Transcript - Catalyst - University of Washington

Topics in Gastroenterology
Melissa (Moe) Hagman, MD, FACP
Associate Professor, University of Washington
Boise Internal Medicine Residency
[email protected]
Disclosure of Financial
Relationships
Melissa (Moe) Hagman, MD, FACP
Has no relationships with any entity
producing, marketing, re-selling, or
distributing health care goods or services
consumed by, or used on, patients.
Outline
• Case-based parade from esophagus to
rectum
• What are the life-threatening diagnoses on
the differential?
• What are the other diagnoses on the
differential?
• How can I go about a thoughtful and
efficient work-up to generate a treatment
plan that will benefit the patient?
Ms. A
• 50 yo woman with acute onset of
severe mid-sternal chest pain while
eating <1 hr ago
• For >6 months she reports that
solid food has tended to “get stuck”
in her mid-chest
• She usually avoids the medical
establishment and has no known
PMH
Consultant. July 2003.
• Clinical Question:
What is your differential diagnosis?
Assess First for
Life-Threatening Diagnoses
• Aortic dissection or rupture
– Risk factors, BP on both UE, aortic insufficiency on
exam, consider CXR/CT
• Myocardial infarction
– Risk factors, ECG
• Pulmonary embolism
– Risk factors, LE exam, consider ABG and VQ scan or
CT chest
• Esophageal rupture
– Risk factors, pleuritic chest pain
Ms. A
• T 37.0C, BP 133/72,
HR 105, O2 sat 97% RA
• Clinical Question:
What else do you notice
on physical exam?
Consultant. July 2003.
Scleroderma and the Esophagus
• Smooth muscle atrophy and fibrosis of distal
2/3rd of esophagus with low LES pressure
• Esophageal dysmotility
• Esophageal stricture – 17-29%
• GERD with Barrett’s
esophagus in up to 40%
– Esophageal cancer
Lower
Esophageal
Sphincter
Diaphragm
Ebert EC. J Clin Gastroenterol. 2006; 40:769-75.
Other Esophageal Motility Disorders
• Achalasia
– Loss of relaxing neurons
in myenteric plexus
– Usually idiopathic
– Solid and liquid dysphagia
– Regurgitation
– Weight loss
Lower
Esophageal
Sphincter
Diaphragm
Achalasia
• Diagnosis
– Manometry – no peristalsis
and high LES pressure
– UGI – “bird’s beak”
• Treatment
– Balloon dilatation
– Surgical myotomy
– Botulinum toxin injections into
LES
– Nitrates, calcium channel
blockers – do not help much
Dehn, Booth. www.nextspace.
co.uk/ lapsurg/images/achalasia
Achalasia – Chaga’s Disease
• Trypanosoma cruzi
–
–
–
–
–
Triatomine insect vectors
South America
GI dysmotility
Cardiomyophathy
Serology
Charles Hedgcock.
Other Esophageal Motility Disorders
• Nutcracker Esophagus
– Hypertensive peristalsis
– Increased distal peristaltic
amplitude (>220mmHg)
and duration (>6 sec)
Lower
Esophageal
Sphincter
Diaphragm
Esophageal Diverticulum
archive.constantcontact.com
Mr. B
• 74 yo gentleman with recurrent
discomfort in the mid upper
abdomen for 3 months.
• No heartburn. Occasional bloating.
• No improvement with OTC H2
blocker.
• Clinical Question:
What additional history do you
need and what is your differential
diagnosis?
Dyspepsia – Alarm Features
• History
–
–
–
–
–
–
New onset >55 yo old
Dysphagia/odynophagia
Early satiety
Vomiting
Anemia/bleeding
Unexplained wt loss
• PMH
– PUD
– Malignancy
– Gastric surgery
• Family Hx
– GI malignancy
• Exam
– Lymphadenopathy
• Sister Mary Joseph sign
– Abdominal mass
Talley NJ, et al. Am J Gastroenterol. 2005; 100:2324-37.
