Disorders of growth and differentiation

Question 1

What are the 3 types of increased growth?

Answer 1

• Hyperplasia
• Hypertrophy
• Combined hypertrophy and hyperplasia

Question 2

What is physiological hypertrophy

Answer 2

Increase in muscle cell size due to use

Question 3

What is an example of pathological hypertrophy?

Answer 3

Right ventricular hypertrophy - Compensation because of decreased blood flow to the lungs. Strain on heart.

Question 4

Give 2 examples of physiological hyperplasia

Answer 4

1. Adaptation to altitude

2. Mammary glands in pregnancy

Question 5

Give an example of a pathological hyperplasia

Answer 5

Psoriasis - auto immune disease in which proliferation is stimulated

Question 6

Describe hyperplasia in tissue repair

Answer 6

• In angiogenesis, wound healing, liver regeneration, heart
• Can be beneficial but also harmful if goes too far- hypertrophic scar
• Cirrhosis- fibrosis scar and regenerative nodules

Question 7

What is decreased growth called?

Answer 7

Atrophy

Question 8

How can atrophy present?

Answer 8

• Reduction in cell size
• Reduction in cell number
• Both
• May require apoptosis

Question 9

Give 2 examples of physiological atrophy

Answer 9

• Thymus goes through regressive alterations with age (medulla and cortex decreases a lot, fat increases)
• Ageing

Question 10

Describe pathological atrophy (5)

Answer 10

• Muscles- fractures
• Nerves- paraplegics
• Blood supply -circulatory problems
• Pressure-bedsores
• Diet - anorexia

Question 11

What may systemic growth disorders be caused by?

Answer 11

• Hormones and growth factors
• Genetics
• Nutrition
• Environmental factors: pollution, lead, housing, foetal alcohol syndrome
• Secondary effect of disease e.g. CF, chronic kidney disease

Question 12

What is Turners syndrome?

Answer 12

• Only one sex chromosome
• XO
• 45 chromosomes total
• Female

Question 13

What is SHOX?

Answer 13

• Homeobox gene

* Transcription factor

Question 14

Describe problems with the SHOX gene

Answer 14

• On the tip of chromosome X and Y
• 2 copies are inherited
• Therefor those with turners syndrome are missing a copy, making them shorter in height

Question 15

Why is SHOX gene not inactivated?

Answer 15

Its in the pseudoautosomal region

Question 16

Which bone cells express SHOX?

Answer 16

Chondrocyte of the growth plate

Question 17

What happens in cells that don’t express SHOX

Answer 17

The cells don’t increase in size

Question 18

What is

Beckwith-Wiedemann syndrome?

Answer 18

• Inherting two copies of a chromosome from one parent and none from the other
• Increased expression of IGF-II (promotes growth and proliferation)
• Decreased expression of H19 (negative regulation of body weight and cell proliferation)
• Overgrowth in early childhood

Question 19

What is pituitary gigantism?

Answer 19

• Increased IGF-1
• Increased growth hormone
• Often as a result from pituitary tumours
- In children = gigantism
- In adults acromegaly = increased hand, foot, jaw and forehead size

Question 20

What is achondroplasia?

Answer 20

• Bone growth disorder- causes dwarfism
• FGFR3
• dominant
• Transmembrane domain G380R remains dimerised - no way to switch off the signal
• Constitutively active

Question 21

What happens if there is a loss of FGFR3?

Answer 21

• Growth is increased

Question 22

What does FGFR3 do?

Answer 22

• Sends negative signals to repress growth

* Specifically proliferative zone of growth or epiphyseal plate affected

Question 23

Which bone cells does an FGFR3 mutation have the greatest effect on?

Answer 23

Chondrocytes

Question 24

What is the FGFR3 mutation expressed by?

Answer 24

• CMV everywhere

* Col II specifically in osteoblasts

Question 25

What is metaplasia?

Answer 25

• Change of differentiated cell type
• Response altered cellular environment
• Often epithelial of mesenchymal cells
• One mature cell type to another - not premalignant

Question 26

What is an example of metaplasia

Answer 26

• Epithelium of trachea and bronchi in smokers- adaptation allows it to cope with the stress of its environment

Question 27

What is dysplasia?

Answer 27

• Increased cell proliferation
• Atypical morphology
• Decreased differentiation
• often premalignant
• Expansion of immature cells

Question 28

What is neoplasia?

Answer 28

• Abnormal uncoordinated excessive cell proliferation

* Persists after the initiating stimulus is withdrawn

Question 29

What are the anomalies of organogenesis?

Answer 29

• Agenesis
• Atresia
• Hypoplasia
• Ectopia/heterotopia
• Maldifferentiation

Question 30

What is agenesis?

Answer 30

Failure to develop an organ or structure

Question 31

What is atresia?

Answer 31

Failure to develop a lumbar

Question 32

What are the conditions caused by failure to close?

Answer 32

• Spina bida

* Cleft palate

Question 33

What is hypoplasia?

Answer 33

• Failure of an organ to develop to normal size

* May only apply to a segment of an organ

Question 34

What is ectopic/heterotopia?

Answer 34

Small areas of mature tissue from one organ present in another e.g. endometriosis

Question 35

What is maldifferentiation?

Answer 35

• Failure of normal differentiation

* Persistence of primitive embryological features

Question 36

What is Wilms’ tumour?

Answer 36

Developmental malignancy