Unit 1a Cell injury and death Flashcards
Adaptation
a change in response to some stimulus or signal
Acute adaptation
resolves on its own, once stimulus /signal is removed
Chronic adaptation
may deteriorate into dx
Atrophy
decrease in cell size, cells have less ER and mitochondria, protein production
Hypertrophy
increase in cell size, increased ER, mitochondria, DNA synthesis
Hyperplasia
-increase in cell number, more cell division
-can only occur in cells that normally divide
Metaplasia
replacement of one mature cell type with another
Dysplasia
deranged cell growth, with no benefit/organization
what causes atrophy?
from lack of use, nutrition, blood supply, hormones
Atrophy examples
-thymus during development, gets smaller as you get older
-Skeletal muscles in bed-ridden ppl
Hypertrophy examples
-skeletal muscles in response to incr workload(working out)
-cardiac myocytes in response to high BP
What causes Hypertrophy
mechanical or trophic signals
What causes hyperplasia
tissue or organ damage
Hyperplasia examples
-callus formation from repeated mechanical stimulus
-endometrial hyperplasia-thickening can resolve on its own or develop into cancer
Metaplasia characteristic
physiological change if temporary
pathological change if permanent
Metaplasia example
-columnar ciliated epithelial cell replaced by stratified squamous epithelial cell in airways=smokers cough
Dysplasia characteristics
-Not a true adaptive change
-abnormal shape, size, organization of cells
-cells cant mature
-cells return to normal or progress to cancer
-common in epithelial tissue; cervix, skin, GI tract, respiratory tract.
-differnt fxn
meta=
mature
plasia=
more cells
dys=
disorgainzed
trophy=
growth
hyper=
increase
cell injury
-mild and transient stress, injury is reversible and cell recovers
-severe and progressive stress, injury is irreversible and cell dies
4 organelles most vulnerable to damage
nucleus, cell membrane, ribosomes, mitochondria
Hypoxia
reduced oxygen availability
most common cause of cell injury
Hypoxia caused by
-reduced oxygen content in air
-loss of hemoglobin
-decrease in RBCs production
-respiratory/CV complications
-poisoning of intracellular oxidative enzymes
-ischemia-most common cause
_________can induce inflammations and make inflamed lesions _____
Hypoxia, Hypoxic
Ischemia
-reduced blood supply
-cell ruptures –> inner components released
Ischemia is caused by
-occluded vessels (effects well-studies in cardiac muscle)
-insufficiency in blood supply –> O2 supply –> ATP production
Ischemia inside the cell:
-accumulation of Na+ and Ca2+
-water follows Na+, cell swells
cell can recover in O2 restored
-accumulated Ca2+ signals self-destruct cascade
-cell ruptures-inner components released
Helpful diagnostic tool for MI
in ischemia after cell ruptures-Troponin released by damaged myocytes after MI-shows up on blood test
Ischemia-reperfusion injury
-restoration of O2 supply following ischemia can cause additional injury
-seen most commonly in: tissue transplant, myocardial, hepatic, renal, and cerebral ischemia
-explosion of ROS, (steal e-)
Reperfusion generates _______ that further damages cell
ROS- Reactive Oxygen Species
ATP consumption leads to build up of purine catabolites____and_______
xanthine and hypoxanthine
Influx of O2 causes rapid metabolism of hypoxanthine and xanthine to create massive amounts of _______and_______
superoxide, hydrogen peroxide
Oxidative stress
-caused by free radicals and ROS
= Endogenous antioxidant systems are overwhelmed
Free radicals
-electriclly uncharged atom (s) with an unpaired e-
-highly unstable!
-naturally generated in mitochondria, usually neutralized by endogenous antioxidants
-mitochondria are biggest source of and target ROS
Effects of oxidative stress
-targets plasma membrane!
-can initiate the destruction of of organelles, entire cell
-fragmentation of proteins/DNA
Antioxidants
-Vit E, C
-Albumin
-Transferrin
-donate free electron to unstable free radical, neutralizing the threat like ROS
Superoxide neutralized by;
Superoxide dismutase
Hydrogen peroxide neutralized by;
Catalase
Hydroxy radical neutralized by;
Glutathione peroxidase
ROS is heavily implicated in..
