Section 1
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fibrosis, cirrhosis
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Date created
Mar 1, 2020
Cards (156)
Section 1
(50 cards)
fibrosis, cirrhosis
Non-alcoholic Fatty liver disease may progress to _____________ and ______________
atrophy
Decreased demand of a certain cell will cause it to decrease in size - this is called ________
steatosis
fatty change is a form of reversible injury known as?
atrophy
decrease in protein synthesis and increased degradation of proteins in cells leads to _______
hypertrophy
Increased demand of a cell will cause the cell to increase in size - this is called ________
macrovesicular
In steatosis, if there's a giant vacuole with triglycerides in it, then it's ________ steatosis
hyperplasia
Increased stimulation of certain cells will lead to an increase in the number of cells doing that job. This is called _________
cloudy swelling
Swelling of mitochondria and endoplasmic reticulum, and impaired Na+ - K+ pump are indications of
steatosis
Accumulation of triglycerides inside liver, heart, muscle, or kidney cells are indications of?
All, a) because loss of cilia
Mr. Rodriguez schedules an appointment with you complaining of a chronic cough that has persisted for one month following a cold. He is employed as a policeman and admits to smoking 2 packs of cigarettes per day since he was in high school. What are the potential consequences if your patient continues to smoke for 10-20 years? A. Repeated episodes of infection - why? B. Lung cancer C. Premature death
Yes, it's frequent
Is adjacent inflammation normal to necrosis?
physiologic
pathological or physiologic apoptosis?: balance between cell death/proliferation in normal tissues
In apoptosis - in the condensation and shrinkage of the nucleus and cytoplasm of cells
Where can you expect to see involvement of parenchymal cells?
drugs, anoxia, pregnancy
Decreased catabolism or oxidation of free acids by mitochondria may cause steatosis. What would this particularly be the result of?
Pyknosis, karyorrhexis, karyolysis
The nucleus in necrosis will?
hypertrophy
physical exercise and weight lifting can stimulate _________ of skeletal muscle.
often physiologic - eliminating unwanted cells. It may be pathologic after some forms of cell injury, especially DNA damage.
Is the outcome of apoptosis pathologic or physiologic?
atrophy
When your arm is in a cast for a long time, what can you expect to see of the skeletal muscles after the cast is taken off?
They selectively cleave DNA between nucleosomal units
What do endonucleases do in apoptosis?
physiological hyperplasia
The proliferation of glandular epithelium in breast tissue at puberty and pregnancy is an example of __________
hypertrophy
systemic hypertension can cause ________ in the left ventricle
No
Is adjacent inflammation normal to apoptosis?
necrosis, apoptosis
The major importance of this distinction between types of cell death is that while ____________ is always a pathological process, ____________ may take a place as a physiological phenomenon that is essential for life.
metaplasia
Chronic chemical or physical irritation (such as cigarette smoking or vitamin A deficiency) may cause a reversible change in differentiation of that cell type. This is called ________
They are eventually engulfed by adjacent cells.
What happens to apoptic bodies?
obesity
Increased uptake of free fatty acids mobilized from adipose tissue may cause steatosis. What would this particularly be the result of?
ubiquitin
nutrient deficiency and catabolic conditions activates _________ ligases
necrosis
Is this necrosis or apoptosis?
Pathologic (it's the culmination of irreversible cell injury)
Is the outcome of necrosis physiologic or pathologic?
stay intact and release in apoptotic bodies
The cellular contents in apoptosis will?
decrease (shrink)
The cell size in apoptosis will?
steatosis
chemical/drug toxicity, ethanol, obesity, diabetes mellitus, anoxia, protein malnutrition, pregnancy these can cause ______
disrupt
The plasma membrane in necrosis will?
autophagy
Atrophy may also be accompanied by _________ - a process by which a starved cell eats its own components
go through enzymatic digestion, they may leak out
The cellular contents in necrosis will?
necrosis and apoptosis
The two types of cell death are?
chemicals, toxins, malnutrition
Decreased secretion of lipoproteins may lead to steatosis. What would this particularly be the result of?
Increase (swelling)
The cell size in necrosis will?
Because they lack cilia
Why does squamous metaplasia predispose to repeated lung infections?
