Chapter 2 - Cell Injury Flashcards Preview

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Flashcards in Chapter 2 - Cell Injury Deck (227):
0

Define hypoxia.

Inadequate oxygenation of tissue.

1

O2 diffusion

O2 in atmosphere → ↑PAO2 → ↑PaO2 → ↑SaO2

2

O2 content equation

O2 content = (Hb g/dL × 1.34) × SaO2 + PaO2 × 0.003

3

How does hypoxia affect ATP synthesis?

Hypoxia: ↓ATP synthesis by oxidation phosphorylation

4

How does the pulse oximeter read if there is a dyshemoglobinemia present?

Pulse oximeter: falsely ↑SaO2 in metHb and COHb

5

How does the co-oximeter read if there is a dyshemoglobinemia present?

Co-oximeter: accurately measures ↓SaO2 in metHb, COHb

6

Clinical finding in hypoxia

Cyanosis

7

Define ischemia.

Ischemia: ↓arterial blood inflow and/or venous outflow

8

Ischemia consequences

Ischemia consequences: atrophy, infarction, organ dysfunction

9

Define hypoxemia.

Hypoxemia: ↓PaO2

10

Define respiratory acidosis.

Respiratory acidosis: CO2 retention in lungs

11

How does ↑Alveolar PCO2 affect Alveolar PO2, PaO2 and SaO2?

↑Alveolar PCO2 = ↓Alveolar PO2 = ↓PaO2 = ↓SaO2

12

Define ventilation defect.

Ventilation defect: lung perfused but not ventilated

13

Give an example of a diffuse ventilation defect.

RDS: diffuse ventilation defect

14

What does a ventilation defect produce?

Ventilation defect: produces intrapulmonary shunting

15

What is a perfusion defect?

Perfusion defect: lung ventilated but not perfused

16

How does a perfusion defect affect dead space?

Perfusion defect: ↑dead space

17

Define diffusion defect.

Diffusion defect: ↓O2 diffusion thru alveolar-capillary interface

18

Give two examples of diffusion defect.

Diffusion defect: interstitial fibrosis, pulmonary edema

19

Define anemia.

Anemia: ↓Hb concentration; ↓O2 content

20

List four causes of anemia.

Anemia: ↓production Hb/RBCs; ↑destruction/sequestration RBCs

21

How does anemia affect PaO2, SaO2, and O2 content?

Anemia: normal Pao2/Sao2; ↓O2 content

22

Define methemoglobinemia.

MetHb: heme Fe3+; cannot attach to O2

23

How is metHb reduced?

MetHb reduction: NADH electrons → cytochrome b5 → cytochrome b5 reductase → heme Fe2+

24

List one cause of metHb.

MetHb: oxidant stresses (drugs, sepsis)

25

Describe the pathogenesis of hypoxia in methemoglobinemia.

MetHb: heme Fe3+; normal PaO2, ↓SaO2

26

How does methemoglobin affect the oxygen binding curve?

MetHb: shifts OBC to left; lactic acidosis

27

How does oxygen administration affect cyanosis in methemoglobinemia?

MetHb: cyanosis is unresponsive to administration of O2

28

What is the treatment for methemoglobinemia and how does it work?

MetHb Rx: IV methylene blue; accelerates NADPH-methemoglobin reductase

29

What is the leading cause of death by poisoning?

Carbon monoxide

30

List three causes of CO poisoning.

↑CO: car exhaust, smoke inhalation, wood stoves

31

Describe the pathogenesis of hypoxia in carbon monoxide poisoning.

CO: high affinity for heme groups

32

Describe the pathogenesis of hypoxia in CO poisoning.

COHb: inhibits cytochrome oxidase; left-shifted OBC; ↓SaO2

33

List two clinical findings in CO poisoning.

CO poisoning: headache, cherry-red discoloration (usually postmortem)

34

List three lab findings in CO poisoning.

CO poisoning: normal PaO2, ↓SaO2, lactic acidosis (hypoxia)

35

What is the treatment for CO poisoning?

Rx CO poisoning: 100% O2 via nonrebreather mask/endotracheal tube

36

What is 2,3-BPG and its role in the OBC?

