1
Q
What are the serum measurements of hepatocyte integrity
A
AST
ALT
Lactate dehydrogenase (LDH)
2
Q
What are the tests that look for biliary excretory fxn
A
Serum bilirubin
- Total: unconjugated and conjugated
- Direct: conjugated only
Urine bilirubin
Serum bile acids: plasma membrane enzymes from damage to bili canaliculus
Serum alkaline phosphatase
Serum y-glutamyl transpeptidase (GGT)
3
Q
What are the tests that look for damage to the bile canaliculus
A
Serum alkaline phosphatase
Serum gamma-glutamyl transpeptidase (GGT)
4
Q
What are the tests that look for hepatocyte synthetic function
A
Serum albumin
Coagulation factors: PT, PTT, Fibrinogen, prothrombin, factors V, VII, IX, X
Hepatocyte metabolism: serum ammonia, aminopyrine breath test
5
Q
Cholestasis
A
Accumulation of bilirubin in liver
6
Q
Cytokine released by kupffer cell
A
TGF-beta
7
Q
Liver hilum is called
A
Porta hepatis
8
Q
Characteristic sign of acute hepatic failure (2)
A
Asterixis (Encephalopathy)
Nonrhythmic, rapid extension-flexion of the head and extremities
Coagulopathy: impaired clotting due to lack of production of Vit K dep factors
- Easy bruising early sign
9
Q
Acute hepatic failure is associiated with (3)
A
1) Disseminated intravascualr coagulation
- liver removes activated coagulation factors
2) Portal HTN (leads to ascites and encephalopathy)
3) Hepatorenal syndrome
- kidneys normal
- hyponuria, elevated BUN and creatine
10
Q
Chronic liver failure is associated with
A
Hepatitis B and C
NAFLD
Alcoholic fatty liver disease
11
Q
Signs of chronic liver failure (4)
A
- Palmar erythema
- Spider angiomata
- Hypogonadism
- Gyencomastia
12
Q
Ultimate cause of death from liver failure
A
- Encephalopathy
- Bleeding from esophageal varices
- Bacterial infections
13
Q
Cirrhosis leads to risk of developing
A
Hepatocellualr carcinoma
14
Q
Hepatitis without chronic or carrier state
A
Hepatitis A virus
15
Q
Hepatitis that is ds-DNA
A
Hepatitis B virus
16
Q
Chronic liver failure w/ hepatitis seen inperson who is 20 or 30 years old
A
Hepatitis B virus
17
Q
Chronic liver failure hepatitis
A
Hepatitis B virus
Hepatitis C virus
18
Q
Hepatitis that is precursor for hepatocellular carcinoma
A
Hepatitis B virus
19
Q
Liver biopsy shows finely granular “ground glass” hepatocytes
A
Chronic Hepatitis B virus
20
Q
Associated with metabolic syndrome
A
HCV
21
Q
HAV
- type
- family
- transmission
- chronic
- diagnosis
- Sudden hepatitis
A
ssRNA
Hepatovirus (picornavirus)
Fecal-oral (contaminated H2O)
Chronic= never
Diagnosis= serum IgM Ab
Acute hepatitis: Yes
22
Q
HBV
- type
- family
- transmission
- chronic
- diagnosis
- Sudden hepatitis
A
dsDNA
hepaDNAvirus
parenteral, sexual contact, perinatal
Chronic: 5-10%
Diagnosis: HBsAg, antiHBcAg; PCR for DNA
Acute hepatitis: Yes
23
Q
HCV
- type
- family
- transmission
- chronic
- diagnosis
- Sudden hepatitis
A
ssRNA
flaviviridae
Parenteral, intranasal cocaine
Chronic: >80%
PCR for DNA, Elisa for Ab
Acute hepatitis: NO
24
Q
Hallmark for increased portal chronic inflammation
A
Portal tract expansion
25
Fatty changes indicate what hepatitis
Chronic HCV
26
Interface hepatitis (piecemeal necrosis)
associated iwth lymphocytic infiltrate into adjacent parenchyma (beyond limiting plate) with destruction of individual hepatocytes along edges
Feature of chronic viral hepatitis
(as well as autoimmune hepatitis & steatophepatitis)
27
Hallmark of progressive chronic liver damage
Scarring
28
Cholangiocarcinoma
Liver flukes
Fasciola hepatica
Thorotrast
29
Acetaminophen involves what mechanism
CYP450
30
Oral contraceptives and anabolic steroids -->
hepatocellualr adenoma
31
Vinyl chloride -->
Angiosarcoma
32
DRB1 alleles
Autoimmune hepatitis
33
Type 1 autoimmune hepatitis
Middle aged older individuals
ANA (anti-nuclear)
ASMA (anti smoot muscle)
Prognosis better
34
Type 2 autoimmune hepatitis
Children, teenagers
| Anti-LKM1 (anti-liver kidney microsome-1) antibodies against CYP2D6
35
Clinical features
1) Steatosis
2) Steatohepatitis
3) Steatofibrosis/ cirrhosis
1) Hepatomegaly
Mildly elevated bilirubin
Mildly elevated alk phos
2) Tender hepatomegaly
Hyperbilirubinemia
AST:ALT 2:1 levels (<300-400)
Elevated Alk phos
3) Hypoproteinemia
