Why do patients with pancreatitis often develop hypocalcemia?

From the Guidelines

Patients with pancreatitis often develop hypocalcemia due to the formation of free fatty acid-albumin complexes, which leads to intravascular sequestration of calcium. This is supported by the study by L. Gianotti et al. 1, which explains that free fatty acids (FFA) released during acute pancreatitis may lead to intravascular sequestration of calcium by creating FFA-albumin complexes.

Key Mechanisms

• Formation of free fatty acid-albumin complexes leading to intravascular sequestration of calcium
• Activation of pancreatic pro-enzymes, proinflammatory cytokines, and free radicals in an acidotic environment
• Increased concentration of lipids in the pancreatic capillaries causing vessel plugging, ischemia, and acidosis

Clinical Implications

• Hypocalcemia is a frequent finding in patients with acute pancreatitis and calcium levels below <2 mmol/l are a well-known negative prognostic factor 1
• Treatment of hypertriglyceridemia may dramatically improve outcomes and can prevent further pancreatic damage
• Monitoring serum calcium levels is essential, as hypocalcemia can lead to severe complications

Management

• Calcium supplementation may be necessary, typically with calcium gluconate 1-2 grams IV for severe symptomatic hypocalcemia
• Oral calcium supplements (1-3 grams elemental calcium daily) may be used during recovery
• Avoiding lipid emulsions in parenteral nutrition may be necessary in cases of hypertriglyceridemia-associated pancreatitis 1

From the Research

Causes of Low Calcium in Pancreatitis

• Hypocalcemia is a common finding in acute pancreatitis, and its development is still not fully understood 2.
• One possible explanation is the role of magnesium deficiency, as patients with acute pancreatitis and hypocalcemia often have low intracellular magnesium content despite normal serum magnesium concentrations 3.
• The correlation between serum calcium and mononuclear cell magnesium content suggests that magnesium deficiency may play a significant role in the pathogenesis of hypocalcemia in patients with acute pancreatitis 3.

Relationship Between Calcium and Pancreatitis Severity

• Hypocalcemia is significantly more frequent in patients with severe forms of acute pancreatitis, and a negative correlation is observed between endotoxemia and serum calcium in acute pancreatitis 4.
• Serum calcium on admission is independently associated with persistent organ failure in acute pancreatitis and may serve as a potential prognostic factor 4.
• A low serum calcium level is an atypical feature of acute pancreatitis, indicating a bad prognosis 2.

Calcium Administration in Pancreatitis

• Calcium therapy is often used to correct hypocalcemia in acute pancreatitis, but its impact on prognosis has not been demonstrated 5.
• A study found that calcium administration had no association with in-hospital, 28-day, or ICU mortality in patients with acute pancreatitis and hypocalcemia, and was significantly associated with prolonged length of stay in the hospital and ICU 5.
• The current evidence suggests that calcium administration may not benefit patients with acute pancreatitis and hypocalcemia 6, 5.