Malabsorption conditions Notes

NOTES NOTES MALABSORPTION CONDITIONS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Impaired ability of gastrointestinal tract to absorb nutrients ▪ Malabsorption may be ▫ Global → impaired function of intestinal cells ▫ Partial → external agent interferes with absorption ▪ Manifestation of underlying illness; may be congenital/acquired/infectious CAUSES ▪ Defects in absorption process of intestinal cells (e.g. change to bowel surface area) ▪ Impaired nutrient digestion (e.g. altered digestive enzymes) SIGNS & SYMPTOMS ▪ Abdominal distention, pain ▪ Chronic diarrhea, malabsorption, dehydration ▪ Weight loss ▪ Clinical manifestations of nutritional deficiencies (e.g. paresthesias from cobalamin deficiency) DIAGNOSIS DIAGNOSTIC IMAGING ▪ Abdominal ultrasound, colonoscopy, intestinal biopsy, serological markers LAB RESULTS ▪ D-xylose test ▫ Test for carbohydrate malabsorption ▪ Fecal fat testing ▪ Complete blood count (CBC) ▫ Look for for infection, anemia OTHER DIAGNOSTICS ▪ Individual history ▫ Pancreatitis ▫ Recent surgeries ▫ Symptoms of vitamin deficiency ▫ Family history TREATMENT ▪ See individual disorders OSMOSIS.ORG 327

CELIAC DISEASE osms.it/celiac-disease PATHOLOGY & CAUSES ▪ Autoimmune disorder of small intestine ▪ AKA gluten-sensitive enteropathy/ nontropical sprue CAUSES ▪ Triggered by foods containing gliadin, a peptide found in foods containing gluten (e.g. grains: wheat, barley, rye, oats) ▫ Gluten consumption → degradation into peptides in small intestine → secretory IgA binds to gliadin in duodenum → IgA-gliadin complex binds to transferrin receptor → IgA-gliadin complex travels across enterocyte into lamina propria → tissue transglutaminase deaminates gliadin → macrophages uptake, present deaminated gliadin in MHC-2 molecules HLA-DQ 2, 8 → CD4+ activation → inflammatory cytokines released (interferon gamma, tumor necrosis factor) → damage/destruction of intestinal villi → B cell activation → antigliadin, anti-tissue transglutaminase, antiendomysial antibodies released → CD8+ cell activation → tissue destruction ▪ On microscopy ▫ Villous atrophy, mucosal inflammation, intestinal crypt hyperplasia ▪ Presence of anti-gliadin, anti-endomysium IgA = pathognomonic SIGNS & SYMPTOMS ▪ Abdominal distention, chronic diarrhea (steatorrhea) ▪ Failure to thrive (children) ▪ Dermatitis herpetiformis ▫ Circulating IgA antibodies attack dermal papillae → generalized rash DIAGNOSIS LAB RESULTS ▪ Anti-gliadin IgA/IgG ▪ Anti-endomysium IgA ▪ Anti-tissue transglutaminase IgA ▫ Tissue transglutaminase: endomysial enzyme released in response to cellular stress ▫ More sensitive, specific Duodenal biopsy ▪ Showing lymphocytic infiltration, villous atrophy, crypt hyperplasia TREATMENT OTHER INTERVENTIONS ▪ Correct nutritional deficiencies related to malabsorption Preventative ▪ Gluten-free diet RISK FACTORS ▪ Northern European ancestry, genetic component MNEMONIC: Grains are BROWn Grains to avoid with Celiac disease Barley Rye Oats Wheat 328 OSMOSIS.ORG

Chapter 38 Malabsorption Conditions Figure 38.1 Histological appearance of a duodenal biopsy in an individual with celiac disease. There is villous blunting, an expansion of the lamina propria by chronic inflammatory cells and an increase in crypt length. A higher magnification would reveal an increase in lymphocyte count in the surface epithelium. Figure 38.2 Clinical appearance of dermatitis herpetiformis. Individual with celiac disease are at increased risk of this condition. LACTOSE INTOLERANCE osms.it/lactose-intolerance PATHOLOGY & CAUSES SIGNS & SYMPTOMS ▪ Decreased ability to digest lactose ▪ Lactose consumption → lactase deficiency/ inactivity → ↑ undigested lactose → fermentation by colonic flora → gas, osmotically active substances produced → bloating, diarrhea ▪ Occur after consuming lactose (e.g. milk, cheese) ▪ Abdominal pain, cramping in lower quadrants ▪ Abdominal distention, flatulence, vomiting, diarrhea (more common in children) CAUSES ▪ Most often acquired due to physiologic weaning off of milk RISK FACTORS ▪ Non-European ancestry (most common) ▪ Increases with age ▪ May be congenital ▫ Rare, autosomal recessive disorder ▪ May be developmental ▫ Most common among premature infants ▪ Underlying intestinal disease DIAGNOSIS ▪ Based on above symptoms LAB RESULTS ▪ Unabsorbed carbohydrates → high stool osmotic gap ▪ Bacterial lactose fermentation → acidic stool pH OSMOSIS.ORG 329

