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Title: Obstetrics and Gynaecology lecture notes
Description: A very comprehensive and detailed set of notes covering all aspects of Obstetrics and Gynaecology. Complete with a nice set of diagrams to aid learning. Useful for medical students.
Description: A very comprehensive and detailed set of notes covering all aspects of Obstetrics and Gynaecology. Complete with a nice set of diagrams to aid learning. Useful for medical students.
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Obstetrics and Gynaecology lecture notes
Reproductive lecture notes: week 1
The human life cycle
SPERMATOGENESIS AND MALE INFERTILITY
Within our bodies are a few types of cells:
•
•
Somatic cells: A somatic cell (diploid cell – 23 pairs of chromosomes) is any biological cell
forming the body of an organism; that is, in a multicellular organism, any cell other than a
gamete, germ cell, or undifferentiated stem cell
...
There are approximately 220 types of
somatic cells in the human body
Germ cells: germ cells are reproductive line diploid cells (23 pairs of chromosomes) that
give rise to haploid gametes (reproductive cells with 23 chromosomes – half the genetic
material to form a baby)
•
Gametes: gametes are haploid cells that fuse during sexual reproduction
...
Ova also contain mitochondrial DNA necessary
for foetal development
...
•
Stem cells: stem cells are multipotent/totipotent cells are cells that can divide through
mitosis and differentiate into diverse specialized cell types
Germ cells
•
A germ cell (diploid) is any biological cell that gives rise to the gametes of an organism that
reproduces sexually
...
There, they undergo cell
division of two types:
! Mitosis: to produce more germ cells (so that germ cells are not all depleted) – self
renew
! Meiosis: to produce gametes (haploid cells)
•
Germ cells are diploid cells (23 pairs of chromosomes: 22 pairs of autosomal + a pair of sex
chromosomes => 46 in total) in the reproductive organs of a multicellular organism that
undergo division and are the precursors of haploid gametes (23 chromosomes in total; 22
autosomal + single sex chromosome), such as a spermatogonium or oogonium
...
! Different timing of maturation: oogenic meiosis is interrupted at one or more
stages (for a long time) while spermatogenic meiosis is rapid and uninterrupted
...
g
...
g
...
g
...
If Y is absent => testicles absent => testicular hormones
absent => then we get development of female external genitalia e
...
vagina and
clitoris + female secondary characteristics
! Gender: perceived genital sex + rearing of individual as male or female => results
in gender identity
...
Everyone is born with both
the Wolffian duct / Mesonephric duct (male duct system) and the Mullerian duct /
Paramesonephric duct (female duct system)
...
The SRY gene (on Y chromosome) is what causes testis to develop
...
SRY is a sex-‐determining gene on the Y chromosome (male
chromosome) in the humans
...
•
Once the testis are developed (in response to activation from SRY), the male duct
(Wolffian/mesonephric) system begins to form
...
•
SRY results in formation of testes => production of testosterone from Leydig cells (later
under control of LSH) => the formation of the testis, including the seminiferous tubules, rete
testis, epididymis, the vas deferns, and seminal vesicles can develop
...
•
Females and males are also born with both the Mullerian and Wolffian duct systems
(bipotential gonad)
...
The Mullerian duct
(paramesoneohric duct) develops (as no Anti-‐Mullerian factor released from Sertollic cells of
testicles) into the female reproductive tract e
...
the uterus, the fallopian tubes, cervix and
upper parts of the vagina
...
•
There are two sex determination stages: One stage determines the gonadal sex internally
(reproductive tract development) and one stage determines the genital sex externally
(external genitalia + secondary sex characteristics)
...
This is why you could have a person with the outer appearance
of a female, but internally their organs are male, and they are not able to produce because
they do not have a uterus
...
•
Fetal testes secretes:
! Testosterone from Leydig cells (later under control of LSH)
! Mullerian inhibiting factors (anti-‐Mullerian factor) from Sertolli cells (later under
control of FSH)
•
Release of Mullerian inhibiting factors (Anti-‐Mullerian) from testes => Mullerian
(paramesonephric) ducts degenerate
•
Release of testosterone from testes => Wolffian (mesonephric) ducts develop into the male
reproductive tract
•
Without stimulus of male testicular hormones (e
...
testosterone and Anti-‐Mullerian), the
fetus will develop female internal genital tract (Mullerian ducts)
•
Testosterone also results in development of external male genitalia and secondary male
characteristics
Females
•
Absent of Y chromosome (absence of SRY/TDF) => development of ovaries (from bipotential
gonad)
•
No testes => lack of testosterone and lack of Mullerian inhibiting factor
•
Lack of Mullerian inhibiting factor => Mullerian ducts develop into the female reproductive
tract e
...
uterus, fallopian tubes, vagina
•
Absence of testosterone => Wolffian ducts degenerate
•
Absence of testosterone => results in development of external female genitalia + female
secondary sexual characteristics
Differentiation of External Genitalia: second stage of sex development
In males the testicles release:
•
Mullerian inhibiting factor (from Sertolli cells) which causes degeneration of Mullerian
ducts / Paramesonephric ducts (female reproductive tract)
•
Testosterone (from Leydig cells) which is converted into dihydrotestosterone which:
! Transforms Wolffian ducts into male reproductive tract
! Causes undifferentiated external genitalia to develop into male genitalia
! Apprreciate that testosterone is important for both internal and external sexual
development and secondary sexual charachteristics
In females:
•
Lack of Mullerian inhibiting factor causes Mullerian ducts to develop into female
reproductive tract e
...
oviducts (fallopian tube) and uterus
•
Absence of testosterone causes:
! Degeneration of Wolffian ducts (male reproductive tract)
! Undifferentiated external genitalia to develop into female genitalia
Summary
Summary
•
•
•
•
Chromosomal sex: 46XX (female) or 46XY (male)
Gonadal sex: internal reproductive tract sex
Genital sex: external reproductive tract sex
“Gender”: way the child is raised
Clinical example: Androgen insensitivity syndrome (testicular feminisation syndrome)
•
Congenital insensitivity to androgens e
...
condition that results in the partial or complete
inability of the cell to respond to androgens (male sex hormones)
•
X-‐linked recessive disorder which only affects male karyotypes (male chromosomal sex)
•
Disorder of male karyotype (46XY) => male chromosomal sex => testis develop
•
Testosterone is secreted, howeer the tissues of the dveelopeing genital tract are
unrepsonsive to it
•
The unresponsiveness of the cells of the developing genital tract to the presence of
androgenic hormones (androgen resistance) can impair or prevent the development of
male reproductive tract and masculinization of the male external genitalia in the
developing fetus, as well as the development of male secondary sexual characteristics at
puberty
•
Testis develop due to presence of SRY on Y choromosome (but do not descend – as this is
under control of testosterone) => testes release androgens (testosterone from Leydig cells)
and Mullerian inhibition factor (from Sertolli cells)
•
Androgen induction of wolffian duct does not occur (due to androgen resistance) =>
internal male reproductive tract does NOT develop
•
Androgen induction of undifferentiated external genitalia is dysfunctional => external
female genitalia may develop
•
Mullerian inhibition does occur (as Anti-‐Mullerian released from Sertoli cells) =>
degeneration of internal female reproductive tract
•
Therefore individuals with complete androgen insensitivity are born with male chromosome
sex, phenotypically external female genitalia (with short vagina), with an absent uterus and
ovaries
...
They are:
! Complete androgen insensitivity syndrome (CAIS), where there is total
insensitivity to androgen and a child (chromosomally male) develops external
genitals that are entirely female
...
Most children born with CAIS are brought up
as girls (but have male chromosomal sex)
! Partial androgen insensitivity syndrome (PAIS), where there is some sensitivity
to androgen; the level of sensitivity will determine how the genitals develop
...
•
In summary: A child born with androgen insensitivity syndrome (AIS) is genetically male
(male chromosomal sex: as X linked condition only affecting males), but their genitals may
appear to be female or somewhere in between male and female
...
The distal end of the penis is called the glans
penis and is covered with a fold of skin called the prepuce or foreskin
...
The arteries of the penis are dilated while the veins are passively compressed so
that blood flows into the erectile cartilage under pressure
...
Its opening, known as the
external urethral meatus, lies on the tip of the glans penis
...
It holds and
protects the testes
...
The scrotum
remains connected with the abdomen or pelvic cavity by the inguinal canal
...
Internal genital organs
•
Testes: The testes are located in the scrotum
...
Testosterone is produced in the testes (by Leydig cells in
response to LH) which stimulates the production of sperm (in the seminiferous tubules; the
process is helped by Sertolli cells which are stimulated by FSH) as well as give secondary sex
characteristics beginning at puberty
...
! Seminiferous Tubules: each testis contains lots of tightly packed seminiferous
tubules
...
The seminiferous tubules are the functional units of the testis, where
spermatogenisis takes place (with the help from “nursing” Sertoli cells and FSH)
...
It
is activated by follicle-‐stimulating hormone FSH, and has FSH-‐receptor on its
membranes
...
Because of this, it has also been called the
"mother cell
...
Sertoli cells are
also stimulated by testosterone
...
They are responsible for secreting the male sex hormones (e
...
testosterone) in response to LH stimulation
•
The two muscles that regulate the temperature (essential for spermatogenesis) of the
testes are the dartos and cremaster muscles:
! Dartos muscle: the dartos muscle is a layer of smooth muscle fibers in the
subcutaneous tissue of the scrotum (surrounding the scrotum)
...
Lowers testes away
from body when they are too warm
...
This muscle is a continuation of
the internal oblique muscle of the abdominal wall, from which it is derived
...
Site of sperm travel:
seminiferous tubules => rete testes => epididymis => vas deferens => ejalucatory duct =>
prostatic urethra
•
Vas deferens: The vas deferens, also known as the sperm duct, is a thin tube approximately
30 centimetres long that joins the epididymis to the seminiferous tubule duct where they
fuse together to form the ejaculatory duct
...
•
The spermatic cord is the cord-‐like structure in males formed by the vas deferens and
surrounding tissue that run from the deep inguinal ring down to each testicle
...
They are the seminal vesicles, the prostate gland, and the
bulbourethral glands
...
They secrete LOTS of fructose to provide an energy source for sperm and
alkalinity to enhance sperm mobility
...
Form most of the
volume of semen
...
The smooth muscle of the
prostate gland contracts during ejaculation (peristalsis) to contribute to the
expulsion of semen from the urethra
...
The
alkalinity of seminal fluid helps neutralize the acidic vaginal pH and permits sperm
mobility in what might otherwise be an unfavorable environment
...
! Bulbourethral glands: The bulbourethral glands also called Cowper's glands are
located below the prostate gland and empty into the urethra
...
This process is androgen-‐dependent => hence whey testes do not descend in
androgen insensitivity syndrome
•
The gubernaculums (ligament like structure) moves the testes from retroperitoneal (near
kidneys) to within the scrotum
•
Normally a boys testes have descended into the scrotum (“dropped”) by birth
•
Why is it important that testes descend? The testes require a lower temp outside body to
facilitate spermatogenesis
...
g
...
The cremaster muscle
which covers the testes and spermatic cord is also important for this function
...
It is a common birth
defect regarding male genitalia
...
Orchiopexy also describes the surgery used to resolve testicular torsion (twisting
of spermatic cord, cutting off the testicle's blood supply => testicular ischemia and severe
pain)
•
If undescended as adult, consider orchidectomy (surgical removal of testes) due to the risk
of cancer e
...
seminoma (6x increase)
Function of Testis
•
Spermatogenesis: occurs in the seminiferous tubules (with help of nursing Sertollic cells) of
the testes
...
Under the control of LH
...
The site of spermatogenesis
•
Occurs in seminiferous tubules
•
Spermatogenesis is the process by which spermatozoa are produced from male primordial
germ cells through mitosis and meiosis
...
In contrast the the one ovum and
three polar bodies produced in meisosis in F
...
This is the cornerstone of sexual reproduction and involves the two gametes both
contributing half the normal set of chromosomes (haploid) to result in a chromosomally
normal (diploid) zygote
...
Otherwise, the offspring will
have twice the normal number of chromosomes, and serious abnormalities may result
...
•
Spermatogenesis takes place within several structures of the male reproductive system
...
•
Maturation of sperm occurs in the epididymis
A spermatozoon
•
A spermatozoon is a motile sperm cell e
...
mobile male gamete (haploid)
•
A spermatozoon joins an ovum to form a zygote (a zygote is a single cell, with a complete set
of chromosomes, that normally develops into an embryo)
•
Features of spermatozoon:
! Acrosome: containing enzymes that play an important role in the penetration
through the zona pellucida of the oocyte
! The midpiece has a central filamentous core with many mitochondria spiralled
around it, used for ATP production for the journey through the female cervix,
uterus and uterine tubes
...
The roles of the Sertoli cells
•
A Sertoli cell is a 'nurse' cell of the testes that is part of the seminiferous tubule
...
Hormonal Control of Spermatogenesis
Gonadotrophin Releasing Hormone (GnRH)
•
•
Decapeptide
Released from hypothalmus in bursts every 2-‐3 hours (begins age 8-‐12 years e
...
near
puberty)
•
Released by the hypothalamus and travels to the anterior pituitary by the portal system
•
Stimulates the anterior pituitary to produce and release LH and FSH
•
Under negative feedback control from testosterone
Luteinizing hormone (LH) and follicular stimulating hormone (FSH)
•
Glycoproteins secreted by anterior pituitary
•
Secretion of LH and FSH is stimulated by gonadotropin-‐releasing hormone (GnRH) from the
hypothalamus
•
Secretion of LH and FSH is under negative feedback control from testosterone
•
Production is non-‐cyclical in males (in contrast to females) => constantly fertility in males
•
Luteinizing hormone (LH):
! Acts on Leydig cells to stimulate testosterone secretion
! Regulated by negative feedback from testosterone
•
Follicle stimulating hormone (FSH):
! Acts on Sertoli cells to enhance spermatogenesis
! Regulated by negative feedback from inhibin
! Regulated by positive feedback from activin which stimulates FSH production
! Regulated by negative feedback from testosterone
Testosterone
•
Produced in Leydig cells in response to LH stimulation
•
Steroid hormone derived from cholesterol
•
Secreted into blood and seminiferous tubules for sperm production
•
Negative feedback on hypothalamus and pituitary gland => high levels of testeosterone
feedback the hypothalamus to decrease GnRH and feedback to the pituitary to decrease LH
and FSH
•
Testosterone Effects:
! Before birth: masculinises internal reproductive tract, induces development of
male external genitalia, and promotes descent of testes
! Puberty: promotes puberty and secondary male characteristics + growth of
external genitalia
! Adult: controls spermatogenesis, secondary sexual characteristics (male body
shape, deep voice, thickens skin), libido, penile erection, aggressive behaviour?
Inhibin and Activin
•
Peptides (closely related)
•
Secreted by Sertoli cells of the seminferous tubules (testes)
•
Feedback on FSH:
! Inhibin inhibits FSH production
! Activin stimulates FSH production
Spermatozoa after ejaculation
•
Liquified (by enzymes from prostate gland eg
...
Mandatory process
...
e
...
Produce most of the fluid in semen
...
The rete testis is an anastomosing network of
delicate tubules that carries sperm from the seminiferous tubules to the efferent
ducts
...
! The epididymis is composed of tightly coiled ducts lying just outside each testis
connecting efferent ducts to vas deferens
...
•
Route of sperm: testes (seminiferous tubules) => rete testes => epididymis => vas
deferens => ejaculatory duct => prostatic urethra => +/-‐ female vagina
•
Erection: blood fills corpora cavernosa (corpus cavernosum) -‐ under parasympathetic
control => point
•
Emission: contraction accessory sex glands and vas deferens (peristalsis) so semen expelled
to urethra
•
Ejaculation: contraction of smooth muscles of urethra and erectile muscles (under
sympathetic control => shoot)
•
Problems if premature or retrograde ejaculation e
...
neuropathy (e
...
DM), prostate surgery
or anticholinergic drugs (blocking of parasymepathetic NS => problems with erection)
Fertilisation in ampullary region of Fallopian Tube
Male infertility
•
Infertility resulting from failure of the sperm to normally fertilise the egg
•
Usually associated with abnormalities in semen analysis
•
Common cause of infertility
•
Idiopathic in approximately 50% cases
•
Male infertility is increasing possibly related to environmental oestrogens
Aetiology of Male Infertility
•
Low sperm count or quality: usually idiopathic
•
Endocrine causes (pre-‐testicular failure):
! Acromegaly (excessive GH)
! Cushings disease (excessive cortisol)
! Hyperprolactinaemia: suppreses LH and FSH resulting in decreased testosterone
production, galactorrhoea, low libido, erectile dysfunction
! Hypogonadotrophic hypogonadism: due to hypothalamic dysfunction (e
...
anorexia, Kallmans, excessive excercise) or pituitary dysfunction (e
...
adenoma
causing decreased LH and FSH production)
...
! Hyper or hypothyriodism
•
Non-‐obstructive (testicular failure) => Hypergonadotrophic hypogonadism:
! Genetic (Klienfelters syndrome 47XXY)
! Chemotherapy or radiotherapy (DNA damage)
! Diseases that affect the testicle, including mumps, orchitis, and testicular cancer
! Undescended testes
! Idiopathic
•
Obstruction to vas deferens (post-‐testicular failure):
! Congenital absence e
...
cystic fibrosis (CF)
! Infection e
...
epididymitis due to Chlamydia infection or orchitis due to mumps
infection (can also cause failure of sertoli cells to produce sperm)
! Vasectomy: minor operation, where the vas deferns (which carry sperm from a
man's testicles to the penis) are cut, blocked or sealed
...
g
...
g
...
It is associated with very low levels of
fertility or even sterility, but many forms are amenable to medical treatment
...
Azoospermia can be classified into four major types as listed below
...
•
Pretesticular azoospermia (hormonal):
! Pretesticular azospermia is characterized by inadequate stimulation of otherwise
normal testicles and genital tract
...
! Hypogonadotropic hypogonadism can occur due to hypothalamic or pituitary
dysfunction e
...
anorexia, illness, pituitary adenoma
...
Therefore lab results will
show low FSH, low LH and low testosterone
...
g
...
•
Testicular azoospermia (testicular failure) => hypergonadotrophic hypogonadism:
! In this situation the testes are abnormal, atrophic, or absent, and sperm
production severely disturbed to absent
...
! Specific causes for testicular failure include congenital issues such as in certain
genetic conditions (e
...
Klinefelter syndrome 47XXY), as well as acquired
conditions by infection (orchitis), surgery, cancer, or other causes
...
! Generally, men with unexplained hypergonadotropic (high FSH/LH) azoospermia
need to undergo a chromosomal evaluation => Klinefelters (47 XXY) is a common
cause of primary testicular failure
! Lab features: low testosterone, high LH, high FSH (hypergonadotropic
hypogonadism)
•
Post-‐testicular azoospermia:
! In post-‐testicular azoospermia sperm are produced but not ejaculated
...
The most common reason is a vasectomy done to induce
contraceptive sterility
...
! Ejaculatory disorders include retrograde ejaculation and anejaculation (inability
to ejaculate); in these conditions sperm are produced but not expelled (e
...
DM)
! Lab features = normal hormone screen
•
Idiopathic azoospermia
! Idiopathic azoospermia is where there is no known cause of the condition
...
! For example, a review in 2013 came to the result that oligospermia and
azoospermia are significantly associated with being overweight (odds ratio 1
...
3) and morbidly obese (odds ratio 2
...
Other factors include alchol, smoking and drugs
...
g
...
g
...
g
...
g
...
g
...
This is the most common type
of fertility testing
...
FSH/LH and testosterone levels are particularly
useful
...
g
...
g
...
Treatment of Male Infertility
Intra-‐uterine Insemination (IUI)
•
Indication: low sperm count (oligozoospermia)
•
Procedure: semen sample prepared to produce concentrated sperm sample
•
Inseminated into uterine cavity around time ovulation (i
...
approx 14 days before
menstration is the time of ovulation)
•
Pregnancy Rate: 15% per treatment cycle
Surgical Sperm Aspiration
•
•
Procedure: sperm aspirated surgically (can be done as diagnostic procedure or at time of
oocyte recovery e
...
in IVF)
...
g
...
The man can still
ejaculate seminal fluid (semen) but this fluid will not contain any sperm
...
•
In cases of non-‐obstructive azoospermia (complete absence of sperm in semen), very small
amounts of sperm may be produced and can be collected directly from the testes
(seminiferous tubules)
...
In
these cases a biopsy will normally be sent to the laboratory for analysis as to the possible
cause of the problem
...
g
...
The fertilised egg (embryo) is then
transferred to the woman’s uterus
...
•
Type of IVF (in-‐vitro fertilisation) e
...
an egg is fertilised by sperm outside the body
•
Indications: very low sperm count (severe oligozoospermia; if non severe oligozoospermia
then can use intra-‐uterine insemination) or azoospermia (if collected by surgical sperm
aspiration)
Procedure: Sperm collected (e
...
via surgical sperm aspiration) and injected into stripped
oocyte obtained during IVF
...
•
Antepartum haemorrhage (APH), also known prepartum hemorrhage, is bleeding from the
vagina during pregnancy from the 24th week gestational age to labour
...
This is because
many pregnancies are lost spontaneously before a woman recognizes that she is
pregnant, and the clinical signs of miscarriage are mistaken for a heavy or late
menses (menstruation)
Types of Spontaneous Miscarriage
Threatened miscarriage
•
This is when you have bleeding early in your pregnancy and your cervix (the opening to your
uterus) is tightly closed (os closed)
...
•
Bleeding not profuse (mild bleeding)
•
Pain –ve (usually little or no pain)
•
Cervical os is closed (as it should be)
•
Uterus size = correct for gestational age
•
FH (fetal heartbeat) +ve
Inevitable miscarriage
•
Bleeding early in your pregnancy and your cervix is open => pregnancy will INEVITABLY be
lost
...
The miscarriage may
happen quickly or take some time
...
When the
clinical examination reveals a dilated cervix (open cervical os), spontaneous miscarriage is
inevitable
...
The vaso-‐vagal effect of the
products of conception passing through the cervix causes a reflex bradycardia and vasovagal
syncope
...
The shock normally resolves spontaneously
...
•
Tenderness and pain +ve
•
Cervix open (cervical os open) – this distuinguishes from missed where cervical os is closed
•
Products of conception (POC) may be present in cervix (cervical canal)
•
FH –ve (this distuinguishes from inevitable miscarriage)
Complete miscarriage
•
This means that you have lost your pregnancy and your uterus is empty
•
History similar to incomplete abortion followed by cessation of bleeding
•
Uterus smaller than < gestation age => as no produts of conception in uterus
•
Cervix closed (cervical os closed)
•
FH –ve
Septic miscarriage
•
Infection following a miscarriage
•
Can cause septic shock (vasogenic shock due to peripheral vasodilation) e
...
presenting with
tachycardia, hypotension, cold clammy skin, increased CRT etc
Missed miscarriage (“silent miscarriage”)
•
Its called a missed miscarriage because you won't realise that anything has gone wrong
...
•
The uterus is small for dates as the foetus is not alive and therefore not growing (uterus <
gestation age)
...
•
Fetus dies in uteruo but is not expelled
•
It may present with a history of threatened miscarriage and persistent, dirty brown
discharge
...
•
FH –ve
•
Cervical os closed
Aetiology of Miscarriage
•
Most cases are idiopathic
•
Chromosomal (abnormal conceptus)
! Chromosomal (50%) e
...
trisomy 15,16,21,22,21
! Turners 45X (despite the excellent postnatal prognosis, 99% of Turner-‐syndrome
conceptions are thought to end in spontaneous abortion or stillbirth)
! Hydratiform mole (molar pregnancy): not strictly called “miscarriage”
•
Uterine abnormalities
! Uterine malformations
! Fibroids (leiomyoma growths)
! Incompetent cervix (dilated cervix): cervix dilates and effaces before pregnancy
has reached term: can treat with cervical cerclage (cervical stitch with sutures)
•
Acquired disease
! Infections
! Hypertension e
...
Pre-‐eclampsia
! Renal disease
! Diabetes mellitus
! Thyroid disorders
•
Toxins
! Alcohol
! Smoking
! Chemotherapy
! Anaesthetic gases
! Immunological e
...
antiphospholipid syndrome (lupus anticoagulant, anti
cardiolupin) – charachterised by recurrent miscarriages, antenatal
complications, recurrent arterial and venous thrombosis
•
Endocrine
! Deficient corpus luteum => deficient progesterone production
! High preovulatory LH (> 10 IU/l)
•
Trauma
! Amniocentesis: Amniocentesis is a test during which your doctor takes a small
sample of amniotic fluid from around the baby
...
This sample is then
examined in a laboratory to check for any abnormalities
...
! Chorionic villous sampling (higher risk than amniocentesis) – usually perfomed at
earlier stage in pregnancy (< 15 weeks)
...
g
...
If recurrent miscarriages =>
further Ix
...
! History of PID, endometriosis, or IUCD/Mirena
•
Hydatiform mole: large for dates, heavy bleed in early pregnancy, very high beta-‐HCG (can
cause beta-‐HCG thyrotoxicosis and hyperemesis gravidarium)
•
Neoplasia e
...
choriocarcinoma
Investigations
•
Transvaginal US: the majority of women will require a transvaginal ultrasound (TVS) and
98% of complete miscarriages can be diagnosed in this way
...
A uterus found to be empty on ultrasound examination (+ closed cervical os) may signal a
completed spontaneous abortion, but the diagnosis is not definitive until ectopic
pregnancy is excluded
...
Serum b-‐hCG is preferred due to higher sensitivity
...
•
hCG enters the maternal circulation almost immediately after implantation of the embryo
(blastocyst) on about day 21 of the menstrual cycle (approximately 7 days after fertilisation)
e
...
gestation = 3 weeks
...
hCG takes over from LH => hCG maintains the
corpus luteum => maintains progesterone production => maintains maternal endometrial
decidua (mucosal layer of endometrium during a pregnancy, which forms the maternal part
of the placenta
...
•
Progesterone enriches the uterus with a thick lining of blood vessels and capillaries
(secretory phase) so that it can sustain the growing fetus
...
•
Beta-‐hCG is produced by the trophoblast cells of the placenta (foetal part of placenta)
The concentration of hCG rises in an exponential manner, doubling approximately every
two days in the first few months of pregnancy
...
•
By day 28 (first day of missed menses in 28 day cycle => 4 weeks gestation) the median hCG
level in serum, plasma or urine is about 100 mIU/ml
...
•
In a normal pregnancy beta hCG doubles every two to three days through to its maximum
level at nine to 10 weeks gestation
...
•
Remember that serum, plasma and urine hCG results can vary widely
...
It can take up to three to four
weeks for the HCG to drop to non-‐pregnant levels after a pregnancy, depending on the
gestation reached
...
•
If the beta HCG is excessively high, suspect molar pregnancy (or multiple pregnancy)
•
However, remember that the dating (gestation) of the pregnancy could be wrong
...
However, it is not so reliable at detecting an ectopic pregnancy
...
In a normal pregnancy the foetal heart beat should be seen on transvaginal ultrasound by
six to seven weeks’ gestation (after only 4-‐5 weeks development!!!)
•
Sometimes the pregnancy is of ‘unknown location’, where the pregnancy test is positive but
there is no sign of the pregnancy on ultrasound scan
...
•
If ectopic pregnancy cannot be ruled out, consider referral to hospital for further
assessment, especially if the woman has pelvic pain
...
Since the placenta isn't putting out hCG, hCG levels will eventually drop
...
•
When hCG levels continue to rise or don't fall appropriately after miscarriage, it's
important that the reason is found
...
g
...
g
...
Anticoagulation appears to prevent miscarriage in pregnant women
...
Prednisolone can also be used (dampens down the
immune mechanism)
...
g
...
g
...
Synthetic oxytocin can be used to induce labour for medical reasons
...
In this case the syntocinon can be used to stimulate release of products
of conception in miscarriage (by causing uterus contraction)
•
Evacuation of uterus: It usually includes a combination of vacuum aspiration, dilation and
curettage, and the use of surgical instruments (such as forceps)
...
Complete miscarriage
•
Conservation management e
...
bed rest, reassurance and pain relief
•
Advice and reassurance
Septic miscarriage
•
Resuscitation if shock is present: ABCDE, fluids, vasopressor e
...
NA or dopamine
•
SEPSIS 6 in one hour
•
Antibiotics
•
Evacuation of uterus: It usually includes a combination of vacuum aspiration, dilation and
curettage, and the use of surgical instruments (such as forceps)
...
The antiphospholipid antibodies, lupus anticoagulant
(misnomer, cause anti coagulation and prolonged APTT in test tubes not in the
body!), and anticardiolipin antibodies may be associated with recurrent
miscarriage before ten weeks
...
Thrombophillic disorder which causes
formation of blood clot
...
Tx with
asprin, LMWH and potentally steroids
...
g
...
g
...
It was also found that
metformin therapy improves the chances of a successful pregnancy in patients with an
abnormal glucose tolerance test
...
•
Assessment for PCOS: US (large follicles), raised testosterone, decreased SHBG, hirsutism
(excessive hair growth in male pattern), amenorrhoea/oligomenorrhea, acne, obesity, raised
LH/FSH ratio
•
Hysteroscopy: where the uterus is examined through the vagina using a special endocscope
called a hysteroscope
•
Hysterosalpingogram (HSG): an X-‐ray test that looks at the inside of the uterus (hystero)
and fallopian tubes (salpinx) and the area around them
...
During a hysterosalpingogram, a dye
(contrast material) is put through a thin tube that is put through the vagina and into the
uterus
...
Pictures are taken using a steady beam of X-‐ray (fluoroscopy) as the
dye passes through the uterus and fallopian tubes
...
A blockage also could prevent
sperm from moving into a fallopian tube and joining (fertilizing) an egg
...
•
Laparoscopy: where the uterus is examined through a small cut in the abdomen, using a
laparoscope
...
•
IVP (intravenous pyelogram)
Treatment
•
TLC + emotional support
•
Treat any underlying course
Ectopic Pregnancy
•
•
Implantation of the conceptus outside the uterine cavity (uterus)
Most occur in the fallopian tubes (tubal ectopic pregnancies), however implantation can
also occur in the cervix, ovaries, and abdomen
...
g
...
Ectopic pregnancies can cause fatal intra-‐peritoneal bleeding
...
It is often used
synonymously with pelvic inflammatory disease (PID), although PID lacks an
accurate definition and can refer to several diseases of the female upper genital
tract, such as endometritis, oophoritis, myometritis, parametritis and infection in
the pelvic peritoneum
! Previous tubal surgery
! Previous tubal ligation
! Endometriosis – adhesions and blockages of fallopian tubes can presevtn the
conceptus moving to the uterus
! IUCD (Mireana IUS or copper IUCD)
Pathophysiology
•
•
Most commonly this invades vessels and will cause bleeding
...
This intratubal bleeding hematosalpinx expels the implantation out of the tubal end as a
tubal abortion
...
The pain is caused by
prostaglandins released at the implantation site, and by free blood in the peritoneal cavity,
which is a local irritant
...
Usually this degree of bleeding is due to delay in diagnosis, but sometimes,
especially if the implantation is in the proximal tube (just before it enters the uterus), it may
invade into the nearby Sampson artery, causing heavy bleeding earlier than usual
...
! Hypovolaemic shock and syncope due to blood loss
! Abdominal guarding and rigidity: may mimic appendicitis (esp if in right fallopian
tube => RIF pain)
! Cervical excitation: in gynecology, cervical motion tenderness or cervical
excitation (chandelier sign), is a sign found on pelvic examination suggestive of
pelvic pathology
...
It is also colloquially known as "chandelier sign”
...
"
! Adnexal tenderness: pain from the ovary and fallopian tube on bimanual exam
! Bulky uterus
Differential diagnosis
•
•
Miscarriage
Early normal pregnancy
•
PID: however the presence of a positive pregnancy test virtually rules out active PID
infection as it is rare indeed to find pregnancy with an active pelvic inflammatory disease
(PID)
...
•
GI disorders e
...
appendicitis
•
Urinary system problems
•
For abdominal pain: GI history, Obs and Gynae history, GU history, and if upper GI also a
cardioresp history
Outcomes
•
Tubal abortion: In a typical ectopic pregnancy, the embryo adheres to the lining of the
fallopian tube (tubal ecotopic pregnancy) and burrows into the tubal lining
...
This intratubal bleeding hematosalpinx expels
the implantation out of the tubal end as a tubal abortion
...
Sometimes the bleeding might be heavy enough to threaten the health or life
of the woman
...
These are the tubal abortions
...
Locations of ectopic pregnancy
Tubular:
•
Ampullary (common site): where fertilisation normally occurs
Non-‐tubular:
•
•
Periotneal
•
Ovarian
Cervical
Diagnosis of Ectopic Pregnancy
•
An ectopic pregnancy should be considered and ruled out as the cause of abdominal pain
or vaginal bleeding or amenorrhoea in every woman who has a positive pregnancy test
(positive beta HCG)
...
•
Ectopic pregnancy can be diagnosed if the ultrasound detects a fetal heart beat (can be seen
from 6-‐7 weeks gestation) or an embryo that is outside of the uterus
...
! Since ectopic pregnancy is a potentially life threatening gynaecological problem
serum beta-‐HCG is preferred (as more sensitive)
! NB: Although hCG is sensitive to ectopic pregnancies, it is clearly not selective!
Beta-‐hCG is raised in normal pregnancies or hydratiform mole or rare germ cell
tumours
...
Not all ectopic pregnancies are life-‐
threatening or lead to a risk to the mother
...
The pregnancy often dies in a way similar to a miscarriage
...
You would need to
have treatment if symptoms become worse
...
•
Laparoscopic salpingotomy: Surgeons use laparoscopy to gain access to the pelvis and can
incise the affected Fallopian and remove only the pregnancy
•
Laparoscopic salpingectomy: surgical removal of the affected fallopian tube with the
pregnancy
•
Methotrexate: Early treatment of an ectopic pregnancy with methotrexate is a viable
alternative to surgical treatment
...
•
Laparotomy if ectopic pregnancy is ruptured: A laparotomy is a surgical procedure involving
a large incision through the abdominal wall to gain access into the abdominal cavity
...
•
Cure rates are excellent for this condition
...
•
Gestational trophoblastic disease (GTD) forms a group of disorders which range from
hydatidform mole to malignant conditions such as choriocarcinoma
...
•
It is the result of abnormal conception (chromosomal)
•
Molar pregnancy is an abnormal form of pregnancy in which a non-‐viable fertilized egg
implants in the uterus results in abnormal development of trophoblast
•
Can be complete (absence of maternal chromosomes) or partial (maternal chromosomes
present)
•
Developmental anomaly of the trophoblast (foetal placenta) in which there is a local or
general vesicular change in the chorionic villi (villi that sprout from the chorion in order to
give a maximum area of contact with the maternal blood)
•
It may cause bleeding in early pregnancy and is usually suspected on an early pregnancy
ultrasound scan
...
However, close follow-‐up is needed after a hydatidiform mole because there is a small
chance of developing a type of cancer (choriocarcinoma)
...
•
Incidence: UK and Europe 1 in 1000 to 1 in 2000
•
A pregnancy that results in a hydatidiform mole is called a molar pregnancy
...
They are 'non-‐viable' pregnancies
...
These villi grow in clusters that resemble grapes (snow
storm)
•
They have a risk of possibility of malignant change to choriocarcinoma, which is a
malignant, trophoblastic cancer, usually of the placenta
...
It belongs to the malignant end of the
spectrum in gestational trophoblastic disease (GTD)
...
Pathophysiology
•
In complete molar pregnancies, all the genetic material comes from the father
...
This is an ovum not carrying any chromosomes
or genetic material
...
But rarely, the ovum doesn't die and implantation takes place
...
Therefore there is no maternal DNA present => no fetal tissue develops
...
This is a complete hydatidiform mole
...
•
In partial molar pregnancies, the trophoblast cells usually have three sets of chromosomes
(triploid)
...
This means
that there is too much genetic material present => also results in the development of too
much trophoblastic tissue
...
There is usually evidence of fetal
tissue or fetal blood cells in a partial molar pregnancy
...
•
Both complete and partial molar pregnancies (hydratiform moles) are 'non-‐viable'
pregnancies
...
•
NB: Trophoblasts are cells forming the outer layer of a blastocyst
...
They are formed during the first stage of pregnancy and
are the first cells to differentiate from the fertilized egg
...
This is the most common
symptom
...
MAY BE HEAVY
...
This is
because a molar pregnancy grows more quickly than a normal pregnancy would, due to the
abnormally developing trophoblastic tissue (placental tissue)
•
‘Doughy’ uterus
•
FH -‐ve
•
Hyperemesis: Hyperemesis gravidarum (HG) is a complication of pregnancy characterized by
intractable nausea, vomiting, and dehydration (due to abnormally high hCG)
•
Pre-‐eclampsia: medical condition characterized by high blood pressure and significant
amounts of protein in the urine of a pregnant woman
...
! Levels of hCG may be of value in diagnosing molar pregnancies but are far more
important in disease follow-‐up
...
•
Definitive diagnosis is made by histological examination of the products of conception
...
Complicated pathology
•
CXR or CT lung: to assess for lung mets
Treatment
•
Evacuation of uterus: hydatidiform moles should be treated by evacuating the uterus by
uterine suction or by surgical curettage as soon as possible after diagnosis, in order to avoid
the risks of choriocarcinoma
•
Prolonged follow-‐up with urinary and serum b-‐hCG: Patients are followed up until their
serum human chorionic gonadotrophin (hCG) level has fallen to an undetectable level
...
g
...
It has the ability to spread locally,
as well as metastasise (early metastatic spread to lungs is common)
Note: molar pregnancy = partial molar pregnancies, where the trophoblast cells usually
have three sets of chromosomes (triploid)
...
It is
characterized by early hematogenous spread to the lungs
...
•
It is also classified as a germ cell tumor and may arise in the testis or ovary
...
•
Clinical features in females:
! increased quantitative β-‐hCG levels (very high levels)
! Vaginal bleeding
! Shortness of breath
! Haemoptysis (coughing up blood)
! Pleurtitic chest pain
! Chest X-‐ray shows multiple infiltrates of various shapes in both lungs
Cervical Incompetence
•
•
When you're not pregnant, the cervical canal remains open a tiny bit to allow sperm to enter
the uterus and menstrual blood to flow out
...
During a normal pregnancy, the cervix remains firm, long, and tightly
closed until late in the third trimester
...
the neck of the uterus
...
•
If you have cervical insufficiency, it means that your cervix is effacing (shortening and
thinning) and dilating prematurely (before your baby is full term and ready to be born)
...
There are usually no contractions or other symptoms
...
•
Internal os opening more than 1 cm is abnormal and cervical length less than 2 cm is
considered diagnostic
...
•
Incidence 1-‐2%
•
Key clinical features: cervical dilation in the absence of any abdominal pain
•
Aetiology
! Cervical dilatation during TOP (termination of pregnancy)
! Cone biopsy of cervix
! Cervical amputation during Manchester repair
! Exposure to DES: Diethylstilbestrol (DES) is a synthetic nonsteroidal estrogen
! Idiopathic in 25% of cases
Management
•
•
Cervical incompetence can be treated using cervical cerclage, a surgical technique that
reinforces the cervical muscle by placing sutures (stitches) above the opening of the cervix
to narrow the cervical canal
...
•
Cervical incompetence is not generally treated except when it appears to threaten a
pregnancy
...
Transabdominal cerclage of the cervix makes it possible to place the stitch exactly at the
level that is needed
...
•
Cerclages are usually performed between weeks 14 and 16 of the pregnancy
...
Cervical cerclage
•
Shirodkar’s suture or McDonald suture
•
Performed usually at 14 weeks of gestation (to prevent inevitable miscarriage)
•
Risk of ROM (ruptures of membranes, also known as amniorrhexis) and infection
•
Removed at 36 weeks of gestation or in early labour, whichever is earlier
EARLY EMBRYOLOGY
Learning objectives
•
Only know the essentials as this is a very complex area of medicine
•
Know what is meant by gastrulation: early phase in the embryonic development during
which the single-‐layered blastula is reorganized into a trilaminar ("three-‐layered")
structure known as the gastrula
...
•
Name the germ layers (ectoderm, mesoderm and endoderm) and what they give rise to
! Ectoderm (derived from epiblast): epidermis and CNS (neural tube) + neural crest
! Endoderm (derived from hypoblast): GI tract lining and respiratory tract lining
! Mesoderm (derived from between epiblast and hypoblast): CV, GU, MSK,
connective tissue (mesenchyme) e
...
blood, bones, tendons, dermis etc
•
•
Know that the thoracic and peritoneal cavities are formed by the division of a single body
cavity
•
Know that the respiratory tract develops from the gut tube as an outpouching (endoderm
forms the lining) and how this impacts on the congenital defects involving the trachea and
oesophagus e
...
tracheooeshageal fistula
Know that there are a number of different components that contribute to the formation of
the diaphragm
•
Know that embryonic folding plays a key role in bringing the septum transversum into the
correct location to contribute to the diaphragm => explains why diaphragm is innervated by
C3,4,5 (3,4 and 5 keeps the diaphragm alive)
First steps in development: Embryogenesis
•
•
The blastocyst is formed on approximately day 5
...
•
Implantation: the blastocyst hatches out of zona pellucida
...
Implantation occur day 6-‐9
...
These three germ layers are known as the ectoderm,
mesoderm, and endoderm
...
•
Cleavage: the zygote undergoes mitotic divisions with no significant growth in size (a process
known as cleavage)
...
The first cleavage occurs on approximately day 1 => resulting in 2 cells
...
At the end of the fallopian tube (usually day 4) the cluster of cells is
called the morula and is still surrounded by zona pellucida (glycoprotein membrane
surrounding the plasma membrane of an oocyte)
...
Fertilisation of the egg cell (oocyte) with sperm cell (spermatozoon) occurs
within fallopian tubes (commonly ampullary region)
...
This also occurs in the third week of
development
...
•
At least four initial cell divisions occur, resulting in a dense ball of at least sixteen cells called
the morula
...
•
The morula then develops into the blastocyst (approximately day 5) as it enters the uterus
•
Implanation of the blastocyst then occurs (approximately day 7-‐10)
•
Produces a cluster of cells that is the same size as the original zygote
...
After implantation the blastula develops into the gastrula in which the germ layers of the
embryo form
...
g
...
•
It possesses an inner cell mass (embryoblast) which subsequently forms the embryo
...
This layer surrounds the
inner cell mass (embryoblast) and a fluid-‐filled cavity known as the blastocoels (cavity made
up of fluid which is essential for the embryo's needed nutrients)
...
It is this part of the blastocysts that
can give rise to GTD
...
•
The blastocyst is a structure formed in the early development of mammals
...
The blastocyst embeds itself into the endometrium (implantation occurs on day 7-‐
10) of the uterine wall where it will undergo later developmental processes, including
gastrulation
...
It can be more a viable method of fertility
treatment than traditional IVF
...
•
At this stage of prenatal development, the embryo is a blastocyst
...
•
Process in which the conceptus actively burrows into the uterine lining (decidua of
endometrium – the outer layer of the uterus)
In humans, implantation of a fertilized ovum is most likely to occur about 7-‐10 days after
ovulation
•
The reception-‐ready phase of the endometrium of the uterus is usually termed the
"implantation window"
...
On average, it occurs during the 20th to the 23rd day after the last
menstrual period (e
...
in third gestational week)
•
The implantation window is characterized by changes to the endometrium cells, which aid in
the absorption of the uterine fluid
...
Progesterone released from the corpus luteum is essential
...
•
Progesterone causes increased blood flow and uterine secretions and reduces the
contractility of the smooth muscle in the uterus to thicken and increase blood flow to
support a developing embryo => deciduas forms (females side if the placenta)
...
So oestrogen causes the endometrium to
proliferate (proliferative phase), but progesterone makes it habitable (secretory phase) and
reduces myometrium activity
...
! The syncytiotrophoblast also produces human chorionic gonadotropin (hCG), a
hormone that maintains the corpus luteum (as very similar in structure to LH its
sister molecule) and therefore stimulates the release of progesterone from the
corpus luteum
...
! The villi begin to branch from the chorion (trophoblast membrane layer) and
contain blood vessels of the embryo
...
! Projections (villi) from trophoblast layer (foetal placenta capillaries) break down
connections of cells in uterine lining (endometrium)
! Blastocyst becomes completely embedded in wall
! Fibrin plug covers area of uterine lining damage (coagulation plug)
•
The placenta also begins to develop upon implantation of the blastocyst into the maternal
endometrium
...
This outer layer is divided into two further layers: the underlying
cytotrophoblast layer and the overlying syncytiotrophoblast layer
...
The inner cell mass is the source of embryonic stem cells,
which are pluripotent and can develop into any one of the three germ layer cells
...
•
Membranes are also beginning to form that will support the embryo:
! Chroion: placenta membrane
! Amnion cells derived from epiblast cells start to form the amniotic cavity which
surrounds the foetus and holds amniotic fluid (amniotic fluid or liquor amnii is the
protective liquid contained by the amniotic sac of a pregnant female)
! Primitive yolk sac: surrounded by Heuser’s membrane
Third developmental week (week five of gestation)
•
Three important structures form during the 3rd developmental week: the primitive streak,
the notochord and the neural tube
...
