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

  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)


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