25.6 Tubular Reabsorption

Tubular reabsorption is the process by which the nephron selectively recovers essential substances from the filtrate, preventing their loss in urine. Without it, you'd lose all the glucose, amino acids, water, and ions that were filtered at the glomerulus. Each segment of the nephron handles reabsorption differently, using distinct transport proteins and responding to different hormonal signals.

Tubular Reabsorption

Transport Mechanisms in Nephron Segments

Proximal Convoluted Tubule (PCT)

The PCT does the heavy lifting, reabsorbing roughly 65% of the filtrate. The $Na^+/K^+$ ATPase pump on the basolateral membrane drives most of this by keeping intracellular $Na^+$ low, which creates a gradient that powers several secondary active transporters on the apical (lumen-facing) side:

• $Na^+$/glucose cotransporter (SGLT): Uses the $Na^+$ gradient to pull glucose into the cell
• $Na^+$/amino acid cotransporter: Same principle, but for amino acids
• $Na^+$/phosphate cotransporter: Recovers filtered phosphate
• $Na^+/H^+$ exchanger (NHE): Reabsorbs $Na^+$ while secreting $H^+$, helping regulate pH

Passive transport also occurs here: water follows solutes by osmosis through aquaporin-1 (AQP1) channels, and urea moves via facilitated diffusion.

Loop of Henle

• Thin descending limb: Freely permeable to water but not solutes. Water leaves by osmosis because the surrounding medullary interstitium is hyperosmotic.
• Thick ascending limb: Impermeable to water. Actively transports $Na^+$, $K^+$, and $Cl^-$ out of the tubule via the $Na^+/K^+/2Cl^-$ cotransporter (NKCC2). $Ca^{2+}$ and $Mg^{2+}$ are reabsorbed paracellularly (between cells), driven by the positive lumen charge that NKCC2 activity generates.

Distal Convoluted Tubule (DCT)

• $Na^+$ and $Cl^-$ reabsorbed through the thiazide-sensitive $Na^+/Cl^-$ cotransporter (NCC)
• $Ca^{2+}$ reabsorbed through the TRPV5 channel (regulated by parathyroid hormone)

Collecting Duct

• ADH increases insertion of aquaporin-2 (AQP2) channels into the apical membrane, allowing water reabsorption
• Aldosterone stimulates $Na^+$ reabsorption via the epithelial $Na^+$ channel (ENaC)
• $K^+$ is secreted (not reabsorbed) through ROMK channels

Membrane Proteins for Tubular Reabsorption

Passive vs. Active Tubular Reabsorption

Passive reabsorption moves substances down their concentration or electrochemical gradient with no ATP cost. Examples: water moving by osmosis through aquaporins, urea diffusing out of the PCT, $Cl^-$ following $Na^+$ through the paracellular pathway.

Active reabsorption moves substances against their gradient and requires energy:

• Primary active transport uses ATP directly. The $Na^+/K^+$ ATPase is the main example.
• Secondary active transport doesn't use ATP directly but depends on a gradient that primary active transport created. The SGLT and NHE are both secondary active transporters: they harness the low intracellular $Na^+$ concentration (set up by the $Na^+/K^+$ ATPase) to move glucose or $H^+$ against their own gradients.

Nephron Permeability in Urine Formation

Each nephron segment has different permeability characteristics, and this is what makes urine concentration possible:

• PCT: Highly permeable to water, glucose, amino acids, and ions. Reabsorption here is isotonic, meaning water and solutes leave together, so the fluid stays at roughly the same osmolarity as plasma (~300 mOsm/L).
• Thin descending limb: Permeable to water, impermeable to solutes. Fluid becomes progressively more concentrated as water leaves.
• Thick ascending limb: Impermeable to water, permeable to ions. Solutes are pumped out, but water can't follow. This dilutes the tubular fluid while making the medullary interstitium more concentrated.
• DCT: Relatively impermeable to water. Selectively reabsorbs $Na^+$, $Cl^-$, and $Ca^{2+}$.
• Collecting duct: Water permeability is variable and controlled by ADH. High ADH means more AQP2 channels, more water reabsorption, and concentrated urine. Low ADH means dilute urine. Aldosterone controls $Na^+$ permeability via ENaC; more aldosterone means more $Na^+$ (and therefore water) reabsorption and reduced urine volume.

