1. Malabsorption
Vikram Gill #1491
Path II

2. What is Malabsorption?
Malabsorption is defined as defective absorption of fats, fat- and water-soluble vitamins, proteins, carbohydrates, electrolytes and minerals, and or water
Malabsorption most commonly presents as chronic diarrhea, and a hallmark feature of malabsorption is steatorrhea- which is a bulky, greasy, foul smelling stool with high fat content
The chronic malabsorptive disorders most commonly encountered in the United States are pancreatic insufficiency, celiac disease, and Crohn’s disease
Malabsorption results from disturbance in at least one of the four phases of nutrient absorption:
1)Intraluminal digestion
2)Terminal digestion
3)Transepithelial transport of absorbed lipids
4)Lymphatic transport of absorbed lipids

3. Four phases of nutrient absorption
Intraluminal digestion- the process where proteins, carbohydrates, and fats are broken down into forms suitable for absorption
Terminal digestion- involves the hydrolysis of carbohydrates and peptides by enzymes in the mucosa of the intestinal brush border
Transepithelial transport- where nutrients, fluid, and electrolytes are transported across and processed within the small intestinal epithelium
Lymphatic transport of absorbed lipids

4. Defects in malabsorptive and diarrheal disease

5. Cystic Fibrosis
Cystic Fibrosis is due to a defect in the CFTR protein channel, which is vital for proper bicarbonate, sodium, and water secretion, ultimately resulting in defective luminal hydration
This insufficient luminal hydration can cause intestinal obstruction, but more commonly in these patients it causes the formation of intraductal concretions within the pancreas
These concretions result in duct obstruction, low-grade chronic autodigestion of the pancreas, and eventual exocrine pancreatic insufficiency in more than 80% of patients
The result is failure of the intraluminal phase of nutrient absorption, which can be effectively treated in most patients with oral enzyme supplementation.

7. Celiac Disease
Celiac Sprue is an immune-mediated (allergic) enteropathy triggered by the ingestion of gluten- containing foods, such as wheat, rye, or barley, in genetically predisposed individuals
Pathogenesis:
1) Gluten is digested by luminal and brush-border enzymes into amino acids and peptides, including a 33-amino acid a-gliadin peptide that is resistant to degradation by gastric, pancreatic, and small intestinal proteases
2) Some gliadin peptides may induce epithelial cells to express IL-15, which in turn triggers activation and proliferation of CD8+ intraepithelial lymphocytes
3) The resulting epithelial damage may enhance passage of other gliadin peptides into the lamina propria; These gliadin peptides interact with HLA-DQ2 or HLA-DQ8 on antigen-presenting cells and, in turn, can stimulate CD4+ T cells to produce cytokines that contribute to tissue damage

8. Celiac Disease cont’d
The genetic variables that control the development of Celiac disease may also contribute associations between celiac disease and other immune diseases, including type 1 diabetes, thyroiditis, and Sjogren syndrome, IgA nephropathy, as well as certain neurologic disorders
Clinical features:
1) In adults, celiac disease presents most commonly between the ages of 30 and 60; detected twice as often in females
2) Pediatric celiac disease, which affects males and females equally, may present with malabsorption or atypical symptoms affecting almost any organ; manifests as irritability, abdominal distention, anorexia, chronic diarrhea, failure to thrive, weight loss, or muscle wasting
3) A characteristic itchy, blistering skin lesion, dermatitis herpetiformis can be present in as many as 10% of patients
4) Individuals with celiac disease have a higher than normal rate of malignancy; enteropathy associated T-cell lymphoma is the most commonly associated malignancy followed by adenocarcinoma
Unfortunately the only treatment available right now is a gluten free diet

9. Celiac Disease

10. Tropical Sprue
Is a malabsorption syndrome occurring almost exclusively in people living in or visiting the tropics, including Peurto Rico, the Caribbean, northern South America, West Africa, India, and Southeast Asia. However it is inexplicably UNCOMMON in Jamaica
Malabsorption becomes apparent from days to weeks of an acute diarrheal infection in visitors, and though no causative organism has been isolated overgrowth of aerobic enteric bacteria has been documented in patients. Also, most patients rapidly recover with broad spectrum antibiotics
Cyclospora and ETEC are suspected etiologic factors
Histologic changes seen in tropical sprue is nearly identical to celiac sprue except that in tropical sprue it is uncommon to see total villous atrophy, and that tropical sprue tends to involve the terminal small bowel
Ileum (terminal small bowel) is where vitamin B12 is absorbed, so tropical sprue is often associated with megaloblastic anemia

11. Tropical Sprue cont’d

12. Autoimmune Enteropathy
Is an X-linked autoimmune disease that occurs most often in young children and is characterized by severe persistent diarrhea
A particularly severe form of autoimmune enteropathy termed IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, and X-linkage) is due to a germ line mutation of the transcription factor FOXP3 which is expressed in CD4+ regulatory T-cells; Results in defective regulation of T-Cells
Production of autoantibodies to enterocytes, goblet cells, parietal, and sometimes even islet cells cause discomfort associated with condition
Intraepithelial lymphocytes within the small intestine may be increased but not nearly to the extent seen in celiac disease, and neutrophils are often present
The treatment regiment includes immunosuppressive drugs (cyclosporine) and in rare cases, even bone marrow transplantation

13. Lactase Deficiency
The disaccharidases, lactase included, are located in the apical brush-border membrane of the villus absorptive epithelial cells
Because the defect is biochemical biopsy histology is usually unremarkable
There are two types of lactase deficiency: Congenital and Acquired.
Congenital lactase deficiency is an autosomal recessive disorder caused by a mutation in a gene encoding lactase. Disease is rare, and presents from birth as explosive diarrhea with watery, frothy stools and abdominal distention on milk ingestion. Symptoms abate when diet is lactose free
Acquired lactase deficiency is caused by down-regulation of lactase gene expression and is particularly common among Native Americans, African, and Chinese populations. Onset of acquired lactase deficiency is sometimes precipitated by an enteric viral or bacterial infection

14. Abetalipoproteinemia
Is a rare autosomal recessive disease characterized by an inability to secrete triglyceride-rich lipoproteins
Caused by a mutation to the microsomal triglyceride transport protein (MTP) that catalyze the transport of triglycerides, cholesterol esters, and phospholipids
Without MTP, enterocytes cannot assemble or export lipoproteins. This results in intracellular lipid accumulation; Because of the triglyceride accumulation, vacuolization of small intestinal epithelial cells is evident and can be highlighted by special stains, such as oil red-O, particularly after a fatty meal
Abetalipoproteinemia presents in infancy and the clinical picture is characterized by failure to thrive, diarrhea, and steatorrhea
Patients also have a complete absence of all plasma lipoproteins containing apolipoprotein B, though the gene that codes apolipoprotein B is not affected
Presence of acanthocytic red blood cells (Burr cells) can be seen in peripheral blood smears because of membrane defects in the RBC’s due to deficiency of essential fatty acids and fat soluble vitamins

15. Robbins and Cotran: Pathologic Basis of Disease
Sources
Robbins and Cotran: Pathologic Basis of Disease
8th Edition
Chpt 17 pages

16. Thank You