Liver (exam 3) Flashcards
1
Q
functions of liver in the body
A
production of bile
clearing of drugs/chemicals from blood
production of proteins for blood plasma
production of cholesterol
conversion of excess glucose to glycogen
regulation of blood levels of aa
processing hemoglobin
2
Q
highest concentration of cells in liver
A
hepatocytes
3
Q
HSC
A
hepatic stellate cells
major storage for vitamin A
serves as an APC
4
Q
functions of HSC as an APC
A
mediate autophagy
controls apoptotic body engulfment
modulates activity of dendritic cells, macrophages and NK cells
5
Q
HSC also produce/respond to various _____________________ that are linked to _________________ immune responses
A
interleukins, ICAM-1, IFN-g, and B7-H1
adaptive/innate
6
Q
carcinogen that can cause liver injury that is in foods
A
nitrocinamines
7
Q
most common stains used for liver
A
H&E
PAS
8
Q
H&E
A
hematoxylin and eosin
identify injury
9
Q
PAS
A
periodic acid-schiff reagent
identify injury and glycogen levels
10
Q
idiosyncratic hepatotoxins
A
unpredictable reactions in a small number of individuals
irreproducible, variable latent period
11
Q
are idiosyncratic hepatotoxins dose dependent?
A
NO!
it is dose-independent and diverse
12
Q
drugs that can cause idiosyncratic hepatotoxins
A
allopurinol
chlorpromazine
INH
phenytoin
chlorpropamide
methyldopa
erythromycin derivative
statins
nitrofurantoin
13
Q
intrinsic hepatotoxins
A
produce liver damage in a predictable manner
dose dependent
14
Q
examples of intrinsic hepatotoxins
A
acetaminophen
ethanol
methotrexate
oral contraceptives
valproic acid
heavy metals
mycotoxins (amatoxins, aflatoxins)
CCl4, CHCl3 (halogenated hydrocarbons)
15
Q
liver conditions tend to have
A
overlapping features
16
Q
necrosis
A
direct damage to liver parenchyma
most common
17
Q
liver levels in someone with necrosis
A
asymptomatic elevation of liver enzymes
elevated serum ALT/AST activities
17
Q
spotty necrosis
A
resembles classic viral hepatitis and involves all acinar zones
18
Q
what is common with massive liver injury?
A
massive inflammation
19
Q
liver infarcts
A
yellow with geographic borders and surrounding hyperemia
19
Q
acetaldehyde gets converted to ________________ by _________________
A
acetate
aldehyde dehydrogenase
20
Q
why are liver infarcts uncommon?
A
because the liver has 2 blood supplies
20
Q
ethanol gets converted to __________________ by _________________________
A
acetaldehyde
alcohol dehydrogenase
20
Q
ethanol can go through an alternative metabolic pathway via
A
cytochrome P-450 oxygenase
(if 2E1)
21
antizol
fomepizole
competitive inhibitor of alcohol dehydrogenase
21
what is antizol used in?
methanol and ethylene glycol poisoning
22
antabuse
disulfiram
inhibits aldehyde dehydrogenase
23
what is Antabuse used in?
aid in management of chronic alcohol patients
causes disulfiram reaction
24
hangover
unpleasant physical and mental symptoms that occur after a bout of heavy alcohol drinking
25
overall symptoms of a hangover
fatigue
headache
muscle aches
n/v
you guys should know the rest lol
26
sensory symptoms of hangover
vertigo
sensitivity to light
27
cognitive symptoms of hangover
decreased attention and concentration
28
mood symptoms of a hangover
depression
anxiety
irritability
29
sympathetic hyperactivity of a hangover
tremor
sweating
increased pulse and systolic BP
30
what is the most important laboratory test to obtain from a seemingly intoxicated patient?
why?
rapid bedside serum glucose measurement
intoxication can cause hypoglycemia --> changes in mental status and seizures
31
the metabolism of ethanol impairs
gluconeogenesis (inc conversion of pyruvate to lactate)
32
who are susceptible to ethanol associated hypoglycemia even when ingesting small amounts?
children
33
mickey finn
date rape drugs/knock out drops
mixture of ethanol and chloral hydrate
have additive sedative effects
34
is there an interaction between ethanol and cocaine?
