Case 7 - Early pregnancy Flashcards
What type of staining helps you tell chromosomes apart on a micrograph
Giemsa staining
What are the and q arms of chromosomes
p = short arm q = long arm
What is significant about the light bands of chromosomes
more transcriptionally active
What is significant about the dark bands of chromosomes
less transcriptionally active
Common chromosomal abnormalities in miscarriage
Triploidy
Trisomy 16
Turner syndrome
Methods of diagnosing Trisomy 21
Nuchal translucency on ultrasound
antenatal screening
Facial appearance at birth
Symptoms of Down’s Syndrome
poor muscle tone heart malformations intellectual disability flattened nose short stature increased risk of thyroid disease and congenital heart disease high rate of dementia in old age
Consequences of mosaicism
Milder symptoms
Can make some unviable trisomys viable
What are the viable trisomys
18 - life limiting
21 - survivable
13 - significantly life limiting
Why can you survive with monosomy X
X inactivation
Chromosomes, treatments and symptoms of Turner syndrome
45, X
short stature broad chest neck webbing heart/kidney defects lack of sexual development in puberty
treatment:
growth hormone in childhood
oestrogen in adolescence
surgery for webbing
Chromosomes, symptoms and treatment of Klinefelter syndrome
47, XXY
pubertal gynaecomastia small testes delayed/incomplete development of secondary sexual characteristics infertility tall stature motor, language and reading delay increased risk of x linked conditions increased risk of 'female' conditions eg, breast cancer
treatment:
surgery for gynaecomastia
testosterone in adolescence
Chromosomes, symptoms and treatment of XYY syndrome
47, XXY
tall stature usually normal intelligence severe acne normal fertility potentially increased aggression/antisocial behaviour
What is a genetic interstitial deletion
An interstitial deletion means that the chromosome has broken in two places and the broken ends have fused, leaving out the deleted segment
Give examples of conditions caused by interstitial deletions
Prader-Willi Syndrome William's syndrome Miller-Dieker syndrome Smith-Magenis syndrome Di George syndrome
what is array-based comparative genomic hybridization used for
Detecting deletions, duplications and inversions in genomic material
What is a Robertsonian translocation
Occur on acrocentric chromosomes and allows two q arms to fuse and 2 p arms to fuse.
What is variable expression of a phenotype
Different presentations of the same genetics
What is reduced penetrance
only affects some people, eg age-related
What is sex limitation
phenotype only develops in one sex
What is phenocopy
occurrence of a condition is not related to family risk due to environmental influence
What is incontinentia pigmenti
- inheritance pattern
- appearance of symptoms
X linked dominant inheritance
blistering
alopecia
hypodontia
wart-like rash
Due to x inactivation, only affects certain regions of the body in females
How do x linked recessive conditions affect females
Due to x inactivation sometimes the affected x chromosomes are activated which can cause mosaicism of the condition
Inheritance of germline mosaicism
Affects the gonads so may be passed to future offspring
What is genomic imprinting
Genomic imprinting, process wherein a gene is differentially expressed depending on whether it has been inherited from the mother or from the father.
How does prader-willi syndrome show genomic imprinting
Inherited from father
How does Angelman syndrome show genomic imprinting
inherited from mother
What is uniparental disomy
when both chromosomes originate from one parent
Which systems are usually affected by mitochondrial conditions
Energy-hungry systems
Antenatal screening available
Early pregnancy ultrasound Foetal abnormality ultrasound Blood groups and antibodies HBV/HCV Sickle cell Down's syndrome HIV
Factors influencing decision to have antenatal screening
personal experience prior knowledge beliefs social background family and friends professional bias age
Purpose of early pregnancy ultrasound
Determines date of conception and viability. Observe nuchal translucency as a sign of Down’s Syndrome. Multiple pregnancy can also be detected here.
Purpose of foetal abnormality ultrasound
Looks for abnormalities and sex of foetus. Terminations may be offered after this point
What do booking bloods test for
Early pregnancy blood tests: Syphilis HIV HBV Rhesus antibodies Down's syndrome sickle cell and thalassaemia FBC Blood group Rubella (no longer routine)
What is the Quad test in pregnancy
Done at 15-18 weeks, detection rate of 75%, uses maternal blood to look for 4 biomarkers indicative of foetal abnormalities (AFP, hCG, uE3, Inhibin A)
What is the combined test in pregnancy
Done at 11-14 weeks, detection rate of 85%, uses maternal blood to look for 2 biomarkers indicative of foetal abnormalities (BhCG, PAPP-A)
What is chorionic villus sampling
CV aspirated through abdomen and tested. Done from 11 weeks, 1-3% risk of miscarriage.
What is amniocentesis
Sample of amniotic fluid taken from 14 weeks. 1% miscarriage risk, usually available more locally.
What is NIPT
Non-invasive pre-natal testing
Uses cell-free foetal DNA in maternal blood to test for aneuploidies. 99.9% detection rate, can be used in twin pregnancies, very safe. Expensive.
