Pathology of Malabsorption Flashcards
What is malabsorption?
defective absorption of fats, vitamins, proteins, carbohydrates, electrolytes, minerals and water.
What will you see with malabsorption?
- chronic diarrhea
- weight loss, fatigue, anemia
- steatorrhea (excessive fecal fat)
What are some mechanisms by which malabsorption can occur?
- intraluminal digestion disturbance= luminal substances are broken down for absorption.
- terminal digestion disturbance= hydrolysis of carbohydrates and proteins in the small intestine mucosa.
- transepithelial transport disturbance= nutrients, fluid, and electrolytes are transported across and enter the small intestine epithelium.
- lymphatic transport disturbance= absorbed lipids can not be transported.
What is CELIAC disease?
immune mediated enteropathy associated with ingestion of gluten in genetically susceptible people.
What is GLUTEN?
a protein in barley, rye, and wheat. The alcohol-soluble fraction of gluten, GLIADIN is what causes the pathology.
What does GLIADIN do?
- some gliadin peptides induce proliferation of CD8 intraepithelial lymphocytes, inducing NK cells to injur enterocytes.
- gliadin can also induce T cells to cause the characteristic mucosal pathology.
*** What major genes have been associated with Celiac disease?
HLA-DQ2 and DQ8 genotypes.
*** What serum antibodies have been associated with Celiac disease?
IgA class ANTITISSUE TRANSGLUTAMINASE (AntitTG), ANTIENDOMYSIAL ANTIBODY (EMA) AND ANTIGLIADIN ANTIBODIES (AGA).
What happens to the villi in celiacs?
they are lost, decreasing surface area for absorption
What are the associated conditions with celiacs?
- family history of celiac disease
- autoimmune diseases
- T1DM
- Thyroiditis
- IgA deficiency
- genetic syndromes (down syndrome, turners…)
What are the clinical features of celiac disease?
- anemia
- osteoporosis
- neurological problems (from not absorbing enough vit B6).
- chronic diarrhea
- weight loss
- DERMATITIS HERPETIFORMIS (an itchy, blistering skin disease that resembles herpes).
- lymphocytic gastritis
- lymphocytic colitis
Can celiac disease present in infancy?
YES, presenting as failure to thrive, diarrhea, abdominal distention, and developmental delay. These symptoms present upon weaning of child from mothers breast milk to normal diet.
How may older children present with celiac disease?
short stature or dental enamel defects.
How may adults present with celiac disease?
diarrhea, constipation, flatus, belching, anemia, weight loss, or vitamin deficiencies.
What are some atypical symptoms of celiac disease?
- few or no GI symptoms
- iron deficiency
- osteoporosis
- infertility
What are the 3 histological categories of celiac disease?
- Marsh I= marked infiltration of villous epithelium by lymphocytes.
- Marsh II= intraepithelial lymphocytosis and elongation and branching of crypts with increased epithelial cells.
- Marsh III= intraepithelial lymphocytosis, crypthyperplasia and villous atrophy.
What is tropical sprue?
- unrelated to gluten sensitivity, but malabsorption (due to partial villous atrophy with lymphocytes) becomes apparent within a few days or weeks of an acute enteric diarrheal infection.
- usually seen in tropics.
- may be related to enterotoxigenic E. coli
To what does tropical sprue respond?
folic acid, vitamin B12, and tetracycline
What is autoimmune enteropathy?
- x linked autoimmune disorder causing persistent diarrhea in young children.
- IPEX= Immune dysregulation, Polyendocrinopathy, Enteropathy, and X linkage due to a germ-line mutation in the FOXP3 gene on the X chromosome.
What happens in autoimmune enteropathy?
- defective T cell regulation
- autoantibodies against enterocytes and goblet cells
What is lactase (disaccharidase) deficiency?
- lactase is the enzyme found on the brush border of villi. A deficiency in this enzyme results in a villous absorptive defect.
If you biopsied a villous in a person with lactase deficiency would it look normal?
YES (aka histology is unremarkable)
What are the 2 types of lactase deficiency?
- congenital= mutation in the gene coding for lactase. Exposure to milk products causes explosive diarrhea.
- Acquired= due to a down regulation of lactase gene expression. Disease presents after childhood and causes abdominal fullness, diarrhea and flatulence.
What is abetalipoproteinemia?
- rare autosomal recessive disease causing an inability to secrete triglyceride rich lipoproteins.
- caused by a mutation in the microsomal triglyceride transfer protein (MTP), which catalyzes transport of triglycerides, cholesterol esters, and phospholipids.
