Embryology Flashcards
when most susceptible to organ damage
3-8 weeks
congenital scoliosis, why susceptible to cardiac defects?
mesoderm
neural tube gives rise to ____
forms the CNS
hindbrain to S2
closes cranial to caudal day 28
syndactyly
bc not have the programmed cell death at APICAL RIDGE
congenital scoliosis
- formation failure (hemivertebrae or wedged vertebrae)
2. segmentation failure (dont separate)
scleretomes
form what?
come together to give rise to the vertebrae
what is
VACTERL
congenital spinal deformities may coexist with a syndrome such as VACTERL ( non-random co-occurrence of birth defects)
Vertebral anomalies Anal atresia Cardiac defects Tracheoesophageal fistula and/or Esophageal atresia Renal Limb defects.
Pre-embryonic
when
what happens
first 3 weeks
fertilization to implantation, placenta formation
(dont know pregnant)
Embryonic
when
what happens
Week 3-8
organogenesis: organs develop
since new structures are developing rapidly the embryo is extremely vulnerable
Fetal Period
when
what happens
Week 8-40
maturation and growth of all structures and organs
Gastrulation
WEEK 3: cell division occurs
Trilaminar layer: 3 primary germ layers are formed
- Ectoderm: skin, CNS, Cranial nerves, sensory nerves, teeth
- Mesoderm: bone, muscle, connective tissue, blood vessels, cardiac, urogenital system
* coexistance of congenital spine and cardiac and kidney defects with congenital bone defects - Endoderm: GI, respiratory
Exctoderm
GASTRULATION: week 3
skin CNS sensory nerves cranial nerves teeth
Mesoderm
GASTRULATION: week 3
bone
connective tissue
muscles
blood vessels
kidney
cardiovascular
*co-existence of congenital spine and cardiac and kidney defects with congenital bone defects
Endoderm
GASTRULATION: week 3
Digestive
Respiratory
Neurulation
complete in 4 weeks
Neural plate: ectodermal cells thicken forming the neural plate
Neural Tube: neural plate folds forming the neural tube
Neural Crest: cells separate from the neural folds and they form the neural crest
Neural plate:
ECTODERM cells thicken forming the neural plate
Neural Tube
neural plate folds forming the neural tube
FORMS THE CNS: extends from hindbrain to S2
closes in cranial to caudal direction by DAY 28
Neural Crest
cells separate from the neural folds and they form the neural crest
FORMS PNS
When does neural tube close
closes in cranial to caudal direction by DAY 28
forms CNS, extends from hindbrain to S2
what forms CNS?
neural tube
what forms PNS?
neural crest
Anencephaly
failure of the neural tube to close cranial side
NTD
Spinal Bifida
failure of neural tube to close caudual side
thoracic or lumbar region
NTD
Causes of NTD
- genetic: siblings of patients with spina bifida have increased incidence of NTD
- nutritional: folic acid taken before/after conception reduce incidence
- environment: certain drugs increase risk of NTD
- -valproic acid (anticonvulsant) causes NTD in 1%-2% of pregnant women, if given in fourth week of development when neural folds are fusing
NTD genetic
genetic: siblings of patients with spina bifida have increased incidence of NTD
NTD nutrition
genetic: siblings of patients with spina bifida have increased incidence of NTD
NTD environment
environment: certain drugs increase risk of NTD
–valproic acid (anticonvulsant) causes NTD in 1%-2% of pregnant women, if given in FOURTH WEEK of development when NEURAL FOLDS ARE FUSING
Endochondral ossification
long bone development from hyaline cartilage
*mesoderm–>mesenchymal cells–>differentiate into chondrocytes
the chondrocytes secrete collagen –form the hyaline cartilagenous embryonic skeleton
Appendicular Skeletal Formation
Primary Ossification Center
DIAPHYSIS
(chondroyctes form from the mesenchymal cells from the mesoderm)
1) chondrocytes proliferate, hypertrophy, synthesize alkaline phosphatase–>
2) this calcifies which inhibits nutrients to the chondrocytes–>
3) as a result the chondrocytes undergo APOPTOSIS–this leaves cavities for blood vessels and osteoblast invasion –>
4) osteoblasts invade causing OSTEOGENESIS!!!
Appendicular Skeletal Formation
Secondary Ossification Center
located at epiphyseal plate “growth plate”
cartilage plate separating epiphysis from diaphysis
endochondral ossification causing longitudinal bone growth
vulnerable for fracture
Appendicular Development
limb buds week 4
early stage of limb development
UPPER LIMBS grow first, lower follow two days later
APICAL ECTODERMAL RIDGE (AER) at the apex of each bud: secretes fibroblast growth factor which induces the limbs to grow
Growth occurs PROXIMAL–> DISTAL
APICAL ECTODERMAL RIDGE
AER
early stage of limb development
at the apex of each bud: secretes fibroblast growth factor which induces the limbs to grow
UPPER LIMBS grow first, lower follow two days later
Growth occurs PROXIMAL–> DISTAL
Appendicular Development
limb buds week 6
distal end forms a paddle like structure
Apoptosis forms space between the digits: fingers and toes are formed
syndactyly
webbed fingers/toes
most common limb anomaly
webbing or fusion of fingers/toes if apoptosis doesn’t occur
Limb bud development
What happens if there is a disturbance
4th week
absent limb formation
Limb bud development
What happens if there is a disturbance
5th week
partial limb formed
Limb bud development
What happens if there is a disturbance
8th week
after 8 weeks teratogens can not cause major limb deficiencies
Achondroplasia
genetic basis
autosomal dominant
FGFR3: new mutations short (p) arm on chromosome 4
FGFR3 limits osteogenesis: mutation increases this effect and LIMITS ENDOCHONDRAL OSSIFICATION
–FGFR interferes converting cartilage to bone (especially long bones)
70% of dwarfism
Dwarfism
autosomal dominant
FGFR3: new mutations short (p) arm on chromosome 4 = achondroplasia
FGFR3 limits osteogenesis: mutation increases this effect and LIMITS ENDOCHONDRAL OSSIFICATION
–FGFR interferes converting cartilage to bone (especially long bones)
responsible for 70% of dwarfism
Clinical manifestations of Achondroplasia
1) cuboid shaped verebrae can cause narrow spinal canal: CORD COMPRESSION
- -20-47% frequency in neurologic complications bc spinal abnormalities
2) spinal stenosis: thoracolumbar stenosis
3) lordosis kyphosis
4) tibia vara
Infants with hypotonia and transient kyphosis
—10-15% kyphosis becomes fixed
- –discourage early unsupported sitting and consider bracing
- –raise the surface up for them
- –hydrocephalus in some cases
What mutation limits endochondral ossification?
The primary function of FGFR3 is to limit osteogenesis. Mutation increases this effect and therefore limits endochondral ossification
What to do for treatment
Infants with hypotonia and transient kyphosis
—10-15% kyphosis becomes fixed
—discourage early unsupported sitting and consider bracing
—raise the surface up for them
Vertebral Column Development
1) MESODERM cells unite to form 42-44 pairs of SOMITES
2) Week 4: somites –> Sclerotomes, myotomes, dermatomes
3) Sclerotomes migrate ventromedially on each side of the notochord to form vertebral bodies
4) vertebral bodies formed from cranial and caudal sclerotome: the union of cells from 2 adjacent scleretomes
*nucleus pulposus
notochord formed from the mesoderm cells degenerates
—>remnants of the notochord become the nucleus pulposus
*annulus fibrosis
scleretome cells form the annulus fibrosis
*vertebral arch:
vertebral body sclerotomes migrate dorsally around the neural tube to form the vertebral arch
ENDOCHONDRAL OSSIFICATION OCCURS
nucleus pulposus
notochord formed from the mesoderm cells degenerates
—>remnants of the notochord become the nucleus pulposus
vertebral arch:
vertebral body sclerotomes migrate dorsally around the neural tube to form the vertebral arch
annulus fibrosis
scleretome cells form the annulus fibrosis
Vertebral Anomalies
- formation failure
- segmentation failure
mixed: combination of both
Vertebral formation defects
–what are they
–cause
–types of defects
absence of a structural vertebral element resulting in a mis-shaped vertebrae
cause: inadequate blood supply to vertebral bodies
types of defects:
1. wedged vertebrae: unilateral partial failure of vertebral formation
- hemivertibrae: 1/2 vertebrae is absent
Types of vertebral formation failure defects
will develop scoliosis from these!!!
- wedged vertebrae: unilateral partial failure of vertebral formation
- hemivertibrae: half of the vertebrae is absent
Vertebral Segmentation Defects
Vertebra do not separate properly:
produce a bar with no growth plate or disk between vertebrae (need growth plate for the bone to lengthen)
–It is a failure of scleretome segmentation
–Segmentation failure causes the vertebra to be mis-shaped or it fuses to another vertebrae
Can develop a scoliosis
(or torticalis)
what causes vertebral segmentation defects?
–It is a failure of scleretome segmentation (vertebrae therefore dont separate properly)
–Segmentation failure causes the vertebrae to be mis-shaped or it fuses to another vertebrae
Congenital spinal deformities:
when?
causes?
WHEN: The failure of normal verebral development during the 4th - 6th week of gestation
CAUSES: of spinal malformation:
1) Neural tube defects
2) Vertebral formation failure
3) Segmentation failure: Vertebra do not separate properly
Location of the anaomaly on the vertebra determines the deformity
—–Lateral deformity-scoliosis most common
—–Anterior deformity-kyphosis
—–Posterior deformity: lordosis least common
- —-Torticolis: If the defect is at the cervical or cervicothoracic region
- -it is not just muscle issue here!!!!!
Segmentation failure
Location of the anaomaly on the vertebra determines the deformity
—–Lateral deformity-scoliosis most common
—–Anterior deformity-kyphosis
—–Posterior deformity: lordosis least common
- —-Torticolis: If the defect is at the cervical or cervicothoracic region
- -it is not just muscle issue here!!!!!
