SEARCH RESULTS FOR: celiac disease

Celiac Disease: Pathogenesis and clinical findings

Celiac Disease: Pathogenesis and clinical findings Associated with other autoimmune disorders (i.e. DM1, thyroiditis, RA, SLE, Addison's) Genetic predisposition -■ (Northern European, Down's syndrome, Associated with HLA DQ 2,8) Note: *The anti-TTG antibody is an IgA anti-body, therefore if the patient is IgA-deficient, absence of anti-TTG does not rule out celiac Anti-TTG in serum* Anti-TTG reacts with TTG in skin Deposition of anti-TTG in renal glomeruli Dermatitis herpetiformis Chronic Kidney Disease Small Bowel Biopsy: Crypts of bowel become enlarged (hyperplasia) with architectural change, villous shortening Legend: Pathophysiology Mechanism Exposure to prolamins (proteins found in wheat, rye, oats, barley) TTG alters prolamin Altered protein fits more easily into HLA HLA activates adaptive immunity IgA generated against prolamin-TTG Wheat prolamin (gliandin) interacts with and activates zonulin signalling Gut epithelium becomes more porous Large dietary proteins in epithelium disrupt tight junctions Author: Matthew Harding Yan Yu Peter Bishay Reviewers: Dean Percy Jason Baserman Usama Malik Kerri Novak* * MD at time of publication Inflammation of Intestinal epithelium Inflammation disrupts structure of bowel mucosa Mechanism Unknown Lymphocytes migrate to site of inflammation Extraintestinal Complications: Arthropathy Ataxia (gluten associated) Infertility Mild Hepatitis Villi of intestine atrophy Risk of Microscopic Colitis (50x) Malabsorption Extraintestinal manifestations: Chronic watery Fatigue Failure to thrive, weight loss Anemia (Fe, B12, folate) Peripheral neuropathy (B12, Ca) Ataxia (Ca) Dysrhythmia (Ca, K) Osteoporosis (Vit D, Ca) diarrhea + Intestinal manifestations steatorrhea: Pale, foul-smelling Abdominal bloating Steatorrhea (fat in stool) Diarrhea

Celiac Disease: Complications

Celiac Disease: Complications Autoimmune response to dietary gluten in genetically predisposed individuals 4 Celiac Disease Note: most common presentation with minor symptoms and iron deficiency Modified gluten peptides activates HLA-DQ2 and DQ8 receptors on T cells Activation of B cells to produce anti-tTG2 autoantibodies 1 tanti-tTG2 Release of pro-inflammatory cytokines Villous Atrophy along duodenum and/or jejunum Loss of brush border Loss of enterokinase Defective mucosal barrier enzyme (failure to produce trypsin) Carbohydrate Protein Fat Secretory maldigestion maldigestion malabsorption diarrhea Legend: Fermentation by gut bacteria 1 Gas production Bloating Fat retained in stool Steatorrhea Abdominal pain Pathophysiology Mechanism Sign/Symptom/Lab Finding Growth Retardation Authors: Yoyo Chan Reviewers: Peter Bishay Usama Malik Sylvain Coderre* * MD at time of publication IgA response Autoimmune IgA deposits Lymphocyte response in sub-epidermal skin layer against enamel Dermatitis Herpetiformis (Chronic pruritic blisters) Nutritional deficiency Dental enamel hypoplasia Vitamin D and calcium deficiency Zinc, selenium Folate Iron Osteoporosis deficiency deficiency deficiency Anemia t Risk of miscarriages

Vitamin K Deficiency

Vitamin K Deficiency: Pathogenesis and Clinical Findings Author: Sean Spence Reviewers: Michael Blomfield, Tony Gu, Tristan Jones, Yan Yu Man-Chiu Poon* Lynn Saviole* * MD at initial time of publication Dietary Deficiency Small bowel bacterial overgrowth Antibiotic use Disruption of normal flora ↓ Gut flora synthesis Vitamin K Deficiency ↓ vitamin K dependent gamma carboxylation of clotting factors II, VII, IX, X Gastrointestinal mucosal diseases (e.g., Celiac disease) Pancreatic insufficiency Cholestasis Malabsorption Exposure to vitamin K antagonists (e.g., warfarin) Inhibition of vitamin K epoxide reductase ↑ bleeding tendency Gastrointestinal tract bleeds Intracranial bleeds Hemarthoses (bleeding into joints) Easy bruising Petechiae, purpura Heavy menstrual bleeds Prolonged PT/INR Note: PT/INR is more sensitive and validated for warfarin monitoring ↓ Activity of intrinsic clotting pathway Prolonged PTT ↓ Activity of extrinsic clotting pathway Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published July 27, 2019 on www.thecalgaryguide.com

