1.2 Cellular Adaptation, Injury and Death Flashcards
(105 cards)
1
Q
What is Hypoxia?
A
Deficiency of O2
Hypoxia refers to a state where there is a lack of oxygen in the tissues.
2
Q
What is Ischemia?
A
Reduced blood flow (deficiency of O2 & nutrients)
Ischemia often results from blocked arteries or veins.
3
Q
List some physical agents that can cause cell injury.
A
- Mechanical disruption
- Extremes of temperature
- Radiation
- Electric current
These agents can lead to significant cellular damage.
4
Q
What are some examples of infectious diseases that can cause cell injury?
A
- Viruses
- Bacteria
- Parasites
These pathogens can disrupt normal cellular functions.
5
Q
What are immunologic reactions?
A
Immunologic reactions against exogenous agents (Hypersensitivity reactions) or endogenous agents (Autoimmune disease)
These reactions can lead to tissue damage.
6
Q
What causes genetic derangements?
A
DNA alterations, inherited or acquired, producing dysfunctional proteins or proteins in insufficient quantities
Genetic derangements can severely impact cellular function.
7
Q
What are nutritional imbalances?
A
Over/under nutrition or imbalances of nutrients
Proper nutrition is vital for cell health and function.
8
Q
What factors determine the outcome of cell injury?
A
Nature, duration & severity of the injury & the type of tissue involved
Different cell types have varying abilities to withstand injury.
9
Q
Which cell type is highly sensitive to ischemia?
A
Neurons
Neurons are particularly susceptible to oxygen deprivation.
10
Q
What is the most common initiating mechanism of cell injury?
A
↓ ATP Synthesis due to reduced availability of O2
ATP depletion is critical for cell survival.
11
Q
What is hypoxemia?
A
↓ partial pressure of O2 in blood
Hypoxemia can result from decreased lung ventilation or diffusion.
12
Q
Fill in the blank: The loss of energy molecules (ATP) leads to a cascade of ______ events.
A
damaging
ATP depletion triggers various pathological processes.
13
Q
What occurs if the Na+ K+ pump fails?
A
Na+ enters cell & K+ escapes, leading to cellular swelling
This can result from ATP depletion.
14
Q
What causes cellular swelling to be reversible?
A
Occurs before significant damage to the membranes
Early intervention can prevent permanent injury.
15
Q
What leads to irreversible injury in cells?
A
Membrane damaging events
Sustained anaerobic glycolysis increases lactic acid and decreases pH.
16
Q
What is oxidative stress?
A
↑ production or ↓ neutralization of oxygen derived free radicals
Oxidative stress is implicated in various pathologies.
17
Q
What are free radicals?
A
Atoms or molecules with an unpaired electron
They are highly reactive and can damage cellular components.
18
Q
What are Reactive Oxygen Species (ROS)?
A
Oxygen derived free radicals including Superoxide radical, Hydrogen Peroxide, Hydroxyl radical
ROS are significant contributors to oxidative stress.
19
Q
True or False: Free radicals are produced only during pathological conditions.
A
False
They are also produced during normal respiration and metabolic reactions.
20
Q
What are antioxidants?
A
Free radical scavengers
They help neutralize free radicals to reduce cellular damage.
21
Q
What is the main free radical scavenger in cells?
A
Glutathione
Glutathione requires ATP for its synthesis.
22
Q
What is the role of Superoxide Dismutase (SOD)?
A
Converts Superoxide Radical to Hydrogen Peroxide
This is an important enzymatic defense against ROS.
23
Q
What can lead to the production of Hydroxyl radicals?
A
- Fenton Reaction
- Radiolysis of water by Ionizing Radiation
- Haber-Weiss Reaction
Hydroxyl radicals are among the most damaging free radicals.
24
Q
What is reperfusion injury?
A
Damage that occurs when blood supply returns to the tissue after a period of ischemia
This can lead to increased oxidative stress and cell death.
25
What are oxidative stress defense mechanisms compromised by?
Ischemia, resulting in ↑ROS
## Footnote
Ischemia leads to an imbalance between the production of reactive oxygen species (ROS) and the body's ability to eliminate them.
26
What do activated leukocytes produce to kill bacteria?
Rapid bursts in ROS
## Footnote
This process can cause collateral tissue damage.
27
Which species are primarily produced by macrophages?
