Liver Pathology and Hepatitis Flashcards
1
Q
What are the major areas of the liver (4)
A
right lobe
left lobe
caudate lobe
quadrate lobe
2
Q
What is the vascular entry into the liver
A
enters through the parenchyma via branches of the hepatic portal vein and hepatic artery
it will empty into the hepatic sinusoid
3
Q
What is the vascular mode of exit from the liver
A
drainage of the sinusoid through the central vein
4
Q
How is the liver divided based on the oxygen supply
A
it is divided into 3 parts
5
Q
zone 1 of liver oxygen supply
A
encircles the portal tracts where the oxygenated blood from the hepatic artery enters. closer to the portal triad
6
Q
zone 2 of liver oxygen supply
A
located in between the central vein and portal triad
7
Q
zone 3 of liver oxygen supply
A
located around the central veins where oxygenation is poor
8
Q
How can you classify diseases of the liver
A
acute
chronic
focal
diffused
mild
severe
reversible
irreversible
9
Q
Most cases of acute liver disease is caused by what
A
viral hepatitis
10
Q
Y/N: Do mild cases of liver disease need medical attention
A
no
11
Q
what is hepatitis
A
hepatitis is an inflammatory process causing liver death by necrosis or by triggering apoptosis
12
Q
What causes hepatitis
A
infection with one or several types of the virus
exposure to drugs or alcohol
13
Q
What drugs may cause hepatitis
A
isoniazid
acetaminophen
14
Q
what are the different types of hepatitis
A
HAV
HBV
HCV
HDV
HEV
15
Q
how long is acute hepatitis
A
< 6 months
16
Q
how long is chronic hepatitis
A
> 6 months
17
Q
HAV characteristics
A
Acute
No lipid bi-layer
mode of transmission = fecal-oral route
ssRNA
18
Q
HBV characteristics
A
Can be acute or chronic
has a lipid bi-layer
mode of transmission = sex, blood, perinatal tube
dsDNA
19
Q
HCV characteristics
A
Can be acute or chronic
has a lipid bi-layer
mode of transmission = blood transfusion
ssRNA
20
Q
HDV characteristics
A
Mainly chronic
mode of transmission = sex blood, perinatal
need co or super infection
ssRNA
(HBV is a precursor)
21
Q
HEV
A
Mainly acute but can progress to chronic
no lipid bilayer
mode of transmission = fecal-oral route
no envelope, ssRNA
(similar to A but no vaccine for it specifically)
22
Q
What is the role of perforins in the pathogenesis of hepatitis
A
forms pores on hepatocytes
23
Q
What is the role of granzymes in the pathogenesis of hepatitis
A
induce apoptosis
24
Q
how do granzymes induce apoptosis
A
cytotoxic t-cells activate:
caspases
mitochondrial pathway
25
What activates cytotoxic T-cells
MHC-1
26
cytotoxic t-cells induce damage via 2 ways
1. preforin & granzyme
2. increased accumulation of viral proteins
(RNA/DNA polymerase, antigen, capsia)
27
What is the mechanism of replication for HAV, HEV, HCV, and HDV (ssRNA)
(7)
1. Attachment
2. Entry
3. Uncoating
4. Translation
5. Replication
6. Maturation and assembly
7. Release
28
What is the mechanism of replication for HBV (dsDNA)
(9)
1. Attachment
2. Entry
3. Uncoating
4. NUCLEAR IMPORT
5. TRANSCRIPTION
6. Translation
7. REVERSE TRANSCRIPTION
8. Maturation and assembly
9. Release
29
What is the ATTACHMENT mechanism of replication for HAV, HEV, HCV, and HDV (ssRNA)
it binds to the receptor on the suface
30
What is the ENTRY mechanism of replication for HAV, HEV, HCV, and HDV (ssRNA)
by endocytosis
31
Where is the UNCOATING mechanism of replication for HAV, HEV, HCV, and HDV (ssRNA) taking place
in the ribosome and removes the capsid and lipid bilayer
32
What is the TRANSLATION mechanism of replication for HAV, HEV, HCV, and HDV (ssRNA)
of viral protein to RNA/DNA
33
What is the REPLICATION mechanism of replication for HAV, HEV, HCV, and HDV (ssRNA)
