Question 12

Describe the physiology (50% marks) and pharmacology (50% marks) of albumin.

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College Answer

The question required an equal treatment of the physiology and pharmacology of albumin. The physiology discussion needed to include synthesis, factors affecting synthesis, distribution in the body (including the proportion divided between the plasma and interstitial space), functions, breakdown, and elimination half-life. Discussion of the pharmacology should have included available preparations (4% and 20% Albumin) and pharmaceutics, distribution, elimination (both the protein and crystalloid components), mechanism of action to expand the plasma compartment, longevity in the plasma compartment, indications, and adverse effects. Oedema, circulatory overload, immunological reactions, and relative contraindication in brain injury were important to mention. There was some confusion regarding the infectious risks of albumin. An outline of the manufacturing process from donated plasma and pasteurisation was expected.


Physiology of albumin:

  • Synthesis: produced by the liver at approximately 10g/day
    • Factors which increase albumin synthesis:

      • High protein diet
      • High caloric intake
      • Decreased colloid oncotic pressure
      • Growth hormone
      • Corticosteroids
      • Insulin
    • Factors which decrease albumin synthesis:

      • Protein malnutrition
      • Decreased caloric intake
      • Increased plasma oncotic pressure
      • Diabetes
      • Liver disease
      • Sepsis
      • Trauma
  • Distribution:
    • Approximately 33% in the circulating blood volume, 66% in the interstitial fluid
    • In total an average person has ~360g of albumin
    • After infusion, about 50% of the infused dose remains in the circulating volume after 24 hours.
  • Function
    • Oncotic function: contributes 75% of the total plasma oncotic pressure;
    • Also adds to the osmotic pressure by attracting sodium into the intravascular volume
      (Gibbs-Donnan effect, because of its negative charge) 
    • Antioxidant scavenging (mainly by binding heavy divalent metal ions such as iron and copper, decreasing their ability to generate free radicals)
    • Binding and carriage of small molecules (bilirubin, fatty acids, drugs, etc)
  • Metabolism and clearance
    • ​​​​​​​Circulating half life of an albumin molecule is ~ 27 days
    • Ultimately degraded in the reticuloendothelial system by macrophages

Pharmacology of albumin, if that's how you want to play it, would end up basically repeating half of the "physiology" section, and so it is unclear exactly what the examiners wanted. Did they really want us to spend another five minutes discussing distribution and elimination? And how exactly is the "mechanism of action" different from its physiological roles? No matter. What the examiners want, they get. 

Class Colloid
Chemistry Human plasma protein
Routes of administration IV
Absorption Zero oral bioavailability
Solubility pKa 6.75; good water solubility
Distribution VOD = 0.07L/kg (effectively confined to the circulating volume);
minimally protein bound (or, rather, things bind to it
Target receptor Various molecules in the bloodstream bind and form complexes
Metabolism Metabolised mainly by the reticuloendothelial system
Elimination Minimal renal excretion, except in cases of protein-losing nephropathy.
Most of it is degraded by reticolendothelial macrophages;
10% is eliminated through the gut
Time course of action Half life of around 27 days
Mechanism of action Multiple roles, including oncotic, immunomodulatory and transport roles.
Acts as a binding substrate for xenobiotics.
Clinical effects Increased circulating volume;
may cause circulatory overload;
small risk of anaphylaxis or allergic reaction; may change the free fraction of highly protein-bound drugs; may worsen the outcome of traumatic brain injury
Single best reference for further information CSL Behring product sheet


CSL has a site which features the full product information on their 20% Albumex bottles.

For those of us crazed with the lonely lust for albumin, Theodore Jr. Peters offers a 432 page ode, entitled “All About Albumin: Biochemistry, Genetics, and Medical Applications”.

Matejtschuk, P., C. H. Dash, and E. W. Gascoigne. "Production of human albumin solution: a continually developing colloid." British journal of anaesthesia 85.6 (2000): 887-895.

Levitt, David G., and Michael D. Levitt. "Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements." International journal of general medicine 9 (2016): 229.

Chien, Shih-Chieh, et al. "Critical appraisal of the role of serum albumin in cardiovascular disease." Biomarker research 5.1 (2017): 1-9.

Taverna, Myriam, et al. "Specific antioxidant properties of human serum albumin." Annals of intensive care 3.1 (2013): 1-7.