Reactive Nitrogen species
## Footnote
These are produced by the conversion of Nitric Oxide to reactive peroxynitrite.
28
What can produce hydroxyl radicals through hydrolysis of water?
Radiation (UV light, X-rays, etc.)
## Footnote
Hydroxyl radicals are highly reactive and can damage cellular components.
29
What is an example of a radical generated from the metabolism of exogenous chemicals?
CCl3• (Trichloromethyl radical) from CCl4
## Footnote
This radical can damage cells similarly to ROS.
30
What drives the Fenton reaction to produce damaging hydroxyl radicals?
Excess metals such as Fe & Cu or defective carrier proteins
## Footnote
The Fenton reaction involves the conversion of hydrogen peroxide into hydroxyl radicals.
31
Why do phagocytes produce free radicals?
To kill bacteria
## Footnote
This is part of the phagocyte's bactericidal respiratory burst.
32
What is the most abundant bactericide in neutrophils?
Leukocyte MPO (Myeloperoxidase)
## Footnote
Myeloperoxidase is crucial for the production of hypochlorite.
33
What is nitric oxide (NO) produced from in macrophages?
L-arginine by iNOS (inducible Nitric Oxide Synthase)
## Footnote
iNOS is induced by inflammatory cytokines or bacterial endotoxins.
34
What is formed when nitric oxide combines with superoxide radical?
Peroxynitrite
## Footnote
Peroxynitrite is cytotoxic and bactericidal but can also damage mitochondria.
35
What triggers the assembly of PhOx components in phagocytes?
Phagocytosis
## Footnote
This leads to the production of superoxide in the phagosome.
36
What is the role of catalase in the oxidative stress response?
Catalase converts H2O2 into H2O and O2
## Footnote
This is a detoxification process that protects cells from oxidative damage.
37
What are some antioxidants that scavenge free radicals?
* Glutathione * Vitamin A * Vitamin C * Vitamin E
## Footnote
These antioxidants play a crucial role in protecting cells from oxidative stress.
38
What condition is associated with free radicals produced by inflammatory cells, especially macrophages?
Atherosclerosis
## Footnote
Oxidized LDL is a key factor in the development of atherosclerotic plaques.
39
What is Chronic Granulomatous Disease (CGD) caused by?
Inherited disabling mutation of NADPH oxidase
## Footnote
This mutation impairs the ability of phagocytes to produce superoxide and kill bacteria.
40
What paradoxical effect can occur during myocardial reperfusion injury?
It can exacerbate injury and cause cell death
## Footnote
This happens due to the formation of free radicals after restoration of blood flow.
41
What is the primary cause of hemochromatosis?
↑ absorption or overload of iron
## Footnote
Tissue damage from iron overload can lead to several health issues including liver cirrhosis and diabetes.
42
What is Wilson Disease characterized by?
Copper accumulation in liver, brain, and eyes
## Footnote
This condition results from a genetic mutation affecting copper metabolism.
43
What is the primary role of the Cytochrome P-450 system?
Metabolizing chemicals/drugs and producing toxic metabolites
## Footnote
This system is a major pathway for drug metabolism, accounting for about 80% of all chemicals.
44
What can induce or inhibit CYP enzymes?
Drugs
## Footnote
Certain drugs can increase or decrease the activity of these enzymes, affecting metabolism.
45
How many CYP enzymes are there, and what percentage of drugs do 6 of them metabolize?
There are over 50 CYP enzymes, and 6 of them metabolize 90% of all drugs.
46
What factors can induce or inhibit CYP enzymes?
CYP enzymes can be induced or inhibited by:
* many drugs (therapeutic & of abuse)
* smoking
* alcohol
* hormones
47
Which CYP enzyme is upregulated in chronic alcohol consumption?
CYP2E1 is upregulated in chronic alcohol consumption.
48
What happens to patients with a highly induced CYP system regarding drug metabolism?
Patients with a highly induced CYP system metabolize drugs faster.
49
What is the consequence of faster drug metabolism in individuals with an induced CYP system?
Drugs may be more toxic to these individuals, and higher doses may be required to reach therapeutic blood levels.
50
True or False: An inhibited CYP may require higher doses of a drug.
False
51
What is the drug of choice for treating acetaminophen overdose?
N-Acetylcysteine (NAC) is the drug of choice.
52
What does N-Acetylcysteine provide for glutathione synthesis?
