Flashcards in More Liver Pathology Deck (79):
Whcih region of liver structure affected first with hepatic injury?
ZONE 3 - zone around the central vein - already low in O2 and P450s need O2!! --> drug induced injury
What are intrinsic drug reactions? characteristics?
What are idiosyncratic drug reactions? characteristics?
What kind of drug induced liver disease morphology with tetracycline?
What kind of drug induced liver disease morphology with methotrexate?
What kind of drug induced liver disease morphology with acetaminophen?
What kind of drug induced liver disease morphology with isoniazid and halothane?
-bridging necrosis (with halothane)
What kind of drug induced liver disease morphology with amiodarone?
What kind of drug induced liver disease morphology with steroids and erythromycin?
Drink some alcohol - immediate change that happens to liver?
-steatosis - fatty liver change that is REVERSIBLE
Severe Drinking of alcohol - change that happens to liver?
-liver cell necrosis
-fatty change - starts out microvesicular and fat coalesces into macrovesicles
Repeated/heavy drinkers - what change that happens to liver?
-hyperplastic nodules - micronodular
Macro-view of the alcoholic fatty liver?
ITS YELLOW - FAT IS YELLOW
what kind of nodular cirrhosis occurs with alcoholic cirrhosis?
What kind of fatty liver change occurs with alcoholic cirrhosis?
Micronodular - due to bridging fibrosis
What are mallory bodies?
glob of protein - hylaine! that aggregates in certain diseases
ex) alcoholic hep and wilsons disease
megamitochondria seen in which liver disease?
Chicken wire fibrosis in space of dis occurs in which liver disease?
alcoholic hepatitis long-term abuse
Alcoholic steatohepatitis Clinical/LABS:
-INC AST and ALT (AST>>ALT)
-INC AP (inc with cholestasis)
Alcoholic liver AST to ALT relationship
AST will be almost twice as high as ALT
(AST - A."S.T." for scotch and tonic)
Non-Alcoholic steatohepatitis- what risks?
-insulin reisistance/metabolic syndrome (obesity, diabetes, hyperlipidemia)
-drug hepatotoxicity (tamoxifen (macrovesicular), nifedipine)
rare bc of dual blood supply!
Ischemic hepatitis, shock liver or hypoxic hepatitis - THINK WHAT PROBLEMS?
**LEFT SIDED/VENTRICULAR HEART FAILURE
shock - centrilobular coagulative necrosis (around central veins - ZONE 3 drup); elevated transaminases; jaundice
Extrahepatic portal vein thrombosis due to:
1) abdominal infection & inflamm
extra ==> send emboli to the liver
Intrahepatic portal vein thrombosis due to?
Issues inside the liver
5) idiopathic PH
Clinical presentation of portal vein hypertension?
portal hypertension (ascites, varices, splenommegaly)
Infarct of Zahn happens with which liver condition?
-not a true infarct bc the cells dont actually die - just atrophic hepatocytes
-INTRAHEPATIC portal vein thrombosis
Budd Ciari syndrome involves what?
hepatic vein obstruction - the LARGER VEINS
Hepatic vein obstruction conditions:
1) Cardiac MORE COMMON - BACK PRESSURE FROM R SIDED FAILURE; constrictive pericaditis; congenital heart issues
-venous passive congestion
-centrilobular hemorrhagic necrosis
2) Budd-Chiari syndrome
First sight of hepatic vein obstruction?
Nutmeg liver seen with which condition- what is it?
-hepatic vein obstruction
-blood backs up and makes nutmeg looking liver
Damage to what zone in the liver?
Zone 3 but this time the cause is NOT hypoxic but rather HIGH BACK-PRESSURE RELATED
Definition of Budd CHiari syndrome:
clotting or obstruction of the hepatic vein and or IVC!
Acute Bud Chiari Syndrome clinical signs:
Chronic Bud Chiari syndrome clinical signs:
-obliterative hepatocavopathy (rare)
Obliterative hepatocavopathy - what is it: causes?
IVC obstruction due to membranous webs that causes edema of the abdominal wall, tortuous abdominal venous pattern, and edema of legs
how does it happen?
VOD - complication following bone marrow transplant or ingestion of certain plant alkaloids
-nonspecific vasculitis arrising in response to an inflammatory challenge = sinusoid obstruction- obstruction of central veins
what is it?
what gene involved??
-abnormal continuous iron absorption through the gut
-deposition of iron throughout the body
-MUTATION IS HFE GENE**
What are the mutant alleles in hereditary hemochromatosis
C282Y and H63D
Early hereditary hemochromatosis
-where are the deposits?