2,3-BPG: glycolysis intermediate; stabilizes taut form Hb (↑release O2)

37

List six causes of left-shifted OBC.

Left-shifted OBC: ↓2,3-BPG, CO, alkalosis, metHb, fetal Hb, hypothermia

38

How do COHb and MetHb affect SaO2, PaO2, and the OBC?

COHb and MetHb: ↓SaO2, normal PaO2, left-shifted OBC

39

List four causes of right-shifted OBC.

Right-shifted OBC: ↑2,3-BPG, fever, acidosis, high altitude

40

How does high altitude affect atmospheric pressure of O2 and percentage of atmospheric O2?

High altitude: ↓atmospheric pressure; normal % atmospheric O2

41

What is the acid-base disturbance when at a high altitude?
How are 2,3-BPG levels and the OBC affected?

High altitude: hypoxemia/respiratory alkalosis; ↑2,3-BPG; right-shifted OBC

42

Name two electron donors in the oxidative pathway.

Oxidative pathway: transfer electrons from NADH, FADH2

43

What does the phosphorylation pathway do?

Phosphorylation pathway: synthesis of ATP

44

How do CO and CN affect the ETC?

CO and CN: inhibit cytochrome oxidase; ETC is shut down

45

List two causes of CN poisoning.

CN poisoning: house fires (most common); excess nitroprusside

46

What two types of poisoning are seen in house fires?

CO + CN poisoning: house fires

47

Describe the pathogenesis of hypoxia common to CO and CN poisoning?

CO + CN poisoning: shutdown of ETC prevents diffusion of O2 from blood to tissue

48

How does the mixed venous O2 content compare to the arterial O2 content in CN poisoning?

CN poisoning: mixed venous O2 content similar to arterial O2 content

49

What enzyme is inhibited by CO and CN and what results?

CO and CN: inhibit cytochrome oxidase; lactic acidosis (hypoxia)

50

Describe the treatment for CN poisoning?

Rx CN poisoning: based on high affinity of CN for metHb and cobalt

51

List two uncouplers of oxidative phosphorylation.

Uncouplers: thermogenin (brown fat), dinitrophenol

52

The presence of dinitrophenol may result in what?

Dinitrophenol: danger of hyperthermia

53

What does thermogenin do?

Thermogenin: stabilizes body temperature in newborns

54

List two mitochondrial toxins. What do they do?

Mitochondrial toxins: alcohol, salicylates; act like “uncouplers”

55

List two watershed areas in the body.

Watershed areas: cerebral arteries, mesenteric arteries

56

What is a complication of global hypoxia?

Watershed infarction in brain: complication global hypoxia

57

Where does ischemic colitis occur?

Ischemic colitis: splenic flexure at junction of superior/inferior mesenteric artery

58

ST-segment depression on ECG indicates what?

ST-segment depression ECG: subendocardial ischemia

59

List two factors resulting in subendocardial ischemia.

Subendocardial ischemia: coronary artery atherosclerosis; cardiac hypertrophy

60

List two locations in the nephron that are susceptible to ischemia.

Nephron locations susceptible to hypoxia: proximal tubule in cortex; thick ascending limb medulla

61

Which is the most adversely affected cell in tissue hypoxia?

Neurons: most adversely affected cell in tissue hypoxia

62

Which hepatocytes are most susceptible to hypoxia?

Zone III hepatocytes: most susceptible to hypoxia

63

What is the primary source of ATP in hypoxia and what is the result?

Anaerobic glycolysis: primary ATP source in hypoxia; lactic acidosis

64

What does increased intracellular lactate do?

↑Intracellular lactate: acid pH denatures structural/enzymic proteins

65

What may lactic acidosis be a sign of?

Lactic acidosis: may be a sign of tissue hypoxia

66

What results from an impaired Na+/K+-ATPase?

Na+/K+-ATPase pump impaired (reversible): intracellular swelling (↑Na+ and H2O)

67

What results from an impaired Ca2+-ATPase pump?

Ca2+-ATPase pump impaired (irreversible): cannot pump Ca2+ out of cytosol

68

What are four lethal effects of increased cytosolic Ca2+?

