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