Common Pathologies in Pregnancy Flashcards
Ovary is a ________ factory
hormone
Fallopian tube – has a uterine end connecting to the uterus and a _______ end which is not fully connected to the ovary
fimbrial
Cervix is the neck to the womb/uterus and the ______ is the recess around the cervix, the role of the cervix is to stop bacteria coming into the uterus but can allow ___________ to come in so important role of cervical mucus
fornix
spermatozoa
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Hormonal cycle – identify the hormones produced by the ovary
First half of the cycle is oestrogen
Second half is the progesterone/progestogen (many different names usually meaning the same thing)
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what has happened?
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Progesterone keeps rising as egg has been fertilized
What does progesterone (or progestogen) do to endometrium?
Main effect is on endometrium – it thickens the lining of the womb
Progesterone = thickening of lining, changes cells
Reaches maximum thickness late in the cycle then it gets shed
Progesterone turns endometrium into decidua
Increases vascularity
Between glands and vessels the stromal cells enlarge and become procoagulant - stops bleeding
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Egg fertilised by sperm = ????
‘chorion’
Outer edge of chorion = ???????
trophoblast cells on outside of fertilised egg
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Trophoblast cells produce which hormone?
Trophoblast produces B-hCG or Beta-human Chorionic Gonadotrophin
Trophic means makes it grow and acts on the gonads (ovary in women)
Its form the chorion
B-hCG – target is _____ ______ in ovary
corpus luteum
Blue is the fertilized egg
Send its hormone off to the ovary to the corpus luteum which has formed from the cells that surrounded the egg that has went to the endometrium
Corpus luteum forms once a month and normally shrivels and dies but B-hCG can keep it alive and it gets bigger
Corpus luteum is then stimulated to make progestogen to stop shedding of the endometrium
what is the function of B-hCG?
function is to stimulate corpus luteum to produce progestogen, which stops decidua from shedding
Allows fertilized egg to have a home in the decidua
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B-hCG:
Forms basis of _________ tests
Stimulates the ovary to produce __________ throughout pregnancy, and stops decidua from _________
pregnancy
progesterone
shedding
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Fertilised egg burrows in to _______
decidua
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Trophoblast cells stream off to invade mother’s _____ _______ and (eventually) link these vessels up with those of the ________
Decidual _______ cells are between the vessels
Trophoblast cells stream off to invade mother’s blood vessels and (eventually) link these vessels up with those of the fetus
Decidual stromal cells are between the vessels
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Trophoblast cell = ??????
placental cell. Only exists in pregnancy. It is a fetal cell
Decidual stromal cells are what?
procoagulant and stop trophoblast cells causing too much bleeding
Projections of chorion (chorionic villi), covered in ________ cells, start to move into the ______ (TOP ARROW)
The decidual cells are ________ and help stop ______ when the trophoblast cells invade mother’s blood vessels (BOTTOM ARROW)
Projections of chorion (chorionic villi), covered in trophoblast cells, start to move into the decidua
The decidual cells are procoagulant and help stop bleeding when the trophoblast cells invade mother’s blood vessels
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Eventually the chorionic villi, covered by trophoblast cells, are bathed in the mother’s blood, forming the forerunner of the _______
Never should foetal ___ _____ _____ and mothers red blood cells mix
placenta
red blood cells
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Rest of this lecture = series of cases – all of these cases are common or relatively common
Case 1:
- Woman, 26 yrs
- Misses period
- Pregnancy test positive (Beta-hCG in her blood and urine as she is pregnant and it is being produced by the fertilized egg)
- Vaginal bleeding 7 weeks after missed period (Had a fertilized egg for 7.5 weeks)
- What has probably happened?
- US scan: No fetus present but membranes and decidua lining uterus still there = miscarriage
- Removal of remaining tissue by obstetrician to avoid bleeding and infection
- Tissue sent to pathology: (Decidua is round about in dark purple, Open at one end where the foetus has probably come out)
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A microscope slide of this case as sent to the pathologist:
what is seen?
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Sac broken at open end where the foetus has come out
Chorionic villi come off in all directions early
Chorion redeveloped into a much bigger structure
This spaces is where the fetus was and has now been lost due to the miscarriage
Case 1 follow up:
- No problems afterwards
- B-hCG returns to normal (ie zero)
Why did miscarriage happen?
