MCB Lecture 56 Changes to Cells Flashcards by Eleanor Nicklason

What are the features of physiological adaptations?

This is a cellular response to a normal stimulus in the body

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What are the two types of adaptation?

Physiological and Pathological

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What are two examples of physiological adaptation?

Hormonal
Endogenous chemical (proteins)

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What are the features of pathological adaptation?

This is a stress response in the cells to avoid injury

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What are the reversible changes that cells undergo?

Hypertrophy
Hyperplasia
Atrophy
Metaplasia

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What is hyperplasia?

This is the increase in number of cells

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What is hypertrophy?

This is an increase in the size of cells

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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

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By what mechanism do cells undergo hypertrophy?

They increase in size by increasing the amount of stuff inside the cells (protein, organelles)

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By what mechanism do cells undergo hyperplasia?

Growth factors acting on:

a. Mature cells
b. Stem cells

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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)

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What is the stimulus for hypertrophy and hyperplasia?

Increased workload of the cells

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What is atrophy?

Shrinking of the cells

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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

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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

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What is the stimulus resulting in atrophy?

Decreased workload

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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

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What is metaplasia?

Replacement of one cell type with another that is supposedly more able to handle the stress

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What is the mechanism for cells undergoing metaplasia?

The stem cell is reprogrammed to produce a different type of cell

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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

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What are the consequences of cell injury?

Recovery or death

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What does failure to adapt cause?

Injury

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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 1. Lipid peroxidation - disrupt cell membrane 2. DNA oxidation - mutation and breaks 3. 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