Dyspepsia - Causes
• GERD
• Peptic ulcer disease
• Functional (non-ulcer) – 60% of cases
Dyspepsia - Treatment
• If alarm features
– EGD
• If no alarm features
– Try to stop any NSAIDS
– Empiric acid suppression
• PPI x 4-8 weeks
– Or, in patient populations with high H. pylori
prevalence, test and treat
Talley NJ. Gastroenterology. 2005; 129:1753-5.
H. pylori testing
• Test in patients with
– Peptic ulcer disease (PUD)
Resolution at
12 months
H. pylori
NOT treated
H. pylori
treated
Gastric ulcer
61%
97%
Duodenal
ulcer
65%
98%
– Gastric mucosa-associated lymphoid tissue
(MALT) lymphoma
• Treatment leads to tumor regression in 60-90%
– Uninvestigated dyspepsia without alarm
features
Chey WD, et al. Am J Gastroenterol. 2007; 102:1808-25.
H. pylori testing
• EGD with gastric biopsy
– Gold standard, associated risks of endoscopy
• Serology
– Inexpensive
– NPV good, PPV depends
– Remains positive for 6-12 mo after eradication
• Urea breath test
• Stool antigen
False negatives within
2 wks of PPI or abx, more
expensive than serology
Chey WD, et al. Am J Gastroenterol. 2007; 102:1808-25.
GERD
• Symptoms or mucosal damage caused by
the abnormal reflux of stomach contents
into the esophagus
• Diagnosis
– Empiric acid suppression
• High dose PPI – sensitivity 75%, specificity 55%
– EGD
– Ambulatory reflux monitoring
– Esophageal manometry
DeVault KR, et al. Am J Gastroenterol. 2005; 100:190-200.
Sensitivity and Specificity
• Sensitivity (SNOUT)
– if a test has high sensitivity, a negative result
rules out disease
=
true positives
true positives + false negatives
• Specificity (SPIN)
– if a test has high specificity, a positive result
rules in disease
=
true negatives
true negatives + false positives
GERD - Treatment
• Lifestyle changes
– Elevate head of bed
–
–
–
–
Paauw et al. IM Clerkship
Guide. 3rd Ed. 2008.
Decrease intake of fat
Avoid chocolate, peppermint, ETOH, coffee
Quit smoking
Avoid recumbency <3hrs after eating
DeVault KR, et al. Am J Gastroenterol. 2005; 100:190-200.
GERD - Treatment
• Patient-directed (OTC) therapy
• Acid suppression
Before breakfast
and dinner
Placebo
H2 blocker
PPI
Symptom
Relief
27%
60%
83%
Healed
Esophagitis
24%
50%
78%
• Promotility agents
• Antireflux surgery
DeVault KR, et al. Am J Gastroenterol. 2005; 100:190-200.
GERD - Complications
• Stricture
• Barrett’s esophagus (premalignant lesion)
• Consider EGD to assess in pts with uncontrolled
GERD symptoms for >5-10yrs
• Esophageal cancer
• Asthma
• Cough
• Hoarseness • Chest pain
DeVault KR, et al. Am J Gastroenterol. 2005; 100:190-200.
Ms. C
• 28 yo previously healthy woman
presents with 1 wk of nausea,
jaundice, fatigue, confusion after
treatment 3wks ago for UTI with
TMP/SMX
• No stigmata of chronic liver
disease
• AST 1240 U/L
ALT 1099 U/L
Tbili 11.6mg/dL
INR 2.3
alb 3.2
• Clinical Question:
What is differential diagnosis?
Acute Liver Failure
• Severe impairment of liver function
(coagulopathy) associated with encephalopathy
within 8-26 weeks of the first symptoms
• INR is best marker of liver function
• DfDx for AST and ALT of >1000 U/L
– Hypoperfusion
– Toxins
– Viruses
Acute Liver Failure - Etiology
• Medications - most common cause in US (> 50%)
–
–
–
–
–
–
–
Acetaminophen (>4g/day)
sulfa-containing
– phenytoin
NSAIDs
– valproate
halothane
– TCN, erythromycin
INH
– terbinafine
MAOI
– herbs
antabuse
– etc., etc., etc.
