complications of development Flashcards

1
Q

what are the causes of mal-development and what proportion does each account for *

A

genetic - 30%

environmental - 15%

multifactorial - 55% - not single/small numebr of factors

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2
Q

prognosis for trisomy 18

A

weeks/months

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3
Q

what are different ways there can be changes in the number of conceptuses/fetuses that develop *

A

twins

triplets

chimera

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4
Q

describe identical twins *

A

one conceptus forms 2 inner cell masses to form 2 genetically identical individuals

ther fertilised egg splits during development

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5
Q

describve chimerism *

A

2 genetically distinct conceptuses combine to form 1 individual

happens early so there is no immunological reaction to the foreign DNA

have 2 different genetic patterns in 1 person

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6
Q

describe conjoined twins *

A

there is incomplete innermass separation - identical twins but the separation is partial

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7
Q

what is the effect of chromosomal abnormalities *

A

the distribution of cells and chromosomes can change development

changes to chromosomes can effect gene expression - can effect development

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8
Q

describe mosaicism *

A

this is non-disjunction - the chromosomes dont split as well as they should into individual cells early in development in mitotic divisions - some cells have different chromosomes to other cells

as number of affected cells increases the impact of the condition increases

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9
Q

what is the effect of abnormalities in the distribution between inner cells and trophectoderm (placenta) *

A

some cells in early blastocyst form bilayer of inner cells that forms the embryo, others form the outer layer of cells that forms the placenta

how the cells distribute depends on quality of cells - normal cells become the inner bilayer, abnormal cells form the placenta because it is easier to make the placenta than the baby

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10
Q

describe the control of eye colour

A

on human chromosome 15

brown is the most common colour world wide, other colours are more common in caucasians

differentiation of eyes occurs about day 22 post fertilisation

therefore event causing abnormal eye colour must occur before day 22

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11
Q

what can the problems with chromosomes be *

A

too many, too few, translocations

they all cause syndromes - interactions between genes is complex, there is cross-talk between systems - therefore there can be compensation between inputs in different systems altering the outcomes of the abnormalities

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12
Q

XY linked conditions where there are too many chromosomes *

A

klinefelter’s - XXY = decreased fertility

XXYY, XXXY, XXXYY = severe forms related to klinefelter’s

normally have X inactivation in females - klinefelters is in males - there is not complete inactivation = x chromosomes exert effects

XYY (XYYY) - very variable - super male - taller and have learning problems

XXX - limited effects, some mental changes

XXXX, XXXXX - more severe because more chromosomes are active and having an effect

X inactivation is targeted at 1 chromosome, rather than ensuring only have 1 x chromosome - otherwise these conditions wouldnt have severe effects

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13
Q

autosomal problems with too many chromosomes *

A

down’s - chromosome 21 - heart problems determine the survival, have widespaced eyes, flat face and are happy - can alter brain function but doesnt necessarily

edward’s - ch18 - most die before born, very few live-born, if they do, they live less than 2weeks

patau’s - ch13 - most die before birth, 80% of live-birth die in 1 year

other chromosome abnormalities of too many are not found in live birth - most are found in spontaneous preg loss tissues (miscarriage/stillborn) - except Ch1 - biggest ch, carries the most genes - therefore development stops immediately on fertilisation because it is so severe

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14
Q

what cases of too many chromosomes result in less severe effects than full trisomies *

A

mosaic/partial extra chromosome material

eg might get modest lip deformation rather than full cleft palate which would be seen in trisomy 13

depends on what the DNA is and where it is

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15
Q

describe chromosomal abnormalities where there are too few chromosomes *

A

XY linked are the only viable ones

  • Turner’s - XO = female, short, infertile
  • YO - not viable

autosomal

  • no complete losses are viable
  • partial loss syndromes are known - variable impact
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16
Q

describe chromosomal abnormalities with altered distributions *

A

translocation

XY linked - get XX male (there is some Y translocated onto x - enough to cause the male phenotype even though XX)

autosomal - linked with the development of tumours (lymphoma, leukaemia, sarcoma) - factors that are to do with growth on a different ch might not be switched off = uncontrolled growth

