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Foundations of Medicine Week 2 > Limb Embryology > Flashcards

Limb Embryology Flashcards

1
Q

During what time is an enbryo most susceptible to birth defects by teratogens?

A

from weeks 4 to 8

this is when the major organ systems are all developing

if the exposure is before this, the likihood is much higher for spontaneous abortion

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2
Q

What does the notochord induce in the ectoderm at week 3-4?

A

It induces the ectoderm to invaginate, forming the neural groove and tube

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3
Q

What will the notochord eventually develop into?

A

the vetrebral bodies and intervertebral discs

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4
Q

Besides signalling the formation of the neural groove/tube and contributing to the spinal cord, what does the notochord do?

A
  1. defines the axes of the embryo
  2. mechanical role in the foldin gprocess
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5
Q

What develops on either side of the notochord?

what signals their formation?

A

the paraxial mesoderm gives rise to somites

their formation is signalled by the neural tube

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6
Q

The lateral mesoderm separates into what two layers? WHat is between them?

A

the somatic and the splanchnic lateral mesoderm

separated by the intraembryonic ceolom

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7
Q

What is embryonic connective tissue called? WHat is it derived from?

A

mesenchyme

it’s derived from mesoderm and neural ccrest cells

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8
Q

What will mesenchymal cells differentiate into?

A

into myoblasts, chondroblasts, osteoblasts and fibroblasts (multipotenti)

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9
Q

What are somites called before they’re “mature” somiates?

A

somitomeres - they’re clusters of mesodermal tissue that appear segmentally in rostral ot caudal progression, derived from parazial mesoderm

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10
Q

WHy is week 4 such a critical period in development?

A

the neural tube begins to close and you get cephalo-caudal and lateral folding

this is also when you start developing the somites, organ systems, phanygenal arches, ear and eyes, and limb buds begin to appear

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11
Q

WHere in the embryo do the somitomeres NOT mature into somites?

A

the first 7 pairs - they will contribute mesoderm to the head and neck region (the next 35 will become somites)

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12
Q

THe somites become segmented into what two sets of cells?

WHat happens in the next division?

A

Somites divide into sclerotome (ventromedially toward notochord and neural tube) and dermomyotome (lateral portions)

THen the dermomyotome divides into the **myotome ** and dermatome (which will be right under the ectoderm)

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13
Q

What does the sclerotome develop into? THe dermatome? THe myotome?

A

sclerotome = bone and some CT

myotome = muscle

dermatome = dermis and hypodermis (epidermis is ectoderm)

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14
Q

WHat are the two types of developmental bone formation?

A

membranous bone formation

endochondral bone formation

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15
Q

Describe membranous bone formation

A

mesenchyme condenses into vascular CT

the mesenchymal cells produce collagen fiber matrix

the cells differentiate into osteoblasts

the osteoblasts lay down mineralized bone matrix

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16
Q

Wher ein the body does membranous bone formation occur?

A

in the flat bone sof the skull

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17
Q

Describe endohcondral bone formation.

A

It’s when hyaline cartilage is laid down first, and is then replaced by bone…..

THe mesenchymal cells differentiate into chondroblasts (instead of osteoblasts) and lay down a hyaline cartilage model of the long bones.

the matrix calcifies around the periphery of the shaft.

On the interior, some cells differentiate into osteoblasts and beging to lay down mineralized bony matrix (the primary ossification center)

BLood vessels invade and stimulate ossification

the diaphysis grows in length toward the ends of the bone

A 2nd ossification center forms in the piphyses and lay down bone in the opposite direction toward the primary ossification center.

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18
Q

What is the space of hyaline cartilage located between the primary and secondary ossification centers called?

A

the epiphyseal growth plate

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19
Q

WHen do primary ossification centers appear during development?

WHen do secondary ossification centers appear?

A

primary - during week 8 of development

secondary - after birth

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20
Q

What happens when there is no more hyaline cartilage between the ossification centers?

A

the epiphyseal plate has closed and the bone won’t grow anymore

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21
Q

Loose mesenchyme between the cartilage models of bones differentiate into what?

A

either fibrous tissue or fibrocartilage depending on the type of joint

Or in the case of synovial joints, programmed apopotsis results in the joint cavity between the adjacent cartilage models

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22
Q

What is marfan syndrome?

A

it’s a connective tissue disorder that causes excessive long bone growth

It’s related to the fibrillin gene

you get long thin limbs

it also affects the heart, vessels, bones lungs, and eyes

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23
Q

What is osteogenesis imperfecta?

A

It’s a defect in type 1 collagen gene

autosomal dominant or recessive

you get extreme bone fragility because you don’t have the colagen to provide resilience for the bone

results in frequent fractures and hypermobile joints and decreased bone density

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24
Q

What happens in achondroplasia?

A

It’s a defect in FGFR3 so that you get a mutated form of the receptor that is actively involved bone growth of long bones

can be autosomal dominant or spontaneous mutation

it’s the most common form of dwarfism

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25
Q

What happens in acromegaly?

