Cellular Injury and Adaptation Flashcards
(174 cards)
1
Q
Homeostasis
A
balance of physiologic and biochemical functions within the body
2
Q
Alteration of homeostasis results in
A
stress to cell, cellular injury or adaptive changes to survive altered environment
3
Q
Reversible injury
A
injury is corrected prior to destruction of cellular repair mechanisms; severity of injury does not exceed the cells ability to repair itself
4
Q
Irreversible injury
A
repair mechanisms are destroyed (removal from altered environment will be insufficient) cell cannot repair itself –> DEATH; injury exceeds the cell’s ability for self-repair, resulting in cell death
5
Q
Cellular Injury
A
Hypoxia, Physical agents, chemicals, infectious agents, immune reactions, genetic derangements, nutritional imbalance
6
Q
Hypoxia
A
Decreased supply of O2 to cell or inability to use O2
7
Q
Anoxia
A
Complete absence of O2
8
Q
Causes of Hypoxia
A
Ischemia (decreased BF), decreased oxygenation of blood, decreased O2 carrying capacity, inability to utilize O2
9
Q
Examples of Physical injury to cell
A
mechanical trauma, temperature extremes, atmospheric pressure variation, radiation, electrical injury
10
Q
Examples of Chemical Injury to cell
A
Simple agents (electrolytes, glucose), Poisons, Pollutants, Insecticides, herbicides, industrial products, drugs (therapeutic or recreational), alcohol
11
Q
Infectious Causes of cell injury
A
bacteria, rickettsia, fungi, virus, parasite
12
Q
Immune Response Causes of cell injury
A
Hypersensitivity reaction
13
Q
4 Key Signs of REVERSIBLE cell injury
A
Decreased aerobic respiration, cellular edema, ribosome detachment from RER, ultrastructural morphological changes
14
Q
Reversible Injury - Decreased Aerobic Respiration Results in
A
Decreased ATP production, increased AMP and anaerobic glycolysis, Increased lactate (decreased pH), decreased cellular glycogen, clumping of nuclear chromatin, decreased protein synthesis
15
Q
Examples of nutritional variations that cause cellular injury
A
deficits, excess, malabsorption, altered use
16
Q
Sites that are altered in cellular injury
A
cell membrane integrity, aerobic respiration, enzyme/protein synthesis, genetic apparatus
17
Q
What causes cellular edema in reversible cell injury?
A
Suppression of Na+ pump with increased [Na+] retention; increased intracellular Na+
18
Q
Ultrastructural Morphological Changes in reversible cellular injury
A
Phospholipid membrane alteration, loss of microvilli, myelin figure formation, mitochondrial swelling, RER swelling
19
Q
Key Signs of IRREVERSIBLE cellular injury
A
ATP Depletion, Cell Membrane Damage
20
Q
Cell Membrane Damage as a result of irreversible damage
A
Phospholipid Depletion, Cytoskeletal breakdown, toxic ROS, Lipid breakdown products, amino acid loss
21
Q
Structural changes in IRREVERSIBLE cell injury include
A
vacuolization of mitochondria, PM damage, Lysosomal swelling, Loss of proteins, enzymes, and RNA
22
Q
What characterizes cell injure as irreversible?
A
ATP depletion, cellular edema -> PM tears and damage, mitochondrial dysfunction (high [Ca2+] intracellularly), Membrane phospholipid depletion, cytoskeleton changes, ROS, lipid breakdown products, and amino acid loss
23
Q
Irreversible Cellular Damage - What is the determining/most important factor?
A
Cellular Membrane Dysfunction
24
Q
Irreversible Cellular Damage - What results from mitochondrial dysfunction?
A
ATP depletion -> increased cytosolic [Ca2+] -> mitochondrial phospholipase activation -> phospholipid breakdown + accumulation of FFA -> altered permeability of PM
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Myelin figures are characteristic of
reversible injury
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cellular edema is characteristic of
reversible injury
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Irreversible Cellular Damage - What causes membrane phospholipid depletion?
increase [Ca2+] intracellular activation of phospholipase AND ATP-dependent maintenance and production of phospholipids
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Irreversible Cellular Damage - What causes cytoskeletal abnormalities?
Hypoxia AND activation of proteases by high intracellular levels of [Ca2+]
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Irreversible Cellular Damage - What causes Toxic oxygen radical production?
sudden repercussion of hypoxic tissue
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Irreversible Cellular Damage - What produces Toxic oxygen radicals?
segmented neutrophils
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Reperfusion Injury
sudden reperfusion of ischemic tissue causes toxic oxygen radical production by segmented neutrophils
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Irreversible Cellular Damage - What produces lipid breakdown products?
phospholipase breakdown of pospholipids, high [FFA]
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Irreversible Cellular Damage - What amino acid is protective?
