Albumin

• Normal Range: 3.5-5.5 g/dL
• SI Units: 35-55 g/L
• Half-Life: ~20 days
• Critical Value: <2.0 g/dL
• Sample Type: Serum or plasma
• Key Point: Marker of hepatic synthetic function and nutritional status

Albumin levels are relatively consistent across populations with minimal variation by sex. Age-related changes occur, with slightly higher values in younger adults and gradual decline in elderly populations.

Hypoalbuminemia (Low Albumin)

Hypoalbuminemia is defined as serum albumin <3.5 g/dL. It is a common finding in hospitalized patients and associated with increased morbidity and mortality. The causes can be categorized by mechanism: decreased synthesis, increased loss, or redistribution.

Hyperalbuminemia (High Albumin)

True hyperalbuminemia is extremely rare. Elevated albumin values almost always represent pseudohyperalbuminemia due to hemoconcentration rather than increased production.

Severity Classification of Hypoalbuminemia

Serum-Ascites Albumin Gradient (SAAG)

The SAAG is used to determine the cause of ascites by measuring the difference between serum and ascitic fluid albumin concentrations. It has superior accuracy to older classification systems.

Corrected Calcium

Approximately 40-50% of total serum calcium is bound to albumin. When albumin is low, total calcium appears falsely low even if ionized (active) calcium is normal. The corrected calcium formula estimates what the total calcium would be if albumin were normal.

Albumin in Prognostic Scoring Systems

Albumin is incorporated into several clinical scoring systems for liver disease:

Factors That Falsely Increase Albumin

• Dehydration/Hemoconcentration: Vomiting, diarrhea, inadequate fluid intake causing volume depletion
• Prolonged tourniquet application: >1 minute tourniquet time can increase albumin by 5-10%
• Upright position: Postural changes cause fluid shifts; sitting vs. supine can alter values
• Assay interference (BCG method): Bromocresol green method can overestimate albumin by binding to other proteins, especially globulins
• Recent IV albumin infusion: Exogenous albumin administration
• Sample hemolysis: May interfere with some assay methods

Factors That Falsely Decrease Albumin

• IV fluid administration: Hemodilution from crystalloid or colloid infusion
• Pregnancy: Physiologic hemodilution, especially third trimester
• Supine position during blood draw: Compared to upright position
• Sample standing time: Prolonged storage before analysis may affect some methods

Medications Affecting Albumin Levels

• Decrease albumin synthesis:
  • Amiodarone (hepatotoxicity)
  • Methotrexate (hepatotoxicity)
  • Oral contraceptives (mild decrease, estrogen effect)
  • Any hepatotoxic medication (acetaminophen overdose, isoniazid, etc.)
• Increase urinary albumin loss:
  • NSAIDs (can cause nephrotic syndrome)
  • ACE inhibitors (initially may increase proteinuria, though long-term renoprotective)
  • Lithium (nephrogenic diabetes insipidus, potential nephrotic syndrome)
• Affect protein binding:
  • High-dose penicillin or cephalosporins (compete for albumin binding sites)
  • Salicylates (compete for binding sites)

Physiologic Variables

• Age: Albumin decreases with age; elderly often have albumin 3.2-4.5 g/dL as normal
• Circadian variation: Minimal (unlike some proteins); albumin relatively stable throughout day
• Exercise: Strenuous exercise can cause transient hemoconcentration and mild elevation
• Inflammation/Acute phase response: Any acute or chronic inflammatory condition decreases albumin synthesis as a negative acute phase reactant

Pre-analytical Errors

• Incorrect tube type: Though albumin stable in most tube types
• Sample contamination: IV fluid contamination from line draws
• Incomplete clotting: Fibrin strands may interfere with analysis
• Lipemia: High triglycerides may interfere with spectrophotometric methods

