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Medicine YEAR 1 > Phase 2 KPH - Week 1 (Foetal development, screening, Down syndrome) > Flashcards

Phase 2 KPH - Week 1 (Foetal development, screening, Down syndrome) Flashcards

1
Q

Describe the events of the first 4 weeks of gestation and when they occur

A 
Day 0 = Zygote formed (fertilisation)
Day 1 = Cleavage begins
Week 1 = Morula formation, blastocyst formation, blastocyst hatching
implantation (day 6)
Week 2 = Bilaminar disc formation
Week 3 = Gastrulation
Week 3-8 = Organogenesis
Week 4 = Heart begins to beat, limb buds form
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2
Q

Describe cleavage

A
  • Mitotic divisions of fertilised oocyte
  • Overall size remains the same - allows passage down isthmus (narrowest part of uterine tube)
  • Surrounded by tough glycoprotein coat - zona pellucida - to prevent immature implantation
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3
Q

Describe morula formation

A

Around day 4, cells maximise contact with each other, forming cluster of cells held together by tight junctions = morula

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4
Q

Describe blastocyst formation

A
  • First cellular differentiation
  • Inner cell mass = forms embryo and extraembryonic tissues
  • Trophoblast = formed from outer cells, contributes to the placenta
  • As embryo enters uterine cavity, fluid enters via the zona pellucida into spaces of the inner cell mass - fluid filled blastocyst cavity (blastocoel) forms
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5
Q

Describe blastocyst hatching

A
  • Blastocyst starts to run out of nutrients - needs to implant
  • Inner cell mass (ICM) cells proliferate, fluid builds up in cavity
  • Blastocyst hatches from zona pellucida to facilitate implantation
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6
Q

When does the blastocyst implant?

A
  • Day 6
  • Must occur to trigger secretion of human chorionic gonadotrophin (HCG) to maintain the corpus luteum
  • Without HCG and the corpus luteum the pregnancy will not continue
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7
Q

Describe implantation of the blastocyst

A
  • Interaction between embryo and endometrium
  • Trophoblast differentiates into inner villus cytotrophoblast and non-dividing outer syncytiotrophoblast
  • Blastocyst attaches to epithelial surface of uterus
  • Trophoblast extensions penetrate between uterine epithelial cells invading the uterine stroma
  • Embryo becomes completely embedded, uterine epithelial cells grow over implantation site
  • Decidual reaction
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8
Q

Describe abnormal implantation of the blastocyst

A
  • Common sites - external surface of uterus, ovary, bowel, Gi tract, mesentery, peritoneal wall
  • Causes ectopic pregnancy
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9
Q

Describe the structure of the embryo following formation of the bilaminar disc

A
  • Amnion, yolk sac + chorion form

- Bilaminar disc forms in centre - top is epiblast, bottom is hypoblast

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10
Q

Amnion

A
  • Continuous with the epiblast
  • Persists until birth
  • Fills with amniotic fluid
  • Protection for the developing embyo
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11
Q

Yolk sac

A
  • Continuous with the hypoblast
  • Important in nutrient transfer in weeks 2-3
  • Disappears around week 20
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12
Q

Chorion

A
  • Trophoblast and extra-embryonic mesoderm
  • Forms the foetal component of the placenta - chorionic plate
  • Chorionic cavity seen in early pregnancy, disappears when amnion expands
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13
Q

Define gastrulation

A

Process of cell division and migration resulting in formation of the 3 germ layers. Bilaminar disc -> trilaminar disc

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14
Q

List the germ layer

A
  • Ectoderm
  • Mesoderm
  • Endoderm
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15
Q

Define the primitive streak

A

Region of migration from the epiblast layer forming the mesoderm and endoderm

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16
Q

Describe the process of gastrulation

A
  • Cells from the epiblast move through the primitive streak
  • Undergo an epithelial to mesenchymal transition in order to delaminate and migrate
  • Once cells have invaginated, some displace hypoblast creating endoderm
  • Others between epiblast and endoderm form mesoderm
  • Remaining cells in epiblast form ectoderm
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17
Q

List the tissues derived from the ectoderm

A
  • Epidermis of skin and its derivatives (sweat glands, hair follicles etc.)
  • Epithelial lining of mouth and anus
  • Cornea and lens of eye
  • Nervous system
  • Sensory receptors in epidermis
  • Adrenal medulla
  • Tooth enamel
  • Epithelium of pineal and pituitary glands
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18
Q