What are the germinal layers of the embryo
the outer layer is the ectoderm, the middle layer is the mesoderm, and the innermost layer is the endoderm
What does the ectoderm give rise to
Epithelial and nervous tissue
What does the mesoderm give rise to
skeletal system, the muscular system, the excretory system, the circulatory system, the lymphatic system, and the reproductive system
What does the endoderm give rise to
intestinal tract and its associated structures and glands, the respiratory and urinary tracts and most of the endocrine glands
How does initial vasculogenesis work
Formation of mesodermal aggregates called blood islands. These blood islands then form endothelial lined vesicles that contain immature blood cells which then join together to form immature vessels
How is angiogenesis triggered in the forming embryo
Embryonic tissue causes secretion of vascular endothelial growth factor which in turn causes cell proliferation, cell migration and secretion of matrix MMPs
How does the heart form embryologically
Clusters of cardiac myoblasts and endocardial cells arises from the mesoderm
These clusters form the heart tube. Other clusters begin forming the dorsal aortae
Heart tube folds and with the pericardial cavity, is pushed to the thoracic region
Heart tube develops 5 dilations which will mature into the chambers
Myocardial proliferation begins to form septum and separate the chambers
Some cardiomyocytes undergo depolarisation and become the SA node
Changes in foetal anatomy at birth
Closure of ductus arteriosus
Closure of foramen ovale
Closure of umbilical artery
Closure of umbilical vein and ductus venosus
Examples of congenital heart defects
Septal defects Heart disease Patent ductus arteriosus Transposition of great vessels Tetralogy of Fallot
Defects in tetralogy of fallot
Overiding aorta
Pulmonic stenosis
Septal defect
right ventricular hypertrophy
Preeclampsia symptoms and treatment
Pre-eclampsia onset is usually in the second half of pregnancy or just after birth. Symptoms include hypertension, proteinuria, vision problems, pain below the ribs, severe headaches and oedema. Exacerbating factors may be diabetes, kidney disease, lupus, family history, multiple pregnancies and being over 40
The treatment is to deliver the baby and so its important to monitor the mother so you only deliver at the latest possible moment. Pre-eclampsia can progress to eclampsia which causes fits in the mother and can be fatal to both mother and baby.
Risks of conception and pregnancy with geriatric mothers
Greater difficulty in initially conceiving a child, with the personal and psychological difficulties that this can cause.
Increased risk of complications for both mother and infant during pregnancy and delivery (although the actual size of the risk may be small).
Greater risk of general maternal health problems, such as high blood pressure, which can contribute to complications.
Higher risk of miscarriage in women above the age of 35.
Higher risk of having twins or triplets, which is itself associated with higher risk of complications.
Increased chance of having a baby with a congenital abnormality, such as Down’s syndrome.
Increased risk of pre-eclampsia.
Increased risk of complications during delivery, such as prolonged labour, need for assisted delivery or Caesarean section, or stillbirth.
Effect of consuming alcohol in pregnancy
Behaviour and attention problems Heart defects Changes in the shape of the face Poor growth before and after birth Poor muscle tone and problems with movement and balance Problems with thinking and speech Learning problems Drinking alcohol appears to be most harmful in the first trimester.
When are structural/functional defects most likely to occur in a pregnancy
Early trimester 1 - structural
Late trimester 1/early trimester 2 - functional
Layers of fetomaternal placental barrier
Syncytriotrophoblast
Cytotrophoblast
Basal lamina
Basal lamina of foetal capillary
What is pelvic inflammatory disease
The abdominal cavity in women, unlike in men, is susceptible to infections and inflammation because it is open to the external environment through the reproductive tract. There is the possibility of bacteria entering via the vagina and travelling up the uterine tubes, thereby causing inflammation. Any infection that follows this path can cause PID. Repeated instances of inflammation can block the uterine tubes and cause infertility
What is endometriosis
Endometriosis and adenomyosis are two reproductive system diseases that are caused by abnormal growth of the endometrium. The endometrium is the tissue that lines the womb or uterus. When this tissue is formed in other parts of the reproductive system like the outside of the uterus, ovaries or fallopian tubes, the condition is termed as endometriosis. If the growth occurs into the muscles surrounding the uterus, it is called adenomyosis. Since all endometrium tissue is pushed out of the body with the completion of the menstrual cycle, abnormal growth can lead to cyclic pain in the abdomen or pelvis.
What is PCOS
This syndrome is caused when the ovaries produce high levels of a particular class of hormones, namely androgens. This increase in hormone levels can hamper the ovulation process and lead to cysts on the ovaries. It can also cause infertility by affecting the release of the ovarian egg in the menstrual cycle. Some symptoms are hair loss, acne, pain in the pelvic region, oily skin, and increases in facial or body hair growth. There is no cure for this female reproductive system disease yet, but the hormone production can be controlled and skin cleared up with hormone therapy.
