Cells in trouble

Question 1

What does a cell need to do to survive?

Answer 1

-To survive, the cell must be able to adapt to changes in its environment or else it will die.

Question 2

What does the cell respond to?

Answer 2

-The cell can respond to stimuli in a number of limited ways and this is controlled by its state of metabolism, differentiation, specialisation and any constraints imposed by neighbouring cells.

Question 3

Cell injury

Answer 3

• Injury can be either reversible or irreversible
• If a normal cell is challenged it can remain as a normal cell or it can adapt
• If a cell undergoes irreversible injury there are three possible outcomes: necrosis, apoptosis and a mixture of necroptosis and pyroptosis

Question 4

What can damage cells? (Oxygen deprivation)

Answer 4

• If you deprive a cell of oxygen, this will reduce oxidative phosphorylation
• As a result the hypoxic cell will stop producing ATP which is the fuel that drives all cell processes
• Ischaemia means hypoxia due to reduced blood flow and if you reduce blood flow to an organ or tissue you will reduce oxygen delivery as most oxygen is transported bound to haemoglobin in the red blood cells.

Question 5

What can damage cells? (Generic causes)

Answer 5

• Mechanical trauma, extremes of temperature, sudden changes in atmospheric pressure, radiation and electric shock are examples of the various physical agents which can cause cell damage.
• Multiple chemicals and drugs can cause cell death for example arsenic, cyanide, insecticides and more commonly something like alcohol.

Question 6

What infectious agents can damage cells?

Answer 6

-The infectious agents which can damage cells include bacteria, fungi, parasites and viruses.

Question 7

What does autoimmune disease do to the cell?

Answer 7

• Your immune system can also begin attacking your cells and this is termed autoimmune disease. An example of an autoimmune disease is lupus erythematosus.
• Genetic abnormalities can cause cell damage and an example here would be a disease such as sickle cell anaemia where there is a genetic abnormality in the haemoglobin genes.
• Starvation, vitamin deficiency and excess of nutrition can also result in cell damage.

Question 8

What happens to cells when they undergo reversible injury?

Answer 8

• Cells which undergo reversible injury start to swell and they may accumulate fat or for example in the brain, become eosinophilic and are very pink.
• The cell membrane starts to bleb and cells will begin to lose microvilli
• Within the cell the mitochondria swell and there will be dilation of the endoplasmic reticulum with detachment of ribosomes.
• Within the nucleus, the chromatin begins to clump

Question 9

What are cell adaptations defined as?

Answer 9

• Cell adaptations are defined as reversible changes in the size, the number, phenotype, metabolic activity or functions of cells in response to changes in the environment.
• They include hypertrophy, hyperplasia, metaplasia and atrophy

Question 10

What is hyperplasia?

Answer 10

• Cells which are capable of division may respond to stress by increasing in number which is termed hyperplasia.
• Hyperplasia is an increase in the number of cells in an organ or tissue in response to a stimulus.
• This stimulus is usually a hormone or a growth factor. -Hyperplasia can only take place if the cells are actually capable of dividing.
• Hypertrophy and hyperplasia can occur together, and hyperplasia can either be physiological or pathological.
• If the body needs to increase the function of an organ for example an increase in milk production by the breast in the setting of pregnancy, the glands of the breast will undergo hyperplasia.

Question 11

What is hypertrophy?

Answer 11

• If the cell has only limited capacity to divide. it can increase in size by synthesising additional intracellular structural components and this increase in size is termed hypertrophy.
• So, hypertrophy is an increase in the size of cells, and this causes an increase in the size of the affected organ. -Hypertrophy can either be physiological or pathological and is related to increased workload. Because muscle has a limited capacity for cell division it will undergo hypertrophy in response to an increased workload.

Question 12

What is atrophy?

Answer 12

• Atrophy means shrinkage.
• It is a reduction in the size of an organ or tissue due to a decrease in cell size and number.
• Atrophy can be physiological or pathological and shows a decrease in the size of the cell and in the size of the organelles within the cytoplasm

Question 13

What is metaplasia?

Answer 13

• Metaplasia is very important.
• This is a reversible change in which one differentiated cell type is replaced by another cell type.
• It is an adaptive response where the replacement cell type is better able to withstand the adverse environment and is caused by reprogramming of stem cells.

