Major blood loss entails the danger of life-threatening circulatory failure, i.e., hypovolemic shock. The immediate threat results not so much from the loss of erythrocytes, i.e., oxygen carriers, as from the reduction in volume of circulating blood.
To eliminate the threat of shock, replenishment of the circulation is essential. With moderate loss of blood, administration of a plasma volume expander may be sufficient. Blood plasma consists basically of water, electrolytes, and plasma proteins. However, a plasma substitute need not contain plasma proteins. These can be suitably replaced with macromolecules ("colloids") that, like plasma proteins, (1) do not readily leave the circulation and are poorly filtrable in the renal glomerulus; and (2) bind water along with its solutes due to their colloid osmotic properties. In this manner, they will maintain circulatory filling pressure for many hours. On the other hand, volume substitution is only transiently needed and therefore complete elimination of these colloids from the body is clearly desirable.
Compared with whole blood or plasma, plasma substitutes offer several advantages: they can be produced more easily and at lower cost, have a longer shelf life, and are free of pathogens such as hepatitis B or C or AIDS viruses.
Three colloids are currently employed as plasma volume expanders— the two polysaccharides, dextran and hydroxyethyl starch, as well as the poly-peptide, gelatin.
Dextran is a glucose polymer formed by bacteria and linked by a 1 instead of the typical 1^4 bond. Commercial solutions contain dextran of a mean molecular weight of 70 kDa (dex-tran 70) or 40 kDa (lower-molecular-weight dextran, dextran 40). The chain length of single molecules, however, varies widely. Smaller dextran molecules can be filtered at the glomerulus and slowly excreted in urine; the larger ones are eventually taken up and de-Lullmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Usage subject to terms and conditions of license.
graded by cells of the reticuloendothelial system. Apart from restoring blood volume, dextran solutions are used for hemodilution in the management of blood flow disorders.
As for microcirculatory improvement, it is occasionally emphasized that low-molecular-weight dextran, unlike dextran 70, may directly reduce the ag-gregability of erythrocytes by altering their surface properties. With prolonged use, larger molecules will accumulate due to the more rapid renal excretion of the smaller ones. Consequently, the molecular weight of dextran circulating in blood will tend towards a higher mean molecular weight with the passage of time.
The most important adverse effect results from the antigenicity of dex-trans, which may lead to an anaphylactic reaction.
Hydroxyethyl starch (hetastarch) is produced from starch. By virtue of its hydroxyethyl groups, it is metabolized more slowly and retained significantly longer in blood than would be the case with infused starch. Hydroxyethyl starch resembles dextrans in terms of its pharmacological properties and therapeutic applications.
Gelatin colloids consist of cross-linked peptide chains obtained from collagen. They are employed for blood replacement, but not for hemodilution, in circulatory disturbances.
: cross-linked peptide chains MW 35, 000
Peptides MW ~ 15, 000 Gelatin MW ~ 100, 000 Collagen MW ~ 300, 000
MW 40, 000
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