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General Pathology > Cell Injury- Week 1 > Flashcards

Cell Injury- Week 1 Flashcards

1
Q

What are the 9 causes of cell injury?

A
  • Oxygen Deficiency
  • Physical Agents
  • Infectious Microbes
  • Nutritional Imbalances
  • Genetic Derangement
  • Workload Imbalance
  • Chemicals, Drugs, and Toxins
  • Immunologic Dysfunction
  • Aging
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2
Q

What is an example of reversible cell injury?

A

Acute Cell Swelling

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3
Q

What is an example of irreversible cell injury?

A
  • Oncotic Necrosis
  • Types of oncotic necrosis
  • Cell death by Apoptosis
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4
Q

What are the Chronic cell injuries and adaptation

A

Chronic injury: Autophagy
Adaptations:
- Atrophy
- Hypertrophy
- Hyperplasia
- Metaplasia
- Dysplasia
(An Animal Has Hefty Metabolic Demands )

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5
Q

What are the 6 final biochemical mechanisms?

A
  1. ATP depletion
  2. Permeabilization of cell membranes
  3. Mitochondrial damage
  4. Lost of Ca homeostasis
  5. Oxidative stress
  6. Damage to DNA
    (A Police Man Loses old Defendant)
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6
Q

What are 3 types of responses to cell injury?

A

1.) Degeneration
2.) Death
3.) Adaptation
(Acronym: DAD)

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7
Q

What are some examples of oxygen deficiency (Hypoxia)

A
  • Inadequate oxygenation of blood (cardiac or respiratory failure)
  • Reduction of vascular perfusion (ischemia) - Reduced 0 2
    transport by erythrocytes (anemia or carbon monoxide
    toxicosis)
  • Inhibition of respiratory enzymes of the cell (cyanide toxicosis)
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8
Q

What is the process taking place in this image? Which of the 9 causes of cell injury is this related to?

A

Anemia ( Reduced O2 Transport by Erythrocyte)

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9
Q

What is the process taking place in this image? Which of the 9 causes of cell injury is this related to?

A

Physical agents. This is Mechanical Trauma

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10
Q

What is the process taking place in this image? Which of the 9 causes of cell injury is this related to?

A

Immersion Foot Syndrome in Horses (Trench Foot)

A Physical Agent.

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11
Q

What is the process taking place in this image? Which of the 9 causes of cell injury is this related to?

A

Infectious Microbes

  • Exotoxins
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12
Q

What are the some infectious causes of cell injury?

A
  • Bacteria
  • Exotoxins
  • Endotoxins
  • Viruses
  • Fungi
  • Parasites
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13
Q

What are some examples of nutritional imbalances that lead to cell injury?

A
  • Imbalances
  • Deficiencies
  • Excesses
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14
Q

What is the process taking place in this image? Which of the 9 causes of cell injury is this related to?

A

Rickets (Vitamin D Deficiency)

Nutritional Imbalances

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15
Q

What is the process taking place in this image? Which of the 9 causes of cell injury is this related to?

A

Polycystic Kidney Disease (Persian Cats)

Genetic Derangement

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16
Q

What are some examples of genetic derangement

A

Mutation Results in:

  • Production of abnormal protien
  • Production of defective enzyme
  • Lack of Necessary enzyme
  • Inactovation of regulatory protien- cell death and/or Neoplasia, ect.
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17
Q

Bonus Question: Where is the mutation located that causes Persian Cats to have Polycystic Kidney Disease?

A
  • PDK-1 and PDK-2
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18
Q

What are some factors that result in cell injury from workload imbalance?

A
  • Overwork or overstimulation
    • Hypertrophy of muscle in weightlifters
    • Myocardial hypertrophy secondary to valvular stenosis, etc
  • Underwork or lack of stimulation
    • Disuse atrophy
    • Denervation atrophy
    • Lack of endocrine stimulation
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19
Q

What is the process taking place in this image? Which of the 9 causes of cell injury is this related to?

A

Myocardial Hypertrophy Seconday to Valvular Stenosis

Workload Imbalance

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20
Q

What is the process taking place in this image? Which of the 9 causes of cell injury is this related to?

A 
Denervation atrophy (secondary to equine protozoal myeloencephalitis)
Workload Imbalance
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21
Q

What are some examples chemicals, drugs, and toxins, causing cell injuries?

