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Medicine Year 1 - Semester 2 - Part 2 > Disorders of Growth & Differentiation > Flashcards

Disorders of Growth & Differentiation Flashcards

1
Q

State the different ways in which cells can grow

A
  • Multiplicative growth
  • Auxetic growth
  • Accretionary growth
  • Combined pattern of growth
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2
Q

Multiplicative growth

A

Cells can grow by making more copies of the identical cell.

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3
Q

Auxetic growth

A

Cells can grow by becoming larger in size.

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4
Q

Accretionary growth

A

Cells can grow by excreting more extracellular matrix.

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5
Q

Combined pattern of growth

A

Cells can grow by a combination of growth methods.

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6
Q

Differentiation

A

Start with cells of one type and end with cells of a different type.

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7
Q

Hyper- meaning

A

Above normal

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8
Q

Hypo- meaning

A

Below normal

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9
Q

Hyperplasia

A

Increased number of cells

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10
Q

Hypertrophy

A

Same number of cells, but they have increased in size.

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11
Q

Combined hypertrophy and hyperplasia

A

Increased number of cells and increase in cell size.

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12
Q

What can increased growth also be perceived as ?

A

Decreased apoptosis

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13
Q

Physiological hypertrophy - example

A

Athletes muscle

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14
Q

Pathological hypertrophy - example

A

Right ventricular hypertrophy

  • cardiac muscle increased in size due to problems in sending blood flow to the lungs
  • So, the heart has to work harder, increases its muscle, although this puts the heart under significant strain
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15
Q

Physiological hyperplasia - example

A

Adaptation to altitude
- Increased number of RBCs in higher altitudes
- Helpful for athletes

Mammary Cycle
- Increase in cells that are able to produce milk during the lactation stage

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16
Q

Pathological hyperplasia - example

A

Psoriasis
- Cells in the epidermis are stimulated to grow
- Abnormal stratum corneum

  • Increased proliferation in epidermis
  • Generation of more keratinocytes that don’t differentiate normally
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17
Q

Hyperplasia in tissue repair

A
  • Angiogenesis
  • Wound healing
  • Liver regeneration
  • Heart
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18
Q

State the stages leading to cirrhotic liver

A

Normal liver
Inflamed liver
Fibrotic liver
Cirrhotic liver

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19
Q

What term is used to describe decreased/regressed growth ?

A

Atrophy

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20
Q

Atrophy

A

Reduction in cell size or number or both

May require apoptosis

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21
Q

Physiological atrophy - example (thymus)

A

Thymus gland
- function is to generate T cells and cell mediated immunity

  • As we age, the bone marrow takes over this function and so we don’t need such a large thymus
  • So, it decreases in size as we age (now mainly made up of fat)
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22
Q

Physiological atrophy - ageing

A

Ageing
- Shrinkage as we age

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23
Q

Pathological Atrophy examples

A

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

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24
Q

State some problems that underlie systemic growth disorders

A

Problems with:

Hormones and growth factors
Genetics
Nutrition
Environmental disease
Secondary effects of disease

25
Q

State some diseases associated with proportionate alterations of skeletal growth

A

Turner’s syndrome
Down syndrome

Beckwith-Wiedemann syndrome
Pituitary Gigantism

26
Q

Turners Syndrome

A

Chromosome 45
XO
Female

  • lack one sex chromosome
  • only have one copy of the SHOX gene
27
Q

SHOX

A

Gene found on the tip of the X and Y chromosome.

Normal individuals have 2 copies of the SHOX gene, one on each sex chromosome.

28
Q

Mutations within SHOX gene

A

SHOX gene is mutated in short stature syndrome.

  • the SHOX mutation is the only mutation that seems to relate to short stature
29
Q

Where is the SHOX gene found ?

A

The pseudo-autosomal region of the X and Y chromosomes.

This region escapes X chromosome inactivation.

30
Q

What is the SHOX gene associated with ?

A

Growth

The SHOX gene is a transcription factor, which binds to a specific sequence in DNA.

31
Q

Where is the SHOX gene expressed ?

A

SHOX is expressed in chondrocytes of the human growth plate.

Mainly seen in the hypertrophic zone.

