Source: Health Products and Food Branch (CA) Revision Year: 2017
Albumin is the predominant product of hepatic protein synthesis and one of the more abundant plasma proteins. Among its multiple physiologic roles that include binding and transport of molecules, free radical scavenging, inhibition of platelet function and antithrombotic effects, and effects on the capillary membrane permeability, human albumin plays an essential part in the generation of colloid-oncotic pressure.
Pharmacotherapeutic group: plasma substitutes and plasma protein fractions
ATC code: B05AA01
Human albumin accounts quantitatively for more than half of the total protein in the plasma and represents about 10% of the protein synthesis activity of the liver.
Human albumin 25% is a hyperoncotic solution.
The most important physiological functions of human albumin result from its contribution to oncotic pressure of the blood and transport function. Albumin stabilises circulating blood volume and is a carrier of hormones, enzymes, medicinal products and toxins.
Under normal conditions the total exchangeable albumin pool is 4-5 g/kg body weight of which 40-45% is present intravascularly and 55-60% in the extravascular space. Increased capillary permeability will alter albumin kinetics and abnormal distribution may occur in conditions such as severe burns or septic shock.
Under normal conditions, the average half-life of albumin is about 19 days. The balance between synthesis and breakdown is normally achieved by feed-back regulation. Elimination is predominantly intracellular and due to lysosome proteases.
In healthy subjects, less than 10% of infused albumin leaves the intravascular compartment during the first 2 hours following infusion. There is considerable individual variation in the effect on plasma volume. In some patients the plasma volume can remain increased for some hours. However, in critically ill patients, albumin can leak out of the vascular space in substantial amounts at an unpredictable rate.
Albumin is a protein of 584 amino acids. It is highly soluble and has a strong negative charge. Several variants in the amino acid sequence, alloalbumins, coexist with normal albumin. Albumin makes up half the normal intravascular protein mass and is responsible for 75%-80% of the plasma colloid osmotic pressure.
In a healthy person, 9-12 grams of albumin are synthesized in the liver per day. The rate of synthesis is controlled primarily by changes in the colloid osmotic pressure and the osmolality of the extravascular space. Insulin, thyroxin, and cortical also stimulate the production of albumin; however, growth hormone has no significant effect on albumin synthesis. Importantly, in severe protein malnutrition, the production of albumin may be decreased.
Albumin is a predominantly extravascular protein with a total extravascular mass of approximately 160 grams, despite a lower interstitial concentration compared with serum concentration. The serum concentration of albumin is about 4 grams/dL in normal individuals and the total intravascular mass is about 120 grams. Under normal circumstances, the albumin concentration in the interstitial space is half that in the intravascular space. The half-life of albumin is 17-19 days.
The catabolism of albumin takes place mainly in the vascular endothelium at a rate of 9-12 grams per day, or 4% of total body albumin. The rate of albumin degradation is related to its concentration. Calorie and protein deprivation also accelerate albumin catabolism. Serum levels of albumin may fall during periods of stress, trauma, or sepsis despite its long half-life. The drop may result from accelerated redistribution from the intravascular space, decreased synthesis, and increased catabolism. Injury and infection result in a decrease of serum albumin level of approximately 1-1.5 grams/dL within 3-7 days.
Under normal circumstances, albumin circulates from the intravascular space across the capillary wall into the interstitial compartment, and returns to the intravascular space through the lymphatic system. Albumin has a circulation half-life of approximately 16 hours. The movement of albumin across the capillary walls can be measured as the transcapillary escape rate (TER), which is defined as the percentage of intravascular albumin leaving the intravascular compartment per hour. In healthy volunteers, TER is around 4%-5%. The TER is determined by the capillary and interstitial free albumin concentrations, the capillary permeability to albumin, solvent and solute movements and, to a lesser degree, the electrical charge across the capillary wall.
Clearance of proteins from the interstitium is dependent upon the lymphatic flow, which in healthy individuals is around 120 mL/h, with a protein content of about 80% of plasma. The flow of lymph itself is dependent upon interstitial fluid pressure, intrinsic pumping by the lymphatic vessels and external compression of vessels by muscle contraction, arterial pulsation, and body movement.
The distribution of exogenous albumin between body compartments has been examined by the injection of radiolabeled albumin. Over the first 2 days, there is a rapid phase of disappearance from the plasma that correlates with the transcapillary exchange rate of 4.5% per hour. The distribution half-time is about 15 hours. Then there is a slower decay of about 3.7% per day with an elimination half time of about 19 days.
The major physiologic functions of albumin are:
Albumin is a normal constituent of the human organism. In animals, single dose toxicity testing is of no relevance, since the high doses required would result in Albumin overload. Repeated dose toxicity testing, and embryo-fetal toxicity studies with albumin preparations are impracticable due to the induction of, and the interference with antibodies. Effects of the preparation on the immune system of new-born animals have not been studied.
Since the clinical experience does not provide any evidence of tumorigenic or mutagenic effects of Albumin, experimental studies, particularly in heterologous species, are not considered to be necessary.
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