Disorders of Growth

Question 1

What is differentiation?

Answer 1

The process by which a less specialized cell becomes a more specialized cell type

Question 2

What is hyperplasia?

Answer 2

An increase in cell number

Question 3

Is hyperplasia always pathological?

Answer 3

No, can be physiological

Question 4

What is hypertrophy?

Answer 4

An increase in cell size

Question 5

Where does hypertrophy tend to occur?

Answer 5

In muscle: skeletal and cardiac

Question 6

What is atrophy?

Answer 6

Reduction in cell size and number in an organ that was normal size

Question 7

What are some of the causes of atrophy?

Answer 7

Ageing

Lack of use/stimulation

Question 8

What is hypoplasia?

Answer 8

Reduced size of an organ - never fully developed to normal size

Question 9

Which of the following - hyperplasia, hypertrophy, atrophy and hypoplasia - is not potentially reversible?

Answer 9

Hypoplasia

Question 10

What is metaplasia?

Answer 10

The replacement of one differentiated cell type with another mature differentiated cell type

Question 11

Give a clinical example of metaplasia.

Answer 11

Barrett’s oesophagus

Question 12

What is dysplasia?

Answer 12

Abnormality of development - alteration in size, shape, and organization of adult cells

Question 13

Which - metaplasia or dysplasia - is pre-malignant?

Answer 13

Dysplasia

Question 14

What are the three cell types?

Answer 14

Labile cells
Stable cells
Permanent cells

Question 15

What are labile cells?

Answer 15

Cells that are continuously dividing e.g. surface epithelium

Question 16

What are stable cells?

Answer 16

Cells with a low level of replicative activity
May divide rapidly when needed - many cells wait in stage G0 of cell cycle for recruitment
e.g. hepatocytes, fibroblasts, endothelium

Question 17

What are permanent cells?

Answer 17

Non dividing cells that are unable to re-enter the cell cycle
e.g. neurones, skeletal and cardiac muscle cells

Question 18

Why is regulation of the cell cycle important?

Answer 18

There are many things that could go wrong (e.g. incorrect DNA replication, too much recruitment of cells from G0) that could result in increased proliferation or mutation, leading to disease

Question 19

What is apoptosis?

Answer 19

Programmed cell death

Question 20

Is apoptosis always pathological?

Answer 20

No

Question 21

What are some inducers of apoptosis?

Answer 21

Withdrawal of growth factors
Viruses
Free radicals
Ionising radiation
DNA damage
Fas ligand/CD95 interaction

Question 22

Name some disorders in which there is increased apoptosis.

Answer 22

Neurodegenerative disorders
AIDS
Reperfusion injury

Question 23

Name some disorders in which there is reduced apoptosis.

Answer 23

Neoplasia

Auto-immune disease

Question 24

What is the Fas ligand/CD95?

Answer 24

A type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family
Its binding with its receptor induces apoptosis

Question 25

What is the p53 gene?

Answer 25

A tumour suppressor gene which regulates the cell cycle

Question 26

What is the Bcl-2 family?

Answer 26

A family of regulator proteins which regulate cell death, by either inducing or inhibiting apoptosis

Question 27

What is thought to be the major cause of replicative senescence?

Answer 27

Progressive telomere shortening

Question 28

Why do telomeres get shorter with each DNA replication?

Answer 28

DNA polymerase cannot replicate DNA at the very ends of chromosomes - the telomeres

Question 29

In which cells is telomerase - the enzyme responsible for maintenance of telomere length - present in?

Answer 29

Germ cells Stem cells Cancer cells

Question 30

What happens to somatic cells when their telomeres become too short?

Answer 30

Growth is arrested - the cells are irreversibly arrested in G0/G1 and lose the ability to respond to growth factors

Question 31

What is a neoplasm?

Answer 31

An abnormal mass of tissue Growth exceeds and is uncoordinated with that of the normal tissues Continues after cessation of the stimuli that evoked the change

Question 32

What are the characteristics of benign neoplasms?

Answer 32

``` They resemble normal tissue and are well differentiated They grow by expansion and do not invade other tissues They are encapsulated No necrosis Normal N:C ratio Few mitotic figures Minimal pleomorphism Do not metastasise ```

Question 33

What are the characteristics of malignant neoplasms?

Answer 33

``` Invasive growth pattern Not encapsulated Necrosis common N:C ratio increased Pleomorphic Mitotic figures more frequent/abnormal May metastasise ```

Question 34

What name is given to a malignant tumour derived from squamous epithelium?

Answer 34

Squamous carcinoma

Question 35

What name is given to a malignant tumour derived from glandular epithelium?

Answer 35

Adenocarcinoma

Question 36

What are the components of a neoplasm?

Answer 36

``` Neoplastic cells Blood vessels Inflammatory cells - macrophages, lymphocytes, pleomorphs Fibroblasts Stroma ```

Question 37

What is the key difference between dysplastic cells and cancer cells?

Answer 37

Dysplastic cells are not invasive

Question 38

What is the definition of metastasis?

Answer 38

Tumour implants that are discontinuous with the primary lesion - "secondary" tumours

Question 39

What are some common sites for metastatic disease?

Answer 39

``` Regional lymph nodes Liver Lung Bone Brain Adrenal gland Skin ```

Question 40

Which tumours tend to spread through the lymphatic route?

Answer 40

Carcinoma

Question 41

Which tumours tend to spread through the haematogenous route?

Answer 41

Sarcoma

Question 42

Which organs are very effective at arresting circulating cancer cells?

Answer 42

Lung and liver

Question 43

Does metastatic spread correlate with blood supply?

Answer 43

No

Question 44

Which cancers are at risk of direct implantation in terms of lymphatic spread?

Answer 44

Mesothelioma | Chondrosarcoma

Question 45

What are some of the key elements that allow cancer development?

Answer 45

``` As the tumour progresses: Escape from senescence Evasion of apoptosis Limitless replication potential Angiogenesis Invasion & metastasis ```

Question 46

Why might cancer cells exhibit genomic instability?

Answer 46

They have defective DNA repair mechanisms - tumours are more likely to express various mutations

Question 47

What are the basic two steps of tumour development?

Answer 47

Initiation - electrophilic molecules, DNA damage | Promotion - stimulation of proliferation

Question 48

How do DNA viruses initiate carcinogenesis?

Answer 48

Do not contain oncogenes - they encode proteins that bind to and inactivate host proteins

Question 49

How do RNA viruses initiate carcinogenesis?

Answer 49

Contain specific viral oncogenes which are highly homologous to human genes

Question 50

What are some of the classical oncogenes?

Answer 50

``` PDGF EGFR ras src myc Bcl2 ```

Question 51

What are the four ways in which proto-oncogenes can be activated?

Answer 51

Amplification Translocation Point mutation (think ras) Insertional mutagenesis

Question 52

What type of virus is the human papilloma virus?

Answer 52

DNA virus

Question 53

How might p53 or other tumour suppressor genes be inactivated?

Answer 53

Point mutation Deletion Degradation Other structural changes

Question 54

What are some of the characteristics of classical oncogenes?

Answer 54

Stimulate cell proliferation Inhibit cell death Are dominant

Question 55

What are some of the characteristics of tumour suppressors?

Answer 55

Inhibit cell proliferation Stimulate cell death Are recessive