Use and Abuse of Albumin in Clinical Practice

Basic Physiology

Albumin has a molecular weight of about 66 000 and compared with other proteins such as fibrinogen or immunoglobulin it is a relatively small molecule. The molecule is a single polypeptide made up of 585 amino acids with several minor variants in its actual configuration. It carries a strong negative charge.

It is synthesised in the polysomes bound to the endoplasmic reticulum of hepatocytes. In a healthy adult it is probable that about 9 - 12 g per day are produced. While only 20 - 30 % of hepatocytes seem to produce albumin at any one time, implying a physiological reserve, there is no storage of albumin in the liver, and therefore no reserve for release on demand. In states of maximal stimulus the synthesis of albumin can only be increased 2 - 3 fold. Control of the rate of production is primarily mediated via changes in the colloid osmotic pressure and the osmolality of the extravascular liver space. Other factors involved in the control of synthesis include raised levels of insulin, thyroxine and cortisol. Growth hormone, despite its effects on reducing total urinary nitrogen loss, has no measurable effect on albumin synthesis in patients.

Amino acid deficiency, particularly of leucine, arginine, isoleucine and valine, can be rate limiting in the production of albumin, although this may only be of clinical significance in severe protein malnutrition states. The role of amino acid supplementation in enhancing synthesis of albumin in the absence of deficiency states remains unclear and in the setting of the critically ill patient unproved.

The catabolism of albumin is still poorly understood. It occurs in or immediately adjacent to the vascular endothelium of tissues, at a rate of some 9 - 12 g per day which is of course very similar to the rate of production. Albumin is pinocytosed into cells at a rate which is related to ANP levels. It has been postulated that because albumin is very low in tyrosine residues it is a poor source of essential amino acids, and thus tends to be relatively spared in starvation and deficiency states.

Distribution of albumin, in man, is a source of considerable interest as albumin is predominantly an extravascular protein. There is more albumin outside the intravascular compartment than within it. As the serum concentration of albumin is normally around 40 g.l^-1, in an average adult with a three litre plasma volume there will be an intravascular mass of ∼ 120 g. The interstitial concentration is considerably lower, at around 14 g.l^-1, and varies in different areas of the interstitium, but with an interstitial volume of some 11 - 12 litres the total extravascular mass of albumin is ∼ 160 g. Some of this albumin is easily mobilised from the loose interstitial tissues, whilst some is ‘bound‘ particularly in the skin. These two ‘compartments‘ are usually in a state of dynamic equilibrium.

Literatur

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