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

We describe an animal model of generalized sepsis, induced in the sheep by cecal perforation, which reproduces the high systemic flow and peripheral vasodilation seen in early human sepsis. Despite volume loading, animals demonstrate a fall in glomerular filtration rate, oliguria, low fractional sodium excretion, maintained urine osmolarity, and increased plasma renin activity. Histologically, kidneys show no consistent abnormality; overall the findings suggest volume contraction or hypoperfusion. This is contradicted, however, by maintained blood pressure and pulmonary capillary wedge pressure, increased cardiac output, and reduced peripheral resistance. Increased Fc lysozyme and low molecular weight proteinuria suggest tubular damage. These paradoxical observations are currently unexplained.
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PMID:The renal response produced by nonhypotensive sepsis in a large animal model. 374 63

We studied the functional effects of intraperitoneal sepsis on systemic hemodynamics in general, and on renal function in particular, in sheep in whom bacterial peritonitis was induced by cecal perforation. In the first group of seven sheep (group 1) fluid was administered throughout the period of sepsis to maintain pulmonary capillary wedge pressure as close to presepsis values as possible. These sheep exhibited hemodynamic changes known to be associated with sepsis in man: increased cardiac output and decreased systemic vascular resistance. In a second group of seven sheep (group 2) fluid intake was restricted; compared with group 1, these sheep demonstrated a smaller increase in cardiac output that did not persist and that was associated with an increase in the systemic vascular resistance during the septic period. Plasma renin levels increased fivefold in group 2 but were unchanged in group 1. Serial renal biopsies during the septic period revealed that all sheep had evidence of tubular cell damage on electron microscopy: cell swelling, loss of the microvillous brush border, and cell necrosis. Both groups of sheep also demonstrated marked tubular proteinuria similar to that found in humans with generalized sepsis. Despite this, sheep in group 1 exhibited no functional renal changes: creatinine clearance levels rose slightly from control values, urine concentrating ability was unimpaired, and fractional excretion of sodium increased appropriately in response to a sodium load. In contrast, group 2 sheep exhibited a fall in creatinine clearance levels but fractional sodium excretion did not fall as would have been expected were renal function entirely normal. The results suggest that generalized "hyperdynamic" sepsis induces tubular cell damage and tubular proteinuria by an unknown mechanism. However, this does not necessarily produce renal impairment since the glomerular filtration rate does not fall unless volume contraction is also allowed to occur.
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PMID:Renal and cardiovascular response to nonhypotensive sepsis in a large animal model with peritonitis. 396 24

Plasma angiotensin II concentration gradients across the pulmonary vascular bed, plasma renin concentration and serum converting enzyme activity were measured in 19 patients. The majority of the patients were critically ill. Nine patients had septicemia with acute respiratory failure, six patients had severe chronic lung disease and four patients had other serious disorders requiring haemodynamic monitoring. Pulmonary angiotensin II generation rates were calculated as the products of the pulmonary plasma flow and the angiotensin II concentration gradient across the lung. Several patients had a highly activated renin-angiotensin system. There was a strictly linear correlation between the plasma angiotensin II concentrations in mixed venous blood and in systemic arterial blood across a wide range, the concentration in arterial blood being 1.4-1.5 times that in mixed venous blood in each of the three groups of patients. Serum converting enzyme activity was not different from the level observed in a group of control patients above 50 years of age, but lower than in younger normal individuals. The maximal angiotensin II production rates in the pulmonary vascular bed of patients with life-endangering pulmonary disease were similar to the rates previously measured in hypertensive patients with renovascular or renal parenchymal disease. In conclusion, the process of angiotensin I conversion in the lung operates without impediment in spite of severe pulmonary injury.
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PMID:Pulmonary angiotensin II production in respiratory failure. 633 56

