Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pathology Midterm > (part 1) Cell injury - Lecture 2 > Flashcards

(part 1) Cell injury - Lecture 2 Flashcards

1
Q

what are ROS?

A

partially reduced oxygen derivatives

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

name 6 ROS

A

hydrogen peroxide
superoxide anion
hydroxyl radical
peroxynitrile
lipid peroxide radicals
hydrochlorous acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

where can O2 be converted to O2-?

A

in the cytosol or mitochondria

if in the cytosol, O2- is reduced to H2O2 by superoxide dismutase (in the cytosol) and finally reduced to WATER

if in the mitochondria, O2- is reduced to H2O2 by mitochondrial SOD and then converted to H2O by glutathione peroxidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

cytosolic H2O2 can be detoxified to H2O by…

A

catalse enzyme in peroxisomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

where does the respiratory burst occur?

A

in neutrophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

explain the respiratory burst

A
  1. NADPH oxidase reduces O2 to O2- and SOD converts O2- to H2O2
  2. OCl- and OH. are produced from H2O2 by myeloperoxidase. O2- and H202 activate granules in neutrophil to release degradative enzymes
  3. bacteria are engulfed by neutrophils and destroyed by ROS nd degradative enzymes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

name 6 factors leading to necrotic cells irreversible changes

A

-decreased ATP
-mitochondrial damage
-entry of calcium
-increased ROS
-membrane damage
-protein misfolding and DNA damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

how does protein folding and DNA damage lead to necrotic cells and irreversible changes?

A

pro apoptotic proteins are activated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how does ischemia injury lead to cell death

A

delivery of O2 decreases and so does energy and nutrients like glucose and fatty acids.

anaerobic glycolysis occurs which leads to lactic acidosis and decreased intracellular pH

pumps are distorted leading to ionic imbalance in the cell

PLA2 (phospholipase A2) is activated and proteases disrupt plasma membrane and cytoskeleton. calcium also activates proteases that attack cytoskeleton and attachment to membrane

-cell dies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what happens when blood flow is restored to an ischemic area?

A

can lead to exacerbated (worse) and accelerated injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is ischemia reperfusion injury

A

injury that occurs when blood flow to an ischemic area is restored

-may contribute to tissue damage in myocardial infarctions and cerebral infarctions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

explain why the injury can be made worse when blood flow is restored to an ischemic area

A

-increases the generation of ROS

-inflammation may increase because of influx of WBC and plasma proteins

-some antibodies deposit in ischemic tissues and when blood flow is restored, complement proteins bind to the deposited antibodies and activate them - making injury worse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

REACTIVE OXYGEN SPECIES

generated by ______
produced by _____
made by _____

A

generated by XANTHINE OXIDASE

produced by NEUTROPHILS

made by MITOCHONDRIA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How is ionic composition altered by ischemic reperfusion

A

rapid pH normalization when the pH was just very acidid

increased Na and Ca

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

true or false

there are multiple reactions that produce ROS

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

true or false

different oxidative radicals cannot be transformed from 1 to another

A

false - they can

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

name 3 detoxifying enzymes and what they detoxify

A

SODs = superoxide dismutases
-inactivate O2-

catalase = in peroxisomes. inactivate H2O2

GPX = glutathione peroxidase
-catalyzes H2O2 and lipid peroxidase reduction in mitochondria in cytosol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what enzyme produces the superoxide anion?

A

NADPH oxidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is lipid peroxidation

A

unsaturated fatty acids converted to lipid radicals by OH. which reacts with O2 to form lipid peroxides
LOOH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

name 4 “scavengers of ROS.”
what is their purpose?

