Cell injury

Question 1

What is the definition of Pathology?

Answer 1

The study of causes of disease and the sequence of events stemming from the cause to the eventual disease process.

Question 2

What is homeostasis?

Answer 2

is a steady state. Closely maintained.

Question 3

What does bone density depend on?

Answer 3

Varies depending on where you are e.g. earth and the moon and what you do e.g. triple jump (amount of stress you put on it)

Question 4

Is the Tyrosine Kinase Pathway tightly controlled or not and what is it important for?

Answer 4

You can tightly control this pathway
But very easy for something to go wrong in this pathway.
really important cancer pathway
Starts with EGFR and ends with transcription and there is a domino effect.

Question 5

What are the roles of CDKs and cyclins?

Answer 5

Each point controlled by a series of cyclin dependent kinases (CDKs) that activate each other and other enzymes in a step-wise fashion.
Each CDK is activated by a specific “cyclin”.
Cyclins vary in concentration throughout cell cycle.
Cyclin D, E, A and B.

Question 6

Can you describe the G1 phase?

Answer 6

Growth 1 Phase
Cells get bigger with increased protein synthesis.
During G1 CDK4 is activated by cyclin D.
CDK4 phosphorylates (i.e. activates) the retinoblastoma protein.

Question 7

What is the role of Rb?

Answer 7

The retinoblastoma protein is important in normal cell growth and in malignancy.
Normally Rb is bound to E2F.
E2F - Kicks off cell division but is stopped from doing so by Rb.
When phosphorylated by CDK4, Rb can’t bind to E2F and therefore E2F is free to give a green light to cell division.

Question 8

Can you describe the S Phase?

Answer 8

Synthesis phase.
E2F initiates DNA replication.
E2F increases levels of cyclin A.
Cyclin A activates CDK2.
CDK2 also promotes DNA replication.
By the end of S phase the cell should contain 2 copies of it's genome.

Question 9

Can you describe G2 phase?

Answer 9

Second growth phase.
Cell gets bigger and more protein synthesis.
Main checkpoint occurs at the end of G2.
Main checkpoint protein in p53.

Question 10

What is the role of p53?

Answer 10

Complex roles - many still being discovered.
Simply put - p53 will check the cell for mistakes.
If mistakes are found the cell cycle is paused.
Repair is then attempted.
If successful - cell can progress.
If not - cell is instructed to commit suicide.

Question 11

Do all cells divide the same number of times?

Answer 11

Not all cells can divide.
Some are terminally differentiated - neurons etc.
Exhibit “replicative senescence”.
Others must divide many times - either to grow or replace lost cells.
Lining of the gut is replaced every few days.
Cells can only divide so many times.
The older a person becomes, the fewer number of times they divide.

Question 12

What is the role of Telomeres?

Answer 12

Chromosomes are capped - provides protection and stops chromosome ends from degradation and fusion.
Consist of TTAGGG repeats.
With every division the number of repeats gets smaller.
Hayflick limit -50-70 divisions
Stem cells can switch on and off telomerase.

Question 13

What is Hyperplasia growth?

Answer 13

Increase in cell number.
Must be in response to an external stimulus.
Will regress on withdrawal of stimulus.
Usually results in increased organ volume.
Can by physiological or pathological.
Hyperplasia is reversible growth.
Reversed on withdrawal of stimulus.
Cancer keeps growing in the absence of a stimulus.
Hyperplastic tissue is an at risk site for the development of cancer.
endometrial cancer - much more common in obese individuals who have a background of hyperplasia.

Question 14

What are examples of Hormonal growth?

Answer 14

Good examples occur at puberty - breast tissue.

Pregnancy - Hyperplasia of lining of womb/endometrial lining of uterus.

Question 15

What is Compensatory and when does it occur?

Answer 15

Providing compensation; making up for a deficiency or loss. Occurs after loss of tissue.
Not common in many tissues
Liver is the obvious example.
Bone marrow.

Question 16

What can the bone marrow do if a person is losing blood cells for some reason?

Answer 16

If a person is losing blood cells for some reason the bone marrow can compensate and turn on more.

Question 17

What is Pathological hyperplasia and how is it induced?

Answer 17

Hormonally induced - excess oestrogen leads to endometrial hyperplasia and abnormal menstrual bleeding. Often post menopausal.
Hormonally induced prostatic hyperplasia. In response to androgens.
Both will regress on withdrawal of stimulus.

Question 18

What are some Stimulus’ for hyperplasia?

Answer 18

Infection.
Lymph nodes contain machinery for fighting infection. Areas in lymph node will undergo hyperplasia in response to infection.