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17
Q

what is the overall effect of mutations *

A

they take away or add functions

receptors that mediate effects can be mutated

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18
Q

what is the effect of altered expression *

A

have more/less of a key regulator - impacts how the cell behaves

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19
Q

effect of loss of function of the KIT receptor *

A

effects skin colouration in midline - have pale heart shape on abdo, and white line on head

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20
Q

describe Halt-Oram syndrome *

A

atrial septal defects - the division between chambers doesnt happen therefore heart pumping is inefficient so it becomes enlarged

range of hand abnormalities - varies even between hands

phenotype due to mutation in TBX5 (TF) - this is required for both heart and hands to develop

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21
Q

describe achondroplasia *

A

there is a dramatic shortening of long bones (particularly in the arms/legs) - the rest of the body is in proportion

there is a gain in function of FGFR3 - it is permenantly on - disrupting development

achondroplasia technically means ‘lack of cartilage’ - in reality there is a defect in conversion of cartilage to bone = lack of bone growth

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22
Q

why have we got to be careful using models as insight for mal-development &

A

they have different numbers of genes - not related to size

microbiome is heavily involved in how our body works

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23
Q

different terms for birth defect *

A

congenital malformation - does not mean there is a genetic involvement

congenital abnormality

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24
Q

what is a birth defect *

A

change in the pattern of development

teratology/dysmorphology - something has affected how development has taken place

