cell injury Flashcards
structures and processes that maintain cell viability include:
- plasma membrane
- mitochondria
- macromolecular synthesis (RNA rep, RNA transcription, translation, cell wall (peptidoglycan) synthesis, fatty acid (lipid) biosynthesis
- nucleus
mechanisms of cell injury
- ATP depletion
- generation of ROS (oxidative stress)
- loss of Ca homeostasis
- altered plasma membrane perm
- mitochondrial/DNA/protein damage
decreased oxygen (hypoxia) or no oxygen (anoxia) is due to:
- impaired absorption of oxygen
- decreased blood flow (ischemia)
- disease of blood or BVs
- inadequate oxygenation of the blood
decreased oxygen due to ischemia impairs ____ in the mitochondria, which leads to a decrease in ____
oxidative phosphorylation; ATP
reduced ATP reduces the ability of the plasma membrane to _____; there is impaired function of the _____ which leads to _____
maintain homeostasis; plasma membrane ATP-dependent Na pump; increased influx of Na, Ca, and water and increased efflux of K (net gain of solute and isoosmotic gain in cytoplasmic water)
gain in isoosmotic water leads to:
- cell swelling with formation of cell surface blebs
- mitochondria swelling
- swelling of ER
swelling of the ER leads to:
detachment of ribosomes/dissociation of polysomes and a decrease in protein synthesis (which can lead to increased lipid deposition)
reduced oxidative phosphorylation leads to increased _____ which produces ____
anaerobic glycolysis; lactic acid and inorganic phosphates
an increase in lactic acid decreases ____ leading to ____
intracellular pH; chromatin clumping
_____ (a mechanism of cell damage by ROS) affects the ____ which plays a role in maintaining homeostasis
lipid peroxidation (oxidative degradation of lipids); cell membrane (disrupted membrane makes it more permeable)
_____ is a final common pathway of cell injury
increase cytoplasmic Ca
high levels of Ca will activate various _____ such as:
degradative enzymes; phospholipases, proteases, endonucleases, ATPase
degree of cell injury is determined in part by:
- cell type/physiologic state of cell
- intensity/duration of insult
- number of exposures to etiologic agent
common etiologies of reversible (sub-lethal) cell injury include:
toxins, infectious agents, hypoxia, and thermal injury
reversible cell injury includes ____ and ____ morphology changes
hydropic ; fatty
morphologic changes in necrosis include: cell ____, ____ yielding a glassy homogenous pink staining cytoplasm, ____ breakdown which may result in a _____ cytoplasm, ____ changes, and ______
- cell swelling
- protein denaturation
- organelle breakdown- vacuolated cytoplasm
- nuclei changes (karyolysis/pyknosis/karyorrhexis/total loss)
- inflammation (acute or granulomatous)
morphologic types of necrosis
- coagulative
- liquefactive
- caseous
- enzymatic (fat)
the type of necrosis is dependent upon patterns of _____ of cells and ECM, the type of ____, and by _____ when present
enzymatic degradation; necrotic debris; bacterial products
in coagulative necrosis (most common form), _____ are coagulated; the ____ is lost, but the _____ of the cell is retained for a short time prior to being removed by the inflammatory response
cytoplasmic proteins; nucleus; eosinophilic outline
in liquefactive necrosis, the tissue is totally digested by the release of _____ during the ______
lysosomal enzymes; acute inflammatory response
liq necrosis often assoc with ____ or _____ (abscesses and wet gangrene), also seen in the _____
focal bacterial; fungal infections; central nervous system (brain)
caseous necrosis assoc with _____ infection; the tissue has a ____ and ____ appearance on gross examination
M. tuberculosis; white; cheesy
caseous necrosis microscopically characterized by ______ material within a ring of _____ and loss of _____
amorphous pink granular; granulomatous inflammation; tissue architecture
fat necrosis common in ____ to the breast or in cases of _____; adipose tissue has a _____ gross appearance; dead adipocytes give a _____ histologic appearance
trauma; pancreatitis; chalky white-yellow; “soap bubble”
diseases of excessive apoptosis
AIDS ischemia neurodegenerative diseases myelodysplasia toxin induced liver injury
diseases of inhibition of apoptosis
cancer (follicular lymphoma, carincinomas of the breast, prostate, ovaries) autoimmune disease (SLE) viral diseases (HSV, poxvirus, adenovirus)
morphologic features of apoptosis include: cell ____, ____ condensation followed by _____, _____ formation, and _____
shrinkage; chromatin condensation followed by fragmentation; apoptotic bodies formation; phagocytosis of apoptosis bodies without sig inflammatory response
signaling involved in mechanisms of apoptosis
- intrinsic system (mitochondrial pathway)
- “death signals”- Fas ligand binding to Pas receptor
- removal of a trophic signal (hormones)
- ROS, radiation, toxins
- effect of cytotoxic T cells
_____ family serve as on and off switches that regulate the _____ of the mitochondria
Bcl-2 gene family; membrane permeability
____ and ____ gene products inhibit apoptosis
Bcl-2; Bcl-x
____ and ____ gene products stimulate apoptosis
Bax; Bak
_____ released from outer mitochondria membrane serves to disrupt the _____ function of bcl-2, _____ apoptosis
cytochrome-c; inhibitory; favoring
cellular adaptations include:
alterations in cell size (hypertrophy/atrophy)
alterations in cell number (hyperplasia)
alterations in cell differentiation (metaplasia)
intracellular accumulations
one adult cell type is replaced by another adult cell type in response to chronic stress
metaplasia
mechanisms of intracellular accumulations
- abnormal metabolism (fatty liver)
- lack of an enzyme (lysosomal storage disease: accumulation of endogenous materials)
- abnormal protein folding or transport (accumulation of abnormal proteins)
- ingestion of indigestible material (accumulation of exogenous materials)
an abnormal accumulation of triglycerides within parenchymal cells of the liver, heart, kidney, and skeletal muscle
steatosis (fatty liver)
cholesterol accumulates primarily in _____
macrophages (foam cells)
3 examples of protein accumulation
alpha1 anti-trypsin deficiency
mallory bodies
neurofibrillary tangles in alzheimer’s disease
in glycogen storage diseases, there is abnormal glycogen metabolism due to _____; ____ accumulates within cytoplasm of cells
enzyme deficiency; substrate
“wear-and-tear” brown-yellow granular pigment”, a lipoprotein complex due to ROS peroxidation of membranes
lipofuscin (endogenous pigment)
black-brown pigment - produced by melanocytes but accumulated in adjacent epidermal cells and in macrophages.
melanotic macule (endogenous pigment)
A yellow-brown pigment represents aggregates of ferritin micelles;Its accumulation arises from excess iron locally due to hemorrhage and can lead to hemosiderosis
hemosiderin (endogenous pigment)
genetic disease assoc with cell death due to uncompensated hemosiderin accumulation
hemochromatosis
a yellow-brown pigment; end product of heme metabolism
bilirubin
bilirubin accumulates in hepatocytes and bile ducts due to ____, _____, and/or _____
hemolysis; obstructed bile flow; hepatocellular disease