List the tissues derived from the mesoderm

A
  • Notochord
  • Skeletal system
  • Muscular system
  • Muscular layer of stomach and intestine
  • Excretory system
  • Circulatory and lymphatic systems
  • Reproductive system (except germ cells)
  • Dermis of skin
  • Lining of body cavity
  • Adrenal cortex
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19
Q

List the tissues derived from the endoderm

A
  • Epithelial lining of digestive tract
  • Epithelial lining of respiratory system
  • Lining of urethra, urinary bladder and reproductive system
  • Liver
  • Pancreas
  • Thymus
  • Thyroid and parathyroid glands
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20
Q

Describe the changes in body form which occur during week 4 of gestation

A
  • Embryo ‘rolls up’ from flat disc -> closed cylinder along its long axis
  • Growth of embryo makes embryo fold laterally
  • Head and tail end curl under fast growth of neural tube
  • Embryo now resembles human form
  • Limb buds develop
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21
Q

Describe the formation of limb buds

A
  • Limb buds made of undifferentiated mesoderm cells, covered by ectoderm
  • Upper limb buds appear first as ridges from ventrolateral body wall
  • Lower limb as small bulges
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22
Q

What is the normal chromosome number?

A

46 chromosomes, 23 homologous pairs

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23
Q

Describe the sex chromosomes

A
  • XX in a normal female
  • XY in a normal male
  • Y is smaller than X, X has genes that Y does not have
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24
Q

How can the difference between the X and Y chromosomes be significant clinically?

A
  • Sex-linked disorders
  • X-linked recessive disorders will affect males more as they don’t have another allele to mask the effect of the harmful allele
  • X-linked dominant disorders where the father is affected will affect females more, as they must get an X from their father, whereas males get the unaffected Y from their father
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25
Q

Give examples of sex-linked disorders

A

Haemophilia, duchenne muscular dystrophy, colour blindness (all X-linked recessive)

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26
Q

List the mutations to chromosomes which can cause genetic disorders

A
  1. Deletions
  2. Duplications
  3. Translocations
  4. Inversions
  5. Insertions
  6. Rings
  7. Isochromosome
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27
Q

Deletion

A

Portion of the chromosome is missing or deleted

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28
Q

Duplication

A

Portion of the chromosome is duplicated, resulting in extra genetic material

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29
Q

Translocation

A
  • Portion of one chromosome is transferred to another chromosome
  • Two types -
  • Reciprocal - segments from to different chromosomes have been exchanged
  • Robertsonian - entire chromosome has attached to another at the centromere
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30
Q

Inversion

A

Portion of the chromosome has broken off, turned upside down and reattached - genetic material is inverted

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31
Q

Insertions

A

Portion of one chromosome has been deleted from its normal position and inserted into another chromosome

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32
Q

Rings

A
  • Portion of a chromosome has broken off and formed a circle/ring
  • Can happen with/without loss of genetic material
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33
Q

Isochromsome

A

Formed by mirror image copy of a chromosome segment including the centromere

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34
Q

Give examples of genetic disorders cause by mutations to chromosomes

A
  1. Colour blindness
  2. Cri-du-chat
  3. Cystic fibrosis
  4. Down syndrome
  5. Duchenne muscular dystrophy
  6. Haemophilia
  7. Sickle cell disease
  8. Tay-sachs disease
  9. Turner syndrome
  10. X-linked severe combined immunodeficiency (X-SCID)
  11. Marfan syndrome
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35
Q

Describe the mutation which causes colour blindness

A

Point mutation on X chromosome (sex-linked)

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36
Q

Describe the mutation which causes cri-du-chat

A

Partial deletion on chromosome 5 - non-dysjunction

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37
Q

Describe the mutation which causes cystic fibrosis

A

Most common is partial deletion on chromosome 7

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38
Q

Describe the mutation which causes Down syndrome

A

Extra chromosome 21 - trisomy 21

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39
Q

Describe the mutation which causes duchenne muscular dystrophy

A

Partial deletion on X chromosome

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40
Q

Describe the mutation which causes haemophilia

A

Point mutation on X chromosome

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41
Q

Describe the mutation which causes sickle-cell disease

A

Point mutation on chromosome 11

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42
Q

Describe the mutation which causes Tay-Sachs disease

A

Point mutation on chromosome 15

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43
Q

Describe the mutation which causes Turner syndrome

A

Female missing an X chromosome

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44
Q

Describe the mutation which causes X-linked severe combined immunodeficiency

A

Point mutation on X chromosome

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45
Q

Describe the mutation which causes Marfan syndrome

A

Point mutation on chromosome 15

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46
Q

Describe the epidemiology of Down syndrome

A
  • 1/700 live births
  • Risk increases with maternal age
  • 20 y/o = 1/2000
  • 35 y/o = 1/365
  • 40 y/o = 1/100
  • 80% born to mothers <35
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47
Q

