RDA; Lecture 1, 2 and 3 - Complexity of Labour, Embryology and Child development Flashcards
(245 cards)
1
Q
What is the difference between the gestational age and post-fertilisation?
A
- Gestational age starts from the first day of the last period;
- post-fertilisation is 2 weeks less than gestational age -> makes a difference at the beginning of the pregnancy, but not really at the end of the pregnancy.
Difference between IVF gestational age and non-IVF GA (around 2/2.5wks) -> important as it can change whether the baby will be resuscitated or not (24 vs 22 wks)
2
Q
What are the main size gains that occur in each trimester?
A
Last 2 trimesters are for growth of foetus, but first trimester is for development
3
Q
What are the carnegie stages of human development?
A
x
4
Q
What occurs in the first trimester?
A
x
5
Q
How are the carnegie stages broken up into weeks of pregnancy?
A
x
6
Q
What is the difference between a blastocyst, embryo and foetus?
A
Red area is the liver as the RBC are produced in the liver in the embryo as there is no bone marrow, yolk is used for nutrition -> very translucent. Embryo is baby up to week 8, foetus is baby for rest of pregnancy
7
Q
What is a conceptus?
A
Everything produced from a fertilized egg
8
Q
What is an embryo?
A
Cells that give rise to everything at the beginning not just the baby -> terms are used in 2 different ways; baby up to week 8 of development OR for the first week then whole conceptus is embryo, after blastocyst differentiation, then only baby tissue is foetus
9
Q
Why does cell proliferation occur?
A
Changes in response to ‘growth factors’
Changes in receptor expression
May be due to changes in cell survival
All paracrine or autocrine regulation
10
Q
Why do cells move?
A
Chemo-attractants (local production, paracrine effects), cognate receptors (expressed on target cells) -> needs facilitation, requiring change in tissue structures; remodelling of tissues (ECM) and proteases and inhibitors need to be produced and activated
11
Q
What are the steps of differentiation that occur in foetus?
A
Paracrine regulation
Receptor expression
Necessary in target cells
Loss of proliferation
Not necessarily in embryo or fetus
Cells can differentiate and proliferate at the same time
12
Q
How does cell loss occur in foetus?
A
Apoptosis -> regulated cell death, controlled by paracrine factors mainly
13
Q
How can concentration of paracrine stimulus affect regulation of cells?
A
Some cells exposed to different regulators and different concentrations, which by working together can bring out how cells behave -> occurs in 3D (shown here in different planes) and looks like a limb bud (occurs in embryo proliferation)
14
Q
How can different regulators work together in the embryo?
A
x
15
Q
How do genetic factors regulate development?
A
Controlled by signals from genes.
Complex gene interactions occur throughout development to form a normal fetus.
Hox genes, with retinoic acid controlling activation of Hox genes
16
Q
What does embryonic development need?
A
Gradients of factors
Combinations of factors
Temporal changes in factors or responses to them
17
Q
What is the bilaminar disc (~9d PF)?
A
Epiblast (yellow) and hypoblasts (blue) -> circular disc cut in the middle
18
Q
What is gastrulation?
A
Becomes more elongated -> Gastrulation is a phase early in the embryonic development of most animals, during which the single-layered blastula is reorganized into a trilaminar (“three-layered”) structure known as the gastrula. These three germ layers are known as the ectoderm, mesoderm, and endoderm.
19
Q
How is the germ layer formed?
A
Proliferating and differentiating to form mesoderm cells, which move towards the hypoblast -> forming the germ layers; hypoblast is bumping into mesoderm cells which then undergo another differentiation stage, forming the endoderm, with hypoblast being lost via apoptosis
20
Q
What does gastrulation result in?
A
Epiblast becomes ectoderm, mesoderm is in the middle, endoderm is where the hypoblast was
21
Q
What do the 3 germ layers become?
A
NB: very few tissues are of one specific type -> skin is both ectoderm and mesoderm
22
Q
What is neurulation?
A
Occurs at the same time as gastrulation -> can see the primitive streak;
Neurulation refers to the folding process in vertebrate embryos, which includes the transformation of the neural plate into the neural tube.
The embryo at this stage is termed the neurula.
Notochord (acts as negative regulator, not allowing certain things to happen) formed from mesoderm, and upper epiblast layer is turning into neural plate which forms the CNS.
Proliferation cells, grow and meet in the middle forming the neural tube which will then become the CNS. Skin overlies the CNS, which explains why some neuroblastomas can affect the skin as well as the NS, as they have the same embryological origin.
By day 21, 3D embryo is developing, with mesoderm becoming more dimensional
23
Q
How does the body cavity close?
A
Umbilical cord is a gap in the body wall, where the yolk was
24
Q
How does the embryo fold head to tail?
A
x
25
What occurs in the 2nd month of development?
Faces developing, hands developing, eyes developing from an early stage; apoptosis used to remove webbing in between fingers and remove our tail
26
When do each of the systems develop?
x
27
How does the CNS develop?
Brain development occurs in 2 separate halves -\> with fusion of tissues and elaboration occurs -\> neuropores then fuse to give a complete tube that is the CNS
28
What is spina bifida?
Twin/two spines, with 2 areas of tissue -\> bulges of tissue and depending where they are and what is in them decides the problems that it is going to cause -\> above the point is normal;
Incidence of 1-2 per 1000 pregnancies;
Surgery can help anatomical but not functional problems and folic acid (need to take it earlier to have enough reserve for baby) can prevent it, primary problem is failure to complete neurulation and problem is present within 4 weeks of fertilisation
29
How is spina bifida caused?
A gap is left where the fusion would have occurred -\> posterior neural chord hasn't closed properly
30
What are the types of spina bifida?
Occulta has a patch of hair, with vertebra not being formed properly; in meningocele is a bulge of CSF; myelomeningocele includes neural tissue and CSF -\> development of bones of spine are controlled by neural tissue, which means it doesn't cut off the neural tissue in spina bifida
31
What is anencephaly?
* Incidence: 1 – 8 per 10,000 births
* Female babies affected more commonly than male.
* Large part of the skull is absent along with the cerebral hemispheres of the brain.
* Folic acid may show benefit, anterior neuropore closure is incomplete
32
How does the heart develop?
Blood is flowing through the tubes from the 20d
33
How do the endocardial tubes moves in developement?
Stay at the sides of the embryo -\> heart is being pushed when the embryo is folded
34
What is the relevance of the secondary heart field?
Joined at the top, and then top point breaks down, with it forming 2 tubes, some formed from primary and some from secondary heart field
35
How does the heart form from the 2 endocardial tubes?
Rotation of 2 structures -\> X left in place but the 2 rotate around each other;
* ventricular structure increases in size,
* and then they continue rotating,
* with the atria rotating behind the ventricles,
* with arteries coming out in front
36
Why does the heart change in development so much?
Compression of atria causes bending of atrium, which then bends round itself, and bends completely -\> more physical force than movement and proliferation
37
How does the fetal heart look?