! The primitive streak is a structure that forms in the blastula (implanted
blastocyst) during the early stages of development
...
! The notochord: The notochord forms during gastrulation and soon after induces
the formation of the neural plate (neurulation), synchronizing the development
of the neural tube
! The neural tube: forms the CNS
...
Gastrulation
•
Critically important: gives 3 germ layers that form all different tissues
•
The embryoblast forms an embryonic disc which is a bilaminar disc (bilaminar blastocyst) of
two layers, an upper layer the epiblast (primitive ectoderm), and a lower layer the
hypoblast (primitive endoderm)
...
•
During the third week a process called gastrulation creates a mesodermal layer between
the endoderm and the ectoderm
...
•
The primitive streak, a linear band of cells formed by the migrating epiblast, appears, and
this marks the beginning of gastrulation, which takes place around the sixteenth day
(week 3) after fertilisation
...
•
A primitive node (or primitive knot) forms in front of the primitive streak which is the
organiser of neurulation (folding process in vertebrate embryos, which includes the
transformation of the neural plate into the neural tube)
•
The bilaminar blastocyst (epiblast and hypoblast) then transforms into a trilaminar structure
(three overlapping flat discs)
! The epiblast transforms into the ectoderm
! The hypoblast transforms into the endoderm
! The mesoderm occurs between the outer ectoderm and inner endoderm
•
The three germ layers are the ectoderm, mesoderm and endoderm, and are formed as three
overlapping flat discs
...
g
...
g
...
g
...
g
...
•
The notochord burrows from primitive node (which forms in front of the primitive streak)
between ectoderm and endoderm
•
The notochord determines the longitudinal axis of the embryo
...
•
Important in regulating development of structures => tells tissues what to become
...
Because of position it is ideally placed for sending signals superior/inferior/lateral to the 3
layers
...
g
...
The amnion is a membranous sac which
surrounds and protects the embryo
...
•
Folding is important for arrangement of membranes surrounding embryo
As the volume of the fluid increases, the amnion expands and ultimately adheres to the
inner surface of the chorion (placental membrane)
•
The chorion (formed from the two layers of the trophoblast) begins to form the foetal part
of the placenta
•
Increasing liquor amnii (amniotic fluid) quantities allow free movements of the fetus during
the later stages of pregnancy, and also protect it
...
Will gradually fill the chorionic cavity
...
•
Differentiate into 3 types:
! Dermatome: dermis
! Myotome: skeletal muscle
! Scleratome: cartilage, tendons, and endothelial cells, bones (contributes to axial
skeleton)
Neural Tube Defects
•
A NTD (neural tube defect) is an opening in the spinal cord or brain that occurs very early in
human development
...
•
Neural tube defects arise because of failure of closure or failure of bony elements that
protect the neural tube
•
Spina bifida: NTD congenital disorder caused by the incomplete closing of the embryonic
neural tube
...
If the opening is large enough, this allows a portion of the spinal cord to
protrude through the opening in the bones
...
Range of
severity
...
This is the mildest form of spina
bifida
...
The splits in the vertebrae are so small that the spinal cord does not
protrude
...
AFP normal
...
In this form, the vertebrae develop normally, but the
meninges are forced into the gaps between the vertebrae
...
In individuals with meningomyocele, the unfused portion of the
spinal column allows the spinal cord (myo) to protrude through an opening
...
•
•
Rachischisis: Vertebrae overlying the open portion of the spinal cord do not fully form and
remain unfused and open, leaving the spinal cord and neural tissue exposed
...
This defect often occurs with anencephaly
...
It is a cephalic disorder that results from a
neural tube defect that occurs when the rostral (head) end of the neural tube fails to close,
usually between the 23rd and 26th day of conception
...
This exposure causes the nervous system tissue to break down
(degenerate) due to the toxic effects of amniotic fluid
...
Almost all babies
with anencephaly die before birth or within a few hours or days after birth
...
However, most of these pregnancies end in miscarriage, so the prevalence of
this condition in newborns is much lower
...
The septum secundum grows
downward from the upper wall of the atrium immediately to the right of the primary septum
and ostium secundum
...
It is an
arterial trunk (the one and only outflow tract) that originates from both ventricles of the
heart that later divides into the aorta (attached to left ventricle) and the pulmonary trunk
(attached to right ventricle)
•
Two parts:
! Muscular part: muscular ridge grows upwards, with expansion of ventricles on
either side of ridge
...
This results in separation of the right ventricle/pulmonary trunk from left
ventricle/aorta
•
Truncal ridges grow downwards in spiral fashion
Cardiac development anomalies
•
•
Transposition of the great vessels: can occur due to absent spiral movement of the ridges
(right to left shunt => cyanotic)
•
Tetraology of Fallot (right to left shunt => cyanotic)
•
Patent foramen ovale (left to right shunt => acyanotic)
•
Persistent truncus arteriosus: can occur due to absent truncal ridges (right to left shunt =>
cyanotic)
Patent ductus arteriousus (left to right shunt = acyantoic)
Congenital cyanotic heart disease
•
Truncus arteriosus: single vessel connected to both right and left ventricles => mixing of
deoxygenstaed blood into systemic circulation => right to left shunt => cyanotic heart
disease
...
•
Transposition of the great vessels: aorta is connected to RV and pulmonary trunk is
connected to LV=> pumping of deoxygenated blood in the systemic circulation (Right to left
shunt)
...
Branches into left and
right lungs
...
g
...
g
...
Folding of the septum transversum carries
nerves (C3,4,5) the phrenic nerve with it as it moves downwards
Formation of Diaphragm
•
•
Vast majority innervated by cervical nerves, but edges may have local innervation
•
Multiple parts need to fuse to form diaphragm => many potential defects
•
Comes to rest in between future throracic and abdomen cavities
Large portion formed from septum transversum
Congenital diaphragmatic hernia
•
A diaphragmatic hernia may result from failure of fusion of its constituent parts (4 parts
form the diaphragm)
•
Most commonly on left side
•
Usual cause is a defect in the formation of the pluroparietal membrane
•
Abdomen contents will herniate through into thoracic cavity
•
Abdomnal contents can compress on lungs => severe impact on lung development =>
pulmonary hypoplasia => small hypoplastic lung => decreased gas exchange
•
Often on left side => left hypoplastic lung and shifting of apex beat to the right
INFERTILITY AND ASSISTED CONCEPTION
•
Assisted conception treatment (ACT) is any treatment in which involves gametes outside
the body
•
One in six couples require assessment of infertility in UK
•
Approximately half of these will require ACT
•
2% of live births in UK are the result of ACT
•
Demand for ACT is rising:
! increasing parental age
! increasing Chlamydia: can affect both male (orchitis or obstruction) and female
(obstruction to tubes due to PID)
! Male factor infertility
! Increasing range of ACT treatments and improved success rates
! Obesity and DM – common cause of subfertility
Infertility
•
Primary infertility refers to couples who have not become pregnant after at least 1 year of
unprotected sex (intercourse)
...
•
Causes:
! Tubal disease e
...
PID (common cause)
! Male factors e
...
poor sperm counts (common cause) – oligozoospermia or
azospermia; or problems with erection or ejaculations
! Endometriosis: can reduce number & quality of eggs, and effect implantation
! Endocrine causes
! Not having enough sex and/or having sex at correct times of cycle
! Lifestyle factors e
...
alcohol, smoking, lack of exercise
! Large number unexplained (idiopathic)
!
Often multiple factors: M and F factors
Other Indications for Assisted Conception Treatment
•
Fertility preservation in cancer patients, before treatments that may affect gametes
•
Treatment to avoid transmission of blood born viruses between patients (e
...
HIV, Hepatitis
B & C)
•
Prenatal diagnosis of inherited disorders (pre-‐implantation genetic diagnosis, e
...
muscular
dystrophy)
•
Treatment of single parents (not allowed on NHS) or same sex couples
•
Others: cryopreservation of gametes for social reasons e
...
to preserve eggs when young to
have babies when older without increased risk of Down’s Syndrome etc
...
Also reduces risk of
complications, e
...
miscarriage, pre-‐eclampisa, gestational diabetes
...
4mg/day preconception until 12 weeks gestation (Some women have an
increased risk of having a pregnancy affected by a neural tube defect, and are advised to
take a higher dose of 5mg/day of folic acid each day until they are 12 weeks pregnant
...
Causes severe congenital
abnormalities
•
Cervical smears: check up to date according to national screening programme
...
g
...
Stably off all drugs (including methadone) for at least a year to get IVF
•
Screen for blood born viruses: hepatitis B/C and HIV and syphilis (minimise transmission
between male, female and foetus)
OVULATION INDUCTION SHOULD BE TRIED BEFORE IVF e
...
clomiphene citrate and GnRH
analogues
What treatments are available?
•
Intra-‐Uterine Insemination (IUI): for mild male factor infertility (e
...
oligozoospermia)
•
IVF
! In Vitro Fertilisation (IVF) – eggs bathed in sperm
! Intra-‐Cytoplasmic Sperm Injection (ICSI-‐IVF): for severe male factor infertility
(azoopsermia or severe oligozoospermia)
•
Others: treatment with donor sperm or eggs, surrogacy (e
...
in Hx of hysterectomy,
congential abnormality), cryopreservation of sperm or eggs
Intra Uterine Insemination (IUI)
•
Indications:
! Unexplained infertility
! Mild or moderate endometriosis
! Mild male factor infertility e
...
mild oligozoospermia (sperm can be collected and
concentrated)
•
Method:
! Can be in natural (lower success rate) or stimulated cycle
! Prepared semen (concentrated) inserted via syringe into uterine cavity around
time of ovulation
•
~ 12% success rate per treatment cycle
In Vitro Fertilisation (IVF)
•
Indications:
! Unexplained (> 3 years durations)
! Pelvic disease (endometriosis, tubal disease, PID, fibroids)
! Male factor infertility (severe oligozoospermia or azoospermia => surgical sperm
aspiration with ICSI IVF)
! Anovulatory infertility e
...
PCOS: 1st line is normally clomifiene citrate +/-‐
metformin, then gonadotrophins (LH/FSH analogues), then IVF
! Others (pre-‐implantation genetic diagnosis)
•
In vitro fertilisation (IVF) is a process by which an egg is fertilised by sperm outside the
body e
...
in vitro
...
g
...
The fertilised egg (zygote) is
cultured for 2–6 days in a growth medium and is then transferred to the mother's uterus
with the intention of establishing a successful pregnancy
...
IVF method
IVF Step 1: Downregulation
•
This step is used in order to "switch off" the womans own reproductive hormone
production (LH and FSH)
•
A woman’s reproductive (menstrual) cycle is controlled by the pituitary gland (LH and FSH)
...
•
This is because these drugs stimulate the production of a “follicle
...
In IVF we want to stimulate as many
follicles to grow as possible
...
•
The drugs used to switch off your reproductive cycle are called gonadotrophin-‐releasing
hormone analogues, or GnRH analogues for short
...
You will need to take these drugs every day
...
•
High doses of GnRH analogues cause reversible down regulation of the pituitary =>
suppression of LH and FSH
•
Having your reproductive cycle turned off tricks your body into thinking it is going through
the menopause
...
Key points
•
Synthetic gonadotrophin releasing hormone analogue (Buserelin) is administered as a
spray or injection and must be taken every day
•
Causes reversible “downregulation” of pituitary due to overstimualtion => suppression of
LH and FSH production => so that we can take control of the cycle!
•
Begin buserelin Tx on Day 21 of cycle (20 days after first day of last bleed)
•
Take daily for 3-‐4 weeks
•
Patient comes back for baseline US scan before beginning step 2
IVF Step 2: Stimulation of Follicle Production: Ovarian hyperstimulation
•
Once LH and FSH is suppressed (pituitary downregulation) the patient will receive drugs to
encourage follicle production (ovarian hyperstimualtion)
•
The patient will need to carry on taking downregulation drugs (eg
...
Follicles can be found on the outer wall of the ovaries
...
A natural hormone called follicle-‐stimulating hormone
(FSH) tells the ovaries when to produce follicles
...
Eventually, there is usually only one dominant follicle that grows to the right size
and bursts (due to LH surge)
...
•
Drugs that are given to encourage follicle production work in a similar way to FSH
...
As follicles contain eggs, this means that there will hopefully
be many more eggs available for collection
...
•
Drugs that are used to encourage follicle production include:
! Gonal-‐F (synthetic FSH) – stimulates the gonads
! Menopur (human menopausal gonadotropin or hMG)
•
They are all given by daily injections which can be self administered (remember Tx with
buserelin must be continued daily)
•
Side effects:
! Mild allergic reactions
! Ovarian Hyperstimulation Syndrome (OHSS)
•
Tx is continued for approximately 8-‐9 days (approx one week)
•
An “action US scan” is then performed before stage 3
Action US scan
•
The scan will enable the ultrasonographer to check that the drugs for downregulation have
worked (e
...
no activity in ovaries e
...
no rupture of follicles)
•
They will also be able to count and measure the follicles growing in your ovaries (to check
that ovary hyperstimulation has worked)
...
8% of cycles are
abandoned due to not enough follicles)
IVF Step 3: Egg maturation and release of egg
•
When the scan shows that your follicles have grown to the right size (and there are a
suitable number of follicles present), you will be given a drug to mature the eggs within the
follicles
...
Remember hCG is a
sister molecule of LH
...
We want to be in control of the LH surge
...
! Needs to be given 36 hours before the egg collection procedure which means
that it may need to be taken late at night
...
Step 4: Preparing the uterus to receive the embryos
•
The uterus needs to be prepared before it can receive the fertilised eggs (embryos)
...
•
The secretory phase is the final phase of the uterine cycle and it corresponds to the luteal
phase of the ovarian cycle
...
Remember that in the normal menstrual cycle, it is the fall of
progesterone, which results in shedding of the endometrium
...
IVF Step 5: Sperm collection
•
Abstinence for 72 hours before hand
•
Collect in pot (in “mens room”) if male is fertile or can use sperm aspiration if male has
fertility issues (azoospermia or oligozoospermia)
•
Assessment:
! Volume
! Density (numbers of sperm)
! Motility: what proportion are moving
! Progression: how well they move
IVF Step 6: Egg collection
•
This procedure is also called “oocyte capture” and “ovum retrieval
...
After
the eggs have been collected, they will be mixed with your partners sperm and allowed to
fertilise
...
A fine needle will then be used to collect the eggs from the follicles
...
•
Embryologist observes under microscope
...
0C (body temp)
•
Normal fertilisation:
! Two pronuclei
! Male and female genetic information
! Approx 60% of eggs fertilise normally
•
Embryo transfer:
! Day 0: Egg collection
! Day 1: Pronuclear stage
! Day 2: Average 4 cell stage
! Day 3: Average 8 cell stage
! Cryopreserve good quality embryos
! Day 2 or 3 embryos are usually used
Can do standard IVF (bathe eggs in sperm) or ICSI IVF (inject sperm into eggs)
...
”
•
Embryos are usually transferred to the uterus approximately three days after fertilisation
has begun
•
Number of embryos to be transferred
! Patients under the age of 40: no more than 2 embryos to be transferred
! Patients aged 40 and over: 3 may be transferred in exceptional circumstances
only
...
! Guidelines to reduce to one embryo in selected patients to minimise the risk of
twins
! Complications of twins: risk of lots of things e
...
cerebral palsy, twin transfusion
syndrome
! Complications of triplets: may selectively terminate
...
•
LH maintains the corpus luteum however during the luteal phase, increasing levels of
progesterone cause LH levels to decrease => the corpus luteum will degenerate unless
fertilisation occurs
...
•
In assisted reproduction techniques (ART) the progesterone or hCG levels, or both, are low
and the natural process is insufficient
...
•
Progesterone analogues should be given before implantation and continued thereafter
•
Drug = cyclogest pessaries (progesterone)
IVF step 10: pregnancy test
•
Pregnancy test 2 weeks after embryo transfer (hCG test)
•
If positive pregnancy test => transvaginal scan 5 weeks after embryo transfer
•
Artificial progesterone for 1st few weeks
Summary of IVF
Intra Cytoplasmic Sperm Injection (ICSI) with IVF – ICSI IVF
•
Indications:
! Severe male factor infertility e
...
azoospermia or severe oligozoospermia
! Previous failed fertilisation with IVF
! NB: In IVF without male factor infertility => the eggs are bathed in washed
sperm => standard IVF
•
Method:
! Form of IVF
! Each egg is stripped
! Sperm is surgically aspirated and then injected into egg
! Surgical Sperm aspiration is indicated for azoospermia (or severe
oligozoospermia)
! Sperm immobilised
! Single sperm injected into egg
! Incubate at 37
...
•
Most cases are mild, but a small proportion are severe
...
g
...
g
...
The risk is further increased by multiple
doses of hCG after ovulation and if the procedure results in pregnancy
...
g
...
! As hCG causes the ovary to undergo extensive luteinization, large amounts of
estrogens, progesterone, and local cytokines are released => inflammation
...
! Overstimulation => leaky capillary membranes => proteins leak out => fluid goes
into abdominal cavity => ascites and increased risk of thromboembolic disease
! Distension and IV depletion affects renal function => increased urea and Cr,
decreased eGFR etc
...
g
...
g
...
Twins and triplets have a long list of complications
...
!
COCP is the most common – multiple other uses including dysmenorrhea, menorrhagia,
and hirsuitism
!
Rates of each vary significantly with age
...
•
Pearl Index (PI) = number of unintended pregnancies which occur if 100 women use the
method for 1 year
...
•
High PI => less effective
PI for no contraception
•
Natural fertility declines with increasing age
...
02
Female Sterilisation
0
...
16
LNG-‐IUS (Mirena)
<0
...
2
IUD
1
...
9
Male condom
3
...
6
Withdrawel (“pull out”)
6
...
9
Natural
15
...
Calendar
•
•
Ovulation occurs on 12-‐16 day (average) of menstrual cycle – usualy 14 days before
menstruation (Luteal phase is usually 14 days)
Allows for survival time of ovum and sperm => intercourse must be avoided between day
10 and 20 of the menstrual cycle (for 28 day cycle)
•
Not very effective
2
...
The vulva will begin to feel slippery (fertile phase)
...
Ovulation occurs no more than
48 hours after the peak
...
Temperature
•
•
Relies on the fact that progesterone released from the corpus luteum raises the basal body
temperature by 0
...
4 C after ovulation (luteal phase) and maintains it until the onset of
next menstruation
Biphasic pattern
...
4
...
5
...
e
...
g
...
!
NB: Female condoms (different from diaphragm) can protect against STDs
...
!
Provides alternative to hormone treatments => often preferred by woman who do not have
sex too frequently
!
Problems:
! Loss of spontaneity (as have to insert)
! Poor vaginal tone
! Patient motivation => needs changed often (max time of 30 hours)
! Psychological aversion
Sterilisation
!
‘Permanent’ (some forms may be reversed) method of contraception for couples who are
certain their family is complete
!
Uptake rates have declined since advent of LARC (long-‐acting reversible contraception)
which provide surgical-‐free alternatives e
...
implanon/explanon (upper limb progesterone
implant which lasts for 3 years), IUS (Mirena: the levonorgestrel/progesterone coil which last
for 5 years), IUCD (copper coil which lasts for 5-‐10 years), Depo-‐provera (progesterone
injection which lasts for 3 months)
!
Male and female methods available
Female Sterilisation
There are two main types of female sterilisation:
!
Laproscopic: tubal occlusion e
...
fallopian tubes are blocked, for example with clips or rings
=> effective immedialtey but more invasive
...
The
presence of the micro-‐inserts causes scar tissue to form in the Fallopian tubes
...
!
Hysteroscopic sterilisation is as effective as laparoscopic sterilisation however the woman
should use an additional form of contraception until the implants have been shown to be
in the correct place
...
Effectiveness depends upon technique used, experience of surgeon and length of follow-‐up
Female sterilisation: Pros and Cons
Pros
!
Effective immediately (although hysteroscopic methods need to be confirmed successful at
3/12 with HSG before withdrawal of other forms of contraception)
!
Women often more motivated than men
!
Non hormonal
!
Permanent
Cons
!
!
Requires specialist skills and facilities
!
Cannot always be reversed nor is it always available on the NHS
!
Risk of operative mortality and morbidity
Higher failure rates than other methods e
...
Mirena (levonorgestrel-‐releasing intrauterine
system e
...
basically a progesterone coil), progesterone implant (nexplanon/implanon) and
vasectomy (male sterilisation)
Counselling for sterilisation
!
Simple description techniques (diagram & leaflet)
!
Risk of laparoscopy
!
Failure rate (1:200 to 2-‐3 in 1000)
!
Ectopic pregnancy risk
!
Prospects of reversal
!
Alternatives: Vasectomy, Mirena (levonorgestrel-‐releasing intrauterine system, 5 years) and
Nexplanon/Implanon (progesterone upper arm implant, 3 years)
!
Implications of relationship breakdown etc
!
Dispelling myths
Female sterilisation: Complications
Short term (operative)
!
Bleeding
!
Infection
!
Pain due to tubal ischaemia
!
Damage to other organs e
...
Bowel injury
Long-‐term
!
Failure/unwanted pregnancy
!
Ectopic pregnancy
!
Psychosexual
!
Risk of regret (approx 7-‐10%)
!
Infertility/request for reversal
Male Sterilisation
!
Diathermy (sealing with heat) or division of the vas deferens (usually under LA)
!
Vas deferens are cut, blocked or sealed
!
Low failure rate (1 in 2000)
!
Requires use of reliable contraception until azoospermia confirmed => two negative
semen samples at 12 and 16 weeks (3 and 4 months)
!
Risks of procedure:
! Haematoma
! Infection
! Chronic testicular pain (~20%)
!
Reversal has low-‐moderate chance of success and not available on NHS
Male vs Female
!
Overall male is more effective and less invasive and has less complications
...
g
...
g
...
g cerazette): not as effective as “the COC pill”
!
Injection (Depo-‐provera): lasts 3 months – can be used with enzyme inducers (e
...
rifampicin, carbamazepine and phenytoin)
...
!
Implant (Nexplanon/Implanon): lasts 3 years – cant be used with enzyme inducers
!
Intrauterine coil system (Mirena): levonorgestrel-‐releasing intrauterine system (basically a
progesterone coil) – lasts 5 years, can be used with enzyme inducers
MIRENA AND DEPROPROVERA CAN BE USED WITH ENZYME INDUCING DRUGS
Mode of action
Oestrogen
!
Inhibit ovulation by suppressing secretion of LH/FSH from pituitary (due to
prolonged negative feedback)
!
Leads to failure of follicular maturation => annovulation (menstrual cycle during
which the ovaries do not release an oocyte; may or may not be associated with
amenorrhoea)
Progestogen
!
Progestogen thickens the mucus (secretory phase) in the cervix, which stops sperm
penetration of cervix => stops sperm reaching egg
...
!
In can also stop ovulation, depending on the type of progestogen (dose/preparation)
=> due to –ve feedback to the hypothalamus and pituitary => decrease LH and FSH
!
Poor secretory activity of the endometrium which resists implantation
! Why does the progesterone only pill inhibit implantation? Progesterone is
essential for implantation! In the absence of oestrogen, progesterone
does not prepare the endometrial wall
...
!
Cervical mucus is more resistant to sperm penetration
!
Interferes with Fallopian Tube transport
Combined Hormonal Contraception (CHC)
Delivery
!
Pills (COC): “the pill” or microgynon
!
Patch (Evra)
!
Vaginal ring (Nuvaring)
SHOULD NOT BE USED WITH ENZYME INDUCING DRUGS => THESE DRUGS DECREASE EFFICACY OF
CONTRACEPTION
Contents
!
Two eostrogens (ethinyl oestradiol E2 and mestranol): many of which have an increased risk
of VTE disease (and ER +ve breast cancer risk, and of cervical cancer)
!
Many progestogens: three of which have a slight increased risk of venousthromboembolic
VTE disease and PgR +ve breast cancer risk
How to take COC
!
Each pill strip contains 21 active tablets taken consecutively
!
Followed by 7 day pill-‐free interval (or 7 placebo pills) => induces withdrawel bleed
!
Always restart next strip on same day
!
Missed pill rules (see clinical skills)
Formulations of COC
1
...
Fixed dose of oestrogen and progestogen: 21 tablets + 7 placebo tablets
3
...
CHC: Advantages
!
Effective (>99%) and convenient method (more effective than POP)
!
Not related to SI (sexual intercourse)
!
Fully reversible (reversibility is fast)
!
Non-‐contraceptive benefits
! Reduces menstrual pain/blood loss/PMS => usefull for dysmenorrhoea, and
menorrhagia (although Mirena is first line for menorrhagia due to DUB)
! Improves acne (some dual licensed) – can be used for acne and for hirsutism in PCOS
! ↓ risk ovarian/endometrial cancer (due to suppression of the menstrual cycle
which is a risk factor)
! ↓ risk colorectal cancer
! ↓ functional ovarian cysts and benign breast disease
! Can be used for hirustism
CHC: disadvantages/risks
!
Side effects:
! headache
! weight gain
! mood changes
! reduced libido
! often settle after 3/12 of use
!
RIsks
! VTE
! Increased cancer risk: breast, cervical
! Liver: metabolic effects
! Arterial disease: HT, MI, stroke – higher risk in migraines with aura, BMI >35,
smokers >35
!
User-‐dependent
!
Drug interactions e
...
CANT be used with certain enzyme inducing drugs
!
Contraindications for use e
...
BMI>35, smoker >35, migraine with aura, previous breast Ca
Drug interactions
!
Hormonal contraceptives are metabolised in liver
!
Certain drugs (liver enzyme inducers) can increase the rate of metabolism thus leading to
reduced plasma levels => ↑ risk pregnancy
!
Liver enzyme inducers include (CRAP GPs):
! Carbamezepine (AED)
! Rifampicin (AB) – king of enzyme inducers
! Alcohol – chronic use
! Phenytoin
! Griseofulvin
! Phenobarbitons
! SUs and St Johns Wort
! Many more
COC contraindications (absolute and relative)
Other contraindications include:
•
Breast cancer and cervix cancer is also a contraindication (due to increased risk of these
cancers in COCP)
•
Pregnancy
•
Breast feeding – POP is preffered during breast feeding
Risk Factors for VTE
!
!
Genetic Predisposition
!
Acquired predisposition e
...
cancer or SLE
!
Immobility
!
Trauma
!
Physiological Factors e
...
dehydration
!
Throbophillic diseases e
...
g
...
Dont forget to ask about family history as well
...
g
...
g
...
The COC + smoking
=> very damaging to the CV system
!
Selected, healthy non-‐smoking women without risk factors can be prescribed low dose
combined preparations up to age of 50 years, provided they are carefully monitored
Evra (transdermal patch)
•
COC transdermal patch
•
Left on for 1 week
•
Apply each week for 3 weeks followed by patch free week
NuvaRing
!
Inserted into vagina for 3 weeks then removed for 1 week (hormone free week induces
withdrawal bleed)
!
New ring reinserted for next cycle
!
Better cycle control than COCP (oral)
!
Overall lower levels of oestrogen vs COCP/patch => decreased VTE risk
Progestogen-‐only methods
!
Pill (“the minipill” e
...
cerazette): every day with no break
!
Injection (deproprovera): every 3 months; can be used with enzyme inducing drugs
!
Implant (implanon/nexplanon): every 3 years, CANT be used with enzyme inducers
!
Mirena IUS (intrauterine system): levonorgestrel-‐releasing intrauterine system e
...
progesterone coil
...
Can be used for up to 5 years
...
Progestogen Only Pill (POP)
!
!
Newer generation: Desogestrel (cerazette)
!
Some women taking the POCP continue to have regular normal periods
...
Some women also
have occasional 'spotting' between periods
...
Indications for POP
!
Contraindications to / or side effects with oestrogen e
...
migraine with aura, HT, smoker
over 35, history of VTE disease, breast cancer, cervical cancer
!
Older women who smoke
!
Lactation (breast feeding) – can actually be good for breast feeding!
!
Mild hypertension
!
Alternative to COC before surgery
!
Sickle cell disease
!
Migraine with aura
Contraindications to POP
Absolute
!
Pregnancy
!
Breast cancer (as may be PG receptor +ve)
!
Severe decompensated liver disease
Relative
!
If irregular bleeding unacceptable (major side effect of POP is irregular bleeding; NOT a
side effect of Mirena and in actual fact Mirena is first line Tx for DUB)
!
Severe CVD/ischaemic stroke
!
Drug interactions e
...
EIDs (enzyme inducing drugs) – such as carbamazepine, rifampicin and
St Johns Wort
MIRENA AND DEPROPROVERA CAN BE USED WITH ENZYME INDUCERS
Injectable prostogens: Deproprovera
!
Long acting reversible contraceptive (LARC) => given every 3 months
!
As well as other progestogenic effects they inhibit ovulation (due to pituitary suppression)
=> annovulation
!
Preperations:
! Depoprovera (medroxyprogesterone acetate) => IM injection given every 12
weeks (3 months)
Indications
!
Unreliable with COC or POP eg
...
Progesterone counteracts
estrogen and inhibits the growth of the ectopic endometrial tissue
Contraindications
!
as for POP e
...
pregnancy, breast cancer
!
Short term contraception
!
Dislike of amenorrhoea (35% at 1 year)
!
Long term use in those at high risk for osteoporosis – as linked to osteroporosis
Effect on BMD
!
!
Greatest concern at extremes of reproductive age
!
Studies have demonstrated that deproprovera ↓ BMD in chronic users => can cause
osteopenia (-‐1 to -‐2
...
5 BMD)
In all women careful re-‐evaluation of risks and benefits should be carried out for those
wishing to take it for more than 2 years
!
In those with lifestyle and/or medical risk factors for osteoporosis other methods should be
considered
!
Modify risk factors for osteoporosis
!
Perform DEXA scan every 2yrs in long term users
Progestogen implant: Implanon/Nexplanon
!
Etonogestrel is a steroidal progestin used in hormonal contraceptives, most notably the
subdermal implant Nexplanon and the vaginal ring NuvaRing (combined contraceptive)
!
Progesterone implant is placed in upper arm, sub dermal
!
Lasts three years => LARC
!
Consider changing earlier if problematic bleeding towards end
!
Inserted between day 1 and 5 of the cycle for immediate effect
!
Not suitable for people taking EIDs (enzyme inducing drugs): Remember depro-‐provera is
the Tx of choice for LARC in patients using EIDs (Mirena also suitable)
!
Almost 100% effective
!
Not suitable for needle phobias as need to give LA!
Side effects
!
!
Skin changes
!
Irregular bleeding
Headaches
!
Weight gain
!
Loss of libido
!
Amenorrhoea
The IUS ‘Mirena’ (“the progesterone coil”)
!
A 52mg levonogestrel (synthetic progestogen) containing Intra-‐Uterine System IUS (coil)
!
Lasts 5 years
!
Mode of Action of Mirena
! Local progestogen (from levongestrel) suppresses endometrium secretory phase
thus preventing implantation
! Alters cervical mucus/intratubal fluid preventing sperm migration
! May be anovulatory in some
Advantages
!
Highly effective (>99%)
!
Lasts 5 years
!
Dual license for treatment of DUB menorrhagia (reduces pain/flow) -‐ first line for DUB in
pts who want contraception
!
High rate of amenorrhoea
!
Can be used as progestogenic component of HRT (4 years)
!
Fully reversible
!
Can be used in patients with epilepsy on AEDs or on other EIDs
Disadvantages
!
!
Requires specialist fitting
!
Irregular bleeding (early months of use)
!
Not many!
‘Lost threads’ e
...
threads from the device lost: expulsion, malposition, perforation
!
PID
!
Ectopic pregnancy
The copper coil (IUCD)
!
Mode of action
! ‘Foreign-‐body effect’ within endometrium
! Direct toxicity of Cu (copper) to sperm
! Altered uterine/tubal fluid
! Less sperm reaching upper genital tract
!
Last 5-‐10 years depending on type
!
Few problems/side effects
!
Avoids use of hormones
Advantages:
!
Last 5-‐10 years (depending on type)
!
Highly effective (>98%)
!
Fully reversible
!
Immediately effective
!
Independent of SI (sexual intercourse)
!
Avoids hormones
!
Also used for EC (emergency contraception) – up to 5 days
!
Long history of use
Disadvantages:
!
!
Heavy, painful periods
Irregular menstrual bleeding
!
Require specialist fitting
!
Insertion risks e
...
perforation, infection
!
‘Lost threads’
!
Ectopic pregnancy
Contraindications to IUDs
Absolute
!
Pregnancy
!
Unexplained vaginal bleeding
!
Current pelvic inflammatory disease
!
Wilson’s Disease/ Copper allergy (only for the copper coil)
Relative
!
<4wks post-‐partum
!
History of ectopic pregnancy
!
Fibroids (distort cavity)
!
Anaemia (does not apply to Mirena)
!
Menorrhagia (does not apply to Mirena)
!
Valvular heart disease
!
High risk STI’s/recent PID
!
Immunosuppressed (steroids, HIV)
Infection and the IUD
!
!
Inserting coil into patient with pre-‐existing STI will worsen symptoms
!
Highest risk in first 20 days after procedure
!
Coils do not cause pelvic infection!!
Therefore risk is related to background risk of STI’s in population
!
RCOG advise screen (chlaymidia CT and gonorrhoea GC) + treat policy prior to insertion in
high risk populations such as UK
LARC: Long Acting Reversible Contraception
!
Cost-‐effective, independent of SI, long acting and highly effective methods
...
!
Types:
! Depoprovera (progestogen IM injection): 3 months
! Progestogen implant: Implanon / Nexplanon: 3 years
! Mirena IUS (levonorgestrel-‐releasing intrauterine system): 5 years
! Copper IUCD: 5-‐10 year
Post-‐Coital Contraception (emergency contraception)
!
Also known as emergency contraception
!
Midcycle risk of pregnancy is 30%
!
Levonelle:
! Levonorgestrel LNG (progestogen) dose up to 72 hours (3 days) after
unprotected SI
! Efficacy decreases over time
!
EllaOne:
! Ulipristal acetate (anti-‐progestogen)
! Dose up to 120 hours (5 days) after unprotected SI
! Twice as effective as LNG
!
Copper IUCD
! Can be fitted up to 5 days after unprotected SI and up to 5 days after the
expected date of ovulation (day 19 of a 28 day cycle)
! MOST EFFECTIVE
When to stop contraception?
!
<50 years: Contraception for 2yrs after LMP
!
>50 years: Contraception for 1yr after LMP
!
Menopause is defined as 1 year after LMP (last menstrual period)
TERMINATION OF PREGNANCY (TOP)
The Abortion Act 1967
!
Two doctors must agree that termination is indicated under one of the grounds (A-‐G):
basically when pregnancy would cause physical or psychological harm to mother
!
Some of these are time limited
!
Legal requirements for notification
Ethics
!
Doctors may refuse to participate in terminations but are obliged to provide necessary
treatment in an emergency when the woman’s life may be jeopardised
!
Doctors with a conscientious objection may not impose their views on others but may
explain their views to patients IF invited to
TOP consultation
!
Determine patient’s wishes/certainty to proceed
!
Perform USS (ultrasound scan) to determine gestation/which options available
!
Explain what procedure involves including risks, anaesthetic, method, hospital stay
!
Full medical/drug/social history
!
Discuss current and future contraception
Methods of Termination
Surgical
!
Vacuum aspiration:
! suction curettage (GA)
! manual vacuum aspiration MVA (outpatient/LA)
! 6-‐13 weeks (NOT before 6 weeks)
!
Dilatation and evacuation
! 13-‐24 weeks (not Scotland)
Medical
!
Early: up to 9 weeks
!
Late: 9-‐12 weeks
!
Mid-‐trimester: 12-‐24 weeks
!
Up to 24 weeks (0-‐24 weeks)
Cervical priming
!
Used to assist surgical abortions or medical abortions
!
This makes the cervix easier to dilate, reducing the later risk of cervical incompetence
...
! Misoprostol (synthetic prostaglandin PG)
! Cervagem (synthetic prostaglandin PG) dilates cervix
Medical Termination of Pregnancy
!
This can be carried out for all gestations (from 0 up to 24 weeks) due to the effect of the
anti-‐progesterone
!
Treatment:
! Anti-‐progesterone (Mifepristone – “missed one”) followed 48 hours later by
vaginal prostaglandin (Misoprostol) – cervical dilation and uterine contractions
! MM: mifeprisotone and misoprostol
!
Action of anti-‐progesterone Mifepristone:
! Causes detachment of the embryo
! Increases myometrial activity (remember that progesterone decreases
myometrial activity => Anti-‐progesterone increases myoemtrial activity)
! Makes the myometrium more sensitive to exogenous prostaglandin
! Causes opening (dilation) and ripening of the cervix
Complications of Termination
Early:
!
Uterine perforation (Specific to surgical methods)
!
Anaesthetic (Specific to surgical methods)
!
Haemorrhage
!
Retained products
!
Infection (strategy for reducing risk)
Late
!
Long term psychological sequelae
!
Cervical incompetence (Specific to surgical methods)
!
Infertility (Specific to surgical methods)
!
Rhesus isoimmunisation: if mother is Rh –ve she may produce Anti-‐D ABs (IgG) which can
cross the placenta of any future pregnancy and cause damage to a Rh +ve foetus
...
NON SEXUALLY AQUIRED GENITAL INFECTIONS
Reminder of common bacteria
!
Streptococcus (gram +ve, blue, strips of cocci):
! Alpha haemolytic: Strep viridians (endocarditis) and Strep pneumonia
(pneumonia and meningitis)
! Beta haemolytic Strep: Strep pyogenes GAS (throat and skin infections) and Strep
agalactiae GBS (neonatal meningitis)
! Gamma haemolytic: Enteroccoccus (gut commensal, UTI)
!
Staphyloccocus (gram +ve, blue, clusters of cocci):
! Cogulase +ve: Staph aureus (wound, skin infections, bone infections,
endocarditis)
! Coagulase –ve: Strep epidermidis (skin commensals, IV line infections)
Normal vaginal flora
!
Lactobacillus sp
...
(fungus)
Non-‐sexually transmitted genital infections
!
Candida (albicans) infection => “Thrush” (candida vaginitis)
!
Bacterial vaginosis (B
...
g
...
, others incl
...
5)
!
Treatment
! Metronidazole orally (very effective AB against anaerobes)
NOTE: HVS is used to diagnose ALL infections (sexual and non sexual) excluding CT and GC
...
Prostatitis
Classification:
!
Acute bacterial prostatitis
!
Chronic bacterial prostatitis: these account for <5% of all prostatitis diagnoses
!
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)
Acute bacterial prostatitis
!
Clinical features
! Symptoms of UTI e
...
dysuria and frequency
! May have lower abdominal/back/perineal/penile pain and tender prostate on
DRE examination
!
Rare complication of UTI
!
Same organisms as UTI:
! E
...
(non-‐haemolytic/gamma Strep)
!
Check for STI in patients <35years (gonorrhoea and chlamydia)
!
Diagnosis:
! Clinical signs
! MSSU (midstream urine sample) for C&S (culture and sensitivity) NOT first pass
(as its is effectively a UTI)
!
Rx (treatment):
! Ciprofloxacin for 28 days (altered depending on culture result) as often caused by
coliforms (this is the AB of choice for severe GI infections)
! Trimethoprim (for 28 days) if high C
...
g
...
Is it a
diagnosis of exclusion
!
Significant impact on psychological/mental health
Management:
!
Important to exclude malignancy and reassure patient
!
No good evidence for antibiotic treatment
!
Some limited evidence that α-‐blockers (alfuzosin/tamsulosin/prazosin) may help => relax
muscle of prostate (these drugs are also used in BPH)
!
Longitudinal studies suggest that for many patients, symptoms ↓over 2 years
SEXUALLY TRANSMITTED INFECTIONS
BACTERIAL INFECTIONS
!
Chlamydia trachomatis (CT) infection causes => chlamydia (CT)
!
Neisseria gonorrhoeae (gonococcus GC) infection causes => gonorrhoea (GC)
!
Non-‐specific urethritis (NSU) => thought to be caused by Ureasplasma and Mycoplasma
!
Treponema pallidum infection causes => syphilis
Chlamydia trachomatis (CT) infection: Chlamydia
•
Chalmydia trachomatis = gram –ve bacteria
•
DOES NOT GRAM STAIN
•
Intracellular organism
•
Can cause a range of infections in human body
Symptoms
Females
!
Asymptomatic: 70% (hence why screening is so important)
...
!
Persistent discharge (micrpurulent, but much less so than GC), often clear
!
Intermenstrual bleeding: vaginal bleeding (other than postcoital-‐ after sex) at any time
during the menstrual cycle other than during normal menstruation
...
g
...
PID can cause scarring inside the reproductive organs, which can
later cause serious complications, including chronic pelvic pain, difficulty becoming pregnant
(infertility), ectopic (tubal) pregnancy, and other dangerous complications of pregnancy
...
!
Symptoms of epididymo-‐orchitis (swollen painful testicle, pain relief on raising testes,
positive urinalysis) => in rare cases can cause infertility
!
NB: Remember that discharge is more common in an STD in comparison to UTI (but both
have similar presentations, and UTIs can present with discharge)
Pathophysiology
!
Bacterial infection, but can only reproduce inside host cell => INTRACELLULAR PATHOGEN
WHICH DOES NOT GRAM STAIN
!
3 types of infection
! Chlamydia conjunctivitis or trachoma (tropical eye infection): serotypes A, B, C
! Genital Chlamydia CT infection: serotypes D – K
! Lymphogranuloma venereum: serotypes L1, L2, L3 (associated with MSM males
who have sex with males)
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
M ceftriaxone (used in bacterial
meningitis e
...
against Meningoccous, which belongs to the same family as Gonoccous; IM is
longer acting) and oral azithromycin (single dose can also be used to Tx Chlamydia)
!
Tx = IM Ceftriaxone + oral azithromycin
!
NB: IM ceftriaxone is used as it is much longer acting than oral
!
Requires two ABs as serious infection with increasing resistance (plus azithromycin will also
target any potential comorbid CT infection)
!
Resistance of N
...
B
...
B
...
g
...
Various other neurological deficits can occur
e
...
tabes dorsalis (slow degeneration of the DCs) and general paralysis of the
insane
!
Congenital syphilis: vertical transmission occurs from 4th month onwards => all mothers still
offered screening at 1st antenatal visit
Latent syphilis
!
Latent stage asymptomatic but low-‐grade infection continues
!
Any organ may be affected
!
Patient becomes less infectious
!
May have relapse of secondary stage symptoms (in early latent period) e
...
syphilis
generalised rash, mouth ulcers, condylomata lata (flat wart-‐like growths)
!
Latent stage may last for 20+ years
!
60% will self-‐cure and some patients will be treated by having antibiotics for something else
Late stage (tertiary) syphilis
!
!
Mimics many other diseases
!
Rarely seen now
Cardiovascular
! Aneurysm of arch of aorta => may rupture => ruptured aortic aneurysm (aortic
dissection) which may present with sudden onset excruciating pain (severity
10/10)
...
The pain will often present with chest pain which may radiate to the back
...
!
Neurovascular
! Tabes dorsalis (giving a wide-‐based gait): syphilitic myelopathy, is a slow
degeneration (specifically, demyelination) of the nerves primarily in the dorsal
columns of the spinal cord
...
! Charcot’s joints (progressive degeneration of joint due to loss of sensation and
proprioception – due to tabes dorsalis => causes chornic unnoticed microtrauma)
! General paralysis of the insane (GPI) => chronic meningoencephalitis that leads to
cerebral atrophy which can result in a variety of neuropsychiatric disorders such
as dementia, seizures, depression and psychosis
! Argyll-‐Robertson pupil (prostitutes pupils): bilateral small pupils which are
reactive focussing on a near object (pupil accommodation) but not reactive to
light
! Syphilis dementia
! Many more
Diagnosis
!
Clotted blood for syphilis serology (diagnostic identification of antibodies in the serum)
!
Details of tests will be given in Practical class
!
Swab of chancre for PCR: test done at Reference Lab only (at present)
Treatment
!
IM Penicillin (long acting, IM) e
...
IM benzylpenicllin
VIRAL STDs
!
Genital warts: HPV 6 and 11
!
Genital herpes: HSV
!
Hepatitis B & C
!
HIV
Genital warts
!
Very common infection, caused by Human papilloma virus (HPV): types 6 and 11
commonest
!
Few strains of HPV associated with increased risk of cervical cancer (Types 16, 18)
...
g
...
g
...
g
...
g
...
g
...
g
...
!
If the test is positive, a copy of the lab result goes to SRH clinic and Health Advisors can
access patient’s telephone number to contact patient directly
!
Ideally, patients should be informed of this BEFORE the tests are taken
Role of Sexual Health Advisors (specially trained nurses)
!
Education and prevention of STIs
!
Partner notification (contact tracing) done for
! syphilis, gonorrhoea, trichomonas, chlamydia, HIV, hepatitis
! SRH clinic gets copies of all positive STI lab results in Tayside
!
Partner notification:
! By patients themselves
! By Health Advisors
! National Network
Reminder of the reproductive cycle
Reproductive lecture notes: week 2
PATHOLOGY OF THE CERVIX, VULVA AND VAGINA
Anatomy review
•
Ovaries: The ovaries are ovum-‐producing reproductive organ (female gonads), often found
in pairs as part of the female reproductive system
...
