Cell Injury Flashcards
1
Q
CELL INJURY
-Cellular injury occurs when_______
A
a stress exceeds the cell’s ability to adapt.
2
Q
Slowly developing ischemia (e.g renal artery ________) results in ______
A
atherosclerosis
atrophy
3
Q
acute ischemia (e.g., renal artery ____) results in ____.
A
embolus
injury
4
Q
Neurons are highly resistant to ischemic injury
T/F
A
F
susceptible
5
Q
skeletal muscle is relatively more resistant to ischemic injury
T/F
A
T
6
Q
CAUSES OF CELL INJURY
Mention 5
A
inflammation
-hypoxia
-trauma
-nutritional deficiency or excess
-genetic mutation
7
Q
HYPOXIA
-is the ______
A
Inadequate oxygenation of tissue
8
Q
Normally, O2 diffuses (up or down?? a gradient from the atmosphere to the ___, to _____, and into the _________, where it attaches to heme groups
A
Down
alveoli
Plasma
red blood cells (RBCs)
9
Q
In hypoxia, there is decreased synthesis of ______
A
adenosine triphosphate (ATP).
10
Q
Causes of Hypoxia
Mention 3
A
ischemia
-hemoglobin related abnormalities
-Hypoxemia
11
Q
Ischemia
-is the _________ or ________
Consequences of ischemia
(1) _____
(2)______
(3)_____
A
decreased arterial blood flow to tissue or venous outflow of blood from tissue.
Atrophy
Infarction of tissue
Organ dysfunction
12
Q
(1) Atrophy ( ________ )
(2) Infarction of tissue (_______)
A
reduction in cell/tissue mass
localized area of tissue necrosis
13
Q
Hypoxemia
-is the __________
A
decrease in Pao2 measured in an arterial blood gas
14
Q
Normal Pao2(oxygen in plasma) depends on
*percent O2 in _____
*_______
*______
*diffusion of O2 from the alveoli into the ______
A
inspired air
Ventilation
Perfusion
pulmonary capillaries
15
Q
Ventilation refers to ______
*Perfusion refers to _____
A
how much air is in alveoli
how much blood gets to lungs
16
Q
Causes of Hypoxemia
-issue with Percent O2 in inspired air e.g ______
-issue with Ventilation e.g ________
-Respiratory acidosis: defined as ________
-Diffusion defect: is the decreased diffusion of O2 through the alveolar capillary interface into the pulmonary capillaries. Examples— _______,______
A
high altitude breathing
Respiratory distress syndrome
retention of CO2 in the lungs
interstitial fibrosis, pulmonary edema
17
Q
Hemoglobin (Hb) related abnormalities
1) ______
2)______
A
Anemia
Carbon monoxide (CO) poisoning
18
Q
Anemia
-is the ________
A
decrease in Hb concentration
19
Q
Causes of anemia include
Decreased production of Hb (e.g., _______)
-causes of anaemia include Increased destruction of RBCs (e.g., ________)
-causes of Anaemia include Decreased production of RBCs (e.g., _____)
-causes of Anaemia include Increased sequestration of RBCs (e.g., ______
A
iron deficiency
hereditary spherocytosis
aplastic anemia
splenomegaly)
20
Q
In Carbon monoxide (CO) poisoning
-Sao2 is __creased
A
De
21
Q
-CO binds hemoglobin more avidly than oxygen
T/F
A
T
22
Q
Classic finding from carbon monoxide poisoning is ______ appearance of skin.
Early sign of exposure is ______
significant exposure leads to _____ and ___
A
cherry-red
headache
coma and death.
23
Q
Clinical findings in HYPOXIA
Mention 4
A
Cyanosis
-Confusion
-Cognitive impairment
-Lethargy
24
Q
TYPES OF CELL INJURY
_____ and ____
A
Reversible and non-reversible
25
Cyanosis
??
bluish discoloration of skin and mucous membranes
26
the characteristic feature of reversible cell injury is _______
the characteristic feature of irreversible cell injury is _____
cell swelling
cell membrane damage
27
In reversible cell injury
-ATP production is ??
-protein synthesis is ??
Reduced
Reduced
28
In reversible cell injury
Which channels or pumps are compromised??
