Cellular Adaptation, Cell Injury, And Cell Death

Front 1

Trophic triggers for hypertrophy

Back 1

Mechanical triggers: stretch

and

Trophic triggers: polypeptide growth factors and vasoactive agents

Front 2

Common causes of pathologic atrophy

Back 2

Decreased work load, loss of innervation, diminished blood supply, inadequate nutrition, loss of endocrine stimulation, aging, pressure

Front 3

Mechanisms of atrophy

Back 3

Protein degradation (lysosomes, ubiquitin, proteasomes), glucocorticoids/thyroid hormone/cytokines (TNF) stimulate proteosome mediated degredtion, increases in autophagic vacuoles

Front 4

Hallmarks of reversible cell injury

Back 4

Reduced oxidative phosphorylation, ATP depletion, cellular swelling
--
general swelling of the cell/organelles, blebbing, ribosome detachment, chromatin clumping

Front 5

Causes of cell injury

Back 5

Hypoxia (ischemia, inadequate oxygenation, reduced oxygen carrying capacity), physical agents, chemical agents, infectious agents, immunologic reactions, genetic derangements, nutritional imbalances

Front 6

Transition to irreversible injury: characteristics

Back 6

Increased swelling, disruption of lysosomes, large amorphous densities in swollen mitochondria, disruption of cellular membranes, profound nuclear changes (pyknosis, karyorrhexis, karyolysis), laminated structures become more pronounced

Front 7

Necrosis v. apoptosis:
cell size

Back 7

N: enlarged
A: reduced

Front 8

Necrosis v. apoptosis:
Nucleus

Back 8

N: Pyknosis, karyorrhexis, karyolysis
A: Fragmentation into nucleosome size fragments

Front 9

Necrosis v. apoptosis:
Plasma membrane

Back 9

N: Disrupted
A: Intact; altered structure, esp. lipid orientation

Front 10

Necrosis v. apoptosis:
Cellular contents

Back 10

N: Enzymatic digestion
A: Intact

Front 11

Cell injury results from abnormalities in one or more of which five essential cellular components

Back 11

Aerobic cell respiration, maintenance of membrane integrity, protein synthesis, intracellular cytoskeleton, integrity of the genetic apparatus

Front 12

Intracellular mechanisms of cell injury

Back 12

ATP depletion, mitochondrial damage, loss of calcium homeostasis, accumulation of oxygen derived free radicals, defects in membrane permeability

Front 13

ATP depletion effects

Back 13

Sodium pump dysregulation (swelling, ER dilation, loss of microvilli), alteration of cellular energy metabolism (reduced pH; decreased enzyme activity, clumping of chromatin), failure of Ca pump, detachment of ribosomes (reduction in protein synthesis; lipid deposition), unfolded protein response

Front 14

Causes of mitochondrial damage

Back 14

Increases in cytosolic Ca, oxidative stress, breakdown of phospholipids through the phospholipase A2 and sphingomyelin pathways, lipid breakdown products

Front 15

Free radical initiation

Back 15

Radiant energy, enzymatic metabolism of exogenous chemicals, normal redox reactions, transition metals, nitric oxide

Front 16

Relevant free radical effects

Back 16

Lipid peroxidation of membranes, oxidative modifications to proteins, lesions in DNA

Front 17

Systems that inactivate free radicals

Back 17

Antioxidants, transition metal binding proteins, free radical scavenging enzymes: catalase, superoxide dismutase, glutathione peroxidase (hydrogen peroxide and superoxide anion)

Front 18

Consistent irreversibility characteristics

Back 18

Inability to reverse mitochondrial dysfunction, and profound disturbances in membrane function

Front 19

Biochemical mechanisms that contribute to membrane damage

Back 19

Mitochondrial dysfunction, loss of membrane phospholipids, cytoskeletal abnormalities, reactive oxygen species, lipid breakdown products

Front 20

Morphologic features of reversible injury

Back 20

Cell swelling and fatty change

--
plasma membrane alterations, mitochondrial changes, dilation of ER, nuclear alterations

Front 21

General necrotic morphology

Back 21

Increased eosinophilia, nuclear changes (p, k, k), glassy appearance (glycogen loss), vacuolated, may attract calcium salts

Front 22

Morphologic appearance of necrosis is the result of?

Back 22

Denaturation of intracellular proteins and enzymatic digestion of the cell

Front 23

Coagulative necrosis

Back 23

Protein denaturation, preservation of cell and tissue framework, characteristic of hypoxic death, either heterolysis or autolysis

Front 24

Liquefactive necrosis

Back 24

Autolysis/heterolysis predominates over protein denaturation, abcesses/brain tissue, focal bacterial/occasionally fungal

Front 25

Caseous necrosis

Back 25

TB lesions, eosinophilic amorphous material with cell debris, fragmented coagulated cells, distinctive inflammatory border

Front 26

Fat necrosis

Back 26

Lipase activation releases fatty acids from triglycerides, then complex with calcium

Front 27

Wet gangrene

Back 27

when bacterial infection is superimposed on coagulative necrosis

Front 28

Ischemia: reversible injury

Back 28

Na/K pump, Ca release, swelling, ER dilation, increase osmotic load, detachment of ribosomes, decreased protein synthesis, altered cellular metabolism

