CELL INJURY DEFINITIONS Flashcards
reversible functional and morphological changes
Reversible cell injury
cell cannot recover from injury resulting in cell death (necrosis or apoptosis)
Irreversible cell injury
reduces aerobic respiration
Oxygen deprivation*
mechanical trauma, extreme temperatures, sudden changes in atmospheric pressure, radiation and electric
shock
Physical agents
glucose or salt in hypertonic concentrations (electrolyte imbalance), oxygen at toxic levels, poisons (arsenic, cyanide, etc.), environmental and air pollutants, insecticides/herbicides, recreational and therapeutic drugs
Chemical agents and drugs
bacteria, fungi, parasites, viruses
Infectious agents
injurious reactions to self-antigens (autoimmunity), inflammation
Immunologic reactions
deficiency of functional proteins (enzyme defects, accumulation of damaged DNA or misfolded proteins)
Genetic derangements
vitamin or protein-calorie deficiency, excess cholesterol
Nutritional imbalances
blebbing, blunting and loss of microvilli
Plasma membrane alterations
swelling and appearance of small amphorous densities
Mitochondrial changes
clumping of nuclear
chromatin, disaggregation of granular and fibrillar elements
Nuclear alterations
ER swelling, cellular swelling, loss of microvilli, blebs
Failed Na+ pumps
decreased glycogen, lactic acid production → acidosis
Increased glycolysis
influx of Ca2+ decreasing phospholipids in membrane
Failure of Ca2+ pumps
structural disruption of protein synthesis and lipid deposition
Depletion of ATP
occur during normal metabolic processes (mitochondrial
respiration and energy generation)
Reduction-oxidation (redox) reactions
weapons for destroying microbes and other substances
Produced in phagocytic leukocytes
vasodilator (important chemical mediator and part of inflammatory response), can act as free radical and be converted to highly reactive ONOO-
Nitric oxide
condition where there are increased amounts of free radicals
Oxidative stress
ischemia and certain toxins cause influx of cytosolic calcium
Loss of calcium homeostasis
decreased ATP
ATPase
decreased phospholipids
Phospholipase
disrupt cell membrane and cytoskeletal proteins
Proteases
damage nuclear chromatin
Endonucleases
(↓ phospholipid synthesis, ↑ phospholipid breakdown) - contents leak into the
membrane
Defects in membrane permeability
sensitive to many types of injurious stimuli (increased cytosolic Ca2+, ROS, oxygen deprivation, etc.), results in biochemical abnormalities
Mitochondrial damage and dysfunction
formation of reactive oxygen species (free radicals)
Abnormal oxidative phosphorylation
ischemia tends to cause more rapid and severe cell and tissue injury than does
hypoxia in the absence of ischemia because aerobic and anaerobic respiration compromised
Reversible ischemia (may become irreversible)
cells proceed to die after blood flow restored; injury is paradoxically exacerbated and proceeds at an accelerated pace
- as a consequence, reperfused tissues may sustain loss of cells in addition to the cells that are
irreversibly damaged at the end of ischemia (contributes to tissue damage during myocardial and cerebral infarction and following therapies to restore blood flow - ex. myocardial infarction, stroke, organ transplantation)
Ischemic/reperfusion injury
major limitation to drug therapy, liver frequent target of drug toxicity
Chemical (Toxic) Injury
some chemicals injure cells directly by combining with critical molecular components
Direct acting chemicals
most toxic chemicals are not biologically active in their native form but convert to
reactive toxic metabolites which then act on target molecules
Convert to toxic metabolites
a single unpaired electron in an outer orbital making it
HIGHLY REACTIVE and UNSTABLE
Free radicals
energy knocks electrons to outer orbitals
Radiation
ex. normal respiration
Endogenous redox reactions
iron (hemoglobin), copper; donate or accept electrons during intracellular reactions and catalyze
free radical formation
(ex. Fenton reaction)
Transition metals
important chemical mediator (vasodilator)
Nitric oxide
unsaturated fatty acids of membrane lipids attacked by O2-
Lipid peroxidation of membranes
free radicals promote oxidation of AA side chains, formation of cross-linkages,
and polypeptide fragmentation;
disrupts conformation of structural proteins enhancing proteosomal degradation of
unfolded and misfolded proteins
Oxidative modifications of proteins
free radicals cause single and double-stranded breaks in DNA, cross-linking of DNA strands and formation of adducts
(ex. cellular aging)
DNA fragmentation
endogenous (self-produced), exogenous (supplements); block initiation of free radical formation and inactivate (scavenge) free radicals
Antioxidants
inherently unstable and spontaneously decay
Spontaneous decay
catalase, superoxide dismutases, glutathione peroxidase
Free radical scavenging enzymes
materials from external environment taken up and degraded
Heterophagy
degeneration of intracellular organelles
*Common phenomenon involved in removal of damaged or senescent organelles
Autophagy
