Regulation of tissue growth and Principles

Question 1

How is normal tissue architecture maintained?

Answer 1

Maintenance of genomic integrity

Question 2

When do quantitative changes to cells occur?

Answer 2

1. occur during development or in post natal life –

2. be physiological and part of normal processes or a consequence of pathological events

Question 3

What is atrophy?

Answer 3

an acquired diminution of growth due to a decrease in the size or number of constituent parts (cells) of a tissue
eg decrease in size of ovaries post menopause

Question 4

What is hypertrophy?

Answer 4

the converse of atrophy - an increase in the size of an organ or tissue due to an increase in the size of individual cells. Hypertrophy is the cellular response to excessive or prolonged demand for increased function. It is seen most dramatically in muscular organs.
eg pregnant uterus- expand to accommodate foetus

Question 5

What happens when the demand for increased work ceases?

Answer 5

the organ returns to normal size unless there have been irreversible changes in the architecture as a consequence of the prolonged demand

Question 6

What is hyperplasia?

Answer 6

an increase in the size of an organ due to an increase in the number of the component cells - increased proliferation. eg lactating breast, prostatic enlargement in older men

Question 7

What are the differences between hyperplasia and neoplasia?

Answer 7

The enhanced proliferation of hyperplasia persists only as long as the “cause” and the architecture of the organ is retained despite the increase in size

Question 8

Describe the cell cycle

Answer 8

DNA replication or synthesis (S phase) and mitotic cell division (M phase) - the Cell Cycle(G1 = Gap 1; G2 = Gap2; G0 = resting/quiescent phase).

Question 9

What are the extrinsic factors affecting the cell cycle?

Answer 9

Physical interactions with the environment
Competence factors
Commitment factors

Question 10

What are physical interactions with the environment?

Answer 10

mammalian cells must adhere to a substratum, such as the extra-cellular matrix or other cells (cell: cell adhesion), before entering the cycle

Question 11

What are competence factors?

Answer 11

growth factor or ligand for a cell surface receptor to be competent to enter the cycle- the effects of these receptor ligand interactions is to effect transcription of critical genes (enter cycle)

Question 12

What are commitment factors?

Answer 12

polypeptide growth factors and hormones, which drive expression of genes required for progression through G1

Question 13

What are the intrinsic factors affecting the cell cycle?

Answer 13

cyclin dependent kinases (cdks) which phosphorylate selected proteins
cyclins so named because their concentrations rise and fall in a regular pattern through the cell cycle
These complexes are regulated by another family of proteins: Cyclin dependent kinase inhibitors (CKIs) effectively the brakes on the cyclin/CDK functions

Question 14

What are the checkpoints of the cell cycle?

Answer 14

G1/S Checkpoint
G2/M Checkpoint
Spindle assembly checkpoint

Question 15

Why is the G1 phase crucial?

Answer 15

Period of intense metabolic activity when many cellular components are duplicated
Duration varies in response to external factors such as growth factors and hormones
it contains a critical checkpoint when the cell is committed to replicate its DNA and is no longer influenced by external factors

Question 16

What are the options for the G1 phase of the cycle to commit to?

Answer 16

1. To “recycle” and embark upon another round of DNA replication, chromosome condensation and cell division.
2. To “decycle” and enter a resting phase Go, a phase from which the cell can re-enter the cycle if conditions so demand/ quiescence
3. To “decycle” permanently and commit itself to functions incompatible with replication – terminal differentiation.

Question 17

How is G1 progressed to S phase?

Answer 17

Inactive CDK-Cyclin D complex activated by phosphorylation, phosphorylates Rb
Different cyclins and CDKs for different checkpoints

Question 18

What are the groups cells in animal and cell populations are classified into?

Answer 18

permanent
Conditional renewal populations
Continuously cycling self renewing populations

Question 19

What are permanent cells?

Answer 19

non-replicating cells such as neurones and striated myocytes which lose the ability to replicate early in post natal life. Fully committed to differentiated function and have a zero or limited proliferative potential, loss of such cells means loss of function

Question 20

What are conditional renewal populations?

Answer 20

hepatocytes, fibrocytes. Rarely divide and are held in Go. In the face of demand - loss or injury or increased function- the cells enter G1 and cycle until the lost tissue is replaced and then return to Go again.
Differentiation and proliferation not incompatible

Question 21

What are self renewing populations?

Answer 21

tissues in which there is a functional differentiated fraction with a defined life span. Requirement for the continuous replacement of those cells by self renewal of other cells. Such populations must always consist of 3 compartments
Stem cells- bone marrow, lymphoid tissue

Question 22

How are tissues organised?

