Water Balance: Urine Concentration and Dilution

Water Balance: Concentration and Dilution of Urine

• Body fluid osmolarity is maintained around 290 mOsm/L (approximately 300 mOsm/L) through osmoregulation.
• Homeostatic hormonal responses correct even minor osmolarity deviations by altering kidney water reabsorption.
• Renal water reabsorption mechanisms are responsible for maintaining consistent body fluid osmolarity.
• Regulation of water balance occurs in the late distal tubule and collecting duct.
• Urine osmolarity varies with water reabsorption, ranging from 50 mOsm/L to 1200 mOsm/L.
• Isosmotic urine has the same osmolarity as blood.
• Hyperosmotic urine has higher osmolarity than blood.
• Hyposmotic urine has lower osmolarity than blood.

Regulation of Body Fluid Osmolarity

• Body fluid osmolarity regulation is exemplified by responses to water deprivation and drinking water.

Response to Water Deprivation

• Water is continuously lost through insensible water loss (sweat, mouth, and nose vapor).
• Increased plasma osmolarity stimulates osmoreceptors in the anterior hypothalamus, particularly those sensitive to changes smaller than 1 mOsm/L.
• Hypothalamic osmoreceptor stimulation leads to thirst (driving drinking) and ADH secretion from the posterior pituitary gland.
• ADH increases water permeability in the principal cells of the late distal tubule and collecting duct.
• Increased water permeability boosts water reabsorption in these segments.
• Urine osmolarity increases, and its volume decreases as more water is reabsorbed.
• Increased water reabsorption returns more water to body fluids.
• Thirst and drinking decrease plasma osmolarity back to normal.
• This system uses negative feedback, where increased plasma osmolarity triggers ADH secretion and water reabsorption to restore normal osmolarity.

Response to Drinking Water

• Ingested water distributes throughout body fluids, diluting solutes and reducing plasma osmolarity.
• Decreased plasma osmolarity inhibits osmoreceptors in the anterior hypothalamus.
• Osmoreceptor inhibition reduces thirst, suppresses drinking, and inhibits ADH secretion from the posterior pituitary gland.
• Reduced ADH secretion lowers ADH levels delivered to the kidneys.
• Lower ADH reduces water permeability in principal cells of the late distal tubule and collecting ducts.
• Decreased water permeability reduces reabsorption in the late distal tubule and collecting ducts.
• Unabsorbed water is excreted, decreasing urine osmolarity and increasing its volume.
• Coupled with thirst inhibition and suppressed drinking, reduced water reabsorption helps plasma osmolarity increase back to normal.

Corticopapillary Osmotic Gradient

• Understanding kidney osmoregulation requires understanding the corticopapillary osmotic gradient.
• The corticopapillary osmotic gradient refers to the osmolarity gradient in the kidney's interstitial fluid, increasing from the cortex to the papilla.
• The cortex has an osmolarity around 300 mOsm/L, like other body fluids.
• Osmolarity progressively increases from the cortex to the outer and inner medulla and papilla. The tip of the papilla can reach as high as 1200 mOsm/L.
• Countercurrent multiplication (in the loop of Henle) deposits NaCl, and urea recycling (in the inner medullary collecting ducts) deposits urea, establishing this gradient.

Countercurrent Multiplication

• Countercurrent multiplication occurs in the loop of Henle.
• It deposits NaCl in the deep kidney regions to form the corticopapillary osmotic gradient.
• The loop of Henle initially has no corticopapillary gradient, with osmolarity at 300 mOsm/L throughout.
• Countercurrent multiplication increases interstitial fluid osmolarity through a repeating two-step process: the single effect and tubular fluid flow.

Single Effect

• In the thick ascending limb of the loop of Henle, NaCl is reabsorbed using the Na+-K+-2Cl- cotransporter.
• The thick ascending limb is water-impermeable, so water isn't reabsorbed with NaCl, diluting tubular fluid.
• NaCl enters the interstitial fluid, increasing its osmolarity.
• The descending limb is water-permeable, so water flows out until its osmolarity matches the adjacent interstitial fluid.
• The single effect decreases ascending limb osmolarity and increases interstitial fluid and descending limb osmolarities.
• ADH enhances the action of the Na+-K+-2Cl- cotransporter, boosting the single effect.
• High ADH levels (e.g., in dehydration) augment the corticopapillary osmotic gradient.
• Low ADH levels (e.g., in central diabetes insipidus) diminish the corticopapillary osmotic gradient.

