Cell Injury

Question 1

Explain the mechanisms of Reactive Oxygen Species (ROS) production.

Answer 1

ROS can be produced through various mechanisms including inflammation, the Fenton reaction, leaky mitochondria, and ionizing radiation.

Question 2

Describe the pathways through which ROS damage cell components.

Answer 2

ROS can damage cell components by inducing oxidative stress, leading to lipid peroxidation, protein modification, and DNA mutations.

Question 3

Differentiate between the impacts of ionizing radiation and UV radiation on DNA.

Answer 3

Ionizing radiation causes direct DNA strand breaks and complex damage, while UV radiation primarily causes thymine dimers and other types of DNA lesions.

Question 4

Give examples of cell defenses against injury.

Answer 4

Cell defenses against injury include mechanisms such as cell turnover, antioxidants, chaperonins, and DNA repair enzymes.

Question 5

Recognize the types of diseases that result from accumulated cell injury.

Answer 5

Diseases resulting from accumulated cell injury include sporadic cancer, neurodegenerative disorders, and hereditary cancer syndromes.

Question 6

Define homeostasis in the context of cell injury.

Answer 6

Homeostasis is the balance between stress or injury and the cell’s defense mechanisms, which maintains cell function.

Question 7

What occurs when injury overwhelms the cell’s defenses?

Answer 7

When injury overwhelms the cell’s defenses, it leads to loss of homeostasis and potentially cell death, resulting in disease.

Question 8

Describe adaptation in response to cell injury.

Answer 8

Adaptation can be a response to injury that is either pathologic (harmful) or physiologic (protective), allowing the cell to cope with stress.

Question 9

Define apoptosis.

Answer 9

Apoptosis is programmed cell death, a controlled process that eliminates damaged cells to maintain tissue homeostasis.

Question 10

Describe necrosis and its consequences.

Answer 10

Necrosis is cell death resulting from direct injury, often leading to inflammation and further tissue damage.

Question 11

Identify the 4 primary sites of cell injury.

Answer 11

• cell membrane
• mitochondria
• ribosomes
• nucleus.

Question 12

How does cell membrane injury affect cell integrity?

Answer 12

Physical, chemical & toxic injury results in membrane
leakiness, disrupting the intracellular milieu

Question 13

Explain the impact of impaired mitochondria on cell survival.

Answer 13

Impaired mitochondria reduce ATP production due to disrupted oxidative phosphorylation, affecting cell survival.

Question 14

Define the role of ribosomes in cell injury.

Answer 14

Disruption in the production and folding of proteins can cause cellular dysfunction

Question 15

How does DNA damage occur in the nucleus?

Answer 15

DNA damage in the nucleus can result from oxidative stress or radiation, leading to mutations or cell death.

Question 16

Compare hypoxia to oxidative injury

Answer 16

Oxygen is vital to all functions in the cell, but its level within the body is a delicate balance. Too little oxygen causes hypoxia but too much oxygen can lead to the production of Reactive Oxygen Species, which are very damaging.

Question 17

What are the 4 primary mechanisms that generate ROS’s?

Answer 17

• Oxidative Bursts (immune cells)
• Oxidative Phosphorylation (mitochondria)
• Fenton Reaction (iron)
• Ionizing Radiation (radiation therapy or nuclear accidents)

Question 18

Describe the generation of reactive oxygen species (ROS) during inflammation.

Answer 18

ROS are produced during the oxidative burst of phagocytes, such as neutrophils, in response to infections.

Question 19

What causes leaky mitochondria and its effects?

Answer 19

Leaky mitochondria occur when electrons leak from the electron transport chain during oxidative phosphorylation, forming superoxide (->hydrogen peroxide), often due to toxins or aging.

A little ROS generation is important for intracellular signaling.

Question 20

Explain the Fenton reaction and its implications.

Answer 20

The Fenton reaction involves iron catalyzing the conversion of hydrogen peroxide into highly reactive hydroxyl radicals, with excessive production possible in conditions like hemochromatosis.

Question 21

How does ionizing radiation contribute to ROS generation?

Answer 21

Exposure to ionizing radiation, such as from radiation therapy or nuclear accidents, leads to ROS generation and DNA damage.

