MCB Lecture 56 Changes to Cells Flashcards
What are the features of physiological adaptations?
This is a cellular response to a normal stimulus in the body
What are the two types of adaptation?
Physiological and Pathological
What are two examples of physiological adaptation?
Hormonal Endogenous chemical (proteins)
What are the features of pathological adaptation?
This is a stress response in the cells to avoid injury
What are the reversible changes that cells undergo?
Hypertrophy
Hyperplasia
Atrophy
Metaplasia
What is hyperplasia?
This is the increase in number of cells
What is hypertrophy?
This is an increase in the size of cells
Which types of cells undergo hyperplasia? Compare with hypertrophy
Hyperplasia: labile or stable cells; ie able to enter the cell cycle and replicate
Hypertrophy: cells that cannot re-enter the cell cycle, Permanent cells
By what mechanism do cells undergo hypertrophy?
They increase in size by increasing the amount of stuff inside the cells (protein, organelles)
By what mechanism do cells undergo hyperplasia?
Growth factors acting on:
a. Mature cells
b. Stem cells
What is an example of hypertrophy?
Increase in the size of muscles in response to lifting weights
Increase in the size of the heart due to hypertension (pathological)
What is the stimulus for hypertrophy and hyperplasia?
Increased workload of the cells
What is atrophy?
Shrinking of the cells
Give some examples of how physiological and pathological adaptations result in hyperplasia
Physiological:
- puberty
- liver hepatocytes compensating
- RBCs at high altitude
Pathological:
- chronic injury eg. Callouses
- hormonal: endometriosis
What is the mechanism that cells undergo for atrophy?
Decrease in amount of stuff in the cell (proteins, organelles)
Decrease in protein synthesis
Increase in protein degradation
What is the stimulus resulting in atrophy?
Decreased workload
Give some examples of stimuli that result in atrophy
Immobilisation Loss of innervation --> immobilisation Loss of blood supply Loss of endocrine stimulation Inadequate nutrition Ageing
What is metaplasia?
Replacement of one cell type with another that is supposedly more able to handle the stress
What is the mechanism for cells undergoing metaplasia?
The stem cell is reprogrammed to produce a different type of cell
Give some examples of cells undergoing metaplasia
Smoking, ciliated columnar cells are replaced with stratified squamous. These cannot beat up mucus and catch all the gross stuff
Chronic gastric reflux: stratified squamous replaced with columnar epithelial
What are the consequences of cell injury?
Recovery or death
What does failure to adapt cause?
Injury
What factors does irreversibility of injury rely on?
The features of the cell and the stimulus:
Cell:
- type: eg. Brain, skeletal, heart
- state: eg. Glycogen store
- adaptability
- genetics: eg. What sort of toxin metaboliser does the cell produce? (Cytochrome P450)
Stress: duration, severity, type
Describe what happens to function in reversible cell injury
There is a decrease in cell function
Describe the time scale of loss of function and seeing morphological changes in irreversible cell damage
Loss of function ->
Death of cell ->
Morphological changes are only seen a while after the cell has died
What are the ways we can see irreversible damage on a macroscopic scale?
Staining
The healthy tissue takes up the stain and the dead tissue doesn’t
What are the ways we can see damage on a microscopic scale?
Haematoxylin and Eosin stain
Describe the different staining of the haematoxylin and eosin stain
Haematoxylin:
Basic stain, nucleic acid takes up the stain, purple colour
Eosin:
Acidic stain, protein and cytoplasm takes up the stain, pink colour
What things happen to the cell in reversible injury?
ER
mitochondria
Cell membrane
Nucleus
ER: swells
Mitochondria: swells
Cell membrane: blebs form
Nucleus: chromatin clumping
What are the things that happen to a cell in irreversible injury?
Organelles
Nucleus
Membrane
Mitochondria: severely swollen and dysfunctional, cytochrome c released into cytoplasm ER: swollen, ribosome detach Lysosomes: burst Nucleus: fragmentation Cell membrane: fragmentation
What is the hallmark of irreversible cell injury?