Question 19

What is Hypertrophy and what are some examples?

Answer 19

Increase in cell size, not cell number.
Often occurs in conjunction with hyperplasia.
Often in isolation in non-dividing cells e.g. cardiac myocytes, skeletal muscle.
Often in response to mechanical stress.

Question 20

What is the definition of Atrophy?

Answer 20

Reduction in cell size.

Can be physiological or pathological.

Question 21

What is Physiological atrophy?

Answer 21

Embryological structures.
Can remain - become pathological.
Uterus undergoes rapid atrophy after parturition.
Can occur for example after a leg is broken and is due to a decreased workload.

Question 22

What are some causes of atrophy?

Answer 22

Loss of innervation
Loss of function after nerve supply is removed.
Blocked blood supply.
Usually in association with atherosclerosis..
Thought to account for decreased brain size with ageing.
Loss of blood supply.
Loss of hormonal stimulation.
Post menopausal uterus.
Inadequate nutrition.
Ageing.
Usually seen in cells that have no replicative ability - heart and brain.
Pressure.
Due to endogenous or exogenous structures.
Can be seen in normal tissue adjacent to tumours.

Question 23

What are the mechanisms of atrophy?

Answer 23

Reduced cellular components.
Protein degradation.n
“digested” in lysosomes and degraded in many cases by ubiquitin proteasome pathway.
Some hormones promote degradation and atrophy - glucocorticoids and thyroid hormone.
Some oppose atrophy and promote growth - insulin.
A balance of growth and atrophy retains homeostasis.

Question 24

What causes Tissue Injury?

Answer 24

Stress on cells results in an attempt at adaptation.
If the cell can’t adapt it may die.
Cells get bigger, more cells, less cells or a change in type of cells.

Question 25

Our bodies are subject to varying stresses, what are some examples?

Answer 25

Environmental

Hormonal

Question 26

If the changes are severe what may happen?

Answer 26

If the changes are severe the cells and organs may be damaged.

Question 27

What happens prior to cells being damaged?

Answer 27

Prior to this there is a period of adaptation to cope with change.

Question 28

What are the adaptations for:
Increased demand
Decreased demand
Altered stimulus?

Answer 28

Increased demand - hyperplasia, hypertrophy
Decreased demand - atrophy
Altered stimulus - metaplasia

Question 29

How can we adapt by growth?

Answer 29

We can grow in only 2 ways.
Our cells get bigger -hypertrophy
Or
We grow more cells - hyperplasia
Growing more cells doesn't just happen. Specific instruction to grow - cell signals and increased cell division.

Question 30

What chains of events that lead to cell division are set off, in response to stress growth factors?

Answer 30

We can:

• Produce more growth factors
• Produce more growth factor receptors.

Question 31

What are the three categories of growth factors?

Answer 31

• Receptors with intrinsic tyrosine kinase.
• 7 transmembrane G protein-coupled receptors.
• Receptors without intrinsic tyrosine kinase activity.

Question 32

What processes are closely controlled?

Answer 32

Instructions for growth are closely controlled.

Cell division is also a carefully controlled stepwise sequence.

Question 33

Mistakes in what are important for cancer development?

Answer 33

Mistakes in signals for growth and in cell cycle progression are important for cancer development.

Question 34

Can you describe the general type of cycle of the cell cycle?

Answer 34

Tightly controlled process.
Stepwise progression through a series of stages.
Domino like effect.
Various checkpoints.
Faulty cells may not perform the desired function.
Faulty cells may predispose to cancers.

Question 35

What are the 4 main stages of the cell cycle?

Answer 35

G1
S
G2
M

Question 36

Why is p53 important in cancer?

Answer 36

If cells can avoid being checked by p53 they can keep dividing despite containing faults in the DNA.
This is an important step in the development of cancer.
Drugs - if we can develop drugs to target this we might cure some cancers.

Question 37

Increased stress or increased need for cell product (hormone) causes adaptation by growth. What are the two different methods of this?

Answer 37

Hyperplasia - More cells

Hypertrophy - Or bigger cells

Question 38

At what point does hypertrophy become hypertrophic and what may it result in?

Answer 38

Hypertrophy becomes pathologic when the heart can no longer function and required more blood supply etc than it is supplied. The muscle also becomes less functional.
May result in heart failure - inability of the heart to pump as normal.

Question 39

Our body is constantly in a state of adaptation at organ and cell level. In some instances the adaptation requires growth in the form of what?

Answer 39

Hyperplasia and hypertrophy.

Question 40

Increasing cell numbers requires activation of what?

Answer 40

Increasing cell numbers requires activation of cell signalling pathways and the cell cycle.