32
Q

Hypertrophic zone

A

Cells are getting larger, but not increasing in number.

SHOX protein is seen as black dots in the histological slides of the hypertrophic zone.

33
Q

Down syndrome

A

Trisomy 21
Small stature

Hypotonia
Heart defects
Learning difficulties

34
Q

Beckwith-Wiedemann syndrome cause

A

Inheriting 2 copies of a chromosome from one parent (paternal) and none from the other.

35
Q

Results of Beckwith-Weidemann Syndrome

A

Increased expression of IGF-II
Decreased expression of H19

Overgrowth especially in early childhood

36
Q

Pituitary Gigantism

A

Increased IGF-1
Increased growth hormone

Often from pituitary tumours

37
Q

What do pituitary tumours cause:

  1. In children
  2. In adults
A
  1. Gigantism
  2. Acromegaly: Increased sized hands, feet, jaw, forehead
38
Q

Disproportionate alterations of skeletal growth - uneven distributions of growth

A

Achondroplasia
- head and trunk normal size
- limbs are shorter than average

They show mutations in FGFR3

39
Q

Achondroplasia

A

Disease inherited in an autosomal dominant manner.

50% chance

40
Q

Describe FGFRs

A

Normal FGFR (fibroblast growth factor receptor)

FGF binds; FGFR forms a dimer

Normal receptors pair, become activated and transmit signal.

41
Q

State the mutation in people with achondroplasia

A

Achondroplasia mutation 98% of cases in transmembrane domain G380R.

The FGFR remains dimerised - so no way to switch off signal.

It is constitutively active.

42
Q

FGFR3 function

A

FGFR3 represses growth

  • sends a negative signal to repress growth
  • long bones are affected
  • specifically proliferative zone of growth or epiphyseal plate affected (hypertrophic zone)
43
Q

What does the mutation of FGFR3 have the most effect on ?

A

Most effect in chondrocytes

44
Q

State some factors that influence differentiation

A

Location
Growth factors
Hormones
Adjacent cells
Autocrine factors

45
Q

What is metaplasia ?

A

Change of differentiated cell type

Response altered cellular environment (e.g. stress)

Often epithelial or mesenchymal cels

46
Q

Example of metaplasia

A

Lungs of smokers.

Epithelium of trachea and bronchi in smokers.

Columnar epithelium –> Squamous epithelium

47
Q

What is dysplasia ?

A

Expansion of immature cells

  • Increased cell proliferation
  • Atypical morphology
  • Decreased differentiation
  • Often pre-malignant
48
Q

What is neoplasia ?

A

Abnormal uncoordinated, excessive cell proliferation.

Persists after initiating stimulus is withdrawn.

48
Q

Example of dysplasia

A

Cervix
- smear for cervical screening
- expansion of immature cells

  • cells continue to proliferate, but remain in their least differentiated form
49
Q

Disorders of differentiation and morphogenesis

A

Anomalies of organogenesis
Congenital abnormalities

50
Q

Abnormalities of organogenesis

A

Agenesis
Atresia
Hypoplasia
Ectopia/heterotopia
Mal-differentiation

51
Q

What is agenesis ?

A

Failure to develop an organ or structure
- Renal agenesis (only developed 1 kidney)

52
Q

What is atresia ?

A

Relating to tube formation/closure:

Failure to develop a lumen
Failure to close

53
Q

Failure to close

A

Spina bifida
Cleft palate

54
Q

What is hypoplasia ?

A

Failure of an organ to develop to a normal size.

May only apply to a segment of an organ

54
Q

Failure to develop a lumen

A

Oesophageal atresia
Duodenal atresia
Imperforate anus

55
Q

What is ectopia / heteropia ?

A

Small areas of mature tissue from one organ present in another

  • Endometriosis
56
Q

What is maldifferentiation ?

A

Failure of normal differentiation.

Persistence of primitive embryological features.

  • e.g. Multicystic renal dysplasia
57
Q

Wilms tumour

A

Developmental malignancy
(defects in growth and differentiation)

  • childhood kidney cancer
  • can weigh up to 2kg
  • tumours can contain cartilage, bone and smooth muscle

Medicine Year 1 - Semester 2 - Part 2 (53 decks)

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