Cell Fate And Injury Flashcards
What is a lethal cell injury?
Results in cell death
What is a sublethal cell injury?
Produce injury not amounting to cell death, may be reversible or progress to cell death
Why might cells be under stress? (2 main reasons)
Physiological e.g. pregnant
Pathological e.g. infection
Physiological vs pathological
Part of natural body’s response
In response to disease
What does stress do to cells?
Stress makes cells adapt and become bigger - hypertrophy
When does stress damage cells?
Initially, the effects of stress are reversible, however if the adaptation is pushed too far and the cell is unable to adapt, it results in cell death
The cellular response to injury depends on?
- Type of injury
- Duration
- Severity
What are the 8 types of cell injury?
- Oxygen Deprivation
- Chemical Agents drugs
- Infectious Agents
- Immunological Reactions
- Genetic Defects
- Nutritional Imbalances
- Physical Agents background radiation bullet
- Ageing
Multiple at once can result in cell death
Consequences of an injurious stimulus depends on:
- Type of cell (e.g. brain and heart need lots of oxygen whereas bone and fat are more resistant to hypoxia)
- Status
- Adaptability
- Genetic makeup
Which 4 systems are more vulnerable?
Cell membrane integrity - the cell recognises self from non-self, so if this functionality is broken, there are issues ATP generation (pretty quick cell death) Protein synthesis Integrity of DNA (consequences severe but takes a long time)
What happens before and after cells die?
Function stops before death
Morphological changes are seen after death
Hence patients with a blocked coronary artery may die before myocardial infarction
What are some cellular adaptations to injury?
Atrophy, Hypertrophy, Hyperplasia, Metaplasia, Dysphasia,
What is atrophy?
Shrinkage in size of cell or organ by the loss of cell substance
What might the brain of a dementia patient be linked to?
Atrophy of the brain
What is denervation atrophy in muscles?
In muscles, the nerves supplying the groups of cells influence protein synthesis in muscle
If the nerve is damaged, cells supplied by the nerve shrink (atrophy)
What is hypertrophy?
Increase in size of cells, and consequently, increase in the size of the organ
Can be due to pathological or physiological reasons
Can be caused by increased functional demand or hormone stimulation
Examples of where hypertrophy occurs?
Happens when building bulk muscle
Can occur in the heart (cardiomyocytes), may be caused by increased demand e.g. higher systolic pressure or physiological changes (pregnancy) and/or hormones
Hypertrophy of the uterus during pregnancy
What is hyperplasia?
Increased number of cells
Physiological (hormonal or compensatory - e.g. loss of tissues) or pathological (excessive hormonal or growth factor stimulation)
Examples of where hyperplasia occurs?
If one kidney removed, the other kidney gets bigger. Compensation for increased demand
Cancer is pathological hyperplasia, there are lots of mitoses
Proliferative Endometrium is physiological hyperplasia, an increase in number of cells in the endometrium (membrane lining the uterus) due to an increase in oestrogen levels
What is metaplasia?
Reversible change in which one adult cell is replaced by another
One adult cell becomes another adult cell
Physiological or pathological
Examples of where metaplasia occurs?
Physiological metaplasia - Cervix - Expansion of cervix during pregnancy due to the exposure of glandular epithelium on the outside of the cervix
Barrett’s Oesophagus ‐ The squamous cells of the oesophagus gets replaced with goblet cells due to long term acid reflux. Goblet cells are supposed to be in the intestine, not the oesophagus
What is dysphasia?
Precancerous cells show genetic and cytological features of malignancy but not invading underlying tissue
If diagnosed early, can be treated easily e.g. cervical cancer screening aims to identify dysphasia
What is cancer?
Cancer needs invasion of underlying tissues
Increase in nuclear:cytoplasmic ratio
Does metaplasia increase risk in developing cancer?
Not directly, metaplasia itself does not cause an increased risk of developing cancer, but metaplasia is more likely to lead to dysphasia, which has an icreased risk of cancer.
e.g. Barrett’s oesophagusis is associated with an increased risk of oesophageal cancer
What are 2 degenerative changes?
- Fatty change
- Cellular swelling
Both light microscopic changes are associated with reversible injury
On an image, how does alcoholic liver disease show alcoholic fatty change and cellular swelling?
Fat accumulation is shown on an image as white holes - this is a result of alcohol consumption
There is ballooning of cells
Both are reversible changed
Necrosis
Confluent cell death AND secondary inflammation (which causes damage to healthy cells surrounding)
Recruits neutrophils to the area
What are the 4 light microscopic changes associated with irreversible injury? (AKA 4 types of necrosis)
- Coagulative necrosis
- Liquefactive necrosis
- Caseous necrosis
- Fat Necrosis
Coagulation
Proteins irreversibly bound to each other
coagulative Necrosis
Coagulative = keeps its shape
The shape / structure of the molecules remain the same, but it is dead e.g. all the nuclei disappear (on an image)
The dead cells are between inflammatory cells (black dots on an image)
Liquifactive necrosis
Death of brain cells often result in round black spots on brain imaging, where the brain has liquified
No solid brain matter in those holes
Granular / Caseous necrosis
Small granule like cells and inflammatory cells (small dark dots)
Associated with pulmonary TB
Fat necrosis
Associated acute pancreatitis
The enzymes released digest what is available e,g, lipases begin to digest fat in pancreas
Free fatty acids are generated, and they bind to Ca2+ in the extracellular fluid to form a precipitate
Bluish area on scan corresponds to calcium, white deposits correspond to fat necrosis
What is an ulcer?
A local defect, or excavation of the surface, of an organ or tissue, produced by sloughing of necrotic inflammatory tissue
What is apoptosis?
Programmed cell death
Nucleus shrinks and breaks off, and so is small and fragmented inside cell
Usually a single cell - no inflammation around it
Fragments eaten my macrophages
Active, energy driven process, requires ATP
What are some causes of apoptosis?
- Embryogenesis - intestines have a lumen because of apoptosis during devlopment
- Deletion of auto-reactive T cells in the thymus
- Hormone-dependent physiological involution - e.g. shedding of endometrium
- Cell deletion in proliferating (rapidly increasing) populations
- A variety of mild injurious stimuli that cause irreparable DNA damage that, in turn, triggers cell suicide pathways
Severe damage vs mild damage
If the damage is severe, generally necrosis takes place
If the damage is mild, generally apoptosis takes place as it is isolated
Apoptosis also takes place if (e.g. DNA is irreversibly damaged)
What are the major differences between necrosis and apoptosis?
- Apoptosis is an active process, requires ATP, but necrosis does not
- Apoptosis is not associated with inflammation, but necrosis is
- Necrosis often causes damage to surrounding healthy cells, but apoptosis is cleaner / isolated
Necroptosis
Programmed cell death with inflammation
Many causes e.g. viral infections