Describe the cause of Down syndrome

A
  • Trisomy 21 (95%)
  • 5% extra chromosome 21 translocated to another chromosome (most common is 14;21, next most common is 21;22) - Robertsonian translocation
  • Can also be 21q21q translocation - extra chromosome 21 is attached to another chromosome 21
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48
Q

List the body systems which are affected by Down syndrome

A
  1. Cardiac
  2. CNS
  3. GI
  4. Endocrine
  5. EENT
  6. Growth
  7. Haematologic
  8. Musculoskeletal
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49
Q

Describe how the cardiac system can be affected by Down syndrome

A
  • Increased risk of congenital heart disease - most often ventricular septal defects and AV canal
  • Increased risk of mitral valve prolapse and aortic regurgitation later in life
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50
Q

Describe how the CNS can be affected by Down syndrome

A
  • Cognitive impairment - mild (IQ 50-75) to severe (IQ 20-35)
  • Motor language delay
  • Autistic behaviour
  • Alzheimer disease
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51
Q

Describe how the GI system can be affected by Down syndrome

A
  • Duodenal atresia
    or stenosis
  • Hirschsprung disease
  • Celiac disease
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52
Q

Describe how the endocrine can be affected by Down syndrome

A
  • Hypothyroidism

- Diabetes

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53
Q

Describe how the EENT system can be affected by Down syndrome

A
  • Opthalmic disorders e.g. congenital cataracts, glaucoma, strabismus, refractive errors
  • Hearing loss
  • Increases incidence of otitis media
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54
Q

Describe how a person’s growth can be affected by Down syndrome

A
  • Short stature

- Obesity

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55
Q

Describe the haematologic problems which can be caused by Down syndrome

A
  • Thrombocytopenia
  • Neonatal polycythemia
  • Transient myelodysplastic disorder
  • Acute megakaryotic disorder
  • Acute lymphocytic leukaemia
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56
Q

Describe how the musculoskeletal can be affected by Down syndrome

A
  • Atlanto-axial and atlanto-occipital instability

- Joint laxity

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57
Q

What is the average life expectancy of a person with Down syndrome?

A
  • 55 y/o

- Less than average due to heart disease, susceptibility to infections and acute myelogenous leukaemia

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58
Q

Describe how reproduction can be affected by Down syndrome

A
  • Affected women have 50% chance of having a foetus with Down syndrome
  • Many affected foetuses abort spontaneously
  • Men with Down syndrome are infertile - except those with mosaicism
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59
Q

List the signs/symptoms associated with Down syndrome

A
  • Neonates - placid, rarely cry, hypotonia
  • Flat facial profile - flattening of the bridge of the nose
  • Unusual physical characteristics develop during infancy
  • Flattened occiput
  • Microcephaly
  • Extra skin around back of neck
  • Eyes slanted upwards
  • Epicanthal folds at inner corners of eyes
  • Brushfield spots (grey to white spots around iris)
  • Mouth often held slightly open
  • Protruding furrowed tongue, lacks central fissure
  • Ears often small and rounded
  • Hands are short and broad, often have simian crease
  • Fingers often short - incurving (clinodactyly) of 5th digit - often only has 2 phalanges
  • Feet may have wide gap between 1st and 2nd toes
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60
Q

When are ultrasound performed on pregnant women?

A

1st scan (dating scan) - 8-14 weeks

2nd scan (anomaly scan) - 18-21 weeks

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61
Q

How is diagnosis of Down syndrome often initially suspected?

A
  • Physical anomalies detected by foetal ultrasound

- E.g. increased nuchal translucency seen during dating scan

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62
Q

Describe how nuchal translucency contributes to the diagnosis of Down syndrome

A
  • Foetuses have collection of nuchal fluid at back of neck
  • Can be measured between weeks 11-14
  • Before week 11 foetus is too small
  • After week 14 nuchal fluid is absorbed by lymphatic system
  • Foetuses with Down syndrome show nuchal thickening - chromosome 21 has gene which codes for type VI collagen, gene is over-expressed, results in connective tissue with more elastic composition
  • NT of less than 3.5mm is normal when foetus measures between 45mm-84mm
  • As NT increases, chance of Down syndrome increases
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63
Q

List the chemical signs which contribute to the diagnosis of Down syndrome

A 
Abnormal levels of:
- Plasma protein A in late 1st trimester
- Alpha-fetoprotein 
- Beta human chorionic gonadotrophin
- Unconjugated estriol 
- Inhibin in early 2nd trimester 
On maternal serum screening
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64
Q

When are diagnostic tests for Down syndrome used?