Coagulation abnormalities
36
Intracellualr eosinophilic aggregates of intermediate filaments (keratin) in ballooning hepatocytes
Mallory-Denk bodies
37
Mallory Denk seen in
Alcohol hepatitis
NAFLD
Wilson
Chronic biliary tract disease
38
Scarring in a chicken wire fence pattern
Alcohol steatofibrosis
39
Laennec cirrhosis
aka micronodular
Chicken wire
alcoholic steatofibrosis
40
Mutation for alcohol intolerance
```
Homozygous ALDH2 (asians)
Flusing nausea lethargy
```
41
Most common in
- alcoholic liver disease
-NAFLD
-
1) Africans
| 2) Hispanics
42
NAFLD has an increased risk of
HCC
43
Pathogenesis of NAFLD
1) Insulin resistance leads to hepatic steatosis (fat deposition in liver)
2) Oxidative injury --> liver cell necrosis
Non-alcoholic steatohepatitis (NASH)
--> NASH cirrosis --> Decompensatin or HCC
44
Metabolic syndrome:
dysfunctional adipose tissue (endocrine organ)
Decreased production of adiponectin
Increased TNF-alpha, IL-6
=hepatocyte apoptosis
45
What also gets activated in NAFLD
Stellate cells via SHH
Levels of SHH correlated to stage of fibrosis of NAFLD
46
NAFLD vs Alcohol liver disease
Mononuclear cells more prominent
Portal fibrosis more prominent
Mallory Denk less common
47
Death of NAFLD most common by
Cardiovascular death
48
Alcohol liver disease death by (5)
```
Hepatic coma
Massive GI hemorrhage
Intercurrent infection
Hepatorenal syndrome
Hepatocelluarl carcinoma
```
49
"A 45-year-old man has had a fever and a productive cough for the past 3 days. On physical examination there is dullness to percussion over the right upper lung. His temperature is 37.9°C. A chest radiograph reveals right upper lobe consolidation. Laboratory findings include serum total protein of 6.0 g/dL, albumin 2.7 g/dL, AST 185 U/L, ALT 98 U/L, total bilirubin 1.0 mg/dL, alkaline phosphatase 31 U/L, and prothrombin time 20 sec. An abdominal CT scan shows hepatomegaly with decreased hepatic attenuation. Which of the following conditions is the most likely underlying cause of death?"
Diabetes Mellitus
NAFLD is associated w/ obesity and diabetes mellitus
50
Metabolic syndrome criteria
One of: DM, impaired glucose tolerance, impaired fasting glucose, insulin resistance
Two of:
- BP >140/90
- TGs ?1.695 and HDL
51
Only metabolic liver disease not AR
NAFLD
Hemochromotosis: AR
Wilson disease: AR
Alpha1-AT: AR
52
Excessive iron absoprtion
Hemochromatosis
53
HFE mutation
Hemochromatosis
C282Y
54
Juvenile hemochromastosis
HJV or HAMP
| More severe
55
Prussian blue stain
Small shrunken liver w/ micronodules
Dark brown black liver
Hemochromastosis
56
```
Pancreas fill w/ brown pigment
Bronze skin
DM
Hypogonadism
Cardiac dysfunction
```
Hemocrhomatosis
57
Hemochromatosis risk of
Hepatocellular carcinoma 200x
58
Prussian blue stains for
iron
59
Mutation ATP7B
Wilson disease
60
Impaired cooper excretion in bile
Wilson disease
61
Parkinsonism movement
| Elevated direct bilirubin
Elevated bilirubin = hemolytic anemia due to copper toxicity to RBC membranes
62
PiZZ
Alpha 1- AT def
63
A1-AT leads to
- age
- mutation causes accumulation of
infants and children
Pulmonary emphysema
Hepatic disease
Accumulation of protein in liver
64
Magenta granules inside hepatocytes
Alpha 1- AT
65
Hereditary hyperbilirubinemias (5)
(Extrahepatic)
```
Crigler Najjar Type 1
Crigler Najjar type 2
Gilbert syndrome
Dubin-johnson syndrome
Rotor syndrome
```
66
Autopsy baby
Unconjugated hyperbilirubinemia
- inheritence
- missing
Crigler-Najjar type I
AR
No UGT1A1 activity
67
```
Clinic baby
Hyperbilirubinemia
Kernicterus
-inheritence
-missing
```
Crigler Najjar type II
AD
Decreased UGT1A1
68
Stressed student with yellow eyes
| hyperbilirubin- indirect
Gilbert
| Decreased UGT1A1
69
Autopsy
| black liver
Dubin johnson syndrome
AR
MDR protein 2 (MRP2)
conjugated hyperbilirubinemia
70
18 y.o
| hyperbilirubin- direct
Rotor syndrome
| AR
71
Infant to pediatrician, yellow skin. Tired weak, floppy arms. Parents first cousins
Crigler Najjar type II
72
Elevated GTT and alk phosphatase
Cholestasis
(impaired bile flow)
Accumulation of bile pigment in hepatic parenchyma
73
Fever, RUQ pain, jaundice
```
Charcot's triad
Ascending cholangitis (gallstones)
```
74
