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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose in this paper is to consider the importance of early nutrition for critically ill patients, briefly reviewing the effects of malnutrition, and the metabolic response to starvation and sepsis. Discussion includes assessment of nutritional status and nutritional requirements, with a suggested enteral feeding regime; and also the combined effect of enteral nutrition and glutamine on gut integrity and its relevance to nosocomial pneumonia, and the ability of the gut to accept food during critical illness.
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PMID:Nutrition and its importance to intensive care patients. 884 27

The development of malnutrition is often rapid in critically ill patients with sepsis and severe trauma. In such patients, a wide array of hormonal and nonhormonal mediators are released, inducing complex metabolic changes. Hypermetabolism, associated with protein and fat catabolism, negative nitrogen balance, hyperglycemia, and resistance to insulin, constitute the hallmark of this response. Critically ill patients demonstrate a marked alteration in the adaptation to prolonged starvation: resting metabolic rate and tissue catabolism stay elevated, while ketogenesis remains suppressed. The response to nutrition support is impaired. Substrate use is modified in septic and traumatized patients. Glucose administration during severe aggression does not suppress the enhanced hepatic glucose production and the lipolysis. This phenomenon, related to tissue insulin resistance, ensures a high flow of glucose to the predominantly glucose-consuming cells, such as the wound, the inflammatory, and immune cells, all insulin-independent cells. In addition, the elevated protein catabolism is difficult to abolish, even during aggressive nutrition support. Thus, in patients with prolonged aggression, these alterations produce a progressive loss of body cell mass and foster the development of malnutrition and it dire complications. In this review, the relevant physiologic data and the nutritional implications related to energy metabolism in septic and injured patients are discussed, while potential therapeutic strategies are proposed.
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PMID:Energy metabolism in sepsis and injury. 929 Jan 9

The daily turnover of protein amounts to 280 g in an adult weighing 70 kg but the metabolic processes responsible for protein turnover are only just beginning to be understood. In cells, the major pathway of protein degradation is the ubiquitin-proteasome pathway and protein flux through this pathway is precisely regulated. In catabolic conditions such as uremia, activity of the ubiquitin-proteasome pathway increases, resulting in degradation of muscle protein. In addition to increased protein degradation, gene transcription is activated, resulting in higher levels of the mRNAs encoding ubiquitin and proteasome subunits. The signals activating this pathway include metabolic acidosis and glucocorticoids but must be more diverse since the pathway is also activated in response to starvation, sepsis, cancer, muscle denervation, thermal injury, and acute diabetes. Understanding how the pathway is controlled could lead to the prevention of muscle loss in uremia and other conditions.
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PMID:Cellular mechanisms controlling protein degradation in catabolic states. 938 15

To determine risk factors for the development and clinical characteristics of hypoglycemia in patients with sepsis, a case-control study was performed in 52 case-patients who developed spontaneous hypoglycemia (plasma glucose < 50 mg/dl) during episodes of sepsis compared with 49 nondiabetic, control-patients who had sepsis as an immediate cause of death and did not develop hypoglycemia. The presence or absence of potential risk factors for the development of hypoglycemia which consisted of the state of starvation, malnutrition, renal insufficiency, acute or chronic liver disease and malignancy were evaluated in both groups as well as the clinical characteristics of hypoglycemia. The mean of the lowest plasma glucose levels in hypoglycemic patients was 23.4 +/- 14.9 (SD) mg/dl (range 3-47). One-third of patients were found having hypoglycemia since the time of arrival to the hospital. About 90 per cent had septic shock at the time of hypoglycemia. The mortality rate was 90 per cent; 80 per cent died within 48 hours after the first episode of hypoglycemia. Among those risk factors, starvation and liver disease were independently associated with the development of hypoglycemia with odd ratios of 6.38 (95% confidence interval 1.95-20.86; P = 0.002), and 3.59 (95% confidence interval 1.09-11.81; P = 0.035), respectively. In conclusion, hypoglycemia in patients with sepsis was associated with a grave prognosis. The risk of developing hypoglycemia increased significantly in patients who had been fasted for more than 24 hours or had acute or chronic liver disease at the time of sepsis.
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PMID:Hypoglycemia in sepsis: risk factors and clinical characteristics. 947 Mar 28

Loss of lean body mass is common in patients with acute or chronic renal failure but the mechanisms causing this loss are only beginning to be understood. One mechanism involves an inability of uremic patients to activate the critical metabolic responses that maintain protein balance when dietary protein is limited. Metabolic responses to dietary protein restriction include a sharp reduction in the degradation of essential amino acids and protein; changes in protein synthesis are less reliable. If uremia prevents suppression of essential amino acid or protein degradation when dietary protein is reduced by anorexia, negative nitrogen balance and loss of lean body mass will ensue. One complication of uremia, metabolic acidosis, stimulates the degradation of branched-chain amino acids and proteins and therefore blocks the ability of the patient to respond to a low-protein diet. The mechanisms require glucocorticoids and involve increased activity of branched-chain keto acid dehydrogenase and the ubiquitin-proteasome proteolytic pathway; there also is increased transcription of genes encoding components of enzymes involved in the pathways. Besides acidosis, a low insulin concentration and cytokines activate the ubiquitin-proteasome proteolytic pathway. Understanding how proteolysis is activated, including how these genes are stimulated, is important because the same pathways are activated in diabetes, cancer, sepsis, burns, starvation, and muscle denervation. Activation of the ubiquitin-proteasome pathway leads to reduced lean body mass.
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PMID:Robert H Herman Memorial Award in Clinical Nutrition Lecture, 1997. Mechanisms causing loss of lean body mass in kidney disease. 949 77