- Unknown in this case (it is very common for no cause to be obvious)
- Causes include: 1. Fetal problem eg chromosomal abnormality (Downs syndrome is one example of a chromosomal abnormality causing miscarriage but many chromosomal abnormalities are lethal early on in pregnancy), 2. Placenta/membranes/cord problem eg infection, 3. Uterus/cervix problem (eg cervical incompetence) and 4. maternal health issues (eg drug taking)
Case 2:
- Woman, 32 years old
- Misses period.
- 8 weeks pregnant = Small amount of bleeding per vagina
- BhCG raised
- Ultrasound: Thickened lining of endometrial cavity. Expanded fallopian tube on 1 side.
- Diagnosis?
First thought is it a miscarriage but expanded fallopian tube makes you question is it a miscarriage of a pregnancy in the fallopian tube
- Diagnosis = ectopic pregnancy
- Considered using methotrexate (good drug for killing trophoblast cells, placenta dies and you expel foetus and its placenta) – but opted for operative removal of fallopian tube - tissue sent to pathology
- Pathology findings:
Case 2:
Pathology = ????
ectopic pregnancy
Fimbrial end next to ovary
Red dots is bleeding
Few decidua cells in the fallopian tube
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Case 2 follow up:
- Woman well 1 week after operation
- B-hCG returned to zero
Note that this woman presented with a ‘miscarriage’, but the pregnancy was miscarrying from the fallopian tube, not the uterus.
Case 3:
- Woman 23 years
- Sudden severe abdominal pain. Collapses.
- Admission to A&E = Pulse fast. BP low.
No knowledge that she is pregnant
Low BP and a fast pulse then that combinations is one of the most worrying things in medicine – circulatory shock – many causes but the three main ones are hypovolemic shock (due to bleeding and no blood volume left), cardiogenic shock (due to heart disease), septic shock (due to infection)
Hypovolemic shock is first place to go as no history of heart disease and young and not ill with fever
- Blood given
- Emergency laparotomy:
- At operation - several litres of blood in abdomen
- Blood flowing from fallopian tube area - clamped, removed and sent to pathology
- Pathology:
Pathology = blood +++, fragmented fallopian tube with placenta and sac
- Microscopy = blood, fragments of fallopian tube and occasional chorionic villi (part of what will become the placenta and therefore tissue which confirms pregnancy)
- Diagnosis = ruptured ectopic pregnancy
Similar to previous case but it has birth and ruptured from the fallopian tube and massive bleeding into peritoneal cavity
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Case 3 follow up:
- B-hCG raised after operation, but returns to normal
- Woman is well 3 weeks later
what is an ectopic pregnancy?
- = Pregnancy in the wrong anatomical site
- Most common in fallopian tube
- Lack of proper decidual layer and small size of tube predispose to haemorrhage and rupture
- If it presents early woman may not even know she is pregnant
Decidual layer in uterus helps stop trophoblast cells from causing bleeding when they invade mother’s blood vessels. No proper decidual layer is present in fallopian tube.
Case 4:
- 32 year old woman
- +ve pregnancy test
- 7 weeks pregnant – minor bleed (Still early pregnancy – first trimester so first 13 weeks (normal pregnancy is 40 weeks))
- Ultrasound: uterine cavity shows some placental tissue but no fetus. Fallopian tubes normal.
- B-hCG raised
- Diagnosis:
- Diagnosis = miscarriage
- Endometrial tissue removed by obstetrician and sent to pathology
- Macroscopic pathology: large chorionic villi are visible as vesicles (like small grapes)
Lost the foetus but the pregnancy in terms of placenta is living on
Case 4:
• Microscopy = enlarged abnormal chorionic villi with abundant trophoblast = ???
= molar pregnancy
Form of pre cancer (dysplasia)
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Normal ovary in adult females:
• Mum to be switches off certain genes in ova (eggs) by _________ them
methylating (Switches off genes by adding methyl groups)
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Normal testis in adult males:
• Dad to be switches off _______ genes in sperm by methylating them
different
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Normal fertilisation:
Mum and dad’s changes lead to _______ genes being swiched off
Mum’s changes promote _____ ____ _______
Dad’s changes promote early _______ _______ via trophoblast proliferation
Overall effect is _________ ______ of baby and placenta
different
early baby growth
placenta growth
balanced growth
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what is the cuase of molar pregnancies?