Preventative ▪ Lactose-free diet ▫ Compensate with lactase TREATMENT OTHER INTERVENTIONS ▪ Optimize calcium, vitamin D intake SMALL BOWEL BACTERIAL OVERGROWTH SYNDROME osms.it/sbbos PATHOLOGY & CAUSES ▪ Excessive colonic bacteria colonizing small intestine ▪ Often occurs secondary to conditions limiting intestinal motility, gastric acid and bile secretion and IgA deficiencies CAUSES ▪ Alteration of factors regulating intestinal flora → aerobic bacteria proliferation → changes in aerobic microclimate of small intestine → migration of colonic anaerobic bacteria → damage to intestinal surface → maldigestion, malabsorption → symptoms ▫ ↑ bacteria → ↑ carbohydrate metabolism → ↑ gas production → bloating ▫ ↑ bacteria → bile acid inactivation → ↑ fat in colon → osmotic effect → diarrhea ▫ ↑ bacteria → intrinsic factor degradation → impaired B12 absorption → B12 deficiency RISK FACTORS ▪ Increases with age ▪ Altered mental status after high carbohydrate meal ▪ Failure to thrive (children) DIAGNOSIS LAB RESULTS ▪ Signs/symptoms of vitamin, electrolyte abnormalities ▫ Weakness, ataxia, paresthesias → B12 deficiency ▫ Perioral numbness, feet paresthesias, muscle cramping → calcium deficiency ▪ Anemia ▫ Macrocytic → B12 deficiency ▫ Microcytic → chronic bleeding ▪ Fecal fat testing ▪ Lactulose/glucose breath testing ▪ Jejunal aspirate, culture ▫ > 103 colony forming units OTHER DIAGNOSTICS ▪ Individual history ▫ Chronic pancreatitis, intestinal surgery, GI neuropathy SIGNS & SYMPTOMS ▪ Abdominal pain/distention, chronic diarrhea, flatulence ▪ Tympanitic abdomen upon percussion 330 OSMOSIS.ORG TREATMENT MEDICATIONS ▪ Antibiotics

Chapter 38 Malabsorption Conditions TROPICAL SPRUE osms.it/tropical-sprue DIAGNOSIS PATHOLOGY & CAUSES ▪ Gastrointestinal disease of uncertain etiology resulting in nutrient malabsorption DIAGNOSTIC IMAGING CAUSES Barium swallow ▪ Shows intestinal wall thickening ▪ Acute intestinal infection (viral/bacterial/ protozoan) → damaged intestinal lining → inflammation → enteroglucagon secretion → decreased intestinal motility → increased intestinal transit time → overgrowth of Klebsiella, E. coli, Enterobacter → production of toxic fermentation byproducts → further inflammation → villous atrophy → malabsorption → depletion of folate, B12 → intestinal villi can’t function normally → further intestinal injury, megaloblastic anemia RISK FACTORS ▪ Most common in individuals living in tropical regions Endoscopy LAB RESULTS ▪ Fecal fat test ▪ D-xylose test ▪ Jejunal biopsy ▫ Shows villous atrophy, inflammation TREATMENT MEDICATIONS ▪ Antibiotics → reduce bacterial overgrowth ▪ Replace folate, B12 SIGNS & SYMPTOMS ▪ Diarrhea, weight loss, dehydration, abdominal pain, fatigue, megaloblastic anemia OSMOSIS.ORG 331

WHIPPLE'S DISEASE osms.it/whipples-disease PATHOLOGY & CAUSES ▪ Rare, malabsorptive infectious disease caused by Tropheryma whipplei ▪ Pathognomonic finding → lamina propria displays numerous macrophages with periodic acid-Schiff (PAS) positive intracellular material CAUSES ▪ Tropheryma whipplei ▫ Gram-positive, non-acid fast, PAS positive bacillus; ubiquitous in environment ▫ Fecal-oral transmission ▪ Readily spreads throughout body, causing multisystem effects ▫ Evades immune response → allows for accumulation of bacilli in tissues ▪ Current hypothesis suggests host immunodeficiency as predisposing factor RISK FACTORS ▪ Middle-aged biological males of European ancestry; exposure to fecal matter (sewage workers, farmers) MNEMONIC: WHIPPLES Features of Whipple’s disease Weight loss Hyperpigmentation of skin Infection with tropheryma whippelii PAS positive granules in macrophage Polyarthritis Lymphadenopathy Enteric involvement Steatorrhea 332 OSMOSIS.ORG SIGNS & SYMPTOMS ▪ Four cardinal signs ▫ Diarrhea, weight loss, abdominal pain, arthralgias ▪ Endocarditis, pericarditis, myocarditis ▪ Skin hyperpigmentation ▪ Pleural disease DIAGNOSIS LAB RESULTS ▪ Biopsy ▫ Shows copious PAS positive macrophages invading lamina propria in intestine ▪ ≥ two positive PCR/PAS tests ▪ Immunohistochemistry for T. whipplei ▪ Laboratory findings suggesting chronic inflammation, nutritional deficits TREATMENT MEDICATIONS ▪ Start with IV antibiotics → ceftriaxone/ penicillin G ▪ Trimethoprim-sulfamethoxazole (1 year)

Chapter 38 Malabsorption Conditions Figure 38.3 Histological appearance of the duodenum in a case of Whipple’s disease. The lamina propria is occupied by numerous foamy macrophages. Electron microscopy would reveal numerous membrane bound bacilli. Figure 38.4 Histological appearance of a duodenal biopsy with the special stain DPAS (diastase periodic acid-Schiff). This stain highlights diastase resistant mucin within the foamy macrophages residing in the lamina propria. The mucin within goblet cells is also positively stained. OSMOSIS.ORG 333