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

We report a female patient presenting with sepsis and multi-organ failure following eclampsia and intrauterine childdeath. In the phase of recovery, the patient developed consciousness disorder and coma characterized by fasciculation, generalized myoclonia and respiratory insufficiency. The clinical picture corresponded to that of Lance Adam's syndrome. A quick change in the composition of body fluids in the polyuric phase of renal insufficiency associated with an antidiuretic hormone deficit was a cause of that disorder. Metabolic dysfunction and hyperexcitability of neurons developed as a result. Hyperexcitability of the caudal part of the medulla oblongata was responsible for the development of myoclonia. Following the correction of that disorder, the patient completely improved.
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PMID:[Disorders of consciousness due to disorders of body fluid composition--case report of a female patient]. 864 63

The immune and endocrine mediators that are released during sepsis (e.g., tumor necrosis factor [TNF] alpha, interleukin [IL]-1, IL-6, transforming growth factor [TGF] beta, prostaglandin [PG] E2, catecholamines, vasopressin, glucagon, insulin, and glucocorticoids) can produce inappropriate detrimental cellular responses contributing to exacerbation of septic injury. Examples of such sepsis-related inappropriate responses are: exaggerated hepatic acute-phase protein (APP) expression and release skeletal muscle insulin resistance, and suppressed T-lymphocyte proliferation. The studies discussed in this article present evidence that the generation of the sepsis-related hepatic, skeletal muscle, and T-lymphocyte responses emanate from alterations in intracellular Ca2+ (Ca2+i) homeostasis. In hepatocytes, there is indication of a sepsis-mediated increase in Ca2+ influx from the extracellular milieu leading to a sustained increase in the apparent resting cell Ca2+i concentration ([Ca2+]i) and its depressed elevation on stimulation with Ca2+-mobilizing hormones such as catecholamines and vasopressin. These Ca(2+)- related changes can affect not only the signaling pathways in which Ca2+i itself serves as a signaling component, but also the signaling systems turned on by other sepsis-induced agonists which may not be dependent on Ca2+ signaling. TGF-beta, IL-1, TNF alpha, and IL-6 activate a primarily protein kinase C (PKC)-dependent intracellular signal system for the elicitation of a normal hepatic APP response (APPR). The increased apparent basal [Ca2+]i in sepsis can hypersensitize PKC activation and thus lead to an exaggerated APPR. In the skeletal muscle, an evident increase in Ca2+ membrane flux during sepsis pointed to an increase in the basal [Ca2+]i resulting from a plausible cytokine-mediated overactivation of the voltage-sensitive Ca2+ channels. The increased basal [Ca2+]i can negatively modulate the insulin-mediated stimulation of GLUT4-dependent glucose transport despite the possibility that Ca2+i might not participate as a component in the insulin-receptor-regulated signaling pathway. Increased [Ca2+]i in skeletal myocytes can either directly promote the phosphorylation of GLUT4 or prevent its dephosphorylation, both of which effectively block insulin stimulation of glucose uptake, thereby contributing to insulin resistance. In T lymphocytes, septic injury appears to induce an attenuation in the mitogen and, thus, presumably a T-cell antigen receptor (TCR)-mediated elevation in [Ca2+]i without affecting the basal [Ca2+]i. This decrease in TCR-related Ca2+i mobilization evidently contributes to the suppression of T lymphocyte proliferation during sepsis, probably via an in vivo action of prostaglandin (PG) E2 on the T cells during sepsis. The blockade of PGE2 production after indomethacin administration to septic animals prevents alterations in both T-cell Ca2+i mobilization and proliferation. PGE2 probably acts through its second messenger, cyclic adenosine 3'5'-monophosphate, which can antagonize Ca2+i signaling in T cells.
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PMID:Alterations in calcium signaling and cellular responses in septic injury. 868 77

Various vasoactive substances are involved in the regulation of the macro- and microcirculation. We have investigated if these regulators change during long-term volume therapy with human albumin (HA) or hydroxyethylstarch solution (HES) in trauma and sepsis patients. To maintain pulmonary capillary wedge pressure (PCWP) at 10-15 mm Hg, either 20% HA (HA-trauma, n = 14; HA-sepsis, n = 14) or 10% low-molecular weight HES solution (HES-trauma, n = 14; HES-sepsis, n = 14) were infused for 5 days, otherwise patient management did not differ between the two groups (trauma/sepsis). Mean arterial pressure (MAP), heart rate (HR), PCWP and cardiac index (CI) were monitored in all patients. Liver function was assessed using the monoethylglycinexylidide (MEGX) test, and gastric intramucosal pH (pHi) was monitored by tonometry to assess splanchnic perfusion. Plasma concentrations of vasopressin, endothelin-1, adrenaline, noradrenaline, atrial natriuretic peptide and 6-keto-prostaglandin F1 alpha were measured from arterial blood samples. All measurements were carried out on the day of admission to the intensive care unit (trauma patients) or on diagnosis of sepsis, and daily over the next 5 days at 12:00. MAP, HR and PCWP did not differ between the corresponding subgroups (trauma/sepsis). Cl increased significantly more in the HES than in the HA groups. pHi and MEGX plasma concentrations did not differ in the trauma patients throughout the study. Both were lower than normal in the sepsis groups and increased more markedly in the HES than in the albumin-treated patients (P < 0.05). In the trauma patients, concentrations of all vasoactive regulators were very similar in both groups. In both sepsis groups, vasopressors (vasopressin, endothelin-1, noradrenaline and adrenaline) were significantly increased above normal at baseline and decreased more markedly in HES than in HA patients. Concentrations of atrial natriuretic peptide increased only in the HA patients (from 159 (SD 31) to 215 (38) pg ml-1 on day 2). Plasma concentrations of 6-keto-prostaglandin F1 alpha decreased significantly only in the HES sepsis patients (from 112 (25) to 47 (15) pg ml-1).
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PMID:Influence of different volume therapy regimens on regulators of the circulation in the critically ill. 2443 72

