Water balance

From Iusmphysiology

• started here on 03/24/11.

Contents 1 Water balance 1.1 Collecting duct review 1.2 Water distribution in the body 1.3 Effects of disturbances on osmolalities and volumes of ICF and ECF 1.4 Daily water balance in an average 70kg man 1.5 Thirst 1.6 AVP 1.7 AVP release 1.8 Factors that increase ADH release 1.9 AVP threshold versus thirst threshold 1.10 Urine osmolality versus plasma osmolality 1.11 Hemorrhaging and AVP release 1.12 The body's response to excess hydration 1.13 Human response to drinking lots of water 1.14 Maintenance of effective arterial blood volume overrides 1.15 AVP increases water permeability of the collecting tubules 1.16 Water permeability along the nephron

[edit] Water balance

[edit] Collecting duct review

• Recall what we learned about the collecting duct:
  • 2/3 principal cells, 1/3 intercalated cells
  • The collecting duct is a tight epithelium
  • ENaC is expressed on the principal cells of the collecting duct and is used to reabsorb Na via loss of K.
    • ENaC is also inhibited by amiloride.
    • Amiloride is a potassium-sparing diuretic because it inhibits reabsorption of Na via ENaC and therefore inhibits the loss of K.
    • Amiloride acts at the very end of the nephron (at the collecting duct on the ENaC channels), so it wastes less potassium.
• Recall that it is the principal cells where AVP works (it causes AQP to be expressed on the apical surface).
  • It is also the principal cells where aldosterone work: increases expression of ENaC on the apical surface.

• Mutations in Liddle syndrome cause a slow down in turnover of the ENaC channels such that increased water reabsorption occurs and hypertension results.
  • So, even at the very distant site of the collecting duct, we can still reabsorb enough Na to cause hypertension.

[edit] Water distribution in the body

• The amount of water as a percent of weight is dependent on age, gender, and amount of adipose tissue.
  • Age generally decreases water as percent of weight.
    • This is primarily due to the loss of muscle which is a high-water tissue.
  • Women generally have less percent body weight in water than men.
  • Increased adipose tissue leads to decreased percent of body weight as water.
    • This makes sense because adipose tissue won't accomadate much water, so when more of your body weight is made of an anti-water material, you'll have less of your body weight percent be from water.

• There are two major compartments for body fluids: intracellular (within cells) and extracellular.
  • The intracellular compartment contains 40% (28 liters) of the body weight.
  • The extracellular compartment contains a total of 20% (14 liters) of the body weight.
    • Within the extracellular compartment there are two other compartments: interstitial water, plasma water.
    • The interstitial water compartment contains 15% (10.5 liters) of the body weight.
    • The plasma water compartment contains 5% (3.5 liters) of the body weight.
• Note how small the plasma water compartment is, relative to the interstitial and intracellular compartments.
• For women, only 50% of the body weight is made up of water and the intracellular compartment makes up 30% of the body weight.
  • That is, women are less water by weight and the water they do have lies more heavily in the intracellular compartment.
  • Women have a higher percent of adipose tissue, so it makes sense that they have less water as percent of body weight.

[edit] Effects of disturbances on osmolalities and volumes of ICF and ECF

• In a healthy, normal state, 28L of the body's water is in the intracellular compartment and 16 liters is in the extracellular compartment.
• In response to water added intravenously, osmolality of the ECF compartment decreases, then osmolality of the ICF will decrease to match the osmolality of the ECF, finally both intracellular and extracellular volumes will be increased in volume proportionally.
• In response to isotonic saline added intravenously, the extracellular compartment will expand but the intracellular compartment will remain fixed.
  • Recall that saline is Na, Cl and water and that Na will not enter the intracellular compartment because of Na / K ATPase.
  • Recall that water follows solute.
  • Since Na will not leave the extracellular compartment, nor will water; thus the ECF compartment expands but the intracellular compartment does not.
• In response to 5% NaCl solution (that is, a Na Cl solution more concentrated than plasma) added intravenously, the ECF compartment will increase in volume (as water flows out of the intercellular compartment, into the ECF) and both compartments will increase in osmolality.
  • Recall that 5% NaCl is a higher osmolality than normal blood and thus the Na and Cl of the solution will increase the osmolality of the ECF.