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25
number of pregancies affected by birth defects
3% affected by major abnormalities (cause 25% of infant deaths) 15% pregnancies affected by minor abnormalities - little health impact
26
what is a teratogen \*
any agent that can disturb the development of an embryo or fetus
27
infectious teratogens and the defects they can cause \*
Rubella virus - Cataracts, glaucoma, heart defects, deafness, teeth Herpes simplex virus - Microphthalmia, microcephaly, retinal dysplasia HIV - Microcephaly, growth restriction Syphilis - Mental retardation, deafness Zika virus – microcephaly
28
physical teratogens and the defects they can cause \*
X-rays & other ionising radiation - Microcephaly, spina bifida, cleft palate, limb defects
29
chemical teratogens and the defects that they can cause \*
Thalidomide - Limb defects, heart malformations Lithium - Heart malformations Amphetamines - Cleft lip and palate, heart defects Cocaine - Growth restriction, microcephaly, behavioral abnormalities Alcohol - Fetal alcohol syndrome, maxillary hypoplasia, heart defects - too much causes damage but 1 drink is unlikely to have significant effects - what is the line chemicals cause variable damage
30
when do teratogens affect development \*
when things are dividing most rapidly teeth, palate and genitalia are vulnerable later ears are vulnerable the whole time there are variable effects
31
symptoms that can be affected in maldevelopment \*
limbs and digits urogenital heart CNS face lungs
32
describe polydactyly \*
can be minor - if the digits themselves are normal the hand will be able to work in the normal way forelimb bud development happens at day 27/8, hindlimb at day29 they grow out from lateral plate mesoderm rapidly under the control of special signalling regions they are fully formed and patterned by day56 can pin down when the mistake happened, but not necessarily what caused it
33
what is wrong with this hand \*
initially you think that the problem is that there is an extra digit in the middle - because the middle digits are not separated at the bottom look closer and 'little finger' is actually like a thumb - so it is actually that the hand has been mirrored down the middle - there are 4 digits and 2 thumbs
34
describe the zone of polarising activity \*
group of cells - controls the pattern of digit development but we dont know what it is if transfer into opposite position of developing chick wing - you get the mirror image development of digits the controlling factor of limb and digit development is called 'sonic hedgehog'
35
describe cleft lip and palate \*
rest of face is normal happens because in development there is the frontonasal prominence - this is lost in a controlled way - the nose and eyes are on the sides of the head until 5th week PF, during this time the precursers of the nose, cheeks, lips, mouth and chin are formed they move centrally across the face for 5wks , then the eyes move to the front through the face during this development grooves are formed that are then filled in - this leads to sequential loss of the frontonasal prominence - if the grooves dont fill in properly = cleft pair of grooves form in lip - filled in by 2 separate things - so can get just 1 side cleft for palate - there are 2 bits of tissue that meet and fuse in the middle - so cleft palate is centrally placed surgery good - healing process is rapid for children - baby heal well = enhanced QOL
36
describe spina bifida \*
twin spine protusion of tissue classically near the lower back, can happen in \>1 place the nerve directs the development of the bone 0 if nerve development is wrong it means that the bone development is also wrong get buldge of tissue - maybe CSF (meningocele)/neural tissue (myelomeningocele), or just be a patch of hair over the damaged area (spina bifida occulata) 1-2/1000 pregnancies surgery can help the anatomical (if tissue vulnerable to locking or damage, ie can cover the neural tissue with skin) but not the functional problems - there is neurological damage below the point of the spina bifida - usually effects the legs
37
describe why spina bifida occurs \*
the spinal column forms as a tubular structure - then the neural tube is sealed if sealing goes wrong you get a gap - this us a neuropore = spina bifida - if doesnt close at this point 21-28days it never will this is failure to complete neurulation
38
how can we prevent spina bifida \*
folic acid in diet decreases the incidence by 70% the source of nutrition for the early embryo is the egg - takes 3 months for the egg to develop before it is released from the follicle, so need to be taking folic acid at least 3 months before you get pregnant
39
describe anacephaly \*
defect in skull and brain development 1-8/10000 births females affected more commonly brain stem is intact, missing the major part of the brain anterior neuropore closure incomplete folic acid given at right time might show benefit
40
describe the effect of thalidamide \*
10000 affected infants known, 50% initial survival rate taken in the 1st trimester for morning sickness limbs affected, deformed eyes, hearts, urinary and ailmentary tracts, blindness and deafness impact is variable between people damage done around day 28
41
is thalidamide used now \*
yes - in some leprosy and cancer treatments it is good because it is stable and doesnt have to be stored at cold temperatures
42
how does thalidamide effect limbs \*
