Lecture 18: Malabsorption & Maldigestion
Malabsorbed Protein: Signs/Sx's Labs
Sx: Wt loss; muscle wasting; edema Lab: low albumin
Malabsorbed Carbohydrate: Signs/Sx's Labs
Sx: distension, flatus, borboyygmi; watery diarrhea Lab: osmotic diarrhea; acid stools; positive breath test
Idiopathic Esophageal Ulcer
~ 30-40% of esophageal ulcers DDx: CMV, pill esophagitis, HSV, neoplasms Pathophysiology: HIV infection - increased number of apoptotic cells Tx: Steroids, THALIDOMIDE
Cryptosporidia
An intracellular protozoan parasite that is associated with gastrointestinal diseases in all classes of vertebrates including mammals Water Borne agent Highly infectious Infects multiple epithelial surfaces Causes refractory diarrhea in HIV Histo: Cryptosporidial enteritis can be diagnosed from hematoxylin and eosin staining; cryptosporidium appears basophilic and occurs either alone or in clusters on the brush border of the mucosal surface. - Because infection can be patchy, biopsy specimens may be less sensitive than stool examination.
Malabsorption/Maldigestion Iron, Folate or B12: Clinical Presentation
Anemia Glossitis (inflammed tongue) Aphthous ulcers
Celiac Disease: Atypical Presentation
Atypical presentation/silent: Osteoporosis Iron deficient anemia Anemia due to B12 or folate deficiency Neuropathies Recurrent aphthous somatitis Infertility Dermatitis Herpetiformis --------------------------- Usually have no diarrhea. Limited amount of intestine involved. Recognized more frequently, greater % of cases
Bacterial Overgrowth: Pathophysiology
Bacteria will: Deconjugate bile salts - remove taurine & glycine •Makes bile salts more lipid soluble & thus passive reabsorbed in the upper small intestine •Decreases of luminal concentration below critical micellar concentration and thus less effective in dispersing fats •Net effect: fat cannot be solubilzied & thus malabsorbed Dehydroxylation at position making bile salts insoluble and unable to form micelles Ferments carbs to hydrogen and carbon dioxide leading to excessive flatulence Depletion of B12 Injury to mucosa which leads to flattened villi
Malabsorption/Maldigestion Vitamin K: Clinical Presentation
Bruising; bleeding
CMV Colitis
CMV colitis is associated with low-grade fever, weight loss, anorexia, malaise, and abdominal pain. Explosive watery diarrhea is common, but can be sporadic Late complication of HIV Reactivated infection Multi-system disease Perivasculitis Dx: Inclusion Bodies Tx: GANCICLOVIR, FOSCARNET, CIDOFIVIR
CMV Esophagitis Pathology
CMV gastrointestinal disease is characterized histologically by mucosal inflammation, tissue necrosis, and vascular endothelial involvement. Characteristically, CYTOMEGALIC CELLS (large cells containing eosinophilic intranuclear and frequently basophilic intracytoplasmic inclusions) are present in mucosal biopsies stained with hematoxylin and eosin (picture 1). Without effective antiviral treatment, the tissue destruction increases and can lead to hemorrhage or perforation
Causes of Maldigestion
Chronic Pancreatitis Bacterial Overgrowth Postgastrectomy - post surgical Bile salt deficiency
Celiac Disease: Classic Presentation
Classical Presentation: ➢Diarrhea, flatuelence, weight loss & fatigue ➢Infants - impaired growth, failure to thrive, diarrhea & abdominal distention ➢Severity depends upon extent of small bowel involved ➢Starts in duodenum ➢In severe cases - down entire length of small intestine ➢ Majority just involve proximal small intestine ➢Diarrhea multifactorial - stool volume & osmotic load increased ➢If only duodenum may be isolated deficiency of iron or calcium ➢Steatorrhea present but less than in pancreatic insufficiency
Cryptosporidia: Diagnosis
Cryptosporidial oocysts which stain acid fast in the stool.