• Know how each of these is corrected the kidney.
  • Think about hydrostatic pressures, ADH signaling, aldosterone signaling, etc.

[edit] Daily water balance in an average 70kg man

• The normal input of water is 2.5 liters from:
  • 1 liter from beverages
  • 1.2 liters from food
  • 0.3 liters from water oxidation
• The normal output of water is 2.5 liters from:
  • 0.9 liters from skin and lungs
  • 0.1 liters from feces
  • 1.5 liters from urine
• Note that the kidneys fluctuate their function to regulate output to match input.

• Recommendations for eight 8 ounce glasses of water each day are unfounded.
• There are good reasons to drink water, but 64 ounces is not an evidence-based rule.
  • Water helps reduce stone formation in at-risk populations.
  • Water helps maintain tooth health by increasing saliva flow.
• One should simply drink when thirsty and enough to generate about 1.5 liters of urine each day.

[edit] Thirst

• There are several mechanisms by which the sensation of thirst is generated.
  • Thirst is generated by stimulating the hypothalamus.
• The hypothalamic response to thirst is to release ADH
  • Recall that ADH arises from the hypothalamus, is released by the posterior pituitary, and causes insertion of aquaporin proteins on the apical surface of principal cells of the DCT and collecting duct of the nephron.
• Thirst is felt at any water loss greater than 3% of total body weight.

• An increase in plasma osmolality can generate thirst:
  • There are two separate groups of osmoreceptors in the CNS: one set in the CNS that generates thirst sensation and another in the hypothalamus that generates ADH release.
  • Osmoreceptors detect changes in the osmolality of the ECF based on how water is flowing across their own cell membrane.
  • When water is flowing outward, the ECF is less dilute (higher osmolality) than the intracellular compartment.
  • It is when water flows out of the osmoreceptors that these two groups of osmoreceptors generate their effects: thirst and AVP release.
  • The osmoreceptors of the hypothalamus are neurons that project to other, larger neurons of the hypothalamus that produce AVP.
    • Upon changes in water flow over the osmoreceptor, it signals to the larger neurons, which deliver AVP to the posterior pituity, and release AVP into the blood at the posterior pituitary.
    • Note that this is a neuroendocrine system.

• A decrease in blood volume can generate thirst:
  • Baroreceptors reside in the large vessels of the body and detect changes in blood pressure which can be indicative of blood volume.
  • There are two types of baroreceptors: high pressure baroreceptors (cardiopulmonary) and low pressure baroreceptors (volume receptors).
  • In regards to thirst, we are discussing the low pressure baroreceptors.
  • Low pressure baroreceptors are found in the large veins, the pulmonary vessels, and the atrial walls.
  • Volume baroreceptors use both innervation and hormones to correct volume changes.
  • Volume baroreceptors (low pressure baroreceptors) use an inhibitory signaling to the hypothalamus to manage thirst and blood volume.
    • That is, when denervated, the body things the blood pressure is low and tries to retain water.
  • Low pressure baroreceptors release renin in response to low pressure and thus cause system-wide vasoconstriction and increased blood pressure.

Do these baroreceptors actually release renin or only signal for renin release?

• • If the blood volume decreases by 10%, baroreceptors decrease their firing rate to the hypothalamus and increase renin release.

• Mouth and throat dryness can generate thirst:
  • Innervation of the mouth and throat can cause the hypothalamus to experience thirst and respond with ADH.

• The GI tract can decrease thirst:
  • As the stomach is distended or water is absorbed, the GI tract sends thirst-inhibiting nerve signals to the hypothalamus.

