CV

Renal Function – Comprehensive Bullet-Point Notes

Renal Anatomy

  • Kidneys are two bean-shaped organs situated retro-peritoneally on either side of the vertebral column.
    • The right kidney is slightly lower than the left due to the position of the liver.
  • Gross structures that enter/leave the hilum: ureter, renal artery, renal vein, lymphatics and nerves.
  • Macroscopic divisions
    • Cortex (outer): contains all glomeruli, proximal & distal convoluted tubules.
    • Medulla (inner): organized into 8–18 renal pyramids whose apices (papillae) drain into minor → major calyces → renal pelvis → ureter.
    • Pelvis: funnel-like collecting cavity continuous with the ureter.
  • Blood flow pathway (arterial): renal → segmental → interlobar → arcuate → interlobular → afferent arteriole → glomerular capillaries → efferent arteriole → peritubular capillaries / vasa recta → venules → interlobular → arcuate → interlobar → segmental → renal vein.
    • ≈ 25\% of resting cardiac output (≈1.25 L min^{-1}) perfuses the kidneys.

The Nephron – Structural & Functional Unit

  • Each kidney possesses >1 \times 10^{6} nephrons.
  • Two major components
    • Renal corpuscle: Bowman’s capsule + enclosed glomerulus.
    • Renal tubule: PCT → Loop of Henle (descending & ascending limbs) → DCT → collecting duct.
  • Two histological types
    • Cortical nephrons (≈85 %): short loops, mainly in cortex.
    • Juxtamedullary nephrons (≈15 %): long loops extending deep into medulla; essential for concentrating urine.

Renal Parenchyma & Vascular Specializations

  • Peritubular capillaries encircle cortical nephron tubules – primary site for rapid reabsorption/secretion.
  • Vasa recta are hair-pin capillaries paralleling juxtamedullary loops & collecting ducts; crucial for counter-current exchange without dissipating the medullary osmotic gradient.

Core Functions of the Kidneys

  • Urine formation (filtration → reabsorption → secretion).
  • Regulation of fluid & electrolyte balance (Na^{+}, K^{+}, Cl^{-}, Ca^{2+}, water).
  • Regulation of acid–base homeostasis via H^{+} secretion & HCO_{3}^{-} handling.
  • Excretion of nitrogenous wastes (ammonia, urea, uric acid, creatinine).
  • Endocrine roles: renin, erythropoietin, activation of vitamin D.
  • Conservation of plasma proteins by preventing their filtration.

Urine Formation – Integrated Overview

  1. Glomerular filtration (production of protein-free filtrate).
  2. Tubular reabsorption (return of 99 % of filtrate to blood).
  3. Tubular secretion (selective addition of substances to tubular fluid).
  4. Excretion (what finally leaves via urethra).
  • Renal plasma flow ≈600–700\,\text{mL min}^{-1}; filtration fraction ≈20\% ⇒ GFR≈120–130\,\text{mL min}^{-1}.
  • Daily figures:
    • Filtrate formed ≈187{,}000\,\text{mL} (≈48 gallons ≈180 L).
    • Urine voided ≈1{,}500\,\text{mL} (≈1 % of filtrate).

Glomerular Filtration Details

  • Driving force: glomerular blood hydrostatic pressure (GBHP) created by the large afferent and smaller efferent arteriole.
  • Filtration membrane layers
    1. Fenestrated endothelium – excludes blood cells & platelets.
    2. Basement membrane – excludes large plasma proteins.
    3. Slit diaphragms between podocyte foot processes – block medium proteins, let small solutes and water cross.
  • Net Filtration Pressure NFP = GBHP - (CHP + BCOP) = 10 \; \text{mm Hg}
    • Promoting force: GBHP (≈55\,\text{mm Hg}).
    • Opposing forces: capsular hydrostatic pressure (CHP ≈15) + blood colloid osmotic pressure (BCOP ≈30).
  • Clinical importance: GFR is primary index of renal function; falls in renal disease, shock, severe dehydration.

Autoregulation & Systemic Control of GFR

Intrinsic mechanisms (maintain constant GFR despite 80-180\,\text{mm Hg} MAP):

  • Myogenic: afferent arteriole constricts when stretched, dilates when pressure falls.
  • Tubulo-glomerular feedback: macula densa senses ↑NaCl delivery → releases less nitric oxide → afferent arteriolar vasoconstriction → ↓GFR.
    Extrinsic mechanisms (override during stress):
  • Neural: sympathetic activation causes afferent vasoconstriction to shunt blood to vital organs.
  • Hormonal: renin–angiotensin–aldosterone system (RAAS).
    • ↓Renal perfusion → juxtaglomerular (JG) cells release renin → converts angiotensinogen → \text{Ang I} → \text{Ang II} (via ACE).
    • \text{Ang II} effects: systemic vasoconstriction, efferent constriction (maintains filtration), stimulates aldosterone → ↑Na^{+}/water retention → ↑BP & blood volume.

