Pathophysiology
Although the mechanisms by which Giardia causes injury have not been fully elucidated yet, the research points to a multifaceted attack. Those putative attack sites include endothelial brush border damage, enterotoxin production, immunological reaction, and alternation of gut motility.
The attachment of trophozoites, of which Giardia lamblia is one, causes loss of brush border surface area, villus flattening, and inhibition of dissachardidase activities. Ultimately, the enteric microbiota of the intestine overgrow and may be the cause of further symptoms. This idea has not been fully investigated. The alteration of the brush border and villi leads to an inability for nutrient and water absorption from the intestine. This results in diarrhea, one of the predominant symptoms. In the case of asymptomatic giardiasis, there can be malabsorption with or without histological changes to the small intestine. The degree to which malabsorption occurs in symptomatic and asymptomatic cases is highly varied.
Interestingly, the species Giardia intestinalis has proteinases that attack the villi of the brush border and appear to increase crypt cell proliferation and crypt length. Crypt cells existing on the sides of the villi.
On an immunological level, activated host T-lymphocytes attack endothelial cells that have been injured in order to remove the cell. This occurs after the disruption of the tight junctions between endothelial cells that make up the brush border. The result is heavily increased intestinal permeability.
There appears to be a further increase in apoptosis by Giardia intestinalis which further damages the intestinal barrier to permeability. There is siginificant up-regulation of the apoptotic cascade by the parasite. Furthermore, substantial down regulation of the anti-apoptotic proteins Bcl-2 and upregulation of the proapoptotic protein Bax. These connections suggest a role of caspase-dependent apoptosis in the pathogenesis of giardiasis.
Giardia protects its own growth by reducing the formation of nitric oxide by consuming all local arginine which is the necessary substrate for the production of nitric oxide. Arginine starvation is known to be a cause of programmed cell death and local removal is a strong apoptotic agent.
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