Ductus arteriosus makes most of the blood get diverted from the pulmonary artery into the aorta as we don't need our lungs until birth -\> blood flows from body to heart to body
38
What changes occur at birth to the heart?
x
39
How do the limbs develop?
x
40
What is achrondroplasia?
Gain of function mutation of FGFR3
41
What is thalidomide?
Didn't directly interfere with FGF8 (apical ectodermal ridge) or Shh (zone of polarising activity), affected vessel formation -\> with prolonged exposure leading to widespread cell death and all signalling/cells lost; short exposure leading to uniform cell death and only partial loss of AER signalling which recovers
42
What is polydactyly?
Extra finger development -\> mild developmental defects
43
How is the kidney developed?
* In early development, early kidney does act as an excretory organ but then can develop into reproductive tract.
* Pronephros: develops first, precursor tissue that directs formation of Mesonephros: which connects to the cloaca. Limited excretory functions
* Metanephros: definitive kidney
* The third urinary organ, the metanephros or permanent kidney appears by the ffth week. Its excretory units develop from the metanephric mesoderm.
* The collecting ducts of the permanent kidney develop from the ureteric bud, an outgrowth of the cloaca.
* The bud penetrates the metanephric tissue and gives rise to the ureter, the renal pelvis, the major and minor calyces and collecting tubules.
* Each newly formed collecting tubule is covered at its end by a metanephric tissue cap form small vesicles which form nephrons.
44
How do the kidneys ascend?
x
45
How is the bladder formed?
x
46
What happens if the development of the kidneys goes wrong?
Renal agenesis
Abnormal shaped kidneys
Abnormal ureter
Pelvic or horseshoe shaped kidney
Bladder exstrophy
47
What is renal agenesis?
x
48
What are the abnormal shapes of kidneys?
Pelvic and horseshoe kidneys
49
What are the ureteric abnormalities?
x
50
How do the gonads develop?
* The gonads arise from intermediate mesoderm within the urogenital ridges of the embryo
* Primordial germ cells are the precursors of all gametes
* The genital ducts arise from paired mesonephric and paramesonephric ducts
* The mesonephric ducts give rise to MALE genital ducts
* The paramesonephric ducts give rise to FEMALE genital ducts
51
What is the early urogenital development?
x
52
How do the ductal systems develop?
Week 7 -\>The genital ducts arise from paired mesonephric and paramesonephric ducts
The mesonephric ducts give rise to MALE genital ducts
The paramesonephric ducts give rise to FEMALE genital ducts
53
How does sexual differentiation occur?
The gonads and reproductive tracts are indifferent up until 7 weeks of development; differentiation is determined largely by the presence or absence of SRY (on the Y chromosome)
Normally: If SRY+, then development proceeds along the male path (~7 weeks onwards)
If SRY-, then development proceeds along the female path (~9 weeks onwards)
54
How does the male reproductive tract develop?
* SRY expression: a gonad develops into a TESTIS containing spermatogonia, Leydig cells, and Sertoli cells.
* Leydig cells produce TESTOSTERONE, which support growth of the mesonephric ducts.
* NOTE: without testosterone, the mesonephric ducts will regress
* Some testosterone is converted into Dihyroxytestosterone (DHT), which supports development of the prostate gland, penis, and scrotum.
* Sertoli cells produce ANTI-MÜLLERIAN HORMONE (AMH, or Müllerian Inhibiting Substance, MIS), which induces regression of the paramesonephric ducts.
* NOTE: in the absence of MIS, the paramesonephric ducts will persist.
55
How does the female reproductive tract form?
In the absence of SRY, the gonad develops into an ovary with oogonia and stromal cells.
Since no testosterone is produced, the mesonephric (Woolfian) ducts regress.
Since there is also no AMH (MIS), the Müllerian (paramesonephric) ducts persist to give rise to the oviducts, uterus, and upper 1/3 of the vagina
The urogenital sinus contributes to the formation of the bulbourethral glands and the lower 2/3 of the vagina
56
What are the female parts and where do they develop from?
* Ureteric bud: ureter
* Mesonephric ducts: trigone of bladder
* Paramesonephric ducts: oviduct, uterus, upper 1/3 of vagina
* Urogenital sinus: bladder (except trigone), bulbourethral gland, urethra, lower 2/3 of vagina
57
Compare the female and male gonadal development.
x
58
When do the testes descend?
The testes arise in the lumbar region but then descend into pelvic cavity and through the inguinal canal to end up in the scrotum
Descent of the testis is due to tethering of the testes to the anterior body wall by the gubernaculum.
With growth and elongation of the embryo coupled with shortening of the gubernaculum, the testes are pulled through the body wall, then the inguinal canal, and finally into the scrotum.
Undescended testes are at increased risk of cancers and don't function normally
59
How do the external genitalia form?
Male structures form under the control of testosterone.
In the absence of testosterone, female structures will form
60
What are the abnormal developments of reproductive system that can occur?
Structural (hypospadias M or uterine abnormalities F), others due to changes in hormone production
61
What are hypospadias?
x
62
What are mullerian duct anomalies and persistent Mulleria Duct syndrome?
Occurs in genetic males with mutations in AMH / MIS or the AMH / MIS receptor
Because testosterone and DHT are produced, there are normal male external genitalia and male (Wolffian) genital ducts
Because there is no inhibition, the paramesonephric ducts persist; i.e. there is a small uterus and paired fallopian tubes
The testes may lay either in what would be the normal position for ovaries (i.e. within the broad ligament) or one or both testes may descend into the scrotum
63
What is androgen insensitivity syndrome?
Occurs in genetic males (XY) with mutations in the androgen receptor (AR)
Lack of virilization of due to inability of AR to bind testosterone or DHT, so androgens have no effect
Relatively normal female external genitalia (no functional androgens) but undescended testes
Mesonephric ducts are rudimentary or lacking due to loss of testosterone signaling
Normal production of MIS from Sertoli cells causes Müllerian duct regression, so no oviducts, uterus, or upper 1/3 of vagina.
Errors in production or sensitivity to testes hormones lead to a predominance of female characteristics under the influence of maternal and placental estrogens.
64
What is congenital adrenal hyperplasia?
x
65
How does the face develop?
Primary structures of face form on sides of head, until at least 5w post fertilisation -\>
precursors of nose, cheeks, lips, mouth and chin also formed during this time period.
Structures move over 5wks to reach expected positions, nose centrally placed and eyes facing forward on face -\>
process of movements of preformed structures like eyes isn't fully understood, but could be continuous formation of clefts in face, then filling in of clefts which leads to subsequential loss of tissue from centre of face and movement of tissues to correct places
66
What is a cleft lip?
The face hasn't joined together, usually occurs in the upper lip -\> cleft lip is usually asymmetrical but cleft palate is symmetrical usually, as halves of palate don't meet and fuse correctly -\> can be surgically cured, as cell turnover in infants is normally very rapid and healing often occurs with little/no scarring
67
How do the lungs develop?