A

Binding receptors, inhibiting or inducing enzymes (altering metabolic pathways), producing free radicals…
• Various metals

  • Pesticides, herbicides, insecticides
  • Poisonous plants, mycotoxins, venom
  • Therapeutic drugs
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22
Q

What is the process taking place in this image? Which of the 9 causes of cell injury is this related to?

A

Snake Bite

Toxins, Chemicals, Drugs

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23
Q

What is the process taking place in this image? Which of the 9 causes of cell injury is this related to?

A

Pyrrolizidine alkaloid containing plants (Senecio sp., Echium plantagineum, Crotalaria sp.)

Chemicals, Drugs, Toxins

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24
Q

What are some examples of cell function caused by Immunological Dysfunction?

A
  • Immunologic deficiencies
  • Allergies or hypersensitivity
  • Autoimmune diseases
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25
Q

What is an autoimmune disease?

A

An autoimmune disease develops when an animal’s immune system produces antibodies against their own cells.

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26
Q

What is the process taking place in this image? Which of the 9 causes of cell injury is this related to?

A

Allergy (Atopic Dermatitis)

Immunologic Dysfunction

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27
Q

What is the process taking place in this image? Which of the 9 causes of cell injury is this related to?

A

Autoimmune (Pemphigus) - the animal’s immune system built antibodies against the epidermis —> bilateral, symmetrical distribution; This is a chronic condition that can be easily treated.

Immunologic Dysfunction

28
Q

What is the process taking place in this image? How did this occur? Which of the 9 causes of cell injury is this related to?

A

Cerebral Cortical Atrophy due to neuronal damage

Aging

29
Q

What happens as an animal ages?

A

As an animal ages, the mechanism of protection starts to fail, leading to tissue damage.

30
Q

What are some causes of cell injury by aging?

A
  • Cumulative damage to cell proteins, lipids, nucleic acids
  • Attributed to Reactive Oxygen Species (ROS), DNA mutations
  • Cumulative damage to DNA predisposes to neoplasia
31
Q

What is an alternative term for reactive oxygen species?

A

Free radicals

32
Q

What is the process taking place in this image? Which of the 9 causes of cell injury is this related to?

A

Penile Squamous cell carcinoma.

Very common in old horses because there is cumulative DNA damage.

Aging

33
Q

What is the initial response of the cell to pertubation of homeostasis in reversible cell injury?

A

Acute cell swelling

34
Q

Reversible cell injury = ?

A

Acute cell swelling = degeneration

35
Q

Cellular response to injury depends on what factors? What will these factors determine?

A
  1. The type of cell/tissue/organ
  2. Time of exposure
  3. Severity of the injury

These factors will determine the type of lesion or the morphology of the lesion.

36
Q

True or False: Once a cell is injured, no matter the severity or duration, the cell will not be able to recover or return to normal.

A

FALSE

If the injury is not too severe or too prolonged, the cell can
recover and return to normal structure and function

37
Q

What are some synonyms for acute cell swelling?

A

Hydropic degeneration, Ballooning degeneration (keratinocytes), cytotoxic edema (astrocytes)

38
Q

What are the 3 ways in which ATP is produced by the cell?

A
  1. Glycolysis (Glucose —> Pyruvate) = 2 ATP
  2. Kreb’s Cycle = 2 ATP
  3. Oxidative Phosphorylation = 32 ATP
39
Q

Where does the Kreb’s cycle take place?

A

In the mitochondria

40
Q

Where does Oxidative Phosphorylation occur?

A

In the mitochondria

41
Q

Where does Glycolysis take place?

A

In the cytosol

42
Q

What is the most productive form of ATP production?

A

Oxidative phosphorylation

43
Q

Of the three ways in which ATP can be produced, which ones are O2 dependent? O2 independent?

A

Glycolysis and Kreb’s Cycle are O2 independent.

Oxidative Phosphorylation is O2 dependent.

44
Q

Why is ATP depletion so detrimental to the cell?

A
  • Reduction in function of cell membrane pumps (sodium-potassium

pump)

  • Sodium/potassium and calcium abnormalities
  • Alterations in cellular metabolism
  • Disruption of protein synthesis
45
Q

After ATP depletion, what electrolyte abnormalities do you see in the cell? How do they change? This can lead to?

