Cell adaptation & cell death Flashcards
List things that can damage cells
- Hypoxia - lack of oxygen = decreases oxidative phosphorylation = less ATP. Ischaemia is hypoxia due to lack of blood supply.
- Physical agents e.g. extremes of temp, radiation, sudden pressure changes.
- Chemical agents & drugs e.g. arsenic, alcohol, cyanide.
- Infections e.g. bacteria, fungi, viruses, parasites.
- Immune system - autoimmune diseases e.g. SLE
Name cellular response to stress (reversible) & noxious stimuli )(irreversible)
Reversible:
- adaptation
- normal cell
Irreversible:
- necrosis
- apoptosis
- necroptosis
Define the 5 reversible cell adaptations which occur in response to a change in environment and give an example of each adaptation
- Hypertrophy. An increase in cell size eg. myocardial hypertrophy in response to sustained high blood pressure.
- Hyperplasia. An increase in cell number eg. endometrial hyperplasia due to prolonged stimulation of the endometrium by the hormone oestrogen or milk glands in breast
- Metaplasia. A change from one differentiated (mature) cell type to another mature cell type which is better able to withstand the adverse environment eg. intestinal metaplasia of the oesophagus (Barretts oesophagus).
- Dysplasia. Disordered cell growth caused by a carcinogen eg. cervical dysplasia caused by human papilloma virus infection.
- Atrophy. A reduction in cell size eg. if a muscle loses its nerve supply it will undergo denervation atrophy
What is necrosis?
Accidental or unregulated form of cell death where damage to membrane causes lysosomal enzymes to be released which digest cell & result in inflammation
Always pathological
List 6 pathological types of necrosis & an example of the diseases in which these occur
- Coagulative necrosis - myocardial ischaemia (necrosis due to lack of blood supply).
- Liquefactive necrosis - stroke (ischaemic necrosis in the brain).
- Gangrenous necrosis - peripheral vascular disease.
- Caseous necrosis - tuberculosis.
- Fat necrosis - pancreatitis.
- Fibrinoid necrosis - vasculitis.
What molecular features characterise necrosis?
Mitochondria damaged- no ATP- no energy dependent functions e.g. influx of Ca to activate enzymes
Free radicals accumulate- damage proteins, lipids and nucleic acids.
Increased membrane permeability- affects plasma membranes, lysosomal membranes & mitochondrial membranes
State the mechanism of necrosis
- Damage to mitochondria stops cell producing the ATP which powers its processes.
- Increase in Ca²⁺ ions - an increase in intracellular calcium **increases mitochondrial permeability, depleting ATP. i.e. loss of membrane integrity.
- Ca²⁺ can also activate a number of enzymes causing membrane, protein, nuclear & DNA damage. - Free radicals - damage to DNA and proteins
What is apoptosis?
Programmed cell death that can be either physiological or pathological. It can be caused by protein or DNA damage.
There is no loss of membrane integrity and no inflammatory reaction.
What exposures/diseases are associated with apoptosis & disrupted apoptosis?
A
Misfolded proteins can accumulate in the endoplasmic reticulum (ER) causing ER stress & subsequent apoptosis.
Viral infections eg. HIV can cause apoptosis directly or by a host immune reaction (via cytotoxic T-cells).
T-cells can cause apoptosis in tumours & in transplants during cellular rejection.
Radiation, hypoxia & cytotoxic drugs can damage DNA & if repair mechanism fail apoptosis is induced to prevent malignancy
p53 is tumor suppressor gene- stops cells diving id DNA is damaged- if their damaged too, apoptosis is triggered
- p53 mutations predispose to cancer
List the two apoptosis pathways
- Intrinsic (mitochondrial) pathway.
- Extrinsic (death receptor) pathway
Explain how intrinsic apoptosis pathway works?
triggered by cell injury, DNA damage or decreased hormone stimulation
Causes inactivation of BCL-2 which is an anti-apoptotic molecule
This inactivation allows cytochrome C to leak from the inner mitochondrial matrix into the cytoplasm of the cell to activate caspases.
Caspases are proteases which can breakdown cell proteins.
Explain how the extrinsic pathway works?
activated by FAS ligand binding to the FAS death receptor on a target cell, activating caspases.
- This is mechanism by which lymphocytes which respond to self can be eliminated
can also be triggered by Tumour Necrosis Factor (TNF) binding to the tumour necrosis factor receptor on a target cell.
Some viruses & normal cells can produce a molecule called FLIP which can block apoptosis.
Once a cell dies by apoptosis, what happens next?
Phosphatidylserine flips from inner to outer aspect of cell membrane & this is recognised by macrophage receptors.
Apoptotic cells secrete factors that recruit macrophages.
- Macrophages phagocytose the apoptotic bodies & dead cells disappear w/in mins
List 4 mechanisms which can cause abnormal accumulations to occur w/in cells. Give 1 example of disease associated w/ each mechanism
- Abnormal metabolism e.g. fat accumulating in liver cells in alcoholic liver disease
- Lack of enzymes e.g. lysosomal storage diseases
- Defect in protein folding or transport e.g. nephrotic syndrome- causes excessive protein loss through kidneys & causes protein accumulation in kidney cells
- Ingestion of indigestible material e.g. carbon accumulation in pneumoconiosis (lung disease seen in coal miners)
Describe 2 forms of pathological calcification
- Dystrophic calcification- occurs when Ca is deposited in tissue which is injured or dead- in this form calcium metabolism is normal
- Metastatic calcification- seen in association w/ hypercalcaemia. May be caused parathyroid tumour or by production of parathyroid hormone by other tumours
- Paget’s disease & multiple myeloma increase osteoclast activity causing hypercalcaemia
- Excessive Vitamin D causes increased Ca & sarcoidosis is a disorder where granulomas form- these macrophages can activate a vitamin D precursor causing hypercalcaemia