↑Ca2+ in cytosol: activates phospholipase, protease, endonuclease, caspases

69

What is the effect of increased Ca2+ in mitochondria?

↑Ca2+ in mitochondria: ↑membrane permeability to cytochrome c → apoptosis

70

Define free radical?

FR: single unpaired electron in outer orbital

71

What do free radicals do?

FRs: “steal” electrons from molecules, which become FRs

72

What do free radicals primarily target?

FRs: damage membranes and nucleic acids

73

Describe the relationship between free radical damage and age.

FR damage accumulates with age

74

Describe two important roles of free radicals.

FRs important in microbial killing by leukocytes
FRs important in reperfusion injury

75

List two transitional metals that generate hydroxyl free radicals.

Iron, copper: transitional metals that generate hydroxyl FRs

76

What is the most destructive free radical?

Hydroxyl FR: most destructive FR

77

What produces superoxide free radicals?

Superoxide FRs: oxidase reactions; exposure to high O2 concentration
Superoxide FRs: NADPH oxidase in phagocyte cell membranes

78

List two sources of nitric oxide free radical gas.

Nitric oxide FR gas: macrophages/endothelial cells; cigarettes

79

Describe the importance of oxidized LDL.

Oxidized LDL: FR important in atherogenesis

80

Describe the enzymatic reaction performed by SOD.

SOD: neutralizes superoxide FRs

81

What does glutathione peroxidase do?

Glutathione peroxidase: neutralizes H2O2, hydroxyl, NAPQ1

82

What does catalase do?

Catalase: neutralizes H2O2

83

What does vitamin E do?

Vitamin E: prevents FR injury of cell membranes

84

What is the best neutralizer of hydroxyl free radicals?

Vitamin C: best neutralizer of hydroxyl FRs

85

What vitamin is reduced in smokers?

Smokers: ↓vitamin C levels

86

What results from acetaminophen poisoning?

Acetaminophen poisoning: diffuse chemical hepatitis due to NAPQ1

87

Alcohol induces the synthesis of which cytochrome P450 isozyme resulting in what?

Alcohol: induces synthesis CYP2E1 isoenzyme
Alcohol: ↑CYP2E1 synthesis; ↑metabolism of alcohol

88

What is the treatment for acetaminophen poisoning and what does it do?

N-Acetylcysteine: Rx acetaminophen poisoning; provides cysteine for GSH synthesis

89

What may result from use of acetaminophen and NSAIDs?

Acetaminophen + NSAIDs: FR injury of kidneys; renal papillary necrosis

90

What is carbon tetrachloride and how does it become a free radical?

CCL4: solvent in dry cleaning; cytochrome P450 converts it into FR

91

List three factors involved in reperfusion injury.

Reperfusion injury: superoxide FRs + ↑cytosolic Ca2+ + neutrophils

92

Retinopathy of prematurity may result in the setting of RDS due to what?

Retinopathy prematurity in RDS: ↑superoxide FRs from O2 therapy

93

How does iron overload affect free radical production?

Iron overload: ↑OH· FRs via Fenton reaction

94

How does excess copper affect free radical production?

Excess copper: ↑OH· FRs via Fenton reaction; hepatotoxic/neurotoxic

95

Salicylates and alcohol affect which cellular organelle resulting in what?

Salicylates, alcohol damage mitochondria; megamitochondria in hepatocytes

96

Phenobarbital increases the synthesis of which cytochrome P450 isozyme resulting in what?

Phenobarbital: ↑CYP2B2 synthesis; converts drug to inactive metabolite

97

Phenytoin increases the synthesis of which cytochrome P450 isozyme resulting in what?

Phenytoin: ↑CYP3A4 synthesis in cytochrome P450 system; ↑metabolism of phenytoin

98

List two effects of SER hyperplasia.

SER hyperplasia: ↑drug metabolism; ↓drug effectiveness

99

List two SER inhibitors.

SER inhibitors: proton/histamine H2-receptor blockers; histamine receptor blockers

100

List two effects of SER inhibition.

