Nephron Function and Water Reabsorption

Study Notes

Substances fully reabsorbed: Na+, K+, Ca++, Mg++, Cl-, HCO3-, glucose, amino acids, proteins, vitamins.
Substances not reabsorbed: Urea and creatinine, considered metabolic end-products.

Proximal tubule reabsorbs about 65% of water via osmotic diffusion.
Thin segment of the descending limb of loop of Henle reabsorbs approximately 15% of water, also through osmotic mechanisms.
Distal tubule and collecting duct reabsorb about 19.3% of water; this process is regulated by Anti-Diuretic Hormone (ADH) and aldosterone.

Concentrated urine results primarily from the presence of ADH and the countercurrent mechanism.
In the presence of ADH, water permeability increases in the late distal tubule and collecting duct, enabling water to be reabsorbed into hyperosmolar medullary interstitium.
The countercurrent multiplier mechanism enhances medullary osmolality due to active transport of Na+, and co-transport of K+ and Cl- in the thick ascending limb of the loop of Henle.

ADH is the key hormone regulating water reabsorption in the kidneys.
It increases the permeability of the nephron to water, facilitating its retention and concentration of urine.

Osmolarity refers to the concentration of solute particles per liter of solvent; osmolality measures particles per kilogram of solvent.
Reabsorbed substances in the proximal tubule maintain constant osmolality at 300 mOsm/L.

Thin descending limb of the loop of Henle: permeable only to water, leading to high osmolality (up to 1200 mOsm/L).
Thick ascending limb: impermeable to water; actively transports Na+, Cl-, and K+, resulting in decreased osmolality (approximately 100 mOsm/L).
Second half of distal tubule and collecting duct typically impermeable to water, but permeable in the presence of ADH, allowing for regulation of urine dilution.

Urine osmolality ranges from 50-1200 mOsm/L, modulated by ADH and aldosterone, influencing water reabsorption and electrolyte balance.

Sodium-glucose transporter (SGLT1) facilitates the reabsorption of glucose concurrent with Na+ transport.
SGLT inhibitors, used clinically, block glucose reabsorption, lowering blood glucose by increasing urinary glucose.

Active transport of Na+ through Na-K-ATPase drives the counter-transport mechanism, where Na+ influx is coupled with the secretion of H+ and K+ into the tubular lumen.
High solute concentration in the interstitium promotes passive water absorption through osmosis, counteracting oncotic pressure from non-permeant plasma proteins.

Podocytes have foot processes that create a slit diaphragm formed by nephrin molecules, enabling size-selective filtration.
Filtrate composition mirrors plasma minus plasma proteins.
Loss of negative charges in glomerular filtration barrier due to immunologic damage (e.g., glomerulonephritis) can result in proteinuria.

Filtrate processing occurs primarily in the nephron, with about 65% of glomerular filtrate reabsorbed in the proximal tubule.
Essential substances reabsorbed include water, Na+, glucose, amino acids, and various electrolytes, while osmolality remains constant at around 300 mOsm/L.

Thin Segment of Descending Limb:
- Passively permeable to water.
- Osmolality increases to approximately 1200 mOsm/L due to water reabsorption.
Thick Segment of Ascending Limb:
- Impermeable to water; utilizes active transport to absorb Na+ and co-transport Cl-, K+.
- Osmolality decreases to about 100 mOsm/L due to solute reabsorption.
Distal Tubule and Collecting Duct:
- Under normal conditions, impermeable to water and urea.
- ADH increases permeability to water and urea, promoting water reabsorption, with osmolality varying from 50-1200 mOsm/L, heavily regulated by ADH and aldosterone.

Concentrated urine excretion relies on:
- Presence of ADH, which enhances water permeability in the distal tubule and collecting duct.
- Countercurrent mechanism, which establishes a hyperosmolar medullary interstitium, enabling osmotic water reabsorption.

Active transport of Na+ from the ascending limb of the loop of Henle into the interstitium contributes to the increased osmolality necessary for water reabsorption.
This mechanism facilitates the concentration of urine by maintaining a gradient for osmotic diffusion.

ADH is critical for regulating water reabsorption in the kidneys, determining urine concentration by increasing nephron permeability to water in response to hydration status.