Front 29

Ischemia: irreversible injury

Back 29

MPT change, release of cytochrome c, activated membrane phospholipases, decreased ATP causes decreased phospholipid synthesis, activated intracellular proteases, accumulation of free fatty acids and lysophospholipids

Front 30

Mechanisms underlying reperfusion injury

Back 30

Increased generation of free radicals, MPT promotion, increased cytokine/adhesion molecule expression causes inflammation that is increased when blood flow resumes, deposition of IgM binds to complement proteins when flow resumes and cause injury and inflammation

Front 31

Apoptosis in physiologic situations

Back 31

embryogenesis, hormone dependent involution, cell deletion in proliferating cell populations, dead of host cells that have served their useful purpose, eliminations of self-reactive lymphocytes, cell death induced by cytotoxic T cells

Front 32

Apoptosis in pathologic conditions

Back 32

Death produced by a variety of injurious stimuli, injury in certain viral diseases, pathologic atrophy in parenchymal organs after duct obstruction, cell death in tumors

Front 33

Biochemical features of apoptosis

Back 33

Protein cleavage by caspases (may also activate DNAases), intranucleosomal cleavage of DNA (200 bp), plasma membrane alterations

Front 34

Cytotoxic T lymphocytes and apoptosis

Back 34

Secretes perforin, then secretes granzyme B, which enters the cell and cleaves proteins, activating caspases. also express FasL on their surface

Front 35

Autophagic vacuole

Back 35

Where intracellular organelles and portions of cytosol are sequestered, formed from ribosome-free regions of the ER; eventually fuse to form autophagolysosome

Front 36

Lipofuscin pigment

Back 36

Undigested material derived from intracellular lipid peroxidation. Composed of complex lipids, phospholipids, and protein

Front 37

Mitochondrial alterations

Back 37

Increase/decrease in number during hypertrophy/atrophy, megamitochondria, mitochondrial myopathies, oncocytomas

Front 38

Cytoskeleton

Back 38

Microtubules, thin actin filaments, thick myosin filaments, intermediate filaments

Front 39

Thin filaments

Back 39

Leukocyte movement/phagocytosis

Front 40

Microtubules

Back 40

Sperm, cilia, leukocyte migration, phagocytosis

Front 41

Intermediate filaments

Back 41

Organizes cytoplasm

Front 42

Abnormalities that result in accumulations

Back 42

Normal, endogenous substance produced at normal/increased rate and rate of metabolism is inadequate; normal/abnormal endogenous compound accumulates bc of genetic/acquired defects in metabolism, packaging, transport, secretion; abnormal exogenous substance accumulates; can be reversible

Front 43

Steatosis

Back 43

Caused by alcohol abuse, protein malnutrition, diabetes, obesity, hepatotoxins, anoxia

Front 44

Steatosis: causes

Back 44

Excessive entry, excessive synthesis, decreased oxidation, increased esterification to triglycerides (due to alpha-glycerophosphate; alcohol), decreased apoprotein synthesis (carbon tetrachloride poisoning, starvation), impaired lipoprotein secretion (alcohol)

Front 45

Cholesterol related pathologic states

Back 45

atherosclerosis, xanthomas, inflammation and necrosis, cholesterolosis, niemann-pick disease type c

Front 46

How altered protein folding causes disease

Back 46

Defective intracellular transport and secretion of critical proteins, and toxicity of aggregated abnormally folded proteins, ER stress

Front 47

Hyaline change

Back 47

Any alteration that imparts a homogeneous, glassy pink appearance in routine H&E staining. Intracellular: proximal tubule epithelial protein droplets, russell bodies, viral inclusions, and aggregated intermediate filaments. Extracellular: damaged arterioles

Front 48

How altered protein folding causes disease

Back 48

Defective intracellular transport and secretion of critical proteins, and toxicity of aggregated abnormally folded proteins, ER stress

Front 49

Hyaline change

Back 49

Any alteration that imparts a homogeneous, glassy pink appearance in routine H&E staining. Intracellular: proximal tubule epithelial protein droplets, russell bodies, viral inclusions, and aggregated intermediate filaments. Extracellular: damaged arterioles

Front 50

Hemosiderin

Back 50

Hemoglobin derived, yellow-brown, composed of aggregated ferritin. Granules formed when there is a local or systemic excess of iron

Front 51

Melanin

Back 51

Formed by enzymatic oxidation of tyrosine to dihydroxyphenylalanine in melanocytes

Front 52

Hemosiderosis

Back 52

Increased absorption of dietary iron, impaired use of iron, hemolytic anemias, transfusions

Front 53

Dystrophic intracellular calcification

Back 53

Occurs in mitochondria

Front 54

Dystrophic extracellular calcification

Back 54

Calcium concentrates in membrane bound vesicles full of phospholipids. Calcium ion binds, phosphatases release phosphate groups which bind to calcium, cycle is repeated, structural change takes place that generates a microcrystal of calcium and phosphate which can perforate the membrane

Front 55

Principal causes of hypercalcemia

Back 55

Increased secretion of parathyroid hormone, destruction of bone tissue, vitamin D related disorders, renal failure

Front 56

Morphologic alterations due to cell aging

Back 56

Irregular and abnormally lobed nuclei, pleomorphic and vacuolated mitochondria, decreased ER, distorted golgi apparatus