Using PF timings -\> enough surfactant in around 30 weeks for lungs to expand
68
How do the lungs develop from week 3-4?
x
69
How do the lungs develop from week 5-8?
x
70
How do the lungs develop at a cellular level?
x
71
What are the cellular components of the mature lung?
x
72
What is respiratory distress syndrome?
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
Time to allow surfactant production to increase
73
How is surfactant produced during pregnancy?
* Surfactant: lipids, proteins and glycoproteins In utero production can be increased by 1 injection of glucocorticoids (2-3 days)
* Composition:
* ~40-45% dipalmitoyl-phosphatidylcholine (DP-PC)
* ~40-45% other phospholipids, mainly other PC
* ~5% surfactant-associated proteins (SAP or SP-A, -B, -C, -D)
* ~5% other proteins
* Cholesterol
* Trace components
Half life of 5-10h, made by type II cells and lower surface tension in alveoli
74
What are teratogens?
Factors which dysregulate patterning, causing defects in development -\> many different factors can act as teratogens (illegal drugs, meds, radiation, infections) but all exert their main effects in the first trimester of pregnancy
75
What is the difference between miscarriage, term and preterm?
x
76
What is labour?
Fundally dominant contractions (push downwards, starting from the top), and cervical ripening and effacement (increasing).
Co-ordinated myometrial contractions (increasing)
Rupture of fetal membranes
Delivery of infant
Delivery of placenta
Contraction of uterus
77
What are the stages of labour?
Longer in first pregnancy, than the next pregnancies
78
How do you initiate labour?
Term: Not really sure - Estrogens; low progesterone?; CRH?; oxytocin?
Preterm: Intrauterine infection, Intrauterine bleeding, Multiple pregnancy, Stress (maternal), Others
79
How does the cervix ripening and effacement occur?
Change from rigid to flexible structure
Remodelling (loss) of extracellular matrix
Recruitment of leukocytes (neutrophils)
Inflammatory process
Prostaglandin E2, interleukin-8
Local (paracrine) change in IL-8
80
How do the coordinated myometrial contraction occur?
Fundal dominance
Increased co-ordination of contractions
Increased power of contractions
Key mediators
Prostaglandin F2a (E2) levels increased from fetal membranes
Oxytocin receptor increased
Contraction associated proteins
81
How does the rupture of the fetal membranes occur?
Loss of strength due to changes in amnion basement component Inflammatory changes, leukocyte recruitment
Modest in normal labour, exacerbated in preterm labour
Increased levels and activity of MMPs Inflammatory process in fetal membranes
82
Summarise the tissues and processes that occur during labour?
x
83
What is NFkB?
Many genes, mostly ‘inflammatory’: COX-2 (prostaglandins - PGs), IL-8, IL-1b, MMPs, Oxytocin receptor, PG receptors;
contraction-associated proteins are activated by NFkB -\> all prolabour genes have NFkB binding domains in promoters
84
What are the causes of preterm labour?
Inflammatory changes are strongly linked with labour -\> activators of inflammation are readily linked with preterm labour
85
How is term labour controlled?
Constitutive PGE2 synthesis occurs, increasing with labour -\> CRH binding proteins increases towards labours, also coinciding with COX2 expression increasing in parallel with CRH; PAF as well signals fetal maturity; IL-1beta also increases during labour
86
What is platelet activating factor?
Part of lung surfactant, surfactant proteins and complexes -\> produced by maturing lung, before birth, with levels in amniotic fluid increasing near term -\> sign of fetal maturity
87
What is the hypothesis for parturition?
Lungs making PAF, driving IL and PGE2 production;
CRH produced in placenta, stimulating ACTH production, which stimulates adrenal gland to make Cortisol and DHEA,
With cortisol going back to the placenta, with cortisol stimulating CRH production, feeding forward and eventually driving labour.
Oestrogens formed from DHEA, which then leads to myometrial contractions
88
What is progesterone used for in pregnancy?
Needed to sustain pregnancy -\> if progesterone blockaed occurs then pregnancy is lost;
progesterone levels remain very high until after delivery of placenta, with effect of progesterone being lost in normal term labour -\> lots of progesterone receptors = normal progesterone function;
high NFkB with low progesterone receptor = negative interaction
89
What happens to the progesterone receptor A and B?
PR-B mediates the main effects of progesterone via gene expression
PR-A is less able to mediate these effects
Ratio of PR-A : PR-B increases at term
Loss or change in PR may lead to ‘functional progesterone withdrawal’
90
What part of labour is affected by progesterone?
x
91
What is development?
x
92
What factors can affect child development?
* Child development is now seen as a bidirectional transactional process in which genetic and environmental influences continuously alter each other in a dynamic manner.
* Various levels of contexts such as parenting, poverty and social networks interact with each other and with genetic expression to create long-lasting consequences for development.
* Environmental factors become even more important determinants of the child’s future in the presence of any biological risk.
* While single or isolated negative environmental factors may have a small, incremental effect, accumulated risk factors make a major contribution to developmental problems.
* Family and social environment most strongly but not exclusively, influences emotional regulation, cognitive and language outcomes, with most negative influence occurring in infancy
93
What are the environmental causes of damage to brain development both antenatally and postnatally?
x
94
What are the periods of susceptibility to teratogenesis?
x
95
Which infectious agents can affect development of the baby?
x
96
What features can babies develop when the mother gets rubella during pregnancy?
x
97
What drugs/substances can cause problems with development?
x
98
Which hormones can cause problems with child development?
Gestational diabetes can give larger babies - \>5kg
99
How can the maternal diet affect the baby?
x
100
What are the complications of spina bifida?
x
101
What are the domains of development?
Milestones are the acquisitions of a key performance skill is referred to as a milestone, with normal range varying widely
102
What is the median age and limit age for milestones?
Median is age when half of a standard popn of children achieve the level -\> limit ages is age by which they should have been achieved (2 s.d. from the mean) - correct for prematurity until 2y
103
What are the gross motor and posture milestones?
Looks at posture and execution of large movements
* Standing
* Walking
* Running
* Kicking a ball
* Climbing stairs
* Peddling a tricycle
104
What are the milestones of movement from newborn to 6-8months?
x
105
What are the milestones of movement from 8-15months?
x
106
What are some intermediate steps that can occur when trying to walk?
x
107
What are the primitive reflexes?
Are protective and have a survival value,
Promote proper orientation,
Promote postural support and balance;
Moro reflexis a grasping motion when dropped slightly;
asymmetric tonic reflex is turning head to one side with that side of limbs extending and opposite side flexing
108
Which reflexes replace the primitive reflexes after 4-5months ?
Called protective/righting responses
109
What are the fine motor and vision milestones that can be found?
Looks at hand function and hand-eye coordination
Can also give some information of cognitive function
* Holding objects
* Picking up objects
* Pointing
* Waving
* Throwing/catching
* Object permanence occurs at 9 months
110
What are the visual milestones from 6 weeks to 7 months?
x
111
What are the visual milestones from 10 months to 2-5y?
x
112
What are the language and hearing milestones?
