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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoglycemia associated with renal failure is more common than generally thought. Its occurrence is often a marker of multisystem failure and has an ominous prognostic implication. Its pathogenesis is frequently complex and involves one or several mechanisms. In the evaluation of uremic hypoglycemia, the first step should be the exclusion of obvious causes such as insulin, oral hypoglycemic agent therapy, and the use of drugs known to cause hypoglycemia. Propranolol, salicylates, and disopyramide are among the most commonly implicated agents. Additional triggering events are alcohol consumption, sepsis, chronic malnutrition, acute caloric deprivation, concomitant liver disease, congestive heart failure, and an associated endocrine deficiency. When no obvious cause can be demonstrated, the hypoglycemia is referred to as spontaneous. Spontaneous uremic hypoglycemia has been attributed to deficiency of precursors of gluconeogenesis, that is, alanine, deficient gluconeogenesis, impaired glycogenolysis, diminished renal gluconeogenesis and impaired renal insulin degradation and clearance, poor nutrition, and, in a few cases, deficiency in an immediate counterregulatory hormone such as catecholamine and glucagon. However, the mechanism(s) seems to differ from one patient to the other. Dialysis also predisposes to hypoglycemia in uremia, possibly because of the chronic state of malnutrition. Postdialysis hypoglycemia is secondary to glucose-induced hyperinsulinemia, which is caused by the high glucose content in the dialysate. In uremic hypoglycemia, neuroglycopenic manifestations predominate because of frequent autonomic nervous system dysfunction and lack of catecholamine release in response to hypoglycemia. Its severity and duration are variable. Hypoglycemia should be suspected in any patient with renal failure who exhibits any change in mental or neurologic status. Detection of hypoglycemia should rely on frequent and careful glucose determinations in any patient with uremia.
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PMID:Hypoglycemia associated with renal failure. 264 22

The present study examined whether sepsis exacerbates the diabetes-induced peripheral and hepatic insulin resistance. Vascular catheters were placed in diabetic (70 mg/kg streptozotocin, 4-wk duration) and nondiabetic rats, and sepsis was produced by subcutaneous injections of live Escherichia coli. Basal glucose metabolism was determined with the use of [3-3H]glucose initiated 18 h after the first injection of bacteria. Thereafter, in vivo insulin action was assessed with the use of the euglycemic hyperinsulinemic clamp technique. Sepsis in nondiabetic rats produced a 57% reduction in the maximal responsiveness for the insulin-induced increase in total glucose utilization compared with nondiabetic nonseptic animals. Diabetes alone decreased both insulin sensitivity and responsiveness. When the septic insult was superimposed on the diabetic condition, the maximum responsiveness was unchanged compared with non-septic diabetic rats, but the 50% maximally efficient dose was reduced from 817 to 190 microU/ml, suggesting an improvement in insulin sensitivity. Sepsis did not alter the insulin-induced suppression of hepatic glucose output in either nondiabetic or diabetic animals. Sepsis increased the plasma concentrations of epinephrine, norepinephrine, glucagon, and corticosterone in both nondiabetic and diabetic rats; however, the elevation in catecholamines and glucagon was 65 to 250% greater in the diabetic animals. These results indicate that hypermetabolic sepsis produces peripheral insulin resistance in nondiabetic rats but does not worsen the preexisting insulin resistance in diabetic animals, despite the higher prevailing blood levels of glucagon and catecholamines.
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PMID:Sepsis-induced changes in in vivo insulin action in diabetic rats. 267 27

Tumor necrosis factor (TNF) has been implicated in the toxic manifestations of overwhelming bacterial infection and in the tissue wasting that often accompanies prolonged infections and malignancy. We have examined a possible role of TNF in the early metabolic alterations following acute tissue injury or sepsis. Recombinant human TNF stimulated rat liver amino acid uptake up to 5-fold in vivo and there was a concomitant increase in plasma glucagon. In vitro TNF had no direct effect on hepatocyte amino acid uptake, but it markedly enhanced the stimulation of amino acid transport by glucagon, without an alteration in binding of glucagon to hepatocytes. This permissive effect of TNF on glucagon action represents an interrelationship between the immune and endocrine systems, and it may help to explain the mechanism of hormonal regulation of both the anabolic and catabolic responses to acute injury.
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PMID:Modulation of endogenous hormone action by recombinant human tumor necrosis factor. 282 98

