Pathogenesis of Vibrio cholera

  • The sequence of events leading to cholera is basically simple and confined to the gut.
  • The food and drink contaminated by cholera vibrios if ingested results to disease though small dosage is present.
  • The organisms begin to multiply in the alkaline medium of the small intestine after passing the acid barrier of the stomach juices.
  • The incubation period varies from 6 hours to 3 days.
  • The human vomitus and faeces or carriers are the main sources of infection.
  • A well-defined sequence of events occurs following the ingestion of V. cholera. They are as follows:

a)Adherence and colonization

  • Virulent forms of V. cholera attach to the epithelium of microvilli at the brush border no sooner it crosses the acid barrier.
  • After that, they multiply increasing their number.

b)Secretion of cholera toxin

  • As they multiply, they produce a potent exotoxin called enterotoxin.
  • Toxin is produced in close proximity to its specific receptors (GM1 ganglioside) on cell membrane lining the villi and crypts of the small intestines.

c)Activation of the A1 subunit

  • After there is binding of the B unit to the receptor of the cell membrane, the A subunit dissociates from the B subunit.
  • The cell membrane gets penetrated during this dissociation.
  • There are two subunits of A-unit: A1 and A2 which are joined by disulphide bond.
  • The bond between A1 and A2 subunits is broken down and subunit A1 gets activated.
  • The ADP ribose is transferred from a nicotinamide adenine dinucleotide (NAD) to a guanosine triphosphate (GTP)-bindind protein by enzymatic action of activated A1 subunit.
  • The adenyl cyclase activity gets regulated by the above event.
  • Adenyl cyclase activity of the cell increases because of the normal GTP “turn off” mechanism is inhibited.
  • This results in an increase and accumulation of intracellular cyclic 3’, 5’-adenosine monophosphate (cAMP).

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  • The increased intracellular cAMP level causes various activities like:

i)Inhibition of reabsorption of Na+, K+ and Cl ions by cells lining the villi, together with

ii)Hyper-secretion of Cl and HCO3

  • The above activities cause a net loss of sodium, potassium and sodium bicarbonate into the intestine, with a corresponding fluid loss to maintain the isotonicity of the intestinal fluid.
  • There is purging diarrhea of “rice water stool” with loss of water and electrolytes.
  • The fluid secreted is isotonic with plasma with a relatively higher concentration of sodium, potassium and bicarbonate and lower concentration of chloride.

 

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Pathogenesis of Vibrio cholera

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