PY7.1-9 | Renal Physiology — Gate Quiz

Correct! Normal GFR ≈ 125 mL/min (180 L/day). Of this, 99% is reabsorbed and only ~1.5–2 L is excreted as urine. GFR is the standard measure of kidney function — CKD is defined as GFR <60 mL/min for >3 months.

Key concept: GFR ≈ 125 mL/min = 180 L/day. Measured by inulin clearance (gold standard) or estimated by creatinine clearance (Cockcroft-Gault). Factors affecting GFR: ↑ by ↑glomerular capillary pressure (afferent dilation/efferent constriction), ↑ filtration surface area; ↓ by ↑oncotic pressure, ↑Bowman's capsule pressure. Autoregulated between 80–180 mmHg MAP.

Incorrect. Normal GFR ≈ 125 mL/min. CKD stages are based on eGFR: Stage 1 ≥90, Stage 2 60–89, Stage 3 30–59, Stage 4 15–29, Stage 5 <15 mL/min.

Correct! Glucose is completely reabsorbed by SGLT-2 transporters (and SGLT-1 further along) in the proximal convoluted tubule up to a transport maximum (Tm) of ~375 mg/min. When filtered glucose exceeds Tm (plasma glucose ~180–200 mg/dL, the "renal threshold"), the excess is not reabsorbed and appears in urine.

Key concept: Glucose Tm = ~375 mg/min. Renal threshold ≈ 180 mg/dL. SGLT-2 reabsorbs 90% in S1 PCT; SGLT-1 reabsorbs remaining 10% in S3. SGLT-2 inhibitors (gliflozins) deliberately cause glycosuria as a diabetes treatment — they lower blood glucose, body weight, and reduce renal/cardiovascular events. Splay = the curve between threshold and Tm due to nephron heterogeneity.

Incorrect. Glycosuria occurs when filtered glucose load exceeds the tubular transport maximum (Tm ~375 mg/min). The renal glucose threshold is plasma glucose ~180–200 mg/dL.

Correct! ADH (V2 receptor → cAMP → PKA) causes the fusion of AQP2-containing vesicles with the luminal membrane of principal cells in the collecting duct, inserting aquaporin-2 water channels. This dramatically increases water permeability, allowing water reabsorption along the osmotic gradient established by the medullary countercurrent system.

Key concept: ADH (posterior pituitary) — stimuli: ↑plasma osmolality (primary, most sensitive), ↓blood volume, pain, stress. Mechanism: V2 receptor → Gs → ↑cAMP → PKA → AQP2 vesicle fusion with luminal membrane. AQP3 and AQP4 are constitutively present on basolateral membrane. Diabetes insipidus: central (↓ADH production) or nephrogenic (↓V2 receptor response).

Incorrect. ADH acts on collecting duct principal cells via V2 receptors → cAMP → PKA → inserts aquaporin-2 (AQP2) into the luminal membrane → increased water permeability → water reabsorption.

Correct! Renin is released from juxtaglomerular cells of the afferent arteriole in response to: (1) decreased renal perfusion pressure (baroreceptor mechanism), (2) low NaCl delivery to macula densa (tubuloglomerular feedback), and (3) increased sympathetic activity (β₁ adrenergic stimulation of JG cells).

Key concept: RAAS cascade — Renin → cleaves angiotensinogen → Ang I → ACE (lung) → Ang II → (1) vasoconstriction via AT1, (2) aldosterone release → ↑Na⁺ reabsorption (collecting duct), (3) ADH release, (4) thirst. ACE inhibitors block Ang II formation; ARBs block AT1 receptor. RAAS inhibition is a key treatment in hypertension, heart failure, and diabetic nephropathy.

Incorrect. Renin release is stimulated by LOW renal perfusion pressure, LOW NaCl at macula densa, and sympathetic activation (β₁). These all signal decreased effective circulating volume.

Correct! In chronic respiratory alkalosis (↓PaCO₂, ↑pH), the kidneys compensate by excreting more bicarbonate (HCO₃⁻) and reducing H⁺ secretion. This reduces plasma HCO₃⁻, partially correcting the pH towards normal. Renal compensation takes 3–5 days.

Key concept: Renal compensation directions — Respiratory acidosis: kidneys RETAIN HCO₃⁻ (↑H⁺ secretion, ↑NH₄⁺ excretion); Respiratory alkalosis: kidneys EXCRETE HCO₃⁻ (↓H⁺ secretion). Renal compensation: takes 3–5 days but more complete than respiratory compensation. Expected compensation: for every 10 mmHg ↓PaCO₂ in resp alkalosis, HCO₃⁻ decreases 2 mEq/L (acute) or 5 mEq/L (chronic).

Incorrect. In respiratory alkalosis (low CO₂, high pH), the kidneys compensate by EXCRETING HCO₃⁻ and REDUCING H⁺ secretion, thereby lowering plasma HCO₃⁻ to restore pH towards normal.

