BIOH12012 – Urinary System Anatomy & Physiology (Week 3)

Functions of the Kidney

  • Maintenance of fluid balance
    • Regulates total body water via filtration, reabsorption and secretion.
  • Maintenance of electrolyte balance
    • Fine-tunes concentrations of Na^+ , K^+, Ca^{2+}, Cl^- and other ions.
  • Regulation of acid–base balance
    • Adjusts urinary excretion of H^+ and HCO_3^- to keep arterial pH ≈ 7.35–7.45.
  • Endocrine functions
    • Renin (blood pressure), erythropoietin (RBC production), calcitriol (vitamin D activation), prostaglandins, and clearance of peptide hormones.

Anatomy of the Nephron

  • Vascular components
    • Afferent arteriole → glomerulus → efferent arteriole → peritubular capillaries/vasa recta.
  • Tubular components
    • Bowman's (glomerular) capsule → proximal convoluted tubule (PCT) → loop of Henle (descending thin + thick ascending limbs) → distal convoluted tubule (DCT) → collecting tubule/duct → papillary duct → minor calyx.
  • Juxtaglomerular apparatus (JGA)
    • Macula densa (DCT) + granular/juxtaglomerular cells (arteriole walls) + extraglomerular mesangial cells.
    • Coordinates renal perfusion pressure and filtrate composition.

Glomerular Filtration Membrane

  • Three layers form a size- and charge-selective barrier:
    • Fenestrated capillary endothelium – blocks formed elements but lets plasma through.
    • Basement membrane – negatively charged protein mesh; hinders proteins > 70 kDa.
    • Visceral layer (podocytes) – interdigitating foot processes create filtration slits; slit diaphragms provide final molecular sieve.
  • Direction of flow: capillary lumen → filtrate within Bowman’s space (large red arrows in electron micrograph).

Urine Formation: Core Processes

  • Filtration (renal corpuscle)
    • Blood pressure forces plasma minus proteins into capsular space → filtrate.
  • Reabsorption (PCT, loop, DCT, collecting duct)
    • Valuable solutes & water returned to peritubular fluid then blood.
  • Secretion (mostly PCT & DCT)
    • Additional wastes, drugs, ions transported from blood → tubular fluid.

Segment-Specific Transport Activities

  • Proximal convoluted tubule
    • Reabsorbs ~65 % H₂O, Na^+, Cl^-; 100 % glucose, amino acids; secretes organic acids/bases.
  • Loop of Henle
    • Descending thin limb: H₂O permeable → water exits.
    • Thick ascending limb: impermeable to H₂O; active Na^+/K^+/2Cl^- reabsorption.
  • Distal convoluted tubule
    • Variable Na^+ reabsorption and K^+, H^+ secretion (aldosterone sensitive).
  • Collecting duct
    • Variable H₂O reabsorption (ADH-regulated); fine-tunes Na^+, K^+, H^+, HCO_3^-.

Juxtaglomerular Complex (JGC)

  • Macula densa (chemoreceptors)
    • Detect ↑/↓ NaCl in DCT filtrate.
    • High NaCl → release adenosine → afferent arteriole vasoconstriction → ↓ GFR.
  • Granular (juxtaglomerular) cells
    • Modified smooth muscle; baroreceptors.
    • ↓ afferent pressure / ↓ filtrate NaCl → secrete renin.
  • Extraglomerular mesangial cells
    • Relay signals between macula densa & granular cells; provide structural support, phagocytosis, filtration regulation.

Glomerular Filtration Pressures & GFR

  • Driving forces
    • Glomerular hydrostatic pressure HP_{gc} (≈ 55 \text{ mmHg}) – outward.
    • Capsular hydrostatic pressure HP_{cs} (≈ 15 \text{ mmHg}) – inward.
    • Glomerular colloid osmotic pressure OP_{gc} (≈ 30 \text{ mmHg}) – inward.
  • Net filtration pressure
    NFP = HP{gc} - (OP{gc} + HP_{cs})
  • Glomerular filtration rate (GFR)
    • Volume of filtrate produced per minute by both kidneys: ≈ 125 \text{ mL min}^{-1} (≈ 180 \text{ L day}^{-1}).

Regulation of GFR

  • Intrinsic (renal autoregulation)
    • Myogenic: afferent arteriole smooth muscle responds to stretch.
      • ↓ BP → vasodilation → maintains HP_{gc}.
    • Tubuloglomerular feedback: macula densa senses filtrate NaCl; modulates afferent tone via adenosine or NO.
  • Extrinsic
    • Sympathetic nervous system: norepinephrine → strong afferent/efferent constriction during hypotension → prioritises MAP.
    • Hormonal RAAS: renin → \uparrow angiotensin II → systemic vasoconstriction & aldosterone release.

