T22 - Cell Injury I Flashcards
What are physiologic adaptations?
response of cells to normal stimuli
What are pathologic adaptations?
response of cells to stress that allow them to modulate structure/function and escape injury
Give an example of a physiologic adaptation.
hormone-induced enlargement of uterus and breasts during pregnancy
Give an example of a pathologic adaptation.
reversible changes in number/size/metabolic activity of cells
What are the four primary morphologic adaptations to stress in cells?
hyperplasia
hypertrophy
metaplasia
atrophy
What cellular processes are associated with hyperplasia? (2)
DNA synthesis
mitosis
What cellular processes are associated with hypertrophy?
synthesis of cell components
What cellular processes are associated with metaplasia?
genetic reprogramming of stem cells
What cellular processes are associated with atrophy?
deeply eosinophilic cytoplasm
What is hyperplasia? (2)
increase in number of cells because of proliferation of differentiated cells by tissue stem cells
this is the response when cells are capable of division
What is hypertrophy?
cells can’t divide, so cells increase in size instead
What is metaplasia?
reversible change from one differentiated cell type to another (i.e. reprogramming of stem cells)
What is atrophy?
decrease in cell size because of loss of cell substance
Give an example of hormonal physiologic hyperplasia.
female breast enlargement at pregnancy and puberty
Give an example of compensatory physiologic hyperplasia.
liver regenerates after resection
Explain how hyperplasia differs from cancer.
if signal abates, hyperplasia disappears (hyperplastic responses remain controlled)
Give two examples of physiologic hypertrophy.
estrogen-stimulated smooth muscle hypertrophy in uterus during pregnancy
striated skeletal muscle hypertrophy in response to weightlifting
Give an example of pathologic hypertrophy.
left ventricle enlargement of heart (cardiomyocytes can’t divide) due to hypertension or aortic valve disease
What is the basis of metaplasia?
reprogramming of stem cells (not due to transdifferention)
Give three examples of metaplasia.
esophagus: stratified squamous → simple columnar
lungs: pseudostratified → stratified squamous
cervix: simple columnar → stratified squamous
What is the basis of atrophy?
decrease in cell size because of loss of cell substance
What system mediates the degradation associated with atrophy?
ubiquitin-proteasome pathway
Give two examples of physiologic atrophy that result from decreased work load.
immobilization of a limb (casts/arthritis)
space flight
What two factors can contribute to physiologic atrophy?
decreased work load
aging
Give an example of aging-induced physiologic atrophy.
postmenopausal atrophy of breast and vaginal tissue because of decreased hormone stimulation
What two factors contribute to pathologic atrophy?
loss of innervation
endocrine stimulation
Give two examples of pathologic atrophy resulting from loss of innervation.
neuromuscular disease
spinal trauma
Give an example of pathologic atrophy resulting from endocrine stimulation.
adrenal cortical atrophy secondary to exogenous steroids
What are the two primary causes of cellular injury?
hypoxia
ischemia
What is hypoxia?
oxygen deficiency due to interference with aerobic oxidative respiration
What is the most common cause of cell injury/death?
hypoxia
What is ischemia?
loss of blood supply in tissue due to impeded arterial flow or reduced venous drainage
What causes hypoxia? (3)
ischemia
pneumonia (inadequate oxygenation of blood)
reduction in oxygen-carrying capacity of blood
What are the histological changes observed following reversible cell injury? (2)
cellular swelling: failure of ion pumps in plasma membrane
fatty change
What are the electron microsocope changes observed following reversible cell injury? (4)
ER swelling
mitochondrial swelling
membrane blebs
clumped chromatin
What is coagulative necrosis? (3)
cell is dead, but underlying tissue architecture intact
affected tissue is firm
characteristic of infarcts in all solid organs except brain
What are three subtypes of coagulative necrosis?
gangrenous
dry gangrene
wet gangrene
What is gangrenous coagulative necrosis?
type of coagulative necrosis applied to necrosis of distal limb
What is dry gangrene?
results from loss of blood supply (common in DM patients)
What is wet gangrene?
gangrene involving bacterial infection that has “wet” appearance due to release of bacterial enzymes and associated neutrophil response
Define pyknosis.
irreversible condensation of chromatin in nucleus of cell undergoing necrosis or apoptosis
Define karyorrhexis.
fragmentation of nucleus of dying cell in which chromatin irregularly distributed throughout cytoplasm
Define karyolysis.
