One map for the whole functional unit: where filtrate goes, which ion is reabsorbed in which segment, how the medulla stays salty, and where every diuretic class actually works.
Everything in this sheet is anchored to where it happens. Cortex holds the glomeruli and convoluted tubules; the medulla is where the loop of Henle and collecting duct build and use a salt gradient. Sodium reabsorption falls steeply along the tubule — 65% → 25% → 5% → 3% — which is exactly why loop diuretics are the most powerful.
The glomerulus is a sieve, not a pump. What crosses into Bowman's space becomes the starting filtrate every downstream segment works on.
Afferent arteriole → glomerular capillary tuft
Blood enters at relatively high pressure. Water and small solutes (Na⁺, K⁺, Cl⁻, HCO₃⁻, glucose, amino acids, urea) are pushed across; cells and large plasma proteins stay in the blood. The barrier is fenestrated endothelium, basement membrane and podocyte slits — and it is negatively charged, which restricts albumin further.
Efferent arteriole → peritubular capillaries / vasa recta
Blood that didn't get filtered leaves via the efferent arteriole, which then branches into the peritubular capillaries (around cortical tubules) and the vasa recta (running alongside the loop of Henle). Everything reabsorbed by the tubule is picked up here and returned to the systemic circulation.
What controls how much gets filtered
Afferent constriction → ↓ flow into glomerulus → ↓GFR. Efferent constriction → blood backs up in the glomerulus → ↑ pressure → ↑GFR (until it's severe, then ↓GFR). This afferent/efferent balance is exactly what ACE inhibitors and NSAIDs disturb.
The numbers
GFR 125 ml/min (180 L/day). Renal blood flow 1000–1250 ml/min, about 20–25% of cardiac output. Filtration fraction = GFR/renal plasma flow ≈ 20%. Net filtration pressure ≈ 55 − (15 + 30) = 10 mmHg. Autoregulated between a MAP of roughly 80–180 mmHg.
Read this as filtrate flowing top to bottom, cortex → medulla → back to cortex → medulla again.
| Segment | Na⁺ | Reabsorbs | Transporter | Water | Key feature |
|---|---|---|---|---|---|
| 1PCT | 65–70% | Na⁺ (with glucose, amino acids), HCO₃⁻, most K⁺, phosphate, ~65–70% of water. Secretes organic acids and bases | NHE3, SGLT2, carbonic anhydrase | High — isosmotic | Glucose/AA reabsorption is transporter-limited (saturable) — a Tm defect spills glucose into urine. Threshold ≈ 10–11 mmol/L |
| Descending thin limb | — | Water only | Aquaporin-1 | High — impermeable to NaCl | Filtrate gets progressively more concentrated as it dips into the salty medulla |
| 2Thick ascending limb | 25% | Na⁺, K⁺, 2 Cl⁻; also Ca²⁺, Mg²⁺ paracellular | NKCC2; K⁺ recycles via ROMK | Impermeable | The "diluting segment" — filtrate leaves dilute, while pumped-out NaCl builds medullary hypertonicity. Lumen-positive potential drives the divalent cations |
| 3DCT | 5–8% | Na⁺ + Cl⁻; Ca²⁺ reabsorption tuned by PTH | NCC; TRPV5 for calcium | Impermeable | Macula densa here senses NaCl and drives tubuloglomerular feedback on GFR |
| 4Collecting duct | 2–3% | Principal cells: Na⁺ in / K⁺ out. Intercalated cells: H⁺ or HCO₃⁻ (acid–base) | ENaC + ROMK (aldosterone); AQP2 (ADH); H⁺ ATPase | Variable — ADH dependent | Final fine-tuning: how concentrated the urine ends up depends entirely on ADH here |
This is the mechanism that lets the kidney make urine more concentrated than plasma — the loop builds the gradient, the vasa recta preserves it.
Countercurrent multiplier — loop of Henle
Descending and ascending limbs run parallel but carry flow in opposite directions. The TAL actively pumps NaCl out without water following, raising interstitial osmolarity. Because the descending limb is water-permeable, it equilibrates with that same interstitium — so filtrate re-entering the loop is already more concentrated than before. Repeating this stepwise along the loop's length multiplies a small single effect into a steep 300→1200 mOsm/L gradient from cortex to papilla.
Countercurrent exchanger — vasa recta
The vasa recta run alongside the loop, also as hairpin loops, also with opposite-direction flow. As blood descends into the hypertonic medulla it loses water and gains salt; as it ascends back out it regains that water and loses the salt. The exchanger doesn't build the gradient — it just carries oxygen and nutrients through the medulla without washing the gradient away.
