الفهرس 
PATHOPHYSIOLOGY & IMPAIRED IMMUNITY IN SEPSISOnly 14 pages are availabe for public view
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Abstract
S
epsis causes disruption of heomeostasis through a currently cascade of excessive inflammation and coagulation.
The pathophysiology of sepsis is complex and results from the effects of circulating bacterial products, mediated by cytokine release, occurring as a result of sustained bacteraemia.
Early in septic shock, the rise in cardiac output is often limited by hypovolemia and a fall in preload because of low cardiac filling pressures. When intravascular volume is augmented, the cardiac output is usually elevated, but the performance of the heart reflected by stroke work is usually depressed and the blood lactate level is elevated. Myocardial depression with peripheral vasodilation and a reduced systemic vascular resistance are the characteristic hemodynamic features found in patients with sepsis.
Fluid resuscitation is a fundamental aspect of the heomodynamic management of patients with septic shock and should ideally be achieved before vasopressors are used, but it is frequently necessary to employ vasopressors early as an emergency measure in patients with septic shock.
The goal of resuscitation should achieve adequate levels of oxygen delivery or avoid flow-dependent tissue hypoxia.
Surgery, trauma, burns and injury induce an inflammatory response that can become excessive and damaging in some patients. This hyper inflammation can be followed by an immunosupresses state which increases susceptibility to infection. The resulting septic syndromes are associated with significant morbidity and mortality.
Nutrients are able to modulate inflammation and to maintain or improve immune function. These include several amino acids, antioxidant vitamins and minerals, long chain n-3 fatty acids, probiotics and nucleotides. Each of these nutrients have a role in surgical, injured or critically ill patients.
One of these immunonutrients is arginine amino acid. Arginine supplementation increases NO formation and the mitotic response of peripheral lymphocytes to standard stimuli in healthy subjects and postoperative patients. Moreover, arginine in combination with other immunonutrients reduces infectious complications, days on ventilator and hospital stays particularly in patients undergoing elective surgery.
Immunonutrition with arginine can be safely used in surgical patients, SIRS, sepsis and organ failure.
Another immunonutrient is glutamine. Glutamine administration reduces GI bacterial translocation and increases the synthesis of DNA and RNA, the activation and proliferation of lymphocytes and macrophages and the expression of interleukins IL-1 and IL-2. Glutamine supplementation protects the GI mucosa in different models of injury probably by preserving intracellular glutathione levels and by stimulating cell proliferation and protein synthesis.
Glutamine supplementation apart from improving GI function, sustains systemic immune function and nitrogen balance. In surgical and critically ill patients, glutamine supplementation reduces the incidence of infection, hospital stay and costs. Glutamine appears to be an ideal and necessary compound of nutrition in severe burn injury.
Enteral provision of glutamine decreased the incidence of pneumonia, bacteraemia and sepsis in critically ill patients. Parenteral glutamine decreased the incidence of infections in recipients of bone marrow transplantation and changed the pattern of mortality in patients in intensive care. These clinical benefits of glutamine seem to be associated with improvements in intestinal integrity and in cellular immune function.
Also glycine has a wide spectrum of protective proprieties against different diseases and injuries. As such, glycine represents a new anti-inflammatory, immuno-mudulatory and cytoprotective agent. Glycine suppresses the inflammatory response, tissue damage and multiple organ failure thus protecting against ischemia-reperfusion injury. Glycine appears to moderate immunological reactions and may prove useful in diminishing rejection after transplantation.
Glycine decreases organ injury and improves survival after hemorrhagic shock and resuscitation so, Glycine therefore could be an effective therapy for shock. Glycine ameliorate liver fibrosis, possesses significant anti-ulcer, cytoprotective activity and anticancer property.
Omega-3 PUFAs also show protective effects against the development of tumors, metastases and cachexia. It seems that among PUFAs only EPA can reverse in vivo the metastatic process. This might explain the prolonged survival observed among patients with metastatic cancer, consuming an w-3 PUFA- enriched diet.
Nucleotide supplementation has become an area of intensive research and significant interest in immuno-modulation for maintenance of cellular immune responses. Exogenous nucleotide supplementation is beneficial in the maintenance and restoration of the immune response during stress condition and in critically ill patients.
Nucleotide infusions have been used in several clinical situations. Infusions of adenosine and ATP produce potent vasodilation in treatment of hemorrhagic shock, tissue ischemia, pulmonary hypertension and intracellular aerobic metabolism. Adenosine therefore acts as a homeostatic.
Plasma antioxidant micronutrient concentrations are decreased during critical illness and especially during sepsis, as the result of losses, low intakes, dilution by resuscitation fluids, and the SIRS-mediated redistribution to tissue creating a circulating antioxidant defense deficit. The evidence revealed an increasing antioxidants supplementation contributes in limiting tissue and organ damage caused by sepsis mediators.
Three antioxidant nutrients already have undergone successful clinical testing reaching a top level of evidence, selenium improves clinical outcome (infections, organ failure), glutamine reduces infectious complication in large trails; and the association of eicosapentaenoic acid and micronutrients blunted endotoxin response. Other antioxidants as N-acetylcysteine, Vitamin E, Vitamin C and Zink have had clinical benefits in critically ill patients in different conditions as antioxidants and diet enhancing immunity.