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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