! Oogenesis starts in the germinal epithelium, which gives rise to the development
of ovarian follicles, the functional unit of the ovary
...
In women, fifty per
cent of testosterone is produced by the ovaries and adrenal glands and released
directly into the blood stream
...
! Oestrogen is responsible for the appearance of secondary sex characteristics for
females at puberty and for the maturation and maintenance of the reproductive
organs in their mature functional state
...
Oestrogen stimulates breast duct growth
...
Progesterone functions with oestrogen by promoting menstrual cycle changes in
the endometrium
...
When an oocyte is developing in an ovary, it is encapsulated in a spherical
collection of cells known as an ovarian follicle
...
This secondary oocyte is then ovulated into the peritoneal cavity
...
The secondary oocyte is caught by
the fimbriated end of the fallopian tube and travels to the ampulla of the uterine tube
where typically the sperm are met and fertilization occurs; meiosis II is promptly
completed
...
After about five days the new embryo (blastocyst)
enters the uterine cavity and on about day 6-‐9 day implants into the wall of the uterus
(endometrium)
...
One end, the cervix, opens into the vagina, while the other is connected to both fallopian
tubes
...
! Endometrium: this is the lining of the uterus
! Myometrium: this is the muscular portion of the uterus (responsible for uterine
contractions)
•
•
Vagina: The vagina is a fibromuscular elastic tubular tract which is a sex organ and has two
main functions: sexual intercourse and childbirth
...
Unlike
males, who have only one genital orifice, females have two, the urethra (external urethral
meatus) and the vagina
...
The external urethral meatus is anterior to the
vaginal opening
...
Vulva: The vulva consists of the external genital organs of the female
...
The cervix
•
The cervix is the inferior, narrow portion of the uterus where it joins with the superior end of
the vagina
...
•
The ectocervix's opening is called the external os
...
! In women who have not had a vaginal birth the external os appears as a small,
circular opening
...
•
•
The passageway between the external os and the uterine cavity is referred to as the
endocervical canal (endocervix)
...
The endocervical canal terminates at the internal os which is the opening of the cervix inside
the uterine cavity
...
When
the endocervix (columnar cells) is exposed to the harsh acidic environment of the vagina it
undergoes metaplasia to squamous epithelium, which is better suited to the vaginal
environment
...
•
The original transformation zone is approximately at the external os premenarche (before
first menstruation)
•
Times in life when this metaplasia of the transformation zone occurs:
! Puberty (menarche): the endocervix everts (moves out) of the uterus =>
columnar epithelium undergoes metaplasia to squamous => TZ moves into the
vagina away from external os
! Menstrual cycle: with the changes of the cervix associated with the normal
menstrual cycle
! Post-‐menopause: the uterus shrinks moving the transformation zone upwards
(inwards) towards the uterus
•
Position of TZ also alters during life as physiological response to:
! Menarche (part of puberty when the first menstrual cycle begins)
! Menstrual cycle
! Pregnancy
! Menopause
•
•
All these changes are normal and the occurrence is said to be physiological
...
g columnar cells of
the endocervic metaplasing to squamous cells) does increase the risk of cancer in this area
=> the transformation zone is the most common area for cervical cancer to occur
Cervical erosion (cervical ectropion/eversion)
•
•
Exposure of delicate endocervical columnar epithelium to acid environment of vagina (e
...
which occurs at menarche) leads to physiological squamous metaplasia of the endocervix
columnar epithelium, and movement of TZ away from the cervix
•
Thus the term cervical erosion is something of a misnomer => Cervical ectropion is more
commonly used
•
Cervical ectropion (or cervical eversion) is a condition in which the central (endocervical)
columnar epithelium protrudes out through the external os of the cervix and onto the
vaginal portion of the cervix (commonly during menarche), undergoes squamous metaplasia,
and transforms to stratified squamous epithelium via metaplasia
...
g
...
Nabothian cyst
•
Nabothian cyst = distended endocervical gland (mucus filled cyst), usually with overlying
squamous metaplasia
...
•
This tissue growth can block the cervical crypts trapping cervical mucus inside the crypts
...
Pathology of the cervix
Inflammatory pathology
Cervicitis
•
Cervicitis = inflammation of the uterine cervix
•
Non-‐specific acute or chronic inflammation
...
g
...
g
...
! non-‐use of barrier contraception
•
•
Smoking: 3 x risk
Immunosuppression
Human Papillomavirus (HPV) Infection
1
...
•
Genital warts often look “mushroom” like
•
Can be itchy
•
Clinical diagnosis
•
NB: A Koilocyte is a squamous epithelial cell that has undergone a number of structural
changes, which occur as a result of infection of the cell by human papillomavirus
...
Koilocytes may have the following cellular changes:
! Nuclear enlargement (two to three times normal size)
! Irregularity of the nuclear membrane contour
! A darker than normal staining pattern in the nucleus, known as Hyperchromasia
2
...
Cervical cancer
•
High risk HPV (16 and 18)
•
Invasive squamous cell carcinoma (SCC): Virus integrated into host DNA
•
The HPV produces oncoproteins that can cause cancer
...
The E6/E7 proteins inactivate two tumor suppressor
proteins, p53 (inactivated by E6) and pRb (inactivated by E7)
...
Less than 1% of CIN
1, approx 5% of CIN 2 and >12% of CIN III will progress to malignancy,
Prevalence of HPV Infection
•
15-‐25years:
30-‐50%
•
26-‐30years:
15-‐20%
•
31-‐35years:
10-‐20%
•
>35years:
5-‐15%
•
80% cumulative prevalence in a lifetime
•
Most develop immunity and clear infection
•
Persistence increases risk of disease (hence why HPV tests are very useful)
Cervical Intraepithelial Neoplasia (CIN)
•
•
Dysplasia of Squamous epithelial cells (particulary at the vulnerable transformation zone):
the ectocervical columnar cells protrude out through the external os and then undergo
metaplasia to squamous cells
...
•
Cervical intraepithelial neoplasia (CIN) is the potentially premalignant transformation and
abnormal growth (dysplasia) of squamous cells on the surface of the cervix
•
CIN is not cancer, and usually clears by itself
...
•
Most cases of CIN remain stable, or are eliminated by the host's immune system without
intervention
...
•
The major cause of CIN is chronic infection of the cervix with the sexually transmitted
human papillomavirus (HPV), especially the high-‐risk HPV types 16 or 18
...
•
Not visible by naked eye and asymptomatic => screening is very important
•
Detectable by cervical screening (ages 20-‐60, every 3 years)
Progressive Degrees of Dysplasia and Neoplasia
•
This slide is a diagram of cervical epithelium showing progressive degrees of dysplasia and
neoplasia, and the correlating terminology
...
•
Dyskaryosis (dysplasia) occurs after koilocytosis
Histology of CIN
•
•
Koilocytosis is very suggestive of high risk HPV infection (HPV 16,18)
•
Dysplasia and koilocytosis
Grade the neoplasia on the level of dyskaryosis
•
Delay in maturation/differentiation (dysplasia)
•
Nuclear abnormalities
! Hyperchromasia (A darker than normal staining pattern in the nucleus due to
increased proliferation)
! Increase in nucleocytoplasmic ratio: due to increased proliferation
! Pleomorphism: variability in the size and shape of cells and/or their nuclei
•
Excess mitotic activity
Staging and grade
•
The stage of a cancer is a measure of how much the cancer has grown and spread => use
TNM classification
•
The grade of a cancer looks at features of the cancer cells, using a microscope or other tests
(e
...
histological and cytoscopical), to identify how abnormal/normal the cancer cells are
e
...
the level of differentiation, mitotic figures, pleomorphism etc
•
The stage and grade of a cancer help to say how advanced it is, and how well it may respond
to treatment
...
•
CIN (non malignant, but may be premalignant) is graded I-‐III depending on severity of:
! Delay in maturation/differentiation
! Nuclear abnormalities e
...
plemorphism, increasd NC ratio, hyperchromasia
! Excess mitotic activity
•
Grading classification
! CIN I (mild dyskaryosis => low grade) => Repeat colposcopy in 3 months -‐ 6
months (may also test for HPV and perform colposcopy depending on result)
! CIN II (moderate dyskaryosis => high grade) => colposcopy => Most often should
be excised
! CIN III (severe dyskaryosis => high grade): also known as ”carcinoma in situ” =>
colposcopy => SHOULD ALWAYS BE EXCISED
•
Often koilocytosis (indicating HPV infection) also present
Natural History of Cervical Lesions
•
Appreciate that most cases of CIN will NOT advance to invasive cancers (HPV is cleared by
the body’s immune system before this occurs)
•
CIN 3 has the highest risk of progressing to cervical SCC (however only 12% will progress to
malignancy!)
Invasive Cervical Squamous Cell Carcinoma (cervical SCC)
•
•
2nd commonest female cancer (worldwide)
•
Incidence reducing in UK due to screening (an hopefully will decrease even further soon
due to HPV vaccination)
•
Increasingly detected in younger women => often found in early asymptomatic stage
•
Develops from pre-‐existing CIN, therefore most cases should be preventable by screening
•
Some are rapidly progressive tumours
•
Appreciate that the highest incidence is between 25 and 45 (cancer of the young!) =>
screening from 20 to 60 every 3 years
•
75-‐95% of malignant cervical tumours are squamous carcinoma (commonly occurring at
TZ)
Pain, PCB, and IMB
Staging
•
Stage 1A: microinvasive
•
Stage 1B: confined to the cervix
•
Stage 2: spread to adjacent organs (vagina, uterus, etc
...
Grading of squamous carcinoma
•
Well differentiated (low grade) => better prognosis
•
Moderately differentiated
•
Poorly differentiated (high grade) => worse prognosis
•
Undifferentiated / anaplastic => worse prognosis
Treatment
•
Treatment and prognosis depend on stage and grade
Symptoms of invasive carcinoma
•
Usually none at microinvasive and early invasive stages (detected at screening) => hence
why screening is so important
•
Abnormal bleeding (especially in younger woman)
! Post coital (after sex) => always perform cervical examination
! Post menopausal (vaginal bleeding that happens at least 12 months after your
periods have stopped): however this is more suggestive of endometrial cancer
! Brownish or blood stained vaginal discharge
! Contact bleeding due to friable epithelium (easily broken or torn)
! IMB => always perform cervical examination?
•
Pelvic pain
•
Haematuria
•
Urinary infections
•
Ureteric obstruction and obstructive renal failure (ureters are in close proximity to cervix)
Pathology of Squamous Carcinoma
•
Variable microscopic appearance
! Sheets of squamous cells
! Keratisation
! Often well differentiated keratinising tumours
...
g
...
g
...
g
...
Vulva pathology
•
Infections:
! Candida (particularly diabetics): Candidal vulvovaginitis (Candidiasis) or vaginal
thrush due to Candida fungal infection (often Candida albicans)
...
May have thick white discharge
...
May be precipitated by ABs
...
Mushrooom like (“I don’t want to have sex with a mushroom”)
...
Tx with cryotherapy, imiquimod or podophyllin
cream
...
Most often caused by HSV 2
...
! Bartholin’s gland abscess (blockage of gland duct)
...
They secrete
mucus to lubricate the vagina and are homologous to bulbourethral glands in
males
...
A Bartholin's cyst is not an infection, although it can
be caused by an infection, inflammation, or physical blockage (mucus or other
impediment) to the Bartholin's ducts (tubes which lead from the glands to the
vulva)
...
•
Non Neoplastic epithelial disorders:
! Squamous hyperplasia: Squamous cell hyperplasia is an abnormal growth of the
skin of the vulva
...
! Lichen Sclerosis: Lichen sclerosis is a relatively uncommon condition in which thin
white crinkly patches appear on the skin
...
S everely
itchy or sore white spots
...
It helps to reduce the inflammation and keep symptoms under
control
...
g
...
This most
commonly occurs after menopause
...
The vaginal mucosa becomes thinner, drier, less elastic and more fragile
...
Can cause painful coitus (dyspareunia) due to dry and thin
vagina
...
g
...
Can also cause vaginal discharge
and urinary problems
...
•
Three grades, like CIN
•
Neoplasia of squamous cells
•
Young women: often multifocal, recurrent or persistent causing treatment problems
...
•
Sometimes HPV related
...
Vulvar Invasive Squamous Carcinoma
•
Keratinising Squamous Cell Carcinoma (SCC)
•
Usually elderly women
•
Can arise from normal epithelium or VIN
...
•
Surgical treatment: radical vulvectomy and inguinal lymphadenectomy
...
•
A crusting rash is characteristic
...
May also have cervical and vulval lesions
...
A disease of
the elderly
...
May appear as a polyp
...
e
...
•
Abnormal cells, directly sampled from cervix, can be identified cytologically
•
CIN1-‐CIN3 is asymptomatic and can persist for some time, allowing time for detection in
preclinical phase and prevention of possible progression to cancer
...
Organisation of the SCSP
•
Three yearly invite
•
Target population
! Women with a cervix
! Age 20 to 60y
Timelines
•
HPV infection => high grade CIN (6 months to 3 years)
•
High grade CIN => invasive cancer (5 to 20 years)
•
Although remember that must CIN HPV infections will be cleared by the body’s immune
system
The cervical smear test
•
Obtain representative samples of cells from surface of transformation zone (the TZ is the
high risk area for cervical cancer) close to the external os
...
Then place in vial
– tap ten and rotate 5
...
•
Stain cells (Papanicolaou => papa stain)
•
Abnormal cells identified by cytologist
Thin prep pap test process
•
Since its introduction over 50 years ago, the pap test has been the single greatest
contributor to the overall decline in cervical cancer
...
Still, even as total cervical cancer deaths are falling, a specific type
of cervical cancer (adenocarcinoma) is on the rise, making regular pap testing as vital as
ever
...
Dispersion (in liquid)
! 2
...
Cell transfer onto slide
Cautions
•
•
Smear may underestimate the grade of underlying CIN
...
Cytological analysis
•
Dyskaryosis: abnormal nucleus (dysplastic nucleus)
•
Dyskaryosis is suggestive of CIN or invasive cancer
...
Management of abnormal smears
•
High grade dyskaryosis (CIN II and CIN III)
! High specificity (~90%)
! Colposcopy indicated
•
Low grade dyskaryosis (CIN I)
! Less specific (~30%)
! Repeat a further one or two smears before referral to colposcopy e
...
repeat
smear in 6 months
Colposcopy
•
Detailed examination of cervix with x10 magnification
•
A microscope (colposcope) with a strong light will be used to look at your cervix
...
•
If any abnormal areas are identified on STAINING, a small sample of tissue (a biopsy) may be
removed for closer examination
...
•
Acetic acid picks out abnormal epithelium
•
If abnormal areas seen they are biopsied -‐ removes cone of abnormal tissue for
histological assessment
•
You may have treatment at the same time as your colposcopy
...
•
Can also be used to
! destroy abnormal tissue by laser (laser burns away the abnormal cells) or cold
coagulation
! remove abnormal tissue by LLETZ (large loop excision of transformation zone) –
form of diathermy under local anaesthetic
...
Management
•
Treatment for CIN 1, which is mild dysplasia, is not recommended if it lasts fewer than 2
years
...
Repeat smear in 6 months
...
g
...
g
...
! Will boosters be necessary? Ab levels higher with vaccine than natural immunity
...
) found widely in the sexually active population
...
•
Sensitivity higher than cytology
•
Test for cure after treatment (began April 2012): test for presence of HPV in cervical smear
•
Detects patients with infection, not disease (CIN) => no persistence => unlikely to develop
cancer
•
High predictive value of a negative HPV test
•
Planning for Primary HPV testing
Important points
•
•
If vaccinated young women wilfully refuse cervical screening, the population rates of cervical
cancer will increase
•
Screening remains important for all women as immunisation does not protect against all
HPV types => even HPV immunised woman should be screened
•
For unimmunised women, screening remains the most effective way to reduce their risk of
cervical cancer
...
g
...
•
Placenta => Chorionic Villus Biopsy/sampling (CVS) < 15 weeks
•
Skin / Urine Cells => Amniocentesis (“amnio”) > 15 weeks
•
Blood => Fetal blood sampling e
...
from umbilical cord
•
Maternal serum => Free fetal DNA analysis (non invasive)
Chorionic villous sampling (CVS)
•
CVS is a form of prenatal diagnosis to determine chromosomal or genetic disorders in the
fetus
...
g
...
•
It is the preferred technique before 15 weeks
...
5 weeks)
...
•
Although this procedure is mostly associated with testing for Down Syndrome, overall, CVS
can detect more than 200 disorders
...
g
...
•
The most common reason to have an "amnio" is to determine whether a baby has certain
genetic disorders or a chromosomal abnormality, such as Down syndrome
...
Women who choose to have this test are primarily those at increased risk for genetic and
chromosomal problems, in part because the test is invasive and carries a small risk of
misscarriage
...
•
Viability of tissues = poor (as not taking a direct tissue sample)
•
Risks: miscarriage risk is approx 0
...
g
...
! check for and treat severe fetal anaemia or other blood problems such as Rh
disease
...
! check for fetal infection
...
•
•
Not commonly used technique
•
Risks: 1-‐2% miscarriage risk
•
Used from 18+ weeks gestation
Viability of tissues = good
Fetal DNA from maternal blood
•
Completely non invasive
•
Can be used from 8 weeks gestation
•
No miscarriage risk
•
“stable” tissue viability
•
Not commonly used due to limited analysis available
...
Summary
Chromosome analysis
•
Array CGH (comparative genomic hybridization): whole genome analysis – rarely used
currently
•
Standard Karyotype (in metaphase): whole genome analysis (takes a few weeks)
•
Fluorescence in-‐situ Hybridisation (FISH): Targeted e
...
tags a specific gene (but can also do
for chromosome analysis)
•
Quantitative Fluorescent PCR (QF-‐PCR): Targeted (but can also do chromosome analsysis)
•
Quantification of fetal DNA in maternal serum: Targeted
Whole genome tests: the catch
•
Mutation: Can be defined as a genetic change that causes disease
•
Polymorphism: Genetic Variation that is not per-‐se disease causing (appears in at least 1%
of population)
•
The arbitrary cut-‐off point between a mutation and a polymorphism is 1 per cent
...
If the frequency is lower that this, the allele is regarded as a
mutation
...
g
...
g
...
For example, a typical
prenatal FISH test will tell you how many number 13, 18, 21, X and Y chromosomes are
present (i
...
, whether there are two copies or three) but will not give you any information
about any of the other chromosomes or any information about the actual structure of
chromosomes
...
g
...
g
...
•
However, the cost of this labour intensive procedure has limited its application mainly to
high-‐risk pregnancies
...
It is much cheaper than FISH
...
g
...
If <15 weeks
=> CVS
...
Non-‐Invasive Prenatal Testing: Free Fetal DNA in maternal circulation
•
Cell-‐free fetal DNA (cffDNA) is fetal DNA circulating freely in the maternal blood stream
...
•
Analysis of cffDNA provides a method of non-‐invasive prenatal diagnosis
...
Currently (not routine):
•
Sex determination: usefull for determining if further tests are required e
...
in X linked
conditions, if shows female embryo => relax!
•
Trisomy testing
Future
•
Chromosome deletions
•
Single gene analysis
•
NB: Cordocentesis = fetal blood sampling from umbilical cord
...
She is 18 weeks pregnant (therefore CVS is CI)
...
Reassurance
2
...
Chorionic Villus sample
4
...
Fetal Blood Sampling
In this case we could go straight to amnio due to AV abnormality found
...
Microarray CGH
2
...
Chromosome analysis
4
...
DNA testing for a point mutation
‘Ideal’ Timeline for Management
•
•
•
At 18 weeks TOP would have to be medical e
...
prostaglandin for cervical ripening,
and anti-‐progesterone (mifepristone) for termination
Medical TOP can be used from 0 to 24 weeks: MM -‐ Misoprostone (anti-‐
progesterone) + misoprost (progesterone)
Surgical TOP can be used from 6 – 13 weeks: vaccum aspiration + PGs
RAPID PRENATAL DIAGNOSIS
•
Rapid techniques are important e
...
for parents anxiety levels, to make further Mx decisions
(e
...
TOP), to Dx within abortion limits etc
•
Rapid techniques (24-‐48 hours):
! Interphase chromosome counting using FISH (Fluorescence In Situ Hybridization):
very expensive
! QF-‐PCR (Quantitative Fluorescent PCR): simple and cheap
! Karoytping is NOT rapid
NB: QF-‐PCR and FISH have the same limitation of detecting only selected chromosome disorders
...
g
...
However,
carriers of balanced reciprocal translocations have increased risks of creating gametes with
unbalanced chromosome translocations leading to miscarriages or children with
abnormalities
...
Usually 1 or 3 copies of some of the genome
...
•
Other translocations occur but do not lead to a viable fetus
...
e
...
A Robertsonian translocation in balanced form results in no excess or deficit of genetic
material and causes no health difficulties
...
She is 10 weeks pregnant
...
What is your best ‘genetic' management?
1
...
Serum Screening
3
...
Amniocentesis
5
...
Direct karyotype or FISH may be available
2
...
Potentially could use FISH
...
Don’t we know that it could either be trisomy 4 or trisomy 9? NOT AS SIMPLE AS ABOVE! See
below
...
‘Ideal’ Timeline for Management
Termination of Pregnancy (TOP)
•
Surgical termination: from 6 weeks to 13 weeks (in Scotland) – vaccum aspiration
•
Induction (medical abortion) before 6 weeks or to 24 weeks e
...
anti progesterone
(mifepristone) + followed by Prostaglandin (misoprostol)
•
No time limit on TOP if there is a risk of serious abnormality in the child or to the health of
the mother
Ultrasound Scanning (USS)
•
Booking Scan: usually 10-‐12 weeks: NT, size of foetus
•
Detailed anomaly scan at 20 weeks
•
To detect specific anomalies
! Cardiac (12-‐20 weeks)
! Microcephaly (Usually after 22 weeks)
! Short Limbs (Usually after 22 weeks)
! Brain malformations
•
A minor scan abnormality may be an indicator of more severe disease
DNA testing, Screening and Pre-‐Implantation Genetic Diagnosis
Gene testing (NOT chromosome) in pregnancy
Chromosome Analysis or Array CGH (Comparative genomic hybridization)
•
General Analysis of the Genome
•
A diagnosis may be suspected
For FISH or DNA analysis
•
You need to suspect a diagnosis
•
Useful for common chromomse deletions
•
This tells you where to look
•
However FISH can be used to tag individual genes to assess for chromosome anueploidies
QF-‐PCR
•
You need to suspect a diagnosis
•
Only analyses specific loci e
...
point mutations
•
Result in 24 hours (4 hours is technically feasible)
•
However QF-‐PCR can be used to tag individual genes to assess for chromosome anueploidies
Next generation sequencing
•
•
Sequence whole genome (<£1,000)
•
Or just all known exons (= £500)
•
Will be cheaper by next year
•
DNA testing finds lots of polymorphisms
•
Now available
•
DNA testing (often via PCR)
If you sequence the whole genome, you will drown in data, 8,000,000 polymorphisms and
you will REALLY need clinical data to tell you which genetic changes are important => Not
currently feasible in prenatal diagnosis
US scanning (USS)
•
Booking Scan : usually 10-‐12 weeks
•
Detailed Scan at 20 weeks
•
To detect specific anomalies
! Cardiac (12-‐20 weeks)
! Microcephaly (Usually after 22 weeks)
! Short Limbs (Usually after 22 weeks)
! Brain malformations
•
A minor scan abnormality may be an indicator of more severe disease
Making a diagnosis
Autosomal dominant
•
•
Disease seen in all generations (usually)
50% risk of affected child if parent is affected
•
Heterozygotes: nucleus, cell or organism possessing two different alleles for a particular
gene
...
g
...
g
...
•
Carrier females will have a 50% chance of affected male and 50% chance of carrier female
•
Affected men will have 100% chance of having carrier female and 0% chance of affected
male
Genes and Maternal Health in Pregnancy
•
It is not just about risk to the baby!
•
Haemophilia A or B: female carriers with haemophillia dont have full blown disease due to X
linked inactivation however they may have significantly lower factor levels than normal =>
therefore during pregnancy they are at higher risk of bleeding complications
•
Hereditary Haemorrhagic Telangiectasia: AD disorders which can cause abnormal bleeding
=> if mum affected can cause bleeding complications
Antenatal testing for specific genetic mutations
Sampling method
•
Chorionic Villus Biopsy at 11
...
g point mutation
•
Usually PCR based e
...
QF-‐PCR: results in 2-‐3 days
•
Appreciate that QF-‐PCR is often used for both detecting chromosomal amueploidies
(unless high risk => aneuplodies or FISH) and specific genetic mutations
•
Occasionally southern blotting: may take 2-‐3 weeks
Example
Mrs Smith comes to see you
...
Her brother Charles was affected with duchenne muscular dystrophy (X-‐linked) and died at the age
of 14
...
What is your best ‘genetic' management ?
1
...
Serum Screening
3
...
5 weeks, and not before
...
After 16 weeks perform amniocentresis
...
4
...
Fetal Blood Sampling
Note: she will have 50% chance of being carrier
...
g
...
If girl => relax!
Communicating Risk and Uncertainty
•
Sometimes genetic testing gives you a definite answer
•
Sometimes it allows assignment of a precise probability
•
Sometimes there is significant uncertainty
Does free fetal DNA help here ?
•
Yes! We can do 8 week “sexing” on free detal DNA in maternal blood
...
If boy =>
perform invasive testing (CVS at 11
...
Screening for Genetic Disorders
•
Antenatal screening is a way of assessing whether the unborn baby (fetus) could develop, or
has developed, an abnormality, or other condition, during pregnancy
...
•
Tests assign a risk of abnormality in a pregnancy
•
Subject to specificity and sensitivity
...
g
...
g
...
It consists of
making a pinprick puncture in one heel of the newborn and soaking the blood into pre-‐
printed collection cards known as Guthrie cards
•
Tests for:
! Cystic Fibrosis
! Phenylketonuria
! Hypothyroidism
! Others
•
Easier to define the benefit
Pre Implantation Genetic Diagnosis (PGD)
•
Perform genetic tesst on embryos before re-‐implanting one with the ‘correct’ genotype
...
g
...
g
...
g QF-‐PCR) based analysis for single gene disorders
•
PCR analysis improved by whole genome amplification
Preimplantation genetic diagnosis: sex determination using FISH
•
Preimplantation genetic diagnosis = PGD
•
Different coloured probes (tags) to label chromosomes X, Y and 18 (control)
•
Individual chromosomes are not visible
•
Use FISH
PGD: Advantages and disadvantages
Advantages
•
Pregnancy less likely to be affected from outset
•
Lower likelihood of requiring T
...
P
...
g
...
g
...
ASK A GENETICIST!!!!
•
Tell us (the geneticists) early if we are needed: if possible at the pregnancy planning stage
Chorionic villous sampling/biopsy (CVS or CVB) can be done at 11 weeks (up until 15
weeks) gestation but carries a risk of miscarriage of 1-‐2%
...
Chorionic villus is also a slightly
weird tissue to work with genetically, and can result in false +ves due to confined placental
mosaicism
...
Risk of miscarriage is
lower (0
...
Most DNA (genes) tests only take about
3-‐4 days following amnio, but full chromosomes can take 2 weeks (usually much faster with
QF-‐PCR if we are testing for specific chromosomal abnormalities; must perform full
karyotyping if we are not testing for the common aneuploidies)
•
Fetal blood sampling is rarely done and later in pregnancy
...
There may be non-‐genetic indications that I am unaware of
...
The test varies on
indication:
!
!
Array CGH is coming in, but not used antenatally in Dundee (it is elsewhere)
...
In
two to three years we will do a CGH as our first line test
...
In this method you get to count
each chromosome stripe
...
g
...
PCR can also be used
to look for point mutations (specific mutations) e
...
Duchennes
Don’t forget the isolation of fetal DNA from maternal serum, which is about to
replace QF-‐PCR and will soon probably replace the others at around 8-‐10 weeks
gestation
PRESENTATION OF BREAT CONDITIONS
Breast symptoms not typically due to cancer
Breast pain (mastalgia)
Breast tenderness
Bilateral nipple discharge
Generalised lumpiness: not definable as single lump (typical of fibrocystic disease -‐
fibroadenosis)
• Disparity in breast size (hardly any women have symmetrical breasts)
• Longstanding nipple inversion (a condition where the nipple, instead of pointing outward, is
retracted into the breast): very common, often bilateral, doesn't require assessment
...
More than 80% of breast cancer cases are
discovered when the woman feels a lump
...
Axillary lump: Lumps (or swellings) found in lymph nodes located in the armpits can also
indicate breast cancer
...
g
...
Peau d'orange is caused by cutaneous lymphatic edema,
which causes swelling
...
This is a normal breast change and nothing to worry about
...
The lining can also become ulcerated and painful as well, although this is
not common
...
Causes
mastitis
...
Most managed by US guided drainage (for abscesses) and antibiotics (e
...
fluclox)
...
If systemically well can be treated as an
outpatient with oral Abs
...
g
...
g
...
The stroma is replaced with
fat as age increases
Lots of individual variation: may still have dense breasts aged 80 => US may be preffered
Don’t generally do mammography <40 unless suspicion of cancer (US is preferred as first line Ix
under 40)
Advantages of Mammography
•
•
•
Images whole both breasts
High sensitivity for detecting Duct carcinoma in situ (microcalcifications, not breeched
basement membrane) & invasive cancer
Only screening modality known to reduce population mortality
Disadvantages of Mammography
•
•
•
•
Non-‐specific: only 1 in 5 to 1 in 10 actually have breast cancer when detected (screen +ve)
Uses ionising radiation
Can be uncomfortable
~ 10 % of cancers are probably over diagnosis
Ultrasound
•
•
•
Useful in symptomatic clinic => useful in breast lump
Indications: palpable mass, work up of a mammographically detected lesion, image guided
biopsy, breast inflammation (can see & drain abscesses), breast problems during pregnancy
(breasts very dense because of proliferation of breast tissue e
...
oestrogen stimulates duct
growth and progesterone stimulates lobule growth)
Advantages:
! Useful for woman <40 with dense breasts (or for woman >40 with dense breasts)
! No ionising radiation
! Not uncomfortable for patient
! Good sensitivity and specificity for detecting invasive cancer
! Quick if examination tailored to one area
! Can differentiate cystic from solid
! Cheap
! Image guided biopsy very easy
Biopsy methods
•
•
There are four types of biopsies:
! Fine-‐needle aspiration (FNA): for fluid filled masses e
...
cyst
! Core-‐needle biopsy: for solids
! Surgical biopsy
! Vaccum
The latter three are the most commonly used on the breast
...
g fluid filled cyst)
Core needle biopsy (image guided cone biopsy): technique most commonly used, core needle
biopsy is the procedure to remove a small amount of suspicious tissue from the breast with a
larger “core” (meaning “hollow”) needle
...
Generally have to biopsy using
mammogram machine
...
g
...
g
...
Cyclical change in lumpiness +/-‐ cyclical mastalgua
...
Though tell to come back if they get another lump
...
> 50 = cancer
Clinical features of Lumps
•
•
•
Benign: smooth, soft, round/oval, mobile, well-‐defined
Suspicious: irregular, stoney hard, ill defined, speculated, fixed, associated lymphadenopathy
(only ~10-‐20%)
Cannot ever tell just from physical charachteristics!
Imaging
•
US best:
! Age <40
! Age > 40 with dense breasts
! Fluid filled e
...
cyst
•
Mammography
! Age >40
! If clinical or US findings are suspicious
! Screening: woman aged 50-‐70 every 3 years, mammography
Spiculate masses
•
•
•
In oncology, a spiculated mass is a lump of tissue with spikes or points on the surface
...
e
...
Suspect carcinoma
Surgical scar can occasionally look similar, as can radial scar (complex sclerosing lesion)
Axillary US
•
•
•
•
•
US axilla
Abnormal nodes identified by cortical thickness and shape
Core biopsy or FNA of abnormal nodes identifies about 40% of node positive women pre-‐
operatively
Chemo/radio/surgical
Sentinel lymph node biopsy: A sentinel lymph node is the first lymph node(s) to which cancer
cells are most likely to spread from a primary tumour
...
A surgeon injects a
radioactive substance, near the tumor to locate the position of the sentinel lymph node
...
Once the
•
sentinel lymph node is located, the surgeon makes a small incision in the overlying skin and
removes the node
...
If no cancer detected => unlikely the cancer has spread
If spread to the axillary lymph nodes => can do surgical clearance of axillary nodes
MRI
Used only on those with particular problems e
...
lobular cancer has very diffuse growth =>
difficult to size and stage accurately => MRI can prevents multiple operations
• MRI used to size tumour => stage tumour size
Staging (TNM)
•
Staging is important for prognosis and treatment decisions
For locally advanced disease or recurrent breast cancer use CT chest, CT abdo and CT pelvis to
look for mets
• Common sites of mets: bones, lung, pleura, liver, brain
• If liver or brain mets => lucky to survive 1 year
...
g
...
Effective if oestrogen-‐receptor positive e
...
oestrogen
receptor protein measurable in primary tumor
...
Used in premenopausal woman
...
! Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer
and ovarian cancer in postmenopausal women
...
In
contrast to premenopausal women, in whom most of the estrogen is produced in the
ovaries, in postmenopausal women estrogen is mainly produced in peripheral tissues of
the body
...
e
...
! Oophorectomy (surgical removal of ovaries) => decrease oestrogen (useful for ER +ve
tumours) and decrease progesterone (useful for PgR +ve tumours)
• Immunotherapy with monoclonal ABs:
! Trastuzumab (Herceptin): a monoclonal antibody to HER2 (human epithermal growth
factor receptor 2) for HER2 +ve breast cancers
Clinical Decision Making
• CPC: Clinical Pathological Conference
• MDT: Multidisciplinary Team Meeting
• Review preoperative decisions
• Review operative pathology
• Plan subsequent management
• Management of recurrent disease
...
Benefits not shown, harm gets worse (overdiagnoses & shorter
life expectancy & breast cancer less aggressive as you get older)
Some evidence that women in 40s should have mammography
BREAST PATHOLOGY 1
Assessment of a patient with breast disease
Triple assessment:
•
Clinical
! History
! Examination
•
Imaging
! Mammography (>40 years)
! Ultrasound (<40 years)
! MRI
•
Pathology
! Cytopathology (cellular level)
! Histopathology (tissue level)
Breast Cytopathology
•
Cytopathology= a branch of pathology that studies and diagnoses diseases on the cellular
level
•
Collection methods:
! Fine Needle Aspiration (FNA)
! Fluid
! Nipple discharge
! Nipple scrape
•
Breast FNA cytology:
! C1 -‐ Unsatisfactory
! C2 -‐ Benign
! C3 -‐ Atypia, probably benign
! C4 -‐ Suspicious of malignancy
! C5 – Malignant
Breast Histopathology
•
Histopathology refers to the microscopic examination of tissue in order to study the
manifestations of disease
...
g
...
•
The development stages of secondary sex characteristics (breasts, pubic hair, menstruation
etc
...
•
During thelarche, the developing breasts sometimes are of unequal size, and usually the left
breast is slightly larger; this asymmetry is transitory and statistically normal to female
physical and sexual development
...
After
initial development of the milk lines they go into remission
...
Most humans have two nipples, but in some cases more than two will
develop
...
•
Hormone driven: many hormones involved e
...
oestrogen (stimulates duct growth),
progesterone (stimulates lobule growth), prolactin (promotes lactation e
...
mik
production) and oxytocin (stimulates smooth muscles of ducts => ejection of milk)
Stages of breast development
•
•
1
...
By the time a female
infant is born, nipples and the beginnings of the milk-‐duct system have formed
...
Puberty: Once ovulation and menstruation begin, the maturing of the breasts begins with
the formation of secretory glands at the end of the milk ducts
...
The rate at
which breasts grow varies greatly and is different for each young woman
...
Adult “resting”: Each month, women experience fluctuations in hormones that make up
the normal menstrual cycle
...
The increasing level of
oestrogen leads to the LH surge and ovulation halfway through the cycle, and
then the hormone progesterone takes over in the second half of the cycle
...
! These hormones are believed to be responsible for the cyclical changes such as
the swelling, pain, and tenderness that many women experience in their
breasts just before menstruation (cyclical changes)
! During menstruation, many women also experience changes in breast texture,
with breasts feeling particularly lumpy
...
If pregnancy does not occur, the
breasts return to normal size
...
! A breast lump(s) that appears during the menstrual cycle, grows rapidly and
shows spontaneous regression with completion of the menses is most
suggestive of fibrocystic changes (fibroadenosis)
...
Fibrocystic changes is most common in
woman 30-‐50
...
Involution: Regression of mammary tissue to a non-‐secreting state, with disappearance
of much of the high density epithelial tissue, and replacement with low density fatty
tissue
...
•
4
...
The areolas begin to swell
followed by the rapid swelling of the breasts themselves (progesterone causes enlargement
of lobules)
...
By the fifth or
sixth month of pregnancy, the breasts are fully capable of producing milk
...
Many other hormones, such as follicle stimulating hormone (FSH),
luteinizing hormone (LH), prolactin, oxytocin, and human placental lactogen (HPL) also play
vital roles in milk production and secretion (lactation)
...
Postmenopausal atrophy: By the time a woman reaches her late 40s and early 50s,
menopause is beginning or is well underway
...
This leads to many of the symptoms commonly
associated with menopause
...
The connective
tissue of the breast becomes dehydrated and inelastic, and the breast tissue, which was
prepared to make milk, shrinks and loses shape => atrophy
...
Tanner stages of female pubertal development
•
Thelarche = breast development (usually occurs first)
•
Pubarche = development of pubic hair (often the second noticeable change in puberty,
usually within a few months of thelarche)
•
Menarche = first menstrual bleed (typically occurs about two years after thelarche)
Normal breast anatomy
•
•
2nd to 6th rib
Sternal edge to anterior axillary line + axillary tail (don’t forget about the axillary tail e
...
on
examination)
•
Lies on pectoralis major fascia and serratus anterior fascia
•
Blood supply: Axillary artery (subclavian artery becomes axillary artery), internal thoracic
artery & intercostal arteries
•
Lymphatic drainage
! Axillary nodes→ Supraclavicular nodes → Cervical nodes
! Internal mammary
! ALWAYS EXAMINE LYMPH NODES
•
Glandular tissues
! Lobules (mammary glands): produce milk during pregnancy and breastfeeding and
pathological states (e
...
hyperprolactinaemia)
...
Stimulated to produce milk by prolactin
...
! Lactiferous ducts: connect the lobules of the mammary gland to the tip of the
nipple
...
Stimulated to grow by
oestrogen
...
Ducts endocrine
control by OO
...
The terminal lactiferous ducts
drain the milk from TDLUs into 4–18 lactiferous ducts, which drain to the nipple
...
g
...
Apocrine metaplasia is a very common finding in the female breast
after the age of 25 especially post menopausal
...
May be a risk factor for breast cancer (controversial)
! Microcyst formation
ANDI Classification of benign breast disorders
•
Disorders of development e
...
fibroadenoma (commonest breast lump in woman less than
30 years, breast mouse, highly mobile)
•
Disorders of cyclical change e
...
mastalgia and nodularity and fibrocystic changes
(generalised lumpiness, also known as fibroadenosis)
•
Disorders of involution: Fibrocystic changes (often cyclical as well) e
...
Cysts, Fibrosis and
Sclerosing adenosis
•
NB: Involution = regression of mammary tissue to a non-‐secreting state, with disappearance
of much of the epithelial tissue
...
Occurs from
approx 30 years old
•
NB: Fibrocystic changes often occur cyclically due to hormonal influences
...
Gynaecomastia
•
•
Pathophysiology: the causes of common gynecomastia remains uncertain, but is thought to
result from an imbalance between the actions of oestrogen and androgens on the breast
tissue
...
•
Breast development in the male
Increased oestrogen to testosterone ratio leads to proliferation of breast ducts and
fibroblastic stroma
...
•
Gynaemocastia = ductal growth without lobular development (due to the excessive
oestrogen; it is progesterone which causes lobule growth)
Causes of gynaecomastia
•
Physiological: Newborn, Adolescence, Increasing age (associated with low testosterone
levels)
•
Lack of testosterone: Congenital absence of testes, Androgen resistance syndrome,
Klinefelter's syndrome (47 XXY)
•
Increased oestrogen levels: Testicular tumours (e
...
Leydig's cell tumour which secrete
estradiol), liver disease (cirrhosis), Adrenal tumours, other tumour, obesity
•
Drugs: Oestrogen (e
...
oral contraceptive pill), Inhibitors of testosterone (e
...
finasteride),
spironolactone (commonest drug induced cause) and digoxin
...
Can
cause discharge
...
It is a disorder of peri-‐ or
post-‐menopausal age
...
•
Acute mastitis/abscess (infection/inflammation of the breast tissue)
•
Fat necrosis: often associated with trauma to breast
Duct ectasia
•
•
Can cause periductal mastitis
•
This is a benign breast disease that can mimic invasive carcinoma clinically
...
As women reach the
menopause and the breasts age, the ducts behind the nipple get shorter and wider (due to
involution) => this is called ectasia
...
•
Sometimes a secretion can collect in the widened ducts and their lining can become
irritated
...
This is a benign (not cancer) condition called duct ectasia
...
The discharge can vary in colour and can be either clear or bloodstained
...
As the ducts shorten this can eventually pull the nipple inwards so it
becomes inverted
...
•
The process that causes the condition is still being debated but histologically it is
characterised by dilation of major ducts in the subareolar region
...
g
...
•
This term is sometimes used interchangeably with mammary duct ectasia
...
•
Periductal mastitis occurs when the ducts under the nipple become inflamed and infected
...
Although the aetiological process is still being researched, bacterial infection is involved
(most commonly S
...
Surgery is occasionally required if there is a residual mass, to confirm the
benign nature of the histology and prevent recurrence of infection
...
! It occurs in a younger age group than mammary duct ectasia (mammary duct
ectasia most commonly occurs in peri-‐ or post-‐menopause woman)
•
Clinical presentation:
! Periductal inflammation
! Pain and inflammation
! Periareolar mass
! Periductal fibrosis
! Scarring and distortion
! Pus discharge from the nipple
...
Associated with smoking
! Sub-‐areolar duct dilatation
Management
•
Treat acute infections e
...
ABs (flucloxacillin empirically as S
...
g
...
It does not
increase your risk of getting breast cancer
...
This is called fat
necrosis (dead tissue)
•
Associated with trauma to breast tissue
•
The damage to the fatty tissue can occur following a needle biopsy, breast surgery (including
breast reconstruction) or radiotherapy to the breast
...
•
Aetiology:
! Local trauma e
...
Seat belt injury, needle biopsy, radiotherapy, surgery
! Warfarin therapy
! Frequently no history
! Link witn obesity
•
Pathophysiology:
! Damage and disruption of adipocytes
! Infiltration by acute inflammatory cells
! “foamy” macrophages
! Subsequent fibrosis and scarring
! Microcalcification
Management
•
•
Confirm diagnosis: triple assessment
Exclude malignancy
Fibrocystic change (Fibroadenosis)
•
Women aged 30-‐50 (majority 40-‐50)
•
Very common
•
Characterized by noncancerous breast lumps (generalised lumpiness or nodularity) in the
breast which can sometimes cause discomfort, often periodically related to hormonal
influences from the menstrual cycle (cyclical)
•
Often cyclical
•
Not usually discrete masses= > nodularity instead
...
Up to
half of women have this problem at some time during their life
...
•
Aetiology: The causes of the condition are not fully understood, though it is known that they
are tied to hormone levels, as the condition usually subsides after menopause and is also
related to the menstrual cycle (cyclical)
•
It is rare in women after menopause, unless they are taking oestrogen
...
•
Usually multiple cysts
...
)
•
Myoepithelioma (benign tumour of glands which may rarely originate in breasts)
•
ID (intraductal) papilloma: small, noncancerous (benign) tumor that grows in a milk duct
(intraductal) of the breast, can cause nipple discharge including blood stained
•
Adenoma: benign tumour of glandular origin
Malignant tumours
•
Ductal carcinoma: carcinoma of the epithelium which lines the ducts (most common breast
cancer; associated with calcification)
•
Lobular carcinoma: carcinoma of the epithleium lining the lobules (unlike ductal cell
carcinoma, lobular carcinoma is NOT associated with calcification)
•
Papillary carcinoma: very rare type of invasive ductal breast cancer
•
Squmaous cell carcinoma: rare
•
Liposarcoma: cancer of fatty tissue
•
Angiosarcoma: cancer of blood vessells
•
Lymphoma: cancer of lymphoid tissue
•
Myoepithelial carcinoma
Terminology
•
Carcinoma = cancer of epithelial origin
•
Sarcoma = cancer of mesenchymal origin e
...
cancer of connective tissues such as blood
vessels, blood, bone etc
...
This is because during the
reproductive years women’s breasts are constantly going through change, from the time of
their development, through pregnancy and the menopause
...
•
Fibrocystic changes are the commonest cause of breast lumps in pre-‐menopausal woman
and present with breast lumpiness and tenderness which is often cyclical
...
Fibrocystic changes are
classed as aberrations in the Normal Development and Involution of the breast (ANDI)
...
g
...
With an estimated incidence of over 60% of women, many consider it a variation
of normal
...
Majority occur aged 40-‐50
...
