Y2 LCRS RDA

Adrenarche

(Precursor of Puberty) § Starts: • Females: 6-9 years. • Males: 7-10 years. § Rise in adrenal 19- carbon steroid production, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). (beginning of adrenal secretion.) when DHEA and DHEAS is made without cortisol. § Manifests clinically as the appearance of axillary and pubic hair, usually about age 8. § Role uncertain -?Precursor to puberty

Normal vs. Abnormal Fetal Grow

* Normal: o Normal but big o Normal but small *Abnormal: o Growth Restriction o Macrosomia o Neonatal Hydrocephalus o Achondroplasia

Syndromes associated with obesity

* short overweight child might have something wrong cushings, prader-willi, Bardet-Biedl syndrome (polydactyly, pigmentation in eye)

Placenta development stages

**(1 pic): § Approx. 9 days PF, the conceptus is completely implanted in the maternal endometrium. § Placenta originates from the cytotrophoblasts layer. **(2 pic): § Cytotrophoblasts proliferate into the syncytium to form a columnar structure which becomes a villous structure. **(3 pic): § The overall structure then does not change but it is modified. o There are fewer cytotrophoblasts present at term so that there can be a closer apposition between the syncytium and placental capillaries.

The Developmental Domains - (1) Gross Motor Performance:

*** Developmental milestones: o New-born - limbs flexed in symmetrical posture, head lag on pulling up. o 6-8 weeks - raises head to 45degrees in prone. o 6-8 months - sits without support. o 8-9 months - crawling. o 10 months - cruising around furniture. o 12 months - walks unsteadily. o 15 months - walks steadily. *** Primitive reflexes - these are protective and serve to promote support, balance and orientation: o Reflexes - should disappear by 4-6 months: § Stepping. § Moro. § Grasp. § Asymmetric tonic reflex - which way babies head is turned, arm outstretches. § Rooting. o Protective reflexes - seen in table in next card and develop FROM 5 months.

Cytotrophoblast shell

**1.IMPLANTATION of conceptus into endometrial epithelium 2.Trophoblast --> cytotrophoblast (CTB, inner) and syncytiotrophoblast (STB, outer) 3.STB sends out PROJECTIONS to embed onto the endometrium 4.LACUNAE form in STB --> gets filled with maternal blood 5.CTB expansion into STB --> PRIMARY CHORIONIC VILLI 6.Mesoderm line these villi --> SECONDARY CHORIONIC VILLI 7.Embryonic blood vessels form in the mesoderm --> TERTIARY CHORIONIC VILLI 8.CTB cells from the villi grow towards the decidua and form a CTB SHELL (this is the disc of the placenta). This has plugs

Fetal and maternal side of placenta

**FETAL SIDE OF PLACENTA: § Disc shaped structure §The side baby will be facing and the umbilical cord which will connect to the fetus §Blood vessels are carrying nutrients from maternal system to baby insertion point near the centre §Fetal membranes thinner in placenta and surrounds the disc §Umbilical cord is very hard and can cause damage to baby if it gets tangled **MATERNAL SIDE OF PLACENTA: §Pieces of tissue with separation between them §The unit of tissue is called a cotyledon, number of them doesn't matter for the growth and development of baby §Large cotyledon is in the centre of placenta (2-3cm) and smaller out §The gaps between cotyledon contains maternal tissue = DECIDUA. Usually stays behind after birth §Very strong contact with vascular system on this side.

How long does folliculogenesis take?

**Folliculogenesis - Important Points: o egg development acc starts before birth. § Time taken for primordial follicle --> secondary oocyte is MORE than one month. o The human ovary contains multiple follicles at ALL stages of development with one dominant (Graafian) follicle at any one time. o It takes more than 2 complete cycles for initiated egg to be released (3 menstrual cycles). The ovaries alternate the release as well (so each one releases one follicle each ~56 days). § Human ovaries contain 2m primordial follicles at birth --> only 400 released at ovulation in a lifetime. § During meiosis, both the 1st and 2nd divisions are paused during follicular development. o Meiosis 1 starts during embryonic development, but halts at diplotene stage of prophase 1 (primary follicle) which is arrested until puberty (meiosis then resumes and 2nd follicles develop). o 2nd follicles then undergo a second arrest. § Key points: o Ovaries - contain ~6m primordial follicles at ~20w development à ~1m at delivery of infant. § 400 released over a lifetime. o Testes - produce 100m sperm/day from puberty onwards. **ladies who have had one ovary removed can still get monthly ovulation - get a number of eggs maturing and only dominant released. can get more than one egg released at a time (e.g. non-identical twins).

How to accurately measure height

**Getting an accurate height and weight is important in assessing growth. a) The equipment should be accurate and maintained properly b) Position the child properly to get an accurate height (read the instructions on the growth chart) c) Make sure you get rid of things which interfere with measuring- shoes off, hair out of the way, clothes off to weigh. d) Calculate the age and plot correctly on the chart. § Centile charts we use are for cumulative height - the total of all the growth they have done up until now. § Height velocity - how fast a child is growing in cm/year (many short children grow at a normal speed).

Age at menarche

**Menarche - the first occurrence of menstruation. o Has decreased over the last 150 years but seems to have been levelling off recently. § Possibly decreased due to nutritional reasons. o Body weight at menarche has remained relatively constant at ~47kg over those years.

Pros & Cons of SFH

**PROS: • Simple • Inexpensive **CONS: • Low detection rate: 50-86%. • Great inter-operator variability. • Influenced by a number of factors (BMI, fetal lie, amniotic fluid, fibroids, wrong LMP date, multiple pregnancy, maternal obesity) § Values that are lower than they should may result from: wrong last menstrual period date, the baby in a transverse lie, or complications including oligohydramnios (low levels of amniotic fluid) or a baby that is small for gestational age (SGA). § Higher values may also be found, due to: wrong last menstrual period date, multiple pregnancy, or maternal obesity. § Complications could include molar pregnancy, fibroids, polyhydramnios or a baby that is large for gestational age (LGA). § This simple and inexpensive measurement may identify gross changes in size, and hence gross complications in the pregnancy, but is generally of limited use, thanks to the many confounders, which include the problems listed above, as well as considerable inter-operator variability.

Gender differences and brain changes in adolescence

**Physical development: 1) Gender differences - girls grow taller, start puberty and are more mature, earlier than boys do. 2) Pubertal changes - girls start puberty around 8 (with breast budding) whilst boys start around 10.5. § Peak for girls is 11-13.5, peak for boys is 13-15. § Early maturing girls and late maturing boys are at risk of - depression, substance abuse, ASBOs, eating disorders and bullying. 3) Brain changes: § Grey matter decreases from 6yo --> adolescence. § Linear increase in white matter until age 20 · ~12yo Frontal and parietal lobes develop peak. · ~16yo Temporal lobes develop peak. § From puberty - increase in density of cortical white matter (more connections). § Pre-frontal cortex (executive function - i.e. planning) - increase in density of grey matter until puberty, then decrease. · Dorso-lateral prefrontal cortex - last area to reach adult full density. § Synaptogenesis followed by pruning (synapse elimination) occurs. § Brain regions associated with more basic functions such as sensory first followed by association areas involved in top-down processing.

Progesterone receptor

**Progesterone receptor (PR): 1) PR-B - mediates main effects of progesterone. 2) PR-A - less able to mediate than PR-B. § Ratio of PR-A: PR-B increases towards term so progesterone has less of an effect. § Loss or change in PR may lead to a "functional progesterone withdrawal" which is physiologically normal towards term labour. § Progesterone can switch off MANY of the labour pathways.

Cognitive assessments in elderly

**Screening tests: a) AMT (10 point test - mainly about memory and orientation), clock drawing test (tell them to draw clock showing particular time) - screen for cognitive impairment. b) Mini Mental State Examination (MMSE) - meant to test short-term memory and orientation in Alzheimer's but doesn't really test anything else. not used really in clinical practice. slightly outdated and less widely used. c) Montreal Cognitive Assessment (MOCA) - replaced MMSE. detailed examination in wide general use. d) Confusion Assessment Method (CAM) and 4AT - tools to help distinguish between dementia and delirium. **Diagnostic tests: a) Addenbrooke's Cognitive Examination (ACE) - 100 point test. Takes 20-45 mins. b) Detailed neuropsychometric testing - takes hours. Done by psychologist

Problems associated with LBW / FGR / Prematurity (Short, medium, long term)

**Short term: Respiratory distress, Intraventricular haemorrhage, Sepsis, Hypoglycaemia, Necrotising enterocolitis, Jaundice, Electrolyte imbalance. **Medium term: Respiratory problems, Developmental delay, Special needs schooling. **Long term: Fetal programming.

Six key hormones in pregnancy

**in pics: weeks go in 0-->5-->10 etc. 1) HCG - produced by placenta after implantation. It supports the function of the corpus luteum, a temporary structure in the ovaries essential in early pregnancy. It's the hormone detected in pregnancy tests. 2) Progesterone - initially produced by corpus luteum and then placenta. Progesterone helps establish the placenta. It stimulates growth of blood vessels that supply the womb and inhibits contraction of the uterus so it grows as the baby does. It also strengthens pelvic wall muscles for labour. 3) Oestrogen - initially produced by corpus luteum and then placenta. Oestrogen helps the uterus grow, maintains its lining, and helps foetal organs develop. Activates and regulates production of other hormones. With progesterone, stimulates breast growth and milk duct development. 4) prolactin - produced by the pituitary gland. Prolactin is the main hormone needed to produce breast milk. It contributes to enlargement of the mammary glands and prepares them for milk production. Progesterone inhibits lactation during pregnancy. 5) Relaxin - initially produced by corpus luteum and then placenta. Relaxin inhibits uterus contraction to prevent premature birth. It relaxes blood vessels, increasing blood flow to the placenta and kidneys. It relates the joints of the pelvis and softens and lengthens the cervix during birth. 6) Oxytocin - produced by the pituitary gland. Oxytocin levels rise at the start of labour, stimulating contractions of uterine muscle. It triggers production of prostaglandins, which increase contractions further. If labour doesn't start naturally, it can be used to induce it.

NF-kB: a pro-inflammatory transcription factor

**key regulatory TF in labour. o Almost all pro-labour genes have NFkB binding domains in their promoters. o Modification of NFkB sites in promoter sequences leads to loss of expression in cells or in expression vectors. o Inflammatory changes are strongly linked with labour. o Activators of inflammation are readily linked with preterm labour (eg intrauterine infection). § NFKB is a pro-inflammatory transcription molecule. o Closely related to - IL-1b, IL-6, COX2, cPLA2, IL-8. § NFKB has MANY initiators and it can then induce MANY effects (mostly inflammatory) through: o COX-2, IL-8, IL-1b, MMPs, oxytocin receptors, PG receptors, contraction-associated proteins. o Evidence for this comes from: § Pro-labour genes have NFKB binding domains in promotor regions. § Modification of NFKB sites in the domains lead to loss of expression of the cells. § PGE2 is constitutively expressed BEFORE any changes can be witnessed that are conducive to labour. o Equally, some tissues could not be stimulated to express PGE2 as the levels are already high.

Principles of management of child development

**objectives of management: ØMaximise mobility ØMinimise discomfort ØPromote speech and language ØPromote social and emotional health. *child development services can help

Approach to to Developmental Assessment

*PARENTS KNOW SOMETHING IS WRONG BEFORE PROFESSIONALS DO. * ask --> observe --> task. o Need to assess: •Milestones preceding age •Expected milestones for age

Sequence of events in FGR

*PI = pulsatility index.

Symphysis fundal height

*SFH: distance over the abdominal wall from the symphysis to the top of the uterus o 12w: at symphysis pubis. o 20 w: at umbilicus. o 20-34w: GA +/- 2 cm. o 36-38w: GA +/- 3 cm. o >38w: GA +/- 4 cm *Smaller: wrong dates, small for gestational age, oligohydramnios ,transverse lie. *Larger: wrong dates, molar pregnancy, multiple gestation, large for gestational age, Polyhydramnios, Maternal obesity, Fibroids.

Causes of pre-term labour

*common exam question*. •So we know labour is triggered by release of CRH, myometrial contraction and inflammation so anything that triggers these 3 factors will cause labour •Stress, twins= increase in CRH •Twins= increase in myometrial contraction •Intra-uterine infection, bleeding= inflammation

Basic placental structure

*within the cotyledon: § Primary subunit is the placental villus that has the branches. o This provides a large surface area for exchange between the maternal and foetal vascular systems. § Note that umbilical veins contain oxygenated blood and the umbilical arteries contain deoxygenated blood as the placenta carries out a parallel function to the lungs during pregnancy. § Note the separation of the maternal and foetal systems despite being near. § Cotyledons - the maternal surface of the placenta is sub-divided into cotyledons (30-60/placenta). Each contains one or more villi. ØVillus is a very highly branched structure, provides a large surface area (~11m2). ØVery effective for transport of molecules between maternal and fetal circulations. ØAlso anchors the placenta (and hence the baby) securely for 9 months. ØIntimate contact between maternal and placenta tissues - interesting immunology as no rejection - maternal immune system switched off!

Cystic hygroma

-Cavernous lymphangioma of the neck C. -Associated with underlying genetic conditions such as Turner's syndrome or trisomies, cardiac abnormalities as well as maternal infection.

When is spina bifida present?

-It is variable, but can be severely disabling -The primary problem is failure to complete neurulation (posterior neuropore) -The problem is present within 4 weeks of fertilisation

Treatment of AN

.....most young people who have parental/carer support with AN should be offered AN focussed family therapy (FT-AN or FBT) in conjoint, separated or multifamily format as first line treatment on an outpatient or if too sick, day patient basis, following a brief (<3 week admission) for medical stabilisation if needed.

Pre-pubertal Depression - two main types?

1) 1st: § More common presentation is with co-morbid behavioural problems, parental criminality, parental substance abuse and family discord. § Course of this resembles that of children with conduct disorder (diff family circumstances and antisocial circumstances) § No increased risk of recurrence in adult life. 2) 2nd: § Less common § highly familial with multigenerational loading for depression. § High rates of anxiety and bipolar disorder. § Recurrences of depression in adolescence and adulthood.

1) What are the advantages of using the predicted parental height? 2) The limitations? 3) What is height velocity? SBA: What milestone should be reached by 2 years of age?

1) Allows inidivdualised correction for the height of parents. Quick and simple way to adjust height expectations. 2) Primitive. May be anomaly?? 3) Height velocity= change in height (cm) / number of years over which this change has happened 4) (Building a 6 block high tower, using phrases when speaking, standing on one foot)

Phases of growth

1) Antenatal - § the most rapid phase of growth. § maternal health and the placenta are important factors. 2) Infancy - § rapid initial growth ~ 23-25cm in first year. § continuation of fetal growth. § nutritionally dependant. § at 9-12 months, get the influence of GH. 3) childhood: § post infancy to adolescence § growth rates in boys and girls similar § GH/IGF-1 axis drives growth § nutrition less impact. 4) stopping growing: § when stop growing, growth plates fuse § the bones mature and epiphyses fuse at the end of puberty. § the final part of growth occurs in the spine and the final epiphyses to fuse are in the pelvis.

Child growth and development- Conditions (4)

1) Autism: •Boys>girls •Usually presents between 2 - 4 years of age •Features include (1) impaired social interaction; (2) speech and language disorder; and (3) imposition of routines with ritualistic and repetitive behaviour. •Comorbidities include learning and attention difficulties, and epilepsy 2) ADHD: •Diagnostic criteria - (1 )Inattention; (2) Hyperactivity; (3) Impulsivity; (4) Lasting > 6 months; (5) commencing < 7 years and inconsistent with the child's developmental level •Risk factors - Boys > girls, ratio 4:1; Learning difficulties and developmental delay •RF- Neurological disorder, e.g. epilepsy, cerebral palsy; first-degree relative with ADHD; family member with depression, learning disability, antisocial personality or substance abuse. 3) Cerebral Palsy: •A disorder of movement and posture arising from a non-progressive lesion of the brain acquired before the age of 2 years. •Learning difficulties, epilepsy, visual/ hearing impairment, poor growth, respiratory problem 4) Learning Disability: •Causes include - (i) chromosome disorders (30%); (ii) other identifiable syndromes (20%); (iii) postnatal cerebral insults (20%); (iv) metabolic or degenerative diseases (1%) •May present with reduced intellectual functioning, delay in early milestones, dysmorphic features, ± associated problems (epilepsy, sensory impairment, ADHD) •

Which fetuses need growth monitoring?

1) Bad Obstetric History: § Previous maternal hypertension § Previous FGR § Stillbirth § Placental Abruption 2) Concerns in index pregnancy : § Abnormal serum biochemistry PAPP-A <0.3 MoM (used in down syndrome testing) § Reduced symphysis fundal height §Maternal systemic disease e.g. hypertension, renal, coagulation § Antepartum haemorrhage

SBA: A mother had her baby at 28 weeks gestation, which of the following is correct A. Delivery at term B. Delivery was pre-term C. Delivery was very pre-term D. Delivery was extremely pre-term SAQ: Name and describe the 3 stages of birth (6 marks) SAQ: Where do contractions start from and where do they spread? (2 marks)

1) C. Delivery was very pre-term 2) •Length of labour varies, around 12-48 hrs •Phase 1: Uterine contractions and cervical changes •Phase 2: Delivery of the of the foetus •Phase 3 (30 min) : Delivery of the placenta 3) Uterine contraction are co-ordinated myometrial contraction with fundal dominance •This just means the uterus is squeezed from the top down, with increasing co-ordination and power

Comprehensive geriatric assessment (CGA) impact

1) CGA in the community: -Reduce admissions to institutional care -Reduce falls -Most benefit in mild or moderate frailty 2) CGA for frail inpatients: -Reduces inpatient mortality -Reduces functional and cognitive decline -Reduces admission to institutional care

CRH and PAF in term labour

1) CRH - produced not only by the pituitary gland but by the human placenta: o Levels rise at the end of pregnancy whilst CRH-binding-proteins drop towards end of pregnancy. o High CRH also correlates with high COX2 molecule expression. 2) PAF: o Part of lung surfactant that is produced by maturing lungs before birth. o Levels in amniotic fluid increase near term (as PAF is part of surfactant that also increases). o Thus, the levels of PAF are a signal of foetal maturity (may stimulate labour). **Both above can upregulate labour - cannot prove whether these are involved though as unethical. o causes increased expression of PGE2 and COX2. o IL-1b (inflammatory mediator) levels --> which drives the further mediators needed for rest of labour.

List some common/ typical developmental problems

1) Cerebral palsy 2) Autism spectrum disorder 3) Attention deficit hyperactivity disorder 4) Learning disability

Detailed process of labour

1) Cervical ripening and effacement: § Change from rigid --> flexible structure. § Remodelling - loss of ECM. § Recruitment - of leucocytes e.g. neutrophils. § Inflammation - Prostaglandin E2, IL-8. Local (paracrine) change in IL-8. 2) Co-ordinated myometrial contractions: § A fundal dominance with increased power and coordination of contractions. § Mediators : Prostaglandin F2a (E2) increased from fetal membranes, oxytocin receptors increased, contraction associated proteins. 3) Rupture of foetal membranes - loss of strength due to changes in amnion BM. § Inflammation and leucocyte recruitment (exacerbated in preterm), increased levels -and activity of MMPs. § Inflammatory process in fetal membranes. **SUMMARY: 1) Cervix: o Prostaglandin E2, IL-8, MMPs. 2) Myometrium: o Prostaglandin F2a (E2) levels increase, oxytocin receptor upregulation, contraction associated proteins. 3) Foetal membranes: o PGs, ILs, MMPs, inflammatory processes **These changes may generally be described as 'inflammatory', as they involve molecules that are present during inflammatory processes anywhere in the human body. It seems that similar mechanisms are involved in labour at all gestational ages, so the changes summarised above will be present during preterm labour at 28 weeks, and during term labour at 40 weeks of gestational age.

Abnormal development: delay vs disorder

1) Delay - slow acquisition of skills. § May occur in one or more domain. · One domain affected = domain-specific. · >= 2 domains affected = global. · All domains affected equally = consonant delay. · All domains affected differently = dissonant delay. 2) Disorder - mal-development of a skill. § Patterns of delay are slow but steady, can plateau or can regress. o Over time, the gap widens so the deficit becomes more apparent.

Summary of the three trimesters

1) FIRST TRIMESTER: 0-13 weeks (LMP): §Greatest changes and risks for the fetus - miscarriage rate ~25-30%!! §If the fetus survives to week 13 (GA), then live birth is ~95% §Limited effect on maternal system, though NB hormones §WE only have approximate data §IVF means that you can calculate the exact dates §Maternal system is quite safe during the first trimester. The only significant stage is during the first trimester §2nd trimester is largely safe for both §Mother's system is adapting §The uterus is beginning to stretch to accommodate the changes §There's not much known in detail during the 2nd trimester. 2) SECOND TRIMESTER: 14-26 weeks (LMP): §Safest time for the baby and the mother §Fetal weight increases from 50g - 1000g §Uterine stretch!! §Not a good time to be born! §Detailed knowledge is limited §MRI looks at overall structural development but no detail on small changes §Progesterone levels continure to increase §Estrogens increase §Maternal Changes: §Increased weight §Increased blood volume §Increased blood clotting tendency §Decreased blood pressure §Altered fluid balance §Altered joints 3) THIRD TRIMESTER: 27-39 weeks (LMP) §Everything grows §Development of key systems §Fetus (infant) ~3.5kg at term §2 kg increase during last trimester §>30cm in length §Maturing of key systems that develop late §Braing §Lungs §Digestion (placenta delivered nutrition before this) §Immune system §These continues to develop after birth §In pre-term babies, none of these are fully developed and therefore heavy support is needed to allow more time for maturation and development §The baby is allowed to leave NICU when it is roughly the full age of full term babies (if born 2 month early, go home 2 months later) §Placenta becomes more efficient in later stages of pregnancy as it needs to drive the accelerated growth of the fetus **Summary: §Infant size increases §Organ systems reach in utero maturity §Uterine system prepares for delivery §Risks connected with delivery process, not with pregnancy per se e.g. bleeding

Social changes in puberty

1) Family - parental surveillance, confiding. 2) Peers: • Increased importance. • More complex & hierarchical. • More sensitive to acceptance & rejection. • Romantic relationships (can be trigger for mental health problems). 3) Social role: education, occupation, etc **Wider social influences: • School. • Work. • Culture ("teen" subculture; migration/culture). • Social influences eg unemployment, poverty/affluence, housing, neighbourhood effects. * time spent on social media isn't the issue; it does harm by bullying, stop you sleeping and stop exercising.

Maternal physiological changes: recognise the maternal anatomical and physiological changes associated with pregnancy

1) First trimester commencing: a) Altered emotional state - Some women will enjoy the whole experience. Others will get depressed and will become very emotional. Post-natal depression is also an issue. b)Altered hormones - Steroid hormones alters and this also has an effect on the brain c) Altered brain function- slightly decreased brain size. Pregnant lady's thinking patterns is altered. d) Altered immune system e) Altered appetite: § GI imbalance. § Part is due to the pressure on the abdomen= squashes the GI tract and stomach. § This means they can't eat as much all in one go and will snack more § Will also cause morning sickness (severe= Hyperemesis gravidarum) § The maternal system needs to feed the baby as well. Therefore if the diet is weak in some aspects, the body will change craving. 2) Second trimester commencing: a) ↑ blood volume - To help feed the infant b) ↑ clotting c) ↓ blood pressure - Opposite effects with BV. 10-20mmHg decrease in blood pressure This creates problems as it causes faint. d) Altered fluid balance - Kidney function increase partly due to increase blood flow to the kidneys= more urine. 3) Third trimester commencing: a) ↑↑ weight b) Altered joints- Less securely attached. The size of the human infancy is right on the limit of what the female pelvis can carry. The pelvis joints must be loose to allow the mother to carry/ support.

Causes of conduct disorder

1) Genetic - weak. 2) Child - difficult temperament. § Family - poor parenting, discord, lack of warmth, inconsistent discipline, coercive interactions and aggression. 3) Wider environment - poor schools and neighbourhoods.

Fetal growth depends on 2 components

1) Genetic potential - derived from both parents - mediated through growth factors eg insulin like growth factors 2) Substrate supply - essential to achieve genetic potential - derived from placenta which is dependent upon both uterine and placental vascularity

Evaluating the child with abnormal development

1) History: •Parental anxiety •Birth history •Family history 2) PMHX: •Developmental history •Current skills 3) Examination: •Developmental assessment, + general and neurological examination. •Investigations - as appropriate

female reproductive system hormonal axis

1) Hypothalamus produces LHRH (aka gnRH) 2) pituitary produce LH and FSH 3) targets ovaries which produce oestrogen and progesterone, which act on uterus. 4) feedback on hypothalamus and pituitary

Influencing factors of foetal growth

1) Maternal factors influencing foetal growth: a) Poverty - more likely to be young (low birth weight) and be less educated on risks. b) Mother's age - too young or too old can impact baby health. optimum is 16-35 years of age. higher risk of preterm labour. longer labour period and risk of downs syndrome for older women. young mothers likely to have less coping capacity and risky behaviours. c) Drug use and alcohol - metabolised and transmitted through placenta. drugs--> birth defects, low birth weight and stillbirths. also cause fetal addiction, miscarriages, increased risk of SIDS, resp problems. alcohol --> CNS disorders, mental retardation, miscarriages, still birth, LBW, fetal alcohol syndrome. d) Smoking and nicotine --> reduces oxygen flow to fetus --> LBW and stillbirth, SIDS, ectopic pregnancy, miscarriages and asthma. e) Diseases --> placenta can't always filter. Babies can be born with venereal diseases transmitted by the mother. f) Mother's diet and physical health - MALNUTRITION is the most important factor in baby growth. A lack of iron results in anemia in the fetus, the lack of calcium can result in poor bone and teeth formation, and the lack of protein can lead to a smaller fetus and mental retardation. g) Mother's prenatal depression - associated with adverse perinatal outcomes such as slower fetal growth rates (due to prenatal maternal cortisol levels) h) Environmental toxins --> miscarriage, sterility, and birth defects 2) Feto-placental factors: a) Different genotypes. b) Gender - males tend to be bigger than females. c) Previous pregnancy - infants are heavier in the 2nd and subsequent pregnancies. d) Hormones - one important hormone is IGF-1 that acts to: · Increase mitotic drive. · Increase nutrient availability for tissue accretion. o Little effect on tissue differentiation (this is mediated by cortisol).

When does miscarriage occur?

1) Miscarriage (<23 weeks of gestation): o ~350,000 p.a., within 13 weeks, ~7,000 late miscarriages. o if placenta isn't anchored properly, the switch to receiving the full blood flow from spiral artery after cytotrophoblastic shell breaks and can't cope with this increased pressure. 2) Term: 37-41 weeks of gestation. o ~700,000 infants p.a. o ~525,000 labour (~75%) o ~175,000 elective Caesarean section (~25%) 3) Preterm: 23-37 weeks of gestation. o ~80,000 infants p.a. o ~45,000 preterm labour o ~35,000 preterm emergency Caesarean section. **either delivered early due to compromise to fetus' health, maternal health or just entered laboyr early,

Cellular distributions

1) Mosaicism (non disjunction) - differences between cells within one individual 2) Distribution of cells between inner cell mass & trophectoderm (placenta). normal cells stay in inner cell man; abnormal cells go to placenta. so placenta could be abnormal whilst feltus is normal. 3) Chimerism - fused multiple zygotes -Non-identical zygotes

Modern Obstetric Practice of examiantion

1) Obstetric Ultrasound Examination 2) a) Dating by LMP: Confounding factors include: Inaccurate (irregular periods; abnormal bleeding; oral contraceptives, breastfeeding) **Importance of correct dating: • SGA or LGA confusion • Inappropriate inductions • Steroids in preterm delivery **Best practice: All pregnancies should be dated by CRL (Crown-rump length) by ultrasound preferably towards the end of the first trimester; variations in fetal size are more limited at this stage of development, so the gestational age of the infant can be estimated more precisely. Except IVF pregnancies

Typical abnormalities of kidney development

1) One kidney may be retained in the pelvis (Figure 5.4.3A), rather than moving to the usual abdominal position immediately under an adrenal gland. 2) Retention of an extra artery (or another problem) may obstruct (partly or fully) the ureter, and cause enlargement of the renal pelvis (Figure 5.4.3C). 3) The kidneys form separately, but may fuse to form a horseshoe kidney (Figure 5.4.3B); the extra tissue makes it impossible for it to move, so it will remain in the pelvis as shown. **All these abnormalities may compromise kidney function. In an adult, one functional kidney may suffice, but this may not always apply during development.

