Session 7

Question 1

What genes code for growth factors?

Answer 1

Proto oncogenes

Question 2

How does increased growth of a tissue occur?

Answer 2

By shortening the cell cycle or by conversion of quiescent cells to proliferating cell by making them enter the cell cycle.

Question 3

What are the main cell cycle checkpoints that sense damaged DNA?

Answer 3

Restriction point (main) towards the end of G1. If this checkpoint is activated the p53 protein suspends the cell cycle and triggers DNA repair or apoptosis if repair is not possible.
G1/S transition checks for DNA damage before replication
S/G2 transition checks for DNA damage after replication

Question 4

What molecules regulate progression through the cell cycle?

Answer 4

Proteins called Cyclins and enzymes called cyclin dependent kinases (CDKs). Activated CDKs drive the cell cycle by phosphorylating critical proteins for the progression of the cell cycle (eg pRb). The activity of cyclin-CDK complexes is regulated by CDK inhibitors.
Growth factors can either increase Cyclins or decrease CDK inhibitors.

Question 5

What is cell adaptation and what are the different types?

Answer 5

The state between a normal unstressed cell and an over stressed injured cell. It is usually reversible.
The main types are regeneration, hyperplasia, hypertrophy, atrophy and Metaplasia.

Question 6

What is regeneration and when is it possible?

Answer 6

The replacement of cell losses by identical cells to maintain the size of the tissue/organ. It can be a normal process (e.g. Replacement of rbcs) or can occur after injury if there is limited tissue damage.
Regeneration is not possible if the harmful agent persists, if there is extensive damage or in permanent tissues and results in a scar.

Question 7

What is hyperplasia?

Answer 7

An increase in tissue/organ size due in increased cell numbers. It is a response to an increased functional demand and/or external stimulation. It only occurs in labile/stable cell populations.

Question 8

What is the difference between hyperplasia and neoplasia?

Answer 8

Hyperplasia is under physiological control and is reversible.
Neoplasia is not under physiological control and is irreversible.
Neoplasia is a risk in hyperplastic tissue as the repeated cell divisions expose the cell to risk of mutations.

Question 9

When does pathological and physiological hyperplasia occur?

Answer 9

Physiological - either hormonal to increase functional capacity or compensatory when there is an increase in tissue mass after damage.
Pathological - usually occurs secondary to excessive hormonal stimulation or growth factor production.

Question 10

Give examples of pathological and physiological hyperplasia

Answer 10

Pathological - epidermal thickening from eczema/psoriasis. Goitre of thyroid.
Physiological - increased bone marrow production of erythrocytes in response to low O2. Proliferation of the endometrium due to oestrogen.

Question 11

What is hypertrophy and where is it seen?

Answer 11

An increase in tissue/organ in size due to an increase in cell size. Cells contain more structural components and are bigger. It is a response to increased functional demand and/or hormonal stimulation.
Especially seen in permanent cell tissues but can also occur alongside hyperplasia in cells where division is possible.

Question 12

Give examples of physiological and pathological hypertrophy

Answer 12

Physiological - skeletal and cardiac muscle in athletes and smooth muscle of uterus (alongside hyperplasia)
Pathological - ventricular cardiac muscle (in systemic hypertension or valvular disease), smooth muscle above an intestinal stenosis and in bladder smooth muscle with bladder obstruction due to enlarged prostate gland.

Question 13

What is the difference between physiological cardiac hypertrophy in athletes and pathological hypertrophy in patients with hypertension or valvular heart disease.

Answer 13

The heart has time to recover between strains. There is relative anoxia in pathological hypertrophy because the number of capillaries does not increase significantly to satisfy the increased muscle mass. Cell damage occurs and fibrosis is seen, decreasing the effectiveness of the muscle.

Question 14

What is atrophy?

Answer 14

The shrinkage of a tissue or organ due to a decrease in the number (apoptosis) and/or size (cellular atrophy) of cells.

Question 15

Why do atrophic organs contain a high proportion of connective tissue?

Answer 15

Organs undergoing atrophy do cell deletion lose parenchymal cells before stroll cells

Question 16

What are examples of physiological atrophy?

Answer 16

Ovarian atrophy in post menopausal women

Decrease in the size of the uterus after childbirth

Question 17

What are examples of pathological atrophy?

Answer 17

Atrophy of disuse
Denervation atrophy - e.g. Thenar wasting after median nerve damage
Inadequate blood supply - e.g. Thinning of legs in peripheral vascular disease
Inadequate nutrition
Loss of endocrine stimulation - e.g. Wasting of adrenal gland with no ACTH
Persistent injury
Aging (senile atrophy- heart and brain)
Immunological mechanisms
Pressure -e.g. Tissues around a benign tumour

Question 18

What is Metaplasia and how does it occur?

Answer 18

The reversible replacement of one differentiated cell type to another more suited to an altered environment.
The stem cells are reprogrammed (varied gene expression) to produce a different type of cell. Cells of one phenotype are removed and replaced by cells of a different phenotype.

Question 19

Where does Metaplasia occur?

Answer 19

Only occurs within varieties of connective tissue or epithelia. Does not occur across germ layers.

Question 20

Give examples of when Metaplasia can be useful.

Answer 20

Myeloid Metaplasia - if bone marrow is destroyed the spleen can undergo Metaplasia to bone marrow
Columnar epithelium lining ducts can change to stratified squamous epithelia secondary to chronic irritation by stones - more resilient.

Question 21

Give examples of when Metaplasia can be detrimental

Answer 21

Bronchial pseudostratified -> stratified epithelium in response to cigarette smoke. No cleansing mucus is produced and there is no cilia to move it along.
Barrett’s oesophagus - stratified squamous -> gastric type epithelium in response to continues acid reflux. Predisposes to cancer.
Traumatic myositis ossificans - Metaplastic none develops in skeletal muscle following trauma. Fibroblasts change to osteoblasts.
Intestinal Metaplasia of the stomach by Helicobacter pylori predisposes to dysplasia and cancer.

Question 22

What is aplasia?

Answer 22

The complete failure of an organ/tissue to develop (embryonic disorder).

Question 23

What is hypoplasia?

Answer 23

The congenital underdevelopment or incomplete development of a tissue/organ. It is in a spectrum with aplasia.

Question 24

What is involution?

Answer 24

The normal programmed shrinkage of an organ. Overlaps with atrophy. E.g. Thymus in early life.

Question 25

What is atresia?

Answer 25

Congenital lack of orifice

Question 26

What is dysplasia?

Answer 26

The abnormal maturation of cells within a tissue. Potentially reversible but often pre cancerous.