Normal hearing is needed for normal speech
* Babbling
* Words
* Sentences
* Social communication
* Need to hear to be able to speak as they learn speaking by mimicry -\> bidirectional
113
What are the language milestones from newborn to 10 months?
x
114
What are the language milestones from 12 months to 2.5-3y?
x
115
What are the social, behaviour and play milestones for development?
Looks at interaction with others and self care skills
* Stranger awareness
* Play
* Feeding/
* Toileting/
* Dressing
* Social interaction
116
What are the social milestones from 6 weeks to 12 months?
x
117
What are the social milestones from 18 months to 3y?
Function of what they are playing with = symbolic play;
parallel play and symbolic play affected in autism
118
What are the skill milestones during development (summary)?
x
119
What are the limit ages for first steps?
* 25% by 11 months
* 50% by 12 months
* 75% by 13 months
* 90% by 15 months
* 97.5% by 18 months
* Any child that isn't walking by corrected 18m is a red flag
120
What are the limit ages for certain skills?
x
121
What is delay vs disorder?
Delay is slow acquistition of skills, disorder refers to maldevelopment of a skill
Delay may occur in one or more domains
* one domain = domain-specific,
* \>2 = global;
* consonant delay = all domains affected to same extent;
* dissonant delay = domains affected to different extent
122
What are the patterns of delay?
* Slow but steady, plateau, regresses = patterns of delay;
* wide age band across which it can be normal to achieve a developmental skill.
* Limit ages denote beyond normal range.
* The gap between normal and abnormal development becomes greater with increasing age and therefore becomes more apparent over time -\> range of normality is very small at the beginning of life with expansion as the years go one.
* Regression = loss of skill which was acquired, with very poor prognosis
123
What are the causes of delay in development?
x
124
How do children present with developmental problems?
Have spot checks -\> 6-8wk by GP, 9m check by health visitor, 12month check by HCP;
preschool 3y check assessed by doctor;
prematurity can increase RF for ADHD and autism;
125
Why would you want to identify if a problem in a child?
* Identification of aetiological factors – avoid “blame”
* Making diagnoses – impact, support, genetic counselling Identification and management of secondary disabilities
* Offering support and signposting to information and services
126
What questions should you ask to identify any problems?
* Is there a problem?
* What are the problems?
* What is the extent/impact of the problem?
* What is the cause of the problem?
* What are the comorbidities?
* What can be done?
127
What are the risks of prematurity with development?
Haemorrhage, periventricular leukomalacia are big problems
128
How would you take a history about development?
* History – risk factors, reported milestones
* Physical examination
* Developmental assessment
* Differential diagnosis + identification of co-morbidities
* Targeted tests
129
How would you carry out a physical examination of the baby for development?
* Use SOGSII (tick what they can achieve, add the number and look at chart to determine skill set),
* Griffiths (looks at skills, with colour coding, testing similar skills and then plot on chart to see achieved centile, takes longer around 1-1.5h), Denver (2 domains)
130
Which targeted examinations/tests would you carry out for developmental problems?
Don't need to do all, need to be specific and give time as well -\> chromosome test, thyroid test, acids and imaging, hearing and vision assessment
131
What are the Child Development Services?
x
132
Summarise the general issues for the child with delayed/abnormal development at a glance.
x
133
What is cerebral palsy?
Disorder of movement and posture due to a non-progressive lesion of motor pathways in the developing brain.
Clinical manifestations emerge over time, reflecting the balance between normal and abnormal cerebral maturation.
Most common cause of motor impairment in children,
Prevalence = 1.5-2.7 per 1000 children
Incidence = 2-2.5 per 1000 live births
134
What are the causes of cerebral palsy?
~ 80% of cases antenatal - genetic syndromes and congenital infection.
~10% of cases are thought to be due to hypoxic-ischaemic injury at birth
~ 10% are postnatal in origin. rise in survival of extremely preterm infants meningitis/encephalitis/encephalopathy, head trauma, symptomatic hypoglycaemia, hyperbilirubinaemia.
135
What is the clinical presentation of cerebral palsy?
* Abnormal limb tone and limb and/or trunk posture in infancy with delayed motor milestones may be accompanied by slowing of head growth
* feeding difficulties, with oromotor incoordination, slow feeding, gagging and vomiting
* abnormal gait once walking is achieved
* asymmetric hand function before 12 months of age
* primitive reflexes may persist and become obligatory
136
What are the classifications of cerebral palsy?
Spastic (70%), ataxic hypotonic (10%), dyskinetic (10%). mixed pattern (10%)
137
What are other problems of cerebral palsy?
x
138
Summarise cerebral palsy.
x
139
What is autism?
x
140
How do you manage ADHD?
Pyschotherapy
Family therapy
Medication – methylphenidate, other
Co-morbidities – medical management
?Diet modification
CAMHS – more complex cases
141
What are the social symptoms of autism?
x
142
What is a learning disability?
x
143
What are the causes of learning disabilities?
x
144
What are the management options for learning disabilities?
Identify a possible cause
MDT
School – statementing required
Associated problems – vision, hearing, epilepsy
Specific diagnosis=specific problems
145
How can learning disabilities affect education?
x
146
What is ADHD?
x
147
What is the function of the assessment in ADHD?
Questionnaires (strength and difficulties, Connors), exclude medical causes (Hyperthyroidism, iron deficiency anaemia), hearingdeficits, ID risk factors and comorbidities
148
What are the testis?
Contains seminiferous tubules which produce sperm and leydig cells which produce testosterone (and some other androgens) which is then released into the circulation, where it can affect the whole body
149
What is the epididymis?
One within each scrotal sac -\> sperm are released from the testis and stored here prior to ejaculation. At ejaculation, sperm passes through the 2 Vas Deferens (which are contractile) and are mixed with fluid from the seminal vesicles; fluid then leaves the ejaculatory duct and passes into the urethra where it mixes with secretions from the prostate gland
150
How does the hypothalamus and pituitary work together to regulate the pathways in the male reproductive system?
A complex interplay between hypothalamic, pituitary and gonadal factors is needed to control the normal production of human sperm.
151
What are the key stages of spermatogenesis?
The overall production of sperm from both testes is estimated to up to 200 million sperm per day.
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.
152
What are the main features of the female reproductive system?
153
What are the ovaries?
Parallel functions to the testes, in that they produces the gametes (oocytes) and the steroids needed for female reproductive function (progesterone and estrogens).
154
What are the fallopian tubes?
Oviduct through which the oocyte reaches the uterus. Provides an appropriate environment to sustain either an oocyte or a conceptus (fertilised oocyte).
155
How does oogenesis occur?
The pic shows 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.
156
What is the menstrual cycle?
