Renal Physiology

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Renal Physiology — Key Facts for NEET PG

• GFR: ~125 mL/min (180 L/day); measured by inulin or creatinine clearance
• Filtration: Glomerular capillaries — no cells or large proteins filtered (size and charge selective)
• Reabsorption: Proximal tubule (65% Na⁺, 100% glucose/amino acids); Loop of Henle (countercurrent multiplication)
• Acid-base: Tubular secretion of H⁺, reabsorption of HCO₃⁻, ammonia synthesis; NH₃ + H⁺ → NH₄⁺ excreted
• ⚡ Exam tip: Glucosuria in non-diabetic patient = proximal tubule defect (Fanconi syndrome, SGLT2 inhibitors)

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Renal Physiology — NEET PG Study Guide

Renal Anatomy

Kidney Structure:

• Cortex: Contains glomeruli, PCT, DCT, collecting ducts
• Medulla: Contains loops of Henle, collecting ducts (papillae project into calyces)
• Renal pyramid: Each pyramid = medullary rays + loop of Henle

Nephron Types:

Type	%	Features
Cortical nephrons	85%	Short loops (only to outer medulla)
Juxtamedullary nephrons	15%	Long loops (extend to inner medulla) — concentrated urine

Components of Nephrons:

1. Glomerulus
2. Proximal convoluted tubule (PCT)
3. Loop of Henle (descending limb, thin ascending limb, thick ascending limb)
4. Distal convoluted tubule (DCT)
5. Collecting duct

Glomerular Filtration

Glomerular Filtration Barrier:

Layer	Function
Fenestrated endothelium	Prevents cells, allows proteins <70 kDa
Basement membrane	Size and charge selective (negatively charged)
Podocytes (visceral epithelium)	Slit diaphragm — prevents proteins

Starling Forces in Glomerulus:

Force	Normal Value	Direction
PGC (capillary hydrostatic)	~60 mmHg	Outward
PBS (Bowman’s space hydrostatic)	~18 mmHg	Inward
πGC (capillary oncotic)	~32 mmHg	Inward
πBS (Bowman’s space oncotic)	~0 mmHg	Negligible

Net Filtration Pressure = PGC − PBS − πGC = 60 − 18 − 32 = +10 mmHg (outward)

GFR Determinants:

• Kf (filtration coefficient): Surface area × intrinsic permeability
• ↑ Kf → ↑ GFR; ↓ Kf → ↓ GFR (e.g., nephrectomy → compensatory hypertrophy)

⚡ Exam tip: RBF = ~25% of cardiac output (1200 mL/min); RPF = plasma flow (~650 mL/min); GFR/RPF = extraction ratio (~0.2)

Tubular Reabsorption

Proximal Tubule (65% of filtered Na⁺ and water):

Substance	% Reabsorbed	Mechanism
Na⁺	~65%	Na⁺/H⁺ exchanger (NHE3), cotransporters
Glucose	100%	SGLT1/SGLT2 (Na⁺-glucose cotransporters)
Amino acids	100%	Na⁺-amino acid cotransporters
HCO₃⁻	~90%	Na⁺/H⁺ exchanger → CA → CO₂ reabsorption
Water	~65%	Osmotic gradient (aquaporins)
Cl⁻	~65%	Concentration gradient

Loop of Henle:

Segment	Function
Descending limb	Permeable to water, impermeable to solutes → water leaves → concentrated tubular fluid
Ascending limb	Impermeable to water, permeable to Na⁺/K⁺/Cl⁻ (NKCC2) → dilute tubular fluid

Countercurrent Multiplication:

• Creates hyperosmotic medullary interstitium (up to 1200 mOsm/kg)
• Medullary osmolarity gradient essential for concentration of urine

⚡ Exam tip: Mannitol = osmotic diuretic; filtered but not reabsorbed → holds water in tubule → diuresis

Distal Tubule and Collecting Duct

DCT:

• Na⁺/Cl⁻ cotransporter (NCC): Thiazide diuretics inhibit here
• Aldosterone-responsive cells (ENaC)
• Calcium reabsorption via TRPV5 channels (PTH regulates)

Collecting Duct:

• Principal cells: ENaC (amiloride blocks), K⁺ channels (secretion)
• α-intercalated cells: H⁺-ATPase (acid secretion), H⁺/K⁺-ATPase
• β-intercalated cells: Cl⁻/HCO₃⁻ exchanger (bicarbonate secretion)

⚡ Exam tip: Aldosterone acts on principal cells → ↑ Na⁺ reabsorption, ↑ K⁺ secretion; ↑ water follows Na⁺ (osmosis) → ↑ blood volume/pressure

Tubular Secretion

Key Secreted Substances:

Substance	Site	Function
H⁺	DCT, CD (α-intercalated)	Acid excretion
K⁺	DCT, CD (principal cells)	K⁺ balance
Organic acids	PCT	Drug excretion (penicillins, salicylates, probenecid)
Organic bases	PCT	Drug excretion (quinine, amiloride)
NH₃/NH₄⁺	PCT	Acid buffering and excretion