Physiologic
pathological or physiologic apoptosis?: Regulation of cellular populations in hormonally sensitive tissues
obesity, type 2 diabetes
What are the predisposing conditions for nonalcoholic fatty liver disease?
fragments of condensed nuclear material and cytoplasm.
What are apoptic bodies?
ubiquitin-proteasome
Degradation of cellular proteins occurs mainly via the ________ pathway
endometrial hyperplasia, pathological hyperplasia
When excess estrogen is in circulation, it causes ___________ in the endometrial glands in the uterus. This is __________ and it is an example of _________ _________
physiologic
pathological or physiologic apoptosis?: Destruction of cells during embryonic development
Fragment into nucleosome-sized fragments
The nucleus in apoptosis will?
cloudy swelling
Hydropic degeneration is a form of reversible injury known as?
be intact - the orientation of the lipids may change
The plasma membrane in apoptosis will?
apoptosis
Is this necrosis or apoptosis?
microvesicular
In steatosis, if there're little tiny vesicles with triglycerides in it, then it's ________ steatosis
Section 2
(50 cards)
glutathione peroxidase, it can turn H2O2 into H2O, or OH+ into H2O
What is GSH?
8
Death receptor from the extrinsic pathway will activate what caspase?
apoptosis of hyperplasic epithelial cells - results in prostatic atrophy
What does a drug that inhibits DHT synthesis induce for people who are struggling with Benign Prostatic Hyperplasia?
necrosis
Calcium overload is indicative of apoptosis or necrosis?
they are substrates for active caspases
cytoplasmic DNase (CAD), cytoskeletal proteins, and nuclear lamins (scaffold of nuclear envelope) all contribute what to apoptosis?
transaminase
Diagnosis of liver cell necrosis is frequently made by assaying serum ________________ activity
Its a metal chelator that binds copper
What does ceruloplasmin do?
cytochrome C
An increase in Bax allows release of __________________ from the mitochondrion.
1. hyperoxia 2. ionizing irradiation 3. reperfusion following ischemia - phagocytic cells release oxidants
What are some external sources of reactive oxygen species?
Apoptosis: - thymic lymphocytes
What are the target cells for toxicants(dioxin) and what results?
the proteasome complex
Misfolded proteins or proteins damaged by oxidants are degraded by _______________
decreased protein synthesis
decreased serum albumin and clotting factors in necrosis are indicative of _________________
1. Respiratory chain enzymes of mitochondria (generate H2) 2. Peroxisomes (generate hydrogen peroxide) 3. NADPH oxidase (in phagocytic cells - make hydrogen peroxide, and hypochlorous acid) 4. NO (made by nitric oxide synthase) - used to kill infections at the expense of damage to adjacent host tissue 5. Cytochrome P450 mixed function oxidase (drug metabolism, hormones, etc) - makes stuff like carbon tetrachloride
What are some biochemical pathways involving cellular oxidases that may generate reactive oxygen metabolites?
apoptotic
In parkinson's disease, is the death of midbrain dopaminergic neurons apoptotic or necrotic?
1. decreased synthesis from fasting or amino acid deficiency 2. products of cytochrome P450 may bind with GSH stores. 3. Redox cycling of chemicals (herbicide, paraquat) - keeps making reactive oxidation species, results in oxidative stress
Depletion of GSH can result from?
It shows that the body is majorly defending itself against oxidant damage
What is reduced glutathione a sign of?
Apoptosis: - prostatic atrophy - breast tissue (cessation of lactation)
What are the target cells for hormonal withrawal and what results?
hormone or growth factor withdrawal, injury
What are the intrinsic (mitochondrial) pathways leading to apoptosis?
phagocytes
in vivo - apoptotic cells are quickly engulfed by _______________, sloughed off into the lumen, or taken up by adjacent cells
pro-apoptotic, antiapoptotic
Bax is a ________________ factor, and Bcl-2 is a _________________ factor
they are metal iron chelators that protect against free radicals
What do transferrin and ceruloplasmin do?