Cognitive development in adolescence

1) Piaget's stages: § Birth --> 2 Sensorimotor stage. § 2 --> 7 Preoperational stage - (represents world with symbols, objects) § 7 --> 11 Concrete operational stage - (reason logically) § 11 --> 15 Formal operational stage - (abstract, idealistic and logical reasoning) 2) Kohlberg's theory of moral development: § Level 1 & 2 Pre-conventional - desire to avoid punishment. § Level 3 & 4 Conventional - to illicit validation from others. § Level 5 & 6 Post-conventional - internal moral code and independent of others. · Sequence of this is fixed and people may never reach the highest levels.

Many genes are found in both animals and humans.

1) Piebaldism in mouse and boy caused by a mild mutation of the KIT receptor. 2) Holt-Oram syndrome - Phenotype due to mutation in TBX5 (transcription factor) - required as both structures develop. 3) acondroplasia -•Gain of function mutation in FGFR3

Neuroendocrine controls: recognise brain pathways associated with pleasure, their contribution to securing procreation, role in human bonding and parental behaviours

1) Pleasure and reward pathway: §Mesolimbic dopaminergic system = reward pathway. §It has been suggested that the brain is the most important sexual organ in the human §Pleasure, reward, fertility, reproduction and parenting pathways are all linked §Therefore pleasure pathway has a role in human bonding and parental behaviours §Activation of the pleasure pathway encourages intercourse → survival of the human race 2) Regulation of penile erections controlled partially by brain--> •Via spinal cord and the efferent nervous system •Afferent system of penis also present (pudendal nerve), e.g. by tactile stimulus •During erection: increased parasympathetic activity to smooth muscle of pudendal artery •Increased nitric oxide synthase (NOS) activity → increased NO → increased cGMP production → dilation of arterial smooth muscle → increased blood flow also compresses venous outflow of blood → leads to increase in size of penis •In female, clitoris increases in size due to same mechanism

General principles of management of FGR pregnancies

1) Problems in the index pregnancy: take history and Manage according to serial fetal biometry, fetal Doppler, BPP and CTG. 2) Screening of "at risk" pregnancies 24/40 Ut A screening. 3) Delivery Aim to deliver when ≥28 weeks and / or ≥500g Caesarean section for compromised fetuses

Birth defects: recall the processes leading to congenital abnormalities, including spina bifida, cleft palate and congenital cardiac abnormalities

1) SPINA BIFIDA: Fusion of the spinal cord should be complete by week 4 but in spina bifida, the posterior neuropore doesn't close properly. •Posterior neuropore fails to close •Tissue hasn't folded over properly to form the spine •Occulta: modest lesion, internal hair patch at base of spone •Outer part of some of vertebrae may not be closed •Meningocele: membranes buldge out> Meninges trapped in vertebrae •Myelomeningocele: neural tissue bulges out. Spinal cord is affected!! •2-3 weeks PF, trilaminar disc- CSF is made •Flat neural plate folds rapidly with a groove down the mddle and folds on eitherside. It elongates a lot •Prevention: folic acid 3 months before pregnancy •In anencephaly - anterior neuropore fails to close. Folic acid (given at the right time) may show benefit -->Implies similar causes to spina bifida 2) CLEFT PALATE: A defect posterior to the incisive foramen. Failure of tissue migration to complete fill the midline grooves. •There are grooves formed in the midline •Masses of tissue migrate from the lateral side of the face in towards the midline to fill in these grooves •Failure to fill these grooves leads to cleft palate or lip •The upper lip consists of two grooves so the defect tends to be asymmetric •A cleft palate is a defect that occurs posterior to the incisive foramen 3) TETRAOLOGY OF FALLOT: Classically 4 defects= Pulmonary stenosis, thickening of right ventricle, ventricular septal defect and malpositioned aorta 4) ATRIAL SEPTAL DEFECT: caused by patent foramen ovale. Blood flows between both atria. 5) HOLT ORAM SYNDROME: •Heart and hands: •Atrial septal defect and range of hand deformaties •Phenotype due to mutation in TBX5 (transcription factor) - required as both structures develop. 6) ACHONDROPLASIA: normal sized torso and short limbs •Gain of function mutation in FGFR3 •Achondroplasia means "lack of cartilage" •Defect is in conversion of cartilage to bone & lack of bone growth 7) POLYDACTYLY: one or more extra finger or toes •Thought to be associated with ZPA •ZPA- is a zone of polarising activity. Gives rise to digits. So in polydactyly you may end up with more ZPAs giving rise to many digits •Expresses sonic hedgehog (Shh)- a protein which stimulates limb development

Emotional development in puberty

1) Self-concept - Harter's 8-dimension model of self-concept: § Scholastic, job, athletic, physical appearance, social acceptance, close friends, romantic appeal and conduct of self - Some Jobs Are Pretty Shit, Can't Really Complain. · Self-concepts have clinical implications - 20-30% adolescents have low self-esteem which can lead to depression, anxiety, poor academia, social isolation, etc. However, people with good self-esteem can also be disposed to this! 2) Identity formation - Erikson's 8-life-span stages: § Don't need to know the stages but one stage is in age's 10-20 which is "Identity vs. confusion". 3) Identity formation - Marcia: § Identity diffusion (no crisis, no commitment) à identity foreclosure (no crisis, commitment) à moratorium (crisis, actively searching for identity) à identity achievement (crisis over). · Only moratorium necessary for identity development. · Identity is associated with higher - achievement, moral reasoning, social skills, etc. 4) Ethnic identity - cultural minorities: § Integration - retain base culture, develop and maintain with mainstream culture as well. ++ § Assimilation - lose base culture, develop and maintain into mainstream culture. -+ § Separation - retain base culture, no development into mainstream culture. +- § Marginalisation - lose base culture, no development into mainstream culture. --

Adolescent Depressive Disorder - outcome

1) Short term: § High rates of persistence and recurrence (20% in 1 yr). 2) Long term: § Significant continuity adolescence --> adulthood. § Adolescent Depressive Disorder: • 40-70% recurrence in adulthood • 2-7x increased risk as an adult. § Impairment relationships/education in adulthood.

Social development in puberty

1) Social domains - adolescents and parents may have different views about who has the final say depending upon the social "domains" - friendships, clothes, etc. - mid-adolescence is most intense negotiations. 2) Family: § Conflict with parents - most adolescents have good relationships, high confiding in mothers. § Family connectedness is associated with - reduced risk behaviours and increased self-esteem. 3) Peer development: § Primary school (7-11) - goal to be accepted by peers, prefer same gender and gain loyalty. § 11-13 - expect genuineness, intimacy, common interests, emergence of cliques. § 13-16 - friendship goals, cross-gender relationships and develop larger groups. § 16-18 - emotional support expected and increase dyadic romantic ties. 4) Gender differences: § Boys - less intimate, disclosing and friendships embedded in larger circles. § Girls - close and confiding relationships but are more brittle. 5) Influence: § Peers influence - interpersonal style, fashion/entertainment. § Parents influence - academic choice, career choice and future aspirations. 6) School - 5 or more A*- C at GCSE factors: § Higher social class, girls > boys, ethnicity (Chinese > Indian > white) - combined effect = ~10%.

Embryo and Foetal Risks

1) The infant: o Most severe risk is in defects in the gametes - chromosome irregularities: a) Loss of any autosome is not compatible with life --> miscarriage. b) Changes in sex chromosomes is generally less severe (loss is more serious than gain). Turners is a loss of a sex chromosome and leads to infertility. 2) The placenta: a) Most serious problem is incomplete anchorage in the 1st trimester. Possibly due to: i) Developmental problems. ii) Detachment in the late 1st trimester. 30%+ pregnancies are lost during the 1st trimester. b) Once the pregnancy passes viability (23 weeks of gestational age), early delivery becomes a problem. About 10% are delivered early, due to: i) Labour starting before term. ii) Deteriorating maternal or foetal health so delivery is the best option (inc. Growth Restricted infants, and Pre-eclamptic pregnancies). c) Infants born before 32w GA are at the greatest risk due to incomplete development of the 4 organs (brain, lungs, digestive and immune systems) = ~1% of all deliveries - Very Pre-term deliveries. **The process of labour has risks for the infant, but these can be minimised by monitoring of fetal health and delivery by Cesarean section if this is indicated.

What challenges does society face as a result of population ageing?

1) Working life/retirement balance - dependency ratio (no. of dependants: no of working in society; hence increasing working and pension age). 2) Extending healthy old age not just life expectancy: LE in England has started plateauing, due to austerity and deprivation. 3) Caring for older people, the sandwich generation: 3% of over 65 live in a care home. Care home means either nursing home (nurses for people with significant needs e.g. NG tube feeding) or residential homes (have carers who are less trained). Sandwich generation - looking after your children and also your parents. 4) Outdated and ageist beliefs/assumptions 5) Medical system designed for single acute diseases - this was relevant in 1948, but now in older people have lots of co-morbidities.

Causes of SGA

1) dating problem: • Consistant growth • Normal dopplers and fluid 2) normal: • Growth may reduce in 2 weeks • Normal dopplers and fluid 3) fetal problem (5%): • Fetal abnormality • Fetal infection 4) placental insufficiency (20%): • Reduction in AC/FL - weight around liver • Reduced liquor - not move as much, pee less and direct blood to brain. • Deranged dopplers

2 concepts of depression

1) dimension: increase symptoms --> increased impairment 2) category: disorder present or not.

The four domains of child development

1) gross motor skills 2) fine motor skills - need eyes to help too 3) social skills 4) speech and language skills

4 areas that change in adolescence?

1) peers 2) biology 3) family 4) cognitive/ emotional changes

Male reproductive system: recall the component parts of the male reproductive system, draw diagrams to illustrate the main cellular components, including testis and seminiferous tubule, and explain the significance of the Sertoli cells and Leydig cells for spermatogenesis and hormone production.

1) seminal vesicle 2) prostate gland 3) vas deferens 4) epididymis 1) Male gonad - testis. 2) Seminiferous tubules: Produce sperm 3) Leydig (interstitial) cells: a)Secrete testosterone b)LH responsive c)Important for sexual differentiation and spermatogenesis 4) Sertoli cells: a)"Nurse cells" b)FSH responsive c)Support spermatogenesis d)Regulate the internal environment of the seminiferous tubules. § All found in the testis. 5) Epididymis: •Sperm are released from the testis and stored here prior to ejaculation. At ejaculation, sperm are released into the contractile Vas Deferens then pass through urethra. During ejaculation sperm are mixed with fluid from the seminal vesicles and the prostate gland.

Two examples of spinal maldevelopment

1) spina bifida 2) anencephaly

Fetal growth: recognise the factors which influence fetal growth and the overlap between normal and abnormal fetal growth

1. Causative factors: a) Maternal: anaemia, DM, smoking, <16, >25 b) Foetal: multiple pregnancy, Chromosome abnormality, inborn errors of metabolism c) Placental: impaired trophoblast invasion and Preeclampsia (image) 2. Major factors controlling growth occur in second half of pregnancy **•RECAP PLACENTA FORMATION: CTB invade STB and form villi which attach to the endometrium. The CTB continues to grow forming a CTB shell which forms the placenta. The villi grow deeper into the myometrium until they come into contact with maternal spiral arteries. Spiral artery remodelling: CTB invade these arteries and cause them to become wider. IF THIS DOESN'T HAPPEN --> PRE ECLAMPSIA = BP > 140/90 and proteinuria > 0.3 g/day. Leads to IUGR because cant have normal exchange of nutrients. •PRE ECLAMPSIA is caused by inappropriate spiral artery remodelling •POHx = past obstetric history of Preclampsia/ fetal growth restriction

Normal fetal growth is characterised by 3 subsequent phases

1. Cellular hyperplasia (first trimester) (increased cell numbers): 4-20 weeks. 2. Hyperplasia and hypertrophy (increased cell size)(mid-trimester): 20-28 weeks 3. Hypertrophy alone (last trimester) - and accumulation of fat, muscle and CT. most fetal weight gain occurs here. : 28-40 weeks. *As the main increase in fetal weight occurs during the final trimester of pregnancy, hypertrophy is a key factor.

Fertilisation process

1. Deposition of sperm near the cervix. a. Cervical mucous is hostile to sperm which forms a physical barrier. b. Cervical mucous changes at mid-cycle to permit sperm to enter the uterus. 2. Passage of sperm through uterus and then fallopian tubes. 3. Sperm moves to fallopian tube ampulla. a. 2mm/min, 12cm/hour. b. Survival of the fittest. c. Capacitation takes place (within the uterus) which matures the spermatozoa. 4. Egg meets sperm fusion of egg with sperm (24 hours post ovulation). a. Acrosome reaction - penetration of zona pellucida (& Coronal cells). b. Calcium flux. c. Resumption of meiosis, release of 2nd polar body. d. Alignment of maternal and paternal chromosomes to generate zygote. 5. Change in Zona Pellucida to stop additional sperm fusing. 6. Initiation of mitotic divisions in embryo.

Fertilisation

1. Deposition of sperm near the cervix. a. Cervical mucous is hostile to sperm which forms a physical barrier. b. Cervical mucous changes at mid-cycle to permit sperm to enter the uterus. 2. Passage of sperm through uterus and then fallopian tubes. 3. Sperm moves to fallopian tube ampulla. a. 2mm/min, 12cm/hour. b. Survival of the fittest. c. Capacitation takes place (within the uterus) which matures the spermatozoa. 4. Egg meets sperm fusion of egg with sperm (24 hours post ovulation). a. Acrosome reaction - penetration of zona pellucida (& Coronal cells). b. Calcium flux. c. Resumption of meiosis, release of 2nd polar body. d. Alignment of maternal and paternal chromosomes to generate zygote. male DNA uncondenses and forms male pronucleus and female pronucleus fuses --> diploid cellS. 5. Change in Zona Pellucida to stop additional sperm fusing. 6. Initiation of mitotic divisions in embryo.

Placental Functions

1. Exchange of nutrients and waste products - Between the vascular systems of the mother and embryo or fetus. 2. Connection/Anchorage - the foetus is bound to the mother's arterial blood supply. The placenta must make sufficiently strong connections with the underlying maternal decidua to last for the 9 months of pregnancy. The placenta is in contact with maternal arterial blood, so anchorage is essential. 3. Separation - despite the close contact, the foetus and the maternal vascular system must remain separated. 4. Biosynthesis - second only to the liver in the biosynthesis functions. makes many hormones (HcG, HPL, progesterone, oestrogen) 5. Immunoregulation - ensures no rejection of conceptus (baby, placenta etc.). This cannot be the function of the uterus as ectopic pregnancies outside of the uterus can still proceed. placental cells contain antigens that signal that they're human, but doesn't define from which human.

Folliculogenesis in the human ovary (inside the ovum)

1. Oogonia: 44+XX (diploid). a. Mitotic division. 2. Primary oocytes: 44+XX (diploid). a. 1st meiotic division. 3. Secondary oocyte (+polar body): 22+X, 22+X (haploid). a. 2nd meiotic division. 4. Ovum (+ polar body): 22+X, 22+X (haploid). § Note that the first meiotic division is completed during the formation of the Secondary follicle, linked to the LH surge. Meiosis II follows immediately after this, but pauses in metaphase II as shown. *two important points to note: 1) Firstly, the time taken for a primordial follicle to develop into a secondary (mature) oocyte is more than one month, so pic does NOT reflect ovarian function fully. There is not a relatively rapid change from a primordial follicle to a 'growing follicle'. The reality is the human ovaries contain multiple follicles at all stages of development (stages 1-4) at any time, with one dominant follicle entering the later stages to form a secondary (Graafian) follicle. The ovaries usually alternate the release of the follicle, so each ovary has approximately 56 days (2 Months) between the release of one secondary follicle, and the release of the next one. In addition, the human ovaries contain about 2 million primordial follicles at the time of birth, and only about 400 of them will be released at ovulation during a reproductive lifetime; 12 per year for 30-35 years on average. 2) meiosis during human oogenesis is an intermittent process. Both the first meiotic division and the second meiotic division are paused during follicle development. Meiosis I starts during embryonic development, but halts at the diplotene stage of PROPHASE I (primary follicle); this persists until puberty when meiosis resumes as secondary follicles develop. Only a sub-population of follicles become secondary follicles, and these undergo another pause in meiosis at the METAPHASE stage of MEIOSIS II. Only fertilisation can cause the completion of meiosis in a human oocyte.

The conceptus starts as a bilaminar disc inside a blastocyst - comprised of....

1. The conceptus starts as a bilaminar disc inside a blastocyst - comprised of an epiblast and a hypoblast layer. a. Buccopharyngeal membrane is also known as the prechordal plate. 2. Gastrulation forms a 3-layer conceptus - the ectoderm, mesoderm and endoderm. 3. Gastrulation occurs down the primitive streak where: a. Epiblast cells migrate towards the centre. b. Epiblasts then differentiate into the mesoderm cells and move down into the new mesoderm layer. c. The hypoblast cells apoptose and are replaced by endoderm cells.

Ageing- Cognitive Assessments

1.Abbreviated Mental Test (AMT) and clock drawing tests are brief screening tests for cognitive impairment 2.Montreal Cognitive Assessment (MOCA) is a more detailed examination in wide general use 3.Mini Mental State Examination (MMSE) is a slightly outdated assessment which is less widely used that previously. 4. Confusion Assessment Method (CAM) and 4AT are tools to help distinguish between delirium and dementia

Regulatory hormones in male reproductive system

1.Gonadotrophin releasing hormone (GnRH): Hypothalamus pulsatile flow 2.Luteinising hormone (LH): Anterior pituitary 3.Follicle stimulating hormone (FSH): Anterior pituitary 4.Testosterone (T): Testis. § Leydig cells - testosterone - LH stimulated. testosterone goes into seminiferous tubule and helps in spermatogenesis. § Sertoli cells of seminiferous tubules- Inhibin (negative feedback) - FSH stimulated. Also produce ABP (androgen binding protein) that binds to testosterone, regulates function of sertoli cells and regulates production of sperm. * testosterone has negative feedback on LH/FSH and gnRH.

Implications for health care services due to increased ageing population and LE

1.Increasing demand for primary, secondary and tertiary health care 2.Increasing complexity 3.Navigating the health and social care divide

Fill in the gaps for the process of fertilisation

1.Sperm enters female tract near CERVIX following intercourse 2.Cervical mucus is normally hostile to sperm --> changes mid cycle to allow sperm entry into uterus 3.Passage of sperm through uterus --> fallopian tube 4.Survival of the fittest --> fertilization window is a few days 5.CAPACITATION: mediated by progesterone release from oocyte à increased motility of sperm and chemotaxis 6.Fusion of egg and sperm within ~24hrs post ovulation 7.ACROSOME REACTION •Digests zona pellucida to allow sperm entry •Hardening of zona pellucida à prevents polyspermy 8.CALCIUM INFLUX •Resumption of meiosis •Release of second polar body 9.Initiation of embryo mitotic cleavage following fusion of maternal and paternal pro nuclei

Fertilisation: recognise the mechanisms of fertilisation

1.Sperm enters female tract near CERVIX following intercourse 2.Cervical mucus is normally hostile to sperm --> changes mid cycle to allow sperm entry into uterus 3.Passage of sperm through uterus à fallopian tube 4.Survival of the fittest --> fertilization window is a few days 5.CAPACITATION: mediated by progesterone release from oocyte --> increased motility of sperm and chemotaxis 6.Fusion of egg and sperm within ~24hrs post ovulation 7.ACROSOME REACTION •Digests zona pellucida to allow sperm entry •Hardening of zona pellucida --> prevents polyspermy 8.CALCIUM INFLUX •Resumption of meiosis •Release of second polar body 9.Initiation of embryo mitotic cleavage following fusion of maternal and paternal pro nuclei

Name 3 causes of FGR

10 Maternal- anaemia, smoking, Diabetes, age under 16 2) Foetal- inborn errors of metabolism, multiple pregnancy 3) Placental- impaired trophoblast invasion

Epidemiology of Depressive Disorder

2-5% adolescents

ELBW (extremely low birth weight)

<1000g. § The last two definitions take no account of gestational age, they simply refer to the weight of the infant at delivery. This is very important - for example, an infant of 2,500g at term would be considered SGA, whereas if delivered at 33 weeks this would be an appropriate weight for a normal infant. § Infants who are inappropriately small at delivery are at increased risk of a range of neonatal complications. In many cases, treatment is best started as soon as possible, so identifying the at-risk infants is important. § It is important to differentiate between infants born preterm, who are of low birthweight simply because they have been born early, and those who are growth restricted; the latter are a greater risk of morbidities and mortality after delivery, and most low birthweight infants are in the former group (and hence at lower risk).

Thecal cells

A layer of cells surrounding the granulosa cells of the follicles in an ovary. Thecal cells help produce the estrogen secreted from the follicle during the first phase of the ovarian cycle. respond to LH.

When does developmental delay present?

Abnormal Development: 1) Causes can include: o Abuse, trauma, drugs, infection. o Autism, deficits in development. o Malnutrition, cerebral palsy, etc. 2) How/when does delay present? o Routine surveillance. o Identified risk factors. o Parents/HCPs worried. o Opportunistic worries raised.

Prediction of eating problems

Adolescent eating problems (symptoms) associated with: § Earlier pubertal maturation, & higher body fat § Concurrent psychological problem e.g. depression. § Poor body image. § Specific cognitive phenotypes

Dating the pregnancy by CRL

All pregnancies should be dated by CRL except IVF pregnancies

Sonic hedgehog (Shh)

An inductive signaling hormone essential for development of the mammalian nervous system; believed to be particularly important for establishing the identity of neurons in the ventral portion of the developing spinal cord and hindbrain.

Implantation of the conceptus

Approximately day 9 post-fertilisation (Figure 3.13), the conceptus is almost completely implanted within the maternal decidualising endometrium. At this stage of development, the outer layer of the conceptus are multinucleated syncytiotrophoblast, which contain fluid-filled lacunae. The underlying layer of cytotrophoblast is proliferating adjacent to the embryo: this is where the placenta will develop.

Bloods and imaging of child for assessment of development

Bloods and imaging: ØFBC and ferritin ØTSH ØChromosomes ØLead ØUS ØCT/MRI

Turner's syndrome

Born with a single X chromosome. (short, webbed neck, different physical sexual development.) § are shorter. give GH and induce puberty in them.

Emergency department (ED) and CGA interaction

CGA takes into account more aspects and much more comprehensive plan.

What is CGA?

Comprehensive geriatric assessment (CGA). § Multidisciplinary assessment: -Medical -Functional -Social -Psychological/psychiatric § Come up with problem list § Then come up with plan

What do the testis contain?

Contains seminiferous tubules (which produce sperm) and Leydig (interstitial) cells which produce testosterone (and some other androgens). Testosterone is released into the circulation, from where it can affect the whole body.

CRH and PAF stimulate what?

Control of labour comes about mainly via CRH and PAF (which then activate other molecules and ultimately MMPs, PGE2 and upregulation of oxytocin receptors). o •CRH and PAF can up-regulate inflammatory pathways in fetal membranes o •Candidate initiators of term human labour

Fetal growth restriction is NOT associated with: A) High resistance umbilical artery Doppler readings B) Preterm delivery C) Increased risk of delivery by Caesarean section D) Neonatal hyperglycaemia E) Neonatal necrotising enterocolitis

D) Neonatal hyperglycaemia

Damage or error theories for ageing

Damage or error theories - accumulation of damage to DNA, cells and tissue. § E.G. loss of telomerases, radiation or oxidative damage. § This theory suggests that we can prevent ageing IF we can prevent this damage. § If restrict diet, then less free radicals, could potentially extend lifespan (worked in mice, but no evidence in humans)

What occurs after gastrulation

Day 17-21. Day 21-28. § After gastrulation has formed 3 layers, the ectoderm proliferates to form the neural plate (with NO proliferation at the neural groove - negative stimulation of notochord) and the neural fold's fold over and form the neural canal. § After day 21, the body cavity then closes by day 28 and pinches off the yolk sac into the umbilical cord (allantois).

fetal growth definition

Definition: Increase in mass that occurs between the end of embryonic period and birth

When does development of lungs begin?

Development of the human lungs begins during the first trimester, but is not completed until after delivery. § Note that the times used are embryological, not gestational ages: the embryonic period starts at week 0 (not labelled, but implied), and Birth is shown at 38 weeks. The production of surfactant begins early in the third trimester of pregnancy (Figure 5.8.1) and gradually increases. Adequate production of surfactant is necessary for normal lung function at birth.

Placental villous development

Development of villi: •Cytotrophoblast proliferate and some fuse with the syncytium (synctiotrophoblast structure) - known as cytotrophoblast column •Branch → villous sprouts •Mesenchyme in the centre of each villus •Where the vascular system develops •Branching continues throughout pregnancy **1.IMPLANTATION of conceptus into endometrial epithelium 2.Trophoblast --> cytotrophoblast (CTB, inner) and syncytiotrophoblast (STB, outer) 3.STB sends out PROJECTIONS to embed onto the endometrium 4.LACUNAE form in STB --> gets filled with maternal blood 5.CTB expansion into STB --> PRIMARY CHORIONIC VILLI 6.Mesoderm line these villi --> SECONDARY CHORIONIC VILLI 7.Embryonic blood vessels form in the mesoderm --> TERTIARY CHORIONIC VILLI 8.CTB cells from the villi grow towards the decidua and form a CTB SHELL (this is the disc of the placenta). This has plugs

Which is outside CTB or STB?

Development of villi: •Cytotrophoblast proliferate and some fuse with the syncytium (synctiotrophoblast structure) - known as cytotrophoblast column •Branch → villous sprouts •Mesenchyme in the centre of each villus •Where the vascular system develops •Branching continues throughout pregnancy **1.IMPLANTATION of conceptus into endometrial epithelium 2.Trophoblast --> cytotrophoblast (CTB, inner) and syncytiotrophoblast (STB, outer) 3.STB sends out PROJECTIONS to embed onto the endometrium 4.LACUNAE form in STB --> gets filled with maternal blood 5.CTB expansion into STB --> PRIMARY CHORIONIC VILLI 6.Mesoderm line these villi --> SECONDARY CHORIONIC VILLI 7.Embryonic blood vessels form in the mesoderm --> TERTIARY CHORIONIC VILLI 8.CTB cells from the villi grow towards the decidua and form a CTB SHELL (this is the disc of the placenta). This has plugs

Differential development of the male reproductive system is dependent on...

Differential development of the male reproductive system is dependent on the activity of sex-determining region Y (SRY) protein, coded for by the SRY gene on the Y chromosome. § The mesonephric ducts give rise to MALE genital ducts. § The paramesonephric ducts give rise to FEMALE genital ducts.

During human development, primitive forms of kidney develop...

During human development, primitive forms of kidney develop (pronephros and metanephros), which do not contribute to the final kidney that develops from the metaneophros. Pic shows this and also shows how the kidney changes position during development, and also the relationship between the nephric tissues and the developing gonad.

Steroidogenesis: recognise pregnancy as a three-way interaction between mother, fetus and placenta with steroidogenesis as an example of this

ENDOCRINOLOGY OF PREGNANCY •hCG peaks around week 9 then rapidly falls •Progesterone, oestrogens (oestriol) and placenta lactogen increase throughout pregnancy 100-1000 fold compared to levels in non-pregnant women *(DRAWING THAT GRAPH WAS A PPQ)*

A summary pic of the process of fertilisation and early human development

Embryological development is usually considered to start with Fertilisation, which leads immediately into Preimplantation Development of the conceptus.

What is FGR?

Failure of the fetus to achieve its predetermined growth potential for various reasons

Domains of social development in puberty

Family development, peer development, friendships, school attainment and parental conflict

Fertilisation summary pics

Fertilisation - pictures flow left --> right: § Cortical reaction - hardening of zona pellucida and exclusion of other sperm. § Picture 3 - meiosis 2 is complete in the maternal nucleus leading to a second polar body and the paternal sperm head undergoes decondensation and expands. § Picture 4 - duplication of both DNA sets occurs to leave 2n chromosomes of both origins.

IUGR (intrauterine growth restriction)

Fetal weight below 10th percentile for gestational age. Failure of the infant to achieve its predetermined (genetic) potential for a variety of reasons.measured by size or umbilical doppler

Early in development embryos of different species look very similar.

Fish, chick, mouse used as model genetic systems to study human diseases - as gene families involved in development are similar. o can use these similarities in other animals to understand more about us. From comparative studies, some careful conclusions can be drawn. o It is necessary to be cautious - should not over-interpret animal links to humans.