A

If ultrasound or maternal screening suggests abnormality or case is high risk (maternal age >35) chorionic villus sampling and/or amniocentesis are offered

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65
Q

Chorionic villus sampling

A
  • Samples chorionic villus of placenta
  • Should contain same chromosome complement as foetus
  • 10-14 weeks of gestation
  • Miscarriage ate = 1-2%
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66
Q

Amniocentesis

A
  • Samples amniotic fluid, contains foetal cells
  • Cells grown in culture, foetal chromosomes analysed
  • 14-16 weeks of gestation
  • Lower miscarriage risk - 1%
  • Results in 1 week
67
Q

Describe how non-invasive prenatal testing can be used to diagnose Down syndrome

A
  • Analyses DNA fragments present in maternal plasma during pregnancy (cell-free maternal DNA), around 10-20% comes from foetus (cell-free foetal DNA)
  • Total amount of chromosome 21 in mother’s blood can be compared with amount of the other chromosomes
  • If the baby has Down syndrome there will be slightly more chromosome 21 present than normal
  • Very accurate prediction of pregnancies where the foetus is likely to have Down syndrome
  • Cell-free foetal DNA comes from the placenta, first detectable from 4-5 weeks gestation
  • Reaches the required level needed to test for Down syndrome by 10 weeks
  • CffDNA cleared from maternal circulation within the first hour after birth - specific to woman’s current pregnancy
68
Q

Explain what is meant by a positive NIPT test

A
  • Predicted to be affected by Down syndrome

- An invasive test should be offered to confirm the result

69
Q

Explain what is meant by a negative NIPT test

A

Highly unlikely to be affected by Down syndrome

70
Q

Explain what is meant by an inconclusive NIPT test

A
  • 4% of cases
  • Usually because proportion of foetal DNA present in sample is not high enough to give accurate result, can be repeated - should be higher cffDNA levels with longer gestation
71
Q

Define health

A

A state of complete physical, mental and social well-being and not merely the absence of disease or infirmity

72
Q

List the domains of quality of life as defined by WHO

A
  • Physical (including body pain)
  • Environment
  • Social relationships
  • Psychological
  • Level of dependence
  • Spiritual
73
Q

Define a life course approach

A

Emphasises temporal and social perspective, looking back across an individual’s or a cohort’s life experiences or across generations for clues to current patterns of health and disease, whilst recognising that both past and present experiences are shaped by the wider social, economic and cultural context

74
Q

List the life course models

A
  1. Critical period e.g. foetal development to early years - limited time window in which an exposure can have adverse or protective effects on development and subsequent health outcome
  2. Accumulation of risk - life course exposures or insults gradually accumulate through episodes of illness and injury, adverse environmental conditions, and health damaging behaviours
  3. Chain of risk model - a sequence of linked exposures that raise disease risk because one bad experience or exposure tends to lead to another and then another
75
Q

Describe the function of the placenta

A
  • The physical attachment of the embryo to the uterus

- Bringing of the foetal/maternal circulations into proximity allowing exchange of gases, nutrients and waste

76
Q

Describe the gross structure of the placenta

A
  • Circular disc-like organ - Size/weight vary (smoking etc.)
  • Chorionic plate - foetal side of placenta
  • Chorionic plate covered with avascular glossy amnion
  • Umbilical cord implants slightly off-centre on chorionic side - 2 arteries, 1 vein
  • Vessels on the surface = chorionic vessels
  • Basal plate = maternal side
  • Top layer adheres to placenta after separation from maternal uterus
  • Made of endometrial + trophoblast cells and fibroid
  • Separated into lobes (cotyledones) - roughly mark underlying villous trees
77
Q

Describe the process which results in the formation of twins

A
  • Cleave days 1-3 = dichorionic/diamniotic
  • Cleave days 4-8 = monochorionic/diamniotic
  • Cleave days 8-13 = monochorionic/monoamniotic
  • Cleave days 13-15 = conjoined
78
Q