GLYCINE
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GLYCINE's protective feature
allows ATP depleted cells to resist high Ca2+ levels
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decreased aerobic respiration is a characteristic of
reversible injury
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increased intracellular pH is a characteristic of
reversible injury
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Increased intracellular AMP is a characteristic of
reversible injury
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Decreased glycogen stores v
reversible injury
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clumping of nuclear chromatin is a characteristic of
reversible injury due to decreased pH
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Ribosome detachment from RER is a characteristic of
reversible injury
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decreased function of sodium pump is a characteristic of
reversible injury
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Increased intracellular sodium is a characteristic of
reversible injury
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decreased protein synthesis is a characteristic of
reversible injury
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swelling of mitochondria is a characteristic of
reversible injury
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loss of microvilli is a characteristic of
reversible injury
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accumulation of lactate metabolites and phosphate is a characteristic of
reversible injury
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blebs is a characteristic of
reversible edema; due to structural alterations in phospholipid membranes
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myelin figures is a characteristic of
reversible injury
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ATP depletion reversible injury
irreversible injury; suppression of ATP-dependent repair mechanisms
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vacuolization of mitochondria is a characteristic of
irreversible injury
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lysosomal swelling is a characteristic of
irreversible injury
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loss proteins/enzymes and RNA is a characteristic of
irreversible injury
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PM tearing/damage is a characteristic of
irreversible injury
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Increased cytosolic [Ca2+] is a characteristic of
irreversible injury
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Increased [Ca2+] causes
activation of mitochondrial phospholipase and lysosomal proteases, ATPases, endonucleases
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Phospholipase
mitochondrial ([Ca2+] activated) breaks down phospholipids of PM
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Accumulation of FFA's is a characteristic of
irreversible injury
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Permeability changes in PM is a characteristic of
irreversible injury
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Membrane phospholipid depletion is a characteristic of
irreversible injury
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Damage to intermediate cytoskeletal filaments is a characteristic of
irreversible injury; hypoxia induced
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Separation of PM and cytoskeleton is a characteristic of
irreversible injury
62
Proteases
lysosomal proteases released and activated by high intracellular [Ca2+]
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Toxic oxygen radicals is a characteristic of
irreversible injury
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reperfusion injury is a characteristic of
irreversible injury
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accumulation of lipid breakdown products is a characteristic of
irreversible injury
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loss of glycine and other amino acids is a characteristic of
irreversible injury
67
Glycine
allows ATP depleted cells to resist high Ca2+ levels
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Reason for decreased protein synthesis in cellular injury?
detachment of ribosomes from RER
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Reason for nuclear clumping in cellular injury?
increased anaerobic glycolysis and decreased pH
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Intracellular release of lysosomal enzymes is a characteristic of
irreversible injury
71
What is a free radical?
Activated oxygen or carbon species that cause cell damage (ROS, COS)
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Unstable free radicals react with?
inorganic and organic chemicals in membrane lipids and nucleic acids
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What generates free radicals?
autocatalytic reactions within the cell, O2 therapy, radiation, oxidative injury, reperfusion, chemicals, inflammation, microbes, gases, aging
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Free radicals can result in
lipid peroxidation, oxidative protein modification, DNA damage
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Examples of Free radicals
Hydrogen Peroxide (H2O2), Superoxide (O2-), Hydroxyl ions (-OH)
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Superoxide dismutase
converts superoxide (O2-) to hydrogen peroxide (H2O2)
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Radiation creates free radicals by
radiolysing H2O into hydroxyl ions (-OH)
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Aging and free radicals
continuous free radical production, decreased anti-oxidant production, decreased anti-oxidant activity
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Agents that are protective against free radicals
Antioxidants: Vitamin E, Glutathione, D-Penicillamine, serum proteins, flavonoids
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Catalase enzyme converts
H2O2 --> H2O and O2
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Glutathione peroxidase
H2O2 --> H20
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Free radical production increases with
AGE
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Direct acting chemicals induce chemical injury by
DIRECTLY combining with critical components of cellular organelle
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By-products of glycolysis
H2O2 and O2-
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Toxic metabolites of chemicals induce chemical injury by
metabolism of drugs create toxic active metabolites that can either directly bind critical components of cellular organelle or induce freed radical formation
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Lipid peroxidation in the liver due to drug metabolites free radical production result in
lipid peroxidation causing damage to RER and PM -> ribosome detachment and decreased protein synthesis (Fatty liver) OR -> PM damage and increased permeability, cell swelling, influx of Ca, necrosis
87
Viral infections cause cell injury by
causing cytolysis or cytopathic changes (degenerative changes)
88
How does a virus directly damage the cell?
