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Flashcards in More Liver Pathology Deck (79):
1

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

2

What are intrinsic drug reactions? characteristics?

-predictable
-dose-dependent
-short latency
-specific lesions

3

What are idiosyncratic drug reactions? characteristics?

-unpredictable
-dose dependent
-variable latency
-variable lesions
-hypersensitivity

4

What kind of drug induced liver disease morphology with tetracycline?

microsteatosis

5

What kind of drug induced liver disease morphology with methotrexate?

macrosteatosis

6

What kind of drug induced liver disease morphology with acetaminophen?

necrosis

7

What kind of drug induced liver disease morphology with isoniazid and halothane?

-hepatitis -
-bridging necrosis (with halothane)

8

What kind of drug induced liver disease morphology with amiodarone?

fibrosis

9

What kind of drug induced liver disease morphology with steroids and erythromycin?

cholestasis

10

Drink some alcohol - immediate change that happens to liver?

-steatosis - fatty liver change that is REVERSIBLE
-perivenular fibrosis

11

Severe Drinking of alcohol - change that happens to liver?

-hepatitis
-liver cell necrosis
-inflammation
-mallory bodies
-fatty change - starts out microvesicular and fat coalesces into macrovesicles

12

Repeated/heavy drinkers - what change that happens to liver?

Cirrhosis
-fibrosis
-hyperplastic nodules - micronodular

13

Macro-view of the alcoholic fatty liver?

ITS YELLOW - FAT IS YELLOW

14

what kind of nodular cirrhosis occurs with alcoholic cirrhosis?

What kind of fatty liver change occurs with alcoholic cirrhosis?

Micronodular - due to bridging fibrosis

macrovesicular

15

What are mallory bodies?

glob of protein - hylaine! that aggregates in certain diseases
ex) alcoholic hep and wilsons disease

16

megamitochondria seen in which liver disease?

alcoholic hepatitis

17

Chicken wire fibrosis in space of dis occurs in which liver disease?

alcoholic hepatitis long-term abuse

18

Alcoholic steatohepatitis Clinical/LABS:

-fever
-leukocytosis
-jaundice
-INC AST and ALT (AST>>ALT)
-INC AP (inc with cholestasis)

19

Alcoholic liver AST to ALT relationship

AST will be almost twice as high as ALT

(AST - A."S.T." for scotch and tonic)

20

Non-Alcoholic steatohepatitis- what risks?

-insulin reisistance/metabolic syndrome (obesity, diabetes, hyperlipidemia)
-drug hepatotoxicity (tamoxifen (macrovesicular), nifedipine)
-pregnancy (microvesiculuar)

21

Liver infarction:
-common?

rare bc of dual blood supply!

22

Ischemic hepatitis, shock liver or hypoxic hepatitis - THINK WHAT PROBLEMS?

**LEFT SIDED/VENTRICULAR HEART FAILURE

heart surgery

shock - centrilobular coagulative necrosis (around central veins - ZONE 3 drup); elevated transaminases; jaundice

23

Extrahepatic portal vein thrombosis due to:

1) abdominal infection & inflamm
-appendicitis
-diverticulitis
-pancreatitis
2) hypercoagulability
3) surgery

extra ==> send emboli to the liver

24

Intrahepatic portal vein thrombosis due to?

Issues inside the liver
1) cirrhosis
2) malignancy
3) stasis
4) pregnancy
5) idiopathic PH

25

Clinical presentation of portal vein hypertension?

-abdominal pain
portal hypertension (ascites, varices, splenommegaly)
-Bowel infarct

26

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

27

Budd Ciari syndrome involves what?

hepatic vein obstruction - the LARGER VEINS

28

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
-cardiac sclerosis
2) Budd-Chiari syndrome

29

First sight of hepatic vein obstruction?

DILATED SINUSOIDS

30

Nutmeg liver seen with which condition- what is it?

-hepatic vein obstruction

-blood backs up and makes nutmeg looking liver

31

Damage to what zone in the liver?

Zone 3 but this time the cause is NOT hypoxic but rather HIGH BACK-PRESSURE RELATED

32

Definition of Budd CHiari syndrome:

clotting or obstruction of the hepatic vein and or IVC!

33

Acute Bud Chiari Syndrome clinical signs:

-abdominal pain
-hepatomegaly
-ascites
-jaundice
-liver failure

34

Chronic Bud Chiari syndrome clinical signs:

portal hypertension
-cirrhosis
-obliterative hepatocavopathy (rare)

35

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

36

Veno-occlusive disease:
how does it happen?
what happens?

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

37

Hereditary hemochromatosis
what is it?
what gene involved??

-abnormal continuous iron absorption through the gut
-deposition of iron throughout the body

-MUTATION IS HFE GENE**

38

What are the mutant alleles in hereditary hemochromatosis

C282Y and H63D

39

Early hereditary hemochromatosis
-where are the deposits?

-Fe in periportal hepatocytes

40

Advanced hereditary hemochromatosis
-where are the deposits?

Fe in Kupffer cells, bile duct epithelium, and fibrous septa

41

What does Hereditary hemochromatosis progress to?