Molar pregnancy – various causes but often caused by 2 sperm fertilising one egg with no chromosomes (Both fertilize this empty ovum)
• Result is imbalance in methylated (switched off) genes
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2 sperm fertilising one egg with no chromosomes - what is the result of this?
May have normal number of chromosomes but typically you have too many of dads methylated genes which cause placental overgrowth as that’s what his genes do
Baby doesn’t grow well and disappears and miscarriages in 2-3 weeks
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Molar pregnancy: 2 lots of dad’s genes
- A problem because in the testis dad has inactivated several genes by adding _____ groups to stretches of DNA;
- massive overgrowth of ________ cells and therefore overgrowth of _______;
- no or all but non-existent _____ growth
methyl
trophoblast
placenta
fetal
Molar pregnancy:
- A form of ________ of trophoblast cells
- If it persists can (rarely) give rise to a malignant tumour called ___________
precancer
choriocarcinoma
Molar pregnancy - what is the treatment?
- If BhCG returns to normal – no further treatment
- If BhCG stays high (persistent disease) = cure by methotrexate
Case 5:
- 40 year old woman
- 10 weeks pregnant
- Scan: nuchal thickening (Thickening of the back of the neck, normal in mammals, Between 8 and 13 weeks, If particularly pronounced then more common in certain chromosomal abnormalities)
- Amniocentesis: Trisomy 21 (Down syndrome)
- Termination Of Pregnancy For Abnormality (TOPFA) at 20 weeks
- Postmortem: what does it show?
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External – various anomalies including:
Done a post mortem as a form of audit to check genetics were correct and see how the baby was
Single palmar crease - Single palmar crease is normal but much more normal in chromosomal abnormalities
Internal - Interrupted duodenum = duodenal atresia (This one is life threatening, Would limit your life if left there)
- External features of Down syndrome (several minor anomalies eg single palmar crease, epicanthic folds, protuberant tongue….and several others)
- Duodenal atresia (a major anomaly)
Decision for TOPFA - Very much the parent’s decision
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Case 6:
- 28 year old mother poorly controlled diabetes mellitus
- Pregnancy doing well until 36 weeks – baby stops kicking
Normal pregnancy is 40 weeks (9months), Term is between 37-42 weeks, Slightly premature at 36 weeks
- Scan: No fetal heart movement = Intrauterine Death or IUD. When born this baby will be called a stillbirth.
- Trial of labour attempted but baby too big = caesarean section (Worried the big baby will in some way obstruct the cervix)
Postmortem =
•Postmortem: huge baby with broad shoulders (‘diabetic cherub’)
Case 6 – Why is baby so big?
- Effects of too much glucose in mother
- Does Glucose cross the placenta? - yes
- Glucose crosses the placenta and raises babies blood glucose. What happens to babies insulin?
- Insulin goes up in baby
- Can baby then reduce its glucose to normal? Baby has a pancreas and is not diabetic so increases its insulin production from its pancreas. Mum is diabetic and baby is not
- Baby cannot reduce babies glucose as mum keeps sending more across the placenta
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Case 6:
- Longterm high insulin and high glucose = massive growth
- Susceptibility to intrauterine death
how does a baby grow so much?
Insulin pushes glucose into fat cells and every cell so the glucose is continuously pushing this glucose into cells
At end of pregnancy the babies growth is meant to slow down
Diabetes in pregnancy – many problems, what are they?
- 1st trimester: Malformations (get some odd ones)
- 3rd trimester: Intrauterine death (probable sudden metabolic and hypoxic problems)
- Labour: Huge babies that obstruct labour
- Neonatal period: hypoglycaemia - as had high glucose but then when born it has low glucose
what needs to be done about diabetes in pregnancy?
