Albumin Physiological Role

     
       

 

         
       

Albumin has a role in maintaining COP, binding and transport, free radical scavenging, acid base balance, coagulation and vascular permeability.

Physiologic Roles of albumin

1.      Maintenance of the colloid osmotic pressure (COP).

2.      Binding and transport, particularly of drugs.

3.      Free radical scavenging.

4.      Acid base balance

5.     Pro and anti-coagulatory effects (inhibits platelet aggregation, enhances the inhibition of factor Xa by antithrombin III).

6.      Effects on vascular permeability.

Binding and transport

Albumin binds drugs and ligands, and therefore reduces the serum concentration of these compounds. An example is the serum calcium, the free (ionized) concentration of which needs to be corrected for albuminThere are actually four binding sites on albumin and these have varying specificity for different substances. Competitive binding of drugs may occur at the same site or at different sites (conformational changes) [eg. warfarin and diazepam]. The drugs that are important for albumin binding are: warfarin (coumadin), digoxin, NSAIDS, midazolam, thiopental. Although one would expect that low serum albumin is related to higher free drug levels, the relevence of a low albumin and drug binding is unknown.

Osmotic pressure

Albumin is responsible for 75 - 80 % of osmotic pressure.

According to Starling’s equation, the flow of fluid out of capillaries is determined by  a filtration constant multiplied by the net force driving fluid out of the capillary (hydrostatic pressure minus oncotic pressure) minus the osmotic gradient pulling the fluid out. Starling's equation: Transcapillary Flow = k [(Pcap + Pi) - (Pi + Pcap )]

Remember that albumin is the main protein both in the plasma and in the interstitium and it is the COP gradient rather than the absolute plasma value that is important: this is what distinguishes hypoalbuminaemia derived from redistribution (capillary leak) from that of pure full body deficiency.

Free Radicals

Albumin is a major source of sulphydryl groups, these "thiols" scavenge free radicals (nitrogen and oxygen species).

Albumin may be an important free radical scavenger in sepsis.

Acid Base Balance

Albumin is a negatively charged protein in high concentration in the plasma. It contributes heavily to what we call the “anion gap”: the concentration of anions and cations in plasma should be equal, classically the anion gap is calculated as (Na + K)- (Cl) = AG (mEq/l). The remaining anions come predominantly from albumin, inorganic phosphate and hemoglobin. Thus, in hypoalbuminemic states, the anion gap should be narrowed.

 Anticoagulant effects

The anticoagulant and antithrombotic effects of albumin are poorly understood this may be due to binding nitric oxide radicals inhibiting inactivation and permitting a more prolonged anti-aggregatory effect. In diabetes, glycosylated albumin may increase the incidence of thrombotic events and atherosclerosis.

Vascular Permeability

It is possible that albumin has a role in limiting the leakage from capillary beds during stress induced increases in capillary permeability. This is related to the ability of endothelial cells to control the permeability of their walls, and the spaces between them. Albumin may plug this gap or may have a deflecting effect, owing to its negative charge. This has led to the hypotheis that colloids are effective at maintaining vascular architecture.

         
                   
       

         
     

       
       

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