May present with generalised lumpiness or multiple soft well
demarcated cysts
...
Fibrocystic breast changes usually involve the entire breast but may be
more severe in the upper, outer area of the breast
...
Occur due to combined effects of involution and cyclical
changes
...
It is usually found in adolescent girls
and women in their twenties
...
It is usually freely moveable (sometimes called
“breast mouse” as very mobile) and painless
...
This mass is solid and no fluid
will be obtained if aspiration is attempted
...
The only way to be sure that a
solid breast lump is a fibroadenoma versus a cancerous mass is to obtain cells
from the breast tissue to examine under a microscope
...
g
...
•
Because breast cancer can also appear as a lump, doctors may recommend a tissue sample
(core needle biopsy) to rule out cancer (esp in older patients)
•
Unlike typical lumps from breast cancer, fibroadenomas are easy to move (not tethered),
with clearly defined edges
•
The typical case is the presence of a painless, firm, solitary, highly mobile, slowly growing
lump in the breast of a woman of child-‐bearing years (particularly in adolescent woman
and women in their 20s)
•
Generally non cyclical (may have a slight cyclical component)
•
A fibroadenoma is usually diagnosed through clinical examination, ultrasound or
mammography, and often a needle biopsy sample of the lump
...
Doctors may recommend a tissue sample
(biopsy) to rule out cancer in older patients
...
•
All forms of phyllodes tumors are regarded as having malignant potential
...
Sclerosis is found in these benign (not cancer) breast conditions:
•
Types:
! Sclerosing adenosis
! Radial scar (complex sclerosing lesion)
•
Combination of epithelial proliferation, stromal fibrosis and sclerosis (hardening)
•
Can cause a mass or calcification
•
May mimic carcinoma (ductal carcinoma presents with calcified mass)
Sclerosing adenosis
•
•
Sclerosis adenosis is a benign breast condition composed of small breast lumps caused by
enlarged lobules which are distorted by scar like fibrous (thickened) tissue
•
Pain, tenderness or lumpiness/thickening
•
Asymptomatic
•
Age 20-‐70
•
Adenosis = enlarged lobules
ANDI (aberrations in the normal development and involution of breast)
•
Related to fibrocystic breast changes (fibroadenosis)
Radial scar
•
Radial scars and complex sclerosing lesions are benign conditions (not cancer) that are
essentially the same thing but are identified by size, with radial scars usually being smaller
than 1cm and complex sclerosing lesions being more than 1cm
...
•
Hsitology: fibrous tissue (forms scar) + epithelial proliferation
•
Wide age range
•
Common
•
Incidental finding often mammographically detected
•
Mimic carcinoma radiologically (due to calcification)
•
Probably not premalignant per se
•
Often show epithelial proliferation
•
In situ or invasive carcinoma may occur within these lesions
Papillary lesions
•
Intraduct papilloma
•
Nipple adenoma
•
Encysted papillary carcinoma
Intraduct papilloma (IDP)
•
•
Usually close to nipple
•
Benign
•
Intraductal papillomas are small growths (wart like) that occur in the ducts of the breast and
can cause nipple discharge – which may be blood stained
Age 35-‐60
•
They are most common in women over 40 and usually develop as the breast ages and
changes
...
g
...
BREAST CARCINOGENESIS
Pathways of breast carcinogenesis
•
Breast cancer emerges by a multistep process which can be broadly equated to
transformation of normal cells via the steps of hyperplasia, premalignant change (dysplasia),
in situ carcinoma and invasive carcinoma
•
Breast carcinoegensis occurs due to progressive epithelial proliferation, dysplasia, and
mutations leading to malignant changes
•
Multistep process
Epithelial Proliferations (hyperplasia)
Ductal
•
Epithelial hyperplasia of usual type
•
Atypical Ductal Hyperplasia
•
Ductal Carcinoma in situ – BM not been breached, microcalcification
Lobular
•
Lobular in situ neoplasia
•
Atypical lobular hyperplasia
•
Lobular carcinoma in situ
Intraductal proliferation: risk of progression to invasive carcinoma
•
Risk of progression to invasive carcinoma:
! Epithelial hyperplasia of usual type => low risk
! Atypical Ductal Hyperplasia => moderate risk
! Ductal Carcinoma in situ (low grade) 25% over following 10 years => high risk
Breast cancer grades
Ductal
•
DCIS (ductal carcinoma in situ):
! Low grade
! Intermediate grade
! High grade
! DCIS can progress in grade e
...
low grade DCIS => intermediate grade DCIS =>
high grade DCIS => G3 (high grade) ductal carcinoma
...
g from low grade DCIS
to G1 (low grade) ductal carcinoma
...
g
...
More time for hormonal
stimulation of breasts
...
! Parity: the number of children borne by one woman; childbearing reduces the
risk of breast cancer (and ovarian Ca)
...
Women who have given birth to five or more children
have half the risk of women who have not given birth
...
That’s probably because
she’s been exposed to more oestrogen
...
So the more menstrual periods
a woman has, the longer these tissues are exposed to oestrogen
...
Oestrogen stimulates
some breast cancers (ER +ve breast cancers) to grow by triggering particular
proteins (receptors) in the cancer cells
...
g
...
Higher oestrogen levels due
to conversion of androgens to eostroens by fatty tissue
...
! Alcohol consumption: Small association with alcohol => higher levels of oestrogen
in alcohol consumers
! Diet: High fat intake associated with small increased risk
...
•
Genetics:
! FH: Affected first degree relative doubles risk
! Also can be associated with familial syndromes => even higher risk e
...
BRCA 1
and BRCA2 plus other rarer mutations
TAKE A FULL OBS AND GYNAE MOSCC HISTORY
Genetics and breast cancer
•
Some genetic susceptibility may play a role in most cases
...
This includes those who carry the BRCA1 and BRCA2 gene
mutation
...
•
BRCA1 and BRCA 2 mutations: Associated with breast and ovarian cancer, as well as
prostate cancer (in males)
BRCA 1 and BRCA 2
•
•
BRCA 1 and BRCA 2 mutations
Each present in 0
...
g
...
g
...
g
...
But even so, most women with CIS never develop breast cancer
•
Confined within basement membrane of acini & ducts
•
Majority of invasive carcinomas originate from in situ carcinoma (pre-‐cancerous epithelial
tumour constrained within BM)
Cytologically malignant but non-‐invasive (pre-‐invasive)
•
Non-‐obligate precursor of invasive carcinoma => e
...
if patients with carcinoma in situ were
followed for a period of time, rather than having the CIS treated, not all the lesions of CIS
will have developed invasive carcinoma
...
•
Classification
! Ductal CIS (most common): associated with calcification
! Lobular CIS: not associated with calcification
Ductal Carcinoma in situ (DCIS)
•
15-‐20% of breast malignancies are DCIS
•
Arises in TDLU (terminal ductal lobular unit)
•
Cytologically malignant epithelial cells
•
Confined within basement membrane of duct
•
May involve nipple skin (Paget’s diease of the nipple and areola: eczematous rash and
crusting)
•
Associated with calcification (and microcalcification) in contast to LCIS
Classification of DCIS
•
Cytological grade (cellular levels)
•
Histological type (tissue level)
•
Presence of necrosis (comedo)
Significance
•
Risk factor for development of invasive carcinoma (ductcal cell carcinoma)
•
True precursor lesion for invasive carcinoma
Management
•
Diagnosis
•
Surgery: Surgical excision aimed at excising all of the abnormal duct elements is a common
treatment
...
•
Chemoprevention (trial)
Paget’s Disease of the Nipple
•
High grade DCIS extending along ducts to reach the epidermis of the nipple
•
Areola can also be affected
•
It produces eczema-‐like symptoms, appearing as an itchy, red rash, crusting on the nipple
that can extend to the darker area of surrounding skin (the areola)
...
•
Can be DCIS (ie non-‐invasive) or invasive ductal carcinoma
•
Key features are eczema like crusty itchy red rash of the nipple which can extend to the
areola
Lobular in situ neoplasia
Two major types:
•
Atypical Lobular Hyperplasia (ALH): <50% of lobule involved
•
Lobular Carcinoma in situ (LCIS): >50% of lobule involved
Features:
•
•
Frequently multifocal and bilateral
•
Incidence decreases after menopause (due to decreased oestrogen levels?) => more
common in pre-‐menopausal woman
•
Not palpable, not visible grossly and usually an incidental finding
•
Intra-‐lobular proliferation of characteristic cells
NOT associated with calcification (in contrast to ducal cell carcinoma and DCIS)
Significance
•
Marker of subsequent risk (10-‐20% risk of malignancy)
•
Also a true precursor lesion
Management:
•
Core biopsy => Excision or vacuum biopsy to exclude higher grade lesion
•
Vacuum or excision biopsy: Follow up and clinical trials
Invasive carcinoma
•
Malignant epithelial cells which have breached the BM (basement membrane)
•
Infiltration of normal tissues
•
Risk of metastasis and death
Microinvasive Carcinoma
•
Rare
•
DCIS (high grade) with invasion of <1mm
•
Treat as high grade DCIS
Invasive Carcinoma Types
•
•
Ductal most common (70%)
Lobular second most common (10%)
Pathological assessment of invasive carcinoma
•
Staging (TNM): CT head, abdo, chest and pelvis
•
Grade (1-‐3)
•
Completeness of excision
•
Prognostic factors
•
Predictive factors
Prognostic factors of breast cancer
•
Grade (1-‐3) depending on histological and cytological features
! Tubular differentiation (1-‐3)
! Nuclear pleomorphism e
...
degree of nuclear shape and size variation (1-‐3)
! Mitotic activity (1-‐3)
•
Stage (TNM):
! Tumour: size, type, invasive versus situ
! Node: lymph node metastasis: number involved, sentinel node biopsy
! Mets: in distant parts of body excluding local lymphatics
•
Completeness of excision
•
We test for the following receptors on tumour cells:
! ER (oestrogen receptor): helps to predict response to treatment e
...
with
tamoxifen (anti oestrogen in breast) in premenopausal woman, and
oophrorectomy (surgical removal of ovaries)
! HER 2 (Human Epidermal growth factor Receptor 2): helps to predict response to
treatment e
...
g
...
Also used to determine need for systemic therapies
...
They grow in response to the hormone oestrogen
...
” They grow in response to another hormone,
progesterone
...
ER expression predicts response to anti-‐oestrogen therapy:
•
•
Tamoxifen: antagonist of the estrogen receptor in breast tissue (prolonged use is a risk
factor for endometrial hyperplasia and cancer)
•
Aromatase inhibitors (Letrozole): block the conversion of androgens to oestrogen =>
decrease oestrogen effects in breast tissue
...
•
Oophorectomy: surgical removal of ovaries
GnRH agonists (Goserilin and buserelin): cause down regulation of pituitary secretion of LH
=> down regulation => decreased oestrogen production (can also be used for Tx of prostatic
cancer)
...
Human Epidermal growth factor receptor 2 (HER 2)
HER2:
•
HER 2 overexpression and amplification seen in ~15%
•
HER 2 overexpression or amplification predict response to Trastuzamab (Herceptin)
•
Trastuzamab (Herceptin) is a MAB (monoclonal AB) which can be used against certain HER 2
+ve breast cancers
Hormone receptors status
•
80% ER positive
•
67% PgR positive
•
14% HER2 positive
Summary
•
•
Breast cancer pathology predicts response to specific therapies e
...
endocrine and MAB
therapies
•
Breast cancer pathology predicts outcome
All rational management of breast cancer depends on the Pathology
•
Nottingham prognostic score
Breast conditions: presentation, surgery and reconstruction
Presentation of breast conditions
•
Patients either present symptomatically through GP (e
...
with lump, pain, nipple
abnormality etc) or the abnormality is found on screening (mammography is recommended
for woman 50 to 70 every 3 years)
•
Patients with an unexplained abnormality are referred to the one stop breast clinic where
triple assessment occurs:
! Clinical (history and examination): FH, risk factors, nipple changes, indrawing,
lump, skin changes, arm changes
! Radiology: mammograms esp >40 years (as less dense breast tissue), ultrasound
<40 years (as more dense breast tissue)
! Pathology (cytology and histology): fine needle aspiration, core biopsy, surgical
biopsy
•
Results can be discussed at the clinical pathological conference => decide on Mx e
...
no
further Mx, follow up, surgery, chemo, radio etc
Management of benign breast problems
Benign conditions:
h Fibroadenoma: possibly excise (vaccuum)
h Sclerosing lesions and radial scar: excise
h Intraductal papilloma: excise (as can be pre-‐malignant)
h Cysts: drain if needed
h Breast sepsis (duct ectasia, mastitis, abscess, fistula): drain if antibiotics fail
h Gynaecomastia: possibly excise
Clinical pathological conference (CPC)
•
For breast cancer the following are discussed:
! Triple assessment
! Tissue diagnosis (e
...
subtype of cancer)
! Grade
! Receptor status: ER (oestrogen receptor), PgR (progesterone receptor), HER2
(human epidermal growth factor receptor 2)
! Staging: TNM (important for Mx and prognosis)
! General fitness of patient
! Patients concerns and preferences
•
Management options:
! surgery
! radiotherapy
! chemotherapy
! endocrine therapy (tamoxifen, oophorectomy, buserelin or goserelin, letrozole)
! immunotherapy with MABs e
...
Herceptin (trastuzumab)
! palliative care
Breast cancer management
•
Surgery:
! Breast: lumpectomy (wide local excision) or mastectomy
! Axillary: sentinel node biopsy, sample, node clearance
! reconstruction
•
•
Endocrine therapy
•
Immunotherapy
•
Chemotherapy
•
Radiotherapy – for all pts with breast conserving surgery (wide local excision)
Bisphosphonates for prophylactic bone protection (e
...
One or more lymph nodes may be biopsied during the surgery;
increasingly the lymph node sampling is performed by a sentinel lymph node biopsy
...
! Quadrantectomy: Removal of one quarter of the breast
...
Breast
conserving surgery, however higher risk that all the cancer will not have been
removed
...
•
Once the tumor has been removed, if the patient desires, breast reconstruction surgery, a
type of plastic surgery, may then be performed to improve the aesthetic appearance of the
treated site
...
Nipple/areola prostheses can be used at any time following the
mastectomy
...
•
Why? For:
! local control of cancer
! prognostic information
! to guide additional (adjuvant) therapy
...
g
...
g
...
The most common donor site for this tissue is the abdomen, but there are
several other choices
...
‘Gold-‐standard’ for breast reconstruction
DIEP flap
•
Latest variation in TRAM flap reconstruction
•
Relies on two or three perforators from the deep inferior epigastric artery
•
Leaves muscle and fascia intact
•
No problems with abdominal wall closure
...
Complications of breast reconstruction
•
•
Necrosis: skin, fat (fat necrosis)
Flap failure
•
Implant exposure
•
Infection
•
Scarring
•
Capsular contracture
•
Lymphoedema
BREAST ONCOLOGY
•
Commonest cancer in women
•
Increasing incidence => due to ageing population (in contrast to cervical SCC which is
decreasing)
•
2nd commonest cause of death from cancer in women
•
Survival improving: 5 year survival improved from 56% in 1970 to 81% in 2003-‐7
Presentation
•
Screening: age 50-‐70 (screened every 3 years via mammography) => small, impalpable
lump, microcalcifactions (if ductal carcinoma)
•
Symptomatic: most often lump in breast
! 84% operable
! 8% with distant metastases => uncurable
! 8% locally advanced/inoperable
Treatment
•
Surgery
•
Radiotherapy
•
Systemic therapy
! hormonal therapy
! cytotoxic chemotherapy
! immunotherapy
Radiotherapy
•
Postoperatively to breast/chest wall and to nodal areas (axilla, supraclavicular fossa, internal
mammary nodes) => used to kill any remaining cancer cells
•
Primary radical for locally advanced
•
Palliatively to painful bony mets, skin deposits, brain mets etc
...
g
...
g large tumour, extensive nodal involvement,
involved margins etc
...
g
...
g
...
g
...
•
Deep venous thrombosis (oestrogen can increase thrombosis risk)
Chemotherapy side effects
•
•
Infertility
•
Alopecia
•
Neutropenia (sepsis): NE < 0
...
•
Drainage of pleural or peritoneal effusions
•
Optimise quality of life and survival
•
Endocrine therapy may be used for elderly patietns with metastatic disease unsuitable for
chemo
BREAST PALLITIVE CARE
•
Palliative care is an area of healthcare that focuses on relieving and preventing the suffering
of patients
•
Palliative care is an approach that improves the quality of life of patients and their families
facing the problem associated with life-‐threatening illness, through the prevention and relief
of suffering by means of early identification and impeccable assessment and treatment of
pain and other problems, physical, psychosocial and spiritual
•
Common targets for palliative care:
! Back pain due to back mets => NSAIDs, opioids, radiotherapy can be used +/-‐
Dexa (if suspect spinal cord compression – holding measure)
! Neurological deficits due to brain mets => radiotherapy can be used
! Respiratory problems due to pleural effusion => drainage +/-‐ pleurodesis (if
recurrent)
! General pain => analgesia
! Nausea and vomiting => domperidone
Back mets
•
Back pain: is it the cancer? Metastatic back pain is usually constant unremetting pain
...
Commonly spine, pelvis or proximal long bones
...
! Radio isotope bone scan: more sensitive but does not show structure or confirm
it is cancer
...
5, wedge fracture and excessive thoracic
kyphosis (kyphosis) in post menopausal women
! Metastases: bone destruction and other lesions in skeleton – often osteolytic but
can be osteosclerotic (e
...
prostate Ca)
! Disc herniation: loss of disc space
IF SUSPECT CORD COMPRESSION OR CES => GIVE DEXA AS HOLDING MEASURE BEFORE SCAN
...
Treatment of bone pain
•
•
Chemotherapy eg breast cancer & myeloma
•
Analgesics: WHO cancer pain guidelines
•
Radiotherapy: effective in 1-‐2 weeks
Bisphosphonates e
...
C via syringe driver)
•
By the clock (adminster next dose BEFORE pain comes back)
•
By the ladder (follow the WHOs pain ladder)
By the clock
•
Give analgesic before the pain comes back => REGULAR prescribing
•
Paracetamol
4 hours (but max 4 grams/day)
•
Codeine
4 hours
•
Tramadol
4hours
•
Morphine
4 hours: can also give SC
•
MST (sustained release morphine) 12hrs
By the ladder
•
Stage 1 = Simple REGULAR analgesic e
...
paracaetamol or NSAID +/-‐ adjuvant (e
...
amitriptyline, pregabalin, or gabapentin for neuropathic pain)
•
Stage 2 = Mild opioid (e
...
tramadol, codeine or co-‐codamol) + stage 1
•
Stage 3 = Strong opioid e
...
morphine or MST (ideally long acting MST twice daily) +/-‐ stage
1
Specific uses of analgesics
•
•
Paracetamol: don’t forget this drug! Very effective with minimal side effects, NSAID and
opiate sparing
...
•
The lymph glands especially the axillary groups but also the internal mammary chain clear
tissue fluid
...
Breast morphology is influenced by these steroid hormones and
changes with the normal menstrual cycle
...
•
Both benign and malignant conditions cause breast symptoms
...
Age and presentation
The benign disorders are particularly found in pre-‐menopausal women whereas some 80 per cent of
breast cancers occur in patients who have passed the menopause
The age of a woman suggests the likely diagnosis of a breast lump:
•
<30 years: normal lumpiness, fibroadenoma, rarely cancer
•
30-‐45 years: normal lumpiness, cyst (often fibrocystic e
...
fibroadenosis), sometimes cancer
•
45-‐60 years: cyst, cancer, normal lumpiness
•
>60 years: cancer until proven otherwise
Evaluation
There are three methods of assessing benign and malignant breast disorders which together make
up the ‘triple assessment’
...
•
The majority of patients presenting with breast cancer in Britain are operable -‐ that is the
staging tests do not reveal evidence of metastases
...
g
...
Treatment of breast cancer: summary
Treatment is thought of in two categories:
•
Local or loco-‐regional treatment (treatment given to the affected breast, chest wall
and the first line lymph nodes in the axilla and along the internal mammary node
chain) => Surgery +/-‐ radiotherapy (i
...
XRT is definitely used in lumpectomy or
wide local based excision, but not necessarily so for mastectomy)
•
Systemic or ‘body-‐wide’ treatment which seeks to eliminate undetectable micro-‐
metastases= > chemotherapy +/-‐ endocrine therapy +/-‐ immuotherapy
Locoregional treatment
•
Conventionally loco-‐regional treatment is by surgery or radiotherapy or a combination of
both
...
•
Since local removal of the tumour (lumpectomy) with lymph nodes enables the patient to
retain her breast this is known as breast conservation
...
•
After a mastectomy the decision whether or not to prescribe post-‐operative radiotherapy
depends on factors such as tumour size, histological grade, presence of lymphatic and/or
vascular invasion and whether nodes are involved with the cancer
...
•
Endocrine treatment, the ‘anti-‐oestrogen’ tamoxifen or, in pre-‐menopausal women,
oophorectomy can be very effective against oestrogen receptor positive cancers
...
The most common
are abnormal sensations in the axilla after surgery and redness and swelling of the breast
after radiotherapy
...
•
Endocrine therapy may cause symptoms of oestrogen withdrawal (hot flushes and mood
swings)
•
Chemotherapy side effects include nausea, GI upset, hairloss, tiredness, susceptibility to
infections
...
Prognosis depends on the size, grade, type of the cancer and number of node metastases at
presentation, the treatments given and, if recurrence of the cancer occurs, how the
recurrence is treated
...
BREAST PAIN (MASTALGIA)
•
Common symptom
•
Rare before menarche and after menopause (as often hormonally caused)
•
Must distinguish between true mastalgia versus referred pain versus MS pain (e
...
pectoralis
major pain)
•
Only 5% of breast cancer are associated with mastalgia
•
Types of mastalgia:
! Cyclical: when the pain intensity is changing during the menstrual cycle
...
This type is less frequent
...
Noncyclical pain has
frequently its root cause outside the breast
...
•
After pregnancy, breast pain can be caused by breastfeeding
...
g
...
30% invasive cancers
! Microcalcifications could indicate ductal carcinoma in situ (DCIS)
•
Mammography just “detects” NOT diagnoses (diagnosis requires full categorisation
including histology)
•
Screening => mammography performed on asymptomatic women at regular intervals (every
3 years between ages 50 and 70) with the aim of detecting clinically occult breast cancer at
an early stage
•
Symptomatic patients => mammography to demonstrate if any abnormality and nature of
abnormality
Indications for Mammography
•
Screening: detects most impalpable cancers
•
all women with a palpable mass over 40y
•
to exclude/confirm malignancy & assess contralateral side
When don’t we use it
Not routinely indicated
•
women <40 y (screening or symptomatic) => US is preferred in woman under 40 (due to
higher density of breast)
•
women over 40 if they have had a mammogram in the past year
•
Consider it in women under 40 shown by US to have a cancer
Mammography limitations
•
Decreased sensitivity in dense breasts
•
Limited contrast inherent in technique: up to 15% cancers are mammographically occult
(hidden)
•
Observer limitations
•
Compression
•
Irradiation
The male breast
•
•
Same principles as for a small female breast
Only if suspicious for carcinoma
•
Not for gynaecomastia or young men!
What about Ultrasound (US)?
Indications:
•
Mammographic abnormalities: differentiation of cystic and solid lesions
•
Palpable lesions, women < 40y
•
Nipple Discharge
•
Breast Implants or augmentation
•
Other e
...
inflammatory conditions (abscesses)
•
Evaluation of axillae
•
Work up after mammography
•
Evaluation of response to chemotherapy
What about MRI?
MRI advanatages:
•
Excellent intrinsic tissue contrast
•
Multiplanar tomographic capacity
•
No compression
•
No ionising radiation
•
Accuracy independent of breast density
•
However MRI is expensive and time consuming => not first line investigation
MRI contraindications:
•
•
Absolute: as for any other MRI exam (cardiac pacemakers, ferromagnetic aneurysm clips,
cochlear implants, renal impairment etc
...
It is the only population based screening method shown to reduce
mortality
•
In younger women (<40 years) and for evaluation of mammographic abnormalities, U/S is
the technique of choice
•
MRI can help – but discuss with radiologist first!
MENSTRUAL DISORDERS
Control of Menstrual Cycle: Pituitary and Ovarian Events (Ovarian cycle)
Follicular phase (approx day 1-‐14):
•
FSH stimulates ovarian follicle development & granulosa cells to produce oestrogens
•
LH stimulates theca cells of follicle to produce testosterone
•
Raising oestrogen & inhibin by dominant follicles inhibit FSH production and LH production
(initially)
•
Declining FSH levels cause follicular atresia (breakdown of follicles) of all but the dominant
follicle
•
Rising oestrogen => endometrium proliferation => proliferative phase
Ovulation (approx day 14):
•
Occurs approximately 14 days before menstruation e
...
approximately day 14 of 28 day or
day 21 of a 35 day cycle
...
•
Occurs due to LH surge (oestrogen levels suddenly reach a threshold and cause +ve
feedback of LH release, instead of the usual –ve feedback of LH release => LH surge occurs)
•
Dominant follicle matures, ruptures and releases oocyte
Luteal phase (approx day 14-‐28):
•
Formation of corpus luteum from the remnant dominant follicle
•
Progesterone is produced by the corpus luteum => causes secretory phase of endometrium
(prepares it for implantation)
•
LH maintains the corpus lutem
•
Luteolysis (degeneration of corpus luteum) occurs by 14 days post-‐ovulation if fertilisation
does not occur
...
Decreasing
levels of LH result in corpus luteum degeneration => decreasing levels of progesterone
...
The flow of menses normally serves as a sign that a
woman has not become pregnant
...
Fibrinolysis inhibits scar tissue formation
Proliferative phase
•
Oestrogen-‐induced growth of endometrial glands and stroma => proliferation of
endometrium
•
As they mature, the ovarian follicles (granulosa cells) secrete increasing amounts of
oestradiol E2
...
•
The oestrogen also stimulates crypts in the cervix to produce fertile cervical mucus, which
may be noticed by women practicing fertility awareness (Billings method)
•
Oestrogen E2 is the key hormone in the proliferative phase (this is why tamoxifen, an
oestrogen receptor agonist in the uterus, can cause endometrial hyperplasia and Ca)
...
•
Progesterone-‐induces glandular secretory activity
•
Decidualisation in late secretory phase = essential for forming the deciduas (maternal
placenta) if fertilisation occurs
...
•
Endometrial apoptosis and subsequent menstruation if fertilisation does not occur (due to
degradation of corpus luteum => decreasing levels of progesterone)
Normal Menstruation and Menstrual Cycle
Menstual loss
•
•
Menstrual loss usually lasting 4 to 6 days (menstrual loss is the numerator in medical
recording of menstrual cycle e
...
4 days of menstrual bleeding with a 28 day cycle => k=
4/28)
Menstual flows peaks day 1-‐2
•
< 80 ml per menstruation (e
...
per cycle) – however it is normally better to go on the
females opinion of wehther or not her bleeds are heavy or not
...
The
presence of clots is very suggestive of menorrhagia
...
g
...
g
...
g
...
g
...
g
...
Common cause of menorrhagia
•
Pelvic inflammatory disease (PID): infection of the female upper genital tract, including the
uterus, fallopian tubes and ovaries
...
Common cause of metorrhagia (IMB)
...
Excess columnar epithelium can cause increased secretions
...
Key symptoms are dysmenorrhoea and dysparenuia
...
g
...
g
...
g
...
g
...
Irregular cycle (>35
days apart => oligomenorrhoea) with heavy menses => oligomenorrhagia
...
High oestrogen to progesterone ratio
causes overgrowth of endometrium (as oestrogen causes proliferation)
...
•
During an anovulatory cycle, the corpus luteum fails to form, which causes failure of normal
cyclical progesterone secretion
•
This results in continuous unopposed production of esotradiol (E2), stimulating overgrowth
of the endometrium
...
•
The end result is overproduction of uterine blood flow => menorrhagia
•
The period is delayed in such cases, and when it occurs menstruation can be very heavy and
prolonged (oligomenorrhagia)
•
Irregular cycle (>35 days apart) with heavy menses => oligomenorrhagia
•
Risk factors = PCOS, obesity, perimenopause, adolescence
Ovulatory DUB
•
10% of cases occur in women who are ovulating
•
In ovulatory DUB, prolonged progesterone secretion causes irregular shedding of the
endometrium
•
Ovulatory DUB (not associated with anovulation) is less common than anovulatory DUB, and
the bleeding, though abnormally heavy, is usually regular (menorrhagia)
Investigations
•
Full blood count: assess for anaemia (particularly iron deficiency anaemia IDA)
•
Endocrine screen: Thyroid function tests (TSH, fT3, fT4), LH/FSH, oestrogen, progesterone,
androgens, prolactin
•
Cervical smear: to assess for CIN (cervical intraepithelial neoplasia) or cervical cancer
•
HVS (high vaginal swab) to assess for PID e
...
CT/GC combined PCR
•
Coagulation screen: PT, APTT, VWF, assessment for other coagulopathies
•
Renal/Liver function tests
•
Transvaginal ultrasound scan:
! Endometrial thickness
! Presence of fibroids and other pelvic masses – US is gold standard for Dx fibroids
•
Endometrial sampling (must rule out endometrial cancer and other pathology):
! Pipelle biopsies
! Hysteroscopic directed
! Dilatation & curettage (D & C)
DUB IS A DX BY EXCLUSION
Management of DUB (dysfunctional uterine bleeding)
Medical management
•
Progestogens (drug of choice): controls the menstrual cycle and prevents excessive
shedding of endometrium
•
Progestogen-‐releasing IUCD: Mirena IUS => FIRST LINE Tx for woman who want
contraception
•
Combined oral contraceptive pill (COCP): particulary usefull if there is dysmenorrhoea as
well (and pt wants contraception)
•
If pt does not want contraception =>
! Transenamic acid for menorrhagia
! Mefenamic acid for menorrhagia and dysmenorrhoea
•
Treatments differ depending on the patients and when in the cycle bleeding occurs
Surgical management
•
Endometrial resection/ablation: to destroy or remove the lining of the uterus (via
hysteroscopy)
•
Hysterectomy: removal of uterus
Comparison between Medical & Surgery Treatments of DUB
•
Medical treatments are clearly better: cheaper, less risks/complications, and fertility can be
retained
Comparison between Hysteroscopic Surgery (endometrial ablation) and Hysterectomy
•
Endometrial ablation is often the preferred method
Reproductive microbiology
Syphilis laboratory confirmation
•
Causal organism is Treponema pallidum (spirochaete bacterium which is spiral in shape)
•
Recent outbreaks in UK cities, primarily amongst men who have sex with men (MSM)
•
Diagnosis is usually made by serological tests e
...
by detecting ABs in the patients serum
...
•
There are two early clinical stages (primary and secondary), a latent stage (which can persist
for a long time) and one late clinical stage (tertiary syphilis)
...
•
Primary stage: isolated painless ulcer (chancre)
...
•
Secondary stage: “copper penny” generalised rash, Condylomata latum (wart like genital
lesions), painless lymphadenopathy, fever and weight loss
•
Latent stage: often asymptomatic , can persist for years and years, can affect near enough
any organ
•
Tertiary stage: cardiovascular syphilis (e
...
arotitis, aortic dissection), neurosyphilis (e
...
Argyl-‐Robertson pupil, Charcot joint, tabes dorsalis of the dorsal columns, dementia and
other neuropsychiatric disorders)
Non-‐specific serological tests
•
Two types of test
! VDRL (Venereal Diseases Research Laboratory)
! RPR (Rapid Plasma Reagin)
•
Non-‐specific tests that indicate tissue inflammation
•
May be falsely positive (e
...
SLE, malaria, pregnancy)
•
Useful for monitoring response to therapy
•
Usually become negative after successful treatment
Specific serological tests
•
•
TPHA (T
...
pallidum particle agglutination assay): a test for specific IgG ABs
Specific for syphilis, but remain positive for life (IgG stays positive for life => natural immune
response to generate immunity)
•
Not useful for monitoring response to therapy (as TPPA IgG remains positive for life)
Other specific serological tests
IgM & IgG ELISA (screening test)
•
Combined IgG & IgM ELISA used as the “screening” test for syphilis (on Tayside microbiology
reports this is stated as “Total AB” e
...
IgG + IgM)
•
If this is positive, further tests are carried out, namely:
! IgM ELISA (marker of recent, untreated acute infection)
! TPPA test for specific IgG (positive for life in anyone who has or has had syphilis)
! VDRL (marker of untreated active infection)
Current practice in Tayside
•
Combined IgG & IgM ELISA screening test => negative => result goes out as negative
•
Combined IgG & IgM ELISA screening test => positive => do further tests:
! IgM ELISA (to assess for recent acute infection)
! TPPA to assess for IgG (+ve lifelong if infected)
! VDRL: to assess for active infection (but note that late untreated syphilis
infection and latent infection may have –ve VDRL)
Typical results in various situations
More examples
1
...
Uninfected (but false +ve screen) => positive screen => -‐ve IgM, -‐ve TPPA (IgG), and –ve VDRL
3
...
Secondary syphilis => positive screen => positive IgM (as still acute) => double positive TPPA (as
more IgG produced at this stage) => double positive VDRL (as more active infection => more tissue
damage)
5
...
Recently treated => positive screening test (IgG will remain for life) => negative IgM => +ve TPPA
=> positive or negative VDRL
Important notes
•
IgG and TPPA tests remain positive for life, even after successful treatment
...
M penicillin)
•
Quite complicated and does not always behave according to the rules above => refer these
patients for Mx with sexual health clinic (they should also receieve full sexual health
screen)
•
It can be difficult serologically to differentiate properly treated syphilis from untreated late
syphilis which is why careful treatment and follow up of early syphilis is essential
...
MICROBIOLOGY PRACTICAL
Case 1
A 28 year old man attends the Sexual Health clinic complaining of pain when he passes urine and a
urethral discharge (think either UTI or STD)
...
You take a urethral swab for microscopy (done at the
clinic) and bacterial culture and a “first pass” urine for combined chlamydia and gonococcal CT GC
PCR
...
You are also provided with the first pass urine PCR
result
...
Remember that CT does not gram
stain
...
Remember that CT is much more common than GC
...
What will
be discussed during that consultation?
•
Contact tracing
•
Safe sex
•
Free condoms
(f) The patient is given an appointment to return to the Sexual Health clinic 12 weeks after the date
of his visit to Amsterdam
...
She had unprotected sex 2 weeks earlier (don’t just
assume that it is an STD because of this) at a party with a new partner, but she is taking oral
contraceptives
...
On examination, the vulva is very red and inflamed and there is a thick white
discharge
...
(a)
What is the diagnosis?
•
Dx= Vaginal thrush (candidiasis): often presents with itchy beefy red vagina and white curdy
discharge
...
(b)
What is the causal organism?
•
Candidia sp
...
g
...
A high vaginal swab (as symptomatic and we
suspect BV/TV) is taken and submitted to the laboratory
...
(a) Describe what you see
...
g
...
He is an asymptomatic carrier
...
Case 4
A 28 year old woman visits her GP complaining of the condition illustrated in this photograph
...
The lesions start as small blisters,
i
...
vesicles and then become pustular
...
The attacks last about two weeks and then resolve
...
An illustration of the condition is provided; and there
is a photomicrograph of the causal organism provided
...
HSV is a lifelong infection
(STD) and can cause asymptomatic shedding of the virus => risk of sexual partners being
contaminated
...
•
Aciclovir
! Can be used acutely (not particularly effective unless given at very early stage)
! Can also be used prophylactically to prevent outbreaks (if occurring frequently)
Topical LA can also be used for analgesia
...
The lesions are
not particularly painful or tender unless he wears tight underpants and the skin becomes chafed
...
An illustration of
the condition is provided
...
HPV viral warts is a clinical Dx
...
(d) Is the girl just fussy or does she have reason to worry about herself?
•
Yes
...
g
...
)
•
One against oncogenic strains + strains which cause viral warts
Case 6
A 30 year old man attends your surgery with an ulcerated lesion on his penis (picture provided)
...
You can feels enlarged lymph nodes in both groins
...
You refer the patient urgently to the Sexual Health clinic
...
Can
present very similar to syphillis initially – use the painful lymphadenopathy as a
distunguisihing factor!
(b) What is the most likely diagnosis in this patient?
•
Dx= primary syphilis
(c) What specimen(s) would you send to the microbiology laboratory in order to confirm the
diagnosis?
•
Clotted blood sample for syphilis serology (combined IgG+IgM ELISA screening test)
•
Would also be wise to perform a full sexual health screen e
...
HIV/HepB/HepC serology and
combined GC/CT PCR test on first pass urine
(d) Examine the first laboratory report
...
Has this
patient been adequately treated?
•
IgM = -‐ve
•
VDRL = -‐ve
•
Therefore treatment has been successful
•
Follow up at 12 months (if HIV +ve requires life long follow up every 12 months)
(g) Would you suggest that this patient has tests for any other infections, and if so, which infections?
•
STD screen:
! CT/GC combined PCR on first pass urine
! HIV, Hep B and syphilis serology +/-‐ Hep C
Reproductive lecture notes: week 3
DOWNS SYNDROME
•
Three types:
! trisomy 21 (non disjunction) – most common (95%)
! partial trisomy 21 (unbalanced translocation) – 4% (in prental Dx, assess with
karyotype of parent has known translocation)
! mosaic trisomy 21 (some cells are normal, other cells have trisomy 21) – 1%
•
•
Affects 1 in 1000 babies
•
Congenital (e
...
born with it)
•
Down syndrome is most commonly caused by trisomy 21 (47, XX +21 for females; 47, XY,
+21 for males)
...
•
Since the introduction of screening, pregnancies with the diagnosis are often terminated
(TOP)
...
Aetiology
•
There are three types of Downs syndrome:
! Nondisjunction (trisomy 21): nondisjunction occurs due to an error in cell
division called nondisjunction
...
Prior to or at
conception, a pair of 21st chromosomes in either the sperm or the egg fails to
separate
...
This type of Down syndrome, which accounts for 95% of cases,
is called trisomy 21
...
In translocation, part of chromosome 21 is duplicated
(partial trisomy) and breaks off during cell division and attaches to another
chromosome, typically chromosome 14
...
! Mosaicism: mosaicism occurs when nondisjunction of chromosome 21 takes
place in some, but not all, of the initial cell divisions after fertilization
...
Those cells with 47 chromosomes
contain an extra chromosome 21 (trisomy 21)
...
•
•
Regardless of the type of Down syndrome a person may have, all people with Down
syndrome have an extra, critical portion of chromosome 21 present in all or some of their
cells
...
The additional partial or full copy of the 21st chromosome which causes Down syndrome
can originate from either the father or the mother
...
•
The cause of nondisjunction (trisomy 21) is currently unknown, but research has shown
that it increases in frequency as a woman ages
...
A 35 year old woman has about a one in 350 chance of conceiving a child with Down
syndrome, and this chance increases gradually to 1 in 100 by age 40
...
•
All 3 types of Down syndrome are genetic conditions (relating to the genes), but only 1% of
all cases of Down syndrome have a hereditary component (passed from parent to child
through the genes)
...
However, in one third of cases of Down syndrome resulting from translocation there is a
hereditary component -‐ accounting for about 1% of all cases of Down syndrome
...
g
...
Clinical features
•
What Does the Extra Chromosomal material do?
•
Causes an excess amount of protein to be present in each cell => disturbs the growth and
development of the foetus
•
Causes common characteristics:
! Eyes: slanted eyes
! Ears: small, low set ears
! Face and head shape: flat head
! Height and weight: stunted growth e
...
short stature and low weight
•
Learning disabilities: mild (IQ 50-‐70) to moderate (IQ 35-‐50) learning disability
•
Some common health issues:
! Congenital heart disease e
...
VSD
! Hypothyroidism
! Poor fertility
•
Global developmental delay: gross motor, fine motor, communication and social,
cognitive, language
Diagnosis
Prenatally (antentally)
•
Prenatal screening now routinely offered to women of all ages
...
If known
Robertosnian translocation in F => full karyotype
...
! Prenatal screens estimate the chance of the fetus having Down syndrome
...
! Diagnostic tests can provide a definitive diagnosis with almost 100% accuracy
...
•
The early (approx 11-‐14 weeks) PAPP and bHCG test, combined with NT can give an
estimate of risk
...
•
The triple blood tests (or serum screening tests) measure quantities of various substances in
the blood of the mother (hCG, AFP and oestriol E3)
...
Together with a woman's
age, these are used to estimate her chance of having a child with Down syndrome
...
g
...
•
The diagnostic procedures available for prenatal diagnosis of Down syndrome are chorionic
villus sampling (CVS) before 15 weeks and amniocentesis after 15 weeks
...
•
Amniocentesis is usually performed in the second trimester after 15 weeks of gestation; CVS
is performed in the first trimester between 9 and 11 weeks
...
•
Because these features may be present in babies without Down syndrome, a chromosomal
analysis called a karyotype is done to confirm the diagnosis
...
They use
special tools to photograph the chromosomes and then group them by size, number, and
shape
...
•
Another genetic test called FISH or QF-‐PCR (QF-‐PCR often preferred over FISH) can apply
similar principles and confirm a diagnosis in a shorter amount of time => used for RAPID
antenatal diagnosis
Facts
•
•
People with Down’s syndrome have different skills and abilities just like everyone else
...
Reading can be one of their strengths
...
It is the lack of work opportunities that is the
problem
...
People with Down’s syndrome who are adults should be treated as such
...
•
Can have a normal life!
PHYSIOLOGY OF PREGNANCY AND LACTATION
Fertilisation and implantation
•
Egg released by ovaries => captured by fimbriae of fallopian tubes
•
Fertilised by sperm in the ampulla of the fallopian tubes
•
Conceptus travels down the fallopian tube and the cells progressively divides and
differentiates in the process called cleavage => results in formation of morula (day 4)
•
The morula becomes a blastocyst as it enters the uterus (day 5)
•
Implantation of the blastocyst (trophoblastic cells invade the endometrium) in the
endometrium of the uterus occurs shortly after (day 6-‐9)
•
Inner cell mass (embryoblast) becomes the embryo
•
Outer trophoblastic cells differentiate and become the foetal part of the placenta
Timeline (development time, NOT gestation)
•
Day 1: Fertilization occurs in the ampulla of the Fallopian Tube
...
The
trophoblast of the blastocyst invades the endometrium to accomplish implantation
...
•
NB: remember that gestation begins on the first day of the LMP
...
Implantation of the Blastocyst
•
Blastocyst:
! Inner cells develop into embryo
...
•
Advancing cords of trophoblastic cells tunnel deeper into endometrium, carving out a hole
for the blastocyst
...
•
When implantation is finished the blastocyst is completely buried in the endometrium
•
Blastocyst becomes fully buried in uterine lining by day 12
Placenta
Placenta development
•
•
Decidua = the mucous membrane of the body of the uterus (outer layer of endometrium)
•
Placenta is derived from both trophoblast (derived from conceptus) & decidual tissue from
endometrium (mucus membrane of uterus/endometrium which is perfectly designed for
nourishing the foetus)
Decidual cells produce the nutrients that keep the foetus going
...
•
Trophoblast cells differentiate into multinucleate cells (syncytiotrophoblasts) which invade
decidua and break down capillaries to form cavities filled with maternal blood
•
Early nutrition of the embryo => occurs due to invasion of synctiotrophoblastic cells into
the decidua
•
Developing embryo sends capillaries into the syncytiotrophoblast projections to form
“placental chorionic villi”
•
Each villi contains foetal capillaries separated from maternal blood by a thin layer of tissue
=> no direct contact between foetal & maternal blood (AV shunt)
•
This results in two way exchange of respiratory gases, nutrients, metabolites etc between
mother and foetus, largely down diffusion gradients
•
The placenta (and foetal heart) is functional by 5th week of pregnancy (gestation = 5
weeks) e
...
after only 3 weeks of development! Remember that gastrulation also occurs in
the third week of development (e
...
Progesterone stimulates
decidual cells to concentrate glycogen, proteins and lipids => energy substrates
for placenta and foetus
...
! Progesterone is essential for maintaining the placenta and foetal development
...
Chorion (chorionic membrane)
•
The chorion is one of the membranes that exist during pregnancy between the developing
fetus and mother
...
g
...
•
The chorion consists of two layers: an outer formed by the trophoblast, and an inner formed
by the somatic mesoderm
•
The trophoblast is made up of an internal layer (cytotrophoblast) and an external layer of
(syncytiotrophoblast: this is what invades the endometrium)
•
The amnion is in contact with the mesoderm
•
The amnion and chorion become adjacent as the foetus is formed and expands
Placenta works as a physiological arteriovenous shunt
•
As the placenta develops, it produces and extends hairlike projections (villi) which burrow
into the uterine wall
...
Developing embryo sends capillaries into
the syncytiotrophoblast projections to form “placental villi”
•
This increases the contact area between the uterus and placenta => allows more nutrients
(from the mother) and waste materials (from foetus) to be exchanged
•
Blood vessels from embryo develop in the villi
...
•
Circulation within the intervillous space acts partly as an arteriovenous shunt
...
Veins usually carry deoxygenated blood (except adult
pulmonary veins), but the single umbilical vein carries oxygenated and nutrient-‐
rich blood from the placenta and delivers it to the right fetal heart (via the ductus
venosus and IVC), which pumps it around the body of the fetus
...