A

excess growth hormone AFTER growth plates have closed, resulting in large, heavy bones especially the face hands and feet

(Andre the giant)

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26
Q

What happens in gigantism?

A

when you have excess growth hormone during childhood BEFORE the growth plates have closed

you get overal large size - height AND organs

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27
Q

What happens in congenital hip dysplasia?

A

It’s incomplete formation of the acetabulum, which holds the femur head into the hip joint

you end up with legs held in positions that don’t match, less movement, uneven leg length - can be complete dislocation or just laxity

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28
Q

The skeletal system is divided into what two classifications?

A

the axial skeleton and the appendicular skeleton

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29
Q

what make sup the axial skeleton? the appendicular skeleton?

A

axial: skull, vertebral column, ribs, and sternum
appendicular: pectoral and pelvic girdles plus limbs

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30
Q

What cells form a sheath around the notochord and neural tube?

A

sclerotome cells from the somites

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31
Q

THe sclerotome from each somite divides into what to segments?

A

a loose CT segment and a dense CT segment

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32
Q

What separates the dense and loose CT segments of the sclerotome?

A

von ebner’s fissures

33
Q

As the sclerodermal cells converge, what do they form?

A

the centrum of the vertebral body

34
Q

During development, the cells in each of the sclerotomes segments migrate where?

WHat does this mean for the composition of individual vertebrae?

A

They migrate away from the von Ebner’s fissures, thus each vertebrae has a component from two somites

35
Q

what will pass through the von Ebner’s fissures?

A

the spinal nerves

36
Q

What composes the occiput and what does this mean for cervical spinal nerves?

A

The occiput is made of the caudal prt of occipital 4 and the cranial part of cervical 1

this is why the C1 spinal nerves come sout ABOVE the C1 vertebra and why the C8 spinal nerve lies beneath the C7 vertebra (on top of the T1 vertebrae)

After the cervical region, all of the spinal nerves run UNDER the vertebra of the same number

37
Q

The mesenchyme lying between the cephalic and caudal parts of the original sclerotome segmetns will fill the space surrouding the notochord and become what?

A

the annulus fibrosis of the intervertebral disc

38
Q

WHat will form the nucleus pulposis of the intervertebral disc?

A

the notochord

39
Q

How is the rest of the vertebra formed?

A

There is also condensation of slcerodermal cells surrounding the neural tube so that there is a cartilaginous structure with processes of hyaline cartilage called the costal processes

Multiple ossification centers form in these costal processes and the neural arch

these ossification centers will grow to form the pedicles, lamina and transver/spinous processes

40
Q

WHere does the ribs form off ot?

A

the costal processes - at first it’s solid, but then costovertebral synovial joints form

41
Q

What forms the sternum?

A

the fusion of multiple ossification centers of sternebrae

42
Q

WHat are the 3 forms of spinal bifida?

A

spina bifida occulta

meningocele

myelomeningocele

43
Q

What happens in spina bifida occulta? WHat can you see on the outside?

A

In spinal bifida occulta the neural tube doesn’t close properly so the neurla rch can’t form and the vertebrae don’t form.

In the lumbosacral area the tube doesn’t close so the vertebrae don’t form right, but the spinal cord and meninges are intact so there isn’t usually any defects

you just get a tuft of hair in that region fo the back

44
Q

What happens in a meningocele?

In a myalomeningocele?

A

meningocele: again, you don’t get formation of the neural arch and the meninges bulgeout and fill with liquid - this you can see from the outside

In a myelomeningocele, the spinal cord bulges out into the meningocele - definitely defects

45
Q

What happpens in Klippel Feil Sydrome?

A

it’s congenital fusion of any of the cervical vertebrae, resultin gin brevicollis (short neck) and often scoliosis

There are often abnormalities in the organ systems as well including heart ,kidney, rib and palate abnormalities

46
Q

What will a hemivertebra cause?

A

congenital scoliosis

if there is only one chondrification/ossification center that forms in the vertebral body, you only get formation of it on on side and this causes the rest of the vertebra to angle around it, resultin gin scoliosis

47
Q

What is the result of a cervical rib?

A

thoracic outlet syndrome

You get an extra rib growing in the cervical region (usually off C7), which compresses the brachial plexus and the axillary artery, so you get numbness, tingling, palor and pain in the arm

48
Q

What is pectus excavatum?

A

excessive growth of the connective tissue during sternum development where the area over the sternum poke inward

can be so severe that it compresses the heart and/or lungs

49
Q

WHen do upper and lower limb buds occur during development?

A

upper limb buds on day 26

lower limb buds on day 28

50
Q

At what point in development are limbs no longer susceptible to teratogen exosures?

A

up to week 8

51
Q

What layer do the limb bud off from?

A

the lateral somatic mesoderm layer - it’s mesenchymal tissue that will proliferate and differentiate

upper limb - from next to the somites related to C5-T1

lower limb from L2-S2

52
Q

What gene controls the location of lumb buds?