Apoptosis: - thymic lymphocytes - intestinal epithelium
What are the target cells for ionizing radiation and what results?
ferritin, transferrin, hemoglobin
What prevents the fenton reaction from happening?
up, down
In necrosis, serum transaminase activity goes __________ and serum albumin and clotting factor levels go ____________
mitochondrial function
What can reactive oxygen species affect inside of the cell?
irreversible
structural breakdown, enzymatic breakdown, and loss of permeability barrier to calcium are signs of _________________ plasma membrane damage
irreversible
inability to generate ATP, release of mitochondrial calcium stores and mitochondrial membrane damage are signs of _____________ mitochondrial damage
FAS, TNF receptor
What are the extrinsic (death) receptor pathways leading to apoptosis?
apoptic protease activating factor
What is Apaf-1?
substrates for active caspases
What are procaspases?
disruption of cell pasma membrane
serum transaminase activity is a sign of _________
1. peroxisomes have catalase 2. Mitochondria have Mn-superoxide dismutase 3. cytosol has Cu-Zn superoxide dismutase 4. Vitamins A, C, and E have antioxidant properties
What are some defense mechanisms we have to chelate iron or break down oxidants as they are made?
Apaf-1, cytochrome C, ATP
________________ binds procaspase 9; this complex is cleaved by ________________. Cleavage requires ________________
intrinsic - because it binds with Caspase- 9 (which is activated in response to injury and hormone withdrawal)
Does Apaf-1 work with the intrinsic pathway or extrinsic?
homologues of ced genes (originally found in C. Elegans)
What are caspases?
Hyperplasia, or cancer may occur
What can happen if a steady state balance between cell proliferation, apoptosis and cell differentiation is disrupted?
proteolysis of cytoskeleton, nuclear laminin transglutaminase cross-linking of proteins, endonuclease activation
After the executioner caspases do their thing, what can you expect to see of the cell?
stromal cells, DHT
In Benign Prostatic Hyperplasia, ___________ cells produce extra ______________ which stimulates the proliferation of epithelial cells and smooth muscle and fibrous tissue in the stroma
vitamins
__________ are effective against damage to lipids initiated by OH+
damage to the plasm a membrane permeability barrier and accumulation of calcium ions in injured cells.
What is the hypotheis for the ultimate mechanism responsible for irreversible cell injury?
8,9
What are the initiator caspases?
growth factor
Extra DHT in the prostate will lead to stromal cells and epithelial cells making more ________ hormone
1. cross-linking at sulfhydryl groups 2. decreased enzyme activity, especially ATP-dependent ion pumps 3. abnormal protein folding or aggregation
Affects of reactive oxidative species on proteins include?
activates pro-apoptotic protease activating factor (Apaf-1) and triggers caspases.
What does cytochrome C leaked from the mitochondrion in apoptosis do?
3,6,7
What are the executioner caspases?
9
Hormone withdrawal or cell injury will activate which caspase?
Ced
_________ genes regulate apoptosis in humans
reactive oxygen species
What can apoptotic stimuli generate intracellular production of?
apoptosis: - cardiac myocytes - neurons (stroke)
What are the target cells for ischemia and reperfusion and what results?
fenton reaction
What is this reaction
Section 3
(50 cards)
ER stress, unfolded protein response
Misfolded proteins accumulate in the endoplasmic reticulum and induce ______________ or the ____________
mitochondria, acetic acid
Where is acetaldehyde metabolized and what does it become?
apoptosis
Accumulation of excess misfolded proteins can trigger _____________
diffuse hepatitis, bile stasis
the antibiotic isoniazid can produce ___________ while estrogens can cause __________ and gallstones.
One risks developing cancer
What happens if the P53 gene has been mutated or deleted?
hydrocarbons
carbon tetrachloride belongs to the group of chemicals known as ____________
Lowest observable adverse effect level
LOAEL is?
2E1
What P450 isozyme works on acetaminophen?
ethanol and barbiturates
Common inducers of cytochrome P450 include?
membrane damage is done to the RER
Lipid peroxidation would result in fatty liver if?
diffuse necrosis (Zone 2 - in the middle))
What kind of necrosis does isoniazid cause? (isoniazid is an antibiotic used to treat tuberculosis)
accumulation of alcoholic hyaline in cells
What are mallory bodies?
hepatitis
What is the disease associated with necrosis in the liver?
cross-links made by acetaldehyde
What causes the mallory bodies in the liver?
