Mechanism of Contraction Alkalosis
Contraction alkalosis occurs when volume depletion concentrates existing bicarbonate in a smaller extracellular fluid volume, while simultaneously activating compensatory mechanisms that prevent renal bicarbonate excretion, thereby maintaining the alkalotic state. 1
Primary Pathophysiologic Mechanism
The fundamental process involves two interconnected components:
Volume contraction concentrates bicarbonate: When extracellular fluid volume decreases (through diuretics, vomiting, or diarrhea), the absolute amount of bicarbonate remains constant but becomes concentrated in a smaller fluid volume, mechanically raising serum bicarbonate concentration 2
Renal bicarbonate retention perpetuates alkalosis: The kidney normally eliminates excess bicarbonate efficiently, but volume depletion triggers multiple mechanisms that prevent this corrective response 2
Key Maintenance Factors
Volume depletion activates several pathways that impair the kidney's ability to excrete bicarbonate:
Enhanced proximal tubule sodium reabsorption: Volume contraction stimulates avid sodium reabsorption in the proximal tubule, which is coupled to bicarbonate reabsorption via the Na-H exchanger, preventing bicarbonate excretion despite systemic alkalosis 1
Aldosterone activation: Volume depletion triggers the renin-angiotensin-aldosterone system, increasing aldosterone levels that promote sodium reabsorption via the epithelial sodium channel (ENaC) in the distal tubule 1
Increased distal hydrogen ion secretion: Enhanced sodium reabsorption in the collecting duct creates a negative luminal charge that drives hydrogen ion secretion (and potassium secretion) to maintain electrical neutrality, paradoxically producing acidic urine despite systemic alkalosis 1
Contributing Electrolyte Abnormalities
Hypochloremia: Chloride depletion independently maintains metabolic alkalosis by limiting the kidney's ability to excrete bicarbonate, as bicarbonate excretion requires chloride availability for electroneutrality 1
Hypokalemia: Potassium deficiency promotes hydrogen ion secretion in the collecting duct as potassium-depleted cells exchange intracellular hydrogen for extracellular potassium, worsening alkalosis 1
Paradoxical Aciduria
A hallmark feature of contraction alkalosis is paradoxical aciduria—acidic urine (pH <5.5) despite systemic alkalosis:
The distal nephron secretes hydrogen ions to maintain electrical neutrality during enhanced sodium reabsorption, overriding the normal response to alkalosis which would be bicarbonate excretion 1
This phenomenon occurs commonly with diuretic therapy, vomiting, or salt-wasting tubulopathies like Bartter syndrome 1
Clinical Scenarios
Diuretic-induced contraction alkalosis is the most common clinical presentation:
Loop diuretics (furosemide) and thiazide diuretics cause volume contraction, chloride depletion, and hypokalemia—all factors that generate and maintain metabolic alkalosis 3, 1
The combination of dicyclomine and hydrochlorothiazide has been reported to produce severe contraction alkalosis through synergistic volume depletion 4
Vomiting or nasogastric suction produces contraction alkalosis through:
- Direct loss of hydrochloric acid (generating alkalosis)
- Volume depletion from fluid loss (concentrating bicarbonate)
- Chloride depletion (impairing bicarbonate excretion) 2
Hemodynamic Consequences
Volume contraction reduces glomerular filtration rate through tubuloglomerular feedback mechanisms, further impairing bicarbonate excretion even when ECF volume is restored 5
Reduced distal chloride delivery to the macula densa triggers afferent arteriolar vasoconstriction, decreasing GFR independent of volume status 5
Treatment Implications
The mechanism dictates that effective treatment requires:
Volume repletion with chloride-containing solutions (normal saline) to reverse the concentration effect and provide chloride for bicarbonate excretion 2
Potassium chloride supplementation to correct hypokalemia and reduce hydrogen ion secretion 1
Discontinuation of offending diuretics when possible to halt ongoing volume and chloride losses 3, 6
Common Pitfall
The critical error is attempting to correct the alkalosis without addressing volume depletion and chloride deficiency—bicarbonate will not be excreted until adequate chloride is available and volume status is restored, regardless of how elevated the serum bicarbonate becomes 1, 2