complete dissolution of chromatin of dying cell due to enzymatic degradation by endonucleases
Where is caseous necrosis most commonly observed?
caseous necrosis most commonly seen in foci of tuberculosis infection
Describe the histologic presentation of caseous necrosis. (2)
tissue architecture lost and replaced with amorphous pink material
surrounded by epithelioid cells and giant cells (granuloma)
What is liquefactive necrosis?
transformation of the tissue into a liquid viscous mass, often in response to focal bacterial or fungal infection
Define homeostasis.
ability of organism/cell to maintain internal equilibrium by adjusting physiological processes
Describe the events that occur in liquefactive necrosis. (2)
microbes attract neutrophils
neutrophilic enzymes digest (liquefy) tissue, producing pus
Hypoxic death in the brain is typically attributed to what cell adaptation?
liquefactive necrosis
What is fat necrosis?
focal areas of fat destruction, typically resulting from release of activated pancreatic lipases into peritoneal cavity and mesenteric fat
Give two examples of diseases/events that can result in fat necrosis.
acute pancreatitis
motor vehicle accidents
In a gross specimen of the pancreas, what features indicate fat necrosis?
chalky white lesions scattered throughout tissue
Describe the process of fat necrosis on a cellular level. (4)
lipases split TGs in adipocytes
liberated fatty acids combine with calcium
results grossly in chalky white areas (saponification of fat)
results histologically in basophilic calcium deposits
What is fibrinoid necrosis?
immune reactions with deposition of antigen-antibody complexes in blood vessels
Describe how fibrinoid necrosis is observed.
can only be observed histologically
immune complexes with fibrin that’s leaked from blood vessels produces bright, pink amorphous appearance
absence of nuclear material
What is dystrophic calcification? (2)
serum calcium is normal
deposition of calcium in degenerating of necrotic tissue
Give an example of dystrophic calcification.
deposition of calcium in arotic valve of person with left ventricular failure
[note: in the image, an antecedent bacterial infection damaged the valve]
What is metastatic calcification?
serum calcium abnormal
ectopic calcification in setting of elevated serum calcium, caused by increased parathyroid hormone
Give three examples of diseases/conditions that can lead to metastatic calcification.
primary parathyroid tumor
parathyroid related hormone (malignant tumors)
renal failure (phosphate retention causes secondary parathyroid hormone)
What is the relationship between dystrophic and metastatic calcification?
metastatic calcification can exacerbate dystrophic calcification
What are the symptoms of benign prostatic hyperplasia?
problems with urinary retention or urinating, caused by urinary obstruction
What causes benign prostatic hyperplasia?
problem with the 5-alpha reductase enzyme, which converts testosterone to dihydrotestosterone
What are the histologic changes associated with benign prostatic hyperplasia?
increase in glandular areas caused by papillary infoldings
intervening stroma that is smaller than normal
What is the relationship between hypoxia and ischemia?
ischemia, a reversible injury, is the most common cause of hypoxia
What are the two mechanisms that can lead to cardiac hypertrophy?
mechanical triggers, such as stretching
trophic triggers, such as growth factors or adrenergic hormones
Describe how trophic triggers lead to cardiac hypertrophy. (4)
turn on genes → stimulate protein synthesis → more myofilaments → increased contractility to meet demand
What are the histological changes observed following irreversible cell injury? (4)
disruption of cell membranes (leakage, dissolution)
pronounced eosinophilia (more eosin binding to cytoplasmic proteins)
changes to nucleus (shrinkage, breakdown)
inflammatory response (lysosomal enzymes)
What are the electron microscope changes observed following irreversible cell injury? (3)
breaks in plasma membrane/organelle membranes
large amorphous densities in mitochondria
marked mitochondrial swelling
(T/F) Pyknosis, karyorrhexis and karyolysis occur in sequence.
False. They do not happen in sequence. The order in which they occur depends on the injury and on time.
What are the five common patterns of necrosis?
coagulative
caseous
liquefactive
fat
fibrinoid
Necrosis most commonly results from (2)
metabolic failure
depletion of ATP
What is an abscess?
inflammatory response to an infectious agent
Caseous necrosis is most commonly observed in which organ?
lung
Which forms of necrosis occur most commonly in the lungs? (2)
coagulative necrosis
caseous necrosis
Which kind of necrosis commonly occurs in the brain?
liquefactive necrosis
