What is the mechanism of injury in giardiasis?

Updated: Oct 01, 2018
  • Author: Hisham Nazer, MBBCh, FRCP, DTM&H; Chief Editor: Burt Cagir, MD, FACS  more...
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Answer

The mechanisms by which Giardia causes diarrhea and intestinal malabsorption are probably multifactorial and not yet fully elucidated. [19] Postulated mechanisms include damage to the endothelial brush border, enterotoxins, immunologic reactions, and altered gut motility and fluid hypersecretion via increased adenylate cyclase activity.

Adhesion of trophozoites to the epithelium has been demonstrated to cause increased epithelial permeability. Giardia- induced loss of intestinal brush border surface area, villus flattening, inhibition of disaccharidase activities, and eventual overgrowth of enteric bacterial flora appear to be involved in the pathophysiology of giardiasis but have yet to be causatively linked to the disease's clinical manifestations.

Marked or moderate partial villous atrophy in the duodenum and jejunum can be observed in histologic sections from asymptomatic individuals who are infected. In addition to disrupting the mucosal epithelium, effects in the intestinal lumen may contribute to malabsorption and the production of diarrhea. [8, 22] Nevertheless, diarrhea can occur in individuals in the absence of obvious light microscopic changes in small intestinal structure.

Varying degrees of malabsorption of sugars (eg, xylose, disaccharides), fats, and fat-soluble vitamins (eg, vitamins A and E) may contribute to substantial weight loss. The histopathologic response to giardiasis varies and imperfectly correlates with the clinical symptoms. [13, 23]

G intestinalis may release cytopathic substances that damage the intestinal epithelium. Giardia species contain thiol-dependent and thiol-independent proteinases, which may find substrates in the microvillus membrane. A 2018 report suggests that three main cysteine proteases (CP14019, CP16160 and CP16779) secreted by G intestinalis disrupt intestinal epithelial cell junctional complexes and degrade chemokines. [24] In addition, the surface mannose-binding lectin of G intestinalis may contribute to epithelial damage. Whatever the mechanism by which G intestinalis damages villous epithelial cells, the result consistently appears to be an increase in crypt length and crypt cell proliferation. [25]

Enterocytic injury is mediated by activated host T lymphocytes. Pathophysiological activation of lymphocytes is secondary to Giardia -induced disruption of epithelial tight junctions, which, in turn, increases intestinal permeability. Loss of epithelial barrier function is a result of Giardia -induced enterocyte apoptosis. [22, 26, 27]


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