Malabsorption CPC Flashcards
What blood tests do you request in someone who is tired all the time (6)
FBC Electrolytes, creatinine, calcium LFTs Blood glucose TFTs Vitamin D
Causes of low MCV (3)
Iron deficiency
Thalassaemia trait
Anaemia of chronic disease
Low Hb
Low Serum Iron
Raised TIBC or transferrin
Low Ferritin
Iron deficiency
Low Hb
Low Serum Iron
Normal or low TIBC or transferrin
Normal or high (acute phase) Ferritin
Anaemia of chronic disease
Normal or low Hb
Normal Serum Iron
Normal TIBC or transferrin
Normal Ferritin
Thalassaemia trait
Hypochromic RBC (pale) Microcytic RBC (small)
Iron deficiency
Thalassaemia trait
Poikolocytes e.g. Tear drop RBC
Iron deficiency
Anisopoikilocytosis e.g. elliptocyte
Iron deficiency
Basophilic stippling - aggregated ribosomal material (4)
Beta thalassaemia trait
lead poisoning
Alcoholism
Sideroblastic anaemia
Hypersegmented neutrophils
Megaloblastic anaemia - reflects impaired DNA synthesis
What are some causes of megaloblastic anaemia (3)
B12 deficiency
Folate deficiency
Drugs
Target cells (4)
Iron deficiency
Thalassaemia
Hyposplenism
Liver disease
What are howell jolly bodies
Nuclear remnants visible in red cells
Howell Jolly bodies
Hyposplenism
Iron deficiency (2)
Hypochromic and microcytic
Anisopoikilocytosis
Megaloblastic anaemia (2)
Hypersegmented neutrophils
Large /macrocytic’ cells
Hyposplenic features (2)
Target cells
Howell Jolly bodies
Causes of iron deficiency (3)
Major blood loss
Poor diet
Malabsorption
Causes of megaloblastic changes (2)
B12 or folate deficiency (poor diet, malabsoprtion, pernicious anaemia)
Causes of hyposplenism (2)
Absent spleen
Poorly functioning spleen
Causes of absent spleen (2)
Therapeutic
Trauma
Causes of poorly functioning sleep (4)
Inflammatory bowel disease
Coeliac disease
Sickle cell disease
SLE
Vitamin D deficneicy
B12/Folate deficiency
Iron deficiency
Hyposplenism
What unifies the above conditions
Bowel disease with malabsorption
Iron deficiency B12 deficiency Folate deficiency Fat deficiency (steatorrhoea/weight loss) Calcium deficiency
Coeliac disease
B12 deficiency
Bile salt deficiency
Crohn’s disease
Fat deficiency (steatorrhoea/weight loss) Calcium deficiency B12 deficiency
Pancreatic disease
Fat deficiency (steatorrhoea/weight loss) Folate deficiency
Infective/Post-infective
What HLA is associated with coeliac disease (2)
HLA DQ2 in 90% of patients
HLA DQ8 in the rest
What is the concordance of coeliac in monozygotic twins
75%
What type of inheritance is coeliac disease
Polygenic auto-immune disease
What immunological function underpins coeliac disease
T cell response to gluten
Peptides from gliadin are deamidated by tissue transglutaminase and presented by APC
CD4 T cells recognise these deamidated peptides presented by HLA DQ2 or DQ8
CD4 T cell activation results in secretion of IFN-g and may indirectly lead to increased IL-15 secretion
IL-15 promotes activation of the intra-epithelial lymphocytes (IEL)
Intra-epithelial lymphocytes kill epithelial cells in an NKG2D dependent manner
The activation and function of the intra-epithelial lymphocytes appears to be independent of engagement of their T cell receptor
What mediates the cell damage in coeliac disease
Damage mediated by gamma-delta TCR expressing IEL
What antibodies are present in coeliac disease (3)
Anti-gliadin antibodies
Anti-tissue transglutaminase
Anti-endomysial antibodies
What are anti-gliadin antibodies
Gliadin is a component of gluten
IgA antibodies more sensitive than IgG antibodies, but both unreliable
Outdated test – but suggested an immune response against a ‘foreign’ protein in food was occurring in patients
What are the specific tests for coeliac disease (3)
IgA anti-endomysial antibody
IgA anti-transglutaminase antibody
IgG or IgA anti-gliadin antibody
What is the first line immunological test in coeliac disease
IgA anti-transglutaminase antibody
What is the gold standard diagnostic test in coeliac disease
Duodenal biopsy
What is characteristic in a duodenal biopsy for coeliac disease
Villous atrophy
What is the normal duodenal villous:crypt ratio
4:1
What is the pathology of villous atrophy is coeliac disease (2)
In coeliac disease, the villous height is reduced and crypts become hyperplastic, resulting in reduced or reversed villous:crypt ratio