Countercurrent System

Loop of Henle Countercurrent Multiplication:

• Descending limb: Water permeable, solutes impermeable → tubular fluid concentrated
• Thick ascending limb: Solutes impermeable to water, NKCC2 reabsorbs Na⁺, K⁺, Cl⁻ → dilutes tubular fluid, concentrates interstitium
• vasa recta: Countercurrent exchange prevents washout of medullary gradient

⚡ Exam tip: Loop diuretics (furosemide) block NKCC2 → ↓ NaCl reabsorption in TAL → ↓ medullary gradient → ↓ water reabsorption → copious dilute urine; Lithium causes nephrogenic DI by blocking aquaporin-2 insertion

Regulation of GFR and Renal Blood Flow

Autoregulation:

• Maintains GFR relatively constant despite BP changes (80–180 mmHg MAP)
• Myogenic mechanism: Afferent arteriole stretch → vasoconstriction
• Tubuloglomerular feedback: ↑ NaCl at macula densa → ↓ GFR

Renal Hormones:

Hormone	Source	Effect
Renin	JG cells	Initiates RAAS
EPO	Fibroblasts	↑ RBC production
1,25-(OH)₂ Vitamin D	Proximal tubule	↑ Ca²⁺ absorption
Prostaglandins	Medulla	Modulate GFR, Na⁺ excretion

⚡ Exam tip: Angiotensin II preferentially constricts efferent arteriole → ↑ glomerular capillary pressure → maintains GFR despite ↓ renal perfusion

Acid-Base Balance

Renal Acid Excretion:

Mechanism	Site	Details
H⁺ secretion	α-intercalated cells	H⁺-ATPase pumps H⁺ into lumen
HCO₃⁻ reabsorption	PCT	CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃⁻
NH₃ synthesis	PCT	Glutamine → NH₃ + α-ketoglutarate
NH₄⁺ excretion	Collecting duct	NH₃ + H⁺ → NH₄⁺ (trapped)

Acid-Base Disturbances — Renal Compensation:

• Metabolic acidosis: ↑ NH₃/NH₄⁺ excretion → ↑ new HCO₃⁻ generation
• Metabolic alkalosis: ↓ H⁺ secretion, ↑ HCO₃⁻ reabsorption

⚡ Exam tip: Renal tubular acidosis (RTA) — Types: I (distal): ↓ H⁺ secretion; II (proximal): ↓ HCO₃⁻ reabsorption; IV: Hypoaldosteronism/hyporesponsiveness

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🔴 Extended — Deep Study (3mo+)

Comprehensive coverage for students on a longer study timeline.

Renal Physiology — Comprehensive NEET PG Notes

Detailed Glomerular Dynamics

Filtration Fraction:

FF = GFR / RPF (normal ~0.2 or 20%)

• RPF (Renal Plasma Flow) measured by PAH clearance
• GFR measured by inulin or creatinine clearance

Clearance:

Cx = (Ux × V) / Px

• Cx = Clearance of substance x
• Ux = Urine concentration of x
• V = Urine flow rate
• Px = Plasma concentration of x

Substance	Clearance	Interpretation
Inulin	= GFR	Filtered, neither reabsorbed nor secreted
PAH	= RPF	Filtered and secreted, nearly complete extraction
Creatinine	≈ GFR	Some tubular secretion
Glucose	0 (normal)	Filtered and completely reabsorbed

⚡ Exam tip: Creatinine clearance overestimates GFR by 10–20% due to tubular secretion; Cystatin C is an alternative marker less affected by muscle mass

Detailed Sodium Handling

Proximal Tubule Na⁺ Transport:

• Na⁺/H⁺ exchanger (NHE3): Major mechanism
• Na⁺-glucose cotransporter (SGLT1/2)
• Na⁺-amino acid cotransporters
• Na⁺-phosphate cotransporters
• Carbonic anhydrase: Intracellular CA converts H₂CO₃ to CO₂ + H₂O

Loop of Henle Na⁺ Transport:

• Descending limb: No Na⁺ transport (impermeable to solutes except some water)
• Thick ascending limb: NKCC2 (Na⁺, K⁺, Cl⁻ cotransporter)

Distal Nephron Na⁺ Transport:

• DCT: NCC (thiazide-sensitive)
• Collecting duct: ENaC (amiloride-sensitive)

Diuretic Sites and Mechanisms:

Diuretic	Site	Mechanism
Acetazolamide	PCT	CA inhibitor → ↓ Na⁺/H⁺ exchange
Furosemide	TAL	NKCC2 inhibitor
Thiazides	DCT	NCC inhibitor
Amiloride	CD	ENaC inhibitor
Spironolactone	CD	Aldosterone receptor antagonist

⚡ Exam tip: Furosemide → ↑ NaCl excretion → ↓ medullary gradient → ↓ ADH effect → dilute urine; Spironolactone blocks aldosterone receptor → ↓ ENaC expression → Na⁺ loss, K⁺ retention

Water Balance — Urine Concentration

ADH (Vasopressin) Mechanism:

