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GI -Episode 186 – Step 1, Step 2CK, Step 3Vignette: 96-hours-old child has not passed poop. Should poop at 48 hours. Diagnosis: Hirschsprung’s disease. Problem is failure of neural crest cells to migrate. Auerbach’s plexus (myenteric plexus) and Meissner’s plexus (submucosal plexus). Associated with Down syndrome.Both plexi are needed for peristalsis and if missing, then food will not move out of that portion of the GI tract. Trypanosoma cruzi can destroy the distal Auerbach and Meissner’s plexus resulting in Hirschsprung’s disease. RET gene mutation (loss of function) results in enteric nervous system not developing properly and resulting in Hirschsprung.RET mutation also seen in MEN2A and MEN2B Aside about RET and MEN2A: clinical symptoms include medullary thyroid cancer, pheochromocytoma, primary hyperparathyroidism.Aside about RET and MEN2B: clinical symptoms include mucosal neuroma, pheochromocytoma, medullary thyroid cancer, and marfanoid body habitus.Aside about Down syndrome: (HY)Down’s child with chronic small bowel obstruction. Diagnosis: annular pancreasDown’s child with bilious vomiting and double bubble on imaging. Diagnosis: duodenal atresiaDown’s child at 5th percentile for weight, secondary hyperparathyroidism from Vitamin D deficiency and rash on extensor surfaces of upper extremities (dermatitis herpetiformis). Diagnosis: celiac diseaseWhat is the most common congenital cardiac anomaly in Down syndrome? Endocardial cushion defect or Atrioventricular Septal Defect.What is a neurological connection? Early onset Alzheimer’s.Vignette: 6-day-old child has bilious vomiting. There is no double bubble or triple bubble on imaging. Diagnosis: malrotation with mid-gut volvulus. Aside about newborn with bilious vomiting. There are only three diagnosis:Midgut volvulus – image not interpretableDuodenal atresia – image of double bubbleJejunal atresia – image of triple bubbleAside about volvulus in the elderly (HY)Cecal volvulus – signs and symptoms of large bowel obstruction – apical part of coffee bean sign faces left upper quadrant (image)Sigmoid volvulus – apical part of coffee bean sign faces right upper quadrant (image)Volvulus – twisting of colon around mesentery and cuts blood flow and results in ischemic bowel disease.Vignette: person presents with sudden abdominal pain around umbilicus and traveling towards right lower quadrant. Diagnosis: appendicitis.Adults: obstruction (fecalith) of appendix and infection builds behind it. Children can have GI viral infection that leads to hyperplasia of mucoid related lymphoid tissue and this is a lead point to lots of inflammation and appendicitis.Physical examination:McBurney’s point: 2/3rd of the way from umbilicus to anteriosuperior iliac spine. Tenderness at this point.Psoas sign: extend hip causes severe pain (pathognomonic)Rovsing sign: Press on the left lower quadrant will elicit pain in the right lower quadrant. (pathognomonic)Children: UltrasoundAdult: CT scanComplications of appendicitis:Rupture of appendixAbscess – periappendical abscess – drain and appendectomyDamage to iliohypogastric nerve during surgery (VHY) will present as burning sensation around the bladder or inguinal region weeks after surgeryMost common location of carcinoid tumor is appendix (VHY)Normal flora of the colon:Bacteroides, E. Coli, C. Diff, Proteus, Klebsiella are all part of the normal colon flora.Help make Vitamin K.The anaerobic bacteria break down sugar to lactic acid (fermentation) and can cause lactic acidosis.Pectinate line or dentate line: (VHY)Demarcates the endoderm (above the line) and ectoderm (below the line)Endoderm:Visceral innervation in endoderm, therefore NO pain and no anesthesia needed.Adenocarcinoma – endodermArterial supply: superior rectal artery branch of Inferior Mesenteric Artery which is branch of Abdominal AortaVenous drainage: superior rectal vein dumps into IMV into portal veinNerve: inferior hypogastric plexusEctoderm:keratinized stratified squamous epithelium present. Therefore, SCC