A

inactivates reactive oxygen species or products of their destruction

-vitamin e
-vitamin c
-retinoids
-no.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

explain how vitamin E is a scavenger of ROS

A

it’s fat soluble and thus protects membranes from lipid peroxidation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what causes the formation of toxic protein aggregates

A

-normal proteins can become damaged by exposure to ROS and become misfolded

-genetic mutations or translational errors can result in misfolded proteins

-the hydrophobic regions of these molecules (usually hidden in the core) are polyubiquinated and can have hydrophobic and ionic reactions and aggregate, leading to degradation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

explain a1-antitrypsin deficiency

A

mutations in a1-antitrypsin gene in the liver. causes liver production of an insoluble protein that is not exported and accumulates in HEPATOCYTES

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Where do lewy bodies occur

A

in neurons of substantia nigra in parkinsons due to accumulation of abnormal proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what are mallory bodies

A

hepatocellular inlusions in alcoholic liver injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what is prion diseases

A

normal alpha helical structure becomes a beta pleated sheet. – intracellular accumulation of abnormal proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what are the 2 types of cell death

A

necrosis and apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

define necrosis

A

the death of a group of cells in a living tissue and complete lysis of these cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

as mentioned, necrosis is the death of a group of cells in a living tissue by complete lysis of these cells.

what types of lysis can occur?

A

autolysis and heterolysis

autolysis = lysis by the cell’s own enzymes

heterolysis = lysis by enzymes from recruited inflammatory cells (like neutrophils and macrophages)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

NECROSIS IS ASSOCIATED WITH _______

A

INFLAMMATION

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

necrosis is the major pathway of cell death resulting from what occurrences?

A

ischemia
exposure to toxins
infections
trauma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

what can you say about necrotic cells

A

they are unable to retain the integrity of their membrane and their contents often LEAK OUT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

what are some microscopic findings in necrotic cells

A

loss of basophilia (blue staining)

when enzymes have digested the organelles, cytoplasm becomes vacuolated and appears “moth eaten”

dead cells may be replaced by MYELIN (large phospholipid masses) that are derived from damaged cell membranes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

cell death is a result of ____ injury

A

IRREVERISBLE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

what nuclear changes occur as a result of coagulative necrosis? define them

A

pyknosis = chromatin continues to clump and nucleus becomes small and deeply basophilic (blue)

karyorrhexis = pyknotic nucleus fragments into many small pieces and is scattered in cytoplasm

karyolysis = pyknotic nucleus may become extruded from the cell or slowly lose chromatin stain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

irreversible injury is marked by what 4 things

A

-nuclear changes
-severe mitochondrial vacuolization
-extensive damage to plasma membrane
-leakage of lysosomal enzymes into the cytoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

explain the morphology of coagulative necrosis

A

the cells are dead, but they basic tissue architecture remains for several days

38
Q

what is liquefactive necrosis

A

dead cells are digested (liquefied) by enzymes of recruited WBC

39
Q

name 6 types of necrosis

A

coagulative
liquefactive
gangrenous
caseous
fat
fibrinoid

40
Q

in coagulative necrosis, the architecture of the dead tissues is preserved for several days.

how

A

the injury denatures proteins and enzymes which blocks the proteolysis of the dead cells

41
Q

ultimately, in coagulative necrosis, how are necrotic cells eventually removed?

A

by phagocytosis of cellular debris by incoming WBC

42
Q

in coagulative necrosis, what cells may persist for weeks?

A

eosinophilic, anucleate cells
(therefore, pic of coagulative necrosis would have little to no nuclei)

43
Q

explain liquefactive necrosis

A

often occurs in pyogenic bacterial infections bc inflammatory cells are recruited and the enzymes of leukocytes digest (LIQUEFY) the tissue

44
Q

_____ often brings about liquefactive necrosis

A

hypoxic death of cells within the CNS

45
Q

explain the morphology of liquefactive necrosis

A

dead cells are completely digested, resulting in transformation of the tissue to a liquid, viscous mass - abscess. the abscess cavity is filled with polymorphonuclear leukocytes.

(if the process was initiated by acute inflammation, the material is PUS)

46
Q

explain the polymorphonuclear leukocytes

A

result from acute inflammatory reaction – have hydrolases that are capable of complete digesting in dead cells

-occurs in bacterial infection

47
Q

gangrenous necrosis is a coagulative ISCHEMIC necrosis + _______

A

bacterial infection

48
Q

gangrenous necrosis is a coagulative necrosis involving….

