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General Pathology > Cell Injury > Flashcards

Cell Injury Flashcards

1
Q

What are the causes of cell injury

A

Anoxia, Physical Injury, Infective, Chemical Injury, Genetic, Nutritional, Immune, Endocrine (+ examples)

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2
Q

What is the difference between reversible and irreversible cell injury + what are the hallmarks

A

Reversible: Functional and morphological changes reversible with removal of injurious stimuli
Hallmarks: Reduced Oxidative Phosphorylation, ATP Depletion, Cell Swelling

Irreversible: Functional and morphological changes irreversible even with removal of injurious stimuli
Hallmarks: Necrosis, Apoptosis

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3
Q

What are the Biochemical Mediators of Cell Damage

A

Reactive Oxygen Species (ROS) - Superoxide Anion, Hydroxyl Radical, Hydrogen Peroxide
ATP Depletion - Ischemia causing decreased oxidative phosphorylation
Mitochondrial Damage - Decreased O2 supply, Increased Toxins and Radiation –> Necrosis; Decrease survival Signals, DNA and protein damage –> Apoptosis
Loss of Calcium Homeostasis - increase Ca2+ levels to cytotoxic levels
Membrane Permeability Defects - caused by phospholipid loss, lipid breakdown products, cytoskeletal damage

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4
Q

Mechanisms of Cell Injury

A 
Cellular Response (depends on type, duration, and severity of injury)
Consequences (depends on type, state and adaptability of cell) - eg. neurons vs striated muscle cells
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5
Q

How does ROS damage cells

A

Peroxidation of membrane lipids - reacts with double bond in unsaturated fatty acids in the membrane (to produce peroxides which are also reactive causing a chain reaction)
Oxidative Modification of Enzymes - yields protein-protein cross links which disrupts enzyme activity
DNA Damage - Reactions with Thymidine produces single stranded breaks in DNA

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6
Q

How are ROS removed

A

Antioxidants - Vit A, C, E and glutathione
ROS binding proteins - Transferrin, Lactoferrin, Ferritin
Scavenging Systems - Catalase (decomposes Hydrogen peroxide into water and oxygen, Superoxide dismutase (converts superoxide into hydrogen peroxide); Gluthathione peroxidase (catalyses ROS breakdown, oxidation of glutathione into glutathione homodimer)

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7
Q

Explain how Anoxia kills cells

A

reduce ATP levels, sodium and calcium pumps fail, ionic inbalance, swelling of cellular organelles, activation of lytic enzymes

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8
Q

Why does reperfusion injury (blood flow restored to reversibly injured due to ischemia cells) occur

A

praradoxically accelerates injury as it

  1. exposes compromised cells to high concentrations of calcium
  2. increased free radical production from compromised mitochondria and circulating inflammatory cells
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9
Q

Explain how ionizing radiation kills cells

A

radiolysis of water generating ROS (indirect effect)

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10
Q

Explain how chemicals kill cells

A

combines with cell constituents

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11
Q

Explain how carbon tetrachloride is toxic

A

It is metabolised by cytochrome p450 in the liver to form trichloromethyl free radical which causes damage by lipid peroxidation

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12
Q

Explain how acetaminophen (Paracetamol) is toxic

A

It is metabolised by cytochrome p450 in the liver to form ROS

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13
Q

Explain how viruses kill cells

A
  1. Directly cytopathic - eg. Polio - virus coded proteins form a pore in the cell membrane which disrupts its membrane permeability
  2. Indirectly cytopathic - eg. Hep B - virus coded proteins are inserted into the cell membrane which recognises these proteins as non-self and attacks the cell
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14
Q

What is Hayflick Number

A

the limited number of times normal cells can divide before showing growth arrest due to cellular senscence

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15
Q

When is Senescence accelerated

A
  • treatment with DNA damaging agents

- patients with defects in genome maintanence that lead to accelerated aging (eg. Werner’s Syndrome)

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16
Q

What is the function of Telomeres

A

They protect chromosomes from degradation and recombination. They get progressively shorter with cell division and when they are critically short, they induce cell senescence

17
Q

What is Hutchinson-Gilford Syndrome caused by

A

Mutation in the LMNA gene (Encodes Lamin A and C) causing Progeria

18
Q

What is the prognosis of those with Hutchinson-Gilford Syndrome

A

Average lifespan of 13 yrs, death by stroke or heart attack

19
Q

What is Werner’s Syndrome caused by

A

Mutation in a gene encoding helicase and endonuclease causing Adult Progeria

20
Q

What is the prognosis of those with Werner’s Syndrome

A

Average lifespan of 44-47 yrs, rapid aging post puberty, death by myocardial or cerebrovascular accidents and malignancy

21
Q

Causes of Cellular Aging

A
  1. Accumulation of DNA damage - defective DNA repair mechanisms + accumulating cellular damage
  2. Replicative Senescence - reduced capacity of cells to divide
  3. Defective protein homeostasis - impaired chaperone and proteasome functions
  4. Nutrient sensing system - overconsumption of calories

General Pathology (10 decks)

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