Lecture 2 - Cell Injury And Cell Death Flashcards
What are the general cell responses to injury?
Cell adapts to the injury
Injured cell repairs if damage is reversible
Cell dies
What happens when the heart becomes damaged?
Myocytes have to work harder
Adaptation - Cardiac myocytes hypertrophy
Ventricular hypertrophy
More O2 for bigger cells needed
Hypoxia
Myocardial infarction/arrhythmia
What are the 2 types of causes to cell injury?
Environmental
Non-environmental
What are some environmental causes of cell injury?
HYPOXIA
TOXINS
Immune mediated
Physical agents
Infection
Nutritional
What are some non-environmental causes of cell injury?
Genetics
Ageing
What is hypoxia?
Oxygen deprivation
What are the 4 different causes of hypoxia
Hypoxaemic hypoxia
Anaemic hypoxia
Ischaemic hypoxia
Histiotoxic hypoxia
What is Hypoxaemic hypoxia?
Arterial content of oxygen is low
What is Anaemic hypoxia??
Haemoglobin has a reduced ability to carry oxygen (Anaemic or CO poisoning etc…)
What is Ischaemic hypoxia?
Interruption to blood supply
What is Histiotoxic hypoxia?
Inability to utilise oxygen due to disabled oxidative phosphorylation enzymes
What may be a cause of Histiotoxic hypoxia?
Cyanide poisoning
How quickly are neurones affected by hypoxia?
Affected after a few minutes
What are some immune mediated cases of hypoxia and what type of reactions are they?
Hypersensitivity reactions (anaphylaxis in allergy)
Autoimmune reactions (Graves disease of the thyroid)
What are hypersensitivity reactions?
Excessive immune response to non self antigens causing injury
What is an autoimmune reaction?
Immune system over reacts to a self antigens causing tissue damage
What do most mechanisms of cell injury lead to which causes damage?
Lack of ATP
What are the 2 main mechanisms of cell injury?
Depletion of ATP
Oxidative stress (free radicals)
What are the 6 mechanisms of cell injury?
Depletion of ATP
Oxidative stress (free radicals)
Direct mitochondrial damage
Direct membrane damage
Disruption to calcium homeostasis
Direct damage to DNA and proteins
How does Hypoxia result in ATP depletion?
Less O2
Less oxidative phosphorylation
Less ATP synthesised by mitochondria
What are the 3 ways reduced ATP affects the cell?
Affects pH
Calcium homeostasis of cells lost (calcium influx)
Protein synthesis
How does reduced ATP lead to pH being affected?
Increased anaerobic respiration
Increased lactic acid build up
How does reduced ATP cause calcium influx into cells?
ATP sensitive Na+/K+ pumps affected
Na+ and water enter cell
Calcium also enters the cells
How does reduced cell ATP lead to protein synthesis being affected?
Ribosomes detach from ER
Reduced protein synthesis
Causes abnormal protein build up
How does calcium influx cause irreversible cell damage?
Calcium activates enzymes like
ATPases
Phospholipases
Proteases
Endonucleases
Why is activation of phopholipases by excess calcium bad?
Breaks down membranes which can lead to cell contents leaking out
What is the affect of activating proteases by excess calcium?
Cleaves proteins
What is the affect of activating endonucleases by excess calcium?
Breaks down DNA
Where are Free radicals generated?
The ETC
Ischaemic-repercussion injury
Cellular ageing
Antimicrobial killing by phagocytosis (respiratory burst)
What are some examples of free radicals/ROS?
Hydroxyl
Superoxide O2-
Hydrogen peroxide H2O2
What are the 3 ways which free radicals cause damage?
Lipids
Proteins
DNA
How do free radicals damage lipids?
LIPID PEROXIDATION
Unsaturated fatty acids get attacked producing more free radicals causing a chain reaction
Damages membranes causing calcium influx
How do free radicals damage proteins?
Causes cross linking (disulphide bonds)
Oxidation of protein is
Cleaving proteins
How do free radicals damage DNA?
Single or double stranded breaks
How do free radicals damage DNA?
Single or double stranded breaks
How does the body control number of free radicals?
Antioxidants
Transport proteins
Enzymes
What are some examples of antioxidants?
Vitamins C and E (Vit C regenerates reduced Vit E)
GSH
Abscorbic acid
What a re one transport proteins which help control free radicals?
Iron binds to transferrin
Copper binds to ceruloplasmin
What is Wilsons disease?
Improper copper metabolism
What are some enzymes which control free radicals in the body?
Superoxide dismutase (SODs)
GSH peroxidase
What is the function of heat shock proteins?
Help deal with free radical damage
Help repair and refold damaged proteins or label them for degradation
What are some indications that injured cells are reversibly injured?
Swelling
Clumped chromatin
Ribosome dispersion
Cytoplasmic blebs
What are some indications that cells have been damaged irreversibly?
Membrane defects
Nuclear changes
Lysis of ER
Lysosome rupture