it may cause a chilling sensation due to the rapid change of body temperature.

### Urethra

Female urethra (labeled at bottom right.)
Male Sphincter urethrae muscle - The male urethra laid open on its anterior (upper) surface. (Region visible, but muscle not labeled.)

The urethra is a muscular tube that connects the bladder with the outside of the body. The function of the urethra is to remove urine from the body. It measures about 1.5 inches (3.8 cm) in a woman but up to 8 inches (20 cm) in a man. Because the urethra is so much shorter in a woman it makes it much easier for a woman to get harmful bacteria in her bladder this is commonly called a bladder infection or a UTI. The most common bacteria of a UTI is E-coli from the large intestines that have been excreted in fecal matter. Female urethra

In the human female, the urethra is about 1-2 inches long and opens in the vulva between the clitoris and the vaginal opening.

Men have a longer urethra than women. This means that women tend to be more susceptible to infections of the bladder (cystitis) and the urinary tract.

Male urethra

In the human male, the urethra is about 8 inches long and opens at the end of the head of the penis.

The length of a male's urethra, and the fact it contains a number of bends, makes catheterisation more difficult.

The urethral sphincter is a collective name for the muscles used to control the flow of urine from the urinary bladder. These muscles surround the urethra, so that when they contract, the urethra is closed.

• There are two distinct areas of muscle: the internal sphincter, at the bladder neck and
• the external, or distal, sphincter.

Human males have much stronger sphincter muscles than females, meaning that they can retain a large amount of urine for twice as long, as much as 800mL, i.e. "hold it".

### Nephrons

A nephron is the basic structural and functional unit of the kidney. The name nephron comes from the Greek word (nephros) meaning kidney. Its chief function is to regulate water and soluble substances by filtering the blood, reabsorbing what is needed and excreting the rest as urine. Nephrons eliminate wastes from the body, regulate blood volume and pressure, control levels of electrolytes and metabolites, and regulate blood pH. Its functions are vital to life and are regulated by the endocrine system by hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone.

Each nephron has its own supply of blood from two capillary regions from the renal artery. Each nephron is composed of an initial filtering component (the renal corpuscle) and a tubule specialized for reabsorption and secretion (the renal tubule). The renal corpuscle filters out large solutes from the blood, delivering water and small solutes to the renal tubule for modification.

#### Glomerulus

The glomerulus is a capillary tuft that receives its blood supply from an afferent arteriole of the renal circulation. The glomerular blood pressure provides the driving force for fluid and solutes to be filtered out of the blood and into the space made by Bowman's capsule. The remainder of the blood not filtered into the glomerulus passes into the narrower efferent arteriole. It then moves into the vasa recta, which are collecting capillaries intertwined with the convoluted tubules through the interstitial space, where the reabsorbed substances will also enter. This then combines with efferent venules from other nephrons into the renal vein, and rejoins with the main bloodstream.

Afferent/Efferent Arterioles

The afferent arteriole supplies blood to the glomerulus. A group of specialized cells known as juxtaglomerular cells are located around the afferent arteriole where it enters the renal corpuscle. The efferent arteriole drains the glomerulus. Between the two arterioles lies specialized cells called the macula densa. The juxtaglomerular cells and the macula densa collectively form the juxtaglomerular apparatus. It is in the juxtaglomerular apparatus cells that the enzyme renin is formed and stored. Renin is released in response to decreased blood pressure in the afferent arterioles, decreased sodium chloride in the distal convoluted tubule and sympathetic nerve stimulation of receptors (beta-adrenic) on the juxtaglomerular cells. Renin is needed to form Angiotensin I and Angiotensin II which stimulate the secretion of aldosterone by the adrenal cortex.

#### Glomerular Capsule or Bowman's Capsule

Bowman's capsule (also called the glomerular capsule) surrounds the glomerulus and is composed of visceral (simple squamous epithelial cells) (inner) and parietal (simple squamous epithelial cells) (outer) layers. The visceral layer lies just beneath the thickened glomerular basement membrane and is made of podocytes which send foot processes over the length of the glomerulus. Foot processes interdigitate with one another forming filtration slits that, in contrast to those in the glomeruluar endothelium, are spanned by diaphragms. The size of the filtration slits restricts the passage of large molecules (eg, albumin) and cells (eg, red blood cells and platelets). In addition, foot processes have a negatively-charged coat (glycocalyx) that limits the filtration of negatively-charged molecules, such as albumin. This action is called electrostatic repulsion.

The parietal layer of Bowman's capsule is lined by a single layer of squamous epithelium. Between the visceral and parietal layers is Bowman's space, into which the filtrate enters after passing through the podocytes' filtration slits. It is here that smooth muscle cells and macrophages lie between the capillaries and provide support for them. Unlike the visceral layer, the parietal layer does not function in filtration. Rather, the filtration barrier is formed by three components: the diaphragms of the filtration slits, the thick glomerular basement membrane, and the glycocalyx secreted by podocytes. 99% of glomerular filtrate will ultimately be reabsorbed.

The process of filtration of the blood in the Bowman's capsule is ultrafiltration (or glomerular filtration), and the normal rate of filtration is 125 ml/min, equivalent to ten times the blood volume daily. Measuring the glomerular filtration rate (GFR) is a diagnostic test of kidney function. A decreased GFR may be a sign of renal failure. Conditions that can affect GFR include: arterial pressure, afferent arteriole constriction, efferent arteriole constriction, plasma protein concentration and colloid osmotic pressure.

Any proteins that are roughly 30 kilodaltons or under can pass freely through the membrane. Although, there is some extra hindrance for negatively charged molecules due to the negative charge of the basement membrane and the podocytes. Any small molecules such as water, glucose, salt (NaCl), amino acids, and urea pass freely into Bowman's space, but cells, platelets and large proteins do not. As a result, the filtrate leaving the Bowman's capsule is very similar to blood plasma in composition as it passes into the proximal convoluted tubule. Together, the glomerulus and Bowman's capsule are called the renal corpuscle.

#### Proximal Convoluted Tubule (PCT)

The proximal tubule can be anatomically divided into two segments: the proximal convoluted tubule and the proximal straight tubule. The proximal convoluted tubule can be divided further into S1 and S2 segments based on the histological appearance of it's cells. Following this naming convention, the proximal straight tubule is commonly called the S3 segment. The proximal convoluted tubule has one layer of cuboidal cells in the lumen. This is the only place in the nephron that contains cuboidal cells. These cells are covered with millions of microvilli. The microvilli serve to increase surface area for reabsorption.

Fluid in the filtrate entering the proximal convoluted tubule is reabsorbed into the peritubular capillaries, including approximately two-thirds of the filtered salt and water and all filtered organic solutes (primarily glucose and amino acids). This is driven by sodium transport from the lumen into the blood by the Na+/K+ ATPase in the basolateral membrane of the epithelial cells. Much of the mass movement of water and solutes occurs in between the cells through the tight junctions, which in this case are not selective.

The solutes are absorbed isotonically, in that the osmotic potential of the fluid leaving the proximal tubule is the same as that of the initial glomerular filtrate. However, glucose, amino acids, inorganic phosphate, and some other solutes are reabsorbed via secondary active transport through cotransport channels driven by the sodium gradient out of the nephron.

#### Loop of the Nephron or Loop of Henle

The Nephron Loop or Loop of Henle.

The loop of Henle (sometimes known as the nephron loop) is a U-shaped tube that consists of a descending limb and ascending limb. It begins in the cortex, receiving filtrate from the proximal convoluted tubule, extends into the medulla, and then returns to the cortex to empty into the distal convoluted tubule. Its primary role is to concentrate the salt in the interstitium, the tissue surrounding the loop.

Descending limb
Its descending limb is permeable to water but completely impermeable to salt, and thus only indirectly contributes to the concentration of the interstitium. As the filtrate descends deeper into the hypertonic interstitium of the renal medulla, water flows freely out of the descending limb by osmosis until the tonicity of the filtrate and interstitium equilibrate. Longer descending limbs allow more time for water to flow out of the filtrate, so longer limbs make the filtrate more hypertonic than shorter limbs.
Ascending limb
Unlike the descending limb, the ascending limb of Henle's loop is impermeable to water, a critical feature of the countercurrent exchange mechanism employed by the loop. The ascending limb actively pumps sodium out of the filtrate, generating the hypertonic interstitium that drives countercurrent exchange. In passing through the ascending limb, the filtrate grows hypotonic since it has lost much of its sodium content. This hypotonic filtrate is passed to the distal convoluted tubule in the renal cortex.

#### Distal Convoluted Tubule (DCT)

The distal convoluted tubule is similar to the proximal convoluted tubule in structure and function. Cells lining the tubule have numerous mitochondria, enabling active transport to take place by the energy supplied by ATP. Much of the ion transport taking place in the distal convoluted tubule is regulated by the endocrine system. In the presence of parathyroid hormone, the distal convoluted tubule reabsorbs more calcium and excretes more phosphate. When aldosterone is present, more sodium is reabsorbed and more potassium excreted. Atrial natriuretic peptide causes the distal convoluted tubule to excrete more sodium. In addition, the tubule also secretes hydrogen and ammonium to regulate pH. After traveling the length of the distal convoluted tubule, only 3% of water remains, and the remaining salt content is negligible. 97.9% of the water in the glomerular filtrate enters the convoluted tubules and collecting ducts by osmosis.

#### Collecting ducts

Each distal convoluted tubule delivers its filtrate to a system of collecting ducts, the first segment of which is the connecting tubule. The collecting duct system begins in the renal cortex and extends deep into the medulla. As the urine travels down the collecting duct system, it passes by the medullary interstitium which has a high sodium concentration as a result of the loop of Henle's countercurrent multiplier system. Though the collecting duct is normally impermeable to water, it becomes permeable in the presence of antidiuretic hormone (ADH). As much as three-fourths of the water from urine can be reabsorbed as it leaves the collecting duct by osmosis. Thus the levels of ADH determine whether urine will be concentrated or dilute. Dehydration results in an increase in ADH, while water sufficiency results in low ADH allowing for diluted urine. Lower portions of the collecting duct are also permeable to urea, allowing some of it to enter the medulla of the kidney, thus maintaining its high ion concentration (which is very important for the nephron).

Urine leaves the medullary collecting ducts through the renal papilla, emptying into the renal calyces, the renal pelvis, and finally into the bladder via the ureter. Because it has a different embryonic origin than the rest of the nephron (the collecting duct is from endoderm whereas the nephron is from mesoderm), the collecting duct is usually not considered a part of the nephron proper.

Renal Hormones

1. Vitamin D- Becomes metabolically active in the kidney. Patients with renal disease have symptoms of disturbed calcium and phosphate balance.

2. Erythropoietin- Released by the kidneys in response to decreased tissue oxygen levels (hypoxia).

3. Natriuretic Hormone- Released from cardiocyte granules located in the right atria of the heart in response to increased atrial stretch. It inhibits ADH secretions which can contribute to the loss of sodium and water.

## Formation of Urine

Urine is formed in three steps: Filtration, Reabsorption, and Secretion.

### Filtration

Blood enters the afferent arteriole and flows into the glomerulus. Blood in the glomerulus has both filterable blood components and non-filterable blood components. Filterable blood components move toward the inside of the glomerulus while non-filterable blood components bypass the filtration process by exiting through the efferent arteriole. Filterable Blood components will then take a plasma like form called glomerular filtrate. A few of the filterable blood components are water, nitrogenous waste, nutrients and salts (ions). Nonfilterable blood components include formed elements such as blood cells and platelets along with plasma proteins. The glomerular filtrate is not the same consistency as urine, as much of it is reabsorbed into the blood as the filtrate passes through the tubules of the nephron.

### Reabsorption

Within the peritubular capillary network, molecules and ions are reabsorbed back into the blood. Sodium Chloride reabsorbed into the system increases the osmolarity of blood in comparison to the glomerular filtrate. This reabsorption process allows water (H2O) to pass from the glomerular filtrate back into the circulatory system.

Glucose and various amino acids also are reabsorbed into the circulatory system. These nutrients have carrier molecules that claim the glomerular molecule and release it back into the circulatory system. If all of the carrier molecules are used up, excess glucose or amino acids are set free into the urine. A complication of diabetes is the inability of the body to reabsorb glucose. If too much glucose appears in the glomerular filtrate it increases the osmolarity of the filtrate, causing water to be released into the urine rather than reabsorbed by the circulatory system. Frequent urination and unexplained thirst are warning signs of diabetes, due to water not being reabsorbed.

Glomerular filtrate has now been separated into two forms: Reabsorbed Filtrate and Non-reabsorbed Filtrate. Non-reabsorbed filtrate is now known as tubular fluid as it passes through the collecting duct to be processed into urine.

### Secretion

Some substances are removed from blood through the peritubular capillary network into the distal convoluted tubule or collecting duct. These substances are Hydrogen ions, creatinine, and drugs. Urine is a collection of substances that have not been reabsorbed during glomerular filtration or tubular reabsorbtion.

## Maintaining Water-Salt Balance

It is the job of the kidneys to maintain the water-salt balance of the blood. They also maintain blood volume as well as blood pressure. Simple examples of ways that this balance can be changed include ingestion of water, dehydration, blood loss and salt ingestion.

### Reabsorption of water

Direct control of water excretion in the kidneys is exercised by the anti-diuretic hormone (ADH), released by the posterior lobe of the pituitary gland. ADH causes the insertion of water channels into the membranes of cells lining the collecting ducts, allowing water reabsorption to occur. Without ADH, little water is reabsorbed in the collecting ducts and dilute urine is excreted. There are several factors that influence the secretion of ADH. The first of these happen when the blood plasma gets too concentrated. When this occurs, special receptors in the hypothalamus release ADH. When blood pressure falls, stretch receptors in the aorta and carotid arteries stimulate ADH secretion to increase volume of the blood.

### Reabsorption of Salt

The Kidneys also regulate the salt balance in the blood by controlling the excretion and the reabsorption of various ions. As noted above, ADH plays a role in increasing water reabsorption in the kidneys, thus helping to dilute bodily fluids. The kidneys also have a regulated mechanism for reabsorbing sodium in the distal nephron. This mechanism is controlled by aldosterone, a steroid hormone produced by the adrenal cortex. Aldosterone promotes the excretion of potassium ions and the reabsorption of sodium ions. The release of Aldosterone is initiated by the kidneys. The juxtaglomerular apparatus is a renal structure consisting of the macula densa, mesangial cells, and juxtaglomerular cells. Juxtaglomerular cells (JG cells, also known as granular cells) are the site of renin secretion. Renin is an enzyme that converts angiotensinogen (a large plasma protein produced by the liver) into Angiotensin I and eventually into Angiotensin II which stimulates the adrenal cortex to produce aldosterone. The reabsorption of sodium ions is followed by the reapsorption of water. This causes blood pressure as well as blood volume to increase.

Atrial natriuretic hormone (ANH) is released by the atria of the heart when cardiac cells are stretched due to increased blood volume. ANH inhibits the secretion of renin by the juxtaglomerular apparatus and the secretion of the aldosterone by the adrenal cortex. This promotes the excretion of sodium. When sodium is excreted so is water. This causes blood pressure and volume to decrease.

