Cell Injury & Death

Question 1

Can cell injury be either reversible or irreversible?

Answer 1

yes

Question 2

What is the first morphologic change in reversible injury?

Answer 2

cellular swelling

Question 3

In reversible injury, what is derived from damaged ER?

Answer 3

• blebs (distorted plasma membrane)
• early chromatin clumping
• cytoplasmic vacuoles

Question 4

What can reversible injury be noted as?

Answer 4

increased turgor, pallor, and weight

Question 5

What can lead to dysfunctional cell membrane transport in reversible injury?

Answer 5

decrease in ATP

Question 6

Reversible injury results in an influx of what?

Answer 6

water and Na+ that appear as cell swelling

Question 7

In reversible injury, decreased oxidative phosphorylation promotes what?

Answer 7

glycolysis

Question 8

Anaerobic respiration leads to what?

Answer 8

lactic acid accumulation and reduced intracellular pH

Question 9

What are the consequences of the glycolytic pathway?

Answer 9

• altered enzyme function
• decreased protein synthesis
• protein structure and folding

Question 10

Reduced protein synthesis is refleted in what from the RER?

Answer 10

detachment of ribosomes

Question 11

The time scale of injury vaties upon what?

Answer 11

the metabolic status of cells

Question 12

In irreversible injury, why are the membranes weaker?

Answer 12

rupture of lysosomes and autolysis

Question 13

What is the main difference between reversible and irreversible injury?

Answer 13

lysosomes are damaged in irreversible injury and intact in reversible

Question 14

What are the 3 nuclear changes in irreversible injury?

Answer 14

karyolysis, pyknosis, and karyorrhexis

Question 15

What is karyolysis?

Answer 15

progressive disruption and random digestion of nucleus fades away

Question 16

What is pyknosis?

Answer 16

chromatin becomes densely clumped appearing hard, dark, and shrunken

Question 17

What is karyorrhexis?

Answer 17

when pyknotic nuclei break up into smaller, dense structures

Question 18

What are the clinical diagnoses of irreversible injury??

Answer 18

1. AST & ALT
2. CK & troponin from myocardial cells
3. lipase and amylase from pancreas

Question 19

What are the 2 major forms of cell death?

Answer 19

necrosis and apoptosis

Question 20

What is necrosis characterized by?

Answer 20

• cell swelling
• protein denaturation
• organelle breakdown

Question 21

When does necrosis occur?

Answer 21

after loss of blood/oxygen supply or exposure to noxious chemical toxin

Question 22

What is apoptosis?

Answer 22

programmed cell death

Question 23

What is apoptosis characterized by?

Answer 23

cell shrinkage, but intact organelles

Question 24

When does the formaton of DNA fragmentation ladder occur?

Answer 24

during apoptosis

Question 25

What type of cell injury has intrinsic and extrinsic pathways with no inflammation?

Answer 25

apoptosis

Question 26

What are the normal physiological processes?

Answer 26

* embryogenesis * hormone-dependent involution in adult organs * hoemstasis

Question 27

What are the pathological processes?

Answer 27

* injury * viral diseases * pathologic atrophy in organs after duct obstruction * immunologic reactions

Question 28

What is the process of intrinsic apoptosis?

Answer 28

1. release of cytochrome-c initiates formation of apoptosome 2. Apaf-1 binds cytochrome-c and recruits pro-caspase-9 to apoptosome 3. caspase 9 is activated and cleaves other caspases -> apoptosis

Question 29

What is the difference between intrinsic and extrinsic apoptosis?

Answer 29

* intrinsic= damage to cell * extrinsic= involves ligand

Question 30

What are the anti-apoptotic proteins?

Answer 30

BCI-2 and livin

Question 31

What are the inhibitor/propoptotic proteins?

Answer 31

* XIAP * c-IAP-1 * c-IAP-2 * survivin * bax, bid, bad

Question 32

What is Fas?

Answer 32

membrane spanning protein

Question 33

What does microscopically apoptosis appear as?

Answer 33

apoptotic bodies

Question 34

Biochemically/molecularly apoptosis appears as what?

Answer 34

DNA fragmentation ladder

Question 35

How does intact DNA, apoptotic DNA, and necrotic DNA appear?

Answer 35

* intact: sits at the top * apoptotic: ladder * necrotic: big mush

Question 36

What are the morphologic changes of apoptosis?

