L4 - Food intolerance Flashcards
Predisposing gene in celiac’s disease
HLA-DQ2
HLA-DQ8
Strong genetic component association with human leukocyte antigen HLA/DQ2 . HLA/DQ8
What is gluten
Storage protein for wheat, barely, rye.
Mixture of proteins including gliadins.
Gliadin - alcohol soluble fraction of gluten
Why is gluten hard to digest
- Gluten protein rich in glutamine, prolamine.
- Hence therefore incompletely digested by gastric, pancreatic and brush border peptidases.
- This leaves large long chain amino acids.
- These remain in intestinal lumen triggering immune response.
- Peptides will pass through epithelial barrier of intestine and enter lamina propia
Coeliac’s disease
Inflammation of upper small bowel that improve when gluten is withdrawn from diet, relapses when gluten is reintroduced.
How may gluten trigger an immune response, as seen in Coeliac patients
- Gliadin peptides pass through epithelium
- deaminated via tissue transglutaminase
- thus increasing their immunogenicity
- gliadin peptides then bind to APC
- APC interacts with CD4+ T cells in lamina propia via HLA class II molecules DQ2 or DQ8
- T cell releases pro-inflammatory cytokines
- cytokines interact with B-cells to produce endomysial and transglutaminase antibodies.
- EMAs are antibodies to gluten
What do Endomysial antibodies do?
- Antibodies to gluten.
- Cause intestinal swelling.
- Prevent nutrient absorption leading to malnutrition.
Clinical features of Coeliac’s disease
Patient with more serious disease may present with
- Affects many females.
- tiredness, malaise associated with anaemia
- more severe disease if steatorrhoea, diarrhoea, abdominal pain and weight loss is present
Diagnosis of Coeliac’s
What might we see
Small bowel biopsy.
Coeliac disease common cause of subtotal villous atrophy.
Crypt hyperplasia.
Chronic inflammatory cells in lamina propia.
Enterocytes become cuboidal with an increase in the number of intra-epithelial lymphocytes.
Dermatitis herpetiformis
- Chronic auto-immune uncommon blistering over elbows, knees, back and buttocks.
- sub-epidermal eruptions of skin associated with gluten sensitive enteropathy.
- enteropathy: disease of intestine
Describe a food allergy
- IgE mediated , occur within mins to hrs
- Acute hypersensitivity: urticaria (hives), vomiting, diarrhoea after eating
Recap pathophysiology of CD
- Gluten peptide deaminated in epithelial cell
- tissue transglutaminase catalyses reaction
- peptide then able to fit the antigen-binding motif on human leukocyte antigen HLA-DQ2, positive APC
- recognition by CD4+ T cells triggers TH1 immune response with generation of pro-inflammatory molecules
- lymphocyte infiltrate lamina propia increase intra-epithelial lymphocytes, crypt hyperplasia and villous atrophy ensue.
Describe primary and secondary lactose intolerance
Primary: lactose deficiency normal
Secondary: occurs as consequence of disorder that damages the jejunal mucosa
Clinical features of lactose intolerance
Patients may present with:
- colicky pain
- abdominal distention
- increased flatus
- borborygmus (rumbling or gurgling)
Common food allergies may result in…
Urticaria (hives)
Angioedema of lips and oropharynx
Why are patients with inflammatory bowel disease IBD more likely to develop osteoporosis?
Effects of chronic inflammation.
Gluccocorticoids.
Weight loss.
Malnutrition and malabsorption.
A patient with microscopic colitis may have…
- persistent watery diarrhoea
- histological examination of biopsies are abnormal
Collagenous colitis
Presence of submucosal band of collagen with chronic inflammatory infiltrate
Define IBS
Recurrent abdominal pain in association with normal defecation in absence of structural abnormality of gut.
Describe physiological factors of IBS
Patient with diarrhoea
- excessive release of 5-HT
Patient with constipation
- deficiency in 5-HT release
Define FODMAP
Some patients have chemical food intolerance’s to poorly absorbed, short chain carbohydrates collectively known as FODMAP.
- Fermentable Oligo Di & Monosaccharides and Polyols
Describe symptoms some patients may have from consuming FODMAPs
- Fermentation of oligo-di-monosaccharides in colon may lead to bloating, pain and wind as well as altered bowel habit.
How may you test for some allergies e.g. peanut allergies?
Skin prick test
- insert small bit of peanut antigen into skin
- if wheel of redness / inflammation is 3mm greater than wheel of control the considered positive reaction
Describe how a allergy skin prick test is carried out?
Lancet used to penetrate skins surface with antigen.
Furthermore:
- Histamine: causes skin response
- Glycerin or saline: does not cause reaction, so if patient reacts they may have very sensitive skin
Describe Looser’s zones
Small fracture not going right the way through the bone.
Osteomalacia
Diagnosing Coeliac’s disease
Blood test: IgA TTG
HLA predisposition: DQ2 / DQ8
What might be seen on endoscopy of a Coeliac patient
Scalloping of duodenal folds.
What might be seen on the histology of a sample taken from a Coeliac patient?
Villi gone.
Crypts longer.
Surface area decreased, leading to malabsorption.
Intra-epithelial lymphocytes interact with peptides
What is an important differential diagnosis for Coeliac’s disease?
Giardia - water parasite
Biopsy looks similar.
Coeliac disease treatment
Avoid gluten.
Follow up:
- Check TTG
- Vitamins
- Bone mineral density
