Metabolic effects of high dose corticosteroids.

Abstract

The improved survival following high-dose corticosteroid (HDC) treatment of septic shock conditions has been suggested to be partly due to the metabolic effects of HDC. Endotoxins are known to deplete glycogen stores, hexose phosphates and phosphoenol-pyruvate. Elevated levels of fructose diphosphate and phosphoglycerates are seen and there is an accumulation of lactate. Endotoxemia also seems to inhibit the utilization of non-carbohydrate precursors for glucose production and hypoglycemia is characteristically seen with time in septic states. In severe shock mitochondrial oxidative metabolism and ion transport capacity are defective and tissue energy store will be depleted. The underlying metabolic pathology in shock states is still not known in detail but endotoxins seem to have direct antiglucocorticoid effects. HDC counteracts the acceleration of glycolysis by the Embden- Meyerhof pathway seen in septic states and prevents the endotoxin-mediated stimulation of enzymes in the hexose monophosphate shunt. The levels of Krebs cycle intermediates and pyruvate in the liver are raised after treatment indicating enhanced gluconeogenesis. The conversion of lactate to glucose is increased and the lactate/pyruvate ratio decreased. Protein catabolism is stimulated by HDC elevating the plasma levels of amino acids and thereby further enhancing the potential for gluconeogenesis. The endotoxin-induced mitochondrial dysfunction is reversed and cellular energy production is improved. The beneficial metabolic effects of HDC may to some extent be indirect. A depressed febrile response will decrease tissue oxygen needs. The vasodilatory effects will improve tissue oxygen availability and thereby reduce tissue hypoxia. Stabilization of cellular membranes may also prevent systemic metabolic effects caused by lysosomal enzymes released from damaged cells.

• Authors: H Haljamäe
• Journal: Acta chirurgica Scandinavica. Supplementum (Acta Chir Scand Suppl) Vol. 526 Pg. 27-36 ( 1985) ISSN: 0301-1860 [Print] Sweden
• PMID: 3911706 (Publication Type: Journal Article, Review)

Chemical References

• Adrenal Cortex Hormones
• Proteins

Topics

• Adrenal Cortex Hormones (pharmacology, therapeutic use)
• Animals
• Carbohydrate Metabolism
• Energy Metabolism (drug effects)
• Glycolysis (drug effects)
• Humans
• In Vitro Techniques
• Lipid Metabolism
• Liver (metabolism)
• Oxygen Consumption (drug effects)
• Pentose Phosphate Pathway (drug effects)
• Proteins (metabolism)
• Shock, Septic (drug therapy, metabolism)