Cell injury Flashcards

1
Q

List 6 causes of cell injury and death

A
  • Hypoxia
  • Physical agents, including trauma
  • Drugs and therapeutic agents
  • Microorganisms
  • Dietary insufficiency or excess
  • Immune mechanisms or genetic abnormalities
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2
Q

Describe the causes and consequences of hypoxia

A
  • Oxygen deprivation to a cell
  • Some cells are less tolerant of this, i.e. neurones
  • If persistent will cause cell adaptation or death
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3
Q

Explain reversible and irreversible hypoxic injury

A
  • Reversible
    • Reduced ATP from oxidative phosphorylation
    • This decreases ATP available for Na/ K pump
    • As a result, Na accumulates inside the cell
    • The cell starts to swell from osmosis (oncosis)
    • Anaerobic respiration reduces pH = damage enzymes
    • Ribosomes detach from ER = lower protein synthesis
  • Irreversible
    • Not a clear cut off point
    • Profound oncosis
    • Loss of membrane integrity = calcium influx
    • Necrosis, as calcium triggers many potent enzymes
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4
Q

Explain the mechanisms of reperfusion injury

A
  • Increased production of ROS
  • Increased supply of neutrophils and ergo inflammation
  • Delivery of complement proteins
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5
Q

What are the three most important biological free radicals?

A
  • OH (hydroxyl)
  • O2- (superoxide)
  • H2O2 (hydrogen peroxide)

Free radicals attack lipids in cell membranes and cause lipid peroxidation. They can also damage proteins, carbohydrates and nucleic acids.

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6
Q

Describe the body’s defence against free radicals

A
  1. Enzymes
    a) superoxide dismutase (makes H2O2 - less harmful)
    b) catalases and peroxidases
  2. Free radical scavengers
    a) vitamins A, C and E
    b) glutathione
  3. Storage proteins which sequester radical catalysts
    a) Transferrin and ceruloplasmin
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7
Q

What are heat shock proteins?

A
  • Proteins consisting of chaperones, unfoldases and stress proteins
  • Triggered by any injury and remain inside the cell
  • Increased HSP synthesis following injury
  • Recognise incorrectly folded proteins and correct them
  • Remove if they can’t be fixed
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8
Q

Define and describe oncosis

A
  • Cell death with swelling
  • Blebbing
  • Typically as a result of hypoxia and ischaemia
  • Three main changes can be seen microscopically
    1) Cytoplasmic - reduced pink staining
    2) Nuclear - chromatin clumping
    3) Abnormal intracellular accumulations
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9
Q

Define and describe necrosis

A
  • Occurs in a living person
  • The morphological change after cell death
  • Occurs typically 4-24 hours after cell death
  • Either coagulative or liquifactive
  • Appearance, not a process
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10
Q

Define and describe apoptosis

A
  • Programmed cell death
  • Either single or small cluster of cells
  • Shrinkage
  • Eosinophillic cytoplasms
  • Cell budding
  • Embryogenesis
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11
Q

What are the types of gangrene? Describe

A
  • Necrosis that is visible to the naked eye
  • Dry gangrene = coagulative necrosis
  • Wet gangrene = infected. Liquifactive necrosis
  • Gas gangrene = infection with anaerobic bacteria
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12
Q

Explain red infarct and where it occurs

A
  • haemorrhagic
  • dual blood supply or anastomoses
  • poor stromal support
  • lungs, intestines
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13
Q

Explain white infarct and where it occurs

A
  • anaemic
  • occurs in structures with good stromal support
  • occlusion of an end artery
  • heart, spleen and kidney
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14
Q

List and explain some abnormal cell accumulations

A

1) water and electrolytes
2) lipids - e.g. steatosis
3) proteins
4) pigments - exogenous (i.e. soot) or endogenous
5) carbohydrates

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15
Q

Describe dystrophic calcification

A
  • Occurs in areas of dying tissue, atherosclerotic plaques, damaged heart valves and tuberculous lymph nodes
  • local calcification
  • hypercalcaemia not normally present
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16
Q

Describe metastatic calcification

A
  • systemic calcification
  • hypercalcaemia normally present
  • increased PTH
  • bone tumours
  • paget’s disease of bone (increased turnover)
17
Q

Briefly explain cellular aging

A
  • decline in ability to replicate
  • ‘replicative scenesence’
  • successively shortening telomeres
  • telomerase is found in stem cells and stops this process
18
Q

Briefly, what are the effects of alcohol on the liver?

A
  • fatty change: steatosis and hepatomegaly
  • acute alcoholic hepatitis: focal necrosis, liver tenderness and jaundice. Usually reversible.
  • Cirrhosis: hard, shrunken liver. Excess collagen.
19
Q

What is hypoxaemia?

A

Arterial content of oxygen is low, i.e. reduced inspired O2 at altitude

20
Q

What is anaemia?

A

Decreases ability of haemoglobin to carry oxygen, i.e. reduced RBC or CO2 poisoning

21
Q

What is ischaemia?

A

An interruption in blood supply to a tissue, normally as a result of infarction

22
Q

Histiocytic

A

Inability to utilise oxygen in cells due to oxidative phosphorylation enzymes

23
Q

What are the 4 essential targets of cell injury?

A
  1. Cell membranes
  2. Nucleus
  3. Proteins
  4. Mitochondria
24
Q

How is apoptosis initiated?

A
  1. Intrinsica) DNA damage or p53 protein (many others)
    b) increased mitochondrial permeability
    c) releases cytochrome C from mitochondria
    d) interacts with APAF1 and caspase 9
    e) activates downstream caspases
  2. Extrinsica) TRAIL or Fas ligands
    b) bind to death receptors on membrane
    c) activation of caspases independent of mitochondria
25
Q

Explain liquifactive necrosis

A
  • predominantly active enzyme degradation
  • mass neutrophil infiltration
  • enzymatic digestion
  • puss formation
  • occurs in the brain (no supportive collagen)
26
Q

Explain coagulative necrosis

A
  • predominantly protein denaturation
  • solid consistency
  • ‘ghost outline’ histologically as structure preserved
27
Q

What is a potassium bomb?

A
  • Release of large amounts of potassium from dead cell
  • Can induce acute hyperkalaemia
  • May cause arrhythmia
  • Result of mass necrosis
    a) tourniquet shock
    b) tumour lysis syndrome
    c) severe burns