The role of superoxide in sepsis-altered hepatocyte Ca2+i regulation was studied by examining the effect of treatment of septic rats with superoxide dismutase-polyethylene glycol (SOD-PEG) on hepatocyte Ca2+ influx and efflux, and cytosolic [Ca2+]. Rats were implanted with sterile or bacteria-laden (Escherichia coli and Bacteroides fragilis) fecal pellets into the abdominal cavity. Eight hours after the implantation, rats were treated with SOD-PEG or its vehicle PEG. Septic and sterile implanted rats were killed 24 h postimplantation, and their livers were removed to isolate viable hepatocytes. Isolated hepatocytes were incubated with traces of 45Ca to assess Ca2+ influx and efflux. The 45Ca exchange assessments also allowed calculation of the intracellular exchangeable Ca2+ contents. [Ca2+]i was quantified by the use of fluorescent dye indo-1 and microfluorometric techniques. There were no differences in the Ca2+ influx, Ca2+ efflux, intracellular exchangeable Ca2+, or [Ca2+]i between the treated or untreated sterile and unoperated controls. However, compared with the nonseptic groups, the septic rats with or without administration of the vehicle (PEG) showed marked increases in Ca2+ influx, intracellular exchangeable Ca2+ and [Ca2+]i but not Ca2+ efflux. When challenged with vasopressin, the hepatocytes from septic rats, administered with PEG alone, did not elevate their [Ca2+]i as was characteristic of the hepatocytes from the nonseptic rats. The treatment of septic rats with SOD-PEG was effective in restoring Ca2+ influx, cellular exchangeable Ca2+, [Ca2+]i, and the [Ca2+]i response to vasopressin to levels found in the control and sterile groups. These findings support the concept that the generation of the superoxide free radical leads to Ca2+i-related derangements and related cell/organ dysfunction in sepsis.
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PMID:Superoxide radical scavenging prevents cellular calcium dysregulation during intraabdominal sepsis. 911 Apr 11

Nitric oxide (NO) is known to be involved in the modulation of neuroendocrine function. To clarify the role of different isoforms of NO synthase (NOS) in the neuroendocrine response to immune challenge, the expressions of neuronal NOS (nNOS) and inducible NOS (iNOS) genes in the hypothalamus following lipopolysaccharide (LPS) injection were examined using in situ hybridization. NOS activity was also determined by NADPH-diaphorase (NADPH-d) histochemistry. LPS (25 mg/kg) or sterile saline was injected intraperitoneally to male Wistar rats and the rats sacrificed 30 min, or 1, 2, 3, 5, 12 or 24 h after injection. nNOS mRNA expression in the paraventricular nucleus (PVN) was significantly increased 2 h after LPS injection. iNOS mRNA, which was not detected until 2 h after LPS injection, was significantly increased in the PVN 3 h after LPS injection. Both RNA expressions had returned to basal levels by 12 h after LPS injection. The number of NADPH-d positive cells was significantly increased 5 h after LPS injection. iNOS expression was more robust in parvocellular PVN, while nNOS was distributed mainly in the magnocellular PVN. Double in situ hybridization histochemistry revealed that some of the iNOS- (48.4%) or nNOS-positive cells (34. 3%) in the parvocellular PVN expressed CRF mRNA. The results demonstrate that LPS-induced sepsis causes significant increases in nNOS and iNOS gene expression with different time-courses and distributions, and that iNOS mRNA was more frequently co-localized with CRF-producing parvocellular neurons in the PVN. Thus, NO produced by iNOS and nNOS may play an important role in the neuroendocrine response to an immune challenge. Distinct differences in the distribution and time-course changes of iNOS and nNOS suggest different roles for the hypothalamic-pituitary-adrenal axis and/or neurohypophyseal system.
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PMID:Distinct distribution and time-course changes in neuronal nitric oxide synthase and inducible NOS in the paraventricular nucleus following lipopolysaccharide injection. 1006 18