Heart disease and neurodegeneration
chemical injury
toxic substance injures cell directly (plasma membrane or other organelle) or with a toxic metabolite
chemical injury examples
-lead/mercury/arsenic-poison
-ethanol
-cyanide
-carbon monoxide
Lead poisoning
-Absorbed through skin or mucous membranes (eyes, nose, throat, stomach)
-mimics other metals (Ca2+, Fe 2+, Zn 2+) in biological processes
-interferes with the production of heme- severe anemia
-toxic to nerve cells
Stored in blood (weeks), soft tissues( mouth) and bone (years)can continuously be released into blood long after exposure
Lead poisoning
Ethanol
-readily absorbed into the blood, easily crosses blood-brain barrier BBB
-needs to be ingested
Acute intoxication
-drunkness
-depression of CNS fxns
-Sedation, drowsiness, loss of coordination, altered behavior,loss of consciousness
-extreme amounts lead to coma, respiratory come, death
Chronic intoxication
-alcoholism
-ALTERS NEARLY EVERY ORGAN TISSUE
-CELL INJURY TO OXIDATIVE STRESS
-fatty live disease, liver cirrhosis, live cancer
Cyanide
-lethal, kills fast
-targets electron transport chain in mitochondria, impairs formation of ATP
-Cytochrome oxidase
-without ATP, cells dysfunction and die quickly
Carbon monoxide
-CO binds to hemoglobin molecules of RBCs
-tissue becomes hypoxic
-treated with hyperbaric oxygen chamber
Infectious agents
Microorganisms invade the body and proliferate, causing damage to cells and tissues
Disease-producing potential of a microorganism depends on its ability to:
-invade and destroy cells
-produce toxins
-produce damaging hypersensitive reactions
Nutritional imbalances
-too much/too little (protein, carbs, lipids, vitamins, minerals)
Protein malnutrition
-most common worldwide
-deficiency reduces absorptive fxn of gut, diminishes hormone secretion, can lead to edema
Vit deficiency
-13 essential vitamins identified
-required for fxn of cells
example: Vit B1 thiamine def–> encephalopathy; presents as psychosis,delusional, common in alcoholics
Immunological rxns
-cell membranes injured by direct contact with components of immune system- ex allergies
Genetic factors
-disorders or dysfunction in genetic info harms cells
-inherited: sickle cell anemia
-acquired-cancer
physical trauma
-mechanical stress
-temp extremes
-sound
-radiation
-atmospheric pressure
-illumination
Cell accumulations
Manifestation of cell injury
Four mechanisms of accumulation
1.excess of normal endogenous substances
2. abnormal substance as result of gene or protein defect
3. endogenous ( in cell) substance not effectively catabolized
4. harmful exogenous (not normally found in the cell) material
water
cell swelling, most common degenerative change
lipids and carbohydrates
-accumulate dues to insufficient enzymes
ex, fatty liver dx from alc abuse
proteins
-disrupts organelle fxn
ex. albumin in kidney
calcium
Ca2+ is essential for signaling but too much is cytotoxic -apoptosis
ex; atherosclerosis, tumor
systemic manifestations of cell injury
-fatigue/malaise
-altered apetite
-pain
-fever
Apoptosis
cell is degraded with minimal effect to surrounding tissue, no inflamm
2 phases of apoptosis
-initiation-activation of caspases (cleaves DNA)
-execution- ACTION OF CAPASES CAUSES DEATH
Necrosis
disorganized, unregulated, cell death and dissolution (autolysis)
-always pathologic, inflammatory
-explosion, burst open
Types of necrosis
-coagulative
-liquefactive
-caseous
-fat
-gangrenous
Coagulation
-kideny, heart, adrenal glads
-protein degranulation
-albumin coagulates-turns opaque like cooked egg
Liquefactive
-neuron, glial cells
-dead brain cells digested by their own hydrolytic enzymes
-tissue liquefies
Caseous
-result of TB so in lungs
-dead cells not completely digested, resembles clumped cheese
fat
-breast, pancreas, other abdominal organs
-lipases dissolve cells into free fatty acids which combine with Ca2+, Mg2+, Na+
-creates soaps, saponification
Gangrenous
-not distinct type of necrosis: larger areas of tissue death
-result of sever hypoxic injury
-dry=frostbite
-wet= bacterial infection
somatic death
-death on entire person
algor mortis
reduced temp
livor mortis
purple skin discoloration
rigor mortis
muscle stiffening
postmortem autolysis
breakdown of cell membranes leads to release of enzymes