if so, what is formed? and what can it cause?
yes
cocaethylene is formed in the liver
can be cardiotoxic and lethal
35
what can explain why some ethnic groups have higher/lower rated of alcohol related problems?
genetic differences in liver enzymes
36
hepatitis
inflammation of liver tissue
release of chemotactic factors
activation of kupffer cells/macrophages
macrophages release endothelial cell GF
activated phagocytes release ROS and BRIs
37
hormonal contraception can cause
structural changes in the liver
38
INH- induced hepatitis can be
mild to fatal
39
amiodarone hepatitis can be
untreatable since the long half life
no effective way to stop exposure of the drug
40
statins can cause
elevation of LFTa
41
is there specific drugs that cause hepatitis?
NO!
any drug can be a cause of hepatitis
42
atorvastatin induced acute hepatitis
mixed parenchymal inflammation
no bile duct damage or fibrosis
43
cholestasis
diminution/cessation of bile flow
44
cholestasis can result from
interference with bile secretion
inhibition of bilirubin uptake from blood
occlusion of the bile duct
45
types of cholestasis
acute or chronic
46
prolonged blockage of the bile duct can cause decrease ____________________ and an increase in ________________________ which is diagnostic for ___________________
elimination of conjugated bilirubin
conjugated bilirubin in the plasma
obstructive jaundice
47
cholestasis patients show
elevated blood levels of bilirubin
normal/mildly elevated ALT and AST
elevated levels of alkaline phosphate
48
any drug causing submissive hepatocellular injury may be followed by
fibrosis. nodular regeneration and cirrhosis
49
in relation to hepatic fibrosis, some agents can produce an _____________________________ with no minimal features of _______________ or ________________
increase in collagen deposition
necrosis
inflammation
50
hepatic fibrosis characteristics
increased number of kupffer cells, endothelial cells, TGF-b activation
release of fibroblast GF and ROS production
51
hepatic fibrosis leads to differentiation and proliferation of _________________ transforming them into _________________
fat storing cells (HSC)
myofibroblasts
52
myofibroblasts
produce large amounts of collagen
responsible for fibrosis of the liver
53
drugs leading the hepatic fibrosis
methotrexate
hypervitaminosis-A
vinyl chloride
heroin
54
biomarkers of liver cell injury
ALT
AST
GLDH
gamma GT
LDH5
55
biomarkers of inflammation
CRP
alpha 2 M
haptoglobin
chemokines
56
biomarkers of fibrogenesis
fibrogenic cytokines
CTGF
circulating fibrocytes
CSF
chemokines
57
biomarkers of fibrosis and ECM turnover
hyaluronan
P3NP
MMPs
TIMPs
laminin
58
myofibroblasts leads to an increase in
collagen
elastin
glycoproteins
proteoglycans
hyaluronan
59
three types of fatty liver
steatosis
steatohepatitis
phospholipidosis
60
steatosis
intracellular accumulation of fat
can be micro vesicular or macro vesicular
61
intracellular fat accumulation is not directly
toxic but reflects abnormal metabolism
62
an example of steatosis
NAFLD
63
causes of a fatty liver
TPN
methotrexate
griseofulvin
tamoxifen
steroids
valproate
amiodarone
diseases
64
fatty livers occurs primarily because of
disrupted liver metabolism
65
in a fatty liver, lipid content is ___________ by weight and there is an ____________________
over 5%
accumulation of TG
66
inhibition of _______________ results in steatosis
why?
protein synthesis
synthesis of lipoproteins is necessary for release of TG from hepatocytes
67
is ALT and AST elevated in a fatty liver?
mild to moderate
68
fatty liver can lead to
cirrhosis and liver failure
69
amiodarone induced steatohepatitis
hepatocyte ballooning
numerous mallory hyaline
minimal steatosis
70
amiodarone induced phospholipidosis
formation of lysosomal inclusion bodies due to accumulation of amiodarone
can be in liver and lung
71
alpha-1antitrypsin deficiency
more likely to develop COPD with pan lobular emphysema
collections of alpha-1-antitrypsin are not being excreted from hepatocytes
72
AAT deficiency can lead to
chronic hepatitis and cirrhosis (COPD as well)
73
_________________ is more likely to occur in children with AAT deficiency, while ______________ occurs in adults
liver disease
lung disease
74
cirrhosis is ______________ and has ____________ prognosis for survival
not reversible
poor
75
cirrhosis usually results from
repeated exposures to chemical toxins
76
chemical toxins that cause cirrhosis
ethanol
viral hepatitis
diabetic liver
77
at early stages of cirrhosis there is increased
incorporation of proline into collagen
78
In cirrhosis, what is impaired?