SER inhibition: ↓drug metabolism; drug toxicity

101

Where are hydrolytic enzymes that are synthesized in the RER transported? Once there, what happens to these enzymes?

Hydrolytic enzymes undergo posttranslational modification in Golgi apparatus

102

Describe the posttranslational modification of hydrolytic enzymes.

Phosphotransferase attaches P to mannose residues on enzymes → mannose 6-P

103

Describe what occurs following posttranslational modification of lysosomal enzymes.

Mannose 6-P on lysosomal enzyme attaches to receptors on Golgi membrane

104

Describe what occurs after vesicles containing receptor-bound lysosomal enzymes pinch off the Golgi apparatus.

Vesicles pinch off Golgi membrane → deliver enzymes to lysosomes; some vesicles return to Golgi

105

What does the phagolysosome contain?

Phagolysosome: contains lysosomal enzymes

106

What is inclusion-(I) cell disease and which enzyme is affected?

I-cell disease: defect in posttranslational modification lysosomal enzymes; deficient phosphotransferase

107

What is lysosomal storage disease?

Lysosomal storage disease: ↓lysosomal enzymes; accumulation of complex substrates

108

What is Chediak-Higashi Syndrome?

CHS: giant lysosomal granules (fusion defect); defect in formation of phagolysosomes

109

What is the cytoskeleton composed of?

Cytoskeleton: microtubules, actin filaments, intermediate filaments

110

Which two chemotherapeutic agents inhibit the synthesis of tubulin? What phase of the cell cycle is affected?

G2 phase defects: etoposide, bleomycin

111

Name three compounds that cause mitotic spindle defects.

Mitotic spindle defects: vinca alkaloids, colchicine, paclitaxel

112

What is ubiquitin?

Ubiquitin: marker for damaged intermediate filaments

113

What are Mallory and Lewy bodies?

Mallory and Lewy bodies: ubiquinated keratin/neurofilament intermediate filaments, respectively

114

What is the most common cause of fatty change in the liver?

Alcohol: most common cause of fatty change

115

What is packaged in the VLDL fraction?

VLDL: liver-synthesized TGs

116

What is the carbohydrate substrate for TG synthesis?

G3-P: carbohydrate substrate for TG synthesis

117

What are the two functions of apoB-100?

ApoB-100: helps form VLDL and secrete VLDL from liver into blood

118

How does kwashiorkor affect TG synthesis?

Kwashiorkor: ↑CHO → ↑DHAP → ↑G3-P → ↑TG synthesis

119

How does alcohol affect TG synthesis?

Alcohol: ↑NADH → ↑conversion DHAP to G-3P → ↑synthesis TG

120

How does alcohol affect FA synthesis in the liver?

Alcohol: ↑acetyl CoA → ↑synthesis FAs in liver

121

List three effects alcohol has on FA.

Alcohol: ↑FAs → ↑synthesis, ↑mobilization from adipose; ↓β-oxidation FAs in mitochondria

122

In kwashiorkor, how is apoB-100 affected and what results?

Kwashiorkor: ↓protein intake → ↓apoB-100 → ↓packaging/secretion of VLDL

123

How does fatty liver affect TG and VLDL?

Fatty liver: ↑synthesis TG; ↓packaging/secretion VLDL

124

What is ferritin?

Ferritin: soluble iron-binding protein in macrophages

125

Where is ferritin synthesized?

Ferritin: synthesized in macrophages and hepatocytes

126

What is a decrease in serum ferritin an indicator of?

Serum ferritin: ↓in iron deficiency anemia

127

What is hemosiderin? What stains hemosiderin positive?

Hemosiderin: ferritin degradation product; Prussian blue positive

128

What is dystrophic calcification?

Dystrophic calcification: calcification of necrotic (damaged) tissue

129

What is the relationship between dystrophic calcification and serum calcium and phosphate levels?

Dystrophic calcification: serum calcium and phosphate are normal

130

What is metastatic calcification?

Metastatic calcification: calcification of normal tissue

131

What is the relationship between metastatic calcification and serum calcium and phosphate levels?

