L4 - Food intolerance

Question 1

Predisposing gene in celiac’s disease

Answer 1

HLA-DQ2
HLA-DQ8

Strong genetic component association with human leukocyte antigen HLA/DQ2 . HLA/DQ8

Question 2

What is gluten

Answer 2

Storage protein for wheat, barely, rye.
Mixture of proteins including gliadins.
Gliadin - alcohol soluble fraction of gluten

Question 3

Why is gluten hard to digest

Answer 3

• 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

Question 4

Coeliac’s disease

Answer 4

Inflammation of upper small bowel that improve when gluten is withdrawn from diet, relapses when gluten is reintroduced.

Question 5

How may gluten trigger an immune response, as seen in Coeliac patients

Answer 5

• 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

Question 6

What do Endomysial antibodies do?

Answer 6

• Antibodies to gluten.
• Cause intestinal swelling.
• Prevent nutrient absorption leading to malnutrition.

Question 7

Clinical features of Coeliac’s disease

Patient with more serious disease may present with

Answer 7

• Affects many females.
• tiredness, malaise associated with anaemia
• more severe disease if steatorrhoea, diarrhoea, abdominal pain and weight loss is present

Question 8

Diagnosis of Coeliac’s

What might we see

Answer 8

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.

Question 9

Dermatitis herpetiformis

Answer 9

• 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

Question 10

Describe a food allergy

Answer 10

• IgE mediated , occur within mins to hrs

- Acute hypersensitivity: urticaria (hives), vomiting, diarrhoea after eating

Question 11

Recap pathophysiology of CD

Answer 11

• 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.

Question 12

Describe primary and secondary lactose intolerance

Answer 12

Primary: lactose deficiency normal
Secondary: occurs as consequence of disorder that damages the jejunal mucosa

Question 13

Clinical features of lactose intolerance

Answer 13

Patients may present with:

• colicky pain
• abdominal distention
• increased flatus
• borborygmus (rumbling or gurgling)

Question 14

Common food allergies may result in…

Answer 14

Urticaria (hives)

Angioedema of lips and oropharynx

Question 15

Why are patients with inflammatory bowel disease IBD more likely to develop osteoporosis?

Answer 15

Effects of chronic inflammation.
Gluccocorticoids.
Weight loss.
Malnutrition and malabsorption.

Question 16

A patient with microscopic colitis may have…

Answer 16

• persistent watery diarrhoea

- histological examination of biopsies are abnormal

Question 17

Collagenous colitis

Answer 17

Presence of submucosal band of collagen with chronic inflammatory infiltrate

Question 18

Define IBS

Answer 18

Recurrent abdominal pain in association with normal defecation in absence of structural abnormality of gut.

Question 19

Describe physiological factors of IBS

Answer 19

Patient with diarrhoea
- excessive release of 5-HT
Patient with constipation
- deficiency in 5-HT release

Question 20

Define FODMAP

Answer 20

Some patients have chemical food intolerance’s to poorly absorbed, short chain carbohydrates collectively known as FODMAP.

• Fermentable Oligo Di & Monosaccharides and Polyols

Question 21

Describe symptoms some patients may have from consuming FODMAPs

Answer 21

• Fermentation of oligo-di-monosaccharides in colon may lead to bloating, pain and wind as well as altered bowel habit.

Question 22

How may you test for some allergies e.g. peanut allergies?

Answer 22

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

Question 23

Describe how a allergy skin prick test is carried out?

Answer 23

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

Question 24

Describe Looser’s zones

Answer 24

Small fracture not going right the way through the bone.

Osteomalacia

Question 25

Diagnosing Coeliac’s disease

Answer 25

Blood test: IgA TTG

HLA predisposition: DQ2 / DQ8

Question 26

What might be seen on endoscopy of a Coeliac patient

Answer 26

Scalloping of duodenal folds.

Question 27

What might be seen on the histology of a sample taken from a Coeliac patient?

Answer 27

Villi gone.
Crypts longer.
Surface area decreased, leading to malabsorption.
Intra-epithelial lymphocytes interact with peptides

Question 28

What is an important differential diagnosis for Coeliac’s disease?

Answer 28

Giardia - water parasite

Biopsy looks similar.

Question 29

Coeliac disease treatment

Answer 29

Avoid gluten.

Follow up:

• Check TTG
• Vitamins
• Bone mineral density