Describe the early development of the placenta

A
  • TB layers differentiates into two layers - proliferating inner villlous cytotrophoblast and the non-dividing outer layer called the syncytiotrophoblast - By day 8, fluid filled spaces called lacunae begin to develop within the STB mass
  • Cords of CTB surrounding them penetrate into the lacunae, side branches of the projections appear by day 13
  • Some trophoblasts migrate into the endometrial stroma between the uterine glands and around the the uterine spiral arteries
  • Initially maternal blood escaping from spiral arteries passes into lacunae before the mouths of the spiral arteries become blocked with trophoblast plugs
  • Trophoblast plugs prevent maternal blood from entering the lacunae or intervillous space for the first 10 weeks of pregnancy
79
Q

Describe the development of the villous tree

A
  • Trophoblasts that had begun to penetrate the lacunae become increasingly branched
  • The lacunae are the precursors of the intervillous space, the site of exchange between maternal and foetal circulation
  • The branches of trophoblasts become the chorionic villi
  • The villous core is known as the stroma and is mostly composed of fibroblast cells
  • Capillaries develop within the villi
80
Q

Describe trophoblast invasion during placental development

A
  • Trophoblasts begin to invade into the maternal endometrium, myometrium then spiral arteries
  • Remodels the arteries from being low flow - high resistance to high flow - low resistance channels
  • Allows increase of blood flow to the foetus
81
Q

Describe the exchange which occurs in the placenta

A
  • Foetal blood (low in oxygen and nutrients) flows through umbilical arteries to capillaries of the villi and returns through umbilical vein to the foetus
  • Maternal blood (rich in oxygen and nutrients) flows from the uterine arteries into large blood sinuses surrounding the villi then back into uterine veins
  • Oxygen and substrates (e.g. glucose, fatty acids, ionic substances, antibodies) diffuse/are transported into foetal blood
  • Waste products from the foetus pass through the placenta into the maternal circulation for disposal
82
Q

Give examples of conditions caused by placental insufficiency

A
  • Pre-eclampsia

- Intrauterine growth restriction (IUGR)

83
Q

Describe the diagnosis of pre-eclampsia

A

Disorder of late pregnancy, diagnosed by blood pressure >140/90mmHg and proteionuria after 20 weeks gestation in women who were previously normotensive

84
Q

Describe the consequences of untreated pre-eclampsia

A

May progress to eclampsia, a life-threatening condition characterised by convulsions

85
Q

Describe how abnormal development of the placenta leads to pre-eclampsia

A
  • Invasion of trophoblasts into the maternal tissue is abnormal in pre-eclampsia
  • Spiral arteries do not undergo full physiological change and hence blood flow to the placenta is reduced
86
Q

Barker hypothesis

A
  • Various factors contributing to demand/supply of nutrients (maternal diet, placental blood flow, transfer foetal genome etc)
  • If nutrient demand exceeds supply this can lead to lower birth weight
  • May also result in altered metabolism in foetus
  • Linked with later adult obesity as well as CVD and other common chronic conditions
87
Q

Why must care be taken when prescribing drugs to pregnant women?

A
  • Most drugs can cross the placenta
  • Can have negative effect on foetus
  • E.g. anti-epileptic drugs
88
Q

Explain the meaning of induction in development

A
  • One cell population/tissue - inductor acts on another tissue - the responder
  • This stimulates a specific developmental pathway in the responding tissues
  • Involves signalling
  • Signals can be protein/peptide growth factors - ligands binding to receptors, often in the cell membrane
  • Signal affects the receptor - signal transduction, intracellular response is triggered
  • Usually involves activation of cytoplasmic protein kinases - phosphorylate target proteins, activate or inactivate them
  • DNA transcription is affected - cellular response
89
Q

What is the notochord derived from?

A

Mesoderm

90
Q

Describe the function of the notochord

A
  • Role in molecular signalling
  • Controls direction of embryonic folding
  • Inductive relationship with overlying ectoderm - notochord (inducer), ectoderm (responder)
  • Signals from notochord induce development in neural plate in overlying ectoderm
91
Q

Describe the structure and position of the notochord

A
  • Flexible rod shaped structure
  • Ventral to the neural tube
  • Overlaid by ectoderm
92
Q

What structure is formed from the notochord?