Answer 36

* organelles remain intact * cell shrinks * blebs form on cell surface * nuclear fragmentation * little or no infllamatory reaction * single cell

Question 37

Does apoptosis have inflammation?

Answer 37

no

Question 38

What is the mitochondrial (intrinsic) pathway?

Answer 38

* growth factor withdrawal * DNA damage * protein misfolding

Question 39

What is the death receptor (extrinsic) pathway?

Answer 39

includes receptor-ligand interactions (Fas and TNF receptor)

Question 40

What is the most common form of cell death?

Answer 40

necrosis

Question 41

What is necrosis?

Answer 41

* hypoxia, toxins * involves areas of tissue

Question 42

What are the morphologic changes that happen to the cell during necrosis?

Answer 42

* cell swells * organelles are disrupted * multiple cells

Question 43

What are the nuclear changes in necrosis?

Answer 43

karyolysis, pyknosis, karyorrhexis

Question 44

Is there inflammation in necrosis?

Answer 44

yes

Question 45

What are the 2 types of necrosis?

Answer 45

coagulative and liquefactive

Question 46

What is coagulative necrosis?

Answer 46

protein denaturation

Question 47

What is liquefactive necrosis?

Answer 47

enzymatic digestion

Question 48

What is the most common form of necrosis?

Answer 48

coagulative

Question 49

Denaturation of cellular proteins causes what?

Answer 49

inhibition of proteolytic enzymes

Question 50

In what type of necrosis is the architecture reserved?

Answer 50

coagulative

Question 51

What is the characteristic of hypoxic death?

Answer 51

myocardial infarction

Question 52

How is proteolysis blocked?

Answer 52

denaturation of proteins and enzymatic proteins

Question 53

What is gangrene?

Answer 53

type of coagulation necrosis that is the gradual ischemia of distal extremities (foot, leg)

Question 54

When can gangrene occur?

Answer 54

with diabetes or frostbite

Question 55

What is the difference between "wet" and "dry" gangrene?

Answer 55

* wet: bacterial superinfection of necrotic material * dry: black-brown, mummified appearance

Question 56

What is the difference between coagulative and liquefactive necrosis?

Answer 56

* coagulative: inhibition of indogenous protease enzymes * liquefactive: enzymes that destroy tissue

Question 57

What is liquefactive necrosis?

Answer 57

digetsion of cells and tissue due to proteolytic activity with loss of structure

Question 58

What are the subtypes of liquefactive necrosis?

Answer 58

caseous and fat

Question 59

What is caseous necrosis?

Answer 59

necrosis due to myobacterial and fungal infections

Question 60

What is the appearance of caseous necrosis?

Answer 60

cheesy, white

Question 61

When does fat necrosis occur?

Answer 61

following pancreatic injury and realease of pancreatic enzymes

Question 62

Lipase digests triglycerides of adjacent what?

Answer 62

adipocytes release of fatty acids

Question 63

What do fatty acids combine with to form soaps?

Answer 63

extracellular Ca+

Question 64

What is the appearance of fat necrosis?

Answer 64

chalky white

Question 65

What are the stimuli resulting in cell injury?

Answer 65

* oxygen deprivation * chemical and physical agents * infectious agents * immunologic reactions * genetic defects * nutritional imbalances * aging

Question 66

What are the biochemical mechanisms affected in injury?

Answer 66

1. depletion of ATP 2. generation of reactive O2 species 3. defects in membrane permeability 4. increased intracellular/loss of Ca 5. mitochondrial damage

Question 67

Proteolysis during ischemia produces what oxidase?

Answer 67

xanthine

Question 68

Xanthine oxidase can act on purines to produce what?

Answer 68

uric acid & superoxide anion

Question 69

How is the CCl3 radical formed?

Answer 69

when CCl4 is acted upon by P450 oxidases

Question 70

How is a free radical injury prevented?

Answer 70

* cellular antioxidant (vitamins E&A) * sequestration of molecules * intracellular enzymes

Question 71

What is Carpal tunnel syndrome?

Answer 71

compression of median nerve

Question 72

What is Tarsal tunnel syndrome?

Answer 72

compression of tibial nerve

Question 73

What is Variant tarsal tunnel syndrome?

Answer 73

compression of deep peroneal nerve

Question 74

In the case study, what was wrong with the ballet dancer?

Answer 74

* bilateral anterior tarsal tunnel syndrome variant * extensor hallucis bervis muscle hypertrophy