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The Regular of Extracellular Fluids – ADH Secretion and Renin-Angiotensin System

CaduceusThe volume of ECF is determined primarily by the total amount of osmotically active solute in the ECF. Excessive loss of Na+ in the stools (diarrhea), urine (severe acidosis, adrenal insufficiency), or sweat (heat prostration) decreases ECF volume markedly and eventually leads to shock.

The regular of extracellular fluids is based on vasopressin (ADH) and renin-angiotensin system. The homeostatic mechanisms for controlling blood volume are focused on controlling sodium balance. In contrast, the homeostatic mechanisms for controlling plasma osmolality, which is largely determined by serum sodium concentration, are focused on controlling water balance.

The extracellular and intracellular concentration of sodium and potassium are maintained by Na+-K+-ATPase (although solutes generally cannot freely cross cell membranes) and these maintained concentration determine the osmolality of extracellular and intracellular fluids. Most cell membranes are freely permeable to water, and thus the osmolality of intra- and extracellular body fluids is the same. Otherwise, water will move from the hypotonic compartments to hypertonic compartments.

The Genesis of Osmosis

When a substance is dissolved in water, the concentration of water molecules in the solution is less than that in pure water, because the addition of solute to water results in a solution that occupies a greater volume than dose the water alone. If the solution is placed on one side of a membrane that is permeable to water but not to the solute, and an equal volume of water is placed on the other, water molecules diffuse down their concentration (chemical) gradient into the solution. This process – the diffusion of solvent molecules into a region in which the membrane is impermeable – is called osmosis.

The tendency for movement of solvent molecules to a region of greater solute concentration can be prevented by applying pressure to the more concentrated solution. The pressure necessary to prevent solvent migration is the osmotic pressure of the solution. Just like shown in picture below.

Screen Shot 2014-10-26 at 3.00.36 PM

Control of Vasopressin Secretion

Plasma osmolality and ECF volume can affect the secretion of ADH.

ADH increases the permeability of the collecting ducts of the kidney, so that more water enters the hypertonic interstitium of the renal pyramids and the urine becomes concentrated and its volume decreases (the hypertonic status of renal pyramid interstitium is caused by the “countercurrent mechanism”. The thin descending limb is only permeable to water. And the thick ascending limb has active transport of Na+ and Clwhich makes the intersitium hypertonic).

The overall effect of ADH is retention of water in excess of solute; consequently, the effective osmotic pressure of the body fluids is decreased. In the absence of vasopressin, the urine is hypotonic to plasma, urine volume is increased, and there is a net water loss; consequently, the osmolality of the body fluid rises.

The secretion of ADH is controlled by mechanisms of osmotic stimuli and volume feedback effect.

When effective osmotic pressure of the plasma is increased above 285 mOsm/kg, the rate of discharge of neurons containing vasopressin increases and vasopressin secretion occurs. Generally, at 285 mOsm/kg, plasma vasopressin is at or near the limits of detection by available assays.

Meanwhile, as plasma osmolality increases, the feeling of thirst gets stronger and people will take more water. The osmotic threshold for thirst is the same as or slightly greater than the threshold for increased vasopressin secretion.

A decreased extracellular volume or major decrease in arterial pressure reflexively activates increased ADH secretion. To say strictly, the effective circulating blood volume affeccts ADH secretion via volume receptors. These receptors are located in low- and high-pressure portions of the vascular system. The response is mediated by neural pathways originating in cardiopulmonary baroreceptors, and if arterial pressure decreases, from arterial baroreceptors. There is an inverse relationship between the rate of ADH secretion and the rate of discharge in afferents from stretch receptors. AngII reinforces the response to hypovolemia and hypotension by acting on the circumventricular organs to increase ADH secretion (but it is not certain which of the circumventricular organs are responsible for the increases in ADH secretion).

Also, volume effects have an inverse relationship with the feeling of thirst (probably by the increased level of ang II).

Some other factors such as pain, nausea, surgical stress, and emotions would affect the secretion of ADH. Alcohol decreases ADH secretion.

Control of Renin-Angiotensin System

The most important angiotensin is ang II. In physiology,

angiotensin II produces arteriolar constriction and a rise in systolic and diastolic blood pressure.

