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MBCHB1 exam > limbs and back week 5 > Flashcards

limbs and back week 5 Flashcards

1
Q

How are long bones, vertebrae pelvis and bones of the base of the skull formed?

A

They are preceded by the formation of a continuously growing cartilage model which is progressively replaced by bone. This process is called endochondral ossification.

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2
Q

What is the benefit of endochondral ossification?

A

It permits functional stress to be sustained during skeletal growth

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3
Q

Describe the growth of the hyaline cartilage template for long bones

A

a small model of the long bone is first formed in solid hyaline cartilage.
This undergoes mainly appositional growth to form an elongated dumbbell shaped mass of cartilage of a shaft (diaphyses) and future articular portions (epiphyses), surrounded by perichondrium

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4
Q

Describe the process of bone formation

A

Ossification starts when proliferated chondrocytes deposit an extracellular matrix containing type II collagen
The chondrocytes in the central region of cartilage undergo hypertrophy and synthesise type X collagen - a marker for hypertrophic chondrocytes
Angiogenic factors are secreted by hypertrophic chondrocytes (VEGF) which induce the invasion of blood vessels from the perichondrium to form a nascent bone cavity
As the cartilage matrix becomes calcified the chondrocytes degenerate leaving spaces for blood vessels to invade
Osteoprogenitor cells and haematopoietic stem cells reach the core of the calcified cartilage through the perivascular connective tissue.
The preosteoblasts differentiate into osteoblasts and aggregate on the surfaces of the calcified cartilage and begin to deposit bone matrix

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5
Q

What is indian hedgehog?

A

a member of the hedgehog proteins, is expressed by early hypertrophic chondrocytes within the endochondral template

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6
Q

What are the functions of Ihh?

A

Stimulates adjacent perichondria chondrocytes to express RUNX2 and differentiate into osteoblasts to continue the bone collar
Stimulates the perichondral cells to produce parathyroid hormone related peptide (PTHrP)

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7
Q

What does PTHrP do?

A

binds to receptor on surface of chondrocytes of the reserve zone to stimulate their proliferation
Binds to receptors of chondrocytes in the proliferation zone to inhibit their differentiation into hypertrophic chondrocytes

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8
Q

What causes growth plate inactivation?

A

An increase in oestrogen secretion

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9
Q

What causes achondroplasia?

A

Heterozygous mutations of fibroblast growth factor 3 receptor. FGF3 mutations activate the FGFR3 signal pathways which is a receptor tyrosine kinase pathway. The ultimate effect of FGFR3 signalling on bone growth is inhibitory.

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10
Q

What is the phenotype of achondroplasia?

A

long trunk, short limbs, especially proximally and a large head.

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11
Q

What is the mutation observed in achondroplasia?

A

gain of function mutation which activates the receptor

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12
Q

How do somites contribute to muscles?

A

musculature of the axial skeleton, body wall, limbs
somites undergo epithelialisation
upper region - dermatome, dorsomedial muscle cells, ventrolateral muscles cells
lower region - vertebrae and ribs

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13
Q

What directs dermatome to form dermis?

A

neurotrophic 3

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14
Q

What do WNT proteins and MBP proteins do?

A

WNT (activation), BMP (inhibitory) combine to activate MYOD- creating a group of muscle precursors that secrete MYF

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15
Q

What do MYOD/MYF5 do?

A

myogenic regulatory factors - activate muscle specific genes, can convert non muscle cells to muscle cells

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16
Q

What induces sclerotome formation?

A

sonic hedgehog and noggin

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17
Q

Describe the lateral somatic frontier

A

well defined border between each somite and the lateral plate mesoderm
Separates primaxial and abaxial domain
LSF also defines border between dermis derived form dermatome, and the dermis derived from the lateral plate mesoderm in the body wall

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18
Q

What signals control primaxial?

A

neural tube and notocord

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19
Q

What signals control abaxial?