N-Acetylcysteine provides cysteine for glutathione synthesis.
53
What percentage of acetaminophen overdoses are due to suicidal intentions?
2/3 of acetaminophen overdoses are suicidal.
54
What is the common clinical significance of acetaminophen overdoses?
Acetaminophen overdoses account for 56,000 ER visits and 50% of cases of acute liver failure.
55
What type of injury does advanced glycation end products (AGEs) contribute to?
AGEs contribute to microvascular and macrovascular damage.
56
What are the reactive compounds derived from nonenzymatic binding of sugars and proteins called?
Advanced Glycation End Products (AGEs)
57
How does hyperglycemia affect the formation of AGEs?
The natural rate of AGE formation is greatly accelerated by hyperglycemia in diabetes.
58
What is the clinical significance of glycated hemoglobin (HbA1c)?
The percentage of glycated RBCs reflects the average blood glucose level for the past 120 days.
59
Fill in the blank: Normally, or ideally, less than _______ of Hb is glycated.
5.7%
60
What defines diabetes according to WHO/ADA current standards?
HbA1c ≥ 6.5% (5.7% to 6.4% is designated as Prediabetes).
61
What are the microscopic morphological changes in reversible cell injury?
Cell swelling and cytoplasmic accumulation of lipids.
62
What type of necrosis is characterized by disorganized cell death due to loss of membrane integrity?
Necrosis
63
What is apoptosis likened to?
A cellular suicide program.
64
What are the morphological changes associated with necrosis?
Pyknosis, karyorrhexis, and karyolysis.
65
What type of necrosis is most common in infarction?
Coagulative necrosis.
66
What is the typical appearance of a coagulative infarct?
Anemic, pale, or white infarct.
67
What is liquefactive necrosis commonly associated with?
Pyogenic bacterial infections.
68
What does caseous necrosis resemble?
Cheese-like appearance.
69
What is gangrenous necrosis?
Necrosis in the distal portion of a limb that has lost its blood supply.
70
What type of necrosis involves necrosis of small vessel walls with fibrin-like staining?
Fibrinoid necrosis.
71
What is Fibrinoid necrosis?
Necrosis of the walls of small vessels with deposition of amorphous, proteinaceous material resembling fibrin
## Footnote
Associated with immune-mediated vasculitis, hyperacute transplant rejection, or conditions with very high blood pressure.
72
What condition is associated with Fat necrosis?
Acute pancreatitis
## Footnote
Caused by fat destruction in the peritoneal cavity due to leakage of pancreatic lipases.
73
What is the process of saponification?
Fatty acids combine with calcium to form a chalky white fatty acid salt
## Footnote
This occurs during fat necrosis.
74
What is the typical diagnosis for a woman with a hard breast lump after an open biopsy?
Fat necrosis with dystrophic calcifications, benign
## Footnote
Confirmed by ultrasound, mammogram, and histology showing lipogranulomata.
75
What does apoptosis mean?
Programmed cell death; a regulated suicide program for eliminating unwanted or irreparably damaged cells
## Footnote
It occurs without accompanying inflammation.
76
What are apoptotic bodies?
Cellular fragments covered by plasma membrane that are phagocytized
## Footnote
They form during apoptosis.
77
What is the difference between necrosis and apoptosis?
Necrosis involves inflammation and cell death of many cells at once, while apoptosis is a controlled process affecting one cell at a time
## Footnote
Apoptosis maintains tissue homeostasis.
78
What triggers apoptosis via the intrinsic pathway?
DNA damage, accumulation of misfolded proteins, and severe atrophy in organs
## Footnote
This pathway is characterized by mitochondrial involvement.
79
What is the role of caspases in apoptosis?
Caspases are cysteine proteases that initiate and execute cell destruction
## Footnote
They cleave proteins and activate other proteases and endonucleases.
80
What happens to DNA during apoptosis?
DNA is broken down into characteristic multiples of nucleosomal sized pieces, resulting in 'DNA ladders'
## Footnote
This can be observed in gel electrophoresis.
81
What is the function of phosphatidylserine during apoptosis?
It flips from the inner to the outer surface of the plasma membrane, signaling macrophages to engulf apoptotic bodies
## Footnote
This flipping is regulated by flippase and caspases.
82
What is the mitochondrial pathway of apoptosis?
The major mechanism of apoptosis activated by sensor proteins that detect cell injury
## Footnote
This pathway involves cytochrome c and caspase activation.