A

homeobox genes (Hox)

53
Q

In limb formation, there is a thickening of the ectoderm layer of the distal border called the…

A

apical ectodermal ridge (AER)

54
Q

How does the apical ectodermal ridge affect limb formation?

A

They induce proliferation of undifferentiated mesenchymal cells using fibroblast growth factors in the adjacent progress zone.

this is what causes lengthening of the limbs - it happens at the distal end

55
Q

At what end of the limb does cartilage/muscle differentiation start?

A

at the proximal end

the AER keeps the distal end from differentiating until the very end so you can continue to get limb lenghtening

56
Q

WHat are the steps for developing the bones of the limbs? WHat kind of bone formation is this?

A
  1. mesenchymal differentate into chondroblast
  2. lay down hyaline cartilage model
  3. mineralized bone
  4. osteoblasts lay down hard bone

this is endochondral bone formation

57
Q

What is the zone of polarizing activity and what does it do?

A

It’s a region proximal to the apical ectodermal ridge along the posterior side of the limb.

It’s where the sonic hedgehog gene is activated to produce Shh proteins

the Shh proteins will differentially affect the tissue closer to the ZPA than those further away

this is what determines where the thumb and the pinky go! - controls anteroposterior axis of the limb

58
Q

How does diigt formation occur?

A

the limb buds flatten into paddle-shaped hands and feet

you then get apoptosis in the AER that separates the paddle into 5 digits

the patterning along the anteroposterior axis (thumb vs. pinky) is acontrolled by Shh from the ZPA

59
Q

In addition to lengthening, what do the limbs have to do?

A

rotate by 90 degrees

the upper limbs rotate 90 degrees laterally to put the thumb lateral

the lower limb roates 90 degrees internally so the great toe is medial

60
Q

WHat does this limb rotation mean for the dermatoms?

A

the dermatomes start out parallel along the limb, but wiht the rotation they also rotate and overlap each other. THey’re not parallel anymore

61
Q

How can the limb rotation explain the funkiness of the brachioradialis?

A

the brachioradialis if a flexor muscle that originate on the posterior side and is innervated by the radial nerve - the extensor nerve!

62
Q

What does thalidamide cause?

A

it was a med given to mothers with morning sickness

It caused limb deformities in the babies

If exposed in week 4 = amelia (no limb)

If exposed in week 5 = meromelia (pertial absence of limbs) or phocomelia (having paddle-like appendages attached almost directly to the torso)

63
Q

What is thalidomide used for now?

A

treatment of leprosy

64
Q

What is polydactyly?

A

It’s th most common hand anomaly - you get an extra digit that may be fully formed or just soft tissue

65
Q

What is syndactyly?

A

You don’t get proper apoptosis between the digits, so you get fully formed digits that are fused together.

66
Q

What is ectrodactyly?

A

lobster claw deformity

it’s due to an absent central digital ray, so you get a deep cleft between the digits - sometimes only 2 digits will form.

67
Q

How can muscles have innervation from multiple spinal segments?

A

fusion of myotomes - each myotome is associated with a neural tube segment

68
Q

What do the mesenchym cells differentiate into in myotomes?

A

spindle-shaped myoblasts which fuse to make myotube which develop myofilaments within their cytoplasm

69
Q

Myoblasts fuse to form what?

A

lon multinucleated myofibers that make up skeletal muscle

70
Q

Where will myotomes migrate?

A

some will go dorsally and others will migrate laterally around the body wall

71
Q

As the myotome differentates from the dermotome, it divides into two more segments….

A
  1. the epimere/epaxial segment (smaller, more dorsal)
  2. the hypomere/hypaxial segment (larger)
72
Q

What does the epimere form? Innervated by what?

A

the deep back muscles

innervated by the dorsal primary rami

73
Q

what does the hypomere form?

A

neck flexors, vetrebral column flexors, the three concentric muscle layers of the thorax/abdomen

supplied by the primary ventral rami

74
Q

The hypaxial myoblasts surround the developing long bones to form what two muscle groups?

Innervated by what?

A

an extensor and a flexor group

extensors supplied by the posterior division fo the ventral rami

flexors supplied by the ventral divisions (lateral and medial cords)

75
Q

Why does the pectoralis major muscle still get innervation from the ventral fibers egen though it’s technically not a limb flexor?

A

it develops from the hypomere anterior to the limb buds

76
Q

WHat is poland syndrome?

A

it’s a congenital malformation or absence of the pectoralis major muscle on one side (usually the right)

it often includes ipsilateral webbing of the fingers

77
Q

What happens in prune belly syndrome?

A

poor development of the abdominal muscles causing the skin to wrinkle over the unprotected abodminal organs

also undescended testicles and UTI problems

78
Q

Where does the GI smooth muscle develop from?

A

the splanchnic mesoderm

79
Q
A

Foundations of Medicine Week 2 (8 decks)

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