Ang II also acts directly on the adrenal cortex to increase the secretion of aldosterone.

Besides, ang II acts on the brain to decrease the sensitivity of the baroreflex, which potentiates the pressor effect of ang II.

Ang II acts on the brain to increase water intake and increase the secretion of ADH.

In general, four factors regulate the secretion of rennin and the resultant ang II and aldosterone. When arteriolar pressure at the level of the JG cells falls, renin secretion is enhanced. Renin secretion is inversely proportional to the amount of Na+ and Cl entering the distal renal tubules from the loop of Henle. Besides, ang II fees back to inhibit renin secretion by a direct action on the JG cells. Finally, increased activity of the sympathetic nervous system increases renin secretion.

Additional Information (updated on Jun 12th 2014)

Thirst

Water intake is increased by increased effective osmotic pressure of the plasma and by decrease in ECF volume (to say strictly, the effective circulating blood volume) and the impact of effective circulating blood volume >the one of effective osmotic pressure (and the Plasma Osmolality – ADH Secretion cluve shifts to the left by decreased effective circulating blood volume).

Osmolality acts via osmoreceptors, receptors that sense the osmolality of the body fluids (more accurately, the plasma). These osmoreceptors are located in the anterior hypothalamus. Decrease in ECF volume stimulate thirst by a pathway independent of that mediating thirst in response to increased plasma osmolality. Generally, the effect of ECF volume depletion on thirst is mediated in part via the rennin-angiotensin system. The angII acts on the subfornical organ (one of the circumventricular organs of the brain), a specialized receptor area in the diencephalon, to stimulate the neural area concerned with thirst. Some evidence suggests that it acts on the OVLT (no BBB) as well.

However, drugs that block the action of angII do not completely block the thirst response to hypovolemia (and decreased effective circulatory pressure).

2 Comments

  1. The Function of AngII

    http://forum.tomhsiung.com/physiology-and-pathophysiology/461-the-function-of-angii.html

    1. Vascular Constriction and Blood Pressure

    AngII produces arteriolar constriction and a rise in systolic and diastolic blood pressure. It is one of the most potent vasoconstrictors known, being four to eight times as active as norepinephrine on a weight basis in normal individuals. However, its pressor activity is decreased in Na+-depleted individuals and in patients with cirrhosis and some other diseases. In these conditions, circulating angII is increased, and this down-regulates the angiotensin receptors in vascular smooth muscle. Consequently, there is less response to injected angII.

    2. Effects On Adrenal Gland and Glomerulus

    AngII acts directly on the adrenal cortext to increase the secretion of aldosterone, and the renin-angiotensin system is a major regulator of aldosterone secretion. Additional actions of angII include facilitation of the release of norepinephrine by a direct action on postganglionic sympathetic neurons, contraction of mesangial cells (located in glomerular capillaries) with a resultant decrease in GFR, and a direct effect on the renal tubules to increase Na+ reabsorption.

    3. Effects On Brain

    AngII acts on the brain to decrease the sensitivity of the baroreflex, and this potentiates the pressor of angII. In addition, it acts on the brain to increase water intake and increase the secretion of ADH and ACTH (where there are circumventricular organs, but which organ is not certained).

    Posted on 29-Jun-14 at pm 10:51 | Permalink
  2. Thread from Pharmacy Profession Forum – The regulation of ECF in body, http://forum.tomhsiung.com/pharmacy-practice/pharmacotherapy/640-regulation-ecf-body.html.

    Generally, five aspect of factors directly affect the volume of ECF, including: 1.Renal plasma flow;2.ADH;3.Renin-angiotensin system;4.Thirst;and 5.Other factors affecting GFR.

    1.Renal plasma flow

    Renal plasma flow would alter GFR positively. Since the increase of renal plasma flow increase the amount of volume of plasma filtrated by glomerular in every unit of time. Besides, as the renal plasma flow increases, the rate of increase in πGC is slow down (flow-limited exchange) and the distance along the glomerular capillaries is prolonged, which makes filtrate increased and the GFR.