Micropipette application of certain vasoconstrictor or -dilator substances onto the surface of arterioles induces both a local vasomotor response and a response which is propagated up- and downstream along the vessel, a so-called conducted vasomotor response. In some vascular beds conducted vasoconstrictor and dilator responses are detectable more than a millimetre from the site of agonist delivery. While agonists such as acetylcholine, noradrenaline, and KCl almost invariably give rise to conducted vasomotor responses others, such as sodium nitroprusside or vasopressin, do not. Conducted vasomotor responses in arterioles appear to rely on passive electrotonic spread of the change in membrane potential induced by the agonist at the tip of the pipette. Presumably the current spreads up- and downstream along the arteriolar wall through endothelial or smooth muscle cell gap junctions. Whether the electrical signal is conducted primarily through the endothelial or the smooth muscle cell layer or both is currently not known, but it may depend on the agonist used. Experiments have suggested that conducted vasodilation in skeletal muscle feed arterioles plays an important role in the development of functional hyperaemia at the onset of exercise. In the kidney, conducted vasoconstriction is believed to be responsible for the upstream contraction of the afferent arteriole and interlobular artery known to occur in response to activation of the macula densa. Therefore conducted vasoconstriction could be important for the tubuloglomerular feedback mechanism. Finally, experimental studies have shown that conduction of vasomotor responses in arterioles may be altered in pathological conditions associated with microvascular dysfunction such as arterial hypertension and sepsis.
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PMID:Conducted vasomotor responses in arterioles: characteristics, mechanisms and physiological significance. 1051 72

Vasopressin (antidiuretic hormone) is emerging as a potentially major advance in the treatment of a variety of shock states. Increasing interest in the clinical use of vasopressin has resulted from the recognition of its importance in the endogenous response to shock and from advances in understanding of its mechanism of action. From animal models of shock, vasopressin has been shown to produce greater blood flow diversion from non-vital to vital organ beds (particularly the brain) than does adrenaline. Although vasopressin has similar direct actions to the catecholamines, it may uniquely also inhibit some of the pathologic vasodilator processes that occur in shock states. There is current interest in the use of vasopressin in the treatment of shock due to ventricular fibrillation, hypovolaemia, sepsis and cardiopulmonary bypass. This article reviews the physiology and pharmacology of vasopressin and all of the relevant animal and human clinical literature on its use in the treatment of shock following a MEDLINE (1966-2000) search.
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PMID:Vasopressin and shock. 1193 28

The reduced pressure response to vasopressin during acute sepsis has directed our interest to the regulation of vasopressin V(1A) receptors. Rats were injected with lipopolysaccharide for induction of experimental gram-negative sepsis. V(1A) receptor gene expression was downregulated in the liver, lung, kidney, and heart during endotoxemia. Inasmuch as the concentrations of proinflammatory cytokines such as interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma were highly increased during sepsis, the influence of these cytokines on V(1A) receptor expression was investigated in primary cultures of hepatocytes and in the aortic vascular smooth muscle cell line A7r5. V(1A) receptor expression was downregulated by the cytokines in a nitric oxide-independent manner. Blood pressure dose-response studies after injection of endotoxin showed a diminished responsiveness to the selective V(1) receptor agonist Phe(2),Ile(3),Orn(8)-vasopressin. Our data show that sepsis causes a downregulation of V(1A) receptors and suggest that this effect is likely mediated by proinflammatory cytokines. We propose that this downregulation of V(1A) receptors contributes to the attenuated responsiveness of blood pressure in response to vasopressin and, therefore, contributes to the circulatory failure in septic shock.
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PMID:Cytokine-mediated downregulation of vasopressin V(1A) receptors during acute endotoxemia in rats. 1189

Vasodilatory shock is a syndrome with high mortality. It is becoming evident that depletion of antidiuretic hormone (ADH) after cardiac surgery or during sepsis plays an important role in the pathogenesis of this condition. Established vasodilatory shock responds well to exogenous ADH infusion. It is possible that preventing ADH depletion at an earlier stage may abrogate the onset of vasodilatory shock, or at least reduce its severity. This paper examines the evidence supporting this concept, and the potential areas of concern in considering this particular type of hormone replacement therapy.
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PMID:Antidiuretic hormone replacement therapy to prevent or ameliorate vasodilatory shock. 1220 65

The antidiuretic hormone (ADH) vasopressin is a simple peptide hormone with a number of complex, essential physiological actions. It is becoming clear that this hormone is developing an important therapeutic role in a number of different conditions. These include vasodilatory shock due to sepsis or cardiac surgery, cardiac arrest, and prolonged/excessive bleeding caused by, for example, variceal haemorrhage. This article reviews the physiology of ADH relevant to these actions and scrutinises the evidence for its therapeutic applications.
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PMID:The physiology and emerging roles of antidiuretic hormone. 1251 Sep 52


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