B50 Malabsorption Flashcards
What are the 4 main processes that can be disturbed to cause malabsorption?
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Intraluminal digestion: Proteins, Carbs, and fats are broken into small polymers
- Pancreatic insufficiency, from chronic pancreatitis in chronic alcoholics and cystic fibrosis patients.
- Inactivation of pancreatic enzymes by excessive gastric acid
- Terminal digestion: Dissacharides, trisaccharides and short polypeptides are broken down into monomers at the intestinal brush border.
- Transepithelial transport / Mucosal Absorption:
- Lymphatic transport / Nutrient delivery
How does malabsorption syndrome present clinically?
What are the 3 most common causes, and 3 other important causes?
As chronic diarrhea, with noticeable steatorrhea, bulky, foamy, greasy, yellow, or clay colored stool.
There is also excessive flatulence**, **bloating and abdominal pain (meteorism), and weight loss
Eventually: Bleeding disorders from Vit K def. and Anemia from B12 deficiency. Osteomalacia from vitamin D deficiency, Neuropathy from vitamin A and B12 deficiency. Many skin disorders from other vitamin deficiencies.
Causes
- Pancreatic insufficiency, from 1) Alcholism and 2) Cystic Fibrosis
- Celiac disease,
- Crohn disease.
Other important causes: Graft versus host disease after HSC transplantation, and Tropical sprue. Hepatic failure or cholestasis –> fat malabsorption
What is the allergen causing Celiac disease and what is its immunogenic metabolite?
Gluten, which is broken down to Gliadin.
Describe the autoimmune reaction in Celiac disease
Gliadin takes a long time to digest. It becomes deaminated and then can bind to HLA2 class molecules on APCs, generating a Th cell response, which then activate B cells.
B cells produce these important antibodies
- anti-deaminated gliadin which is an IgA antibody
- anti-transglutaminase both IgA and IgGs
- anti-endomysium (these are used to diagnose)
These antibodies elicit autoimmune reactions against the gliadin bound in the brush border, and also cause activation of Tc cells which destroy the mucosa and gradually cause mucosal flattening.
Where does Celiac disease cause intestinal damage?
What does it look like histologically?
In the duodenum and proximal jejunum.
Biopsy from these regions is used to diagnose the disease.
Histology:
- Atrophy and flattening of the villi
- Hyperplasia of the crypts (crypts of leiberkuhn, presumably because of the stem cell hyperplasia)
- Lymphocytosis of the epithelium
What are the various clinical types of celiac disease?
Silent, with atrophy and auto-abs, but no clinical symptoms
Latent, with auto-abs but no atrophy or symptoms.
Adult celiac disease usually appears between age 30 and 60, appears with the intestinal symptoms and also with iron def anemia or less often pernicious anemia.
Pediatric celiac disease appears in the 1st or 2nd year of life. Irritability, intestinal symptoms, slow growth, anorexia, weight loss, muscle loss, and failure to thrive. About 10% develop a characteristic dermatitis herpetiformis, skin blisters.
What are the causes of impaired mucosal absorption?
Abetalipoproteinemia: congenital lack of Aapolipoprotein B. ApoB is essential for chylomycrons and VLDL formation. Causes lipid malabsorption, and deficiencies of all the fat soluble vitamins, as well as deficient cholesterol/TAG absorption, causing membrane abnormalities and burr cells
Lactose intolerance: In its congenital form is rare, and caused by total deficiency of lactase. causes severe diarrhea and GI bacterial proliferation in infants.
What are causes of malabsorption due to reduces intestinal surface area?
Celiac disease
Crohn’s disease
Tropical sprue
Whipple disease
both tropical sprue and whipple are intestinal infections
What malignancies are associated with Celiac disease?
Enteropathy associated T cell lymphoma - an aggressive intraepthelial T-cell Tumor.
Small intestinal adenocarcinoma.
These tumors should be considered when symptoms re-emerge in a celiac patients with a well controlled diet.
