Cell Injury and Death Flashcards by tcarlso 3

Cell response to injury is dependent on what four factors?

Dose
Duration
Type of injury
Type of cell

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Cell injury results when what happens?

Cells are stressed so severely that they are no longer able to adapt

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What types of cells are most affected by chemo?

Epithelial cells of the intestine, or any cells that replicate continuously

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What are the three permanent cell types?

Skeletal muscles cells
Cardiac cells
Neurons

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What are the two outcomes of irreversible injury to a cell?

Necrosis or apoptosis

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What are the five main cellular components (processes/structures) that are damaged during cell injury?

Aerobic respiration
Integrity of cell membranes
Protein synthesis
Cytoskeleton
Genetic apparatus

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What are the three components of cell that undergo damage?

Membranes
Proteins
DNA

(MPD)

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What are the five major biochemical mechanisms of cell injury?

Ca influx into cell
ROS accumulation
ATP Depletio
Mito damage
Permeability of membrane changes

(CRAMP)

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Are all free radicals bad?

No–we need them

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Excess Ca causes what? (2)

Activation of enzymes

Changes permeability of Mitochondria, restricting ATP production

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What are the four major enzymes that Ca influx activates?

Phospholipases
Proteases
Endonucleases
ATPase

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What are the three major sources of Ca excess?

ER stores
Malfunction of Na/Ca pumps
Extracellular Ca

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What is the main organelle that is affected by Ca influx?

Mito

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How is damage to the mito by Ca influx effected?

Breakdown of phospholipids (A2 and sphingomyelin) via enzymes activated by Ca. These lipids can be damaging

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What happens when the Mitochondrial membrane is damaged?

Loss of H+ gradient, therefore loss of ATP

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A decrease in oxygen affects the mitochondria how? (4)

Decrease ATP generation

ROS go up and leak out

Increase in proapoptotic proteins

Decrease in anti-apoptotic proteins

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What is the effect of CN?

Inhibits the ETC, (cyt C) inhibiting ATP production

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What happens when oxidative phosphorylation cannot proceed and ATP levels decrease? (3)

Na is not able to be pumped out, causing water influx and efflux of K

Anaerobic glycolysis (lactic acid)

Detachment of ribosomes (decreased protein synthesis)

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What happens to the DNA when pH decreases?

Chromatin clumping (DNA damage)

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What happens to out membranes with age? What is the consequence of this?

Leaky membranes, leaking ROS

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True or false: normal metabolism leads to ROS production?

True

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Why are ROS bad?

Bind to whatever double bond that’s around

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What happens when someone is put on 100% O2?

ROS production

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Reperfusion injury is caused by what?

ROS production increases but enzymes to take care of it are not around

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Why do PMNs produce ROS?

Part of immune response

What are the four major ROS?

O2- OH - ONOO - Lipid peroxide radicals

Where do ROS affect lipid membranes? What is produced?

The double bonds of FAs This leads to peroxide formation, and continues

What are the vitamins that are antioxidants (4)?

C, E, A and beta-carotene

What happens to proteins with ROS? (2)

Side chain oxidation leads to change in structure (enzymes die) Form disulfide bonds

Free radical interaction with thymine leads to what? What can this lead to?

Single-stranded breaks in DNA CA

What is the function of superoxide dismutase?

O2 to H2O2

What are the ROS enzymes that reduce free radicals? (3)

Superoxide dismutase Glutathione peroxidase Catalase

What are the steps of the respiratory burst of PMNs? (hint there are three enzymatic steps)

O2 converted to superoxide by NADPH oxidase. SOD to H2O2 packed in granules for release Myeloperoxidase also packs HOCl and Oh radical

What is chronic granulomatous disease?

The NADPH oxidase is malfunctioning Pts die of infection early d/t granuloma infection

Damage to membrane permeability causes what three damaging process?

Release and activation of phospholipases Decreased phospholipid re-acylation Cytoskeleton damage via protease activation

What happens in reversible cell injury (4)?

Swelling of ER and mito, Membrane blebs produced Detachment of ribosomes from ER Chromatin clumping

What happens in irreversible cell injury (6)?

