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Pathology 2420 Part 1 > Cellular Stress - Injury, Adaption, and Cell Death > Flashcards

Cellular Stress - Injury, Adaption, and Cell Death Flashcards

1
Q

What occurs when the environmental changes exceed the capacity of the cell?

A

Cell injury

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2
Q

What are the different agents that can cause cell injury? (7)

A
  • Hypoxia
  • Physical agents ex. radiation, extreme temp
  • Chemical agents ex. poison, drugs
  • Biological/Infectious agents ex. microorganisms
  • Immunologic reactions ex. allergens
  • Genetic alterations
  • Nutritional Imbalances
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3
Q

What are the four cell components that are particularly vulnerable?

A
  • cell membranes critical for ionic and osmotic homeostasis
  • mitochondria and the generation of energy via ATP
  • protein synthetic machinery
  • cellular DNA
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4
Q

What occurs when there is persistent sub lethal injury to the cell?

A

The cell adapts to the environment; the cell achieves a new steady state and preserves cells viability

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5
Q

What are some of the adaptive responses of cells to injury? (5)

A
  • regulation of cell receptors
  • changes in cell protein synthesis and turnover
  • adaption to cell size (atrophy or hypertrophy)
  • adaption to cell number (hyperplasia)
  • adaption to phenotype and organization of cells (metaplasia, dysplasia)
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6
Q

What is Hypertrophy?

A
  • Increase in the size of existing cells, due to the increase in synthesis of cellular protein and structural components and organelles responsible for producing them
  • can be pathological or physiological in response to increasing functional demand or specific hormonal stimulation
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7
Q

What is Hyperplasia?

A

Increase in number of cells caused by cell division

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8
Q

What are some physiological examples of Hyperplasia and Hypertrophy?

A
  • hyperplasia and hypertrophy of uterine smooth muscle occur in pregnancy in response to estrogen
  • compensatory hyperplasia occurs when a portion of tissue is removed
  • hypertrophy of skeletal muscle occurs as a normal physiological response in weight training
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9
Q

What are some pathological examples of Hyperplasia and Hypertrophy?

A
  • hypertrophy of cardiac muscle fibers occurs in response to increased workload as a result of systemic hypertension
  • excessive stimulation of the normal uterus by estrogen may result in endometrial hyperplasia
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10
Q

What is Metaplasia?

A

When certain types of cells, change into different types of cells due to the long-term environment that they are in becoming unsuitable for them

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11
Q

What is Dysplasia?

A
  • an alteration in the size, shape and organization of the cellular components of a tissue
  • may be reversible after the irritating cause has been removed
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12
Q

Where does Dysplasia often occur?

A

In metaplastic squamous epithelium of the respiratory tract and cervix

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13
Q

What is Atrophy?

A
  • a decrease in mass due to the shrinkage in cell size
  • due to diminished blood supply or diminished nutritional or trophic factors, a new steady state is reached in which a smaller cell is able to survive
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14
Q

What are some physiological and pathological examples of Atrophy?

A
  • normal aging (ex. Shrinkage and loss of brain cells with age
  • Disuse of skeletal muscle in an immobilized limb
  • degeneration following loss of nerve input to the muscle
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15
Q

What is a Reversible injury?

A

When the injurious stimulus is mild and transient, and the cell is capable of recovery and return to normal state

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16
Q

What occurs when the injury stimulus is severe or progressive, and the cell undergoes irreversible damage?

A

Death of the cell

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17
Q

What are the 2 mechanisms by which cells die?

A
  • Apoptosis
  • Necrosis
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18
Q

What is Apoptosis?

A

The death of cells which occurs as a normal and controlled part of an organism’s growth and development

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19
Q

What is Necrosis?

A

The death of body tissue, which occurs when there is too little blood flow to the tissue

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20
Q

What is Cellular Proliferation?

A

The division and reproduction of cells
Including:
- replication of DNA
- synthesis of all cellular constituents for a new cell
- equal division of all these things between the original cell and new daughter cell during mitosis

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21
Q

What are the 4 phases of the cell cycle?