it is highly dependent on RNA polymerase to increase ssRNA
34
Where is the MATURATION AND ASSEMBLY mechanism of replication for HAV, HEV, HCV, and HDV (ssRNA) happening
in the endoplasmic reticulum
35
What is the RELEASE mechanism of replication for HAV, HEV, HCV, and HDV (ssRNA)
via exocytosis and they will effect other hepatocytes
36
How does the mechanism of replication for HBV (dsDNA) differ from that of HAV, HEV, HCV, and HDV (ssRNA)
the inclusion of nuclear import, transcription, and reverse transcription
no replication
37
What does TRANSCRIPTION do in the mechanism of replication for HBV (dsDNA)
makes 2 types of RNA:
viral RNA
pregenomic RNA
VIA RNA POLYMERASE
38
What does NUCLEAR IMPORT do in the mechanism of replication for HBV (dsDNA)
DNA repair enzyme for complete dsDNA
39
What does REVERSE TRANSCRIPTION do in the mechanism of replication for HBV (dsDNA)
RNA to DNA via reverse transcriptase
40
What are the phases of viral hepatitis
(3)
Prodromal
Icteric
Convalescent
41
what are characteristics of the PRODROMAL phase of viral hepatitis
Fever, via:
1. Hepatotoxins and cytokines (IL-1, IL-6, and TNF-alpha) from the liver go into circulation
2. they activate PGE2 and PGF2 in the enteric center of the brain stell
Nausea, and flu-like symptoms via:
leads to retroperistotic action = back flow of food up the esophagus
42
what are characteristics of the ICTERIC phase of viral hepatitis
1. Icterus in the eyes
2. yellowish skin discolorations in the palms and soles
3. dark urine
4. clay stools
5. hepatomegaly with pain in the upper right quadrant of the abdomen
43
what creates the DARK URINE characteristics of the ICTERIC phase of viral hepatitis
increased levels of unconjugated bilirubin
44
what creates the ICTERUS AND YELLOWISH DISCOLORATION characteristics of the ICTERIC phase of viral hepatitis
1. increased bilirubin
2. increased unconjugated bilirubin
3. increased bile salts
in circulation make deposits at different areas in the body that build up over time
45
what creates the CLAY STOOLS characteristics of the ICTERIC phase of viral hepatitis
1. decreased bile =
2. decreased bilirubin =
3. decreased urobilinogen =
4. decreased sterocobilin (what colors stools)
46
what creates the HEPATOMEGALY characteristics of the ICTERIC phase of viral hepatitis
1. decreased bile production
due to
2. decreased bilirubin
47
what is hepatomegaly
enlargement and pain of the liver due to inflammation
48
what are characteristics of the CONCALESCENT phase of viral hepatitis
1. Body resolving the infection
2. flu-like symptoms diminish
3. jaundice, yellow sclera, hepatomegaly, urine, and stool clear up/return to normal
49
what are extrahepatic manifestations of liver infection
1. arthritis
2. vasculitis
3. myocardial and pericarditis
4. thrombocytopenia
5. atypical lymphocytes
6. chronic hepatitis
50
what is the root cause of extrahepatic manifestations of liver infection
Chronic infection of HBV and HCV (HDV because HBV is needed to get to it)
51
what is the mechanism of extrahepatic manifestations of liver infection
antibodies make deposits of immune complex into different tissues around the body causing inflammation in those areas
52
what are the pathways to get CHRONIC HEPATITIS as an extrahepatic manifestations of liver infection from HBV HCV or HDV?
1. fibrosis leads to the risk of cirrhosis
2. regeneration of cells by mitosis = lots of replication = hepatocellular carcinoma
53
What are the characteristics of acute hepatitis?
1. minimal portal tract inflammation
2. lobular hepatitis or apoptosis
3. mononuclear cell infiltrate
4. confluent necrosis around central vein progressing to central-portal necrosis
54
What are the characteristics of chronic hepatitis?