• "Low albumin doesn't always mean liver disease": Hypoalbuminemia is common in hospitalized patients due to inflammation, malnutrition, volume overload, or renal/GI losses. Always consider the clinical context and rule out non-hepatic causes before attributing low albumin to liver dysfunction.
• "The 20-day rule": With a half-life of approximately 20 days, albumin takes 60-100 days to reach a new steady state after changes in synthesis. This makes it useless for acute liver injury (use INR/PT instead) but excellent for assessing chronic liver disease or nutritional status over weeks to months.
• "SAAG beats the old system": The serum-ascites albumin gradient (SAAG ≥1.1 g/dL = portal hypertension) has 97% accuracy and replaced the outdated exudate/transudate classification (which was based on Light's criteria designed for pleural effusions, not ascites).
• "Albumin is a negative acute phase reactant": During any acute illness, inflammation, or infection, the liver prioritizes production of positive acute phase proteins (CRP, ferritin, fibrinogen) and decreases albumin synthesis. This is why ICU patients commonly have low albumin even without liver disease or malnutrition - it's part of the stress response.
• "Don't reflexively replace low albumin": IV albumin replacement is expensive, short-lived (redistributes rapidly), and only indicated for specific conditions: large-volume paracentesis (>5L removed), hepatorenal syndrome, spontaneous bacterial peritonitis in some cases, and occasionally nephrotic syndrome. It's NOT indicated for nutritional repletion or to "boost" a low number without clear clinical benefit.
• "Use ionized calcium when albumin is abnormal": The corrected calcium formula is a rough estimate. When albumin is <2.0 g/dL or >5.0 g/dL, or in critically ill patients with acid-base disturbances, order ionized calcium directly - it's the definitive test for calcium status and eliminates guesswork.
• "Cirrhosis trinity - albumin, bilirubin, INR": These three markers assess the liver's critical synthetic functions. Unlike AST/ALT (which measure hepatocyte injury), these tests measure what the liver actually does: make proteins (albumin, clotting factors) and conjugate bilirubin. All three are incorporated into Child-Pugh scoring.
• "The edema threshold": Clinically significant edema typically doesn't appear until albumin drops below 2.5-3.0 g/dL. The oncotic pressure gradient becomes insufficient to retain fluid in vasculature. However, other factors (heart failure, renal dysfunction, medications) can cause edema with normal albumin.
• "Rule out the simple causes first": When faced with hypoalbuminemia, check urinalysis for proteinuria (nephrotic syndrome), assess volume status and recent IV fluids (dilution), review medication list (hepatotoxins), and consider CRP/ESR (inflammation) before assuming chronic liver disease or malnutrition.
• "Albumin predicts mortality independently": In multiple studies across different disease states (sepsis, cirrhosis, heart failure, malignancy), low albumin independently predicts increased mortality even after adjusting for other factors. Each 1 g/dL decrease is associated with 24-56% increase in mortality depending on the population.
• "BCG vs BCP controversy": Many labs still use bromocresol green (BCG) method which overestimates albumin, especially in critically ill patients. If your ICU patient has a surprisingly "normal" albumin despite obvious critical illness, consider that it may be falsely elevated by the assay. Bromocresol purple (BCP) is more accurate but less widely available.
• "Pre-albumin is NOT a mini-albumin": Despite the name, prealbumin (transthyretin) is a completely different protein. With a half-life of 2-3 days vs. albumin's 20 days, prealbumin is more sensitive for acute nutritional changes or acute phase response. However, it's also a negative acute phase reactant, limiting its use in inflamed/infected patients.
• "Volume status check before interpretation": Always assess the patient's volume status. A patient with anasarca and massive volume overload may have a low albumin that's 50% real and 50% dilutional. Conversely, a dehydrated patient with normal albumin might have underlying hypoalbuminemia masked by hemoconcentration.
• "Nephrotic syndrome = massive albuminuria": If albumin is low and urinalysis shows 3-4+ protein, think nephrotic syndrome. The classic tetrad is: proteinuria >3.5 g/day, hypoalbuminemia, edema, and hyperlipidemia. The kidneys can lose more albumin than the liver can make, leading to progressive hypoalbuminemia.

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