Gastroenterology Cases

Nav Saloojee MD

April 2008

• 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.

Case 1 ODYNOPHAGIA

Filling defects on barium study.Esophageal plaques on EGD

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

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.

•Nystatin ( topical therapy ) for oral thrush

•Fluconazole 100mg for 14 days for esophageal candidiasis

•Ampho B if neutropenic

Treatment

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

Daignosis?

• 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

Barrett’s Esophagus

Case 245 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

Case 2Lab

CBC, Lytes, Glucose, Urea, Creatinine normal. Anion Gap normal.

AST 210 ALP 103ALT 105 GGT 620Bilirubin normal INR 1.1Albumin 34

CXR / 3V Abdo normalIV Fluid, Thiamine started

Next Step?

Acetaminophen Hepatotoxicity

Acetaminophen level 150 ug/mL ( 1000uM/ L)

ETOH level positive

Remainder of tox screen negative

Acetaminophen Hepatotoxicity

Acetaminophen

Acetaminophen-SulphateAcetaminophen-glucuronide

P-450

Glutathione Conjugation Hepatocyte Protein conjugation

Cell Death

Urine

Toxic intermediate metabolite ( ? NAPQI )

Metabolism of toxic doses of Acetaminophen depletes glutathione and saturates glucuronide and sulphate conjugation pathways

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

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

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

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

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%

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

Acetaminophen Hepatotoxicity

Contact Transplant Centre

• Rising INR

• Acidosis

• Renal Failure

• Encephalopathy

– Remember that the early signs are subtle

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?

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

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 )

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

•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?

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.

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?

Case 3.

• 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 )

Ascending Cholangitis

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 Albumin 24

Case 4

What is the cause of bleeding?

What is the differential diagnosis?

What are the indicators for urgent endoscopy?

Causes of Upper GI Bleeding

Jutabha et al. Med Clin North Am 1996

UCLA. Prospective series of 1000 patients.

PUDVaricesMallory WeissTumourVascularDieulafoyOther

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 BleedingHemodynamic instability DESPITE resuscitationHematemesisRed Blood per rectum in a suspected UGIB

– ? Multiple Comorbidities

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

Causes of Portal Hypertension

Be wary of Splenic Vein Thrombosis

Case 4

What is the management of variceal bleeding?

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

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

Endoscopic Therapy

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)

Refractory Bleeding• Balloon Tamponade.

• Complications : Aspiration Pneumonia, Esophageal ulceration or

perforation

• High rate of rebleed when balloon deflated

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

• Precipitants of Hepatic encephalopathy

•GI Bleed•Uremia•Dehydration•Hypokalemia•Constipation•Excess dietary protein•Infection•Sedatives•Metabolic alkalosis

• Treatment : Treat underlying causeLactulose

•

Secondary Prophylaxis

• Both B Blockade and Banding reduce risk of rebleed

• Which is better is open to debate

• No proof for using both

Gastric Varices

Gastric Varices

•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

Case 5 . Lower GI Bleed

•DDX

• Diverticular Bleed

• Angiodysplasia

• Colon Cancer

• Ischemic Colitis

• Consider a brisk upper GI bleed

• Other causes less common

Lower GI Bleed

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

Lower GI Bleed

Colon Cancer

Rarely Severe LGIBPresentation ( R vs L) ?

Endoscopic Management of Acute Lower GI Bleeding

Approach to Lower GI Bleed

Acute Lower GI Bleed

EGD if UGIB suspected

Bleeding Stops Bleeding Persists

Angiogram to localize bleed

Refer to surgery

Colonoscopy after bowel preparation

Resuscitate

• What is the difference between Ulcerative colitis and Crohn’s?

Ulcerative Colitis Crohn’s

Th2 Th1

Superficial inflammation Transmural Inflammation

May be granulomata

Bleeding more common Weight loss and pain more common

Continuous Discontinuous

Colon only Anywhere in GI tract

Predilection for terminal ileum

Inflammatory Inflammatory Fibrostenosing Fistulizing

Better with smoking Worse with smoking

Surgery curative Recurs after surgery

Ulcerative Colitis and Crohn’s Disease

Case 6

• 57-year-old man• Recently diagnosed as having ulcerative colitis• Presents with persistent bloody diarrhea• Abdominal pain• He had a fever of 38.8 degrees. HR 120. BP 110 / 70• Decreased bowel sounds, and a tense, mildly distended abdomen.• WBC 15

Case 6

Diagnosis?

Treatment ?

Toxic Megacolon

• Differentiate from ileus where there is no colonic inflammation

• Inflammation leads to colonic paralysis

• Can result from IBD / Ischemia / Infectious colitis

• X-ray evidence of colonic distension. > 6 cm in transverse colon

• Fever, tachycardia, high WBC

• High mortality with perforation

• Remember, perforation can occur in ulcerative colitis ( or other forms of colitis ) without toxic megacolon

Toxic Megacolon : Treatment

• NPO, F&E, NG

• IV Solumedrol 20 mg q8h for 24 hours

• Immediate surgical consult

• Colectomy if fails to resolve in 24-48 hours or if peritoneal signs

Case 7• 69 year old man hospitalized for pneumonia

• After treatment with antibiotics, develops small volume, non bloody, profuse diarrhea

•Medications noncontributory

• Physical exam noncontributory

• Bloodwork noncontributory

•Sigmoidoscopy as shown below