Malabsorptive conditions Flashcards
What is malabsorption
Failure to fully absorb nutrients wither because of the destruction to epithelium or due to a problem in the lumen meaning food can’t be digested
Before malabsorption is diagnosed, what needs to be ruled out
Insufficient intake must be rules out to ensure it is actually malabsorption
How can pancreatic disorders cause malabsorption
- Pancreas produce most enzymes for digestion such as amylase
- Pancreatitis damages glands meaning no enzymes are released
- Cystic fibrosis blocks pancreatic duct due to excess mucus meaning enzymes fail to be released
Name two ways defective bile secretion can result in malabsorption
- Biliary obstruction
2. Ileal resection (we reabsorb bile salts in the terminal ileum so if removes bile uptake will decrease)
What other factor causes malabsorption
Bacterial overgrowth
How does coeliac’s disease cause malabsorption
Villi are short if present at all, villous atrophy and crypt hyperplasia
Lots of lymphocyte sin epithelium
How does Crohn’s cause malabsorption
- Inflammatory damage to lining of bowel = cobblestone mucosa with significant reduction in absorptive SA
What is Giardia lambda and how does it cause malabsorption
- Extensive surface parasitisation of villi and microvilli
2. Parasites coat surface of cilli and food can’t be absorbed
How does disaccharidase deficiency cause malabsorption
- Cannot break down lactose in milk into glucose which can then be absorbed. Undigested lacrosse passes into colon where bacteria eat it and produce CO2 (gas and diarrhoea)
What is abetalipoproteinaemia
Lack of transporter protein to transport lipoprotein across cell
What defective epithelial transport conditions result in malabsorption
Abetalipoproteinaemia
Primary bile acid malabsorption (Mutations in bile acid transporter protein)
What lymphatic diseases can result in malabsorption
Lymphatic obstruction
- Lymphoma
- TB
What is coeliac’s disease
Condition in which there is inflammation of the mucosa of the upper small bowel the improves when gluten is withdrawn from diet (relapses when gluten is reintroduced)
Pathophysiology of coeliac’s disease
T-cell mediated autoimmune disease of small bowel in which prolamin intolerance causes villous atrophy and malabsorption
What are prolamins
Groups of plant storage proteins
Component of gluten proteins
What prolamin are found inn wheat
Gliadin
What prolamin is found in barley
Hardens
What prolamin is found in rye
Secalins
When should you suspect Coeliac’s disease
Diarrhoea, Weight loss or Anaemia (iron or B12 deficient with no cause)
What gender does Coeliac’s effect
males and females
Causes of coeliac’s
Gluten
Risk factors for Coeliac’s
- Autoimmune dieases: Type 1, Thyroid and Sjorgren’s
- IgA deficiency
- Breast Feeding
- Age of introduction to gluten into diet
- Rotavirus infection in infancy increases risk
What part of the gluten in wheat is toxic
Prolamin a-GLIADIN
What is Prolamin a-GLIADIN resistant to
Digestion by pepsin and chymotrypsin because of high glutamine and proline content
How does prolamin a-GLIADIN trigger immune responses
By remaining in the intestinal lumen
What happens to gliadin peptides
Pass through epithelium and are deaminated by tissue transglutaminases = increases their immunogenicity
How do gliadin peptides trigger inflammation
Bind to antigen-presenting cells after deamination
APC interacts with CD4+ T cells in LAMINA PROPRIA via HLA class II molecules
T cells then produce pro-inflammatory cytokines and initiate cascade
What HLA class II molecules does gliadin interact with
DQ2 or DQ8
How do DQ2 AND DQ8 EFFECT T CELLS
Activate the gluten-sensitive T cells
End product of inflammatory cascade in Coeliac’s
Metaloproteinkinases and inflammatory mediators that cause:
VILLOUS ATROPHY
CRYPT HYPERPLASIA