Cranial - caudal folding of the embryo

Folding of the embryo occurs both laterally, which fuses the ventral midline (chest and abdomen) of the embryo, and in the anterio-posterior direction, which folds the PGCs into the hind gut, and the developing heart progenitors under the head of the embryo (Figure 5.2.9). the yolk sac retains its contact with the gut. § These changes continue during development of the urogenital system and heart, which continue from weeks 3-4 of development. §By the end of week 4 of development, the precursors of all internal tissues have been laid down, and many external structures are also developing. Development during weeks 5-8 involves mostly the elaboration of the tissues generated during the early weeks. §Urogenital, cardiac, facial and lung development all proceed rapidly during the second month of development. In addition to these structures, limb development occurs over this same time-frame, as the initial limb buds grow, and the terminal regions are converted to hand or foot plates that in turn develop digits.

Definition of obesity

For adults BMI of over 25 kg/m2 is overweight and over 30 kg/m2 is obese. Children have lower BMI than adults and this changes with age so these figures do not apply, and obesity is assessed on the BMI centile position.

Developmental mismatch hypothesis in adolescence

Grey, white & dopaminergic pathway changes increase vulnerability to risk taking. *mismatch between control and reward pathways. There is miscalculation of risks in adolescence. e.g. teenage pregnancy, self-harm.

Dating the pregnancy by HC

HC is used if first scan is done after 14 weeks (CRL>84mm)

What are the two types of IUGR?

IUGR early vs late

Factors influencing growth in childhood

If you plot a child on a centile chart, their current height position on the centile looks at all the growth they have done from conception up to this point. This can be influenced by: 1) Events before birth- poor fetal growth, low birth weight, prematurity. 2) Medical issues in childhood- malnutrition, chronic disease, endocrine problems including growth hormone deficiency. 3) Genetic factors- the height of the family and any inherited disorders of growth. 4) Randomness. Not every child of the same parents will be the same adult height, and tall parents can occasionally have a short child. There are multiple genes which determine adult height, and these are randomly distributed at conception.

In babies who are still-born, .... is the most common identifiable factor.

In babies who are still-born, IUGR is the most common identifiable factor.

Abnormalities in development of the reproductive systems.

In male embryos, the most common mal-developments are the result of either (a) the 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. 1) One example is Androgen Insensitivity Syndrome (also know as Testicular Feminisation Syndrome) (AIS or TFM, respectively). Occurs in genetic males with mutant androgen receptor. There is no or limited virilisation of external genitalia (which show relatively normal female structures). Internally, the mesonephric (Woolffian) ducts are rudimentary or lacking. Testis structure is variable, and they do not descend. AMH production from Sertoli cells is relatively normal, so Mullerian (paramesonephric) ducts regress and no female structures (uterus, oviducts) are present. Note that mild, moderate and complete forms of AIS have been described, which can have very variable phenotypes. 2) A parallel female disorder is Congential Adrenal Hyperplasia (CAH). This usually results from a mutation in Cytochrome P450 21-hydroxylase enzyme (CYP 21A2), so cortisol production from the fetal adrenal is very limited as this enzyme is key in cortisol synthesis. The lack of cortisol means that there is no negative feedback on pituitary ACTH output, leading to high ACTH, and over-stimulation of the fetal adrenals, which make weak androgens (e.g. androstenedione). These cause partial virilisation of the genitalia. The internal systems are female, as there is no SRY (no testicular development), no male ducts (no testosterone) and female ducts develop (no AMH, as no Sertoli cells).

Conjoined twins

Incomplete inner cell mass separation e.g. siamese twins. o extent of conjoining determines their survival.

When does increased impedance in the umbilical arteries become evident?

Increased impedance in the umbilical arteries becomes evident only when at least 60% of the placental vascular bed is obliterated. o high resistance, reverse flow and hypoxia --> acidosis.

Historical data on fetal size

Initial information on the actual size of the fetus, and hence on fetal growth was obtained from miscarriages of pregnancy (Figure 6.3). While the did give information of interest, this did not take account of the possible causative relationship between low fetal growth leading to miscarriage, and hence such data may be inaccurate. It can be seen that fetal weight continues to increase during pregnancy, while fetal length changes less in the later stages.

Dementia vs delirium

It's important to distinguish between dementia and delirium, which are both diagnoses, and terms such as confusion, cognitive impairment, being muddled etc, which are nonspecific and can refer to either. 1) Dementia - chronic, progressive, degenerative; causing a decline in cognition. § Most common types (Alzheimer's and vascular) start with memory problems and progress to include all cognitive functions. § Dementia is more common with increasing age. § Mild cognitive impairment - people that have MILD cognitive impairment, not enough to warrant a dementia diagnosis. 2) Delirium - acute episode of confusion, usually with a clear precipitant (i.e. infection or medication changes). § Usually resolves but can progress to dementia. § Much more common in people that already have dementia.

LE and healthy LE

LE for women is 83, but healthy LE is 64. Hence we want to try and compress morbidity (increase healthy LE) rather than just increase LE. More well-off, more healthy LE.

Regulation of limb development

Limb Development Days 27-56. *Regulation of limb development: 1) Areas: o Shh - Sonic Hedgehog protein - zone of polarising activity. o FGF8 - Fibroblast-like Growth Factor-8 - apical ectodermal ridge. 2) Thalidomide: o Interferes with the blood vessel development which led to apoptosis and death of developing cells. o Amelia - "prolonged exposure" to thalidomide. o Phocomelia - "short exposure" to thalidomide. 3) Another condition that can affect limb development is polydactyly.

The circulation within the fetal heart

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. § The provision of oxygen to the embryo and fetus from the placenta is linked to the main structural difference between the heart in utero, and after delivery. As little blood flow to the lungs is needed, there is a gap between the atria, the foramen ovale (Figure 5.5.2). This allows blood returning to the heart (which is relatively high in oxygen) to pass from the right atrium to the left atrium, thence to left ventricle, from where it is pumped through the aorta to the body. The other major difference is that the main artery from the right ventricle is connected to the aorta by the ductus arteriosus (Figure 5.5.2), diverting blood that would normally go to the lungs into the rest of the arterial system. § At birth, the ductus arteriosus and foramen ovale should close, converting the circulation to the 'figure of 8' system and allowing oxygenation within the lungs.

What is frailty?

Loss of biological reserve across multiple organ systems, leading to vulnerability to physiological decompensation and functional decline after a stressor event. o E.G. young person with mild pneumonia may need AB treatment at home but will recover fine. o E.G. old person with mild pneumonia may end up in hospital because pneumonia causes delirium and reduces mobility. § genetic and environmental factors --> cumulative cellular and molecular damage --> contribute to frailty. e.g. we lose neurones as get older, loss of biological reserve. § divide into mild (basically independent), moderately and severely frail (in nursing home)

How many right and left primary bronchi?

Lung Development Weeks 3-4 (Days 18-28) (Embryonic). § There are 3 right and 2 left primary bronchi. § Surfactant is produced from week 25 PF. § Stages of development are - embryonic (W3-4), pseudoglandular (W5-16), canalicular (W16 -26), saccular (W26-birth) and alveolar (M8-childhood). o From PG --> canalicular, blood capillaries migrate closer to the bronchioles.

Child Growth and Development- Hormonal contr

Main hormonal control is by growth hormone

What are most cardiac abnormalities? Hence what treatment?

Maldevelopment of the heart is relatively common, and can have a severe impact on the infant. As most abnormalities are structural, surgical procedures have been developed to correct some abnormalities. As these complications may become clinically significant at the time of birth (as the blood flow needs to be changed to include the lungs), surgery may need to be done shortly after delivery. *Two examples: tetralogy of fallot and transposition of great arteries.

Midparental height equations

Midparental height equations: § Boys = (Mother's height + Father's height)/2 + 7cm. § Girls = (Mother's height + Father's height)/2 - 7cm. **can see here is that although it looks like he's below the centile, for the genetics, he's normal. correction for the height of parents.

Which drug is most likely to be the cause of a hospital admission? NSAID/opioid/ warfarin/ digoxin/ antidepressant

NSAIDs --> may cause heart failure, GI bleeding etc.

Is social care free in England?

No, it is means tested. Depends on the money you have. This has costs --> people selling homes to pay for care. Workers overworked and underpaid. Low quality of care, market fragility, disjointed care. Postcode lottery. § In Scotland, it is free.

Schematic of the ascent of kidneys during development

Note that the ureters, which connect the kidneys to the bladder, extent in length during this process, retaining the kidney-bladder connections; in contrast the kidneys form new connections with the developing arterial system as they move, so that renal arteries break down and re-form during this process.

Epididymis

One within each scrotal sac. Sperm are released from the testis and stored here prior to ejaculation. At ejaculation sperm pass through the two Vas Deferens (which are contractile), and are mixed with fluid from the seminal vesicles. The fluid then leaves the ejaculatory duct, and passes into the urethra where it mixes with secretions from the prostate gland.

Summary of Placental development (MM)

PLACENTAL DEVELOPMENT: 1. Implantation of conceptus 2.• Development of villi and anchoring 3.• Contact with maternal tissues 4.• Hypertrophy of decidual glands (histotrophic nutrition) 5.• Spiral arteries: a) Remodelling of cytotrophoblast plugs b) Haemotrophic nutrition **STAGES OF DEVELOPMENT in detail: 1) Implantation of conceptus: •Trophoblasts → placenta. •Cytotrophoblast layer. •Syncytiotrophoblast. 2) Development of villi: •Cytotrophoblast proliferate and some fuse with the syncytium (synctiotrophoblast structure) - known as cytotrophoblast column •Branch → villous sprouts •Mesenchyme in the centre of each villus •Where the vascular system develops •Branching continues throughout pregnancy 3) CONTACT OF CONCEPTUS WITH MATERNAL TISSUES: As conceptus invades... 1. Endometrial contact 2. Brief contact with maternal capillaries (Cut off by cytotrophoblast shell) 3. Decidual glands 4. Spiral arteries 4) CONTACT WITH DECIDUAL GLANDS: Histotrophic nutrition • Nutrition comes from glands in the maternal decidua in the first trimester • Conceptus not in contact with maternal arterial blood until end of first trimester •Haemotrophic nutrition 5) SPIRAL ARTERIES: •Invaded by cytotrophoblasts •→ remodelling •Loss of smooth muscle •Can no longer vasoconstricts •Narrow vessels → wide •Can carry more blood to placenta •Cytotrophoblast plug gradually breaks down to expose placenta to maternal blood •NB: Fetus never comes in contact

What is conduct disorder?

Persistent failure to control behaviour appropriately within socially defined rules. § Clinical features: o Loses temper and argues, Tantrums o Defiance o Defies adult requests or rules o Cruelty to animals Destructiveness o Bullies, fights or intimidates o Fire-setting, steals and breaks things o Truanting, runs away ** Developmental considerations - as you develop, these happen which may predispose to conduct disorders: a) Family changes - less direct surveillance and physical closeness. b) Peer changes - increased involvement with peers may amplify ASBOs. c) Experimentation and risk taking - rule violation, drugs and alcohol exposure.

Ageing population - why do we have it?

Population ageing refers to the increasing age of an entire country, due to increasing life spans, and falling fertility rates. Population ageing is simply increasing average life expectancy - life expectancy in increasing in almost country. § this is due to mainly better public health (sanitation, less infectious disease), but also better nutrition, less violence, advances in medicine and better education. o Population ageing reflects the successes of public health policies, education and socioeconomic development, but brings extra burden to society - e.g. cost.

Summary of conversion of an embryo into a morula and blastocyst

Preimplantation development normally occurs within the Fallopian tube (oviduct) over a period of ~6 days, and is characterised by a series of cleavage divisions, which sequentially double the number of cells in the conceptus (2, 4, 8, 16 cells) to produce a ball of undifferentiated cells (the Morula). The Morula differentiates so that the inner cells differ from those on the outside. This then develops into the Blastocyst, a structure that has an outer layer of trophectoderm, an inner cell mass, and a fluid-filled cavity.

Why do preterm infants often suffer from RDS?

Preterm infants often suffer from lung complications due to low levels of surfactant (Respiratory Distress Syndrome, RDS). Delaying the birth of a preterm infant may give more time for surfactant to be produced, and this can be accelerated by an injection of glucocorticoid to the mother, which also increases surfactant production in the infant's lungs. Optimal timings are not fully established, although 24-48 hours between administration and delivery of the infant or infants is often the aim. Artificial surfactant has also been developed, and this can be administered to preterm infants while their lungs develop sufficiently to produce enough surfactant to allow normal function.

Risk of preterm labour on mother

Preterm labour and delivery does not pose any additional risk to the mother; the smaller size of the infant in preterm deliveries may lead to less affect on maternal tissues.

Sexual reproduction definition

Production of offspring that differ genetically from both parents. * Sexual intercourse required for: sexual reproduction, Sexual activity, Sexual pleasure, Human bonding.

Structure of placenta diagram

STRUCTURE § Spiral arteries: provide blood supply to foeto-placental unit. § Placental villous trees- Massive surface area. § Umbilical vessels- As in lung, vein = oxygenated blood, arteries - deoxygenated blood. § Countercurrent flow. § Cotyledon = functional unit of placenta.

Flowchart of oogenesis

Summary: Egg --> meiosis 1: freezes at PROPHASE 1 1 when still inside of mums tummy (remember girls are born with all the eggs they'll ever have). --> once they're born and reach puberty the hormonal changes cause ovulation --> during ovulation, meiosis 1 finishes and the cell is divided into 2 daughter cells BUT one daughter cell gets less cytoplasm (this is the first polar body) --> the big daughter cell then enters meiosis 2 and freezes at METAPHASE 2 --> it then travels down the fallopian tube looking to get fertilized --> if a sperm finds it, there will be a chemical reaction when they touch causing meiosis 2 to finish and release a second polar body. The sperm DNA then enters the the egg (so now you have 2 pro nuclei (one is the mums and one is the dads)).

Abnormal growth despite normal hormones

Syndromes: § turner syndrome XO § down syndrome § skeletal dysplasia o significant illnesses can interfere with growth, because of inflammation, poor nutrition and the effects of drugs such as steroids.

When does embryonic development cease?

Technically, embryonic development ceases after 8 weeks post-fertilisation, as the conceptus is now clearly human, and is therefore classified as a fetus - so fetal development would be the correct terminology. § It is clear that this is more semantic than real, as development of the face, urinary and reproductive systems, and lungs all continue beyond the end of week 8. § Trimesters two and three of human pregnancy are more about growth and maturation of structures, than the development of tissues. This means that tissues will need to undergo changes (increased size and remodelling) as the fetus increases in size from ~7 cm and 50g at the end of the first trimester to ~30cm and 3500g at term.

How many sperm produced a day

Testes produce about 100 million sperm per day, from puberty onwards.

The first week of development after fertilisation

The cells of the embryo are undergoing mitotic (cleavage) division, deriving their nutrients from the secretions of the Fallopian tube.

What does conceptus start of as?

The conceptus starts as a bilaminar disc inside a blastocyst - comprised of an epiblast and a hypoblast layer.

Renal development

The development of the kidney proceeds through a series of successive phases, each marked by the development of a more advanced kidney: 1) Pronephros is the most immature form of kidney. 2) Mesonephros, an intermediate phase. 3) Metanephros is most developed and persists as the definitive adult kidney.

What is purpose of first half of pregnancy?

The first half of pregnancy is a time of preparation for the demands of rapid fetal growth in the second half of pregnancy. Alterations in maternal physiology to facilitate transfer of nutrients to the fetus

Incidence of spina bifida

The incidence of spina bifida is 1-2 per 1000 pregnancies, with variation between study populations. This makes it one of the most common developmental defects.

Hormonal changes during the human menstrual cycle

The key changes in the four main hormones are summarised, showing the time-frames of the changes. Note that the basal body temperature rises slightly (about 0.5°C) around the time of ovulation. 1. Gradual rise of oestradiol by developing follicle (FSH). 2. Follicles grow and -ve feedback on LH and FSH. 3. Dominant follicle selected and produces lots of E2 --> -ve feedback switch to +ve feedback --> LH surge. 4. Ovulation. 5. Corpus luteum produces E2 and progesterone --> -ve feedback on LH and FSH. 6. No fertilisation --> E2 and progesterone fall and endometrium enters secretory phase.

Structure of placental villi at different gestational ages

The overall structure of a placental villus does not change throughout pregnancy (Figure 3.15), but there are modifications. In brief, there are fewer cytotrophoblast present at term, so that there can be a closer apposition between the syncytium and the placental capillaries. This will maximise the efficacy of nutrient transfer into the fetal blood, and enhance fetal growth in later pregnancy.

What are the two main functions of the main reproductive system?

The two main functions are: 1) the provision of androgens (primarily testosterone) to initiate and sustain the necessary male phenotype. 2) production of mature sperm.

Polypharmacy

The use of many different drugs concurrently in treating a patient, who often has several health problems.

Child growth and development- Milestones

These questions come up every year, I would recommend not learning the whole thing just some of the basics they can test you on like number of blocks in the tower at different ages

Paramesonephric and mesonephric duct lead to

UGS Development Weeks 4-8. §Paramesonephric duct - Mullerian ducts --> female ductal systems. § Mesonephric duct - Wolffian duct --> male ductal systems. § The cells that give rise to gametes are primordial germs cells (give rise to eggs and sperm) and are found outside the embryo in the yolk sac to begin with and then they MOVE INTO THE EMBRYO and then move into the developing genital ridges (the gonads are "indifferent" before the PGCs move in and they are identical in males and females to begin with).

Abnormal development of UGS

UGS Development Weeks 4-8. Abnormal development - structural or due to changes in or responses to, hormones. 1) Hypospadias - fusion of urethral folds' incomplete - urethra exits penis early. 2) Mullerian duct anomalies (abnormal fusion of ducts) - e.g. two uteruses. 3) Persistent Mullerian duct syndrome (males): o Occurs in males with mutations in AMH/MIS or receptor. § No inhibition so paramesonephric ducts persist. § Testis either sit by ovaries or one/both can descend. o Testosterone/DHT is produced so normal external genetalia/ducts. 4) Androgen Insensitivity ("Testicular Feminisation") Syndrome (males): o Occurs in genetic (XY) males with mutations in the androgen receptor. o Lack of virilisation (androgens have no effect on receptor). § Normal female external genetalia but undescended testes. § Mesonephric ducts rudimentary due to loss of testosterone. § Normal production of MIS from Sertoli cells causes Mullerian duct regression so not oviducts, uterus or upper 1/3rd of vagina. 5) Congenital adrenal hyperplasia (female analogue to AIS): o Occurs in genetic females with no 21-OH enzyme (no cortisol). § Causes overproduction of ACTH and overactive adrenal glands. o Leads to increased weak androgen production (DHEAS) à weak virilisation. § Enlarged clitoris, partial or complete labia majora fusion. o Internal genetalia are all female - testes absent (no SRY), no mesonephric ducts as no testosterone to support, no AMH/MIS so Mullerian ducts persist.

When does UGS development occur

Weeks 4-8.

Pic summarising the events that take place during fertilisation

While this figure 2.18 summarises the events that take place during fertilisation, it is far too simplistic, and omits many of the key events that take place during fertilisation. In addition, it is in error in suggesting that there is an 'egg nucleus' - that should be an egg (oocyte for preference) pronucleus; also the 'nuclei' do not 'fuse'. This is included to remind you that information may be incomplete or wrong, even though it has been published

Can we treat frailty?

Yes, we can, but difficult: •Exercise mainly ! •Nutrition - increase protein intake •Drugs (possibly) § Depends on the type of frailty too (mild, moderate or severe). **Prevention is better than cure! ** not all old people are frail: only 30% are.

Can we prevent dementia?

Yes, with diet, exercise, stopping smoking and alcohol.

Hormonal control: draw a diagram to illustrate fluctuations in hormonal levels over the menstrual cycle, including oestradiol, progesterone, luteinizing hormone and follicle stimulating hormone

You need to know two cycles: OVARIAN & ENDOMETRIAL 1.OVARIAN CYCLE: •Main phases: follicular, ovulatory, luteal a) Follicular: § Development and growth of several follicles (although only one is selected to ovulate) § Stimulated by FSH § Leads to increased production of oestrogen which inhibits FSH and LH secretion b) Ovulatory: § Follicle continue to grow, producing more oestrogen. § Dominant follicle is selected for ovulation § Oestrogen begins to stimulate secretion of LH and FSH of pituitary leading to LH surge in ovulation c) Luteal § After ovulation, follicle develops into corpus luteum § Corpus luteum produces progesterone (and some oestrogen) 2) ENDOMETRIAL CYCLE: •Main phases: menstrual, proliferative, secretory a) Menstrual § Day 1-5 of cycle § Shedding of blood and endometrial lining of uterus § Remaining basal endometrium very thin 2) Proliferative and repair - ESTROGEN: § Day 5-14 of cycle § Stimulation of endometrial cell proliferation, increase in thickness, increase in number and length of glands, increased in length of arteries 3) Secretory - PROGESTERONE: § Day 15-28 of cycle § Production of nutrients and other factors § Epithelial glands widen, endometrium thickens, increased coiling of spiral arteries. Endometrial lining maintained by progesterone **Importance of PROGESTERONE: •If there is no pregnancy, progesterone falls and endometrium sheds → menstruation again. •If there is a pregnancy, corpus luteum will continue to maintain progesterone levels → no menses.

ZPA (zone of polarizing activity)

a small block of mesodermal tissue near the posterior junction of the young limb bud and the body wall that specifies the anterior-posterior axis of the developing limb through the action of the paracrine factor Sonic hedgehog; right below AER. Sonic Hedgehog (shh) is the polarizing factor for limb development. o controls pattern of limb and digit development.

History in child development

a) Antenatal - illnesses/infections; medications; drugs; environmental exposures b) Birth -Prematurity, Prolonged/complicated labour c) Postnatal - illnesses/infections; Trauma d) Consanguinity - increases chances of chromosomal or autosomal recessive conditions e) Developmental milestones from parent

Examination in child development

a) Growth parameters - height, weight and head circumference b) Dysmorphic features c) Neurological examination and skin d) Systems examination to identify associations, syndromes e) Standardised developmental assessment - SOGSII, Griffiths

The pleasure pathway has a role in human bonding and parental behaviours The mesolimbic dopaminergic system links the pleasure, reward pathway with the fertility and parenting pathways. a)TRUE TRUE (REASON) b)TRUE TRUE (NOT REASON) c)TRUE FALSE d)FALSE TRUE e)FALSE FALSE

a)TRUE TRUE (REASON)

•a. List 3 advantages of MOCA (3) •b. List 3 disadvantages of MOCA (3) c. 4 things to consider when doing cognitive test on elderly (4)

a. List 3 advantages of MOCA (3)Easily and quickly administered, covers several domains and is readily available b. List 3 disadvantages of MOCA (3)Ceiling and floor effects (the test is too hard or too easy) , education level may affect results, test can be poorly administered c. 4 things to consider when doing cognitive test on elderly (4)They may have shorter attention span, the may have slower processing and reaction time, hearing impairment, visual impairment and physical problems can affect their ability to write. Moca also assumes the patient is literate- educational effect

Incidence of anencephaly

compromised development of the head and skull is a rarer complication, with an incidence of ~0.2/1000 births. The general aetiology is thought to be similar to spina bifida, though the result of a lack of closure of the anterior neuropore. Some studies have suggested that folic acid can also decrease the incidence of anencephaly, although the smaller numbers make it difficult to determine the scale of the benefit.

Ductus venous

connects the umbilical vein to the inferior vena cava. in fetal circulation, allows oxygenated blood from placenta to bypass the liver.

Intersex

describes sexual development that is neither 100% female or 100% male, and may not match the chromosomes present in the cells of the individuals. It is estimated to occur in ~0.5/1000 births. This is a complex and controversial topic, so the focus will be on describing what can be observed.

What are the five phases of lung development?

embryonic, pseudoglandular, canalicular, saccular, alveolar

Cause of spina bifida

failure of the osseous spine to close - neurulation

Why is obesity an issue?

fat children --> fat adults. § widespread § prevalence is high § consequences are costly **Worldwide obesity figures: § Obesity is getting more common although there are still a lot of adults and children in the world who are undernourished. § However looking at the statistics tells us that the situation is quite complicated: a) Rates of obesity and overweight have increased but may not continue to go up at the same rate for the future b) There are some nations who have a much higher rate of obesity than others. There are some cultures where overweight has traditionally been seen as a desirable feature indicating wealth and high status. In some areas of the world obesity is a feature of poverty and in others associated with affluence. c) Some ethnic groups have less "tolerance" of obesity and are more likely to get complications like type 2 diabetes at a lower BMI

Obesity and eating disorders

for obese people --> more eating disorders

LD score regression

genetic correlations between AN and diverse phenotypes. o often genetics are in combo with individual environment

What makes us age differently?

genetics, where we live, health behaviours (diet, exercise, alcohol, smoking), access to health care

historical data derived from failed pregnancies (e.g. miscarriages and still-births) has been superseded by...

historical data derived from failed pregnancies (e.g. miscarriages and still-births) has been superseded by data derived from ultrasound imaging. §Initial information on the actual size of the fetus, and hence on fetal growth was obtained from miscarriages of pregnancy. While they did give information of interest, this did not take account of the possible causative relationship between low fetal growth leading to miscarriage, and hence such data may be inaccurate. It can be seen that fetal weight continues to increase during pregnancy, while fetal length changes less in the later stages. Such summaries have now been replaced by data from in utero scanning.

Social care changes

less funding to social care. Workers are also paid less. Often workers are migrants from outside UK.

genetic material during fertilisation

male DNA decondenses and forms male pronucleus and female pronucleus. both duplicate (2n) and then undergo mitosis and align together--> 2 diploid cellS. *after fertilisation: ØMeiosis of maternal chromosomes resumes, forming female pronucleus (23 chromatids), and 2nd polar body. Ø Sperm chromosomes decondense to form male pronucleus (23 chromatids). Ø Chromatids in both pronuclei are duplicated Ø They align on the mitotic spindle, and are separated into 2 identical 'daughter' cells (1st cleavage division of the embryo).

Oligodactyly

missing digits

fetal weight during pregnancy

most in 2nd/third trimester

Dementia prevalence

much is undiagnosed. West London is pretty good. § Rates of dementia diagnosis have been low historically due to - only 70% of those with dementia are diagnosed: o Misinterpretation - older people have worse memory anyway. o Fatalism - can't do anything about it so no reason to diagnose it. o Social isolation - so no one notices it.

What type of disease dominates global burden of disease in adolescents?

non-communicable diseases (NCDs)

Disease presentation in older age

non-specific presentations - presentations where the underlying pathology is not immediately obvious, or clearly linked to the presentation. Falls, delirium and reduced mobility are all very common reasons for older people seeking medical attention, and can be due to a huge variety of underlying problems, including stroke, myocardial infarction, infections and changes to medications. § Older people are more likely to have an atypical or non-specific presentation of a disease. o Atypical - symptoms of pathology don't immediately link to the disease - i.e. falls, delirium. § "Giants of geriatric medicine" - immobility, intellectual impairment, instability, incontinence, iatrogenic (problems due to receiving healthcare) problems. o Non-specific presentations - symptom is attributed to another cause or "old age" --> delays in treatment.

Can we prevent ageing?

not much can do about DNA or inheritance. But can limit free radial production (eat healthily), alcohol, smoking and do exercise. Can see people who were most unhealthy had lower LE.

Developing brain at 8 weeks

now also have cerebellum. cerebellum grows 4 times it's size in first year of life. responsible for movement and gait. *brain is underdeveloped so it can pass through pelvis during birth

Fetal growth velocity

o 14-15 wks: 5g /day o 20 wks: 10 g/day o 32-34 wks: 30- 35g/day o >34 wks: growth rate decreases

Carnegie Stages of Human Development

o 23 stages - A summary of the stages in the development of a fertilised human oocyte, to an embryo, to a fetus. This is the process through which a single cell (fertilised human oocyte) develops into a recognisable human being over a period of about 8 weeks.