#### Hypernatremia

An increase in plasma sodium levels above normal is hypernatremia. Sodium is the primary solute in the extracellular fluid. Sodium levels have a major role in osmolarity regulation. For excitable cells the electrochemical gradient for sodium across the plasma membrane is critical for life. Water retention and an increased blood pressure usually are signs of hypernatremia. If the plasma sodium levels are below normal it is called hyponatremia. Signs of this are low plasma volume and hypotension.

#### Diuretics

A diuretic (colloquially called a water pill) is any drug that elevates the rate of bodily urine excretion (diuresis). Diuretics also decrease the extracellular fluid (ECF) volume, and are primarily used to produce a negative extracellular fluid balance. Caffeine, cranberry juice and alcohol are all weak diuretics. In medicine, diuretics are used to treat heart failure, liver cirrhosis, hypertension and certain kidney diseases. Diuretics alleviate the symptoms of these diseases by causing sodium and water loss through the urine. As urine is produced by the kidney, sodium and water – which cause edema related to the disease – move into the blood to replace the volume lost as urine, thereby reducing the pathological edema. Some diuretics, such as acetazolamide, help to make the urine more alkaline and are helpful in increasing excretion of substances such as aspirin in cases of overdose or poisoning. The antihypertensive actions of some diuretics (thiazides and loop diuretics in particular) are independent of their diuretic effect. That is, the reduction in blood pressure is not due to decreased blood volume resulting from increased urine production, but occurs through other mechanisms and at lower doses than that required to produce diuresis. Indapamide was specifically designed with this is mind, and has a larger therapeutic window for hypertension (without pronounced diuresis) than most other diuretics. Chemically, diuretics are a diverse group of compounds that either stimulate or inhibit various hormones that naturally occur in the body to regulate urine production by the kidneys. Alcohol produces diuresis through modulation of the vasopressin system.

## Diseases of the Kidney

Diabetic nephropathy (nephropatia diabetica), also known as Kimmelstiel-Wilson syndrome and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nodular glomerulosclerosis. It is due to longstanding diabetes mellitus, and is a prime cause for dialysis in many Western countries.

An image of a kidney stone.

In medicine, hematuria (or "haematuria") is the presence of blood in the urine. It is a sign of a large number of diseases of the kidneys and the urinary tract, ranging from trivial to lethal.

Kidney stones, also known as nephrolithiases, urolithiases or renal calculi, are solid accretions (crystals) of dissolved minerals in urine found inside the kidneys or ureters. They vary in size from as small as a grain of sand to as large as a golf ball. Kidney stones typically leave the body in the urine stream; if they grow relatively large before passing (on the order of millimeters), obstruction of a ureter and distention with urine can cause severe pain most commonly felt in the flank, lower abdomen and groin. Kidney stones are unrelated to gallstones.

Case Study I was 34 weeks pregnant when I noticed blood in my urine. I immediately went to my OBGYN where I was told that I had a bladder infection and given an antibiotic. The next morning I experienced the most intense pain. I was rushed to the ER where I was told that I had kidney stones. The doctors explained that there was nothing they could do as long as I was pregnant. The next 3 weeks of my life were filled with intense pain and multiple painkillers. After I delivered my baby, CAT scans were done and I was informed that I had 6 kidney stones. It took three more weeks for me to pass all of the stones the largest measuring 5 mm. The stones were tested and I was informed that my body had been building up calcium due to my pregnancy and this was the cause of the kidney stones. I continued to have kidney pain for 6 months after passing the stones. I now live my life on a low calcium diet and the hope that my body will not develop more kidney stones.

Pyelonephritis When an infection of the renal pelvis and calices, called pyelitis, spreads to involve the rest of the kidney as well, the result is pyelonephritis. It usually results from the spread of fecal bacterium Escherichia coli from the anal region superiorly through the urinary tract. In severe cases, the kidney swells and scars, abscesses form, and the renal pelvis fills with pus. Left untreated, the infected kidney may be severely damaged, but administration of antibiotics usually achieve a total cure.

glomerulonephritis Inflammation of the glomerular can be caused by immunologic abnormalities, drugs or toxins, vascular disorders, and systemic diseases. Glomerulonephritis can be acute, chronic or progressive. Two major changes in the urine are distinctive of glomerulonephritis: hematuria and proteinuria with albumin as the major protein. There is also a decrease in urine as there is a decrease in GFR (glomerular filtration rate). Renal failure is associated with oliguria (less than 400 ml of urine output per day).

Renal Failure Uremia is a syndrome of renal failure and includes elevated blood urea and creatinine levels. Acute renal failure can be reversed if diagnosed early. Acute renal failure can be caused by severe hypotension or severe glomerular disease. Diagnostic tests include BUN and plasma creatinine level tests. It is considered to be chronic renal failure if the decline of renal function to less than 25%.

## Diabetes Insipidus

This is caused by the deficiency of or decrease of ADH. The person with (DI) has the inability to concentrate their urine in water restriction, in turn they will void up 3 to 20 liters/day. There are two forms of (DI), neurogenic, and nephrogenic. In nephrogenic (DI) the kidneys do not respond to ADH. Usually the nephrogenic (DI) is characterized by the impairment of the urine concentrating capability of the kidney along with concentration of water. The cause may be a genetic trait, electrolyte disorder, or side effect of drugs such as lithium. In the neurogenic (DI), it is usually caused by head injury near the hypophysisal tract.

## Urinary tract infections (UTI's)

The second most common type of bacterial infections seen by health care providers is UTI's. Out of all the bacterias that colonize and cause urinary tract infections the big gun is Escherichia coli. In the hospital indwelling catheters and straight catheterizing predispose the opportunity for urinary tract infections. In females there are three stages in life that predispose urinary tract infections, that is menarche, manipulation between intercourse, and menopause. However, a small percentage of men and children will get urinary tract infections. In men it is usually due to the prostate gland growth which usually occurs in older age men. In children it can occur 3% to 5% in girls and 1% in boys, uncircumcised boys it is more common than circumcised ones to have a urinary tract infection, in girls it may be the result of onset of toilet training, some predispositions for getting urinary tract infection include family history and urinary tract anomalies. In neonates urinary tract infections is most common when bacteremia is present.

## Dialysis and Kidney Transplant

Plugged into dialysis

Generally, humans can live normally with just one kidney. Only when the amount of functioning kidney tissue is greatly diminished will renal failure develop. If renal function is impaired, various forms of medications are used, while others are contraindicated. Provided that treatment is begun early, it may be possible to reverse chronic kidney failure due to diabetes or high blood pressure. If creatinine clearance (a measure of renal function) has fallen very low ("end-stage renal failure"), or if the renal dysfunction leads to severe symptoms, dialysis is commenced. Dialysis is a medical procedure, performed in various different forms, where the blood is filtered outside of the body.

Kidney transplantation is the only cure for end stage renal failure; dialysis, is a supportive treatment; a form of "buying time" to bridge the inevitable wait for a suitable organ.

The first successful kidney transplant was announced on March 4, 1954 at Peter Bent Brigham Hospital in Boston. The surgery was performed by Dr. Joseph E. Murray, who was awarded the Nobel Prize in Medicine in 1990 for this feat.

There are two types of kidney transplants: living donor transplant and a cadaveric (dead donor) transplant. When a kidney from a living donor, usually a blood relative, is transplanted into the patient's body, the donor's blood group and tissue type must be judged compatible with the patient's, and extensive medical tests are done to determine the health of the donor. Before a cadaveric donor's organs can be transplanted, a series of medical tests have to be done to determine if the organs are healthy. Also, in some countries, the family of the donor must give its consent for the organ donation. In both cases, the recipient of the new organ needs to take drugs to suppress their immune system to help prevent their body from rejecting the new kidney.

## Review Questions

Answers for these questions can be found here

1.While reading a blood test I notice a high level of creatinine, I could assume from this that

A) There is a possibility of a UTI
B) There is a possibility of diabetes
C) There is a possibility of kidney failure
D) There is nothing wrong, this is normal

2.Direct control of water excretion in the kidneys is controlled by

A) Anti-diuretic hormone
B) The medulla oblongata
C) Blood plasma
D) Sodium amounts in the blood

3. Nephrons

A) Eliminate wastes from the body
B) Regulate blood volume and pressure
C) Control levels of electrolytes and metabolites
D) Regulate blood pH
E) All of the above

4. If I am dehydrated, my body will increase

A) ATP
C) Diluted urine

5.Which part of the nephron removes water, ions and nutrients from the blood?

A ) vasa recta
B ) loop of henle
C ) proximal convuluted tubule
D ) peritubular capillaries
E ) glomerulus

6.Kidneys have a direct effect on which of the following

A ) Blood pressure
B ) How much water a person excretes
C ) Total blood volume
D ) pH
E ) all of the above

7. Why do substances in the glomerulus enter the Bowman's capsule?

A ) the magnetic charge of the Bowman's capsule attracts the substances
B ) the substances are actively transported into the Bowman's capsule
C ) blood pressure of the glomerulus is so great that most substances in blood move into capsule
D ) little green men force it in with their ray guns

8. What happens in tubular excretion?

A ) urine bonds are formed between the wastes
B ) wastes are diffused from the tubule
C ) wastes move into the distal convoluted tubule from the blood
D ) blood pressure forces wastes away from the kidney

9. The countercurrent exchange system includes_________and_________.

A ) glomerulus and macula densa
B ) proximal convoluted tubule and distal convoluted tubule
C ) loop of Henle and collecting tubule
D ) afferent arteriole and efferent arteriole

10. The function of the loop of the nephron in the process of urine formation is:

A ) reabsorption of water
B ) production of filtrate
C ) reabsorption of solutes
D ) secretion of solutes

11. Name the six important roles of the kidneys.

## Glossary

Antidiuretic: lessening or decreasing of urine production or an agent that decreases the release of urine.

Catheterisation: a catheter is a tube that can be inserted into a body cavity, duct or vessel. Catheters thereby allow drainage or injection of fluids or access by surgical instruments. The process of inserting a catheter is catheterisation. In most uses a catheter is a thin, flexible tube: a "soft" catheter; in some uses, it is a larger, solid tube: a "hard" catheter.

Dehydration: condition resulting from excessive loss of body fluid.

Diabetes: a general term for a disease characterized by the beginning stages and onset of renal failure. It is derived from the Greek word diabaínein, that literally means "passing through," or "siphon", a reference to one of diabetes' major symptoms—excessive urine production.

Diuresis: secretion and passage of large amounts of urine.

Diuretic: increasing of urine production, or an agent that increases the production of urine.

Erythropoietin: hormone that stimulates stem cells in the bone marrow to produce red blood cells

Fibrous Capsule: the kidney's loose connective tissue

Glomerulus: capillary tuft that receives its blood supply from an afferent arteriole of the renal circulation.

Gluconeogenesis: the cycle of producing a glucose form fat or protein; preformed by the kidney in times of long fasting, initially gluconeogenesis is preformed by the liver

Juxtaglomerular (JG) cells: Renin-secreting cells that are in contact with the macula densa and the afferent arterioles of the renal nephron.

Juxtaglomerular apparatus (JGA): A site of juxtaglomerular cells connecting with the macula densa where renin is secreted and sensor for control of secretion of golmerular filtration rate.

Loop of Henle/ Nephron Loop: u-shaped tube that consists of a descending limb and ascending limb; primary role is to concentrate the salt in the interstitium, the tissue surrounding the loop

Medullary Pyramids or Renal Pyramids: the cone shaped masses in the kidney

Micturition: another name for excretions

Nephron: basic structural and functional unit of the kidney; chief function is to regulate water and soluble substances by filtering the blood, reabsorbing what is needed and excreting the rest as urine

Podocytes: filtration membrane, in the visceral layer of the bowman's capsule

Renal Calculi: kidney stones, solid crystals of dissolved minerals in urine found inside the kidneys

Renal Cortex: outer portion of the kidney

Renal Lobe: each pyramid together with the associated overlying cortex

Renal Pelvis: a central space, or cavity that transmits urine to the urinary bladder via the ureter

Renin: hormone released by the Juxtaglomerular (JG) cells of the kidneys when blood pressure falls

TURP: transurethral resection of the prostate. During TURP, an instrument is inserted up the urethra to remove the section of the prostate that is blocking urine flow. This is most commonly caused by benign prostatic hyperplasia (BPH). A TURP usually requires hospitalization and is done using a general or spinal anesthetic. It is now the most common surgery used to remove part of an enlarged prostate.

Urethra: a muscular tube that connects the bladder with the outside of the body

Ureters: two tubes that drain urine from the kidneys to the bladder

Urine: liquid produced by the kidneys, collected in the bladder and excreted through the urethra

Urinary Bladder: a hollow, muscular and distensible or elastic organ that sits on the pelvic floor

Urinary System: a group of organs in the body concerned with filtering out excess fluid and other substances from the bloodstream

## References

• Graaff, Van De (2002). "Human Anatomy, Sixth Edition". New York: McGraw-Hill.
• Mader, Sylvia S. (2004). Human Biology. New York: McGraw-Hill.
• Smith, Peter (1998). Internet reference, The Role of the Kidney. Department of Clinical Dental Sciences,The University of Liverpool.
• McCance, Katherine L., Heuther, Sue E. (1994). "Pathophysiology: The Biological Basis for Disease In Adults and Children, Second Edition". Mosby-Year Book, Inc.

# The Respiritory System

The Respiratory System is vital to every human being. Without it, we would cease to live outside of the womb. Let us begin by taking a look at the structure of the respiratory system and how vital it is to life. During inhalation or exhalation air is pulled towards or away from the lungs, by several cavities, tubes, and openings.

The organs of the respiratory system make sure that oxygen enters our bodies and carbon dioxide leaves our bodies.

The respiratory tract is the path of air from the nose to the lungs. It is divided into two sections: Upper Respiratory Tract and the Lower Respiratory Tract. Included in the upper respiratory tract are the Nostrils, Nasal Cavities, Pharynx, Epiglottis, and the Larynx. The lower respiratory tract consists of the Trachea, Bronchi, Bronchioles, and the Lungs.

As air moves along the respiratory tract it is warmed, moistened and filtered.

The lungs flank the heart and great vessels in the chest cavity. (Source: Gray's Anatomy of the Human Body, 20th ed. 1918.)

## Functions

In this chapter we will discuss the four processes of respiration. They are:

1. BREATHING or ventilation
2. EXTERNAL RESPIRATION, which is the exchange of gases (oxygen and carbon dioxide) between inhaled air and the blood.
3. INTERNAL RESPIRATION, which is the exchange of gases between the blood and tissue fluids.
4. CELLULAR RESPIRATION

In addition to these main processes, the respiratory system serves for:

• REGULATION OF BLOOD pH, which occurs in coordination with the kidneys, and as a
• DEFENSE AGAINST MICROBES
• Control of body temperature due to loss of evaporate during expiration

## Breathing and Lung Mechanics

Ventilation is the exchange of air between the external environment and the alveoli. Air moves by bulk flow from an area of high pressure to low pressure. All pressures in the respiratory system are relative to atmospheric pressure (760mmHg at sea level). Air will move in or out of the lungs depending on the pressure in the alveoli. The body changes the pressure in the alveoli by changing the volume of the lungs. As volume increases pressure decreases and as volume decreases pressure increases. There are two phases of ventilation; inspiration and expiration. During each phase the body changes the lung dimensions to produce a flow of air either in or out of the lungs.