Sepsis and trauma result in increases in epinephrine, glucagon, and cortisol secretion as well as alterations in respiratory pattern that is characterized by increased minute ventilation, decreased tidal volume, and increased frequency. Six male subjects were infused for 5.5 hours with cortisol, epinephrine, and glucagon in amounts designed to simulate plasma levels seen in patients following trauma. During the initial 20 minutes of the hormone infusion, minute ventilation (VE), oxygen consumption (VO2), and carbon dioxide production (VCO2) increased above preinfusion values. VCO2 increased more than VO2 resulting in an increase in respiratory quotient (RQ) from 0.93 to 1.14. The increase in VE was due to increased tidal volume and not frequency (f). After 4.5 hours, the VE, VO2, and VCO2 were still above preinfusion levels but the RQ had decreased to 0.98 because of a decrease in VCO2. Frequency had increased from 19 +/- 4.8 breaths/min preinfusion to 22 +/- 4.7 after 4.5 hours. After 4.5 hours, VT was still above preinfusion levels while pH and PaCO2 had decreased below them. The latter was associated with an increase in serum lactate. At no time was a decrease in tidal volume observed. Therefore, the infusion of these hormones does not simulate all the alterations observed during trauma and sepsis.
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PMID:The metabolic and ventilatory response to the infusion of stress hormones. 308 92

Although nutritional support is vital to treatment of severe sepsis, the septic patient does not respond normally to glucose infusion. We have used the hyperglycemic glucose clamp technique to investigate the initial hormonal and metabolic responses of the septic patient to glucose under controlled conditions. The plasma glucose concentration was raised to and maintained at 12 mmol/liter for 2 hr in 12 septic patients and 11 normal controls. Glucose utilization, assessed from the amount infused, was significantly depressed in the patients, despite similar plasma insulin concentrations in the two groups. Forearm glucose uptake was similarly impaired. Despite very similar plasma free fatty acid concentrations in the two groups, which were suppressed equally by the glucose infusion, whole-body fat oxidation was elevated in the patients compared with the controls, and suppressed to a lesser extent in response to glucose. Glycerol and ketone body concentrations were elevated in the patients in keeping with a picture of accelerated release, clearance, and oxidation of fatty acids. Plasma cortisol, epinephrine, and norepinephrine concentrations were elevated in the septic patients in a severity-related manner, but not to high levels compared with experimental work. Norepinephrine showed no response to the glucose infusion in either group. Plasma glucagon concentrations were not significantly elevated in the septic patients. We conclude that the hyperglycemic glucose clamp provides a useful model for studying glucose intolerance in sepsis. Impaired glucose utilization in septic patients is associated with increased fat oxidation, although the hormonal basis for these changes is still unclear.
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PMID:Hormonal and metabolic responses to glucose infusion in sepsis studied by the hyperglycemic glucose clamp technique. 311 25

The metabolic response to trauma and sepsis is characterized by a negative nitrogen balance, accelerated muscle proteolysis, increased ureagenesis, and stimulated acute-phase protein synthesis in liver. Inhibited uptake of amino acids and accelerated protein breakdown in muscle increase the flux of amino acids from the periphery to the liver. Concomitantly, hepatic uptake of amino acids is stimulated and protein synthesis and gluconeogenesis in the liver are enhanced. These events are important to the survival of patients with sepsis. Stimulated ureagenesis resulting in nitrogen loss from the body is another important aspect of hepatic nitrogen metabolism following trauma and sepsis. The mediator(s) initiating metabolic changes is not yet exactly defined, although regulatory protein(s) released from stimulated macrophages (particularly interleukin 1 and tumor necrosis factor) may play a major role in altered amino acid and protein metabolism in muscle and liver during sepsis. However, these factors alone are probably not responsible for the metabolic disturbances, since the catabolic hormones cortisol, glucagon, and the catecholamines can simulate the metabolic pattern observed in sepsis. Other possible mediators include prostaglandins and thyroid hormones. It is possible that the interaction between different types of mediators is necessary for the full manifestation of host responses to severe injury and sepsis.
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PMID:Current concepts of protein turnover and amino acid transport in liver and skeletal muscle during sepsis. 329 52