CMV in pregnancy

o 30% risk of transmission of CMV in pregnancy and the risk to the baby is highest in the first trimester. o Normal outcome or associated with neurodevelopmental delay and deafness. o Cannot be excluded by ultrasound alone. o Amniocentesis: for CMV PCR. o Ideally >6 weeks from the point of infection. o Miscarriage (0.5-1%) or rupture of membranes. o Patient is committed to pregnancy and declined invasive testing

Pentasomy X

o 49,XXXXX, is a rare chromosomal abnormality in which a female has five X chromosomes instead of the normal two. o Variable phenotype. o Signs may include intellectual disability, short height, low-set ears, decreased muscle tone, and developmental delay

Chromosomal translocations

o Altered distribution - translocations. 1) XY linked: -"XX male" - XY translocation 2) Autosomal: -Linked with development of tumours; lymphoma; leukaemia; sarcoma

Obstetric Ultrasound Examination assess what

o Assessment of fetal "wellness" not just size o Looking at trends in growth o Predicting fetal metabolic compromise o Anticipating the need to deliver prematurely o Liaising with Neonatal Services

Anorexia nervosa cardinal features

o Cardinal features: § Body weight is maintained 15% below expected weight (or BMI < 17.5). § Weight loss is self-induced § Psychopathology - dread of fatness and preoccupation with this. § Endocrine abnormalities - amenorrhoea, delayed growth (in younger people).

Causes of Anorexia Nervosa

o Causes - genetics, perfectionism, temperaments, subcultures, abuse and adversity, high social class.

Cervical changes during labour

o Cervical ripening (becoming softer and flexible) and dilatation (becoming thinner and being stretched sideways). o This requires extensive remodelling of the extracellular matrix of the cervix, a process that can take many hours. This process is also accelerated by the increasing pressure of the fetal head on the cervix, caused by the increasing strength and decreasing gaps between myometrial contractions.

Anencephaly

o Defect in skull and brain development o Incidence: 1 - 8 per 10,000 births •Female babies affected more commonly than male o female babies more affected. o Folic acid (given at the right time) may show benefit o Implies similar causes to spina bifida o Anterior neuropore closure incomplete

Initiation of labour (term vs pre-term)

o During term - not sure - may be oestrogen: progesterone high ratio, CRH or oxytocin. o Pre-term - intrauterine infection, bleeding, multiple pregnancy, stress (maternal).

Factors affecting child development

o Environmental causes of damage to brain development: § Antenatal - infections maternally, toxins, drugs: · Infectious agents - TORCH - Toxoplasmosis, O (Syphilis/HIV/HepC), Rubella, Cytomegalovirus, Herpes. · Hormones - androgenic agents, DES, maternal diabetes, maternal obesity. · Drugs - listed above right - focus VALPROIC ACID and ALCOHOL. § Postnatal - infections, metabolic disorders, toxins, trauma, domestic violence (maltreatment), malnutrition, maternal mental health disorders.

Epidemiology of Anorexia nervosa

o Epidemiology - ~0.5-1.0% of adolescent females (only 10% of sufferers are male).

Achondroplasia- gene found in both animals and humans.

o Gain of function mutation in FGFR3 - seems paradoxical. o Achondroplasia means "lack of cartilage" o Defect is in conversion of cartilage to bone & lack of bone growth. o dramatic shortening of long bones - esp. legs and arms.

Regulation of the male reproductive system

o GnRH released from hypothalamus. o stimulates release of LH and FSH from anterior pituitary. o Leydig cells have LH receptors and produce testosterone which stimulates spermatogenesis, has other T effects and negative feedback on pituitary and hypothalamus. o Sertoli cells in seminiferous tubules have FSH receptors. Release ABP (regulates spermatogenesis) and Inhibin (-ve feedback). *A complex interplay between hypothalamic, pituitary and gonadal factors is needed to control the normal production of human sperm.

Short and long term sequelae of FGR

o IUGR is the most common factor identified in stillborn babies. o In addition, it has serious consequences for babies who survive. o Furthermore, there is an increased risk of IUGR and intrauterine death (IUD) in mother's subsequent pregnancy.

Multiple pregnancy & chimerism

o Identical twins / triplets: one conceptus forms 2/ 3 inner cells masses --> 2/3 genetically identical individuals o Chimerism: 2 genetically distinct conceptuses combine to form one individual (pic shows changes in skin from response to different genes - Blaschko's lines). so 2 genetically different patterns in one person.

Bulimia nervosa

o Like anorexia nervosa but involves a preoccupation with eating and then involves purging.

Median and limit age

o Median age - age when half of the standard population of children achieve that level. o Limit age - age by which they should have achieved the level and is equal to 2 S. Ds from the mean age. § Both corrected for prematurity until age 2.

Mosacism

o Mosaicism (non disjunction) - differences between cells within one individual e.g. calico cats (males can't show three colours), heterochromia

Folliculogenesis - oogenesis

o NB. Looks monthly, but is not monthly. o Meiosis incomplete within the ovary Folliculogenesis (INSIDE THE OVUM). 1. Oogonia: 44+XX (diploid). a. Mitotic division. 2. Primary oocytes: 44+XX (diploid). a. 1st meiotic division. 3. Secondary oocyte: (+polar body) 22+X, 22+X (haploid). a. 2nd meiotic division. 4. Ovum: (+ polar body) 22+X, 22+X (haploid). Note - 1st meiotic division is linked to the LH surge, meiosis 2 follows immediately after this BUT pauses in metaphase 2 (as shown). Note - the second polar body is generated after the 2nd meiotic division which occurs in the fertilised cell. **Folliculogenesis - Important Points: o egg development acc starts before birth. § Time taken for primordial follicle --> secondary oocyte is MORE than one month. o The human ovary contains multiple follicles at ALL stages of development with one dominant (Graafian) follicle at any one time. o It takes more than 2 complete cycles for initiated egg to be released (3 menstrual cycles). The ovaries alternate the release as well (so each one releases one follicle each ~56 days). § Human ovaries contain 2m primordial follicles at birth --> only 400 released at ovulation in a lifetime. § During meiosis, both the 1st and 2nd divisions are paused during follicular development. o Meiosis 1 starts during embryonic development, but halts at diplotene stage of prophase 1 (primary follicle) which is arrested until puberty (meiosis then resumes and 2nd follicles develop). o 2nd follicles then undergo a second arrest. § Key points: o Ovaries - contain ~6m primordial follicles at ~20w development à ~1m at delivery of infant. § 400 released over a lifetime. o Testes - produce 100m sperm/day from puberty onwards.

Two theories for onset of puberty

o Onset of puberty is due to two theories: 1) Maturation of the CNS affecting GnRH neurones (increased pulsatile release). 2) Altered set-point to gonadal steroid negative feedback. o Not sure what triggers this but may be environmental. There is evidence of a secular trend towards earlier puberty which suggests environmental factors: a) improved health care. b) improved socio-economic factors (photoperiod? nutrition?) **Menarche - the first occurrence of menstruation. o Has decreased over the last 150 years but seems to have been levelling off recently. § Possibly decreased due to nutritional reasons. o Body weight at menarche has remained relatively constant at ~47kg over those years. **Adrenarche - early sexual maturation stage (10 or 11) when DHEA DHEAS is made without cortisol.

Respiratory distress syndrome

o Respiratory distress syndrome (RDS), respiratory distress syndrome of newborn (RDSN), surfactant deficiency disorder (SDD); previously called hyaline membrane disease (HMD). Overall incidence: ~1% of all births; ~100% at GA 24 weeks; ~50% at GA 26-28 weeks; ~25% at GA 30-31 weeks.

Kinetics of surfactant production during pregnancy

o Surfactant: lipids, proteins and glycoproteins. builds up to birth and increases even after. o In utero production can be increased by 1 injection of glucocorticoids (2-3 days) - so give injection in premature infant and aim to deliver in next couple days.

What are teratogens? What are the different types of agents?

o Teratogen: Any agent that can disturb the development of an embryo or fetus a) infectious agents e.g. rubella, HSV, HIV, syphilis, zika b) physical agents - X-rays and other ionising radiation c) chemical agents - thalidomide, lithium, amphetamine, cocaine and alcohol.

Definitions of development

o The global impression of a child which encompasses growth, increases in understanding, acquisition of new skills and more sophisticated responses and behaviour. o A dynamic process of growth, transformation, learning and acquisition of abilities to respond to and adapt to the environment in a planned, organised and independent manner. o A process by which each child evolves into an independent adult.

The increases in progesterone, oestrogens and human placental lactogen parallel the...

o The increases in progesterone, oestrogens and human placental lactogen parallel the increased size of the placenta, and a range of studies underline the importance of the placenta in producing these hormones. It must be emphasised that hCG is also produced by the placenta, but regulation of its production is obviously very different, as the peak production is in the first trimester. § Human Chorionic Gonadotrophin (hCG) shows peak levels in maternal plasma in the first trimester, and declines thereafter, while the other main hormones (or hormone families) increase as pregnancy progresses. § Levels of progesterone (up to 1µM) and estrogens (up to 20nM) greatly exceed the levels seen during the normal menstrual cycle, so they may have potent effects on the maternal system in pregnancy. The very high levels of progesterone are of particular importance, as progesterone is the key hormone in allowing the pregnancy to continue. Low progesterone levels, or administration of a progesterone antagonist, will lead to loss of the pregnancy at all gestational ages. § The maternal endocrine system is modified substantially during pregnancy, with the high levels of steroids suppressing the HPG, leading to very low levels of LH and FSH throughout pregnancy, and hence no cyclic ovarian or uterine functions.

Fetal Growth Restriction (FGR) determination

o The term FGR should only be used for fetuses with definite evidence that growth has altered. o Growth is a dynamic process of a change of size over time and, therefore, it can only be assessed by serial observation. minimum 10-14 days?

Small for Gestational Age (SGA)

o The terms 'small for gestational age' (SGA) and 'small-for-dates' are statistical definitions of weight at birth (below a subjective centile on charts of birth weight standards). o The centiles most commonly employed are the tenth, fifth or third.

treatment of anorexia nervosa

o Treatment - family intervention, cognitive behavioural therapy (for abnormal eating attitudes and depression), (small %) need admission for weight restoration. o Outcome: § Community sample 50% recover after 5 years. § Clinic sample 37% recover, 25% weight gain (no menstruation), 37% still underweight (with symptoms) after 1 year.

Genes in man, mouse, flea

o We do not always know the details of causes and effects in humans. o Models can give insight but - differences in genes o in humans, microbiome contributes greatly to how our body works.

Choosing centiles

o When choosing which centile to use, a balance between sensitivity and specificity is being made - the tenth centile is most sensitive and the third centile is most specific. o The tenth centile will capture all babies with FGR, but will also include those babies that are just small for gestational age, i.e. you get a number of false positives. o All babies recorded using the third centile will have FGR, but some FGR babies may be missed, i.e you get a number of false negatives. § Age on x-axis and weight on y-axis. § The 10th centile is most sensitive and the 3rd centile is most specific.

How used to measure fetal growth externally

o abdominal palpation o Symphysis fundal height

Holt-Oram syndrome - gene found in both animals and humans.

o atrial septation defects and oversized heart o hand abnormalities -thumb is developed like a finger in one hand, in other hand thumb is relatively normal. o Phenotype due to mutation in TBX5 (transcription factor) - required as both structures develop. has variable effects. can cause different effects within same person.

Why is getting fat bad for you?

o barker hypothesis o when relate BW to risk of death - see correlation. risk of death if UW, OW or obese. § Overweight and obesity makes you more likely to get a range of disorders including type 2 diabetes, cardiovascular disease, some cancers, orthopaedic problems.

Cleft lip formation due to

o cleft lip formation normal part of face formation, they are then filled in. o cleft lip usually off-centre and cleft palate usually centrally placed (tissues aren't meeting up and joining together) o failure of fusion of the maxillary and medial nasal process...formation of primary palate. § It seems that repeated formation of clefts in the face, and then filling in of the clefts, leads to sequential loss of tissue from the centre of the face, and the movement of tissues to the correct places.

Fetal growth and development during pregnancy

o diminished supply of nutrients is main cause for decreased growth

Fetal side of placenta

o disc 20cm across o fetal membrane around it that surrounds amniotic fluid that keeps baby safe during pregnancy. o umbilical cord connects to fetus.

Placental villous tree

o early pregnancy starts as simple branched structure o as pregnancy proceeds, the branched structure gets more complex, convoluted and longer with a larger SA.

normal face formation

o faces develop in two halves o eyes start where ears are, ears are by necks and nose in front. o eyes move to front by week 10 o loss of frontonasal prominence in controlled way --> nose moves centrally and eye moves centrally o part of this formation involves developing clefts in top lip, and then they're filled in as tissue breaks down. § The primary structures of the face form on the sides of the head - for example the eye. This pattern persists until at least 5 weeks post-fertilisation.The precursors of the nose, cheeks, lips, mouth and chin are also formed during this time period. These structures then move over a period of about 5 weeks until the reach the expected positions, with the nose centrally placed, and the eyes facing forwards on the face. his requires the movement of pre-existing structures (e.g. eyes) through the tissues of the developing face, a process that is not fully understood. § The development of the facial tissues on the separate sides of the head is common in vertebrate development; most fish and birds retain this arrangement, with the eyes remaining on the side of the head into adult life. There are exceptions - birds that hunt for moving prey (e.g. raptors and owls) have varying degrees of binocular vision.

Baby (start to finish)

o fertilised egg - has 2 polar bodies, zona pellucida and some attached cells on outside. o baby

Why can the results be so good for cleft lip?

o healing process is v rapid and often without scarring

Fetal organ growth

o heart and kidney grow gradually. o brain and liver grow steeply and then decrease in third trimester o doubling of DNA each week

Why uterus must contract at end of pregnancy?

o in uterus there is remodelled spiral arteries o when placenta delivered, these blood vessels are open into uterine cavity and they don't have VSMCs to contract and be closed. o uterus must contract to stop mother bleeding out. placenta must be delivered as it's keeping these spiral arteries open, so need to make sure all delivered.

Polydactyly interesting case

o initially think there just fusion in middle o but acc there's 4 digits and 2 thumbs on each side with central fusion

pre-eclampsia and IUGR

o lose VSMC to allow it to open much more. o for pre-eclampsic- spiral arches are very narrow and hence higher resistance to get the blood through. § There is a close link between IURG and pre-eclampsia. o Due to main cause of pre-eclampsia is diminished remodelling of spiral arteries by cytotrophoblasts. This causes decreased blood flow and hence decreased nutrient supply to the placenta and foetus. § Pre-eclampsia - hypertension and proteinuria. o Occurs in ~5% of pregnancies.

Maternal side of placenta

o made up of cotyledons (basic unit), each contains one or more villi. o gaps between cotyledons caused by maternal tissue o around 30-60 of them in a placenta. o bigger in middle of centre o can see maternal blood clotted too.

Can we predict which fetuses become growth restricted ? What sort of "host" is the mother ?

o maternal history

survival and short-term morbidity in preterm infants

o morbidity = respiratory distress, sepsis, intraventricular haemorrhage, necrotising enterocolitis. o good survival rates - baso 100% at 30 weeks

changes in the female HPO axis in menstruation cycle (ovarian cycle)

o ovarian cycle - diff from menstrual cycle (which occurs in uterus). o GnRH from pituitary --> Lh and FSH --> estradiol which negatively feedbacks on hypothalamus and pituitary. o midcycle - estradiol is now a positive regulatory instead. GnRH and FSH/LH are increased and get increased estradiol again much. o after ovulation - progesterone produced and this is again negatively feeding back. **midcycle is where there is change in feedback.

Factors which affect the developing human at any times in the lifecyle?

o prenatal, perinatal or postnatal: nutritional aspects (folic acid), teratogens (alcohol - fetal alcohol syndrome)

Spina bifida

o protrusion of tissue from spine classically at base of spine o bulge of tissue may just be CSF or contain neural tissue. o neural tissue > spinal cord directs formation of spinal bones. •Incidence: 1-2 per 1000 pregnancies. •Surgery can help anatomical, but not functional problems

Development & teratogens

o sites and timing of actions of teratogens in early development. o teratogens derange development. o embryo most vulnerable during first trimester (before 8 weeks) when tissue is developing most rapidly, but CNS is v vulnerable even later. o Other complications of human development, including spina bifida and cleft palate, also occur in this early stage of development. o All these risks are mainly in the first trimester of pregnancy. There are few known risks to the fetus specifically in the second trimester. The main risks to the fetus in the third trimester are those concerned with birth.

Pregnancy lengths

o smaller species tend to have shorter pregnancy lengths. o but depends, because whales have relatively short pregnancies.

Thalidomide‐induced limb defects: resolving a 50‐year‐old puzzle

o thalidomide messed up BV development in developing limb --> cell death. if short-exposure it recovers, it long-exposure it causes widespread cell death. o •Thalidomide - affects rapidly developing blood vessels, thus depriving the adjacent cells of nutrients and preventing their proper growth and development. In humans, it seems that the timing of thalidomide administration (8 weeks of pregnancy onwards, as this is the starting point for severe cases of morning sickness), matches with upper limb development, 6 weeks post-fertilisation. § Also the upper limb blood vessels seem to be particularly sensitive to thalidomide, giving rise to the decreased limb development often observed. o Blood vessel affects can be generic, hence the range of effects observed. o •Still used to treat leprosy and some cancers - in parts of Africa

Maternal changes during pregnancy

o usually increased BP and blood clotting tendency go together; but in pregnancy they go opposite directions. § Main maternal changes: 1) Increased weight - (+10-15kg) - baby, placenta, amniotic fluid, increased fluid retention, increased stores. [3rd trimester] 2) Increased hormone levels - hCG, progesterone, oestrogens, lactogen. [1st and later] 3) Increased body temperature - possibly by thermogenic role of progesterone. Also, mediated by increased foetal size. [increases in 2nd half of menstrual cycle, reverses during menstruation, and is sustained into the first trimester]. 4) Increased blood volume and clotting - protective against losing blood at delivery. [2nd and later] 5) Decreased BP- is lowest during 2nd trimester and is why pregnant women should not stand for long. [2nd trimester] 6) Increased breast size - changes start in 1st trimester and continue throughout - due to all hormones! 7) Increased vaginal mucus- more clear mucus produced. 8) "Morning sickness" - affects 80%, more severe version is "Hyperemesis gravidarium". Unknown cause but maybe linked to hCG levels being high in the first trimester. 9) Altered brain function- due to high levels of steroids, such as progesterone. size of the brain decreases very slightly, but this may not be of functional significance. 'baby brain'. [1st and later] 10) Altered appetite - due to +height of uterus fundus, stomach may be impinged. This can decrease the distensibility of the stomach, and in late pregnancy the mother may need to have up to 6 smaller meals per day, rather than 3 bigger meals. [1st and later] 11) Altered fluid balance - kidney functions change --> ~50%+ in blood plasma fluid volume by term. Urinary frequency increases 1st trimester, normalises in 2nd and increases in 3rd. The changes in the first trimester are generally thought to be due to changes in the maternal hormones, regulating altered kidney function. Increasing abdominal size also puts pressure on bladder so more frequent urination in 3rd trimester. [2nd and later] 12) Altered emotional state - due to hormone levels and can vary in people (e.g. happy --> post-natal depression) [1st and later] 13) Altered joints - changes in pelvis to make connections more flexible to permit child-birth. [3rd] 14) Altered immune system [1st and later]- 2 main points should be considered: a) Production of factors - suppress the maternal immune system from the utero-placental interface. This results in a reduction of Th1 responses and increased Th2 responses. b) Placenta expresses unusual HLA - placental HLA are almost invariant (HLA-G has 5 known sequence variants - normal HLA-A and others have millions of variants) and very simple. This is thought to identify the tissue as human but due to its simplicity, no other information is given. HLA-G can also supress some leucocytes and down-regulate maternal immune responses. **The first eight items in the list show clear directionality of change (increase or decrease), whereas the others are all affected as pregnancy progresses, but vary between individuals. The extent of the changes varies at different times within the 9 months of pregnancy, so it is important to identify the way that the timings in pregnancy are organised.

Delivery in pregnancies complicated by FGR

o • Timing delivery in these pregnancies depends on balancing the risks to the fetus if it remains in utero and the hazards from the prematurity, which decrease as the gestation advances. o Evidence of fetal compromise on CTGs or abnormal Dopplers/ ultrasound finding / maternal compromise. o Corticosteriods should be administered (if not already given) at gestations < 36 weeks in order to improve neonatal wellbeing

What are other names for birth defects?

o •Birth defect = congenital malformation = congenital abnormality o •Changes in the PATTERN of development o Teratology or dysmorphology o Major abnormalities ~3% of pregnancies (cause 25% of infant deaths. o Minor abnormalities ~15% (little health impact)

Placenta period

o10-12 weeks is the period of placentation. o Rapid early growth prepares way for fetal growth. o Trophoblast cells use same molecular mechanisms as tumors, but are highly regulated and controlled. o Maintains immunological distance between mother and fetus. o Special endocrine organ: produces protein-peptides and steroid hormones and functions as a "transient hypothalamo-pituitary-gonadal axis". o Responsible for exchange of nutrients, gases & metabolic waste products between maternal and fetal circulation

Cerebral palsy

paralysis caused by damage to the area of the brain responsible for movement. cerebrocortex damage. § cause can be prenatal due to infection or trauma. § - walk on toes (lot of flexion) - balance of extensor and flexor is impaired. due to inhibitory pathways are affected.

Why do we measure growth?

poor growth in infancy is associated with high childhood morbidity and mortality. § growth is best indicator of health § demonstration of normality of growth by age and stage of puberty. § identify disorders of growth. § assess obesity

Spermatogenesis

production of sperm cells (in testes seminiferous tubules). 1. Germ cells: 44+XY (diploid). a. Mitotic division. 2. Primary spermatocyte: 44+XY (diploid). a. 1st meiotic division. 3. Secondary spermatocyte: 22+X, 22+Y (haploid). a. 2nd meiotic division. 4. Spermatids :22+X, 22+Y (haploid). 5. Spermatozoa: 22+X, 22+Y (haploid). 200m sperm/day, starts at puberty. **keeps on during life of man. millions of sperm produced a day and many can acc be faulty (96%), but because so many produced its okay.

Which of the following is normal in a 70 year old? poor short term memory/ poor autobiographical memory/ reduction in problem solving ability/ getting lost in a familiar environment/ forgetting how to work a TV they've had for 10 years.

reduction in problem solving ability - part of executive function in frontal lobe. There is small reduction in executive functions as get older. this starts around age 45. The other ones symptoms not normal often seen in dementia. Poor autobiographical memory is acc a rare symptoms, usually those with dementia acc usually are good at this.

Anti-social behaviours vs delinquency vs conduct disorder

same thing defined by different fields. § Anti-social behaviour - defined by society. § Delinquency/offending - defined by the law. § Conduct disorders - defined by psychiatry.

Frailty and death

scores 1 -3: not frail. score 4: pre-frail. score 5-7: mild, moderate, severe frailty, If frail, are 4x more likely to have died or end up in institutional care during observational study.

Protective reflexes

seen in table in and develop FROM 5 months.

What is SGA?

small for gestational age: birth weight < 10th centile.

Doppler ultrasound

study that uses high-frequency sound waves for detection of blood flow within the vessels.

Pubertal changes in boys and girls

tanner stages of puberty (there are 5). § variation in which age these occur.

There are 4 main organs or systems in the fetus that develop relatively late in pregnancy, during the last few weeks...

the lungs, the digestive system, the immune system and the brain. § The fetus has limited need of them in utero, whereas they become much more important after birth, so their late development is logical. However, this means that in a preterm infant, they may not function correctly, and thereby cause illness or death to the infant.

granulosa cell

the majority of the cells surrouding an oocyte in a follicle. Granulosa cells secrete estrogen during the follicular phase of the ovarian cycle (before ovulation). respond to FSH

Can we prevent frailty?

with controlling exercise, diet, smoking and alcohol

Sandwich generation

§ 1.25m sandwich carers in the UK: •caring for an older relative •whilst bringing up children § 68% are women women § 78% are also in paid work § 88 000 (84% women) provide more than 35h of care/week

Puberty, marriage and childbirth timings

§ 1950s: puberty later and marriage earlier

How many children have special educational needs?

§ 20%. 2% have severe disability.

Development of embryological structures in first 8 weeks

§ 2nd week - Development of bilaminar disc. § 3rd week - Formation of trilaminar disc (mesoderm), CNS & somites.Blood vessel initiation. Formation of placental villi. (3mm). § 4th week - Closure of neural tube. Heart, Face, arm initiated. Umbilical cord. Elaboration of placental villi. (4mm). § 5th week - Face & limbs continue. (5-8mm). § 6th week - Face, ears, hands, feet, liver, bladder, gut, pancreas. (10-14mm). § 7th week - Face, ears, fingers, toes. (17-22mm). § 8th week - Lungs, liver, kidneys, (28-30mm). o All of this takes place in a low oxygen environment (~3%) o Week 8 of embryonic development = Week 10 of gestation

Population perspective on unhealthy eating and eating disorders

§ 30-50% of females dislike their body § 20-30% will be obsese and around 1-2% will get AN.

Prognosis of conduct disorders

§ 40% of 7 and 8 year olds with CD became recidivist delinquents as teenagers. § Over 90% of recidivist juvenile delinquents had conduct disorder as children. § Predictor of: a) Antisocial PD in adulthood (~50%) b) Alcoholism & drug dependence c) Unemployment and relationship difficulties § Intergenerational transmission § HENCE IMPORTANCE OF PREVENTION!

Fetal movement countings

§ A reduction in fetal movements may precede fetal death by a day or more; therefore, fetal movement counting may be of value in assessing fetal wellbeing. o In the UK, the Cardiff kick chart is the most commonly used method. o Mothers record the time taken each day to feel ten fetal movements. o Women who report a reduction in fetal movements, and particularly those who report an absence of fetal movements, need cardiotocography (CGT) and/or an ultrasound assessment of the fetus to reassure the mother and ensure fetal wellbeing.

4 requirements of anorexia nervosa

§ A. Restriction of energy intake relative to requirements leading to significantly low body weight in the context of age, sex, developmental trajectory and physical health. § B. Intense fear of gaining weight or becoming fat, or persistent behaviour that interferes with weight gain. § C. Disturbance in experience of weight/shape, undue influence of wt/shape on self-evaluation, or persistent lack of recognition of seriousness of low body weight. § D. Amenorrhoea NOT in DSM-5! ** Subtype: Restricting vs. Binge-eating/Purge. ** can be implicit or explicit signs.

Stages of child development

§ Abnormal development refers to the slow acquisition of skills and follows three main patterns: (1) slow but steady; (2) plateau; and (3) regression. § Delay may occur in one or more domain. § Biological factors may impact on development - e.g. folate deficiency increases the risk of neural tube defects which, in its most severe form, can result in limb paralysis, neurogenic bladder and bowel; and intellectual impairment. § Children may present with developmental concerns either through (i) identification of antenatal or postnatal risk factors; (ii) developmental screening; or (iii) concerns raised by parents or other healthcare professionals. Thus, these children may present at any age.

What are the three main patterns of abnormal development?

§ Abnormal development refers to the slow acquisition of skills and follows three main patterns: (1) slow but steady; (2) plateau; and (3) regression. § Delay may occur in one or more domain. § Biological factors may impact on development - e.g. folate deficiency increases the risk of neural tube defects which, in its most severe form, can result in limb paralysis, neurogenic bladder and bowel; and intellectual impairment. § Children may present with developmental concerns either through (i) identification of antenatal or postnatal risk factors; (ii) developmental screening; or (iii) concerns raised by parents or other healthcare professionals. Thus, these children may present at any age.

Summary of heart development

§ Abnormalities in cardiac development occur in 0.8-1% of pregnancies; the severity of the abnormalities can be very variable. This is a high incidence which may be related to the complex nature of heart development, and the importance of the heart. § Heart development is a complex process in humans, involving a series of interlinked changes. The main components of the process are summarised in Figure 5.5.1. In brief the 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.

Prognosis of AN

§ About 40% respond to first line interventions alone. § Up to 80% recover overall within 5 years. § Around 30% develop binge eating at some point during recovery. § Around 20% run a more chronic course. § Mortality e.g. at 20 years: 5-10% of which 1 in 5 is suicide. § Duration of illness predicts recovery therefore adolescent onset better prognosis because earlier help seeking. § Early treatment response is the only robust predictor of outcome but more extreme social difficulties are a factor

Ageing brain and cognition

§ Age-related changes - assessed with MRIs and CTs: § LHS is younger brain. § Grey matter reductions - mainly in size and no of connections between neurons, not in neuron no. § White matter reduction § brain volume is higher in younger people, as get older get atrophy. o CSF within the surrounding brain increases. o Ventricles enlarge. o Gaps between major gyri widen. o 50% of normal elderly people show a degree of white matter change. § The brain attains a maximum weight at about 20 years of age and remains at this weight until 40-50 years of age. 2-3% decrease in brain mass from age 40/50 per decade eventually reaching 10% below maximum brain mass by around age 80.