effects rapidly growing bv - effects can be generic - hence the range of things that are seen - all embryonic tissue relys on normal vascular tissue for the provision of nutrients effects bv development in limb buds = cell death - therefore limbs cant bud in development timing of thalidamide usage matches with limb development (now used for cancer to cut off the blood supply - dont want to give it to women of reproductive age)
43
describe respiratory distress syndrome \*
also called respiratory distress syndrome of the newborn, surfactant deficiency disorder (SDD); previously called hyaline membrane disease (HMD). 1% of all births lungs wont expand because there is a high surface tension, because there is no surfactant give injection of steroids in uteri 2-3 days before birth if possible it is a functional, not a structural problem lung surfactant increases in last trimester - so 100% babies born at 24wks gave RDS, 50% at 26-28wks, and 25% at 30-31wks surfactant levels continue to increase after birth
44
describe the main events that contribute to human embryology \*
start with implantation that leads immediately to preimplantation development of the conceptus preimplantation development occurs in the fallopian tube over approx 6days - characterised by a series of cleavage divisions which double the number of cells in the conceptus to produce a ball of undifferentiated cells - the morula the morula differentiates so inner cells differ from the outer - this develops into the blastocyst - which has an outer layer of trophectoderm, an inner cell mass and a fluid filled cavity the blastocyst then hatches from the ZP at day 6 and implants in uterine lining - complete 10days PF inner cell mass has become a bilayer disk composed of hyoblast and epiblast cells - gives rise to all cells of fetus
45
describe the conversion of the blastocyst to an embryo \*
grastulation - bilayer is converted into a trilayer embryo containing ectoderm, mesoderm and endoderm days 14-18PF * there is proliferation of the epiblast cells, then they differentiate to form mesoderm cells, they move into the space between the epiblast and the hyoblast * the mesoderm cells are throught to differnetiate further to generate the endoderm, which replaces the hyoblast cells which are lost by apoptosis before gastrulation is complete - neurulation has begun - differentiation of the epiblast (ectoderm) to generate the CNS under control of the notocord in the mesoderm of the developing embryo at the same time; precursers of other tissues are developing and embryo is converted from flat structure to 3D at the same time (14-21days) at least 2 groups of cells are present outside the embryuo proper - the primordal germ cells in the yolk sac endoderm at the caudal end of the embryo, and the cardiac and vascular progenitors in the primary heart field at the cranial end of the embryo folding of the embryo occurs laterally which fuses the ventral midline (chest and abdomen) of the embryo, and the anterio-posterior direction, which folds the primordal germ cells into the hind gut, and the developing heart progenitors under the head of the embryo these changes continue during the development of the urogenital system, which continue from weeks 3-4 of development by the end of week 4 of development teh precursers of all internal tissues have been laid down, and many external features are also developing development during weeks 5-8 involves elaboration of the tissues generated during the early weeks urogenital, cardiac, facial and lung development all procede rapidly during the second month of development limb development occurs over the same time frame, as the initial limb buds grow, and the terminal regions are converted to hand or foot plates that in tern develop digits
46
why is the formation of the 3 germ layers important \*
they are the precursers to all the tissues in the body ectoderm gives rise to skin and the CNS mesoderm to the muscles, blood, skeleton, heart and kidney endoderm to gut, lungs and liver muscular and vascular tissue are generally of mesodermal origin so tissues are usually a mix of germ layer types
47
describe the development of the neuroplate \*
happens in neurulation develops as 2 folds which increase in size until they meet over the neural groove and fuse to form the neural tube the fusion process continues over week 4 of development as the CNS becomes a sealed tube the structure of the neural folds is much more complex at the cranial side of the embryo -- brain development has started by this stage
48
illustrate the lateral folding of the embryo and time frames \*
19, 20,21,24,28 days respectively
49
illustrate the development of weeks 5-8 PF and time \*
50
illustrate the development of the limbs and time \*
51
when does embryonic development end and why
8 weeks - it is clearly human so is now fetal development at this point it is 1cm wide
52
size at end of trimester 1
7cm and 50g
53
what is oligodactyly
loss of digits
54
summarise the production of the limbs \*
happens over many weeks - formation is integrated with the rotation of these structures upper limb bud at 24 days, lower limb at 26 at 47days get fingers at 52 days fingers can touch at 56 limbs rotate to definitive orientation
55
describe the development of the kidney \*
pronephros is the most immature kidnye mesonephros, an intermediate phase metanephros is the most developed kidney and persists as the definitive adult kidnye
56
describe the descent of the kidneys \*
the ureters extend during the process - so that kidneys stay connected to the bladder however, the kidneys form new connections with the developing arterial system as they move - renal arteries break down and reform
57
mal developments in the urogenital tract \*