Arteries usually carry oxygenated blood (except adult pulmonary
artery), but the two umbilical arteries collect deoxygenated blood from the body
of the fetus and carry it to the placenta
...
Umbilical arteries arise from internal
iliac arteries
...
•
The exchange takes place between maternal oxygen-‐rich blood (received from maternal
arteries e
...
uterine arteries) and the umbilical blood (umbilical vein) => AV shunt (occurs in
intervillous space)
•
Oxygen diffuses from the maternal vessels (uterine arteries) into the fetal circulation system
(umbilical vein) as PO2 maternal uterine artery > PO2 fetal umbilical vein
•
Carbon dioxide follows a reversed gradient from umbilical arteries to maternal circulation
(uterine veins) (as PCO2 foetal umbilical arteries > PCO2 maternal uterine veins)
•
Fetal, oxygen saturated blood, returns to the fetus via the umbilical vein
...
•
But how then is sufficient oxygenation of the fetus possible? The supply of the fetus with
oxygen is facilitated by three factors:
! Fetal HbF (alpha 2, gamma 2) => increases ability to carry O2 (HbF has a greater
affinity for O2 and a greater capacity for O2 compared to HbA) e
...
shift to the
left of Hb dissociation curve
...
! Higher Hb concentration in fetal blood (50% more than in adults)
! The Bohr effect (shift to right of Hb dissociation curve) allows rapid release of O2
in response to hypoxia, hypercapnia, and acidosis
...
Therefore the foetus is very
good at compensating during hypoxia (due to greater capacity for carrying O2
and greater capacity to release O2 via the Bohr effect)
...
g
...
g
...
Exchange increases during
pregnancy up to the 35th week (3
...
•
Electrolytes follow water (iron and calcium only go from mother to child)
...
Allowing her antibodies to pass across the
placenta and into the fetus is important in providing protection for the fetus, and later the
newborn baby, against the same infectious agents
...
However, the placenta cannot prevent the transfer of alcohol, other drugs and viruses to
the fetus
...
•
Teratogens are substances or environmental agents which cause the development of
abnormal cell masses during fetal growth, resulting in physical defects in the fetus
(teratogenesis)
•
Teratogens can cross the placental barrier and can cause damage to the developing foetus
•
Most sensitive time is the first trimester
•
Drugs (excluding alcohol) => 3% of all congenital malformations
•
Causes of teratogenesis can broadly be classified as:
! Teratogens: toxic substances such as drugs and environmental toxins in
pregnancy
...
For example, lack of folic acid in the nutrition in pregnancy for
humans can result in spina bifida
...
•
Produced from approximately week 5 of pregnancy
•
Effects on mother:
! Its structure and function is similar to that of human growth hormone
...
! hCS/hPL has anti-‐insulin properties => decreases insulin sensitivity in mother (e
...
g
...
Maternal HT and oedema can occur
...
g
...
The increase is mainly caused due to an increase in plasma volume (50%) through increased
aldosterone
...
•
Flow murmurs are common due to increased CO
Heart rate
•
Heart rate (HR) increases up to 90/min to maintain CO and manage to pump all the excess
fluid
Blood pressure
•
Blood pressure (BP) drops during 2nd trimester: uteroplacental circulation expands
(resistance decreases) & peripheral resistance decreases
•
With twins BP drops more
•
Rises back up to pre-‐prenancy BP in third trimester
Haematological changes
•
•
Erythropoesis (RBC) increases (25%) => red cell volume increase is less than plasma volume
increase
•
Thus Hb (and HCT) is decreased by dilution (approximately 25%) => this decreases blood
viscosity and can cause dilutional anaemia (as plasma volume increase > erythropoiesis
increase)
•
Plasma volume increases (aldosterone effects) proportionally with cardiac output (50%):
The plasma volume increases to provide for the greater circulatory needs of the maternal
organs and the uteroplacental circulation
A pregnant woman will also become hypercoagulable (physiological change to prevent
haemorrhage particularly PPH) due to increased liver production of coagulation factors,
mainly fibrinogen and factor VIII
...
This
hypercoagulable state along with the decreased ambulation (exercise involving legs)
causes an increased risk of both DVT and PE
•
Iron requirements increases significantly (partly due to increased erythropoisesis) => most
women require iron supplements (amount from diet and iron stores is usually insufficient)
Respiratory changes
•
•
Progesterone has a very interesting direct action on the mother's respiratory center
(medulla oblongata of brain stem)
...
As a result, the removal of carbon dioxide from the fetus's
bloodstream is facilitated!
•
Progesterone signals the brain to lower CO2 levels by increasing CO2 sensitivity in
respiratory centres
•
Progesterone is responsible for a decreased amount of carbon dioxide in the blood of
pregnant women
...
This accounts for the feeling of shortness of
breath, dyspnea, or heightened awareness of the need to breathe reported by many
pregnant women
...
The growing uterus can therefore decreases pO2 slightly => SOB
•
In summary: The high level of progesterone a hormone produced continuously during
pregnancy, causes the brain to increase ts sensitivity to CO2 levels which results in lowering
of the levels of carbon dioxide in the blood
...
She may breathe deeper and faster also because the enlarging uterus limits how much
the lungs can expand when she breathes in
...
Virtually every pregnant woman becomes somewhat more out of breath
when she exerts herself, especially toward the end of pregnancy (when uterus exerts
pressure on diaphragm)
...
Urinary system
•
During pregnancy, maternal plasma volume increases (due to aldosterone increase) to meet
the greater circulatory needs of the placenta and maternal organs (e
...
uterus, breasts, skin,
uteroplacental circulation)
•
Like the heart, the kidneys work harder throughout pregnancy
...
•
Glomerulate filtration rate (GFR) and renal plasma flow (RPF) increases
•
Increased re-‐absorption of ions and water due to:
! placental steroids
! maternal steroids and aldosterone (aldosterone is the major stimulus at increasing
the maternal plasma volume)
•
•
The uterus presses on the bladder, reducing its size so that it fills with urine more quickly
than usual
...
g
...
g
...
It is unlikely you will notice these signs, but
they should be picked up during your routine antenatal appointments
...
g
...
•
Kidney function declines in pre-‐eclampsia
! Renal blood flow and Glomerular filtration rate decreases
...
g
...
•
Single most significant risk is having had pre-‐eclampsia previously
...
Severe cases should
be seen in hospital
•
What causes pre-‐eclampsia?
! The cause of pre-‐eclampsia is not fully understood
...
This is the attachment between
the foetus and the uterus
...
! Vasoacitve moleculres realises form placenta cause maternal vasoconstriction
leading to ischaemia of organ
! This may also affect the transfer of oxygen and nutrients to the foetus => can
cause IUGR (assess with umbilical artery Doppler)
! Pre-‐eclampsia can also affect various other parts of the maternal body
...
Assess with
umbilical artery Doppler scan
...
Ocurs due to placenta inflammation
...
However may present with pain and tense uterus without bleeding
...
g
...
2kg
! Extra-‐embryonic fluid/tissues: 1
...
7kg
! Fat accumulation: 1
...
5mg/kg/min
! Appreciate that the foetus requires more glucose than the mother in the third
trimester! Hence why human chorionic somatomammotropin (hCS) / human
placental lactogen causes maternal insulin resistance in last trimester
...
last trimester) => foetal anabolic phase / maternal catabolic phase (accelerated
starvation)
•
high metabolic demands of the fetus (requires more glucose than mother)
•
accelerated starvation of the mother
•
Maternal insulin resistance => more glucose available for foetus
! Insulin resistance caused by HCS human chorionic somatomammotropin (GH
like e
...
anti-‐insulinic), cortisol and growth hormone
•
Increased transport of nutrients through placental membrane
•
Lipolysis => increase FAs for foetus
Special nutritional need in pregnancy
•
Higher energy uptake (eating for two)
•
High protein diet
•
Iron supplements: 300mg ferrous sulphate (increased erythropoesis)
•
B-‐vitamins for erythropoesis
•
Folic acid (folate) => reduces risk of neural tube defects e
...
spina bifida
•
Vitamin D3 and Ca2+ supplements
•
Before parturition => K vitamin: prevention of haemorrhagic disease of the newborn due to
Vit K deficiency => prevention of foetal intracranial bleeding, (and other bleeding e
...
GI)
during the labour
•
Most often prophylaxis for haemorrhagic disease of the newborn is Vit K IM injection after
parturition (e
...
after birth)
Parturition (birth of baby)
•
Toward the end of pregnancy, uterus becomes progressively more excitable (preparing for
birth)
•
Estrogen:Progesterone ratio increases => increasing excitability and preparing for labour:
! Estrogen increases contractility => increases density of oxytocin receptors in
uterus
...
! Progesterone inhibits contractility
•
•
Fetal hormones: oxytocin and prostaglandins control timing of labour
•
Oxytocin (from maternal posterior pituitary gland): increases uterine contractions and
excitability
Stretch:
! Mechanical stretch of uterine muscles increases contractility by positively feeding
back to the hypothalamus to increase oxytocin release
...
However, they are not usually felt until the second trimester or third trimester of pregnancy
...
Braxton Hicks contractions are a tightening of the uterine muscles for one to two minutes
and are thought to be an aid to the body in its preparation for birth
...
Parturition: Initiation of Labour
•
Braxton Hicks contractions: increase toward the end of pregnancy (preparation for true
labour contractions)
•
Eostrogen from ovaries prepares the uterus for contractions:
! Induces oxytocin receptors on uterus
! Stimulates PG release
! Increases gap junction in myometrium
•
Fetal hormones released : oxytocin and PGs
•
Oxytocin from foetus and mothers posterior pituitary initiates and sustains contractions:
! stimulate uterus to contract (“contractions”)
! stimulate placenta to make prostaglandins (PGs) => PGs stimulate more vigorous
contractions of uterus
•
Distension/stretch of the cervix and uterus by foetus positively feedback to the placenta
and posterior pituitary (via nervous APs) => even further increased release of oxytocin and
PGs => more vigorous uterine contractions
•
Strong uterine contractions and pain from the birth canal cause neurogenic reflexes from
spinal cord that induce intense abdominal muscle contractions
Labour (parturition)
•
Increasing uterine contractions + uterine retraction (progressive shortening of uterine fibres
=> uterus becomes smaller) result in foetus dropping lower in uterus
•
This results in increased cervical stretch
•
Increased cervical stretch results in:
! More release of oxytocin from posterior pituitary (+ve feedback) => increased
uterine contractions and increased PGs released from uterine wall, which also
results in increased uterine contractions
! Increased uterine contractions (directly)
•
•
PGs also cause cervical dilation and effacement
•
Increased uterine contractions continue to drop foetus lower into uterus = increase cervical
stretch => positive feedback continues => magnifying uterine contractions until baby is
foetus is born
NB: The “foetus” is called a baby after it is born
The Stages of Labour
•
•
2nd stage: expulsion of baby stage: passage of the baby through birth canal (typically a few
min to 30 min, however may take up to 2 hours in nuliparous woman, and 1 hours in
multiparous, who have NOT had regional anaesthesia e
...
spinal or epidural
...
•
1st stage: cervical dilation/effacement stage (8-‐24 hours; on average the cervic dilates at
1cm per hour and is maximally dilated 10 hours later when it is 10cm) + uterine
contractions (increasing in frequency and duration)
3rd stage: ejection of placenta: Placenta is usually released just after birth
...
Normally occurs within 30 minutes
...
g
...
Duct system = OO
= osterogen for growth of ducts and oxytocin for contraction of ducts and expulsion of milk
...
g
...
Lobules = PP => progesterone for development of lobules and prolactin for
production of milk
...
Most species
will generate colostrum just prior to giving birth
...
Colostrum feeds the baby until milk can be fully
produced in the breast
! 1-‐7 days after birth, prolactin induces high milk production
...
Can inhibit PIH
(prolactin inhibiting hormone e
...
dopamine) => inhibits dopamine release onto anterior
pituitary => increased prolactin released from anterior pituitary => stimulates milk
production
...
g
...
g
...
•
The fertilization age (also called embryonic age and later fetal age) is the time from the
fertilization
...
g
...
This estimation assumes that conception occurs on day 14 of a 28 day
cycle
...
Basing GA on the LMP tends to result in an overestimation
...
Size can be misleading in the presence of multiple
pregnancy, uterine fibroids, or a full bladder (always empty bladder before
hand!)
...
Can also measure the fundal-‐symphiseal height in cm which
correlates with gestation +/-‐ 2 cm from 20 weeks gestation
...
Most pregnant women have a first trimester scan (booking
scan at 10 weeks), followed by a detailed scan for anomalies in the second
trimester (approx 20 weeks)
...
g
...
Very important to
investigate for it, as pre-‐eclamsia may be asymptomatic
...
g
...
•
Symphysis to fundal height: Fundal height is a measure of the size of the uterus used to
assess fetal growth and development during pregnancy
...
It
should correlate with foetal age +/-‐2 cm from 20 weeks gestation
...
For example longitudinal lie => foetal backbone (axis) is parallel to maternal
backbone (axis) => results in either cephalic (head first) or breech (legs or buttocks first)
presentation
...
•
Engagement of presenting part: Engagement is when largest diameter of presenting part
reaches pelvic inlet (transvere diameter > AP diameter => OT is the preffered presentation at
this stage) and can be detected by vaginal (pelvic) exam
...
•
Fetal heart auscultation: sonicaid (US) or pinard
Screening and specific testing for fetal anomaly
•
Screening
•
Specific prenatal (antental) testing
The triple test (16 weeks)
•
Usually performed at 16 week
•
The triple test measures the following three levels in the maternal serum
! alpha-‐fetoprotein (AFP) – low in Downs
! human chorionic gonadotropin (hCG) – raised in Downs
! unconjugated estriol (UE3) – low in Downs
US Screening (18-‐20 weeks)
•
Ultrasound for fetal anomaly at 18-‐20 weeks (mid pregnancy scan)
•
Assess growth, organs, bones, etc
•
Objectives:
! Reduction in perinatal mortality and morbidity
! Potential for in utero treatment
! Identification of conditions amenable to neonatal surgery
! Identification of malformations
Down syndrome
•
Incidence dramatically increases with increasing maternal age => older woman in high risk
group (however more Downs children are born to younger woman, as younger woman have
more children)
•
Most common cause is full trisomy 21 (due to non-‐disjunction) => complete extra
chromosome 21
Downs syndrome risk assessment
First trimester (0-‐13 week’s gestation)
•
At 11-‐13 weeks: measure of skin thickness behind fetal neck using ultrasound => this is the
nuchal thickness (NT)
...
•
At 11-‐13 weeks: HCG (Human chorionic gonadotropin) and PAPP-‐A (Pregnancy-‐associated
plasma protein A)
•
Risk assessment in first trimester uses
! NT (increased NT is indicator of Downs)
! HCG (increased HCG is indicator of Downs)
! PAPP-‐A (low PAPP-‐A is indicator of Down)
Second trimester (13-‐26 weeks gestation)
•
Maternal blood sample at 15-‐20 weeks => the triple test
•
The triple test usually performed at 16 weeks is an assay of:
! HCG – increased in Downs
! AFP (alpha-‐fetoprotein) – decreased in Downs
! Estriol E3 – decreased in Downs
For both first and second trimester
•
Incorporation of these measurements (NT, and triple test: HCG, AFP and E3) and results
with maternal age and gestation to give a personal risk (maternal age is a big risk factor)
•
>1:250 => high risk and requires further diagnostic investigation (e
...
amniocentesis >15
weeks or CVS <15 weeks)
...
Risk of Downs syndrome according to maternal age and serum levels
•
Alpha-‐fetoprotein (AFP) is made in the part of the womb called the yolk sac and in the fetal
liver, and some amount of AFP gets into the mother's blood
...
•
•
Estriol (E3) is a hormone produced by the placenta, using ingredients made by the fetal liver
and adrenal gland
...
This test may not
be included in all screens, depending on the laboratory
...
A specific smaller part of the hormone, called the beta
subunit beta-‐hCG is increased in Down syndrome pregnancies
...
In the first trimester, low levels of this protein are seen
in Down syndrome pregnancies
...
The correct analysis (comparison to “normal ranges”) of the different serum components
depends on knowing the gestational age precisely
...
•
Once the blood test results are determined, a risk factor is calculated based on the "normal"
blood tests for the testing laboratory
...
" Test results are sometimes
reported to doctors as "Multiples of the Median (MoM)
...
0 MoM
...
0 MOM
...
0 MoM
...
•
The final calculated risk from the lab results based on the fetal age is used to modify the risk
already statistically calculated based on the mother's age
...
g
...
g
...
g
...
•
Good tissue viability
•
Carries a miscarriage rate of 1-‐2% (higher than amnio, as performing on a younger foetus
and invading foetal placenta)
...
Amniocentesis (amnio)
•
•
Procedure in which a small sample of amniotic fluid is drawn (urine and skin cells are
colleceted) out of the uterus through a needle inserted in the abdomen
•
Usually performed after 15 weeks
Carries a miscarriage rate of 1% (less than CVS)
•
Poor tissue viability
Downs syndrome key points
•
Requires accurate pregnancy dating => essential to know correct gestation age to calculate
MoM blood values and NT (Nuchal thickness)
•
Triple blood test: hCG, AFP and estriol are useful predictors of risk
•
High risk (>1/250) => diagnostic tests indicated
•
Increasing maternal age is also a key risk factor (and taken into account in risk calculation)
•
Requires detailed counselling
•
‘Low risk’ does not exclude Down syndrome
PRE-‐TERM BIRTH
Pre term birth
•
Term (full-‐term) = 37-‐42 weeks gestation
•
Pre-‐term = Delivery between 24 (24+0) weeks and 36+6 (36 weeks and 6 days):
! moderate to late preterm (32 to <37 weeks)
! very preterm (28 to <32 weeks)
! extremely preterm (<28 weeks)
•
Post term= > 42 weeks
•
Prevalence of pre term birth: Approx 6-‐7%
•
Survival rates of pre term birth:
! 24 weeks approx 20-‐30%
! 27 weeks 80%
! 32 weeks >95%
Pre-‐term birth: Aetiology
•
Infection: infections (e
...
UTIs, PIDs, chorioamnionitis) play a major role in the genesis of
preterm birth and may account for 25–40% of events
...
Further the decidual response may include release of
matrix-‐degrading enzymes that weaken fetal membranes leading to preterm
premature rupture of membranes (ROMs)
...
Micro-‐organisms may reach the decidua in a
number of ways, ascending, hematogeneous, iatrogenic by a procedure, or
retrograde through the fallopian tubes
...
! Early rupture of membranes causes almost a third of all premature births
...
If a mother's waters break before the baby has reached full term, the
medical term is preterm premature rupture of the membranes (PPROM)
...
Give
prophylactic ABs for PPROM (e
...
erythromycin)
! Therefore it is very important to screen for asymptomatic bacteruria via MSSU
(M and C)
...
•
‘Over distension’ – stiumates uterne contractions:
! Multiple pregnancies: Multiple pregnancies (twins, triplets, etc
...
! Polyhydramnios: excess of amniotic fluid in the amniotic sac (amnion)
! Macrosomia – large baby (e
...
in poorly contolled DM)
! Placental abruption: Abruptio placentae is defined as the premature separation
of the placenta from the uterus
...
Vaginal bleeding (APH) usually follows,
although the presence of a concealed hemorrhage in which the blood pools
behind the placenta is possible
...
Build up of blood in the myometrium
causes increased pressure => stimulates uterine contractions
...
The myometrium in this area
becomes weakened and may rupture with increased intrauterine pressure during
contractions
...
Placenta abruption is painful with a
tense, tender uterus, +/-‐ APH
...
Causes
uterine overdistension => initiates uterine contractions and labour (see above)
! Placenta previa: obstetric complication in which the placenta is inserted partially
or wholly in lower uterine segment (low placenta)
...
If the placenta does
overlie the lower segment, as is the case with placenta praevia, it may shear off
and a small section may bleed
...
It is a leading cause of
antepartum haemorrhage (vaginal bleeding >24 weeks and before birth)
...
Placenta previa is
painless (in comparison to placenta abruption which is painful)
...
•
Intercurrent illness:
! Pyelonephritis / UTI
! Appendicitis
! Pneumonia
! Pre-‐eclampsia
•
Cervical incompetence: medical condition in which a pregnant woman's cervix begins to
dilate (widen) and efface (thin) before her pregnancy has reached term
...
! For example, a woman who is described as 'gravida 2, para 2 (sometimes
abbreviated to G2 P2) has had two pregnancies and two deliveries after 24
weeks
...
! In Tayside we use Para X+Y, where X= the number of deliveries beyond 24 weeks
(only include after the birth); the second is the number of pregnancies ending
before 24 weeks without signs of life
...
Remember that the first figure includes deliveries beyond 24 weeks,
NOT necessarily live births
! Example 2: A woman at 8 weeks into her first pregnancy => Para=0+0 (parity does
not become 1 until after birth)
...
If this woman gave birth to a baby after 24 weeks (alive or stillborn) =>
Para 1+0
...
Small for dates may be due to
! Small for gestational age (SGA): IUGR or constitutionally small
! Wrong dates
! Oligohydraminos: low volume of liquor amnii
! Transverse lie
•
Small for gestational age (SGA) can be due to:
! Intra uterine growth restriction (IUGR) which is also called pathological SGA:
pathological state where growth is normal in the early part of pregnancy, but
slows in utero by at least two measurements, normally ultrasound
...
They have a wasted appearance with
little subcutaneous fat
...
! Constitutionally small (familial): basically a genetic trait of the baby
...
They are light-‐for-‐dates, but otherwise
healthy
...
Intra Uterine Growth Restriction (IUGR)
•
Intrauterine growth restriction (IUGR) refers to poor growth of a baby while in the mother's
uterus during pregnancy
...
g
...
•
Intrauterine growth restriction can result in baby being small for Gestational Age (SGA),
which is most commonly defined as a weight below the 10th percentile for the gestational
age
...
Aetiology
•
Poor growth can be caused by:
! Maternal factors
! Fetal factors
! Placental factors
•
Maternal factors:
! Poor nutrition
! Maternal disease e
...
pre-‐eclampsia, hypertension, gestational diabetes, CV
disease, respiratory disease
! Smoking
! Alcohol
! Drugs
! Poor weight gain during pregnancy
! Age
•
Fetal factors:
! Vertically transmitted infections e
...
rubella, CMV, toxoplasma
! Congenital anomalies e
...
absent kidneys (renal agenesis)
! Chromosomal abnormalities e
...
Down’s syndrome
•
Placental factors:
! Often secondary to hypertension e
...
preeclampsia
! Infarcts
! Placental insufficiency: Placental insufficiency or Utero-‐placental insufficiency is
insufficient blood flow to the placenta during pregnancy
! Placenta abruption: complication of pregnancy, wherein the placental lining has
separated from the uterus of the mother
...
It is less commonly known as global growth restriction, and indicates that
the fetus has developed slowly throughout the duration of the pregnancy and was thus
affected from a very early stage
...
Since most neurons are
developed by the 18th week of gestation, the fetus with symmetrical IUGR is more likely to
have permanent neurological sequelae
...
In
asymmetrical IUGR, there is restriction of weight followed by length
...
A lack of subcutaneous fat leads to a
thin and small body out of proportion with the head
...
In these cases, the embryo/fetus has
grown normally for the first two trimesters but encounters difficulties in the third, usually
secondary to pre-‐eclampsia
...
This type of IUGR is most commonly caused by extrinsic factors that
affect the fetus at later gestational ages
...
g
...
This causes a reduction in the fetus’ stores of
glycogen and lipids
...
6 mmol/L)
...
•
Antenatal / in labour complications:
! Risk of hypoxia and or death: If the cause of IUGR is extrinsic to the fetus (e
...
maternal or uteroplacental IUGR), transfer of oxygen and nutrients to the fetus is
decreased
...
6)
! Effects of asphyxia e
...
CP (cerebal palsy)
! Hypothermia
! Polycythaemia: polycythemia can occur secondary to increased erythropoietin
production caused by the chronic hypoxemia
...
Unconjugated hyperbilirubinaemia can cause kernicterus
...
It is the opposite of polyhydramnios
...
•
Reduced fetal movements
Assessing fetal wellbeing in IUGR
•
•
Cardiotocography (CTG)
•
Assessment of growth
Biophysical assessment: BPS (biophysical profile score)
•
Doppler ultrasound – umbilical artery
Assessment of growth
•
Fetal growth charts:
! head circumference
! abdominal circumference
•
Assess if symmetrical (worrying) or asymmetrical/head-‐sparing (less worrying) IUGR
Cardiotocography
•
Cardiotocography (CTG) is a technical means of simultaneously recording the fetal
heartbeat and the uterine contractions during pregnancy, typically in the third trimester
...
•
CTGs purpose is to monitor foetal well-‐being & allow early detection of foetal distress
...
g
...
g
...
This indicates good reflex
activity of the fetal circulation
...
•
Decelerations: A decrease in fetal heart rate
! Early decelerations: often not worrying
...
! Late decelerations: Any deceleration whose lowest point is past the peak of the
contraction i
...
decelerations with lag time
...
•
Loss of baseline variability (uncomplicated) is worrying: Baseline fetal heart rate variability
of less than 5 beats per minute
...
In general, the less variability present, the greater the possibility of asphyxia
USE DR C BRAVADO
Biophysical assessment (US)
•
Ultrasound assessment
•
Considers:
! Movement
! Tone
! Fetal breathing movements
! Liquor volume (amniotic volume): low amniotic volume (oligohydraminos) is not
a good sign
•
Score out of 10:
! 8-‐10 satisfactory
! 4-‐6 repeat
! 0-‐2 deliver
Doppler ultrasound
•
Umbilical arterial Doppler scan
•
Particulary usefull for assessing IUGR
•
Uses ultrasound
•
Umbilical arterial Doppler assessment is a useful tool in the evaluation of fetal compromise
in high-‐risk pregnancies such as those with intra-‐uterine growth restriction (IUGR) or
suspected pre-‐eclampsia
...
•
Measures placental resistance to flow
•
In growth-‐retarded fetuses and fetuses developing intra-‐uterine distress, the umbilical artery
(vessel which takes blood back to the foetus) blood velocity waveform usually changes in a
progressive manner as below
! reduction in end diastolic flow
! absent end diastolic flow (AEDF)
! reversal of end diastolic flow (REDF) e
...
flow of blood travelling back to the
foetus
Delivery
•
Most infants with intrauterine growth restriction are born at term
...
•
Obstetricians often induce labour in cases of intrauterine growth restriction for fear of
neonatal morbidity and later stillbirth
...
For these reasons, expectant management with
maternal and fetal monitoring is a commonly followed strategy
...
Induction of labour to prevent the
uncommon outcome of stillbirth might be the more appropriate strategy in some
settings, especially if intensive surveillance is not feasible
...
g
...
g
...
However cervical ripening with PGs may be used
...
•
It may be due to a variety of reasons such as prolapse or occlusion of the umbilical cord,
placental infarction and maternal smoking
...
! IUGR can cause hypoxia due to placental dysfunction + other causes
•
Intrauterine hypoxia can cause cellular damage that occurs within the central nervous
system (the brain and spinal cord)
...
•
Oxygen deprivation in the fetus and neonate has been implicated as either a primary or as a
contributing risk factor in numerous neurological and neuropsychiatric disorders such as
epilepsy, ADHD, eating disorders and cerebral palsy
...
•
If small for gestational age babies have been the subject of intrauterine growth restriction
(IUGR) the term SGA associated with IUGR is used
...
g
...
It has a number of purposes, including protecting the fetus from trauma
and infection, allowing lung development and facilitating the development and movement
of the limb and other skeletal parts
...
g
...
Polyhydramnios is therefore linked to fetal abnormality
...
g
...
It occurs when abnormal
amounts of fluid buildup in two or more body areas of a fetus or newborn
...
Various causes including Rhesus
incompatibility, heart problems, lung problems, anaemia (e
...
thalassameia),
infection (erythrovirus B19), and other genetic and developmental problems
! Intrauterine infections
! Idiopathic
•
Clinical features:
! Discomfort
! Large for dates
! Difficult to hear foetus heart rate (due to excess amniotic fluid around baby)
•
Complications:
! Premature labour: due to the additional pressure (distension) stretching the uterus
=> stimulates contractions
! Membrane rupture due to increased pressure => can also cause premature labour
! Cord prolapse: The extra fluid in the uterus makes it difficult for the foetus to settle
its head down into the pelvis
...
If this happens, you may need
an emergency caesarean section
...
Zygosity is the degree of
identity in the genome of twins
...
However the resvese is not true, as
can have dizygotic twins with one chorion (chorionic membrane)
•
Dichorionicity (lambda sign on US) does NOT => dizygotic
...
However, whether they are monygotic or dizygotic,
dichorionicity is reassuring as there are more complications in monochorinic prgenancies
...
Zygosity
•
Zygosity is the degree of identity in the genome of twins
...
•
The three most common variations are all dizygotic (fraternal or non-‐identical; come from
seperate eggs and seperate sperms):
! Male–female dizygotic twins are the most common result: 50 percent of dizygotic
twins are male-‐female and the most common grouping of twins
...
Monochorionic: If they share a placenta (monochorionicity), the pregnancy is at greater
risk, and you’ll be monitored more closely, so that any complications can be prevented or
treated e
...
polyhydraminos and preterm labour
...
However the
reverse isn’t true, monozygozity does NOT => monochrorionic
...
Can be monozygotic (identical) or dizygotic
(non-‐identical)
...
These are the highest risk pregnancies but they are also very rare
...
•
Non-‐identical twins (dyzygotic) come from two eggs that are fertilised by two different
sperm
...
They are in separate sacs
...
Two thirds of all twin pregnancies are non-‐identical
...
•
Identical twins (monozygotic) come from a single egg that is fertilised by a single sperm,
which then divides into two identical embryos
...
! If the division into two embryos happens in the first three days after fertilisation,
the twins will develop their own placenta and membranes
...
g
...
g
...
! If the division happens between the fourth day and the ninth day, the twins will
share a placenta and outer membrane, but each will have their own inner
amniotic membrane => monochorionic diamniotic
...
! If division happens after the ninth day, the twins will be in a single sac =>
monochorionic monoamniotic
...
! If division happens after the 12th day after conception, the result will be
conjoined twins (identical monozygotic twins joined in utero)
...
•
•
Finding this out early is important because babies who share a placenta have a higher risk of
health problems
...
If your babies share a placenta (monochorionic) it means they are identical
('monozygotic')
...
This is because 30% of monozygotic twins do not share a
placenta (monozygotic and dichorionic)
...
But if monozygotic twins separate early enough (in the first three
days after fertilisation), the arrangement of sacs and placentas in utero is indistinguishable
from dizygotic twins
Complications
•
•
Twin-‐to-‐twin transfusion syndrome (TTTS): Twins who share a placenta (monozygotic and
monochorionic) also share a blood supply
...
The
other twin will get too little blood, and may not grow very well (e
...
IUGR)
...
Twins sharing a placenta are usually scanned every two weeks from 16 weeks to look for
early signs of TTTS, so treatment can be given to correct the imbalance
...
Having regular scans will help to spot the
early signs and allow the condition to be treated
...
But it is more likely that
your twins will have separate (dichorionic) rather than shared placentas
...
•
Dichorionic-‐Diamniotic: these twins have the lowest mortality risk at about 9 percent,
although that is still significantly higher than that of singletons
...
Because of this, there is an increased chance
that the newborns may be miscarried or suffer from cerebral palsy due to the lack of oxygen
...
Chorionicity: how can we tell before birth?
•
Ultrasound:
! Number of placental masses
! Twin peak sign at 12 weeks: The sign (lambda sign) describes the triangular
appearance to chorion insinuating between the layers of the inter twin
membrane and strongly suggests a dichorionic (two chorionic membranes) twin
pregnancy
...
However it does reassure us that we have Dichorionic pregnancy
which has significantly less complications associated with it
...
g
...
g
...
g placenta praevia
•
Twin to twin transfusion: Twins who share a placenta (monochorionic) also share a blood
supply
...
The other twin will get too little blood, and may not
grow very well
...
Management of multiple pregnancy
•
More frequent antenatal visits
•
Detailed anomaly scan at 18 weeks
•
Regular scans from 28 weeks for growth
•
Routine iron supplementation
•
Warning to mother e
...
risk and signs of pre term labour
Multiple pregnancy: delivery
•
Triplets or more => Caesarean section
•
Twins: if twin one is cephalic presentation (head down) then aim for vaginal delivery
•
Much greater risk of Caesarean section (approx 50%)
•
Epidural analgesia
DIABETES IN PREGNANCY
•
Pre-‐existing
! T1DM
! T2DM
•
Gestational DM (usually occurs from 28 weeks)
Gestational DM
•
Gestational DM: carbohydrate intolerance resulting in hyperglycaemia of variable severity
with onset or first recognition during pregnancy
•
Incidence:
! Increasing
! 2-‐18%
! Ethnic variation e
...
South Asian, Middle Eastern and Black Caribbean
•
Risk factors:
! Family history of diabetes
! Previous big baby (macrosomia)
! Previous unexplained still birth
! Recurrent glycosuria
! Maternal obesity
! Previous gestational diabetes
GDM pathophysiology
•
Placental hormones cause maternal insulin resistance and insulin deficiency
! Cortisol: anti-‐insulinic
! Progesterone
! Human placental lactogen (hPL) which is also known as human chorionic
somatomammotropin hCS: GH like effects e
...
anti-‐insulinic => causes insulin
resistance and high levels of glucose – particulary in the third trimester (foetus
anabolic state and maternal starving state)
•
•
This is primarily a response to increase maternal serum glucose so that the foetus has
access to more glucose (in the third trimester)
...
6 (when constant maternal glucose infusion is removed + high foetal insulin levels)
Consequences
•
Overgrowth of insulin sensitive tissues => macrosomia (large foetus) => large for dates
uterus => increased risk of preterm birth
•
Hypoxaemic state in utero: Fetal hyperinsulinaemia and increased anabolism leads to
decrease level of arterial O2
...
g
...
6)
•
Long term metabolic complications: Fetal metabolic reprogramming (thrifty phenotype)
leading to increase long term risk of obesity, insulin resistance and diabetes
Gestational Diabetes: Screening and Diagnosis
•
Women screened for GTT (glucose tolerance test) based on risk factors or random blood
glucose at booking and 28 weeks gestation (approaching third trimester: the anabolic state
of foestus / starvation state of mother)
•
Diagnosis based on GTT at 28 weeks
•
Diagnostic values (for 75g oral glucose dose):
! 0 hour (fasting) > 5
...
5 mmol/l (lower than the usual definition of 11 in non pregnant
individuals; in non pregnant individuals a OGTT between 8 and 11 would be
impaired glucose tolerance test a form of prediabetes)
Diabetes in pregnancy: complications
•
All relate to poor control
•
Specific to pre-‐existing DM:
! Congenital anomalies
! Miscarriage
! Intra uterine death
•
Common to pre-‐existing and gestational DM:
! Macrosomia (large for gestational age baby): due to fetal hyperinsulinaemia
stimulation foetal tissue growth => can cause dystocia (obstructed labour)
...
! Pre eclampsia: unknown pathophysiology
! Polyhydramnios due to foetal polyuria => can cause pre-‐term labour
...
At delivery
the baby should be checked for congenital abnormalities
! Neonatal hypoglycaemia (<2
...
It is diagnosed when the shoulders fail to deliver shortly after the fetal
head
...
The baby cannot begin to breathe because its chest is being
compressed
...
One characteristic of a minority of shoulder dystocia
deliveries is the turtle sign, which involves the appearance and retraction of the
fetal head (analogous to a turtle withdrawing into its shell), and the
erythematous (red), puffy face indicative of facial flushing
...
Complications include Erbs
palsy (upper brachial plexus injury), foetal hypoxia, cord compression, and death
...
6)
•
Importance of glycaemic control
•
Increased risk for the baby of obesity and diabetes in later life
•
Increased risk of type 2 diabetes for the mother with gestational DM
Prevention of hyperglycaemia
•
Monitoring blood glucose
...
5 – 5
...
8 mmol/l
•
Diet
•
Weight control
•
Exercise
•
Pharmacological therapy
Pharmacological therapy for gestational diabetes
•
Consider when:
! diet and exercise fail to maintain targets
! macrosomia on ultrasound or other complication such as polyhydraminos
•
Choice of agent:
! tailored to glycaemic profile
! individual woman
! Oral medication or insulin?
•
Potential advantages of oral anti-‐diabetic agents:
! Avoidance of hypoglycaemia associated with insulin
! Less weight gain
! Less ‘education’ required to ensure safe / effective administration
! Avoid sulphonylureas (e
...
glibenclamide, glicazide, and tolbutamide) as
potentially teratogenic
Obstetric care of DM patients
•
Regular monitoring for pre-‐eclampsia: BP measurements and urinalysis for proteinuria
•
Growth: 2-‐4 weekly FAC (fetal abdominal circumference) from 28 weeks or diagnosis =>
assessing for macrosomia
•
Assess for polyhdraminos
•
Fetal wellbeing: Research has shown that umbilical arterial Doppler in high risk pregnancies
is more beneficial compared to CTG (cardiotocography) and BPP (biophysical profile)
•
Offer delivery from 38 weeks gestation
Timing of Delivery
•
Offer delivery from 38 weeks gestation
•
Case dependent
Mode of Delivery
•
•
‘Diabetes should not in itself be considered a contraindication to attempting vaginal birth’
•
‘Pregnant women with diabetes who have ultrasound diagnosed macrosomia should be
informed of the risks of vaginal birth and Caesarean section’
CS (C-‐section) remain high even when diabetes well controlled and no evidence of
macrosomia
Future development of Type 2 diabetes from GDM
•
Risk up to 70%
•
Main risk factors:
! Obesity
! Use of insulin during pregnancy
! Fasting glucose levels abnormal during pregnancy
! IGT (impaired glucose tolerance) post partum
! Ethnic groups e
...
South Asian and Middle Eastern
Type 1 & 2 Diabetes in pregnancy: Additional management points
•
Pre pregnancy counselling
•
Fetal anomaly scan at 18 weeks
•
Regular eye checks for retinopathy (fundoscopy) – pregnancy can accelerate damage
•
BP and urinalysis (assess kidney function AND assess for pre-‐eclampsia)
•
Diabetic foot exam and peripheral vascular exam (as DM can cause peripheral vascular
disease and neuropathy)
Key Points
•
Large for dates aetiology:
! Wrong dates
! Multiple pregnancy
! Macrosomnia
! DM => macrosomnia and polydraminos
! Polyhydramnios
! Fibroids
! Distended bladder
! Hydratiform mole in first trimester
•
Multiple pregnancy (particulary monochorionic) associated with significant higher perinatal
morbidity and mortality and require specialist obstetric care (particularly if monochorionic)
•
Incidence of diabetes (types 2 and GDM) in pregnancy increasing as a consequence of
obesity epidemic
•
Care of diabetics in pregnancy is multidisciplinary
•
In some women, gestational diabetes will respond to changes in diet and exercise
...
Can cause foetal renal dysfunction and
oligohdraminos
...
g
...
g
...
Function between weeks 6-‐10
then regress
! Metanephric blastoma: develops into nephron
! Ureteric bud: derived from mesonephric ducts (Wolffian duct)
...
The failed induction will thereby cause the subsequent degeneration
of the metanephros by apoptosis and other mechanisms
...
Therefore, the
means by which the fetus produces urine and transports it to the bladder for excretion into
the amniotic sac has been severely compromised (in the cases of URA), or completely
eliminated (in the cases of BRA)
...
This compression
can cause many physical deformities of the fetus, most common of which is Potter facies
...
It later develops into a conduit for
urine drainage from the kidneys (e
...
collecting system), which, in contrast, originate from
the metanephric blastema
...
As kidneys ascend into abdomen, they receive
their blood supply from the aortic branches closest to them
...
Normally the more caudal blood vessels degenerate as they are no longer needed
...
•
The cloaca is the common end of the rectal tube and the urogenital tract
...
! The spongy part of the urethra and the urethral glands
! The prostate
•
In females from the definitive urogenital sinus endoderm arises:
! Urethra
! Lower 2/3rds of vagina: In females, the pelvic part of the UG sinus gives rise to
the sinovaginal bulbs, structures that will eventually form the inferior two
thirds of the vagina
...
g
...
•
Male duct system = Mesonephric duct (Wolffian duct)
The prostate forms from the definitive urogenital sinus and the efferent ducts form from
the mesonephric tubules
...
Testosterone binds to and activates androgen receptor, affecting intracellular signals and
modifying the expression of numerous genes
...
•
From the mesonephric duct (Wolffian) arise:
! Epididymis
! Deferent duct
! Seminal vesicle
! Ejaculatory duct
Descent of the Testis
•
The testes descend to the scrotum under the control of the gubernaculums (ligament like
structure) under the control of testosterone
Female Ducts (Paramesonephric)
•
Female = Mullerian ducts = Paramesonephric ducts
•
In the female, there is an absence of anti-‐Müllerian hormone secretion by the sertoli cells =>
absence of Müllerian apoptosis
•
The Mullerian duct (paramesonephric duct) persists and forms female genital tract
•
The Wolffian duct regresses, due to the absence of testosterone
•
From the paramesonephric duct (Müllerian) arises:
! Fallopian tube
! Uterus
! Upper 1/3 of vagina
! NB: Remember that the lower 2/3rd of the vagina are formed from the sinovaginal
bulbs (derived from definitve urogenital sinus)
Development of Uterus
•
The paramesonephric ducts develop qnd into the fallopian tubes, uterus, cervix and upper
1/3 of vagina
...
•
Later, these genital swellings form the scrotum (males) or labia major (females)
•
Controled by the presence or absence of testsosterone
•
Testsosterone present => male external genitalia
•
The external genital (like the intenal reproductve organs) also have an indifferent stage
Testsosterone absent or androgen insensitivity sydrome => female external genitalia
develops
Male genitalia development
•
The genital tubercle becomes longer and out of it forms the penis
•
The two genital swellings also fuse in the middle and form the scrotum
...
•
From the genital swellings arise the labia majora
•
The urethral folds also do not fuse
...
Learning objectives
•
Name the nephric systems involved in kidney development:
! Metanephric blastoma (from mesoderm) => nephron
! Ureteric bud is a protrusion from the mesonephric duct => collecting system
! Metanephros (develops into fully functioning kidney) forms from Metanephric
Blastoma (nephron) and ureteric bud (collecting system)
...
•
Know that the permanent kidney is derived from the metanephros = metanephric blastoma
+ ureteric bud (protrusion of Mesonephric/Wolffian duct)
•
Know the parts of the kidney derived from the ureteric bud (collecting duct system) and the
parts derived from the metanephros (filtration via nephron)
•
Know the types of anomalies that arise from failure of the kidneys to ascend
! Pelvic kidney: If a kidney does not ascend as it should in normal foetal
development it remains in the pelvic area and is called a pelvic kidney,
! Horseshoe kidney: Horseshoe kidney is a congenital disorder affecting about 1 in
500 people
...
The fused part is the isthmus
of the horseshoe kidney
...
g
...
g
...
BP falls
in first and second trimester and then rises back to pre pregnancy BP in third trimester
...
Incidence
•
Hypertension (HTN) in pregnancy: 10-‐15%
•
PET: 3-‐5%
! Severe PET 5/1000
•
Eclampsia: 5/10000
Leading Causes of Child and Mother Deaths: NOT TO BE MISSED
•
Sepsis
•
Pre-‐eclampsia/eclampsia
•
Thromboembolism
Pre-‐eclampsia
Aetiology
•
Placental pathology:
! VASOCONSTRICTIVE MOLECULES
! It appears likely that there are substances released from the placenta that can
cause endothelial dysfunction in the maternal blood vessels of susceptible
women
...
! Key part of pathogenesis: Vasocontrictive factors released which systemlly act on
maternal endothelium
! More common in twins
! Resolves after delivering placenta
! Does not occur before 20 weeks
•
Prostaglandin imbalance -‐ excess: aspirin is used to help treat => aspirin (PG inhibitor)
decreases prostaglandins
...
•
Genetic: If mother had PET => increases risk by 20-‐40%
Pathophysiology
•
It all has to do with vasoconstriction => maternal hypertension and decreased blood flow to
organs, in particular kidneys and liver
•
Vasoconstrcition to systemic arterioles => HT
•
Vasoconstriction to kidey arterioles => kidney dysfunction => proteinuria (>300 mg /24 hours
– albuminuria)
•
Specific to pregnancy
•
Placental cause
•
Manifestation is variable, unpredictable, and widespread
•
Complex pathophysiology of vasoconstriction, procoagulation and IV thrombosis all
resulting in tissue ischaemia
...
g
...
Fibrin forms crosslinked networks in the small blood vessels
...
Additionally, platelets are consumed
...
Other organs can be similarly affected
...