The body is able to stay at the dimensions of the lungs because of the relationship of the lungs to the thoracic wall. Each lung is completely enclosed in a sac called the pleural sac. Two structures contribute to the formation of this sac. The parietal pleura is attached to the thoracic wall where as the visceral pleura is attached to the lung itself. In-between these two membranes is a thin layer of intrapleural fluid. The intrapleural fluid completely surrounds the lungs and lubricates the two surfaces so that they can slide across each other. Changing the pressure of this fluid also allows the lungs and the thoracic wall to move together during normal breathing. Much the way two glass slides with water in-between them are difficult to pull apart, such is the relationship of the lungs to the thoracic wall.

The rhythm of ventilation is also controlled by the "Respiratory Center" which is located largely in the medulla oblongata of the brain stem. This is part of the autonomic system and as such is not controlled voluntarily (one can increase or decrease breathing rate voluntarily, but that involves a different part of the brain). While resting, the respiratory center sends out action potentials that travel along the phrenic nerves into the diaphragm and the external intercostal muscles of the rib cage, causing inhalation. Relaxed exhalation occurs between impulses when the muscles relax. Normal adults have a breathing rate of 12-20 respirations per minute.

### The Pathway of Air

When one breathes air in at sea level, the inhalation is composed of different gases. These gases and their quantities are Oxygen which makes up 21%, Nitrogen which is 78%, Carbon Dioxide with 0.04% and others with significantly smaller portions.

Diagram of the Pharynx.

In the process of breathing, air enters into the nasal cavity through the nostrils and is filtered by coarse hairs (vibrissae) and mucous that are found there. The vibrissae filter macroparticles, which are particles of large size. Dust, pollen, smoke, and fine particles are trapped in the mucous that lines the nasal cavities (hollow spaces within the bones of the skull that warm, moisten, and filter the air). There are three bony projections inside the nasal cavity. The superior, middle, and inferior nasal conchae. Air passes between these conchae via the nasal meatuses.

Air then travels past the nasopharynx, oropharynx, and laryngopharynx, which are the three portions that make up the pharynx. The pharynx is a funnel-shaped tube that connects our nasal and oral cavities to the larynx. The tonsils which are part of the lymphatic system, form a ring at the connection of the oral cavity and the pharynx. Here, they protect against foreign invasion of antigens. Therefore, the respiratory tract aids the immune system through this protection. Then the air travels through the larynx. The larynx closes at the epiglottis to prevent the passage of food or drink as a protection to our trachea and lungs. The larynx is also our voicebox; it contains vocal cords, in which it produces sound. Sound is produced from the vibration of the vocal cords when air passes through them.

The trachea, which is also known as our windpipe, has ciliated cells and mucous secreting cells lining it, and is held open by C-shaped cartilage rings. One of its functions is similar to the larynx and nasal cavity, by way of protection from dust and other particles. The dust will adhere to the sticky mucous and the cilia helps propel it back up the trachea, to where it is either swallowed or coughed up. The mucociliary escalator extends from the top of the trachea all the way down to the bronchioles, which we will discuss later. Through the trachea, the air is now able to pass into the bronchi, bronchioles and finally alveoli before entering the pulmonary capillaries. There is lots of oxygen and then there is less carbon dioxide when the air comes in, but when it diffuses, the amounts exchange. All of this happens in seconds.

### Inspiration

Inspiration is initiated by contraction of the diaphragm and in some cases the intercostals muscles when they receive nervous impulses. During normal quiet breathing, the phrenic nerves stimulate the diaphragm to contract and move downward into the abdomen. This downward movement of the diaphragm enlarges the thorax. When necessary, the intercostal muscles also increase the thorax by contacting and drawing the ribs upward and outward.

As the diaphragm contracts inferiorly and thoracic muscles pull the chest wall outwardly, the volume of the thoracic cavity increases. The lungs are held to the thoracic wall by negative pressure in the pleural cavity, a very thin space filled with a few milliliters of lubricating pleural fluid. The negative pressure in the pleural cavity is enough to hold the lungs open in spite of the inherent elasticity of the tissue. Hence, as the thoracic cavity increases in volume the lungs are pulled from all sides to expand, causing a drop in the pressure (a partial vacuum) within the lung itself (but note that this negative pressure is still not as great as the negative pressure within the pleural cavity--otherwise the lungs would pull away from the chest wall). Assuming the airway is open, air from the external environment then follows its pressure gradient down and expands the alveoli of the lungs, where gas exchange with the blood takes place. As long as pressure within the alveoli is lower than atmospheric pressure air will continue to move inwardly, but as soon as the pressure is stabilized air movement stops.

### Expiration

During quiet breathing, expiration is normally a passive process and does not require muscles to work (rather it is the result of the muscles relaxing). When the lungs are stretched and expanded, stretch receptors within the alveoli send inhibitory nerve impulses to the medulla oblongata, causing it to stop sending signals to the rib cage and diaphragm to contract. The muscles of respiration and the lungs themselves are elastic, so when the diaphragm and intercostal muscles relax there is an elastic recoil, which creates a positive pressure (pressure in the lungs becomes greater than atmospheric pressure), and air moves out of the lungs by flowing down its pressure gradient.

Although the respiratory system is primarily under involuntary control, and regulated by the medulla oblongata, we have some voluntary control over it also. This is due to the higher brain function of the cerebral cortex.

When under physical or emotional stress, more frequent and deep breathing is needed, and both inspiration and expiration will work as active processes. Additional muscles in the rib cage forcefully contract and push air quickly out of the lungs. In addition to deeper breathing, when coughing or sneezing we exhale forcibly. Our abdominal muscles will contract suddenly (when there is an urge to cough or sneeze), raising the abdominal pressure. The rapid increase in pressure pushes the relaxed diaphragm up against the pleural cavity. This causes air to be forced out of the lungs.

Another function of the respiratory system is to sing and to speak. By exerting conscious control over our breathing and regulating flow of air across the vocal cords we are able to create and modify sounds.

### Lung Compliance

Lung Compliance is the magnitude of the change in lung volume produced by a change in pulmonary pressure. Compliance can be considered the opposite of stiffness. A low lung compliance would mean that the lungs would need a greater than average change in intrapleural pressure to change the volume of the lungs. A high lung compliance would indicate that little pressure difference in intrapleural pressure is needed to change the volume of the lungs. More energy is required to breathe normally in a person with low lung compliance. Persons with low lung compliance due to disease therefore tend to take shallow breaths and breathe more frequently.

Determination of Lung Compliance Two major things determine lung compliance. The first is the elasticity of the lung tissue. Any thickening of lung tissues due to disease will decrease lung compliance. The second is surface tensions at air water interfaces in the alveoli. The surface of the alveoli cells is moist. The attractive force, between the water cells on the alveoli, is called surface tension. Thus, energy is required not only to expand the tissues of the lung but also to overcome the surface tension of the water that lines the alveoli.

To overcome the forces of surface tension, certain alveoli cells (Type II pneumocytes) secrete a protein and lipid complex called ""Surfactant””, which acts like a detergent by disrupting the hydrogen bonding of water that lines the alveoli, hence decreasing surface tension.

### Control of respiration

#### central control

GO LOOK UP THE INFORMATION ON A TRUSTWORTHY WEBSITE

#### Peripheral control

CO2 is converted to HCO3; most CO2 produced at the tissue cells is carried to lungs in the form of HCO3

• CO2 & H2O form carbonic acid (H2CO3)
• changes to H CO3 & H+ ions
• result is H+ ions are buffered by plasma proteins

## Respiratory System: Upper and Lower Respiratory Tracts

For the sake of convenience, we will divide the respiratory system in to the upper and lower respiratory tracts:

### Upper Respiratory Tract

The upper respiratory tract consists of the nose and the pharynx. Its primary function is to receive the air from the external environment and filter, warm, and humidify it before it reaches the delicate lungs where gas exchange will occur.

Air enters through the nostrils of the nose and is partially filtered by the nose hairs, then flows into the nasal cavity. The nasal cavity is lined with epithelial tissue, containing blood vessels, which help warm the air; and secrete mucous, which further filters the air. The endothelial lining of the nasal cavity also contains tiny hairlike projections, called cilia. The cilia serve to transport dust and other foreign particles, trapped in mucous, to the back of the nasal cavity and to the pharynx. There the mucus is either coughed out, or swallowed and digested by powerful stomach acids. After passing through the nasal cavity, the air flows down the pharynx to the larynx. I am stressed

### Lower Respiratory Tract

The lower respiratory tract starts with the larynx, and includes the trachea, the two bronchi that branch from the trachea, and the lungs themselves. This is where gas exchange actually takes place.

1. Larynx

The larynx (plural larynges), colloquially known as the voice box, is an organ in our neck involved in protection of the trachea and sound production. The larynx houses the vocal cords, and is situated just below where the tract of the pharynx splits into the trachea and the esophagus. The larynx contains two important structures: the epiglottis and the vocal cords.

The epiglottis is a flap of cartilage located at the opening to the larynx. During swallowing, the larynx (at the epiglottis and at the glottis) closes to prevent swallowed material from entering the lungs; the larynx is also pulled upwards to assist this process. Stimulation of the larynx by ingested matter produces a strong cough reflex to protect the lungs. Note: choking occurs when the epiglottis fails to cover the trachea, and food becomes lodged in our windpipe.

The vocal cords consist of two folds of connective tissue that stretch and vibrate when air passes through them, causing vocalization. The length the vocal cords are stretched determines what pitch the sound will have. The strength of expiration from the lungs also contributes to the loudness of the sound. Our ability to have some voluntary control over the respiratory system enables us to sing and to speak. In order for the larynx to function and produce sound, we need air. That is why we can't talk when we're swallowing.

1. Trachea
2. Bronchi
3. Lungs

## Homeostasis and Gas Exchange

Gas exchange

Homeostasis is maintained by the respiratory system in two ways: gas exchange and regulation of blood pH. Gas exchange is performed by the lungs by eliminating carbon dioxide, a waste product given off by cellular respiration. As carbon dioxide exits the body, oxygen needed for cellular respiration enters the body through the lungs. ATP, produced by cellular respiration, provides the energy for the body to perform many functions, including nerve conduction and muscle contraction. Lack of oxygen affects brain function, sense of judgment, and a host of other problems.

### Gas Exchange

Gas exchange in the lungs and in the alveoli is between the alveolar air and the blood in the pulmonary capillaries. This exchange is a result of increased concentration of oxygen, and a decrease of C02. This process of exchange is done through diffusion.

### External Respiration

External respiration is the exchange of gas between the air in the alveoli and the blood within the pulmonary capillaries. A normal rate of respiration is 12-25 breaths per minute. In external respiration, gases diffuse in either direction across the walls of the alveoli. Oxygen diffuses from the air into the blood and carbon dioxide diffuses out of the blood into the air. Most of the carbon dioxide is carried to the lungs in plasma as bicarbonate ions (HCO3-). When blood enters the pulmonary capillaries, the bicarbonate ions and hydrogen ions are converted to carbonic acid (H2CO3) and then back into carbon dioxide (CO2) and water. This chemical reaction also uses up hydrogen ions. The removal of these ions gives the blood a more neutral pH, allowing hemoglobin to bind up more oxygen. De-oxygenated blood "blue blood" coming from the pulmonary arteries, generally has an oxygen partial pressure (pp) of 40 mmHg and CO2 pp of 45 mmHg. Oxygenated blood leaving the lungs via the pulmonary veins has an O2 pp of 100 mmHg and CO2 pp of 40 mmHg. It should be noted that alveolar O2 pp is 105 mmHg, and not 100 mmHg. The reason why pulmonary venous return blood has a lower than expected O2 pp can be explained by "Ventilation Perfusion Mismatch".

### Internal Respiration

Internal respiration is the exchanging of gases at the cellular level.

#### The Passage Way From the Trachea to the Bronchioles

There is a point at the inferior portion of the trachea where it branches into two directions that form the right and left primary bronchus. This point is called the Carina which is the keel-like cartilage plate at the division point. We are now at the Bronchial Tree. It is named so because it has a series of respiratory tubes that branch off into smaller and smaller tubes as they run throughout the lungs.

#### Right and Left Lungs

Diagram of the lungs

The Right Primary Bronchus is the first portion we come to, it then branches off into the Lobar (secondary) Bronchi, Segmental (tertiary) Bronchi, then to the Bronchioles which have little cartilage and are lined by simple cuboidal epithelium (See fig. 1). The bronchi are lined by pseudostratified columnar epithelium. Objects will likely lodge here at the junction of the Carina and the Right Primary Bronchus because of the vertical structure. Items have a tendency to fall in it, where as the Left Primary Bronchus has more of a curve to it which would make it hard to have things lodge there.

The Left Primary Bronchus has the same setup as the right with the lobar, segmental bronchi and the bronchioles.

The lungs are attached to the heart and trachea through structures that are called the roots of the lungs. The roots of the lungs are the bronchi, pulmonary vessels, bronchial vessels, lymphatic vessels, and nerves. These structures enter and leave at the hilus of the lung which is "the depression in the medial surface of a lung that forms the opening through which the bronchus, blood vessels, and nerves pass" (medlineplus.gov).

There are a number of terminal bronchioles connected to respiratory bronchioles which then advance into the alveolar ducts that then become alveolar sacs. Each bronchiole terminates in an elongated space enclosed by many air sacs called alveoli which are surrounded by blood capillaries. Present there as well, are Alveolar Macrophages, they ingest any microbes that reach the alveoli. The Pulmonary Alveoli are microscopic, which means they can only be seen through a microscope, membranous air sacs within the lungs. They are units of respiration and the site of gas exchange between the respiratory and circulatory systems. A good way to remember lober is by remembering loafer or loaf.

### Cellular Respiration

First the oxygen must diffuse from the alveolus into the capillaries. It is able to do this because the capillaries are permeable to oxygen. After it is in the capillary, about 5% will be dissolved in the blood plasma. The other oxygen will bind to red blood cells. The red blood cells contain hemoglobin that carries oxygen. Blood with hemoglobin is able to transport 26 times more oxygen than plasma without hemoglobin. Our bodies would have to work much harder pumping more blood to supply our cells with oxygen without the help of hemoglobin. Once it diffuses by osmosis it combines with the hemoglobin to form oxyhemoglobin.

Now the blood carrying oxygen is pumped through the heart to the rest of the body. Oxygen will travel in the blood into arteries, arterioles, and eventually capillaries where it will be very close to body cells. Now with different conditions in temperature and pH (warmer and more acidic than in the lungs), and with pressure being exerted on the cells, the hemoglobin will give up the oxygen where it will diffuse to the cells to be used for cellular respiration, also called aerobic respiration. Cellular respiration is the process of moving energy from one chemical form (glucose) into another (ATP), since all cells use ATP for all metabolic reactions.

