Describe the physiology (50% marks) and pharmacology (50% marks) of albumin.
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:
Factors which increase albumin synthesis:
Factors which decrease albumin synthesis:
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.
|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.