Lecture 1 - Cell Death, Insult Flashcards
What is the name of the process whereby a tissue’s blood supply is reinstated?
Reperfusion
What are the outcomes of reperfusion?
Restoration of blood flow brings about:
• recovery of tissue
• Reperfusion injury: damage is increased
What are the different ‘types of insult’?
- Hypoxia
- Chemical
- Infections
- Physical
- Immune
- Nutrition
What are the ways that pharmaceuticals have toxic effects?
- directly
* effect exerted through metabolites (eg. alcohol metabolism to acetaldehyde)
How can electrical currents be damaging?
Directly disrupt cell membranes
How can changes in pressure be damaging?
eg. Hitting one’s thumb with a hammer; cellular disruption
What do cytokines effect?
- Gene expression
* Cellular metabolism
Describe the insult of ‘nutrition’
- Nutritional deficiency
* Nutritional excess
What are free radicals?
Highly reactive molecules that have an unpaired valence electron, and will ‘steal’ electrons from other molecules, leading to injury
How do free radicals arise?
- Irradiation
- Carcinogens
- Endogenous, normal metabolic processes
- Transition metals
- NO (a paracrine commonly found in the body)
- Toxins
How are free radicals removed?
Normal decay
Antioxidants
• Vit E
• Vit A
Storage proteins
Enzymes
• SOD
Describe the damage that free radicals cause to cellular structures
Lipids:
• Lipid peroxidation
Protein:
• Protein cross linking
DNA
• Single stranded breaks
What are heat shock response genes?
A set of genes in our genome that are unregulated when the cell is stressed.
They serve to protect proteins in the cell
What are the factors that determine the degree of injury?
- Duration of injury
- Type of injury
- Severity of injury
Describe why time is a critical factor in reversible/irreversible cell injury
As time elapses, the cell function decreases.
Then once the cell is dead, it takes some time for morphological changes to be recognisable
What changes to cells can be observed by light microscopy?
Nuclear changes:
• Pyknosis, Karyorrhexis, Karyolysis
Cell membrane changes
Cytoplasmic changes:
• Increased eosinophilia
What is the cellular hallmark of irreversible injury?
Massive accumulation of intracellular calcium
What are the morphological differences between reversible and irreversible cell injury?
Reversible:
• surface blebs
• increased eosinophilia
Irreversible: • necrosis • loss of nuclei • fragmentation of cells • leakage
What happens during apoptosis? Size Nucleus Plasma membrane Cellular contents Adjacent inflammation Physiologic or pathologic role
Size: decrease in cell size Nucleus: condenses & fragments Membrane: intact, but altered structure Cellular contents: intact Adjacent inflammation: none Role: often physiological, but can occur in pathological situations (e.g. DNA damage)
What happens to chromatin in apoptosis?
Endonucleases digest it down into nucleosome-sized fragments
What happens during necrosis? Size Nucleus Plasma membrane Cellular contents Adjacent inflammation Physiologic or pathologic role
Size: swelling Nucleus: fragments Membrane: disrupted Cellular contents: enzymatic digestion Adjacent inflammation: frequent Role: invariably pathological
What happens to the nucleus in necrosis?
Non specific breakdown of DNA:
• Pyknosis: condensation and increased eosinophilia
• Karyorrhexis: fragmentation of condensed nucleus
• Karyolysis: nucleases break down DNA
What is necrosis?
Death of groups of contiguous cells in tissue or organ
What are the various patterns of necrosis?
- coagulative
- liquefactive
- caseous
- fat necrosis
- (gangrene)
- (infarct)
