Alterations in lipid and carbohydrate metabolism in sepsis

The effects of sepsis on lipid metabolism may be summarized as follows: The increased plasma catecholamine concentration stimulates adipose tissue FFA release. The increased FFA mobilization and plasma concentration results in an enhanced FFA uptake by the liver which promotes TGFA synthesis and output. Thus, triglyceride appearance rate also can be increased during hypermetabolic sepsis. In severe sepsis, the regulatory signals to increase FFA release from adipose tissue may be counterbalanced by blood flow limitations that inhibit FFA release, possibly due to the inadequate availability of the plasma carrier, albumin. Under such conditions, the arterial FFA concentration may be unchanged or decreased along with similar changes in the rate of peripheral FFA utilization. Trigliceride metabolism can also be altered during septic conditions in which plasma levels of cytokines are very high. Cytokines, notably TNF and IL-1, suppress synthesis of lipoprotein lipase which decreases the rate of TGFA clearance. Thus, hypertriglyceridemia can develop in the absence of elevated plasma FFA levels. The plasma concentration of cytokines necessary to inhibit LPL and how often this form of hypertriglyceridemia occurs in human sepsis are unknown at present. The sequence of events describing the influence of sepsis on carbohydrate metabolism is postulated to be the following: The presence of bacteria, or their products (eg, endotoxin) either directly or indirectly (via stimulating mononuclear phagocytes to release cytokines) activate the immune tissues. Glucose utilization by these tissues, which are predominantly glycolytic, is thereby stimulated resulting in increased lactate production. At the same time, glucose uptake by skeletal muscle and lactate release are also elevated. The increased precursor concentration in the presence of maintained hepatic blood flow, stimulates gluconeogenesis. The increased gluconeogenic rate is present in spite of the decreased activity of phosphoenolpyruvate carboxykinase, an enzyme that is considered to be rate controlling in gluconeogenesis. Activated mononuclear phagocytes release an array of cytokines. Of these various mediators TNF is known to stimulate the production of the catabolic hormones (catecholamines, glucagon, etc) which serve to reinforce the stimulation of gluconeogenesis. In addition, these hormones enhance glycogenolysis, thereby further increasing the recycling of glucose carbons. During hypermetabolic sepsis, the combination of these changes in lipid and carbohydrate metabolism enables the body to continue to rely on fatty acid oxidation as a prime source of energy, while satisfying the special needs of some tissues for glycolytic substrates. Thus, in the nutritionally nonsupported state, adipose tissue fatty acids stores slowly decrease while the attempt to preserve glucose carbons via increased recycling is maintained.