A

MULTIPLE TISSUE LAYERS

49
Q

gangrenous necrosis may be…..

A

dry
wet
gas (in case of clostridia infectioN)

50
Q

name 3 potential final outcomes of necrosis

A

-resolution - restoring normal tissue function and structure

-organization - replacement of necrotic tissue by granulation tissue and fibrosis

-calcification - DYSTROPHIC calcification. precipitation of calcium salts

51
Q

necrosis may result in what kind of calcification

A

dystrophic

52
Q

what is programmed cell death

A

apoptosis

53
Q

true or false

apoptosis is a passive process that does not require energy

A

FALSE

active process that requires energy

54
Q

inhibition of apoptosis can result in what 3 things

A

cancer progression
autoimmune disease
inflammatory disease

55
Q

true or false

in necrosis, the membrane is lost but in apoptosis it is not

A

TRUE

56
Q

HYPERACTIVE apoptosis can lead to what

A

neurodegenerative diseases
bone marrow aplasia
skin disease

57
Q

while necrosis is always a ______ process, apoptosis……

A

necrosis is always a PATHOLOGICAL PROCESS

apoptosis serves many normal functions and is NOT necessarily associated with pathological cell injury

58
Q

programmed cell death is also a ____ mechanism to eliminate:

A

self defense mechanism to eliminate

-cells infected with pathogens
-cells carrying genomic alteration

59
Q

there are ___(how many) pathways for the initiation of apoptosis. name them

A

2 pathways:

intrinsic (mitochondrial)
extrinsic (death receptors)

60
Q

mutations in _____ are considered to be important in tumor development and progression

A

p53

61
Q

excessive apoptosis leads to what kind of disease?

A

neurodegenerative – intracellular proteins accumulate within neurons and trigger apoptosis

62
Q

differentiate between the type of control of apoptosis vs necrosis

A

in apoptosis, control is genetic

in necrosis, there is no gene control

63
Q

differentiate between the “lyses of cells” between apoptosis vs necrosis

A

in apoptosis, the cells do not lyse but only reduce in size

in necrosis, the complete lyses of many cells occur (release of contents)

64
Q

differentiate between the type of stimuli between apoptosis vs necrosis

A

the type of stimuli for necrosis is pathologic stimuli ONLY

the type of stimuli for apoptosis is physiological or pathologic stimuli

65
Q

differentiate between the number of cells affected between apoptosis vs necrosis

A

single or small groups of cells are affected in apoptosis

in necrosis, large groups of cells are affected

66
Q

differentiate between the tissue reaction of apoptosis vs necrosis

A

in apoptosis, there is NO inflammation around the dead tissue

in necrosis, there are inflammatory cells around the dead tissue. inflammation is induced

67
Q

________ viruses often inhibit apoptosis

A

oncogenic

HPV inactivates p53 which increases chance that infected cells will progress to cancer

68
Q

explain how the intrinsic pathway of apoptosis is INDUCED

A

intrinsic stress alters the mitochondrial membrane potential, increases ROS, and Ca, and decreases pH.

this causes MPTP pore to open and breaks the MOM (mitochondrial outer matrix)

69
Q

explain what happens in intrinsic apoptosis after the MOM is broken

A

molecules attached to the inner membrane or in the intermembranous space become detached and exit through the outer membrane holes. (SMACS, Cyt C, AIF)

these molecules are what activate the caspases that cause apoptosis

70
Q

name 3 proapoptotic proteins

A

cytochrome c
SMACs
AIF

71
Q

how do the proapoptotic proteins leave the mitochondria?

A

proapoptotic Bak/Bax with antiapoptotic Bcl-2 family – normally reside at the outer membrane. this association prevents apoptotic activity.

when BH3 only members of the Bcl-2 clan are activated, Bak/bax proteins are freed and form a PORE (MAC) in the outer mitochondrial membrane where the proapoptotic proteins can exit

72
Q

once the proapoptotic proteins (Cyt C, SMAC, AIF) enter the cytosol via the MAC pore, what happens

A

these proteins facilitate the activation of the CASPASE CASCADE

73
Q

cytochrome c is a pro apoptotic protein. what 2 things does it activate?