1. ↑ plasma osmolarity OR ↓ blood volume → posterior pituitary releases ADH
2. ADH binds V2 receptors on collecting duct principal cells
3. cAMP → PKA → inserts AQP2 water channels
4. Water reabsorption → concentrated urine

Mechanism of Urine Concentration:

• Hyperosmotic medullary interstitium (1200 mOsm/kg at papilla)
• ADH makes collecting duct permeable to water
• Water moves from collecting duct into hyperosmotic medullary interstitium
• Urine concentrated up to 1200 mOsm/kg (maximum in humans)

Vasa Recta Function:

• Peritubular capillaries following Loop of Henle
• Countercurrent exchange maintains medullary gradient
• Slow flow = equilibration = washout prevention

⚡ Exam tip: SIADH = inappropriate ADH secretion → water retention → dilutional hyponatremia; Diabetes Insipidus = ↓ ADH (central) or ↓ ADH response (nephrogenic) → massive dilute urine

Potassium Balance

K⁺ Handling:

Nephron Segment	Process	Notes
PCT	~65% reabsorption	Paracellular
TAL	~25% reabsorption	NKCC2 (creates lumen-positive charge)
DCT/CD	Variable	Principal cells: K⁺ secretion
α-intercalated	K⁺ reabsorption	H⁺/K⁺-ATPase

Factors Regulating K⁺ secretion in Collecting Duct:

Factor	Effect on K⁺ Secretion
↑ Aldosterone	↑
↑ Flow rate	↑ (dilution effect)
↓ luminal [K⁺]	↑
Metabolic alkalosis	↑
Thiazides	↑ (flow-dependent)
Loop diuretics	↑ (flow-dependent)
Amiloride	↓
Spironolactone	↓

⚡ Exam tip: Hypokalemia activates H⁺-K⁺-ATPase in α-intercalated cells → H⁺ secretion → metabolic alkalosis (contraction alkalosis from diuretic use)

Calcium and Phosphate Balance

Calcium Handling:

• Filtered Ca²⁺: ~60% reabsorbed in PCT (paracellular, passive)
• TAL: ~20% reabsorbed (paracellular, regulated by PTH)
• DCT: ~9% reabsorbed (TRPV5 channels, regulated by PTH)
• Collecting duct: Minimal

Phosphate Handling:

• Filtered: ~85% reabsorbed in PCT (NaPi cotransporters)
• PTH: ↓ phosphate reabsorption (PTH acts on DCT)

PTH Effects on Kidney:

1. ↑ Ca²⁺ reabsorption (DCT)
2. ↓ phosphate reabsorption (PCT)
3. ↑ 1-α-hydroxylase activity → ↑ active vitamin D

⚡ Exam tip: PTHrP (PTH-related peptide) in malignancy → hypercalcemia of malignancy; PTH and PTHrP share PTH1 receptor

Renal Calculi

Stone Types:

Type	Cause	X-ray	Composition
Calcium oxalate	Hypercalciuria	Radiopaque	Most common
Calcium phosphate	Renal tubular acidosis	Radiopaque	Brushite, apatite
Struvite	Urease-producing bacteria	Radiopaque	Magnesium ammonium phosphate
Uric acid	Gout, ↓ urine pH	Radiolucent	Purine metabolism
Cystine	Cystinuria	Faintly radiopaque	Rare, hereditary

Formation Theories:

1. supersaturation → nucleation
2. Inhibitor deficiency (citrate, magnesium)
3. pH (uric acid stones form in acidic urine)

Clinical Correlations

Acute Kidney Injury (AKI):

Parameter	Prerenal	Intrinsic	Postrenal
BUN/Cr	>20:1	<15:1	>20:1 (late)
Urine Na⁺	<20 mEq/L	>40 mEq/L	Variable
FENa	<1%	>2%	Variable
Response to fluids	Improves	No	No

Chronic Kidney Disease (CKD):

• ↓ GFR → azotemia, electrolyte imbalances
• ↑ Phosphate → ↓ Ca²⁺ → secondary hyperparathyroidism → renal osteodystrophy
• ↓ EPO → anemia (normocytic, normochromic)
• ↓ Vitamin D activation → osteomalacia, hyperparathyroidism
• Metabolic acidosis → bone buffering

⚡ Exam tip: HUS (Hemolytic Uremic Syndrome) = microangiopathic hemolytic anemia + thrombocytopenia + AKI; typical after Shiga toxin-producing E. coli O157:H7 infection

Practice Questions for NEET PG

1. Calculate creatinine clearance using the Cockcroft-Gault equation.
2. Describe the countercurrent multiplication mechanism in detail.
3. Explain how loop diuretics cause metabolic alkalosis.
4. A patient has hyponatremia with euvolemia. What is the likely diagnosis and how do you differentiate from other hyponatremias?
5. Describe the mechanisms of renal calcium reabsorption.
6. What is the role of ADH in water balance? Explain the mechanism of action.
7. Describe the differences between prerenal, intrinsic, and postrenal AKI.

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