Disorders of Growth and Differentiation Flashcards
What are the different kinds of growth ? Can growth be a mixture of these ?
A. Multiplicative growth (increased number of cells)
B. Auxetic growth (enlargement of an existing cell)
C. Accretionary growth (Growth of extracellular matrix)
Yes.
What are possible types of increased growth ?
A. Hyperplasia (increased growth in cell number)
B. Hypertrophy (increased growth in cell size)
What is physiological hypertrophy ?
Temporary increase in size of cells to provide for a natural increase of function.
Give examples of physiological hypertrophy.
Walls of the uterus
Athlete’s muscle
Give an example pathological hypertrophy.
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)
Give examples of physiological hyperplasia.
Adaptation to altitude (high altitude training, increased number of RBCs in blood)
Mammae during pregnancy
Tissue repair (angiogenesis, wound healing)
Give examples of pathological hyperplasia.
Psoriasis (Abnormal epidermis, with lots of proliferation of cells, especially keratinocytes) Tissue repair (keloid scar, scarring of liver in cirrhosis)
What is atrophy ?
Decrease in the number or volume of cell or both
What is one possible way for cells numbers to decrease ?
Apoptosis
Give examples of physiological atrophy ?
-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
What are examples of pathological atrophy ?
- 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)
What are possible causes of systematic growth disorders ?
- Hormones and growth factors
- Genetics
- Nutrition
- Environmental factors (pollution, housing, alcohol)
- Secondary consequence of disease (cystic fibrosis, kidney disorder)
What is Turner’s Syndrome ?
- Only 45 chromosomes, XO chromosomes (not XX or XY)
- Always female
- Short stature
What is the genetic basis of Turner’s Syndrome ?
- 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
What is Beckwith-Wiedemann Syndrome ?
• Overgrowth in early childhood, especially large tongues
What is the genetic basis of Beckwith-Wiedemann
Syndrome ?
- Inheriting two copies of a chromosome from one (paternal) parent and none from mother
- Increased expression of IGF-II
- Decreased expression of H19
What is the genetic basis of pituitary gigantism ?
- Increased IGF-1
* Often due to pituitary tumours
What is the difference between gigantism and acromegaly ?
In children, the genetic changes result in gigantism
In adults, they result in acromegaly (size of hands, feet, jaw, forehead increase)
What is Achondroplasia ?
Condition affecting long bones, resulting in dwarfism
What is the genetic basis of achondroplasia ?
- 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)
Describe the relative sizes of proliferative and hypertrophic zones in:
1) Loss of FGFR3
2) Mutant FGFR3
1) Loss of FGRF3: Increased proliferative zone
2) Mutant FGFR3: Reduced proliferative zone compared to hypertrophic zone
What are some factors affecting differentiation ?
Positional Factors (e.g. vitamin A) Paracrine growth factors Autocrine factors External factors (e.g. mutagens) Hormones
What is metaplasia ? Which kind of cell does metaplasia usually affect ?
Change of differentiated cell type, in response to altered cellular environment
Usually affecting epithelial or mesenchymal cells
Give an example of metaplasia.
Epithelium of trachea and bronchi in smokers from normal columnar to squamous type of epithelia.
What is dysplasia ?
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)
What is neoplasia ?
Abnormal uncoordinated excessive cell proliferation
Does neoplasia persist after the stimulus is withdrawn ?
Yes, can even move towards more extreme cases persisting after initiated stimulus is withdraw
Are more aggressive tumour cells more or less differentiated ?
More aggressive tumour cells less differentiated (whereas low grade tumour, cells will still look like OG cell type)
Give examples of disorders of differentiation and morphogenesis.
• Anomalies of organogenesis – Agenesis – Atresia – Hypoplasia – Ectopia/heterotopia – Maldifferentiation
• Congenital abnormalities
– Genetic or teratogenic causes
What is organogenesis ?
process by which the three germ layers, the ectoderm, endoderm, and mesoderm develop into the internal organs of the organism
What is agenesis ? Give an example.
Failure to develop an organ or structure (e.g. renal agenesis)
What is atrasia ? Give examples.
• Failure to develop a lumen
– Oesophageal atresia
– Duodenal atresia
– Imperforate anus
Give examples of failures of closing.
Spina bifida, and cleft palate
What is hypoplasia ?
Failure of organ or segment of an organ to develop to normal size
What is ectopia/heterotopia ? Give an example.
Small areas of mature tissue from one organ present in another
– Endometriosis (Patches of endometrium growing on outside of womb)
What is maldifferentiation ? Give an example.
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.
What is Wilm’s Tumour ? What histological abnormalities may you find ?
Developmental malignancy, usually in children, in the kidney
Within kidney, may find evidence of cartilage bound and smooth muscle
