Contents · 12 sections
In a nutshell. The kidneys perform 4 processes: filtration (glomerulus, 180 L/day), reabsorption (99% in the tubules), secretion (elimination of ions, creatinine, drugs), and concentration (loop of Henle via the countercurrent multiplier mechanism). GFR = 90–120 mL/min/1.73 m², regulated by RAAS and tubuloglomerular feedback. Key hormones: RAAS (volume, Na⁺), ADH (water, in the collecting ducts), ANP (natriuresis), PTH / 1,25-D (Ca²⁺, P), erythropoietin (erythropoiesis). The kidney is the primary regulator of acid-base balance (HCO₃⁻ reabsorption + NH₄⁺, H₂PO₄⁻ excretion).
1. Kidney functions
- Excretory: elimination of end products (urea, creatinine, uric acid).
- Osmoregulation and water-electrolyte balance.
- Maintenance of acid-base balance (HCO₃⁻ reabsorption, H⁺ secretion).
- Blood pressure regulation (RAAS, ADH, ANP, prostaglandins).
- Endocrine: erythropoietin, 1,25-(OH)₂-D₃, renin.
- Gluconeogenesis (up to 20% during starvation).
2. Glomerular filtration
- Filtration barrier: fenestrated endothelium, basement membrane, podocytes with slit diaphragms.
- GFR = 90–120 mL/min/1.73 m² in adults; increases by 40–50% in pregnancy.
- Filtration fraction = GFR / renal plasma flow ≈ 0.2 (20%).
- Formula: GFR = K_f × (P_{GC} - P_{BS} - π_{GC}), where K_f is the ultrafiltration coefficient, P is hydrostatic pressure, and π is oncotic pressure.
- Autoregulation: maintained at SBP of 80–180 mmHg (myogenic reflex + tubuloglomerular feedback via the macula densa).
- The afferent arteriole is constricted by angiotensin II at high pressure, while the efferent arteriole constricts more strongly, resulting in ↑ glomerular pressure.
3. Proximal convoluted tubule
- Reabsorbs 65% of Na⁺, 65% of water, 100% of glucose (SGLT2/SGLT1 + GLUT2), 100% of amino acids, 80% of HCO₃⁻, 65% of K⁺, P, Ca²⁺, and uric acid.
- Na⁺/H⁺ exchanger NHE3 + carbonic anhydrase (IV on the brush border and II in the cytoplasm) are the main mechanism for bicarbonate reabsorption.
- Secretion: organic cations (OCT), anions (OAT); creatinine, penicillins, diuretics.
- Isoosmotic reabsorption — water follows the solutes.
- Site of action of carbonic anhydrase inhibitors (acetazolamide) and SGLT2 inhibitors (gliflozins).
4. Loop of Henle
- Descending limb — permeable to water, impermeable to solute → urine concentration (toward the hairpin turn).
- Thin ascending limb — impermeable to water, passively secretes NaCl.
- Thick ascending limb — NKCC2 (Na-K-2Cl cotransporter, site of action of furosemide); reabsorbs 25% of NaCl without water → urine dilution.
- Countercurrent multiplier mechanism: creates a hyperosmotic medullary interstitium (up to 1200–1400 mOsm in humans).
- Vasa recta (countercurrent exchange) maintains this gradient.
- Urea acts as a secondary osmotic "agent" in the deep medullary gradient.
5. Distal convoluted tubule (DCT)
- Reabsorbs 5–10% of Na⁺ via NCC (Na-Cl cotransporter; site of action of thiazide diuretics).
- Ca²⁺ reabsorption under the control of PTH (TRPV5, calbindin, PMCA, NCX).
- Mg²⁺ via TRPM6 (mutations cause Gitelman syndrome).
- Impermeable to water.
6. Collecting ducts
- Principal cells: Na⁺ via ENaC (blocked by amiloride), K⁺ via ROMK; regulated by aldosterone.
- Intercalated α-cells: H⁺-ATPase, H⁺/K⁺-ATPase, HCO₃⁻/Cl⁻ exchanger — H⁺ secretion.
- Intercalated β-cells: HCO₃⁻ secretion (during alkalosis).
- ADH → V2 receptor → insertion of aquaporin-2 (AQP2) into the apical membrane → water reabsorption.
- AQP3/4 — located on the basolateral membrane, constitutively present.
7. RAAS
- Renin is secreted by juxtaglomerular (JG) cells in response to ↓ afferent arteriole perfusion, ↓ NaCl at the macula densa, and ↑ sympathetic activity.
- Renin → angiotensinogen (liver) → angiotensin I → ACE (lungs, endothelium) → angiotensin II.