Why do people age?

§ Ageing/senescence - biological process of growing old, with associated changes in physiology and increased susceptibility to disease and increased likelihood of dying § Why organisms age - two main categories of thought: 1) Damage or error theories - accumulation of damage to DNA, cells and tissue. § E.G. loss of telomerases or oxidative damage. § This theory suggests that we can prevent ageing IF we can prevent this damage. 2) Programmed ageing theories - genetic, hormonal and immunological changes lead to the cumulative deficits we see as ageing. § These theories suggest ageing is part of an inescapable/programmed process. § No single theory explains all that we know about ageing.

What are the two theories of ageing?

§ Ageing= biological process of growing old, with associated changes in physiology and increased susceptibility to disease and increased likelihood of dying. Theories on ageing: 1) Damage or error theories describe the accumulation of damage to DNA, cells and tissue. For example, loss of telomeres or oxidative damage as the cause of ageing. If we could repair this damage, we could prevent ageing. 2) Programmed ageing theories describe how genetic, hormonal and immunological changes over the lifetime of an organism lead to the cumulative deficits we see as ageing. These theories suggest that this is part of an inescapable biological timetable, just as growth and puberty are programmed to occur. •Life expectancy= statistical measure of the number of years a person can expect to live. 79.2 for males and 89.2 for females.

Rehabilitation in elderly

§ Aim is to restore or improve functionality § Multidisciplinary § Rehabilitation alongside acute illness -Preventing deconditioning § Prehabilitation - get them better before the surgery to improve chances of success.

Monitoring height growth in children

§ All children should have height and weight measured occasionally and plotted in their red book. § If there are concerns about growth the child should be measured accurately and plotted on a centile chart over a period of time (at least a year). § If a child is growing fast enough to continue to grow on the same centile they are not likely to have a problem even if they are at the bottom of the centile chart. § Timing of puberty can impact on height- children who are late in developing can fall behind in height.

Types of dementia

§ Alzheimer's (more memory changes and orientation early on), vascular (more processing speed changes early on) or mixed dementia.

Teratogens: summarise how teratogens affect embryo development

§ Any agent that can disturb the development of an embryo or fetus. E.g. 1) Infectious= rubella virus, herpes simplex virus, HIV 2) Physical agents= X-rays & other ionising radiation - Microcephaly, spina bifida, cleft palate, limb defects 3) Chemical agents: a)Thalidomide - Limb defects, heart malformations b)Lithium - Heart malformations c)Amphetamines - Cleft lip and palate, heart defects d)Cocaine - Growth restriction, microcephaly, behavioral abnormalities e)Alcohol - Fetal alcohol syndrome, maxillary hypoplasia, heart defects. **THALIDOMIDE: •~10,000 affected infants known, ~50% initial survival rate. •Limbs affected. •In addition, deformed eyes and hearts, deformed alimentary and urinary tracts, blindness and deafness. •Used in some leprosy and cancer treatments at present. •Effects on upper limbs generally most common, but lower limbs and internal organs can also be affected •Thalidomide - affects rapidly developing blood vessels, notably those of upper limbs •Blood vessel affects can be generic, hence the range of effects observed. **Ebstein anomaly is a rare heart defect in which the tricuspid valve — the valve between the upper right chamber (right atrium) and the lower right chamber (right ventricle) of the heart — isn't formed properly. As a result, blood leaks back through the valve and into the right atrium. **The classic triad for congenital rubella syndrome is:[3] •Sensorineural deafness •Eye abnormalities—especially retinopathy, cataract, glaucoma, and microphthalmia •Congenital heart disease—especially pulmonary artery stenosis and patent ductus arteriosus.

Changes in the fetal heart at delivery.

§ At birth, the ductus arteriosus and foramen ovale should close, converting the circulation to the 'figure of 8' system and allowing oxygenation within the lungs.

BMI in children

§ BMI is adjusted for children. § assess by percentile again

Neurulation

§ Before Gastrulation is complete, Neurulation has been initiated. § Neurulation is the differentiation of the Ectoderm (Epiblast) to generate the central nervous system (Brain and Spinal cord), under the control of the notocord in the mesoderm of the developing embryo. The early stages are shown in Figure 5.2.6, with development of the neural plate; this develops two folds, which increase in size until the meet over the neural groove and fuse to form the neural tube

Fusion to form the neural tube

§ Before Gastrulation is complete, Neurulation has been initiated. § Neurulation is the differentiation of the Ectoderm (Epiblast) to generate the central nervous system (Brain and Spinal cord), under the control of the notocord in the mesoderm of the developing embryo. The early stages comprise development of the neural plate; this develops two folds, which increase in size until the meet over the neural groove and fuse to form the neural tube. § This fusion process continues during week 4 of development, as the central nervous system becomes a sealed tube. § Note that the structure of the neural folds is much more complex at the upper (cranial) end of the embryo; brain development has started by this stage.

Blastocyst two parts within it

§ Blastocyst - epiblast and hypoblast present at ~9 days and is around 0.1cm wide. § Embryo - small developing conceptus present at ~5-6 weeks and is around 1cm wide. o Can include everything from day 1 onwards and includes not just the baby but placenta as well. § Foetus - developing conceptus present at ~3 months and is now around 7cm wide. o Conceptus - anything derived from a fertilised egg. Note - the red part is the liver developing and is where the RBCs are made before the spleen kicks into action.

Completion of the process of fertilisation, and the initiation of embryonic development

§ Both pronuclei are now visible; note that by this stage duplication of the DNA in both pronuclei has been duplicated, making 2n chromosomes of maternal and of paternal origin. The next stage is development is a mitotic division, giving 2 daughter cells, which must have the same chromosomal complement, so duplication is required at this stage. Maternal and paternal chromosomes mix for the first time, as the metaphase plate of the first cleavage division is formed. § Separation of the male (blue) and female (red) chromatids can be seen; each cell should receive one paternal copy and one maternal copy of each chromosome, so the 2 cells shown in (F) have an identical chromosomal complement. § The source of this data is not given.

The Ovarian and Endometrial Cycles

§ Both the ovarian and endometrial cycles have end-points that occur approximately once per month. § The human menstrual cycle lasts approximately 28 days, but this varies substantially between human females, and also in individuals. a normal range: 21 - 35 days in adult females, but in younger teenagers, the length may be up to 45 days. At the other end of the reproductive spectrum, when a woman is approaching the menopause, her menstrual cycle is likely to become irregular in length; shorter or longer, or perhaps skip a month or two before resuming. § human menstrual cycle integrates the changes that affect the uterus (the endometrial cycle) with those that involve the ovaries (the ovarian cycle). **menstrual cycle: § Composed of the endometrial & ovarian cycles. o Endometrial - menstrual, repair and proliferative, secretory phases. o Ovarian - follicular, luteal phase. 1. FSH & LH stimulate the follicular phase which results in oestradiol production à stimulates the endometrial proliferation. 2. Oestradiol (E2) production continues at a greater pace and -ve feedback switches to +ve and ovulation occurs. 3. Corpus luteum produces progesterone and E2 and the endometrium enters the secretory phase.

Average height and weight of baby

§ By the time of birth the fetus has grown from the size of a single fertilized egg to (if the baby is born at term) an average of 50cm long and 3.3kg weight. § Growth in height is completed over the next 12-16 years. § The pattern of growth in normal children is very consistent and centile charts are a way of checking that growth is normal. A number of factors can adversely affect growth in height- nutrition, hormone problems, genetic diseases.

Pronuclei after fertilisation

§ By this stage, Meiosis II in the maternal chromosomes is completed, leading to the formation of polar body II, and the female pronucleus. § The head of the sperm is undergoing decondensation, with the previously tightly packed paternal chromosomes forming a much looser structure. Both pronuclei are haploid at this stage of fertilisation. § Both pronuclei are now visible; note that by this stage duplication of the DNA in both pronuclei has been duplicated, making 2n chromosomes of maternal and of paternal origin. The next stage is development is a mitotic division, giving 2 daughter cells, which must have the same chromosomal complement, so duplication is required at this stage. § Maternal and paternal chromosomes mix for the first time, as the metaphase plate of the first cleavage division is formed.

Factors associated with FGR and the SGA fetus

§ Causes of IUGR: o Generally, develops in the 2nd and 3rd trimesters as the 1st stage focuses on embryology (up to 50g weight). o Divided into 4 categories: 1) Maternal medical factors - infection, pre-eclampsia, uterine abnormalities, etc. 2) Maternal behavioural factors - i.e. alcohol. 3) Foetal factors - i.e. multiple pregnancy. 4) Placental factors - i.e. placental cysts, impaired trophoblast invasion

causes of IUGR - 4 categories

§ Causes of IUGR: o Generally, develops in the 2nd and 3rd trimesters as the 1st stage focuses on embryology (up to 50g weight). o Divided into 4 categories: § Maternal medical factors - infection, pre-eclampsia, uterine abnormalities, etc. § Maternal behavioural factors - i.e. alcohol. § Foetal factors - i.e. multiple pregnancy. § Placental factors - i.e. placental cysts, impaired trophoblast invasion.

The body repeats the below 4 simple processes to achieve embryology.

§ Cells must - proliferate, move, differentiate & be able to undergo cell loss: 1) Proliferate - in response to - GF, receptor expression, cell survival - all via para- or autocrine signalling. 2) Move - chemoattractants, cognate receptors, facilitated (via remodelling and proteases). 3) Differentiate - paracrine regulation, receptor expression, loss of proliferation. 4) Cell loss - PCD controlled by mainly paracrine factors.

Measuring children and using centile charts

§ Centile charts are a way of looking at the range of height and checking that growth patterns are normal. Every child has a handheld record which includes their growth charts- the "Red book". **What a centile chart tells you: § There are centile charts for a range of growth measurements- height, weight, head circumference and BMI are the commonest. § They are based on surveys of large numbers of children- in the UK we use both UK population based charts and ones from the WHO which look at an international population. § To use a centile chart you plot the age (x axis) against height (y axis). 50% of children will be shorter than the 50th centile, 25% shorter than the 25th centile, and so on. § Centile charts are not a "normal range", they are just a way of looking at where height is compared to others § There are centile charts for girls and boys.

Changes in tissue structures during the normal human menstrual cycle

§ Changes in endometrial thickness during the cycle are shown, as are the roles of estrogen (proliferative or follicular phase) and of progesterone in combination with estrogen (secretory or luteal phase). § Oestrogen dominates the proliferative or follicular phase. § Progesterone dominates the secretory or luteal phase. § Terminology used depends upon what is being described: o Endometrium/Uterine - proliferative/secretory. o Ovarian - follicular/luteal. § Thinnest - 2-4mm. § Thickest - 7-16mm. ** Note the terminology used: a focus on endometrial or uterine function will employ proliferative and secretory, as these describe endometrial function; for an ovarian emphasis, the terms would be follicular and luteal, as these summarise the state of the dominant ovarian follicle in the cycle.

GH treatment

§ Children with confirmed GH deficiency will get a significant improvement in their adult height with treatment, and there are a number of other disorders of growth where there is some benefit from treatment. § There have been multiple trials of GH treatment in children who do not have anything wrong with them but are just short ("short normal children"). Treatment is not given to these children because the tiny improvement in height seen is not worth the time, effort and expense of treatment.

How are grooves in face development filled in?

§ Cleft lip and palate show failure to correctly form the face. § Development the face involves grooves forming in the face which should normally fill in (don't fill in when you have clefting). o The "pink" mesenchyme must disappear (apoptose) and this pulls the eyes and nostrils towards the midline. o The grooves are filled in by bulk tissue movement (not wound healing). o This results in two different halves of the face (not so symmetric). § Clefting can be fixed well with surgery.

Psychological changes in puberty

§ Cognition e.g. morality. § Identity. § Increased self-awareness. § Affect expression and regulation

Interventions in Depressive disorder

§ Cognitive behavioural therapy § Interpersonal psychotherapy § Family intervention for associated family problems § Antidepressants - selective serotonin reuptake inhibitors e.g. fluoxetine for moderate - severe depression.

Complications of spina bifida cystica

§ Complications of spina bifida cystica (due to failure of fusion of the ant. Or post. Neuropore): o Neurogenic bowel and bladder incontinence. o Lower limb paralysis. o Fractures and joint contractures. o Developmental deformities and learning disabilities. o Hydrocephalus and meningitis.

Ova in ovaries in birth --> infant --> reproductive life time

§ Contain ~6 million primordial follicles at ~20 weeks of development. § By delivery of the infant, this has fallen to ~1 million per ovary. § About 400 follicles will be ovulated during the reproductive life-time.

Risk of preterm labour on fetus

§ Delivery at term normally has few specific risks for the infant, but delivery at gestations less than 32 weeks are much more likely to cause infant morbidities or mortality. Data from one study serves to emphasise the main points: Survival increased rapidly with increasing gestational age so that by 26 completed weeks of pregnancy, nearly 80% of babies left hospital alive. The great majority of these infants had major morbidities (87%), so that their quality of life, and life expectancy will be severely affected. Ongoing medical support may well be needed. § Many of these extremely preterm labour cases are linked to intrauterine infection, or other uterine complications such as bleeding, but not all causes have been identified. § In addition to the risks of early delivery, linked to incomplete development of lungs, brain, digestive or immune systems, it seems that the fetal brain is particularly sensitive to inflammatory mediators. As labour is an inflammatory process, and one clear cause of preterm labour is intrauterine infection, the incidence and severity of brain damage is particularly high in these extremely preterm infants. § Therefore understanding the causes, and identifying possible treatments, for preterm labour has been a focus of considerable study. The improvements in outcome have been relatively modest - and have generally permitted an increase in the survival of extremely preterm infants, without an increase in overall health (see Table 3.1).

The process and main events of Fertilisation

§ Deposition of sperm within female system following sexual intercourse. § Sperm are deposited near cervix. § Cervical mucus is normally hostile to sperm. § This forms a physical barrier to sperm. § Cervical mucus changes at mid-cycle. § This change permits sperm to enter uterus. § Passage of sperm through uterus. § Passage of sperm into Fallopian tube. § Swim from there to Fallopian tube ampulla. (30 µm/sec average speed; 2 mm/min; 12 cm/hour). § Survival of the fittest (a few days). § Capacitation - takes time within uterus. § Capacitation is essential preparation before the sperm meet the oocyte. §Meeting of egg with sperm. § Fusion of egg and one sperm (within 24 hours post ovulation). § Acrosome reaction: penetration of Zona Pellucida (& Coronal cells). § Calcium flux. § Resumption of meiosis, release of 2nd polar body. § Alignment of maternal and paternal chromosomes to generate zygote. § Change in Zona Pellucida to prevent additional sperm fusing with zygote. § Initiation of mitotic (cleavage) divisions in embryo.

Depression - symptom clusters, developmental contributing factors and interventions

§ Depression affects 2-5% of adolescents, § Depression- Symptom Clusters (ABC): •Affective - sadness, loss of enjoyment, irritability. •Biological - disturbed sleep, reduced appetite. •Cognitive - self-blame, hopelessness, guilt. § Developmental factors that can contribute: •Endocrine change - especially female may increase risk low mood •Changes in family relationships -physical closeness, joint activities, family conflict •Peers - increased involvement with peers; peer rejection and conflict •Responsibilities and hassles: life events, exams, etc

What may depression refer to?

§ Depression may refer to a single symptom, a symptom cluster or a disorder. § Symptoms: 10% of 10 year olds - parents report; 40% of 14 years olds - self report. § Symptom Cluster: a) Affective - sadness, loss of enjoyment, irritability b) Biological - disturbed sleep, reduced appetite c) Cognitive - self-blame, hopelessness, guilt. --> May reach threshold for disorder **Developmental considerations: § Endocrine change - especially female may increase risk low mood. § Changes in family relationships -physical closeness, joint activities, family conflict. § Peers - increased involvement with peers; peer rejection and conflict. § Responsibilities and hassles: life events, exams, etc

Types of depression by course

§ Depressive episode (~ 50% recur) § Recurrent depression § Dysthymia - consistent low mood that gets better and worse over time § Bipolar depression - mood swings § Psychotic depression - associated with hallucination § Atypical depression § Seasonal affective disorder (SAD) § ?Inflammatory subtype

What are the four domains or normal development?

§ Development is the global impression of a child which encompasses growth, increase in understanding, acquisition of new skills and more sophisticated responses and behaviour. It serves to endow the child with increasingly complex skills in order to function in society. § Four domains or fields - (1) gross motor and posture; (2) fine motor and vision; (3) language and hearing; and (4) social, emotional and behaviour. § Developmental progress depends on the interplay between biological and environmental influences. It follows a constant pattern, although at variable rates, among children. § Limit ages are the age by which they should have been achieved = 2 standard deviations from the mean. They indicate cause of major concern. § Developmental progress can be monitored or identified either through developmental screening or by the use of standardised developmental tools.

Typical developmental problems 3/4 - Attention deficit hyperactivity disorder

§ Diagnostic criteria - (1 )Inattention; (2) Hyperactivity; (3) Impulsivity; (4) Lasting > 6 months; (5) commencing < 7 years and inconsistent with the child's developmental level. § Diagnosis via: o Questionnaires - SDQ (Strengths and Difficulties Questionnaire), Connors. o Exclude medial causes such as hyperthyroidism. o Hearing deficits. o Identify risk factors and co-morbidities. § These features should be present in more than one setting, and cause significant social or school impairment. § These children also have an increased risk of: conduct disorder, anxiety disorder & aggression § Risk factors - Boys > girls, ratio 4:1; Learning difficulties and developmental delay § Neurological disorder, e.g. epilepsy, cerebral palsy; first-degree relative with ADHD; family member with depression, learning disability, antisocial personality or substance abuse. § A significant proportion of children with ADHD will become adults with antisocial personality and there is an increased incidence of criminal behaviour and substance abuse. **Management: § Psychotherapy - Behavioural therapies § Family therapy § Drugs - If behavioural therapy alone insufficient; stimulants, e.g. methylphenidate (Ritalin), amphetamines (dexamphetamine) § Diet - Some children benefit noticeably from exclusion of certain foods from their diet, e.g. red food colouring

When does ductal system develop?

§ Ductal system development around week 7: o Under influence of SRY gene, male ductal system begins to form. § Male - mesonephric tube becomes the testes. § Female - the mesonephric duct is NOT connected to the ovaries and it has developed separately. § Development of sexual tissues: o Gonads arise from intermediate mesoderm within urogenital ridges. o PGCs are precursors for gametes. o Mesonephric duct becomes male genital ducts. o Paramesonephric ducts become female genital ducts.

Endocrine signalling in embryo development?

§ During embryo development, there isn't much vasculature made so this doesn't occur much.

What occurs during 2nd month of embryological development?

§ During the 2nd month of development: o Limbs develop - days 28-56. o Face develops. o Internal tissues develop - heart, lungs and gut. § The conceptus will look human (foetal) by day 56.

Source of oestrogens during pregnancy

§ During the early weeks of pregnancy, the corpus luteum also produces the oestrogens needed for pregnancy (mainly 17beta-oestradiol). Once the luteo-placental shift has completed, the production of oestrogens in human pregnancy changes as outlined in Figure 3.5, involving a complex interaction between the placenta and the fetal adrenal glands. § The human placenta does not express the enzyme (Cytochrome P450 17A1, or CYP 17, or Cytochrome P450 17,20-lyase) that converts pregnenolone to androgens, so this part of biosynthesis takes place in the fetal adrenals (which are large and well-developed even in the first trimester). The weak androgen produced (dehydroepiandrosterone, DHEA) is sulphated as well to give DHEA-S, which is inactive. Hence a female fetus is not exposed to an androgen during development. The DHEA-S circulates to the placenta, where it is converted to 17beta-oestradiol as shown. § In human pregnancy, very high levels of oestriol are found, which are produced by a parallel mechanism (Figure 3.5), which includes hydroxylation of DHEA-S in the fetal liver to produce the precursor 16OH-DHEA-S. §There is a tendency to consider the three major compartments of human pregnancy independently, but these interactions needed to produce steroids show the interdependence between mother, fetus or embryo and placenta.

Embryology first trimester

§ Embryological timings are usually about 2 weeks less than the gestational time frames. o E.G. 12 weeks GA is 10 weeks embryologically. o GA time frames - starts after the beginning of the last menstrual period. § Embryological changes are stated in red in the left image. § There is a lot of embryological changes in the first few weeks of development. § Weight rapidly increases past the 1st trimester: o 1st (50g) --> 2nd (1050g) --> 3rd (2100g). § Development is measured in Carnegie stages

What do endoderm, mesoderm and ectoderm form?

§ Endoderm --> gut, liver and lungs. § Mesoderm --> skeleton, muscles, kidneys, the heart and blood. § Ectoderm --> skin and the CNS.

The Developmental Domains - Limit Ages

§ Examples of limit ages: o Walking independently: 18 months. o Fixes and follows visually: 3 months. o Joins words: 2 years. o Symbolic play: 2-2.5 years.

Historical methods for the assessment of fetal growth.

§ External determination of size: Perhaps the simplest to understand are attempts to determine the size of the infant by palpation of the maternal abdomen. § This is the basis of determination of the Symphysis Fundal Height (SPH). § while changes in SPH reflects generic changes in uterine size, it is vulnerable to a variety of errors that could lead to a mis-interpretation of the data. § Values that are lower than they should may result from: wrong last menstrual period date, the baby in a transverse lie, or complications including oligohydramnios (low levels of amniotic fluid) or a baby that is small for gestational age (SGA). § Higher values may also be found, due to: wrong last menstrual period date, multiple pregnancy, or maternal obesity. § Complications could include molar pregnancy, fibroids, polyhydramnios or a baby that is large for gestational age (LGA). § This simple and inexpensive measurement may identify gross changes in size, and hence gross complications in the pregnancy, but is generally of limited use, thanks to the many confounders, which include the problems listed above, as well as considerable inter-operator variability.

FGR vs SGA

§ FETAL GROWTH RESTRICTION (FGR) = Failure of the fetus to achieve its predetermined growth potential for various reasons § SMALL GESTATIONAL AGE (SGA) = Birth weight < 10th centile § 3rd centile is most specific (All babies recorded using the third centile will have FGR, but some FGR babies may be missed, i.e you get a number of false negatives) § 10th centile is most sensitive (The tenth centile will capture all babies with FGR, but will also include those babies that are just small for gestational age, i.e. you get a number of false positives) § So you can be a low birth weight baby but if you are within your centile you are not considered to be growth restricted. § Many FGR babies are delivered prematurely. § 3-10 fold increase in prenatal mortality short- and long-term morbidity. § LBW, FGR and preterm delivery are closely associated pathologies. ***Test sensitivity is the ability of a test to correctly identify those with the disease (true positive rate), whereas test specificity is the ability of the test to correctly identify those without the disease (true negative rate).

Imaging: explain why ultrasound is the preferred imaging choice for the assessment of fetal growth and identify the role of ultrasound in the assessment of fetal wellbeing

§ FETAL GROWTH= Increase in mass that occurs between the end of embryonic period and birth 1) Symphysis Fundal Height (SFH): Top of uterus to pubic bone (symphysis). § Pros= Simple, inexpensive. § Cons= Low detection rate: 50-86%, Great inter-operator variability, Influenced by a number of factors (BMI, fetal lie, amniotic fluid, fibroids) § Reason for it being smaller than normal= wrong dates, small for gestational age, oligohydramnios, transverse lie. § Reasons for it being bigger than normal= wrong dates, molar pregnancy, multiple gestation, large for gestational age, Polyhydramnios, Maternal obesity, Fibroids. 2) Ultrasound Examination: 1.Crown Rump Length (CRL) 2.Head Circumference (HC) 3.Bi parietal diameter (BPD) 4.Abdominal circumference (AC). **Why do we do USS? a)Understanding of normal fetal growth facilitates good obstetric management of cases with abnormal fetal growth b)Assessment of fetal "wellness" not just size c)Looking at trends in growth d)Predicting fetal metabolic compromise e)Anticipating the need to deliver prematurely f)Liaising with Neonatal Services § These factors are combined to give the estimated fetal weight (EFW). Normative growth curves have been constructed from these ultrasound measurements (expressed in centiles). Used clinically to identify a normal intrauterine growth and detect risk of obstetric and neonatal complications. For any infant, the changes in each parameter can be plotted, and the growth over time visualised. In a normal pregnancy, each parameter is expected to follow a centile, showing steady increase in size.

Female reproductive system: recall the component parts of the female reproductive system, draw diagrams of the ovary to illustrate the main stages in the maturation of an oocyte, and explain the significance of the granulosa cells and thecal cells for sex steroid hormone production

§ FSH --> Granulosa cells --> Oestrogen + Inhibin (+ follicle maturation) § LH --> Theca cells --> Progesterone.U § structure of fallopian tube: Isthmus --> ampulla --> infundibulum --> fimbriae (IAIF) to ovary. 1) Female gonad: - ovary a) Produce mature oocytes monthly b) Produces steroids needed for female reproductive function - progesterone and oestrogens 2) Fallopian tube - where released oocyte is fertilised, pathway through which fertilised oocyte (conceptus) reaches uterus 3) Uterus - where conceptus normally implants and is supported throughout pregnancy 4) Follicle - oocyte in ovary surrounded by granulosa cells: § As follicle develops, oocyte grows, granulosa cells proliferate § Theca cells of developing follicles produce oestrogen in first half of the cycle § Granulosa-luteal cells produce oestrogens and progesterones during second half of the cycle § PRIMORDIAL FOLLICLE!!

Causes of Depressive Disorder

§ Familial aggregation; genetic factors known § Effects of family interaction e.g. criticism § Life events, adversities

Faulty neurulation and spina bifida

§ Formation of the neural tube, the precursor of the central nervous system occurs early in pregnancy, about 3 weeks after fertilisation. § Fusion should occur through the neural tube, but in spina bifida this process is not completed. The location of the gap in the fusion process will determine the location of the spina bifida defect, and hence the effect on the infant

The source of progesterone during pregnancy

§ From the time of fertilisation to about 8 weeks gestation, the corpus luteum is the main source of progesterone, and this production is sustained by the rapidly increasing levels of hCG. § The placenta can also produce progesterone, but in the earliest weeks of pregnancy, the small size of the placenta means that its net contribution to maternal progesterone levels is limited. § Increasing placental size means that it contributes increasingly to the levels of progesterone in the maternal circulation, and by 10 weeks of gestation the placenta is the source of all progesterone. § From about 6 weeks of gestational age, the corpus luteum gradually produces less progesterone (despite the very high hCG levels), and by about 9 weeks it has ceased to make steroids. This change in the source of progesterone to sustain pregnancy is the 'luteo-placental shift'. The placenta produces progesterone constitutively at increasing levels for the rest of pregnancy.

Endocrine control of growth

§ GH is the most important hormonal growth factor. § GH secretion: o Stimulated by GHRH - pulsatile release mainly overnight. o Inhibited by SS. § Effects of GH: o Some direct effects. o Secretion of IGF-1 from liver and growth plate - then directly influences growth. **GH-IGF-1 axis regulator of human linear growth. GH is a single chain polypeptide. Somatotroph cells of anterior pituitary. Pulsatile secretion: influenced by nutrition, sleep, exercise and stress.

Appearance of mother throughout pregnancy

§ General changes - abdominal changes in the mother only become apparent during the 2nd trimester +. o and spinal curvature changes too to accomodate for baby --> aches and pains.

The hormonal control of growth and growth hormone secretion

§ Growth hormone (GH) is the most important hormonal factor in growth. § GH secretion is controlled by the hypothalamus, which secretes growth hormone releasing hormone (GHRH) which stimulates secretion and somatostatin which suppresses secretion. GH is released by the pituitary as pulses most of which occur overnight. § GH has some growth effect itself and also stimulates the release of IGF1 (insulin like growth factor !). § IGF 1 circulates bound to a number of binding proteins and stimulates growth in all the tissues of the body

Causes of language delay

§ Hearing loss § Learning disability § Autistic spectrum disorder § Lack of stimulation § Impaired comprehension of language -Developmental dysphasia § Impaired speech production -stammer, dysarthria

Definition of human labour

§ Human labour defined as "The process of expulsion of the fetus and the placenta from the uterus. § The stages of labor include: first stage, beginning with the onset of uterine contractions through the period of dilation of the os uteri; second stage, the period of expulsive effort, beginning with complete dilation of the cervix and ending with expulsion of the infant; third stage or placental stage, the period beginning at the expulsion of the infant and ending with the completed expulsion of the placenta and membranes." § process of labour can last for 48 hours. This is mainly because the uterus and cervix, which are the main tissues involved in labour, have to undergo a substantial change in structure and functions as they transition from what is needed for pregnancy (in which state they have been for 9 months) to what is needed for the delivery of the infant.