It is in the mitochondria of the cells where oxygen is actually consumed and carbon dioxide produced. Oxygen is produced as it combines with hydrogen ions to form water at the end of the electron transport chain (see chapter on cells). As cells take apart the carbon molecules from glucose, these get released as carbon dioxide. Each body cell releases carbon dioxide into nearby capillaries by diffusion, because the level of carbon dioxide is higher in the body cells than in the blood. In the capillaries, some of the carbon dioxide is dissolved in plasma and some is taken by the hemoglobin, but most enters the red blood cells where it binds with water to form carbonic acid. It travels to the capillaries surrounding the lung where a water molecule leaves, causing it to turn back into carbon dioxide. It then enters the lungs where it is exhaled into the atmosphere.

## Lung Capacity

The normal volume moved in or out of the lungs during quiet breathing is called tidal volume. When we are in a relaxed state, only a small amount of air is brought in and out, about 500 mL. You can increase both the amount you inhale, and the amount you exhale, by breathing deeply. Breathing in very deeply is Inspiratory Reserve Volume and can increase lung volume by 2900 mL, which is quite a bit more than the tidal volume of 500 mL. We can also increase expiration by contracting our thoracic and abdominal muscles. This is called expiratory reserve volume and is about 1400 ml of air. Vital capacity is the total of tidal, inspiratory reserve and expiratory reserve volumes; it is called vital capacity because it is vital for life, and the more air you can move, the better off you are. There are a number of illnesses that we will discuss later in the chapter that decrease vital capacity. Vital Capacity can vary a little depending on how much we can increase inspiration by expanding our chest and lungs. Some air that we breathe never even reaches the lungs! Instead it fills our nasal cavities, trachea, bronchi, and bronchioles. These passages aren't used in gas exchange so they are considered to be dead air space. To make sure that the inhaled air gets to the lungs, we need to breathe slowly and deeply. Even when we exhale deeply some air is still in the lungs,(about 1000 ml) and is called residual volume. This air isn't useful for gas exchange. There are certain types of diseases of the lung where residual volume builds up because the person cannot fully empty the lungs. This means that the vital capacity is also reduced because their lungs are filled with useless air.

## Stimulation of Breathing

There are two pathways of motor neuron stimulation of the respiratory muscles. The first is the control of voluntary breathing by the cerebral cortex. The second is involuntary breathing controlled by the medulla oblongata.

There are chemoreceptors in the aorta, the carotid body of carotid arteries, and in the medulla oblongata of the brainstem that are sensitive to pH. As carbon dioxide levels increase there is a buildup of carbonic acid, which releases hydrogen ions and lowers pH. Thus, the chemoreceptors do not respond to changes in oxygen levels (which actually change much more slowly), but to pH, which is dependent upon plasma carbon dioxide levels. In other words, CO2 is the driving force for breathing. The receptors in the aorta and the carotid sinus initiate a reflex that immediately stimulates breathing rate and the receptors in the medulla stimulate a sustained increase in breathing until blood pH returns to normal.

This response can be experienced by running a 100-meter dash. During this exertion (or any other sustained exercise) your muscle cells must metabolize ATP at a much faster rate than usual, and thus will produce much higher quantities of CO2. The blood pH drops as CO2 levels increase, and you will involuntarily increase breathing rate very soon after beginning the sprint. You will continue to breathe heavily after the race, thus expelling more carbon dioxide, until pH has returned to normal. Metabolic acidosis therefore is acutely corrected by respiratory compensation (hyperventilation).

## Regulation of Blood pH

Many of us are not aware of the importance of maintaining the acid/base balance of our blood. It is vital to our survival. Normal blood pH is set at 7.4, which is slightly alkaline or "basic". If the pH of our blood drops below 7.2 or rises above 7.6 then very soon our brains would cease functioning normally and we would be in big trouble. Blood pH levels below 6.9 or above 7.9 are usually fatal if they last for more than a short time. Another wonder of our amazing bodies is the ability to cope with every pH change – large or small. There are three factors in this process: the lungs, the kidneys and buffers.

So what exactly is pH? pH is the concentration of hydrogen ions (H+). Buffers are molecules which take in or release ions in order to maintain the H+ ion concentration at a certain level. When blood pH is too low and the blood becomes too acidic (acidosis), the presence of too many H+ ions is to blame. Buffers help to soak up those extra H+ ions. On the other hand, the lack of H+ ions causes the blood to be too basic (alkalosis). In this situation, buffers release H+ ions. Buffers function to maintain the pH of our blood by either donating or grabbing H+ ions as necessary to keep the number of H+ ions floating around the blood at just the right amount.

The most important buffer we have in our bodies is a mixture of carbon dioxide (CO2) and bicarbonate ion (HCO3). CO2 forms carbonic acid (H2CO3) when it dissolves in water and acts as an acid giving up hydrogen ions (H+) when needed. HCO3 is a base and soaks up hydrogen ions (H+) when there are too many of them. In a nutshell, blood pH is determined by a balance between bicarbonate and carbon dioxide.

Bicarbonate Buffer System. With this important system our bodies maintain homeostasis. (Note that H2CO3 is Carbonic Acid and HCO3 is Bicarbonate)

CO2 + H2O <---> H2CO3 <---> (H+) + HCO3

• If pH is too high, carbonic acid will donate hydrogen ions (H+) and pH will drop.
• If pH is too low, bicarbonate will bond with hydrogen ions (H+) and pH will rise.

Too much CO2 or too little HCO3 in the blood will cause acidosis. The CO2 level is increased when hypoventilation or slow breathing occurs, such as if you have emphysema or pneumonia. Bicarbonate will be lowered by ketoacidosis, a condition caused by excess fat metabolism (diabetes mellitus).

Too much HCO3 or too little CO2 in the blood will cause alkalosis. This condition is less common than acidosis. CO2 can be lowered by hyperventilation.

So, in summary, if you are going into respiratory acidosis the above equation will move to the right. The body's H+ and CO2 levels will rise and the pH will drop. To counteract this the body will breathe more and release H+. In contrast, if you are going into respiratory alkalosis the equation will move to the left. The body's H+ and CO2 levels will fall and the pH will rise. So the body will try to breathe less to release HCO3. You can think of it like a leak in a pipe: where ever there is a leak, the body will "fill the hole".

## Problems Associated With the Respiratory Tract and Breathing

The environment of the lung is very moist, which makes it a hospitable environment for bacteria. Many respiratory illnesses are the result of bacterial or viral infection of the lungs. Because we are constantly being exposed to harmful bacteria and viruses in our environment, our respiratory health can be adversely affected. There are a number of illnesses and diseases that can cause problems with breathing. Some are simple infections, and others are disorders that can be quite serious.

Carbon Monoxide Poisoning: caused when carbon monoxide binds to hemoglobin in place of oxygen. Carbon monoxide binds much tighter, without releasing, causing the hemoglobin to become unavailable to oxygen. The result can be fatal in a very short amount of time.

Mild Symptoms: flu like symptoms, dizziness, fatigue, headaches, nausea, and irregular breathing
Moderate Symptoms: chest pain, rapid heart beat, difficulty thinking, blurred vision, shortness of breath and unsteadiness
Severe Symptoms: seizures, palpitations, disorientation, irregular heart beat, low blood pressure, coma and death.

Pulmonary Embolism: blockage of the pulmonary artery (or one of its branches) by a blood clot, fat, air or clumped tumor cells. By far the most common form of pulmonary embolism is a thromboembolism, which occurs when a blood clot, generally a venous thrombus, becomes dislodged from its site of formation and embolizes to the arterial blood supply of one of the lungs.

Symptoms may include difficulty breathing, pain during breathing, and more rarely circulatory instability and death. Treatment, usually, is with anticoagulant medication.

## Upper Respiratory Tract Infections

The upper respiratory tract consists of our nasal cavities, pharynx, and larynx. Upper respiratory infections (URI) can spread from our nasal cavities to our sinuses, ears, and larynx. Sometimes a viral infection can lead to what is called a secondary bacterial infection. "Strep throat" is a primary bacterial infection and can lead to an upper respiratory infection that can be generalized or even systemic (affects the body as a whole). Antibiotics aren't used to treat viral infections, but are successful in treating most bacterial infections, including strep throat. The symptoms of strep throat can be a high fever, severe sore throat, white patches on a dark red throat, and stomach ache.

Sinusitis
An infection of the cranial sinuses is called sinusitis. Only about 1-3% of URI's are accompanied by sinusitis. This "sinus infection" develops when nasal congestion blocks off the tiny openings that lead to the sinuses. Some symptoms include: post nasal discharge, facial pain that worsens when bending forward, and sometimes even tooth pain can be a symptom. Successful treatment depends on restoring the proper drainage of the sinuses. Taking a hot shower or sleeping upright can be very helpful. Otherwise, using a spray decongestant or sometimes a prescribed antibiotic will be necessary.
Otitis Media
Otitis media in an infection of the middle ear. Even though the middle ear is not part of the respiratory tract, it is discussed here because it is often a complication seen in children who has a nasal infection. The infection can be spread by way of the 'auditory (Eustachian) tube that leads form the nasopharynx to the middle ear. The main symptom is usually pain. Sometimes though, vertigo, hearing loss, and dizziness may be present. Antibiotics can be prescribed and tubes are placed in the eardrum to prevent the buildup of pressure in the middle ear and the possibility of hearing loss.
Photo of Tonsillitis.
Tonsillitis
Tonsillitis occurs when the tonsils become swollen and inflamed. The tonsils located in the posterior wall of the nasopharynx are often referred to as adenoids. If you suffer from tonsillitis frequently and breathing becomes difficult, they can be removed surgically in a procedure called a tonsillectomy.
Laryngitis
An infection of the larynx is called laryngitis. It is accompanied by hoarseness and being unable to speak in an audible voice. Usually, laryngitis disappears with treatment of the URI. Persistent hoarseness without a URI is a warning sign of cancer, and should be checked into by your physician.

## Lower Respiratory Tract Disorders

Lower respiratory tract disorders include infections, restrictive pulmonary disorders, obstructive pulmonary disorders, and lung cancer.

### Lower Respiratory Infections

Acute bronchitis
An infection that is located in the primary and secondary bronchi is called bronchitis. Most of the time, it is preceded by a viral URI that led to a secondary bacterial infection. Usually, a nonproductive cough turns into a deep cough that will expectorate mucus and sometimes pus.
Pneumonia
A bacterial or viral infection in the lungs where the bronchi and the alveoli fill with a thick fluid. Usually it is preceded by influenza. Symptoms of pneumonia include high fever & chills, with headache and chest pain. Pneumonia can be located in several lobules of the lung and obviously, the more lobules involved, the more serious the infection. It can be caused by a bacteria that is usually held in check, but due to stress or reduced immunity has gained the upper hand.

### Restrictive Pulmonary Disorders

Pulmonary Fibrosis
Vital capacity is reduced in these types of disorders because the lungs have lost their elasticity. Inhaling particles such as sand, asbestos, coal dust, or fiberglass can lead to pulmonary fibrosis, a condition where fibrous tissue builds up in the lungs. This makes it so our lungs cannot inflate properly and are always tending toward deflation.
Diagram of the lungs during an asthma attack.
Asthma
Asthma is a respiratory disease of the bronchi and bronchioles. The symptoms include wheezing, shortness of breath, and sometimes a cough that will expel mucus. The airways are very sensitive to irritants which can include pollen, dust, animal dander, and tobacco. Even being out in cold air can be an irritant. When exposed to an irritant, the smooth muscle in the bronchioles undergoes spasms. Most asthma patients have at least some degree of bronchial inflammation that reduces the diameter of the airways and contributes to the seriousness of the attack.
Emphysema
Emphysema is a type of chronic obstructive pulmonary disease. Typically characterized by a loss of elasticity and surfactant in the alveoli, a loss of surface area decreases the gas exchange in the lungs. These patients have difficulty with too little expiratory pressure, not retaining inspired air long enough for sufficient gas exchange to happen.
Chronic Bronchitis
Another type of chronic obstructive pulmonary disease, Chronic Bronchitis is caused by overproduction of mucus in the airways, causing an inadequate expiration of inspired air. Retention of air in the lungs reduces gas exchange at the alveoli, and can lead to a hypoxic drive. These patients are known as "blue bloaters", vulnerable to cyanosis and often have increased thoracic diameters.

## Respiratory Distress Syndrome

Pathophysiology

At birth the pressure needed to expand the lungs requires high inspiratory pressure. In the presence of normal surfactant levels the lungs retain as much as 40% of the residual volume after the first breath and thereafter will only require far lower inspiratory pressures. In the case of deficiency of surfactant the lungs will collapse between breaths, this makes the infant work hard and each breath is as hard as the first breath. If this goes on further the pulmonary capillary membranes become more permeable, letting in fibrin rich fluids between the alveolar spaces and in turn forms a hyaline membrane. The hyaline membrane is a barrier to gas exchange, this hyaline membrane then causes hypoxemia and carbon dioxide retention that in turn will further impair surfactant production.

Etiology

Type two alveolar cells produce surfactant and do not develop until the 25th to the 28th week of gestation, in this, respiratory distress syndrome is one of the most common respiratory disease in premature infants. Furthermore, surfactant deficiency and pulmonary immaturity together leads to alveolar collapse. Predisposing factors that contribute to poorly functioning type II alveolar cells in a premature baby are if the child is a preterm male, white infants, infants of mothers with diabetes, precipitous deliveries, cesarean section performed before the 38th week of gestation. Surfactant synthesis is influenced by hormones, this ranges form insulin and cortisol. Insulin inhibits surfactant production, explaining why infants of mothers with diabetes type 1 are at risk of development of respiratory distress syndrome. Cortisol can speed up maturation of type II cells and therefore production of surfactant. Finally, in the baby delivered by cesarean section are at greater risk of developing respiratory distress syndrome because the reduction of cortisol produced because the lack of stress that happens during vaginal delivery, hence cortisol increases in high stress and helps in the maturation of type II cells of the alveoli that cause surfactant.

Treatment

Today to prevent respiratory distress syndrome are animal sources and synthetic surfactants, and administrated through the airways by an endotracheal tube and the surfactant is suspended in a saline solution. Treatment is initiated post birth and in infants who are at high risk for respiratory distress syndrome.

## Sleep Apnea

CPAP is the most common treatment for obstructive sleep apnea.

Sleep apnea or sleep apnoea is a sleep disorder characterized by pauses in breathing during sleep. These episodes, called apneas (literally, "without breath"), each last long enough so one or more breaths are missed, and occur repeatedly throughout sleep. The standard definition of any apneic event includes a minimum 10 second interval between breaths, with either a neurological arousal (3-second or greater shift in EEG frequency, measured at C3, C4, O1, or O2), or a blood oxygen desaturation of 3-4 percent or greater, or both arousal and desaturation. Sleep apnea is diagnosed with an overnight sleep test called polysomnogram. One method of treating central sleep apnea is with a special kind of CPAP, APAP, or VPAP machine with a Spontaneous Time (ST) feature. This machine forces the wearer to breathe a constant number of breaths per minute.