Answer 22

1. Stem cell: self renewing & slowly proliferating in niche, stem cell phenotype strictly controlled
2. Transit amplifying: commitment to a differentiated lineage & rapid proliferation occur together
3. Terminal differentiation: full differentiation (for function), but proliferation is incompatible

Question 23

Which tissues consists of these populations?

Answer 23

All covering epithelia - skin, gut, urinary, genital etc.

Bone marrow, lymphoid tissues

Question 24

What is metaplasia?

Answer 24

replacement of one differentiated cell type by another
almost always a response to persistent injury and most commonly involves the replacement of a glandular epithelium by a squamous one

Question 25

What sites are most commonly affected by metaplasia?

Answer 25

exposure of the bronchial epithelium persistently to tobacco smoke
exposure of the endocervix of the uterus to acid pH, infection, semen leads to squamous metaplasia

Question 26

What is squamous metaplasia?

Answer 26

Multi layered, stratified, fall off top
New squamous epithelium replaces original glandular epithelium, response to persistent injury, reversible- tissue reverts to normal after injury removed

Question 27

What is dysplasia?

Answer 27

part of the spectrum of changes of pre-invasive neoplasia, dysplastic changes do not necessarily revert to normal once the injury is removed

Question 28

What is dysplasia morphologically?

Answer 28

the regular organised appearance of the epithelium is disturbed by:
variations in the shape and size of cells
enlargement of nuclei – increased N:C ratio
pleomorphism – irregularity with variation in nuclear size, shape, chromatin staining,
hyperchromatic (darkly staining) nuclei
increased mitosis
distortion of the proliferating compared to the differentiating compartment

Question 29

What is a neoplasm?

Answer 29

New growth, irreversible
Is an abnormal mass of tissue
the growth of which exceeds and is uncoordinated with that of the normal tissue
persists in the same excessive manner after the stimulus is removed.

Question 30

What are the essential features of neoplasia or tumour growth

Answer 30

• composed of living cells
• differ from cells of the normal organ from which the tumour is derived- division/differentiation controls operating in that organ have been deregulated or lost.
• The control of division, differentiation and death may have been lost to the extent that the tumour
  (a) loses partially or totally specialised functions (cell appearance changes)
  (b) acquires new functions- invasion and metastasis

Question 31

What is invasion?

Answer 31

the capacity to infiltrate the surrounding tissues and organs

Question 32

What is metastasis?

Answer 32

The ability to spread to and proliferate in distant parts of the body after tumour cells have been transported by lymph or blood or along body spaces

Question 33

What is a benign neoplasm?

Answer 33

Those which proliferate and divide but do not invade the surrounding tissues nor metastasize
growth is not life threatening, their clinical course is predictable. They may cause problems due to pressure, obstruction or excessive hormone production.

Question 34

What is a malignant neoplasm?

Answer 34

Neoplasms which invade and/or metastasize

progressive and unless adequate therapy is available the patient will eventually die as a result of the disease

Question 35

What are the symptoms of destructive invasive growth?

Answer 35

Blood loss – ulceration and haemorrhage
Pressure and destruction of adjacent tissue
Obstruction or constriction of flow in vital organs
Metabolic effects
general - cachexia
specific – tumour specific products

Question 36

What are the shapes of neoplasms?

Answer 36

Sessile- sits on top of surface
Pedunculated polyp- tag shape
Papillary- seaweed like
Fungating- growing outward
Ulcerated- crater
Annular- tubular

Question 37

What do benign tumours look like?

Answer 37

Intact surface, exophytic growth, homogenous cut surface, circumscribed or encapsulated edge

Question 38

What do malignant tumours look like?

Answer 38

Heterogenous cut surface due to necrosis, ulcerated surface, endophytic growth, vascular permeation, irregular infiltrated edge

Question 39

Overview of benign neoplasms

Answer 39

Do not invade or metastasise
Slow growing
Low mitotic rate
Clearly demarcated from surrounding tissue- encapsulated or pseudo capsule
Nuclear morphology often normal
Mitotic figures normal
Clonal chromosome abnormalities- not aneuploid

Question 40

Overview of malignant neoplasms

Answer 40

Invade and metastasise
Not demarcated clearly
Surface often ulcerated and necrotic
Cut surface heterogenous
Often high mitotic rate
Rapid growth
Nuclei pleomorphic, hyper chromatic
Abnormal mitoses
Usually aneuploid