History and Definition of Celiac Disease:
By definition, Celiac disease is a systemic autoimmune response triggered by dietary gluten in people with the susceptible genetic composition (Fasano and Catassi, 2012). Artaeus, who described a patient with chronic diarrhea and degrading health, most likely gave the first description of Celiac disease in the 2nd century AD. In his frankly comical ignorance, he described the disease as an “atony of the heat which digest, and refrigeration of the stomach”. According to Artaeus, the heat dissolves the food but does not digest it, which causes the food to essentially change into diarrhea. He did, however, discern a reasonable treatment, in that he treated his patients with restricted diets (Paveley, 1988).
Celiac disease was not again relevant until the late 19th century, when Dr. Gibbons described four children afflicted with the disease as frail and weak. He eventually lectured in the early 20th century, in which he suggested that the disease was the result of a “digestive disturbance”, and that bread and starch were the main causes of aggravating of the condition (Paveley, 1988).
Believe it or not, the next important development in the disease came in 1924, when Sidney Haas successfully treated eight afflicted individuals with a “banana diet”. His diet was designed to specifically exclude bread, potatoes, crackers, and cereals. This dietary treatment continued to be implemented until the 1950’s, so much so that during the second world war, children with Celiac were allowed extra rations of bananas (Paveley, 1988).
An extremely important shortage of bread occurred in the Netherlands around the time of the second world war. During this shortage, incidences of Celiac disease supposedly decreased. This led Christopher Boothe Dicke and his coworkers to eventually make the association between wheat and Celiac disease (van Berge-Henegouwen, 1993). Eventually, in conjunction with van de Kamer and Meyers, Dicke was able to determine that that the alcohol soluble portion of wheat, gliadin, was the pathogenic aspect of the food. Eventually, the gluten free diet evolved to subsist of any foods that do not contain wheat, rye, or barely, and in the United States, due to processing, oats as well (van Berge-Henegouwen, 1993).
Recent years have seen the dramatic increase in the number of gluten free foods in circulation. In part, this is because the disease has been demonstrated to be incredibly prevalent (at least 1 in 100 people), and has therefore gained popularity. The increase in foods can also be attributed, however, to the development of the gluten free diet as a “fad diet”, which radically expanded the market for gluten free foods.
Symptoms Associated With Celiac Disease
Clinically, patients are defined to present with classical, atypical, or silent celiac disease. Classical presentation generally results in the first two years of an individual’s life, where after the introduction of gluten in the child’s diet, the child begins to show symptoms of malabsorption (Iwańczak, et. al, 2013). These symptoms include chronic diarrhea, failure to thrive, abdominal distension and pain, growth delay and iron deficiency anemia. Atypical presentation is characterized by presentation of less clinical symptoms, often later in life. These symptoms include a lack of body mass increase and growth retardation, anemia, dental enamel hypoplasia, osteoporosis, or pubertal delay. Silent diagnosis of the disease occurs in asymptomatic individuals who are characterized as high risk for the disease. High-risk markers include other immune associated diseases such as diabetes or IgA antibody deficiency (Iwańczak, et. al, 2013).
Diagnosis of Celiac Disease:
Although symptoms can be indicative of the disease, The most commonly used and effective diagnosis for Celiac disease is testing for the presence of IgA antitissue transglutaminase antibodies. This test is generally over 95% effective at diagnosing Celiac disease in individuals. Blood testing for the HLA-DQ2 haplotype have been shown to have similar diagnostic effectiveness. Upper endoscopic biopsies of the duodenum are also commonly used to confirm the Celiac diagnosis. This test falls short, however, in that not all areas of the small intestine and duodenum are equally effected, and biopsying an unaffected region could lead to false negatives (van der Windt et. al, 2010).
Symptomatic diagnoses, given the variety of symptom presentations, are not commonly used to diagnose the disease, although the symptoms can be powerful indicators of the disease. Anemia tests and other symptomatic assays are generally used to confirm complications of the disease after diagnosis has occurred (Barrartt et al., 2013).
Metabolic Context of Celiac Disease
The overall process of digesting proteins involves breaking down the proteins into amino acids, dipeptides, and tripeptides, which can subsequently be easily absorbed into enterocytes. After eating in general, protein stimulation of gastric mucosa results in the release of gastrin. Gastrin in turn stimulates the release of pepsinogen and HCl. The acidic environment acatalytically converts pepsinogen into pepsin, denatures globular proteins, and kills any bacteria that accompany the food into the stomach. However, in vitro studies have shown that gluten proteins are only partially degraded by pepsin and arrive at high concentration and high molecular weight in the small intestine. This is because gluten prolamins, in particular, are predominantly comprised of proline residues, making them difficult for the human body to digest as they are resistant to degradation by peptidases (Caminero, et. al, 2014).
Once in the small intestine research has demonstrated that the high concentration of proline in gluten proteins (10-15%) endows the proteins resistance to brush border membrane and pancreatic proteases as well. This is primarily because these enzymes lack prolyl-endopeptidasic activity, which is the ability to cleave at the C-terminal side of proline residues. In normal gluten metabolism, the partially digested gluten peptides are too large to be transported by PEPT-1, the canonical amino acid, dipeptide, and tripeptide transporter. These large peptides, therefore, remain in circulation in the lumen of the small intestine. There is some evidence that shoes the gram negative bacteria that reside in the small intestine might have catalytic activity capable of digesting large oligopeptides and therefore might aid in the digestion of partially digested gluten in the lumen. Canonically, large gluten peptides pass through the small intestine, into the large intestine, and are passed as waste. The high concentration of bacteria in the lower digestive tract, however, leads to the belief that some of these bacteria might participate in the digestion of gluten proteins (Caminero, et. al., 2014).
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