Campylobacter Enterocolitis

This comma-shaped, flagellated, gram-negative organism was once classified with the vibrios. When special culture conditions permitted its isolation in the 1970s, it became apparent that

Campylobacter was an important cause of enterocolitis and septicemia in humans. In the United States, Campylobacter jejuni is responsible for twice the enteric disease of Salmonella and

four times that of Shigella. Most infections with Campylobacter are sporadic and are associated with ingestion of improperly cooked chicken, which may be contaminated with

Campylobacter and/or Salmonella. Sporadic infections may also be associated with contact with infected dogs. Outbreaks of Campylobacter are usually associated with unpasteurized milk

or contaminated water.

Pathogenesis.

Invasiveness is strain dependent. Flagella of Campylobacter, which give the organism its comma shape and motility, are necessary for the bacterium to penetrate mucus covering epithelial

surfaces. Three clinical outcomes of Campylobacter infection are possible: (1) diarrhea, which is independent of bacterial invasion; (2) dysentery with blood and mucus in the stool; and (3)

enteric fever when bacteria proliferate within the lamina propria and mesenteric lymph nodes. Postinfectious complications of Campylobacter infections include reactive arthritis in HLAB27

carriers (as with Shigella infection) and Guillain-Barré syndrome, a demyelinating disease of peripheral nerves due to autoantibodies against gangliosides GM1 and GQ1b, described in

Chapter 27 . Recently, C. jejuni was found to be associated with the development of immunoproliferative small intestinal disease (discussed later).

Cholera

Vibrio cholerae are comma-shaped, gram-negative bacteria that have been the cause of seven great long-lasting epidemics (pandemics) of diarrheal disease. Many of these pandemics

began in the Ganges Valley of India and Bangladesh, which is never free from cholera, and then moved east. Although there are 140 serotypes of V. cholerae, until recently only the 01

serotype was associated with severe diarrhea. Beginning in 1992, a new V. cholerae serotype (0139, also known as Bengal) has been associated with severe, watery diarrhea.[53]

Pathogenesis.

The vibrios never invade the epithelium but instead remain within the lumen and secrete an enterotoxin, which is encoded by a virulence phage. Flagellar proteins involved in motility and

attachment are necessary for efficient bacterial colonization, as has been described for Campylobacter. (This is in contrast to Shigella species and certain E. coli strains, which are

nonmotile and yet invasive.) The Vibrio hemagglutinin, which is a metalloprotease, is important for detachment of Vibrio from epithelial cells.

The secretory diarrhea characteristic of the disease is caused by release of cholera toxin ( Fig. 17-32 ). Cholera toxin is composed of five binding peptides B and a catalytic peptide A. The

B peptides, serving as a "landing pad," bind to carbohydrates on GM1 ganglioside on the surface of epithelial cells of the small intestine, enabling calveolar-mediated endosomal entry of

toxin subunit A into the cell. Reverse transport of the subunit A from the endosome into the cell cytoplasm is followed by cleavage of the disulfide bond linking the two fragments of

peptide A (A1 and A2). Catalytic peptide A1 is generated, leading to the following sequence:

• A1 interacts with 20-kD cytosolic proteins called ADP-ribosylation factors (ARF).

• The ARF-A1 complex catalyzes ADP-ribosylation of a 49-kD G-protein (called Gsa ).[54]

• Binding of NAD and GTP generates an activated Gsa , which in turn binds to and stimulates adenylate cyclase. ADP-ribosylated Gsa is permanently in an active GTP-bound

state, resulting in persistent activation of adenylate cyclase.

• The activated adenylate cyclase generates high levels of intracellular cAMP from ATP.

• Cyclic AMP stimulates secretion of chloride and bicarbonate, with associated sodium and water secretion. Chloride and sodium resorption are also inhibited.

Figure 17-32Mechanisms of cholera toxin action.

Figure 17-33Shigella enterocolitis. Segment of colon showing pale, granular, inflamed mucosa with patches of coagulated exudate.

Figure 17-34Pseudomembranous colitis from C. difficile infection. A, Gross photograph showing plaques of yellow fibrin and inflammatory debris adherent to a reddened colonic mucosa.

B, Low-power micrograph showing superficial erosion of the mucosa and an adherent pseudomembrane of fibrin, mucus, and inflammatory debris.

Figure 17-35Entamoeba histolytica in colon. High-power view of the organisms. Note some of the organisms ingesting red blood cells.

Figure 17-36Giardia lamblia. Trophozoite (arrow) of the organism immediately adjacent to the duodenal surface epithelium.

Figure 17-37Graft-versus-host disease of the colon. Note the apoptotic cell in the crypt (arrow).

TABLE 17-9-- Major Malabsorption Syndromes

Date: 2016-04-22; view: 822