Cellular Adaptations

Question 1

What determines the size of a cel population?

Answer 1

• Depends on rate of cell proliferation, cell
  differentiation and cell death by apoptosis
• Increased numbers are seen with increased proliferation or decreased cell death
• Cell proliferation occurs in physiological and pathological conditions
• Excessive physiological stimulation can become pathological, e.g., prostatic hypertrophy
• Proto-oncogenes regulate normal cell proliferation

Question 2

How is cell proliferation controlled?

Answer 2

• Largely by chemical signals from the
  microenvironment, mainly growth factors, which either stimulate or inhibit cell proliferation
• When a signalling molecule binds to a receptor it results in the modulation of gene expression - proliferation, halt, or apoptosis
• Receptors usually in cell membrane but can be in the cytoplasm or nucleus (e.g., steroid receptors)

Question 3

What can chemical signals make the cell do?

Answer 3

Survive – resist apoptosis
Divide – enter cell cycle
Differentiate – take on specialised form and function
Die – undergo apoptosis

Question 4

How can a cell population increase its numbers?

Answer 4

Increased growth occurs by
- shortening of the cell cycle
- conversion of quiescent cells to proliferating by making them enter the cell cycle
G0 - can go back into cell cycle i required, unless they become totally differentiated in which case they exit the cycle?

Question 5

Can you see the cell cycle by light microscopy?

Answer 5

Everything we see is in mitosis and cytokinesis - dont see interphase

Question 6

Can cells with damaged DNA replicate? And what are the checkpoints?

Answer 6

Dont want them to replicate -
Neoplasia is a result of changes in genetic material
Don’t want them to replicate
3 main checkpoints to prevent them from completing cell cycle
1 at end of g1 - restriction joint
B/w g1 and s - makes sure that dna is ok before its is replicated
B/e g2 and m - makes sure there is no problem with dna after replicated

Question 7

What is the restriction point?

Answer 7

Period during which cells re responsive to mitogenic GFs and to TGF-beta
• Most critical checkpoint
• Majority of cells that pass R point will complete cell cycle – point of no return
• Most commonly altered checkpoint in cancer cells
• Checkpoint activation delays cell cycle and triggers DNA repair mechanisms or apoptosis via p53

If checkpoint is not functioning properly, cells with abnormal dna can proliferate
• if checkpoint is activated p53 protein halts cell cycle and tries to get dna repaires
• I it cant be repaired p53 will push cell into apoptosis

Question 8

How is the cell cycle controlled?

Answer 8

• Cyclins and cyclin dependent kinases (CDKs)
• CDKs become active by binding with cyclins
• also CDK inhibitors
  Different cyclins are åre produced at different phases - bind with CDC’s - allows cell to pass through cell cycle
  Cyclin bind with cdk and activate it - CDK phosphorylates target protein - this then allows cell to pass around cycle
  Cyclin bind to CDK and target protein which allows target to be phosphorylated

Question 9

How many times can cells divide?

Answer 9

• Leonard Hayflick discovered Hayflick numbers/limits in 1961
• Humans = 61.3
  Number varies according to species - size of the organism being considered
  Humans 60-70

Question 10

How can cells adapt?

Answer 10

• Hyperplasia – cells increase in number above normal
• Hypertrophy – increase in tissue or organ size due to cells increase in size
• Atrophy – Shrinkage of a tissue or organ due to an acquired decrease in size and/or number of cells
• Metaplasia – cells are replaced by cells of a different type - reversible

Question 11

Are cellular adaptations reversible?

Answer 11

Stress on cell - cell has to adapt - if pushed further if may get injured then killed
Cell adaptations are generally reversible though

Question 12

In which type of tissues does hyperplasia occur?

