Pathology Study Guide (Cell Injury and Death)

Question 1

in considering the cellular response to injury, what cellular changes are reversible?

Answer 1

dilation of organelles, ribosome disaggregation, blebbing

Question 2

in considering the cellular response to injury, what cellular changes are irreversible

Answer 2

mitochondrial swelling and rupture, disruption of the integrity of the cellular membrane

Question 3

what growth factors are involved in hypertrophy

Answer 3

TGF-beta, IGF-1 (insulin-like growth factor), fibroblast growth factor

Question 4

what vasoactive substances are involved in hypertrophy

Answer 4

alpha adrenergic agonists, endothelin-1, angiotensin II

Question 5

what pathway is important for muscle hypertrophy

Answer 5

phosphoinositide-3 kinase/Akt signalling pathway

Question 6

give examples for hyperplasia, hypertrophy, atrophy, and metaplasia

Answer 6

hyperplasia (breast tissue for lactation, endometrium during menses, callouses); hypertrophy (muscle, uterus during pregnancy); atrophy (denervation or disuse atrophy of muscle); metaplasia (ciliated columnar epithelium of lung of smoker changing to squamous cell)

Question 7

in what ways does the hypertrophic heart resemble the fetal heart

Answer 7

during hypertrophy, the heart produces the beta isoform of myosin heavy chain (instead of the adult alpha isoform), ANF (atrial natriuretic factor) which is upregulated in the fetus, but downregulated in adults is reupregulated in cardiac hypertrophy

Question 8

name two kinds of physiologic hyperplasia (hint: what causes the hyperplasia/ what role does it serve)

Answer 8

hormonal hyperplasia and compensatory hyperplasia

Question 9

how is hyperplasia different from cancer

Answer 9

cancer results from uncontrolled cell growth while hyperplasia is excessive growth resulting from a controlled process (i.e. hormones or signalling pathways)

Question 10

coagulative necrosis can occur in all solid organs except ________

Answer 10

the brain

Question 11

in coagulative necrosis, in the days immediately following, the tissue architecture is _______(destroyed or preserved)

Answer 11

preserved

Question 12

liquefactive necrosis occurs in the _____ or as a result of ________

Answer 12

occurs in the CNS or as a result of focal bacterial or fungal infection

Question 13

gangrenous necrosis is:

Answer 13

necrosis (coagulative) of the limb involving multiple tissues; when there is an element of liquefactive necrosis it is called wet gangrene

Question 14

caseous necrosis often occurs due to ______ and is characterized by cheesy, white/yellow, bordered areas of necrosis known as _________

Answer 14

TB infection, granuloma

Question 15

fat necrosis is often seen in the _________ (part of the body) due to leakage of ________

Answer 15

peritoneum;

activated pancreatic lipases (that break down fat leading to chalky white saponified fat deposits)

Question 16

name three conditions that contribute to mitochondrial injury

Answer 16

1. increased ROS (reactive oxygen species)
2. increased intracellular Ca2+
3. oxygen deprivation

Question 17

explain the cell’s reaction to increased cytosolic Ca2+

Answer 17

1. increased phospholipase activity and protease activity break down the cell membrane and cytoskeleton
2. increased endonuclease activity breaks down DNA
3. increased ATPase activity lowers ATP reserves

Question 18

what molecule, released by damaged mitochondria, induces apoptosis

Answer 18

cytochrome c

Question 19

name three ways that ROS can be increased in the body

Answer 19

1. radiation (UV, x-ray)
2. exogenous chemicals (tetrachloride), Tylenol overdose (over-activity of P450)
3. release from leukocytes during inflammation

Question 20

name major antioxidant enzymes/ molecules

Answer 20

superoxide dimutase;
glutathione peroxidase (breaks down H2O2);
catalase (breaks down H2O2);
vitamin A, C, E and beta-carotene

Question 21

name the three main ways ROS cause damage (oxidative stress= damage due to build up of ROS)

Answer 21

1. peroxidation of lipids (breaking of double bonds) (this leads to more ROS)
2. damage DNA by reacting with thymine to form single strand breaks
3. cross-linking via sulfhydryl groups
4. polypeptide fragmentation

Question 22

does accumulation of damaged DNA and or misfolded proteins cause necrosis or apoptosis

Answer 22

apoptosis (via accumulation of p53)

Question 23

describe the “unfolded protein response”

and what happens if it fails

Answer 23

• increased production of chaperones that aid in folding
• decreased translation
• activation of ubiquitin-proteosome pathway for degredation of proteins
• ->caspases are recruited to initiate apoptosis if the unfolded protein response fails

Question 24

name the Fenton reaction (reactants and products)

Answer 24

Fe2+ (active) + H2O2 ==> Fe3+ (inactive) + 2 hydroxyl radicals

Question 25

what’s the difference between hypoxia and ischemia

Answer 25

hypoxia and ischemia both cause poor perfusion of oxygen to tissues; in hypoxia, this is due to poor O2 availability, in ischemia this is due to hindered blood flow; as a result, ischemic tissues also have reduced anaerobic capability because glycolytic reactants can’t get to the site

Question 26

why is inflammation associated with reperfusion injury

Answer 26

cytokines recruite neutrophils that release ROS; complement system can bind to deposited antibodies when blood flow resumes and initiate response

Question 27

list examples of physiologic apoptosis

Answer 27

• loss of hormonal maintenance,
• programmed death during embryogenesis, -destruction of unneeded cells in proliferating populations,
• elimination of self-reactive lymphocytes, -regular life cycle/ death of old cells no longer needed

Question 28

list examples of pathologic apoptosis

Answer 28

DNA damage, unfolded protein accumulation, viral infections, tumors, graft rejection

Question 29

describe the intrinsic pathway of apoptosis

Answer 29

in the absence of survival signals (i.e. growth factor), sensors (BH3-only proteins) are activated which antagonize anti-apoptotic molecules like bcl-2 and activate pro-apoptotic molecules like Bax and Bak, resulting in leakage of cytochrome c, leading to caspase activation => apoptosis

Question 30

describe the extrinsic pathway of apoptosis

Answer 30

ligand (Fas ligand) binds death receptor (TNFR1 and Fas) and death receptors cluster; clustered death receptors bind FADD (Fas associated death domain); caspase 8 is recruited and cleaved; caspase activation cascade initiates and results in apoptosis

Question 31

what is FLIP (in the context of apoptosis)

Answer 31

binds and inhibits caspase-8; produced by some viruses to avoid Fas-mediated apoptosis

Question 32

which caspases are executioner caspases and what do they do to execute apoptosis

Answer 32

caspase 3 and caspase 6; they cleave inhibitors of DNAases and degrade parts of the nuclear membrane

Question 33

what are apoptotic bodies and what is their fate

Answer 33

apoptotic bodies are small fragments of the cell that get phagocytized

Question 34

what categories of diseases are associated with too little apoptosis

Answer 34

1. cancer (p53 is the most common mutation)

2. autoimmune disease (inability to apoptose self-reactive cells)

Question 35

what categories of diseases are associated with inappropriate apoptosis

Answer 35

1. neurodegenerative diseases
2. ischemic injury
3. death of some viral infected cells