A

Apaf 1 and caspase 9

74
Q

what is the:
-initiator
-executioner
-inhibitor

of the intrinsic apoptotic pathway

A

initiator = caspase 9

executioner = caspase 3

inhibitor = IAPs – bind caspases

75
Q

what activates caspase 3? (intrinsic apoptosis)

A

caspase 3 is the executioner and is activated by caspase 9

76
Q

what happens when caspase 3 is activated by caspase 9

A

procaspase 3 becomes caspase 3 and binds to IAPS.
Smac/diablo binds IAPs and forces them to liberate the bound caspases, causing apoptosis

77
Q

activated p53 goes where?
how is it activated?

A

to the nucleus
activated by stress/DNA damage

78
Q

when activated p53 goes to the nucleus, what does it do?

A

if the DNA damage is irrepairable, p53 promotes transcription of proapoptotic proteins which then migrate to the mitochondria

p53 also DECREASES the transcription of prosurvival (antiapoptotic) Bcl-2

the balance is altered so that proapoptotic outweighs anti because p53 is bound to Bcl-2 family.

apoptosis occurs

79
Q

the death receptor (extrinsic) apoptotic pathway is initiated by what

A

ligand binding to death receptors (members of TNF receptor family)

ligand could be TNFa

80
Q

the extrinsic apoptotic pathway is responsible for the elimination of what

A

self reactive lymphocytes and damage by cytotoxic T lymphocytes

81
Q

explain the extrinsic pathway of apoptosis

A

ligans (TNFa is example) binds to death receptor to form DISC (death induced signaling complex) which binds and activates procaspase-8 to caspase-8

caspase 8 activates procaspases 3,6, and 7 to caspases 3,6, and 7 (EXECUTIONERS)

caspase 3 activates endonucleases

caspase 6 and 7 cleaves nuclear and cytoskeleton proteins, respectively

82
Q

explain how the intrinsic and extrinsic pathways of apoptosis overlap

A

caspase 8 (from extrinsic pathway) activates Bid which yields a truncated derivative - tBid which transports to the mitochndria ACTIVATES THE INTRINSIC PATHWAY

83
Q

what is necroptosis

A

a mix of apoptosis and necrosis.

starts as extrinsic apoptosis and ends with loss of integrity of the plasma membrane and necroptosis

84
Q

what is anoikis

A

when the cell’s integrins lose attachment to the ECM, the survival signals are eliminated and apoptosis proceeds via death receptor (extrinsic) pathway AND intrisnic because their pathways are no longer blocked

85
Q

under normal conditions…..

A

alpha and beta integrins of cells are bound to the ECM. these molecules activate survival signals and block both apoptotic signaling pathways. give survival signal and the cell survives

86
Q

________ can be caused by granzymes of cytotoxic leukocytes (T cell)

A

a type of apoptosis that leads to nuclear fragmentation

87
Q

what is a type of apoptosis caused by injurious agents - both infective and irritative

A

pyroptosis

88
Q

explain how pyroptosis works

A

cell is exposed to injurious agents. inflammasomes recognize them. inflammasomes contain procaspase 1 and when inflammasome linked receptors are activated, procaspase 1 is converted to its active form - caspase 1 which forms pores in the plasma membrane, damages the nucelus, etc

89
Q

explain netosis

A

neutrophils recognize pathogens and autophagy and NADPH oxidase are activated and NADPH oxidase produces ROS.

chromatin disperses and cytoplasmic granule membranes disintegrate. antimicrobial molecules adsorb to the condensed chromatin and a CHROMATIN NET is released.

the reactive oxygen species are concentrated within the trap so damage is limited. pathogens are trapped and destroyed in the net

90
Q
A

Pathology Midterm (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions