Hepatic Proteins

Diagnosis

Indications for Testing

• Known disease that would cause compromised nutritional status (eg, cancer, malabsorption)
• Failure to thrive in children

Laboratory Testing

• Albumin – usual first-line test in evaluating nutritional status
  • Elevated concentrations – dehydration
  • Decreased concentrations are very common
    • Impaired synthesis
      • Primary (eg, liver disease)
      • Secondary (eg, low protein intake)
    • Increased catabolism – result of tissue damage and inflammation
    • Reduced absorption of amino acids – malabsorption or malnutrition
    • Excessive protein loss in urine, feces, or skin – glomerulonephritis, nephrotic syndrome, protein-losing enteropathy
    • Altered distribution that sequesters large amounts of albumin in extravascular compartment
      • Nephrotic syndrome
      • Congestive heart failure
  • Albumin measurement in urine may aid in early detection of renal involvement in chronic diseases
• Prealbumin – may be a better early screening test due to short half-life
  • Used as marker of nutritional status in
    • Premature infants
    • Cancer patients
    • Surgical patients
  • Negative acute phase reactant – concentrations fall in the following diseases due to decreased synthesis
    • Inflammation
    • Malignancy
    • Cirrhosis of the liver
    • Protein-wasting diseases of the gut or kidney
  • Recommended test for protein measurement in evaluation of nutrition in hospitalized patients
• Retinol-binding protein (RBP), transferrin, and fecal alpha-1-antitrypsin – less widely used as screening tests
  • Decreased concentrations of RBP – cystic fibrosis, liver disease
  • Elevated concentrations of transferrin
    • Malnutrition
    • Acute inflammation
    • Infection
    • Renal disorders
    • Red blood cell disorders (eg, iron deficiency)
    • High concentrations can occur in pregnancy and during estrogen administration
  • Decreased concentrations of transferrin
    • Transferrin is a negative acute phase reactant
    • Low concentrations occur in
      • Inflammation
      • Malignancy
      • Chronic liver disease
      • Protein loss
  • Elevated fecal clearance of alpha-1-antitrypsin in protein-losing enteropathy
• Vitamin/mineral assay testing also recommended

Background

Etiologies

• Starvation
• Chronic disease
  • HIV
  • Malignancy
  • Chronic liver disease
  • Chronic kidney disease
  • Chronic obstructive pulmonary disease (COPD)
• Anorexia
• Malabsorption
• Critical illness or trauma

Pathophysiology

• Albumin
  • Function – carrier protein for minerals, fatty acids, vitamins, and hormones
  • Most abundant protein in human plasma – 55-65% of total protein content
  • Most commonly monitored protein – long half-life (20 days) makes it a relatively insensitive marker
• Prealbumin (transthyretin)         
  • Function – carrier protein for thyroid hormone
  • 2-day half-life
    • Short half-life makes it a good indicator for early monitoring
    • Unaffected by hydration status
• Retinol-binding protein (RBP)
  • Function – responsible for binding and transporting retinol (vitamin A)
  • Short half-life (11 hours) makes it an excellent indicator of early malnutrition
• Transferrin
  • Function – carrier protein for iron
  • Presence of transferrin in serum and other body fluids aids in differential diagnosis
• Alpha-1-antitrypsin (fecal)
  • Function – protease inhibitor

Clinical Presentation

• Constitutional – weight loss, muscle wasting, fatigue, failure to thrive (children)
• Skin changes from vitamin deficiencies may occur in chronic loss
• Extremes – kwashiorkor manifesting with ascites, edema