Lee. Clin Persp Gastro. 2001; 4:101-110.
Acute Liver Failure - Etiology
• Other Toxins
– mushrooms (amanita phalloides)
– yellow phosphorus
– illicit drugs
– CCl4
• cocaine
• ecstasy
mushroomexpert.
com
• Viral Hepatitis ~10-20% in USA
– A, B, D, E, HSV, EBV
– worldwide HBV is the leading cause of ALF
Acute Liver Failure - Etiology
• Metabolic
– Wilson’s disease
•
•
•
•
•
•
young age of onset
h/o psychiatric d/o, athetoid movements
Kayser-Fleischer ring in cornea
check serum ceruloplasmin and copper
lethal without transplantation if presents with FHF
Rx D-penicillamine or trientine in non-FHF
– Acute fatty liver of pregnancy
Acute Liver Failure - Etiology
• Other
– Autoimmune hepatitis
• check ANA
–
–
–
–
Portal vein thrombosis
Budd-Chiari syndrome – blockage of venous outflow
Ischemic (“shock liver”)
Malignant infiltration
Acute Liver Failure - Rx
• Stop offending drug/toxin
• Start N-acetylcysteine (even in nonacetaminophen-induced liver failure)
Lee WM. Gastroenterology. 2009; 137:856-64.
• Refer to liver transplantation center
– Improves survival by 20% if pts with fulminant hepatic
failure are managed at specialist ICU facilities
– At least 12 hrs required to do screening and to list patient
for transplantation
Lee, Larson, Stravitz. AASLD Position Paper. 2011.
Mr. D
• 45 yo gentleman presents with
hematemesis
• Takes NSAID for arthritis in
hands at MCP joints
• T37.3C, BP 90/52, HR 122
• Stigmata of chronic liver disease
• Clinical Question:
What is differential for GIB in
this patient? What are you
going to do now?
GIB
• Two large bore IVs
• Check coagulation studies
• Call GI to consider endoscopy
• Esophageal varices due to portal HTN
– Octreotide
– EGD with banding
– After stable, use β-blocker (propranolol,
nadolol or carvedilol)
Hemorrhage of Esophageal Varices
• Risk of death from hemorrhage as high as
20% in 6 months after bleed
• Secondary prophylaxis after initial
hemorrhage - reduces relative risk of bleeding
by about 50%
– β-blockers (propranolol, nadolol, carvedilol)
• Push dose to maximum tolerated
– Band ligation
• Repeat every 1-2 weeks until varices obliterated
Garcia-Tsao G, et al. Hepatology. 2007;46:922-38.
Grace ND, et al. Hepatology. 1998;28:868-80.
Hemorrhage of Esophageal Varices
• Guidelines recommend screening EGD at time
of diagnosis of cirrhosis
• Primary prophylaxis with β-blocker or ligation if
– Medium to large varices (NNT = 10 to prevent 1
bleeding episode)
– Decompensated cirrhosis and small varices
• Repeat EGD
– 2-3 yrs in compensated disease and no varices
– 1-2 yrs in setting of small varices
– 1 yr in decompensated liver disease with or without
varices
Garcia-Tsao G, et al. Hepatology. 2007;46:922-38.
