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2. General Pathological Mechanisms > Cell Injury, Death and Degeneration > Flashcards

Cell Injury, Death and Degeneration Flashcards

1
Q

List the 7 main causes of cell injury.

A 
Physical agents
Chemical agents
Infections
Hypoxia/ischaemia
Genetic defects
Immunological reactions
Nutritional imbalance
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2
Q

Outline the 5 main mechanisms of cell injury.

A

Damage to mitochondria
-Disrupted ATP synthesis

Damage to cell membranes

  • Disrupted ion concentrations
  • Disrupted osmotic imbalance
  • This causes cell oedema and bursting

Damage to cytoplasm (including ribosomes)

  • Disrupted protein/enzyme synthesis (includes architectural proteins)
  • Therefore abnormal function and structure

Damage to nucleus

  • DNA damage and disrupted DNA repair
  • Gene expression is altered

Oxidative stress

  • Caused by ROS/free radicals
  • Formed due to hypoxia, toxic substances, radiation
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3
Q

List 5 types of reversible cell damage.

A

“Cloudy swelling” - i.e. osmotic imbalance leads to high ion concentrations and influx of water

Cytoplasmic blebs

Disrupted microvilli

Swollen mitochondria

“Fatty change” - formation of lipid vacuoles due to faulty lipid metabolism

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4
Q

Give 2 examples of irreversible cell damage.

A

Cell membrane rupture

Pyknotic nucleus

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5
Q

What is the difference between necrosis and infarction?

A

Necrosis - un programmed, pathological cell death

Infarction - necrosis due to loss of blood supply

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6
Q

List 3 cellular features of necrosis.

A

Disruption of cell membranes (including organelle membranes)

  • Cell swelling
  • Vacuolation

Cell lysis and release of cell contents

  • Damage to adjacent cells
  • Acute inflammation

DNA disruption
-DNA hydrolysis

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7
Q

What are the 4 different types of necrosis?

A

Coagulation (haemorrhagic or gangrenous)

Colliquitive

Caseous

Fat

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8
Q

What are the features of coagulative necrosis?

A

Firm

Retains tissue shape

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9
Q

What are the features of colliquitive necrosis?

A

Tissue becomes liquid

Tissue structure is lost

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10
Q

What are the features of caseous necrosis?

A

Combination of coagulative and colliquitive necrosis

Cheese-like appearance

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11
Q

Give 5 examples of physiological apoptosis.

A

Hormone dependent involution of uterus/breasts/ovaries

Embryological development

Self-reactive T cells in the thymus

Deletion of cells in proliferating populations

Deletion of inflammatory cells after an inflammatory response

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12
Q

Draw a simple diagram outlining what causes cell injury and eventual cell death.

A

(See diagram in notes)

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13
Q

What are the 4 cellular features of apoptosis?

A

Cell shrinkage
Chromatin condensation
Cell membranes remain intact
Cytoplasmic blebs and apoptotic bodies

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14
Q

Define depositions.

A

“Abnormal intra- or extracellular accumulation of substances.”

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15
Q

What are the 4 different types of deposition?

A

Intracellular
Extracellular
Endogenous substances
Exogenous substances

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16
Q

Give 5 examples of intracellular depositions of endogenous substances.

A 
Melanin
Haemosiderin
Bile
Lipid
Degeneration products (e.g. lipofuscin)
17
Q

Give 3 examples of extracellular depositions of endogenous substances.

A

Amyloid
Fibrosis
Calcium

18
Q

Give 3 examples of depositions of exogenous substances.

A

Tattoo pigment
Carbon
Asbestos

19
Q

What are the 2 causes of amyloid depositions?

A

Abnormal folding of soluble protein fibrils creating abnormal insoluble aggregates

Many different proteins can do this

20
Q

Describe the pathogenesis of amyloid depositions.

A

Excessive production/accumulation of normal protein

Production/accumulation of abnormal protein

Tendency of protein to misfold

21
Q

What are the 2 types of amyloid deposition occurring due to excessive production of normal protein?

A

AL amyloid

AA amyloid

22
Q

What does AL amyloid deposition consist of?

Give an example of a disease which might cause this.

A

Consists of: immunoglobulin light chain

Example: B lymphocyte neoplasms, e.g. multiple myeloma

23
Q

What does AA amyloid deposition consist of?

Give an example of a disease which might cause this.

A

Consists of: serum amyloid associated protein (normal; produced in liver)

Example: chronic inflammation, e.g. RA

24
Q

Give 5 examples (other than amyloid) of pathological depositions.

A 
Steatosis (liver)
Lipofuscin (liver)
Iron (liver)
Iron (macrophages)
Carbon (lungs)
25
Q

What are the 2 types of calcification?

A

Dystrophic - deposition in abnormal tissue with normal serum calcium

Metastatic - deposition in normal tissue with raised serum calcium

26
Q

List 2 causes of raised serum calcium.

A

Increased levels of parathyroid hormone

  • Primary: parathyroid gland tumour
  • Secondary: kidney disease

Systemic effect of cancer

27
Q

What are the 3 types of DNA disruption associated with necrosis?

Briefly describe each.

A

Karyolysis - nuclear fading

Pyknosis - nuclear condensation

Karyorrhexis - nuclear fragmentation

28
Q

Give 3 examples of pathological apoptosis.

A

Viral infection
DNA damage
Hypoxia/ischaemia

29
Q

What are the 2 pathways of apoptosis?

A

Intrinsic (mitochondrial) pathway

Extrinsic (death receptor initiated) pathway

30
Q

Describe the intrinsic pathway of apoptosis. (4)

A
  1. ROS and oxidative stress causes release of pro-apoptotic factors from the mitochondria (e.g. cytochrome C)
  2. These pro-apoptotic factors activate caspase enzymes
  3. Caspases breakdown intracellular organelles
  4. Remnants are packaged into vesicles, which form cytoplasmic blebs and then apoptotic bodies
    a. Apoptotic bodies are then phagocytosed by macrophages
31
Q

Describe the extrinsic pathway of apoptosis. (4)

A
  1. TNF alpha binds to receptors and activates FADD (Fas-associated death domain) and TRADD (TNF receptor associated death domain)
  2. FADD and TRADD activate caspases
  3. Caspases break down intracellular organelles
  4. Remnants are packaged into vesicles, which form cytoplasmic blebs and then apoptotic bodies
    a. Apoptotic bodies are then phagocytosed by macrophages

2. General Pathological Mechanisms (4 decks)

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