CMV Esophagitis
Cytomegalovirus (CMV) gastrointestinal (GI) disease is an uncommon but serious complication of AIDS. The most common gastrointestinal sites of CMV involvement are the esophagus and the colon. Symptom presentation depends on the anatomic location of the infection. CMV esophagitis presents with fever, odynophagia, and nausea, and is occasionally accompanied by substernal burning pain. CMV most commonly causes multiple ulcers at the lower esophageal sphincter, but diffuse esophagitis is also described
Bacterial Overgrowth: Definition Causes
Definition: >10^5 bacteria in the upper small intestine ➢Normal small bowel should not have any significant am't of bacteria ➢All bacteria that ingested should be killed by gastric acid in stomach Causes: Hypochlorhydria •In postgastectomy & pernicious anemia •Theoretically in PPIs but not seen Altered motility - diabetes & scleroderma b/c need MMC III to sweep out bacteria Stasis due to structural probs - strictures, small intestinal diverticula, blind loops
Celiac Disease: Diagnosis
Diagnosis Serum IgA antigliadin antibody (+) - historical Deaminated gliadin peptide (DGP) antibody Serum IgA antiendomysial antibody (+) Serum IgA anti-tissue transglutaminase antibody (+) Antiendomysial/tissue transglutamnase - very specific Best combo - tTg IgA + DGP False Negatives - IgA deficiency, partial villous atrophy
Bacterial Overgrowth: Diagnosis Treatment
Diagnosis - difficult ➢Quantitative colony counts - culture of intestinal aspirate ➢C14 D-xylose breath test Treatment: ➢Antibiotics ➢Surgery for area of stasis if necessary
Whipple's Disease: Diagnosis Treatment
Diagnosis: small bowel biopsy ➢Reveals PAS + macrophages in small intestine lamina propria ➢Requires high clinical suspicion Treatment: Bactrim for 6 months to 1 year. Nutrient supplementation/repletion. Most patients respond within 1 to 3 months. Relapses common
Candida Esophagitis
Dx: The diagnosis of oropharyngeal candidiasis is usually suspected clinically and is readily confirmed by scraping the lesions with a tongue depressor and performing a Gram stain or KOH preparation on the scrapings. Budding yeasts with or without pseudohyphae are seen. -This is a light micrograph of pseudohyphae in an esophageal biopsy stained with PAS. (400X) Has a natural history of recurrence. Tx: FLUCONAZOLE -Fluconazole resistance: higher doses, ITRACONAZOLE, encapsulated oral AMPHOTERICIN, IV amphotericin
Celiac Disease: Environmental Factors
ENVIRONMENTAL FACTORS Breast feeding Cesarean section Timing of gluten ingestion GI Infections other factors ??
Encephalocytozoon intestinalis vs. Enterocytozoon bieneusi
Encephalocytozoon intestinalis: Located in enterocytes and macrophages Disseminates Spores in urine Albendazole response Enterocytozoon bieneusi: Higher prevalence Located only in enterocytes
Tests for Protein Absorption
Fecal nitrogen - diff to measure, rarely done Fecal a1-antitrypsin - false pos in occult blood loss due to any blood in stool
CMV Esophagitis Treatment
GANCICLOVIR FOSCARNET CIDOFIVIR
Causes of Malabsorption
Gluten sensitive enteropathy/Sprue/Celiac disease Non-tropical sprue Whipple's Disease Lactase Deficiency Giardiasis/Cryptosporidiosis Intestinal Lymphangectasia Apetolipoproteinemia Crohn's Disease AIDS enteropathy
Malabsorption/Maldigestion Vitamin A: Clinical Presentation
Hyperkeratosis Night blindness
Diagnostic Tests: Folate
Low in mucosal diseases involving the small bowel. May be high in bacteria are producing it in teh small bowel
Maldigestion vs Malabsorption
Maldigestion: A defect or impairment of nutrient hydrolysis. Malabsorption: The defective mucosal absorption of nutrients. In clinical practice malabsorption is usually used as a global term to encompass all aspects of impaired digestion and absorption.