Although height of villi are reduced, mucosal thickness remains the same due to crypt hyperplasia
Villous atrophy results in decreased surface area = malabsorption
What causes malabsorption in coeliac disease
Villous atrophy
What is the pathology RE IELs in coeliac disease
Normal duodenal villi contain less than 20 intraepithelial lymphocytes/100 epithelial cells
In coeliac disease, this is increased to >20 IELs/100 epithelial cells
These lymphocytes are gamma-o T cells
What are IELs
Intra-epithelial lymphocytes
What is the normal IEL ration
5/100 epithelial cells
What is the coeliac IEL presentation
> 20/100 epithelial cells
What are the causes of increased epithelial lymphocytes (8)
Coeliac disease Dermatitis herpetiformis Cows milk proteins sensitivity IgA deficiency Tropical sprue Post infective malabsorption Drugs (NSAIDs) Lymphoma
What are some causes of villous atrophy (10)
Coeliac disease Giardiasis Troipical sprue Crohn's disease Radiation/chemotherapy Bacterial overgrowth Nutritional deficiencies Graft versus host disease Microvillous inclusion disease Common variable immunodeficiency
What are the histological features of coeliac disease (6)
Subtotal villous atrophy
Increased intraepithelial lymphocytes
Crypt hyperplasia
Increased inflammatory cells in the lamina propria
No evidence of Giardia
Consistent with coeliac disease, need to correlate with serology and clinical picture
What are the principles of management of coeliac disease (5)
Dietary management Advice re long term complications Implications for family Sources of patient information Ongoing monitoring
What are the principles of a gluten free diet for coeliac disease (3)
Gluten is present in wheat, barley rye and oats (some)
Strict adherence is important in eliminating symptoms and preventing complications
Good dietetic support is vital
What are the complications of coeliac disease (5)
Malabsorption Osteomalacia and osteoporosis Neurological disease (Epilepsy, Cerebral calcification) Lymphoma Hyposplenism
What are the practical implications of a gluten free diet
Cost of a gluten free diet
Do all the family have to eat gluten free?
What are the prognostic indicators for coeliac disease
genetic component - HLA0-DQ2 - increased risk in other family members
What is essential to provide the patient in a newly diagnosed coeliac disease
VERY important to provide support and information (patient support groups, dieticians, medical staff, family)
What are the follow up investigations for patients with coeliac disease (4)
Haematology - FBC, iron level, TIBC, ferritin, vitamin B12, folate, prothrombin time
Biochemistry - U&Es, creatinine, calcium, phosphate, LFTs, albumin and total serum protein levels
Serological tests, IgA antitransglutaminase antibody or IgA endomysial antibody
Imaging - DEXA of spine and hip - every 3-5 years
Key features for dietary adherence in coeliac disease
Strict adherence is vital
Additives to gluten free foods can catch out the unwary
- Processed starch, and processed foods
- Mustards, salad dressings
- Some ice cream thickeners
Some patients have problems adhering to diet
- Inconvenient
- Foods are not always labelled clearly
- Specific problems of adolescents, elderly
How many patients present with typical coeliac disease symptoms
10%
Where is coeliac disease most common
North Africa
What are the consequences of undiagnosed coeliac disease (3)
Often have undiagnosed deficiencies - iron, folate, B12, vitamin D and K.
Dietary compliance protects against malignancy
Often feel better physically and psychologically when treated.
What is the mortality in untreated coeliac disease
Mortality rate is 2-3 times greater than the general population (malignancy, (especially lymphoma), infection)
The excess mortality returns to normal after 3-5 years on gluten free diet.
What is coeliac disease associated with
Other auto-immune disorders
What auto-immune disorders is coeliac disease associated with (4)
Dwrematitis herpetiformis (100% prevalence)
T1DM (7% prevalence)
Autoimmune thyroid disease
Down’s syndrome
What is the commonest presentation of coeliac disease (3)
Microcytic anaemia, past or present
Family history of coeliac disease
Feeling tired all the time