Digestion and Absorption of Macromolecules

Digestion and Absorption of Macromolecules Authors: Krisha Patel Reviewers: Parker Lieb, Sunawer Aujla Ran (Marissa) Zhang, Shyla Bharadia, Mao Ding Sylvain Coderre* *MD at time of publication Lipids (triglycerides) Gastric lipase breaks down triglycerides into diglycerides and fatty acids (little digestion of triglycerides occur in stomach) Bile, produced by the liver, and pancreatic lipase enter the small intestine through the common bile duct The hydrophobic and hydrophilic properties of bile allow it to effectively bind hydrophobic fats with hydrophilic pancreatic lipases Pancreatic lipases break down triglycerides into monoglycerides, fatty acids, and glycerol as a result of emulsification by bile Monoglycerides and fatty acids are absorbed through bile-stabilized chylomicrons (lipid molecules arranged in spherical form) Triglyceride-rich chylomicrons are transported through the lymphatic system and require the activity of tissue lipoprotein lipase when they arrive at the tissue Triglycerides enter systemic circulation for metabolism, energy source, and fat storage Ingestion of nutrition sources containing macromolecules Carbohydrates (oligosaccharide) Salivary amylases in the mouth break down oligosaccharides and starch into shorter polysaccharides Pancreatic amylases break down polysaccharides into monosaccharides, disaccharides, and oligosaccharides in the stomach Brush border enzymes in small intestinal villi break down disaccharides into Proteins (peptides) Pepsinogen is secreted by the stomach wall Hydrochloric acid activates pepsinogen to pepsin in the stomach Pepsin breaks down protein peptides into oligopeptides and amino acid chains The pancreas generates trypsinogen and other enzymes to be released into the duodenum Trypsinogen undergoes cleavage in the duodenum through the action of duodenal enteropeptidases to form trypsin Intravenous proton pump inhibitors used in upper gastrointestinal bleeds stabilize pepsinogen, and prevent pepsin from breaking down clotting factors (proteins) enabling clotting Maltose Maltase monosaccharides: Sucrose Sucrase Glucose + fructose Lactose Lactase Glucose + galactose Glucose + glucose Conditions affecting the duodenum (e.g., Celiac disease) can lead to lower enteropeptidase levels, resulting in impaired protein digestion Activation of trypsinogen to trypsin within the pancreas, rather than in the duodenum, contributes to autodigestion observed in acute pancreatitis Absorption of glucose and galactose through active transport via SGLT-1 carrier protein in the Jejunum and Ileum Absorption of fructose through facilitative diffusion via transporter GLUT5 in the Jejunum and Ileum Pancreatic enzymes (trypsin, chymotrypsin, carboxypeptidase) break down oligopeptides and amino acid chains into amino acids, dipeptides, and tripeptides in the duodenum Monosaccharides enter systemic circulation for energy use and storage Active Na+ cotransporters facilitate amino acid absorption in the jejunum and ileum PEPT1 enzymes facilitate absorption of dipeptides and tripeptides, which are then immediately cleaved into amino acids in the jejunum and ileum Amino acids enter systemic circulation for building & repairing muscles Legend: Pathophysiology Mechanism Treatment Effect Complications Published May 18, 2023 on www.thecalgaryguide.com

Constipation in Children

Constipation in Children: Pathogenesis and clinical findings Neonate / Infant (≤1 years old) Older Child (>1 years old) Dietary (e.g., lack of fluids / fiber) Mechanical (e.g.,. intestinal Atresia, anal atresia) Congenital malformation (narrowing, absence, or malrotation) of structure of intestine / anus Interrupted flow of bowel contents Genetic (e.g., cystic Fibrosis) Mucous blocks pancreatic duct Inability of pancreatic enzymes to reach small intestine ↓ Digestion after a meal Large, thickened stool Neurologic (e.g., Hirschsprung's disease) Congenital disruption of the migration of neural crest cells to the distal colon Affected segment of the colon fails to relax Progressive secondary dilation of the healthy proximal colon Systemic (e.g., hypothyroidism) Thyroid hormone deficiency Reduction in the stimulation of gut tone & contractility by thyroid hormones ↓ Peristalsis (intestinal contractions) of the bowel Dietary (e.g., lack of fluids/ fiber) Mucosal (e.g., celiac disease) Inappropriate immune response against gluten Intestinal mucosal injury Malabsorpti on of water and other nutrients Functional (e.g., pain) Prolonged stool retention in bowel ↑ Time in bowel causing over- absorption of water from stool into the large intestine Mechanical (e.g., bowel obstruction) Mechanical obstruction in the intestines Interrupted flow of bowel contents Intestinal obstruction Neurologic (e.g., neglect, physical abuse) Disturbance in brain-intestine axis Mechanisms not fully understood Visceral hyper- sensitivity (increased pain sensation) Withholding behaviour Lack of soluble fiber ↓ Attractive forces between water & stool Prevention of secretion of water into stool Lack of insoluble fiber ↓ Stool bulk and laxation ↓ Secretion of water & mucous into stool Lack of soluble fiber ↓ Attractive forces between water & stool Prevention of secretion of water into stool Lack of insoluble fiber ↓ Stool bulk and laxation ↓ Secretion of water & mucous into stool Formation of dry & hard stool Formation of dry & hard stool Difficulty passing stool Difficulty passing stool Authors: Jennifer Wytsma Reviewers: Sophia Khan, Shahab Marzoughi, Sylvain Coderre* * MD at time of publication Intestinal obstruction Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Dec 15, 2024 on www.thecalgaryguide.com