Mycobacterium Avium Complex: Treatment
Management HAART Combination Antimycobacterial therapy Prophylaxis for low CD4 count
Cryptosporidia: Pathophysiology and Tx
Mechanism of diarrhea Disrupts intestinal architecture with villous atrophy and crypt hyperplasia due to adherence Enterotoxin production Host response to infection Therapy None rare cases respond to azithromycin/paramomycin Improve Immune Function Supportive care
Lactase Deficiency
Most common malabsorptive disorder •Usually presents as a late onset "acquired" deficiency Most of world's adult pop is lactase deficient - b/c humans not deisnged to drink milk after infancy Lactase is a brush border enzyme that breaks down lactose ➢Lactase more susceptible to mucosal disease than other brush border enzymes ➢Can complicate other diseases of the small intestine Symptoms: flatulence, diarrhea & abdominal cramping Pathophysiology: unabsorbed lactose reaches the colon where bacteria metabolize lactose to volatile fatty acids, H2 and CO2 Diagnosis: lactose breath test Treatment: avoid dairy products or consume exogenous lactase
Whipple's Disease: Pathogenesis
Mucosal invasion with Tropheryma whippleii (Gram + bacteria). Mesenteric lymphadenopathy leads to lymphatic obstruction. Routine histology - PAS-positive "FOAMY" macrophages in lamina propria.
Large Bowel Movements
Multiple small volume bowel movements Regular in freq Lower abdominal pain Tenesmus No malabsorption or dehydration
Malabsorption/Maldigestion B12: Clinical Presentation
Neuro sequelae
Microsporidia
Obligate intracellular SPORE FORMING parasite Found in the small intestine Asymptomatic until immune depression Destroys Enterocytes; infection resulting in diarrhea with progressive wt loss Identified on biopsy with BROWN-BREN, GEIMSA & MODIFIED TRICHROME STAIN (eosinophilic) stain Disappearing Infection Tx: E. bieneusi - ? Thalidomide E. intestinalis - albendazole
Chronic Pancreatitis
Pancreatic insufficiency Triad of presentation: chronic pain, steatorrhea, brittle diabetes Alcohol is leading cause and usually calcifies the gland •Need to lose 90% of gland to be symptomatic Results in fat malabsorption due to insufficiency of lipase ➢May see oil droplets in stool ➢Carb and protein maldigestion but not to a clinically significant degree Most patients also have insulin requiring diabetes mellitus - diff to control b/c destruction of islets Diagnosis: tests for steatorrhea, imaging where identify pancreatic calcifications on abdominal x-ray Treatment: exogenous pancreatic enzymes - mainly lipase & some protease 7 amylase
Malabsorption/Maldigestion Ca or Mg: Clinical Presentation
Paresthesia Tetany
Celiac Disease: Pathology
Pathology: villous atrophy, crypt hyperplasia & lack of differenitation, increase in T cells & plasma cells in lamina propria ➢Most severe in proximal small intestine Associated blister skin disease called dermatitis herpetiformis
Management of Esophageal Symptoms in AIDS
Patient is able to eat/drink -> antifungal and look for response; if no response move toward tx based on EGD If patient is unable to eat/drink used EGD and tx based off results.
Celiac Disease: Prognosis
Prognosis: Celiac disease may be fatal if severe and untreated. Malignant disease higher in celiac disease patients (especially if poorly treated): - Lymphomas - Esophageal cancer - Small intestinal adenocarcinomas (80x higher than in normals)
Idiopathic Diarrhea
Proposed etiologies: - Occult Enteric Infections - Abnormal GI Motility - Autonomic Denervation - Bacterial Overgrowth - HIV as an Enteric Pathogen Most patients do well long term
Postgastrectomy - post surgical Malabsorption
Purposes of surgery: was for peptic ulcer disease, now gastric cancer & complicatiosn of ulcer disease, RYGB for morbid obesity Causes weight loss due to: ➢Ineffective mixing of digestive juices ➢Stasis & hypochlorhydria - which favors bacterial overgrowth ➢Iron & calcium normally absorbed in duodenum but not bypassed ➢Secretin & CCK normally stimulated when fat & acid enter duodenum and now not ➢Vitamin B12 deficiency due to decreased IF production Weight loss post RYGB: ➢Due to small gastric pouch ➢Iron deficiency in 50% ➢Other common deficiencies: vitamin B12, folate, rarely thiamine or copper ➢Must be on life long multivitamins & supplements
Tests for Fat Absorption
Quantitative fecal fat analysis - 72 hr collection from pt eating 100 g fat /day •Difficult for pt and staff to perform Qualitative fecal fat - Sudan staining on routine fecal sample •Sensitivity only w/ severe steatorrhea
Whipple's Disease Definition Sx's
Rare, mostly men ➢Caused by gram pos bacteria - mucosa invasion and leads to lymphatic obstruction Clinical symptoms: diarrhea, fever, arthralgias & neurologic symptoms ➢Also can see cough, fever, arthritis, dementia and congestive heart failure.