Causes of Cirrhosis
• Chronic viral hepatitis
• Alcohol
• Biliary diseases
– primary biliary cirrhosis
– primary sclerosing
cholangitis
• Autoimmune hepatitis
• Venous outflow
obstruction
– Budd-Chiari syndrome
– veno-occlusive disease
– chronic heart failure
• Metabolic diseases
– hemochromatosis
– Wilson’s Disease
– alpha-1 antitrypsin
deficiency
– glycogen storage diseases
– porphyria
• Drugs and toxins
• Sarcoidosis
• Intestinal bypass for
obesity
• NASH
Causes of Cirrhosis
• Primary sclerosing cholangitis (PSC)
• Male > female
• Diagnosis – US and ERCP
• Primary biliary cirrhosis (PBC)
• Female > male, age 30-50
• + antimitochondrial antibody (AMA)
• Diagnosis - US and liver biopsy
Causes of Cirrhosis
• Hemochromatosis
• Iron overload
• Arthritis – classically 2nd and 3rd MCP with
hook-like osteophytes on xray
• CHF, DM, skin color changes, hypogonadism
• Screening test is transferrin saturation (>45%)
• HFE gene
• Rx – phlebotomy to ferritin <50 ng/ml
Cirrhosis - Complications
•
•
•
•
•
•
•
•
•
Hepatic encephalopathy
Ascites
Spontaneous bacterial peritonitis (SBP)
Hepatocellular carcinoma
Hemorrhage of esophageal varices
Hyponatremia
Coagulopathy
Hepatorenal dysfunction
Hepatopulmonary syndrome
Hepatic Encephalopathy Asterixis
Number or Figure Connection Test
Normal < 30 seconds
Gitlin N. Am J Gastroenterol. 1988; 83:8.
Physical Exam for Ascites
• Best findings arguing for ascites
– Fluid wave; up to 6L of fluid needed before
detection possible (+LR 5)
– LE edema (+LR 3.8)
• Best findings arguing against ascites
– Absence of flank dullness; approximately
0.5-1.1L of fluid needed before detection
possible (-LR 0.3)
– Absence of LE edema (-LR 0.2)
McGee, S. Evidence-Based Physical Diagnosis. 2001.
Likelihood Ratios
• LR of 2, 5, 10 increase probability
15%, 30%, and 45% respectively
• LR 0.5, 0.2, 0.1 decrease probability
15%, 30%, and 45% respectively
Diagnostic Paracentesis (30cc)
• Albumin
– SAAG (serum-ascites albumin gradient) >1.1g/dL is
consistent with portal HTN
• Cell count
– >250 PMN/µL = spontaneous bacterial peritonitis (SBP)
• Culture into blood culture bottles at the bedside
Runyon B, et al. J Clin Microbiol. 1990; 28:2811-12.
• Total protein
– If <1.5g/dL, consider SBP prophylaxis
Runyon BA. AASLD Guidelines. 2012.
Terg R, et al. J Hepatol. 2008; 48:774-9.
Fernandez J, et al. Gastroenterol. 2007; 133:818-24.
SBP Prophylaxis
• Indications for prophylaxis
– Prior episode of SBP
– Ascites protein <1.5g/dL and either renal
impairment (Cr ≥1.2, BUN ≥25) or hepatic
impairment (Childs ≥9, bili ≥9)
– During acute UGIB in cirrhosis
• 7 days of ceftriaxone or similar to reduce SBP and
other infections such as UTI
Runyon BA. AASLD Guidelines. 2012.
Moderate Volume Ascites - Rx
• Low sodium diet (90mmol/day)
• Diuretic Regimen
– Optimal ratio
• Furosemide (Lasix) 40mg po qday
• Spironolactone (Aldactone) 100mg po day
– Maximum dose
• Furosemide 160mg/day
• Spironolactone 400mg/day
• Goal diuresis
• 300-500g/day if no peripheral edema
• 800-1000g/day if peripheral edema
Gines P, Cardenas A. Sem Liver Dis. 2008; 28:43-58.
Large Volume Ascites - Rx
• Total paracentesis with IV albumin
– Albumin 6-8g IV per liter of ascites removed
(as long as 5 liters ascites removed)
– For example,
• If 4 liters removed, no albumin
• If 5 liters removed,
give 5 x 6-8g albumin
Gines P, Cardenas A. Sem Liver Dis. 2008; 28:43-58.