Intraepithelial lymphocytes
^ Causes malabsorption
What structure of the GI is primarily effected in Coeliac’s
Proximal small bowel mucosa
How does Coeliac’s result in anaemia
Damage to mucosa means B12, folate and iron can’t be absorbed
How does the severity of the mucosa change as we approach the ileum
Mucosal damage decreases as gluten is broken down into small non-toxic fragments
Clinical Presentation of Coeliac’s
- 1/3 are asymptomatic (detected on routine blood tests)
- Stinking stools/fatty stools (steatorrhoea)
- Diarrhoea
- Bloating
- Abdo pain
- Nausea + vomiting
- Angular stomatitis
- Weight loss
- Fatigue
- Anaemia
- Osteomalacia
- Dermatitis hepetiformis
What is angular stomatitis
Inflammation of one or both corners of the mouth
What is osteomalacia
Softening of bones due to impaired bone metabolism due to lack of phosphate, calcium and fit D leading to osteoporosis
What is dermatitis hepetiformis
Red raised patches, often with blisters thet burst on scratching, commonly seen on elbows, knees and buttocks
How is Coeliac’s disease diagnosed
Maintain gluten for at least 6 weeks before testing to get correct results:
FBC
Duodenal biopsy (GOLD STANDARD)
Serum antibody testing
What should be seen on blood tests for Coeliac’s
- Low Hb
- Low B12
- Low ferritin
How does a duodenal biopsy help with diagnosing coeliac’s
- See villous atrophy
- Crypt hyperplasia
- Increased intraepithelial WCC
- IgA serum
On gluten free diet would we see villous atrophy and crypt hyperplasia on duodenal biopsy
No
Name two IgAs looked for in serum antibody tests for coeliac’s
- Endomysial antibody
2. tTG (Tissue transglutaminase antibody
How is Coeliac’s treated
Lifelong gluten-free diet (no prolamins)
Correction of vitamins and mineral deficiencies
DEXA scan to monitor osteoporotic risk
What would a gluten-free diet look like
- Eliminate wheat, barley and rye
- Oats can be tolerated (no flour which can contaminate them in production
- Meat, dairy, fruits and veg are gluten-free
Complications of coeliac’s
- Diet may not improve things (non-responsive coeliac’s disease)
- Anaemia
- Secondary lactose intolerance
- T-cell lymphoma
- Increased risk of malignancy (gastric, oesophageal, bladder, breast and brain) due to increased cell turnover
- Osteoporosis
What is Tropical Sprue
- Severe malabsorption (of two or more substances) with:
Diarrhoea
Malnutrition
Where is tropical sprue seen
Visitors or residents to tropical areas where disease is endemic (most of asia, carribbevn, puerto rico and parts of SA)
What is the cause of tropical sprue
UNKNOWN but patients improve on antibiotics
What happens to the GI tract in tropical sprue
Villous atrophy (malabsorption)
Describe the onset of tropical sprue
Acute and occurs either a few days or many years later being in the tropics
Clinical presentation of tropical sprue
- Diarrhoea
- Anorexia
- Severe malabsorption
- Weight loss
- Abdominal distention
- Chronic diarrhoea
How is tropical sprue diagnosed
- First we need to exclude acute INFECTIVE causes of diarrhoea (Giardia intestinal - produces similar symptoms)
- Blood tests
- JEJUNAL biopsy
What should blood tests show for tropical sprue
- Anaemia due to malabsorption of B12, folate and iron
What should a jejunal biopsy show for tropical sprue
- Jejunal mucosa is abnormal showing partial villous atrophy (complete atrophy in coeliac)
How is tropical sprue treated
- Leave area
- FOLIC ACID and antibiotics daily
- Severe cases: resuscitation with fluids and electrolytes for dehydration and nutritional deficiencies should be corrected and B12 given
- Excellent prognosis
- Mortality is only associated with water and electrolyte depletion particularly in epidemics
What antibiotic is given for tropical sprue
TETRACYCLINE
What is inflammatory bowel disease
- CHRONIC AUTOIMMUNE CONDITIOINS