A

Nucleus pulposus of IV discs

93
Q

List the signals which come from the notochord to induce development in the neural plate

A

Noggin - inactivates BMP4 - absence of BMP4 causes patterning of the neural tube and somites

Chordin
- BMP antagonist

94
Q

Describe the development of the neural plate

A
  • Appearance of notochord and mesoderm induces overlying ectoderm to thicken and form neural plate
  • Cells of plate make up neuroectoderm - initial event in the process of neurolation
  • Neural plate folds - after plate is induced, lengthens and lateral edges elevate, forms neural folds
95
Q

Describe the folding of the neural plate

A
  • By day 19 - lengthens and lateral edges elevate
  • Neural folds form - depressed mid-region forms median hinge point, dorsolateral hinge points form on lateral edges
  • Cell wedging - microtubules and microfilaments change cell shape to allow folding
  • Neural folds approach midline, where they fuse
96
Q

Describe fusion of the neural tube

A
  • Fusion begins in the cervical region, proceeds in cephalic and caudal directions - open ends form anterior and posterior neuropores - connect with overlying amniotic cavity
  • Closure occurs in week 4, anterior day 25, posterior day 27
97
Q

What structures are formed from the neural tube?

A

Brain + spinal cord

98
Q

Describe the role of sonic hedgehog

A
  • Potent inductive signal
  • Part of sequence of master genes
  • Critical role in development, patterning of brain and spinal cord (+ limb development/somite patterning)
  • Works at short range
  • Causes cells in ventral somite (sclerotome) to undergo epithelia-mesenchymal transformation
  • They can then - migrate, move towards signal source, form the vertebral column around the notochord
  • Signal also affects dermomyotome - induces competence to respond to signals from surface ectoderm
99
Q

Explain the cause of neural tube defects

A
  • Result of failure or incomplete closure of neural tube
  • Failure in anterior neuropore = anencephaly
  • Failure in posterior neuropore = spina bifida
100
Q

List the types of spina bifida

A
  1. Spina bifida occulta
  2. Spina bifida cystica - meningocoele
  3. Spina bifida cystica - myelomenincoele
101
Q

Spina bifida cystica - meningocoele

A
  • Lump at bottom of spine
  • Cyst of fluid w/ nervous tissue
  • Spinal cord is still inside spinal column
102
Q

Spina bifida cystica - myelomeningocoele

A
  • More nervous tissue in cyst
  • Loss of sensation/mobility
  • Bladder/bowel control in lower limbs
103
Q

Describe the diagnosis of neural tube defects

A
  • Ultrasound

- Raised levels of alpha-fetoprotein

104
Q

How can neural tube defects be prevented?

A

Folic acid taken prior to conception and in early stages of pregnancy reduces incidence of neural tube defects

105
Q

Describe the different modes of closure of the neural tube which occur at different levels of the spine

A

Upper spine = dorsolateral hinge points not needed - only medial, due to inhibition by BMP2. SHH expression is strong which inhibits noggin

Lower spine = SHH is reduced as dorsolateral hinge points are needed, noggin is uninhibited, and it antagonises BMP2 which allows DLHPs to form

106
Q

Explain the effect of abnormal SHH pathway activity

A
  • Increased SHH pathway activity in neural tube leads to neural defects in low spinal region
  • At low spine levels, where a medial hinge point doesn’t form, suppression DLHPs inhibit closure and leads to neural tube defects
107
Q

Describe the cascade involved with SHH signalling

A
  • Requires 2 other genes to encode transmembrane proteins - patched and smoothened (G-linked)
  • Triggers cascade which leads to activation or repression of target genes by transcription factors in Gli family
  • Patched inhibits smoothened - blocks downstream signalling via Gli which will transduce SHH signal
  • If SHH binds to patched (its receptor) - removed patched inhibition of smoothened. Activation of smoothened up-regulates downstream pathways - bind to DNA and controls effector genes in SHH pathway
  • SHH is synthesised as inactive precursor - needs cholesterol to become active, release from plasma membrane via protein dispatched allowing it to establish the concentration gradient characteristic of its action as a morphogen
108
Q

List the causes of congenital defects

A 
5% = environmental 
10-15% = chromosomal
20-25% = multifactorial genetic predisposition with environment correct for ecpression
50-60% = unknown
109
Q

Give examples of minor anomalies present at birth

A
  • Pigmented sports
  • Small ears
  • Short palpebral fissures
110
Q

List the types of abnormal development

A

Abnormalities of individual structures:

  • Malformation
  • Disruption
  • Deformation

Defects involving more than one structure:

  • Sequence
  • Syndrome
  • Association
111
Q

Describe malformation anomalies

A

Structural defect of part or the whole organ caused by an abnormal process intrinsic to its development e.g. spina bifida

112
Q

Describe disruption anomalies

A

Defect in an organ or body part caused by a process that interferes with an originally normal developmental process e.g. Thalidomide induced phocomelia

113
Q

Describe deformation anomalies

A

Structural abnormalities caused by mechanical forces e.g. amniotic band constriction

