GI- Pathology II Flashcards
What pts most commonly get colorectal cancer?
50+ yo with ~25% having a family Hx
What are the risk factors for colorectal cancer?
- adenomatous and serrated polyps
- familial cancer syndrome
IBD
tobacco use
diet of process meat with low fiber
Where in the colon does cancer most commonly occur?
rectosigmoid > ascending > descending
How do ascending colorectal cancers present?
An exophytic mass, iron deficiency anemia, and weight loss
How do descending colorectal cancers present?
as an infiltrating mass, partial obstruction, colicky pain, and hematochezia
Colorectal cancer rarely presents with ________ bacteremia
Strept. Bovis
How is colorectal cancer diagnosed?
iron deficiency anemia in males (especially 50+) and postmenopausal females raises suspicion
screen pts 50+ with colonoscopy, flexible sigmoidoscopy, or stool occult blood test
How does colorectal cancer appear on a barium swallow test X-ray?
Apple core lesion
What is a good tumor marker for CRC?
CEA- good for MONITORING recurrence, but not for screening
What are the 2 molecular pathways that can lead to CRC?
1) Microsatellite instability pathway (~15%): DNA mismatch repair gene mutations (sporadic and Lynch syndrome)
2) APC/B-Catenin pathway (~85%) (sporadic cancer)
Describe the order of mutations in the APC/B-Catenin CRC pathway
Normal colon- loss of APC gene (decreases intercellular adhesions and increases proliferation)
Colon at risk- KRAS mutation (unregulated intracellular signal transduction)
Adenoma- loss of p53
Carcinoma
What is cirrhosis?
diffuse bridginf fibrosis and nodular regeneration via stellate cells disrupts normal liver architecture (increases the risk for hepatocellular carcinoma)
What are some common causes of liver cirrhosis?
alcohol (60-70%)
chronic viral hepatitis
biliary disease
genetic/metabolic disorders
What are the main effects of portal HTN?
-esophageal varices (leading to hematemesis)
peptic ulcers (leading to melena)
Splenomegaly
Caput medusae, ascites
anorectal varices
What are the main effects of liver cell failure?
- hepatic encephalopathy
- scleral icterus
- fetor hepaticus (musty smelling breath)
- Gynecomastia, spider nevi, and testicular atrophy (due to icnreased free estrogen)
- jaundice
- ankle edema
- liver ‘flap’ (asterixis) (coarse hand tremor)
- bleeding tendency
What are some conditions in which ALP would be elevated?
-cholestatic and obstructive hepatobiliary disease
HCC
infiltrative disorders
bone disease
What are some conditions in which AST and ALT would be elevated?
viral hepatitis (ALT > AST)
alcoholic hepatitis (AST > ALT)
What are some conditions in which amylase would be elevated?
acute pancreatitis, mumps
What are some conditions in which ceruloplasmin would be suppressed?
Wilson disease
What are some conditions in which y-glutamyl transpeptidase (GGT) would be elevated?
elevated in liver and biliary diseases but not in bone disease like ALP
associated with alcohol use
Elevated lipase is most specific for what?
acute pancreatitis
What is Reye Syndrome?
A rare, often fatal childhood heaptic encephalopathy caused by aspirin use in children (typically for home tx of viral infections such as VZV and influenza B
What are some findings with Reye Syndrome?
mitochondrial abnormalities
fatty liver and hepatomegaly
hypoglycemia
vomiting
How does aspirin cause Reye syndrome?
aspirin metabolites decrease B-oxidation by reversible inhibition of mitochondrial enzymes (avoid aspirin in children except in Kawasaki disease)
What are some alcoholic liver diseases?
- hepatic steatosis
- alcoholic hepatitis
- alcoholic cirrhosis
this is a progression
Describe the histology of hepatic steatosis
Macrovesicular fatty change that may be reversible with alcohol cessation
Describe the histology of alcoholic hepatitis
this is marked by:
- swollen and necotirc hepatocytes with neutrophilic infiltration
- Mallory bodies (intracellular eosinophilic inclusions of damaged keratin filaments- below)
T or F. Alcoholic hepatitis requires sustained, long-term consumption
T.