Primary hepatolithiasis
Disease of intrahepatic gallstone formations
Leads to repeat bouts of ascending cholangitis, progressive inflammatory destruction of hepatic parenchyma, and predisposes to biliary neoplasia
75
Hepatolithiasis
gallstones in bilary ducts of liver
76
Cholestasis
flow of bile stops
77
Panlobular giant-cell transformation of hepatocytes
Neonatal hepatitis
78
Most common form of biliary atresia
Perinatal form
Rotavirus, CMV, autoimmune
79
Jaundice longer than 2 weeks
| Acohlic stools
Biliary atresia
80
Inflammatory destruction of intrahepatic ducts
primary biliary cirrhosis (PBC)
81
Inflammatory destruction of intrahepatic adn extrahepatic bile ducts
Priamry sclerosing cholangitis (PSC)
82
FLorid duct lesions
Primary biliary cirrhosis (PBC)
83
Antimitochondrial Ab
Primary biliary cirrhosis (PBC)
84
Beading on X ray
Primary sclerosing cholangitis (PSC)
85
PANCA
atypical perinuclear anti-neutrophilic cytoplasmic antibodies
PSC
86
Onion skin fibrosis
PSC
87
PSC associated with
IBD
| Pancreatitis
88
PBC associated with
Sjogren syndrome
Scleoderma
Thyroid disease
89
AMA positive
| ANA positive
PBC
90
Choledochal cysts
congenital dilations of the common bile duct
Females before age 10
Jaundice
Recurring abdominal pain
Cysts may form segmental or cylindric dilations
91
Von Meyen complexes
indicative of fibropolycystic disease FPD
92
Caroli disease
biliary cysts that occur w/ congenital hepatic fibrosis
indicative of fibropolycystic disease FPD
93
Congenital hepatic fibrosis
portal tracts enlarged by irregular broad bands of collagenous tissue that form septa to divide liver into irregular islands
indicative of fibropolycystic disease FPD
94
Schistosomiasis
parasitic worm
95
Obstruction of two or more hepatic veins leads to hepatomegaly, pain ascites
Budd-Chiari syndrome
96
Liver is swollen red-purple
Budd-chiari syndrome
| Obstruction two or more hepatic veins
97
Obliteration of terminal hepatic venules by subendothelial swelling and collagen depostiion
-Causes
Sinusoidal obstruction syndrome
(Veno-occlusive disease)
- Jamaican bush tea drinkers
- 3 weeks after stem cell transplant
98
Hemolysis
Elevated liver enzymes
Low platelets
Pregnant
HELLP
| Preeclampsia
99
Maternal HTN
Proteinuria
Peripheral edema
Coagulation problems
Preeclampsia
Becomes eclampsia w/
- hyperreflexia convulsons occur
100
Third trimester
Elevated serum aminotransferases
Bleeding, nausea vomiting
Jaundice
Acute fatty liver disease
101
```
Pregnant 3rd trimester
Dark urine
Light acholic stools
Jaundice
Bile salt level increased greatly
```
-risk (3)
Intrahepatic cholestasis of pregnancy
- fetal distress
- stillborn
- prematurity
102
Autopsy
Plump hepatocytes are surrounded by rims of atrophic hepatocytes
Multiple nodules on liver
No fibrosis
Nodular regenerative hyperplasia (NRH)
103
Single well demarcated lesion with central scar on liver
Focal nodular hyperplasia FNH
104
Blood vessel tumor of liver
Cavernous hemangioimas
105
Red blue nodules under capsule
Cavernous hemangiomas
106
Tumor of liver associated with oral contraceptives
Hepatocellualr adenoma
| - beta-catenin
107
3 types hepatocellular adenomas
1) HNF1-alpha
-inactive
no risk
2) Beta-Catenin
- active
- high risk
- oral contraceptives
3) Inflammatory
- small risk
Assoc w/ NAFLD
108
Single large scirrhous tumor with fibrous bands coursing through it
<35
well differentiated cells rich in mitochondria in cords separated by parallel lamellae of dnse collagen bundles
Fibrolamellar carcinoma
109
Perihilar tumors located at junction of hepatic ducts
Klatskin tumors
| Cholangiocarcinoma (CCA)
110
Liver flukes
Opisthorchis
Clonorchis
Cholangiocarcioma CCA
111
Most common gallbladder anomaly
Phrygian cap
Fundus that folded inward
112
Cholelithiasis
Gallstones
113
Family history, female, fat, fourty, fertile, fair risk factors for
Cholelithasis gallstones
114
Pigment stones
Stones of unconjugated bilirubin
Bacterial contamination
Brown stones
115
Cholesterol stones
only in gallbladder
| pale yellow --> black (sterile bile duct)
116
Carcinoma of gallbladder
adenocarcinoma
women
risk factor gallstones
117
ERBB2 (HER2) oncoprotein overexpressed
Carcinoma of gallbladder
| Adenocarcinoma