83
What is the extrinsic pathway of apoptosis?
Initiated by death receptors on the target cell membrane, often activated by cytotoxic T-cells
## Footnote
Examples include FAS and TNFR1 receptors.
84
What role does P53 play in apoptosis?
P53 accumulates in response to DNA damage and can induce apoptosis if the damage is beyond repair
## Footnote
It also arrests the cell cycle to allow for repair.
85
What is FLIP in the context of apoptosis?
A protein that inhibits extrinsic apoptosis pathways
## Footnote
It is produced by some normal cells and viruses to avoid CD8+ T-cell induced apoptosis.
86
Fill in the blank: Apoptosis induced by misfolded proteins occurs via the _______ pathway.
Mitochondrial (Intrinsic) pathway
## Footnote
This pathway is activated when cells are stressed due to misfolded proteins.
87
What is a common feature of the intrinsic pathway of apoptosis?
Involvement of mitochondrial sensors and release of cytochrome c
## Footnote
This is critical for the activation of caspase cascades.
88
True or False: Apoptosis is always associated with inflammation.
False
## Footnote
Apoptosis occurs without an inflammatory response.
89
What is Granzyme?
A serine protease secreted by Cytotoxic T-Lymphocytes that activates Caspases to induce Apoptosis.
## Footnote
Granzyme enters the target cell through a pore created by Perforin.
90
What pathway activates Apoptosis via Cytotoxic T-Lymphocytes?
Extrinsic pathway via MHC-I binding.
## Footnote
This pathway involves the secretion of Perforin and Granzyme.
91
What is the role of Perforin in the apoptosis process?
Opens a pore in the target cell membrane to allow Granzyme entry.
## Footnote
Perforin is secreted by Cytotoxic T-Lymphocytes.
92
What is the primary function of Caspases in apoptosis?
To execute the apoptotic program by cleaving specific substrates.
## Footnote
Caspases are a family of cysteine proteases.
93
What is the preferred receptor for deleting auto-reactive immune cells?
FAS Death Receptor.
## Footnote
This receptor is part of the extrinsic pathway of apoptosis.
94
What is the predominant pathway for deleting viral infected or tumor cells?
Perforin-Granzyme pathway.
## Footnote
This pathway is associated with Cytotoxic T-Lymphocytes.
95
What happens when the p53 protein detects DNA damage?
It accumulates and arrests the cell at G1 for repair.
## Footnote
If the damage is irreparable, p53 activates pro-apoptotic proteins to induce apoptosis.
96
What is the most common genetic abnormality found in human cancers?
Mutated p53.
## Footnote
Defective p53 leads to decreased apoptosis and potential cancer development.
97
What viral protein inactivates p53 and decreases apoptosis?
HPV E6 protein.
## Footnote
This results in epithelial hyperplasia due to failure in apoptosis.
98
What are some disorders associated with dysregulated apoptosis?
Cancer, infections, autoimmune disorders, neurodegenerative disorders.
## Footnote
These conditions arise from either increased or decreased apoptosis.
99
What is Necroptosis?
Caspase-independent programmed necrosis that morphologically resembles necrosis.
## Footnote
It is often induced by TNF signaling.
100
What triggers the formation of the necrosome in necroptosis?
Failure to activate Caspase-8, leading to the formation of an activated RIP complex.
## Footnote
This can occur due to viral FLIP or other inhibitions.
101
What is Pyroptosis?
Necrosis-like cell death with inflammation characterized by IL-1 release.
## Footnote
It involves the activation of the inflammasome.
102
What is the role of the inflammasome in cell death?
Induces the activation of Caspase-1 in response to PAMPs and DAMPs.
## Footnote
It is triggered by products of damaged cells and bacterial products.
103
What is the impact of alcohol exposure during pregnancy on the developing brain?
Triggers widespread acute apoptotic death of cells in both gray and white matter regions.
## Footnote
This is particularly noted during early or late third-trimester gestation.
104
What defines reversible injury in cells?
Mild cell injury where the injurious agent is removed, allowing the cell to heal or recover.
## Footnote
This contrasts with irreversible injury leading to cell death.
105
What are advanced glycation end-products (AGEs) associated with?
Inducing chondrocyte apoptosis in osteoarthritis.
## Footnote
AGEs cause protein misfolding and ER stress in cells.
