Metabolic Alkalosis & Aciduria

Paradoxical aciduria – Formation of acidic urine in face of alkalosis

Gastric outlet obstruction

• Large volume projectile vomiting
  • Hypovolaemia → Contraction alkalosis
  • Cl^– loss → increased SID → metabolic alkalosis

Compensation

• Respiratory compensation of metabolic alkalosis
  • Decreased plasma [H⁺] causes hypoventilation → CO2 increases
  • PaCO2 = 0.7 [HCO₃^–] + 20

• Renal compensation – Renal handling of HCO3
  • PCT
    • 85% reabsorbed in PCT via H2O and CO2 (due to carbonic anhydrase)
    • In PCT cell, H2O and CO2 reform HCO3^– and H+ (via CA)
    • H+ secreted into tubular lumen via H+ ATPase
    • Increased plasma CO2 due to repiratory compensation of alkalosis, increases intracellular CO2 and causes increased absorption of HCO3 → inhibits HCO3 elimination
  • LoH
    • 10% reabsorbed
  • DCT
    • Type B intercalated cells secrete HCO3^–
    • Via Pendrin antiporter (Secretes HCO3^– in exchange for Cl-) on luminal membrane. H⁺ ATPase on basolateral membrane
    • HCO3^– eliminated and Cl^– reabsorbed leading to decreased SID andcompensation
    • However, due to hypochloridaemia from hyperemesis, this mechanism is retarded

• Effects due to volume contraction, stress
  • RAAS system activated by decreased Na⁺ and Cl^– reaching DCT and macula densa.
  • JGA secretes renin → angiotensin → aldosterone
  • Aldosterone effect on kidney
    • DCT
      • Increased Na reabsorption due to upregulation of basolateral Na/K ATPase and luminal ENaC
      • Increased Na/K ATPase activity causes increased K⁺ allowing K secretion → This leads to hypokalaemia

• Defense of total body K⁺
  • Total body K⁺ approx 50mmol/kg.
  • K⁺ in glomerular filtrate reabsorbed in the PCT (65%) and LoH (30%) with remaining DCT accounting for secretion or reabsorption depending on body balance
  • With hypokalaemia, K⁺ reabsorbed by intercalated cells of DCT via H⁺/K⁺ antiporter
  • Leads to H⁺ secretion into DCT/Collecting ducts

Sakurai 2016

Answer by Sakurai