Gines A, et al. Gastroenterology. 1996; 111:1002-10.
Albumin - Large Volume Paracentesis
• Assists with plasma volume expansion
• Tries to balance the increased activity
of renin-angiotensin-aldosterone system
• Attempts to prevent renal impairment
– 20% of pts with circulatory dysfunction
after LV paracentesis develop hepatorenal
syndrome and/or dilutional hyponatremia
• Has not been shown to have direct
survival benefit
Gines P, Cardenas A. Sem Liver Dis. 2008; 28:43-58.
Gines A, et al. Gastroenterology. 1996; 111:1002-10.
HCC Surveillance
• Serum AFP and liver ultrasound Q6 months
• Initiate surveillance in pts with cirrhosis due to:
–
–
–
–
–
HCV
HBV
Primary biliary cirrhosis (PBC)
ETOH
Hemochromatosis
• Unclear benefit in pts with cirrhosis due to:
– Autoimmune hepatitis
– Alpha-1-antitrypsin
– Non-alcoholic steatohepatitis
Bruix J, Sherman M.
Hepatology. 2005; 42:1208-36.
HCC Surveillance
• Serum AFP and liver ultrasound Q6 months
• Also recommended in HBV carriers without
cirrhosis who are:
–
–
–
–
Asian men ≥ 40 yo
Asian women ≥ 50 yo
African men or women ≥ 20 yo
Family history of HCC
Bruix J, Sherman M. Hepatology. 2005; 42:1208-36.
Surveillance for HCC
• RCT, >18,000 ESLD pts with HBV
• Every 6 month serum AFP and hepatic
ultrasound vs no surveillance
– Reduced HBV associated mortality by 37%
in surveillance group
Zhang BH, et al. J Cancer Res Clin Oncol. 2004;130:417-22.
Mr. D
• 45 year-old gentleman with ESLD
secondary to hemochromatosis
• PE: moderate ascites
• Labs:
– bilirubin 3.1mg/dL
– albumin 2.8g/dL
- INR 1.8
- Cr 1.7mg/dL
• Clinical Question:
How can we classify the severity of
Mr. D’s liver disease?
Child-Turcotte-Pugh Class
1
2
3
Albumin
>3.5
2.8 - 3.5
<2.8
Bilirubin
INR
Ascites
Encephalopathy
<2
<1.8
None
None
2-3
1.8 – 2.3
Mild
1-2
>3
>2.3
Mod
3-4
Child’s Class C
Class
A 5-6
B 7-9
C 10-15
Model for End-Stage Liver
Disease (MELD) Score
• MELD =
9.57 x loge creatinine (mg/dL) +
3.78 x loge bilirubin (mg/dL) +
11.20 x loge INR + 6.43
• Predicts risk of death with TIPS
• Predicts overall risk of death at 3 months & 1 yr
• Predicts peri-operative mortality
• Used to prioritize organ allocation for liver
transplantation since Feb 2002
http://www.unos.org/resources/MeldPeldCalculator.asp
MELD –
Overall Mortality Prediction
MELD Mortality (3mo)
<9
2%
• List for transplant at
MELD >9
10-19
6%
20-29
20%
• Equal chance of 3-month
survival with disease vs
30-39
53%
transplantation at
>40
71%
MELD 14-15
Our pt’s MELD = 22
Wiesner R, et al. Gastroenterol. 2003;124:91-6.
Amer Assoc Study of Liver Disease
• www.AASLD.org – Liver Learning
Zhang BH, et al. J Cancer Res Clin Oncol. 2004;130:417-22.
Mr. E
• 68 yo gentleman presents with
epigastric pain of 1 day duration
• h/o HTN
• Drinks 2 glasses of wine a day
• Clinical Question:
What further history do you want
and what is your differential
diagnosis?
