Gastroenterology Cases

1. Gastroenterology Cases Nav Saloojee MD April 2008

2. Case 1 ODYNOPHAGIA • 35 y.o homosexual male presents with odynophagia. • HIV for about 5 years. CD4 100. VL 5000. • Hep C from IV drug use • No AIDS defining illnesses and has been noncompliant with antiretrovirals therapies. • Physical exam is unremarkable except for the presence of oral thrush.

3. Filling defects on barium study. Esophageal plaques on EGD

4. Odynophagia • Infection • Candida • CMV • HIV ulcers • HSV • Pill esophagitis • Tetracycline/doxycycline • NSAIDS • Slow K • Iron • Others • Inflammatory • ( Severe GERD, Crohn’s, Behcet’s, Pemphigoid, • Chemo / radiation ) • Toxic ingestion • Lye

5. Esophageal Disease In HIV • Esophageal candidiasis • most frequent AIDS defining illness • ~80% will develop esophageal symptoms but some asymptomatic • CD4 generally <200 • colonization by oral flora • occurs in combination with other pathology in ~25% ( CMV, HIV ulcer, HSV) • Common in other immunocompromised states • CRF, steroid use, hematologic malignancy, radiation, chemotherapy, etc.

6. Treatment • Nystatin ( topical therapy ) for oral thrush • Fluconazole 100mg for 14 days for esophageal candidiasis • Ampho B if neutropenic

7. Daignosis? l squamocolumnar junction is located in the tubular esophagus proximal to the anatomic GE junction Biopsy shows specialized intestinal metaplasia. Mucosa resembles intestine in that it is villiform , numerous goblet cells are present and epithelium is columnar

8. Barrett’s Esophagus • Barrett’s is premalignant • In a 5 year follow up of 50 patients with Barrett’s and High Grade Dysplasia, 32 % developed adenocarcinoma • PPI probably does not reverse changes but is recommended as lifelong treatment of the underlying reflux • The length of Barrett’s is important. • There is a recommendation for once in a lifetime endoscopy for a patient with longstanding reflux symptoms to exclude Barrett’s

9. Case 2 45 year old woman History of alcohol abuse Presents to Emergency with intoxication, nausea and vomiting No other history available Physical examination VSS. Afebrile. Mucous membranes dry Abdomen soft. Non tender. No mass. No HSM. No stigmata of chronic liver disease Remainder of exam normal

10. Case 2 Lab CBC, Lytes, Glucose, Urea, Creatinine normal. Anion Gap normal. AST 210 ALP 103 ALT 105 GGT 620 Bilirubin normal INR 1.1 Albumin 34 CXR / 3V Abdo normal IV Fluid, Thiamine started Next Step?

11. Acetaminophen Hepatotoxicity Acetaminophen level 150 ug/mL ( 1000uM/ L) ETOH level positive Remainder of tox screen negative

12. Acetaminophen Hepatotoxicity Acetaminophen P-450 Acetaminophen-Sulphate Toxic intermediate metabolite ( ? NAPQI ) Acetaminophen-glucuronide Urine Glutathione Conjugation Hepatocyte Protein conjugation Cell Death Metabolism of toxic doses of Acetaminophen depletes glutathione and saturates glucuronide and sulphate conjugation pathways

13. Hepatotoxicity produces necrosis. Inflammation is minimal. Recovery is associated with complete resolution without fibrosis

14. Acetaminophen Hepatotoxicity • Safe in doses of 1 to 4 grams /day • Single doses greater than 10 g can result in liver injury • Severe Liver injury ( ALT > 1000) or fatality associated with doses of 15 –25 g. • Chronic ingestions of 4-6/ g day can lead to injury • Among heavy drinkers fatal doses of 6 g have been described • Most common cause of drug induced liver injury • An important cause of Fulminant Hepatic Failure • Rapid development of hepatocellular dysfunction ( jaundice, coagulopathy) • Encephalopathy

15. Risk Factors for Acetaminophen Hepatotoxicity • Older Age • Dose • Blood Level of Acetaminophen • Chronic Alcohol Ingestion Lower threshold for injury as ETOH depletes GSH / induces p450 • Fasting • Concomitant Medication p450 induction ( Barbituates, INH, Dilantin) • Late Presentation Best outcome if Rx within 12 hours