regeneration
79
_________________ appear in network of collagen throughout large portions of the liver
single necrotic cells
80
what causes fibrotic changes in cirrhosis
increased generation of hydroproline
81
what type of prolonged therapy can lead to cirrhosis?
methotrexate
INH
ticynafen
perhexiline
enalapril
valproic acid
82
macronodular cirrhosis
nodules are larger than 3 mm
caused by ongoing liver damage with liver cell necrosis followed by fibrosis and hepatocyte regeneration
83
examples of macro nodular cirrhosis
viral hepatitis B or C (most common)
Wilson's disease
alpha-1-antitrypsin deficiency
84
iron accumulation may lead to
micro nodular cirrhosis
85
hemosiderosis vs hemochromatosis
hemosiderosis - benign accumulation of iron
hemochromatosis - organ dysfunction occurs
86
when there is an excess of iron in the liver, hepatocytes and kupffers cells get full of
granular brown deposits of hemosiderin
87
in what conditions of hepcidin does iron accumulate in the cells?
high hepcidin conditions
88
in the presence of hepcidin, iron is _____________ which eventually shed from the intestinal tract and ________________
retained in duodenal enterocytes
block iron absorption from the diet
89
granulomatous hepatitis
granulomas are part of a broader inflammatory reaction involving the liver
evidence of hepatocellular dysfunction
90
drugs implicated with granulomatous hepatitis
carbamazepine (common)
sulfonamide
sulfonylurea
phenytoin
quinidine
hydralazine
91
allopurinol is known to cause
granulomas with a fibrin ring
92
granuloma formation are regarded as a
host attempt to protect against poorly soluble exogenous/endogenous irritants
93
autoimmune hepatitis
active necroinflammatory lesions with prominent plasma cells
leads to progressive damage of the liver
94
autoimmune hepatitis symptoms
fatigue
anorexia
weight loss
jaundice
ascites
portal HTN
hepatomegaly
splenomegaly
95
serology used to look for autoimmune hepatitis
anti smooth muscle antibody
anti nuclear antibody
lupus erythematous factor with elevated gamma globulin levels
96
treatment for autoimmune hepatitis
prednisone and azathioprine (Imuran)
NO CURE
97
most common form of autoimmune hepatitis
type I
found in association with other autoimmune disorders
98
minocycline induced autoimmune hepatitis
necroinflammatory activity with numerous plasma cells
99
venoocclusive disease
drugs than injure sinusoids, hepatic veins and hepatic arteries
100
________________ can cause VD in patients with renal transplant, bone marrow transplant, and on long term treatment for IBD
azathioprine
101
what can lead to VD with or without necrosis?
alcohol
excessive vitamin A
floxuridine
102
budd chiari syndrome
thrombosis of the hepatic vein and inferior vena cava can lead to an enlarged liver, abdominal pain, ascites, and liver failure
103
drug that causes Budd chiari syndrome
birth control pills
104
how do oral contraceptives cause VD?
can cause focal sinusoidal dilations --> peliosis hepatis
105
how do herbal tea preps cause VD?
alkaloids may cause acute ascites, rapid weight gain, abdominal pain, hepatomegealy
reversible
106
chemically induced neoplasia
tumors derived from hepatocytes/bile duct cells
malignant angiosacrcomas from sinusoidal lining cells
107
hepatocellular cancer
linked to abuse of androgens
high prevalence of aflatoxin-contaminated diets
108
agents linked to malignant hepatic neoplasms
vinyl chlorine and thorium dioxide
109
examples of liver carcinogens
dimethylnitrosamine
aflatoxin
arsenic
polycyclic aromatic hydrocarbons
DMBA
TCDD