A

G1 - where cells grow in mass
S - where DNA is synthesized
G2 - where further growth occurs
M - the mitotic phase where the cell divides

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22
Q

What is the G0 phase?

A

additional phase of quiescent cells that are not actively cycling
- Stable cells such as Hepatocytes rest in the phase

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23
Q

How can cells enter the G1 phase?

A
  • from the geno-quiescent cell pool
  • after completing a round of mitosis if they are continuously replicating
  • label cells such as stem cells of the skin or GI tract
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24
Q

What permanent cells exit the cell cycle permanently and do not replicate?

A

Neutrons and cardiac muscle cells

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25
Q

By what is the cell cycle regulated?

A

By activators and inhibitors

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26
Q

What are the activators that regulate the cell cycle?

A

cyclones and their associated enzyme, cyclin dependent kinases CDK’s

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27
Q

How is the cell cycle controlled?

A

By CDK inhibitors, which delay cell cycle progression at the G1 to S and G2 to M transition points to check for DNA damage

28
Q

What occurs if damage is detected in the cell cycle?

A

DNA repair mechanisms are initiated

29
Q

What occurs if the damage detected in the cell cycle is too severe?

A

The cell will either undergo death by apoptosis, or it may enter Senescence, a non-replication state

30
Q

How may a Malignant Tumour develop?

A

If CDK inhibitors are defective, there is the potential for cells with damaged or mutated DNA to divide, forming the tumour

31
Q

What is the Warburg Effect?

A

It involves increased cellular uptake of glucose and glutamine, increased glycolysis, and decreased oxidative phosphorylation. These changes become fixed cancer cells

32
Q

What are Stem cells?

A
  • cells that during development give rise to all differentiated tissues
  • in adults, stem cells replace damaged cells and maintain tissue populations
33
Q

What are the different types of Stem cells?

A
  • Embryonic
  • Tissue
34
Q

What are Embryonic Stem cells?

A
  • cells that are present in inner cell mass of blastocyst
  • they have virtually limitless self-renewal capacity
  • type: totipotent
35
Q

What are Totipotent stem cells?

A

stem cells that can give rise to any type in the body

36
Q

What are Tissue Stem Cells?

A
  • cells that are found admired with differentiated cells in tissues
  • Can only generate certain differentiated cells - usually only those that are normal constituents of that tissue
37
Q

What is Ischemia?

A

a condition in which the blood flow (and thus oxygen) is restricted or reduced in a part of the body

38
Q

What occurs during Ischemia? (4)

A
  • cell injury
  • coagulative necrosis
  • disappearance of oxygen and substrates for glycolysis
  • disappearance of continued ATP generation
39
Q

What are the sequence of steps that as a result of reduced levels of O2 during ischemia results in Necrosis? (5)

A
  • decreased O2 compromises respiration in mitochondria damaging the ability to produce ATP
  • decreased ATP causes the accumulation of Na in the cell and the diffusion of K out of the cell
  • accumulation of Na causes cells to swell, resulting in damage or rupture of the cell membranes
  • More acidic environment due to increased anaerobic glycolysis and the depletion of glycogen resulting in buildup of lactic acid
  • decreased ATP and pH levels cause ribosomes to detach from the rough endoplasmic reticulum (RER) with a reduction in protein synthesis
40
Q

What occurs if Ischemia is not relieved? (4)

A
  • worsening mitochondrial function
  • increasing membrane permeability
  • proteolytic enzymes are released due to the acidic environment, inducing widespread damage
  • calcium increases in the cells, leading to many enzyme systems to activate inappropriately
41
Q

What are blood serum samples used to measure in regards to cell injury and death?

A

they are used to measure the leakage of cell proteins across the degraded cell membrane into the peripheral circulation

42
Q

What are the 4 major mechanisms of cell injury?

A
  • Mitochondrial damage
  • Entry of Ca2+
  • Membrane damage -> plasma membrane, lysosomal membrane
  • Protein misfolding, DNA damage -> activation of pro-apoptotic proteins
43
Q

What can occur at early stages or in mild forms of injury?

A

The functional and morphological changes are entirely reversible if the stimulus is removed

44
Q

What are the two types of cell death?

