Pathophysiology-metabolic-alkalosis

(CJASN 2020;15:1848)

Saline-responsive etiologies require

1. initiating event and
2. maintenance phase

Initiating event: net HCO3− reabsorption (due to loss of volume, Cl-, and/or K+) or loss of H+

• Loss of H+ (± Cl-) from GI tract, kidneys, or transcellular shift in hypokalemia
• Contraction alkalosis: loss of HCO3—poor fluid → extracellular fluid “contracts” around fixed amount of HCO3- → ↑ HCO3- concentration
  • 流失掉酸液
• Exogenous alkali:
  • iatrogenic HCO3- (with renal impairment),
  • milk-alkali syndrome
• Posthypercapnia:
  • resp. acidosis →
  • compensation with H+ excretion and HCO3- retention;
  • rapid correction of hypercapnia (eg, intubation) → transient excess HCO3-

Maintenance phase

• Volume depletion
  • → ↑ ATII
  • → ↑ PCT reabsorption of HCO3- & ↑ aldosterone (see below)
• Cl- depletion
  • → ↓ Cl- uptake in macula densa
  • → ↑ RAS & ↑ CCD Cl-/HCO3- exchanger
• Hypokalemia
  • → transcellular K+/H+ exchange;
  • intracellular acidosis
  • → HCO3- reabsorption and ammoniagenesis & ↑ distal H+-K+-ATPase activity
  • → HCO3- retention
• Hyperaldosteronism (1° or 2°)
  • → ↑ CCD α-intercalated H+ secretion w/ HCO3- retention & Na+ reabsorption in principal cell → H+ secretion (for electrical neutrality)