Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma kallikrein releases bradykinin when activated by gram-negative septicemia or irreversible hemorrhagic shock. Pancreatitis releases glandular kallikrein causing hypotension and increased vascular permeability. Bradykinin in the brain produces hypertension. Renal kallikrein is released by high arterial pressure, vasodilators, low doses of noradrenaline, angiotensin II, mineralocorticoids and rapid volume expansion. It has a biphasic relation to sodium excretion. In essential hypertension, kallikrein release into the blood and urine is low and facilitates hypertension. High renin in Bartter's syndrome is balanced by high PGE and kallikrein without hypertension.
 ...
PMID:Kallikrein, kininogen and kinins in control of blood pressure. 37 13

In conclusion, patients on chronic maintenance dialysis have an increased incidence of death from cardiovascular disease. Hypertension plays a major role, and these patients must be carefully monitored for complete control of blood pressure. Adequacy of ultrafiltration to maintain normal extracellular volume is an essential part of the dialytic treatment. Hypertensive patients should be screened for excessive renin secretion because of its possible role in unresponsive hypertension in patients on dialysis. Nephrectomy should be used when necessary, where dialysis and antihypertensive medication have not adequately controlled blood pressure. Patients must be monitored for the presence of pericardial disease to avoid subsequent pericardial effusion and the development of constrictive pericarditis with its adverse effect on myocardial function. When constrictive pericarditis is present, it obviously should be relieved by appropriate surgery. Efforts should be made to minimize cardiac output in hemodialysis patients. Whether or not routine transfusions to maintain a higher hematocrit are indicated is a question that cannot yet be answered. However, patients with marginal cardiovascular function who are accepted on hemodialysis and must have an arteriovenous shunt should be supported in any manner to minimize an increase in cardiac output. Early and aggressive treatment of known episodes of sepsis is important in the elimination of valvular endocarditis in this patient population. Perhaps one of the finer indicators of adequacy of hemodialysis will be K rate and peak immunoreactive insulin levels. Continued abnormality of these parameters may contribute to cardiovascular disease. Clearly, further study of the effect of abnormal carbohydrate metabolism on lipid metabolism is in order. Serum triglyceride, serum cholesterol and lipid electrophoretic pattern should be followed to evaluate the beneficial effects of drug therapy and changes in dialytic technique on the development of cardiovascular disease. Careful monitoring of calcium, phosphorus, bone films and parathyroid hormone levels is indicated to assess parathyroid status. The use of aluminum binders and parathyroidectomy to prevent vascular and myocardial calcification is important in the therapy of these patients. The use of cardiac catheterization, coronary artery arteriography, and possibly cardiac vascular repair, should be considered in the chronic hemodialysis patient with coronary artery disease if he is otherwise well. Adequacy of hemodialysis perhaps can be evaluated through its effect on all of the above parameters. Whether or not changes in artificial kidney treatments can correct the final vascular disease remains to be seen.
 ...
PMID:Cardiovascular disease in uremic patients on hemodialysis. 109 1

The protease inhibitor aprotinin was given a) in experimental septic shock, and b) in patients with hepatic cirrhosis and ascites, since in both conditions, activation of the plasma kallikrein-kinin system is associated with pathological systemic vasodilatation, which may trigger reflex neuroendocrine activation and renal solute retention. Given early in experimental sepsis, aprotinin maintained the arterial pressure, systemic vascular resistance (SVR), creatinine clearance and sodium excretion, all of which fell in controls. Aprotinin also blocked increases in pulmonary artery pressure and plasma renin activity (PRA). Given late in sepsis, aprotinin caused a rapid rise in arterial pressure and SVR towards baseline levels. In cirrhosis, aprotinin increased SVR in patients with low baseline values, and improved glomerular filtration rate, renal plasma flow and sodium excretion in all subjects; PRA was suppressed by aprotinin. Aprotinin reverses pathological systemic vasodilatation in these two conditions, and this is associated with a reduction in renin release and improved renal function.
 ...
PMID:Vasoactive effects of aprotinin. 128 72

A hyperdynamic sepsis model was developed in dogs. It is based on a 3-hour clamping of the arteries supplying the middle portion of the jejunum. The ensuing sepsis has a course of several days, during which the animals were studied in the conscious state. 2/3 of the animals developed a sustained 32-108 per cent increase in cardiac output, and survived 7 days or more. In the other 1/3 of the animals, the cardiac output was lower than the control value and all these animals died within 5 days. There were no differences between the two groups in other parameters examined. Sepsis caused a steady, slight decrease in mean arterial pressure, an increase in heart rate, and leukocytosis. The plasma levels of epinephrine and norepinephrine showed a sustained, significant elevation. The level of thromboxane B2 was high only on the first day of sepsis, and that of plasma renin activity on the first 2 days. Necrosis and edema of jejunal villi were demonstrated histologically in the early period. Hemocultures were positive in only 5 of 11 animals examined, suggesting the predominant role of absorbed toxins. This model simulates human sepsis well and is suitable for the study of pathophysiologic mechanisms in hyperdynamic sepsis.
 ...
PMID:A canine model of hyperdynamic sepsis induced by intestinal ischemia. 207 25

Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome, and pregnancy. In recent years, the use of a sensitive radioimmunoassay for plasma vasopressin has implicated the role of nonosmotic vasopressin release in the water retention of these edematous disorders. In experimental studies and studies in man, it has been found that the nonosmotic release of vasopressin is consistently associated with the activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin (carotid and aortic baroreceptors) and in the activation of the renin-angiotensin system (renal beta-adrenergic receptors). These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. In this context, neither total extracellular-fluid (ECF) volume nor blood volume are determinants of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by either a fall in cardiac output (e.g. ECF volume depletion, low-output cardiac failure, pericardial tamponade, or hypovolemic nephrotic syndrome) or peripheral arterial vasodilation (e.g. high-output cardiac failure, cirrhosis, pregnancy, sepsis, arteriovenous fistulae, and pharmacologic vasodilators). With a decrease in effective arterial blood volume (EABV). initiated by either a fall in cardiac output or peripheral arterial vasodilation, the acute response involves vasoconstriction mediated by angiotensin, sympathetic mediators, and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The renal vasoconstriction which accompanies those states that decrease EABV, by either decreasing cardiac output or causing peripheral arterial vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A unifying hypothesis of sodium and water regulation in health and disease. 210 96

Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome and pregnancy. In recent years the use of a sensitive radioimmunoassay for plasma vasopressin has implicated the role of nonosmotic vasopressin release in the water retention of these edematous disorders. In experimental studies and studies in humans it has been found that the nonosmotic release of vasopressin is consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin (carotid and aortic baroreceptors) and activation of the renin-angiotensin system (renal beta-adrenergic receptors). These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. In this context neither total extracellular fluid (ECF) volume nor blood volume are determinants of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by either a fall in cardiac output (e.g. ECF volume depletion, low-output cardiac failure, pericardial tamponade or hypovolemic nephrotic syndrome) or peripheral arterial vasodilation (e.g. high-output cardiac failure, cirrhosis, pregnancy, sepsis, arteriovenous fistulae and pharmacologic vasodilators). With a decrease in effective arterial blood volume (EABV), initiated by either a fall in cardiac output or peripheral arterial vasodilation, the acute response involves vasoconstriction mediated by angiotensin, sympathetic mediators and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The renal vasoconstriction which accompanies those states that decrease EABV, by either decreasing cardiac output or causing peripheral arterial vasodilation, limits the distal tubular delivery of sodium and water thus maximizing the water-retaining effect of vasopressin and impairing the normal escape from the sodium-retaining effects of aldosterone. The elevated glomerular filtration rate and filtered sodium load in pregnancy allows increased distal sodium and water delivery in spite of a decrease in EABV, thus limiting edema formation during gestation.
 ...
PMID:Pathophysiology of vasopressin in edematous disorders. 269 4

The time course of the components of the renin-angiotensin system was investigated in the plasma of three patients on the intensive care unit. Two of them, which were both polytraumatized, suffered from adult respiratory distress syndrome (ARDS). All patients had sepsis and impaired pulmonary and renal function. Plasma samples were investigated for up to two weeks, in which time all three patients showed a decrease in their angiotensin converting enzyme (ACE) plasma concentration. Two of the patients with deteriorating renal function had three to four times elevated angiotensinogen (Ao) plasma levels, which were measured by both the direct and indirect radioimmunoassay. The ratio of the mean values between both assays was 1:1 in two patients and shifted to higher values in the direct assay in the third patient. This suggests that higher amounts of des-AngI-angiotensinogen were present in the latter patient, because "inactive" Ao is also detected by the direct assay. The decrease in active Ao may be caused by an up to twenty times elevated plasma renin activity (PRA). The PRA was correlated with the angiotensin I (AngI) plasma levels. However, at PRA values higher than 200 pmol AngI/ml/h this correlation decreased because of the rapid substrate consumption. In addition there was a good correlation between AngI and AngII plasma levels in two patients which could not be observed in the patient with the highest PRA and AngII values. A relationship between plasma ACE concentration and AngII formation could not be observed. Thus in two of the three septic patients the components of the renin angiotensin system were extremely stimulated at very low blood pressure values. These data show, that it is reasonable to follow the time course of the components of the renin angiotensin system in single patients. In addition it is demonstrated that the direct measurement of Ao is a valid supplement in the diagnosis of the renin angiotensin system.
 ...
PMID:Renin-angiotensin system in sepsis. 282 Jun 28