The ubiquitin-proteasome proteolytic system is stimulated in conditions causing muscle atrophy. Signals initiating this response in these conditions are unknown, although glucocorticoids are required but insufficient to stimulate muscle proteolysis in starvation, acidosis, and sepsis. To identify signals that activate this system, we studied acutely diabetic rats that had metabolic acidosis and increased corticosterone production. Protein degradation was increased 52% (P < 0.05), and mRNA levels encoding ubiquitin-proteasome system components, including the ubiquitin-conjugating enzyme E214k, were higher (transcription of the ubiquitin and proteasome subunit C3 genes in muscle was increased by nuclear run-off assay). In diabetic rats, prevention of acidemia by oral NaHCO3 did not eliminate muscle proteolysis. Adrenalectomy blocked accelerated proteolysis and the rise in pathway mRNAs; both responses were restored by administration of a physiological dose of glucocorticoids to adrenalectomized, diabetic rats. Finally, treating diabetic rats with insulin for >/=24 h reversed muscle proteolysis and returned pathway mRNAs to control levels. Thus acidification is not necessary for these responses, but glucocorticoids and a low insulin level in tandem activate the ubiquitin-proteasome proteolytic system.
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PMID:Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting. 1032 62

Both starvation and sepsis are characterized by growth hormone (GH) insensitivity, which leads to a reduction in circulating insulin-like growth factor (IGF)-I. Because of the anabolic properties of this growth factor, its decline may contribute to the growth arrest and the catabolic reaction observed in starvation and sepsis. This review focuses on the mechanisms responsible for the reduction in circulating IGF-I and impairment of GH responsiveness that occur during starvation and sepsis. A clearer understanding of the complex nature of GH resistance should lead to the development of new therapeutic strategies aimed at restoring the beneficial effects of anabolic agents such as GH and IGF-I.
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PMID:Regulation of insulin-like growth factor-I in starvation and injury. 1043 29

Tissue carnitine levels have been measured in man and the dog. Skeletal muscle carnitine levels rise in the dog with starvation to roughly twice the normal level. An equal degree of starvation plus peritonitis is associated with unchanged skeletal muscle carnitine levels. In the presence of peritonitis, sequential skeletal muscle biopsies show a progressive fall in the tissue carnitine levels with a subsequent rise in those animals which survive and clear their peritonitis. Normal human skeletal muscle levels are essentially the same as in the dog. A combination of sepsis and starvation in man is associated with essentially unchanged skeletal muscle carnitine levels, whereas pure sepsis without starvation is associated with decreased skeletal muscle carnitine levels. It is suggested that these changes are in the direction expected for a limitation of fat catabolism and, in the presence of a limited exogenous source of glucose, that this would result secondarily in a protein catabolic state to supply glucose for the body's energy needs.
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PMID:Carnitine levels in severe infection and starvation: a possible key to the prolonged catabolic state. 1048 66

We analyzed clinical, biochemical, and histo- logic parameters of ten infants with parenteral nutrition-induced hepatobiliary dysfunction. The data were compared with the results of a rabbit model. All infants were born prematurely with low birth weight. Their clinical diagnoses were necrotizing enterocolitis (6), gastroschisis (1), intrauterine volvulus (1), and lung hypoplasia (2). All required total (TPN) or partial parenteral nutrition for at least 8 weeks. All had repeated episodes of infections or sepsis. A rise in bilirubin and aminotransferase levels occurred after a minimum of 5 weeks; peak bilirubin levels ranged from 4 to 14 mg% and aminotransferases from 40 to 140 IU/l. One child later developed gallstones. Liver biopsies after 1 to 24 months showed fibrosis, bile-duct proliferation, cholestasis, and hydropic degeneration. All of the above-mentioned clinical factors have been accused of causing the observed biochemical and histologic changes. In our rabbit model we were able to produce almost identical symptoms by TPN alone: gallbladder distension, sludge, and stones developed after 1-4 weeks of TPN as well as uncharacteristic changes in aminotransferases and bilirubin after 4 weeks. Liver histology revealed severe hydropic degeneration of zone 3 as early as 1 week after beginning TPN. A rise of fibrosis and bile-duct proliferation after 1 to 4 weeks of infusion was statistically significant. Cholestasis, as was observed in the infants, could not be detected. In our model, all alterations observed could be attributed exclusively to TPN. We therefore assume that TPN was the true cause of the dysfunction. In a second experimental series infusions were reduced to 80% PN and free access to lab chow. These animals produced normal feces, indicating physiologic enteral stimulation. They developed the same degenerative and proliferative histologic changes, whereas gallbladder distension, sludge, and stones were not noted. We conclude that: (1) The TPN solution itself is responsible for the histologic changes in the liver, which is supported by the fact that hydropic degeneration of zone 3 is typical of a direct toxic effect; and (2) Complete enteral starvation with an absence of enteral stimulation causes disease of the lower biliary tract.
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PMID:Parenteral nutrition-induced hepatobiliary dysfunction in infants and prepubertal rabbits. 1052 3

The liver shows net glutamine uptake after a protein-containing meal, during uncontrolled diabetes, sepsis and short-term starvation, but changes to net release during long-term starvation and metabolic acidosis. Some studies report a small net release of glutamate by the liver. The differential expression of glutamine synthetase (perivenous) and glutaminase (periportal) within the liver indicates that glutamine is used for urea synthesis in periportal cells, whereas glutamine synthesis serves to detoxify any residual ammonia in perivenous cells. Experiments in vivo suggest that changes in net hepatic glutamine balance are due predominantly to regulation of glutaminase activity, with the flux through glutamine synthetase being relatively constant.
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PMID:Glutamine and glutamate metabolism across the liver sinusoid. 1073 66


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