CMV Esophagitis Diagnosis
Routine Histology - low Sensitivity. Immunohistochemistry may be helpful - biopsy ulcer base. Serology and culture: poor specificity CMV gastrointestinal disease is most accurately diagnosed by a triad of the cardinal symptoms, visualization of mucosal ulcers or erosions, and histologic evidence of tissue destruction with presence of viral inclusion bodies Obtain at least 10 biopsies
Test for Vitamin B12
Schilling Test: Tests B12 absorption, gastric function, ileal absorption & pancreatic function Stage 1 - test for excreted B12 in urine (after giving 100ng of b12 to saturate receptors in body) and if lack then B12 malabsorption tho don't know etiology (If greater than 7% is in urine -OK) Stage 2 - also given exogenous IF and if urine level increases, due to pernicious anemia Stage 3 - give oral pancreatic enzymes and diagnose pancreatic insufficiency Stage 4 - give antibiotics to see if ileal disease or bacteria
Small Bowel Movements
Several large volume bowel movements a day Irregular in frequency Mid-abdominal pain Flatulence Malabsorption Dehydration Absence of blood or WBC's in the stool.
Tropical Sprue
Small intestinal mucosal atrophy •Occurs to ppl in "tropics" Differs from celiac disease: involves entire small intestine, atrophy is less severe Etiology unclear ➢Perhaps related to infectious etiology Evidence for: gram neg organism found •Evidence again: no person to person spread & never transmitted to pts outside of tropica areas Common folate & B12 deficiency •Diagnosis: pts from endemic area w/ foalte or B12 deficiency & small intestine villous atrophy Treatment: antibiotics, nutrient & vitamin supplementation for several months
Mycobacterium Avium Complex
Spore forming obligate intracellular protozoan parasite Found in the small intestine. Ubiquitous; disseminatd throughout the body if found in the GI tract. Occurs in late stage disease Infects mucosal macrophages Infiltrates lamina propria Obstructs lymphatic flow Results in: thickened bowel wall and enlarged mesenteric lymphoid follicles
Tests for Carb absorption
Stool pH - become more acidic secondary to bacterial fermentation of malabsorbed carbs,, pH<5.5 D-xylose Test: pentose sugar that crosses mucosa by passive diffusion & isn't metabolized so focuses only on malabsorption not maldigestion •Tested in urine or serum level •Abnormal result means mucosal disease •If steatorrhea and d-xylose normal, pancreatic or biliary insufficiency is cause Breath tests - H2 breath test - increased hydrogen b/c fermented carbs •C14 xylose test - broken down & diagnosed in breath ➢Both indicate bacterial overgrowth
Malabsorbed Fat: Signs/Sx's Labs
Sx: Fatty stools, watery diarrhea; wt loss labs: steatorrhea, low serum carotene
Malabsorbed Bile Salts: Signs/Sx's Labs
Sx: Water Diarrhea Lab: Secretory diarrhea
Celiac Disease: Pathogenesis
aka Gluten sensitive Enteropathy, non-tropical Sprue Pathogenesis: ➢Immune rxn in the small intestinal mucosa to gluten ➢Leads to villous flattening & atrophy of mucosa ➢Immune rxn mediated by lamina propria T cells Gluten - protein found in wheat ➢Similar proteins found in rye, barley & oats ➢Alcohol soluble protein components of the grains called prolamins are the toxins ➢Unknown how prolamins cause toxicity Genetic susceptibility - express specific genes Common in Northern European descent, tho worldwide distribution Pediatric disease but can also occur in 3rd or 4th decade
Malabsorption/Maldigestion Zinc: Clinical Presentation
poor taste, acrodermatitis (form of dermatitis selectively affecting the hands and feet)
Malabsorption/Maldigestion Vitamin D: Clinical Presentation
rickets, osteomalacia, tetany