What is the AST:ALT ratio in alcoholic hepatitis?
1.5+
Describe alcoholic cirrhosis
This is the final and irreversible form of alcoholic liver disease marked by jaundice and hypoalbuminemia
How does the liver grossly appear with alcoholic cirrhosis?
micronodular, and irregularly shrunken with ‘hobnail’ appearance
In alcoholic cirrhosis, sclerosis is most prominantly seen in which zone?
around the central vein (zone III)
Describe non-alcoholic fatty liver disease
This is a metabolic syndrome of insulin resistance marked by fatty infiltration of hepatocytes and cellular ‘ballooning’ and eventual necrosis independent of alcohol use
May cause cirrhosis and HCC
Which is more elevated in non-alcoholic fatty liver disease, ALT or AST?
ALT over AST
How does hepatic enchapelopathy arise?
cirrhosis causes portosystemic shunts, leading to decreased NH3 metabolism which directly causes the neuropsychiatric dysfunction
How does hepatic encephalopathy present?
can range from disorientation/asterixis (mild) to difficult arousal/coma (severe)
What are some triggers of hepatic enchepalopathy?
- increased NH3 production and absorption (due to dietary protein, GI bleed, constipation, or infection)
- decreased NH3 removal (due to renal failure, diuretics, bypassed hepatic blood flow post TIPS)
What is the Tx of hepatic encephalopathy?
lactulose (increases NH4+ generation) and rifaximin
What is the most common primary MALIGNANT tumor of the liver in adults?
Hepatocellular carcinoma/hepatoma
What are some associations with hepatocellular carcinoma?
- HBV (+/- cirrhosis)
- all other causes of cirrhosis (including HCV, alcoholic and non-alcoholic fatty liver disease, hemochromatosis, a1-antitrypsin deificiency, and Wilson Disease)
- carcinogens such as aflatoxin from Aspergillus
Gross picture of hepatoceullar carcinoma
CT of hepatocellular carcinoma
How might a HCC present?
- jaundice
- tender hepatomegaly
- ascites
- polycythemia
- anorexia
How do HCC spread?
via heme
How are HCC diagnosed?
increased a-fetoprotein
ultrasound or contrast CT/MRI
biopsy
Histology of HCC
What are some other common liver tumors?
- cavernous hemangionas
- heptaic adenoma
- angiosarcoma
- METs
Describe cavernous hemangiomas
common, BENIGN liver tumors typically occurring at ages 30-50
T or F. Suspected cavernous hemangiomas should be biopsied
F. Due to risk of hemorrhage
Describe hepatic adenomas
Rare, benign liver tumors often related to oral contraceptive or anabolic steroid use
These may regress spontaneously or rupture causing abdominal pain and shock
Describe liver angiosarcomas
These are malignant tumors of endothelial origin associated with exposure to aresnic and vinyl chloride
What is the most common cancer of the liver?
METs
What places like to MET to the liver?
GI, breast, and lung
What is Budd-Chiari Syndrome?
Thrombosis or compression of hepatic veins with centrilobular congestion and necrosis causing congestive liver disease (leading to hepatomegaly, varices, abdominal pain, and eventual liver failure)
May cause nutmeg liver
T or F. Budd-Chiari Syndrome is marked by the absence of JVD
T.
What are some associations of Budd-Chiari Syndrome?
- hypercoagulable states
- poylcythemia vera
- postpartum state
- HCC
How does a1-antitrypsin deficiency affect the liver?
Misfolded gene products cause accumulation in the hepatocellular ER causing cirrhosis with PAS + globules (below) in the liver
NOTE: it causes panacinar emphysema in the lungs due to uninhibited elastase activity
What causes jaundice?
billrubin deposition at high (2.5+ mg/dL) levels in blood secondary to increased production of defective metabolism
What are some causes of unconjugated (indirect) hyperbilirubinemia?
- hemolytic states
- physiologic in newborns
- Crigler-Najjar syndrome
- Gilbert syndrome
What are some causes of conjugated (direct) hyperbilirubinemia?