[edit] AVP

• AVP = arginine vasopressin = ADH = antidiuretic hormone
• AVP is encoded by an mRNA for a translation product called preproneurophysin.
• Preproneurophysin is made up of the AVP prohormone, neurophysin, and a glycopeptide.
• AVP (the active hormone) is only 9 aa long and has a plasma half-life of 9 minutes because of metabolism by the kidney and liver.
  • Recall that one of the kidney's jobs is to destroy all the peptide hormones.
• We call AVP arginine vasopressin because of the arginine at the 8th position.
  • Some other mammals like pigs, hippos, and some marsupials use lysine vasopressin with lysine at the 8th position.
  • Lysine vasopressin can be used in human therapy, too.

[edit] AVP release

• AVP is released when osmolality of the ECF increases.
  • The AVP release system is more sensitive to increases in plasma osmolality when the volume contracted.
  • The opposite also remains true; the AVP release system is less sensitive to plasma osmolality changes when the ECF volume is elevated.

This makes sense, but how?  Is it a function of signaling threshold at the hypothalamus where APs from both osmoreceptors and baroreceptors hit threshold more often than when only received from osmoreceptors?

• Osmolality is the more acute signal than blood pressure:
  • AVP is released when plasma osmolality increases by only 1%.
  • AVP is released when circulating volume decreases by 5-10%.
• Note that a normal plasma osmolality is 285-290 mOsm.
  • ADH release occurs at around 280 mOsm.
  • So we have a normal, small amount of AVP in the blood most of the time.

[edit] Factors that increase ADH release

• There are several factors that will increase the release of ADH in the body, several of which we have mentioned.
• Cellular dehydration will cause an effective increase in plasma osmolality and thus increase ADH release.
  • High salt diets can cause cellular dehydration.

What causes cellular dehydration?  What causes cellular dehydration without a proportional dehydration of the ECF?  Does high salt diet really cause cellular dehydration?

• Hypovolemia will result in an effective decrease in arterial blood volume and increased signaling from baroreceptors.
• Pain, trauma, emotional stress, nausea, fainting, nicotine, morphine, angiotensin 2, and most anesthetics will increase ADH release.
  • Recall that one of the body's responses to stress is to retain water.
  • Recall SIADH (syndrome of inappropriate ADH secretion) which aberrantly increases ADH release and therefore increase water retention.

• There are also ways to decrease ADH release:
  • Ethanol: recall that after alcohol intake, one feels increased urge to pee.
  • Atrial natriuretic: recall that atrial natriuretic peptide is released when the atria detect high blood pressure, thus decreasing the stimulus to the kidney to retain water.
    • Naturesis = loss of Na at the kidney.

[edit] AVP threshold versus thirst threshold

• The threshold for AVP release is about 280 mOsm.
• Humans generally demonstrate a plasma osmolality of about 285 mOsm, meaning AVP is released at some baseline level.
• Thirst, however, does not manifest until over 290 mOsm such that we do not feel the sensation of thirst all the time.

[edit] Urine osmolality versus plasma osmolality

• In a healthy state, urine has a higher osmolality than plasma.
  • It makes sense that urine has a higher osmolality than plasma because we reabsorb so much of the water from urine but leave so many of the solutes.
• As AVP secretion increases, urine osmolality increases.
  • That is, as AVP increases, water reabsorption increases and urine solute : water ratio goes up.
  • We can concentrate urine to a maximum of about 1200 mOsm.
  • At 1200 mOsm, increasing AVP does not cause increased concentration of the urine.
• When AVP release is very, very low, urine osmolality is less than plasma osmolality.

• What happens to AVP release when:
  • The weather is cold: blood is shifted away from the skin, which is interpreted by the baroreceptors as an increase in volume and thus causes a decrease in AVP release and an increase in urine production.
  • Swimming: the bouyancy provided by swimming allows the blood that usually sits down in the legs to distribute more evenly throughout the body. Thus, baroreceptors detect higher blood pressure, release less AVP, and more urine is produced.