A

lateral plate mesoderm

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20
Q

Give a summary of muscle formation

A

Most muscle derived from mesoderm
somites give rise to muscles of the body wall, skeleton and limbs
lateral somatic frontier operates two mesoderm domains in embryo
epaxial muscles are innervated by dorsal primary rami
hypaxial muscles innervated by ventral primary rami
molecular signals for muscle induction rise from tissue adjacent to prospective muscle cells

21
Q

What are all the main development mechanisms?

A

cell differentiation
pattern formation
morphogenesis
growth

22
Q

Describe limb development

A

limbs develop from small buds of undifferentiated mesoderm, which are covered by ectoderm (starts about week 4)

23
Q

How do the upper limb buds first appear?

A

ridges from the ventrolateral body wall

24
Q

How do the lower limb buds first appear?

A

small bulges

25
Q

When does limb morphogenesis take place?

A

weeks 4-8

26
Q

Describe limb musculature

A

1st sign is appearance of a condensation of mesenchyme near the limb buds
mesenchyme is served from the dorsolateral mesoderm cells of the somites
mesenchymal connective tissue
no nerves in early limb bud

27
Q

Describe limb development

A 
limb buds consist of mesenchyme core
covered by a layer of cuboidal ectoderm
ectoderm at the distal border thickens
apical ectodermal ridge (AER)
inductive relationship with mesoderm
remains undifferentiated
28
Q

Describe the apical ectodermal ridge

A

as the limb grows, the cells furthest from the AER begin to differentiate into cartilage and muscle
without AER limbs don’t develop
position of AER corresponds to border between dorsal and ventral ectoderm

29
Q

Describe the specification of dorsoventral axis

A

dorsal ectoderm expresses a signalling molecule - Radical Fringe
Ventral ectoderm expresses a transcription factor - Engrailed 1

30
Q

What does AER do?

A

promotes mitosis, prevents differentiation

31
Q

Describe the control of limb development

A

limb outgrowth regulated by FGF10
FGFs at distal ends keep cells undifferentiated
Retinoid acid at the proximal end starts differentiation
Radical fringe in dorsal limb districts AER at distal tip
FGF4 and FGF8 from AER maintain the undifferentiated cells

32
Q

What does polydactyl mean?

A

extra digits - defect in mesoderm

33
Q

What happens at week 6?

A

terminal portion of the limb buds become flattened - hand plates and foot plates formed
separated from the proximal segments by constructions
a second construction further divides the proximal portion into segments

34
Q

What are the three segments of the limbs formed by constructions?

A

stylopod - humerus and femur
zeugopod - radius/ulna, tibia / fibula
auto pod - hands and feet

35
Q

What regulates the positioning of limbs?

A

HOX genes

36
Q

Which T box transcription factors are expressed in the upper limbs?

A

TBX-5

37
Q

Which T box transcription factors are expressed in the hind limbs?

A

TBX-4 and PITX1

38
Q

Describe digit formation

A

cell death in AER separates ridges into 5 parts
mesenchyme condense to form cartilaginous digits
by day 56 digit separation is complete

39
Q

When does limb rotation occur?

A

during week 7

40
Q

Which way does the upper limb rotate?

A

90 laterally

41
Q

which way does the lower limb rotate?

A

90 medially

42
Q

Give examples of appendicular abnormalities

A 
failure of formation 
failure of differentiation
duplication 
overgrowth
undergrowth
construction band syndromes
generalised anomalies and syndromes
43
Q

What is impairment?

A

is due to illness, injury or congenital condition that causes or likely to cause a difference of physiological and psychological function

44
Q

What is disability ?

A

a person who has a physical or mental impairment - even if controlled by drugs or an aid

45
Q

How is disability caused in young people?

A 
prenatal
premature
birth injury
congenital 
accident
infection
violence 
disease
46
Q

What are the impacts of not working?

A

economic
social
health
quality of life

47
Q

What does the equality act include?

A 
disability
race
gender
ethnicity
age
religion
48
Q

Give some examples of work related diseases

A

asthma
lung cancer
cardiovascular disease
musculoskeletal disorders

49
Q

What aspects are used to evaluate a person’s functional capacity?

A 
personal care
dressing
walking stairs and distances
domestic tasks
driving
work tasks
financial affairs

MBCHB1 exam (28 decks)

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