Segmental Tubular Processing

Proximal Convoluted Tubule (PCT)

  • Reabsorbs ≈65 % of filtered water & Na^{+}, 100 % of glucose, amino acids, vitamin C, lactate.
  • Mechanisms
    • Na^{+}/K^{+}-ATPase on basolateral membrane drives downhill Na^{+} entry via symporters (glucose, amino acids) or antiporter (H^{+}).
    • Water follows osmotically through aquaporin-1 and paracellular gaps.
  • Secretion: drugs, creatinine, H^{+}, NH_{4}^{+}.

Loop of Henle

  • Descending limb: highly permeable to water, impermeable to solutes → filtrate becomes hyperosmotic.
  • Ascending thin limb: passive NaCl diffusion.
  • Ascending thick limb: active Na^{+}/K^{+}/2Cl^{-} cotransport; impermeable to water → filtrate dilutes.
  • Multiplies osmotic gradient (counter-current multiplier).

Distal Convoluted Tubule (DCT)

  • Further NaCl reabsorption via Na^{+}/Cl^{-} symporter.
  • Impermeable to water unless antidiuretic hormone (ADH) present.

Collecting Duct

  • Final 5 % of filtrate handled.
  • Cell types
    • Principal cells: aldosterone-sensitive Na^{+} reabsorption, K^{+} secretion; ADH-responsive aquaporin-2 insertion for water reabsorption.
    • Intercalated cells: secrete H^{+} (\alpha-type) or HCO_{3}^{-} (\beta-type) for pH regulation.

Counter-Current Mechanism & Urine Concentration

  • Medullary interstitium exhibits progressive osmolarity (≈300 mosm L^{-1} cortex → 1200 mosm L^{-1} inner medulla).
  • Generated by
    • Loop of Henle (multiplier).
    • Vasa recta (exchange) – preserves gradient while delivering nutrients/oxygen.
    • Urea recycling from inner medullary collecting duct.
  • ADH increases collecting duct permeability → water drawn out along gradient → concentrated urine (up to 1200 mosm L^{-1}).

Acid–Base Regulation

  • Buffer pairs: \text{CO}{2} + \text{H}{2}\text{O} \leftrightarrow \text{H}{2}\text{CO}{3} \leftrightarrow \text{H}^{+} + \text{HCO}_{3}^{-}.
    • Lungs modulate \text{CO}_{2} (acid component).
    • Kidneys modulate H^{+} excretion & HCO_{3}^{-} regeneration (base component).
  • PCT: Na^{+}/H^{+} antiporter secretes H^{+}; filtered HCO_{3}^{-} reclaimed.
  • Intercalated \alpha-cells:
    • H^{+} actively secreted via H^{+}-ATPase & H^{+}/K^{+}-ATPase.
    • New HCO_{3}^{-} produced enters blood.

Nitrogenous Waste Excretion

  • Ammonia
    • Produced by deamination of amino acids; neurotoxic.
    • Detoxified in liver → urea (urea cycle).
  • Urea
    • Quantified clinically as Blood Urea Nitrogen (BUN).
    • Filtered freely; 40–50 % passively reabsorbed in PCT; contributes to medullary gradient.
    • BUN less specific for renal function than GFR; elevates in dehydration, high protein intake, GI bleed.
  • Uric Acid
    • End-product of purine metabolism, higher in males.
    • Filtered, both reabsorbed & secreted; accumulates in chronic renal failure → gout-like hyperuricemia.
  • Creatinine
    • From steady non-enzymatic breakdown of muscle creatine.
    • Filtered, not reabsorbed; minimal secretion → creatinine clearance ≈ GFR surrogate.

Endocrine (Hormonal) Functions

  • Renin – initiates RAAS → systemic BP & perfusion maintenance.
  • Erythropoietin – released by peritubular fibroblasts in response to hypoxia; stimulates RBC production in bone marrow.
  • Vitamin D activation – hydroxylation of 25\,(OH)\,D to active 1,25\,(OH){2}\,D{3} (calcitriol) in proximal tubule; essential for calcium & phosphate homeostasis, bone mineralization.

Regulation of Glomerular & Systemic Hemodynamics (Integrated Flow Chart)

  • Low renal perfusion triggers dual responses:
    1. Intrinsic autoregulation (myogenic + tubulo-glomerular) → afferent arteriole dilation restoring GFR.
    2. Extrinsic neural/hormonal (sympathetic & RAAS) → systemic vasoconstriction & Na^{+}/water retention raising arterial pressure.
  • Aldosterone on distal nephron ↑Na^{+} reabsorption, ADH on collecting duct ↑water permeability, together restoring blood volume & pressure.

Clinical & Ethical Notes

  • Preserving GFR is vital; nephrotoxic drugs (NSAIDs, aminoglycosides) or prolonged hypotension can irreversibly damage nephrons.
  • Creatinine-based eGFR guides drug dosing and staging of chronic kidney disease – ethics of equitable access to renal replacement therapy.
  • Understanding renal physiology underpins management of acid–base disorders, diuretic therapy, hypertension, and electrolyte emergencies.