1. mononuclear portal tract infiltration
2. interface hepatitis spills out into other hepatocytes
3. fibrosis bridge fibrosis and cirrhosis
4. bile duct proliferation
55
What are the histological characteristics of chronic hepatitis? (HBV)
Ground glass
ER swollen by HBsAg (a viral protein that fills up the hepatocyte)
56
What are the histological characteristics of chronic hepatitis? (HCV)
1. lymphoid aggregates or fully formed follicles in the portal tract
2. fatty changes of scattered hepatocytes
3. ballooned or swollen/rounded hepatocytes
57
How do you test for HAV
Anti-HAV IgM test
Anti-HAV IgG test
58
What markers to focus on with HAV testing
IgG
IgM
59
In HAV testing, IgM indicates what?
Active infection
60
In HAV testing, IgG indicates what?
recovery or vaccination
61
How do you test for HBV
3 antigens:
AHBsAg
HBeAg
HBcAg
62
what does AHBsAg detect
surface antigen
63
what does HBeAg detect
e antigen
64
what does HBcAg detect
core antigen
65
what is the treatment for HAV
supportive care
rehydration
rest
66
what is the treatment for HBV
vaccine with HBsAg to stimulate antibodies
HBsAb for prevention (serum immunoglobins)
67
what are the tests for HCV?
ELISA
HCV RNA with PCR
68
what is the gold standard test for HCV ?
RNA test with PCR
69
what is the test for HDV
anti-HDV IgM or IgG for active infection
vaccine for HBV
70
T/F: IgG is a protective antibody for HDV
FALSE
71
what is the test for HEV
Anti HEV IgM for active infection
Anti HEV IgG for recovery or vaccination
72
what is the treatment for HEV
supportive care
rehydration
rest
no vaccine
73
(alcoholic liver disease) Toxin-induced liver disease
liver injury caused by excess amount of alcohol
74
Toxin-induced liver disease often has a comorbidity of what forms of hepatitis?
HCV
HBV
75
How many grams of alcohol consumption is recommended
14g
76
what is the normal metabolic pathway of alcohol metabolism
ethanol > acetaladehyde > AcytlCoA > water + CO2
77
where is the normal metabolic pathway of alcohol metabolism
hepatocyte
78
acetaladehyde converts to AcetylCoA where
Mitochondria
79
what 2 substrates are involved in normal alcohol metabolism
ADH
ALDH
80
what is the metabolic pathway of alcohol metabolism when binge drinking
the addition of CYP450 to CYP2E1
H2O2 Catalase
81
WHERE is the metabolic pathway of alcohol metabolism when binge drinking with CYP450
Hepatocyte + ER
82
What is a byproduct of CYP450 and CYP2E1
ROS
83
WHERE is the metabolic pathway of alcohol metabolism when binge drinking with C2O2 Catalase
peroxisome
84
what is the route of alcohol metabolism
stomach > small intestine > liver > hepatocyte
85
How does the route of alcohol metabolism lead to the liver
portal vein
86
What percentage of alcohol is absorbed in the liver
80%
87
the synthesis of alcohol decreases what
NAD. It is needed to transform ActylCoA to ATP
without it goes through FA synthesis and stored in the body as triglycerides
88
what effect does liver injury have on the colon decrease gut bacteria
damages good bacteria
89
filtration of toxins in the liver occurs how
by kupffer cells in the sinusoid
90
ROS, fat storage, and LPS may lead to what
liver cirrhosis
91
LPS
gram negative bacteria from kupffer cells in the liver
92
ethanol can cause what to the mitochondria and cell membrane
damage and dysfunction
93
alcohol stimulated sinusodial endothelial cells to release endothelin. in return this does what?