Both the ovarian and endometrial cycles have end-points that occur approximately once per month; this superficial similarity disguises some differences that need to be considered if the complexities of oocyte production are to be identified correctly -\> lasts approx, 28d but varies between persons, usually between 21-35d in adult females, with younger girls (menarche) = \<45d and menopause = skip a month, shorter, longer, irregular
157
Summarise the hormone regulation during the human menstrual cycle
x
158
What are the changes in tissue structures that occur during the normal 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).
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.
159
Summarise the 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.
160
How does folliculogenesis occur?
* Time taken for primordial follicle to develop into a secondary oocyte is more than one month;
* Human ovaries contain multiple follicles at all stages with one dominant follicle entering the later stages to form a Graafian follicle;
* usually the ovaries take turns, so each ovary has 56 days to release the secondary follicle.
* Human ovaries contain 2 million primordial follicles at birth but only ~400 are released at ovulation during repro lifetime;
* human oogenesis is intermittent, both 1st/2nd mitotic division are paused during follicle development, with meiosis 1 beginning during embryonic development and halting at diplotene stage of prophase I, persisting until puberty where meisosi resumes as 2ry follicles develop;
* only fertilisation can cause completion of meiosis in an oocyte
161
What is sex?
Sexual reproduction -\> genetically different offspring; sexual intercourse -\> (required for sexual reproduction) sexual activity, pleasure and human bonding; Biological sex -\> M/F? identifies gender, result of chromosomes, production of gametes
162
How is the brain involved in sex?
Associations between parenting, fertility, reward, pleasure all link with human bonding; pleasure pathways encourage intercourse, continuing human race
163
How is the penis' function regulated?
Partly under control of brain (limbic system) via spinal cord and efferent nervous system; also tactile stimulus can activate the afferent system (pudendal) involving a more direct interaction between spinal cord and penis
164
What are the changes that occur during an erection and to the clitoris?
The clitoris and the penis both increas in size due to increased blood flow -\> with the same mechanism: • Initiated by: increased PSNS activity releasing ACh • The ACh increases the activity of Nitric Oxide Synthase (NOS), and hence nitric oxide (NO) in vascular endothelial cells • NO increases production of cGMP which induces dilatation of pudendal artery smooth muscle. • counteracts SNS-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: cGMP is normally de-activated by a phosphodiesterase enzyme, and this will reverse the changes leading to penile erection
165
Where does viagra act on?
Viagra inhibits the phosphodiesterase enzyme which deactivates cGMP in the penis, thus potentiating the effects of cyclic GMP.
166
What are the 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, forming a physical barrier to sperm
* Cervical mucus changes at mid-cycle, allowing sperm to enter uterus.
* 1) Fusion of sperm with egg, ZP digested by enzymes released during sperm capacitation.
* 2) Cortical reaction initiated, leading to herdening of ZP and exclusion of other sperm.
* 3) Meisois II in maternal chromosomes is completed, so polar body II and female pronucleus is formed. Head of sperm is undergoing decondensation, with previously tightly packed paternal chromosomes, forming a much looser structure; both pronuclei are haploid.
* 4) Pronuclei visible, DNA in both has been duplicated; next stage is mitotic division, maternal and paternal chromosomes mix for the first time, as metaphase plate of first cleavage division is formed.
* 5) Separation of male/female chromatids can be seen, and each cell should receive one paternal and one maternal copy.
167
What is the 'term' period in pregnancy?
37-41 weeks of gestation, with deliveries either side of these limits being preterm/post-term
168
What are the main maternal changes of pregnancy?
* Increased weight
* Increased hormone levels / altered endocrine system
* Increased blood clotting tendency
* Decreased blood pressure
* Increased basal body temperature
* Increased breast size
* Increased vaginal mucus production
* Increased nausea and vomiting (‘morning sickness’)
* Altered brain function
* Altered appetite
* Altered fluid balance and urination frequency
* Altered emotional state
* Altered joints
* Altered immune system
NB: extent of changes varies at different times in 9m so important to ID the way the timings in pregnancy are organised
169
How much is the maternal weight change in pregnancy?
Variable -\> 10-15kg, including fetus, amniotic fluid and placenta; increased fluid retention, increased nutritional stores -\> concentrated in 2/3rd trimesters
170
What are the hormonal changes that occur in pregnancy?
* hCG peaks in maternal plasma in 1st trimester then declines.
* Increase in P, O and lactogen parallel increase in size of placenta (hCG also produced by placenta but regulation is different).
* P and O exceed levels in normal menstrual cycle, so have potent effects on maternal system, with P being key hormone to letting pregnancy continue.
* High negative feedback means very low LH/FSH so no ovarian/uterine functions.
171
Where does progesterone come from during the pregnancy?
Fertilisation to 8 wks = corpus luteum main source, with hCG sustaining it. By 10 wks, placenta is the source of all P (steadily increasing). From wk6 corpus luteum produces less P and at ~9wks it stops, luteo-placental shift occurs
172
Where does oestrogen come from during the pregnancy?
Early wks = corpus luteum makes O, mainy 17b-oestradiol; once luteo-placental shift occurs, then O made with fetus, and maternal liver/adrenals.
Placenta doesn't have CYP450, so takes part in fetal adrenals.
DHEA is sulphated into inactive DHEA-S, so female fetus isn't exposed to androgens during development/ DHEA-S circulates to placenta, converted into 17b-oestradiol;
Oestriol levels are very high produced by parallel mechanis, including OH of DHEA-S in fetal liver into 16OH-DHEA-S
173
What happens to blood clotting tendency in pregnancy?
Maternal blood clots more readily, starts early in pregnancy, greatest at term -\> thought to be protective at delivery and important in interactions between placenta and maternal blood throughout pregnancy
174
What happens to blood pressure during pregnancy?
BP is lowest during 2nd trimester and increases fainting tendency. Tends to increase during 3rd trimester but should still remain under HTN level
175
What happens to basal body temp during pregnancy?
Increases by 0.5C in the 2nd half of the menstrual cycle after ovulation, reverses during menstruation and continues during 1st trimester (Prog role in thermogenesis) -\> as fetus increases, it contributes to maternal temp, so may exceed 38C
176
What happens to breast size during pregnancy?
Dependent changes occur due to prolactin, human placental lactogen and oestrogens; with changes starting in 1st trimester and continuing through rest of pregnancy, with changes greatest at delivery. Size increases
177
What happens to vaginal mucus production during pregnancy?
Clear mucus during most of the pregnancy -\> if blood stained, coloured or has offensive odour then go to the Dr
178
What is morning sickness during pregnancy?
Increased Nausea/vomiting -\> affecting 80% of pregnancies, in some can be very severe and can cause weight loss (hyperemesis gavidarum); thought to be linked with hCG levels, highest in 1st and declining during 2nd trimester
179
What happens to brain function during pregnancy?
Baby brain -\> High levels of steroids (prog), thought to influence brain function; brain size decreases very slightly, may not be significant; altered brain function
180
What happens to appetite during pregnancy?