(CPAP), or continuous positive airway pressure, in which a controlled air compressor generates an airstream at a constant pressure. This pressure is prescribed by the patient's physician, based on an overnight test or titration.

## Nutrition for COPD (Chronic Obstructive Pulmonary Disease) Patients

Nutrition is particularly important for ventilator-dependent patient. When metabolizing macronutrients carbon dioxide and water are produced. The respiratory quotient (RQ) is a ratio of produced carbon dioxide to amount consumed. Carbohydrates metabolism produces the most amount of carbon dioxide so they have the highest (RQ). Fats produce the least amount of carbon dioxide along with proteins. Protein has a slightly higher RQ ratio. It is recommended that this kind of patient not exceed a 1.0 respiratory quotient (RQ). Lowering carbohydrates and supplementing fat or protein in the diet might not result in maintaining the desired outcome because, excess amounts fat or protein may also result in a respiratory quotient (RQ) higher than 1.0.

• Please reference source and fact accuracy. It seems like by definition, it is impossible to exceed a respiratory quotient (RQ) of 1.0. *

## Case Study

Cystic Fibrosis

This disease is most common in Caucasians and will happen to 1 in every 2500 people. It is most known for its effects on the respiratory tract although it does effect other systems as well. The respiratory passages become clogged with a thick mucus that is difficult to expel even with vigorous coughing. Breathing becomes difficult and affected individuals run the risk of choking to death on their own secretions unless strenuous effort is made to clear the lungs multiple times every day. Victims frequently will die in the 20's of pneumonia. All of us secrete mucus by certain cells in the epithelium that line the respiratory passageways. In normal cases the cells also secrete a watery fluid that will dilute the mucus making it easier to pass through the airways. In cystic fibrosis that secretion of watery fluid is impaired. This makes the mucus thicker and difficult to clear from the passageways. A recent discovery found that in cystic fibrosis is caused by a defect in a type of chloride protein found in apical membranes of epithelial calls in the respiratory system and elsewhere. This defect directly impedes the chlorine ions transport, which will then indirectly effect the transport of potassium ions. This causes the epithelium, to not create its osmotic gradient necessary for water secretion. It has been known for a long time that cystic fibrosis is caused by a recessive gene inheritance. This gene codes for a portion of the chloride channel protein, which can malfunction in a variety of ways, each with specific treatment required.

# The Gastrointestinal System

## Introduction

Which organ is the most important organ in the body? Most people would say the heart or the brain, completely overlooking the gastrointestinal tract (GI tract). Though definitely not the most attractive organs in the body, they are certainly among the most important. The 30+ foot long tube that goes from the mouth to the anus is responsible for the many different body functions which will be reviewed in this chapter. The GI tract is imperative for our well being and our lifelong health. A non-functioning or poorly functioning GI tract can be the source of many chronic health problems that can interfere with your quality of life. In many instances the death of a person begins in the intestines.

The old saying "you are what you eat" perhaps would be more accurate if worded "you are what you absorb and digest". Here we will be looking at the importance of these two functions of the digestive system: digestion and absorption.

The Gastrointestinal System is responsible for the breakdown and absorption of various foods and liquids needed to sustain life. Many different organs have essential roles in the digestion of food, from the mechanical disrupting by the teeth to the creation of bile (an emulsifier) by the liver. Bile production of the liver plays an important role in digestion: from being stored and concentrated in the gallbladder during fasting stages to being discharged to the small intestine.

In order to understand the interactions of the different components we shall follow the food on its journey through the human body. During digestion, two main processes occur at the same time;

• Mechanical Digestion: larger pieces of food get broken down into smaller pieces while being prepared for chemical digestion. Mechanical digestion starts in the mouth and continues into the stomach.
• Chemical Digestion: starts in the mouth and continues into the intestines. Several different enzymes break down macromolecules into smaller molecules that can be absorbed.

The GI tract starts with the mouth and proceeds to the esophagus, stomach, small intestine (duodenum, jejunum, ileum), and then to the large intestine (colon), rectum, and terminates at the anus. You could probably say the human body is just like a big donut. The GI tract is the donut hole. We will also be discussing the pancreas and liver, and accessory organs of the gastrointestinal system that contribute materials to the small intestine.

## Layers of the GI Tract

The GI tract is composed of four layers also known as Tunics. Each layer has different tissues and functions. From the inside out they are called: mucosa, submucosa, muscularis, and serosa.

Mucosa: The mucosa is the absorptive and secretory layer. It is composed of simple epithelium cells and a thin connective tissue. There are specialized goblet cells that secrete mucus throughout the GI tract located within the mucosa. On the mucosa layer there are Villi and Micro Villi.

Submucosa: The submucosa is relatively thick, highly vascular, and serves the mucosa. The absorbed elements that pass through the mucosa are picked up from the blood vessels of the submucosa. The submucosa also has glands and nerve plexuses.

Muscularis: The muscularis is responsible for segmental contractions and peristaltic movement in the GI tract. The muscularis is composed of two layers of muscle: an inner circular and outer longitudinal layer of smooth muscle. These muscles cause food to move and churn with digestive enzymes down the GI tract.

Serosa: The last layer is a protective layer. It is composed of avascular connective tissue and simple squamous epithelium. It secretes lubricating serous fluid. This is the visible layer on the outside of the organs.

## Accessory Organs

Teeth, Tongue, and Salivary Glands
1. Salivary glands
• Parotid gland, submandibular gland, sublingual gland
• Exocrine gland that produces saliva which begins the process of digestion with amylase
2. Tongue
• Manipulates food for chewing/swallowing
• Main taste organ, covered in taste buds
3. Teeth
• For chewing food up
4. Liver
• Produces and excretes bile required for emulsifying fats. Some of the bile drains directly into the duodenum and some is stored in the gall bladder.
• Helps metabolize proteins, lipids, and carbohydrates.
• Urea, chief end product of mammalian metabolism, is formed in liver from amino acids and compounds of ammonia.
• Breaks down insulin and other hormones.
• Produces coagulation factors.
• Bile storage.
6. Pancreas
• Exocrine functions: Digestive enzyme secretion.
• Stores zymogens (inactive enzymes) that will be activated by the brush border membrane in the small intestine when a person eats protein (amino acids).
• Trypsinogen – Trypsin: digests protein.
• Chymotypsinogen – Chymotrypsin: digests proteins.
• Carboxypeptidases: digests proteins.
• Lipase-lipid: digests fats.
• Amylase: digests carbohydrates.
• Endocrine functions: Hormone secretion.
• Somatostatin: inhibits the function of insulin. Produced if the body is getting too much glucose.
• Glucagon: stimulates the stored glycogen in the liver to convert to glucose. Produced if the body does not have enough glucose.
• Insulin: made in the beta cells of the Islets of Langerhans of the pancreas. Insulin is a hormone that regulates blood glucose.
7. Vermiform appendix
• There are a few theories on what the appendix does.
• Vestigal organ
• Immune function
• Helps maintain gut flora

## The Digestive System

The first step in the digestive system can actually begin before the food is even in your mouth. When you smell or see something that you just have to eat, you start to salivate in anticipation of eating, thus beginning the digestive process.

Food is the body's source of fuel. Nutrients in food give the body's cells the energy they need to operate. Before food can be used it has to be broken down into tiny little pieces so it can be absorbed and used by the body. In humans, proteins need to be broken down into amino acids, starches into sugars, and fats into fatty acids and glycerol.

During digestion two main processes occur at the same time:

• Mechanical Digestion: larger pieces of food get broken down into smaller pieces while being prepared for chemical digestion. Mechanical digestion starts in the mouth and continues in to the stomach.
• Chemical Digestion: several different enzymes break down macromolecules into smaller molecules that can be more efficiently absorbed. Chemical digestion starts with saliva and continues into the intestines.

The digestive system is made up by the alimentary canal, or the digestive tract, and other abdominal organs that play a part in digestion such as the liver and the pancreas. The alimentary canal is the long tube of organs that runs from the mouth (where the food enters) to the anus (where indigestible waste leaves). The organs in the alimentary canal include the mouth( for mastication),esophagus, stomach and the intestines. The average adult digestive tract is about thirty feet (30') long. While in the digestive tract the food is really passing through the body rather than being in the body. The smooth muscles of the tubular digestive organs move the food efficiently along as it is broken down into absorb-able atoms and molecules. During absorption, the nutrients that come from food (such as proteins, fats, carbohydrates, vitamins, and minerals) pass through the wall of the small intestine and into the bloodstream and lymph. In this way nutrients can be distributed throughout the rest of the body. In the large intestine there is re absorption of water and absorption of some minerals as feces are formed. The parts of the food that the body passes out through the anus is known as feces.

Mastication

Digestion begins in the mouth. A brain reflex triggers the flow of saliva when we see or even think about food. Saliva moistens the food while the teeth chew it up and make it easier to swallow. Amylase, which is the digestive enzyme found in saliva, starts to break down starch into simpler sugars before the food even leaves the mouth. The nervous pathway involved in salivary excretion requires stimulation of receptors in the mouth, sensory impulses to the brain stem, and parasympathetic impulses to salivary glands.

Swallowing your food happens when the muscles in your tongue and mouth move the food into your pharynx. The pharynx, which is the passageway for food and air, is about five inches (5") long. A small flap of skin called the epiglottis closes over the pharynx to prevent food from entering the trachea and thus choking. For swallowing to happen correctly a combination of 25 muscles must all work together at the same time. Salivary glands also produce an estimated three liters of saliva per day.

Enzyme Produced In Site of Release pH Level
Carbohydrate Digestion:
Salivary amylase Salivary glands Mouth Neutral
Pancreatic amylase Pancreas Small intestine Basic
Maltase Small intestine Small intestine Basic
Protein Digestion:
Pepsin Gastric glands Stomach Acidic
Trypsin Pancreas Small intestine Basic
Peptidases Small intestine Small intestine Basic
Nucleic Acid Digestion:
Nuclease Pancreas Small intestine Basic
Nucleosidases Pancreas Small intestine Basic
Fat Digestion:
Lipase Pancreas Small intestine Basic

## Esophagus

The esophagus (also spelled oesophagus/esophagus) or gullet is the muscular tube in vertebrates through which ingested food passes from the throat to the stomach. The esophagus is continuous with the laryngeal part of the pharynx at the level of the C6 vertebra. It connects the pharynx, which is the body cavity that is common to both the digestive and respiratory systems behind the mouth, with the stomach, where the second stage of digestion is initiated (the first stage is in the mouth with teeth and tongue masticating food and mixing it with saliva).

After passing through the throat, the food moves into the esophagus and is pushed down into the stomach by the process of peristalsis (involuntary wavelike muscle contractions along the G.I. tract). At the end of the esophagus there is a sphincter that allows food into the stomach then closes back up so the food cannot travel back up into the esophagus.

Histology

The esophagus is lined with mucus membranes, and uses peristaltic action to move swallowed food down to the stomach.

The esophagus is lined by a stratified squamous epithelium, which is rapidly turned over, and serves a protective effect due to the high volume transit of food, saliva, and mucus into the stomach. The lamina propria of the esophagus is sparse. The mucus secreting glands are located in the submucosa, and are connective structures called papillae.

The muscularis propria of the esophagus consists of striated muscle in the upper third (superior) part of the esophagus. The middle third consists of a combination of smooth muscle and striated muscle, and the bottom (inferior) third is only smooth muscle. The distal end of the esophagus is slightly narrowed because of the thickened circular muscles. This part of the esophagus is called the lower esophageal sphincter. This aids in keeping food down and not being regurgitated.

The esophagus has a rich lymphatic drainage as well.

## Stomach

The stomach is a thick walled organ that lies between the esophagus and the first part of the small intestine (the duodenum). It is on the left side of the abdominal cavity, the fundus of the stomach lying against the diaphragm. Lying beneath the stomach is the pancreas. The greater omentum hangs from the greater curvature.

A mucous membrane lines the stomach which contains glands (with chief cells) that secrete gastric juices, up to three quarts of this digestive fluid is produced daily. The gastric glands begin secreting before food enters the stomach due to the parasympathetic impulses of the vagus nerve, making the stomach also a storage vat for that acid.

The secretion of gastric juices occurs in three phases: cephalic, gastric, and intestinal. The cephalic phase is activated by the smell and taste of food and swallowing. The gastric phase is activated by the chemical effects of food and the distension of the stomach. The intestinal phase blocks the effect of the cephalic and gastric phases. Gastric juice also contains an enzyme named pepsin, which digests proteins, hydrochloric acid and mucus. Hydrochloric acid causes the stomach to maintain a pH of about 2, which helps kill off bacteria that comes into the digestive system via food.

The gastric juice is highly acidic with a pH of 1-3. It may cause or compound damage to the stomach wall or its layer of mucus, causing a peptic ulcer. On the inside of the stomach there are folds of skin call the gastric rugae. Gastric rugae make the stomach very extendable, especially after a very big meal.

The stomach is divided into four sections, each of which has different cells and functions. The sections are: 1) Cardiac region, where the contents of the esophagus empty into the stomach, 2) Fundus, formed by the upper curvature of the organ, 3) Body, the main central region, and 4) Pylorus or atrium, the lower section of the organ that facilitates emptying the contents into the small intestine. Two smooth muscle valves, or sphincters, keep the contents of the stomach contained. They are the: 1) Cardiac or esophageal sphincter, dividing the tract above, and 2) Pyloric sphincter, dividing the stomach from the small intestine.

After receiving the bolus (chewed food) the process of peristalsis is started; mixed and churned with gastric juices the bolus is transformed into a semi-liquid substance called chyme. Stomach muscles mix up the food with enzymes and acids to make smaller digestible pieces. The pyloric sphincter, a walnut shaped muscular tube at the stomach outlet, keeps chyme in the stomach until it reaches the right consistency to pass into the small intestine. The food leaves the stomach in small squirts rather than all at once.

Water, alcohol, salt, and simple sugars can be absorbed directly through the stomach wall. However, most substances in our food need a little more digestion and must travel into the intestines before they can be absorbed. When the stomach is empty it is about the size of one fifth of a cup of fluid. When stretched and expanded, it can hold up to eight cups of food after a big meal.

Gastric Glands

There are many different gastric glands and they secret many different chemicals. Parietal cells secrete hydrochloric acid and intrinsic factor; chief cells secrete pepsinogen; goblet cells secrete mucus; argentaffin cells secrete serotonin and histamine; and G cells secrete the hormone gastrin.

Vessels and nerves

Nerves in the lower abdomen.
Arteries: The arteries supplying the stomach are the left gastric, the right gastric and right gastroepiploic branches of the hepatic, and the left gastroepiploic and short gastric branches of the lineal. They supply the muscular coat, ramify in the submucous coat, and are finally distributed to the mucous membrane.
Capillaries: The arteries break up at the base of the gastric tubules into a plexus of fine capillaries, which run upward between the tubules, anatomizing with each other, and ending in a plexus of larger capillaries, which surround the mouths of the tubes, and also form hexagonal meshes around the ducts.
Veins: From these the veins arise, and pursue a straight course downward, between the tubules, to the submucous tissue; they end either in the lineal and superior mesenteric veins, or directly in the portal vein.
Lymphatics: The lymphatics are numerous: They consist of a superficial and a deep set, and pass to the lymph glands found along the two curvatures of the organ.
Nerves: The nerves are the terminal branches of the right and left urethra and other parts, the former being distributed upon the back, and the latter upon the front part of the organ. A great number of branches from the celiac plexus of the sympathetic are also distributed to it. Nerve plexuses are found in the submucous coat and between the layers of the muscular coat as in the intestine. From these plexuses fibrils are distributed to the muscular tissue and the mucous membrane.

