http://ebooksmedicine.net malabsorption and excessive intestinal secretion), flatus, abdominal pain, and weight loss. Inadequate absorption of vitamins and minerals can result in anemia and mucositis due to pyridoxine, folate, or vitamin B12 deficiency; bleeding due to vitamin K deficiency; osteopenia and tetany due to calcium, magnesium, or vitamin D deficiency; or neuropathy due to vitamin A or B12 deficiency. A variety of endocrine and skin disturbances may also occur. Mycobacterial infection, which can be lead to lymphatic transport defects, is discussed with infectious causes of diarrhea in the next section.
Cystic fibrosis is discussed in greater detail elsewhere (Chapter 7). Only the malabsorption associated with cystic fibrosis is considered here. Owing to mutations of the epithelial cystic fibrosis transmembrane conductance regulator (CFTR), individuals with cystic fibrosis have defects in intestinal and pancreatic ductal ion transport. This abnormality interferes with bicarbonate, sodium, and water secretion, ultimately resulting in inadequate luminal hydration. The viscous luminal contents may result in meconium ileus, which is present in up to 10% of newborns with cystic fibrosis. In the pancreas the ducts are plugged by thick mucus. This leads to obstruction, low-grade chronic autodigestion of the pancreas, and eventual exocrine pancreatic insufficiency in more than 80% of patients. The result is failure of the intraluminal phase of nutrient absorption, which can be effectively treated in most patients with oral enzyme supplementation.
Celiac disease, also known as celiac sprue or gluten-sensitive enteropathy, is an immune-mediated enteropathy triggered by the ingestion of gluten-containing cereals, such as wheat, rye, or barley, in genetically predisposed individuals. In countries whose populations consist predominantly of whites of European ancestry, celiac disease is a common disorder, with an estimated prevalence of 0.5% to 1%. The primary treatment for celiac disease is a gluten-free diet, which results in symptomatic improvement for most patients.
Celiac disease is an intestinal immune reaction to gluten, the major storage protein of wheat and similar grains. Gluten is digested by luminal and brush border enzymes into amino acids and peptides, including a 33–amino acid gliadin peptide that is resistant to degradation by gastric, pancreatic, and small-intestinal proteases (Fig. 15.21 ). Gliadin is deamidated by tissue transglutaminase and is then able to interact with HLA-DQ2 or HLA-DQ8 on antigen-presenting cells and be presented to CD4+ T cells. These T cells in lamina propria produce cytokines that likely contribute to the tissue damage and characteristic mucosal histopathology. An antibody response follows: This includes production of antibodies against tissue transglutaminase, deamidated gliadin, and, perhaps as a result of cross-reactive epitopes, anti-endomysial antibodies, which can be diagnostically useful. They may also be used to monitor disease, as titers typically fall after 3 to 6 months of gluten-free diet. However, whether these antibodies contribute to celiac disease pathogenesis or are merely markers of immune activation remains controversial. In addition to CD4+ cells, there is an accumulation of CD8+ cells that are not specific for gliadin but may play an ancillary role in causing tissue damage. It is thought that deamidated gliadin peptides induce epithelial cells to produce the cytokine IL-15, which in turn triggers activation and proliferation of CD8+ intraepithelial lymphocytes that become cytotoxic and kill
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