Flashcards in GI Disease Deck (72):
How do you diagnose acute pancreatitis?
For diagnosis of acute pancreatitis, need 2 of 3:
– Abdominal pain characteristic of disease
– Amylase and/or lipase elevated at least 3x upper limit of normal (ULN)
– Characteristic imaging findings
Why is lipase (compared to amylase) often preferred in diagnosing pancreatitis?
• Lipase is preferred: more sensitive and
more specific for acute pancreatitis
• Neither enzyme has accepted prognostic value
• Lipase remains elevated longer than amylase
• Current recommendations are for lipase measurement alone.
How does sensitivity/specifity compare for diagnosis of pancreatitis w/ lipase and amylase?
What else besides acute pancreatitis can cause elevations in pancreatic enzymes?
• Renal failure
• Acute appendicitis
• Intestinal ischemia or obstruction
• Peptic ulcer disease
• Gynecological disease
• Diabetes (higher lipase, so diagnostic cutoff is >3-5 ULN, but no consensus on actual value)
• Parotid/salivary gland disease (amylase only)
What are causes of acute pancreatitis?
• Gallstones and alcohol are most common
• Hypercalcemia, hypertriglyceridemia
• Post-ERCP, trauma/injury
• Drugs (e.g., azathioprine, sulfonamides, NSAIDs, steroid, tetracycline)
• Viral infections (e.g., mumps, rubella, EBV, CMV, hepatitis)
bruising around umbiliccus
bruising around spleen/flank
What are first tier LFTs?
– ALT, AST
• Alkaline phosphatase, γ-glutamyl transferase (GGT)
• Prothrombin time/INR
What are second tier LFTs?
• Hepatitis viral serologies and molecular
• Fe, ferritin, Cu
• Alpha-1 antitrypsin
• Autoantibody tests
What are the three classifiaitons of liver disease?
1. hepatocellular injury/necrosis (damage/death to hepatocytes)
ALT,AST > AP
2. Cholestatic (obstruction of bile outflow from liver)
AP > ALT or AST
3. Infiltrative (neoplasm, amyloid)
elevated AP w/ normal ALT, AST or AP > ALT, AST
What are transaminases and how do they differ?
• ALanine aminotransferase (ALT) (SGPT)
• ASpartate aminotransferase (AST) (SGOT)
• These “leak” from damaged hepatocytes
• ALT is more SPECIFIC for LIVER disease
– AST is found in MUSCLE and RED
– With extensive muscle breakdown, both ALT and AST rise
• ALT has a LONGER half-life
Where does AP come from?
• Present on hepatocyte membrane
bordering the bile canaliculi
• Isoenzymes: liver, bone, placenta
– Elevation is not a specific marker for liver disease
• Bone, GI, kidney
When would you order GGT?
to confirm a liver source
What are reference intervals for AST/ALT?
• AST 0-45 U/L, female; 0-55 U/L, male
– Children higher to age 2
• ALT 0-50 U/L, female; 0-70 U/L, male
What are reference intervals for AP?
• Alkaline phosphatase 40-150 U/L
What are markers of liver function?
– Half-life of 21 days, but can fall more rapidly with severe inflammation
– Can fall with renal or GI losses, or burns
• Prothrombin time (PT, INR)
What causes an acute rise in transaminases?
Drug induced hepatitis
Ischemic (shock liver)
Acute duct obstruction
Diagnostic test: Hep A
Diagnostic test: Hep B
HBsAg, IgM angti-HBc
Diagnostic test: drug induced hepatitis
improvement on stopping
Diagnostic test: alcoholic
improvement iwth abstinence
Diagnostic test: shock liver
improvement iwth restoration of circulation
Diagnostic test: acute duct obstruction
Diagnostic test: wilson disease
liver Cu measurement
Diagnostic test: autoimmune hepatitis
anti-smooth muscle (f actin)
anti-LKM type 1
How high can ALTL be with acute hepatitis?
If ALT over 5000 consider....
unusual viruses like HSV
stones can cause transient elevations to...
alcoholic hepatitis cuases modest elevations to...
less than 400 (bili is often elevated more)
What are common cuases of chronic hepatitis?
HepC/B (anti-HCV, RNA, HBsAg)
NASH (US, liver bx)
Alscoholic liver disease (liver bx)
How do you define chronic hepatitis?
transaminases usually 205 fold elevated
pt can be asymptomatic
what characterizes cholestatic disrorders?
rise in AP and bili
blockage of microscopic ducts
primary biliary cholangitis
blockage of large ducts
ca of head of pancreeas
blockage of large and small dcuts
primary sclerosing cholangitis
What are common causes of cholestasis?