A
  • Necrosis
  • Apoptosis
45
Q

What are the two types of Reversible Cell Injury?

A
  • Hydropic Swelling
  • Fatty Changes
46
Q

What is Hydropic Swelling?

A
  • Injury caused by a variety of agents producing a characteristic cellular or hydropic swelling when seen under the microscope
  • an increase in cell volume characterized by a large, pale, and vacuolated cytoplasm and a normally located nucleus
47
Q

What does Hydropic Swelling cause?

A
  • Impairment of the process that controls ionic concentrations in the cytoplasm
  • can impair the energy-dependent Na-K plasma membrane pump leading to an accumulation of Na in the cell
48
Q

What does Hydropic Swelling lead to?

A

An increase in water in the cell to maintain isosmotic conditions and the cell swells

49
Q

What is Fatty change?

A

a form of reversible adaptation to cell stressors, the abnormal accumulation of triglycerides within cells

50
Q

How does Fatty change occur? (3)

A
  • an increased delivery of fat to the cell
  • an impairment of fat metabolism within the cell
  • decreased synthesis of apolipoproteins for transport out of the cell
51
Q

What occurs during Fatty change?

A

Small vacuoles of fat appear throughout the cytoplasm or may coalesce to form one large vacuole that displaces the nucleus as a result of:
- toxin exposure
- protein malnutrition or starvation
- diabetes
- obesity
- anoxia

52
Q

Where does Fatty change occur? (4)

A
  • liver
  • heart
  • kidney
  • skeletal muscle
53
Q

What are the characterizations of Necrosis?

A
  • Eosinophilia (pinkness) of the cytoplasm
  • Pyknosis (shrinkage) of the nucleus
  • Karyorrhexis (pyknotic nucleus fragments or breaks up) the nucleus
  • Karyolysis (dissolution) of the nucleus
54
Q

What are the different types of Necrosis?

A
  • Coagulative
  • Liquefactive
  • Fat
  • Caseous
55
Q

What is Coagulative Necrosis?

A
  • most common form
  • cells appear like “ghosts”
  • typical of ischemia
  • ex. in heart cells
56
Q

What is Liquefactive Necrosis?

A

Rapid loss of tissue architecture and digestion of the dead cells
- most seen in CNS
- typical of bacterial infection or death of brain tissue

57
Q

What is Fat Necrosis?

A

Released enzymes digest fat that complexes with calcium to form chalky-white deposits
- specific to fat (adipose) tissue
ex. pancreatitis, damage to breast tissue

58
Q

What is Caseous Necrosis?

A
  • Soft, friable, “cheesy” material
  • characteristic of tuberculosis
59
Q

What is Gangrenous necrosis?

A

coagulative necrosis when there is superimposed infection with a liquefactive component
- most frequently of a limb

60
Q

What is Dry Gangrene?

A

If the necrotic tissue dries out (with no infectious component, and it becomes dark black and mummified

61
Q

What is Apoptosis?

A
  • morphological manifestation of programmed cell death
  • an energy-dependent process specifically designed to switch off unneeded or damaged cells and eliminate them
62
Q

How can Apoptosis occur?

A
  • Physiological
  • Pathological
63
Q

What is Physiological Apoptosis?

A
  • during embryogenesis is shaping of fingers and toes
  • physiological involution of the thymus during development or the endometrium during the menstrual cycle
  • removal of an infected or damaged cell
64
Q

What is Pathological Apoptosis?

A
  • following radiation injury
  • some cancers
65
Q

How do Apoptotic cells initiate their own death?

A

by the activation of proteases that breakdown the cell nucleus and cytoskeleton

66
Q

What occurs in Apoptosis?

A
  • The cell nucleus collapses due to chromatin condensation and fragmentation
  • the cell then shrinks and is cleaved into cytoplasmic buds enclosing organelles
  • finally, phagocytosis of the extruded apoptotic bodies
67
Q

What are the signs of necrosis?

A
  • chromatin clumping
  • organelle swelling
  • membrane damage

Pathology 2420 Part 1 (6 decks)

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