Placenta
•
•
Placental abruption (complication of pregnancy, wherein the placental lining has separated
from the uterus of the mother) => severe uterine pain, tense uterus, APH + contractions
(due to blood in myometrium causing stretching of the myometrium) + premature delivery
(due to contractons)
•
↓ blood flow to placenta and baby => IUGR => ↓ size of baby (SGA <10th centile) =>
monitor with umbilical artery Doppler
Intra uterine death
Risk Factors
•
Risk assessment is key
•
High and moderate risks: consider giving these patients aspirin (prostaglandin inhibitor)
High risk
•
Previous HT or PET
•
Chronic hypertension
•
Chronic kidney disease
•
Autoimmune condition: SLE, APS
•
Type 1/2 diabetes
Moderate risk
•
1st pregnancy and age > 40
•
Pregnancy interval > 10 years
•
BMI ≥ 35
•
Family history of pre-‐eclampsia
•
Multiple pregnancy
Other important risk factors
•
Mother had PET
•
History of hydatidiform mole
•
Triplets: can present with PET < 24 weeks
Clinical Presentation of PET
•
BP ≥ 140/90 (hypertension)
•
Significant proteinuria:
! ≥ +1 on urine dipstick
! 30 mg/mmol (0
...
g
...
However, post-‐partum pre-‐
eclampsia may occur up to six weeks following delivery even if symptoms were not present
during the pregnancy
...
Hypertension can
sometimes be controlled with anti-‐hypertensive medication, but any effect this might have
on the progress of the underlying disease is unknown
...
•
Interplay of three key factors (the 3 Ps):
! Power: Uterine Contractions (power, frequency and duration) + retraction
! Passage: Maternal Pelvis (shape, size)
! Passenger: Fetus (shape, size, lie, presentation, position)
Physiological considerations in labour
•
Progesterone keeps the uterus quiet e
...
prevents early labour
! Progesterone prevents formation of gap junctions => hinders contractibility of
myocytes (SMCs of myometrium) => decreases uterine contractability
•
Oestrogen makes the uterus contract:
! Eostrogen simulates prostaglandin production => prostaglandins increase uterine
contractions, increase sensitivity to oxytocin and soften the cervix
! Increases oxytocin receptors => increases effects of oxytocin
! Net effects => Increases uterine contractibility and promote cervical dilation and
effacement
•
Oxytocin initiates and sustains contractions:
! Few receptors in late pregnancy
! Peak level in early labour (oestrogen stimulates expression) => stimulates uterine
contractions
! Enhances prostaglandin synthesis
! Increases cytosolic calcium and myo-‐contractibility
! Can be used to enhance labour or induce labour (e
...
syntocinon)
! Positive feedback effects
Initiation of labour
•
Mechanism uncertain: foetal initiation?
•
Complex interaction between maternal, placental and fetal factors:
! Change in the estrogen:progesterone ratio => increased oestrogen:progesterone
ratio is believed to play a key role (oestrogen prepares and stimulates uterine
contractions)
! Fetal adrenals and pituitary hormones may control the timing of the onset of
labour => directly affect placenta by decreasing progesterone and increasing
oestrogen
! Myometrial stretch due to foetus increases the excitability of myometrial fibres
=> +ve feedback loop
...
Duration of latent phase is very variable: can be a few days or
much shorter
...
Cervix
softens & shortens (effacement)
...
! Active phase: cervix dilates from 4 cm to 10 cm (full dilatation is approximately
10cm): in the active first stage the cervix begins to dilate more rapidly, and
contractions are longer, stronger, and closer together
...
Presenting part descends more deeply
...
! NB: The cervix dilates at an average of approximately 1cm per hour
...
•
Second stage of labour:
! The second stage begins with full dilatation (approx 10cm)
! Powerful sustained uterine contractions + lots of pushing from mother + uterine
retraction => delivery of baby
! Approx 1-‐2 hours in multiparous and 2-‐3 hours in primparous
•
Third stage of labour:
! Expulsion of placenta
! Usually approx 30 mins
First stage of labour (cervical dilation and effacement)
•
Characteristics:
! regular uterine contractions which are progressively more rhythmic / stronger /
painful
! Progression to complete cervical dilatation (10cm)
! Presenting part (usually head) has descended into pelvis through the pelvic inlet
(engagement) – usually OT position
•
latent phase and an active phase
•
latent phase:
! mild, irregular uterine contractions
! cervix softens, thins and shortens (effacement)
•
Active phase:
! cervix dilates from 4 cm to full dilation (10cm)
! contractions progressively more rhythmic / stronger / painful
! descent of the presenting part into the pelvis through the pelvic inlet
(engagement)
! SO DESCENT AND ENGAGEMENT OCCUR IN FIRST STAGE
•
•
Monitor progress with Bishops score: cervical effacement, cervical dilation, cervical
position, cervical consistency, and foetal station
PGs are used in stage 1 to help with cervical ripening (effacement and shortening)
and are indicated with low Bishops score (e
...
Bishops <6)
Second stage of labour (birth)
•
Begins with full dilation of the cervix, continues to complete formation of the curved birth
canal and ends with birth of the baby
•
Complete dilatation (approx 10cm) => delivery of the fetus can occur
•
Expulsive stage, with stronger and more frequent contractions
•
In nulliparous women (a woman who has never completed a pregnancy beyond 24 weeks):
second stage is considered prolonged if it exceeds 3 hours (with regional anaesthesia e
...
spinal or epidural) or 2 hours (without regional anaesthesia)
•
In multiparous women (pregnancies of ≥24 weeks gestation ending in birth, which was
either live or stillborn), the second stage should be considered prolonged if it exceeds 2
hours (with regional anaesthesia) or 1 hour (without)
...
•
NB: epidural can slow down contractions and can decreases mothers awareness of
contractions => she does not know when to push
•
So normal durations of second stage of labour (without regional anaesthesia)
•
Nulliparous => two hours
•
Multiparous => one hour
•
Consider stimulating labour if second stage is prolonged due to problems with uterine
contractions (e
...
with syntocinon -‐ no need for PGs as the cervix is fully dilated)
•
NB: PGs are used in stage 1 to help with cervical ripening (effacement and shortening) and
are indicated with low Bishops score (<6)
Third stage of labour
•
Begins with delivery of the baby and ends with expulsion of the placenta & fetal membranes
•
Expulsion of the placenta and foetal membranes e
...
chorion (membrane which is part of
the placenta) and amnion (membrane which surrounds amniotic fluid)
•
Usually occurs within 10 minutes, however may last 30 minutes
•
Two methods of managing:
! Traditional / Expectant management (active monitoring) => spontaneous
delivery of the placenta and membranes, with no interference (takes longer and
may be associated with heavy blood loss e
...
postpartum haemorrhage)
! Active management – most commonly used: prophylactic administration of
oxytocin (syntocinon) and ergometrine
...
Combination of
syntocinon (oxytocin) and ergometrine = syntometrine
...
Contraction of the
uterus can prevent against PPH
...
•
Cervical effacement: cervical effacement refers to a thinning and shortening of the cervix
...
Prior to effacement, the cervix is like a long bottleneck,
usually about four centimeters in length
...
When the cervix effaces, the mucus plug is
loosened and passes out of the vagina
...
Effacement (thinning
and shortening) is accompanied by cervical dilation
...
g
...
Neither Braxton Hicks
or true labour
Braxton-‐Hicks contractions
•
Braxton Hicks contractions are sporadic uterine contractions that sometimes start around six
weeks into a pregnancy
...
•
Once or twice per hour, and often just a few times per day
•
Irregular, do not increase in frequency or intensity
•
Resolve with ambulation (walking about) or a change in activity
•
Painless tightening of the uterus
•
Thought to prepare the uterus for true contractions
True Labour Contractions
•
•
Accelerate to 1 every 2-‐3 minutes (e
...
3 to 5 /10)
•
Start infrequently 1 every 10-‐15 minutes (measured in ten minute intervals e
...
1/10 mins)
Longer and more intense than Braxton-‐Hicks
•
Painful
•
Progressive cervical change (ripening/softening, effacement and dilation)
•
Do not resolve with change of position
Characteristic of uterine contraction
•
The myometrium is the middle layer of the uterine wall, consisting mainly of uterine smooth
muscle cells (also called uterine myocytes)
•
Uterine muscle: smooth muscle (myocyte) in connective tissue (collagen & elastin)
...
•
Cervical tissue: collagen tissue, smooth muscle, elastin, held together by connective tissue
ground substance
•
Contraction and retraction => shortening of the muscle fibres => propelling fetus forward
down the birth canal
•
NB: retraction = contraction without regaining normal length => musle fibres shorter with
every contraction => cause shortening of the muscle fibres and uterus becomes
progressively smaller
...
g
...
•
Synchronisation of contraction waves from both ostia (spread together)
•
Uterine pacemaker cells is same type of muscle as rest of uterus (unlike cardiac pacemaker)
•
Polarity:
! Upper segment contracts & retracts (e
...
muscle fibres shorten with each
contraction => uterus becomes smaller)
...
The resting period is important to allow the woman and uterus
muscle to rest
...
Intensity of contractions
•
magnitude of uterine systole (contraction)
•
maximum intensity during second stage (birth of baby)
•
grades: mild, moderate, strong (measured on palpation during contraction)
Frequency
•
normal: up to 4 every 10 mins (4 in 10) during stage 2
•
allows time for resting tone
•
The resting period is essential for “rest” so that the woman and uterus is not overworked
...
g
...
Therefore babies normally
engage transversely (ROT or LOT position)
...
•
Shape of passage changes as baby progresses downwards through the pelvic cavity
•
At pelvic outlet: AP diameter > transverse diameter
! Pelvic outlet narrower => baby internally rotates head through cavity & outlet
! The ideal position for the foetus to pass through the pelvic outlet is in the
occipito-‐anterior (direct OA, LOA or ROA) position e
...
the foetus should
internally rotate from transverse (ROT or LOT) to OA (direct OA, ROA or LOA) as it
passes through the pelvic cavity
! The position of the foetus head as it comes through the pelvic outlet is usually
left occiput anterior (LOA), however occasionally the baby may be right occiput
anterior (ROA)
Types of Pelvis
•
There are four main pelvic types:
! Gynecoid (“female”) pelvis: It has an almost round brim and will permit the
passage of an average-‐sized baby with the least amount of trauma to the mother
and baby in normal circumstances
...
! Android (“male”) pelvis: It has a heart-‐shaped brim and is quite narrow in front
...
The pelvic cavity and outlet is often narrow, straight and
long
...
Women with this shape pelvis may have
babies that lie with their backs against their mothers’ backs and may experience
longer labours
...
Baby can get
caught if android pelvis
...
The
outlet is large, although some of the other diameters may be reduced
...
! Platypelloid pelvis: It has a kidney-‐shaped brim and the pelvic cavity is usually
shallow and may be narrow in the antero-‐posterior (front to back) diameter
...
During labour the baby may have difficulty entering the
pelvis, but once in, there should be no further difficulty
...
Liquor is contained within the amniotic sac/cavity (amnion)
...
It is in close contact with the amnion
...
Very rare!
•
Rupture can sometimes initiate labour e
...
preterm labour
•
Important to assess for meconium stating of the liquor which can suggest foetal distress,
particularly with an abnormal CTG
Fetal Position
Normal position
•
Lie:
! The lie is the relationship between the longitudinal axis of fetus and the
longitudinal axis of the mother
! Longitudinal lie is the normal and ideal situation (with cephalic presentation)
! Longitudinal lie => axis of baby is parallel to axis of mum => either cephalic or
breech presentation
•
Presentation:
! The presentation = the leading part of the fetus which occupies the lower pole of
the uterus
! The cephalic presentation (head first) is the normal and ideal presentation
! Can also be breech
•
Presenting part:
! The presenting part is the portion of the foetal body that is either foremost
within the birth canal or in close proximity to it
...
! Cephalic presentation can result in vertex (crown e
...
top of head) presenting
part or brow presenting part
! Breech can result in buttock presenting part etc
! Normal = vertex presenting part
•
Engagement
! Engagement = occurs when widest diameter of presenting part has entered pelvis
through pelvic inlet
! Corresponds with foetal station 0
! The fetus is engaged if the widest leading part (typically the widest circumference
of the head) has passed through the pelvic inlet
...
g
...
! For a cephalic presentation the denominator is the occiput, and for a breech the
denominator is the sacrum
...
•
Flexed head e
...
chin at chest is normal
Abnormal presentation (malpresentation) and position (malposition)
•
Lie:
! Longitudinal lie with breech
! Oblique lie
! Transverse lie (labour will not go ahead if transverse)
...
Can cause small for dates on obs exam
...
The 2 parietal bones may also slip under each
other
...
•
Occiput = area behind posterior fontanelle
•
Vertex (crown) = area between anterior and posterior fontanelle and between parietal
eminences
...
•
Brow = area between anterior fontanelle and root of face (can get brow presenting part in
cephalic presentation)
Mechanism of labour
•
The Cardinal Movements: change position of foetus head in pelvis
•
Described in relation to a “normal” vertex (crown: area between anterior and posterior
frontanelles) presentation
...
Engagement of the babies head downwards from abodmen into the pelvis
through the pelvic inlet: occipito-‐transverse (ROT or LOT) – as the transverse
diameter of the pelvic inlet > AP diamter
2
...
Flexion of head => chin close to chest
4
...
Crowning and extension (of head) resulting in delivery of the head
6
...
Expulsion (firstly the anterior shoulder under the symphysis pubis, followed by
the rest of baby)
Normal variations
•
Engagement of head in multigravida (woman who have been pregnant more than once):
only in late labour does the head suddenly come down then traverses quickly
•
Moulding: The five separate bones (2 frontal, 2 parietal and 1 occipital) of the fetal skull are
joined together by membranous sutures, which are quite flexible during the birth
...
Movement in the sutures and fontanels allows
the skull bones to overlap each other to some extent as the head is forced down the birth
canal by the contractions of the uterus
...
Bones overlap during birthing
...
Once born, come apart
...
g crown) during labour and delivery
(presenting part e
...
crown) due to pressure effects
...
More likely to occur the longer it takes to dilate
...
Can cross sutures
...
Descent of head
•
Abdominal fifths:
! Foetal head is divided into fifths in the coronal plane
! If you are able to feel the entire head in the abdomen it is 5/5th’s palpable =>
not engaged
! When only two-‐fifths of the fetal head is palpable, the widest part has descended
into the pelvis => therefore the head is engaged (3/5ths engaged) => corresponds
to foetal 0 station
! If you are not able to feel the head at all abdominally it is 0/5th’s palpable => fully
engaged
•
Cervical assessment
! Bishops score (cervix score) can indicate behaviour and progression of cervix
...
It has also been
used to assess the odds of spontaneous preterm delivery
...
g vaginal PGs
! A score of 9 or more indicates that labour will most likely commence
spontaneously
...
NB: Crowning = the appearance of a large segment of the fetal scalp (region between the anterior
and posterior fontanelle) at the vaginal orifice in childbirth
...
Partogram
•
Partogram is a composite graphical record of key data (maternal and fetal) during labour
entered against time on a single sheet of paper
...
•
Three major components: progression of labour, maternal condition and medication, and
foetal condition
•
Progression of labour
! Contraction pattern: frequency, amplitude (measured via palpation), duration
! Cervical os dilation
! Bishops score
! Descent e
...
foetal station
•
Fetal condition:
! Fetal HR and pattern
! Fetal monitoring in a graph: CTG (Cardiotocography)
! Character of the amniotic fluid (liquor) and volume: should be clear (assess for
meconium staining): clear (C) or meconium staining (M)
! Presence of moulding
! Presence of caput
•
Maternal condition
! BP and pulse rate
! Temperature
! Urine volume
! Urine for protein, glucose, and acetone
! Medications e
...
oxytocin (syntocinon) and pain releif
Parotgram is essential for deciding what interventions need done
...
It has also been used to assess the odds of
spontaneous preterm delivery
•
Components (4Cs + F):
! Cervix position
! Cervix consistency (cervical ripening): firm, intermediate or soft
! Cervical effacement (thinning and shortening of cervix): Effacement is a measure
of the stretch already present in the cervix
...
! Cervical dilation: Dilation is a measure of the diameter of the stretched cervix
...
! Fetal station: Fetal station describes the position of the fetus' head in relation to
the distance from the ischial spines, which can be palpated deep inside the
posterior vagina (approximately 8–10 cm) as a bony protrusion
...
Positive numbers => baby has made more of a descent
...
For example, with a positive foetal
station and enagement, mid cavity forceps can be used
...
•
A Bishops score of 5 or less (<6) suggests that labour is unlikely to start without induction
e
...
vaginal PGs
...
Usueful for prolonged labour
...
g
...
Often first line for C-‐section; unless emergency => GA (as
spinal is trickier to perform and more time consuming)
...
It is also helpful just before an episiotomy
...
Continuous support for women
during childbirth can reduce the incidence of operative vaginal delivery (15 trials; n=13 357; RR
0
...
82–0
...
Use of any upright
or lateral position in the second stage of labour compared with supine or lithotomy positions
was associated with a reduction in the number of assisted deliveries (20 trials; n=6135; RR 0
...
69–0
...
Epidural analgesia compared with non-‐epidural methods is associated with an
increased incidence of operative vaginal deliveries, (presumably due to increasing the duration of
the second stage of labour) (17 trials; n=6162; OR 1
...
24–1
...
60; 95% CI –3
...
3
...
The fetus must be in a cephalic presentation, and the sutures should be palpated to
determine the position as occipitoanterior or occipitoposterior
...
Vacuum-‐assisted delivery should not be performed if the fetus has a suspected bone
mineralization or bleeding disorder, or if cephalopelvic disproportion exists
Although there is little supportive evidence, it is recommended that vacuum
deliveries not be routinely performed in pregnancies at less than 34 weeks' gestation
because of the potential increased risk of fetal intracranial hemorrhage
When the presenting part is at the ischial spines the station is 0 (synonymous with
engagement)
...
Clinical evidence of
engagement on examination exists when the leading edge of the fetal skull is at or
below the ischial spines (+0 station)
Blood loss
Normal
•
Volume < 500 mls during delivery
Abnormal
•
Before delivery (APH): any significant loss apart from bloody “show” (passage of a small
amount of blood or blood-‐tinged mucus through the vagina near the end of pregnancy
...
)
•
After delivery (post partum haemorrhage PPH) > 500 mls
Placental separation
•
Separation takes place through the spongy layer of decidua basalis (mucosa epithleial layer
of uterus), as a result of the uterine contractions being added to the retraction (shrinking)
of the uterus that occurs after the birth of the child
•
Plane of separation: Spongy layer of decidua basalis (mucus membrane in the pregnant
uterus)
•
Mechanics: Shearing force (inelastic placenta / reduced surface area on the placental bed
due to the sustained contraction of the uterus )
•
Membrane separate by being thrown into folds in the upper part of the uterus and by being
sheared off during expulsion in the lower part
...
•
Syntometrine (ergometrine + syntocinon) or syntocinon can be given in the third stage of
labor to prevent postpartum hemorrhage by causing smooth muscle tissue in the blood
vessel walls to narrow, thereby reducing blood flow
...
Occurs in the 6
weeks post-‐natally
...
! Oxytocin contracts smoothe muscle of breasts => secretion of milk
! Colostrum (initial discharge) rich in immunoglobulin, protective
...
g
...
g
...
Inject anaesthetic
into the epidural space
...
Due to its hypotensive
effects, it is the preffered analgesia in pre-‐eclampsia
...
Engaged when foetal head has reached +0
station
...
•
Signs of obstruction
Suspected Delay (Stage 1)
•
Nulliparous: <2cm dilation in 4 hours
•
Parous: <2cm dilation in 4 hours or slowing in progress
•
Use Bishops score
•
Rememeber on average, females dilate at approx 1cm per hour
Suspected Delay (Stage 2)
•
Nulliparous:
! No birth of baby in 2 hours (no regional anaesthesia)
! No birth of baby in 3 hours (with regional anaesthesia)
•
Parous-‐ multiparous:
! No birth of baby in 1 hour (no regional anaesthesia)
! No birth of baby in 2 hours (with regional anaesthesia)
Suspected Delay (Stage 3)
•
Plancenta not expulsed in 30 mins
Causes of failure to Progress: the 3 P’s
•
Power:
! Inadequate contractions: frequency, duration and/or strength
•
Passages:
! Short stature
! Trauma
! Shape e
...
android pelvis
•
Passenger:
! Big Baby (macrosomia)
! Malposition: Usually the fetal head engages into the pelvis through the pelivic
inlet in the occipito-‐transverse position (e
...
ROT or LOT) due to the wide pelvic
inlet (transverse diameter > AP diameter) and then undergoes a short internal
rotation to occipito-‐anterior (direct OA, LOA or ROA) in the mid-‐cavity for exiting
the pelvic outlet (where AP diameter is > than transverse diameter)
...
Anything but OA (direct OA, ROA and LOA) is classed as malposition
...
g
...
5cm and AP diameter 11cm => transverse > AP =>
right/left occipito-‐transverse (ROT or LOT) preferred for engagement
...
5cm => AP > transverse =>
occipito-‐anterior (ROA, LOA or direct OA) presentation preferred
...
The Passenger Attitude (flexion/extension)
•
•
The head should be sharply flexed so that the chin is in close contact with the chest
•
As a general rule, the fetus forms a shaped mass roughly to the shape of the uterus
•
The fetal attitude is the posture of the foetus
The head extends once the foetus has travelled through the pelvic outlet (“crowning”)
Assessing Progress: The Partogram
•
A graphic representation of the progress of labour, maternal well being, and foetal well
being
•
Commence as soon as woman enters labour ward
•
Three major categorises of measurement:
! Maternal well being: HR, BP, temp, medications etc
! Foetal well being: HR, amniotic fluid characteristics, descent, obstruction e
...
moulding
! Labour progression: cervical dilation, effacement, contractions, Bishops score
Identifying Fetal Distress
Intra-‐partum Fetal Assessment
•
Doppler auscultation of fetal heart (assess HR – should be 110-‐160)
! Stage 1 of labour: During and after a contraction or every 15 minutes
! Stage 2 of labour: Every 5-‐10 minutes
•
Cardiotocograph (CTG) +/-‐ STAN (ST segment analysis on fetal ECG)
•
Colour of amniotic fluid: normally the amniotic fluid is colourless
...
Blood may also be present in the amniotic fluid (recorded
as B on partogram)
...
This means that
the baby has had a bowel movement before or during labour, and it is a sign that the baby
possibly is, or has been, in distress, or that the baby's gut is mature
...
Amniotic fluid is normally clear, often with flecks of white vernix
...
The midwife can tell from the colour of
the waters whether the meconium is fresh or old
...
If the waters are brownish or golden, this suggests the meconium is
old, i
...
was passed some time ago
...
•
Epidural analgesia
•
VBAC (vaginal birth after caesarean)
•
PROM (prelabour rupture of the membranes) >24h
•
Sepsis
•
Induction and augmentation of labour
Continuous monitoring of fetal heart is essential
...
If foetal distress on CTG + meconium staining => strong indication for C-‐section
...
It is the one of the most common pathological cause of
late pregnancy bleeding (antepartum haemorrhage APH)
...
If a large amount of the placenta
separates from the uterus, the baby will probably be in distress until delivery and
may die in utero, thus resulting in a stillbirth
...
Bleeding may be absent per vagina! Bleeding into the myoemtrium can
cause early contractions and preterm labour
...
May or may not present with foetal distress depending on the severity of
the placenta abruption
...
These vessels
course within the membranes (unsupported by the umbilical cord or placental
tissue) and are at risk of rupture when the supporting membranes rupture
...
Charachterised by foetal distress shortly after ROMs
...
It is an obstetric emergency during
pregnancy or labor that imminently endangers the life of the fetus
...
! Placenta dysfunction
! Uterine Rupture
! Feto-‐maternal Haemorrhage
! Uterine Hyperstimulation
! Regional Anaesthesia
! NB: Vasa praevia = low set fetal blood vessel (close proximity to internal os);
placenta praevia = low set placenta (e
...
placenta attachment in close proximity
to internal os)
! NB: Placenta praevia does not often cause foetal distress unless it transforms into
placenta abruption
•
Subacute:
! Hypoxia
CTG Assessment
CTG Interpretation
•
Use the pneumonic “DR C BRAVADO”:
! DR: Determine Risk
! C: Contractions
! BRa: Baseline Rate
! V: Variability
! A: Accelerations
! D: Decelerations
! O: Overall impression
Define risk
•
You first need to assess if this pregnancy is high or low risk
•
This is important as it gives more context to the CTG reading e
...
If the pregnancy is high
risk, your threshold for intervening may be lowered
•
Reasons a pregnancy may be considered high risk are shown below
Maternal medical illness
•
Gestational diabetes
•
Hypertension
•
Asthma
Obstetric complications:
•
Multiple gestation
•
Post-‐date gestation
•
Previous cesarean section
•
Intrauterine growth restriction
•
Premature rupture of the membranes
•
Congenital malformations
•
Oxytocin induction/augmentation of labor (avoid medical induction in foetal distress)
•
Pre-‐eclampsia
Other risk factors
•
No prenatal care
•
Smoking
•
Drug abuse
Contractions
•
Record the number of contractions present in a 10 minute period e
...
3 in 10
•
Each big square is equal to 1 minute, so you look how many contractions occurred in 10
squares
•
Individual contractions are seen as peaks on the part of the CTG monitoring uterine activity
•
You should assess contractions for the following:
! Frequency: How often do they occur? E
...
3 in 10 minutes
! Duration: how long do the contractions last?
! Intensity: how strong are the contractions? (assessed by magnitude of
contraction on CTG and by palpation)
Baseline rate (Bra) of foetal heart
•
•
Look at the CTG & assess what the average heart rate has been over the last 10 minutes
•
Ignore any Accelerations or Decelerations
•
The baseline rate is the average heart rate of the foetus in a 10 minute window
A normal foetal heart rate is between 110-‐150 bpm
Foetal Tachycardia
•
Foetal tachycardia is defined as a baseline heart rate greater than 160 bpm
•
Can indicate foetal distress
•
It can be caused by:
! Foetal hypoxia
! Chorioamnionitis: if maternal fever also present
! Hyperthyroidism
! Foetal or Maternal Anaemia
! Foetal tachyarrhythmia
Foetal Bradycardia
•
Foetal bradycardia is defined as a baseline heart rate less than 120 bpm
...
•
Causes of prolonged severe bradycardia are:
! Prolonged cord compression
! Cord prolapse
! Epidural & Spinal Anaesthesia
! Maternal seizures
! Rapid foetal descent
! Placenta abruption
•
If the cause of severe prolonged bradycardia cannot be identified and corrected,
immediate delivery is recommended
Variability
•
Baseline variability refers to the variation of foetal heart rate from one beat to the next
•
Variability occurs as a result of the interaction between the nervous system,
chemoreceptors, baroreceptors & cardiac responsiveness
...
•
This is because a healthy foetus will constantly be adapting it’s heart rate to respond to
changes in its environment
•
Normal variability is between 10-‐25 bpm (e
...
large variability)
•
To calculate variability you look at how much the peaks & troughs of the heart rate deviate
from the baseline rate (in bpm)
•
Variability can be categorised as:
! Reassuring: ≥ 5 bpm
! Non-‐reassuring : < 5bpm for between 40-‐90 minutes
! Abnormal : < 5bpm for >90 minutes
•
Reduced variability can be caused by:
! Foetus sleeping: this should last no longer than 40 minutes (most common cause)
! Foetal acidosis (due to hypoxia): more likely if late decelerations also present
! Foetal tachycardia
! Drugs : opiates, benzodiazipine’s, methyldopa, magnesium sulphate
! Prematurity: variability is reduced at earlier gestation (<28 weeks)
! Congenital heart abnormalities
Accelerations
•
Accelerations are an abrupt increase in baseline heart rate of >15 bpm for >15 seconds
•
The presence of accelerations is reassuring
•
Antenatally there should be at least 2 accelerations every 15 minutes
•
Accelerations occurring alongside uterine contractions is a sign of a healthy foetus (uterine
contractions cause decreased O2 delivery to foetus due to pressure effects => compensatory
acceleration of HR)
•
However the absence of accelerations with an otherwise normal CTG is of uncertain
significance
Decelerations
•
Decelerations are an abrupt decrease in baseline heart rate of >15 bpm for >15 seconds
•
There are a number of different types of decelerations, each with varying significance
Early deceleration
•
•
This is due to increased foetal intracranial pressure causing increased vagal tone (Cushing
reflex) => bradycardia
•
Early decelerations start when uterine contraction begins & recover when uterine
contraction stops
It therefore quickly resolves once the uterine contraction ends & intracranial pressure
reduces
•
This type of deceleration is therefore considered to be physiological & not pathological
•
Appreciate belowthat the decelleations are directly above the uterine contractions => early
decelerations
Variable deceleration
•
Variable decelerations are seen as a rapid fall in baseline rate with a variable recovery phase
•
They are variable in their duration & may not have any relationship to uterine contractions
•
They are most often seen during labour & in patients with reduced amniotic fluid volume
(oligohydraminos)
•
Variable decelerations are usually caused by umbilical cord compression => WORRYING
Late deceleration
•
Late decelerations begin at the peak of uterine contraction & recover after the contraction
ends
...
25) it indicates significant foetal hypoxia & the need
for emergency C-‐section or operative vaginal delivery (hypoxia causes acidosis due to
tissue anaerobic glycolysis)
•
We use C-‐section, as medical induction of labour can increase foetal distress
•
Appreciate below that the decelerations begin at peak of uterine contraction and continue
after the uterine contraction
Prolonged deceleration
•
A deceleration that last more than 2 minutes
•
If it lasts between 2-‐3 minutes it is classed as Non-‐Reasurring
•
If it lasts longer than 3 minutes it is immediately classed as Abnormal
•
Action must be taken quickly e
...
Foetal blood sampling / emergency C-‐section / operative
vaginal delivery (if possible)
Overall impression
•
•
Once you have assessed all aspects of the CTG you need to give your overall impression
The overall impression can be described as either:
! Reassuring
! Suspicious
! Pathological
•
The overall impression is determined by how many of the CTG features were either
reassuring, non-‐reassuring or abnormal
...
Actually no! The variability is of the baseline, excluding
accelerations and decelerations
...
! Accelerations: None
! Decelerations: Late deccelerations (occurring at max of uterine contractions &
recovering after contraction ends)
! Overall impression: The presence of late decelerations is taken seriously & foetal
blood sampling for pH is indicated
...
g
...
These drugs are also useful for when delivery would result in premature
birth as also buys time for the administration of betamethasone, a glucocorticoid drug which
greatly accelerates fetal lung maturity (increases surfactant production which prevents
against RDS), but takes one to two days to work
...
g
...
This is because
palpation can cause local placental separation and precipitate massive
antepartum hemorrhage (APH)
•
Fetal blood sampling for blood gases
•
Operative Delivery: can go straight to C-‐section if severe signs of distress
Fetal Blood Sampling
•
Fetal scalp pH testing is a procedure performed when a woman is in active labor to
determine if the baby is getting enough oxygen
...
25 -‐ 7
...
20 -‐ 7
...
20 => deliver with surgical methods e
...
operative vaginal
delivery with forceps or ventouse suction (medical induction e
...
with
syntocinon and PGs is contraindicated in foetal distress) or C-‐section
Operative Vaginal Delivery
•
“Standard” Indications:
! Delay (failure to progress during stage 2; the cervic must be fully dilated
and the foetus must be engaed before considering operational vaginal
delivery) e
...
due to malposition (e
...
ROP, OP or LOP)
! Fetal distress
•
“Special” Indications:
! Maternal cardiac disease
! Severe PET (preeclampsia) or eclampsia
! Intra-‐partum haemorrhage (haemorrhage during labour)
! Umbilical cord prolapsed during stage 2
•
•
No indication is absolute
...
They're
curved to fit around the baby's head
...
With a contraction and your pushing, an
obstetrician gently pulls to help deliver your baby
...
Some forceps are specifically designed to turn the baby to the right position to be
born, for example, if your baby is lying in an abnormal position (malpositon) such as facing
upwards (occipito-‐posterior position) or to one side (occipito-‐transverse position)
...
! More commonly used when babys head is high in the pelvis (but must be
engaged) or when baby is in malposition
•
Use the most appropriate instrument for individual circumstances
...
Caesarean section (C-‐section)
•
Rate is increasing (NHS Tayside 27%)
•
Main indications:
! Previous CS (C-‐section)
! Fetal distress
! Failure to progress in labour and operative delivery CI (e
...
not engaged)
! Breech presentation
! Maternal request
•
4 X greater maternal mortality associated with CS (C-‐section)
•
Morbidity:
! Sepsis
! Haemorrhage
! VTE= > LMWH propylaxis
! Trauma
! TTN (transient tachypnoea of the newborn)
! Subfertility
! Regret
! Complications in future pregnancy
Conclusions
•
•
Progress determined by 3 P’s: power of contractions (frequency, duration and strength),
passage, and passenger
•
Partogram + Bishops score is used to identify and manage failure to progress
•
Fetal distress is common but recognition and appropriate management will reduce perinatal
morbidity
•
Labour is process leading to expulsion of fetus (stage 2) and placenta (stage 3)
Most women will have a spontaneous vaginal delivery (SVD)
COMMON SURGICAL PROBLEMS OF THE NEONATE
•
In medical contexts, newborn or neonate refers to an infant in the first 28 days after birth
...
g
...
g
...
Incarceration is the most common cause of bowel obstruction in
infants and children
...
In cases of strangulation,
ischemic necrosis develops, and intestinal perforation may result, representing a
true medical emergency
...
•
DD: In boys, differentiating between a hernia and a hydrocele is not always easy
...
Can get above a hydrocele but
cant get above a hernia
...
Emesis caused by an obstruction
proximal to the ampulla of Vater is usually of gastric content
...
In distal ileal obstructions, vomit is
feculent
...
•
Newborns with jejunoileal atresia or stenosis present with bilious vomiting and obstructive
(conjugated hyperbilirubinaemia) jaundice; these infants may not pass meconium in the
first day of life
...
•
Abdominal distention occurs more often in patients with ileal atresia
...
•
Patients (often infants) present acutely with midgut volvulus (twisting of a loop of intestine
around its mesenteric attachment site), manifested by bilious vomiting, crampy abdominal
pain, abdominal distention, and the passage of blood and mucus in their stool
...
•
Malrotation can also be entirely asymptomatic
...
•
Meconium ileus is often the first sign of cystic fibrosis
...
•
In patients with meconium ileus, symptoms depend on the level of the obstruction (which is
usually the terminal ileum) and may include vomiting (usually bile-‐stained), failure to pass
meconium in the first 48 hours of life, and possible abdominal distension
...
•
Causes of delayed passage of meconium = CF and Hirschprungs
Necrotising enterocolitis (NEC)
•
Necrotizing enterocolitis (NEC) is a medical condition primarily seen in premature infants,
where portions of the bowel undergo necrosis (tissue death)
...
•
Initial symptoms include feeding intolerance, increased gastric residuals, abdominal
distension and bloody stools
...
•
Often occurs after RDS
•
Breast feeding is the best intervention to prevent NEC
•
CF is among the most common causes of obstruction in neonate
•
AR genetic disorder
•
CF results in the production of thick secretions
•
The meconium sometimes becomes thickened and congested in the ileum, a condition
known as meconium ileus
...
In cystic
fibrosis, the meconium can form a bituminous black-‐green mechanical obstruction in a
segment of the ileum
...
Thus, it allows oxygenated blood from the
placenta to bypass the liver
! Foramen ovale: R to L shunt (to bypass lungs) from R atrium to L atrium
! Ductus arteriosus: R to L shunt from pulmonary trunk to proximal descending
aorta
•
Oxygenated blood from placenta travels to the foetus via the single umbilical vein
•
The oxygenated blood bypasses the liver via the ductus venosus
•
Arrives in right atrium via IVC
•
Majority travels from right atrium to left atrium via foramen ovale (R to L shunt)
...
•
Blood which does not travel through the foramen ovale travels from right atrium into right
ventricle and then into the pulmonary trunk
...
Surfactant deficiency => decreases lung
compliance => restrictive lung disease which makes it harder to inhale and inflate lungs, as
the alveoli are prone to collapsing
...
It is
essential that fluid be breathed into the lungs in order for them to develop normally
...
Therefore amniotic fluid prepares the lungs, kidneys and GI tract for their
extra-‐uterine job
...
This triggers it to take
the first breath, within about 10 seconds after delivery
...
Stimulus causes chest expansion and diaphragm contraction => huge negative intrathoracic
pressure => results in large breaths
•
Cries: baby breathes out against partially closed cords, generates PEEP (positive end
expiratory volume) => Drives fluid back into interstitium, which is then absorbed and
transported by lymphatics
•
With the first breaths, there is a fall in pulmonary vascular resistance and an increase in the
surface area available for gas exchange
...
Oxygenated blood
now reaches the left atrium and ventricle, and through the descending aorta reaches the
umbilical arteries
...
As the pulmonary circulation increases there is an
equivalent reduction in the placental blood flow which normally ceases completely after
about three minutes
...
•
Closure of formaen ovale: The increase in pulmonary venous return results in left atrial
pressure being slightly higher than right atrial pressure (reverse from foetal pressure
differences LA pressure >> RA pressure), which closes the foramen ovale
...
Within minutes or up to a few days after birth, the ductus arteriosus closes due to a
decrease in PGs (due to removal of placenta, which is a major source of foetal PGs; PG
inhibitors can cause premature closure of duct; PG infusions can keep duct open which is
important for duct dependent cyanotic heart defects) and increased O2 tension
...
•
The higher blood oxygen content of blood within the aorta, and the removal of the placenta,
stimulates the constriction and ultimately the closure of this fetal circulatory shunt
...
During this transition, some types of congenital
heart disease that were not symptomatic in utero during fetal circulation will present with
cyanosis or respiratory signs
...
5kPa (fetal level) to 9-‐13kPa => baby changes colour
from blue to pink
! Decrease in pulmonary vascular resistance + reduced flow back to placenta =>
increased pulmonary blood flow => pressure in left heart > pressure in right heart
•
Detachment from placenta and clamping of cord:
! Transition from the placenta to the lungs must take place quickly but not
instantly
...
This leads to a number of changes which are not completely
understood
...
This differential in resistance results in a high flow through the
placenta and a low flow through the pulmonary circulation
...
The output of the heart does
not change so the output is reduced to the other organs, especially the placenta
as a result of constriction within the umbilical arteries (due to increased PP of
O2)
...
The two effects co-‐operate to redirect blood to the newborn infant’s
lungs and away from the placenta so that within a few minutes, sometimes in
less than a minute in a vigorous baby, the pulmonary circulation is fully opened
up and the placental circulation completely closed down
...
This facilitates detachment of
the placenta
...
However we must balance the risk with
the benefits of delayed clamping
...
In this
review, delayed clamping, as contrasted to early (< 1 minute), resulted in no
difference in risk of severe maternal postpartum hemorrhage or neonatal
mortality
...
5 g/dL with half the risk of being iron deficient at three and six
months, but an increased risk of jaundice requiring phototherapy
...
Remember that prostaglandins cause the ductus arteriousus to remain open
...
However, pathological processes such as PTE
can cause RA pressure > LA pressure which can even result in an embolism from a
DVT travelling into the systemic circulation and causing a stroke (paradoxical
embolism)
•
Ductus arteriosus
! Becomes ligamentum arteriosus
! Persistent ductus arteriosus (PDA) if persists: causes L to R shunt (Acyanotic)
which allows allows oxygen-‐rich blood from the aorta to mix with oxygen-‐poor
blood from the pulmonary artery
...
If pulmonary HT
continues, the pressures in R can become > than L => Eisenmengers syndrome
can occur (cyanotic R to L shunt)
...
g
...
6
Nutrition
•
Gut prepared by in utero swallowing of amniotic fluid => produces meconium
•
Endocrine factors: Thyroxine and corticosteroids have a role in maturing the gut
•
Feeding: Introduction of milk causes increase in intestinal enzymes
•
Breast milk: Growth factors in breast milk regulate adaptive changes
•
Bacteria: The gut becomes colonised with bacteria following delivery (some bacteria are
important for Vit K production, one factor for why newborns are sometimes deficient in Vit
K)
Breast Feeding
•
Baby starts to suckle (stimulus) => signals sent to hypothalamus => feedback loop causes
increase in supply
•
Hormones:
! Oxytocin (posterior pituitary): smooth muscle contraction => milk ejection
! Prolactin (anterior pituitary) => milk production
•
Composition changes:
! Colostrum (IgA rich)
! Foremilk and hindmilk
Benefits of breast feeding
•
Passive immunity:
! IgA => less colds, coughs, ear infections
! Cells
! Promotes healthy colonisation
! Prevents against NEC
•
Growth factors
•
Bonding
•
Maternal health
•
Financial
Haematology
•
Fetal haemoglobin (HbF= alpha 2, gamma 2)
! Becomes disadvantageous
! HbF has a greater affinity for oxygen (shift to left) due to lack of fetal
hemoglobin's interaction with 2,3-‐bisphosphoglycerate (2,3-‐BPG)
! In adult HbA, increase in 2,3 BPG shifts curve to right => gives up O2 more readily
=> useful effect
•
Haematopoiesis moves to bone marrow (which takes over from Liver)
•
Adult HbA (alpha 2, beta 2) synthesised more slowly than Fetal Hb broken down
! Physiological anaemia can occur: Nadir (lowest point) of Hb at 8-‐10 weeks
! Physiological jaundice can also occur due to RBC breakdown and immaturity of
liver
Liver
•
Enzyme pathways present but immature
•
Physiological Jaundice:
! Does NOT occur on first day of life
...
•
Water loss up to around 10% of body weight is important part of adaptation
Adaptation problems
•
Some important ones: not an exhaustive list
! Persistent pulmonary hypertension of newborn or persistent fetal circulation
! Transient tachypnoea of the newborn: associated with C-‐section
! Hypothermia
! Hypoglycaemia (<2
...
•
It can be associated with pulmonary hypertension
...
•
Lung vascular resistance fails to fall => pressure on right side of heart remains > left side of
heart
•
Therefore R to L cyanotic shunts remain:
! Right to left flow at PFO (patent foramen ovale with a R to L shunt)
! Right to left flow at PDA (patent ductus arteriosus with a R to L shunt)
•
Cyanotic heart problem due to R to L shunt (pumping of deoxygenated blood into systemic
circulation) => Blue baby (cyanosis)
•
Causes pulmonary hypertension and right heart strain (due to increased lung resistance)
•
Large difference between pre and post ductal oxygen saturation e
...
large differences
between SpO2 of right arm (pre-‐ductal) and left leg (postductal) due to the R to L shunt PDA
...
g
...
! Eisenmengers: secondary pulmonary HT due to long term L to R shunt can also
result in L to R shunt
! With normal L pressures > R pressures => L to R shunt => acyantoic => no notable
difference between pre and post duct sats (more common)
•
•
Surgery may be required
•
Note: If duct dependent cyanotic heart disease we can keep the duct open with PG infusion
•
PDA can be treated with NSAIDS (e
...
indamethacin and aspirin) which decrease PG activity
=> stimulate closure of the duct
Aspirin should be avoided during the third trimester due to possible bleeding complications
and premature closure of the ductus arteriosus, which may lead to pulmonary vasculature
abnormalities and pulmonary hypertension in the newborn
Transient Tachypnoea of Newborn
•
Lung fluid fails to clear completely
•
Lungs remain waterlogged and stiff
•
Decreased gas exchange
•
Increased work of breathing: Grunting, tachypnoea, recession, nasal flaring – usually
resolves within 1-‐2 days
•
Oxygen requirement
•
Need to consider and exclude:
! Infection
! surfactant deficiency (infant respiratory distress syndrome)
! cardiac disease
! congenital anomalies
•
Risk factors:
! Caesarean section (as vaginal birth helps to clear the fluid from the lungs)
! Especially if not in labour
Hypothermia
•
Babies need help with maintaining temp
! Dry – first stage in neonatal recussitation (in all circumstances)
! Hat
! Clothes
! Blankets
! Skin to skin cuddles
! Incubator +/-‐ humidity
•
More at risk if small or premature
! Low stores of brown fat (thermogensis from fat is key source of heat production
in neonates)
! Little subcutaneous fat (thermogensis from fat is key source of heat production
in neonates)
Hypoglycaemia
•
In neonate, hypoglycemia should be diagnosed if blood glucose is <2
...
g
...
g
...
g
...
g
...
g
...
Immunoglobulin G (IgG) antiplatelet antibodies recognize membrane
glycoproteins and coat the platelets, which then are destroyed by the
reticuloendothelial system, predominantly in the spleen
...
! As part of DIC (thrombocytopenia, low clotting factors, low fibrin and high FDPs)
! HELLP: haemolytic anaemia, elevated liver enzymes, low platelets – seen in
preeclampsia
•
Von Willebrand’s Disease (vWF deficiency): low VWF and prolonged APTT (as VwF binds
Factor VIII), prolonged bleeding time test (in contrast to Haemohillia)
Consequences of failure of Platelet Plug Formation
•
Spontaneous Bruising, Purpura and Petechia
•
Mucosal Bleeding
! Conjunctival
! Epistaxes
! Gastrointestinal
! Menorrhagia – obviously not in pregnancy!
! Post Partum Haemorrhage (PPH)
•
•
Neonatal intracranial haemorrhage: 10% of babies may have thrombocytopenia in
maternal ITP: In ITP, antiplatelet antibodies (IgG) may cross the placenta and cause
significant fetal thrombocytopenia which could result in bleeding complications in the
neonate
Retinal haemorrhages
Screening Tests for Primary Haemostasis
•
Platelet count
•
vWF assay
•
Bleeding time: prolonged with primary haemostasis problems
•
NB: vWD can result in prolonged APTT (secondary haemostatic problem) as VWF is a carrier
protein for FVIII (vWF protects the factor VIII from rapid breakdown within the blood)
...