causes vasoconstriction and contraction of stellate cells
94
vasoconstriction and contraction of stellate cells do what
increase the pressure of the portal and central vein causing hypertension
95
what are key histological findings of hepatic steatosis
micro-vesicular nodules that become macro vesicuilar globules
96
alcoholic hepatitis causes what
hepatocyte ballooning and necrosis
97
Mallory-Denk bodies are clumps of
keratin and proteins
98
what is steatofibrosis
scarring from fat storage caused by alcohol
99
alcohol steatofibrosis begins with
central vein sclerosis and spreads outward
100
in alcohol steatofibrosis clusters of hepatocytes resemble
chicken wire fence
101
What is the most important way to diagnose alcohol steatofibrosis
liver biopsy
But
blood test, liver function test, and ultrasound/CT is an option
102
what are the most common causes of chronic liver disease
steatosis
steatohepatitis
fibrosis
cirrhosis
103
What causes non-alcoholic liver disease
fat deposition in the liver
it is not related to alcohol or a viral cause
104
what systemic diseases can cause non-alcoholic liver disease
obesity
hypertension
diabetes
hypertyriglyceridemia
hyperlipidemia
105
what is the pathogenesis of non-alcoholic liver disease
strong association with insulin resistence
Unsaturated FA are vulnerable to ROS which increases free radicals
106
what is the end result of non-alcoholic liver disease
steatohepatitis
107
steatohepatitis is called what without alcohol
NASH
108
what is the difference between NASH and alcoholic hepatitis
alocholic:
less steatosis
more balloon hepatocytes
neutrophil infiltration
obliteration of the central veins
can progress to cirrhosis
more AST
NASH:
more ALT
109
what is liver cirrhosis
Inflammation and damage of the liver caused by the development of fibrotic and scar tissue
110
what are the risk factors of liver cirrhosis
excessive alcohol consumption
prolonged attack of HBV, HCV, HCD
medications
drugs
fatty liver
111
What are common histological notes of liver cirrhosis
regenerative nodules
fibrotic tissue and collagen
112
what cells mediate fibrosis
hepatic stellate cells (HSC)
113
where are HSCs located
between the sinusoid and hepatocyte (perisinusoidal space)
114
what do healthy HSCs do
Store vitamin A
Quiescent or dormant mode
Natural wound healing
115
What do injured HSCs do
lose vitamin A
secrete TGF-beta1 (produces collagen)
increases the build-up of fibrotic tissue
EFFECTS LEAD TO FIBROSIS
116
What are the complications of liver cirrhosis
Portal hypertension
Esophageal varices
Portosystemic Shunt
Hepatorenal failure
Hepatic encephalopathy
Asterixis
Decreased estrogen metabolism
Jaundice
Bleeding
Increased Liver enzymes
Hypoalbuminemia
(12)
117
What happens in portal hypertension
sinusoidal and portal veins become compressed
increase in pressure
118
What happens in ascites
high portal hypertension pushes fluid from the the blood into peritoneal spaces (large cavities) and its excess of fluid is what causes it
119
what happens in in esophageal varices
collateral vessels are formed as an alternative circulation pathway to bypass the obstructed flow within the liver
120
what happens in portosystemic shunt
blood to the liver is diverted because of high pressure and shunts away to a point of low resistance back toward the heart.