Acute Pancreatitis
• Etiology
– Gallstones, ETOH, mass, pancreas divisum,
trauma (MVA, ERCP), scorpion sting,
autoimmune
– If young person with pulm or GI disease,
think about cystic fibrosis
• APACHE II score ≥8
– Better predictor of severe pancreatitis than
Ranson criteria
• Complications
– Necrosis, pseudocyst
Chronic Pancreatitis
• Watch for signs of pancreatic insufficiency
– DM
• Treat as for type 1 DM
– Steatorrhea
• Treat with pancreatic enzymes
• Pancreatic calcifications on KUB
• Amylase/lipase may not rise much with
acute on chronic pancreatitis
Ms. F
• 72 yo woman calls with c/o watery
loose stools several hours after a
picnic. Other family members have
similar symptoms.
• No fever. No blood in stool. Nausea
without emesis. Otherwise well.
• Clinical Question:
What work-up is necessary and
what treatment would you
recommend?
Acute Diarrhea
• Food-borne disease
– Sxs start within 6 hrs – S. aureus, B. cereus
– Sxs start within 8-14 hrs – C. perfringens
– Sxs start >14hrs – viral or E. coli
• E. coli O157:H7 – 10% of infected pts get
HUS or TTP
• Watch for giardia if unfiltered H2O
ingestion
Acute Diarrhea
• Work-up/Treatment
– Hydration and watchful waiting unless
• Symptoms >7 days
• Fever
• Abdominal pain
• Hematochezia
– Avoid antimotility agents with E. coli
suspected
Mr. G
• 21 yo gentleman presents with
8-10 bloody bowel movements per
day, abd pain, and tenesmus x
3 months
• Clinical Question:
What additional information do
you want?
Chronic Diarrhea
• Is patient immunocompromised?
• Is diarrhea…?
– Bloody/Inflammatory
• Guaiac, fecal leukocytes +
– Osmotic/Malabsorption
• Stool osm > 340 mosm/kg
• Resolves with fasting, no nocturnal symptoms
• Lactase deficiency most common
– Secretory
• Large volume, watery
• No change with fasting, nocturnal sxs present
Inflammatory Bowel Disease
Ulcerative Colitis
Crypt abscesses and
superficial
inflammation
colon/rectum only
p-ANCA positive in
75%
Anti-saccharomyces
cerevisiae antibodies
(ASCA) present 10%
Crohn’s Disease
Linear ulcerations
with “skip” areas
involving entire GI
tract
p-ANCA positive in
10%
ASCA present 60%
Smoking alleviates
symptoms
Smoking risk factor
for disease
IBD – Extra-Intestinal
Manifestations
• Uvetitis, episcleritis
• Erythema nodosum
– red nodules most classically on shins
• Pyoderma gangrenosum
– erythematous papules or pustules
• Arthritis
• Primary sclerosing cholangitis (PSC)
• Venous thromboembolism
Mr. F
• Colonoscopy and EGD most consistent
with Crohn’s disease
• Started on prednisone and then
azathioprine after symptoms improved
• Develops new vague diffuse abdominal
pain that is different than prior
symptoms
• No fever, BP 100/60, HR 90
• Mild diffuse TTP. No rebound/guarding.
• Clinical Question:
Why does Mr. F have new pain?
Mr. F
Bowel Perforation and Steroids
• In patients on >20mg/day of prednisone,
abdominal tenderness is the only
consistent symptom/sign of abdominal
perforation
• Delay in diagnosis up to 8 days from
onset of symptoms
• Mortality approximately 85%
ReMine SG, et al. Ann Surg. 1980;192:581-6.
Celiac Sprue
• Symptoms
– chronic diarrhea, steatorrhea, bloating, wt loss, abd
pain
• PE
– pruritic papulovesicular rash on extensor surfaces =
dermatitis herpetiformis
• Associated with autoimmune disease (i.e. DM1)
• Dx
– IgA anti-tissue transglutaminase
– IgA anti-endomysial antibody test
– Biopsy of proximal small bowel
• Rx - Gluten-free diet