- Effects of Ang II: vasoconstriction (primarily of the efferent arteriole), ↑ aldosterone, ↑ ADH, ↑ thirst, ↑ sympathetic tone, Na⁺ retention.
- Aldosterone (zona glomerulosa) → ENaC + Na⁺/K⁺-ATPase → ↑ Na⁺ reabsorption, K⁺ and H⁺ secretion.
- Inhibitors: ACE inhibitors, ARBs (sartans), direct renin inhibitors (aliskiren), mineralocorticoid receptor antagonists (spironolactone, eplerenone, finerenone).
8. ADH and ANP
- ADH (vasopressin): synthesized in the hypothalamus (paraventricular and supraoptic nuclei), secreted by the posterior pituitary.
- Triggers: ↑ osmolarity > 280 mOsm/kg, ↓ blood volume (> 10%), nausea, stress.
- Effect via V1a (vascular vasoconstriction) and V2 (renal principal cells).
- Pathology: diabetes insipidus (↓ ADH or insensitivity); SIADH (↑ ADH — oncology, CNS pathology, drugs).
- ANP (atrial) and BNP (brain) — upon myocardial stretch; vasodilation, natriuresis (via RAAS antagonism, ↑ GFR, ↓ Na⁺ reabsorption in collecting ducts).
9. Acid-Base Balance
- The kidneys reabsorb almost all filtered HCO₃⁻ (PCT — 80%, thick ascending limb — 15%, CNT + collecting duct — 5%).
- H⁺ secretion: 1) as free ions, 2) with buffers (NH3 → NH4⁺, HPO4²⁻ → H₂PO4⁻).
- Titratable acidity = H⁺ on phosphate buffer.
- Ammonium ion (NH4⁺) — main adaptive mechanism; ↑ in chronic acidosis.
- Net acid excretion = NH4⁺ + titratable acidity − urinary HCO₃⁻.
- In metabolic acidosis — ↑ ammoniagenesis, formation of "new" HCO₃⁻.
10. Endocrine Functions
- Erythropoietin — by cortical interstitial fibroblasts; in hypoxia (HIF stabilization).
- In CKD — anemia due to EPO deficiency.
- 1α-hydroxylase in PCT → 1,25-(OH)₂-D3 (calcitriol); stimulated by PTH and ↓ P, inhibited by FGF-23.
- Renin — described above.
- The kidney responds to PTH (↑ Ca²⁺ reabsorption in CNT, ↓ P reabsorption in PCT) and to FGF-23 (↓ P reabsorption).
11. Clearance and Function Assessment
- Clearance = U × V / P (volume of plasma cleared of a substance per minute).
- Inulin — GFR gold standard (freely filtered, not reabsorbed, not secreted).
- Creatinine — used in practice; slightly secreted → clearance increased by 10–20%.
- GFR estimation formulas: Cockcroft-Gault (clearance), MDRD, CKD-EPI 2021 (without race coefficient — preferred).
- PAH (para-aminohippuric acid) — almost completely cleared in 1 pass → estimation of renal plasma flow.
- Fractional excretion of Na⁺ (FeNa) < 1% — prerenal AKI; > 2% — renal.
12. FAQ
Why do diuretics act on different segments?
Each drug binds to its specific transporter: acetazolamide — carbonic anhydrase in PCT; furosemide — NKCC2 in the thick ascending limb; thiazides — NCC in CNT; amiloride/triamterene — ENaC in collecting ducts; aldosterone antagonists — mineralocorticoid receptor.
What is tubuloglomerular feedback?
The macula densa (in the CNT, adjacent to the glomerulus) measures NaCl concentration. When NaCl ↑ → constriction of the afferent arteriole → GFR ↓. The mechanism is mediated by adenosine and ATP.
Why do gliflozins protect the kidneys?
SGLT2 inhibitors block glucose and Na⁺ reabsorption in the PCT → NaCl ↑ in the macula densa → constriction of the afferent arteriole → reduction in intraglomerular pressure and slowing of fibrosis. This is in addition to the hypoglycemic effect.
How to differentiate prerenal AKI from acute tubular necrosis?
Prerenal: FeNa < 1%, urinary Na⁺ < 20, osmolality > 500. ATN: FeNa > 2%, urinary Na⁺ > 40, osmolality 250–350 (isosthenuria).
Why does urine concentrate during dehydration?
The hypertonic medullary interstitium (created by the loop of Henle) "pulls" water out of the collecting ducts when AQP2 expression is high (under the influence of ADH). The higher the gradient and the more ADH, the more concentrated the urine.
See also: CKD · AKI · ABB · RAAS and Hypertension · Physiology Catalog