Glucocorticoids and shock, what are we doing now? (Proceedings)
Shock can be classified into general categories: hypovolemic, maldistribution, and cardiogenic. Hypovolemic shock is due to a diminished volume of fluids and can occur in severe dehydration (Parvoviral gastroenteritis, hemorrhagic gastroenteritis) or hemorrhage. Maldistribution shock occurs when blood flow is shunted away from major organs and pools in the periphery. Examples of maldistribution shock are sepsis, endotoxemia, anaphylaxis, gastric dilatation with volvulus (GDV), neurogenic, and even due to severe pain. Cardiogenic shock occurs when cardiac output is markedly decreased in conditions such as myocardial disease, arrhythmias, pericardial tamponade, and pulmonary thromboembolism.
Glucocorticoids, mechanisms of actionGCs increase the circulating pool of mature neutrophils (PMNs) due to release of PMNs from the marginal pool which decreases migration into inflamed tissues. The effect is due to decreased expression of adhesion molecules, reduced adhesion to the vascular epithelium, and reduced movement through the vasculature into the tissues. Anti-inflammatory doses of GCs affect PMN trafficking more than function as minimal effects on phagocytosis and lysosomal stability occur. GCs decrease the circulating pool of lymphocytes, monocytes, eosinophils, and basophils primarily due to their movement from the vasculature to the lymphoid tissues. GCs alter the function of macrophages and other antigen presenting cells by reducing the cells ability to respond to antigens. The ability of macrophages to engulf and kill microorganisms is markedly inhibited. The production of cytokines such as TNF-α, interleukin-1 (IL-1), metalloproteinases, and plasminogen activator by macrophages are also markedly inhibited. GCs also decrease the production of IL-12 and interferon-γ by lymphocytes and macrophages which are important inducers of T-helper cell activity and cellular immunity. T-cells are more affected by GCs then B-cells with minimal affects on B-cell production of immunoglobulins at anti-inflammatory doses. However, high doses of GCs can decrease immunoglobulin production.
GCs also reduce the production of prostaglandins and leukotrienes by the arachidonic acid pathway. The primary effect on the arachidonic acid pathway is thought to be through inhibition of phospholipase A2, but some effects on cyclooxygenase-2 (COX-2) may also occur. GCs also have a variety of effects on blood vessels. GCs improve the microvascular integrity and circulation, and decrease vessel permeability. It is unclear as to the precise mechanisms by which these effects occur, but may be due to inhibition of vasoactive substances such as histamine, serotonin, and prostaglandins among others. The clinical benefits of the vascular effects have not been identified as a clinical benefit