To study the role of thromboxane in systemic sepsis and renal failure, peritonitis was induced surgically in 22 sheep, leading to local and systemic sepsis. A selective thromboxane synthetase inhibitor, U63,557A (Upjohn Co, Kalamazoo, MI) was given before surgery in five animals and 30 minutes after surgery in five animals. A typical picture of volume-loaded, normotensive, vasodilated septic shock developed in all animals. Twenty four hours after induction of sepsis, the control group showed a marked reduction in glomerular filtration rate (GFR), urine volume, and urinary sodium excretion. Pretreated animals showed no change in GFR and a smaller reduction in urine volume and sodium excretion. The posttreatment group showed no change in any parameters of renal function. Plasma renin activity, urinary TXB2 excretion, and urinary 6-keto PGF1 alpha excretion increased after 24 hours only in the control group. Urinary TXB2 excretion was reduced by 80% in animals given U63,557A before surgery. The results indicate a significant protective effect of U63,557A on renal function during septic shock, probably related to reduced thromboxane synthesis, with no apparent deleterious systemic effects. The results support a role for thromboxane in the pathogenesis of acute renal failure in systemic sepsis.
 ...
PMID:The protective effect of thromboxane synthetase inhibition on renal function in systemic sepsis. 291 66

We investigated the association between plasma catecholamines and the renal response to nonhypotensive sepsis. Arterial plasma catecholamines were measured in 16 sheep, before and 24 h after surgical induction of peritonitis. Animals were volume loaded with lactated Ringer's solution (8 L/24 h) before and after surgery; non became hypotensive. For analysis, animals were retrospectively divided into those with increased serum creatinine after 24 h of sepsis (group 1, n = 8) and those without (group 2, n = 8). Group 1 showed increased cardiac index and decreased systemic vascular resistance typical of severe sepsis, with decreased glomerular filtration rate (GFR), oliguria, sodium retention, increased plasma renin activity (PRA), decreased urinary kallikrein excretion, and increased urinary 6-keto-prostaglandin-F1 alpha excretion. Group 2 showed insignificant hemodynamic disturbance, and no significant renal response. Plasma catecholamines were equal in both groups at baseline. In group 1, there were uniform increases after 24 h in plasma norepinephrine (474 +/- 115 to 1183 +/- 158 [SEM] pg/ml; p less than .01) and plasma epinephrine (108 +/- 8 to 309 +/- 70 pg/ml; p less than .05). In group 2, neither plasma norepinephrine (343 +/- 59 to 330 +/- 56 pg/ml) nor plasma epinephrine (116 +/- 16 to 116 +/- 13 pg/ml) changed significantly. Plasma norepinephrine correlated inversely with GFR; plasma epinephrine correlated with PRA. The sympathetic nervous system may be involved in the renal response to nonhypotensive sepsis, both directly and via effects on other vasoactive hormone systems.
 ...
PMID:Association between renal and sympathetic responses to nonhypotensive systemic sepsis. 316 6

The pathophysiology of renal dysfunction in generalized sepsis remains unknown. In this study, 24 hours after surgical induction of peritonitis in 20 volume-loaded sheep, three patterns of renal function were seen. In group 1 (n = 8), glomerular filtration rate (GFR) decreased by 70%, urine volume by 85%, absolute sodium excretion by 95%, and fractional sodium excretion by 83%. Group 2 (n = 4) exhibited similar sodium retention but GFR did not fall. Group 3 (n = 8) showed no change in GFR or urine volume and only minimally reduced sodium excretion. Mean arterial pressure fell 17% in group 1 only; central venous pressure, pulmonary capillary wedge pressure, and plasma volume were maintained at or above presepsis values in all groups. Cardiac index was either increased or unchanged, and renal plasma flow was maintained in all groups; there was thus no hemodynamic evidence to suggest volume contraction. Histologic examination showed only minor changes with no consistent pattern. Renal functional changes correlated with other manifestations of severe sepsis--GFR and sodium retention correlated significantly with increased cardiac index, decreased systemic vascular resistance, pulmonary arterial hypertension, leukopenia, hypoproteinemia, and hypoglycemia. All of these changes were most marked in group 1. In groups 1 and 2, plasma renin activity (PRA) increased and urinary kallikrein excretion decreased. PRA correlated inversely with GFR, urine volume, and sodium excretion; urinary kallikrein excretion correlated positively with urine volume and sodium excretion. Urinary excretion of 6-keto-PGF1 alpha was increased in groups 1 and 2 and correlated inversely with mean arterial pressure in group 1 animals. During sepsis, urinary thromboxane B2 excretion continued at presepsis values in all groups. The results suggest that unusual reciprocal changes in activity of the renin-angiotensin and renal kallikrein-kinin systems may play a role in the renal response to sepsis. PGI2 synthesis is increased and may affect systemic hemodynamics and renal function; the role of thromboxane A2 in this context is unknown.
 ...
PMID:Vasoactive hormones in the renal response to systemic sepsis. 327 70


1 2 3 4 5 6 7 8 9 Next >>