Hypoalbuminemia

Etiology

Extravascular Protein Loss

  • Nephrotic Syndrome: proteinuria (may be massive, 3.5g or more/24hrs)
    • Normally, albumin is filtered by the glomerulus and catabolized by the renal tubules into amino acids, which are recycled
    • However, in presence of glomerular and tubular renal disease, excessive protein filtration may overwhlem this capacity, resulting in albumin loss and increased degradation
    • Note: in this setting, albumin synthesis will only increase when albuminuria exceeeds 100 mg/kg/d with an adequate dietary protein intak
  • Protein-Losing Enteropathy (see Protein-Losing Enteropathy, [[Protein-Losing Enteropathy]])
    • Normally, <10% of the total albumin is lost through the intestine
    • In these cases, intestinal protein loss may be exacerbated by other factors which impair albumin synthesis (sepsis, inflammation, etc)
  • Burns
    • Skin is the major site for extravascular albumin storage (and is the major exchangeable albumin pool needed to maintain plasma levels)
    • Hypoalbuminemia results from direct albumin loss from tissue damage, compromised hepatic blood flow due to volume loss, and from inhibitory tissue factors (TNF, IL-1, IL-6) released at the burn sites

Hemodilution

  • Ascites (of Any Etiology): increases volume of distribution, resulting in hypoalbuminemia
    • Note: therefore, in this setting, serum albumin level is not a good index of the residual synthetic capacity of the liver (actual radioisotopic measurements of production are required)
  • Large-Volume IV Fluid Resuscitation

Other

  • Cirrhosis (see End-Stage Liver Disease, [[End-Stage Liver Disease]])
    • Physiology
      • Decreased Albumin Synthesis
        • Loss of Hepatic Cell Mass
        • Decreased and Poorly-Distributed Portal Blood Flow: resulting in maldistribution of nutrients and oxygen to hepatocytes
        • Impact of Ascites on Albumin Synthesis
        • In patients without ascites, decreased albumin synthesis occurs
        • In patients with ascites, increased albumin synthesis may occur (due to a change in hepatic interstitial colloid levels, which may stimulate albumin synthesis)
      • Ascites-Associated Increased Volume of Distribution with Hemodilution: resulting in decreased serum albumin concentration
  • Congestive Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]])
    • Physiology
      • Normal Albumin Synthesis
      • Increased Volume of Albumin Distribution
  • Hypergammaglobulinemia (see Hypergamaglobulinemia, [[Hypergamaglobulinemia]])
    • Physiology: increased serum oncotic pressure -> increased hepatic interstitial volume -> downregulation of albumin synthesis
  • Protein Malnutrition
    • Physiology
      • Deficient protein intake -> rapid loss of cellular ribonucleic acid and disaggregation of the endoplasmic reticulum–bound polysomes -> decreased albumin synthesis
      • Albumin synthesis can decrease by more than 33% during a 24-hour fast
      • Albumin synthesis may be stimulated by amino acids produced in the urea cycle (such as ornithine)
  • Acute/Chronic Inflammation
    • Epidemiology
      • Hypoalbuminemia is present in hospital admission in 20% of patients
    • Physiology: TNF and IL-6 released as part of the inflammatory response (to infection, surgery, trauma) decrease serum albumin by mulitple mechanisms
      • Increased Vascular Permeability: allows albumin to diffuse into the extravascular space
      • Increased Albumin Degradation
      • Decreased Albumin Synthesis: TNF-alpha, which decreases transcription of the albumin gene
  • Zinc Deficiency

Physiology

  • Decreased Serum Oncotic Pressure: seen only when serum albumin is <1.5 g/dL)

Clinical Manifestations

Pulmonary Manifestations

  • Pleural Effusion (see Pleural Effusion-Transudate, [[Pleural Effusion-Transudate]])
    • May cause pleural effusion in hosiptalized AIDS and other chronic disease patients
    • Usually small-moderate and bilateral (without cardiomegaly)

Other Manifestations

  • Anasarca: always seen
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Treatment

  • Treatment of Underlying Etiology
    • Optimize Nutrition
    • Prevent Protein Loss

Time Course of Resolution of Hypoalbuminemia

  • Acute Inflammation-Related Hypoalbuminemia: hypoalbuminemia due to acute inflammation should normalize within weeks of resolution of the inflammation

References

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