abnormalities of human development Flashcards
What causes mal-development
30% genetic
Environmental – 15%
Multifactorial – 55%
How are identical twins formed
Identical twins / triplets: one conceptus forms 2 / 3 inner cells masses to form 2 / 3 genetically identical individuals
How is a chimera formed
Chimerism: 2 genetically distinct conceptuses combine to form one individual
What is mosaicisim
Mosaicism (non disjunction) – differences between cells within one individual
Give an example of mosaicism
Type of Down’s syndrome or heterochromia
Which chomoasome is eye colour on?
15
When does differentiation of eye colour occur
day 22 pf
What does mutation in the KITr gene cause
Piebaldism
What is the manifestation of Holt-Oram syndrome
Heart defects and triphalengeal thumb
What causes achondroaplasia
Chr 3 gain in FGFR3 function
After how many weeks is the conceptus a foetus
8
when does pre-implantation take place
over 6 days
what is a morula
ball of undifferentiated cells
whats a blastocyst
structure that has an outer layer of trophectoderm, an inner cell mass, and a fluid-filled cavity.
when does implantation occur
10 days post fertilisation
what does the inner cell mass become
bilayer disk, composed of hypoblast and epiblast cells
what is gastrulation
converts the bilayer of hypoblast and epiblast cells into a trilaminar embryo, containing the three layers of Germ Cells (Ectoderm, Mesoderm and Endoderm), occurring during days 14-18 postfertilisation.
what does the ectoderm give rise to
skin and the central nervous system
What does the mesoderm give rise to
muscles, blood, skeleton, heart and kidney
What does the endoderm give rise to
gut, lungs and liver
when have precursors for all internal tissues been laid down
week 4
what develops in weeks 5-8
mostly the elaboration of the tissues generated during the early weeks
How does thalidomide cause birth defects
affects growth of blood vessels, depriving cells of nutrients, and ability to grow. 8 weeks = arm deformation
name the stages of kidney development
Pronephros is the most immature form of kidney
Mesonephros, an intermediate phase
Metanephros is most developed and persists as the definitive adult kidney.
When do gonads show sign of differentiation
7 weeks
What gives rise to male genital ducts
mesonephric ducts
What gives rise to female genital ducts
paramesonephric ducts
Describe relationship of developing kidney with ureters and arteries
ureters change length, and grow with kidney, arteries break down and re-form during this process.
Name some kidney mal-developments
Pelvic kidney, horseshoe kidney, enlarged renal pelvis
when are meso and paramesonephric pathways developed
week 5
where does gonadal precursor develop
mesonephric mesoderm
What is the role of the primordial germ cell in gondal development
give rise to the gametes within the gonads
What is the pathway of the primordial germ cell
hey originate in the epiblast, but then migrate to the caudal part of the yolk sac (Figure 5.4.5A). Once the main caudal structures of the embryo proper have developed, the PGC migrate through the hind-gut and dorsal mesentery to the mesonephros and thence to the developing gonads.
What is a key regulator of male devlopment
testosterone from lyedig cells under regulation of maternal Hcg
What causes regression of paramesonephric ducts in males
sertoli cells produce anti-Mullerian hormone,
What is a common cause of male mal-development
inability to produce the appropriate hormones (testosterone and anti-Mullerian hormone (AMH) or (b) the inability of target tissues to respond to these hormones, normally the result of defects in the cognate receptors
What is Androgen Insensitvity syndrome
mutant androgen receptor. There is no or limited virilisation of external genitalia (which show relatively normal female structures). No mesonephric ducts, non descended testis, but no Mullerian duct because sertoli and AMH is normal.
What is CAH
21-hydroxylase enzyme (CYP 21A2), so cortisol production from the fetal adrenal is very limited as this enzyme is key in cortisol synthesis.
High ACTH leads to androgen production, virilisation of female
Describe heart development
cardiogenic cells develop in a U (or horseshoe) pattern outside the embryo proper. These form a pair of heart tubes, which fuse to form a single heart tube by ~21 days post-fertilisation. This tube is already able to pump blood unidirectionally.
Looping of the heart and septation give rise to the 4-chambered structure of the normal human heart. During this process the vascular connections are maintained, so that the major veins are connected to the atria, and major arteries to the ventricles. Valves develop, to ensure that blood flows unidirectionally within the heart.
Describe foetal heart differences
formamen ovale and ductus arteriousus
Describe implications of the RV Aorta, LV PA issue
The aorta is connected to the right ventricle, and the pulmonary artery to the left ventricle. This generates two separate blood flows; oxygenated blood is cycled through the left side of the heart via the lungs; de-oxygenated blood through the right side of the heart to the rest of the body. Before birth, this does not matter, as the foreman ovale and ductus arteriosus allow mixing of the blood flows sufficiently to sustain fetal growth and development. The closure of these connections after delivery separates the blood flows, so the infant becomes cyanotic (‘blue baby syndrome’). Immediate treatment may involve administering prostaglandins to keep the ductus arteriosus open, and perhaps opening of a link between the atria. Definitive treatment would usually involve the switching of the two arteries, to restore the normal blood flows.
How is spina bifida prevented
3 months pre-conception folate
Describe the process of lung developmetn
embryonic 3-8 weeks pseudoglandular 5-18 week cannalicular 16-20 weeks saccular 24-36 weeks alveolar 36->
When is surfactant produced
3rd trimester
what is an issue with pre-term babies
(Respiratory Distress Syndrome, RDS)