Answer 12

• Labile or stable tissues - cells can divide
• Caused by increased functional demand or hormonal stimulation
• Remains under physiological control and is reversible (cf neoplasia) - Not under physiological control in neoplasia
• Can occur secondary to a pathological cause but the proliferation itself is a normal response (cf neoplasia – the proliferation itself is abnormal)
• Repeated cell divisions exposes the cell to the risk of mutations and neoplasia - Hyperplasia can open the door to neoplasia - when cells divide -prone to getting abnormality in dna - if you have repeate cell divisions - many chances for dna problems to arise

Question 13

What exazmpels are there of physiological hyperplasia?

Answer 13

Proliferative endometrium under influence of oestrogen

Bone marrow produces erythrocytes in response to hypoxia

Question 14

What examples are there of pathological hyperplasia?

Answer 14

Eczema - epidermis thickens - hypoplastic response

Thyroid goitre in iodine deficiency - thyroid undergoes hyperplasia

Question 15

In which type of tissue does hypertrophy occur?

Answer 15

• Labile, stable but especially permanent tissues
• Like hyperplasia, caused by increased functional demand or hormonal stimulation
• Cells contain more structural components – workload is shared by a greater mass of cellular components
• In labile and stable tissues hypertrophy usually occurs along with hyperplasia- Classically seen a lone in permanent.

Question 16

What examples are there of physiological hypertrophy?

Answer 16

Skeletal muscle

Pregnant uterus - (hypertrophy up to 70% size and hyperplasia)

Question 17

What examples are there of pathological hypertrophy?

Answer 17

Ventricular hypertrophy - if heart is having to work hard eg hypertension or valvular heart disease - cells undergo hypertrophy
Pathological cardiac hypertrophy - increase in capillaries but not as much as required for myocytes - results re little area o fibrosis secondary to ischaemia throughout heart - heart not working efficiently - can affect action potential - arrhythmia problems
Atheete has time to rest but in hypertension there is no rest time

bladder hypertrophy due to enlarged prostate

Stenosis - smooth muscle hypertrophy proximal to bowel stenosis as cells working harder to propel contents

Question 18

What is compensatory hypertrophy?

Answer 18

Paired organ - if one malformed etc. The other will increase in a compensatory way so body can mange with one eg kidney

Question 19

What is happening in the cell in atrophy?

Answer 19

Cell atrophy,
issue/organ atrophy - shrinkage of cells as well as apoptosis
- Shrinkage in the size of the cell to a size at which survival is still possible
- Reduced structural components of the cellphone at it can just about do without
- May eventually result in cell death

Question 20

Is tissue atrophy only a result of cell atrophy?

Answer 20

 Organ/tissue atrophy typically due to
combination of cellular atrophy and apoptosis
 Is reversible but only up to a point - if stress prolonged then it becomes irreversible

Question 21

What happens in tissue atrophy?

Answer 21

Cells which become atrophied and apoptosis cells are often parenchyma cells ie cells that are doing the job - process continues - those cells die and become replaced by connectivetissue
Eg stone blocking pancreatic duct - this can cause atrophy of secreting organ being blocked - vale pale area of fibrosis of connective tissue - paranchymal cells undergone strophe
In pancreas its the exocrine cells that are most affected by blocking - left with longer larger ducts and endocrine islets
Also occurs in panreatitis
Exocrine tissue replaced by fibrosis
Structural components broken down in autophagosomes - parked in residual bodies

Question 22

What examples are there of physiological atrophy?

Answer 22

Ovarian atrophy in post menopausal women
Withdrawal
Decrease in size of uterus - component of atrophy

Question 23

What examples are there of pathological atrophy?

Answer 23

• Reduced functional demand/workload = atrophy
of disuse: muscle atrophy after disuse, reversible with activity
• Loss of innervation = denervation atrophy: wasted
hand muscles after median nerve damage
• Inadequate blood supply: thinning of skin on legs with peripheral vascular disease
• Inadequate nutrition: wasting of muscles with malnutrition

Question 24

What examples are there of pathological atrophy?

