Defective Intraluminal Digestion

Digestion of fats and proteins

• Pancreatic insufficiency, owing to pancreatitis or cystic fibrosis

• Zollinger-Ellison syndrome, with inactivation of pancreatic enzymes by excess gastric acid secretion

Solubilization of fat, owing to defective bile secretion

• Ileal dysfunction or resection, with decreased bile salt uptake

• Cessation of bile flow from obstruction, hepatic dysfunction

Nutrient preabsorption or modification by bacterial overgrowth

Primary Mucosal Cell Abnormalities

Defective terminal digestion

• Disaccharidase deficiency (lactose intolerance)

• Bacterial overgrowth, with brush border damage

Defective epithelial transport

• Abetalipoproteinemia

• Primary bile acid malabsorption owing to mutations in the ileal bile acid transporter

Reduced Small Intestinal Surface Area

Gluten-sensitive enteropathy (celiac disease)

Crohn disease

Lymphatic Obstruction

Lymphoma

Tuberculosis and tuberculous lymphadenitis

Infection

Acute infectious enteritis

Parasitic infestation

Tropical sprue

Whipple disease (Tropheryma whippelii)

Iatrogenic

Subtotal or total gastrectomy

Short-gut syndrome, following extensive surgical resection

Distal ileal resection or bypass

• Alimentary tract: diarrhea, both from nutrient malabsorption and excessive intestinal secretions, flatus, abdominal pain, weight loss, and mucositis resulting from vitamin

deficiencies

• Hematopoietic system: anemia from iron, pyridoxine, folate, and/or vitamin B12 deficiency and bleeding from vitamin K deficiency

• Musculoskeletal system: osteopenia and tetany from calcium, magnesium, and vitamin D deficiency

• Endocrine system: amenorrhea, impotence, and infertility from generalized malnutrition; hyperparathyroidism from protracted calcium and vitamin D deficiency

• Epidermis: purpura and petechiae from vitamin K deficiency, edema from protein deficiency, dermatitis and hyperkeratosis from deficiencies of vitamin A, zinc, essential fatty

acids and niacin

• Nervous system: peripheral neuropathy from vitamin A and B12 deficiencies.

The passage of abnormally bulky, frothy, greasy, yellow, or gray stools (steatorrhea) is a prominent feature of malabsorption, accompanied by weight loss, anorexia, abdominal distention,

borborygmi, and muscle wasting. The malabsorptive disorders most commonly encountered in the United States are celiac disease, pancreatic insufficiency, and Crohn disease.

Pancreatic insufficiency, primarily from chronic pancreatitis or cystic fibrosis, is a major cause of defective intraluminal digestion. Typical features of defective intraluminal digestion are

an osmotic diarrhea from undigested nutrients and steatorrhea. Excessive growth of normal bacteria within the proximal small intestine (bacterial overgrowth, discussed earlier) also

impairs intraluminal digestion and can damage mucosal epithelial cells, causing impaired terminal digestion and epithelial absorption.

CELIAC DISEASE

Celiac disease (also referred to as celiac sprue, gluten-sensitive enteropathy) is a chronic disease, in which there is a characteristic mucosal lesion of the small intestine and impaired

nutrient absorption, which improves on withdrawal of wheat gliadins and related grain proteins from the diet. [63] Celiac disease occurs largely in Caucasians and is rare or nonexistent

among native Africans, Japanese, and Chinese. Its prevalence in the United States is somewhat difficult to define; in Europe the prevalence is in the range of 1:100 to 1:200.[64] The disease

was first described more than a century ago, but its connection to gluten was not known until the 1940s, changing its clinical management.

Pathogenesis.

The fundamental disorder in celiac disease is a sensitivity to gluten, which is the alcohol-soluble, water-insoluble protein component (gliadin) of wheat and closely related grains (oat,

barley, and rye). The hallmark of this disease is a T-cell mediated chronic inflammatory reaction with an autoimmune component, which most likely develops as a consequence of a loss of

tolerance to gluten. Interplay between genetic predisposing factors, the host immune response, and environmental factors is central to disease pathogenesis. The small intestinal mucosa,

when exposed to gluten, accumulates intraepithelial CD8+ T cells and large numbers of lamina propria CD4+ T cells, which are sensitized to gliadin. The recognized epitopes are confined

to residues 57–75 of gliadin. [65]

It has been long known that family history is important in celiac disease. Almost all individuals with celiac disease share the major histocompatibility complex class II HLA-DQ2 or

Figure 17-38Celiac disease (gluten-sensitive enteropathy). A, A peroral jejunal biopsy specimen of diseased mucosa shows diffuse severe atrophy and blunting of villi, with a chronic

inflammatory infiltrate of the lamina propria. B, A normal mucosal biopsy.

Figure 17-39Whipple disease. A, Note foamy macrophages in the lamina propria. B, PAS stain showing the positive granules in the foamy macrophages. C, Electron micrograph of a

lamina propria macrophage showing many bacilli within the cell (arrow) and in the extracellular space (arrowhead). Inset, Higher magnification of macrophage cytoplasm showing crosssectional

profiles of bacilli and their cell walls (small arrows). (C, courtesy of George Kasnic and Dr. William Clapp, University of Florida, Gainesville, FL.)

Figure 17-40Crohn disease of ileum, showing narrowing of the lumen, bowel wall thickening, serosal extension of mesenteric fat ("creeping fat"), and linear ulceration of the mucosal

surface (arrowheads).

Figure 17-41Crohn disease of the colon; a deep fissure extending into the muscle wall, a second, shallow ulcer (on the upper right), and relative preservation of the intervening mucosa.

Abundant lymphocyte aggregates are present, evident as dense blue patches of cells at the interface between mucosa and submucosa.

Figure 17-42Crohn disease of the colon. A noncaseating granuloma is present in the lamina propria of an uninvolved region of colonic mucosa (arrow).

Figure 17-43Comparison of the distribution patterns of Crohn disease and ulcerative colitis, as well as the different conformations of the ulcers and wall thickenings.

Figure 17-44Ulcerative colitis. Ulcerated hemorrhagic surface with knobby pseudopolyps. (Courtesy of Dr. Kim Bechard, Brigham and Women's Hospital, Boston, MA.)

Figure 17-45Ulcerative colitis. Low-power micrograph showing marked chronic inflammation of the mucosa with atrophy of colonic glands, moderate submucosal fibrosis, and a normal

muscle wall.

Figure 17-46Toxic megacolon. Complete cessation of colon neuromuscular activity has led to massive dilatation of the colon and black-green discoloration signifying gangrene and

impending rupture.

Figure 17-47Ulcerative colitis. Microscopic view of the mucosa, showing diffuse active inflammation with crypt abscess and glandular architectural distortion.

TABLE 17-10-- Distinctive Features of Crohn Disease and Ulcerative Colitis *

Date: 2016-04-22; view: 840