Celiac Disease - Sprue, Nontropica sprue

The presentation may give you an idea abouth the disease, its pathophysiology, signs, symptoms, diagnosis, treatment....Thanks toall the websites which helped me to make this presentation.

1. CELIAC SPRUE By, Devi Priya Sugathan MSc Biochemistry and Molecular Biology

2. CONTENT History of Celiac Celiac Disease Gluten Genetic changes Molecular mechanisms Epidemiology Signs and symptoms Types of CD Diagnosis Celiac Iceberg Inheritance Pattern Treatment

3. HISTORY OF CELIAC Aretaeus from Cappadochia (now Turkey) in the 2nd century AD described a chronic malabsorptive condition. He named this disorder " koiliakos ” which is Greek for "suffering in the bowels.” Booth, CC. History of celiac disease. BMJ 1989; 298:527.

4. The first clear description of celiac disease was given by Samuel Gee in 1888. He suggested that dietary treatment might be of benefit. In the early 20th century various diets were tried, with some success, but without clear recognition of the toxic components. The doctoral thesis of Wim Dicke of 1950 established that exclusion of wheat, rye and oats from the diet led to dramatic improvement. Samuel Gee Wim Dicke

5. DEFINITION Celiac disease is a condition caused by inflammatory injury to the mucosa or lining of the small intestine. This damage is caused by sensitivity to gluten . The damaged intestine does not absorb the needed components of food (fat, protein, carbohydrates, vitamins, iron, water). Other terms for celiac disease include: Gluten Sensitive Enteropathy , Non-Tropical Sprue & Celiac Sprue .

6. GLUTEN Gluten is a family of proteins found in grains like wheat, rye ,barley, oats. Of the gluten containing grains, wheat is by far the most commonly consumed. The two main proteins in gluten are glutenin and gliadin . Gliadin is responsible for most of the negative health effects .

7. Gluten is composed of about 75-86% protein, while the other components are carbohydrates and lipids. Glutenin becomes a tough and rubbery mass upon hydration, while gliadin becomes a viscous, fluid mass. This is what allows gluten to exhibit both elastic and viscous properties in dough and lends to its properties of extensibility, resistance to stretch, mixing tolerance, and gas holding ability

8. Gliadin and Glutenin are connected by disulfide bridges. In bread and other baked goods, yeasts consume sugar and produce carbon dioxide via fermentation. The carbon dioxide becomes trapped in this molecular mesh structure of gluten, causing bread to “rise.” Finally, when the dough is baked, the gluten hardens , giving the bread its structure.

9. When a person with sprue eats food that contain gluten, the immune system responds by damaging villi in the small intestine. Without the action of the villi , a person can become malnourished to matter how much the food is eaten. Sprue is an autoimmune disorder causing the bodys own immune system to turn against or damage the body.

10. GENETIC CHANGES The risk of developing celiac disease is increased by certain variants of the HLA-DQA1 and HLA-DQB1 genes . These genes form receptors that bind to gliadin peptides tightly and intiate the immune reponse . The HLA-DQA1 and HLA-DQB1 genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.

11. Almost all people with celiac disease have specific variants of the HLA-DQA1 and HLA-DQB1 genes, which seem to increase the risk of an inappropriate immune response to gliadin . These variants are also found in 30 percent of the general population, and only 3 percent of individuals with the gene variants develop celiac disease. It appears such as environmental factors and changes in other genes, also influence the development of this complex disorder.

12. Molecular Mechanism on the toxic effects of Gluten Usually food proteins are degraded into small peptides and aminoacids by peptidases before they can be transported across the epithelium. The high proline content in gliadin and similar proteins of wheat and related cereals, renders these proteins resistance to complete proteolytic digestion in the human intestine. Therefore toxic oligopeptides with high concentration of proline and glutamine are accumulated in the small intestine and can exert toxic effects in genetically susceptible subjects. Two groups of gliadin peptides are found: serine containing and tyrosine containing. The serine-containing group of peptides appears to be essentially cytotoxic , whilst the tyrosine-containing group has the capacity to trigger immunological reactions in CD patients .

13. Imunomodulatory Effects of Gluten Peptides The “immunogenic” peptides binds to HLA-DQ2 or DQ8 of antigen presenting cells and stimulates T-cells. The secretion of cytokines activates the release of enzyme matrix  metalloproteinases  that can damage the intestinal  mucosa with a loss of villous structure. The cytokines increase epithelial permeability and increase the passage of gluten peptides and peptides binding to DQ2 and DQ8 molecules on APC. These events contribute to the damage of the mucosal matrix. 

14. This deamidated gliadin peptides can be strong activators of the T cells and also possess more specific isotopes for the circulating antibodies.

15. No-Immune Mediated Cytotoxicity of Gluten OXIDATIVE STRESS Some α- gliadin peptides possess the ability to penetrate cells . Therefore they are internalised by endocytic uptake. Peptide accumulation in lysosomes leads to activation of some signal transduction pathways and to increased levels of free radicals. The increase in oxidative damage could induce alterations of cell morphology, apoptosis and cell viability.