•
No simple screening tests for other components of primary haemostasis
Secondary Haemostasis: Fibrin Clot Formation
•
Extrinsic pathway:
! Tissue factor and platelets activate the clotting cascade to make thrombin
...
! Factor VII important
...
! PT and INR (modified PT) is a measure of the extrinsic pathway function
...
! F VIII and F IX important
! APTT is a measure of the intrinsic pathway function
•
•
Common pathway: F I, II, V and X
See haematology notes
Failure of Fibrin Clot Formation: causes
•
Single clotting factor deficiency
! Usually hereditary
! Haemophilia A: factor VIII deficiency => affects intrinsic pathway => prolongs
APTT
...
g
...
! Haemophilia B: factor IX deficiency => affects intrinsic pathway => prolongs APTT
...
! NB: Haemophilia does NOT usually manifest clinically in females (as X linked
disorder => females have another X chromosome to compensate), however due
to X linked inactivation females do often have lower levels of clotting factors =>
may cause problems in pregnancy e
...
peri-‐partum haemorrhage (during
labour) or post-‐partum haemorrhage (PPH)
•
Multiple clotting factor deficiencies
! Usually acquired
! Disseminated Intravascular Coagulation (DIC)
! Vit K deficiency (F 2,7,9 and 10)
! Warfarin use (F2, 7, 9 and 10)
! Liver disease: impaired synethesis and/or Vit K deficiency (due to impaired bile
production)
•
Increased fibrinolysis
! usually part of complex coagulopathy
Consequences of failure of Fibrin Clot Formation (secondary haemostasis)
•
Often no characteristic clinical syndrome however may present with deep bleeds
•
Deep bleeds:
! Bleeding in to joints (haemarthrosis)
! Soft tissue bleeds e
...
intramuscular bleed or subcut bleeds
•
May be combined primary/secondary haemostatic failure
•
Pattern of bleeding depends on
! Single/multiple abnormalities
! The clotting factors involved
Disseminated Intravascular Coagulation
•
•
Wide spread inflammation results in innapropriate activation of coagulation cascade
•
DIC leads to the formation of small blood clots inside the blood vessels throughout the
body
...
g
...
•
The small clots also disrupt normal blood flow to organs by occulsion (such as the kidneys),
causing ischemia which may malfunction as a result (end organ damage)
•
Disseminated intravascular coagulation (DIC) is a pathological activation of coagulation
(blood clotting) mechanisms that happens in response to a variety of diseases
...
g
...
•
Triggers of this process in pregnancy include endothelial damage, the release of placental
tissue, amniotic fluid (amniotic fluid embolism), incompatible red cells or bacterial products
into the maternal circulation
...
•
DIC is essentially an abnormal response to tissue damage and represents a complex
interaction between the inflammatory and coagulation pathways
...
g
...
g
...
f
...
g
...
g
...
g
...
If it
happens before you are due to give birth, it might be a sign of early labour
...
Can transform into placenta abruption
...
g
...
Majority of the time, bleeding occurs after the 36th week
•
Classification: Type I – IV:
! Type I: Placenta in lower uterine segment, but the lower edge does not reach
internal os
! Type II: Lower edge of placenta reaches internal os, but does not cover it
! Type III: placenta covers internal os partially (placenta covers cervix / internal os,
but would not cover in labour when dilated)
! Type IV: Placenta covers cervix internal os completely (would still cover in full
dilatation)
•
Minor vs
...
This is because the
placenta can block the presenting part from entering the internal os
...
May have been a low-‐lying placenta in a previous US, or may have been previously normal
•
Soft uterus (usually) => fetus easy to palpate
•
High presenting part: head not engaged e
...
head not entered pelvis through pelvic inlet
(placenta is stopping head from engaging)
•
Malpresentation: Breech or transverse Lie (as placenta is stopping head from engaging)
! If patient presents with high presenting part / breech / transverse lie => scan, as
bleeding may not be present in placenta praevua
•
CTG: usually no fetal distress as blood loss is usually small (can use to distinguish from
placental abruption)
Diagnosis
•
Ultrasound Scan, NOT clinical diagnosis
•
DO NOT PERFORM DIGITAL VAGINAL EXAMINATION UNTIL PLACENTAL PRAEVIA HAS BEEN
EXCLUDED – can provoke massive obstetric haemorrhage
Management
•
•
Admit to ward: IV access, blood tests, cross match
•
Rescan after interval
•
Anti-‐D if rhesus –ve mother
•
DO NOT PERFORM VAGINAL EXAMINATION UNTIL PLACENTA PRAEVIA HAS BEEN
EXCLUDED: pelvic exam may cause massive bleeding
Steroids if expectant management (PP can cause preterm labour due to preterm premature
rupture of membranes => preterm infents at risk of NRDS => steroids can help mature lungs
by encouraging surfactant production)
•
Caesarean section (if <2cm distance from internal os to placenta) at 38 weeks if clinically
stable: deliver sooner if significant haemorrhage
Placenta Accreta
•
Abnormally deep attachment (adherence) of the placenta to the myometrium (middle
muscular layer of the uterus) without penetrating it => placenta grows completely through
endometrium
•
Very significant complication: assoc
...
Placenta can implant over a uterine scar from a
previous C-‐section => trophoblast can penetrate through scarred decidua and myometrium
...
Majority will require
hysterectomy, unless area of adherence is small
•
The safest and most common treatment is a planned elective caesarean section (+/-‐
hysterectomy) if placenta accreta is diagnosed before birth
•
The haemorrhage is frequently accompanied by DIC => anticipate in women with Hx of C-‐
section
Variations
•
Placenta accreata: The placenta attaches strongly to the myometrium, but does not
penetrate it
...
•
Placenta Increta: villi invade into, but not through, the myometrium
•
Placenta Percreta: villi invade through the full thickness of myometrium to the serosa; may
cause uterine rupture
...
This variant can lead to the
placenta attaching to other organs such as the rectum or bladder
Placental abruption (abruption placentae)
•
•
Normally sited placenta
•
Placental abruption is a serious condition where the placenta starts to come away from the
inside of the uterus wall
...
If it
happens close to your baby's due date, the baby may be delivered early
...
•
Post partum Haemorrhage (PPH) can also occur from the damaged attachment site
•
Associated with DIC: thromboplastins released from damaged vessels => widespread
intravascular coagulation
...
Patients often present with reduced fetal movement and abdominal pain
...
g
...
g
...
•
Large for dates uterus (uterus full of blood => stretching of uterus => increased uterine
activity)
•
Difficult to feel fetal parts
•
Small or large volume blood loss – vary variable level of APH
May have associated polyhdraminos – cause distension of uterus and then when water
breaks we cget a sudden pressure change and the placenta may rupture (waters should
always be brokwn slowly in polyhydraminos)
•
CTG:
! May be poor due to foetal distress (decreased blood supply to foetus)
! Placental abruption assoc
...
with maternal morbidity)
•
Vaginal birth is usually preferred over caesarean section unless there is fetal distress (e
...
abnormal CTG and/or meconium staining)
•
Caesarean section may be contraindicated in cases of disseminated intravascular
coagulation
...
Excessive bleeding from uterus may
necessitate hysterectomy
•
Anti-‐D if Rh –ve mother
•
Steroids if expectant management
Local causes of APH
•
•
Local causes, e
...
vulval or cervical infection, trauma, tumours or polyp
Tend to be small volume of blood loss
•
Painless
•
Often a provoking factor e
...
coitus (vaginal-‐penis penetration)
•
Uterus soft, non tender
•
Normal fetal presentation
•
No fetal distress
•
Normally sited placenta
Treatment
•
Cervical causes: colposcopy
•
Infection: swabs / specific treatment
Compare and contrast: Placenta Praevia, placenta abruption and local pathology
Vasa Praevia
•
Vasa Praevia = fetal vessels within the membranes due to low set foetal vessels (e
...
•
Integrity of the myometrial wall is breached
•
Incomplete rupture = peritoneum still intact
•
Complete rupture = contents of the uterus may spill into the peritoneal cavity / broad
ligament
•
Life-‐threatening for mother and baby
•
Usually occurs during labour, may occur late pregnancy
•
1 in 500 risk if Hx C-‐section (C-‐section weaknes uterine wall due to scars)
•
1 in 2000 risk of losing baby
•
About 40% of women who have uterine rupture had prior surgery of their uterus, including
Caesarean section (CS)
...
•
Other risk factors for uterine rupture include:
! More than four pregnancies
! Trauma
! Excessive use of oxytocin
! Shoulder dystocia
! Placenta percreta
! Some forceps deliveries
•
The rupture may occur before or during labour or at the time of delivery
...
g
...
g
...
She may well not feel any symptoms but may feel
light headed
...
•
A good sign of significant hypovolaemia is if the pulse rate is above her systolic blood
pressure
...
•
As more blood is lost she will look pale with cold clammy skin (vasoconstriction =>
increased TPR => increased MAP => another compensatory mechanism)
•
Decreased UO is another compensatory mechanism
•
About 30% of circulating volume needs to be lost before hypotension sets in
(decompensated)
•
By the time she drifts into unconsciousness she will have lost around 40% of her circulating
volume
...
Management of APH
History
•
Bleeding: site, onset, character (colour, clots), associated symptoms, timing, exacerbating
and relieving factors, severity (volume)
•
Pain: distinguishes between Placenta Praevia (painless) & placenta abruption (painful)
•
Contractions: placenta abruption can fill the uterus with blood (couvelaire uterus) =>
stimulates contractions
...
•
Fetal movements: may be reduced in abruption (foetal distress)
•
Provoking factors:
! Post-‐coital? (after sex) => suggestive of local pathology e
...
cervical polyp
! RTA => may be suggestive of placental abruption
•
Cervical smear history: exclude cervical cancer
•
Scan history: previously low placenta? (Placenta praevia has low placenta)
•
Associated discharge?
Examination / Assessment
•
•
Assess for signs of hypovolaemia e
...
tachycardia, low BP, increased CRT (capillary refill
time), decreased skin turgor, dry mucous membranes
•
Assess volume of APH
•
Fundal height: large for dates in Abruption
•
Uterine tenderness: tender in Abruption
•
Uterine activity: contractions in Abruption (due to blood causing distension)
•
Fetal lie and presentation: high presenting part in Placenta Praevia +/-‐ malpresentation (e
...
breech or transverse)
•
ABCDE is the first priority: record all vital signs
Auscultation of Fetal Heart and CTG: confirm baby still alive (most likely to be compromised
in Abruption, Vasa Praevia or Uterine Rupture)
•
Key point: foetal distress most likely in placenta abruption, vasa praevia or uterine rupture
Initial Management
•
ABCDE
•
IV Access
•
Full Blood Count +/-‐ cross match and group and save
•
Coagulation Screen
•
Rhesus status:
! The Kleihauer test, is a blood test used to measure the amount of fetal
hemoglobin transferred from a fetus to a mother's bloodstream
...
It is usually
performed on Rhesus-‐negative mothers to determine the required dose of Rh(D)
immune globulin (Rh Ig) to inhibit formation of Rh antibodies in the mother and
prevent Rh disease in future Rh-‐positive children
...
g
...
•
Placenta abruption: C/S versus vaginal (vaginal usually preferred unless there is fetal
distress)
•
Vasa praevia: Caesarean section (CS)
•
Uterine rupture: laparotomy / CS
•
Cervical causes: colposcopy (a procedure where the surface of the cervix is closely examined
using a magnifying instrument called a colposcope)
•
Infection: swabs and specific treatment
•
PTL (preterm labour): steroids +/-‐ tocolysis (e
...
terbutaline)
...
The therapy also buys time for the administration
of betamethasone, a glucocorticoid drug which greatly accelerates fetal lung maturity, but
takes one to two days to work
...
•
The disease ranges from mild to severe, and typically occurs only in some second or
subsequent pregnancies of Rh negative women where the fetus's father is Rh positive,
leading to a Rh+ foetus
...
! Haemorrhage (at any time)
! Invasive procedures, e
...
RTA, amniocentesis
•
Pathophysiology:
! Fetal Rh+ve red cells enter maternal circulation (Rh –ve mother)
! Mother recognises as foreign
! Produces antibodies against Rh D – this is IgG which can cross placenta
...
•
Does not usually affect initial pregnancy: primary response is IgM antibodies => cannot
cross placenta
•
Next pregnancy: antibody response is amplified, IgG antibodies produced, cross placenta =>
destroy rhesus +ve red cells in baby => foetal transfusion reaction
•
Note: ABO antibodies are nearly always IgM => we do not often see ABO mismatch causing
problems
•
Antibodies can cause:
! Haemolytic anaemia and reticulocytosis: Profound anaemia can cause high-‐
output heart failure, with pallor, enlarged liver and/or spleen, generalized
swelling, and respiratory distress
...
After delivery bilirubin is no longer cleared (via the placenta) from the neonate's
blood and the symptoms of jaundice (yellowish skin and yellow discoloration of
the whites of the eyes) increase within 24 hours after birth
...
! Fetal hydrops (fluid builds up around heart, blood in fetal abdomen): The
prenatal manifestations are known as hydrops fetalis (accumulation of fluid, or
edema, in at least two fetal compartments)
...
! Can be fatal
•
•
Routine prophylaxis: Rh disease is generally preventable by treating the Rh –ve mother
during pregnancy with an intramuscular injection of anti-‐RhD (anti-‐D) immunoglobulin
(Rho(D) immune globulin)
...
g
...
Measure quantity of rhesus antibodies, if above a certain level => US scan & Doppler to find
out if anaemic => refer, transfuse baby, intra-‐uterine transfusion
Steroids
•
Promote fetal lung surfactant production: induce type II alveolar cells to produce surfactant
=> decrease alveolar surface tension => increase pulmonary compliance
•
↓ neonatal respiratory distress syndrome (RDS) by up to 50% if administered 24-‐48h
before delivery (take time to work), in babies that need delivered early (e
...
in
haemorrhage)
•
Administer up to 36 weeks
...
Proven benefit up to 1
week
•
Betamethasone is preferred to Dexamethasone
•
Can administer tocolytic (e
...
terbutaline) to decrease contraction and prolong preamature
labour until steroids have had effect (24-‐48 hours for maximal effect)
Post-‐partum Haemorrhage (PPH)
•
Classically defined as vaginal bleeding > 500ml
! Primary PPH: within 24h
! Secondary PPH: >24h to 6/52
•
Severity can be categorised as:
! Minor PPH <500ml
! Moderate PPH: 500-‐1500ml
! Major PPH = >1500ml
•
Up to 4% of all vaginal deliveries => common
•
In Scotland major obstetric haemorrhage (>1500ml) complicates 3
...
PPH more
common after e
...
forceps delivery, C-‐section
...
Uterine atony is the inability of the uterus to contract and retract
after delivery, which may lead to continuous bleeding
...
If bleeding not stopped => clots fill uterus =>
distends even more => bleeds further
...
g
...
Aetiology of secondary PPH:
! Infection: endometritis: This occurs in 1-‐3% after spontaneous vaginal delivery
...
Risk factors are: Caesarean section, prolonged rupture of membranes, severe
meconium staining in liquor, long labour with multiple examinations, manual
removal of placenta, mother's age at extremes of the reproductive span, low
socio-‐economic status, maternal anaemia, prolonged surgery, internal fetal
monitoring and general anaesthetic
...
PPH: Prevention
•
Identify antenatal risk factors
! Anaemia: checked before labour and treated, reduces effects of haemorrhage if it
occurs
! previous caesarean section
! Placenta praevia (low placenta): Cause of APH and risk factor for PPH
...
! Placenta accreta (attaches strongly to myometrium but does not penetrate it):
Cause of APH and risk factor for PPH
...
! Placenta increta (penetrates myometrium): Cause of APH and risk factor for PPH
...
! Placenta perceta (penetrates entire myometrium) : Cause of APH and risk factor
for PPH
...
! Previous PPH or retained placenta
! Multiple pregnancy
•
Identify intrapartum risk factors
! prolonged labour
! operative vaginal delivery / caesarean section
! retained placenta
•
Active management of third stage (delivery of placenta)
! Use of oxytocic drug (stimulates uterus) e
...
sytocinon or syntometrine
(syntocin/oxytocin & ergometrine)
! Clamping & cutting umbilical cord: between 1 and 3 minutes
! Controlled cord traction to deliver placenta
NICE guidelines
Identifying aetiology
•
•
Usually this requires transfer to theatre for an examination under anaesthesia and possible
laparotomy to arrest the bleeding
...
Inverted uterus = rare obstetric emergency
Immediate management of PPH
•
ABCDE
•
Stimulate uterine contractions
! Uterine massage to treat atonic uterus: Uterine massage is done by making
gentle squeezing movements repetitively with one hand on the woman’s lower
abdomen in order to stimulate the uterus
...
Treats atonic uterus, and it is 1st assumed
that this is cause, as it is the most likely
...
g
...
g
...
g
...
g
...
g
...
Review whether drug therapy necessary
1st trimester
•
Risk of early miscarriage
•
Organogenesis
•
Period of greatest teratogenic risk: 4th -‐11th week (embryogenesis)
•
Avoid drugs if at all possible unless maternal benefit outweighs risk to foetus
Teratogenic drugs
•
ACE inhibitors/ARB e
...
lisonopril/rapimril (ACE-‐I) or losartan/valsartan (ARBs): can cause
renal dysfunction and oligohydraminos
•
Androgens
•
Antiepileptics
•
Cytotoxics
•
Lithium
•
Methotrexate
•
Warfarin
2nd + 3rd trimesters
•
Growth of foetus (end of embryogenesis)
•
Functional development
! Intellectual impairment
! Behavioural abnormalities
•
Toxic effects on foetal tissue
Around term
•
Adverse effects of drugs on labour
! Progress of labour
! Adaptation of foetal circulation: Premature closure of ductus arteriosus e
...
due
to NSAIDs (cause decreased PGs)
! Suppression of foetal systems: Opiates => can cause respiratory depression
! Bleeding: Warfarin (avoid all together in pregnancy => use heparin instead)
•
Adverse effects of drugs on baby after delivery
! Withdrawal syndrome: opiates, SSRIs
! Sedation
Delayed effects
•
Diethylstilbestrol (oestrogen)
! Previously used to prevent recurrent miscarriage in pregnant women
! Vaginal adenocarcinoma in girls aged 15-‐20 years whose mothers were exposed
to diethylstilbestrol
Chronic conditions and pregnancy
•
Need to discuss risk/benefit balance with patient: Ideally pre-‐conception
•
Compliance with medication may be poor
•
Many women avoid taking their asthma inhalers in pregnancy
•
Up to 20% of women discontinue antiepileptic medication in pregnancy
Epilepsy
•
•
Incidence of congenital malformations higher in untreated women with epilepsy than
women without epilepsy
Increased seizures in 10% of women
! Non-‐compliance
! Changes in plasma concentrations of drugs e
...
due to persistent vomiting and
increased renal clearance
•
Frequent seizures during pregnancy are associated with lower verbal IQ in child, hypoxia,
bradycardia, antenatal death, maternal death
•
Antiepileptics increase risk of congenital malformations
! 20-‐30% risk if on 4 drugs
! Monotherapy preferred
•
Avoid valproate and phenytoin
•
Folic acid 5mg daily
•
96% of babies born to women taking antiepileptics will not have major congenital
malformations
•
Benefits of treatment outweigh risks in most cases
Diabetes
•
Insulin thought to be safe
•
Requirements change during pregnancy
•
Poor control increases risk of congenital malformations and intra-‐uterine death
•
Sulfonylureas (e
...
glicazide, glibenclamide and tolbutamide) not safe => convert to insulin
Hypertension
•
BP falls during 1st and 2nd trimester, then rise back up to normal in third trimester
•
If need to treat, use one of (LMN):
! Labetalol (alpha and beta blocker)
! Methyldopa
! Nifedipine
•
•
Avoid ACE inhibitors / ARB (teratogenic)
Beta blockers may inhibit foetal growth in late pregnancy
Common acute problems
•
Nausea and vomiting: Cyclizine
•
UTI: Amoxicillin or cefalexin
•
Pain: Paracetamol
•
Heartburn: Antacids
Prevention of venous thromboembolism in pregnancy
•
Pregnancy has 10-‐fold increased risk of VTE (versus non-‐pregnant) as pregnancy induces a
hypercoagulabale state (physiological mechanism to prevent postpartum haemorrhage PPH)
•
Highest risk of VTE is in the 6 week postpartum period
•
VTE is leading cause of maternal death in pregnancy
•
Thromboprophylaxis reduces the risk
•
All pregnant women should be assessed for risk of VTE
•
Regardless of risk, all women who are pregnant, in labour or in the puerperium should be
encouraged to mobilise and be adequately hydrated
•
Those with significant risk factors should receive thromboprophylaxis with LMWH ➢ at
delivery and up to 7 days post-‐partum (as this is the highest risk period)
! 2 or more risk factors e
...
obesity, age>35yrs, smoking, para >3, previous DVT,
Caesarean delivery (CS)
! any pt with previous unprovoked DVT/PE
LOW THRESHOLD FOR INTERVENTION
Treatment of venous thromboembolism in pregnancy
•
•
Avoid warfarin in early pregnancy, as warfarin is teratogenic
•
Treat suspected or established DVT or PE with therapeutic dose LMWH
Avoid warfarin in late pregnancy, as risk of haemorrhage during delivery (peri-‐partum
haemorrhage)
•
AVOID WARFARIN FULL STOP
•
LMWH is the anti-‐coagulant of choice in pregnancy
Breastfeeding
•
Most drugs enter breast milk, especially
! Small molecules
! Fat soluble (lipophilic) drugs
•
Few enter in sufficient quantities to cause a problem
•
Immature metabolism – drugs may accumulate
•
Some drugs are actively concentrated in breast milk
•
POP is the OCP of choice when breast feeding – the progesterone is good for the milk
production too!
•
Paroexetine is the SSRI of choice when breast feeding
Summary
•
All women of childbearing age are potentially pregnant
! Check before you prescribe
! BNF or UK Teratology Information Service
•
Pre-‐conception counselling
•
Balance risk vs benefits
•
Treat if necessary
! Safest drug, lowest effective dose, shortest possible time
Quiz
Question 1
...
Also avoid in children up to age 12 years
...
•
Which ‘drug’ taken in excess in early pregnancy could have caused this facial appearance?
•
Answer= Alcohol => Fetal alcohol syndrome
Question 3
•
Which antiepileptic drug is particularly associated with the following congenital anomaly?
•
Answer= Phenytoin (more likely) or carbamazepine=> cleft lip and palate
Question 4
•
Which antiepileptic drug is particularly associated with the following defects?
•
Answer: Valproate => neural tube defects e
...
spina bifida and anencephaly
PHYSIOTHERAPY MANAGEMENT OF GYNAECOLOGICAL CONDITIONS
Pelvic Floor Dysfunction
•
The pelvic floor is related to more than one system
...
The function of the
pelvic floor is to support the pelvic organs
...
Practical inconveniences include frequent change of
clothing and bed linen and bathing more often
•
Interference with sexual activities and night-‐time incontinence are associated with greater
reported impact on quality of life
...
•
Prevalence: in middle age and older adults in range of 30-‐60% of population
...
It is present in all age groups and
both genders increasing in prevalence with age from 1
...
•
Many women post-‐natally can have bowel disorders
...
6–9
...
•
NB: episotomy= planned, surgical incision on the perineum and the posterior vaginal wall
during second stage of labor (helps with delivery of the baby)
Vagina symptoms
•
Pelvic organ prolapse: Loss of support (from PFMs) for uterus, bladder, colon or rectum
leading to prolapse of one or more of these organs into the vagina
...
Key diagnostic test for urinary incontinence
...
g
...
They relax at the same time as the bladder contracts (tightens) in order to let the
urine out
...
g
...
g
...
g
...
•
Thrush: caused by Candida albicans
...
Always consider other causes of breast pain
...
•
Worsens at the start of feeding
•
Breasts may also be engorged
•
Redness, blisters, bleeding and scabs
•
Baby may vomit blood
Treatment/Management:
•
•
Discuss/demonstrate the principles of good positioning and attachment
•
Hand expressing where appropriate e
...
express some milk to soften the areola to lubricate
the nipple before breast feeding
•
Observe and assess a breastfeed
Creams, sprays and heat treatments are generally of little value
•
Nipple shields can be used as a last line of management to prevent the mother from giving
up
...
Always
consider other causes of breast pain
...
•
Can be passed between mother and baby
...
•
Swab for candida albicans
•
Essential to continue feeding directly from breast to prevent engorgement/reduced milk
supply/mastitis
Clinical features
•
Itching or burning of the skin over the nipples /areola
•
Soreness of the skin to start with
•
Severe pain when the baby initially latches on to the breast which becomes progressively
worse with each re-‐latch
•
Bilateral
•
NB: no white rash or discharge as seen in oral and vaginal thrush
Management:
•
•
Observe breastfeed
•
Dummies, teats boiled 20minutes daily
•
Bras, towels washed in hot wash
•
Observe breast
Essential to continue feeding directly from breast to prevent engorgement, reduced milk
supply and mastitis
•
Antifungal Tx
! Miconazole cream (superficial infection) for mum
! Oral fluconazole (for deep infection) for mum
! Nystatin or miconazole for infant
•
If symptoms have not improved at all after a 10 day course combined with topical
treatment, re-‐consideration should be given to whether the diagnosis was correct rather
than continuing to treat the mother and child
Engorgement
•
Breast engorgement occurs in the mammary glands due to expansion and pressure exerted
by the synthesis and storage of breast milk
...
•
While it is normal for the breasts to enlarge, one study found that the more minutes the
newborn spent nursing during the first 48 hours the less painful breast engorgement was
•
When breastfeeding is unrestricted, mothers are less likely to be painfully engorged
...
•
The breast(s) may be red
•
The mother may be feverish
...
•
Ensure good attachment and complete emptying of at least one breast per feed with the
second side also softened by the baby feeding or by expressing fore milk
...
g
...
•
Antibiotics are unhelpful and may lead to Candida infections
...
Mastitis
•
Inflammation of breast tissue
•
May be caused by a plugged duct (duct ectasia) and/or an infection
•
A plugged duct:
! Comes on gradually
! May shift location
! The mother feels little or no warmth in the area
! The pain is mild and localised
! The mother feels generally well
! Temperature is lower than 38
...
4 degrees Celcius
...
g
...
aureus
! Erythromicin (if penicillin allergy)
•
Abscess:
! ABS e
...
flucloxacillin
! Aspiration) of abscess if no response to ABs
...
g
...
THE HEALTHY TERM INFANT
•
Term = 37 to 42 weeks gestation
•
Preterm = < 37 weeks gestation
! Very preterm < 32 weeks
! Extremeley preterm <28 weeks
! Fetal loss < 23 weeks
•
•
Post-‐term = > than 42 weeks gestation
Epidemiology is not a strict cut-‐off, but a spectrum e
...
can get problems of “prematurity”
at 37 weeks gestation
Birth weight of term baby
•
Birth weight is often talked about
•
Corrlated with prognosis
•
3
...
5kg is low
! Less than 1
...
Adults
would probably die if subjected to this level of hypoxia => foetal adaptations are important
•
Foetal adaptions include metabolic and haematological adaptions e
...
HbF (left shift) and
increased Hb concentration
•
Fetal Hb (alpha 2, gamma 2) increases oxygen binding capacity, due to shift of the
haemoglobin dissociation curve to the left => resulting in enhanced oxygen affinity in the
blood
...
g
...
Various hormonal and environmental stimuli make the baby
take at least a breath if not a cry which inflates the lungs
•
Alveolar expansion: Move from relying on the placenta for oxygen to relying on the lungs
•
Decreased pulmonary arterial pressure
•
Change from fetal to newborn circulation (pressure in left heart becomes greater than right
heart; ducts close)
•
Increased PaO2
•
Apgar score: Apgar score describes how well the baby is adapting to extra-‐uterine life
...
•
Simple things like drying the baby, keeping next to mum’s skin, putting a hat on, if necessary
using more advanced measures like transwarmers or incubators
•
DRYING BABY IS FIRST STAGE OF NEONATAL RECUSSITATION GUIDELINES
Feeding
•
Well grown term infants have little calorific intake in the first 24 hours
•
Dramatic change from continuous glucose infusion (via placenta) to intermittent bolus
enteral feeds
•
Blood sugar of 2-‐2
...
6
•
Gluconeogenesis is the most important mechanism here
•
Brain can also survive on other fuels such as ketones (different if sick of pre-‐term)
•
Skin to skin contact important for establishing breast feeding
Attachment
•
To parents their baby is always beautiful
•
Babies often very alert immediately after delivery
•
Hormonal and emotional response to infant
•
Feeding and warming are very important to attachment
•
Poor attachment in early life dramatically changes relationship further down the line
•
Post-‐natal depression is much higher in mothers whose children have been admitted to
NICU
Haemorrhagic disease of the newborn (HDN)
•
Haemorrhagic disease of the newborn is an uncommon UK problem now (more in other
parts of the world)
•
Vit K is essential for the production of F2,7,9 and 10 in the liver
...
They have low vitamin K
stores at birth, vitamin K passes the placenta poorly, the levels of vitamin K in breast milk are
low and the gut flora has not yet been developed (vitamin K is normally produced by
bacteria in the intestines)
...
g
...
g
...
g
...
If you know there’s a maternal history of these diseases or drug abuse, consider
screening the baby, as may be able to treat
...
g
...
GBS is a major cause of sepsis and meningitis in neonates
•
Hepatitis B: vaccination and immunoglobulin to at risk neonates
•
Hepatitis C: no vaccination
•
HIV: can offer mum HAART (irrelevant of CD4) to decrease viral load and reduce chance of
transmission
...
Breast feedng CI even on
HAART
...
g
...
•
Moulding: head contours to shape of the pelvis
...
More likely to occur in prolonged stage 1 of
labour
...
•
Cephalohaematoma: subperosteal bleed, cant cross sutures
...
g
...
g
...
•
Ophthalmoscopy for diminished red reflex (loss of red reflex may be a sign of cataracts and
retinoblastoma)
•
Aggressive early management improves visual outcomes
•
Conjunctivitis
Ears
•
Position
•
External auditory canal -‐ patent
•
Family history of hearing loss
•
Tags/pits
Mouth
•
Shape
•
Philtrum: vertical groove in the middle area of the upper lip, common to many mammals,
extending from the nose to the upper lip
...
Feel with little finger
...
Unusual
for a routine newborn midwife exam to pick this up, but still look for it just in case
Cardiovascular
•
Inspection, palpation, percussion and auscultation
•
Colour: Colour is important but we are bad at picking up cyanosis => so routine sats
monitoring has become part of newborn care in some areas
•
Saturation: SaO2 or SpO2 (preductal and postductal)
•
Pulses: femoral
! Reduced/absent femoral pulses is a sign of coarctation of the aorta and aortic
stenosis
...
Although radiofemoral delay unlikely to be
detected in neonates due to the short distance!
•
Apex
•
Heaves and thrills
•
Heart sounds
•
Hepatomegaly – early sign of HF
Abdominal
•
Inspection, palpation, percussion and auscultation
•
Moves with respiration
•
Distension
•
Bile stained vomiting
•
Passage of meconium: Lack of meconium passage is associated with CF or obstruction
•
Anus: Look for patency of anal passage (may be anal atresia or abnormal position)
...
Barlow and Ortolani manoeuvres try to dislocate and relocate the hips
...
US all babies with
risk factors
...
•
Ensure baby is in proportion e
...
no skeletal dysplasia
Neurological
•
Posture
•
Tone
•
Movement
•
Reflexes
•
Primitive reflexes (e
...
grasp, moro)
...
•
Every baby in the UK gets this on day 5
Health promotion
•
•
Weaning from 6 months
•
Breast feeding exclusively to 6 months (when weaning should begin) and recommended to
at least 2 years (unexclusively)
No cows milk before 12 months
•
Smoking cessation
•
Alcohol limitation to recommended limit
•
Drug use
•
Diet: balanced
•
Now good evidence that health as babies and toddlers strongly impacts on adult health:
particularly diabetes, cardiovascular disease, some data on cancers now
•
If there’s an opportunity to try to raise issues of lifestyle change, give it a go: however some
will continue drinking, smoking etc
•
Most parents highly motivated to change for their children
THE SICK TERM INFANT
Causes of sick term infant
•
Asphyxia
•
Cardiac
•
Metabolic
•
Infection
•
Congenital anomalies
•
Respiratory
Perinatal asphyxia
•
•
Hypoxic damage can occur to most of the infant's organs (heart, lungs, liver, gut, kidneys),
but brain damage is of most concern and perhaps the least likely to quickly or completely
heal
...
In the more pronounced cases, an infant will survive, but with damage to the brain
manifested as either mental, such as developmental delay or intellectual disability, or
physical, such as spasticity (cerebral palsy)
...
g
...
! Can also occur due to inadequate circulation or perfusion, impaired respiratory
effort, or inadequate ventilation
...
•
Clinical features
! Poor apgar scores
! Multi organ damage due to tissue hypoxia
! Resuscitation required
! Seizures/neurological abnormalities
! Renal failure
! Liver dysfunction
Infection
•
Septicaemia: E-‐coli, Strep agalactiae (GBS) and Listeria monocytogenes are the commonest
pathogens in the neotal period
...
Coli – gram –ve coliform
•
Listeria myogenes – gram +ve aerobic bacilli
•
Staphloccus aureus – gram +ve, coagulase +, aerobic cooci
•
Often Tx with Benpen and Gent – also used prophylactically
Cardiac
•
Congenital heart disease
! Tetralogy of Fallots: pulmonary stenosis, right ventricular hypertrophy,
ventricular septal defect and overriding aorta
...
R to L shunt occurs as pressure in right ventricle
is higher than left
...
When a patient has a coarctation, the left ventricle has to work harder
...
If the narrowing is severe enough, the left
ventricle may not be strong enough to push blood through the coarctation, thus
resulting in lack of blood to the lower half of the body
...
Radio-‐femoral delay of pulses is characteristic of co-‐
arctation of the aorta
...
Many causes e
...
anaemia, heart
failure, haemolytic disease of the newborn etc
•
Failure to adapt to postnatal life
! PPHN (persistent pulmonary hypertension of the newborn): The baby's lungs are
not used during pregnancy
...
This means most of the baby's blood does not need to
pass by the lungs
...
The
blood flow should switch so that it will pass by the lungs
...
The blood does not flow to the lungs as it should
...
PPHN
can be caused by a variety of factors
...
Therefore measurement
of pre-‐duct sats and post duct sats is useful in the Dx (R to L shunt => cyanotic
shunt => difference between pre-‐duct an post duct)
...
Note: If duct dependent cyanotic heart defect => give PG infusion to keep the ductus arteriosus
open
...
5mmol/l)
! related to Low Birth Weight (low glycogen stores)
! related to large birth weight (macrosomia) with maternal diabetes
! side effect of poor feeding
! evidence of more complex metabolic disorder
•
Acidosis (pH <7
...
! Most common cause of respiratory distress in term neonates
! It consists of a period of rapid breathing >60 breaths per minute (higher than the
normal range of 40-‐60 times per minute in the neonate)
...
! Usually, this condition resolves over 24–48 hours
...
The chest X-‐Ray shows
hyperinflation of the lungs (due to excess fluid) including prominent pulmonary
vascular markings, flattening of the diaphragm, and fluid in the horizontal fissure
of the right lung
...
! On CXR we see decreased lung volumes (alveolar collapse) and ground glass
appearance
! Most cases of infant respiratory distress syndrome can be ameliorated or
prevented if mothers who are about to deliver prematurely can be given
glucocorticoids, one group of hormones
...
g
...
! Spina bifida: developmental congenital disorder caused by the incomplete closing
of the embryonic neural tube
...
If the opening is large enough, this
allows a portion of the spinal cord to protrude through the opening in the bones
...
•
Renal
! Potters syndrome: atypical physical appearance of a fetus or neonate due to
oligohydramnios experienced in the uterus
...
Oligohydramnios is the causative
agent of Potter sequence, but there are many things that can lead to
oligohydramnios
...
•
Muscular
! Myotonic dystrophy: chronic, slowly progressing, highly variable, inherited
(genetic) multisystemic disease
...
Two types of myotonic dystrophy exist
...
Assessment
•
History
! Maternal
! Infant
•
General examination and APGAR
! APGAR: appearance (colour), pulse (HR), grimace (reflexes), activity (muscle
tone), respiratory effort
! Perform APGAR at 1 and 5 minutes +/-‐ 10 minutes
! Level of arousal
•
Vital signs: record on NEWS chart (neonatal observing chart) => helps focus on those who
need monitoring
•
Respiratory
! Rate (normally 40-‐60 in the neonate)
! Effort e
...
sterna recession, intercostals recession, nasal flare, grunting, stridor,
use of accessory muscles
•
CVS
! HR (normally 120-‐150 in neonate)
! CRT: capillary refill time (normally less than 2 seconds in neonate)
! BP (significantly lower compared to adults)
•
Abdomen
! Urine
! Stool/meconium
! Bile
! Distension
•
Neurological
! Tone
! Seizures
! Cry
! Posture
Apgar score
•
Appearance (colour): 0-‐2
•
Pulse (heart rate): 0-‐2
•
Grimace (reflex activity): 0-‐2
•
Activity (muscle tone): 0-‐2
•
Respiratory effort: 0-‐2
•
Total score is out of 10
•
Scores 7 and above are generally normal, 4 to 6 fairly low, and 3 and below are generally
regarded as critically low
...
g
...
g
...
9% saline
•
Investigations to find cause
•
Further support and treatment
! Ventilation
! Drugs
! Surgery
•
Care of the family
THE PRETERM INFANT
Terminology
•
Term: a birth between 37 weeks and 42 weeks of gestation
•
Preterm: a birth that occurs after 22 weeks but before 37 completed weeks of gestation
! Very preterm = 28-‐32 weeks
! Extremely preterm = 23 to 28 weeks
! Fetal loss = < 23 weeks
•
Post terms: a birth that occurs after 42 completed weeks of gestation
Infants according to their weight
•
Small for Gestational Age (SGA): <10th centile in weight expected for gestation
•
Appropriate for gestational age (AGA) : 10th-‐90thcentile in weight expected for gestation
•
Large for Gestational Age (LGA): >90th centile in weight expected for gestation
Low birth weight
•
In developed countries, the average birth weight of a full-‐term newborn is approximately 3
...
5kg) or less
•
Very low birth weight (VLBW): birth weight 1500g (1
...
g
...
g
...
g
...
g
...
4% before 28 weeks
•
0
...
9% at 32–36 weeks
•
93
...
“Resuscitation”
•
Most very preterm babies need help with transition to air breathing => assistance not
resuscitation
•
Careful assessment and gentle support
•
Though these babies may well require a similar general approach to that we have developed
for asphyxiated term babies they need these interventions for slightly different reasons
...
Generally speaking they will be born
in good condition
...
Cord clamping
•
•
Because these babies are generally in reasonable condition at delivery you will almost
always be able to pause for a minute to allow placental transfusion to take place, provided
you can keep the baby warm during the process
...
Keep warm
•
Keeping these very small babies warm is best achieved by placing them immediately, while
still wet, in a suitable plastic bag and later under a radiant heater
...
If you overinflate
(e
...
This damage will set in
motion an inflammatory cascade which will predispose to bronchopulmonary dysplasia
(chronic lung disease of newborn)
Summary of management of preterm infant at birth
•
Allow at least one minute for placental transfusion (e
...
allow at least one minute before
cord clamping and cutting)
•
Keep the baby warm – straight into incubator (different to term neonatal recussitation
protocol where we dry babies initially)
•
Assess the situation: APGAR
•
Airway
•
Breathing: Inflation breaths (be careful of baro trauma)
•
Chest compressions (only if brachial pusle<60bpm)
Common concerns in preterm infant
•
Temperature control: due to low fatty tisse
•
Feeding/nutrition
•
Sepsis
•
System immaturity / dysfunction
! Respiratory distress syndrome (RDS)
! Patent ductus arteriosus (PDA)
! Intraventricular haemorrhage (IVH)
! Nectrotising enterocolitis (NEC)
•
Others:
! Metabolic e
...
hypoglycaemia and hyponatremia
! ROP (retinopathy of prematurity)
Hypothermia
•
Low admission temperature is an independent risk factor for neonatal death
•
Increases severity of all preterm morbidities
•
In the newborn is due more to lack of knowledge than lack of equipment
•
Why is thermal regulation ineffective ?
! Low BMR
! Minimal muscular activity
! Subcutaneous fat insulation is negligible
! High ratio of surface area to body mass
•
Methods for keeping warm:
! Skin to skin contact
! Clothing and hats
! Wraps or bags
! Prewarmed incubator
! Tranwarmer mattress
Growth and Nutrition
•
•
Limited nutrient reserves
•
Increased risk of potential nutritional compromise
Immature metabolic pathways
•
Increased nutrient demands
•
Medical / surgical conditions commonly associated with prematurity have the potential to
alter nutrients requirement and complicate adequate nutrient delivery
•
Plot growth charts with gestational correction:
! Head circumference
! Height
! Weight
Plotting preterm infants
Mortality in neonates
•
Approximately 5 million neonatal deaths a year
•
98% occurring in developing countries
•
Major causes
! Infection (32%)
! Prematurity (29%)
! Birth asphyxia (24%)
•
Infections: septicaemia, meningitis, respiratory infections, diarrhoea, and neonatal tetanus
Neonatal sepsis
•
Early onset (EOS): mainly due to bacteria acquired before and during delivery e
...
GBS from
mothers vagina, E-‐coli, and Listeria monocytogenes
•
Late onset (LOS)
! acquired after delivery
! Nosocomial or community sources e
...
Staph
Clinical features of neonatal sepsis
•
Remember that the very young and very old can have atypical presentations e
...
may
present with low temperature during infection
•
Look for focal signs of infection e
...
respiratory, GI, skin, CNS, ear, pharynx
•
Measure all vital signs
•
Signs of neonatal sepsis include:
! Increases respiratory rate >60 breaths per minute
! Tachycardia >150 bpm
! High or low temperature
! Decreased consciousness
! Reduced movements
! Not able to feed
! Convulsions
! Crepitations (lung infection)
! Bulging frontanelle (CNS infection)
MOST VERY NON SPECIFIC
Organisms causing Neonatal Sepsis
•
Gram negative organisms (gut pathogens):
! Klebsiella
! Escherichia coli
! Pseudomonas
! Salmonella
•
Gram positive organisms:
! Group B streptococcus (GBS) e
...
Strep agalactiae (beta/complete haemolysis)
! Listeria monocytogenes
! Staphylococcus aureus (coagulase +ve)
! Coagulase negative staphylococci (CONS) e
...
Staph epidermidis
! Streptococcus pneumonia (alpha/partial haemolysis)
! Streptococcus pyogenes GAS (beta/complete haemolysis)
Management
•
Prevention
•
Hand washing
•
Super vigilant and infection screening and risk assessment
•
Sensible use of antibiotics (ABx)
•
Optimum supportive measures
•
NB: Incubators increases infection
Respiratory complications of prematurity
•
•
Respiratory distress syndrome (RDS)
Apnoea of prematurity: cessation of breathing by a premature infant that lasts for more
than 15 seconds and/or is accompanied by hypoxia or bradycardia
...
A secondary stimulus is hypoxia
...
•
Bronchopulmonary dysplasia (chronic lung disease of prematurity): most commonly occurs
in premature infants who have needed mechanical ventilation and oxygen therapy for infant
respiratory distress syndrome
...
Respiratory distress syndrome (Hyaline Membrane Disease)
•
Primary pathology
! Surfactant deficiency => increased alveolar surface tension and alveolar
collapse => decreased pulmonary compliance (restrictive lung disease)
! Structural immaturity
•
Secondary pathology
! Alveolar damage
! Formation of exudate from leaky capillaries
! Inflammation
! Repair
•
Common: 75% of infants born before 29 week, 10% in infants born after 32 weeks
Clinical features of RDS
•
Respiratory distress
! Tachypnoea
! Grunting
! Intercostal recessions
! Nasal flaring
! Hypoxia and Cyanosis
•
•
Ground glass appearance of lungs on CXR
•
Worsen over minutes to hours
Natural history: Gradual worsening to a nadir (peak) at 2-‐4 days then gradual improvement
•
NB natural history is modified with active treatment
Management of RDS
•
Maternal steroid: can give tocolytic (e
...
terbutaline) to prolong labour until steroids have
an effect (approx 48 hours)
•
Surfactant (curosurf)
•
Ventilation
•
Invasive / non invasive ventilation
Cardiovascular concerns in preterm infants
•
Patent ductus arteriosus
•
Systemic hypotension
Patent Ductus Arteriosus
•
•
Duct does not respond to “close” signals e
...
decrease of PGs and increase in PO2
•
Leads to symptoms of congestive heart failure => L to R shunt results in fluid overload for
heart and lungs which can cause RHF and hydrops fetalis if severe
•
Machinery murmur – heard loustes at upper left sternal border, may radiate to back
•
Premature infants at risk
Oxygen requirements are high due to hypoxia – as a result of HF
•
Exacerbates RDS
•
RDS is also a risk factor: as hypoxia prevents closure of the duct
•
RDS is a major risk factor for many of the common preterm complications e
...
