Can liver failure cause metabolic acidosis?

Can Liver Failure Cause Metabolic Acidosis?

Yes, liver failure can cause metabolic acidosis, primarily through impaired lactate clearance and accumulation of unmeasured anions, with the severity correlating directly with the degree of hepatic dysfunction and mortality risk.

Mechanisms of Metabolic Acidosis in Liver Failure

Acute Liver Failure (ALF)

In acute liver failure, impaired hepatic lactate clearance is the dominant mechanism causing metabolic acidosis. 1 The subtotal loss of hepatocellular function results in:

• Impaired lactate clearance - The liver normally metabolizes lactate, and this capacity is severely compromised in ALF 1
• Accumulation of unmeasured anions - Beyond lactate, other organic acids accumulate due to loss of hepatic metabolic function 2
• Impaired gluconeogenesis leading to hypoglycemia, which can worsen lactic acidosis 1

Research demonstrates that combined severe hepatic failure and acute renal failure produces unique acid-base changes with mean lactate concentrations of 6.4 mmol/L and anion gaps of 25.8 mmol/L 2. Notably, this acidosis is partially attenuated by hypoalbuminemia (which creates alkalosis) and hypochloremia, but is severe enough to require marked compensatory hypocapnea to maintain near-normal pH 2.

Chronic Liver Disease/Cirrhosis

Cirrhotic patients, especially those progressing to acute-on-chronic liver failure (ACLF), develop marked metabolic acidosis from lactate and unmeasured anions. 3 The severity escalates with ACLF grade:

• 62% of ACLF grade III patients have acidemia (pH <7.35) compared to only 19% of cirrhosis patients without ACLF 3
• Metabolic acidosis in cirrhosis is characterized by elevated lactate, increased unmeasured anions, hyperchloremic acidosis, and coexisting hypoalbuminemic alkalosis 3
• Patients with pH <7.1 have 100% mortality 3

Clinical Presentation and Precipitating Factors

In chronic liver disease, metabolic acidosis typically requires an acute precipitating event rather than occurring from cirrhosis alone 4. Common triggers include:

• Sepsis (identified in 4 of 9 patients in one series) 4
• Gastrointestinal hemorrhage (3 of 9 patients) 4
• Tissue hypoxia from any cause 5

In acute hepatic failure, metabolic acidosis can occur without additional precipitants, particularly when associated with paracetamol overdose, where severe acidosis may precede clinical hepatic failure and be associated with hypoglycemia 6.

Prognostic Significance

The presence and severity of metabolic acidosis in liver failure carries grave prognostic implications:

• Mortality in patients with combined lactic acidosis and acute renal failure reaches 80%, significantly higher than ARF alone (66.7%) 5
• Acidosis attributable to lactate and unmeasured anions is independently associated with 28-day mortality in liver cirrhosis 3
• No long-term survivors were observed in chronic liver disease patients who developed lactic acidosis 4

Important Clinical Distinctions

Acute versus chronic liver failure present different acid-base patterns:

• Acute hepatic failure typically shows striking prolongation of prothrombin time (always present initially) and dramatic alterations in hepatic function tests, with 3 of 7 patients surviving in one series 4
• Chronic liver disease patients who develop lactic acidosis show less dramatic changes in hepatic function tests but have universally poor outcomes 4

Paradoxically, alkalaemia is more common than acidemia in early fulminant hepatic failure (present in 49 of 65 observations), primarily due to respiratory alkalosis from hyperventilation 6. However, as hepatic failure progresses, metabolic acidosis from lactate and organic acid accumulation predominates 3, 2.

Critical Monitoring Requirements

When liver failure is present, monitor for:

• Arterial blood gases to assess pH, bicarbonate, and compensatory respiratory changes 3, 2
• Lactate levels - elevations correlate with severity and mortality 5, 3, 2
• Anion gap - typically elevated (mean 25.8-30.0 mEq/L in severe cases) 5, 2
• Blood glucose - hypoglycemia can worsen lactic acidosis and in some cases glucose administration alone rapidly lowers lactate 4
• Prothrombin time - notable prolongation antedates other hepatic function abnormalities in acute failure 4

Treatment Considerations

For severe metabolic acidosis with liver failure, bicarbonate-buffered (not lactate-buffered) replacement fluids should be used during renal replacement therapy, as lactate-containing solutions may worsen acidosis in patients unable to metabolize lactate 7, 8. Continuous renal replacement therapy with bicarbonate-buffered fluids is recommended for severe acidosis with renal failure 8.