Large bile duct obstruction
Primary biliary cholangitis
Usually men 20-50; ulcerative colitis
primary sclerosing cholangitis
large bile duct obstruction (stone, tumor)
Malignancy, sarcoid, amyloid
adult bili ref range
.2 - 1.3
first 2 wks of life bili
bilirubinuria is = ...
insoluble, carried by albumin
elevation means hemolysis
elevations mean liver disease (parenchyma/biliary tract)
When is jaundice visible?
bili > 2.5 mg/dL
What causes unconjugated hyperbilirubinemia?
• Hemolysis, resorption of a large hematoma,
ineffective erythropoiesis (e.g., B12 deficiency)
• Neonatal physiologic hyperbilirubinemia
• Gilbert syndrome
What is Gilbert syndrome?
– Benign defect in UDPGT activity
– 3-7% of the population, M:F 2-7:1
– Manifests in stress conditions, including fasting – Bilirubin < 6.0 mg/dL
– LFTs normal, Hb normal
– No treatment, just reassurance
What suggests conjugated hyperbijjlirubinemia?
– Suggested by abdominal pain, fever, palpable gall bladder
– Ultrasound reveals duct dilation, unless very transient (e.g., passage of a gall stone)
– A transient rise in aminotransferase levels can be seen with acute large duct obstruction
• Hepatocellular injury
• AST> 2xALT, but AST <400UL
• Bilirubin increase and PT/INR better indices
What viruses classically cuase viral hepatitis?
Hep A, B (D,C,E)
What should you exclude before diagnosing autoimmune hepatitis?
chronic viral hepatitis
assoc w/ Hashimotos thyroiditis
WHat is primary biliary cirrhosis?
• Typically middle aged women (40-60 yrs)
• Presents with fatigue and pruritus
• Increased levels of AP and IgM
• Fat soluble vitamin deficiencies and metabolic bone disease, increased cholesterol (HDL), later increased bilirubin
• Granulomatous infiltration of septal bile ducts
• Anti-mitochondrial antibodies present in over 90-95%
Autoimmune hepatitis vs PBC
anti-smooth muscle Ab 90%
What causes toxic hepatitis?
– Predictable (e.g., acetaminophen) – Idiosyncratic (e.g., isoniazid)
– Vinyl chloride
– Jamaica bush tea
– Kava kava
– Amanita phalloides or A. verna (mushrooms)
acetaminophen toxicity: 0-24 hrs
Anorexia, nausea, vomiting
acetaminophen toxicity: 24-72
Right upper quadrant abdominal pain (common)
AST, ALT, and, if poisoning is severe, bilirubin and PT (usually reported as the INR) sometimes elevated
acetaminophen toxicity: 72-96
Vomiting and symptoms of liver failure Peaking of AST, ALT, bilirubin, and INR Sometimes renal failure and pancreatitis
acetaminophen toxicity: >5
Resolution of hepatotoxicity or progression to multiple organ failure (sometimes fatal)
What is hte rumack matthew nomogram
Hours vs. Plasma acetaminophen (can determine if hepatotoxicity likely given level and how many hours out)
What causes Fe overload?
Multiple blood transfusions (talassemia major)
Consider in adults w/ liver disease (men)
What should you consider in a pt with transferrin saturation >55% and ferritin > 200?
Liver bx with Fe measurement
Where does Cu accumulate in wilsons disease?
defect in wilson disease
ATP7B gene (increased Cu absorption, decreased excretion)
What are sxs of Wilson diesase?
• Hepatitis, splenomegaly, hypersplenism, Coombs neg. hemolytic anemia, portal hypertension, neuro-psychiatric disease
• Can cause chronic or fulminant hepatitis
• Kayser-Fleischer ring seen on slit-lamp exam
Wilson disease is usually diagnosed in what population?
adolescent or young adult
Labs diagnostic of WIlsons?
• Increased urinary Cu (> 40 μg/24 h)
• Low serum ceruloplasmin (<20 mg/dL; <5 mg/dL is diagnostic) (Cu binding protein)
• Increased hepatic Cu (>250 μg/g dry wt.)
What is Crigler Najjar type 1?
• Very rare, newborns
• Unconjugated hyperbilirubinemia
• Bilirubin > 20 mg/dL
• Fatal disease, kernicterus – Liver transplant
• ABSENT UDPGT activity
What is Crigler Najjar type 2?
• More common than type 1
• Unconjugated hyperbilirubinemia • Can survive to adulthood
• Bilirubin 5-25 mg/dL
• Milder DEFICIENCY of UDPGT
– Enzyme can be induced by phenobarbital
What are dubin johnson and rotor syndromes?
• Both are rare, benign disorders with asymptomatic jaundice
• Often present in 2nd decade of life
• Increased direct (conjugated bilirubin)
• Dubin-Johnson caused by mutations in multiple drug resistance protein 2
• Rotor syndrome mechanism unclear
Neonatal jaundice affects what % of newborns?
acute encephalopathy > kernicterus