Cell injury Flashcards
List 6 causes of cell injury and death
- Hypoxia
- Physical agents, including trauma
- Drugs and therapeutic agents
- Microorganisms
- Dietary insufficiency or excess
- Immune mechanisms or genetic abnormalities
Describe the causes and consequences of hypoxia
- Oxygen deprivation to a cell
- Some cells are less tolerant of this, i.e. neurones
- If persistent will cause cell adaptation or death
Explain reversible and irreversible hypoxic injury
- 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
Explain the mechanisms of reperfusion injury
- Increased production of ROS
- Increased supply of neutrophils and ergo inflammation
- Delivery of complement proteins
What are the three most important biological free radicals?
- 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.
Describe the body’s defence against free radicals
- Enzymes
a) superoxide dismutase (makes H2O2 - less harmful)
b) catalases and peroxidases - Free radical scavengers
a) vitamins A, C and E
b) glutathione - Storage proteins which sequester radical catalysts
a) Transferrin and ceruloplasmin
What are heat shock proteins?
- 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
Define and describe oncosis
- 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
Define and describe necrosis
- 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
Define and describe apoptosis
- Programmed cell death
- Either single or small cluster of cells
- Shrinkage
- Eosinophillic cytoplasms
- Cell budding
- Embryogenesis
What are the types of gangrene? Describe
- Necrosis that is visible to the naked eye
- Dry gangrene = coagulative necrosis
- Wet gangrene = infected. Liquifactive necrosis
- Gas gangrene = infection with anaerobic bacteria
Explain red infarct and where it occurs
- haemorrhagic
- dual blood supply or anastomoses
- poor stromal support
- lungs, intestines
Explain white infarct and where it occurs
- anaemic
- occurs in structures with good stromal support
- occlusion of an end artery
- heart, spleen and kidney
List and explain some abnormal cell accumulations
1) water and electrolytes
2) lipids - e.g. steatosis
3) proteins
4) pigments - exogenous (i.e. soot) or endogenous
5) carbohydrates
Describe dystrophic calcification
- Occurs in areas of dying tissue, atherosclerotic plaques, damaged heart valves and tuberculous lymph nodes
- local calcification
- hypercalcaemia not normally present