    Factors that alter renal plasma include constriction of renal blood arterial vessels, afferent arteriolar, low effective circulatory volume etc affect GFR as described above, and stimulation of the renal nerves (sympathetic efferent fibers) also cause the vasoconstriction of renal blood arterial vessels.

    2.ADH

    Effective osmotic pressure of the plasma is increased above 285 mOsm/kg, the rate of discharge of neurons containing vasopressin increases and vasopressin (ADH) secretion occurs.

    ECF volume also affects ADH secretion. To say strictly, the effective circulating blood volume affeccts ADH secretion via volume receptors.

    AngII reinforces the response to hypovolemia and hypotension by acting on the circumventricular organs to increase ADH secretion (but it is not certain which of the circumventricular organs are responsible for the increases in ADH secretion).

    Some other factors such as pain, nausea, surgical stress, and emotions would affect the secretion of ADH.

    Alcohol decreases ADH secretion.

    3.Renin-angiotensin system

    When arteriolar pressure at the level of the JG cells falls, renin secretion is enhanced.

    Renin secretion is inversely proportional to the amount of Na+ and Cl- entering the distal renal tubules from the loop of Henle.

    The stimulation of renal sympathetic fibers increases secretion of renin.

    Besides, ang II feeds back to inhibit renin secretion by a direct action on the JG cells.

    Finally, increased activity of the sympathetic nervous system increases renin secretion.

    4.Thirst

    Osmolality acts via osmoreceptors, receptors that sense the osmolality of the body fluids (more accurately, the plasma). These osmoreceptors are located in the anterior hypothalamus.

    Decrease in ECF volume stimulate thirst by a pathway independent of that mediating thirst in response to increased plasma osmolality. Generally, the effect of ECF volume depletion on thirst is mediated in part via the rennin-angiotensin system. AngII’s effects on thirst (the brain) can be antagonised by Natriuretic Hormones (ANP, BNP, CNP).

    5.Other factors affecting GFR

    Formula, GFR = k[(PGC – PT) – (πGC – πT)]

    PGC is the mean hydrostatic pressure in the glomerular capillaries, PT is the mean hydrostatic pressure in the tubule, πGC is the oncotic pressure of the plasma in the glomerular capillaries, and πT is the oncotic pressure of the filtrate in the tubule. Normally, the πT is negligible and can be ignored. So the GFR can be calced as follows:

    GFR = k[(PGC – PT) – πGC]

    Changes in glomerular capillary hydrostatic pressure would affect GFR directly as explained in the formula above.

    The constriction of efferent arteriolar would increase the glomerular capillary hydrostatic pressure and to maintain the GFR to some degree (When renal blood flow decreases, the constriction of efferent arteriolar due to effect of AngII help to maintain the GFR).

    ANP and BNP in the circulation act on the kidneys to increase fluid and Na+ excretion and injected CNP has a similar effect. ANP: atrial natriuretic peptide (ANP), BNP: brain natriuretic peptide, and CNP: C-type natriuretic peptide. They appears to produce this effect by dilating afferent arterioles and relaxing mesangial cells. Both of these actions increase GFR.

    Changes in hydrostatic pressure in Bowman’s capsule.

    Changes in Kf. For example, the contraction of mesangial cells produces a decrease in Kf that is largely due to a reduction in the area available for filtration.

    Changes in glomerular capillary permeability.

    Changes in effective filtration surface area.

    References:

    1.The Regular of Extracellular Fluids – ADH Secretion and Renin-Angiotensin System Tom “Prophet” Hsiung » The Regular of Extracellular Fluids – ADH Secretion and Renin-Angiotensin System

    2.Factors That Affect GFR Tom “Prophet” Hsiung » Factors That Affect GFR, http://www.tomhsiung.com/wordpress/2014/04/factors-that-affect-gfr/.

    Posted on 09-Mar-15 at pm 5:52 | Permalink

One Trackback/Pingback

  1. […] The regular of extracellular fluids is based on vasopressin (ADH) and renin-angiotensin system. The detail regulation mechanisms of ADH and RAS can be found here (http://www.tomhsiung.com/2014/03/the-regular-of-extracellular-fluids-adh-secretion-and-renin-angiote…). […]

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