Disorders of the Stomach

Disorders of the stomach are common. There can be a lot of different causes with a variety of symptoms. The strength of the inner lining of the stomach needs a careful balance of acid and mucus. If there is not enough mucus in the stomach, ulcers, abdominal pain, indigestion, heartburn, nausea and vomiting could all be caused by the extra acid.

Erosions, ulcers, and tumors can cause bleeding. When blood is in the stomach it starts the digestive process and turns black. When this happens, the person can have black stool or vomit. Some ulcers can bleed very slowly so the person won't recognize the loss of blood. Over time, the iron in your body will run out, which in turn, will cause anemia.

There isn't a known diet to prevent against getting ulcers. A balanced, healthy diet is always recommended. Smoking can also be a cause of problems in the stomach. Tobacco increases acid production and damages the lining of the stomach. It is not a proven fact that stress alone can cause an ulcer.

Histology of the human stomach

Like the other parts of the gastrointestinal tract, the stomach walls are made of a number of layers.

From the inside to the outside, the first main layer is the mucosa. This consists of an epithelium, the lamina propria underneath, and a thin bit of smooth muscle called the muscularis mucosa.

The submucosa lies under this and consists of fibrous connective tissue, separating the mucosa from the next layer, the muscularis externa. The muscularis in the stomach differs from that of other GI organs in that it has three layers of muscle instead of two. Under these muscle layers is the adventitia, layers of connective tissue continuous with the omenta.

The epithelium of the stomach forms deep pits, called fundic or oxyntic glands. Different types of cells are at different locations down the pits. The cells at the base of these pits are chief cells, responsible for production of pepsinogen, an inactive precursor of pepsin, which degrades proteins. The secretion of pepsinogen prevents self-digestion of the stomach cells.

Further up the pits, parietal cells produce gastric acid and a vital substance, intrinsic factor. The function of gastric acid is twofold 1) it kills most of the bacteria in food, stimulates hunger, and activates pepsinogen into pepsin, and 2) denatures the complex protein molecule as a precursor to protein digestion through enzyme action in the stomach and small intestines. Near the top of the pits, closest to the contents of the stomach, there are mucous-producing cells called goblet cells that help protect the stomach from self-digestion.

The muscularis externa is made up of three layers of smooth muscle. The innermost layer is obliquely-oriented: this is not seen in other parts of the digestive system: this layer is responsible for creating the motion that churns and physically breaks down the food. The next layers are the square and then the longitudinal, which are present as in other parts of the GI tract. The pyloric antrum which has thicker skin cells in its walls and performs more forceful contractions than the fundus. The pylorus is surrounded by a thick circular muscular wall which is normally tonically constricted forming a functional (if not anatomically discrete) pyloric sphincter, which controls the movement of chyme.

Control of secretion and motility

The movement and the flow of chemicals into the stomach are controlled by both the nervous system and by the various digestive system hormones.

The hormone gastrin causes an increase in the secretion of HCL, pepsinogen and intrinsic factor from parietal cells in the stomach. It also causes increased motility in the stomach. Gastrin is released by G-cells into the stomach. It is inhibited by pH normally less than 4 (high acid), as well as the hormone somatostatin.

Cholecystokinin (CCK) has most effect on the gall bladder, but it also decreases gastric emptying. In a different and rare manner, secretin, produced in the small intestine, has most effects on the pancreas, but will also diminish acid secretion in the stomach.

Gastric inhibitory peptide (GIP) and enteroglucagon decrease both gastric motility and secretion of pepsin. Other than gastrin, these hormones act to turn off the stomach action. This is in response to food products in the liver and gall bladder, which have not yet been absorbed. The stomach needs only to push food into the small intestine when the intestine is not busy. While the intestine is full and still digesting food, the stomach acts as a storage for food.

## Small Intestine

Diagram showing the small intestine

The small intestine is the site where most of the chemical and mechanical digestion is carried out. Tiny projections called villi line the small intestine which absorbs digested food into the capillaries. Most of the food absorption takes place in the jejunum and the ileum.

The functions of a small intestine is, the digestion of proteins into peptides and amino acids principally occurs in the stomach but some also occurs in the small intestine. Peptides are degraded into amino acids; lipids (fats) are degraded into fatty acids and glycerol; and carbohydrates are degraded into simple sugars.

The three main sections of the small intestine are the duodenum, the jejunum, the ileum.

The duodenum

In anatomy of the digestive system, the duodenum is a hollow jointed tube connecting the stomach to the jejunum. It is the first and shortest part of the small intestine. It begins with the duodenal bulb and ends at the ligament of Treitz. The duodenum is almost entirely retro peritoneal. The duodenum is also where the bile and pancreatic juices enter the intestine.

The jejunum

The jejunum is a part of the small bowel, located between the distal end of duodenum and the proximal part of ileum. The jejunum and the ileum are suspended by an extensive mesentery giving the bowel great mobility within the abdomen. The inner surface of the jejunum, its mucous membrane, is covered in projections called villi, which increase the surface area of tissue available to absorb nutrients from the gut contents. It is different from the ileum due to fewer goblet cells and generally lacks Peyer's patches.

The ileum

Its function is to absorb vitamin B12 and bile salts. The wall itself is made up of folds, each of which has many tiny finger-like projections known as villi, on its surface. In turn, the epithelial cells which line these villi possess even larger numbers of micro villi. The cells that line the ileum contain the protease and carbohydrate enzymes responsible for the final stages of protein and carbohydrate digestion. These enzymes are present in the cytoplasm of the epithelial cells. The villi contain large numbers of capillaries which take the amino acids and glucose produced by digestion to the hepatic portal vein and the liver.

The terminal ileum continues to absorb bile salts, and is also crucial in the absorption of fat-soluble vitamins (Vitamin A, D, E and K). For fat-soluble vitamin absorption to occur, bile acids must be present.

## Large Intestine

The large intestine (colon) extends from the end of the ileum to the anus. It is about 5 feet long, being one-fifth of the whole extent of the intestinal canal. It's caliber is largest at the commencement at the cecum, and gradually diminishes as far as the rectum, where there is a dilatation of considerable size just above the anal canal. It differs from the small intestine in by the greater caliber, more fixed position, sacculated form, and in possessing certain appendages to its external coat, the appendices epiploicæ. Further, its longitudinal muscular fibers do not form a continuous layer around the gut, but are arranged in three longitudinal bands or tæniæ.

The large intestine is divided into the cecum, colon, rectum, and anal canal. In its course, describes an arch which surrounds the convolutions of the small intestine. It commences in the right iliac region, in a dilated part, the cecum. It ascends through the right lumbar and hypochondriac regions to the under surface of the liver; here it takes a bend, the right colic flexure, to the left and passes transversely across the abdomen on the confines of the epigastric and umbilical regions, to the left hypochondriac region; it then bends again, the left colic flexure, and descends through the left lumbar and iliac regions to the pelvis, where it forms a bend called the sigmoid flexure; from this it is continued along the posterior wall of the pelvis to the anus.

There are trillions of bacteria, yeasts, and parasites living in our intestines, mostly in the colon. Over 400 species of organisms live in the colon. Most of these are very helpful to our health, while the minority are harmful. Helpful organisms synthesize vitamins, like B12, biotin, and vitamin K. They breakdown toxins and stop proliferation of harmful organisms. They stimulate the immune system and produce short chain fatty acids (SCFAs) that are required for the health of colon cells and help prevent colon cancer. There are many beneficial bacteria but some of the most common and important are Lactobacillus Acidophilus and various species of Bifidobacterium. These are available as "probiotics" from many sources.

The pancreas, liver, and gallbladder are essential for digestion. The pancreas produces enzymes that help digest proteins, fats, and carbohydrates, the liver produces bile that helps the body absorb fat, and the gallbladder stores the bile until it is needed. The enzymes and bile travel through special channels called ducts and into the small intestine where they help break down the food.

Pancreas

The pancreas is located posterior to the stomach and in close association with the duodenum.

In humans, the pancreas is a 6-10 inch elongated organ in the abdomen located retro peritoneal. It is often described as having three regions: a head, body and tail. The pancreatic head abuts the second part of the duodenum while the tail extends towards the spleen. The pancreatic duct runs the length of the pancreas and empties into the second part of the duodenum at the ampulla of Vater. The common bile duct commonly joins the pancreatic duct at or near this point.

The pancreas is supplied arterially by the pancreaticoduodenal arteries, themselves branches of the superior mesenteric artery of the hepatic artery (branch of celiac trunk from the abdominal aorta). The superior mesenteric artery provides the inferior pancreaticoduodenal arteries while the gastroduodenal artery (one of the terminal branches of the hepatic artery) provides the superior pancreaticoduodenal artery. Venous drainage is via the pancreatic duodenal veins which end up in the portal vein. The splenic vein passed posterior to the pancreas but is said to not drain the pancreas itself. The portal vein is formed by the union of the superior mesenteric vein and splenic vein posterior to the body of the pancreas. In some people (as many as 40%) the inferior mesenteric vein also joins with the splenic vein behind the pancreas, in others it simply joins with the superior mesenteric vein instead.

The function of the pancreas is to produce enzymes that break down all categories of digestible foods (exocrine pancreas) and secrete hormones that affect carbohydrates metabolism (endocrine pancreas).

• Exocrine

The pancreas is composed of pancreatic exocrine cells, whose ducts are arranged in clusters called acini (singular acinus). The cells are filled with secretory granules containing the precursor digestive enzymes (mainly trypsinogen, chymotrypsinogen, pancreatic lipase, and amylase) that are secreted into the lumen of the acinus. These granules are termed zymogen granules (zymogen referring to the inactive precursor enzymes.) It is important to synthesize inactive enzymes in the pancreas to avoid auto degradation, which can lead to pancreatitis.

The pancreas is near the liver, and is the main source of enzymes for digesting fats (lipids) and proteins - the intestinal walls have enzymes that will digest polysaccharides. Pancreatic secretions from ductal cells contain bicarbonate ions and are alkaline in order to neutralize the acidic chyme that the stomach churns out. Control of the exocrine function of the pancreas are via the hormone gastrin, cholecystokinin and secretin, which are hormones secreted by cells in the stomach and duodenum, in response to distension and/or food and which causes secretion of pancreatic juices.

The two major proteases which the pancreas are trypsinogen and chymotrypsinogen. These zymogens are inactivated forms of trypsin and chymotrypsin. Once released in the intestine, the enzyme enterokinase present in the intestinal mucosa activates trypsinogen by cleaving it to form trypsin. The free trypsin then cleaves the rest of the trypsinogen and chymotrypsinogen to their active forms.

Pancreatic secretions accumulate in intralobular ducts that drain the main pancreatic duct, which drains directly into the duodenum.

Due to the importance of its enzyme contents, injuring the pancreas is a very dangerous situation. A puncture of the pancreas tends to require careful medical intervention.

• Endocrine

Scattered among the acini are the endocrine cells of the pancreas, in groups called the islets of Langerhans. They are:

Insulin-producing beta cells (50-80% of the islet cells) Glucagon-releasing alpha cells (15-20%) Somatostatin-producing delta cells (3-10%) Pancreatic polypeptide-containing PP cells (remaining %)

The islets are a compact collection of endocrine cells arranged in clusters and cords and are crisscrossed by a dense network of capillaries. The capillaries of the islets are lined by layers of endocrine cells in direct contact with vessels, and most endocrine cells are in direct contact with blood vessels, by either cytoplasmic processes or by direct apposition.

Liver

The liver is an organ in vertebrates, including human. It plays a major role in metabolism and has a number of functions in the body including glycogen storage, plasma protein synthesis, and drug detoxification. It also produces bile, which is important in digestion. It performs and regulates a wide variety of high-volume biochemical reaction requiring specialized tissues.

The liver normally weighs between 1.3 - 3.0 kilograms and is a soft, pinkish-brown "boomerang shaped" organ. It is the second largest organ (the largest being the skin) and the largest gland within the human body. Its anatomical position in the body is immediately under the diaphragm on the right side of the upper abdomen, The liver lies on the right side of the stomach and makes a kind of bed for the gallbladder.

The liver is supplied by two main blood vessels on its right lobe: the hepatic artery and the portal vein. The hepatic artery normally comes off the celiac trunk. The portal vein brings venous blood from the spleen, pancreas, and small intestine, so that the liver can process the nutrients and byproducts of food digestion. The hepatic veins drain directly into the inferior vena cava.

The bile produced in the liver is collected in bile canaliculi, which merge from bile ducts. These eventually drain into the right and left hepatic ducts, which in turn merge to form the common hepatic duct. The cystic duct (from the gallbladder) joins with the common hepatic duct to form the common bile duct. Bile can either drain directly into the duodenum via the common bile duct or be temporarily stored in the gallbladder via the cystic duct. The common bile duct and the pancreatic duct enter the duodenum together at the ampulla of Vater. The branching's of the bile ducts resemble those of a tree, and indeed term "biliary tree" is commonly used in this setting.

The liver is among the few internal human organs capable of natural regeneration of lost tissue: as little as 25% of remaining liver can regenerate into a whole liver again. This is predominantly due to hepatocytes acting as unipotential stem cells. There is also some evidence of bio potential stem cells, called oval cell, which can differentiate into either hepatocytes or cholangiocytes (cells that line bile ducts).

The various functions of the liver are carried out by the liver cells or hepatocytes.

• The liver produces and excretes bile, required for dissolving fats. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder
• The liver performs several roles in carbohydrate metabolism:
• gluconeogenesis (the formation of glucose from certain amino acids, lactate or glycerol)
• Glycogenolysis (the formation of glucose from glycogen)
• Glycogenesis (the formation of glycogen from glucose)
• The breakdown of insulin and other hormones
• The liver is responsible for the mainstay of protein metabolism.
• The liver also performs several roles in lipid metabolism:
• cholesterol synthesis
• The production of triglycerides (fats)
• The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, X and XI, as well as protein C, Protein S and antithrombin.
• The liver breaks down hemoglobin, creating metabolites that are added to bile as pigment
• The liver breaks down toxic substances and most medicinal products in a process called drug metabolism. This sometimes results in toxication, when the metabolite is more toxic than its precursor.
• The liver converts ammonia to urea.
• The liver stores a multitude of substances, including glucose in the form of glycogen, vitamin B12, iron, and copper.
• In the first trimester fetus, the liver is the main site of red blood cell production. By the 32nd weeks of gestation, the bone marrow has almost completely taken over that task.
• The liver is responsible for immunological effects; the reticuloendothelial system of the liver contains many immunologically active cells, acting as a 'sieve' for antigens carried to it via the portal system.