What are uterine fibroids
Sometimes it is possible that tumours grow in the muscular wall of the uterus; however, these tumours are not cancerous. They are called uterine fibroids and can cause increased urination, pain in the lower back, heavy bleeding and pain during the menstrual period, pain during intercourse, miscarriages and infertility. Surgery and pain relief methods are used to treat this condition. The Centers for Disease Control and Prevention (CDC) state that around 20 percent of women younger than 50 years of age develop such tumours.
Physical aftereffects of pregnancy
Incontinence
Separated stomach muscles
Back pain
Prolapse
What are postpartum blues
Occurs within 1 week following delivery
50-70% incidence rate
Causes tearfulness, anxiety and insomnia
Usually resolves on its own and is the results of hormonal changes
What is postnatal depression
Insidious onset 2-3 months post birth
10-15% incidence rate
Causes excessive insomnia, anxiety and depressed mood
Usually requires medication or CBT/counselling
What is postpartum psychosis
Onset 2-4 weeks after birth
0.1-0.2% incidence rate
Causes agitation, euphoria, delusions, disorganised behaviour, depressed mood and irritability
Medical emergency, often requiring temporary hospitalization and medication
hCG in pregnancy
Increased to peak at around 16 weeks and then gradually decreases
Progesterone in pregnancy
Remains relatively low and then peaks around 5 weeks before delivery before falling again
Oestrogen in pregnancy
Increases throughout pregnancy and peaks around 5 weeks before delivery before suddenly dropping off at birth
Prolactin in pregnancy
Increases throughout
Relaxin in pregnancy
Peak in first trimester then gradually decreases
Oxytocin in pregnancy
Peaks just before birth
Symptoms of pregnancy
Morning sickness could be caused by changes in hormone levels and blood pressure. Tiredness is caused by hormonal changes. Sore breasts Frequent urination Strange tastes, smells and cravings
Nutrition in pregnancy
400 micrograms of folic acid every day – from before you’re pregnant until you’re 12 weeks pregnant – to avoid spina bifida
Vitamin D – a supplement of vitamin D is recommended for most adults between September and March anyway, promotes strong bones.
Iron – pregnant women can become anaemic, and pregnancy can exacerbate pre-existing anaemia.
Vegetarians and vegans should take B12 and iron in pregnancy
Medication in pregnancy (general advice)
If a mother is on medication for her own health, ie anti-depressants, epilepsy medications, then a consultation with their GP is needed to determine the risk-benefit of continuing to take their medication. Generally all medication should be avoided, including painkillers.
What are examples of high risk pregnancies
Advanced maternal age
Lifestyle of mother (drinking/drugs/smoking)
Hypertension, diabetes, heart disease of mother
Rhesus sensitisation
Multiple pregnancy
Previous pre-eclampsia
Previous premature birth
An abnormal ultrasound or abnormal lab screens
A family history of certain birth defects
Previously had a child or pregnancy with a birth defect
What are the abortifacient drugs
Mifepristone followed by misoprostol. Mifepristone can cause heavy vaginal bleeding and bacterial infections. Misoprostol can cause diarrhoea and abdominal pain and in rare cases uterine rupture.
Placental pathologies
Placenta accreta, when the placenta implants too deeply, all the way to the actual muscle of uterine wall (without penetrating it)
Placenta praevia, when the placement of the placenta is too close to or blocks the cervix
Placental abruption/abruptio placentae, premature detachment of the placenta
What is the placenta needed for
Respiration
Nutrition
Excretion
Protection
Endocrine
Immunity
Purpose of human placental lactogen hPL
Regulates amount of glucose available for baby
Causes mother to use more fats to produce her own energy (decreases maternal insulin sensitivity) and decrease use of her glucose
Glucose required for growth of baby
Increases in amount along pregnancy
Released by syncitiothrophoblast
Proliferates breast tissue in preparation for breast feeding
Types of surgical abortion
Aspiration abortions (the most common type of surgical abortion)
dilation and evacuation (D&E) abortions
Which type of abortion is most appropriate when?
If a woman is 10 or more weeks into her pregnancy, she is no longer eligible for a medical abortion. Women up to 15 weeks pregnant can have an aspiration abortion, while D&E abortions are typically performed at 15 weeks or after.
Potential complications of surgical abortions
Infection: can be serious and may require hospitalization. Symptoms include fever, abdominal pain, and unpleasant-smelling vaginal discharge. The chance of infection increases if you have a sexually transmitted infection.
Cervical tears or lacerations: can often be resolved with stitches after the procedure if necessary.
Uterine perforation: which can occur when an instrument punctures the uterine wall.
Hemorrhaging: which can result in bleeding sufficient that a blood transfusion or hospitalization is needed.
Retained products of conception: when part of the pregnancy is not removed.
Allergic or adverse reactions to medications: including pain medication, sedatives, anesthesia, antibiotics, and/or dilation medication.
