- 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.
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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).
- The increased intracellular cAMP level causes various activities like:
- Inhibition of reabsorption of Na+, K+ and Cl– ions by cells lining the villi, together with
- 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.
Pathogenesis of Vibrio cholera