Physiology: Homeostasis

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Contents 1 Homeostasis 1.1 Thermoregulation 1.2 Body Composition 1.3 Controlling Force 1.4 Body Fluid Distribution 1.5 Dehydration and Volume Depletion 1.6 Water Balance 1.7 Sodium Balance 1.8 Potassium Balance 1.9 Calcium and Phosphate Balance

[edit] Homeostasis

Homeostasis is the maintenance of a constant environment. It depends critically on a negative feedback system which depends upon a 'receptor' monitoring the concentration or other aspect of a variable and transmitting a signal which returns that variable to a predetermined set point. A positive feedback system increases the rate of a reaction or variable and is not compatible, without other controls, with homeostasis. To achieve homeostasis requires a balance of positive and negative forces so that input equals output, thereby maintaining constancy.

A positive feedback system by itself is incompatible with homeostasis as it increases the rate of reaction which leads to a further increase in that variable (eg. increased rate of processes leads to increased heat causing higher temperature). Positive feedback systems do occur (e.g. contractions during parturition or during homeostasis) but are intrinsically unstable and are regulated by negative feedback processes. Failure of this regulation may be the cause of disease. The set point of a parameter is not constant and is controlled in many cases by the hypothalamus. Also surface area to volume ratio affects the rate of metabilism. This is an inverse relation betweeen them. The larger the surface area to ratio the lower the rate of metabolism, and vise versal. Homeostasis is controlled by both voluntary and involuntary processes. The mediation of this control is by the nervous system (autonomic and somatic) and the endocrine (hormonal) system. The set point of many variables is controlled by the hypothalamus but can be varied by a variety of inputs. As the set point is varied, the homeostatic processes adjust to act around the new set point. The endocrine and neural systems' activity interacts at the hypothalamic-pituitary region of the brain. The anterior pituitary gland is connected to the hypothalamus by a "portal" system, which then orchestrates the release of hormones from many different endocrine organs around the body.

Hormonal substances can be endocrine, neurocrine, paracrine, autocrine or a combination of these. An endocrine is released into the blood and acts on tissue at a distant site. A neurocrine is similar to an endocrine but is released from a nerve cell. A paracrine is released and acts locally. An autocrine acts on the cell that secreted it and may also not be secreted but act internally on itself. Most hormones are peptides, proteins or steroids (there are some other substances as well).

Hormones act by binding to a receptor. This receptor may be on the cell membrane or inside the cell (cytoplasm or nucleus). Peptide hormones act on a membrane receptor as they are not lipid-soluble and do not cross the cell membrane. They activate secondary message systems (eg. cyclic AMP) which exert the effect in a different part of the cell. Steroid hormones are lipid-soluble and can cross the cell membrane, exerting their effect by binding to cytoplasmic or nuclear receptors. They commonly have this effect by altering DNA and thus mRNA production, thereby altering protein production. Peptide hormones usually act immediately but there may be a considerable delay before the action of a steroid hormone is observed.

[edit] 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 irespective of temperature of surrounding environment. This capability of maintaining body temperature is called thermoregulation.--Vkghai 06:48, 18 February 2006 (UTC)

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 vasoconstriction 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 adjustment in cold is to shiver to increase heat production.

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 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.

[edit] 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

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 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. 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.

[edit] Controlling Force

Electrolytes are transported via many mechanisms. These include:

Primary active transport

Na+-K+-ATPase
K+-K+-ATPase
Ca2+-Mg2+-ATPase

Secondary active transport

Cotransport
Counter transport

Passive Transport

Diffusion
Channels or pores
Carriers

Concentration gradient (if uncharged)

Electrochemical gradient (if charged)

Water:
 Osmolality
 Osmotic pressure

[edit] 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 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

[edit] 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.

[edit] Water Balance

Vasopressin is the principal compound controlling water balance by decreasing water output by the kidney. 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 klkølk (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.

[edit] 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.

[edit] Potassium Balance

	Amount	Concentration
Amount in body	4000 mmol
Intracellular	3000 + mmol	110 mmol/l
Extracellular	52 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.

[edit] 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 reabsorption, 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.