Metastatic calcification: ↑serum calcium and/or phosphate

132

What is nephrocalcinosis and what does it produce?

Nephrocalcinosis: metastatic calcification of collecting ducts; produces diabetes insipidus

133

What is atrophy?

Atrophy: ↓size/weight of tissue or organ

134

List four causes of atrophy.

Atrophy: ↓hormone stimulation, ↓innervation, ↓blood flow, ↓nutrients

135

What does increased luminal pressure result in? Which two organs may be affected?

Atrophy: ↑luminal pressure → compression atrophy (pancreas, kidney)

136

What occurs during autophagy?

Autophagy: vacuoles with organelles fuse with lysosomes; enzyme degradation of organelles

137

What is brown atrophy?

Brown atrophy: ↑lipofuscin in cells (undigested lipid)

138

List two mechanisms of atrophy.

Atrophy: cell shrinkage (loss of cytosol/organelles); apoptosis

139

What is hypertrophy?

Hypertrophy: ↑cell size

140

What does cardiac muscle hypertrophy occur in response to?

Cardiac muscle hypertrophy: ↑preload (↑volume in ventricle) or ↑afterload (↑resistance ventricle must contract against)

141

What occurs to the remaining kidney postnephrectomy?

Remaining kidney postnephrectomy: undergoes compensatory hypertrophy

142

Why does CMV hypertrophy of the cell occur?

CMV hypertrophy of cell: due to ↑iron uptake causing ↑cell growth

143

What is hyperplasia?

Hyperplasia: ↑number of cells

144

Give an example of hyperplasia due to increased hormone stimulation.

↑Hormone stimulation: estrogen → endometrial hyperplasia

145

Give an example of hyperplasia due to increased hormone sensitivity.

↑Hormone sensitivity: DHT → prostate hyperplasia

146

Give three examples of chronic irritation resulting in hyperplasia.

Chronic irritation: skin thickening (scratching), bronchial mucous gland hyperplasia (smokers), regenerative nodules in cirrhosis (alcohol excess)

147

List an example of chemical imbalance resulting in hyperplasia.

Chemical imbalance: ↓serum Ca2+ → parathyroid gland hyperplasia

148

How does iodine deficiency affect the thyroid?

Iodine deficiency → goiter (hyperplasia/hypertrophy)

149

Give an example of hyperplasia resulting from stimulating antibodies.

Hyperplasia stimulating antibodies: Graves disease

150

Give an example of hyperplasia resulting from a viral infection.

Hyperplasia: HPV → epidermal hyperplasia (common wart)

151

What must be true for hyperplasia to occur?

Hyperplasia only occurs if cells can enter the cell cycle

152

What do labile cells do? Give an example of labile cells.

Labile cells: continuously divide; e.g., stem cells in bone marrow

153

What are stable cells? Give two examples of stable cells.

Stable cells: resting cells in G0 phase cell cycle; e.g., hepatocytes, smooth muscle cells

154

Permanent cells cannot do what? Give three examples of permanent cells.

Permanent cells: cannot divide; e.g., neurons, skeletal/cardiac muscle

155

There is the risk of what in hyperplasia? Give two examples.

Cancer risk in hyperplasia: endometrial hyperplasia, regenerative nodules in cirrhosis

156

What is metaplasia?

Metaplasia: one adult cell type replaces another

157

Give an example of squamous to glandular epithelium.

Squamous to glandular epithelium: acid reflux distal esophagus (Barrett esophagus)

158

Give an example of glandular to other glandular epithelium.

Glandular to other glandular epithelium: atrophic gastritis due to Helicobacter pylori

159

Give two examples of glandular to squamous epithelium.

Glandular to squamous epithelium: bronchus in smoker; endocervix

160

Give an example of transitional to squamous epithelium.

Transitional to squamous epithelium: Schistosoma haematobium infection of urinary bladder

161

What is mesenchymal metaplasia?

Mesenchymal metaplasia: bone developing in area of muscle trauma

162

What is the mechanism of metaplasia?

Mechanism: reprogramming stem cells to utilize progeny cells with different gene expression

163

List three examples of stimuli for reprogramming in metaplasia.