Calcium channel and Na/K pump
29
Ribosomal detachment occurs in ____ stage of cell injury
Reversible
30
Mitochondrial swelling occurs in ____ stage of cell injury
Reversible
31
There are no plasma membrane changes in reversible cell injury stage
T/F
F
There is blebbing
32
What nuclear changes are associated with reversible cell injury
Chromatin clumping
33
Myelin figures are mainly associated with what stage of cell injury
Reversible
34
What are myelin figures
Aggregation of peroxidized lipids of the cell membrane
35
Breakdown of cell membrane is associated with what stage of cell injury
Irreversible
36
Influx of _____ activates the degradative enzymes in the cell
This is a characteristic of _____ stage of cell injury
Calcium ion
Irreversible
37
Abnormal increase in ATP levels and production in irreversible cell injury stage
T/F
F
38
Rupture of lysosomes occurs in _____ cell injury stage
Irreversible
39
Steps of nuclear destruction
List them
Pyknosis
Karyorrhexis
Karyolysis
40
Pyknosis - _______
Karyorrhexis- ______
Karyolysis - _______
Nuclear condensation
Nuclear fragmentation
Nuclear dissolution
41
Presence of amorphous inclusions in the mitochondria is associated with ______ cell injury stage
reversible
42
Cell injury occurs at the limit of _____.
adaptation
43
A cell’s ability to adapt depends on:
the ______________
as well as the ________
nature of the stress (duration and aetiology)
nature of
the cell/tissue (brain/colon cells in hypoxia)
44
Intracellular accumulations: The _______ of _______ may persist in some cells
after effects
reversible injury
45
Reversible injury:__________ (within or outside?) a cell’s tolerance limit
Mild to moderate stressors
Within
46
Irreversible injury: ______ and _____ stressors
Persistent and severe
47
In reversible injury
offending stimulus is _______
Key features:
• Reduced _______
• Changes in ion concentration
lead to _________ and ______
removed
oxidative phosphorylation
water influx and cell swelling
48
In irreversible injury
Damage has reached point of _____
E.g. is heart muscle. With increased hemodynamic load , _______ results and it is (reversible or irreversible?).
Persistently increased load leads to ________
no return.
hypertrophy; reversible
point of no return (cell death).
49
Causes of cell injury
1._______/______
2.______ agents e.g. _______,________ etc
3._______ agents/drugs: Eg ___,____,____
4.______ agents:____,____,_____
Hypoxia /Ischaemia
Physical; mechanical trauma, extreme heat/cold
Chemical; Acid, insecticides, narcotics
infectious; Bacteria, viruses, fungi
50
Hypoxia (reduced _______)
Ischaemia (reduced ______)
O2 supply
blood flow
51
Which is most common between hypoxia and ischemia
Ischemia
52
Hypoxia (reduced O2 supply) / Ischaemia (reduced blood flow) -
•________ failure
• Reduced ______
• Reduced _____ capacity of blood (e.g. carbon monoxide, sickle cells)
•______ loss
Cardiorespiratory
blood flow
O2 carrying
Blood
53
causes of cell injury
4._______ agents
5._____ derangement
6.________ imbalances
Immunologic
Genetic
Nutritional
54
Genetic derangements :
•_________ abnormalities e.g ______
• Susceptibility to _____ agents
• Deficiency of ________ (e.g. inborn errors of metabolism)
Chromosomal; Down’s syndrome
injurious
functional proteins
55
Which can survive hypoxia longer
Skeletal or cardiac muscle
Skeletal
56
ATP depletion resulting from cell injury
Mechanisms
• Most commonly results from
———— , ______ damage or ______
• The cell may resort to ______
ischaemia/hypoxia, mitochondrial, toxins
anaerobic glycolysis
57
Consequences of ATP depletion in a cell
• Defective ___________ pump; ___ gain, ______
• Anaerobic glycolysis, reduction in
________, _______ , reduced IC enzyme activity
• Failure of __ pump, ____ (influx or efflux?) , ________ stimulation
•_______ synthesis disruption
•________ proteins
NA/K ATP-dependent ; H20; swelling
glycogen stores
lactic acidosis
Ca; Ca influx
enzyme
Protein
Misfolded
58
Mitochondrial damage resulting from cell injury
Mechanism
• Damaged by increased ________,______,_____
Also,
• Toxins
• Genetic mutations
cytosolic Ca, ROS, hypoxia
59
Consequences of mitochondrial damage
• Formation of _____, failure of
__________, ____ depletion
• Increased ______ formation
• Leakage of _______, & ______ , stimulation of ________
MPTP; oxidative phosphorylation
ATP
ROS
cytochromec & caspases
apoptosis
60
Calcium influx resulting from cell injury
Consequence
•______, failure of ____ generation
• Activate ________ (______ damage), _____ (_______ damage), _______ (fragment ___, chromatin), ATPases (ATP
depletion)
MPTP
ATP
phospholipases; membrane
protease; cytoskeletal
endonuclease; DNA; chromatin
61
Reactive oxygen species
Mechanism
• Generation: _________ during normal metabolic process, absorption of ______,
_______, breakdown of ______
• Removal: _________,
__________, enzymes eg
________, SOD etc,
Oxidation/reduction
radiant energy
leukocytes; drugs
spontaneous decay; antioxidants (Vit E,A)
catalase
62
Consequences of reactive oxygen species
• Lipid _______, _____
damage
•________ of proteins, ______ enzymes
•_____________ breaks.