viral replication interferes with cellular mechanisms
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How does a virus inadvertently cause cell damage?
induces immunologic response: viral tropism (supporting growth of virus) result in phagocytosis, endocytosis or direct fusion of host cell
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Viral infections may cause host cell
lysis, cytoskeletal alterations, syncytial/giant cell formation, or inclusion formation
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Physiologic and biochemical mechanisms resulting in cellular injury may cause
morphological alterations in the cell
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Ultrastructural morphological changes include
PM alterations: swelling, blood formation, microvilli destruction, myelin figures;
Mitochondria: swelling, densities and granule formation
ER: swelling
Lysosome: swelling, rupture
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What morphological changes may be seen with the LIGHT microscope?
Reversible Injuries: Cellular swelling and intracellular accumulations
Irreversible Injuries: cell death
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Cell Death morphologic changes result from
Progressive degradation: enzyme digestion of cellular components and denaturation of proteins
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Autolysis
cellular digestion and denaturation cause by enzymes produced by necrotic cell
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Heterolysis
cellular digestion and denaturation cause by enzymes produced by cells other than the one affected
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General morphologic appearance of necrotic cell cytoplasm under the microscope?
eosinophilic (pink with H&E), glassy (loss of glycogen), and vacuolated
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General morphologic appearance of necrotic cell nucleus under the microscope?
clumped chromatin, pyknosis (shrunken nucleus), karyolysis (degraded nucleus), karyorrhexis (breakup of nucleus)
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Pyknosis
shrunken nucleus (as seen with necrotic cells)
100
Karyolysis
degraded nucleus (as seen with necrotic cells)
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Karyorrhexis
breakup of nucleus (as seen with necrotic cells)
102
Apoptosis
type of necrosis of an individual cell death by fragmentation and phagocytosis of fragments
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Coagulation Necrosis
Lose of nucleus due to denaturation of nuclear proteins and lysosomal enzymes (thus preventing proteolysis); cell shape maintained, eosinophila prominent
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Organs typically with coagulation necrosis
heart, kidney, and skeletal muscle
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Liquefeaction Necrosis
affected cell is completely digested by hydrolytic enzymes, resulting in a soft, circumscribed lesion consisting of pus
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Liquefeaction Necrosis hydrolytic enzymes are produced by
autolysis (self) or heterolysis (others)
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Liquefeaction Necrosis occurs primarily in the
brain, abdominal viscera and tissues infected with bacteria
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Liquefeaction Necrosis may result in _________ formation
abscess
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coagulation necrosis may progress to
Liquefeaction Necrosis
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Fat Necrosis
lipases cause saponification of fat -> resultant chalky white consistency
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Fat necrosis may result in ______
calcification
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Fat necrosis primarily occurs in
pancreas (after lipase and amylase release) and trauma to adipose tissue
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Caseation Necrosis is a combination of
coagulation and liquefaction necrosis
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Caseation Necrosis leads to ____ formation
granuloma
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Caseation Necrosis is characterized by
soft, granular, "cheesy" proteinacious material, surrounded by multinucleate giant cells, lymphocytes, and macrophages
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Caseation Necrosis primarily occurs in
any tissue infected with Mycobacterium tuberculosis and certain fungal infections
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Gangrenous Necrosis occurs primarily in
ISCHEMIC necrotic tissues, subsequently infected by anaerobic bacteria (Clostridium)
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Dry Gangrene
ISCHEMIA + necrosis and drying of the tissue -> black, mummified appearance
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Dry gangrene is typically caused by
arterial occlusion
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Dry gangrene microscopically shows ___________ necrosis
COAGULATION
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Wet gangrene is characterized by
soft, green-black, foul smelling purulent consistency
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Wet gangrene microscopically shows ___________ necrosis
Liquefaction following the release of autolytic, heterlytic, and bacterial enzymes
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Wet gangrene is typically caused by
arterial occlusion or traumatic injury
124
Intracellular accumulations include
normal substances, abnormal substances, pigments; accumulation within the cell
125
Intracellular accumulations may be:
harmful or harmless, within the cytoplasm or nucleus, produced by cell or elsewhere
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Types of intracellular accumulations
lipid, protein, glycogen, complex lipids, complex carbohydrates, pigments
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Lipid intracellular accumulations are characterized by
fatty change (fatty degeneration/infiltration)