-Fe in periportal hepatocytes
Advanced hereditary hemochromatosis
-where are the deposits?
Fe in Kupffer cells, bile duct epithelium, and fibrous septa
What does Hereditary hemochromatosis progress to?
-pigmented micronodular cirrhosis
Labs/Diagnosis of Hereditary hemochromatosis?
-INC serum Fe > 300mg/dL
-inc Transferrin saturationg>2X
-INC serum ferritin>2X
-INC hepatic Fe index>2
**--> if transferrin and ferritin are both high then genetic testing for C282Y or H63D***
hereditary hemochromatosis on microscopy-
A lot of brown pigment deposition in stuff
or iron looks blue with prussian blue stain
Secondary iron overload -
mnemonic to remember outcomes
-A-alimentary (bantu siderosis) - from diet
-A-Anemia, congenital (thalessemia)
Most commonly due to anemia
Secondary hemochromatosis vs hereditary?
-not as much in hepatocytes but a lot more in kupffer cells
Coppuer function -
essential for pigment formation, neurotransmitter production, peptide formation, connective tissue biosynthesis and antioxidant defense --THINK WILSONS DISEASE
-What is the problem
-where is the accumulation?
-TOO MUCH COPPER - hereditary (autosomal recessive) - body retains copper
Some in basal ganglia
younger disease 6- 20 yo but sometimes in 40yo+
What is the protein that copper binds to?
What are the labs in WIlsons disease?
-DEC serum ceruloplasmin250microg/g tissue
-inc urinary copper up to 100microg/24 rs
-Kaiser fleischer rings
Main Organs damaged in wilsons disease?
What is mutation in Wilsons disease?
mutation in ATP7B copper transporter
Progression of wilsons disease?
steatosis --> hepatitis --> cirrhosis
-degeneration of basal ganglia
Adults with wilsons disease usually present with?
neurologic and psychiatric issues --> deposits in the brain
What are Kaiser-Fleisher rings?
-eyes have brown ring on outside rim of iris
Alpha1 antitrypsin deficiency
-normal gene is PiMM - PiZZ genotype (PiZ protein made)
-misfolded protein --> accumulation of PiZ in hepatocytes-->reduced intracellular protein degredation and increased autophagocytosis
Diagnosis/LABS for alpha1 antitrypsin def:
-low serum alpha1-antitrypsin
-abnormal electrophoresis of the protein
-liver biopsy (PAS+ = pink/magenta color)
-tumor like conditions:
-feature of each?
-nodular regenerative hyperplasia = NO FIBROUS TISSUES MAKING MULTIPLE NODULES
-focal nodular hyperplasia = single lesion
focal nodular hyperplasia
-what is it?
-benign liver tumor
-women - usually associated with estrogen
Features of focal nodular hyperplasia:
-Solitary mass with central scarring
nodular regenerative hyperplasia
*-causes what main issue?
-nodules without fibrous septa
**-cause of non-cirrhotic portal hypertension
What is the TIPS procedure?
bypass of liver from portal vein to hepatic vein - for nodular regenerative hyperplasia
-most common benign hepatic tumor
-more common in women - associated with oral contraceptives
-asymptomatic or abd pain
-risk of rupture and hemorrhage -- no biopsy bc itll bleed!
most common benign hepatic tumor?
liver cell adenoma
-oral contraceptives; glycogen storage disease
-may rupture in pregnancy; may harbor HCC (if more than 10 lesions)
-males, african amerincas
-Asia and africa
-associated with HepB transmission at birth
Most common primary malignant liver tumor?
Main risk factor for HCC/
-alflatoxin from aspergillus
How does HCV cause HCC?
genomic instability - inflammation drive toward cancer
-no particular proteins involved
How does HBV cause HCC?
- has viral DNA integration damage AND LHBS mutant protein --> genomic instability
PROTEINS IN HBV contribute to HCC while HCV is only genomic.
What is the only "good" variant of HCC? What age patients get this?
fibrolamellar HCC - better prognisosis - broad bands of fibrosis
Cholangiocarcinoma - what is proliferating tissue?
-what is it?
-malignant primary tumor of the bile duct epithelium
-primary sclerosing cholangitis
-thorotrast (come contrast agent we dont use anymore)
-caroli disease (dilation of biliary system)
-liver flukes - clonorchis opistorchis**
-AFP is very high!
most common primary malignant hepatic tumor in children?
-what population? age?
-exposure to what inc risk?
-exposure to thorotrast, ***vinyl chloride***, arsenic, androgenic steroids
*most common tumor of the liver?
cancer that has spread to the liver