peroxidation
membrane
Oxidative modification
damaged
Single & double strand DNA
63
Mechanism of defect in membrane permeability
•______
• Decreased _______ synthesis (from ___ depletion)
• Increased _____ breakdown (from
__________ )
• _______ damage by ______
ROS
phospholipid ; ATP
phospholipid; phospholipases
Cytoskeletal; proteases
64
Consequences of defect in membrane permeability
• Mitochondrial membrane:
reduced ____ generation
• Plasma membrane: _________
• Lysosomal membrane: ______ of the cell
ATP
Cell content leakage
Enzymatic digestion
65
Ischemic-hypoxic injury
Decreased generation of cellular ____.
• Failure of __ pump, influx of _____
•___ influx/release, enzyme activation
• Reduced ______ synthesis
• Reduced cell _____
• Destruction of ______, membrane _____
ATP
Na; H20; Ca
protein
glycogen
cytoskeleton
blebs
66
Ischemic-hypoxic injury
1) ________,_________,_______ cells are solely dependent on
aerobic respiration and are rapidly susceptible to damage.
CNS neurons, myocardial and kidney
67
Ischemic-hypoxic injury
2. Due to low oxygen supply and subsequent anaerobic respiration, there
is increased _____ accumulation in the cell (______) which leads to a (rise or fall?) in intracellular pH and clumping of _______
lactic acid
lactic acidosis; fall
nuclear chromatin
68
Ischemic-hypoxic injury
3. Reduced ATP generation also affects the integrity of the _____ There is reduced synthesis of ____ which are useful for membrane repair, impaired function of ______ pump ( _______ ) and impaired ___ pump resulting in excess ___ influx
plasma membrane.
phospholipids
NA-K ATPase; hydropic swelling
Ca; Ca
69
Irreversible injury is associated with:
• Severe ______
• Extensively damaged _____
•________ swelling/damage
mitochondrial swelling
plasma membranes
Lysosomal
70
Hypothermic therapy
• Mechanism: Reduction of temperature leads to reduction in ______, production of ______ and _______.
• Current meta-analyses: (useful or Not useful?) , infact may cause _______
cellular metabolic demands
free radicals
host immune response
Not useful; more mortality.
71
Ischemia-Reperfusion injury
•Occurs as a result of ______ of _____ to _____ tissue.
• It may result in additional __________.
• Commonly seen in tissue damage ff M.I. & ________
restoration; blood flow; ischaemic
death of reversibly damaged cells
cerebral infarction
72
Ischemia-Reperfusion injury
Mechanisms:
• Oxidative stress: Increased ____ generation
• Intracellular ___ overload
• Increased _________
• Activation of ________ by binding Ab e.g. ____
ROS
Ca
inflammation
complement system
IgM
73
Chemicals induce injury by:
•________
• Conversion of __________
Direct cytotoxicity
chemicals to reactive metabolites
74
Direct cytotoxicity:
• Mostly affects cells which are ____________ of such
chemicals E.g. HgCl, Cyanide, Chemotherapy drugs
• HgCl poisoning: Hg binds -___ grp of cell membrane proteins, increased
__________. Mostly affects cells of the _____
• Cyanide: Targets _____________, reduction in _____ generation
directly involved in the metabolism
SH; membrane permeability
GIT, Kidney
mitochondrial cytochrome oxidase
ATP
75
Conversion to reactive metabolites:
• The chemical agent is metabolized to yield the ____ which interacts
with the target cells. Usually by _____ in ___ of ____.
• Mechanism: Formation of _______
• E.g. is _______(CCl4), ________.
toxin
cytochrome P450
sER; liver
free radicals
Carbon tetrachloride
Acetaminophen
76
Microscopic features of reversible injury
Microscopic
•——— secondary to failure of energy dependent ion pumps responsible for maintaining homeostasis
• Fatty change. Seen in _____ and ———— cells ff hypoxic/toxic injury
Ultrastructural
• Plasma membrane alterations
e.g. ________,________,______
• Mitochondrial changes e.g._______
•_____ dilation
• Nuclear alterations
Cellular swelling; hepatocytes and myocardial
blebbing. Blunting, loss of microvilli
amorphous densities
Endoplasmic reticulum
77
The point of transition from reversible to irreversible injury is m clear
cut.
