Disorders of Growth and Differentiation

Question 1

What are the different kinds of growth ? Can growth be a mixture of these ?

Answer 1

A. Multiplicative growth (increased number of cells)
B. Auxetic growth (enlargement of an existing cell)
C. Accretionary growth (Growth of extracellular matrix)

Yes.

Question 2

What are possible types of increased growth ?

Answer 2

A. Hyperplasia (increased growth in cell number)

B. Hypertrophy (increased growth in cell size)

Question 3

What is physiological hypertrophy ?

Answer 3

Temporary increase in size of cells to provide for a natural increase of function.

Question 4

Give examples of physiological hypertrophy.

Answer 4

Walls of the uterus

Athlete’s muscle

Question 5

Give an example pathological hypertrophy.

Answer 5

Right ventricular hypertrophy (if something reducing blood flow to the lungs and bod body needs to compensate which enlarges size of cells in right ventricles)

Question 6

Give examples of physiological hyperplasia.

Answer 6

Adaptation to altitude (high altitude training, increased number of RBCs in blood)
Mammae during pregnancy
Tissue repair (angiogenesis, wound healing)

Question 7

Give examples of pathological hyperplasia.

Answer 7

Psoriasis (Abnormal epidermis, with lots of proliferation of cells, especially keratinocytes)  
Tissue repair (keloid scar, scarring of liver in cirrhosis)

Question 8

What is atrophy ?

Answer 8

Decrease in the number or volume of cell or both

Question 9

What is one possible way for cells numbers to decrease ?

Answer 9

Apoptosis

Question 10

Give examples of physiological atrophy ?

Answer 10

-Thymus gland, increases in size until age 10.
Later on in life, generation of T cells transfers more to bone marrow, and regression of thymus (loss of cortex and medulla).
-Ageing

Question 11

What are examples of pathological atrophy ?

Answer 11

• Muscle – fractures (causes muscle wasting)
• Nerves - paraplegics (causes muscle wasting)
• Blood supply – circulatory problems (e.g. diabetic foot)
• Pressure – bedsores (loss of tissue)
• Diet - anorexia (loss of tissue)

Question 12

What are possible causes of systematic growth disorders ?

Answer 12

• Hormones and growth factors
• Genetics
• Nutrition
• Environmental factors (pollution, housing, alcohol)
• Secondary consequence of disease (cystic fibrosis, kidney disorder)

Question 13

What is Turner’s Syndrome ?

Answer 13

• Only 45 chromosomes, XO chromosomes (not XX or XY)
• Always female
• Short stature

Question 14

What is the genetic basis of Turner’s Syndrome ?

Answer 14

• One copy of SHOX gene on each of X and X chromosome in females
• In affected individuals, only one X chromosome so half the number of copies of gene
• Protein encoded by the gene is a homeodomain protein, acting as a transcription factor
• SHOX is expressed in chondrocytes of the human growth plate (in hypertrophic zone of the cartilage plate)
• Without SHOX, not able to stimulate cells to increase in size so much

Question 15

What is Beckwith-Wiedemann Syndrome ?

Answer 15

• Overgrowth in early childhood, especially large tongues

Question 16

What is the genetic basis of Beckwith-Wiedemann

Syndrome ?

Answer 16

• Inheriting two copies of a chromosome from one (paternal) parent and none from mother
• Increased expression of IGF-II
• Decreased expression of H19

Question 17

What is the genetic basis of pituitary gigantism ?

Answer 17

• Increased IGF-1

* Often due to pituitary tumours

Question 18

What is the difference between gigantism and acromegaly ?

Answer 18

In children, the genetic changes result in gigantism

In adults, they result in acromegaly (size of hands, feet, jaw, forehead increase)

Question 19

What is Achondroplasia ?

Answer 19

Condition affecting long bones, resulting in dwarfism

Question 20

What is the genetic basis of achondroplasia ?

Answer 20

• Mutations in growth factor receptor FGFR3 (normal role of receptor is to repress cell division, works on chondrocytes in cartilage only)
• Autosomal dominant manner
• Normally: When FGFR (in cell membrane) binds to FGF, dimerises, triggering structural rearrangement of the part of receptor inside the cell –> results in activation of enzymatic active site leading to phosphorylation cascade –> signal degraded
• In Achondroplasia: mutation causes significantly reduced proliferative zone compared to hypertrophic zone. receptor remains dimerised and is not possible to switch off signal (hence, FGF independant signalling)

Question 21

Describe the relative sizes of proliferative and hypertrophic zones in:

1) Loss of FGFR3
2) Mutant FGFR3

Answer 21

1) Loss of FGRF3: Increased proliferative zone

2) Mutant FGFR3: Reduced proliferative zone compared to hypertrophic zone

Question 22

What are some factors affecting differentiation ?

Answer 22

Positional Factors (e.g. vitamin A)
Paracrine growth factors
Autocrine factors
External factors (e.g. mutagens) 
Hormones

Question 23

What is metaplasia ? Which kind of cell does metaplasia usually affect ?

Answer 23

Change of differentiated cell type, in response to altered cellular environment
Usually affecting epithelial or mesenchymal cells

Question 24

Give an example of metaplasia.

Answer 24

Epithelium of trachea and bronchi in smokers from normal columnar to squamous type of epithelia.

Question 25

What is dysplasia ?

Answer 25

Increased cell proliferation accompanied by decreased differentiation (resulting in increased immature cells + less cells at the terminal stages)
Often pre-malignant (as progresses into more severe phenotype, more likely for changes in morphology to make it turn cancerous)

Question 26

What is neoplasia ?

Answer 26

Abnormal uncoordinated excessive cell proliferation

Question 27

Does neoplasia persist after the stimulus is withdrawn ?

Answer 27

Yes, can even move towards more extreme cases persisting after initiated stimulus is withdraw

Question 28

Are more aggressive tumour cells more or less differentiated ?

Answer 28

More aggressive tumour cells less differentiated (whereas low grade tumour, cells will still look like OG cell type)

Question 29

Give examples of disorders of differentiation and morphogenesis.

Answer 29

• Anomalies of organogenesis 
– Agenesis
– Atresia
– Hypoplasia
– Ectopia/heterotopia 
– Maldifferentiation

• Congenital abnormalities
– Genetic or teratogenic causes

Question 30

What is organogenesis ?

Answer 30

process by which the three germ layers, the ectoderm, endoderm, and mesoderm develop into the internal organs of the organism

Question 31

What is agenesis ? Give an example.

Answer 31

Failure to develop an organ or structure (e.g. renal agenesis)

Question 32

What is atrasia ? Give examples.

Answer 32

• Failure to develop a lumen
– Oesophageal atresia
– Duodenal atresia
– Imperforate anus

Question 33

Give examples of failures of closing.

Answer 33

Spina bifida, and cleft palate

Question 34

What is hypoplasia ?

Answer 34

Failure of organ or segment of an organ to develop to normal size

Question 35

What is ectopia/heterotopia ? Give an example.

Answer 35

Small areas of mature tissue from one organ present in another
– Endometriosis (Patches of endometrium growing on outside of womb)

Question 36

What is maldifferentiation ? Give an example.

Answer 36

Failure of normal differentiation and persistence of primitive embryological features
E.g. Multicystic renal dysplasia (MRD) is a malformative condition of the kidneys characterized by an abnormal metanephric differentiation and a renal cystogenesis.

Question 37

What is Wilm’s Tumour ? What histological abnormalities may you find ?

Answer 37

Developmental malignancy, usually in children, in the kidney

Within kidney, may find evidence of cartilage bound and smooth muscle