[edit] Hemorrhaging and AVP release

• An experiment in rats shows that when blood loss exceeds 10% of the normal volume, AVP release increases rapidly and acts as a vasoconstrictor.
  • AVP release is 10 times as much as standard water-maintaining AVP release levels.
• In this traumatic situation (large blood loss), AVP as a systemic vasoconstrictor in addition to acting as a water-retaining signal.
  • Vasoconstriction increases blood pressure to the vital organs.

[edit] The body's response to excess hydration

• The body's response to hydration is similar to dehydration in that it functions through ADH modulation and is detected through osmoreceptors and baroreceptors.
• Upon excess hydration, the plasma osmolality decreases.
  • Recall that water follows the osmolarity gradient; in the gut, the interstitum will have a much higher osmolality than the lumen, therefore water will flow into the body (the extracellular compartment).
  • As the osmolality decreases, water will flow into the osmoreceptors of the hypothalmus and they will release less ADH, thus allowing the kidney to lose water.
• Upon excess hydration, the plasma volume increases.
  • Recall that water will flow into the interstitium at the gut, then into the lymph and into the blood (plasma).
  • Increased blood pressure will cause cardiovascular stretch receptors (in the atria) to signal for decreased ADH release from the hypothalamus / posterior pituitary.

Do these atrial stretch receptors signal via nervous firing?  Do they signal to the hypothalamus, the post pit, or to the medulla?

[edit] Human response to drinking lots of water

• When humans drink lots of water, ADH can be completely shut off.
• Without any ADH expression, the collecting duct will not reabsorb any water but the PCT reabsorption will not change.
  • The collecting duct becomes impermeable to water without ADH expression (that is, without aquaporin).
• Note that most of the excess water consumed was excreted within an hour of consumption.
• Also, recognize that water reabsorption is only moderated at the collecting duct which is only responsible for 10% of water reabsorption.
  • However, because the kidney sees so much flow, we can retain or lose lots of water by just controlling that 10%.
  • Recall, 10% of the kidney's filtrate volume is 18L / day of controllable volume.

[edit] Maintenance of effective arterial blood volume overrides

• Because AVP is important for regulating both plasma osmolality and blood volume, we wonder which one takes precedence.
• It seems that effective arterial blood volume (EABV) takes precedence over maintaining a certain plasma osmolarity.
  • That is, when blood pressure is low, AVP will be released inspite of the fact that osmolality is decreased.
  • This is important in disease states like congestive heart failure where the EABV (effective arterial blood volume) can appear low because the heart is not moving blood properly.
  • While EABV (effective arterial blood volume) will be maintained via ADH, the osmolality of the plasma will decrease which can cause cellular swelling.
    • Cellular swelling is especially bad in fixed volume areas like the cranium!
• That is, arterial blood volume will be restored at the expense of osmolality--even to the point of making the patient hyponatremic.

[edit] AVP increases water permeability of the collecting tubules

• Recall that AVP increases expression of the aquaporin proteins on the tubular cells of the collecting duct.
• AVP binds to the V2 receptor which uses a g-protein and adenylyl cyclase to increas cAMP.
  • Thus AVP activates PKC and other proteins.
• Ultimately, AVP signaling through cAMP and PKC causes vesicles holding AQP (aquaporin) to be released such that aquaporin is integrated into the apical surface of the tubular cells.
• Increased AQP2 on the apical surface allows water to follow Na reabsorption.
• Also, AVP increases synthesis of the AQP2.
• Note, too, that AQP3 and AQP4 are always expressed on the basal surface of the principal cells.

[edit] Water permeability along the nephron

• Recall that water reabsorption occurs primarily in the PCT, the PST (proximal straight tubule), and the thin descending limb of Henle (tDLH).
• Also, water reabsorption can be increased via ADH's effect on the cortical collecting duct and the inner medullary collecting duct.
• In comparison, the proximal sections are nearly twice as water permeable as the distal regions even when the distal sections are AVP stimulated.