Ch. 1 - Cell Growth, Injury, and Death Flashcards
differentiate hypertrophy from hyperplasia
hypertrophy: inc in size
hyperplasia: inc in number of cells
(hypertrophy/hyperplasia) involves gene activation, protein synth, and production of organelles
hypertrophy
t/f: hypertrophy and hyperplasia tend to happen together
true
What are the permanent tissues that cannot undergo hyperplasia and can only hypertrophy?
cardiac muscle
skeletal muscle
nerve
pathologic hyperplasia leads to…
dysplasia and cancer
atrophy is the opposite of…
BOTH hyperplasia and hypertrophy
dec in cell number in atrophy occurs as a result of increased….
apoptosis
dec in cell size occurs via (blank) mediated proteosome degradation of the cytoskeleton and autophagy of cellular components
ubiquitin
what part of the cytoskeleton is tagged with ubiquitin?
intermediate filaments
autophagic vacuoles fuse with what other organelle to break down cellular stuff?
lysosomes
what is the most common type of metaplasia?
change in one type of surface epi to another (eg squamous to columnar)
t/f: metaplastic cells are better able to handle the stress that creates them
true
t/f; metaplasia is reversible
true
what vitamin deficiency can lead directly to metaplasia?
vitamin A
with a vit. A def, goblet and columnar cells of the conjunctiva metplast into what cell type?
keratinizing squamous epi
t/f: connective tissue can undergo metaplasia
true
dysplasia results from….
long standing pathologic hyperplasia
t/f: dysplasia is reversible
true
neurons are particularly susceptible to what type of injury?
ischemia
slowly developing ischemia results in (blank), whereas acute ischemia results in (blank)
chronic ischemia: atrophy
acute ischemia: injury
How does hypoxia lead to cell injury?
lack of ATP production
What are the three general causes of decreased flow through an organ?
- dec arterial perfusion
- dec venous drainage
- shock state
What are the measured cutoffs for ischemia?
PaO2 <90%
High altitude lowers what O2 sat?
PAO2
Hypoventilations lowers which O2 sat?
inc. PACO2 leads to dec PAO2
A diffusion defect has a normal PAO2 but results in hypoxemia because…
the PAO2 is not able to push as much O2 into the blood due to a thicker diffusion barrier
Describe how a V/Q mismatch leads to hypoxemia
blood bypasses oxygenated lung (shunting) or oxygenated air cannot reach the blood (atelectasis)
t/f: in anemia, both the PaO2 and SaO2 are normal
true
Which O2 sat decreases in CO exposure?
SaO2
what is the classic finding in CO poisoning?
cherry red skin
Methemoglobinemia, in which Fe is oxidized to Fe3+, is commonly seen after what?
oxidant stresses like sulfa and nitrate drugs OR in newborns
what is the treatment for methemoglobinemia?
methylene blue
what is the weird ass classic presentation of methemglobinemia?
cyanosis with chocolate colored blood!
As a result of decreased ATP from hypoxia, what are the three major processes that are impaired?
- water buildup from impaired Na/K ATPase
- Ca buildup in the cytosol
- Lactic acid buildup and pH lowering from anerobic glycolysis b/c no more aerobic glycolysis
What is the histological hallmark of reversible cellular injury?
cellular swelling
Cytosol swelling results in the loss of (blank) and membrane (blanking)
loss of microvilli
membrane blebbing
Swelling of the rER leads to dissociation of the ribosomes and what result?
dec protein synth
What is the histological hallmark of irreversible cell injury?
membrane damage
Plasma membrane damage leads to what two things?
- cytosol enzymes leaking into the serum
2. buildup of Ca in the cell
Mitochondrial membrane damage leads to what two things?
- loss of electron transport if the inner membrane is damaged
- Apoptotic activation via cytochrome C leaking into the cytosol
Lysosome membrane damage releases lysozymes into the cytosol which are activated by….
the already elevated intracell Ca
what is the histologic hallmark of cell death?
loss of the nucleus
What are:
pyknosis
karyorrhexis
karyolysis
nuclear condensation
fragmentation
dissolution
t/f: the tissue remains firm in coagulative necrosis
true
t/f: cell shape and organ structure are preserved in coagulative necrosis
true
coagulative necrosis is indicative of an ischemic infarction in any organ except the…
brain
in coag. necrosis, the infarct is (blank) shaped and pale
wedge
When do you get a red coag. infarction?
when blood reenters a loosely organized tissue (lung or testicle)
Liquefactive necrosis is seen primarily in which three processes?
brain infarction
abscess
Pancreatitis
Gangrenous necrosis resembles mummified tissue and is a subtype of what type of necrosis?
coagulative
If gangrenous necrosis of dead tissue occurs, then liquefactive necrosis takes over and this is known as…
wet grangrene
Caseous necrosis is the combo of which two types of necrosis?
coagulative and liquefactive
Caseous necrosis is characteristic of what type of infection?