Stimuli for reprogramming: hormones (estrogen), vitamins (retinoic acid), chemicals (cigarette smoke)

164

There is the risk of developing what in the setting of metaplasia and hyperplasia? The risk greater in metaplasia or hyperplasia?

Metaplasia and hyperplasia: risk for developing dysplasia; metaplasia > hyperplasia

165

What is dysplasia?

Dysplasia: disordered cell growth

166

List two risk factors for developing dysplasia.

Risk factors: endometrial hyperplasia; Barrett esophagus

167

List one risk factor for developing dysplasia related to infection.

Risk factor: HPV -> squamous dysplasia cervix

168

List one risk factor for developing dysplasia related to chemicals.

Risk factor: cigarette smoke -> squamous dysplasia bronchus

169

Name the type of dysplasia related to UV light.

Risk factor: UV light -> squamous dysplasia

170

List one risk factor of dysplasia related to chronic skin irritation.

Risk factor: chronic skim irritation (3rd degree burn) -> squamous dysplasia

171

What may dysplasia progress to?

Dysplasia may progress to cancer.

172

How does dysplasia affect cell proliferation and mitotic activity?

Dysplasia: disorderly proliferation of cells;↑mitotic activity

173

What three types of epithelium may be affected by dysplasia?

Dysplasia: may involve squamous, glandular, transitional epithelium

174

What is necrosis?

Necrosis: death of groups of cells + inflammation

175

What is coagulation necrosis?

Coagulation necrosis: preservation of structural outlines

176

List three causes of coagulation necrosis due to denaturation of enzymes and structural proteins.

Coagulation necrosis: ↑intracellular lactic acid; ionizing radiation; heavy metals

177

Name one microscopic feature of coagulation necrosis.

Coagulation necrosis: indistinct cell outlines in dead tissue

178

What is an infarction?

Infarction: gross manifestation of coagulation necrosis

179

Name two types of infarction.

Infarctions: pale and hemorrhagic types

180

Pale infarctions are seen in what type of tissue? List three organs that may be affected by a pale infarction.

Pale infarctions: dense tissue; heart, kidney, spleen

181

Hemorrhagic infarctions occur in what type of tissue? List three organs that may be affected by a hemorrhagic infarction.

Hemorrhagic infarctions: loose tissue; lung, bowel, testicle

182

What type of necrosis is present in the setting of dry gangrene?

Dry gangrene: predominantly coagulation necrosis

183

What is likely if a thrombus overlies an atherosclerotic plaque in a coronary artery?

Infarction likely if thrombus overlies atherosclerotic plaque in coronary artery

184

Name two scenarios in which an infarction is less likely.

Infarction less likely: dual blood supply (lungs), collateral circulation (arcade system in superior/inferior mesenteric arteries)

185

In what two scenarios are infarctions more likely?

Infarctions more likely: preexisting disease in tissue; end arteries

186

Describe the mechanism by which liquefactive necrosis occurs.

Liquefactive necrosis: lysosomal enzyme destruction tissue by neutrophils

187

What type of necrosis occurs in the setting of cerebral infarction?

Cerebral infarction: liquefactive not coagulative necrosis (exception to the rule)

188

What type of necrosis occurs in a bacterial abscess?

Bacterial abscess: liquefactive necrosis

189

Wet gangrene is predominantly what type of necrosis?

Wet gangrene: predominantly liquefactive necrosis

190

Caseous necrosis is a variant of what type of necrosis?

Caseous necrosis: variant of coagulation necrosis

191

What is responsible for the cheesy appearance of granulomas?

Lipid from cell wall Mycobacterium/systemic fungi → cheesy appearance in granulomas

192

What is the most common cause of caseous necrosis?

Tuberculosis: most common cause of caseous necrosis

193

Gummatous necrosis is what type of necrosis and is associated with what type of disease?

Gummatous necrosis: type of coagulation necrosis; associated with spirochetal disease (e.g., syphilis)

194

What are the two most common sites for gummas?

Gummas: skin, bone most common sites

195

Acute pancreatitis is associated with what type of necrosis?