Studies of plasma renin activity (PRA) and plasma aldosterone in burn patients treated with a low volume colloid resuscitation regimen revealed very high levels of both hormones. Highest hormone levels occurred in the 5 days post burn with the correlation between PRA and plasma aldosterone r = +0.787 (p less than 0.001). The negative correlation between 24 hour urinary sodium excretion and PRA (r = +0.671, p less than 0.001), was closer than that between 24 hour sodium excretion and plasma aldosterone (r = -0.556, p less than 0.01). Secondary elevations of PRA and plasma aldosterone occurred in 2 patients (7-14 days after injury) associated with clinical deterioration and systemic sepsis.
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PMID:Observations on the activity of the renin-angiotensin-aldosterone (RAA) system after low volume colloid resuscitation for burn injury. 634 11

We present the case of a 60 year old C6 complete tetraplegic patient who developed profound hypotension following initiation of the angiotensin-converting enzyme inhibitor lisinopril to control blood pressure. Other causes of hypotension, such as myocardial infarction and sepsis was ruled out. Inhibition of the renin-angiotensin-aldosterone system was the probable cause of hypotension. This case demonstrates the critical importance of the renin-angiotensin-aldosterone axis in the maintenance of blood pressure in tetraplegic patients, who may lack input from the brain to sympathetic neurons, and therefore have increased reliance on the renin-angiotensin-aldosterone axis for the maintenance of blood pressure. Angiotensin-converting enzyme inhibitors should be avoided in tetraplegic patients, unless other treatment modalities are ineffective.
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PMID:Profound hypotension in a tetraplegic patient following angiotensin-converting enzyme inhibitor lisinopril. Case report. 770 26

This article describes some of the alterations that occur in the neuroendocrine system during sepsis. With a goal of better management of the patient with sepsis, an overview of the endocrine system, its hormones, and its close relationship to the nervous system is presented. The importance of hormone target cell receptor coupling, specific mechanisms of action that result in physiological changes, and regulation of hormone secretion are detailed. The roles and effects of catecholamines, glucagon, cortisol, and growth hormone are explored. Sick euthyroid syndrome, alterations in ADH, the renin-angiotensin-aldosterone axis, and PTH secretion are also examined.
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PMID:Hormonal response in sepsis. 794 87

A new method for ascites recirculation, consisting of a cellulose diacetate filter to remove substances with molecular weight > or = 300,000, cell debris and bacteria, followed by the concentration of ascitic fluid prior to i.v. infusion, was used 24 times in 19 patients with cirrhosis and massive or refractory ascites. The amount of ascites removed was 7.67 +/- 0.49 l, which was reduced to 407 +/- 37 ml. The procedure took 367 +/- 22 min to complete. No statistically significant changes in liver function tests, coagulative parameters, platelet count or natremia were found. The activity of coagulation and fibrinolytic systems was further assessed in six patients. No changes suggesting an activation of intravascular coagulation and/or primary fibrinolysis were disclosed. An asymptomatic fall in mean arterial pressure (from 88.6 +/- 2.6 to 80.3 +/- 3.0 mmHg; p = 0.02) occurred after paracentesis and was still present 48 h after ascites reinfusion. Plasma renin activity significantly decreased at the end of the procedure, but was not associated with a proportional reduction of plasma aldosterone concentrations. Both variables returned to baseline values 48 h later. A significant increase in the glomerular filtration rate occurred just after the end of the procedure (from 50.4 +/- 9.1 to 73.1 +/- 23.5 ml/min; p < 0.05) and subsided 48 h later. In contrast, no significant changes in diuresis and renal sodium excretion were found. Complications due to volume overload and sepsis did not occur; in one case, spontaneous bacterial peritonitis developed 3 days after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ascites apheresis, concentration and reinfusion for the treatment of massive or refractory ascites in cirrhosis. 800 9