The gallbladder is a pear shaped organ that stores about 50 ml of bile (or "gall") until the body needs it for digestion. The gallbladder is about 7-10cm long in humans and is dark green in appearance due to its contents (bile), not its tissue. It is connected to the liver and the duodenum by the biliary tract.

The gallbladder is connected to the main bile duct through the gallbladder duct (cystic duct). The main biliary tract runs from the liver to the duodenum, and the cystic duct is effectively a "cul de sac", serving as entrance and exit to the gallbladder. The surface marking of the gallbladder is the intersection of the midclavicular line (MCL) and the trans pyloric plane, at the tip of the ninth rib. The blood supply is by the cystic artery and vein, which runs parallel to the cystic duct. The cystic artery is highly variable, and this is of clinical relevance since it must be clipped and cut during a cholecystectomy.

The gallbladder has an epithelial lining characterized by recesses called Aschoff's recesses, which are pouches inside the lining. Under the epithelium there is a layer of connective tissue, followed by a muscular wall that contracts in response to cholecystokinin, a peptide hormone synthesized in the duodenum.

The gallbladder stores bile, which is released when food containing fat enters the digestive tract, stimulating the secretion of cholecystokinin (CCK). The bile emulsifies fats and neutralizes acids in partly digested food. After being stored in the gallbladder, the bile becomes more concentrated than when it left the liver, increasing its potency and intensifying its effect on fats.

## Anus

The human anus is situated between the buttocks, posterior to the perineum. It has two anal sphincters, one internal, the other external. These hold the anus closed until defecation occurs. One sphincter consists of smooth muscle and its action is involuntary; the other consists of striated muscle and its action is voluntary. In many animals, the anus is surrounded by anal sacs. Role of the anus is when the rectum is full, the increase in intra-rectal pressure forces the walls of the anal canal apart allowing the fecal matter to enter the canal. The rectum shortens as material is forced into the anal canal and peristaltic waves propel the feces out of the rectum. The internal and external sphincters of the anus allow the feces to be passed by muscles pulling the anus up over the exiting feces.

## Conditions Affecting the Esophagus

There are two different types of conditions that may affect the esophagus. The first type is called congenital: meaning a person is born with it. The second type is called non-congenital: meaning the person develops it after birth. Some examples of these are:

Tracheoesophageal fistula and esophageal atresia

Both of these conditions are congenital. In Tracheoesophageal fistula there is a connection between the esophagus and the wind pipe (trachea) where there shouldn't be one. In Esophageal atresia the esophagus of a newborn does not connect to the stomach but comes to a dead end right before the stomach. Both conditions require corrective surgery and are usually detected right after the baby is born. In some cases, it can be detected before the baby is born.

Esophagitis

Esophagitis is inflammation of the esophagus and is a non-congenital condition. Esophagitis can be caused by certain medications or by infections. It can also be caused by gastroesophageal reflux disease (gerd), a condition where the esophageal sphincter allows the acidic contents of the stomach to move back up into the esophagus. Gastroesophageal reflux disease can be treated with medications, but it can also be corrected by changing what you eat.

## Conditions Affecting the Stomach and Intestines

Everybody has experienced constipation or diarrhea in their lifetime. With constipation, the contents of the large intestines don't move along fast enough and waste material stays in the large intestines so long that almost all water is extracted out of the waste and it becomes hard. With diarrhea you get the exact opposite reaction: waste moves along too fast and the large intestines can't absorb the water before the waste is pushed through. Common flora bacteria assists in the prevention of many serious problems. Here are some more examples of common stomach and intestinal disorders:

Acute Appendicitis: An exemplary case of acute appendicitis in a 10-year-old boy. The organ is enlarged and sausage-like (botuliform). This longitudinal section shows the angry red inflamed mucosa with its irregular luminal surface. Diagnosed and removed early in the course of the disease, this appendix does not show late complications, like transmural necrosis, perforation, and abscess formation.

Appendicitis

Appendicitis is the inflammation of the appendix, the finger-like pouch that extends from the cecum. The most common symptoms are abdominal pain, loss of appetite, fever, and vomiting. Children and teenagers are the most common victims of appendicitis, which must be corrected by surgery. While mild cases may resolve without treatment, most require removal of the inflamed appendix, either by laparotomy or laparoscopy. Untreated, mortality is high, mainly due to peritonitis and shock.

Celiac Disease

Celiac disease is a disorder in which a person's digestive system is damaged by the response of the immune system to a protein called gluten, which is found in rye, wheat, and barley, and also in foods like breakfast cereal and pizza crust. People who have celiac disease experience abdominal pain, diarrhea, bloating, exhaustion, and depression when they eat foods with gluten in them. They also have difficulty digesting their food. Celiac disease runs in families and becomes active after some sort of stress, like viral infections or surgery. The symptoms can be managed by following a gluten free diet. Doctors can diagnose this condition by taking a full medical history or with a blood test.

Diverticulitis

Benign gastric ulcer

Diverticulitis is a common disease of the bowel, in particular the large intestine. Diverticulitis develops from diverticulosis, which involves the formation of pouches (diverticula) on the outside of the colon. Diverticulitis results if one of these diverticula becomes inflamed. In complicated diverticulitis, bacteria may subsequently infect the outside of the colon if an inflamed diverticula bursts open. If the infection spreads to the lining of the abdominal cavity (peritoneum), this can cause a potentially fatal peritonitis. Sometimes inflamed diverticula can cause narrowing of the bowel, leading to an obstruction. Also, the affected part of the colon could adhere to the bladder or other organ in the pelvic cavity, causing a fistula, or abnormal communication between the colon and an adjacent organ.

Gastritis and Peptic ulcers

Usually the stomach and the duodenum are resistant to irritation because of the strong acids produced by the stomach. But sometimes a bacteria called Helicobacter pylori or the chronic use of drugs or certain medications, weakens the mucous layer that coats the stomach and the duodenum, allowing acid to get through the sensitive lining beneath. This can cause irritation and inflammation of the lining of the stomach, which is called gastritis, or cause peptic ulcers, which are holes or sores that form in the lining of the stomach and duodenum and cause pain and bleeding. Medications are the best way to treat this condition.

Gastrointestinal Infections

Gastrointestinal infections can be caused by bacteria such as Campylobacter, Salmonella, E. coli, or Shigella. They can also be caused by viruses or by intestinal parasites like amebiasis and Giardiasis. The most common symptoms of gastrointestinal infections are abdominal pain and cramps, diarrhea, and vomiting. These conditions usually go away on their own and don't need medical attention.

Inflammatory Bowel Disease

Inflammatory bowel disease is the chronic inflammation of the intestines, which usually affects older children, teens and adults. There are two major types, ulcerative colitis and Crohn's disease and indeterminate colitis, which occurs in 10-15% of patients. Ulcerative colitis usually affects just the rectum and large intestine, while Crohn's disease can affect the whole gastrointestinal tract from mouth to anus along with some other parts of the body. Patients with these diseases also suffer from extraintestinal symptoms including joint pain and red eye, which can signal a flare of the disease. These diseases are treated with medications and if necessary, Intravenous or IV feeding, or in the more serious cases, surgery to remove the damaged areas of the intestines.

Polyp

A polyp is an abnormal growth of tissue (tumor) projecting from a mucous membrane. If it is attached to the surface by a narrow elongated stalk it is said to be pedunculated. If no stalk is present it is said to be sessile. Polyps are commonly found in the colon, stomach, nose, urinary bladder and uterus. They may also occur elsewhere in the body where mucous membranes exist like the cervix and small intestine.

## Disorders of the Pancreas, Liver, and Gallbladder

Disorders of the pancreas, liver, and gallbladder affect the ability to produce enzymes and acids that aid in digestion. examples of these disorders are.

Cystic Fibrosis

Cystic fibrosis is a chronic, inherited illness where the production of abnormally thick mucous blocks the duct or passageways in the pancreas and prevents the digestive fluids from entering the intestines, making it difficult for the person with the disorder to digest protein and fats, which cause important nutrients to pass through without being digested. People with this disorder take supplements and digestive enzymes to help manage their digestive problems.

Hepatitis

Hepatitis is a viral condition that inflames a person's liver which can cause it to lose its ability to function. Viral hepatitis, like hepatitis A, B, and C, is extremely contagious. Hepatitis A, which is a mild form of hepatitis, can be treated at home, but more serious cases that involve liver damage, might require hospitalization.

Cholecystitis

Acute or chronic inflammation if the gallbladder causes abdominal pain. 90% of cases of acute cholecystitis are caused by the presence of gallstones. The actual inflammation is due to secondary infection with bacteria of an obstructed gallbladder, with the obstruction caused by the gallstones. Gallbladder conditions are very rare in kids and teenagers but can occur when the kid or teenager has sickle cell anemia or in kids being treated with long term medications.

Cholestasis

Cholestasis is the blockage in the supply of bile into the digestive tract. It can be "intrahepatic" (the obstruction is in the liver) or "extrahepatic" (outside the liver). It can lead to jaundice, and is identified by the presence of elevated bilirubin level that is mainly conjugated.

Biliary colic

This is when a gallstone blocks either the common bile duct or the duct leading into it from the gallbladder. This condition causes severe pain in the right upper abdomen and sometimes through to the upper back. It is described by many doctors as the most severe pain in existence, between childbirth and a heart attack. Other symptoms are nausea, vomiting, diarrhea, bleeding caused by continual vomiting, and dehydration caused by the nausea and diarrhea. Another more serious complication is total blockage of the bile duct which leads to jaundice, which if it is not corrected naturally or by surgical procedure can be fatal, as it causes liver damage. The only long term solution is the removal of the gallbladder.

## Gastrointestinal Dysfunctions

As we age, the amount of digestive enzymes produced by the body drops way down. This leads to decreased and slower digestion, slower absorption of nutrients and increased accumulation of fecal mater in the intestinal tract. Undigested food material and metabolic waste can also build up due to slow elimination, starting a series of health problems.

When digestion slows, it turns the intestines into a toxic environment. Helpful organisms cannot live in toxic environments. When the beneficial organisms die they are replaced by harmful organisms, such as yeasts and parasites, the most common being Candida albicans. This leads to changes in the intestinal wall which produce leaky gut syndrome, which allows many toxic chemicals to be introduced into the bloodstream. As a result, the entire toxic load of the body is increased, causing a bigger burden on the liver, kidneys and other body organs. When this happens the organs that are normally used for eliminating waste and supplying nutrients to the GI tract become a large dump for waste. This problem can be made worse by the use of prescriptions and over-the-counter medications, antibiotics, and a diet that is too low in fiber or contains 'junk food'.

Most people never think about their GI tract. We are concerned about what the outside of our bodies look like, but we completely ignore the inside. Because our bodies a very resilient, deterioration of the digestive system can go on for years with no symptoms or side-effects. When symptoms finally do appear they are usually very non-specific, and include: decreased energy, headaches, diarrhea, constipation, heartburn, and acid reflux. Over the years these symptoms become more serious, including: asthma, food allergies, arthritis, and cancer.

Poor digestion, poor absorption, and bacterial imbalance can be traced to many chronic conditions. Every organ in the body receives nutrients from the GI tract; if the GI tract is malfunctioning then the whole body suffers.

It is possible to return good health to your GI tract by improving digestion, consuming the right amount of fiber, and cutting out junk food and refined sugars.

You can improve the function of the intestines by taking fiber supplements and vitamins (especially B12 and vitamin K). Some doctors suggest herbal or vitamin enemas to cleanse and relieve constipation and to help stimulate peristaltic movement which will help to move the bowels.

Irritable Bowel Syndrome

Irritable Bowel Syndrome (IBS) is a disorder with symptoms that are most commonly bloating, abdominal pain, cramping, constipation, and diarrhea. IBS causes a lot of pain and discomfort. It does not cause permanent damage to the intestines and does not lead to serious diseases such as cancer. Most of the people affected with IBS can control their symptoms with stress management, diet, and prescription medication. For others IBS can be debilitating, they may be unable to go to work, travel, attend social events or leave home for even short periods of time.

About 20 percent of the adult population has some symptoms of IBS, making it one of the most common intestinal disorders diagnosed by physicians. It is more common in men than women and in about 50 percent of people affected it starts at about age 35.

Researchers have not found out what exactly causes IBS. One idea is that people with IBS have a large intestine (colon) that is sensitive to certain foods and stress. The immune system may also be involved. It has also been reported that serotonin is linked with normal GI functioning. 95 percent of the body's serotonin is located in the GI tract (the other 5 percent is in the brain). People with IBS have diminished receptor activity, causing abnormal levels of serotonin in the GI tract. Because of this, IBS patients experience problems with bowel movement, motility, and the sensation having more sensitive pain receptors in their GI tract. Many IBS patients suffer from depression and anxiety which can make symptoms worse.

There is no cure for IBS, but medications are an important part of relieving symptoms. Fiber supplements or laxatives are helpful for constipation. Anti diarrhoeals such as Imodium can help with diarrhea. An antispasmodic is commonly prescribed for colon muscle spasms. Antidepressants and pain medication are also commonly prescribed. [12]

Gastrointestinal Stromal Tumor

Gastrointestinal Stromal Tumors or GIST is an uncommon type of cancer in the GI tract (esophagus, stomach, small intestine, and colon). These types of cancers begin in the connective tissue like fat, muscles, nerves, cartilage, etc.

GIST originates in the stroma cells. Stroma cells are strung along the GI tract and are part of the system that helps the body to know when to move food through the digestive system. Over half of GISTs occur in the stomach. Most cases occur in people between the ages of forty and eighty, but they can also occur in a person of any age.

All GISTs of any size or location have the ability to spread. Even if a GIST is removed, it can reappear in the same area, or may even spread outside of the GI tract.

In the early stages, GIST is hard to diagnose because early-stage symptoms cannot be recognized. In the later stages a person can have vague abdominal pain, vomiting, abdominal bleeding that shows up in stool or vomit, low blood counts causing anemia, and having an early feeling of being full, causing a decrease in appetite.

GIST is now recognized as an aggressive cancer that is able to spread to other parts of the body. People who have been diagnosed with GIST should get treatment as soon as possible.

Food Allergies

Food allergies occur when the immune system thinks that a certain protein in any kind of food is a foreign substance and will try to fight against it.

Only about eight percent of children and two percent of adults actually have a food allergy. A person can be allergic to any kind of food, but the most common food allergies are to nuts, cow's milk, eggs, soy, fish, and shellfish. Most people who have a food allergy are allergic to fewer than four different foods.

The most common signs of food allergies are hives, swelling, itchy skin, itchiness, tingling or swelling in the mouth, coughing, trouble breathing, diarrhea, and vomiting. The two most common chronic illness that are associated with food allergies are eczema and asthma.

Food allergies can be fatal if they cause the reaction called anaphylaxis. This reaction makes it hard for the person to breathe. This can be treated by an epinephrine injection.

GERD, Heartburn, Acid Reflux

GERD, or Gastroesophageal Reflux Disease occurs when the lower esophageal sphincter is not able to close properly. When this happens, contents from the stomach, called reflux, leak back into the esophagus and the stomach.