As uterus increases during later stges of pregnancy, increasing pressure on stomach/GIT, can decrease distensibility of stomach -\> 6 smaller meals rather than 3 bigger ones; nutritional needs of fetus can affect maternal appetite
181
What happens to fluid balance and urination frequency during pregnancy?
Kidney function changes -\> increased fluid retention and higher plasma volume, with a 50% increase by end of pregnancy. Urinary frequency increases during 1st (hormonal), normalises in 2nd and increases in 3rd trimester (uterus exerts pressure on bladder).
182
What happens to emotional state during pregnancy?
Mostly due to hormonal changes -\> varies between women and pregnancies. Some women 'glow', some may be very happy but very labile (crying for no reason), or may be depressed which can continue into post natal depression (or can occur spontaneously after the pregnancy)
183
What happens to joints during pregnancy?
Maternal pelvis -\> connections more flexible to permit delivery of infant; parallel changes in other joints, which generally persist after pregnancy
184
What happens to immune function during pregnancy?
At utero-placental interface some factors are produced, which suppress Th1 and increase Th2 systems. Placental HLA-G is invariant, with only 5 known sequence variants, which provides maternal immune system with human marker but not saying which human, so not 'non-self'. Also HLA-G can suppress activity of some leukocytes and down-regulate maternal immune system within uterus.
185
What are the risks to the fetus during each trimester?
1st: teratogenesis, complications to human development. 2nd: few known risks 3rd: risks concerned with birth
186
What are the 4 organ systems which develop late during pregnancy?
During the last few weeks -\> Lungs, digestive system, immune system and the brain as the fetus doesn't really need these in utero; can prove a problem for preterm babies
187
What are the functions of the placenta?
1) Exchange of nutrients (M -\> f) and waste products (f -\> M) between vascular systems of mother and embryo/fetus. 2) Connection (anchorage) -\> placenta should connect strongly with underlying maternal decidua for 9m and also for maternal arterial blood. 3) Separation -\> Fetal and maternal vascular systems must remain separated. 4) Biosynthesis -\> placenta synthetically active, second only to liver in functions. 5) Immunoregulation -\> interaction between placenta and maternal tissue ensuring no rejection of conceptus during pregnancy
188
What is the structure of the placenta?
* Primary subunit is the placental villus which has the complex branched structure -\> provides large SA for exchange of maternal/fetal vascular systems -\> primary requirement for exchange function.
* In each villus, arterial and venous vessels connected to smaller capillaries in terminal portions of villus -\> arterial system = deoxygenated, venous = oxygenated.
* Fetal and maternal blood supplies are separated from each other.
* Maternal surface of placenta subdivided into cotyledons which contain one or more villi, larger cotyledons, containing more.
* Variability in shape and size of cotyledons doesn't affect placenta function
189
How does the placenta develop?
Day 9 post fertilisation, conceptus is almost completely implanted in maternal decidualising endometrium, with outer layer of conceptus being multinucleated syncytiotrophoblast (fluid filled lacunae are contained) and the under layer of cytotrophoblasts proliferating adjacent to embryo, which will become the placenta. Implantation -\> cytotrophoblasts proliferate into syncytium, cytotrophoblast column formed then undergoes branching (villous sprouts). Centre of each villus are mesenchymal cells from which villus vascular system develops, with branching continuing throughout pregnancy
190
What modifications occur to the placental villus during the pregnancy?
Overall structure doesn't change, but fewer cytotrophoblasts present at term, so that there can be closer apposition between syncytium and the pplacental capillaries -\> maximise efficacy of nutrient transfer into fetal blood and enhance fetal growth in later pregnancy
191
How does the placenta make contact with then maternal tissues and how does the nutrient supply change to the placenta and fetus during pregnancy?
Early preg: Conceptus in contact with maternal endometrial cells -\> as it grows, there is transient contact with the maternal capillaries but rapidly proliferating cytotrophoblast cells form a shell around conceptus isolating from maternal blood (4wks post fert). Decidual glands hypertrophy during 1st trimester of human preg and provide nutrients for placenta (normal function occurs but uses decidual glands - histotrophic nutrition - for nutriition rather than maternal blood - haemotrophic nutrition) and baby. Cytotrophoblast shell remains in place until 10wks GA and spiral arteries blocked by cytotrophoblast plugs. During 10-12wks GA, the plugs gradually break down, 1st peripherally then those near centre, with spiral arteries providing maternal blood to placenta forming main supply of nutrients to placenta and fetus (risky if placenta not correctly anchored then increase pressure can detach placenta and lead to miscarriage). Placenta is about 5cm at pregnancy, reaching ~20cm around 2/3rd trimester, due to increased size and branching of villi. Remodelling of spiral arteries leads to loss of vascular endothelium and underlying smooth muscle, replaced by cytotrophoblast -\> begins 1st trimester and ends wks 16-18 of gestation = good for converting narrow vasoactive spiral arteries into wide vessels, whihc can ransport very large volumes if materal blood to the placenta and provide nutrients needed and lack of smooth muscle means they cannot respond to vasoconstrictors. No nervous system so no pain during delivery and umbilical cord can be cut after delivery
192
How is the placental growth regulated?
Autocrine mechanisms, so regulate its own growth and development -\> produce a range of different growth factors and other proteins -\> maternal decidua seems to modulate placental growth and development so it is optimal for both the mother and the fetus
193
What are the maternal risks in pregnancy?
Relatively few risks to mother -\> process of labour and delivery that poses the dominant risk and is commonest cause of maternal death -\> remodelling of placenta means large volumes of blood can be lost, which should be diminished by contraction of uterus after placenta delivered All placenta should be delivered as it is relatively inflexible and any left within the uterus prevents contraction of uterine tissue and permits continued blood flow into uterine lumen. If mother has poor health at the beginning of pregnancy then additional strain could be dangerous
194
What are the risks to the infant in pregnancy?
Defects in production of gametes, so too many/few chromosomes -\> autosome loss isn't compatible with life and the only trisomy with long term viability is Down's syndrome (21); addition in sex chromosomes are less severe, and may show some phenotype and have variable fertility, but loss of chromosome is serious with infertility in Turner's 44XO and 44YO is not viable. Partial chromosome loss, exchange of sequences between chromosomes, chimeras and mosaics all show variable effects on phenotype (mild to life threatening)
195
What are the problems that can occur in the placenta to cause risk in the pregnancy?
Incomplete anchorage of placenta (lead to miscarriage/early delivery - most common in 1st trimester). Loss of pregnancy due to developmental problems affecting embryo/fetus or placenta, others due to detachment of placenta in late 1st trimester. Once after 23wks, early delivery is key problem -\> 10% delivered early, with half due to early labour and other due to deteriorating maternal/fetal health (Growth restricted infants and pre-eclamptic pregnancies); before 32wks (very preterm) are at greatest risk due to incomplete development of lungs, digestive/immune system and brain. Labour can have risks but these can be minimised by monitoring fetal health and delivery by C-section
196
What is stillbirth?
