article : Bacterial Endotoxin

Endotoxin: Complex bacterial toxin; lipopolysaccharide (LPS) component of Gram-negative cell walls is composed of Lipid A + Core Polysaccharide + O Antigen (a.k.a., O polysaccharide side chain) and is released upon lysis of the cell during infection ; Lipid A component is responsible for endotoxin activity effects on the host; O side chain is the antigenic portion of the LPS molecule

Septic shock (sepsis): Associated with overwhelming infection resulting in vascular system failure with sequestration of large volumes of blood in capillaries and veins; Activation of the complement and kinin systems and the release of histamines, prostaglandins, and other mediators may be involved

Endotoxemia: Endotoxin in the blood

Effects of Endotoxin

Binds to specific receptors on macrophages, B lymphocytes and other cells

Stimulates release of acute phase immunoreactants and lymphokines (e.g., IFN-g, IL-1, TNF-alpha, IL-6, histamine, prostaglandins)

Stimulates growth of B cells (mitogenic)

Fever (Pyrogenicity):

Any elevation of the body temperature above the normal; functions to speed up immune reactions and to limit/slow bacterial growth and multiplication

Activation of alternative complement pathway: C3a; C5a

Circulatory system effects:

Leukopenia followed by leukocytosis:

Leukopenia: an abnormal reduction in the number (-penia) of leukocytes inthe blood, (specifically a count of 5000 or less per cubic millimeter)

Leukocytosis: an abnormal increase in the number (-cytosis) of leukocytes in the blood, as during hemorrhage, infection, inflammation, or fever (specifically a count of 12,000 or more per cubic millimeter), respectively

Increased vascular permeability (vasodilation)

Decreased peripheral circulation

Decreased perfusion (blood flow) of blood to major organs

Capillary leakage; microhemorrhage; formation of petechiae (round, purple lesions caused by intradermal or submucosal microvascular hemorrhaging)

Hypotension (low blood pressure)

Effects on blood coagulation:

(DIC) Disseminated intravascular coagulation:

Disorder characterized by a reduction in the elements involved in blood coagulation due to their utilization in widespread blood clotting within the vessels; Late stages marked by profuse hemorrhaging

Activation of clotting pathway

Thrombosis: Formation of blood clot (thrombus) in heart or blood vessel

Thrombocytopenia: Abnormally low numbers of blood platelets

Effects on metabolic and liver functions

Decreased iron availability

Hypoglycemia: Abnormally low glucose levels

Cellular death (cytotoxicity)

Organ necrosis:

Sum of morphological changes indicative of cell death and caused by the progressive degradative action of enzymes

Shock:

Characterized by failure of the circulatory system to maintain adequate blood flow to the vital organs

Symptoms include: Hypotension; Weak pulse; Rapid and shallow breathing; Low body temperature; CNS (central nervous system) effects (e.g., nausea)

Death

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Revised: September 2003
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