Enzymatic fat necrosis: acute pancreatitis

196

What occurs during saponification? What commonly occurs in areas of saponification?

Saponification: calcium combined with fatty acids; dystrophic calcification

197

Trauma of fat tissue is related to what type of necrosis? Is this type of necrosis enzyme-mediated?

Traumatic fat necrosis: related to trauma of fat tissue; not enzyme-mediated

198

What mediates fibrinoid necrosis?

Fibrinoid necrosis: necrosis of immune-mediated disease

199

What is apoptosis?

Apoptosis: programmed cell death

200

List four examples of normal destruction of cells during embryogenesis.

Embryogenesis: MIS → apoptosis müllerian structures male Embryogenesis: lost tissue between fingers/toes; shaping inner ear; cardiac morphogenesis

201

How does a drop in estrogen and progesterone affect endometrial tissue?

Drop in estrogen/progesterone → menses

202

How does a decrease in stimulating hormones affect the target tissue?

↓Stimulating hormones → atrophy of target tissue

203

What occurs to the thymus with increasing age?

Normal involution of thymus

204

Cytotoxic CD8 T cells target which two cell types resulting in what?

death tumor cells/virus infected cells by cytotoxic CD8 T cells

205

Corticosteroids destroys what two cell types? What is its role in acute inflammation?

Corticosteroid destroys B/T cells; removes acute inflammatory cells in acute inflammation

206

List three things that damage DNA resulting in apoptosis.

DNA damaged by radiation/FRs/toxins

207

Apoptosis is associated with the removal with what type of proteins?

misfolded proteins removed

208

Defects in apoptosis can lead to what two types of diseases?

Defects in apoptosis → cancer, autoimmune disease

209

What does the extrinsic pathway of apoptosis require?

Extrinsic pathway of apoptosis: requires TNF-α

210

What does TNF-alpha activate?

TNFR1 is a death receptor activated by TNF-α

211

What is the main source of TNF-alpha? What other cell types produce TNF-alpha?

TNF-α: produced by macrophages (main source); endothelial and cardiac cells, and neurons

212

What does TNFR1 binding with TNF-alpha activate?

TNFR1 binding with TNF-α activates initiator caspases 8 and 10

213

What do initiator caspases activate?

Caspases: initiator caspases activate effector caspases (proteases, endonucleases)

214

Which is the most important of the two pathways of apoptosis?

Intrinsic pathway of apoptosis: most important of the two pathways

215

Name the genes and gene types of the BCL gene family.

BCL gene family: antiapoptotic genes (BCL-2 gene) and antiapoptotic genes (BAX, BAK genes)

216

What type of gene is BCL-2 and what does it do?

BCL-2 gene: antiapoptosis gene; protein maintains mitochondrial membrane integrity to prevent leakage of cytochrome c

217

What does BAK/BAX activation result in?

BAX/BAK activation: mitochondrial channels in membrane leak cytochrome c into cytosol

218

Once leaked into the cytosol, what does cytochrome c do?

Cytochrome c → activates caspases in cytosol → apoptosis

219

Once activated, what is the role of effector caspases?

Proteases destroy cytoarchitecture, endonucleases destroy nucleus

220

In apoptosis, what do cytoplasmic buds contain?

Cytoplasmic buds contain nuclear/mitochondrial/other organelle fragments

221

What do cytoplasmic buds do and become?

Cytoplasmic buds separate from membrane → apoptotic bodies

222

What happens to apoptotic bodies?

Apoptotic bodies phagocytosed by neighboring cells/macrophages

223

Describe three microscopic features of apoptosis?

Apoptosis: deeply eosinophilic cytoplasm; pyknotic nucleus; minimal inflammation

224

What is pyroptosis?

Pyroptosis: proinflammatory cell death using caspase-1

225

In pyroptosis, what three cell types and what three microbial pathogens may be destroyed?

Pyroptosis: monocyte/macrophage/dendritic cell destruction Salmonella, Shigella, Legionella

226

Pyroptosis has been implicated in the pathogenesis of what five diseases?

Pyroptosis: MI, neurodegenerative disease, IBD, cerebral ischemia, endotoxic shock