Bcl-2
What protein blocks apoptosis by preventing leakage of cytochrome C from the mitochondria?
CCl4, ethanol, nitrosamines
Acetaminophen (and anesthetics) metabolism results in what carcinogens or toxicants?
Periportal necrosis (zone 1 - near portal vein)
What kind of necrosis do metals cause?
yes
Is fatty liver reversible?
hepatocytes around the central vein
The highest level of activity of cytochrome p450 is?
Bax
What other protein does P53 protein induce?
Catalase
What metabolizes the conversion of ethanol to acetaldehyde in peroxisomes?
1. microsomes 2. cytosol 3. peroxisomes
What are the 3 major pathways of liver metabolism?
phase I metabolism
The hepatotoxicity of the chlorinated hydrocarbons, in particular carbon tetrachloride, results after the hydrocarbon undergoes _____________, resulting in free radical formation
hepatitis
Mallory bodies are associated with which liver disease?
1. oxidation of bases 2. DNA crosslinks 3. DNA breaks
Effects of reactive oxidative species on DNA include?
It maintains structural integrity of cellular DNA. When DNA is damaged, the p53 protein goes from the cytoplasm to the nucleus. It then turns on the genes that lead to apoptosis.
What does p53 protein do?
Cyp2E1
metabolism of the following drugs is induced by induction of what isozyme? Carbon tetrachloride Cocaine Acetaminophen Anesthetics
centrilobular (Zone III) necrosis
The common histopathologic pattern for hepatoxicity by free radical formation is?
1. necrosis 2. fatty liver
What can lipid peroxidation result in? (2 things)
cytochrome p450 mixed function oxidase system
A major site of drug and chemical metabolism is the ________________________ system in the liver
centrilobular necrosis (zone 3 - near hepatic vein)
What kind of necrosis do carbon tetrachloride, ethanol, and acetaminophen cause?
3A4 - induced by herbal medicines (st.John's wort)
What cytochrome p450 can accelerate catabolism of drugs (birth control pills, theophylline, anti-HIV therapy) and decrease their therapeutic effect?
1. mitochondrial injury 2. depleted glutathione 3. excess ROS by ethanol metabolism 4. protein cross-links made by acetaldehyde
What causes alcoholic hepatitis?
accumulations of misfolded proteins - parkinsons.
What are lewy bodies?
when firbrosis hyperplastic nodules form on the liver
Cirrhosis is what?
1. metabolism of ethanol uses up all the NAD - and NAD is required for fatty oxidation 2. ethanol impairs microtubular function, limiting the secretion of lipoproteins 3. Increases expression of genes (SREBPs) leading to increased synthesis of triglycerides
With too much alcohol, why does the liver become fatty?
misfolded proteins in the brain
Parkinson's, alzheimer's and even prions may be the result of?
CYP2E1
What metabolizes the conversion of ethanol to acetaldehyde in microsomes?
ubiquitin
________ is a heat shock protein that binds to damaged proteins and targets them to the proteasome complex for degradation.
xenobiotics
What do you call exogenous chemicals in the environment that enter the body through ingestion, skin contact or inhalation?
1. peroxidation of plasma and intracellular membranes 2. Free radicals attack double bonds of unsaturated fatty acids
Effects of reactive oxidative species on Lipids include?
LD50 (measured in mg/kg)
What is the classic measure of toxicity?
acetaldehyde
What is the intermediate product of ethanol metabolism?
the products of lipid peroxidation are released
Lipid peroxidation would result in necrosis if?
glucorionidation and sulfation
The major pathways of acetaminophen metabolism are?
smooth endoplasmic reticulum in the liver
The p450 system is located where?
ADH
What metabolizes the conversion of ethanol to acetaldehyde in the cytosol?
alcoholic hepatitis
this disease is accompanied by fat accumulation, fever, liver tenderness, jaundice, and necrosis of hepatocytes...what is it?
portal vein, metals like iron are an example, they are absorbed in the GI tract and cause periportal injury
Direct acting toxicants cause damage closest to what in the liver? What is an example?
when misfolded proteins accumulate
What is proteotoxicity?
Section 4
(6 cards)