Pathology

Surgical or autopsy specimens highlight the two characteristic features of amebic lesions; a) minimal inflammatory response, and b) extensive cellular destruction. Experimental animal studies at the molecular level have shown that organic tissue damage is not caused directly by the parasite, but actually by the liberated lisosomal enzymes from lysis of leukocytes and monocytes. Intracecal inoculation of E. histolytica trophozoites has nearly reproduced the spectrum of superficial erosions, ulcers, and deep lesions giving origin to amebomas or perforations similar to those observed in human amebiasis.

Early lesions - Adherence and Lysis.

The keys to pathogenesis and virulence of E. histolytica are the lectins and lytic substances produced by trophozoites. The lectins enable trophozoites to adhere to mammalian cells and then destroy them with lytic substances which include proteolytic enzymes, glycosidases, and pore-forming proteins. It is especially interesting that the pore-forming protein is essentially identical to a pore-forming protein of human T lymphocytes. Human defenses against amebiasis are most likely the antibodies and the enhanced cell-mediated immunity stimulated by exposure to these lectins and lytic substances. Without these lectins and lytic enzymes, E. histolytica would be just another commensal of the intestine, lacking the ability to adhere, erode, invade, produce ulcers or spread to the liver and other organs and cavities. The earliest lesions of man have not been studied but infections in experimental animals reveal early stages of increased mucin production by goblet cells, then adherence of trophozoites to surface epithelium, hyperplasia of crypts, edema of and hemorrhage into the lamina propria, and finally lysis and sloughing of epithelium. Thus, amebiasis begins when trophozoites adhere to surface epithelial cells. Next follows destruction of epithelial cells and then erosion and ulceration. Figure 1.3 is a dramatic illustration of the adherent and lytic effects of E. histolytica. A phalanx of trophozoites has eroded both the superficial epithelium and supporting lamina proptia at every point of contact, and the line of destruction is as straight as the phalanx of trophozoites. This is one of the earliest and most dramatic lesions studied, because it demonstrates the two essential features of pathogenesis: adherence to, and lysis of, host cells.

Neutrophiles and eosinophiles are found in the superficial early lesions; eosinophiles are no longer present in the chronic lesions. The destructive nature of the amebic parasite and its capacity to generate tissue lysis has justified the awarding of the histolytica appelation. Liberation of toxins, enzymes, avid phagocytic activity, and an efficient cytoplasm rapidly degrade the cellular and extracellular ingested material. It is generally accepted that the incipient lesions of invasive amebiasis demonstrate an intense inflammatory reaction, followed by extensive necrosis secondary to ischemia and the cytolytic action of the lysosomal enzymes liberated by the lysed leukocytes. An impressive feature of invasive amebiasis is the restitutio ad integrum of the affected organ. The regenerated tissues usually return to normal without the process of cicatrization. This is particularly evident in the colon, liver, and skin. This phenomenon is probably due to the lack of fibroblast activity, resulting in little inflammatory response, most likely due to the fibroblast-inhibiting factors generated by the parasite.

Intestinal Amebiasis

Invasive amebiasis can generate a variety of morphological alterations in the affected bowel with specific patterns, including: a) ulcerative amebic rectocolitis, b) toxic megacolon, c) fulminant colitis, d) ameboma, and e) amebic appendicitis.

Ulcerative Amebic Proctocolitis

The earliest recognizable lesion in the ulcerative form of amebic colitis is one or more erosions of the colonic epithelium. These are followed by ulcers which usually occur at several closely linked sites; there is almost always healthy tissue between the areas of lytic necrosis. The ulcers are small, almost always multiple, and chiefly distributed in the cecum, sigmoid colon, and rectum (Figs.1.5, 1.6, 1.7). They are elevated rounded lesions with a necrotic irregular center surrounded by an edematous ring. In the submucosa, small capillaries and venules become inflamed and sometimes thrombosed, which contributes to the mucosal necrosis. Amebae which are the progeny of the primary colonies may he squeezed out of, or overflow, the ulcers and be carried further down the bowel; the same process is repeated at multiple levels. At this stage, hitherto separate areas of pinhead ulceration spread below the mucosa and merge into large areas of lytic necrosis, causing the undermined flask-shaped ulcers characteristic of amebiasis (Fig. 1.5). Irregular and serpiginous ulcers of 1 to 5 cm length associated with edematous thickening of the colonic wall can also be observed. This process may be accompanied by bacterial invasion, and deeper penetration into the muscularis will occur (Fig. 1.6). Less commonly, deep penetration may be caused by the lytic action of the trophozoites.

Fig. 1.6 Amebic ulcers of the colon-gross photographs. (A) Hyperemia and edema of the colonic mucosa with scattered superficial erosions and ulcers. (B) Amebic ulcers with ragged, heaped-up edges covered by an amorphous grey fibrinous exudate. X75. AFIP 69-3234. (C) Vertical section of the same colon as (B). Note the deep, ragged ulcers extending through the mucosa and submucosa but not through the muscularis. The colon is irregular, thickened, and rigid. AFIP 69-3550. (D) Deep, bleeding ulcers resulting from slough of necrotic tissue. These penetrating ulcers produce a "buffalo hide" appearance of the colon and may extend through the wall to the serosa. (E) Chronic amebic colitis with numerous well-defined, relatively small ulcers extending through the mucosa and submucosa to expose the muscularis. Many mucosal bridges are recognizable. AFIP 58-4840-3. (B from C. H. Binford, D. H. Connor (eds): Pathology of Tropical and Extraordinary Diseases. Washington, DC, Armed Forces Institute of Pathology, 1976. D from J. E. Ash, S. Spitz: Pathology of Tropical Diseases. Philadelphia, Saunders, 1945).