16. Therapy Activated Charcoal may be useful in first 4 hours N- Acetylcysteine ( NAC ) • Acetaminophen level should be determined at presentation • Recognize that levels within 4 hours of ingestion are unreliable due to delayed gastric emptying • After 4 hours, levels are a reliable indicator of the risk of liver injury • NAC given orally in U.S., given IV in Canada • NAC stimulates hepatic synthesis of GSH, may bind NAPQI, may be a sulphate precursor • Side Effects of NAC : GI upset and Allergic reactions • If a patient has known NAC hypersensitivity, Methionine can be used as an antidote

18. Therapy N- Acetylcysteine ( NAC ) • Severe liver injury virtually abolished if NAC given within 12 hours for patients with a toxic Acetominophen level: Hepatotoxicity Death NAC within 12 hours <8% 1% NAC 12-16 hours 34% 2-3%

19. Therapy N- Acetylcysteine ( NAC ) • After 16 hours, NAC less likely to affect liver necrosis • Nevertheless, late presenters should receive NAC as studies have shown decreased mortality when given in this group • Remember, the nomogram is only useful in an acute ingestion • Also, the nomogram was developed for nonalcoholic patients • NAC should be given in a chronic ingestion if hepatotoxicity is suspected • If an acetaminophen level can not be done quickly, NAC should be given • Follow Enzymes, INR, Mental Status, Acetominophen level • Consider prolonged NAC until acetominophen levels fall

20. Acetaminophen Hepatotoxicity Contact Transplant Centre • Rising INR • Acidosis • Renal Failure • Encephalopathy • Remember that the early signs are subtle

21. Transaminase Elevation What is the differential diagnosis for a patient with elevated transaminases ? What is the differential if transaminase levels >1000? What tests should one do in a patient with elevated transaminases?

22. Transaminase Elevation ( ie hepatocellular injury) • Drugs Acetominophen, etc • Alcohol • NAFLD • Viral Hepatitis • Ischemic Liver Injury • Hemochromatosis • Wilson’s disease • Autoimmune hepatitis • Alpha one antitrypsin deficiency • Common Bile Duct Stone

23. Marked Transaminase Elevation Few Causes of Transaminase Elevation >1000 • Drugs • Viral Hepatitis • Ischemic Liver Injury • Autoimmune hepatitis • Common Bile Duct Stone ( Not much more than 1000 )

24. Transaminase Elevation : Tests • Drugs Clinical, levels • Alcohol Clinical, GGT, AST>ALT • NAFLD U/S. Exclude other Dx • Viral Hepatitis Serology • Ischemic Liver Injury Clinical • Hemochromatosis Ferritin, % sat, gene test • Wilson’s disease Ceruloplasmin • Autoimmune hepatitis ANA, Anti Smooth m • Alpha one antitrypsin deficiency Level • Common Bile Duct Stone U/S

25. Case 3 • 40 year old woman presents to Emergency • For 2 years, intermittent RUQ/ epigastric discomfort. • Episodes last 2 or 3 hours and then resolve. • No previous investigation • Now presents with RUQ pain that is not resolving • No significant past history. No meds. • Afebrile. Physical exam is normal aside from mild RUQ tenderness • AST and ALT 1.5 times normal. Alkaline Phosphatase and GGT three times normal. Bilirubin 1.5 times normal. Normal INR and Albumin • She is admitted • Diagnosis?

26. Case 3. • Choledocholithiasis. History of biliary colic. • Ultrasound confirms CBD dilation and intrahepatic duct dilation. Stones seen in gallbladder. • ERCP below shows filling defects due to stones which are removed.

27. Case 3. • Post ERCP she feels well and liver enzymes normalize. • Cholecystectomy is suggested but she declines. • Three months later she presents with fever, jaundice, and RUQ pain • She looks unwell. Marked tenderness in RUQ • WBC 18. Liver enzymes show cholestatic picture and increased bilirubin • Diagnosis?

28. Ascending Cholangitis • CBD obstruction with bile stasis and bacterial infection in biliary tree • Pus under pressure in the bile ducts leads to sepsis • 85% of cases due to CBD obstruction from stone • RUQ pain, fever and jaundice are Charcot’s triad. • This is a medical emergency • Treatment • Blood Cultures • Antibiotics ( ex Ampicillin / Cefotaxime / Flagyl ) • Decompression of CBD with ERCP or PTC ( percutaneous transhepatic cholangiography )

29. Case 4 • 58 year old man presents to the emergency department with hematemesis. No abdominal pain. • Long history of alcohol abuse. • No past medical history • On no medications • On exam, BP 90/ 50 and HR 130. Postural changes. • Palmar erythema, dupuytrens contracture, telangiectasia on chest, gynecomastia. No asterixis. • Abdomen soft. Non tender. Liver not palpable. Spleen tip palpable. Bulging flanks. Rectal reveals melena • Hb 110 MCV 99 Platelets 125 Urea 15 Creatinine 89 • Normal AST/ ALT /ALP Bili 88 INR 1.5 Albumin24

30. Case 4 What is the cause of bleeding? What is the differential diagnosis? What are the indicators for urgent endoscopy?