Congenital Scoliosis:
dx
signs of defect
fetal ultrasound can diagnosis it or may not be diagnosed until childhood
Signs of defect:
1) patch of hair
2) midline skin hemangioma
3) congenital heart defects
4) kidney defects
5) LLD (leg length discrepancy, mesoderm)
what conditions can be associated with congenital spinal abnormality
Congenital spinal deformities may also be diagnosed during the workup of:
Either of these conditions can be associated with a congenital spinal abnormality:
Plagiocephally (flattening of the skull bones on one side) or
Torticollis: a tilted rotational position of the head
Klippel-Feil Syndrome
****Segmentation failure (vertebra do not separate properly)
Congenital fusion of 2 or more cervical vertebrae
Classic clinical triad:
1) Low posterior hairline
2) Short neck
3) Cervical range of motion limitation seen in 40-50% of patients. The decrease in motion most commonly is in lateral bending and rotation
VACTERL
congenital spinal deformity may co-exist with a syndrome
VACTERL association is a disorder that affects many body systems.
V= vertebral defects A= anal atresia C= cardiac defects T= tracheo-esophageal fistula R = renal anomalies L= limb abnormalities.
VACTERL
V
vertebral defects
VACTERL
A
anal atresia
anus does not open to outside of the body
VACTERL
C
cardiac defects
VACTERL
T
tracheal abnormalities–tracheaoesophogeal fistula
VACTERL
E
esophogeal atresia: esophagus does not connect to the stomach
VACTERL
R
renal
VACTERL
L
limb abnormalities
absent or displaced thumbs, extra fingers (polydactyly), fused fingers (syndactyly(, or a missing bone in the arm or legs
: absent or displaced thumbs, extra fingers (polydactyly) fused fingers (syndactyly), or a missing bone in the arms or legs
Congenital Spinal Deformities
what other defects can also occur
Congenital heart defects occur in 30% of the patients:
a. Atrial or ventral septal defects
b. Patent Ductus Arteriosus
c. Tetrology of Fallot
Chest wall deformities: may present with multiple rib fusions, this chest wall restriction inhibits growth and development of the lungs
Skull development
what happens
what doesnt it need
when does it occur
what happens if exposed to teratogens
1) Mesenchymal cells derived from NEURAL CREST and mesoderm cells encircle the brain and form the flat bones of the cranium
2) Interosseus Ossification:
Intramembranous Ossification: the mesenchyme cells differentiate directly into the osteocytes, without forming the hyaline cartilage model (DOES NOT NEED CHONDROCYTES, DOES NOT FORM HYALINE CARTILAGE!!!!)
3) 4-8 Weeks: (Note: Organ Genesis Period)
All major external and internal structures are established
By the end of this organogenetic period, all of the main organ systems have begun to develop
***Exposure of embryos to teratogens during this period may cause major congenital anomalies
Teratogens:
what are they
what does vulnerabilty of fetus to teratogens depend on
Any agent affecting fetal development: birth defects
The vulnerability of the fetus to teratogens depends on:
1) Timing: Critical Periods when cellular differentiation and morphogenesis is at its peak
2) Magnitude—how much exposed to it
3) Duration of exposure
4) Ability to cross the placenta barrier
Examples of teratogens:
***Drugs/chemicals
1) Alcohol: Fetal Alcohol Syndrome
2) Cocaine: prematurity congenital abnormalities
3) Prescribed drugs to threat the mother
Ie anticonvulsant: Valprocic acids = NTDs
***Infections: maternal infections that can be passed to the fetus STORCH • S: syphilis • T: toxoplasmosis • O: other ie HIV • R: rubella • C: cytomegalovirus • H: herpes
STORCH
- S: syphilis
- T: toxoplasmosis
- O: other ie HIV
- R: rubella
- C: cytomegalovirus
- H: herpes
***Infections: maternal infections that can be passed to the fetus
STORCH
S
syphilis
***Infections: maternal infections that can be passed to the fetus
STORCH
T
taxoplasmosis
***Infections: maternal infections that can be passed to the fetus
STORCH
O
other
ie hiv
***Infections: maternal infections that can be passed to the fetus
STORCH
R
rubella
***Infections: maternal infections that can be passed to the fetus
STORCH
C
cytomegalovirus
***Infections: maternal infections that can be passed to the fetus
STORCH
H
herpes
***Infections: maternal infections that can be passed to the fetus
Fetal Alcohol Syndrome:
10-20% of all cases of mental retardation
most common cause of non-genetic MR (mental retardation, the number one is Down’s syndrome)
GDD
Small size in weight in height before and after birth
Poor coordination
ADD/ADHD
Poor memory
Poor reasoning and judgment skills-FRONTAL LOBE DISORDER
Sleep and sucking problems as a baby-failure to thrive
Vision or hearing problems
Problems with the heart, kidney, or bones
Hypotonia
Learning disabilities
Speech and language delays