Countercurrent Mechanisms & Urine Concentration

  • Countercurrent multiplier (loop of Henle)
    • Opposite flow + differential permeabilities create medullary osmotic gradient (≈ 300→1200 \text{ mOsm}).
  • Countercurrent exchanger (vasa recta)
    • Preserves gradient by passive H₂O/solute exchange.
  • Role of ADH in collecting duct
    • Inserts aquaporin-2 channels → water follows medullary gradient → concentrated urine when body needs to conserve H₂O.

Endocrine Controllers of Fluid & Electrolytes

  • Renin–Angiotensin–Aldosterone System (RAAS)
    1. ↓ renal perfusion / ↓ Na^+ sensed by JGC → renin release.
    2. Renin cleaves angiotensinogen → angiotensin I.
    3. ACE (lungs) converts angiotensin I → angiotensin II.
    4. Angiotensin II effects:
    • Potent vasoconstriction → ↑ SVR & BP.
    • Stimulates aldosterone (adrenal cortex) → ↑ Na^+ & H₂O reabsorption, ↑ K^+ secretion.
    • Stimulates ADH secretion + thirst.
  • Antidiuretic Hormone (ADH / vasopressin)
    • Released by posterior pituitary when hypothalamic osmoreceptors detect ↑ plasma osmolarity or when baroreceptors sense ↓ blood volume/pressure.
    • Actions: ↑ H₂O reabsorption in collecting ducts → ↓ urine volume; stimulates thirst.
  • Aldosterone
    • Stimulated by ↑ K^+, angiotensin II, or ↓ Na^+.
    • Acts on DCT & collecting duct principal cells: up-regulates ENaC & Na^+/K^+-ATPase.
    • Consequence: ↑ Na^+ (and Cl⁻, H₂O) reabsorption, ↑ K^+ secretion → expands ECF volume.
  • Natriuretic peptides (ANP, BNP)
    • Released by atrial/ventricular stretch.
    • Promote diuresis & natriuresis: inhibit RAAS & ADH, dilate afferent arteriole → ↑ GFR.

Body Fluid Compartments & Electrolyte Distribution

  • Intracellular fluid (ICF)
    • ~2/3 total body water; high K^+, HPO_4^{2-}, Mg^{2+}, proteins.
  • Extracellular fluid (ECF)
    • Interstitial fluid + plasma + CSF, lymph, synovial, etc.
    • High Na^+, Cl^- , HCO_3^- , Ca^{2+}.
  • Milliequivalent distribution diagram (see Martini Fig 27-2) reflects relative ionic composition.

Major Electrolytes & Imbalances

Sodium (Na⁺)

  • Normal serum 135–145 \text{ mmol L}^{-1}.
  • Hyponatraemia (<135)
    • Water shifts into cells → cerebral oedema.
    • Causes: excess H₂O intake, heart failure, vomiting, diarrhoea, renal disease, diuretics.
    • S/S: lethargy, confusion, seizures, hypotension, tachycardia.
  • Hypernatraemia (>145)
    • Cells shrink (crenate).
    • Causes: dehydration, inadequate ADH, fever.
    • S/S: thirst, agitation, seizures, coma.

Potassium (K⁺)

  • Normal serum 3.5–5.2 \text{ mmol L}^{-1}.
  • Hypokalaemia (<3.5)
    • Causes: diarrhoea, vomiting, diuretics, insulin therapy.
    • S/S: muscle weakness, cramps, arrhythmias, flattened T-waves.
  • Hyperkalaemia (>5.2)
    • Causes: renal failure, tissue breakdown, ACE-inhibitors.
    • S/S: peaked T-waves, ventricular fibrillation, diarrhoea, muscle twitching.

Calcium (Ca²⁺)

  • Normal serum total 2.25–2.75 \text{ mmol L}^{-1} (ionised ≈ 1.1–1.3).
  • Hypocalcaemia (<2.1)
    • Causes: hypoparathyroidism, vitamin D deficiency, renal failure.
    • S/S: tetany, Chvostek & Trousseau signs, laryngospasm, seizures.
  • Hypercalcaemia (>2.6)
    • Causes: hyperparathyroidism, malignancy, immobility.
    • S/S: polyuria, kidney stones, constipation, arrhythmias, mental changes.

Net Effects of RAAS on BP, Volume & Urine

  • Vasoconstriction ↑ SVR
  • Aldosterone-mediated Na^+/H₂O retention ↑ blood volume
  • ADH-mediated water retention & thirst ↑ volume
  • Result: ↑ BP, ↓ urinary output until homeostasis restored.

Integration & Clinical Relevance

  • Effective renal perfusion & intact JGA crucial to BP regulation; ACE inhibitors & ARBs exploit RAAS pathway for hypertension therapy.
  • Electrolyte monitoring essential in heart failure, kidney disease, postoperative care – subtle shifts precipitate life-threatening arrhythmias or CNS dysfunction.
  • Countercurrent mechanism underpins ability to produce urine from dilute (