Iatrogenic harm in elderly

§ Iatrogenic problems are illnesses caused by receiving healthcare treatments and are more common in older people. They include mistakes in providing care, and known complications of treatment. **E.g. scenario: 79F with high blood pressure: •Given amlodipine •Gets ankle swelling •Hence, gives furosemide as well. •But then get postural hypotension •Fall and Colles fracture **Iatrogenic harm: 1) Adverse reactions to medications 2) Nosocomial conditions: a) Deconditioning (lose muscle mass and BMD due to bed rest; can lose 1 kilo of pure muscle mass in one week of bed-rest) b) Infections e.g. hospital acquired pneumonia, c) Pressure sores, d) Constipation e) Delirium f) Malnutrition g) Incontinence 3) Falls 4) Psychological/cognitive damage

Biological sex

§ Identifies gender, Result of chromosomes, Production of gametes. §The production of gametes, and the process of fertilisation, are essential precursors to human pregnancy. § It has been suggested (often) that the most important sexual organ in humans is the brain.

Lateral folding of the embryo to close the gut tube and form the main body cavities.

§ In parallel with neurulation, the precursors of other tissues are developing within the embryo, and it is being converted from a flattened structure into a 3-dimensional embryo. § In addition to structures developing within the embryo during this third week of development (days 14-21), at least two groups of cells are present outside the embryo proper; the primordial germ cells (PGC) 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 both laterally, which fuses the ventral midline (chest and abdomen) of the embryo, and in the anterio-posterior direction, which folds the PGCs into the hind gut, and the developing heart progenitors under the head of the embryo.

Summary of the movement of primordial germ cells during early development

§ In parallel with the developing reproductive tissues, the primordial germ cells (PGC) are following a separate developmental pathway. § PGC will give rise to the gametes within the gonads, and seem to have a very different development compared with most cells in an embryo. They 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. § By week 7 of development, the embryo has an indifferent reproductive system, which can differentiate to form either female or male structures.

The indifferent reproductive system, and its subsequent differentation to the male (left) or female (right) tracts and gonads pic

§ In the human, development of the male system depends on the expression of Sex-determining Region Y (SRY) from the Y chromosome, which causes the conversion of the indifferent system to the male tract, gonadal and genital pattern during the next 3 weeks. § In the absence of SRY, the female tract, gonads and genital pattern develops; this starts a little later (weeks 8-9 post fertilisation). § The key regulators in male development are testosterone, which is produced from the testis Leydig cells, under the stimulation of hCG from the maternal circulation. Male development starts in weeks 7-8 (weeks 9-10 gestational age), which is when maternal hCG levels are close to their peak. Testis Sertoli cells produce anti-Mullerian hormone (AMH), which causes the regression of the Mullerian (paramesonephric) ducts. Testosterone support development of the Wolffian ducts, which give rise to the male reproductive tract.

Post-fertilisation timings of development of the external genitalia.

§ In the human, development of the male system depends on the expression of Sex-determining Region Y (SRY) from the Y chromosome, which causes the conversion of the indifferent system to the male tract, gonadal and genital pattern during the next 3 weeks. § In the absence of SRY, the female tract, gonads and genital pattern develops; this starts a little later (weeks 8-9 post fertilisation). § The key regulators in male development are testosterone, which is produced from the testis Leydig cells, under the stimulation of hCG from the maternal circulation. Male development starts in weeks 7-8 (weeks 9-10 gestational age), which is when maternal hCG levels are close to their peak. Testis Sertoli cells produce anti-Mullerian hormone (AMH), which causes the regression of the Mullerian (paramesonephric) ducts. Testosterone support development of the Wolffian ducts, which give rise to the male reproductive tract. § The indifferent genitalia of the early embryo can be converted into the male or female structures. The key regulator seems to be dihydrotestosterone (DHT), a potent androgen that is produced from testosterone originating in the Leydig cells of the testis.

Hormonal changes during pregnancy

§ Increased hormone levels: o hCG - peaks 1st trimester and decreases thereafter but still present. produced by placenta --> stimulates corpus luteum to continue making progesterone and oestrogen. HCG starts to rise before end of menstruation. Occurs a week after implantation takes place. Thought maybe HCG might match up with morning sickness. o All other hormones (progesterone, oestrogens, lactogen) - slowly increase as the pregnancy progresses. § Progesterone is key to maintaining the pregnancy - progesterone antagonists --> loss of pregnancy at ALL gestational ages. ** Progesterone source: a) Fertilisation --> 8 weeks' gestation - corpus luteum source via hCG. b) 8+ weeks - placenta supplies progesterone. § The change-over = "Luteo-placental shift". **Oestrogen source: a) Fertilisation --> Luteo-placental shift - corpus luteum. b) 8+ weeks - complex interplay between foetal/maternal adrenals and placenta. § Human placenta - does not express the enzymes needed to convert pregnenolone --> androgens so this occurs in foetal adrenals. · The weak androgen produced (DHEA) is sulphated to give DHEA-S which is inactive (so female foetus is not exposed to androgens). · DHEA-S goes to the placenta to be converted to 17b-oestradiol. § High levels of oestriol are produced by a parallel mechanism including hydroxylation of DHEA-S in foetal liver to give 16OH-DHEA-S. § High steroid levels suppress HPG-axis -->low FSH and LH throughout.

Associated problems with depression

§ Increased risk of self-harm. § Association with anxiety disorders; eating disorders [females]; conduct problems; substance misuse. § Familial aggregation (genetic and learning)

The changes during erection

§ Initiated by: increased parasympathetic activity to smooth muscle of pudendal artery. § Increases the activity of Nitric Oxide Synthase (NOS), and hence nitric oxide (NO). § NO increases production of cyclic GMP which induces dilatation of arterial smooth muscle. § Counteracts sympathetic-maintained myogenic tone. § increases blood flow in corpus cavernosum which compresses the dorsal vein, restricting the outflow of blood. § The urethra is protected from increased pressure by surrounding corpus spongiosum (less turgid). ** Note: Cyclic GMP is normally de-activated by a phosphodiesterase enzyme, and this will reverse the changes leading to penile erection. Viagra inhibits the phosphodiesterase, thus potentiating the effects of cyclic GMP. **Overall: 1. (ESEED) increased PNS to SM of pudendal artery. 2. Increase activity of NOS and thus NO release. 3. NO stimulates cGMP --> vasodilation. a. cGMP inactivated by phosphodiesterase. 4. Counteracts SNS-maintained myogenic tone. 5. Increases blood flow in corpus cavernosum. a. Compress dorsal vein restricting outflow of blood. b. Urethra not compressed due to corpus spongiosum.

Management in child development

§ Investigations - depends on suspected cause but may include cytogenetic studies; metabolic screen (thyroid, renal, liver and bone profiles); blood ammonia and lactate; urine and blood organic and amino acids; creatine kinase; imaging - CT, MRI; EEG; nerve and muscle biopsy. § Other professionals - referral to members of the multidisciplinary team (MDT) would help identify problems and target input. § The multidisciplinary team - the many professionals who may be involved in the care of children with developmental problems.

Signs of Adolescent Depressive Disorder

§ Irritability instead of sadness/low mood Especially in boys. § Somatic complaints and social withdrawal are common § Psychotic symptoms rare before mid-adolescence

What is growth due to?

§ Is due to the GONADAL STEROIDS (particularly ANDROGENS) working in conjunction with other hormones, particularly.... § SOMATOTROPHIN (Growth Hormone) from the adenohypophysis

KISS gene in puberty

§ KISS gene: o Kisspeptin stimulates GnRH and the GnRHR. o Increased leptin can stimulate Kisspeptin and thus stimulate more GnRH. § Childhood obesity --> early puberty

Definition of labour

§ Labour involves cervical effacement, myometrial contractions and rupture of foetal membranes. This results in delivery of the infant and placenta. **What is effacement? •The cervix undergoes changes to turn it from rigid to flexible •This happens by 3 mechanisms: remodelling of the ECM, leukocyte recruitment and inflammation (PGE2 and IL8) • Effacement is shortening and thinning of cervical walls **We don't fully know what starts labour.

Labour definition

§ Labour is defined as - increasing fundally dominated contractions of myometrium combined with increasing cervical ripening and effacement. o this means uterus is performing coordinated contractions starting from fundus to cervix. o cervical ripening means cervix becomes more flexible. o myometrium changes from non contracting to contracting. o Fetal membrane remodelling occurs. o Lower segment relaxation §The stages of labor include: first stage, beginning with the onset of uterine contractions through the period of dilation of the os uteri; second stage, the period of expulsive effort, beginning with complete dilation of the cervix and ending with expulsion of the infant; third stage or placental stage, the period beginning at the expulsion of the infant and ending with the completed expulsion of the placenta and membranes." It is derived from the same word as labour meaning "work", which seems appropriate as the process of labour can last for 48 hours. This is mainly because the uterus and cervix, which are the main tissues involved in labour, have to undergo a substantial change in structure and functions as they transition from what is needed for pregnancy (in which state they have been for 9 months) to what is needed for the delivery of the infant *The main tissues involved in human labour are shown in Figure.

Low Birthweight (LBW)

§ Low birthweight (LBW): Less than 2,500g at delivery. Currently ~7% of live births (UK). § Very low birthweight (VLBW): Less than 1,500g at delivery. Currently ~1% of live births (UK). § Extremely low birthweight (ELBW): Less than 1,000g at delivery. Currently ~0.2% of live births (UK). **note: take no account of gestational age, they simply refer to the weight of the infant at delivery. This is very important - for example, an infant of 2,500g at term would be considered SGA, whereas if delivered at 33 weeks this would be an appropriate weight for a normal infant. It is important to differentiate between infants born preterm, who are of low birthweight simply because they have been born early, and those who are growth restricted; the latter are a greater risk of morbidities and mortality after delivery, and most low birthweight infants are in the former group (and hence at lower risk). o Epidemiological studies use BW alone, not GA. o Most LBW neonates are NOT growth restricted. o Many FGR babies are delivered prematurely to prevent stillbirth. o 3-10 fold increase in perinatal morbidity and mortality. o LBW, FGR and preterm delivery have closely associated pathologies

Prognosis of Depressive Disorder

§ Major depression: Duration § In specialist CAMHS settings: 6-9 months § Primary care: 2-3 months § High risk recurrence § Prepubertal onset - better prognosis § Small number in adolescence - bipolar (mania, hypomania)

Treatments for depression

§ Mild depression: • Cognitive behavioural therapy [Individual or group]. • Interpersonal psychotherapy for adolescents. • Brief Psychosocial Intervention. § Moderate-Severe Depression: • Antidepressants e.g. SSRI's: fluoxetine • Could be SSRI + CBT • Combined treatment --> highest rate of symptomatic remission in 37% combined vs 20% fluoxetine alone.

The Developmental Domains - (4) Social, Behaviour & Play:

§ Milestones: o 6 weeks - smile responsively. o 6-8 months - puts food in mouth. o 10-12 months - wave bye, play peek-a-boo. o 12 months - drink from cut with two hands. o 18 months - can eat by themselves. o 18-24 months - symbolic play. o 2 years - potty trained. o 2.5-3 years - parallel play.

The Developmental Domains - (3) Language & Hearing:

§ Milestones: o New born - startles. o 3-4 months - vocalises alone or when spoken to. o 7 months - turns to soft sounds out of sight. o 7-10 months - uses sound indiscriminately or discriminately. o 12 months - two to three words other than dada or mama. o 18 months - six to ten words. o 20-24 months - makes simple phrases. o 1.5-3 years - talk constantly in 3-4 word sentences.

Maternal risks in pregnancy

§ Most risks to the mother lie in delivery and labour. § Risks: 1) Remodelling of the spiral arteries means that vessels can lose relatively large amounts of blood after delivery - this should be limited by contractions of the uterus after the placenta has been delivered. Sometimes it is necessary for drugs to be given to ensure this happens correctly. 2) Placenta must be checked carefully to make sure all has been delivered as it is quite inflexible and any left in the uterus may lead to ineffective uterine contractions, and permit continued blood flow through the spiral arteries into the uterine lumen. Surgery may be required to remove any retained placenta, as it is vital that no placental tissue remains in the uterus. *In previous centuries, maternal death rates were up to 5% per pregnancy; in conjunction with an absence of contraceptives, and multiple sequential pregnancies, the risks of pregnancy can well be understood.

Why do older people take more drugs?

§ Multimorbidity § Guidelines/QOF/NICE - drive increased prescriptions. Due to is mainly for acute conditions, don't take into account co-morbidities. § Undetected non adherence - many people don't take their drugs. so then keep prescribing more. § Infrequent review - need to remove drugs after it is not required. can't de-prescribe if don't review. § Poor communication

Multimorbidity

§ Multimorbidity is two or more chronic conditions. Increases with ageing. **Implications: o Conditions impact on one another. o Treatment for one condition may impact on another o Negative impacts of multimorbidity: a) Worse QoL, more likely to be depressed b) Increased functional impairment c) Burden of treatment d) Polypharmacy

seminiferous tubules

§ Narrow, coiled tubules that produce sperm in the testes. § The overall production of sperm from both testes is estimated to up to 200 million sperm per day. includes change from diploid precursor cells to haploid gametes. § Once the process of spermatogenesis starts (at puberty) it normally continues for the rest of adult life. The quality and quantity of sperm produced may decline with increasing age, but men are capable of fathering children at well over 70 years of age.

Theories of ageing - take home points

§ No proven specific anti-ageing therapies in humans § People age at different rates: -Chronological age vs biological age. e.g. if had bad lifestyle then chronically age might be 63, but due to damage to body, biologically body is 83 as she has aged more rapidly. § Genetic inheritance (20-30% of age you reach is probs genetically inherited) § Both the damage/error and programmed ageing theory probs play a part.

Circulating hormones in menstrual cycle

§ Note basal body temperature raises around ovulation. 1. Gradual rise of oestradiol by developing follicle (FSH). 2. Follicles grow and -ve feedback on LH and FSH. 3. Dominant follicle selected and produces lots of E2 (peak)--> -ve feedback switch to +ve feedback --> LH surge and FSH surge. 4. Ovulation. 5. Corpus luteum produces E2 and progesterone --> -ve feedback on LH and FSH. 6. No fertilisation --> E2 and progesterone fall and endometrium enters secretory phase.

Regulation of hormones during the human menstrual cycle

§ Note the change in regulation of the hypothalamic-pituitary axis, changing from negative feedback to positive feedback, to cause the LH surge and ovulation. § Menstrual cycles last ~28 days (21-35 days). o In younger people, it may be longer. o Older people, shorter OR longer.

he Developmental Domains - (2) Fine Motor & Vision

§ Object permanence is attained at 9 months of age - the idea that when out if sight, not out of mind. § Milestones: o 6 weeks - turns head to follow object. o 4 months - reaches out to toys. o 4-6 months - palmar grasp. o 7 months - transfers between hands. o 10 months - mature pincer grip. o 16-18 months - marks with crayons. o 14 months-4 years - towering. o 2-5 years - ability to draw without seeing how it's done (after seeing it can be done 6m earlier).

What causes obesity

§ Obviously this is the balance of energy taken in as food versus energy expenditure. § Hunger is regulated by the hypothalamus and there are a number of factors (including leptin) which regulate this. There are a very small number of individuals with single gene mutations affecting one of these hormones which results in an excessive appetite and can lead to severe obesity. § In the population there are some gene variants (for example the FTO gene) which can affect eating behaviour and appetite and make an individual more likely to eat in a way that makes them gain weight.

Change in tissue structures during menstrual cycle

§ Oestrogen dominates the proliferative or follicular phase. § Progesterone dominates the secretory or luteal phase. § Terminology used depends upon what is being described: a)Endometrium/Uterine - proliferative/secretory. b) Ovarian - follicular/luteal. **§ Thinnest uterine lining- 2-4mm. § Thickest - 7-16mm (by end of proliferative phase) § then goes back to 2-4mm after shedding (due to decrease in progesterone). § firstly proliferation - by oestrogen; later by oestrogen and progesterone.

Disease presentation in older people

§ Older people are more likely to have an atypical or non-specific presentation of disease. § Frailty- decreased reserve and resistance to stressors resulting from cumulative decline across multiple physiologic systems and causing vulnerability to adverse outcomes § Changes in pharmacokinetics and pharmacodynamics can make drug treatments in older people cause harm. Drug trials tend to use younger people, affecting treatment evidence. **For example, the frail, older person with pneumonia has three problems- mild pneumonia, delirium and reduced mobility

Why is medicine for the elderly a multidisciplinary specialty?

§ Older people often present with multiple problems, which all need to be managed simultaneously. Using the example above, a young person with mild pneumonia has only one problem but the frail, older person described has three - mild pneumonia, delirium and reduced mobility. All these problems need to be managed simultaneously for a successful outcome. § For this reason, Medicine for the Elderly is a multidisciplinary specialty, involving doctors, nurses, therapists, social workers etc. Geriatricians never practice alone!

Management of IUGR and pre-eclamptic pregnancies

§ Once IUGR or pre-eclampsia have been identified, it is very difficult to treat these complications and reverse their impact on the infant. § Timing DELIVERY in these pregnancies depends on BALANCING the risks to the fetus if it remains in utero and the hazards from the prematurity, which decrease as the gestation advances. § Evidence of fetal compromise on CTGs or abnormal Dopplers/ultrasound finding / maternal compromise. § CORTICOSTEROIDS should be administered (if not already given) at gestations < 36 weeks in order to improve neonatal wellbeing, notably the development of the LUNGS. In the particular case of pre-eclampsia (with or without IUGR), as the placenta is the primary cause, the ultimate 'treatment' is DELIVERY. § As indicated above, it is the balance between risks that is important in making the decision about the timing of delivery. In some pregnancies, the health of mother or infant (or both) can deteriorate rapidly, making an emergency Cesarean section a necessity.

cleft lip vs palate

§ One result of this need to form the face from two separated halves is that the process may not function completely, which can give rise to clefts in the lip (usually upper lip, Figure 5.7.3. left) or in the palate. Clefting in both lip and palate may also be found. Note that cleft lip is often asymmetric, as only one of the two clefts shown in Figure 5.7.2. does not function correctly, whereas cleft palate is usually symmetric as the halves of the palate do not meet and fuse correctly. § These structural defects can be modified by surgery.

Conduct disorder behaviours

§ Oppositional behaviour, defiance. § Tantrums. § Excessive levels of fighting or bullying, assault. § Running away from home. § Truancy § Cruelty to animals § Stealing § Destructiveness to property § Fire-setting

Outcome and interventions of conduct disorder

§ Outcome: o Poorer outcome when there are more problems in the child and family. o Males - greater risk of ASBOs in males. o Females - range of emotional and personality disorders. § Interventions: o Children - problem solving skills. o Treat underlying co-morbidities - depression, hyperactivities. o Address problems across contexts e.g. in school o Parenting programmes, family intervention.

Within how many hours does egg need to be fertilised?

§ Ovulation = release of mature oocyte (egg) from the ovary § Oocyte is 2n at this stage, in meiotic arrest (metaphase II) § Enters the Fallopian tube (where fertilisation takes place). § Needs to be fertilised within 24 hours of ovulation, as it degenerates after this. so ovulation and fertilisation occur v close together.

Hypothesis for parturition

§ PAF is directly made by the lungs which acts to create ILs which stimulate PG production. § CRH is made primarily by the placenta which stimulates the baby hypothalamus and then the adrenals to produce cortisol (a STRESS hormone). o Oddly, the cortisol +ve feedbacks on CRH production in the placenta. o adrenal gland also makes precursor for oestrogens (DHEAS) which stimulate myometrial contractions.

Constitutive PGE2 synthesis in term labour

§ PGE2 is constitutively expressed BEFORE any changes can be witnessed that are conducive to labour. o Equally, some tissues could not be stimulated to express PGE2 as the levels are already high.

Regulation of growth/development of placenta

§ Placenta regulates its own growth/development through autocrine functions. § The maternal decidua mainly seems to restrain (modulate) placental growth/development so the placenta is optimal both for the baby and mother.

When is pregnancy counted from?

§ Pregnancy is counted from the first day of the last menstrual period (LMP), with other events dated from this time. o This is important as an embryologist and an obstetrician would use different time-scales. An embryologist would start the count from fertilisation. § IVF pregnancy timing - fertilisation occurs 2-3 days before implantation: o There will be a difference in time of 2-2.5w from the gestational age (GA, derived from LMP) and the GA in an IVF pregnancy - this can make a large difference when determining viability (22 vs 24 weeks for example).

How many trimesters in pregnancy?

§ Pregnancy is divided into 3 trimesters (0-13; 13-26; 26-39). § Spontaneous loss of pregnancy (miscarriage) in the first trimester is very common (1/3rd of all) but once 1st trimester completed, loss is minimal. § The end of the 2nd trimester marks the limit of infant survival (after this, the child is viable). o Modern care can push this back to 22 weeks. § Term (39-40 weeks) is expected delivery time and is stated as ~280 days (40 weeks) since LMP. §Three bars: a) maternal changes occur throughout b) embryo --> fetus --> viability --> term c) placental changes mostly occur in first half.

Typical developmental problems 2/4 - Autism spectrum disorder

§ Prevalence is 3-6 per 1000 live births. § Boys>girls. § Usually presents between 2 - 4 years of age. § Features include: (1) impaired social interaction; (2) speech and language disorder; and (3) imposition of routines with ritualistic and repetitive behaviour. § Comorbidities include: learning and attention difficulties, and epilepsy **Management: Intensive support for child and family

Typical developmental problems 4/4 - Learning disability

§ Prevalence of moderate learning difficulty is 30 per 1000 children § Prevalence of severe learning difficulty is 4 per 1000 children § 25% of children with severe learning disability have no identifiable cause § Causes include - (i) chromosome disorders (30%); (ii) other identifiable syndromes (20%); (iii) postnatal cerebral insults (20%); (iv) metabolic or degenerative diseases (1%) § Classified as mild, moderate, severe or profound § May present with reduced intellectual functioning, delay in early milestones, dysmorphic features, ± associated problems (epilepsy, sensory impairment, ADHD). **Management: Involves establishing a diagnosis and input from the multidisciplinary team with long term follow up. Also school recognition via the education acts and SEND: o SEND - Special Education Needs and Disability.

Normal cognitive changes in older people

§ Processing speed slows (due to loss in white matter) § Working memory slightly reduced (remembering something for short time) § Simple attention ability preserved, but reduction in divided attention (e.g. drive and maintain convo) § Executive functions generally reduced § No change in nondeclarative memory (implicit memory of HOW to do stuff) § No change in visuospatial abilities § No overall change in language (some reduction in verbal fluency).

Progesterone and labour pathways

§ Progesterone can switch off MANY of the labour pathways.

Anorexia Nervosa & Body Shape: variations between gender and cultures

§ Psychological implications of pubertal development - for boys the changes of puberty may be welcome (i.e. increased height and muscle gain) but for girls, the feelings may be more ambivalent (i.e. increased adiposity). o Cultural variation - white English girls are most negative about body shape than African Caribbeans. o The body shape dissatisfaction may bring about the anorexia (or other extreme weight loss diets). Reduced weight may induce dysphoria ( unhappiness) and repeated attempts to control weight. It also significantly increases the risk of an eating disorder including anorexia nervosa.

Puberty and eating disorders summary

§ Psychosocial factors mediate the relationship between pubertal development and onset of emotional, behavioural, eating & weight controlling behaviours. § Biological, temperamental and neuropsychological factors are implicated in vulnerability. § Treatment improves the outcome (v natural history).

Endocrinology of Puberty

§ RHS: adrenally driven production of pubic hair, axillary hair and acne. GnRH--> LH and FSH. § LHS: gonadally mediated. CRH--> ACTH. leads to breast and penis development

Conduct disorders and types

§ Repetitive & persistent (> 6 months) pattern of dis-social, aggressive or defiant behaviour. § Frequency & severity beyond age appropriate norms. **types: § Unsocialised CD. § Oppositional CD. § Socialised CD (well integrated in peer group). § Depressive CD. § Hyperkinetic CD. **worst prognosis is unsocialised as doing it by yourself.

Intra-uterine growth restriction (IUGR): define, recall the aetiology of, explain the management of and summarise the screening and detection used to identify intra-uterine growth restriction (IUGR)

§ Screening of 'at risk' patients at 24 weeks GA: PAPP-A < 0.4 MoM, POHx PET / FGR: (•POHx is past obstetric history of Preclampsia/ fetal growth restriction •Pregnancy associated plasma protein A (PAPP-A) •PET= preeclampsia •Early IUGR: 1%, usually linked to maternal disease e.g. PEC, difficult to manage because of risk of prematurity •Late IUGR: 5-7%, rarely linked to PEC, difficult to differentiate from SGA, easily managed by delivery) § Maternal systemic disease e.g. HT, renal, sickle. § Uterine artery Doppler 1st/ 2nd trimester - blood flow through uterine arteries: identify high resistance flow § Serial foetal biochemistry. Deliver at ≥ 28 weeks and/or ≥500g by C-section. Timing is v important - balance between risks in utero and prematurity. If born less than 36 weeks, baby needs corticosteroids § Late IUGR is easier to manage than early

Stillbirth

§ Stillbirth - death of the infant within the uterus, so that it is delivered without signs of life. o Some definitions include the viability limit (23w) so any dead births before this are miscarriages and any after this are stillbirths. § Stillbirth may be linked to labour but it is also a complication of pregnancy. § Stillbirth can occur at any GA and may be a shock to the parents. § Rates of stillbirth vary greatly - lowest rates in 1st world (0.2-0.5% of deliveries) countries and highest in 3rd world countries (up to 4.5% deliveries). § Detection - via monitoring of foetal wellbeing: o Ultrasound - monitor foetal movements. o Foetal blood flow assessment - Doppler ultrasound. § If abnormalities are detected, C-section must be undertaken immediately. § Causes - not well understood: o 50% due to labour. o Possibly increased risk of still birth with subsequent pregnancies. ***Better maternal health, and better healthcare can decrease many of the risks, but at present none of them can be eliminated completely.

Composition of surfactant

§ Surfactant: o Composition - lipids, proteins and glycoproteins. § ~40-45% DP-PC. § ~40-45% other phospholipids. § ~5% other proteins. Trace cholesterol and other components.

Most effective treatment for spina bifida

§ Surgery can be use to address anatomical problems; rather than have an exposed spinal cord, skin can be placed to protect the neural tissue. This will not address any functional problems; defects in the spinal cord often lead to damage to the nerves supplying associated tissues, and a range of linked complications eg inability to walk. § The MOST effective treatment is folic acid; if the maternal diet is low in folate, then the risks of spina bifida increase. It has been calculate that about 70% of cases of spina bifida are due to low maternal folate, so this does not explain all of this developmental abnormality. The timing of spinal development is early, so folate needs to be given before conception, preferably about 3 MONTHS BEFORE CONCEPTION.

Complications of obesity and associated features

§ T2D - more severe if younger § orthopaedic problems § PCOS § CV risk § psychological problems § cancer § resp problems

What is pre-term delivery classified as?

§ Term: 37-41 weeks. § Post-term: 42 weeks or more. § Pre-term: 22-37 weeks. § Extremely preterm: 22-28 weeks. § Very preterm: 28-32 weeks. § Moderate to late preterm: 32-36 weeks. § Miscarriage: Less than 22 weeks (non viable infant delivered). § Early miscarriage: First trimester. § Late miscarriage: Second trimester less than 22 weeks. o Normal term births: ~700,000 per year (UK). o Preterm labour births: ~45,000 per year. o Extremely preterm labour births ~4,500 per year. **Note that the numbers of preterm infants stated above does not reflect the total numbers per year, as this only includes those born after labour. About 35,000 babies each year are born prematurely following Caesarean section delivery for medical reasons, most notably pre-eclampsia and related complications. See the section on Fetal Growth for additional information (Chapter 5). The incidence of early miscarriage is difficult to estimate, but thought to be ~350,000 per year in the UK; it is considered that the majority of these reflect major developmental complications, so the pregnancy is not viable for more than a few weeks after conception.

Male reproductive tract

§ Testis - contain seminiferous tubules (to produce sperm) and Leydig cells which produce testosterone. § Epididymis - one within each scrotal sac. Sperm are stored in these and at ejaculation, sperm pass through the vas deferens (contractile) and are mixed with fluid from the seminal vesicles. The fluid then leaves the duct and passes into the urethra to mix with prostate secretions. § urethra - both urine and semen

What is a centile chart?

