Disorders of growth and differentiation Flashcards
What are the 3 types of increased growth?
- Hyperplasia
- Hypertrophy
- Combined hypertrophy and hyperplasia
What is physiological hypertrophy
Increase in muscle cell size due to use
What is an example of pathological hypertrophy?
Right ventricular hypertrophy - Compensation because of decreased blood flow to the lungs. Strain on heart.
Give 2 examples of physiological hyperplasia
- Adaptation to altitude
2. Mammary glands in pregnancy
Give an example of a pathological hyperplasia
Psoriasis - auto immune disease in which proliferation is stimulated
Describe hyperplasia in tissue repair
- 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
What is decreased growth called?
Atrophy
How can atrophy present?
- Reduction in cell size
- Reduction in cell number
- Both
- May require apoptosis
Give 2 examples of physiological atrophy
- Thymus goes through regressive alterations with age (medulla and cortex decreases a lot, fat increases)
- Ageing
Describe pathological atrophy (5)
- Muscles- fractures
- Nerves- paraplegics
- Blood supply -circulatory problems
- Pressure-bedsores
- Diet - anorexia
What may systemic growth disorders be caused by?
- Hormones and growth factors
- Genetics
- Nutrition
- Environmental factors: pollution, lead, housing, foetal alcohol syndrome
- Secondary effect of disease e.g. CF, chronic kidney disease
What is Turners syndrome?
- Only one sex chromosome
- XO
- 45 chromosomes total
- Female
What is SHOX?
- Homeobox gene
* Transcription factor
Describe problems with the SHOX gene
- 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
Why is SHOX gene not inactivated?
Its in the pseudoautosomal region
Which bone cells express SHOX?
Chondrocyte of the growth plate
What happens in cells that don’t express SHOX
The cells don’t increase in size
What is
Beckwith-Wiedemann syndrome?
- 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
What is pituitary gigantism?
• 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
What is achondroplasia?
- Bone growth disorder- causes dwarfism
- FGFR3
- dominant
- Transmembrane domain G380R remains dimerised - no way to switch off the signal
- Constitutively active
What happens if there is a loss of FGFR3?
• Growth is increased
What does FGFR3 do?
- Sends negative signals to repress growth
* Specifically proliferative zone of growth or epiphyseal plate affected
Which bone cells does an FGFR3 mutation have the greatest effect on?
Chondrocytes
What is the FGFR3 mutation expressed by?
- CMV everywhere
* Col II specifically in osteoblasts
What is metaplasia?
- Change of differentiated cell type
- Response altered cellular environment
- Often epithelial of mesenchymal cells
- One mature cell type to another - not premalignant
What is an example of metaplasia
• Epithelium of trachea and bronchi in smokers- adaptation allows it to cope with the stress of its environment
What is dysplasia?
- Increased cell proliferation
- Atypical morphology
- Decreased differentiation
- often premalignant
- Expansion of immature cells
What is neoplasia?
- Abnormal uncoordinated excessive cell proliferation
* Persists after the initiating stimulus is withdrawn
What are the anomalies of organogenesis?
- Agenesis
- Atresia
- Hypoplasia
- Ectopia/heterotopia
- Maldifferentiation
What is agenesis?
Failure to develop an organ or structure
What is atresia?
Failure to develop a lumbar
What are the conditions caused by failure to close?
- Spina bida
* Cleft palate
What is hypoplasia?
- Failure of an organ to develop to normal size
* May only apply to a segment of an organ
What is ectopic/heterotopia?
Small areas of mature tissue from one organ present in another e.g. endometriosis
What is maldifferentiation?
- Failure of normal differentiation
* Persistence of primitive embryological features
What is Wilms’ tumour?
Developmental malignancy