Question 14

What is dysplasia?

Answer 14

-The most important learning point about metaplasia is that if the stimulus which has caused the metaplastic changes persists, this can cause disordered growth in the epithelium which is termed dysplasia, and this can then progress in time to form an invasive carcinoma.

Question 15

What is necrosis?

Answer 15

• This is an accidental or unregulated form of cell death where damage to membranes causes lysosomal enzymes to be released which digests the cell.
• The leakage of cell contents also causes an inflammatory reaction.
• The causes of necrosis include ischaemia, toxins, infections and trauma and the process is always pathological.

Question 16

Patterns of necrosis

Answer 16

-These are the various patterns of necrosis which we see:
=Coagulative necrosis is caused by ischemia. =Liquefactive necrosis can be caused by bacterial infection or a stroke.
=Gangrenous necrosis is also caused by ischemia. =Caseous necrosis is seen in the setting of tuberculosis. =Fat necrosis can be caused by release of pancreatic enzymes in the setting of pancreatitis while fibrinoid necrosis is seen in the setting of vasculitis or inflammation of blood vessels, often due to deposition of immune complexes in the vessel wall.

Question 17

What mechanisms cause cell injury in necrosis?

Answer 17

• The mechanisms which cause the cell injury in necrosis include damage to mitochondria which basically stops the cell producing the ATP which powers its processes.
• Calcium ions are critical mediators of cell injury and depleting calcium can protect cells from injury. An increase in intracellular calcium opens the mitochondrial permeability transition pores depleting ATP. Calcium also activates a number of enzymes causing membrane, protein, nuclear and DNA damage.
• Free radicals can accumulate, and these can damage proteins, lipid and nucleic acids. Increase membrane permeability can affect plasma membranes, lysosomal membranes or mitochondrial membranes usually ending in necrosis. Accumulation of damaged DNA and misfolded proteins trigger apoptosis.

Question 18

What are free radicals?

Answer 18

• Free radicals have a single unpaired electron in an outer orbit.
• Unpaired electrons are highly reactive, and these free radicals can attack and modify other molecules such as proteins lipids carbohydrates and nucleic acids.
• Molecules which interact with free radicals can also be converted into free radicals in so called autolytic reactions.
• Antioxidants such as vitamins A, C, E and glutathione either block free radical formation or inactivate free radicals by donating electrons.

Question 19

What is the most common form of cell injury?

Answer 19

• The most common form of injury is ischaemic/hypoxic injury.
• In hypoxia energy production can continue using anaerobic glycolysis but in ischemia the substrates needed for glycolysis cannot be supplied and any aerobic energy production also stops.

Question 20

What is apoptosis?

Answer 20

• Apoptosis is programmed cell death and the word is derived from the Greek word for falling off.
• This is a cell death pathway that is induced by a tightly regulated suicide programme in which cells destined to die activate enzymes that can degrade the cells own DNA and proteins.

Question 21

More information on apoptosis

Answer 21

• Apoptosis is highly regulated and is caused by damage to either DNA or proteins.
• The cell effectively kills itself by dissolving its nucleus and fragmenting its cytoplasm.
• There is no loss of membrane integrity in the setting of apoptosis and there is no inflammatory reaction.
• Apoptosis serves many normal functions and is not necessarily associated with cell injury.

Question 22

The phases and pathways of apoptosis

Answer 22

-Apoptosis has two phases and two pathways. The phases are called the initiation and execution phases and the pathways are called the intrinsic or mitochondrial pathway and the death receptor or extrinsic pathway.

Question 23

The intrinsic pathway

Answer 23

• The intrinsic pathway is triggered by cell injury, DNA damage or decreased hormone stimulation.
• There is inactivation of a molecule called BCL-2 which is an anti-apoptotic molecule normally.
• 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.

Question 24

The extrinsic pathway

Answer 24

• The extrinsic pathway can be activated by FAS ligand binding to the FAS death receptor on a target cell, activating caspases.
• This is the mechanism by which lymphocytes which respond to self can be eliminated.
• This pathway can also be triggered by Tumour Necrosis Factor (TNF) binding to the tumour necrosis factor receptor on a target cell.
• Some viruses and normal cells can produce a molecule called FLIP which can block apoptosis.