§ The "Red Book" is the book that documents child growth. § Centile charts are a way of expressing variation within the population; they tell you: o Height/length, weight, head circumference, leg length, BMI, growth velocity and lots of specialist specialist charts. o Based on surveys of large groups of children. o Age (x-axis) against height (y-axis). § height centile express how many people in the population are at particular height at any age - 25% of children will be shorter than the 25th centile and 75% will be taller. o Note - 50% of the population will be shorter than average (50th centile).

Centile charts

§ The "Red Book" is the book that documents child growth. § Centile charts tell you: o Height, weight, head circumference, BMI. o Based on surveys of large groups of children. o Age (x-axis) against height (y-axis). § 25% of children will be shorter than the 25th centile and 75% will be taller. o Note - 50% of the population will be shorter than average (50th centile). ** Attaining an accurate measurement: o Use well-maintained and accurate equipment. o Position the child appropriately. o Get rid of interfering items - i.e. shoes off. o Calculate age and plot correctly on the chart. § Centile charts we use are for cumulative height - the total of all the growth they have done up until now. § Height velocity - how fast a child is growing in cm/year (many short children grow at a normal speed).

Schematic on an implanting blastocyst, about 9 days post-fertilisation

§ The Blastocyst hatches from the Zona Pellucida (within which it has developed up to this time, about day 6 after fertilisation), and begins to implant in the uterine lining (Session 3.3), a process which is complete about 10 days post-fertilisation. By this time the inner cell mass, which was a group of undifferentiated cells, has become a bilayer disk, composed of hypoblast and epiblast cells . This bilayer disk gives rise to all the tissues of the human fetus, through a complex series of changes. § The first of these is gastrulation, which 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. **Embryology Timeline Day 9-16: 1. The conceptus starts as a bilaminar disc inside a blastocyst - comprised of an epiblast and a hypoblast layer. a. Buccopharyngeal membrane is also known as the prechordal plate. 2. Gastrulation forms a 3-layer conceptus - the ectoderm, mesoderm and endoderm. 3. Gastrulation occurs down the primitive streak where: a. Epiblast cells migrate towards the centre. b. Epiblasts then differentiate into the mesoderm cells and move down into the new mesoderm layer. c. The hypoblast cells apoptose and are replaced by endoderm cells.

A summary of the process of gastrulation

§ The Blastocyst hatches from the Zona Pellucida (within which it has developed up to this time, about day 6 after fertilisation), and begins to implant in the uterine lining, a process which is complete about 10 days post-fertilisation. By this time the inner cell mass, which was a group of undifferentiated cells, has become a bilayer disk, composed of hypoblast and epiblast cells. This bilayer disk gives rise to all the tissues of the human fetus, through a complex series of changes. § The first of these is gastrulation, which 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. There is the proliferation (P) of epiblast cells, which then differentiate (D) to form mesoderm cells; these move (M) into the space between the epiblast and hypoblast. These mesoderm cells are thought to differentiate further to generate the endoderm, which replaces the hypoblast cells which are lost by apoptosis (A). This shows how the application of basic cell biology can help in understanding the processes of embryology. § Formation of the three germ layers is a key stage in embryology, as they are the precursors to all the tissues in the body. Ectoderm gives rise to skin and the central nervous system; mesoderm to muscles, blood, skeleton, heart and kidney; endoderm to gut, lungs and liver. Muscular and vascular tissue are generally of mesodermal origin, so tissues are normally a mixture of germ layer types (e.g. muscle in the skin and gut). § Before Gastrulation is complete, Neurulation has been initiated

Transposition of the great arteries

§ 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. § The precise pattern of vascular changes can be very variable, so the best treatment can vary considerably between individual patients.

What is height velocity?

§ The centile charts we use are for cumulative height - how tall the child is now, (the total of all the growth they have done up to now, from conception). § Height velocity is how fast a child is growing in cm per year, usually this is calculated over a whole year. Most short children are growing at a completely normal speed. § Other useful information when assessing growth is the height of family members- parents and siblings. Ideally measure them yourself because people can be very inaccurate in assessing their own height.

The main stages of human parturition

§ The clinical definition of labour includes both the changes in the cervix, and in the myometrium, which are integral to the first stage of labour (Figure 4.2). Rupture of the fetal membranes also normally occurs during the first stage. This stage of labour is usually the longest lasting for ~8 hours - this is likely to be longest in a woman having her first baby, and shorter in subsequent pregnancies. Note that this stage is very variable, with both shorter and longer times being quite common. § Delivery of the infant is the second stage of labour; this usually last about 30 minutes, but again can be longer in a first pregnancy and shorter in following pregnancies. § The third stage is delivery of the placenta, which should occur within 30 minutes of delivery of the infant. Delivery of the placenta is associated with very powerful contractions of the uterus, leading to a rapid decrease in overall size - this is referred to as involution. Once the placenta has been delivered, this involution of the uterus is very important, as this is the primary process through which blood flow through the spiral arteries is stopped. This process is linked to increased maternal levels of oxytocin - if it does not occur spontaneously, an injection of oxytocin (or similar muscle contracting agent) can be given to accelerate the process.

Causes of short growth

§ The commonest concern about growth is short stature. The majority of short children have a normal growth pattern, and do not have anything wrong with them. If a child grows slower than normal over a significant period of time they will fall in their centile position. § This is abnormal and a cause should be looked for: a) Poor nutrition b) Chronic disease c) Endocrine causes- GH deficiency, thyroid hormone deficiency d) Genetic disorders affecting bone growth (eg achondroplasia, Turner syndrome, Down syndrome). e) Psychological distress and neglect.

changes in the oocyte following fertilisation

§ The cortical reaction is initiated, leading to hardening of the zona pellucida and the exclusion of other sperm. § and the cumulus cells, will still be present at the stage shown in Figure 2.14, although they play no further role in the process. § By this stage, Meiosis II in the maternal chromosomes is completed, leading to the formation of polar body II, and the female pronucleus. The head of the sperm is undergoing decondensation, with the previously tightly packed paternal chromosomes forming a much looser structure. Both pronuclei are haploid at this stage of fertilisation.

Till how many weeks do spiral arteries remodel in pregnancy?

§ The cytotrophoblast (ctb) cells remodel the spiral arteries during the 1st trimester until ~16-18w GA. § The remodelling converts the narrow bore spiral vessels into wide-bore vessels to transport more volumes of blood. o The ctb cells replace the vascular endothelium and VSMCs which is important as it means the vessels here cannot respond to vasoconstrictors. § The placenta has no nerves , so it is not regulated by such systems at any stage of pregnancy. This means that it can feel no pain during delivery, and the umbilical cord can be cut after delivery without any impact on the infant.

When is the fastest phase of growth after birth?

§ The fastest phase of growth after birth is in the first 2 years of life. Children can move up and down through the centiles at this phase of growth. § Most children will move to a centile position by 2 to 3 years of age and then continue on this centile position through childhood. Normal children grow fast enough to keep on the same centile and movement up or down is unusual. § There is a phase of fast growth at puberty- the PUBERTAL growth spurt. The timing of this depends on the age at which the child enters puberty. § The skeleton matures as the child grows, the epiphyses FUSE at the end of puberty, and growth stops.

Female erectile tissue

§ The female equivalent of the penis is the clitoris. § The clitoris, like the penis, increases in size as a result of an increased blood flow into the tissue. § The mechanism is the same (i.e. release of NO)

When does forelimb bud and hind limb bud appear?

§ The forelimb bud appears at day 27/28, hind limb bud at day 29. § Budding is growth from the lateral plate mesoderm which is done rapidly under control of special signalling regions. § The limbs are fully formed and patterned by day 56. **§ Achondroplasia - FGF23 gain of function mutation: o Concerns the elongation of limbs and not primary formation and so detail is there, they just aren't long limbs. o The mutation stops conversion of cartilage to bone.

The gonads and reproductive tracts are indifferent up until...

§ The gonads and reproductive tracts are indifferent up until 7 weeks of development; differentiation is influenced largely by the presence or absence or SRY (on the Y chromosome). § If SRY+, then development proceeds along the male path. § If SRY-, then development proceeds along the female path. § Within the mesonephros, the mesonephric and paramesonephric ducts develop, and are readily identifiable by week 5 post fertilisation. At the same time, the gonad precursor is developing from the mesonephric mesoderm, and is covered by coelomic epithelial cells.

What do gonads arise from?

§ The gonads 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 about Week 7 post fertilisation

female reproductive system

§ The ovary - produce the gametes and steroids (oestrogens and progesterone's). § The fallopian tubes - oviduct - sustains oocyte or conceptus. § Uterus - conceptus implants here.

Female reproductive system diagram

§ The ovary parallel functions to the testes, in that they produces the gametes (oocytes) and the steroids needed for female reproductive function (progesterone and estrogens). § The Fallopian tube (oviduct) through which the oocyte reaches the uterus. Provides an appropriate environment to sustain either an oocyte or a conceptus (fertilised oocyte). § The uterus, in which the conceptus normally implants and is supported throughout pregnancy. **Progestogens - maintain endometrium. **Oestrogens - stimulate proliferation of the endometrium.

primary subunit of human placenta

§ The primary subunit is the placental villus, which have the complex branched structure shown. This provides a very large surface area (estimated to be 11 square metres) for exchange between the maternal and fetal vascular systems, thus meeting a primary requirement for exchange functions. § Anchorage to the maternal decidualised endometrium is also shown. Within each villus there is a complex blood supply, including arterial and venous vessels, connected to smaller capillaries in the terminal portions of each villus. Note that the arterial system contains de-oxygenated blood, and the venous blood is oxygenated - because the placenta has a parallel function to the lungs for the fetus during pregnancy. § The maternal surface of a placenta is sub-divided into cotyledons (30-60 per placenta). Each cotyledon contains one or more villi, with larger cotyledons containing more villi. The variability in the shape and size of cotyledons does not affect placenta function.

In what direction does primitive heart tube turn?

§ The primitive heart tube undergoes an anti-clockwise turning motion which results in the ventricles being at the bottom with the atria at the apex. § The atria rotate BEHIND the arteries. § From day 17-28, the head-tail folding is also occurring which aids rotation of the heart and the movement of the heart more internally. § The folding of the head and tail is what turns the heart in the anti-clockwise motion as seen on the left. o Pressure of the folding head pushes the heart to the centre of the body which squishes the atria (less muscular than ventricles). o The squished atria then spring out and straighten. o The final twisted form then resembles...

Theories drawn from partuition hypothesis

§ Theories drawn for labour: o Anything that increases CRH may --> labour (stress, multiple infants). o Anything that increases muscle contraction may --> labour (excess stretch of uterus). o Anything that activates inflammatory cascades may --> labour. § All the above also apply to pre-term labour - i.e. stress due to intrauterine bleeding.

Meningocele & Myelomeningocele (Meningomyelocel)

§ There are three main types of spina bifida: Spina bifida occulta, Meningocele and Myelomeningocele. 1) Spina bifida occulta: Spina bifida occulta is the mildest and most common form of this disorder. It usually only involves a minimal portion of the spine; it usually shows no symptoms, and it does not require treatment. When an infant is born with spina bifida occulta, the skin covers the deformity of the spinal bone. 2) Meningocele In this least common type of spina bifida, the meninges (membrane surrounding the spinal cord) protrude through the opening causing a lump or sac on the back. More severe than spina bifida occulta, meningocele can nevertheless be repaired through surgery with little or no nerve damage resulting. The surgery is performed at any time during infancy. With meningoceles, the spinal cord has developed normally and is undamaged. The child has no neurological problems. 3) Myelomeningocele Myelomeningocele is the most severe form of spina bifida. The spinal cord does not form properly and a portion of the undeveloped cord protrudes through the back. A sac containing cerebrospinal fluid and blood vessels surrounds the protruding cord, which is usually not covered by skin so that the nerves and tissues are exposed. Often experience hydrocephalus. Infants born with myelomeningocele often have paralysis or weakness below the level of the spinal lesion. This affects the lower limbs along with problems with bladder and bowel function. In extreme cases, the trunk and upper extremities are involved.

Main components of the human ovary

§ This schematic summarises the changes in follicular structure as they develop and increase in size, but also notes that follicles may not develop all the way to ovulation - atresia is common, as shown. § The thecal cells of the developing follicles are responsible for the production of estrogens, and the granulosa-luteal cells produce estrogens and progesterone during the second half of the ovarian cycle.

MOCA - Montreal Cognitive Assessment

§ Top left: executive - ask to connect numbers and letters in ascending order e.g. 1,A,2, B .... § ask them to draw clock § name animals § memory test - 5 words to remember § maths (attention) § language - repeating sentences, naming words beginning with F § abstraction § delayed recall § orientation. **adds up to 30 points. Takes about 20 mins. **Advantages of MOCA: §Covers a variety of domains of cognitive function §Brief to administer (10 mins) §Validated in a range of populations §Available in translated versions §Widely used **Problems with MOCA: §Education level will affect results §Language level will affect results §Floor and ceiling effects §Can be poorly administered §Possibly practice/coaching effects

Risk of undescended testes

§ Undescended testes - increased risk of cancer, do not function normally. § Female reproductive tracts (SRY -ve): o Gonads develop into an ovary - containing oogonia and stromal cells. o No testosterone is produced so mesonephric tubes (Wolffian tubes) regress. o No AMH/MIS so Mullerian (paramesonephric) ducts persist. o Summary: § Ureteric bud - ureter. § Mesonephric ducts - trigone of bladder. § Paramesonephric ducts (Mullerian) give rise to - oviducts, uterus, upper 1/3rd of vagina. § Urogenital sinus gives rise to - bulbourethral glands, lower 2/3rd of vagina. § Testosterone is needed about 8 weeks PF (post-fertilisation) but the hCG peak is 8 weeks after LMP (last menstrual period). hCG drives the testosterone production. **•Y chromosome --> SRY gene --> AMH --> regression of paramesonephric/mullerian duct --> testis.

Adverse drug reactions and drug intake

§ Up to 17% of hospital admissions are due to drug reactions. § The more medications taken, the greater the risk

Potentially inappropriate polypharmacy (PIP)

§ Up to 40% of prescriptions are inappropriate § Polypharmacy is associated with bad outcomes: -Falls, -Increased length of stay, -Delirium, -Mortality.

Maternal Doppler assessment

§ Uterine Artery Doppler Screening

Ageing- Brain

§ Volume of CSF within the surrounding brain increases with age, the ventricles enlarge and the gaps between the major gyri widen. Brain reaches a maximum weight at around 20 years and remains the same till around 40-45 years, after which it decreases in weight at a rate of 2-3% per decade. § Dementia- chronic, progressive, degenerative disease which cause a decline in cognition. The most common types (Alzheimer's and vascular) often start with memory problems, but over time include all cognitive functions § Delirium- acute episode of confusion, usually with a clear precipitant such as infection or medication changes.

Weights of conceptus at trimesters

§ Weights: o First trimester - 50g. o Second trimester - 1050g - viable at 500-820g stage (21-24 weeks). o Third trimester - 2100g.

Limb development in summary

§ a process that occurs over a number of weeks. Formation of the main structures is integrated with rotation of these structures, to give the final correct outcomes.

Mental health in young people stats

§ adolescence is when majority of mental health problems start. **self awareness/ comparison to others is a risk factors for this. Girls are much more vulnerable to this than boys by comparing on social media.

Pubertal development in girls: secular trends

§ age of puberty has decreased over years (17 --> 12) § mainly due to improved nutrition. § those overweight more likely to get period earlier

Are centiles a normal range?

§ are not a normal range. can be taller of shorter than the centile lines and still be completely normal and healthy. § most children set out on a centile by about 2 years and grow on the same centile during childhood. § pattern of growth is more important than position on the centiles. Most very tall or very short people are healthy and grow in a normal pattern. § a child who falls significantly in centile position is not growing normally, whatever their height.

Neuropsychology of Anorexia Nervosa Executive Function deficits

§ association of AN with spectrum. § Weak central coherence in ED's: • Global processing difficulties [review]. • Poorer global processing =>Weak central coherence § Impaired set shifting.

Etiology of anorexia nervosa

§ biopsychosocial interaction. § biggest risk factor for eating disorder: Being female, and then diet and behaviours. Boys and girls both feel fat, but girls more likely to diet. Boys want to gain more muscle. Get eating disorders across all ethnicities.

Bone age

§ bone develops from membrane or cartilage --> ossify. § in X-ray can only see ossified bits. § cell growth at growth plates § when stop growing, growth plates fuse § the bones mature and epiphyses fuse at the end of puberty. § the final part of growth occurs in the spine and the final epiphyses to fuse are in the pelvis.

Aetiology of conduct disorders

§ child factors, family factors, environmental factors

Height velocity chart

§ cm/year § in utero grow loads, then decreases and is stable height present childhood § then peak at puberty again § then decreases and eventually stops. § measured as: (height now - height last visit)/(age now - age last visit). § interval approx 6 months. § Normal growth can be influenced by (causes variations in growth in the population): o Events before birth - i.e. poor foetal growth, LBW, etc. o Medical issues in childhood - i.e. malnutrition, chronic disease. o Genetic factors. o Randomness - presence of multiple genes and the environment. § The fastest phase of growth is between the ages of 0-2 years old - children move up and down through the centiles around this time but will move to a centile position by about 2-3 years old. o There is another phase of fast growth at puberty. o The skeleton matures as the child grows, the epiphyses fuse at the end of puberty and growth stops. **Monitoring height growth: o Use of the "Red Book" - concerns should invoke the use of the red book for at least a year. o Timing of puberty can impact on height - late developers can fall behind in height.

Epidemiology of conduct disorder

§ commonest psychiatric disorder of childhood. § Anti-social behaviour: • Adolescent-limited • Life course persistent o 5-10 years old: 4% (5% from ages 5-15 overall). o 10-15 years old: 6%. § Higher in deprived city-centre areas. § 3x more likely in men (3: 1, Boys: Girls). § Age of onset varies. § Associated with - larger family size, lower socio-economic status.

Common problems seen in child development

§ delayed walker § clumsy child (cerebellum) § delayed speech and language (wernicke and broca's) § odd social interaction - ASD/ aspergers § hyperactivity - (issue with prefrontal cortex - affects dopamine levels). § common behaviours - sleep onset/freq night waking, eating, toileting § specific learning difficulties

Embryologist timing vs gestational timings

§ developmental embryologists start from the point of fertilisation; Such timings will be shown as post-fertilisation (PF). § this is about 2 weeks after the LMP gestational timings conventionally used in the timings of pregnancy. § Note that the term 'embryo' has two separate meanings; during this first week (PF), the whole conceptus is the embryo. After differentiation to form a blastocyst, the embryo refers to the cells that contribute to (or are) the baby alone; other tissues have separate identities. § Once the main structures of the baby have formed during the first months of pregnancy, the rest of pregnancy is more concerned with growth of the fetus, and the maturation of the structures that have been developed.

Customised growth chart

§ differences in infant sizes are most likely to be due to genetic effects, most notably the size of the parents. If the parents are both on the 95th centile for height, then their infant would be expected to be of a similar size. For these reasons, customised fetal growth charts may be used, which allow for a more individualised assessment. § The customised standard defines the individual fetal growth potential by three underlying principles: 1. Adjusted to reflect maternal constitutional variation maternal ht, wt, ethnicity, parity. 2. Optimised by presenting a standard free from pathological factors such as diabetes and smoking 3. Based on fetal weight curves derived from normal pregnancies. *for second chart, because mums small and babies small is normal.

Typical developmental problems 1/4 - Cerebral palsy

§ disorder of movement and posture arising from a non-progressive lesion of the brain acquired before the age of 2 years. § Incidence 1-2 per 1000 live births § Most causes (~80%) are antenatal- genetic syndromes and congenital infection. 10% due to hypoxic-ischaemia injury at birth, 10% due to postnatal origin (infection, trauma). § Presentation may evolve and vary with age: o Abnormal limb tone and delayed milestones. o Feeding difficulties. o Abnormal gait once walking achieved. o Asymmetric hand function before 12 months. o Primitive reflexes persist. § Types: a) 70% Spastic - stiff limbs or legs o 10% (each): b) Ataxic hypotonic- floppy not stiff c) Dyskinetic- jerky movements d) Mixed Pattern - elements of all the above 3 § Associated problems exist - learning difficulties, epilepsy, visual impairment, hearing loss, feeding difficulties, poor growth, and respiratory problems. **Management: Aim is to minimise spasticity and manage associated problems

Obesity harms children and young people

§ emotional and behavioural. § high cholesterol § high BP § pre-diabetes § bone and joint problems § breathing problems § increased risk of adulthood obesity

age of attaining peak cortical thickness

§ extensive cortical thickening and then thinning in adolescence. § cross-over from grey matter to white matter (pruning) - neurones most utilised dominate, and those not used are pruned away. This also increases vulnerability to risk taking.

Formulation framework

§ for mental health disorders. a) predisposing (e.g. genetics, bullying, family) b) precipitating (trigger) e.g. bullying, relationship problems. c) perpetuating (keeping it going) (e.g. isolation, isolation, reward) d) protective factors. § individual, family, systemic. * use this as there is no single cause for mental disorder.

Grey matter in bone

§ frontal cortex - concentration, exec function § primary motor cortex and premotor cortex - movement § parietal - sensation § occipital - visual association § temporal - hearing and language

Causes of short stature

§ genetic - parents § pubertal and growth delay - girls start from age 8-13; boys age 9 - 13.5. § IUGR/SGA - 15% of babies don't catch up in height § Dysmorphic syndromes - Down's and Turner's § Endocrine disorders - GH deficiency, hypothyroid in child § chronic paediatric disease - lots of inflammation in body. GH attaches to GHR and causes intracellular signalling and production of IGF-1. inflammatory mediators block the intracellular signalling and production of IGF-1. § psychosocial depravation - GH pulsatility decreases. when put in foster home can increase growth. **Overall: o can be short but have normal growth pattern. o most short children have a normal growth pattern and no medical problem. o they are usually the children of short parents. o not all children with IUGR catch up completely. Growth will be normal in childhood but they have lost some height in the antenatal period.

Programmed ageing theory

§ genetic, hormonal and immunological changes lead to the cumulative deficits we see as ageing. § Ageing is built into your DNA. § The Hayflick limit, or Hayflick phenomenon, is the number of times a normal human cell population will divide before cell division stops. Telomeres perform this counting limit, gets shorter each time cell divides. § This is to protect us as well. e.g. from cancer. § If we could stop telomeres shortening - perhaps could expand lifespan?? Experimenting in mice currently. § These theories suggest ageing is part of an inescapable/programmed process. **No single theory explains all that we know about ageing.

Girls & Boys Growth Patterns in Puberty

§ girls average two years early. § for girls - growth spurt is early pubertal event. for boys is a late pubertal event. § between ages 11-15 - see biggest discrepancy between boys and girls.

Height velocity chart for boys and girls

§ girls get a beginning of puberty. boys at end. § sex steroids and GH synergy --> pubertal growth spurt.

Endocrine problems causing reduced height and growth velocity

§ hypothyroidism § growth hormone deficiency § steroid excess

Organisation of the spinal cord in motor tracts

§ if injure most of back of spine - sacral and lumbar affected more. § coordination from cerebellum by reticulospinal tract § vestibulospinal tract - balance § olivospinal tract on lateral side

Autism typical signs seen

§ impairments in communication and repetitive behaviours § less likely to play with friends § avoidance of gaze of father § preoccupation with objects and light §

classic structure of spina bifida

§ literally 'two spines', showing parallel tissues either side of the spine itself. In the other images, alternative presentations are shown; the spinal defect is often found towards the lower part of the back, and therefore affects the lower limbs, but the central image shows that spina bifida is not necessarily a single defect, nor is the defect always on the lower back.

Head circumference

§ measures brain development. § babies have fontanelles to allow brain to develop. § if head not growing, brain not growing. § helps see if brain trauma or damage. § if sudden increase - hydrocephaly (medical emergency). § when bones of head fuse - don't measure anymore

Obesity prevalence by deprivation

§ more deprived --> more obesity. § to do with diet and exercise

Rates of different types of disorder in 5-19 year olds

§ most emotional disorders in 17-19. § 17% of pop by the time they reach 19 would have had a mental health disorder.

Is this child normal height?

§ no - doesn't match midparental centile and growth is not parallel to centile charts. § so do: a) FBC, CRP, serum iron b) liver, thyroid and kidney function c) coeliac screen d) IGF1 e) bone age. *child had problem with pituitary and GH picked up by MRI pituitary and pituitary function testing.

Key pathways in the human brain involved in reproduction

§ pic indicates the associations between systems involved in parenting, fertility, reward, and pleasure, which in turn link human bonding with reproduction and parenting. § Meso-limbic DA system - reward & pleasure pathways. § Nigro-striatal tract - control of movements. § Neuro-endocrine pathways - regulating fertility and parenting. § Activation of pleasure pathways therefore encourages intercourse, thus continuation of the human race. These brain functions complement the role of the brain in controlling the production of gametes (hypothalamic-pituitary-gonadal axes).

Genetics of weight

§ polygenic inheritance § weight heighly heritable trait (40-70%) § monogenic obesity syndromes (rare) - leptin deficiency (leptin treatment) - leptin receptor deficiency (can't use leptin as treatment) - POMC deficiency (altered pigmentation too) - PC-1 deficiency - MC4R deficiency

Achondroplasia and growth

§ skeletal dysplasia § take standing height and sitting height (measure from back side to head and then subtract from total height --> subischial leg length) § so can see that although sitting height is normal, the leg height is very small.

Causes of tall stature

§ tall parents § early puberty -In precocious puberty the pubertal growth spurt occurs very early and so children with this can present with tall stature. However growth stops early as well so they can then be short as adults. § syndromes e.g. Marfans and Soto syndrome. § GH excess- from a pituitary tumour. This is very rare indeed, most of the "tallest men and women in the world" have had this diagnosis

Control of penile erection

§ the regulation of penile erection is also partly under the control of the brain, via the spinal cord and efferent nervous system. § This is not the complete picture, as tactile stimulus of the penis can activate the afferent system (pudendal nerve) as shown, involving a more direct interaction between the spinal cord and penis. § Penile erection pathways: 1) Sexy thoughts in brain OR tactile stimulus to penis. § Brain - limbic system. 2) Spinal cord - efferent to penis, afferent back. § Pudendal nerve.

Patterns of abnormal development

§ there is a wide normal range. § children that are worrying are: slow but steady, plateau and regress

Guide to accurate measurement

§ when young and if can't stand up, lie them down and measure head to toe. § when older, stand up and measure. § Attaining an accurate measurement: o Use well-maintained and accurate equipment. o Position the child appropriately. o Get rid of interfering items - i.e. shoes off. o Calculate age and plot correctly on the chart. § Centile charts we use are for cumulative height - the total of all the growth they have done up until now. § Height velocity - how fast a child is growing in cm/year (many short children grow at a normal speed).

Process of labour

§ •Independent of gestational age. Labour involves: 1) Cervical ripening and effacement - INCREASING. 2) Co-ordinated myometrial contractions - INCREASING. 3) Rupture of foetal membranes. 4) Delivery of infant --> then delivery of placenta. 5) Contraction of uterus. § The stages up to term involve 3 trimesters and then the 3 phases with the baby delivered in P2 and placenta in P3. ** Labour lasts 12-48h and the phases get shorter.

Miscarriage and stillbirth: explain the difference between miscarriage and stillbirth and recognise how ultrasound imaging and fetal dopplers are used in fetal assessment

§ •Viability limit = 24 weeks. § •<24 weeks - miscarriage § >24 weeks - stillbirth §Most miscarriages occur in the first trimester (highest risk to foetus) §The causes of stillbirth are not well understood. 50% occur during the process of labour. 60% of cases may not have obvious cause. §Foetal monitoring of movement and blood flow (e.g. Ultrasound scans, and doppler USSs) may indicate increased risk but cannot predict: Detect via foetal USS monitoring: decreased fetal movements --> increased risk perhaps coupled with assessment of the fetal blood flow (doppler ultrasound). If foetal compromise is detected, then Ceasarean section as soon as possible is needed.

Adolescence and Puberty- Mood disorders (conduct disorder)

§Conduct disorder- Persistent failure to control behaviour appropriately within socially defined rules. §Features: child that looses temper and argues, defies adult requests or rules, bullies, fights or intimidates, commits crimes and steals §Contributing developmental factors: changes in family relationships, peer pressure §Epi- 4% at ages 5-10 years; 6% at ages 10-15 years; overall 5% at ages 5-15 years, Higher in deprived inner-city areas, Boys: girls 3:1 §Interventions: For child - problem solving skills, Parent training, Family intervention, Address problems across contexts e.g. in school

Advantages of MOCA

§Covers a variety of domains of cognitive function §Brief to administer (10 mins) §Validated in a range of populations §Available in translated versions §Widely used

What is dementia?

