Hyperchloremic Metabolic Acidosis in Cirrhosis
Cirrhosis causes hyperchloremic metabolic acidosis primarily through dilutional mechanisms and altered renal handling of electrolytes, where hypoalbuminemic alkalosis is offset by both hyperchloremic acidosis and dilutional acidosis, creating a complex equilibrium of competing acid-base disturbances. 1
Primary Pathophysiological Mechanisms
Hyperchloremic Component
The hyperchloremic acidosis in cirrhosis develops through several interconnected mechanisms:
Dilutional acidosis occurs as cirrhotic patients retain sodium and water due to activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, leading to relative hyperchloremia as bicarbonate becomes diluted 2
Altered renal chloride handling results from the kidney's compensatory response to maintain electroneutrality when bicarbonate is lost or diluted, leading to increased chloride reabsorption 1, 3
Hypoalbuminemic alkalosis paradoxically coexists with the acidosis—the reduced albumin (a weak acid) creates an alkalinizing effect that is counterbalanced by the hyperchloremic and dilutional acidosis 1, 3
The Equilibrium Concept
The key insight is that cirrhotic patients exist in an equilibrium of offsetting metabolic disturbances rather than a single acid-base disorder:
In stable Child-Pugh A cirrhosis, mild hypoalbuminemic alkalosis predominates with otherwise normal acid-base status 1
In Child-Pugh B and C cirrhosis, the net metabolic acid-base state remains surprisingly normal (Base excess -1.0 mmol/L vs 1.1 mmol/L in controls) because hypoalbuminemic alkalosis is balanced by both dilutional acidosis and hyperchloremic acidosis 1
Respiratory alkalosis becomes the dominant net acid-base disorder in advanced cirrhosis, not metabolic acidosis 1, 3
Additional Contributing Factors in Decompensated Disease
When Metabolic Acidosis Becomes Clinically Apparent
In critically ill cirrhotic patients, particularly those with acute-on-chronic liver failure (ACLF), the equilibrium shifts dramatically:
Lactate accumulation and unmeasured anions (not chloride) become the dominant causes of metabolic acidosis in ACLF, with 62% of ACLF grade III patients developing frank acidemia 4
Renal dysfunction (hepatorenal syndrome) impairs acid excretion and worsens both hyperchloremia and overall acidosis through reduced GFR 2
Systemic inflammation from bacterial translocation (PAMPs) and liver injury (DAMPs) contributes to lactic acidosis and unmeasured anions rather than hyperchloremic acidosis specifically 2
Clinical Implications and Pitfalls
Important Caveats
Traditional acid-base models fail to identify the multiple competing disorders in cirrhosis—physicochemical models that account for albumin, sodium, chloride, and water balance are superior for understanding the true acid-base status 1, 3
Normal pH or bicarbonate does not mean normal physiology—it reflects balanced opposing forces (hypoalbuminemic alkalosis vs. hyperchloremic/dilutional acidosis) 1
Severe acidemia (pH <7.1) in cirrhosis carries 100% mortality, but this is typically driven by lactate and unmeasured anions in ACLF, not hyperchloremic acidosis alone 4
Specific Scenarios
Diuretic therapy can worsen hyperchloremic acidosis through volume contraction and altered renal chloride handling 2
Cholestyramine (used in cholestatic liver disease) can directly cause hyperchloremic metabolic acidosis through chloride exchange mechanisms 5
Hyponatremia (common in cirrhosis) contributes to dilutional acidosis as part of the overall electrolyte disturbance 6, 3, 7
Summary of Mechanism
The hyperchloremic metabolic acidosis in cirrhosis is not a primary disorder but rather one component of a complex equilibrium where:
- Hypoalbuminemia creates alkalosis 1, 3
- Sodium and water retention (from RAAS activation) causes dilutional acidosis 2, 1
- Compensatory renal chloride retention creates hyperchloremic acidosis 1, 3
- These forces balance each other in stable cirrhosis 1
- In decompensated disease, lactate and unmeasured anions overwhelm this equilibrium, causing true metabolic acidosis 4