SEPSIS SYNDROME

R.A.S HEMAT, MB;BCh, FRCSI, DUL.

Urosepsis, a subset of an infectious septic process, is defined as an inflammation of the upper urinary tract that causes seeding of the blood with bacteria resulting in local and distant destruction of tissues. Urosepsis pathobiology is a complex and not fully understood mechanism. Lipopolysaccharide (LPS) complex act as endotoxin, but its rule is controversial. Septic shock is the most common cause of death in medical and surgical ICU. Patients with sepsis present with evidence of infection and clinical manifestations of inflammation, severe sepsis is the development of hypoperfusion with organ dysfunction in a septic patient, and septic shock is hypoperfusion and persistent hypotention in a septic patient.

Mediators of pathobiology of bacteraemia:
1- Endogenous pyrogens (leukocyte endogenous mediator, IL1).
2- Catecholamines.
3- Serotonin.
4- Histamine
5- Acetylcholine.
6- Glucocorticoids.
7- Kinins.
8- Complement components (anaphylatoxins).
9- Coagulation components.
10- Prostaglandin.
11- Lysosomal components.
12- Slow-reacting substance.
13- Macrophages and lymphocyte products.
14- Myocardial depressant factor.

NO may promote cytokine-mediated injury by increasing TNF production from human phagocytic cells, and thus NOS inhibitor may have anti-inflammatory activity. Moderate to severe infection is associated with 150-200% increase in glucose production rate. TNFa induces hyperglycaemia and relatively insulin resistance. TNFa induces hyperglycaemia and relatively insulin resistance. TNFa induces circulatory shock, DIC, and death. Endoxaemia and cytokinaemia are involved in the development of DIC. Hyperketonaemia is related to the usually relatively high insulin levels encountered in septic patients. Lactate levels in the blood become elevated, even in the absence of hypoxia. Bacterial translocation denotes the passage of bacteria from the intestine lumen.

Neuroendocrine and sympathetic nervous system are activated during sepsis. Sepsis is associated with persistently elevated levels of epinephrine, norepinephrine, ACTH, cortisol, growth hormone, and glucagon. Cell death may generate an endocrine response that will rapidly utilise energy reserves necessary during MOSF. Opioids are released as part of the hormone cascade in response to stress, cause vasodilation which worsens failing organs by decreasing oxygen exchange. Corticotropin causes the production, release, and circulation of cortisol and glucagon at damaging level.

In critically ill patients, most of the protein and potassium that is lost from the body comes from the cells. Glutamine released from skeletal muscle accounts for about 30% of the nitrogen released from peripheral tissues during sepsis. The kidney extracts glutamine from the blood stream and utilises an ammonium ion from the glutamine to neutralise excess hydrogen ions. Depletion of glutamine to combat acidosis may be another reason for the accelerated nitrogen loss observed in septic patients.
The systemic inflammatory response syndrome (SIRS) at best defines the population at risk for MODS, not all SIRS patients develop MODS. MODS is the consequence of a dysregulated biological response mediated by inappropriate and excessive secretion of endogenous inflammatory mediators into the general circulation. In 1980, it was reported that Gram-negative sepsis is the most common predecessor of MODS. Bacterial endotoxin, the lipopolysaccharide component of the cell membrane, was identified as a likely cause of the syndrome following Gram-negative infection. By the mid-1980s, it was reported that between one third and two thirds of patients with MODS failed to demonstrate bacteraemia. MODS changes the functional relationships among organs, and that restoration of these functional relationships is necessary to recover. Age is an important predictor of the irreversibility of MODS (death).

MOF, MODS, and SIRS are not diseases or even syndromes. They are the final pathway to death in the modern organ-supporting ICU. IL6 rather than TNFa is relevant as a mediator for the induction of the procoagulant response in sepsis.

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Dr. R.A.S HEMAT declares no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, stock holdings, gifts, or honoraria.