Tb or fungal
what does fat necrosis look like?
chalky white due to Ca deposition
Fat necrosis happens after what?
trauma to fat or pancreatic mediated
What is dystrophic calcification?
Necrotic tissue acts as a nidus for calcification in NORMAL serum Ca
What is metastatic calcification?
HIGH serum Ca or PO4 leads to calcium deposition in normal tissues
what is fibrinoid necrosis?
necrosis of a Blood vessel
How does a BV look that has fibrinoid necrosis?
bright pink wall
fibrinoid necrosis is characterstic of what dzs?
malignant HTN
vasculitis
Describe the histologic changes of the cell that is undergoing apoptosis (3)
- Cell shrinks; cytoplasm more eosinophilic
- Nucleus condenses and fragments
- Apoptotic bodies form
What are the the things that activate the intrinsic mitochondrial pathway of apoptosis?
- cell injury
- DNA damage
- dec. hormonal stim which leads to inactivation of Bcl2
Lack of Bcl2 lets (blank) leak out of the IMM into the cytosol to activate caspases
ctyochrome C
Which ligand pair activates the extrinsic apoptotic pathway?
- FAS ligand binds the death receptor CD95 on the target cell
- TNf binds the TNF receptor on the cell
Explain how CTLs kill virally infected cells
- perforins make holes in the membrane
2. granzymes get into the cell and activate caspase
what are the causes of pathological generation of free radicals?
- ionizing radiation - Water hydrolyzed to free radical OH
- inflammation - NADPH oxidase makes superoxide ion
- copper and Iron - Fe2+ via Fenton rxn
- Drugs and chemicals- P450 system during detox
how doe free radicals cause cellular injury?
peroxidation of lipids
oxidation of DNA and proteins
what are the four common intracellular antioxidants? (hint: three are vitamins!)
- glutathione
- Vit. A
- Vit. C
- Vit. E
What are the three antioxidant enzymes and where are they found in the cell?
- Superoxide dismutase: mito
- Glutathione peroxidase: mito
- Catalase: peroxisomes
What are the two metal carrier proteins that prevents iron oxidation in our blood?
transferrin
ceruloplasmin
Describe the free radical damage caused by CCl4 in dry cleaning?
converted to CCl3 by P450
cell injury; swelling of rER
Dec apolipoproteins leads to fatty liver changes
Describe the free radical injury in reperfusion injury
return of blood to ischemic tissue produces O2 free radicals
Where does amyloid deposit wrt the cell?
in the extracellular space
What are the shared features of deposisted amyloid proteins?
b-sheet config
CONGO RED STAINING WITH APPLE GREEN BIREFRINGENCE
From what protein is the AL amyloid derived from in primary amyloidosis?
immunoglobulin light chain
What dz is primary amyloidosis associated with?
plasma cell dyscrasias d/t multiple myeloma
From what protein is the AA amyloid derived from in secondary amyloidosis?
serum amyloid associated protein
SAA is a (blank) type protein
acute phase reactant
SAA is elevated in chronic inflammatory states, malignancy, and in Familial (blank)
familial Mediterranean fever
How does FMF present?
episodes of acute fever and acute serosal inflamm that can mimmic appendicits, arthritis, or MI
High levels of SAA in FMF attacks leads to..
deposition of AA amyloid in normal tissue
What are the three classic findings in systemic amyloidosis?
Nephrotic syndrome: KIDNEY IS MOST COMMONLY INVOLVED
Restrictive cardiomyopathy/arrhythmia
Tongue enlargement, malabsorption and HSM
What test must be done to Dx systemic amyloidosis?
biopsy of abd fat pad or rectum
t/f: amyloid cannot be removed
true; damaged organs must be transplanted
In senile cardiac amyloidosis, what protein deposits in the heart? what familial disorder is this associated with?
non-mutated serum transthyretin; assc’d with familial amyloid cardiomyopathy
deposition of mutated serum transerythrin in the heart leads to….
restrictive cardiomyopathy
5% of what particular minority carries the gene for familial amyloid cardiomyopathy
blacks
What type of amyloid deposits in the pancreas in type II DM
amylin
Which amyloid deposits in the brain in Alzheimer’s?
amylin in the islets of the pancreas
the Gene for b-APP in alzheimers is present on which chromosome?
21
In dialysis-associated amyloidosis, which protein deposits in the joints?
b2-microglobulin
“tumor cells in an amyloid background” are characteristic of calcitonin deposits in what type of tumor?
Medullary carcinoma of the thyroid