Reabsorption Along the Nephron

PCT (~65% of filtrate reabsorbed)

• Water: Osmosis through AQP1
• Glucose and amino acids: Secondary active transport (SGLT, $Na^+$/amino acid cotransporters)
• Urea: Facilitated diffusion
• $Na^+$: Basolateral $Na^+/K^+$ ATPase + apical secondary active transporters
• $Cl^-$: Paracellular diffusion (follows $Na^+$)
• $HCO_3^-$: Reabsorbed indirectly through the NHE; $H^+$ secreted into the lumen combines with filtered $HCO_3^-$ to form $CO_2$ and $H_2O$, which enter the cell and regenerate $HCO_3^-$

Loop of Henle

• Thin descending limb: Water reabsorbed passively
• Thick ascending limb: $Na^+$, $K^+$, $Cl^-$ reabsorbed via NKCC2

DCT

• $Na^+$ and $Cl^-$ via NCC
• $Ca^{2+}$ via TRPV5

Collecting Duct

• Water reabsorption regulated by ADH/AQP2
• $Na^+$ reabsorption regulated by aldosterone/ENaC
• $K^+$ secretion via ROMK

Urine Concentration by the Loop of Henle

The loop of Henle and vasa recta work together to build and maintain a concentration gradient in the renal medulla. This gradient is what ultimately allows the collecting duct to produce concentrated urine.

Countercurrent Multiplication (Loop of Henle)

1. The thick ascending limb pumps $Na^+$, $K^+$, and $Cl^-$ into the medullary interstitium via NKCC2.
2. This makes the interstitium hyperosmotic (up to ~1200 mOsm/L at the deepest part of the medulla).
3. The thin descending limb, which is water-permeable, loses water by osmosis into this concentrated interstitium. The tubular fluid inside becomes more concentrated as it descends.
4. Because fluid flows in opposite directions in the two limbs (countercurrent flow), the gradient is continuously reinforced along the entire length of the loop.

Countercurrent Exchange (Vasa Recta)

The vasa recta are hairpin-shaped capillaries that run parallel to the loop of Henle. Blood flows in opposite directions in the descending and ascending portions. As blood descends into the medulla, it passively picks up solutes and loses water. As it ascends, the reverse happens. This passive exchange prevents the blood from "washing out" the medullary gradient while still supplying the tissue.

Producing Concentrated Urine

When ADH is present, the collecting duct becomes water-permeable. As the duct passes through the increasingly concentrated medulla, water is drawn out by osmosis, and the urine becomes concentrated. Without ADH, the collecting duct stays impermeable to water, and dilute urine is excreted.

Sites of Tubular Secretion

Tubular secretion is the opposite of reabsorption: substances move from the peritubular capillaries into the tubular fluid. This helps eliminate waste and regulate pH.

PCT

• Organic anions (PAH, bile acids, uric acid) via organic anion transporters (OATs)
• Organic cations (creatinine, histamine) via organic cation transporters (OCTs)
• $H^+$ via the NHE and $H^+$-ATPase
• $K^+$ via apical $K^+$ channels

DCT and Collecting Duct

• $K^+$ via ROMK channels (this is the main site of regulated $K^+$ secretion)
• $H^+$ via $H^+$-ATPase and $H^+/K^+$-ATPase
• $NH_4^+$ secretion for acid-base balance

Reabsorption Regulation and Efficiency

Renal threshold is the plasma concentration at which a substance begins to appear in the urine. For glucose, this is about 180 mg/dL. Below that level, all filtered glucose is reabsorbed. Above it, the transport proteins become saturated.

Tubular maximum ($T_m$) is the maximum reabsorption rate for a given substance. Once all available carriers are occupied, any additional filtered substance passes into the urine. For glucose, $T_m$ is approximately 375 mg/min.

Obligatory vs. facultative reabsorption:

• Obligatory reabsorption happens constantly and isn't hormone-regulated. The PCT's reabsorption of $Na^+$, water, glucose, and amino acids falls into this category.
• Facultative reabsorption is adjusted based on the body's needs through hormonal control. Water reabsorption in the collecting duct (regulated by ADH) and $Na^+$ reabsorption in the collecting duct (regulated by aldosterone) are the key examples.