Answer 24

• Loss of endocrine stimuli: breast, reproductive organs
• Persistent injury: polymyositis (inflammation of skeletal muscle)
• Aging = senile atrophy: brain, heart
• Pressure: tissues around an enlarging benign tumour (probably secondary to ischaemia)
-Calf muscle atrophy after plaster cast
Thenar atrophy
Tumour causing atrophy or brain tissue
Aneurism causing atrophy and erosion through terbium

Question 25

What is atrophy of extracellular matrix?

Answer 25

In osteoporosis - lack of bone tissue

Common in people who dont have mechanica stress on bone eg astronaughts or ppl who are bedbound

Question 26

What is metaplasia?

Answer 26

Reversible change of one differentiated cell type to another

• Due to altered stem cell differentiation
• May represent adaptive substitution of cells that are sensitive to stress by cell types better able to withstand the adverse environment
• Metaplastic cells are fully differentiated and the process is reversible (cf dysplasia and cancer)
• Sometimes a prelude to dysplasia and cancer
• No metaplasia across germ layers - Within germ layers not across
• Occurs only in labile or stable cell types
• Involves expression of a new genetic programme

Question 27

What examples are there of metaplasia?

Answer 27

Bronchial pseudostratified ciliated epithelium -> stratified squamous epithelium due to effect of cigarette smoke
Stratified squamous epithelium -> gastric glandular epithelium with persistent acid reflux (Barrett’s oesophagus)
Occasionally metaplasia is helpful - problem with bone marrow - spleen takes on fucntions of boe marryow by undergoing metaplasia
Traumatic myosmthing somthcans Condition where fibroblasts undergo metaplasia to osteoblasts - young ppl who haven’t let injury recover and start excercising

Question 28

Does metaplasia predispose to cancer?

Answer 28

 Epithelial metaplasia can be a prelude to
dysplasia and cancer.
- Barrett’s epithelium and oesophageal adenocarcinoma
- Intestinal metaplasia of the stomach and gastric adenocarcinoma - glandular epithelium cancer
 Why is not understood

Question 29

What is aplasia?

Answer 29

• Complete failure of a specific tissue or organ to develop
• An embryonic developmental disorder
   Examples:
• Thymic aplasia - infections and auto-immune problems
• Aplasia of a kidney
• Also used to describe an organ whose cells have ceased to proliferate, e.g. aplasia of bone marrow in aplastic anaemia

Question 30

What is hypoplasia?

Answer 30

• Underdevelopment or incomplete development of tissue or organ at embryonic stage, inadequate
  number of cells.
• In a spectrum with aplasia
• Not opposite of hyperplasia as it is a congenital condition.
• Cf atrophy which occurs when existing part wastes away but this is a failure to develop.

 Examples:

• Renal
• Breast
• Testicular in Klinefelter’s syndrome
• Chambers of the heart

Question 31

What is involution?

Answer 31

• Overlaps with atrophy
• Normal programmed shrinkage of an organ
• Uterus after childbirth, thymus in early life, pro-and mesonephros

Question 32

What is reconstruction?

Answer 32

Replacement of a lost part of the body
More complex than regeneration - whole arts of the body are complex tissues that have interactions between different cells - lizards tail, antlers of a deer - grow abt 18mm a day

Question 33

Can reconstitution occur in humans?

Answer 33

Generally not - eg a scar - no sweat glands melanocytes etc
Can get reconstitution of blood vessels - blood vessels are. Number of cell types and a bit complex
If a small child under 4 loses tip of finger distal to distal interphalangeal joint, that finger caan grow back perfectly

Question 34

What is atresia?

Answer 34

‘No orifice’
- Congenital imperforation of an opening
 Examples:
- Pulmonary valve
- Anus
- Vagina
- Small bowel

Question 35

What is dysplasia?

Answer 35

• Abnormal maturation of cells within a tissue
• Potentially reversible
• Often pre-cancerous condition