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