Pathophysiology of Celiac Disease
Characteristic of Celiac Sprue
Malabsorption after ingestion of gluten - Small intestinal villous atrophy - Improvement after a gluten-free diet
Tropical Sprue Etiology
Mucosal damage similar to Celiac - Villous atrophy and IELs Upper small bowel is affected early, then ileum Atrophic gastritis and colonic lymphocytes
Tropical Sprue presentation
Presents often with an acute diarrheal episode, followed by: - Chronic diarrhea - Bloating - Malabsorption
What bothers people with celiac disease?
Wheat, barely, rye
Histology
1. Columnar absorptive cells become more flattened 2. Microvilli shortened and fused 3. Tight junctions weakened 4. Less ER (less production of enzymes) 5. Increase in lysosomes due to vacuolization of mitochondria and cytoplasm
Tropical Sprue Pathology
1. Villous atrophy 2. Increase in crypt death 3. EM shows fusion of microvilli (increase in lysosomes) 4. Thickened basement membrane with increased collagen
Tropical Sprue Pathophysiology
B12 and other deficiencies - Impaired absorption of fat is most consistent finding - Motility often decreased
Celiac Clinical Features
Can be asymptomatic 1. Diarrhea 2. Dyspepsia 3. Weight loss 4. Failure to thrive 5. Iron Deficiency Anemia Maybe mild LFT abnormalities
Celiac Diagnosis
Celiac antibodies - TTG - Endomysial - DGP Small bowel biopsies - Villous atrophy - IELs HLA DQ2/DQ8 (not usually used)
Endomysium
Connective tissue structure which surrounds smooth muscle
Tropical Sprue
Disease of small intestine, but also stomach and colon - Mostly in SE Asia and Caribbean
Immune Response in Celiac
Endomysium contains tissue transglutaminase (TTG) 1. TTG deaminates the glutamine on the gliadin peptides 2. Deaminated glutamic acid fits better into the antigen binding groove of the HLA DQ2 (strength immune response)
Celiac Treatment
Gluten free diet! - Vitamin supplementation - Immunosuppression
Pathogenesis of Celiac Sprue
Gluten is a water-soluble protein - Gliadins are the type of gluten in wheat - Secalins and Hordeins are glutens of rye and barely (high immune cross-reactivity with gliadin)
Pathophysiology
Gluten is ingested and presented to the small bowel - The gliadin peptides are taken by APCs and presented to T-cells - APCs express HLA DQ2 antigens - T-cells activated B-cells leading to antibody production and cytokine release - INF-g and TNF-a damage the enterocyte and cause more HLA 2 antigen expression Vicious cycle
Notable pathology seen with Celiac
Highest severity in the proximal small intestine 1. Flattened villi 2. Increased number and size of crypts 3. Increased intraepithelial lymphocytes (IELs) and plasma cells
Antibody subtypes that can be tested for celiac
IgA and IgG
