MBC - Cell Fate and Injury Flashcards
How do cells die?
Cell injury
How do cells get injured?
Either through an injurious stimulus or an inability to adapt to a stress/increased demand
What is lethal injury?
Injury which leads to death
What is sub- lethal injury?
Reversible injury or can lead to cell death
Explain how a cardiac myocyte responds to a stress?
It may either increase in size (hypertrophy) in response to increased load (stress), or injury such as ischaemia may cause reversible injury. Continued ischaemia will then cause cell death.
What are the 8 causes of cell injury with examples?
Ageing - acquisition of changes/mutation Physical agents - e.g. gunshot trauma Immunological reactions Genetic defects e.g. SCD Chemical agent e.g. weed killer Oxygen deprivation Infection agents e.g. viruses Nutritional e.g. obesity/starvation/malnutrition
How would oxygen deprivation cause myocardial infarction?
Ischaemia from coronary heart disease will arise from atheromatous plaque, this leads to oxygen deprivation and subsequent cell death.
What factors affect the cell response to injurious stimuli?
Type of injury
Duration
Severity
What do the consequence of the stimuli themselves depend on?
- Cell type - e.g. bone cells can survive without O2 much quicker than nerve cells.
- Status - proliferating cells are much more prone to mutating
What are the 4 vulnerable intracellular mechanisms?
ATP production
Cell membrane integrity
Protein synthesis
Integrity of genetic apparatus
How would damage to cell membrane integrity or ATP production arise?
Rapidly/almost immediately
How would damage to protein synthesis or DNA damage arise?
May show up in the later stages of life
How are ATP production and membrane integrity interlinked?
ATP production being affected will lead to the cell’s inability to maintain its membrane, thus compromising its integrity. Loss in membrane integrity may then cause a loss in intracellular regulation, thus having a negative effect on ATP production. Processes are inter-dependent
Give on example where injury precedes death, and death precedes morphology changing.
For example, myocytes will stop contracting having been injured and before cell death. Following cell death, they will undergo morphological changes.
What is atrophy?
A shrinkage in cell/organ size due to a loss in cell substance.
Give an example of atrophy.
Alzheimer’s - cerebrocortical atrophy
Muscle denervation leads to muscle atrophy.
What is hypertrophy?
Increase in cell size and thus organ size
What is the difference between physiological and pathological hypertrophy? (use examples)
- Physiological hypertrophy is normal in healthy individuals e.g. an increase in uterus size during pregnancy.
- Pathological hypertrophy is part of disease process e.g. cardiac myocytes increase in size due to abnormal increases in demand
How does hypertrophy come about?
Can occur as a result of increased functional demand or some sort of hormonal stimulus.
What is hyperplasia?
Increase of cell number in an organ.
What is physiological hyperplasia?
Can be compensatory or can be hormonal e.g. oestrogen stimulates endometrial glands to increase the size of the uterus by inducing proliferation.
What is pathological hyperplasia?
Can be due to excessive hormone or growth factor stimulation e.g. carcinoma.
What is metaplasia?
The reversible change in which one adult cell type is replaced by another.
What occurs in physiological metaplasia?
E.g. metaplasia of cervix during pregnancy, when columnar epithelial cells are replaced by squamous cells due to the low pH of the vagina. This change is reversed at the end of the pregnancy.
Give an example of pathological metaplasia.
Barrett’s oesophagus. There are squamous cells lining the oesophagus however columnar cells lining the stomach. Acid reflux leads to squamous cells of the oesophagus being replaced by columnar cells. This can be reversed with weight loss/antacids.
What is dysplasia?
Precancerous cells which show the cytological and genetic features of malignancy, however they do not invade underlying tissue
What (light) microscopic changes do we see with reversible injury?
Degenerative changes associated with tissue damage:
- Fatty change
- Cellular swelling
Give an example of fatty change from reversible injury
Alcoholic fatty change in the liver - appearance of fat cells.
Give an example of cellular swelling from reversible injury
Ballooning degeneration - damaged cytoskeleton of hepatocytes (liver) cause swelling.
What is necrosis?
Confluent cell death associated with inflammation.
What are the 4 types of necrosis?
Coagulative
Liquefactive
Caseous
Fat
What is coagulative necrosis?
This means that structures become fixed. E.g. myocardial infarction leads to inflammation between muscle fibres.
What is liquefactive necrosis?
Tissue becomes liquified. E.g. old cerebral infarct leads to holes appearing in the brain as parts of the brain liquify, this is because there is a loss of connective tissue to maintain structure.
What is caseous necrosis?
‘Cheesy’ - oozing necrosis/structureless. E.g. pulmonary TB - white cheese like appearance from fine granular necrotic material.
What is fat necrosis?
Fat is liquified. E.g. acute pancreatitis - pancreatic enzymes are activating leading to the digestion of surrounding tissue, such as lipase liquifying fat.
Why do we see calcium deposition in fat necrosis?
Free fatty acids released from lipase activity bind to calcium and thus cause it to precipitate and deposit.
What is apoptosis?
Programmed cell death of individual cells.
What is the difference between apoptosis and necrosis in terms of inflammation?
Necrosis: associated with inflammation
Apoptosis: not associated with any inflammation
What is the difference between apoptosis and necrosis in terms of membrane loss?
Necrosis: blebbing of membrane leads to membrane breaking off and leakage of cellular components
Apoptosis: Blebbing is controlled and remains in tact to form apoptotic bodies which are then digested via phagocytes.
What is the difference between apoptosis and necrosis in terms of energy?
Necrosis: passive
Apoptosis: active - requires energy
What is the difference between apoptosis and necrosis in terms of physiology?
Necrosis: pathological
Apoptosis: physiological or pathological
What are the causes of apoptosis?
Embryogenesis
Deletion of auto-reactive T cells in thymus
Hormone dependent physiological involution
Cell deletion in proliferating populations
Mild irreparable DNA damage
Where do we see apoptosis with embryogenesis?
E.g. with solid intestine being hollowed out, or webbed feet become de-webbed.
When do we see hormone dependent apoptosis?
Menstruation
When do wee see proliferative cell deletion apoptosis?
Normal cell death such as in the liver
What is necroptosis?
New programmed cell death that can be considered a hybrid of apoptosis and necrosis
What does necroptosis have in common with apoptosis?
Energy dependent - active
What does necroptosis have in common with necrosis?
Inflammatory
How may necroptosis arise?
Viral infection
What does inflammation from necrosis cause?
Healthy bone damage