Correct! Aldosterone acts on principal cells of the cortical collecting duct (CCD) and late distal tubule. It binds to cytoplasmic mineralocorticoid receptors → gene transcription → ↑Na⁺ channel (ENaC) on luminal membrane → ↑Na⁺/K⁺-ATPase on basolateral membrane → ↑Na⁺ reabsorption and K⁺ secretion.

Key concept: Aldosterone (mineralocorticoid from zona glomerulosa) → cytoplasmic MR receptor → nuclear transcription → ↑ENaC (Na⁺ channel) + ↑Na⁺/K⁺-ATPase in collecting duct principal cells. Effect: ↑Na⁺ reabsorption, ↑K⁺ secretion, ↑H⁺ secretion. Conn's syndrome (↑aldosterone): hypertension, hypokalaemia, metabolic alkalosis. Loop diuretics act on TALH; thiazides on DCT; amiloride/spironolactone on collecting duct.

Incorrect. Aldosterone acts primarily on principal cells of the cortical collecting duct, increasing luminal ENaC and basolateral Na⁺/K⁺-ATPase to reabsorb Na⁺ (and excrete K⁺ and H⁺).

Correct! Inulin (a fructose polysaccharide) is the ideal substance for GFR measurement because: (1) freely filtered at the glomerulus, (2) not reabsorbed, (3) not secreted, (4) not metabolised by the kidney, (5) not toxic, (6) not protein-bound. Therefore, clearance of inulin = GFR exactly.

Key concept: Clearance formula: C = (U × V) / P. For inulin: C_inulin = GFR. Creatinine clearance slightly overestimates GFR (tubular secretion of creatinine) but is practical. GFR estimating equations: CKD-EPI, MDRD (clinical use). Para-aminohippuric acid (PAH) clearance ≈ renal plasma flow (RPF) — it is filtered + maximally secreted.

Incorrect. Inulin is the gold standard because it is freely filtered AND neither reabsorbed NOR secreted — so its clearance exactly equals GFR. Creatinine is secreted, slightly overestimating GFR.

Correct! Furosemide (and other loop diuretics: bumetanide, torasemide) block the NKCC2 co-transporter in the thick ascending limb (TAL) of the loop of Henle. The TAL is the main diluting segment — NKCC2 block destroys the medullary concentration gradient, preventing maximum water reabsorption in the collecting duct. This is the most potent class of diuretic.

Key concept: Diuretic mechanisms — Loop (furosemide): NKCC2 in TAL → most potent; Thiazide (HCTZ): NCC in DCT → moderate; K⁺-sparing (amiloride): ENaC in CCD; (spironolactone): aldosterone antagonist in CCD; Carbonic anhydrase inhibitor (acetazolamide): PCT → weak, used for altitude sickness/glaucoma. Loop diuretics cause hypokalaemia + metabolic alkalosis (↑aldosterone secondary to volume loss).

Incorrect. Furosemide blocks NKCC2 (Na-K-2Cl co-transporter) in the thick ascending limb of the loop of Henle — disrupting medullary hypertonicity and producing powerful diuresis.

Correct! The countercurrent multiplier (loop of Henle) creates a progressively hypertonic medullary interstitium (up to 1200 mOsm/L at the papilla). The descending limb is permeable to water; the thick ascending limb actively pumps NaCl without water (impermeable to water). This gradient drives water reabsorption from the collecting duct when ADH is present.

Key concept: Countercurrent multiplier (loop) + exchanger (vasa recta) + ADH-controlled collecting duct = the urine-concentrating mechanism. Medullary osmolality: cortex 300 → papilla 1200 mOsm/L. Max urine osmolality = 1200–1400 mOsm/L with ADH; minimum = 50–60 mOsm/L without ADH. Urea also contributes to medullary hypertonicity via UT-A1/UT-A3 transporters in inner medullary CCD.

Incorrect. The countercurrent multiplier creates medullary hypertonicity — the osmotic gradient that allows the collecting duct to concentrate urine in the presence of ADH.

Correct! The glomerular filtration barrier has a charge barrier (negatively charged sialoproteins and heparan sulphate proteoglycans that repel negatively charged albumin). In nephrotic syndrome (e.g., minimal change disease), the charge barrier is lost — albumin passes through despite its normal size, causing massive proteinuria and hypoalbuminaemia.

Key concept: Glomerular filtration barrier — Endothelium (fenestrated), GBM (type IV collagen, laminin, heparan sulphate = charge barrier), podocytes with slit diaphragm (nephrin, podocin = size barrier). Nephrotic syndrome: proteinuria >3.5 g/day, hypoalbuminaemia, oedema, hyperlipidaemia. Minimal change disease (children): electron microscopy shows podocyte foot process effacement — charge barrier loss.

Incorrect. In minimal change nephrotic syndrome (most common cause in Indian children), the primary defect is loss of the charge barrier (negative sialoproteins), allowing albumin to cross the filtration membrane.