Flow of Tubular Fluid

• Glomerular filtration is continuous, meaning fluid continuously goes through the nephron.
• New fluid enters the descending limb from the proximal tubule and an equal volume of fluid must exit the ascending limb into the distal tubule.
• New fluid entering the descending limb has an osmolarity of 300 mOsm/L because it comes from the proximal tubule.
• The high-osmolarity fluid in the descending limb, as a result of the single effect, goes down the loop of Henle.
• Step 1: NaCl is reabsorbed out of the ascending limb into the interstitial fluid, leaving water behind, so interstitial fluid osmolarity rises to 400 mOsm/L, and fluid in the ascending limb dilutes to 200 mOsm/L. Fluid in the descending limb equilibrates with the interstitial fluid, and its osmolarity also rises to 400 mOsm/L.
• Step 2: New fluid with an osmolarity of 300 mOsm/L enters the descending limb from the proximal tubule, displacing fluid from the ascending limb. The high-osmolarity fluid in the descending limb (400 mOsm/L) is "pushed down" toward the bend of the loop of Henle.
• Step 3: NaCl is reabsorbed again out of the ascending limb and deposited in interstitial fluid, and water remains behind. The osmolarity of the interstitial fluid and descending limb fluid increases, adding to the gradient that was established in the previous steps, while the osmolarity of the fluid of the ascending limb decreases further (is diluted).
• Step 4: New fluid with an osmolarity of 300 mOsm/L enters the descending limb from the proximal tubule, which displaces fluid from the ascending limb. As a result of the fluid shift, the high-osmolarity fluid in the descending limb is pushed down toward the bend of the loop of Henle. The gradient of osmolarity is now larger.
• Repeating both steps establishes the corticopapillary gradient.
• Each repeat multiplies the gradient.
• The gradient's size depends on the length of the loop of Henle.
• The osmolarity of interstitial fluid at the bend of the loop of Henle is 1200 mOsm/L in humans but can reach 3000 mOsm/L in species with longer loops (e.g., desert rodents).
• When ADH levels is high (as in water deprivation) differential permeability effects occur and urea is recycled into the inner medulla, which adds to the corticopapillary osmotic gradient.
• When ADH levels are low (as in water drinking or diabetes insipidus), the differential permeability effects do not occur, and urea is not recycled. ADH increases corticopapillary gradient by stimulating Na+-K+-2Cl- cotransport and countercurrent multiplication. The corticopapillary osmotic gradient is greater when ADH levels are high than when ADH levels are low.

Vasa Recta

• The vasa recta are capillaries serving the kidney's medulla and papilla that follow the loop of Henle.
• Only 5% of renal blood flow serves the medulla, and blood flow through the vasa recta is low.
• The vasa recta facilitate countercurrent exchange.
• Countercurrent multiplication is an active process, while countercurrent exchange is passive, helping maintain the gradient.
• Vasa recta are permeable to small solutes and water, and the slow blood flow allows solute and water movement.
• Blood entering the descending limb has an osmolarity of 300 mOsm/L.
• Because the vasa recta is capillaries, NaCl and urea diffuse into the descending limb, while water diffuses out, allowing the blood to equilibrate with the gradient.
• At the bend, the blood has an osmolarity of 1200 mOsm/L.
• The opposite occurs in the ascending limb, with solutes diffusing out and water diffusing in.
• Blood leaving the vasa recta has an osmolarity of 325 mOsm/L (slightly higher than entering blood).
• Some solute is carried back to circulation, but countercurrent multiplication and urea recycling replace lost solute.

Antidiuretic Hormone

• ADH increases water permeability in the principal cells of the late distal tubule and collecting ducts.
• ADH increases the activity of the Na+-K+-2Cl- cotransporter in the thick ascending limb, enhancing countercurrent multiplication and the corticopapillary osmotic gradient's size.
• ADH increases urea permeability in inner medullary collecting ducts, enhancing urea recycling and the gradient's size.
• The permeability effect is the best known.
• In the absence of ADH, the principal cells are impermeable to water
• In the presence of ADH, water channels or aquaporins are water permeable

Production of Hyperosmotic Urine

• Hyperosmotic urine is more concentrated than blood.
• Increased ADH causes hyperosmotic urine, which occurs during water deprivation or SIADH.

Steps in Production of Hyperosmotic Urine

• Osmolarity values indicate points along the nephron and the interstitial fluid.
• Heavily outlined segments of the thick ascending limb and early distal tubule are impermeable to water.
• Arrows indicate water reabsorption in different nephron segments.
• Initial glomerular filtrate has the same osmolarity as blood at 300 mOsm/L.
• Urine osmolarity can reach up to 1200 mOsm/L.
• The corticopapillary osmotic gradient results from countercurrent multiplication and urea recycling.
• One question concerns HOW the kidney produces urine that is more concentrated than blood.
• The other questions concerns WHAT determine show high the urine osmolarity will be?
• The glomerular filtrate has the same osmolarity as blood because water and small solutes are freely filtered.
• The osmolarity remains at 300 mOsm/L along the entire proximal convoluted tubule, because water is always reabsorbed in exact proportion to solute; that is, the process is isosmotic.
• The process also can be expressed in terms of [TF/P] osm . In glomerular filtrate, [TF/P] osm = 1.0.
• In the thick ascending limb of the loop of Henle, NaCl is reabsorbed via the Na+-K+-2Cl- cotransporter. Cells in the thick ascending limb are impermeable to water, so water reabsorption cannot coexist with the solute reabsorption, which causes the water to be left behind and the tubular fluid to be diluted. Tubular fluid osmolarity leaving this segment is 100 mOsm/L. Thus the thick ascending limb also is called the diluting segment.
• In the early distal tubule, NaCl is reabsorbed by an Na+-Cl- cotransporter. Like the thick ascending limb, cells of the early distal tubule are impermeable to water, and water reabsorption cannot follow solute reabsorption.
• Here, the osmolarity of tubular fluid becomes even more dilute, as low as 80 mOsm/L.
• The early distal tubule also is called the cortical diluting segment (cortical because the distal tubule is located in the cortex).