Session 1 Flashcards
What does the degree of cell injury depend on?
- Duration of injury
- Severity of injury
- Type of injury
- Type of tissue
What can cause cell injury?
- Hypoxia
- Toxins
- Physical agents (eg. direct trauma, changes in temperature like burns, changes in pressure)
- Microorganisms
- Radiation (internal organ injury)
- Dietary insufficiencies
- Immune mechanisms (eg. autoimmune, allergy)
What is the difference between hypoxia and ischaemia?
- Hypoxia: reduced oxygen supply.
- Ischaemia: loss of the blood supply into an area and therefore reduced delivery of O2 and nutrients
What can cause ischaemia?
- Arterial occlusion
- Global hypotension (sepsis)
What is hypoxaemic hypoxia?
Low arterial content of oxygen
What are the causes of hypoxaemic hypoxia?
- Reduced O2 partial pressures at altitude
- Reduced O2 absorption (lung disease, poor O2 exchange)
What is anaemic hypoxia?
Decreased ability of haemoglobin to carry oxygen
What are causes of anaemic hypoxia?
- Anaemia
- CO poisoning
What is ischaemic hypoxia?
Interruption to the blood supply (most important clinically!)
What are the causes of ischaemic hypoxia?
- Blockage of a vessel
- Heart failure
What is histiocytic hypoxia?
Inability to utilise oxygen in cells due to disabled oxidative phosphorylation enzymes (when tissue cells are poisoned and can’t use O2)
What can cause histiocytic hypoxia?
Cyanide poisoning
Why can the brain not survive without oxygen for too long?
- Neurones have a higher and quicker demand for O2
- Other cells (eg. fibroblasts) can survive for longer
How can the immune system damage cells in the body?
- Hypersensitivity: overly vigorous immune reactions
- Autoimmune reactions: failure to distinguish self from non-self
Which cell components are most susceptible to injury?
- Plasma/organelle membranes
- Nucleus (DNA)
- Proteins (structural, metabolic enzymes)
- Mitochondria (oxidative phosphorylation)
What happens in hypoxia when the injury is reversible (short term)?*
- Oxidative phosphorylation can’t function, so less ATP is produced
- Less ATP means reduced function of sodium pump which causes an increase in Ca2+, Na+ and H2O, K+ efflux
- Causes oncosis, blebs, ER swelling, myelin figures
- Less ATP means increased glycolysis, causing lower pH and therefore chromatin clumping
- Lower ATP causes less protein synthesis leading to lipid deposition
What happens in prolonged hypoxia?*
- Increased Ca2+ inhibits: ATPase: reduced ATP Phospholipase: decreased phospholipids Protease: disruption of protein Endonuclease: nuclear chromatin damage
What are free radicals?
Reactive oxygen species which have a single unpaired electron in the outer orbit and therefore have an unstable configuration that can react with other molecules and produce further free radicals.
What are the 3 significant free radicals that can cause damage?
- Hydroxyl
- Superoxide
- Hydrogen peroxide
When are free radicals produced?
- Oxidative phosphorylation (can escape the electron transport chain)
- Oxidative burst of neutrophils (inflammation)
- Radiation causing lysis of H2O
- Contact with unbound metals within body (Fenton reaction)
- Drug metabolism
How does the body control free radicals?
- Antioxidant scavengers that donate electrons to free radicals (Vit. A, C, E)
- Metal carrier and storage proteins (transferrin, ceruloplasmin) that make metals unavailable for reactions
- Enzymes that neutralise free radicals
Which enzymes neutralise free radicals?
- Superoxide dismutase
- Glutathione peroxidase
- Catalase
How do free radicals injure cells?
- Cause lipid peroxidation in the lipids in cell membranes
- Generates further radicals and creates a chain reaction
How do free radicals affect DNA?
- Can oxidise proteins, carbohydrates and DNA
- Molecules can become broken or crosslinked
- Made mutagenic and therefore carcinogenic