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PY7.1-9 | Renal Physiology — Part 2

Tubular Reabsorption: Getting Back What You Need

Of the 180 L filtered daily, the body excretes only 1–2 L as urine. The remaining 178–179 L is reabsorbed by the tubules. This is not passive leakage — it is a precisely regulated, segment-specific recovery operation.

Figure: Tubular Reabsorption: Getting Back What You Need

Proximal convoluted tubule (PCT) — reabsorbs ~65–70% of filtered water, Na⁺, Cl⁻, K⁺, HCO₃⁻, glucose, amino acids, phosphate, and uric acid. The PCT has a brush border (microvilli) that massively increases surface area.

Key transporters in the PCT:
- Na⁺-glucose co-transporter (SGLT2): Reabsorbs glucose with Na⁺ (secondary active transport). Glucose follows Na⁺ gradient created by Na⁺-K⁺-ATPase on the basolateral side. SGLT2 inhibitors (gliflozins) block this — used in Type 2 diabetes to increase glucose excretion.
- Na⁺-H⁺ exchanger (NHE3): Secretes H⁺ and reabsorbs Na⁺ and HCO₃⁻.

Loop of Henle — thin descending limb reabsorbs water; thick ascending limb reabsorbs Na⁺, K⁺, Cl⁻ (via NKCC2 co-transporter). Impermeable to water. Loop diuretics (furosemide) block NKCC2.

DCT and collecting duct — fine-tuning under hormonal control:
- Aldosterone (adrenal cortex): Increases Na⁺ reabsorption and K⁺ secretion via ENaC channels
- ADH (vasopressin): Inserts aquaporin-2 channels → water reabsorption in collecting duct

Transport Maximum (Tm) and Glucose Titration

Many transporters in the PCT are carrier-mediated — they can become saturated. The maximum rate at which a substance can be reabsorbed is its transport maximum (Tm).

Figure: Transport Maximum (Tm) and Glucose Titration

Glucose as the example:
- Normal plasma glucose: 70–100 mg/dL → filtrate glucose: ~100 mg/dL
- Renal threshold for glucose: ~180 mg/dL (plasma level at which glucose first appears in urine)
- Tm for glucose: ~375 mg/min (maximum reabsorptive capacity)

Below the threshold: all filtered glucose is reabsorbed, urine glucose = 0
Above the threshold but below Tm: some glucose appears in urine (glycosuria begins)
Above Tm: fixed amount reabsorbed; excess excreted proportional to plasma level

Clinical correlation: In uncontrolled diabetes, plasma glucose may reach 300–500 mg/dL. At 300 mg/dL, filtered load = 300 × 125/100 = 375 mg/min — exactly at Tm. Any higher plasma level means glycosuria. The glucose in the tubule exerts an osmotic effect — it prevents water reabsorption, causing osmotic diuresis (polyuria), which leads to dehydration and polydipsia.

Tubular secretion adds substances TO the tubular fluid from peritubular capillaries. Important secreted substances: H⁺, K⁺, organic acids (PAH, penicillin, uric acid), creatinine (small amount). Secretion of PAH is used to measure effective renal plasma flow (ERPF).

The Counter-Current System: How the Kidney Concentrates Urine

The most elegant mechanism in renal physiology — the kidney can produce urine from 50 mOsm/kg (maximally dilute, with excess water) to 1200 mOsm/kg (maximally concentrated, with water deficit). This range allows the body to regulate plasma osmolality within ±2 mOsm/kg of 290 mOsm/kg.

Figure: The Counter-Current System: How the Kidney Concentrates Urine

The system depends on the counter-current arrangement of the loop of Henle (the multiplier) and the vasa recta (the exchanger) — and on the osmotic gradient that builds up in the medullary interstitium.

Counter-current multiplier (Loop of Henle):
- Thin descending limb: Permeable to water, impermeable to solutes. Water flows OUT into hypertonic medullary interstitium → tubular fluid becomes progressively more concentrated (hyperosmotic).
- Thick ascending limb: IMPERMEABLE to water but actively reabsorbs Na⁺, K⁺, Cl⁻ via NKCC2 → tubular fluid becomes progressively more dilute (hypoosmotic).
- Net effect: The hairpin turn allows energy spent at one segment to amplify the osmotic gradient — at the tip of the loop, interstitial osmolality reaches 1200 mOsm/kg (versus plasma at 290 mOsm/kg).

Counter-current exchanger (Vasa recta):
Blood flowing through the vasa recta would normally wash out the gradient. But the hairpin arrangement of vasa recta means solutes move OUT of descending limb and back IN to ascending limb, preserving the gradient.

Collecting duct as the final regulator:
Fluid entering the collecting duct is hypoosmotic (~100 mOsm). ADH (released when plasma osmolality rises) inserts aquaporin-2 channels → water diffuses out into the hypertonic medullary interstitium → urine is concentrated.

Without ADH (diabetes insipidus): water cannot leave the collecting duct → dilute urine 50 mOsm → large volumes (polyuria up to 15–20 L/day).