[OS 206] E03-T05-Urine Concentration and Dilution_compressed

• Urine concentration and dilution are key kidney functions.

Nephron Blueprint

• Glomerulus and Bowman's capsule are responsible for blood filtration and filtrate collection.
• The proximal convoluted tubule is where the bulk reabsorption of water, solutes, and organic molecules occurs.
• The loop of Henle helps form the medullary osmotic gradient.
• Water reabsorption occurs in the descending limb.
• Solute reabsorption occurs in the thin ascending limb via passive diffusion.
• Solute reabsorption occurs in the thick ascending limb via active transport.
• Fine-tuning of solute reabsorption occurs in the distal convoluted tubule.
• Water and urea are reabsorbed/recovered in the collecting duct.

Loop of Henle

• The loop of Henle generates and maintains the concentration gradient in the interstitial fluid by moving NaCl out of the loop.
• The goal is to create a concentrated medullary interstitium for concentrating urine.

Transport Systems

• Passive diffusion involves the net movement of particles from high to low concentration areas.
• Osmosis describes the tendency of a solvent (typically water) to diffuse down its concentration gradient across a selectively permeable membrane.
• Active transport involves the movement of particles from low to high concentration areas, requiring energy (ATP).

Types of Nephrons

• Cortical nephrons have glomeruli in the outer cortex and short loops of Henle that penetrate a short distance into the medulla.
• The tubular system of cortical nephrons is surrounded by peritubular capillaries, lacking vasa recta.
• Juxtamedullary nephrons have glomeruli at the cortex-medulla junction.
• Juxtamedullary nephrons' loops penetrate deeply into the medulla and are more effective at concentrating urine.
• Efferent arterioles in juxtamedullary nephrons give rise to the vasa recta.

Countercurrent Multiplier

• Creates a hyperosmotic medullary interstitium and an osmotic equilibrium of water in the medullary interstitium and collecting tubules.
• Countercurrent flow and differences in permeability between tubules play a role.
  • Thin descending loop: permeable to water but impermeable to salt.
  • Thick ascending loop: impermeable to water but permeable to salt.
• ATP provides the energy.

Production of Concentrated Urine

• Baseline osmolarity is 300 mOsm/L.
• The thick ascending limb (TAL) is a diluting limb.
• Active NaCl reabsorption (without water) occurs in the TAL via the Na/K/Cl (NKCC) cotransporter on the apical side.
• Na, K, and Cl are reabsorbed from the urine via secondary active transport.
• K+ leaks back into the lumen via the ROMK channel, leading to a net positive charge and paracellular reabsorption of Ca2+ and Mg2+.
• Loop diuretics inhibit the NKCC cotransporter in the TAL, decreasing NaCl reabsorption and water reabsorption, increasing urine output.
• The basolateral side has a Na/K ATPase pump and a Cl channel for pumping Na and Cl into the interstitium.
• Isosmotic fluid from the PCT equilibrates osmotically with the hyperosmotic interstitium in the descending limb (DL) through aquaporin 1.
• Water diffuses out of the DL, increasing osmolarity.
• Juxtamedullary nephrons can create more concentrated urine because of the thin ascending limb (tAL), which is impermeable to water but permeable to solutes via passive transport, and urea.
• The concentrated fluid from the DL flows countercurrent up the TAL, where NaCl is passively reabsorbed, to further concentrate the medullary interstitium and concentration rises markedly with ADH.
• Some urea exits the CD into the interstitium in the inner medulla, then reenters the tAL, enhancing water reabsorption from the PCT and into the DL.
• Distal convoluted tubule (DCT) is responsible for fine-tuning and water reabsorption.
• The collecting duct (CD) is responsible for water reabsorption.
• Antidiuretic hormone (ADH) opens aquaporin channels in the CD, increasing water reabsorption when fluid osmolarity rises and decreasing water reabsorption when fluid osmolarity reduces, to permit water reabsorption.
• Urea concentration rises in the CD because aquaporins permit water reabsorption.
• Around 50% of medullary tonicity is due to urea.

Countercurrent Exchange

• The vasa recta prevents water reabsorbed into the DL and CD from diluting the medullary interstitium.
• The vasa recta maintains osmotic gradient by returning the NaCl and water reabsorbed to systemic circulation and low blood flow in its vessels.
• Blood flow in the vasa recta should be slow to allow for the exchange of solutes.
• Descending vasa recta: Water comes out
• Ascending vasa recta: Water goes in

Renal Circulation

• Steps of countercurrent mechanism include pumping out of NaCl in the TAL, water exiting in DL and water exiting the cortical collecting duct (with ADH).
• High urea in the tubule and low urea in the interstitium causes urea to passively move out to the medullary interstitium.
• Water then moves out more effectively, raising the sodium content in the DL and creates passive diffusion gradient of sodium to passively diffuse into the interstitium.
• The afferent arteriole originates from the interlobular artery, which arises from the arcuate arteries.
• Vasa recta are blood vessels that help in concentrating urine.

Production of Dilute Urine

• Water ingestion leads to dilute urine via a decrease in plasma ADH (vasopressin) and production of washout of cortical papillary concentration gradient.
• Water ingestion lowers the need to retain water and lowers plasma osmolarity and decreases ADH secretion to secrete excess water.
• Water ingestion dilutes the cortical interstitium, removing the concentration gradient.

Clinical Correlates

• Dehydration indicates a response to high ADH levels, correlated with high water reabsorption and concentrated urine.
• Loop diuretics (e.g., furosemide) block the Na+/K+/2Cl pump in the thick ascending loop of Henle.
• Patients urinate a lot because their countercurrent mechanism does not work anymore.
• Mannitol elevates blood flow in the vasa recta, decreasing the time to reabsorb water, resulting in polyuria.
• ADH overproduction (SIADH) results in concentrated urine and commonly leads to hyponatremia.
• ADH underproduction (diabetes insipidus) results in diluted urine and leads to hypernatremia.
• High concentration of urea needed in the tAL for countercurrent mechanism.
• Urea deficiency (e.g., malnutrition) leads to an inability to concentrate urine.
• High protein intake can help one to concentrate urine.
• High protein can contribute to hyperfiltration, which causes damage to the glomerular filtration barrier and leads to proteinuria and nephron loss.

Explore urine concentration and dilution as key kidney functions. Learn about the nephron's role, including the glomerulus, Bowman's capsule, and the loop of Henle. Understand how the loop of Henle maintains the concentration gradient for urine concentration.