Protein synthesis and degradation are particularly sensitive to malnutrition and catabolic states. Intracellular protein degradation is determined by the conformation, molecular weight, isoelectric point, and carbohydrate content of the proteins. ATP-stimulated endoproteases appear to catalyse the rate-limiting steps. In the liver, proteolysis is reduced by amino acids and/or insulin, whereas glucagon stimulates protein degradation, probably due to depletion of intracellular gluconeogenic amino acids. In the muscle, protein degradation is promoted by interleukin-1 and inhibited by Ep-475, which specifically inactivates cathepsin B,H, and L. Myofibrillar alkaline proteinase activity increases postoperatively and in patients suffering from malignant tumors, whereas normal proteinase values were observed in these patients following total parenteral nutrition. Increased alkaline proteinase activity is also observed in diabetes mellitus and is normalized by insulin. Extracellular proteolysis has been reported in patients with hypercatabolic acute renal failure and in patients with sepsis or acute pancreatitis. Plasma fractions obtained from hypercatabolic patients with postoperative acute renal failure were proteolytic. Plasma proteinase activity decreases during hemodialysis due to elimination of a metallo-proteinase. Plasma alpha 2-macroglobulin decreases in patients with acute renal failure and also during acute pancreatitis. Proteolytic degradation of parathyroid hormone by sera obtained from patients with acute pancreatitis has been observed. Also, there is a decrease of high molecular weight kininogen during experimental acute pancreatitis. Granulocyte elastase increases postoperatively, mainly in patients with sepsis. Sepsis also causes increased proteolytic activity in the urine. In conclusion, intracellular protein degradation can supply important precursors for hepatic and renal gluconeogenesis during malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proteinases in catabolism and malnutrition. 331

Inhibited amino acid transport in skeletal muscle during sepsis has been demonstrated previously. In the present study we investigated the effects in vitro of plasma from septic animals or fractions of septic plasma that contain solutes with a molecular weight less than 30,000 daltons or less than 2000 to 3000 daltons on amino acid transport in incubated rat soleus (SOL) muscles. The influence of interleukin-1 (IL-1), prostaglandin E2 (PEG2), and the "catabolic" hormones corticosterone, glucagon, and epinephrine on muscle amino acid uptake was also investigated. Amino acid transport was studied with 3H-alpha-aminoisobutyric acid (AIB). Whole-septic plasma and the two low molecular-weight fractions of the septic plasma reduced muscle amino acid uptake by about 20%. IL-1 or PGE2 did not affect amino acid transport. When the catabolic hormones were added individually to incubated SOL muscles, no changes in AIB uptake were noticed. When glucagon or epinephrine was added in combination with corticosterone or when all three hormones were added together, amino acid transport was reduced by 10% to 15%. The results suggest that inhibited muscle amino acid uptake in sepsis is caused by a circulating factor(s) with a molecular weight less than 2000 to 3000 daltons. A synergistic action among the catabolic hormones may be one important factor for reduced muscle amino acid transport in sepsis.
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PMID:Reduced muscle amino acid uptake in sepsis and the effects in vitro of septic plasma and interleukin-1. 348 96

Host responses to sepsis and trauma are complex and their mediators are not well understood. To examine the roles of "endocrine" and "inflammatory" mediators, we studied healthy volunteers in four experimental groups: continuous 72-hour infusion of normal saline; continuous 72-hour infusion of hydrocortisone, glucagon, and epinephrine; daily intramuscular injection of the inflammatory agent etiocholanolone; and combined etiocholanolone injection--hormone infusion. In this model hypermetabolism, hyperglycemia, hyper-insulinemia, insulin resistance, negative nitrogen balance, and accelerated protein flux were mediated predominantly by infusion of the counterregulatory hormones. Etiocholanolone injection resulted in fever, acute-phase--protein synthesis, and hypoferremia. Leukocyte, temperature, and C-reactive--protein responses reflected major interactions between these stimuli. Both inflammatory and endocrine mediators are necessary for the complete manifestation of host responses to critical illness.
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PMID:Both inflammatory and endocrine mediators stimulate host responses to sepsis. 351 87

To determine the relationship between hepatic glucose clearance and elevated epinephrine levels in sepsis, dogs with gangrenous cholecystitis were anesthetized and received either propranolol hydrochloride (mean dose, 0.29 mg/kg) or saline solution before intraduodenal glucose injection (2.5 g/kg). The amounts of glucose, insulin, and glucagon in the portal vein, the hepatic artery, and the hepatic vein were determined from the concentrations and the blood flows in these vessels over a two-hour period. Normal dogs served as controls. The amounts of glucose, insulin, and glucagon reaching the livers of both septic groups were the same. However, propranolol treatment increased the percent of glucose extracted by the liver without affecting the extractions of insulin or glucagon. Propranolol reverses the limitation of hepatic glucose extraction in sepsis by a direct effect. Whether the extracted glucose is utilizable as an energy substrate needs to be established.
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PMID:Beta-adrenergic blockade increases the hepatic extraction of glucose in sepsis. 351 91


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