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Lipid intracellular accumulations occur in
liver, heart, kidney, or skeletal muscle
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Lipid intracellular accumulations may be composed of
triglycerides, cholesterol, or both
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Protein intracellular accumulations may occur
in any tissue as HYALINE or plasma cells as RUSSELL BODIES
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Russell bodies
protein accumulation in plasma cells
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Protein intracellular accumulations often occur in
kidney, liver, or joints
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Glycogen intracellular accumulations
Common in diabetics (many tissues) and in glycogen storage diseases (specific or many tissues)
134
Fatty liver
Fat accumulation in hepatocytes due to metabolic abnormality
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Lysosomal storage disease
accumulation in cells due to lack of enzyme
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Pigment intracellular accumulation
Normal or abnormal, produced endogenously or exogenously (uptake of indigestible material)
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Exogenous pigment accumulation include:
carbon (tattoo, anthracosis)
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Endogenous pigment accumulation include:
melanin, lipofuscin, hemosiderin, bilirubin and carotene
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Subcellular Alterations
changes occurring in the cell at the level of organelle
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Lysosome mechanism
vesicle from RER - Golgi - cytoplasm as primary lysosome fuses with phagosome to become secondary lysosome; hydrolytic enzymes digest phagosome particles
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Heterophagocytosis
type of phagocytosis of a compound outside the cell begin brought into the cell
142
Heterophagocytosis is carried out by
neutrophils and macrophages
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Autophagocytosis
type of phagocytosis where lysosomes phagocytose damaged organelle originate ding within the same cell
144
SER subcellular alterations due to injury
SR is broken down after PM damage
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Mitochondrial subcellular alterations due to injury
mitchondrial permeability transition pore -> loss of mitochondrial membrane potential -> loss of OXphos and ATP
146
Lipofuscin pigment granules
finely granular yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion (aging process)
147
What causes mitchondrial permeability transition pore formation?
increased Ca2+, free radicals, toxins, hypoxia
148
Cytoskeleton/Cell membrane sub cellular alteration due to injury are characterized by
changes in the filaments and microtubules
149
Damage to cytoskeletal filaments and MT's result in
altered cellular structure, impaired phagocytosis, impaired mitosis, impaired sperm motility
150
Mallory Bodies
characteristic cytoskeletal change (twisted rope appearance) indicative of alcoholic liver disease
151
Neurofibrillary tangles
characteristic cytoskeletal change - aggregates of hyperphosphorylated tau protein that are a primary marker of Alzheimer's Disease
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Atrophy - cellular adaptation
decreased cell size due to loss of cell substance
153
Atrophy may be caused by
decreased workload (disuse), loss of innervation, decreased blood supply, inadequate nutrition, loss of endocrine stimulation, aging, pressure
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Hypertrophy
increase in cell size; increased demands of cell or increased stimulation by hormones
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Physiologic hypertrophy
uterine and breast enlargement during pregnancy
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Pathologic hypertrophy
cardiac hypertrophy in HTN or valvular incompetence
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Hyperplasia
increase in cell number (with hypertrophy depending on stimulus)
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Hyperplasia cannot occur in
nerve, skeletal, or cardiac muscle
159
Physiologic Hyperplasia
Hormonal: epithelium of breast during puberty
Compensatory: to account for damaged tissue
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Pathologic Hyperplasia
Abnormal hormonal stimulation (endometrium, breast, adrenal)
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Metaplasia
Reversible change in cell type as a result of stress, divergent differentiation
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Metaplasia may lead to
pre-malignant (dysplastic) changes
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Dysplasia
Deranged development due to stimulation to proliferate with atypical cytological alterations
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Dysplasia may be
precursor to cancer
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Calcification
Calcium salt + other ions precipitate and deposit in tissues
166
Dystrophic calcification
deposition of calcium as a sequelae to necrosis or tissue injury and inflammation; intra- or extracellular
167
Examples of Dystrophic calcification
arteriosclerosis, fat necrosis
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Metastatic Calcification
Systemic hypercalcemia -> deposition of calcium in viable tissue
169
What condition is known for systemic increased levels of Ca?
Hyperparathyroidism -> systemic metastatic calcification deposition
170
Hyaline
translucent, albuminoid protein which is the product of amyloid degeneration
171
Intracellular hyaline deposition may occur
in plasma cells + viral infection, hepatocytes + chronic alcohol abuse
172
Extracellular hyaline deposition may occur
arterial walls and in scar tissue following chronic inflammatory processes
173
Desmoplasia
associated with malignant neoplasms, which can evoke a fibrosis response by invading healthy tissue.
174
Fibrosis
formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process