abnormalities in the development of the kidneys are common - the human body can function normally with 1 kidney - so the impact may be limited intersex - neitheer 100% male or female nad may not match the chromosomes present in the cells of the individuals
58
maldevelopments in development of the kidney \*
one kidney may be retained in the pelvis retention of an extra artery may restrict the ureter, and cause enlargement of the renal pelvis the kidneys may fuse to form a horseshoe kidney - the extra tissue makes it impossible to move so it will remain in the pelvis
59
describe gonadal development \*
they arise from intermediate mesoderm within the urogenital ridges of the embryo the genital ducts arise from paired mesonephric and paramesonephric ducts gonads show no differentiation in development until week 7 PF differential development of the male reporductive system is dependant on the activity of SRY protein, coded by SRY gene on Y chromosome mesonephric ducts give rise to male genetial ducts, paramesonephric to female within the mesonephrus the mesonephric and paramesonephric ducts develop - identifyable ta 5 weeks PF at the same time the gonad precurser is developing from the mesonephric mesoderm and is covered by coelomic epithelial cells
60
describe the development of teh gametes \*
happens at the same time as the developing reproductive tissues the primordal germ cells give rise to gonads they originate in the epiblast, then migrate to the caudal part of the yolk sac when the main caudal structures of the embryo proper have developed, the PGCs migrate through the hindgut and dorsal mesentry to the mesonephros and to the gonads by week 7 the embryo has an indifferent reproductive system the SRY causes the development pattern in the next 3 weeks satrting from week 7-8, the female development starts later 8-9wks PF the key regulator in male development is testosterone which is converted into dihydrotestosterone (supports development of the wolffian ducts whcih give rise to male circulation) - produced in testes leidig cells under stimulation opf hCG from the maternal circulation - male development starts when hCG is at its peak sertoli cells produce anti-mullerian hormone (AMH) that causes regression of the paramesonephric ducts
61
abnormalities in the development of the reproductive system \*
in male - inabiolity to create the correct hormones or the inability to respond to them eg androgen insensitivity syndrome/testicular feminisation syndrome occurs in genetic males with mutant androgen receptor - no./limited virilisation, internally the woolffian ducts are rudimentary or lacking , testes structure is variable and they dont descend. AMH production is normal so there is regression of the mullerian ducts in female - congenital adrenal hyperplasia - mutation in CYP 21A2 so cortisol production limited = no -ve feedback on ACTH = overstim of adrenals which make weak androgen - androstenedione = partial virilisation of the genitailia - the internal organs are female as no male testosterone/AMH
62
describe cardiac development \*
complex - convert tube to 4 chambers main events - folding of teh embryo and heart tube fusion, heart looping, septation the cardiogenic cells develop in a U outside the mebryo proper, they form a pair of heart tubes which fuse to formn single heart tube by 21days PF - can pump blood unidirectionally looping of the heart and septationngive rise to the 4 chambered structure of the normal hunan heart - the vascualr connections are made so that major veins are connected to the atria, and arteries to the ventricles, valves develop the foramen ovale is between the atria -little blood flow to lungs is needed - allow blood to pass for R (high O2) to L atria - then to L vent - then through aorta the pul artery is connected to aorta by the ductus arterosus - diverting blood that would normally go into lungs round rest of arterial system at birth foramen ovale and ductus arterosus should close
63
describe cardiac abnormalities \*
tetralogy of Fallot - pulmonary stenosis (thickened, narrow pul outflow tract - allow less blood to lungs), thickened right ventricle wall, ventricular septal defect (allow deox blood to R vent), aorta overrides septal defect transposition of the great arteries - ie ox blood flows from L vent into pul artery to lungs, deox from R into aorta - baby is cyanotic on birth - treatment is prostaglandins to keep the ductus arteriosus open and open a link between the atria; definitive treatment would involve switching the 2 arteries to restore normal blood flow
64
describe lung development \*
development begins in the 1st trimester but is not completed until after delivery production of surfactant begins in the 3rd trimester and gradually increases artificial surfactant can be given to preterm infants
65
summarise the events during the first 2 months of pregnancy \*
week 1 - fertilisation to implantation week 2 - bilaminar disk forms, trophoblast with lacunae, extraembryonic mesoderm develops, uteroplacental circulation begins week 3 - laterality established, formation of germ layers, trilaminar embryonic disk, CNS induction, neural folds elevate week 4 - neural tube closure, villus formation continues in the placenta, pharyngeal arches present, neurulation is complete 5 - arm and legs bud, developing face, gut, optic cup and lens placode develop, brachial arches and clefts develop 6 - physiological umbicilical hernia, developing face, muscel development, endodermal derivitives, auricular hillocks, atrial septum formed, digit formation week 7 - limb cartiliges and digital rays, developing face, conotruncal and ventricular septa, external genitalia, facial prominences fused, digits present and eyelids form