Question 22

What are the 3 common types of damage caused by ROS? Think of the major macromolecules.

Answer 22

Lipid peroxidation
Protein Degradation
DNA Mutations

Question 23

Lipid peroxidation: Describe the effects of Reactive Oxygen Species (ROS) on cell membranes.

Answer 23

ROS depolarizes membranes by oxidizing the lipid core. This reduces membrane potential & inhibits ion channels.

Question 24

How do Reactive Oxygen Species (ROS) affect proteins in the body?

Answer 24

ROS can oxidize amino acid residues, leading to protein misfolding or loss of function.

Question 25

Define the impact of Reactive Oxygen Species (ROS) on DNA.

Answer 25

ROS induce mutations by causing strand breaks in DNA.

Question 26

What chronic diseases are associated with Reactive Oxygen Species (ROS)?

Answer 26

ROS are implicated in many chronic diseases, including cancer, atherosclerosis, emphysema, and aging.

Question 27

Explain the effects of ionizing radiation on DNA.

Answer 27

Ionizing radiation causes double-strand breaks (DSBs) in DNA and generates ROS that further oxidize DNA, leading to mutations or cell death.

Question 28

How does UV radiation damage DNA?

Answer 28

UV radiation induces thymine dimers, which distort the DNA structure, interfering with replication and transcription, and can lead to mutations associated with skin cancers.

Question 29

Describe the role of high turnover tissues in cell injury recovery.

Answer 29

High turnover tissues, such as gut epithelium, skin, and red blood cells, regularly replace damaged cells, reducing the accumulation of injury.

Question 30

What is a downside of high turnover tissues in relation to mutations?

Answer 30

High turnover tissues increase the likelihood of non-repaired mutations due to frequent cell replacement.

Question 31

Explain the vulnerability of low turnover tissues to damage.

Answer 31

Low turnover tissues, like neurons and cardiac muscle, are more prone to accumulate protein aggregates and other damage over time, contributing to neurodegenerative diseases.

Question 32

Define the role of antioxidants in protecting against oxidative damage.

Answer 32

Antioxidants, such as Glutathione and vitamins E, A, and C, act as electron donors to neutralize ROS, preventing oxidative damage.

Question 33

Expand on the antioxidant activity of glutathione. Which mineral is an important cofactor of Glutathione Peroxidase

Answer 33

Glutathione Peroxidase reduces hydrogen peroxide into water using glutathione - many isotypes
Selenium is a critical component of glutathione peroxidase, without which ROS accumulated in the heart causing myocyte death

Question 34

Describe the role of enzymes like catalase and superoxide dismutase in cellular protection.

Answer 34

These enzymes catalyze the breakdown of reactive oxygen species (ROS), protecting cells from oxidative stress.

Question 35

Define chaperonins and their function in the cell.

Answer 35

Chaperonins, also known as heat shock proteins, assist in refolding damaged proteins or targeting them for ubiquitin-mediated degradation.

Question 36

How does impaired function of chaperonins relate to diseases?

Answer 36

Impaired function of chaperonins is implicated in diseases such as Alzheimer’s, Parkinson’s, and ALS.

Question 37

Explain the importance of DNA repair enzymes in cellular health.

Answer 37

DNA repair enzymes correct DNA damage caused by ROS and radiation, preventing genetic disorders.

Question 38

What is Xeroderma Pigmentosum and its connection to DNA repair enzymes?

Answer 38

Xeroderma Pigmentosum is a genetic disorder involving defects in nucleotide excision repair, highlighting the critical role of DNA repair enzymes.

Question 39

Describe the link between sporadic cancer and DNA damage.

Answer 39

Sporadic cancer often results from accumulated mutations due to unrepaired DNA damage over time.

Question 40

How are neurodegenerative disorders related to protein damage in cells?

Answer 40

Neurodegenerative disorders like Alzheimer’s, Parkinson’s, and ALS are linked to the accumulation of damaged proteins in cells with low turnover rates.

Question 41

Define hereditary cancer syndromes and their genetic basis.

Answer 41

Hereditary cancer syndromes are caused by mutations in DNA repair genes, such as BRCA1/2, which predispose individuals to cancers like breast and ovarian cancers.