Cell Injury 3 Flashcards
What is considered to be “cellular suicide”?
apoptosis
Explain the physiologic process of apoptosis?
Involution after hormone withdrawal
elimination of self reactive lymphocytes
age-related thymic involution
Pathologically, what can lead to apoptosis?
viral infections
gland involution following duct blockage (mastitis)
accumulation of misfolded proteins
immune mediated
What is the difference between necrosis and apoptosis
cell death by cell membranes rupturing vs cell suicide which is tightly regulated
What do both apoptotic pathways lead to activation of?
caspase cascade
What is the caspase cascade?
culminates in DNA degradation and apoptosis
Explain what the extrinsic pathway of apoptosis does as far as binding goes
binding of cell surface death receptors
TNF family receptors - FAS
Increased mitochondrial permeability would lead to what?
intrinsic pathway
In response to increased mitochondrial permeability how does the intrinsic pathway of apoptosis respond?
release of pro-apoptotic molecules in cytoplasm - specifically cytochrome c
What are the characteristic morphological features associated with apoptosis?
cell shrinkage
condensed chromatin
cytoplasmic buds - apoptotic bodies
NO INFLAMMATION
In apoptosis, there is cell shrinkage. How does this differ from necrosis?
swelling and rupture vs shrinkage
How are apoptotic bodies taken care of?
eaten up by resident macrophages
What are the two abnormal mechanisms in which calcification occurs?
Dystrophic
Metastatic
Where does dystrophic calcification occur?
Areas of necrosis
Where does metastatic calcification occur?
occurs in normal tissue around body secondary to hypercalcemia
What are some examples that would lead to metastatic calcification?
renal failure
vitamin D toxicosis
Elevated PTH or PTHrp (primary hyperparathyroidism)
neoplastic bone destruction
With cellular aging, what is there a decline in?
cell functionality/viability
What is myocardial mineralization? In other words which type of mineralization is this related to?
dystrophic - secondary to myocardial necrosis
What are common areas of mineralization and why?
Stomach, lung, kidneys - acid metabolism and mineral metabolism
What does cellular aging occur due to? What does it lead to a reduction in?
progressive exposure to exogenous influences and accumulation of cellular damage
leads to reduced oxidative phosphorylation and reduced protein/nucleic acid synthesis
Cellular aging has decreased cellular replications. Why is this important?
Progressive telomere shortening - once telomere reaches its stop signal the cell cannot function any more
What is an instance where a cell will never die?
Telomerase activity in somatic cells have allowed for them to use telomerase to their advantage leading to neoplasia
Why does intracellular accumulations occur?
Dysregulation of cellular metabolism
What are 4 different instances in which intracellular accumulations would occur?
Normal product but inadequate removal leading to fatty changes in liver
Normal product but defective enzymatic removal leading to lysosomal storage dx
Abnormal product due to gene mutation
Abnormal exogenous substances such as carbon or silicon
Explain the pathogenesis of Hepatic lipidosis such as seen in cats
accumulation of intracellular triglycerides due to increased supply of FFA or decreased metabolism/excretion of lipoproteins
mobilizing peripheral fat stores - liver cant keep up
How can you reverse hepatic lipidosis in cats?
Get them to eat again
What are examples of hepatic lipidosis?
early lactation dairy cows
obese animals suddenly off fed
What are the morphological features of hepatic lipidosis grossly and histopathologically?
Gross - pale tan, friable/greasy
Histo - distinct, clear, smooth walled cytoplasmic vacuoles
What are exogenous and endogenous sources of abnormal intracellular accumulation of substances such as pigment?
exogenous - carbon, tattoo ink
endogenous - melanin, lipofusion, hematogenous pigments
What are some causes of glycogen intracellular accumulation?
corticosteroids
diabetes melitus
glycogen storage diseases