- biliary tract obstruction (gallstones, cholangiocarcinoma, pancreatic or liver cancer, liver fluke)
- biliary tract disease (primary sclerosing cholangitis or primary biliary cirrhosis)
- excretion defects (Dubin-Johnson syndrome, Rotor syndrome)
What are some causes of mixed hyperbilirubinemia?
hepatitis and cirrhosis
What causes physiologic neonatal jaundice?
At birth, immature UDP-glucuronosyltrasnferase leads to unconjugated hyperbilirubinemia causing jaundice and/or kernicterus
What is kernicterus?
bilirubin deposition in the brain, especially the basal ganglia
What is the tx for neonatal jaundice?
phototherapy (converts unconjugated bilirubin to water-soluble forms)
What is Gilbert Syndrome?
Mildly decreased UDP-glucuronosyltransferase conjugation and impaired bilirubin uptake leading to an asymptomatic or mild jaundice state, and increased unconjugated bilirubin without overt hemolysis
Bilirubin increases with fasting and stress
What is Type I Crigler-Najjar Syndrome?
Absent UDP-glucuronosyltransferase that presents as jaundice, kernicterus, and high levels of unconjugated bilirubin early in life (pts. die within a few yrs)
NOTE: Type II is less severe
How is type I Crigler-Najjar Syndrome tx?
plasmapheresis and phototherapy
How is Type II Crigler-Najjar Syndrome tx?
responds to phenobarbital, which increases liver enzyme synthesis
Describe Dubin-Johnson Syndrome
Benign syndrome of conjugated hyperbilirubinemia due to defective liver excretion (MRP-2 is absent) causing a grossly black liver (note that Rotor syndrome is similar but milder and does not cause black liver)
What enzyme converts unconjugated bilirubin to conjugated (water soluble) bilirubin?
UDP- glucuronosyltransferase (aka UGT 1A1)
What are some sources of neonatal jaundice?
Infant UGT 1A1 is underdeveloped AND breast milk contains B-glucuronidase which can deconjugate bilirbuin
Kernicterus is a clinical set of symptoms caused by deposition of bilirubin in the brain, particularly the _______
basal ganglia
How is bilirubin made?
bilirubin is a breakdown product of hemoglobin and is made by:
- heme oxygenase releasing the central Fe2+ to create bilverdin, and
- bilverdin reductase using NADPH to create bilirubin
What happens to bilirubin once its made?
it is bound to albumin an transferred via portal circulation to the liver for uptake
What is Wilson disease?
A hepatic/neuro disease caused by inadequate excretion/circulation of copper in the copper
What causes Wilson disease?
lack of ATP7B gene impairs the ability of copper to be loaded to ceruloplasmin
What labs suggest Wilson disease?
- elevated free copper
- low levels of ceruloplasmin
- high urine copper
Why are ceruloplasmin levels low in Wilson Disease?
ceruloplasmin is relased from the liver without copper and thus is rapidly degraded
What are the symptoms of Wilson Disease?
- Cirrhosis
- Hemolytic Anemia
- Basal ganglia degeneration
- Asterixis
- Dyskinesia
Copper is Hella BAD
What is the MOI of Wilson Disease? Chromosome?
AR; 13
What is the tx of Wilson Disease?
All will require liver transplant and in the meantime give:
-penicillamine or trientine and zinc
What is this?
Kayser-Fleischer ring in Wilson Disease
What is hemochromatosis?
deposit of excess iron in the body (4 types)
What is the most common (85-90%) cause of hemochromatosis?
C282Y mutation of hepcidin
What are the symptoms of Hemochromatosis?
- micronodular cirrhosis
- DM
- skin pigmentation
- testicular atrophy
Iron is best seen with a _______-____ stain
Prussian Blue
What is the main tx of hemochromatosis?
phlebotomy
How does biliary tract disease typically present?
-pruritis, jaundice, dark urine, light-colored stool, and HSM
What are the main types of gallstones?
- cholesterol stones
- pigment stones
What are the main risk factors for gallstones?
4F’s:
Female, Fat, Fertile, Forty
What is this?
Porcelain gallbladder
What is a Porcelain gallbladder?
a calcified gallbladder due to chronic cholecystitis usually found incidentally on imaging
Pancreatic adenocarcinoma (terrible prognosis: 1 yr) is associated with what serum marker?
CA 19-9