A

Sodium, Water, and Calcium will increase (causing acute cell swelling)

Potassium will decrease.

This can lead to Hydropic Degeneration —> Hypoxia, Ischemia

46
Q

What happens when there is an increase in extracellular Ca?

A

When the Na/K pump stops working, extracellular Ca enters the cell. The mitochondria and ER will release their Ca contents into the cytoplasm of the cell. Increased levels of calcium in the cytoplasm activates 4 enzymes: ATPase, Endonuclease, Protease, Phospholipase.

47
Q

What is the function of the enzyme ATPase?

A

ATPase degrades ATP

48
Q

What is the function of the enzyme Endonuclease?

A

Damages DNA

49
Q

What is the function of the enzyme Protease?

A

Damages structural proteins

50
Q

What is the function of Phospholipase?

A

Phospholipase causes cell membrane damage.

51
Q

What can be used as protection against Reactive Oxygen Species? What does each one do?

A

Antioxidants:
• Block formation or scavenge (sacrifice themselves)
- Vit A, C, E, Selenium = without these, no protection from ROS —> cell & tissue injury

• Sequestration of inducing agents (transport proteins for copper and iron)
- Ferritin and Ceruloplasmin bind to iron to prevent formation of ROS.

  • Enzymes (decomposes H2O2, OH, O2-)
  • Catalase, Superoxide dismutases (SOD), Glutathione peroxidase = produced by the cell to protect it from ROS damage.
52
Q

What are effects of ROS?

A
  1. Lipid peroxidation —> membrane damage
  2. Protein modifications —> Breakdown, misfolding
  3. DNA damage —> mutations
53
Q

What is a reperfusion injury?

A

It’s the tissue damage caused when blood supply returns to tissue (re-perfusion)
after a period of ischemia or lack of oxygen (anoxia or hypoxia)

54
Q

What is the 4 mechanisms of reperfusion injury?

A
  • Oxidative stress (ROS)
  • Intracellular calcium overload
  • Inflammation
  • Activation of complement system
55
Q

What are the Ultrastructural morphology of cell swelling?

A
  • Generalized swelling of the cell and its organelles (especially mitochondria)
  • Blebbing of the plasma membrane
  • Detachment of ribosomes from ER
  • Clumping of nuclear chromatin
  • Myelin figures (from damaged organelles membrane
56
Q

What leads to the detachment of ribosomes from the ER?

A

Swelling of the ER.

57
Q

Organelle membrane damage leads to?

A

Myelin formation

58
Q

What is the main difference between reversible and irreversible cell injury?

A

Blebbing but no rupture.

59
Q

What are the microscopic morphology of acute cell swelling?

A
  • Swollen
  • Pale eosinophilic, and finely vacuolated cytoplasm
  • Besides water (hydropic degeneration), lipids and glycogen also can accumulates in reversible cell injury (Discussed in more detail later in these lectures)
60
Q

Explain what is going on in this image:

A

Diffused cell injury in organ on the left leads to an increased volume and weight of organ due to an increase in water.

Left Liver: Liver lobes are enlarged and rounded.

61
Q

What are the gross morphology of cell swelling?

A
  • Increases the volume and weight of organs (if diffuse)
  • Imparts pallor
  • Swollen and rounded edges (liver)
62
Q

What Generates Reactive Oxygen Species during cell injury?

A
  • Mitochondrial damage
  • Reperfusion injury
  • Ionizing radiation
  • Transition metals (iron, copper)
  • Leukocytes
63
Q

How do Leukocytes generate ROS?

A

Leukocytes destroy bacteria and microorganisms by producing ROS/free radicals.

64
Q

Name three situations in which an animal would have a decreased supply of Oxygen?

What is produced as a result?

A
  1. Radiation, Toxins, Reperfusion
  2. Leads to the production of ROS including: Superoxide, Hydrogen peroxide, and Hydroxyl radical
65
Q

What injurious agents can lead to mitochondrial damage?

A
  • Hypoxia
  • Toxic agents
  • Increased levels of cytosolic calcium
  • Oxidative stress
  • Phospholipid breakdown

General Pathology (18 decks)

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