Causes of Hypoalbuminemia
Primary Mechanisms
Hypoalbuminemia results from four main pathophysiological mechanisms: decreased hepatic synthesis, increased catabolism/loss, redistribution from intravascular to interstitial spaces, and dilution from fluid overload. 1
Decreased Hepatic Synthesis
- Inflammatory cytokines directly downregulate hepatic albumin synthesis, even when protein and caloric intake are adequate 1
- Liver dysfunction impairs synthetic capacity, particularly in cirrhosis and advanced liver disease 2, 3
- Malnutrition with inadequate protein intake (though this alone causes slow development of hypoalbuminemia compared to inflammation) 4
- Corticosteroid therapy increases net protein loss and drives catabolism, particularly in Crohn's disease patients 1
Increased Protein Loss
- Nephrotic syndrome causes urinary protein losses exceeding synthetic capacity 3, 5
- Protein-losing enteropathy from gastrointestinal tract infiltration by neoplastic cells or inflammatory bowel disease 2, 5
- Dialysate losses in peritoneal dialysis patients (requiring 1.3 g/kg/day protein intake vs 1.2 g/kg/day for hemodialysis) 1
- Albumin loss through dialyzer membranes during hemodialysis, particularly with newer medium cut-off membranes 6
- Serous losses from ascites or pleural effusions 4
Redistribution and Capillary Leak
- Systemic inflammation increases capillary permeability, causing albumin transfer from vascular to interstitial compartments 7
- Increased transcapillary escape rate in heart failure and inflammatory states 5
- Sepsis-induced capillary leak with increased fractional catabolic rate of albumin 7
Dilution
- Hemodilution from crystalloid overload rapidly decreases measured albumin concentration 5, 4
- Fluid retention in heart failure, cirrhosis, and kidney disease 5
Disease-Specific Contexts
Liver Disease
- Cirrhosis causes both decreased synthesis and increased losses through ascites 3
- Portal hypertension with ascites development reflects aggressive liver disease 2
Kidney Disease
- Chronic kidney disease predisposes to protein-energy wasting, with approximately 60% of hemodialysis patients having albumin <4.0 g/dL 6
- End-stage renal disease combines multiple mechanisms: inflammation, inadequate nutrition, and dialysis-related losses 1
Cardiac Disease
- Heart failure causes hypoalbuminemia through malnutrition, inflammation, cachexia, hemodilution, and protein-losing enteropathy 5
- Cardiogenic states may involve liver dysfunction and increased transcapillary escape 5
Inflammatory/Catabolic States
- Sepsis combines inflammation-driven decreased synthesis with capillary leak 3
- Advanced systemic mastocytosis with gastrointestinal infiltration causes worsening nutritional status 2
- Postoperative states typically show 10-15 g/L decrease due to inflammatory cytokines and transcapillary loss 1