T/F
F
It’s not
78
Pathogenesis of irreversible injury
1) Membrane damage: excess accumulation of ____ in __________ due to ____ influx disabling its function
2. Ca ion influx : leads to phospholipase activation that ________ and destroy _____
3. Intracellular proteases are also activated and leads to destruction of
________
4. Activated endonucleases damage the ________.
5. Lysosomal membranes are compromised leading to leakage of their _______ (e.g. hydrolase, DNAase etc) digest cellular components
Ca; mitochondria; Ca ion
degrades membrane phospholipids ; cell membrane
cytoskeletal proteins
DNA in the nucleus
hydrolytic enzymes
79
Damage of the nucleus in irreversible damage occur in 3 forms: ____,____,_____
Pyknosis, karryohexis, karyolysis
80
Enzymes released from the cell can be detected by laboratory assays.
Examples include:
•________,_____ (myocardial infarction)
•______,______ (Acute pancreatitis)
•_________/________ (hepatocyte damage)
Cardiac troponins, CK-MB
Amylase, Lipase
Aspartate/Alanine aminotransferase
81
Histology of reversible injury
Two major changes:
•_____
•______
• Others include increased ______ (_____ change)
Cellular swelling
Fatty change
eosinophilia
hyaline
82
• Cellular swelling : results from failure of ____ in the _______ leading to ion and fluid imbalance.
• Fatty change : seen most especially in cells dependent on _______ e.g.
________,_________ cells.______ are seen within the cytoplasm
pumps
plasma membrane
lipid metabolism
hepatocytes, myocardial
Vacuoles
83
the first manifestation of cell injury is usually _____
Cellular swelling
84
Classic physical find in a patient with CO poisoning?
Cherry red appearance of skin
85
Early sign of exposure to CO poisoning is ______?
Headache
86
MPTP
Mitochondrial permeability transition pore
87
The response of a cell to stress or injurious stimuli includes
Intracellular accumulation
T/F
T
88
The response of a cell to stress or injurious stimuli includes
Pathologic calcification
T/F
F
89
The response of a cell to stress or injurious stimuli includes
Neoplasia
T/F
T
90
Cellular nonlethal injury is sometimes
called ________ or _______ .
hydropic change or vacuolar degeneration
91
The CYTOPLASM of injured cells appears ______ and ______ when stained
with hematoxylin and eosin (H&E) due to loss of cytoplasmic RNA, which binds the blue hematoxylin dye.
red (eosinophilc)
92
The eosinophilia becomes (more or less?) pronounced with progression toward necrosis.
More
93
A breakdown product of DNA that commonly leaks out of the cell into the ecf is _______
Uric acid
94
In injured cells
Cardiac muscle cells, for example, express cardiac-specific variants of the contractile protein _____, while bile duct epithelium expresses a specific isoform of the enzyme ________ and hepatocytes express _________
troponin
alkaline phosphatase
transaminases
95
Cardiac-specific troponins can be detected in the blood as early as _____ after myocardial cell necrosis
2 hours
96
Necrotic cells show increased CYTOPLASMIC _____ in H&E stains, attributable in part to the loss of _______ and in part to accumulation of denatured cytoplasmic _____ (which bind the red dye eosin).
eosinophilia
cytoplasmic RNA
proteins
97
In coagulative necrosis ,
Presumably, the injury denatures not only _____ but also ___ and so blocks the proteolysis of the dead cells; as a result, intensely ___philic cells with indistinct or ____ nuclei may persist for days or weeks
structural proteins
enzymes
eosino; reddish
98
In liquefactive necrosis
The necrotic material is frequently ________ (color) because of the presence of leukocytes and is called pus.
creamy yellow
99
Ischemia-reperfusion injury:
Refers to the exacerbation of existing injury upon restoration of blood flow
to a tissue
T/F
T
100
Ischemia-reperfusion injury Contributes to tissue damage following reperfusion in ______ infarction and ______ infarction
myocardial
cerebral
101
Ischemia-reperfusion injury
Inflammation is not a contributory mechanism
T/F
F
It is
102
Ischemia-reperfusion injury
Involves decreased generation of free radicals
T/F
F
Increased
103
Most common cause of budd chiari syndrome is ???
Polycythemia Vera
104
Classic finding in methemoglobinemia is ________________ And the patient would be _________
Chocolate-colored blood
Cyanotic
105
Treatment of methemoglobinemia
It (reduces Or oxidizes?) iron from —— to ____
IV methylene blue
Reduce
3+ to 2+
