Disorders of Growth and Differentiation Flashcards

1
Q

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

A

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

Yes.

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2
Q

What are possible types of increased growth ?

A

A. Hyperplasia (increased growth in cell number)

B. Hypertrophy (increased growth in cell size)

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3
Q

What is physiological hypertrophy ?

A

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

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4
Q

Give examples of physiological hypertrophy.

A

Walls of the uterus

Athlete’s muscle

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5
Q

Give an example pathological hypertrophy.

in heart

A

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

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6
Q

Give examples of physiological hyperplasia.

A

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

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7
Q

Give examples of pathological hyperplasia.

A

Psoriasis (Abnormal epidermis, with lots of proliferation of cells, especially keratinocytes)

Tissue repair (keloid scar, scarring of liver in cirrhosis)

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8
Q

What is atrophy ?

A

Decrease in the number or volume of cell or both

may require apoptosis

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9
Q

What is one possible way for cells numbers to decrease ?

A

Apoptosis

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10
Q

Give examples of physiological atrophy ?

A

-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

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11
Q

What are examples of pathological atrophy ?

A
  • 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)
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12
Q

What are possible causes of systematic growth disorders ?

A
  • Hormones and growth factors
  • Genetics
  • Nutrition
  • Environmental factors (pollution, housing, alcohol)
  • Secondary consequence of disease (cystic fibrosis, kidney disorder)
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13
Q

What is Turner’s Syndrome ?

A
  • Only 45 chromosomes, XO chromosomes (not XX or XY)
  • Always female
  • Short stature
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14
Q

What is the genetic basis of Turner’s Syndrome ?

A
  • 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
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15
Q

What is Beckwith-Wiedemann Syndrome ?

A
  • Overgrowth in early childhood, especially large tongues
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16
Q

What is the genetic basis of Beckwith-Wiedemann Syndrome ?

A
  • Inheriting two copies of a chromosome from one (paternal) parent and none from mother
  • Increased expression of IGF-II
  • Decreased expression of H19
17
Q

What is the genetic basis of pituitary gigantism ?

A
  • Increased IGF-1
  • Increased growth hormone
  • Often due to pituitary tumours
18
Q

What is the difference between gigantism and acromegaly ?

A

In children, the genetic changes result in gigantism

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

19
Q

What is Achondroplasia ?

A

Condition affecting long bones, resulting in dwarfism

20
Q

What is the genetic basis of achondroplasia ?

A
  • 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)
21
Q

Describe the relative sizes of proliferative and hypertrophic zones in:

1) Loss of FGFR3
2) Mutant FGFR3

A

1) Loss of FGRF3: Increased proliferative zone (increases growth)

2) Mutant FGFR3: Reduced proliferative zone compared to hypertrophic zone (suppresses growth)

22
Q

What are some factors affecting differentiation ?

A

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

23
Q

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

A

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

24
Q

Give an example of metaplasia.

A

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

25
Q

What is dysplasia ?

A

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)

26
Q

What is neoplasia ?

A

Abnormal uncoordinated excessive cell proliferation

27
Q

Does neoplasia persist after the stimulus is withdrawn ?

A

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

28
Q

Are more aggressive tumour cells more or less differentiated ?

A

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

29
Q

Give examples of disorders of differentiation and morphogenesis.

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

• Congenital abnormalities
– Genetic or teratogenic causes

30
Q

What is organogenesis ?

A

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

31
Q

What is agenesis ? Give an example.

A

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

32
Q

What is atresia ? Give examples.

A
  • Failure to develop a lumen
    – Oesophageal atresia
    – Duodenal atresia
    – Imperforate anus
33
Q

Give examples of failures of closing.

A

Spina bifida, and cleft palate

34
Q

What is hypoplasia ?

A

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

35
Q

What is ectopia/heterotopia ? Give an example.

A

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

36
Q

What is maldifferentiation ? Give an example.

A

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.

37
Q

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

A

Developmental malignancy, usually in children, in the kidney

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

38
Q

Features of Down Syndrome

A