1. Lysosome rupturing 2. Nuclear condensation 3. Myelin figures produced 4. Ribosome loss d/t swollen ER 5. Holes in the membrane 6. Swollen mito

What happens to renal tubules with reversible damage?

Raggedness, but nuclei are still intact

What happens to renal tubules with IRReversible damage?

Nucleus breaks and dissolved

Are renal tubule cells able to reproduce?

Yes

Is there a particular point when reversible to irreversible injury occurs?

What are the two forms of cell death?

Necrosis | Apoptosis

True or false: apoptosis and necrosis are always pathologic

False--apoptosis can be physiologic, but true for necrosis

What happens in necrosis that is so bad?

Leakage of cellular contents leading to inflammation

What is necrosis?

Uncontrolled cell death that does not require signals or activation of genes

What are the cytoplasmic changes with necrosis (3)?

Eosiniphilia Glassy appearance Vaculoation

What are the three nuclear changes with necrosis?

Pyknosis Karyorrhexis Karyolysis

Hypoxia can be the result of what factors?

1. Loss of blood supply 2. Decrease in oxygen carrying capacity of the blood 3. Poisoning of the enzymes of the oxidative phosphorylation

Chemical injury to a cell leads to what?

to a disruption of the physical structure of the cell or to a breakdown of the biochemical processes of the cell

What is kwashiorkor?

inadequate protein intake

What is marasmus?

inadequate calorie intake

What are the six specific biochemical process seen in the process of cell necrosis? (what happens to ATP prodcution? Ca? ROS? Membrane permeability? Mitochondira? Cytoskeleton)?

1. ATP depletion 2. Loss of Ca 3. Free radicals 4. Defective membrane permeability 5. mito damage 6. Cytoskeletal damage

What is oxidative stress?

The accumulation of damage caused by oxygen-derived free radicals

What nucleic acid do free radicals react with to cause DNA damage?

Thymine

What is the function of Glutathione peroxidase?

Converts OH- to H2O2

What is the function of Superoxide dismutase?

Converts O2 radical to H2O2

What are the three areas of the cell that are affected by free radicals?

Membrane (lipids/FA) Proteins DNA

What are the changes seen in chronic cell injury?

Mito changes | Cytoskeletal changes

What is Pyknosis?

Nuclear material becomes condensed

What is Karyorrhexis?

Nuclear material breaks apart

What is Karolysis?

Nuclei have totally dissolved

How can aerobic respiration affected in cell injury?

Decreased ATP synthesis leads to lower Na/Ca pump activity, causing Ca influx

How can a compromise in integrity of the cell membrane lead to cell injury?

Increase in Ca influx or ROS leakage from cells

How can protein synthesis be affected in cell injury?

Either disulfide bonds are formed where there should be none, or there may be other changes in AAs Also, ribosomes may fall off

What cause the chromatin clumping seen in cell injury?

Lowered pH, caused by increase in glycolysis

What happens to lysosomes during cell injury?

Can leak, causing severe damage to the cell

What happens to the ER in cell injury?

Swells, possibly leading to ribosome detachment

What happens to the mitochondria during cell injury? (4)

1. Swelling 2. loss of phospholipids reacylation/synthesis 3. Decreased ATP 4. Increased ROS

What happens to the cytoskeleton during cell injury?

Broken down d/t increase protease activity from Ca influx

What happen to the nucleus during cell injury?

fibrillar and granular components of the nucleolus may segregate Can also undergo pyknosis

What are the three mechanisms of reducing ROS in a normal cell?

Superoxide dismutase Glutathione peroxidase Catalase

What is the reaction catalyzed by superoxide dismutase?

O2- to hydrogen peroxide

What is the reaction catalyzed by glutathione peroxidase?

OH radical to hydrogen peroxide

What is the reaction catalyzed by catalase?

Hydrogen peroxide to water and oxygen

When ROS react with lipids, what do they form? What is the consequence of this?

Peroxides, causes chain reaction

What are the four major changes that a loss of ATP leads to?

1. Cellular organelle swelling 2. Activated enzymes 3. Chromatin clumping 4. Decreased protein synthesis