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    Biochem CC Diarrhea.doc Biochem CC Diarrhea.doc Document Transcript

    • Biochemistry Clinical Correlation Diarrhea 4-25-2001 DIARRHEA [Note from Me: For those of you who weren’t at lecture, he showed an awful lot of slides, with lots of information, pretty fast. He didn’t always explain everything on them. What I have here is everything that was on each slide, with explanations where he gave one, but some things may not make sense. Hopefully these things won’t be on the test] Diarrhea and abdominal pain are the most common complaint seen by GI docs. Causes of Diarrhea 2 categories: 1) Osmotic (most common); osmotic gradient pulls water into intestine 2) Secretory; either a toxin or hormone causes enterocytes to secrete too much and/or absorb too little Specific causes Anatomical causes: operative removal of jejunem or other part of the gut Pancreatic causes: Pancreatitis, pancreatic cancer, CF Biliary causes: Obstructive jaundice decreases bile acids Mucosal Injury: cells damaged (celiac disease, Whipple’s disease [an infection of the mucosa], alactasia Infection: tropical sprue, blind loop syndrome, bacterial overgrowth Infestation: worms, giardiasis Inflammatory: Crohn’s disease Other causes: irradiation, ischemia, thyrotoxicosis, drugs Osmotic causes Lactose intolerance, Glucose/Galactose malabsorption, Fructose malabsorption, ingestion of Mannitol/Sorbitol (in some chewing gum), Lactulose therapy (treatment for hepatic encephalopathy, mimics lactose intolerance), Magnesium sulfate (Epsom salts) and other magnesium antacids, Short Bowel Syndrome, jejuno-ileal bypass, enteric fistula --Get a good history to see what OTC’s they’re on
    • Examination of stool (can’t just say “diarrhea”, because it varies, and people’s concept of diarrhea varies) : --Appearance, weight/volume, pH, laxative screening (some people self-induce diarrhea), osmolality, fecal electrolytes, Micro exam (methylene blue, gram stain, qualitative fat), occult blood test --Consistency: Formed, Semi-formed, Viscous soupy or watery Steatorrhea – Yellowish color, not well-formed; ask patient about “flushability” and odor, because steatorrhea smells really bad and takes more flushes because of the fat Iron is absorbed high (duodenum); most everything else is absorbed in the jejunem (carbs, fat, protein, Ca, Mg, trace minerals, vitamins) Ileum: B12 and bile salts. The whole gut absorbs water and electrolytes. Short Bowel Syndrome Reasons for bowel removal: ½ the time - Crohn’s disease 1/8 the time- Ischemia 1/8 the time - Radiation (usually for cancer in other nearby organ) ¼ the time - Other (Strangulated bowel, trauma, tumor, jejunoileal bypass [to lose weight], neonatal disorders 8.5 L into the gut daily; 8.4 L reabsorbed daily Malabsorption: Acid hypersecretion, transit too rapid, loss of surface area, bacterial overgrowth (especially if you lose the ileocecal valve), bile acid wasting (terminal ileum removal), impaired residual bowel Vitamin deficiencies: B12/Folate (Anemia, stomatitis, glossitis, ataxia); lack of B12 can further cause diarrhea because the enterocytes need it, so you get a vicious cycle. D/Calcium/Magnesium (osteopenia, tetany) Zinc (diarrhea, enteropathic dermatitis seen around mouth) A (night blindness) K (bleeding) E (parasthesias, ataxia) -- Taking out the small bowel is worse than the colon. Factors determining severity of Small Bowel Syndrome: Extent of resection, Site of resection, residual disease (if you removed because of Crohn’s disease, but Crohn’s is still there in the part that remains), age (very old and very young tend to have problems)
    • 1) Jejenual removal: adequate absorption unless > 75% removed, because of ilial adaptation (becomes jejunem-like). Good B12 and salt absorption, normal transit. 2) Ilieal removal: adequate carb. and fluid absorption. Loss of B12 and bile salts (no jejunal adaptation). Impaired lipid absorption unless you help them out. Intestinal transit too rapid. Enteric Hyperoxaluria: With ileal resection  bile salt wasting  lipid malabsorption. Normally Calcium Oxalate (CaOx) is excreted. With no lipid absorption, the calcium binds the fatty acids  free oxalate enters the colon. The colonic epithelium is damaged by the bile in the colon, and the oxalate is absorbed. This causes high levels of blood oxalate, which causes oxaluria (oxalate in the urine), and eventually oxalate stones build up in the kidney. Treat with a diet that is low in oxalate. For ileal resection: 100 cm is the magic number for removal in order to maintain some bile acid and B12 absorption. Give cholestyramine to bind the bile acids and prevent inflammation (also an antimotility agent). Monitor their bone density, fat-soluble vitamin levels, and oxalate. They can be on a standard diet, with a multivitamin. If >100 cm resected, big time steatorrhea, and no bile acids absorbed. 3) Extensive removal: bad. Large fluid losses. Nutrient malabsorption, poor jejunal adaptation. Acid hypersecretion, rapid gastric emptying and transit. May need IV for sustenance. Diet: low in oxalate and fat. Supplement B12 and Ca++ Change fat in diet to Medium-Chain Fatty Acids, because they can be absorbed directly, without the use of micelles (unlike long-chain FA). Problem is they smell bad and are expensive. As needed: provide acid suppression and oral rehydration. Vitamin D: If you lose Calcium from diet because of malabsorption of Vitamin D, Parathyroid hormone pulls calcium out of bones. Watch out for femoral head and vertebral bodies especially. Infections: 1) Invasive: Damage enterocytes directly. Examples: Salmonella, Shigella, E. coli, C. difficile. Cause bloody diarrhea, with constitutional signs (fever, increased WBCs) 2) Non-invasive: damage with toxins (cholera), or viruses (Rotavirus, Norwalk Agent). Cause watery diarrhea.
    • Cholera: Secretes a toxin with α and β subunits. The β subunit binds to a ganglioside receptor (The receptor is located in all tissues, but only the gut gets exposed to cholera). The α subunit moves through the cell and interacts with adenylyl cyclase, and ribosylates the α subunit of adenylyl cyclase. This keeps adenylyl cyclase from being turned off, so cAMP levels rise dramatically. This leads to increased Protein Kinase A, which phosphorylates the CFTR Chloride channel, and opens it. You get high levels of Chloride and water secretion. Enterocytes have a high rate of turnover (~ 5 days). The poisoned cells gets sloughed, and you get rid of the toxin. The trick is keeping the patient alive for the 5 days or so. If no IV is available (Third world counties), give Oral Rehydration Therapy (antibiotics also help, but they don’t kill the toxin, only the bacteria). Oral Rehydration Therapy: Targets the Glucose/Na+ Cotransporter (SGLT 1). Boost Glucose and sodium, and transport increases a lot. Water follows by osmotic gradient. Chloride will also follow to maintain electrical gradient.