31. Causes of Upper GI Bleeding Jutabha et al. Med Clin North Am 1996 UCLA. Prospective series of 1000 patients.

32. Early Endoscopy for Upper GI Bleeding • Overall, 80 % of UGIB self limited. • But 8-10% mortality • Early Endoscopy • Suspected Variceal Bleed ex. Cirrhotic patient • Indicators of Profuse Bleeding Hemodynamic instability DESPITE resuscitation Hematemesis Red Blood per rectum in a suspected UGIB • ? Multiple Comorbidities

33. Natural History of Variceal Bleeding • Esophageal varices develop in 50 % of patients with cirrhosis • 30% of patients with varices will have a bleed within 2 years of diagnosis • After one variceal bleed, the risk of a second is high. 60 to 70 % will rebleed within 2 years. • Variceal bleeding accounts for 20 – 33 % of deaths in cirrhotics

34. Causes of Portal Hypertension Be wary of Splenic Vein Thrombosis

35. Case 4 What is the management of variceal bleeding?

36. Management of Variceal Bleed • Volume Resuscitation • Correct coagulopathy. Vit K and FFP. +/- platelets • Pharmacotherapy : IV Octreotide 50 ug bolus and then • 50ug /hour • Antibiotics • Endoscopic Therapy • Balloon Tamponade • TIPS • Watch for encephalopathy • Secondary Prophylaxis

37. Pharmacotherapy. • IV Octreotide has a net impact of splanchnic vasoconstriction reducing variceal blood flow • Several trials show octreotide alone to be comparable to endoscopy alone in control of variceal hemorrhage • RCTs show beneficial effect in control of initial bleed ( ie octreotide + endoscopic therapy better than endoscopy alone) • IV octreotide shown to prevent early in hospital rebleed after control of initial hemorrhage. Continue for 48-72 hours

38. Endoscopic Therapy

39. Endoscopic Therapy • Banding or Sclerotherapy • Both can control acute bleed in about 90% • Banding may be difficult due to poor visualization • Current standard of care is combined endoscopic and pharmacotherapy (octreotide)

40. Refractory Bleeding • Balloon Tamponade. • Complications : Aspiration Pneumonia, Esophageal ulceration or perforation • High rate of rebleed when balloon deflated

41. Refractory Bleeding • TIPS ( Transhepatic Intrahepatic Portosystemic Shunt ) • A technically successful TIPS will decompress the portal circulation and control bleed in almost all patients • Main complication is encephalopathy

42. Precipitants of Hepatic encephalopathy • GI Bleed • Uremia • Dehydration • Hypokalemia • Constipation • Excess dietary protein • Infection • Sedatives • Metabolic alkalosis • Treatment : Treat underlying cause • Lactulose

43. Secondary Prophylaxis • Both B Blockade and Banding reduce risk of rebleed • Which is better is open to debate • No proof for using both

44. Gastric Varices

45. Gastric Varices

46. Case 5 . Lower GI Bleed • 74 year old woman • Presents to the Emergency with 4 episodes of passing blood per rectum that day • No abdominal pain, or other GI symptoms • Past history of mild chronic renal failure due to hypertension • On an ACE inhibitor. No other medications • BP 150/90. HR 90. No postural changes • Physical exam normal except red blood on rectal exam • Hb 120. MCV normal. Urea 17. Creatinine 210. Other labs normal. • Receives appropriate supportive care

47. Lower GI Bleed • DDX • Diverticular Bleed • Angiodysplasia • Colon Cancer • Ischemic Colitis • Consider a brisk upper GI bleed • Other causes less common

48. Lower GI Bleed Diverticular bleeding Bleeding spontaneously ceases in about 80% Roughly 25 % rebleed Of these, 50 % bleed again Angiodysplasia Mostly right sided Again, around 80 % subside spontaneously

49. Lower GI Bleed • Colon Cancer • Rarely Severe LGIB • Presentation ( R vs L) ?

50. Endoscopic Management of Acute Lower GI Bleeding