-pigmented micronodular cirrhosis
-HCC

42

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***

43

hereditary hemochromatosis
-disease outcomes:

-diabetes
-cardiomyopathy
-hypogondism
-skin pigementation
-pseudo-gout

44

hereditary hemochromatosis on microscopy-

A lot of brown pigment deposition in stuff

or iron looks blue with prussian blue stain

45

Secondary iron overload -
mnemonic to remember outcomes

THALAS
-T-Transfusions
-H-hemochromatosis, neonatal
-A-alimentary (bantu siderosis) - from diet
-L-Liver disease
-A-Anemia, congenital (thalessemia)
-S-Sideroblastic anemia

Most commonly due to anemia

46

Secondary hemochromatosis vs hereditary?

-not as much in hepatocytes but a lot more in kupffer cells

47

Coppuer function -

essential for pigment formation, neurotransmitter production, peptide formation, connective tissue biosynthesis and antioxidant defense --THINK WILSONS DISEASE

48

Wilson Disease
-What is the problem
-where is the accumulation?
-who affected?

-TOO MUCH COPPER - hereditary (autosomal recessive) - body retains copper

-BRAIN-LIVER- EYE**
Some in basal ganglia

younger disease 6- 20 yo but sometimes in 40yo+

49

What is the protein that copper binds to?

ceruloplasmin

50

What are the labs in WIlsons disease?

-DEC serum ceruloplasmin250microg/g tissue
-inc urinary copper up to 100microg/24 rs
-Kaiser fleischer rings

51

Main Organs damaged in wilsons disease?

BRAIN
LIVER
EYE

52

What is mutation in Wilsons disease?

mutation in ATP7B copper transporter

53

Progression of wilsons disease?

steatosis --> hepatitis --> cirrhosis
-degeneration of basal ganglia
-aminoaciduria
-hemolytic anemia
-cardiomyopathy

54

Adults with wilsons disease usually present with?

neurologic and psychiatric issues --> deposits in the brain

55

What are Kaiser-Fleisher rings?
What disease

-Wilsons disease
-eyes have brown ring on outside rim of iris

56

Alpha1 antitrypsin deficiency
-hereditary inh?
-gene involved?
-what happens?

-auto recessive
-normal gene is PiMM - PiZZ genotype (PiZ protein made)
-misfolded protein --> accumulation of PiZ in hepatocytes-->reduced intracellular protein degredation and increased autophagocytosis

57

Diagnosis/LABS for alpha1 antitrypsin def:

-low serum alpha1-antitrypsin
-abnormal electrophoresis of the protein
-liver biopsy (PAS+ = pink/magenta color)

58

-tumor like conditions:
-feature of each?

-nodular regenerative hyperplasia = NO FIBROUS TISSUES MAKING MULTIPLE NODULES
-focal nodular hyperplasia = single lesion

59

focal nodular hyperplasia
-what is it?
-sex prevalence?

-benign liver tumor
-women - usually associated with estrogen

60

Features of focal nodular hyperplasia:

-Solitary mass with central scarring
-fibrous septa

61

nodular regenerative hyperplasia
-definition/characteristics:
*-causes what main issue?

-nodules without fibrous septa
**-cause of non-cirrhotic portal hypertension

62

What is the TIPS procedure?

bypass of liver from portal vein to hepatic vein - for nodular regenerative hyperplasia

63

hemangioma
-prevalent sex?
-symptoms?
-risk?

-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!

64

most common benign hepatic tumor?

hemangioma

65

liver cell adenoma
-benign/malig?
-prevalent sex?
-predisposing factors?
-risk?

BENIGN
-women
-oral contraceptives; glycogen storage disease
-may rupture in pregnancy; may harbor HCC (if more than 10 lesions)

66

HCC
-predominant sex?
-common where?

-males, african amerincas
-Asia and africa
-associated with HepB transmission at birth

67

Most common primary malignant liver tumor?

HCC

68

Main risk factor for HCC/

cirrhosis
alcoholism
HBV HCV
hereditary hemochromatosis
-alpha1 antitrypsin
-alflatoxin from aspergillus
-tyrosinemia

69

How does HCV cause HCC?

genomic instability - inflammation drive toward cancer
-no particular proteins involved

70

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.

71

HCC diagnosis/LABS

-ultrasound
-angiography
-CT
-MRI
-INC AFP>1000*****

72

What is the only "good" variant of HCC? What age patients get this?

fibrolamellar HCC - better prognisosis - broad bands of fibrosis

young patients

73

Cholangiocarcinoma - what is proliferating tissue?

GLANDS

74

Cholangiocarcinoma
-what is it?
-risk factors:

-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**

75

hepatoblastoma
-age?
-associated conditions?
-markers?

-<3 yo
-congenital
-AFP is very high!

76

most common primary malignant hepatic tumor in children?

heptoblastoma

77

Angiosarcoma
-what population? age?
-exposure to what inc risk?

-men 50s-60s
-exposure to thorotrast, ***vinyl chloride***, arsenic, androgenic steroids
POOR PROGNOSIS

78

*most common tumor of the liver?

cancer that has spread to the liver

79

What are the common primary sites for metastatic tumors in liver?

-GI, breast, lung, pancreas, melanoma