What causes a sudden drop in albumin levels?

What Causes a Sudden Drop in Albumin Levels?

A sudden drop in albumin levels is most commonly caused by acute inflammation and critical illness, not malnutrition or inadequate protein intake. 1

Primary Mechanism: Acute Phase Inflammatory Response

Albumin levels decline rapidly during acute inflammation due to reprioritization of hepatic protein synthesis, regardless of nutritional status. 1 The liver shifts its synthetic capacity away from albumin production toward acute-phase proteins during critical illness, resulting in hypoalbuminemia within hours to days. 1

Key inflammatory conditions causing sudden albumin drops include:

• Sepsis and severe infections - Critical illness with systemic inflammation triggers rapid albumin decline through altered hepatic synthesis and increased vascular permeability. 1
• COVID-19 and acute respiratory illness - Severe COVID-19 causes marked hypoalbuminemia; each 10 g/L decrease in baseline albumin is associated with 5-fold increased ARDS risk and 2-fold increased mortality. 1
• Acute kidney injury - Inflammation combined with urinary albumin losses in nephrotic syndrome causes hypoalbuminemia through both increased fractional catabolic rate and urinary losses. 2
• Post-surgical states - Serum albumin drops precipitously by 10-15 g/L postoperatively due to inflammatory cytokine suppression of synthesis and transcapillary loss. 1

Secondary Mechanisms

Increased Albumin Losses

• Nephrotic syndrome - Massive urinary protein losses (>3 g/day) combined with inappropriately increased fractional catabolic rate cause rapid albumin depletion. 2
• Peritoneal dialysis - Albumin losses across the peritoneal membrane contribute to hypoalbuminemia, though less severe than nephrotic syndrome due to compensatory decreased fractional catabolic rate. 2
• Large volume paracentesis - Removal of ascitic fluid containing albumin can acutely lower serum levels. 3

Reduced Synthesis

• Acute liver failure - Sudden loss of hepatocyte mass eliminates the body's sole source of albumin production. 4, 5
• Severe malnutrition with inflammation - The combination of inadequate protein/caloric intake AND inflammation synergistically reduces albumin synthesis, though inflammation is the dominant factor. 6

Critical Clinical Distinction

Albumin is an inflammatory marker, not a nutritional marker. 1 ASPEN guidelines explicitly state that albumin indicates inflammation rather than malnutrition. 1 This distinction is crucial because:

• Hypoalbuminemia in acute illness reflects disease severity and inflammatory burden, not protein deficiency. 1
• Simply administering albumin or increasing protein intake does not improve outcomes when inflammation is the underlying cause. 1, 6
• Albumin levels <35 g/L in critically ill patients predict poor outcomes including increased mortality, ICU transfer risk, and complications. 1

Common Pitfall to Avoid

Do not interpret sudden albumin drops as primarily nutritional deficiency requiring albumin infusion. 1 The 2024 CHEST guidelines explicitly recommend against using IV albumin to increase serum albumin levels in critically ill patients (excluding thermal injuries and ARDS). 1 The cause of hypoalbuminemia—inflammation and critical illness—rather than low albumin itself, drives morbidity and mortality. 6

Diagnostic Approach

When encountering sudden albumin decline, evaluate for:

• Inflammatory markers - Check C-reactive protein, procalcitonin, and white blood cell count to assess acute inflammation. 1
• Infection sources - Blood cultures, urinalysis, chest imaging for pneumonia, and other infection workup. 1
• Renal function - Serum creatinine, urine protein-to-creatinine ratio to identify nephrotic-range proteinuria or acute kidney injury. 1, 2
• Liver function - Transaminases, bilirubin, INR to assess hepatic synthetic function. 4, 5
• Volume status - Assess for third-spacing, capillary leak, or dilutional effects from aggressive crystalloid resuscitation. 1

The priority is identifying and treating the underlying inflammatory or pathologic process, not correcting the albumin number itself. 6