can arise from HPV 16, 18, 31 and 33.Somatic sensation innervation, so external hemorrhoids are painful, and anesthesia is needed for removalArterial supply: middle rectal artery and inferior rectal artery. IRA is branch of internal pudendal which is branch of internal iliac arteryVenous drainage: middle rectal vein and inferior rectal vein. IRV dumps into internal pudendal vein which dumps into internal iliac vein which dumps into IVC in the end.Vignette: person with chronic constipation finds blood on the toilet paper after pooping. Diagnosis: anal fissure. These are painful. Treat: sitz bath.Inflammation of rectum with ulcerative colitis: Proctitis. Treat: topical corticosteroids.Vignette: 55-year-old guy presents with microcytic anemia and stools are guaiac positive. Diagnosis: colon cancer. Third most common cancer and cancer death in US (VHY).Colon cancer arises from polypsHyperplastic polyps: most common kind of polyp. Found around sigmoid colon and rectum. These are NOT cancerous (VHY). Must be removed in colonoscopy and seen under microscope.Adenomatous polyps: three types (HY)Tubular – some cancer potential but not badVillous - highest malignancy potential. Contain no glands and look like finger.Tubulovilous – in between in cancer potentialThese polyps can produce mucus which can cause diarrheaFamilial adenomatous polyposis (FAP): Autosomal dominant fashion and associated with APC gene mutation.APC is tumor suppressor gene and 1 mutation can cause increased risk for colon cancer.Aside about APC gene:APC gene mutation in person who has FAP and posterior fossa mass growing along the vermis of the cerebellum and imaging shows dropped metastasis to the cord. Diagnosis: medulloblastoma and Turcot syndrome.APC gene mutation with soft tissue tumors and hyperplasia of retina (visual difficulty). Diagnosis: Gardner’s syndrome.Juvenile polyposis syndrome: children with lots of polyps with no malignant potential. Slightly increased risk for colon cancer but most polyps are benign. Polyps in stomach, small intestine and large intestine.Hereditary Non-Polyposis Colorectal cancer (HNPCC) or Lynch Syndrome: Colon cancer not developing from a polyp. P53 mutation occurs first. Autosomal dominant inheritance. DNA mismatch repair defects – MHS2 or MHS6 genes (VHY). Colon cancer can arise in distal or proximal colon. Proximal colon cancer is Lynch syndrome (VHY). Microsatellite instability pathway.Increased risk for endometrial cancer or ovarian cancer (CEO cancer)Chromosomal instability pathway - APC tumor suppressor gene mutation → high risk for adenomas. Add to that, KRAS oncogene mutation → high risk for adenomatous polyp. Add to that, DCC mutation or P53 mutation → full blown colon cancer. (VHY)Ulcerative colitis → colon cancer (P53 mutation). Different mechanism from APC gene mutation. No polyp found here. Surgery will involve removing entire rectum and colon. If colon cancer in one region, then other regions will also have colon cancer (VHY).Screen: 8 years after first diagnosis of ulcerative colitisOverexpression of cyclooxygenase leads to increased colon cancer. COX leads to PGE and leukotrienes both of which cause inflammation. Increased inflammation leads to higher risk of cancer. Inhibit COX2 can lower risk for colon cancer. Treatment: NSAIDs.Vignette: hyperpigmentation of lips and colon cancer. Diagnosis: Peutz-Jeghers syndrome. These people have higher risk for other malignancies, especially pancreatic cancer (HY). Hamartomatous disorder (HY) (crowded normal tissue). Endocarditis: culture grows Strep bovis or Strep gallolyticus. Next step? Colonoscopy to find colon cancer.Guidelines for colon cancer screening:Start at 50Colonoscopy every 10 yearsFIT testFOBT testFlexible sigmoidoscopyCT colonography (but don’t pick on exam as answer)If first degree relative has colon cancer, then screen patient 10 years before. If relative was 52 years when diagnosed, then screen at 40. If 32 years diagnosed, then screen at 22.Left sided colon cancer tends to obstruct!Right sided colon cancer tends to bleed – microcytic anemia!Apple core sign in barium swallow – colon cancer.Vignette: 25-year-old guy has bloody diarrhea for 6 months. Diagnosis: ulcerative colitis. [Young guy has chronic diarrhea].Associated with primary sclerosing cholangitis (PSC) which is fibrosis of intra- and extra-hepatic bile ducts. Conjugated bilirubinemia and p-ANCA are buzzwords for PSC.UC affects rectum and colon. Lesions are continuous (HY) and only involves mucosa (maybe submucosa). Lead pipe pattern on barium enema because haustra lost in UC.Crypt abscesses found in UC.Most serious complication of UC → toxic megacolon (massive distention of transverse colon). Immediate surgery needed.Aside: toxic megacolon can be a complication of c.diff or Trypanosoma cruzei (HY)UC can cause arthritis (HLA-B27)Aside: PAIRPsoriatic arthritisAnkylosing spondylosisIBD associated arthritis (Crohn’s and UC)Reactive arthritis (Reiter’s arthritis)UC can also cause uveitisPyoderma gangrenosum – UC not to be confused with Erythema nodosum – Crohn’s diseaseAside: Erythema nodosum is also found in sarcoidosis and coccidioidomycosis.Treat UC: inhibit COX will help with inflammation. Start with 5-ASA compound (NSAID that primarily works in the colon since bacteria in colon converts it for use), 6MP or Azathioprine. Cure UC: take out rectum and colon.Immunology: mediated by T Helper 2 cells (humoral immunity). High risk for colon cancer. (Crohn’s doesn’t have such a high risk as UC)Crohn’s disease – skipped lesion, involves every layer of the GI tract and spares the rectum. Affects the terminal ileum BUT it can affect any part of the GI tract (not rectum). Mediated by T Helper 1 cells (cell-mediated immunity). Antibody association: anti-Saccharomyces cerevisiae antibodies (ASCA). Think: “chronic watery diarrhea” and not “bloody diarrhea” as that is UC.Non-caseating granulomas are found. Crohn’s causes transmural inflammation and fistulas can form from colon to skin or colon to vagina or colon to bladder. Fistula from colon to bladder can also form in diverticulum.String sign seen in barium swallow. Terminal ileum affected. Results in:Fat malabsorption Bile salts reabsorbed in terminal ileum. If bile acids are not reabsorbed at the terminal ileum, calcium oxalate crystals develop in kidney causing a type of nephrolithiasis. (VHY) Buzzword: “flank pain radiating to groin”.B12 lost so megaloblastic anemia results.Treat: Start with 5 ASA compounds (NSAID that primarily works in the colon since bacteria in colon converts it for use – Balsalazide, Mesalamine, Olsalazine). Or TNF inhibitors or high dose of IV corticosteroids.Vignette: 65-year-old has painless, bloody diarrhea and microcytic anemia. Diagnosis: Diverticulosis – outpouching of colon that are asymptomatic. (Think: painless, bloody bowel movements in the elderly (HY)). If you see “lower GI bleeds in the elderly, think diverticulosis.”Do barium enema to diagnose diverticulosis. (LOOK UP IMAGING – must identify)What are risk factors for diverticulosis?Chronic constipationStanding all the time – increased intraabdominal pressureOld person with fever, left lower quadrant pain = diverticulitis. When fecalith is stuck in diverticulosis, then it is a diverticulitis. CT scan with IV contrastAbx: ampicillin, metronidazole, gentamycin OR cipro and metro OR TMX-SMX and plications: Colon perforation. So, don’t do colonoscopy during acute attack. Perforation can cause fistula.Colovesicular fistula: fistula from colon to bladder. Most common cause: diverticulitis. (Before Crohn’s). Vignette: pneumaturia – gas bubbles in urine is buzzword for colovesicular fistula.Differentiate between true diverticulum and false diverticulum: Two true diverticula: includes all layers of the GI tract.Meckel’s diverticulum: painless bloody bowel movements in child. Traction diverticulum in mid esophagus.False diverticulum: includes only some layers like mucosa and submucosa.Zenker’s diverticulumDiverticulosis Arise in regions of weakness of muscularis externa ................
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