Cell injury Flashcards
Revision
What is the definition of Pathology?
The study of causes of disease and the sequence of events stemming from the cause to the eventual disease process.
What is homeostasis?
is a steady state. Closely maintained.
What does bone density depend on?
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)
Is the Tyrosine Kinase Pathway tightly controlled or not and what is it important for?
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.
What are the roles of CDKs and cyclins?
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.
Can you describe the G1 phase?
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.
What is the role of Rb?
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.
Can you describe the S Phase?
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.
Can you describe G2 phase?
Second growth phase.
Cell gets bigger and more protein synthesis.
Main checkpoint occurs at the end of G2.
Main checkpoint protein in p53.
What is the role of p53?
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.
Do all cells divide the same number of times?
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.
What is the role of Telomeres?
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.
What is Hyperplasia growth?
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.
What are examples of Hormonal growth?
Good examples occur at puberty - breast tissue.
Pregnancy - Hyperplasia of lining of womb/endometrial lining of uterus.
What is Compensatory and when does it occur?
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.
What can the bone marrow do if a person is losing blood cells for some reason?
If a person is losing blood cells for some reason the bone marrow can compensate and turn on more.
What is Pathological hyperplasia and how is it induced?
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.
What are some Stimulus’ for hyperplasia?
Infection.
Lymph nodes contain machinery for fighting infection. Areas in lymph node will undergo hyperplasia in response to infection.
What is Hypertrophy and what are some examples?
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.
What is the definition of Atrophy?
Reduction in cell size.
Can be physiological or pathological.
What is Physiological atrophy?
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.
What are some causes of atrophy?
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.
What are the mechanisms of atrophy?
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.
What causes Tissue Injury?
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.