121
what happens in hepatorenal failure
a change in portal flow trigger renal vasoconstriction
lowers kidney blood flow
reduces filtration
leads to kidney failure
followed by liver failure
122
what happens with hepatic encephalopathy
loss/reduced kidney function
less detoxification
toxins accumulate and enter the brain
mental deficit
123
what happens in asterixis
ammonia produced din the GI gets into circulation
reaches the brain
get a tremor/jerky reaction when hands are extended
increased build up = coma
124
what happens in decreased estrogen metabolism
increase in blood due to damage = gynecomastia
spider angiomata and palmar erythema
125
what happens in jaundice
increased conjugated and unconjugated bilirubin
126
what are the factors of liver cirrhosis
(2)
compensated
decommpensated
127
what is compensated liver cirrhosis
liver can still function
asymptomatic with weight loss, weakness or fatigue
128
what is decompensated liver cirrhosis
extensive fibrosis
liver cant function
129
how do you diagnosis liver cirrhosis
the gold standard is to do a liver biopsy
130
what are common lab findings of liver cirrhosis
elevated serum bilirubin
elevated liver enzymes (AST, ALP, GGT)
thrombocytopenia
131
what are treatment options for liver cirrhosis
prevent further damage by not drinking alcohol and to get an antiviral treatment of HBV, HDV, and HCV
liver transplant
132
What is jaundice
a yellow discoloration of due to bilirubin in the skin, mucus membrane, and the eyes
133
what part of the eyes is bilirubin seen in
the conjunctiva over the sclera
134
what happens with the liver is damaged
bilirubin metabolism is disrupted
cant release UCB
hepatocytes die
Increased UCB and CB in circulation
135
what are normal levels of total serum bilirubin
0.3-1.2mg/dl
136
what level of total serum bilirubin indicates jaundice
2-2.5 mg/dl
137
What combination of bilirubin causes jaundice
UCB or CB or UCB/CB
138
what disorders cause jaundice
extravascular hemolytic anemia
ineffective hematopoiesis
139
what is the normal mechanism for bilirubin metabolism
RBCs eaten by macrophages
Heme is broken down (heme + globulin)
heme is broken down (Fe, protoporphyrin, UCB)
Albumin binds to UCB and is taken to the hepatocyte
UGT converts UCB to CB
CB exits with bile
in the duodenum, it is converted to urobilinogen
dark color urine
140
what happens when newborns get jaundice
their hepatocytes dont have enough UGT to conjugate enough UCB to keep a normal load
If UBC is too high, Kernicterus causes brain damage or death
141
what is the treatment for jaundice in newborns
phototherapy to induce structural changed
142
what is dublin-johnson syndrome
an autosomal recessive disorder where there is a low carrier protein and CB builds-up in hepatocytes
143
what carrier protein causes the problem in dublin-johnson syndrome
MRP2
144
what carrier protein takes over with a decrease in MRP2
MRP3
145
Where does MRP3 direct CB
into circulation and not the bile canaliculus
146
What does the CB in dublin-johnson syndrome get excreted as
dark urine
147
What does the CB in dublin-johnson syndrome do to the liver
makes it dark
148
Jaundice in the form of high CB can be seen as what disorder(s)
Dublin-Johnson syndrome
Obsructive Jundice
149
What happens in obstructive jaundice
blockage of the bile flow
bile is made up of CB
150
what effect does blockage of the bile flow have in obstructive jaundice
gallstones
pancreatic carcinomas
cholangiocarcinomas
parasites
151
what happens when the bile is made up of CB
the blockage causes and increase in pressure in the bile ducts
bile leaks through the tight junctions between hepatocytes
bile acids, salts and cholesterols leak into the blood
152
what are the complications of obstructive jaundice
pruritus
hypercholesterolemia
xanthomas
dark urine
stratorrhea
fat-soluble vitamin deficiency
(6)
153
What happens with high UCB and CB
viral hepaptitis
154
what is viral hepatitis
an increase in both UCB and CB in the blood due to hepatocyte infection
155
What is wilson disease
an autosomal genetic defect characterized by the accumulation of copper in various tissues due to a lack of the protein carrier ATP7b
156
what tissues can copper accumulate in
brain
liver
eyes
157
how much copper does our bodies need per day
.75 (the rest is excreted)
158
How is copper excreted
90% bile
10% urine
159
what can copper react with in the body and form
free radicals
reactive oxygen species
160
what is normal copper metabolism
stomach
small intestine
enterocytes
portal vein to the liver
161
what is the special transporter for copper in the liver
ATP7b
162
what does wilson disease look like in the liver
acute hepatitis to cirrhosis to liver failure
163
what does wilson disease look like in the brain
basal gaglia - parkinson's disease movement
cortex - neuronal death and dementia
164
what does wilson disease look like in the eye
cornea - kayser-fleisher ring (green to brown)
165
how do you diagnosis wilson's disease
decreased level of ceruloplasmin in the blood
high level of free copper in the blood and urine
166
what are treatment options for wilson disease
penicillamine
zinc and ammonium tetrathiomolybdate
liver transplant