16. EPIDEMIOLOGY Until the 1970s the estimated global prevalence of celiac disease in the general population was 0.03%. The currently estimated prevalence is 1%, with a statistical range of probability of 0.5–1.26% in the general population in Europe and the USA. Even taking into account that the actual occurrence rate of celiac disease has been underestimated for many decades, the prevalence of this disease is increasing. IN INDIA Celiac disease was recognized in northern India, primarily in children, since the 1960s. A community-based study in Ludhiana that involved a step-wise approach to case detection and diagnosis estimated that celiac disease prevalence in this city was at least 1 in 310 individuals . Celiac disease affecting adults is also now well recognized in northern India. The prevalence of celiac disease in southern India is not known.

17. SIGNS AND SYMPTOMS Gastrointestinal symptoms Gastrointestinal symptoms may include the following: Diarrhea 45-85% of patients Flatulence 28% of patients Weight loss 45% of patients; in infants and young children with untreated celiac disease, failure to thrive and growth retardation are common Weakness and fatigue 78-80% of patients; usually related to general poor nutrition Severe abdominal pain 34-64% of patients

18. Extraintestinal symptoms Extraintestinal symptoms may include the following: Anemia 10-15% of patients Osteopenia and osteoporosis 1-34% of patients Neurologic symptoms 8-14% of patients Skin disorders 10-20% of patients Hormonal disorders Including delayed menarche, and infertility in women and impotence and infertility in men

19. Physical examination A physical exam may reveal the following: A protuberant and tympanic abdomen Evidence of weight loss Peripheral edema Hyperkeratosis or dermatitis herpetiformis Cheilosis and glossitis Evidence of peripheral neuropathy

20. TYPES OF CELIAC DISEASE Classic celiac disease  refers to the presence of mild to severe symptoms of malabsorption such as diarrhea, failure to thrive, and weight loss . Non-classic celiac disease  refers to celiac disease without prominent gastrointestinal symptoms or malabsorption but can have abdominal pain, bloating, vomiting and constipation. Silent celiac disease refers to lack of symptoms in the presence of a positive celiac-associated antibody screen. Individuals with silent celiac disease are most often identified through an affected family member or through screening programs

21. Refractory celiac disease (RCD) refers to persistence of symptoms of frank malabsorption with persistent intestinal inflammation and villous atrophy despite a strict gluten-free diet for at least six to 12 months. All individuals with refractory sprue are older than age 20 years.

22. DIAGNOSIS In terms of serology, celiac disease is associated with a variety of autoantibodies , including endomysial , tissue transglutaminase ( tTG ), and deamidated gliadin antibodies. Although the IgA isotype of these antibodies usually predominates in celiac disease, individuals may also produce IgG isotypes , particularly if the individual is IgA deficient. The most sensitive and specific serologic tests are tTG and deamidated gliadin antibodies.  The definitive diagnosis of celiac disease is made by identification of characteristic histologic changes on biopsy of the duodenum during upper gastrointestinal endoscopy. Genetic testing

23. CELIAC ICEBERG Since only the tip of the CD iceberg is above the waterline and a much large portion remains under water undetected, it can be expected that prevalence of the disease will increase continuously .

24. INHERITANCE PATTERN Celiac disease tends to cluster in families. If we carry HLA DQ2 and/or DQ8, your risk of developing celiac disease is 3% instead of the general population risk of 1%. Parents, siblings, or children (first-degree relatives) of people with celiac disease have between a 4 and 15 percent chance of developing the disorder. However, the inheritance pattern is unknown.

25. If Celiac Disease goes untreated? Lactose intolerance Vitamin and mineral defeciency Osteopenia and osteoporosis Iron deficiency anemia Lymphoma Fertility problems Nervous system disorders

26. TREATMENT Celiac disease cannot be cured. Your symptoms will go away and the villi in the lining of the intestines will heal if you follow a lifelong  gluten-free diet. Do not eat foods, drink beverages, or take medicines that contain wheat, barley, rye, and possibly oats. Your health care provider may need to prescribe vitamin and mineral supplements. When you are diagnosed, get help from a registered dietitian who specializes in celiac disease and the gluten free diet.

27. Vitamin C and E, which have antioxidant activity can be supplemented to CD patients. Fruits and vegetables containing polyphenols and carotenoids can be helpful since they have anti-inflammatory and anti-oxidant properties. Fatty acids are also helpful since it could influence inflammation.

28. GLUTEN FREE FLOUR Gluten free flour is a term that is applied to flours that are made of non-gluten containing products. There are many kinds of gluten free flours available at supermarkets these days, along with many “all purpose” gluten free flour blends that are designed to be an easy to use replacement for wheat flour. Commercially available gluten free flours are all made with different mixtures and these mixtures vary widely from brand to brand. They might contain rice flour, teff flour, tapioca flour, sorghum flour, potato starch, garbanzo flour or buckwheat flour.

29. These flours could also contain nut flours, made from very finely ground almonds or other nuts. Xanthan gum is a binder that is frequently added to gluten free flour mixes to give the flour some elasticity and make it easy to use right out of the bag. Since the base ingredients for gluten free flour can be very different, different brands can produce very different results in baked goods, giving a recipe a completely different taste and texture.

30. The Celiac Sprue Association (CSA) is a member based organization dedicated to helping individuals with celiac disease worldwide through research, education and support. The Celiac Sprue Association gives a trusted source of information about the gluten-free products that consumers rely on and enjoy every day. CELIAC SPRUE ASSOCIATION