1. We continuously recorded systemic and renal haemodynamic changes, and arterial, renal venous and urinary concentrations of thromboxane B2, 6-keto-prostaglandin F1 alpha and prostaglandin E2, and determined their relationship to renal function in an ovine model of progressive hyperdynamic sepsis. 2. Nine chronically instrumented unanaesthetized sheep were given a continuous intravenous infusion of Escherichia coli endotoxin (20 ng min-1 kg-1) for 3 days. 3. Within the first 12 h of infusion, endotoxin induced a major hypotensive septic syndrome, including a persistent 30% reduction in mean arterial pressure, a 50% decrease in systemic vascular resistance and a 50% increase in mean pulmonary artery pressure, associated with severe lactacidaemia. 4. Renal blood flow decreased by 40%, and creatinine clearance, urine flow, and fractional sodium excretion decreased by more than 75%, of baseline values. After 12 h of endotoxin infusion, cardiac output increased two-fold and renal blood flow recovered to baseline values, whereas creatinine clearance remained depressed. Four sheep died between 13 and 22 h of endotoxaemia; these animals (allocated to group 1) presented a significantly and persistently more reduced renal blood flow (-23%) and creatinine clearance (-77%) after 4 h than the remaining five sheep (allocated to group 2), which survived more than 36 h (-16% and -21%, respectively), whereas systemic and pulmonary haemodynamic and gas exchange data remained similar in both groups. 5. The more pronounced decreases in renal blood flow, creatinine clearance and urine flow in group 1 were associated with higher plasma renin activity and plasma 6-keto-prostaglandin F1 alpha concentrations and a lower fractional urinary excretion of 6-keto-prostaglandin F1 alpha than in group 2, whereas plasma thromboxane B2 concentrations were similarly increased in both groups. Plasma prostaglandin E2 concentrations and urinary excretion were not notably affected by endotoxin infusion in either group. 6. Our results are not in favour of a significant renal production of any of these three prostanoids during endotoxaemia. In both groups, values of creatinine clearance were linearly correlated with simultaneous mean arterial pressure values after starting endotoxin infusion (group 1: creatinine clearance = 1.99 x mean arterial pressure--105, r = 0.95; group 2: creatinine clearance = 2.06 x mean arterial pressure--104, r = 0.80).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Time course of systemic and renal plasma prostanoid concentrations and renal function in ovine hyperdynamic sepsis. 803 13

alpha2-HS glycoprotein is a major protein of human plasma whose function is still obscure. A proteolytically processed form of alpha2-HS glycoprotein lacking a segment of 40 amino acid residues bridging its heavy and light chain portions ("connecting peptide") has been described suggesting that this peptide is released by post-translational processing to fulfill biological role(s) of alpha2-HS glycoprotein. To test this hypothesis we investigated how the connecting peptide is released from the parental molecule by limited proteolysis. We developed monoclonal antibodies to various portions of the connecting peptide and its NH2-terminal flanking region which cross-react with the native alpha2-HS glycoprotein. Purified alpha2-HS glycoprotein from human plasma was subjected to limited proteolysis by proteinases including trypsin, chymotrypsin, elastase plasmin, kallikrein, thrombin, and renin. Immunoprint analysis of the proteolytic digests indicated that alpha2-HS glycoprotein is readily cleaved in its connecting peptide region. NH2-terminal amino sequence analysis of the generated fragments demonstrated that a single proteinase, chymotrypsin, cleaves the critical Leu-Leu bond flanking the NH2-terminal portion of the connecting peptide region. Most but not all of the other proteinase cleavage sites map to a short stretch of 9 residues located in the center portion of the connecting peptide region. Immunoprint analysis of plasma samples from patients with sepsis demonstrate that the connecting peptide region is cleaved under pathological conditions. Our results indicate that the connecting peptide and/or fragments thereof are readily releasable from alpha2-HS glycoprotein in vitro and in vivo.
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PMID:Limited proteolysis of human alpha2-HS glycoprotein/fetuin. Evidence that a chymotryptic activity can release the connecting peptide. 894 Jan 98

Nitric oxide (NO) is formed in the endothelium by the constitutive enzyme NO synthase from the substrate amino acid L-arginine. As an endogenous vasodilator it contributes to renal arteriolar tone and modulates relaxation of the mesangium, thus contributing to regulation of glomerular microcirculation. NO also plays a role in regulating renal sodium excretion and renin release. It has antiplatelet and antithrombogenic effects and thus helps prevent thrombosis within the glomerular capillaries. In sepsis and sepsis-related syndromes, NO has a renoprotective role in that it aids in maintaining renal vasodilation and inhibiting platelet adhesion and aggregation. More knowledge of these effects may lead to the design of therapeutic interventions for preventing glomerular injury.
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PMID:Pathophysiology of the vascular wall: the role of nitric oxide in renal disease. 899 94


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