•Need good glucose control before conception (to prevent malformations) and then all the way through (to prevent metabolic complications)
Case 7:
- 35 year old woman
- Well throughout pregnancy
- 36 weeks – spontaneous labour
- Labour progresses well but mum has fever
- Heart beat lost minutes before birth
- Resucitation unsuccessful
- ‘Fresh’ stillbirth
- Examine placenta in all cases of stillborn babies (and babies who go to neonatal unit…….)
what is seen onplacenta exam?
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Placental examination – cut off membranes - microscopy
Membranes contain neutrophils
- Trilobed nucleus is easily deformable and allows them to move easily into tissues.
- Phagocytose (ingest) and destroy micro-organisms
examine cord – take 2 cross sections - microscopy shows neutrophils in cord
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Placental examination – examine cord – take 2 cross sections - microscopy shows neutrophils in cord
Look at the cord with its 3 vessels
Placental microscopy – cut placenta and take sections
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Case 7 – Diagnosis = acute chorioamnionitis
what is it?
•Acute inflammation = neutrophils present in membranes (chorioamnionitis), cord, and fetal plate of placenta
Acute chorioamnionitis = Ascending infection
•Bacteria are typically perineal or perianal flora (eg E.coli) which ascend vagina and get into the amniotic sac
Nearly always bacterial and not viral
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what is the Presentation of ascending infection?
- Mother ill: has fever and raised neutrophils in blood
- But: Mother can be well
what is the presentation in the baby?
- Intrauterine death
- Ill in 1st days of life = neonatal unit
- Cerebral palsy later on in life
How does ascending infection affect baby’s brain?
Neutrophils prodcuce cytokine ‘storm’. This activates some brain cells, which then get damaged by normal hypoxia of labour
Cerebral palsy is one of the biggest causes of long term disability
Very common cause of premature labour
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Case 8:
- 24 year old woman
- Intravenous heroin addict
- Also on methadone (Methadone – liquid opiate (green liquid) – handed out by the pharmacist), cocaine, temazapam, + other drugs
- Do opiates cross the placenta?
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•Opiates do cross the placenta
Opiates are very small molecules and so can cross the placenta.
Baby becomes an addict to the opiates
Case 8:
- Becomes pregnant
- Pregnancy and labour proceeds uneventfully (Opiates tend not to affect pregnancy unless the mother doesn’t eat)
- Prebooked to deliver in large maternity unit beside neonatal unit. Why?
So that baby can be admitted to neonatal unit and treated for heroin withdrawal
Discharge home after 5 days in unit
At 3 weeks baby ‘overfeeds’ with constant mouthing movements (? Methadone withdrawal) then gets better
Opiates:
- Pregnancy often proceeds well if mother _______ properly
- Immediate __________ from heroin when baby is born
- Later withdrawal from _________
eating
withdrawal
methadone
Also worried this women is taken cocaine as it is a vasoconstrictor and if it is taken at any time in pregnancy it can constrict vessels going to baby and can cause a miscarriage
Case 9:
- 32 year old woman
- Normal pregnancy to term
- Decreased movements of baby at 40 weeks
- Scan – No heart movement
Diagnosis = itrauterine death
Postmortem findings = Baby morphologically normal
Postmortem findings of placenta, cord and membranes - what are they?
Cord is abnormal
Twisting of a cord too much and it gets too tight then risk of babies own blood supply not going down the cord
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what is the cause of an overtwisted cord?
- Common cause of intrauterine death and neonatal illness
- Probably caused by normal, active, baby moving and twisting round it’s own cord
Case 10:
- 33 year old woman
- Hypertension during pregnancy
- Vaginal bleed at 35 weeks
Ultra sound: Separation of part of the placenta from uterus with collection of blood (a haematoma) behind placenta. Haematoma enlarging during ultrasound
treatment - Emergency caesarian section
what is the outcome?
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- Baby has low APGARS
- Unwell in neonatal unit for 5 days then much better.
Abruption:
- Means separation of placenta from uterine wall
- Results in hypoxia in baby
- Often causes antepartum haemorrhage in mother
Not a pathology diagnosis, diagnosis made clinically and ultrasound
Often an emergency
Hemorrhage before the baby is born
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Any separation of placenta from uterine wall decreases baby’s supply of _______ from mother
oxygen
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what are the causes of abruption?
- Hypertension
- Trauma
- Other: for example cocaine