Loss of mitochondrial function
Describe the changes in ATP concentration in damaged cells
ATP concentration decreases because
- mitochondria no longer make it
- reduced blood flow (nutrients and O2)
What causes acidosis?
What does acidosis lead to?
Acidosis is caused by a build up of lactic acid in the cell
This is caused by
- increased anaerobic respiration
What causes ribosomes to detach?
What does this result in?
The swelling of ER due to increased ion influx into the cell
Results in a halt in protein synthesis
What causes ion pumps to fail?
What does this result in?
Ion pumps require ATP
When this stops being produced, they can no longer pump ions
There is a net influx of ions (including calcium) into the cell
What changes occur to mitochondria in cell injury?
Swell and lose their function
Cause: increase in calcium, ROS, lipid per oxidation
Cytochrome c is lost to the cytosol
Aerobic respiration can’t occur
What happens to cytochrome c?
What does this then cause?
An influx of calcium to the cell causes cytochrome c to be lost from the mitochondria
This then causes the cell to undergo apoptosis
What happens to calcium in cell injury?
Influx of calcium into the cytosol from outside the cell, the ER and the mitochondria
This
- activates many proteins that start to degrade molecules in the cell
- membrane damage
- activates caspases
What causes calcium concentration in the cell to rise?
Failure of the ion pumps which normally pump it out of the cell
Describe how enzymes in the cell become activated, and what this then leads to
Enzymes become activated due to the influx of calcium the cell
This leads to degradation of many macromolecules
- phospholipids of membrane degraded
- membrane and cytoskeletal proteins degraded
What causes membrane damage?
- Action by phospholipases
- action by proteases
- lipid per oxidation by ROS
- decrease in phospholipid recycling (no ATP)
What does caspase activation lead to?
How is caspase activated?
Apoptosis
It is activated by increased cytosolic calcium
Cytochrome c release by the mitochondria
What happens to reactive oxygen species during cell injury?
Normally they are neutralised by scavengers, but in cell injury, there is a decrease in scavenging, or an increase in ROS production
What is the normal function of ROS?
Killing intracellular pathogens
Byproduct from respiration
Which membranes are affected during cell injury?
Nuclear membrane
Plasma membrane
Lysosome
Mitochrondrial
Hypoxia is an example of …
Irreversible cell injury
What are the causes of hypoxia?
Ischemia Pneumonia Anaemia CO poisoning Occlusion
What are the direct consequences of hypoxia?
Decrease in aerobic respiration
Increase in anaerobic respiration
What does decreased aerobic respiration lead to?
Decrease in ATP production
Decreased synthesis of macromolecules
How can damage be characterised (ie either reversible or irreversible) during myocardial infarction?
Monitor the levels of proteins in the serum that should normally only be found inside the cell
Which enzymes are released by my oxygen during MI?
Creating kinase
Contractile troponin
Why is cytochrome P450 important?
Different individuals have different versions that are better able to metabolise toxins.
This is an example of genetics determining your susceptibility to cell injury
Describe what happens in transient ischemia of the heart
Reversible
However, some loss of function
Due to the transiently non-contractile myocytes
In hypoxia of the heart, decreased synthesis and increased digestion of macromolecules leads to …
- Cell membrane damage
- Cytoskeleton damage
Describe what damage ROS can do
When are ROS released? And from where?
ROS are released from the mitochondria
During pathological injury to cells, they aren’t scavenged, so they cause damage to cells
- Lipid peroxidation - disrupt cell membrane
- DNA oxidation - mutation and breaks
- Protein oxidation - loss of function
Describe the appearance of heart cells after hypoxia damage
Eosinophilia: Increased eosin staining of the proteins in the cytoplasm
Oedema
Reduced nuclei (reduced haematoxylin staining)
Inflammatory cells