Urea recycling
The inner medullary collecting duct is permeable to urea, which adds to medullary osmolarity and contributes roughly half of the final papillary gradient alongside NaCl.
Where ADH fits in
None of this concentrates the urine itself unless the collecting duct is water-permeable. ADH (vasopressin) inserts aquaporin-2 channels into principal cells, letting water leave the collecting duct down the gradient the loop already built — so final urine osmolarity tracks ADH, not the loop.
Same segment order as above. Potency tracks the fraction of sodium handled at that site — that single idea explains the whole ranking.
| Class | Site | Target | Na⁺ lost | Notable effects |
|---|---|---|---|---|
| Osmotic mannitol | PCT + descending limb | Non-reabsorbed solute holds water in the tubule | Variable | ↑ water excretion, little effect on Na⁺. Uses: raised ICP, IOP. Expands ECF first — dangerous in cardiac failure and pulmonary oedema; contraindicated in established anuria. Risk of rebound |
| Carbonic anhydrase inhibitor acetazolamide | PCT | Blocks HCO₃⁻ reabsorption | ~5% | Mild, self-limiting diuresis with hyperchloraemic metabolic acidosis and hypokalaemia. Used more for glaucoma, altitude sickness and metabolic alkalosis than for diuresis |
| SGLT2 inhibitor dapagliflozin, empagliflozin | PCT | Blocks SGLT2 glucose reabsorption | Osmotic | Glycosuric osmotic diuresis with cardiorenal benefit. Euglycaemic DKA is the anaesthetic concern — withhold about 3 days before surgery |
| Loop furosemide, bumetanide | Thick ascending limb | Blocks NKCC2 (Na⁺/K⁺/2Cl⁻) | 20–25% most potent |
Abolishes the medullary gradient. Hypokalaemia, hypocalcaemia, hypomagnesaemia, hypochloraemic metabolic alkalosis, hyperuricaemia, ototoxicity. Venodilates before diuresis in acute pulmonary oedema. Still works at low GFR |
| Thiazide bendroflumethiazide, indapamide | DCT | Blocks NCC (Na⁺/Cl⁻) | 5–8% | Hypokalaemia, hyponatraemia (classically in the elderly), hypercalcaemia, hyperglycaemia, hyperuricaemia, hyperlipidaemia. Ineffective once GFR < 30 ml/min |
| K⁺-sparing amiloride, triamterene | Collecting duct | Blocks ENaC directly on principal cells | 2–3% | Weak diuresis, spares K⁺. Hyperkalaemia — care with ACE inhibitors or ARBs |
| Aldosterone antagonist spironolactone, eplerenone | Collecting duct | Blocks the mineralocorticoid receptor | 2–3% | Hyperkalaemia, gynaecomastia (spironolactone; eplerenone is more selective). Mortality benefit in heart failure. Slow onset over days |
| Vasopressin antagonist tolvaptan | Collecting duct | Blocks the V2 receptor, so AQP2 is not inserted | Aquaresis | Water excretion without much Na⁺ loss — used in SIADH and hypervolaemic hyponatraemia. Risk of over-rapid sodium correction. Lithium causes the same end-effect as an unwanted toxicity, producing nephrogenic diabetes insipidus |
| Hormone | Site | Action |
|---|---|---|
| Aldosterone | Collecting duct principal cells | ↑ ENaC and Na⁺/K⁺ ATPase → Na⁺ and water retention, K⁺ and H⁺ loss |
| ADH (vasopressin) | Collecting duct, V2 | Inserts aquaporin-2 → water reabsorption. V1 elsewhere causes vasoconstriction. Most sensitive stimulus is plasma osmolality from ~280 mosmol/kg |
| Angiotensin II | Efferent arteriole, PCT | Efferent constriction maintains GFR; stimulates PCT Na⁺ reabsorption and aldosterone release |
| ANP / BNP | Collecting duct, afferent arteriole | Afferent dilation ↑ GFR; inhibits Na⁺ reabsorption and renin — the natural counterweight to RAAS |
| PTH | PCT and DCT | ↑ Ca²⁺ reabsorption (DCT), ↓ phosphate reabsorption (PCT), activates vitamin D |
| Renin trigger | Juxtaglomerular apparatus | Released by ↓ renal perfusion pressure, ↓ distal tubular Na⁺ at the macula densa, and sympathetic β1 stimulation |