§Decline in ALL cognitive functions, not just memory. §Impairment of function. §Progressive. §Degenerative. §Irreversible.

Contact of placenta and maternal blood system

§Early, the conceptus is in contact with endometrial cells. § As it grows, the conceptus makes transient contact with maternal capillaries but rapidly proliferating cytotrophoblasts cells form a capsule around the conceptus, isolating it about 4 weeks PF (2 weeks LMP GA). o Cytotrophoblast shell limits blood (oxygen) supply to embryo during early development (so not high blood flow during 1st trimester). This is important because 1st trimester embryo is most vulnerable, low blood supply means placenta and embryo developing in low oxygen environment and hence less oxygen free radicals which are damaging. o Decidual glands hypertrophy during the 1st trimester to provide nutrients for placenta and baby. The placenta functions normally but it is the source of nutrients rather than the maternal blood that is different. § Cytotrophoblast shell (plugs) remains in place until ~8w PF (~10w GA), this blocks the spiral artery formation. o The cytotrophoblast is still important in remodelling later though. o Remodelling of spiral arteries allows high volume blood supply from mother in trimesters 2 and 3, when infant growth is greatest. § During weeks 10-12 GA, the Cytotrophoblast plugs break down (from the periphery directed centrally) and the spiral arteries form to supply the foetus with blood normally. o This is a risk-time in the pregnancy - if the placenta is not anchored properly, the increased pressure as it is exposed to the maternal blood supply can lead to a detach and a miscarriage. § During the 1st trimester, the placenta is ~5cm diameter but this increases to ~20cm during 2nd and 3rd, but the key structural components do not change. Most of the growth is due to increased size and branching of the villi.

Any problems with the MOCA?

§Education level will affect results §Language level will affect results §Floor and ceiling effects - if v educated, could be demented but still score well. §Can be poorly administered - can be administered by people without training. but now need to have some training before administering it. §Possibly practice/coaching effects

Non-specific presentation of frailty

§Falls §Reduced mobility §Recurrent infections §Confusion §Weight loss §"Not coping" §Iatrogenic harm **Older people are less likely to have common, "textbook" symptoms of disease: a) ACS •Less likely to have chest pain •More likely to have shortness of breath b) PE: •Less likely to have pleuritic chest pain •Less likely to have haemoptysis •More likely to have syncope **hence can be difficult to get right diagnosis and treatment. § Atypical & non-specific presentations can lead to delays in treatment. § Older people often present with multiple problems which all need to be managed simultaneously. o For this reason, geriatrics is a multi-disciplinary speciality. § Changes in pharmacokinetics and pharmacodynamics can make drug treatments more dangerous in older people. § Many drug trials have low numbers of older people, so the evidence for treatment is often extrapolated from younger people which may not always be accurate.

Problems with cognitive assessments in general

§Hearing and visual impairment may limit testing §Physical problems may limit testing - e.g. can't hold up pencil to draw clock. §Most assume numeracy and literacy §Most assume some basic cultural knowledge §Depression can masquerade as dementia §Not valid in acute illness §Normal cognitive changes (slower processing speed, slower reaction times) may affect administration **HENCE: INTERPRET THEM IN CONTEXT.

recall homeostasis mechanisms within the hypothalamo-pituitary-gonadal axis

§Hypothalamic-pituitary-ovarian (HPO) axis §Hypothalamus secretes GnRH which stimulates pituitary gland §Pituitary gland release LH and FSH which stimulate theca and granulosa cells in ovaries §Theca and granulosa cells secrete steroid hormones oestrogen and progesterone which inhibit pituitary secretion (except at ovulation)

Changing nature of older population

§Increasing numbers of BAME older people. §Increasing education of older people (this is strongly protective against dementia). §Reduction in poverty. §More people are working for longer. §More complex/nuanced retirement process.

What is pre-eclampsia?

§Multisystem disease that usually manifests as hypertension and proteinuria. §classifed as: BP: >140/90mmHg and proteinuria: >0.3g/24hour (PCR>30). a) Mild: 140-149/90-99mmHg b) Moderate: 150-159/100-109mmHg c) Severe ≥160/110mmHg. **arising de novo. ** after the 20th week of gestation in a previously normotensive woman and resolving completely by the 6th postpartum week o HBP in 10% all pregnancies. o Only 1-2% severe form. o "Fetal syndrome" is relatively rare

Why are older people at increased risk of harm from drug prescription?

§Reduced physiological reserve §Impaired compensation mechanisms §Comorbidities §Polypharmacy §Cognitive impairment

Tetralogy of Fallot

§The Tetraology of Fallot is summarised above, and shows the 4 features listed in the pic. § Perhaps the most important aspects are the septal defect between the ventricles (which tends to allow deoxygenated blood into the left ventricle, and the stenosis of the pulmonary artery (decreasing blood flow to the lungs).

Chromosomal problems that can occur

§Too many, too few, translocations. §ALL give rise to syndromes § Cross-talk between systems

Placental development

Ø Approx. 9 days Post-Fertilisation, the conceptus is completely implanted in the maternal endometrium. At this stage of development, the outer layer of the conceptus are multinucleated syncytiotrophoblast, which contain fluid-filled lacunae. The underlying layer of cytotrophoblast is proliferating adjacent to the embryo: this is where the placenta will develop. o Placenta originates from the cytotrophoblasts layer in the blastocyst. Ø Following implantation, cytotrophoblasts proliferate and differentiate into the syncytium to form a columnar structure which becomes a villous structure. Ø Form simple branched structure, expands iteratively. Ø At the centre of each villus are mesenchymal (extra-embryonic mesoderm) cells, from which the villus vascular system develops. The branching process continues through out pregnancy, giving rise to the complex branched villi. o The overall structure then does not change but it is modified. o There are fewer cytotrophoblasts present at term so that there can be a closer apposition between the syncytium and placental capillaries.

Focussed Physical examination of child for assessment of development

Ø Look of child Ø Growth Ø OFC - occipitofrontal circumference Ø Hearing and vision Ø Skin Ø Genitalia

Hand formation

Ø-Forelimb bud appears at d27/8 Ø-Hindlimb bud at d29 Ø-Grow out from lateral plate mesoderm rapidly under control of special signalling regions Ø-Fully formed and patterned by d56. *Urogenital, cardiac, facial and lung development all proceed rapidly during the second month of development. In addition to these structures, limb development occurs over this same time-frame, as the initial limb buds grow, and the terminal regions are converted to hand or foot plates that in turn develop digits.

MDT team in child development management

ØAssessment ØDiagnosis and disclosure ØManagement programme ØSocial support

Causes of motor developmental delay

ØCerebral palsy ØGlobal delay eg Down's syndrome ØCongenital dislocation hip ØSocial deprivation ØMuscular dystrophy-Duchenne's ØNeural tube defects: spina bifida ØHydrocephalus

Causes of global development delay

ØChromosomal abnormalities e.g. Down's syndrome, Fragile X ØMetabolic e.g. hypothyroidism, inborn errors of metabolism ØAntenatal and perinatal factors: Ø Infections, drugs, toxins, anoxia, trauma, folate def ØEnvironmental-social issues ØChronic illness

What is a conceptus? Embryo? Fetus? Infant?

ØConceptus - everything resulting from the fertilised egg (baby, placenta, fetal membranes, umbilical cord). blastocyst is a bilayer of cells. ØEmbryo - the baby before it is clearly human. the baby up to week 8 of development. ØFetus - the baby for the rest of pregnancy. ØInfant - less precise, normally applied after delivery. **red patch is liver - this is where they make RBCs because don't yet have a BM. *in embryology (e.g. in these pics) -it describes time frame since fertilisation. *when decribing pregnancy: first day of last menstrual period is used as start point for pregnancy (2 weeks after this implantation occurs). used as this is easy to identify easily. * if mix these two timings up, can deliver a preterm baby. § Again, remember that timings used to discuss embryology are usually from point of fertilisation, 2 weeks after LMP timings used in timings of pregnancy - the embryology timings are PF - Post-Fertilisation.

Eye colour development

ØHuman chromosome 15. ØBrown most common colour; others mostly in Caucasians. ØDifferentiation of eyes begins about Day 22 PF. ØEvent must predate Day 22.

Key regulator of labour?

ØLabour strongly resembles an inflammatory response in fetal membranes and cervix ØThe main active tissues are myometrium and cervix ØThe key regulator seems to be NFkB ØTerm and preterm labour differ mainly in the initiating factors ØMaternal progesterone levels remain high during labour - 'functional progesterone withdrawal

Consequences of placental mal-development

ØMiscarriage (late first trimester) ØMiscarriage (second trimester) ØPre-eclampsia (early delivery) ØFetal growth restriction (small infant)

Progesterone & human pregnancy

ØProgesterone is NEEDED to sustain pregnancy. Progesterone receptor blockade: pregnancy loss ØProgesterone levels remain very high until AFTER delivery of the placenta (unlike sheep) o This means that the effects of progesterone must be LOST in normal term labour which means the PR receptor must be disrupted. § High levels of NFKB before term can BLOCK the PRs and thus reduce the effect of progesterone to sustain pregnancy so labour can begin (and NFKB is high towards term). NFkB high then stimulates labour. **Progesterone receptor (PR): 1) PR-B - mediates main effects of progesterone. 2) PR-A - less able to mediate than PR-B: § Ratio of PR-A: PR-B increases towards term so progesterone has less of an effect. § Loss or change in PR may lead to a "functional progesterone withdrawal" which is physiologically normal towards term labour. § Progesterone can switch off MANY of the labour pathways.

Commonly used assessment tools for child development

ØStandardised tests. ØSchedule of Growing Skills (II). ØGriffiths developmental scale. ØBailey developmental scale. ØDenver developmental screening tests **OFFER THE RIGHT TOOLS, OBSERVE, LISTEN

Male reproduction starts when?

ØStarts at puberty ØFunctions continually ØNormally continues throughout the rest of life ØSperm quantity and quality generally decreases with increasing age ØLH stimulates testosterone production ØFSH and testosterone sustain Sertoli cell function ØSertoli cells support spermatogenesis

When does female reproductive function start?

ØStarts at puberty ØFunctions cyclically ØNormally operates until ~45 years of age ØEgg quality generally decreases with increasing age ØFSH stimulates (some) development of ovarian follicles & 17b-estradiol synthesis ØLH stimulates progesterone production ØThe steroids regulate uterine endometrium

How can we observe pregnancy?

ØWe can observe it (in utero, or outside). ØMeasurements can be made of circulating factors, or dimensions. ØThe correct Ethics of research make is very difficult to study mechanisms.

Thalidomide

Ø~10,000 affected infants known, ~50% initial survival rate. ØLimbs affected. ØIn addition, deformed eyes and hearts, deformed alimentary and urinary tracts, blindness and deafness. Ø Thalidomide - affects rapidly developing blood vessels, notably those of upper limbs. Ø Blood vessel affects can be generic, hence the range of effects observed. ØUsed in some leprosy and cancer treatments at present in parts of Africa. o thalidomide messed up BV development in developing limb --> cell death.

Concerns in index pregnancy as they arise

• Abnormal serum biochemistry. • Reduced symphysis fundal height. • Maternal systemic disease e.g. PET. • Antepartum haemorrhage. • Multiple pregnancy

Definition of adolescence?

• Adolescence - phase between childhood & adulthood. New adolescence is 10-25. Definition is expanding. • Pubertal development may be start of adolescence. • Adulthood: legally, culturally variable. • UN: children < 18 years. § Developmental stages of adolescence: o Early 11-14. o Middle 14-17. o Late 18-21.

Sex: distinguish between biological sex, sexual reproduction, and sexual intercourse

• Biological sex= Gender, chromosomes (XX vs XY) • Sexual reproduction= Produces offspring that differ genetically from parents • Sexual intercourse= Sexual activity required for sexual reproduction

Ultrasound assessment of fetal growth

• Fetal growth is assessed by 4 biometrical parameters (BPD, HC, AC, FL) and their combination (EFW). • Normal growth curves constructed from ultrasound measurements are expressed in centiles. • They are used clinically to identify a normal intrauterine growth and detect risk of obstetric and neonatal complications. § Normative growth curves have been constructed from these ultrasound measurements, and are expressed in centiles. They are used clinically to identify a normal intrauterine growth and detect risk of obstetric and neonatal complications. In many cases, it is not single measurements that are most important, but sequential measurements. Note that ultrasound can also be used to assess fetal wellbeing, which can be a more important use of the technology. § For any infant, the changes in each parameter can be plotted, and the growth over time visualised. In a normal pregnancy, each parameter is expected to follow a centile, showing steady increases in size. The use of the centiles is important, because this allows compensation for different sizes of infants that are growing and developing normally.

The mode of delivery will depend upon:

• Gestation of the pregnancy. • Condition of the pregnancy. • State of the cervix. • Presentation of the fetus. • Other factors: oligohydramnios - labour may be poorly tolerated due to cord compression - hence may offer C-section.

Vessels: Ductus venosus

• Longitudinal through upper abdomen. • Parallel, anterior to the right of the aorta. • Receives 40% of umbilical venous flow. • Directs oxygenated blood to the L ventricle

Depression Symptoms

• Low mood/sadness. • Loss of enjoyment (anhedonia). • Loss of energy. • Also: o Symptoms pervasive (occurs regardless of where you are) o Impairing your functioning. o Present for at least 2 weeks **Symptoms and impairment--> distinguish mild, moderate & severe

Screening of "at risk" pregnancies at 24 weeks

• PAPP-A < 0.3 MoM, POHx PET / FGR. • Maternal systemic disease e.g. HT, renal, sickle. • Uterine artery Doppler 1st/ 2nd trimester - blood flow through uterine arteries: identify high resistance flow.

Intervention for conduct disorders

• Should be targeted at major modifiable risk factors and should begin at an early age. • Managing underlying hyperactivity. • Parenting programmes. • Cognitive problem-solving skills training. • Interventions at school. • Multi-systemic therapy

Child growth and development- Delay

•Abnormal development refers to the slow acquisition of skills and follows three main patterns: slow but steady, plateau (good progression which then stops) or regression (loss of skills previously acquired). **Examples: •Biological factors such as folate deficiency can increase the risk of neural tube defects. •Global developmental delay due to down's syndrome, fetal alcohol syndrome, meningitis, trauma. •Delay in talking due to stammering, hearing deficit, maturational delay, environmental factors. •Delay in walking due to maturation delay, severe learning disabilities, cerebral palsy. **Signs: •Antenatal- illnesses/ infections; medications; drugs •Birth- premature; prolonged/ complicated labour •Postnatal- illness/infections; trauma •Consanguinity- increases chances or chromosomal and recessive conditions •Developmental milestones delayed •Growth parameters- height, weight and head circumference •Dysmorphic features. Standardised developmental assessments- SOGSII, Griffiths, Denver **Clinical approach: •Paediatrician •Specialist health visitors •Speech and language therapists •Occupational therapists physiotherapists psychologist

Pubertal changes in girls and boys

•Adolescence is the transition between childhood and adulthood •Brain development underpins cognitive changes in adolescence. In the prefrontal cortex, there is an increase in grey matter up to puberty. •Puberty- physical changes through which a child's body matures into an adult body capable of sexual reproduction. •Girls- 10-14 years, Pubertal changes include breast budding, growth of pubic hair, growth spurt, first period, growth of underarm hair and a change in body shape. Peak in puberty is generally earlier in girls compared to boys. •Boys-12-16. Pubertal changes include growth of scrotum and testes, change in voice, lengthening of penis, growth of pubic hair, growth spurt, growth of facial and underarm hair and a change in body shape. **After puberty, grey matter density decreases to early adulthood. From puberty onwards, there is an increase in cortical white matter.

Causes of Intrauterine Growth Restriction

•Advanced diabetes. •High blood pressure or heart disease. •Infections such as rubella, cytomegalovirus, toxoplasmosis, and syphilis. •Kidney disease or lung disease. •Malnutrition or anemia. •Sickle cell anemia. •Smoking, drinking alcohol, or abusing drugs.

MOCA advantages and disadvantages

•Advantages: covers variety of domains, brief and quick to do, validated, translations are available. •Disadvantages: education level will affect results, language level will affect results, floor and ceiling effects, can be poorly administered, possible practice/coaching effects

What is ageing?

•Ageing is the process of growing older. Involves changes in: -Biological -Psychological/cognitive -Social functions § Ageing or senescence is the biological process of growing old, with associated changes in physiology and increased susceptibility to disease and increased likelihood of dying. § There are multiple theories about why organisms age. They fall into two broad categories. 1) Damage or error theories describe the accumulation of damage to DNA, cells and tissues, for example loss of telomeres or oxidative damage, as the cause for ageing. Damage theories implicitly hold that if we could prevent or repair this damage then we could prevent ageing. 2) Programmed ageing theories describe how genetic, hormonal and immunological changes over the lifetime of an organism lead to the cumulative deficits we see as ageing. Programmed ageing theories tend to suggest this is part of an inescapable biological timetable, just as growth and puberty are programmed to occur. **No single theory explains all that we know about ageing, and there is widespread, active research into ageing from molecular to societal levels.

Labour and NF-kB

•Almost all pro-labour genes have NFkB binding domains in their promoters. •Modification of NFkB sites in promoter sequences leads to loss of expression in cells or in expression vectors. •Inflammatory changes are strongly linked with labour •Activators of inflammation are readily linked with preterm labour (eg intrauterine infection). § NFKB is a pro-inflammatory transcription molecule. o Closely related to - IL-1b, IL-6, COX2, cPLA2, IL-8. § NFKB has MANY initiators and it can then induce MANY effects (mostly inflammatory) through: o COX-2, IL-8, IL-1b, MMPs, oxytocin receptors, PG receptors, contraction-associated proteins. o Evidence for this comes from: § Pro-labour genes have NFKB binding domains in promotor regions. § Modification of NFKB sites in the domains lead to loss of expression of the cells. § PGE2 is constitutively expressed BEFORE any changes can be witnessed that are conducive to labour. o Equally, some tissues could not be stimulated to express PGE2 as the levels are already high

Child Growth and Development- Centile Charts

•Centile charts are based on surveys of large numbers of children with age (x axis) plotted against height (y axis). 50% of children will be shorter than the 50th centile, 25% of children shorter than the 25th centile etc. •Centile charts are for cumulative height •Height velocity= change in height (cm) / number of years over which this change has happened

What are the 4 developmental domains?

•Development is the global impression of a child which encompasses growth, increase in understanding, acquisition of new skills and more sophisticated responses and behaviour. •4 developmental domains: •1) gross motor and posture •2) fine motor and vison •3) language and hearing •4) social, emotional and behaviours

Folic acid and spina bifida

•Folic acid in diet decreases incidence by ~70%. •Folic acid - WHEN should folic acid be given? - >3 months before conception as egg takes 3 months to mature (3 cycles before menstrual cycle) and nutrition for embryo first is egg.

Child Growth and Development- Obesity

•For adults, BMI > 25kg/m2 = overweight; BMI >30kg/m2 = obese. •For children, obesity is assessed on the BMI CENTILE POSITION. •Obesity occurs due to the balance between energy taken in as food VS energy expenditure. **There is a small number of individuals with a single gene mutation affecting leptin which causes excessive appetite and can lead to severe obesity. There are some gene variants (FTO gene) in the population that can affect eating behaviour and appetite, making an individual more likely to eat in a way that makes them gain weight

Adolescence and Puberty- Mood disorders (anorexia)

•For girls, puberty causes increased adiposity à body shape dissatisfaction •Key features: a) Body weight maintained 15% below expected weight, or BMI < 17.5. b) Self-induced weight loss c) Psychopathology- dread of fatness and a preoccupation with this d) Endocrine disturbances- amenorrhoea, or delayed growth and puberty in younger sufferers. § Causes: genetic predisposition, perfectionist temperament, specific subcultures, childhood abuse, higher social class § Treatment: family intervention, CBT (for abnormal eating attitudes and depression), hospital administration for weight restoration.

Causes of mal-development

•Genetic - 30% •Environmental - 15% •Multifactorial - 55% e.g. eye mosaic, trisomies, cleft lip, polydactyly, chimerism, thalidomide, spina bifida.

Mal-development generally occurs when?

•Helps to identify when the conceptus is most vulnerable. •Generally during embryology, but there are exceptions

Control of term labour

•Inflammatory changes are strongly linked with labour •Activators of inflammation are readily linked with preterm labour (eg intrauterine infection). What about term labour? **CRH and PAF: § Control of labour comes about mainly via CRH and PAF (which then activate other molecules and ultimately MMPs, PGE2 and upregulation of oxytocin receptors). o PAF - Platelet Activating Factor. o CRH - Corticotrophin Releasing Hormone.

Causes of labour

•Inflammatory changes are strongly linked with labour •Activators of inflammation are readily linked with preterm labour as linked with infection often (eg intrauterine infection). •What about term labour? have increased prostaglandin production. have PAF and CRH.

What are the 3 stages of labour?

•Length of labour varies, around 12-48 hrs 1) Phase 1: Uterine contractions and cervical changes 2) Phase 2: Delivery of the of the foetus 3) Phase 3 (30 min) : Delivery of the placenta **The 3 anatomical tissues in labour: cervix, myometrium (uterus) and foetal membranes •The foetal membranes are the fused chorion and amnion • Cervix- narrow passage forming the lower end of the uterus

What is Life Expectancy?

•Life expectancy is a statistical measure of how long a person can expect to live. Can be defined at birth or later e.g. at age 65. o Has been rising for many years: § In England, the LE of a baby girl born today is 83 years old. (79 boy). § 80 years for a baby girl born in 1998 (75 boy). § This graph shows the impact of this; it's predicted there will be small increases in the number of younger people, but the largest increase will be in older people

Systems malformations

•Limbs and digits - polydactyly •Urogenital •Heart •Central nervous system (spine and head) - spina bifida •Face - cleft lip and palate •Lungs **multi-system problems from thalidomide.

Menarche and adrenarche

•Menarche= first menstrual cycle •Adrenarche: stimulation of the adrenal glands to make DHEA and DHEAS, this occurs prior to onset of puberty •Increase in adrenal androgen production •Occurs between ages 6-10. Females 6-9 years and males 7-10 years. **Age at menarche has decreased over the last 150 years and has levelled off over the last 3-4 decades. **DHEA is a hormone made by your adrenal glands and to a lesser degree by the ovaries and testes. DHEA is changed into DHEA-S in your adrenal glands and liver. In both men and women, the sex hormones estrogen and testosterone depend on DHEA. DHEA also has a role in the making of insulin growth factor-1 (IGF-1).

Mosaic or partial extra chromosome material vs trisomies

•Mosaic or partial extra chromosomal material •Less severe symptoms than in complete trisomies.

Function of gene product problems

•Mutations •Altered expression

Child Growth and Development- Abnormal Growth causes

•Normal children will keep growing on the line for a certain centile •When a child falls in their centile position, this is abnormal •Causes of abnormal growth: Genetic syndromes- turner's, downs and skeletal dysplasias, IUGR, endocrine disorders, psychosocial deprivation. **Turner syndrome, a condition that affects only females, results when one of the X chromosomes (sex chromosomes) is missing or partially missing. Turner syndrome can cause a variety of medical and developmental problems, including short height, failure of the ovaries to develop and heart defects.

Placental delivery

•Placental delivery, there are some haemostatic changes that occur here to prevent maternal haemorrhage. •Haemostatic changes: increased clotting through pregnancy and powerful uterine contraction which will squeeze the maternal blood supply.

Ageing population

•Population ageing refers to the increasing age of an entire country, due to increasing life spans and falling fertility rates. •Social care in England include home carers, sheltered housing, care homes (residential and nursing), personal budgets.

Main risk to maternal health (or life) in pregnancy

•Relatively little risk in the early parts of pregnancy. •Main risk to maternal health (or life) linked to delivery § Chromosomal abnormalities: o Too few sex chromosomes - Turner's syndrome - 45 X0. o Too many sex chromosomes - Klienfelter's syndrome - 47 XXX, 47 XYY, etc. o Too few autosomes - non-viability, as does 45 Y0. o Too many autosomes - Downs Syndrome - trisomy 21. § Most risks to the pregnancy occur in the first trimester of pregnancy. The main risks associated with pregnancy in the 3rd trimester is to do with the birth. o There are 4 main organs (lungs, digestive system, immune system and brain) that have limited use in utero so late development is logical but problems developing here become apparent at birth. § This also may cause problems with pre-term birth.

What is classed as term delivery, moderate pre-term, very pre-term and extremely pre-term?

•Term delivery is 37-41 weeks gestation •Moderate or late pre-term delivery is between 32-37 weeks •Very pre-term: 28-32 weeks gestation •Extremely pre-term: <28 weeks **Remember gestation is the duration since the woman's last menstrual period (LMP)

Cells and chromosomes influence on development

•The distribution of cells and chromosomes can change development. •Changes to chromosomes can affect gene expression. •Mosaicism (non disjunction) - differences between cells within one individual. •Distribution of cells between inner cell mass & trophectoderm (placenta). •Chimerism - fused multiple zygotes -Non-identical zygotes

Labour- The Biochem Stuff

•The main factors involved are: NFkB, progesterone and progesterone receptor, CRH and PAF. 1) NFkB •The is a pro inflammatory transcription factor. •Most pro labour genes bind NFkB domains to transcribe mediators involved in labour 2) CRH and PAF: •PAF (platelet activating factor) is a sign of fetal maturity made by the mature lungs which are the last to develop. It is part of lung surfactant. •CRH- corticotrophin releasing hormone EG anything that will cause stress •CRH and PAF rise before labour and upregulate inflammatory pathways 3) Progesterone: •Insufficient levels of progesterone can cause pregnancy loss or labour so it's usually high throughout pregnancy. •NFkB and progesterone have opposing effects, NFkB induces labour whereas progesterone is anti-inflammatory (inflammation triggers labour) •2 types of progesterone receptor: A and B •PR B will mediate progesterone's effects in pregnancy whereas PR A reduces its effects. At term PR A: B ratio increases, so you get progesterone withdrawal --> labour.

What is 'water breaking'?

•This is the rupture of the foetal membranes. •Rupture of these membranes happens due to inflammatory changes and membrane remodelling •There are changes to the amnion basement component, leukocyte recruitment, increase in inflammatory processes: Loss of strength due to : • changes in amnion basement component. • Leukocyte recruitment (neutrophils) and other inflammatory processes • ↑MMPs (recruitment and activity) • PGs and ILs

Chromosome problems -too few

•Too few 1) XY linked -Turner's syndrome - X0. Female, short stature, infertile -Y0 is NOT viable 2) Autosomal -NO complete losses are viable -Partial chromosome loss syndromes known and characterised

Autosomal chromosomal problems - too many

•Too many •Autosomal: a) Down's syndrome (ch21) (1 / 1000 live births): Heart problems determine survival. b) Edward's syndrome (ch18) (1 / 6000 live births) •Most die before birth, very few live-born, live ≤2 weeks. c) Patau's syndrome (ch13) (1 / 15,000 live births) •Most die before birth, 80% live-born die within 1 year. -Others not found in live birth, most detected in some spontaneous pregnancy loss tissues. - BUT, Ch1 trisomy not found in pregnancy loss tissues, this is the biggest chromosome and has most genes, so issue here means development stops almost immediately, doesn't even implant.

Sex Chromosomes too many

•Too many •XY linked: ØKleinfelter's syndrome (XXY). Decreased fertility ØXXYY, XXXY, XXXYY, etc - severe forms related to KS ØXYY (XYYY) - very variable (taller, learning problems) ØXXX. Limited effects, some mental changes ØXXXX, XXXXX. More severe effects. *X-inactivation: one X chromosome is randomly knocked out. this only works on one chromosome. hence as X's increase, the severity increases as more active X chromosomes.

Labour- Uterine contraction - what are the key mediators?

•Uterine contraction are co-ordinated myometrial contraction with FUNDAL dominance •This just means the uterus is squeezed from the top down, with increasing co-ordination and power. •What are the key mediators for uterine contraction? - Prostaglandin F2 alpha from foetal membranes, oxytocin receptor activation and CAPs. *CAPs= contraction associated proteins. CAPS- oxytocin receptors (OTR), connexin-43 (Cx-43), and prostaglandin F2 alpha, receptors (FP) (don't need to know these apart from oxytocin receptor)