Death of an infant in the uterus so that it is delivered without any signs of life -\> may include GA and fetal weight limits -\> can use viability limit so \<23wks is miscarriage and \>23wks is stillbirth; given that viability \<28wks is so variable its hard to provide completely rigourous time definition
197
What causes stillbirth?
NB: stillbirth can occur at any GA including term, so shock to the parents (esp. mother) to undergo normal pregnancy and end with stillbirth is devastating. Detection depends on fetal monitoring -\> decrease in/lack of fetal movements may indicate risk -\> use US and doppler US to detect blood flow, with C-section immediately if fetal compromise detected -\> causes not well understood by about 50% during labour (emergency C-section required in such cases) and no obvious cause in up to 60% of cases.
198
Name the GA of a fetus that is: Term, preterm, posterm, extremely preterm, very preterm, moderately to late preterm, miscarriage, early miscarriage and late miscarriage?
Term = 37-41, preterm = 22-37, post-term = \>42, extremely preterm = 22-28, very preterm = 28-32, moderately to late preterm = 32-36, miscarriage = \<22, early miscarriage = 1st trimester and late miscarriage = second trimester up to 22
199
What are the main events of human labour?
Cervical ripening and effacement; coordinated myometrial contractions (preceded by Braxton Hicks contrations or contractures); rupture of fetal membranes; delivery of infant; delivery of placenta; involution (contraction) of uterus to limit maternal blood loss
200
What is human labour?
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 -\> can last 48h because uterus and cervix need to undergo a substantial change in structure and function as they transition from what is needed for pregnancy to what is needed for delivery of infant
201
What are the main tissues involved in human labour?
Vagina, cervix, placenta, umbilical cord, uterus, fetus and amniotic fluid
202
What is the first stage of labour?
Changes to cervix and myometrium (integral), then rupture of fetal membranes (usually) -\> lasts for ~8h, longest phase, and longest in first pregnancy
203
What is the second stage of labour?
Delivery of infant, usually lasting about 30min but can be longer in first pregnancy
204
What is the 3rd stage of labour?
Delivery of the placenta, which should occur within 30 min of delivery of infant -\> associated with very powerful contractions of the uterus, leading to rapid decrease in overall size (involution), which is the primary process through which blood flow through spiral arteries is stopped -\> linked to oxytocin levels in mother
205
What are the changes that occur to the cervix?
Cervical ripening (becoming softer and flexible) and dilatation (becoming thinner and being stretched sideways) -\> requires extensive remodelling of ECM of the cervix and can take many hours -\> also accelerated by increasing pressure of fetal head on cervix, caused by increasing strength and decreasing gaps between myometrial contractions
206
What are the factors that are most important in regulating the cervix, myometrium and fetal membranes?
Cervix -\> PGE2, IL-8, MMPs. Myometrium -\> PGF2a (E2) from fetal membranes, oxytocin receptor increased, contraction associated proteins increased. Fetal membranes -\> inflammatory process in fetal membranes, prostaglandins, interleukins, MMPs
207
What are the fetal risks at labour?
Delivery at term has few specific risks, but under 32 wks has infant morbidity and mortality -\> survival increases with increased GA and the babies born with less than 27wks, 87% had major morbidities, so QoL is affected -\> many linked to intrauterine infection, or other uterine complications, such as bleeding. Also -\> early delivery = incomplete development of lungs, brain, digestive and immune system, with fetal brain being sensitive to inflammatory mediators, which as labour is inflammatory and a preterm labour cause is intrauterine infection, brain dmage severity is quite high in these extremely preterm infants
208
What is fetal growth?
The increase in mass that occurs between the end of the embryonic period and birth.
209
How do you determine externally the size of the fetus?
Determine size by palpation of maternal abdomen, basis of symphysis fundal height -\> ID the distance between the pubic symphysis and the top of the uterus -\> reflects generic changes in uterine size, its vulnerable to errors
210
What are the errors that can occur when taking the SPH (symphysis fundal height)?
Lower values than should be: wrong last period date, baby in transverse lie, complications including oligohydramnios or baby small for gestational age. Higher value than should be: wrong last menstrual period, multiple pregnancy, maternal obesity, molar pregnancy, fibroids, polyhydramnios or baby large for gestational age
211
What are the factors responsible for fetal growth?
Genetic potential from both parents, mediated by IGFs; substrate supply -\> sufficient nutrients from placenta and uterine vascularity
212
What is the ultrasound assessment for fetal growth?
Assessed by 4 biomedical parameters -\> biparietal diameter, head circumference, abdominal circumference, and femur length, all to give estimated fetal weight; with normative growth curves derived to give centiles; clinically used to ID normal IUG and detect risk of obstetric/neonatal complications. Good to use centile chart as you can compensate for different sized infants that are growing and developing normally
213
What is the use of the fetal growth chart?
Based on fetal weight curves for normal pregnancies; adjusted to reflect maternal constitutional variation and are optimised by presenting standard free from pathological factors such as diabetes and smoking
214
What is the growth velocity of an infant in pregnancy?
14-15 wks: 5g /day 20 wks: 10 g/day 32-34 wks: 30-35g/day \>34 wks: growth rate decreases
215
What is normal fetal growth characterised by?
Cellular hyperplasia (increased cell numbers): 4-20 weeks 2. Hyperplasia and hypertrophy (increased cell size): 20-28 weeks 3. Hypertrophy dominates: 28-40 weeks as main growth occurs
216
What are the factors that can affect correct dating of a pregnancy?
Irregular length of periods; abnormal endometrial bleeding; the use of oral contraceptives; breastfeeding. A couple hoping to start a family are likely to take careful note of LMP timings, whereas in the case of an unplanned pregnancy, maternal information on her last menstrual period may not be so precise. Correct dating is important as it can change definition of LGA and SGA, also clinical decisions can be altered (glucocorticoids given before preterm delivery to increase surfactant production); BEST time for ageing is end of first trimester where variation in fetal size are limited, using crown-rump length via USS
217
What are the maternal factors influencing fetal growth?
Poverty -\> malnutrition, poor prenatal care, lack of education (smoking, alcohol, drugs). Mother's age -\> \<16 and \>35: longer labour, higher risk of preterm labour, increase down syndrome risk \>40y, more exposed to miscarriage, premature births and birth defects. Drug use -\> narcotics: risk of birth defects, low birth weight, ^ rate of stillbirths/death as infant; may lead to irritability, crying and risk for SIDS, can cause addiction in baby; Cannabis slows fetal growth rate and premature delivery, low birth weight, shortened gestational period and complications in delivery; heroin: interrupted fetal development, stillbirths, birth defects, premature delivery, miscarriage, facial abnormalities and head size, GI abnormalities, CNS disturbances and SIDS; cocaine = in low birthweight, smaller brain, learning disabilities, stillborn risk ^, CNS and motor dysfunction. Alcohol: disrupts fetal brain development, maturation of CNS and interferes with fetus cell development, major organ defect, behavioural problems, facial abnormalities (smaller eyes, thin upper lip and lack of groove in upper lip; increase risk of miscarriages and still birth, low birth weight = FAS. Smoking and nicotine -\> nicotine reduces blood flow to fetus, CO reduces O2 flow to fetus, results in stillbirth, low weight, ectopic pregnancy, ^ SIDS, asthma risk. Diseases -\> placenta can't always filter out pathogens. Mother's diet and physical health -\> lack of iron = anaemia, lack of calcium = poor bone and teeth formation, lack of protein = smaller fetus and maental retardation. Prenatal depression. Environmental toxins -\> ^ miscarriage, sterility and birth defects, inc. lead, mercury, ethanol or hazardous env
218
What are the feto placental factors influencing fetal growth?