When the stomach refluxes, stomach acid touches the lining of the esophagus and causes it to have a burning feeling in the throat or the chest. This is what heartburn is. When you taste the fluid in the back of your throat, it is called acid indigestion. It is common for a person to get occasional heartburn, but when it occurs more than twice a week it can be considered to be GERD. GERD can occur in people of all ages including infants.

Some symptoms of GERD include having a pain in your chest, hoarseness, having trouble swallowing, or having the feeling of food being stuck in your throat. The main symptoms are having persistent heartburn and acid regurgitation. GERD can also cause bad breath and a dry cough.

No one knows why people get GERD. Some things that could contribute to GERD are alcohol use, pregnancy, being overweight and smoking. Certain foods might also contribute like citrus fruits, caffeine, spicy, fatty, and dried foods, and also mint flavorings.

Over-the-counter antacids or medications that help stop acid production and help the muscles empty the stomach are commonly used to treat GERD.

Constipation

Not everyone is on the same schedule for having a bowel movement. Depending on the person, a "normal" schedule can range anywhere from three times a day to three times a week. If you start having bowel movements less than your own personal schedule, then you might be getting the signs of constipation.

Constipation is when you have trouble having bowel movements. The stool is very hard, making it difficult to pass and causing a person to strain. You may even feel like you have to have a bowel movement even after you have already had one.

When you digest food, the waste products go through your intestines by the muscles contracting. When in the large intestine, most of the water and salt from the waste products are reabsorbed because they are needed by the body for our everyday functions. You can become constipated if too much water is absorbed, or if waste products move too slowly.

Not getting enough fluids, a low fiber diet, age, not being physically active, depression, stress and pregnancy can all contribute to constipation. Medications and narcotics can also cause a person to get constipated. Chronic constipation may be a symptom of a liver problem such as a urea cycle disorder.

The best way for a person to treat constipation is to make sure that they are getting enough fluids as well as fiber in their diet. By doing this, the bulk of their stool is increased and made softer, so that it can move through the intestines more easily. Being more active and increasing daily exercise also helps keep bowel movements regulated.

Hemorrhoids

Hemorrhoids (also known as haemorrhoids, emerods, or piles) are varicosities or swelling and inflammation of veins in the rectum and anus.

Two of the most common types of hemorrhoids are external and internal hemorrhoids.

• External hemorrhoids are those that occur outside of the anal verge (the distal end of the anal canal). They are sometimes painful, and can be accompanied by swelling and irritation. Itching, although often thought to be a symptom from external hemorrhoids, is more commonly due to skin irritation.
• If the vein ruptures and a blood clot develops, the hemorrhoid becomes a thrombosed hemorrhoid.
• Internal hemorrhoids are those that occur inside the rectum. As this area lacks pain sensory receptor|receptors, internal hemorrhoids are usually not painful and most people are not aware that they have them. Internal hemorrhoids, however, may bleed when irritated.
• Untreated internal hemorrhoids can lead to two severe forms of hemorrhoids: prolapsed and strangulated hemorrhoids.
• Prolapsed hemorrhoids are internal hemorrhoids that are so distended that they are pushed outside of the anus.
• If the anal sphincter muscle goes into spasm and traps a prolapsed hemorrhoid outside of the anal opening, the supply of blood is cut off, and the hemorrhoid becomes a strangulated hemorrhoid.

## Bleeding in the Gastrointestinal tract

Bleeding in the gastrointestinal tract doesn't always mean you have a disease, it's usually a symptom of a digestive problem. The cause of the bleeding may not be that serious, it could be something that can be cured or controlled such as hemorrhoids. However, locating the source of the bleeding is very important. The gastrointestinal tract contains many important organs like the esophagus, stomach, small intestine, large intestine or colon, rectum, and anus. Bleeding can come from one or more of these area from a small ulcer in the stomach, or a large surface like the inflammation of the colon. Sometimes a person doesn't even know they are bleeding. When this happens, it is called hidden, or occult bleeding. Simple tests can detect hidden blood in the stool.

What Causes Bleeding in the Digestive Tract

Esophageal bleeding may be caused by Mallory-Weiss syndrome which is a tear in the esophagus. Mallory-Weiss syndrome is usually caused by excessive vomiting or may be caused by childbirth, a hiatal hernia, or increased pressure in the abdomen caused by coughing. Various medications can cause stomach ulcers or inflammations. Medications containing aspirin or alcohol, and various other medications(mainly those used for arthritis) are some examples of these.

Benign tumors or cancer of the stomach may also cause bleeding. These disorders don't usually produce massive bleeding. The most common source of bleeding usually occurs from ulcers in the duodenum. Researchers believe that these ulcers are caused by excessive stomach acid and a bacteria called Helicobacter Pylori.

In the lower digestive tract, the most common source of bleeding is in the large intestine, and the rectum. Hemorrhoids are the most common cause of bleeding in the digestive tract. Hemorrhoids are enlarged veins in the anal area which produces bright red blood that you see in the toilet or on the toilet paper.

How do you Recognize Bleeding in the Digestive Tract

The signs of bleeding in the digestive tract vary depending on the site and severity of the bleeding. If the blood is coming from the rectum, it would be bright red blood. If it was coming from higher up in the colon or from the small intestine, the blood would be darker. When the blood is coming from the stomach, esophagus, or the duodenum, the stool would be black and tarry.

If the bleeding is hidden, or occult, a person may not notice changes in the stool color. If extensive bleeding occurs, a person may feel dizzy, faint, weak, short of breath, have diarrhea or cramp abdominal pain. Shock can also occur along with rapid pulse, drop in blood pressure, and difficulty urinating. Fatigue, lethargy, and pallor from anemia will settle in if the bleeding is slow. Anemia is when the bloods iron-rich substance, hemoglobin, is diminished.

Common Causes of Bleeding in the Digestive Tract

• Hemorrhoids
• Gastritis (inflammation)
• Inflammation (ulcerative colitis)
• Colo rectal Polyps
• Colo rectal Cancer
• Duodenal Ulcer
• Enlarged Veins
• Esophagitis (inflammation of the esophagus)
• Mallory-Weiss Syndrome
• Ulcers

Iron and beets can also turn the blood red or black giving a false indication of blood in the stool.

How Bleeding in the Digestive Tract is Diagnosed

To diagnose bleeding in the digestive tract the bleeding must be located and a complete history and physical are very important. Here are some of the procedures that diagnose the cause of bleeding.

Endoscopy

An endoscopy is a common diagnostic technique that allows direct viewing of the bleeding site. Since the endoscope can detect lesions and confirm the absence or presence of bleeding, doctors often use this method to diagnose acute bleeding, the endoscope can also be used to treat the cause of bleeding as well.

The endoscope is a flexible instrument that can be inserted through the mouth or rectum. The instrument allows the doctors to see inside the esophagus, stomach, duodenum(esophagoduodenoscopy), sigmoid colon(sigmoidoscopy), and rectum(rectoscopy, to collect small samples of tissues, take pictures, and stop the bleeding. There is a new procedure out using a long endoscope that can be inserted during surgery to locate a source of bleeding in the small intestine.

Capsule Endoscopy

Capsule endoscopy helps doctors to see and examine the lining of the middle part of the gastrointestinal tract, which includes the three parts of the small intestine (duodenum, jejunum, ileum). The capsule is a small pill sized video camera called an endoscope. It has its own lens and light that transfers the images to a monitor so the doctor can view them outside of the body. This process is also referred to as small bowel endoscopy, capsule endoscopy, or wireless endoscopy.

The most common reason for doing a capsule endoscopy is to look for the causes of bleeding that is coming from the small intestine. It is also able to help detect ulcers, tumors, and Crohn's disease.

Angiography

Angiography is a technique that uses dye to highlight blood vessels. This procedure is used when the patient is bleeding badly enough that it allows the dye to leak out of the blood vessels and identifies the bleeding site. In some situations, Angiography allows the patient to have medication injections that may stop the bleeding.

Radionuclide scanning is a non-invasive screening technique used for locating sites of acute bleeding, especially in the lower GI tract. This procedure injects small amounts of radioactive material that either attach to the persons red blood cells or are suspended in the blood. Special pictures are taken that allows doctors to see the blood escaping. Barium x-rays, angiography, and radionuclide scans can be used to locate sites of chronic occult bleeding.

How to Recognize Blood in the Stool and Vomit

• Bright red blood coating the stool
• Dark blood mixed with the stool
• Black or tarry stool
• Bright red blood in the vomit
• Grainy appearance in vomit

Symptoms of Acute Bleeding

• Weakness
• Shortness of breath
• Dizziness
• Cramp abdominal pain
• Diarrhea

Symptoms of Chronic Bleeding

• Fatigue
• Shortness of breath
• Lethargy
• Pallor

## Colonoscopy

A colonoscopy is a test to look at the inside of your colon. Everyone should have a colonoscopy by the time they are 50 to check for diseases of the colon. Colonoscopy is best known for its use in early detection of colorectal cancer, the second leading cause of cancer deaths in the United States. Colon cancer develops from growths like polyps within the intestinal wall. These growths often take 5-10 years to develop usually without symptoms. You are at a higher risk to have this disease if you have a close relative who has had it. If you are going to develop a polyp, you will probably do so after age 50. So the American College of Gastroenterology (the digestive specialists) recommends screening examinations every 5 years for early detection and removal of these cancer-causing growths after that age. Don't make excuses! It's not so bad and it may save your life!

## Case Study

Bob had a history of chronic pain in his intestinal area, and wasn't sure what it was. His doctor suspected what it was and gave Bob antibiotics, which helped. It so happened that whenever Bob ate popcorn or nuts he would get this pain. Sometimes it would just go away... other times he had to go on antibiotics. The doctor ordered some tests, and told Bob he would have to stay away from nuts, popcorn, tomatoes, strawberries, and anything else with seeds or hard parts; something in his bowels couldn't tolerate those foods. Bob ate a pretty healthy diet so he couldn't understand what was happening. A few years later, Bob had another series of painful episodes. The pain was so great Bob could hardly stand, let alone go to work. This time the doctor did more tests and found out that his lower intestine was almost blocked. Surgery was ordered. What did Bob have?

## Glossary

Amebiasis
An inflammation if the intestines caused by infestation with Entameba histolytica (a type of ameba) and characterized by frequent loose stools flecked with blood and mucus
Amylase
An enzyme produces in the pancreas and salivary glands that help in the digestions of starches.
Bile
A bitter, alkaline, brownish-yellow or greenish-yellow fluid that is secreted by the liver, stored in the gallbladder, and discharged into the duodenum and aids in the emulsification, digestion, and absorption of fats. Also called gall.
Biotin
Biotin is used in cell growth, the production of fatty acids, metabolism of fats, and amino acids. It plays a role in the Krebs Cycle. Biotin is also helpful in maintaining a steady blood sugar level. It is often recommended for strengthening hair and nails.
B12
A vitamin important for the normal formation of red blood cells and the health of the nerve tissues. Undetected and untreated B12 deficiency can lead to anemia and permanent nerve and brain damage
Candida Albicans
Found in animals and in man. Has been isolated from the skin and mucosa of man, but has also been recovered from leaves, flowers, water, and soil. Reported to be allergenic. A common cause of superficial infection, oral and vaginal infection, sepsis, and disseminated disease. Cells from the organism are usually not airborne and are considered to be normal component of the flora of the mouth and other mucous membranes on the body.
Chemical digestion
Is a chemical breakdown of food when being in the mouth (oral cavity). Is the digestive secretions of saliva that moistens food and introduces gastric juices and enzymes that are produced in the stimulation to certain macronutrients, such as, carbohydrates. In this, the mouth saliva carries an enzyme called amylase for breaking down carbohydrates.
Cholecystokinin (CCK)
Cholecystokinin (also called pancreozymin), this is a hormone in the small intestinal cells (intestinal mucosa) that is produced in response to food. This hormone regulates the release of secretions of many organs that aid digestion, such as, bicarbonate from the pancreas to reduce the acidity of digestive juices like the chyme that enters the small intestine form the stomach that contains hydrochloric acid (HCL).
Chylomicrons
The lipoproteins first formed after absorption of lipids form food.
Chyme
The thick semi fluid mass of partly digested food that is passed from the stomach to the duodenum.
Crohn's Disease
Described as skip lessions in the large and small bowel it is a malabsorption disorder that can affect the gastrointestinal tract for the mouth to the anus.
Deamination
When an amino acid group breaks off an amino acid that makes a molecule of ammonia and keto acid.
Emulsifier
A mixture of two immiscible (unblendable) substances.
Gastrin
The stomach mucosa secretes a hormone gastrin that increases the release of gastric juices.
GI tract
Gastrointestinal Tract, The tube that extends from the mouth to the anus in which the movement of muscles and release of hormones and enzymes digest food.
Hydrochloric
The chemical substance hydrochloric acid is the water-based solution of hydrogen chloride (HCI) gas. It is a strong acid, the major component of stomach acid and of wide industrial use.
Lactobacillus Acidophilus
Important resident inhabitant of the human small and large intestines, mouth, and vagina. Secretes natural antibiotic substances which strengthen the body against various disease-causing microbes
Leaky gut syndrome
Abnormal level of intestinal permeability
Lingual lipase
An enzyme produced only in infancy to aid digestion of long-chain fatty acids.
Lipase
An enzyme produced by microorganisms that split the fat molecules into fatty acids which create flavor
Mechanical digestion
The crushing of the teeth and rhythms made by the movement of the tongue, the teeth aid in tearing and pulverizing food, while the tongue helps with peristalsis (movement), of food down the esophagus.
Micelles
A product of lipids and bile assist in lipid absorption.
Microvilli
On the villi in the small intestine is mivrovilli, these projections called brush border microvilli secrete specific enzymes for disaccharide hydrolysis, these further aid the absorption of the carbohydrate by yielding a monosaccharide that then can go through portal circulation to liver circulation to be further processed into immediate use for energy or glycogen storage.
Peristalsis
The wavelike muscular contractions of the intestine or other tubular structure that propel the contents onward by alternate contraction and relaxation.
Pharynx
Proliferation
The process of reproduction or division of cells
Proteases
Protein enzyme
Rennin
Only produced during infancy and is a gastric protease and functions with calcium to clot with milk proteins casein, to slow the movement of milk so that digestion is prolonged.
Serotonin
chemical messenger in the brain that affects emotions, behavior, and thought
Synthesize
To create something, such as chemicals in the body, from simpler, raw materials
Ulcerative Colitis
Villi
A minute projection arising from a mucous membrane, especially one of the vascular projections of the small intestine.
Vitamin K
A substance that promotes the clotting of blood

Case Study Answer Bob has diverticulitis. The doctor was afraid that if he had another bad infection that scar tissue would eventually block his colon completely and burst, which would necessitate a colostomy. Bob ended up having to have surgery to remove the damaged part of his colon. The doctor removed almost 18 inches of Bob's large intestine. Bob is doing fine now and most importantly, he can now eat his favorite food - nuts! Note: Sometimes a diet rich in fiber can help you avoid this dreaded problem. Sometimes, like in Bob's case, the predisposition to have this problem runs in the family. All of his siblings and his father suffered from this same ailment. Stress is another factor that can exacerbate this disease. So.. don't worry, be happy and eat fiber!