114
Q

Describe sequence anomalies

A

A pattern of multiple malformations stemming from a disturbance of developmental processes/mechanical factor e.g. Potter sequence

115
Q

Describe syndrome anomalies

A

A group of malformations of different structures due to a single primary cause, but acting through multiple developmental pathways e.g. Down syndrome

116
Q

Describe association anomalies

A

A group of anomalies seen in more than one individual that cannot yet be attributed to a definitive cause e.g. VACTERL

117
Q

Define teratology

A

Study of abnormal development of congenital defects

118
Q

Define teratogen

A

An agent that can disturb the development of an embryo or foetus

119
Q

Describe the effect of teratogens during weeks 1-2 of gestation

A
  • Teratogens either have no effect or the conceptus will be aborted
  • If one or two cells are killed, then the embryo can compensate - regulative development
  • If more cells are killed, the embryo is lost, often before pregnancy is confirmed
120
Q

Describe the effect of teratogens during weeks 3-8 of gestation

A
  • Organ systems are becoming established
  • Most teratogens are highly effective at this stage
  • Each organ system has its own period of maximum sensitivity
  • Type of defect seem depends on which organ system is most vulnerable at a particular time that the teratogen acts
121
Q

Describe the effect of teratogens during weeks 9-38 of gestation

A
  • Functional deficits and minor abnormalities are produced by teratogens acting at this stage
  • Susceptibility is reduced
  • Differentiation is occurring at this stage - any organ still differentiating is still vulnerable e.g. urogenital system, nervous system
122
Q

List the types of teratogens

A
  1. Drugs and chemicals
  2. Industrial pollutants
  3. Hormones
  4. Infectious agents
  5. Mechanical factors
123
Q

Explain the effect of thalidomide during development

A
  • Limb development affected - total absence (amelia) or partial absence of limbs (meromelia) - wide spectrum
  • May cause blood vessels in limbs to ‘leak’ causing damage to cells in the progress zone of the early limb bud - proximal structures don’t develop
124
Q

Describe the effect of antibiotics during development

A
  • Tetracyclines cross the placenta. Deposited in bones and teeth at sites of calcification - teeth can become discoloured from 18 weeks prenatal life to 16 years, enamel formation affected
  • Streptomycin - high doses can cause inner ear defects
125
Q

Give examples of prescribed drugs which can cause anomalies

A
  1. Epilepsy medication
  2. Methotrexate (folic acid inhibitor)
  3. Antineoplastic drugs
  4. Vitamin A
126
Q

Describe the risk factors for foetal alcohol syndrome

A

Mothers who are chronic alcoholics/binge drinkers are at risk

127
Q

List the characteristics of foetal alcohol syndrome

A
  • Facial deformities
  • Low birth weight
  • Small head circumference
  • Developmental delay
  • Poor co-ordination/motor skills
  • Memory problems
  • Behavioural problems
128
Q

List the facial deformities associated with foetal alcohol syndrome

A
  • Microcephaly
  • Epicanthal folds
  • Minor ear anomalies
  • Low nasal bridge
  • Micrognathia
  • Thin upper lip
  • Indistinct philtrum
  • Short palpebral fissures
129
Q

Explain how foetal alcohol syndrome develops during pregnancy

A
  • Alcohol crosses placenta
  • Foetal liver not fully developed - cannot metabolise alcohol
  • Foetus has high blood alcohol concentration - lacks oxygen and nutrients, white matter development affected
  • Timing critical - facial features develop during week 6-9 so drinking excessively in this period often results in facial deformities
130
Q

Describe the effects of heroin use during pregnancy

A

Babies born with dependency

131
Q

Describe the effects of cocaine use during pregnancy

A
  • Premature labour
  • Spontaneous abortion
  • Malformations of the heart
  • Genitourinary system and behaviour issues
  • Hard to assess as women who use cocaine often use other drugs, especially alcohol
132
Q

Describe the effect of infectious agents in pregnancy

A
  • Can cross placenta

- Mostly viral

133
Q

Describe the effect of rubella virus exposure in pregnancy

A

6th week - cataracts
9th week - destruction of the organ of Corti (deafness)
CNS and ear may be affected up to 25th week

134
Q

Describe the effect of cytomegalovirus exposure in pregnancy

A

Causes spontaneous abortion in 1st 3 months, later can lead to cerebral palsy/deafness

135
Q

Describe the effect of herpes simplex virus exposure in pregnancy

A

Often transmitted around time of birth, can cause mental retardation

136
Q

Describe the effect of toxoplasma gondii exposure in pregnancy

A
  • Toxoplasmosis infection
  • Foetus may have microcephaly, hydrocephalus, mental retardation
  • Mother can be symptomless
  • Parasite found in raw uncooked meat, unwashed fruit and vegetables, cat litter
137
Q