Different genotypes. Gender (M\>F). Previous pregnancy. Hormones -\> iGF, insulin (^ mitotic drive and nutrient availability), cortisol (tissue differentiation and maturation, can switch IGF-II [early embryonic development] to IGF-I [infant growth]), T4 (both tissue accretion and differentiation), GH (little part in fetal growth). Fetal glucocorticoid affects tissue differentiation and prenatal devleopment of lungs (surfactant), liver (glycaemia control), intestines (enzymes and prolif of villi). EGFs are strongly mitogenic and form molecules that bind to same receptors. TGFs,FGFs, Embryonic ChE (active in morphogenesis, ChE inactivates NT), IL-1 elongs to cytokines
219
What is small for gestational age?
Birth weight \<10th centile
220
What is intrauterine growth restriction?
Failure of infant to achieve predetermined potential for variety of reasons
221
What is low birth weight?
\<2,500g at delivery
222
What is very low birthweight?
\<1500g at delivery
223
What is extremely low birthweight?
\<1000g at delivery
224
Why is birthweight important?
Early delivery are at increased risk of range of neonatal complications, so IDing the at-risk infants is important, important to differentiate between infants born at preterm and low weigth due to preterm or those growth restricted (higher morbidities/mortalities after delivery) -\> 10th centile is most sensitive, third centile most specific
225
How would you identify a IUGR?
Use serial measurements, plotted on a growth chart, to see that the infant isn't growing along centile
226
What are the consequences of IUGR?
IUGR is most common ID factor in still-born; babies with IUGR have increased complications, more severe than in normally grown infants. Short term: Respiratory distress, Intraventricular haemorhage, Sepsis, Hypoglycaemia, Necrotising enterocolitis, Jaundice, Electrolyte imbalance. Medium term: Resp problems, developmental delay, special needs schooling. Long term: fetal programming
227
What are the causes of IUGR?
Generally develops in the 2/3rd trimesters, with the first concentrating on the development of embryonic and fetal structures and almost all weight gain occurs later in preg, so main causes are apparent then -\> these factors can be combined which increases IUGR
228
How do pre-eclampsia and IUGR interact?
Close link, so often occur together -\> main cause of preeclamsia is diminished remodelling of spiral arteries by cytotrophooblasts, so decreased blood flow and decreased nutrient supply to placenta and fetus
229
What is preeclampsia?
Gestational HTN of \>140/90mmHg on more than 2 occasions, \>4h apart AND proteinuria of \>300mg in a 24-urine collection, arising de novo after 20th week gestationand resolving by 6th pst-partum week
230
How do you manage IUGR and pre-eclamptic pregnancies?
Once IUGR/pre-eclampsia have been ID, difficult to treat and reverse effect on infant; timing delivery of baby in relation of risks to fetus remaining in utero and prematurity hazards. Can ID problems using CTGs, Doppler/US finding/maternal compromise. Corticosteroids admin at gestation \<36wks to improve neonatal wellbeing (LUNGS). Just pre-eclampsia treatment is to deliver, but balance risks of fetus, which can compromise health of mother and infant, making C-section necessary
231
What is height velocity?
How fast a child is growing in cm/y usually, calculated over a whole year
232
What factors do you need to consider when looking at height and growth of the child?
Centile charts are used for cumulative height; height velocity is important as a short child could have a normal height velocity; should use height of family members
233
What factors affect normal growth?
Events before birth -\> poor fetal growth, low birth weight, prematurity; medical issues in childhood -\> malnutrition, chronic disease, endo problems; genetic factors -\> height of family and diisorders of growth (inherited); randomness
234
How do children grow?
Fastest phase of growth is in the first 2 years of life, can move up and down centiles through this phase; most children move into a centile position by 2-3y of age and then contnue on this centile position through childhood, with children growing fast enough to stay in one centile. Phase of fast growth at puberty, which depends on age of puberty for each child, and at end of puberty epiphyses fuse and growth stops
235
How can you monitor children's height growth?
Measured in the red book, if concerns about growth then height should be measured accurately and plotted for a year; if they maintain on the centile then their growth rate is fine; puberty can leave a lot of children shorter than their peers
236
What are the hormones controlling growth?
GH is most important which is controlled by the hypothalamus, secreting GHRH (+) and somatostatin (-) - mostly released as pulses at night. GH also stimulates release of IGF1 which circulates bound to binding proteins and stimulates growth in all tissues of the body
237
What factors can cause short stature in children?
Most short children have normal growth pattern but if they grow slower than normal then they fall in centile -\> caused by: poor nutrition, chronic disease, endocrine causes (GH/thyroid hormone deficiency), genetic disorders (achondroplasia, Turner's and Down's), psychological distress and neglect
238
What are the causes of tall statures?
Most tall children don't have anything wrong with them but: syndromes of overgrowth (Marfan's and Soto's syndromes), GH excess from pit tumour (very rare), precocious puberty can have a very early pubertal growth spurt, so children can present with tall stature but growth stops early, so will be short adults.
239
What is obesity in children?
Children have lower BMI than adults and changes with age, so obesity is assessed on the BMI centile position. -\> some ethnic groups have less tolerance of obesity and are more likely to get complication like T2DM at lower BMI
240
What are the complications of obesity?
Makes you more likely to get a range of disorders such as T2DM, CVD, some cancers and orthopaedic problems
241
Why does obesity happen?
Imbalance of energy taken in as food vs energy expendtiure -\> hunger regulated by hypothalamus and factors which regulate this and some individuals have single gene mutations which can result in excessive appetite, hence severe obesity. FTO gene affects eating behaviour and appetite making an individual more likely to eat in a way that makes them gain weight
242
What are the main hormones involved in growth?
Gonadal steroids (androgens) with GH
243
What are the 2 theories of onset of puberty?
Maturation of CNS affecting GnRH so increased pulsatile release AND altered set point to gonadal steroid negative feedback
244
What triggers the maturation of CNS to cause puberty?
Secular trend towards earlier puberty, which suggests environmental factors, such as improved health care, improved socioeconomic factors
245
What is the age at menarche?
Evidence that age has decreased over the last 150 years and has leveled off the last 30/40y, or could be increasing again, but body weight has remained relatively constant at 47kg at menarche