Describe the effect of ionising radiation exposure during pregnancy

A
  • Rapidly kills proliferating cells

- Produces virtually any kind of defect depending on time and dose

138
Q

Give examples of a malformation which is the result of too little growth

A
  • Microcephaly caused by Zika virus

- Congenital renal agenesis - due to failure of uretic bud formation

139
Q

Define adolescence

A

Adolescnence = age 10-19
A variable period between childhood and adulthood largely bounded by 10 and 20 years of age and characterised by rapid development of psychological, social and biological domains

140
Q

Describe brain development during adolescence

A
  • Increase in number of neurones in the frontal cortex
  • Synaptic pruning - loss of approx 15% of grey matter
  • Myelination of axons
141
Q

Explain the effects of drinking alcohol on the adolescent brain

A
  • Poor decision making - damages the prefrontal cortex
  • Tolerance - more they drink the more they need to drink to get same effect = more damage
  • Risk taking - connections between prefrontal cortex and ventral striatum (brain’s reward system) are still maturing
  • Memory problem - small amounts of alcohol result in forgetting things recently learned (hippocampus)
142
Q

List the maternal outcomes associated with teenage pregnancy

A
  • Increased obstetric complications (anaemia, raised BP, postnatal depression)
  • Poor educational outcomes
  • Decreased employment opportunities
  • Reliance on benefits
  • More likely to live in poverty/poor housing/poor nutritional state
143
Q

List the child’s outcomes associated with teenage pregnancy

A
  • Decreased birth weight
  • Increased risk of SIDS (sudden infant death syndrome)
  • Increased risk of hospitalisation for non-accidental injury
  • Developmental delay in preschool years
  • More likely to live in poverty/poor housing/poor nutritional state
  • Increased risk of being a teenage mother
144
Q

Which cell types are important for ensuring remodelling of the maternal spiral arteries occurs?

A

Extravillous cytotrophoblast

145
Q

Which molecule is inactivated by Noggin?

A

BMP4

146
Q

Which molecules are transported by active transport across the placenta?

A

Amino acids

147
Q

What type of sample would be most appropriate for screening for neural tube defects?

A

Maternal blood

148
Q

Which organ system would be affected by rubella infection in the 6th week of pregnancy?

A

Eyes

149
Q

Which structure contributes to the foetal portion of the placenta?

A

Chorion

150
Q

Which structure contributes to the maternal portion of the placenta?

A

Basal surface

151
Q

Define primary prevention

A

Measures taken in a well population to prevent the development of disease

152
Q

Give examples of methods of primary prevention

A
  • Immunisation

- Folic acid supplementation in women of child-bearing age

153
Q

Define secondary prevention

A

Measures taken to detect early disease which has no symptoms, when the outcome can be improved

154
Q

Give examples of secondary prevention

A
  • Screening programmes

- Treatment of risk factors of a disease

155
Q

Define tertiary prevention

A

Measures taken in established, symptomatic disease to manage the disease and actively reduce complications

156
Q

Give examples of tertiary prevention

A
  • Preventing pain and damage
  • Halting progression/complications of the disease
  • Restoring health of individual affected
157
Q

List the types of intervention taken by health systems

A
  1. Prevention

2. Therapeutic activities

158
Q

Define cause

A

A person or thing that gives rise to an action, phenomenon or condition

159
Q

What criteria are used to explain apparent association?

A
  • Chance
  • Bias
  • Confounding
160
Q

Explain how chance can be used to explain apparent association

A
  • Epidemiological studies and clinical trials use samples to represent the wider reference population
  • Samples may differ from the wider reference population due to chance
  • Inadequate sample size is common cause for apparent association due to chance
161
Q

Define bias

A

Bias = systematic error in the design, conduct or analysis of a study that results in mistaken estimates of any given factor on the risk of diease

162
Q

List the types of bias

A

Selection = differential allocation to groups

Measurement = differential measurement between two groups

163
Q

Explain how confounding variables can be used to explain apparent association

A

The observed result between a given factor and disease occurs because of the influence of a third variable

164
Q

List the causal guidelines outlined by Bradford Hill

A
  • Strength of the association
  • Consistency
  • Specificity
  • Temporality
  • Biological gradient
  • Plausibility
  • Coherence
  • Experiment
  • Analogy

Medicine YEAR 1 (18 decks)

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