PDA, NEC
and IVH
Intraventricular Haemorrhage
•
Form of intracranial haemorrhage that occurs in preterm infants, which begins with bleeding
into the subependymal germinal matrix
...
•
Wide spectrum of clinical manifestations:
! Clinically silent (25-‐50%)
...
6) and hyponatraemia
! Late : osteopenia of prematurity
Complications of prematurity
•
Higher mortality
•
Morbidity
•
Neurodevelopmental outcome
! Motor deficits including mild fine or gross motor delay, and cerebral palsy
! Sensory impairment including vision and hearing losses
! Behavioral and psychological problem
•
Chronic health issues: have higher rates of chronic medical conditions compared with
children who were born full term
•
Growth issues: more likely to exhibit poor growth compared to those born full-‐term
•
Effect on adult health
Risk factors for preterm birth
•
Carrying more than one baby (twins, triplets, or more)
...
•
Certain infections during pregnancy => can cause inflammation of membranes and
premature rupture (common cause)
...
•
Cigarette smoking, alcohol use, or illicit drug use during pregnancy
Preventing preterm birth
•
Lowering the risk of having a premature baby
•
Even if a woman does everything "right" during pregnancy, she still can have a premature
baby
•
Tocolytics (e
...
terbutaline or salbutamol) may be used to delay labour in order for maternal
steroids to have effect
Summary
•
Survival rates for extremely preterm infants have improved
•
Antenatal steroids and surfactant replacement has contributed to improved preterm care
...
•
Impairments may have an adverse effect on family life, impact on social, education, and
health service resources
...
•
Also used to monitor progression of labour
•
It has also been used to assess the odds of spontaneous preterm delivery
...
The duration of labor is inversely correlated with the Bishop score; a score that exceeds 8
describes the patient most likely to achieve a successful vaginal birth
...
g
...
Methods of IOL
•
Prostaglandins: PGE2 Dinoprostone or misoprostol: used for cervical ripening (paritculary if
low Bishops score <6) and stimulation of uterine contractions
...
•
Syntocinon (oxytocin) IVI (intravenous infusion): stimulates uterine contractions
...
If the woman has fully dilated but
uterine contractions are insufficient then can use sytocinon
...
•
Mechanical
! Membrane sweep: the practitioner moves her finger around the cervix to
stimulate and/or separate the membranes around the baby from the cervix
...
! Extra-‐amniotic saline infusion: Foley Balloon Catheter is inserted into the cervix
and the distal portion expanded to dilate it and to release prostaglandins
...
The membranes
may be ruptured using a specialized tool, such as an amnihook or amnicot, or they may be
ruptured by the proceduralist's finger
...
Terbutaline (beta 2 agonist: SABA) is an example of a tocolytic agent
...
Reproductive lecture notes: week 5
URINARY INCONTINENCE (UI) AND PELVIC ORGAN PROLPASE (POP)
Pelvic anatomy
Aetiology of UI and POP
•
Many causes and risk factors:
! Aging
! Childbirth
! Neurological – ALWAYS CONSIDER NEURO CAUSES
! Muscular
! Medications
! Co-‐morbidities
! Infections
! Debility
! Many more
Urinary Incontinence (UI)
•
UI = involuntary loss of urine which can be objectively demonstrated and is a social or
hygienic problem
•
Types:
! Stress urinary incontinence (SUI): leakage of urine during raised intra-‐abdominal
pressure e
...
coughing, sneezing, laughing or lifting heavy objects
! Overactive bladder (OAB), also called urge incontinency: leakage associated with
urgency, usually with overactive detrusor activity
...
Also perform
MSK exam (particulary back) to assess for any spinal lesions
...
g
...
g
...
g
...
g
...
Remember the detrusor muscle receives parasympathetic stimulation (S2-‐S4) from
the sacral plexus
...
•
Remember that anti-‐muscarinic drugs can cause urinary retention
Surgical (rarely used)
•
Botox injections
•
Sacral nerve modulation
•
Augmentation cystoplasty
•
Bladder overdistension
Investigation of urinary incontinence
•
History:
! Onset and timing and duration
! Character: frequency, urgency (strong urge preceding urination?), stress (e
...
associated with coughing or sneezing?)
! Radiation: bowel problems?
! associated symptoms (e
...
dysuria, pelvic/abdominal pain, haematuria, back pain,
neurological deficits such as sciatica, back pain, bladder/bowel dysfunction, and
perineal anaesthesia)
! Precipitating factors e
...
lose urine when coughing sneezing or laughing?
! Relieving factors
! Severity: volume of leakage, effects on QOL
•
Examination: important to perform neurological examination, as the incontinence may have
a neurological cause e
...
spinal cord conpression
•
Investigations:
! Urodynamics (gold standard)
! Urinalysis: assess for UTI or kidney abnormality
! Blood for renal function if suspect renal impairment
! Bladder Chart (records voided volumes, frequencies and UI episodes)
! Pad test (quantifies urine leakage over specified time)
! Others: electromyography, imaging renal tract, cystourethroscopy
Urodynamics
•
•
Includes uroflowmetry and cystometry
•
Uroflowmetry: Flow rate enables you to measure peak flow, mean flow and voided volume
(minimum of 200mls void is required)
•
Useful to differentiate between stress urinary incontinence and overactive bladder in
patients in whom surgery considered
Cystometry is a method by which the pressure/volume relationship of the bladder is
measured during filling, provocation and during voiding
Pelvic organ prolapse
•
•
Common (up to 50% of parous woman, 10-‐20% symptomatic)
•
Lifetime risk of surgery: 11%
•
20% of patients on gynaecology waiting lists
•
Increasing incidence: women’s life expectancy is increasing and increased expectations for
quality of life
•
Occurring in women of all ages, it is more common as women age, particularly in those who
have delivered large babies or had exceedingly long pushing phases of labor
...
Minor prolapse can be treated with exercises to strengthen the pelvic floor muscles; more
serious prolapses require pessary use or reconstructive surgical treatment (e
...
anterior or
posterior repair)
...
•
The rectum or urinary bladder may also prolapse as a result of changes in the integrity of
connective tissue in the posterior or anterior vaginal walls, respectively
...
•
Prolapse is almost never painful, but the change in position of organs may cause urinary or
bowel symptoms
...
Rectum bulging into vagina
...
•
Enterocele (pouch of Douglas containing small bowel): remember the pouch of Douglas is
also called the rectouterine pouch, which is an extension of the peritoneal cavity between
the rectum and the posterior wall of the uterus
...
•
Vaginal vault: occurs when the upper portion of the vagina loses its normal shape and sags
or bulges down into the vaginal canal
•
Uterus prolapse
•
Cytocele (bladder): due to weakness in anterior vaginal wall
...
Anterior repair
...
Urethrocoele is the bulging of
the urethra into the lower one third of the anterior vaginal wall
...
Cervical prolapse
Classification of pelvic organ prolapse
•
1st degree (in vagina)
•
2nd degree (at vaginal interiotus)
•
3rd degree (outside vagina)
•
Procidentia (entirely outside vagina)
Symptoms of pelvic organ prolapse
•
Any prolapse:
! asymptomatic
! worry
! coital difficulties (sexual intercourse difficulties)
•
Cystourethrocele (bladder/urethra prolapsed through anterior vaginal wall):
! stress urinary incontinence
! urinary retention
! recurrent UTI
•
Uterine/vault prolapse
! backache
! ulceration if procidentia (completely out of vagina)
•
Rectocele (rectum prolapsed through posterior wall):
! constipation
! dyschezia (difficulty defecating)
Assessment of Prolapse Organ Prolapse
History
•
Age and Parity
•
PC: urinary symptoms, bowel symptoms, sexual symptoms, other symptoms
•
PMH: including past Obs and Gynae history and past surgical history
•
FH
•
DH
•
Allergies
•
SH and occupational history
•
Concerns and expectations
Examination
•
•
BP
•
Urinalysis
•
Weight, height and BMI
Abdominal Examination
•
Pelvic Examination:
! Urinary incontinence and evidence of pelvic prolapse on coughing
! Uterine size and position
! Adnexal mass: lump in tissue of the adnexa of uterus, usually in the ovary or
fallopian tube
...
g
...
It is designed to support
areas of pelvic organ prolapse
...
THE MENOPAUSE AND HRT
•
Menopause is the cessation of a woman's reproductive ability, the opposite of menarche
...
g
...
The
perimenopause describes a six to ten year phase ending 12 months after the last menstrual
period e
...
ending at the menopause
•
Premateur menopause = < 40 years
•
Early menopause < 45 years
•
Contaception during menopause:
! If < 50 => contraception for 2 years after LMP
! If > 50 => contraception for 1 year after LMP
Reminder of normal menstrual cycle
•
Follicular phase (begins on first day of menstruation and lasts approximately 14 days in a 28
day cycle):
! Follicle-‐stimulating hormone (FSH) is released from anterior pituitary in response
to GnRH stimulation
...
! FSH stimulates granulosa cells (cellular layer which surrounds follicles in the
ovaries) to convert androgens (coming from the thecal cells) to estradiol (E2) by
aromatase during the follicular phase of the menstrual cycle
! With the rise in oestrogens E2 (from granulosa cells), LH receptors are also
expressed on the maturing follicle, which causes it to produce more estradiol
(and prepares follicles for LH surge)
! LH supports theca cells in the ovaries that provide androgens and hormonal
precursors for estradiol production
...
This "LH surge"
triggers ovulation, thereby not only releasing the egg from the follicle, but also
initiating the conversion of the residual follicle into the corpus luteum that, in
turn, produces progesterone to prepare the endometrium for a possible
implantation
•
Luteal phase (approximately day 14-‐28 of 28 day cycle):
! After ovulation (triggered by LH surge) the granulosa cells turn into granulosa
lutein cells (corpus luteum) that produce progesterone
...
! If fertilisation/implanatation does not occur then rising levels of progesterone
released from the corpus luteum will –vely feedback to the hypothalamus and
pituitary => will cause a decrease in LH which will cause regression (degeneration)
of the corpus luteum
...
•
Ovaries produce oestrogen (mostly eostradiol E2), progesterone and testosterone
(androgens also produced in adrenals)
...
g
...
Estriol is only produced in significant amounts during pregnancy as it is made by
the placenta
...
g
...
•
Hormone levels fluctuate and become unpredictable
Effects of the menopause
•
Effects of menopause can be classified as:
! Acute symptoms
! Medium term effects
! Long term consequences
Acute symptoms
!
Vasomotor (effects majority of woman)
! Hot flushes
! Nights sweats
!
General
! Headache
! Fatigue
! Insomnia
! Arthralgia
! Dizziness
! Many other non specific features
!
Psychological
! Poor memory
! Loss concentration
! Irritability
! Low mood
! Anxiety
! Reduced libido
Medium term effects
!
Vaginal
! Dryness/itch/burning: atrophic vaginitis
! Dyspareunia (pain during sex) due to vaginal dryness
! Sexual dysfunction
! Prolapse
! Atrophy which may cause vaginal bleeding
!
General
! Dry skin
! Hair thinning
!
Urinary tract
! Urinary frequency/nocturia
! Urgency
! Stress/urge incontinence
! Recurrent UTI
Many of these effects primarily occur due to oestrogen depletion in skin in urogenital tissues
...
Oestrogen reduces LDL, increases HDL,
reduces cholesterol deposition and fat distribution => “normal” levels of oestrogen are CV
and cerebrovascular protective
...
!
Osteoporosis (decreased BMD < -‐2
...
Occurs due to loss of protective
effect from oestrogen in premenopausal state (oestrogen protects bones)
...
Hip fracture 30% mortality rate
...
High burden to society
...
Management of the menopause
•
To minimise symptoms and reduce risk long term consequences (e
...
CV disease and
osteoporosis)
•
Lifestyle measures: healthy diet, regular exercise, stop smoking
•
HRT if young onset or decreased QoL (e
...
due to symptoms)
...
This is in contrast to COCP, which increases the levels of
hormones in the body
...
g
...
g
...
This is because progesterone is essential for maintaining endometrial
protection
...
Subtotal hysterectomy => may also need progestogens (some endometrium may remain)
!
If woman have uterus => must use combined oestrogen and progestogen HRT
!
NB: The Mirena is now licensed for use with Oestrogen only HRT for 4 years
...
In women
with an intact uterus, oestrogen HRT stimulates the growth of the womb lining
(endometrium), which can lead to endometrial cancer if the growth is unopposed
...
In this case you are technically giving them combined HRT, except the mirena is
better because the progesterone is less systemically absorbed so that's why you can give it
to people who have a uterus, because the mirena is protecting their uterus without needing
to give them a progesterone pill
...
Also usefull if woman wants a form of contraception (as
they may still be fertile during the peri-‐menopause)
...
Sequential Combined HRT
!
!
Oestrogen for 28 days – continuous oestrogen
!
Progesterone for 10-‐14 days => then a 14-‐18 day progesterone free period
!
Mimics normal menstrual cycle, oestrogenic proliferation of endometrium (in the follicular
phase / proliferative phase) followed by shedding in 2nd half cycle (luteal phase => corpus
luteum regression causes falling levels of progesterone => shedding of the endometrium)
!
For use in peri-‐menopausal women with uterus (as simulates normal cycle)
!
Sequential oestrogen and progestogen
Progestogen protects the endometrium and leads to a regular bleed
!
Single named product available as patch/tablet or combine two different preparations
Continuous Combined HRT
!
Continuous Combined HRT (CCT: continuous combined therapy)
!
Oestrogen combined with progestogen for 28 days => inhibits monthly bleeds
!
This should not be started until 1 year after the LMP (menopause) or aged 54
!
Single named products available as tablets/patches
!
No monthly bleed (after 1st 6 months)
When to start/switch?
!
Sequential combined HRT (14-‐18 day progesterone free period)
! Started when required in perimenopausal women (may still have periods) – as
simulates natural cycle
! Prolonged use can increase the risk of endometrial cancer (due to oestrogen
induced hyperproliferation) => max duration 5 years
!
Continuous combined HRT (no progesterone free period)
! This should not be started until 1 year after the LMP (menopause) or aged 54
! Should also be used after 2 years of sequential therapy if under the age of 54
Key points
•
Over 54 or LMP> 1yr (menopause) => start CC HRT (continuous combined HRT) – in woman
with uterus
•
Under 54 and/or peri-‐menopause => Sequential HRT (progesterone free period) for 2 yrs
then switch to CC (continuous combined) HRT – in woman with uterus
Tibolone (Livial®)
!
!
Alternative to CC HRT (postmenopausal women)
Synthetic steroid → weak oestrogenic, progestogenic and androgenic properties (non-‐
selective)
!
Licensed for vasomotor, psychological and libido problems
!
Conserves bone mass and reduces risk fractures (not hip)
!
The risk: benefit ratio similar to HRT in women under 60, but over 60 increased risk of stroke
!
Slightly increased risk for endometrial cancer (due to oestrogen component)
!
Less risk of breast cancer: similar risk to E2 only HRT (less than combined HRT)
Testosterone
!
Testosterone levels may drop by up to 50% after menopause or BSO (Bilateral salpingo-‐
oophorectomy)
...
g
...
g
...
Benefits of HRT
Menopausal Symptoms:
!
HRT shown to effectively relieve vasomotor symptoms e
...
relieve hot flushes and night
sweats (one of the main reasons woman start HRT)
!
In most cases, <5 years therapy is sufficient
!
Symptoms may recur for a short time after stopping it
Colorectal cancer:
!
HRT reduces the risk of colorectal cancer
!
This is likely to be the anti-‐oxidant effect of oestrogen
Osteoporosis:
!
Used in prevention and treatment
!
Reduced risk of osteoporotic fractures with HRT in RCTs
!
Not 1st line in older women as Tx osteoporosis as less risky alternatives e
...
bisphosphonates
e
...
pamidronate
Osteoporosis: risk factors
Minor
!
Cigarette smoking
!
Sedentary lifestyle
!
Low Calcium intake – must ask about calcium intake
Moderate
!
FH of osteoporosis
!
Underweight
!
High alcohol consumption
Major
!
Early menopause
!
Prolonged steroid therapy – must take life long steroid history
!
Prolonged amenorrhoea
HRT is a very good option in younger perimenopausal women if other risk factors present
...
Major secondary causes of osteoporosis = GI malabsorption (coeliac and crohns), iatrogenic
(steroids), endocrine (Cushings, DM, thyroid), etc
...
g
...
Progesterones have the dominant effect in HRT as the levels of progesterone are high in HRT
(similar to levels in OCP)
...
ER +ve and PgR +ve breast cancers can be stimulated by combined HRT
...
Combined
significantly higher than oestrogen only
...
!
Higher with combined HRT than oestrogen-‐only (although oestrogen is major risk factor,
progesterones may contribute)
!
More common in the first year of use
!
Risk may be lowered by transdermal route/changing progestogen
Stroke and CV disease:
!
In RCT’s HRT increased the risk of stroke (mostly ischaemic) compared with placebo
!
Older women have a greater absolute risk of stroke
!
Risk may depend on oestrogen dose
!
No significant difference between E2 only/combined preparations
!
HRT may raise BP
Therfore it is important to also perform a CV assessment at initial HRT consultation (similar
consultation initating COCP): migraine with aura, previous cerebrovascular accident or CV
accident, CV risk factors, personal or family history of DVTs, personal or family history of O&G
cancers, smoking status, BMI, BP
HRT Uncertainties: CVD
!
Initially thought to be beneficial
!
Re-‐analysis WHI study suggests a cardio-‐protective effect if HRT taken in the early
menopausal years
!
Increased risk of CVD in women who started combined HRT more than 10 years after the
menopause
!
No increased risk of CVD has been identified to date with oestrogen-‐only HRT
!
Oestrogen can raise BP => may act as a CV risk factor
!
Increased absolute excess risk the longer after menopause it is started
...
! Premature menopause (<45 years)
•
Starting HRT in women over the age of 60 years is generally not recommended
...
•
Current indications for the use of HRT are:
! For the treatment of menopausal/perimenopausal symptoms where the
risk:benefit ratio is favourable, in fully informed women
...
HRT contraindications
HRT may not be suitable if you are pregnant or have:
•
•
a history of heart disease or stroke
•
untreated high blood pressure (your blood pressure will need to be controlled before you
can start HRT), high BMI, smoker or have other DVT risk factors
•
a history of blood clots, DVTS or PTEs
•
a history of breast cancer, ovarian cancer or endometrial cancer
liver disease
VERY SIMILAR TO COCP!
HRT: In summary
!
Serum FSH level > 30 IU/l on 2 separate occasions + low oestrogen => ovarian failure =>
often menopause (primary ovarian failure) in woman of middle ages (in younger woman
<45 must rule out secondary causes)
!
Offer HRT to if very symptomatic => Lowest possible dose to control symptoms for the
shortest possible time
!
Offer HRT if early (<45) or premature (<40) menopause
Non-‐oestrogen based therapy
!
Clonidine: no firm evidence in clinical trials but some women get benefit for ‘hot flushes’
...
Antidepressants may also act on
thermogenic centres of brain therefore may provide some relief from hot flushes although
unproven in trials
...
g
...
g
...
•
While we can not endorse their efficacy or safety, we should be able to provide unbiased
information to aid choice
...
g
...
g
...
Herbal methods
often marketed as ‘food supplements’ so not subject to same regulations as conventional
drugs therefore should be used with caution
...
g hot flushes, night sweats, irritability)
! Longer term: bone loss, CVS and stroke risk, cognitive decline/dementia,
reduced fertility and infertility (due to anovulation), ↓ life expectancy
Premature ovarian failure causes
Primary causes
! Idiopathic
! Chromosomal e
...
Turners 45X, Down syndrome, Fragile X
! AI: Hypothyroidism, Addisons, DM, SLE, RA
! Enzyme deficiencies: Galactossaemia
Secondary causes
•
Chemotherapy/radiotherapy
•
Surgery: bilateral oophrectomy, hysterectomy
•
Infection: TB, mumps
POF: Treatment
!
Hormone replacement (HRT) required to keep tissues healthy and reduce long term
complications
!
HRT (higher doses) or COCP (optional pill free week) to age 52
!
Sequential combined HRT as simulates natural cycle
!
Testosterone as patch or implant
!
Additional vaginal oestrogen may be needed
!
Risks at this age are due to non-‐use of HRT (e
...
early CV disease and bone disease) rather
than use (on HRT same risk as age-‐equivalent population for breast cancer, VTE etc; this is
because we are just “normalising” hormone levels) => patients with POF should definitely
be on HRT
!
No studies have clearly shown best replacement hormones (HRT vs OCP)
PATHOLOGY OF THE OVARY AND FALLOPIAN TUBE
Anatomy reminder
Physiological Ovarian Cysts
1
...
g
...
Corpus Luteum Cyst
•
>3cm diameter
•
Derived from post-‐ovulatory follicle
•
May rupture => haemoperitoneum
Ovarian Tumours
•
Functional tumours usually present when small i
...
secreting oestrogen or androgens
•
Extremely large tumours may be benign
•
Non-‐functioning tumours present late due to inaccessible location of ovaries
•
Malignant ovarian tumours, mainly epithelial (adenocarcinoma), generally have a poor
prognosis
...
•
Can be benign, borderline or malignant
•
Malignant tumors of this type are also called ovarian adenocarcinoma
...
•
No solid areas
•
Can weigh several kg and cause abdominal distension
...
•
Pathology: papillary pattern (pappilary cores) covered by serous type epithelium similar to
the Fallopian tube
...
e
...
•
The COCP is also protective for ovarian cancer and endometrial cancer; however is a risk
factor for breast and cervical cancer
•
Aetiology
! Repeated ovarian surface trauma due to ovulation is the probable aetiological
factor
! Therefore pregnancy (multigravida) and oral contraception decrease the risk (as
generate an anovulatory state)
Ovarian adenocarcinoma
•
Surface epithelial-‐stromal tumour, also known as ovarian glandular epithelial carcinoma or
ovarian adenocarcinoma
•
Most common type of ovarian cancer
•
It includes serous adenocarcinoma, endometrioid adenocarcinoma and mucinous
cystadenocarcinoma
...
Features of epithelial ovarian cancer
•
Presents late, vague symptoms:
! Dyspepsia like picture
! Abdominal pain and swelling and bloating
! Early satiety
! Ascites
! Pressure effects on other organs e
...
urinary symptoms
•
Spreads throughout peritoneal cavity
•
Poor prognosis: 5 year survival 43%
•
6th commonest female malignancy
•
Kills more women each year than all other gynaecological cancers combined
Mucinous Adenocarcinoma
•
•
Multiloculated cysts, solid areas, necrosis, haemorrhage
...
•
Invasive
•
pseudomyxoma peritonei – as mucus filled tumour
Serous Adenocarcinoma
•
Cancer of fallopian tube type epithelium
•
Often bilateral
•
Solid/cystic tumour with necrosis
•
Papillary projections from outer surface of capsule
...
•
Sex cord-‐stromal tumours retain bisexual potential
...
Most cases of endometrial hyperplasia result from high
levels of estrogens, combined with insufficient levels of the progesterone-‐like hormones
which ordinarily counteract estrogen's proliferative effects on this tissue
...
! If the patient is postmenopausal, she usually presents with abnormal uterine
bleeding (due to uterine endometrial hyperplasia) e
...
PMB
! If the patient is of reproductive age, she would present with menometrorrhagia
(prolonged or excessive uterine bleeding occurs at usual time of menstrual
periods and IMB)
...
•
Behaviour difficult to predict
...
•
However, thecomas often secretes oestrogen => can cause endometrial hyperplasia => can
cause abnormal uterine bleeding
! Pre-‐menopause: IMB (inter-‐menstrual bleeding) or menometorrhagia
! Post menopause: PMB (post menopausal bleeding)
•
Yellow colour, due to lipid in cells
...
A rare type of thecoma, called a Sertoli-‐
Leydig tumor, produces testosterone, so women with this type of thecoma may develop
masculine characteristics such as a deepening voice and excess facial hair e
...
virilisation
...
•
Sertoli-‐Leydig cell tumours often secrete androgens, which can cause virilisation
(masculinisation):
! Voice deepening
! Clitomegaly
! Excessive hair growth (hirsutism)
•
Acne can also occur due to increased testosterone levels
•
Masculinization (virilisation) is preceded by anovulation, oligomenorrhoea, amenorrhoea
and defeminization
...
•
Serum testosterone level is high
...
Most common germ cell tumour
...
•
Choriocarcinoma (produces HCG): Extra-‐embryonic germ cell malignant tumour producing
tumours of placental tissues
...
•
Endodermal sinus tumor (EST), also known as yolk sac tumor (produces AFP): Extra-‐
embryonic germ cell malignant tumour producing tumours of placental tissues
...
•
Dysgerminoma: undifferentiated germ cell tumour (malignant)
Benign cystic teratoma (Dermoid cyst)
•
•
Does not produce hormones
•
Benign
Common, up to 20% of all ovarian tumours
...
•
Can also produce thyroxine from ectopic thyroid tissue
Metastatic Tumours
•
7% of lesions presenting as ovarian tumours are metastatic
...
•
Krukenberg tumour: solid, fibrotic, metastatic tumour with signet-‐ring cells, often from
stomach
...
In contrast, salpingitis only refers to infection and inflammation in the fallopian
tubes
...
•
Anyythich which can obstruct the path of the fertilised egg from tube to uterus is a risk
factor for ectopic pregnancy
•
Risk factors:
! PID and Tubal obstruction
! I
...
C
...
(intrauterine copper device) and Mirena (Levonrgestrel-‐IUS)
Fallopian Tube Tumours: Adenocarcinoma
•
•
Serous adenocarcinoma – commonest
Rare
•
Presents late
•
Poor prognosis
PELVIC MASSES
Anatomy
Pelvic mass: non gynaecological causes
•
Bowel
! Constipation!
! Caecal carcinoma
! Appendix abscess
! Diverticular abscess (partciulary in LIF)
•
Bladder/Urological
...
g
...
Pelvic mass: Gynaecological causes
•
Uterine
! body
! cervix
•
Tubal & para-‐tubal
•
Ovarian e
...
Can
become very large
...
It is effectively endometriosis of the myometrium
...
•
Usually few cm, but may be much bigger & multiple
•
Therefore common cause of pelvic mass
•
Presentation:
! May be asymptomatic/incidental finding
! Menhorrhagia (heavy menstruation loss >70ml)
! Pelvic mass or “bulky uterus”
! Pain/tenderness
! Red degeneration: A rare complication of a fibroid during pregnancy is a problem
known medically as red degeneration
...
This usually happens in the middle
trimester (three months) of pregnancy and is thought to result from the
leiomyoma (fibroid tumour) growing rapidly and outgrowing its blood supply
...
Can also occur in menopause
...
g
...
! MRI for more precise localisation
•
Management:
! Expectant if asymptomatic (after menopause fibroids shrink and it is unusual for
fibroids to cause problems
...
In contrast to a hysterectomy the
uterus remains preserved and the woman retains her reproductive potential
...
! Hysteroscopic Resection
...
•
Occasionally asymptomatic until large chocolate cyst, which may rupture
...
g
...
g
...
g Krukenberg tumor: signet cells) and GI
primaries
...
! Bloating
! ‘Pressure’ symptoms (especially bladder e
...
incontinence)
! Change of bowel habit
! SOB/ Pleural effusion
! Leg oedema or DVT
! Even generalised oedema if low albumin
...
B There may not be a pelvic mass
...
B: OCP is protective
•
This is in contrast to cervical cancer: where younger age, multiparity and OCP are risk
factors
•
The menstrual cycle causes damage to ovarian cells over a long period of times => therefore
suppression of menstrual cycle (e
...
multiparity and OCP) decreases the risk of ovarian
cancer
Investigation of suspected ovarian CA
•
Triple assessment
•
History & examination
•
Tumour markers
! CA 125 (cancer antigen 125): particularly a sign of ovarian serous
adenocarcinoma (most common ovarian cancer)
! Carcino-‐embryonic antigen CEA
•
Imaging
! USS better for imaging nature of cyst
! CT better for assessing disease outwith ovary especially omental disease,
peritoneal disease and lymph nodes
...
•
Normal level does not exclude cancer
•
Moderate elevation seen in numerous situations e
...
! Endometriosis
! Peritonitis/infection
! pregnancy
! Pancreatitis
! Ascites from any cause
...
g
...
•
CEA is classically associated with cololrectalCa
Diagnosis of ovarian cancer: suspicious USS findings
•
Complex mass with solid & cystic area
•
Multi-‐loculated
•
Thick septations
•
Associated ascites
•
Bilateral disease
•
Any ovarian cyst/mass in older woman is red flag and should be removed
Diagnosis of ovarian cancer ‘Risk of Malignancy’ index
•
RMI (risk of malignancy index) combines three pre-‐surgical features:
! Serum CA125
! Menopausal status (M)
! Ultrasound score (U)
•
The RMI is a product of the ultrasound scan score, the menopausal status and the serum
CA125 level (IU/ml)
...
Treatment of ovarian cyst/mass
•
Removal or drainage if likely benign
•
Malignant: removal of ovaries (oophorectomy) and uterus (hysterectomy) withwith
removal/biopsy of omentum, ‘debulking’ of tumour and complete examination/inspection of
all peritoneal surfaces (laproscopically)
! Total abdominal hysterectomy (TAH) with bilateral salingo-‐oophorectomy and
omenal debulking
•
Chemotherapy may be given pre-‐surgery or after surgery e
...
platinum based
•
Cure unlikely unless confined to ovary at presentation
...
g
...
•
Speed of onset/duration of all symptoms
Family history
•
Previous gynaecological and surgical history
...
Describe the mass
•
Three C’s, three S’and three T’s: colour, contour, consistency, shape, size, site, tethered,
texture, tempetrature
! Location
! Size: cms or ‘weeks gestation’
! Consistency e
...
soft, firm, hard, fluid filled
! Surface: Smooth, irregular, speculated, craggy
! Tenderness
! Mobility: tethered, mobile
THE PATHOLOGY OF THE UTERUS AND ENDOMETRIOSIS
Endometrium: Normal endometrial cycle
1
...
As they mature, the ovarian follicles secrete increasing amounts of
estradiol E2
...
The estrogen also
stimulates crypts in the cervix to produce fertile cervical mucus, which may be noticed by
women practicing fertility awareness (Billings method)
2
...
During the secretory phase, the corpus luteum produces
progesterone, which plays a vital role in making the endometrium receptive to
implantation of the blastocyst and supportive of the early pregnancy, by increasing blood
flow and uterine secretions and reducing the contractility of the smooth muscle in the
uterus
...
Menstrual phase
•
Loss of functional layer as hormone levels decrease (particularly progesterone): corpus
luteum releases progesterone which –vely feedsback to the hypothalamus resulting in
decreasing levels of LH => regression of corpus luteum (if implantation does not occur) =>
decreasing levels of progesterone and oestrogen => shedding of the endometrium
...
The decidua becomes part
of the placenta; it provides support and protection for the gestation
...
The corpus luteum is
maintained by hCG released from the trophoblasts of the placenta
...
OCP/Hormone therapy:
•
Appearances depend on type and dose of hormone e
...
HRT has much lower levels of
oestrogen compared to OCP (but similar progesterones)
•
Oral contraceptives "fool" the pituitary gland so that it produces less follicle stimulating
hormone and luteinizing hormone
...
•
The primary contraceptive mechanism of the combination OCP is to prevent ovulation by
inhibiting gonadotropin secretion at both the level of the pituitary gland and the
hypothalamus
...
The progestin component of the OCP suppresses luteinizing hormone (LH) secretion and
thus reliably prevents the LH surge which triggers ovulation
•
Oral contraceptives have two other main effects:
! They thin the inner lining of the uterus (called the endometrium), depleting it of
glycogen (ie, a type of sugar), and decreasing its thickness
...
In a normally menstruating woman
who is not taking contraceptive hormones, progesterone is only present in
appreciable quantities during the luteal phase (uterine secretory phase) of the
menstrual cycle, after the development of the endometrium (uterine proliferative
phase)
...
The result is a thin (as oestrogen is not properly doing its job in repro tract),
decidualized endometrium with atrophied glands that is not receptive to
embryo implantation
...
I
...
C
...
g
...
Pregnancy
•
Hypersecretory pattern as corpus luteum does not regress
•
‘Arias-‐Stella’ reaction (chorionic tissue)
•
If a blastocyst implants, then the thick secretory endometrial lining remains as decidua
...
4
...
•
Drop in hormone levels (drop in oestrogen and progestogens => increased LH and FSH)
Cystic change
Endometritis: Inflammation of endometrium
1
...
U
...
D
...
Chronic
•
May follow acute or be chronic from start
•
Associated with pelvic inflammatory disease and I
...
C
...
•
Lymphocytes and plasma cells present
3
...
g
...
g
...
g
...
g
...
Even though it is an oestrogen receptor antagonist in breast tissue (and used to target ER
+ve breast cancers) it acts as partial agonist on the endometrium and has been linked to
endometrial cancer in some women
...
•
Risk of adenocarcinoma increases with the degree of atypia
...
•
Hysterectomy usually indicated
...
g
...
The high levels of progesterone produced during
pregnancy has a protective effect against endometrial cancer
...
g
...
g
...
g oestrogen only HRT or tamoxifen
! Some types are not oestrogen-‐related e
...
DM
! Pelvic irradiation implicated occasionally
Pathology of Endometrial Adenocarcinoma
•
Diffuse endometrial thickening or polypoid mass
...
•
Grades 1 (low), 2 (intermediate) and 3 (high)
•
Most are Grade 1 (well differentiated)
Diagnosis
•
•
Transvaginal ultrasound to examine the endometrial thickness in women with
postmenopausal bleeding is increasingly being used to aid in the diagnosis of endometrial
cancer
In the United Kingdom, both transvaginal ultrasound and an endometrial biopsy are used
for diagnosing endometrial cancer
...
Ultrasound findings alone are not conclusive in cases of
endometrial cancer, so another screening method (for example endometrial biopsy) must be
used in conjunction
...
Endometrial biopsy is the less invasive option, but it may not give
conclusive results every time
...
CT scans are used for preoperative imaging of
tumors that appear advanced on physical exam or have a high-‐risk subtype (at high risk of
metastasis)
...
These include a
chest x-‐ray, liver function tests, kidney function tests, and a test for levels of CA-‐125, a
tumor marker that can be elevated in endometrial cancer
...
•
Distant spread (liver, lung) occurs late
...
Treatment
•
•
Radiation therapy, hormonal therapy, and chemotherapy are additional treatments (called
adjuvant therapy)
...
•
Most women with endometrial cancer, except those with stage IV disease, are treated with
hysterectomy
...
Hysterectomy is
traditionally performed through an incision in the abdomen (laparotomy), however,
endoscopic surgery (laparoscopy) with vaginal hysterectomy is also being used
...
This may be necessary because endometrial cancer often spreads
to the ovaries first
...
The lymph nodes in the pelvic region may also be biopsied or removed to check for
metastasis
...
•
Malignant glands and stroma => carcinosarcoma
•
Elderly women
•
Poor prognosis (~ six months)
•
Rapidly growing, bulky necrotic mass
•
Heterologous elements:
! malignant cartilage
! skeletal muscle
Tumours of the myometrium
Leiomyoma (fibroids)
•
A leiomyoma is a benign smooth muscle neoplasm
•
Arise from smooth muscle of uterine wall (myometrium)
•
Very common (fibroids)
! 20% of women over 35 years
! 40% of women over 50 years (more common in older woman)
•
Usually multiple and can be very large => bulky uterus, large for dates in pregnancy
•
May transform into leiomyosarcoma (malignant)
•
Occur in three main sites:
! Submucosal: A submucosal fibroid lies just under endometrium
! Intramural: An intramural fibroid that lies completely within the myometrium of
the uterus
! Subserosal: serosal or subserosal fibroid lies on the outer part of the uterus, just
under the covering of the outside of the uterus, which is called the serosa
...
! Histopathology: Interweaving smooth muscle bundles in benign leiomyoma
Leiomyosarcoma (cancerous fibroid)
•
Malignant smooth muscle tumour
•
Older women
•
Rare compared with leiomyoma
•
Poor prognosis
•
Mostly solitary, some arise from benign leiomyoma
...
e
...
•
Endometrial cells in areas outside the uterus are also influenced by hormonal changes and
respond in a way that is similar to the cells found inside the uterus
...
•
The pain often is worse with the menstrual cycle and is the most common cause of
secondary dysmenorrhea
...
g
...
As endometriosis can lead to anatomical distortions and
adhesions (the fibrous bands that form between tissues and organs following
recovery from an injury)
...
! Pelvic pain: A major symptom of endometriosis is recurring pelvic pain:
dysmenorrhoea (painful menstruations), dyspareunia (pain during sex), dysuria
(painful micturition), chronic pelvic pain
! Catamenial pneumothorax is a condition of collapsed lung (pneumothorax)
occurring in conjunction with menstrual periods (catamenial refers to
menstruation), believed to be caused primarily by endometriosis of the pleura
(the membrane surrounding the lung)
Endometriosis: occurs anywhere in genital tract
•
Ovary: Endometrioma (‘chocolate cysts’) – commonest site
•
Fallopian tube
•
Pouch of Douglas / rectouterine pouch (pelvic peritoneum) – can cause dyparenuia
•
Wall of intestine, appendix
•
Ureters, bladder
•
Surgical scars e
...
Caesarean section
•
NB: Adenomyosis is endometrial glands & stroma within the myometrium of the uterus
...
Can cause a boggy uterus
...
However, smaller endometriosis implants cannot be visualized with ultrasound technique
...
These tumours are not common, and they appear when cells in the uterus
(trophoblast cells of the conceptus placenta) start to proliferate uncontrollably
...
The trophoblasts are derived from the
blastocyst
...
•
Partial and complete hydatidiform moles will not produce a live baby (they are 'non-‐
viable' pregnancies)
•
A pregnancy that results in a hydatidiform mole is called a molar pregnancy
...
It is
usually due to two sperm fertilising one normal ovum (which should not usually happen)
...
The growth of the trophoblastic tissue overtakes the growth of any
fetal tissue and the fetus does not develop normally (unviable foetus; however unlike
complete Hydratiform mole the foetus does initially develop (abnormally) because both
maternal and paternal DNA are present)
...
•
Complete Hydratiform mole: Sometimes, during conception, a sperm (23,X or 23,Y) fertilises
an 'empty' egg (ovum)
...
Under normal circumstances, the fertilised empty ovum would die and not implant in the
uterus
...
Complete
Hydratiform mole is caused by a single sperm combining with an egg which has lost its DNA
(the sperm then reduplicates forming a "complete" 46 chromosome set)
...
The
combination 46,YY (diploid) is not observed (as X is essential to even initiate
embryogenesis)
...
This is a complete hydatidiform mole
...
g
...
A hydatidiform mole conception may be categorized in medical terms as one type of non-‐
induced (natural) "missed abortion", referred to colloquially as a "missed miscarriage",
because the pregnancy has become non-‐viable (miscarried) but was not immediately
expelled (therefore was "missed")
...
•
Ovarian cancer is the 6th most frequency diagnosed cancer in women in Scotland in 2011
...
In women in scotland with no FH the life time risk of
developing ov cancer is 1in 55
...
It is not a “silent killer”
...
CA125 blood serum level should be measured and urgent pelvic ultrasound carried out
...
Cheap and effective screening test
...
Risk of malignancy index (RMI)
•
So, once the diagnosis is suspected, how do we go on to make the diagnosis? Of course
CA125 can be raised in other benign conditions such as endometriosis and patient with
ovarian cancer can have a normal CA125
...
•
Pathology is the “gold standard”: usually from a CT guided biopsy of an omental deposit or
following laparoscopy guided biopsy of an abnormal ovary
•
Calculate the RMI based on:
! US features: high risk feature include multinodular cyst, solid areas, bilateral
lesions, ascites, intra-‐abdominal masses
! Menopausal state: post menopausal has higher risk => higher score
! CA125 levels
•
RMI= US score * menopause score * CA125 levels
•
Patients with an RMI >200 should be referred to a gynaecology-‐oncology multidisciplinary
team
...
•
CT scan is performed before surgery
•
NO TISSUE BIOPSY REQUIRED FOR Dx
Ovarian Cancer: Pathology
•
Pathology is the “gold standard” for diagnosis and “typing”
...
g
...
transcoelomic spread/ peritoneal seeding within pelvis → abdominal cavity
2
...
incidence of brain metastases in ovarian cancer <2%
Ovarian Cancer: Treatment
•
Surgery:
! Bilateral salpingo-‐oophorectomy (BSO): removal of both ovaries and both
fallopian tubes
! Total abdominal hysterectomy TAH
! Omentectomy: part or all of the abdominal lining is removed
...
It is used only in specific malignancies, as generally
partial removal of a tumor is not considered a worthwhile intervention
...
•
Surgery and chemotherapy: hope for cure
...
•
Chemotherapy: chemo alone can be used in incurable relapsing/remitting chronic disease to
prolong life
•
Hormone therapy
Ovarian Cancer: Hormone Manipulation
•
Tamoxifen (oestrogen modulator): 10% ovarian cancers respond to tamoxifen with about
30% achieving disease stabilisation
...
However, remember that it is a risk factor for endometrial cancer
...
BRCA Ovarian cancer
•
Caused by the BRCA mutations: causes high risk of breast and ovarian cancer (+ prostate
cancer in men)
•
Often a significant FH of BRCA related cancers (but not necessarily so)
•
Younger age at presentation
•
Most BRCA ovarian cancers are papillary serous subtypes
•
Do not present typically:
! High incidence of visceral disease at presentation and relapse including brain
metastases
! Good responses to numerous courses of platinum based chemotherapy
! long remissions
! unusual patterns of relapse
! Improved overall survival stage for stage
•
•
Increasing numbers of referrals for BRCA testing based on characteristics of a patients
cancer rather than FH (e
...
young age, papillary serous type, early spread to brain)
Different management of this “different” disease
The role of prophylactic salpingo-‐oophorectomy
•
Women with a family history that appears to place them at high risk of developing ovarian
cancer should be offered referral to a Clinical Genetics Service for assessment, confirmation
of family history and consideration of genetic testing of an affected family member
...
g
...
Women with ovarian cancer who have a family history of breast or
ovarian cancer should have a genetic risk assessment
...
•
Prophylactic salpingo-‐oophorectomy: “Women with genetic mutations of BRCA1 or BRCA2
genes should be offered prophylactic oophorectomy and removal of fallopian tubes at a
relevant time of their life
...
Hormone replacement can be used after oophorectomy until the
time of natural menopause without losing the benefits of breast cancer risk reduction
...
”
Screening
•
A large US study showed there is no benefit in screening
...
BEAT ovarian cancer
•
B for bloating that is persistent and doesn't come and go
•
E for eating less and feeling fuller
•
A for abdominal pain
•
T for telling your GP
Summary
•
Ovarian cancer is not an asymptomatic condition
...
All studies
identify abdominal distension/bloating as the most important symptom together with
early satiety and abdominal/pelvic pain
...
This is likely because the clinical
features is very similar to the presentation of dyspepsia, a very common GI condition
...
Why is cytoreduction (surgical debulking) essential?
• Immediate reduction of tumour mass (improvement of bowel function, diet)
• Chemotherapy is more effective if tumour volume is small (perfusion)
...
•
However it can be used as a palliative treatment for metastatic bone or brain lesions or of
localized recurrence to alleviate the pain
...
in 3 years)
Colposcopy
•
Magnified inspection of cervix
•
Use of stains to identify abnormality => cant take biopsy or remove (LLETZ)
•
Colposcopist -‐ assessment of abnormality
•
Options (usually outpatient):
! Biopsy and follow up
! Biopsy and treat with cold coagulation
! LLETZ
Following assessment
•
Biopsy gives histology results:
! CIN1 => follow up in 6 months (cervical smear)
! CIN 2 => treat e
...
cold coagulation or LLETZ
! CIN 3 => treat e
...
cold coagulation or LLETZ
! cGIN (cervical glandular interepithelial neoplasia)
! Cancer => treat e
...
cold coagulation or LLETZ +/-‐ chemo and/or radio
•
Treatment:
! Cold Coagulation (destructive): Hot probe which causes cells to burst
! LLETZ (Excisional): Electosurgical wire (cautery) can cut through tissue (loop)
Following treatment: Follow up
•
To identify treatment failures
•
To identify patients with recurrence early
•
While not causing significant anxiety to those who are not at risk
•
Test of Cure:
! Combined smear and HPV test: assessing for CIN (smear) and HPV
! Double negative: 3 yearly repeat smear
! If positive need further colposcopic assessment
Reassure patients with knowledge and be empathetic
•
Knowledge of procedure
•
Knowledge of relevance of HPV
•
Knowledge of follow up
•
Knowledge of vaccination programme for the future
•
Patient leaflets and website links
Counselling for an Abnormal Cervical Smear
The following points should be covered when counselling patients about a dyskaryotic smear:
•
•
The smear does not indicate cancer
Abnormal cells have been identified
...
•
Further investigation and treatment is required with the aim of preventing the development
of cancer in the future
•
Investigation includes colposcopy and a description of what this involves
•
Biopsies will be taken
•
Treatment will be carried out by ‘coagulating’ the cervix, destroying the abnormal cells/area
either by laser or surgery (large loop excision of transformation zone LLET2)
...
Sometimes the treatment
will be undertaken when the results of the biopsy are known
...
•
Test of cure at 6 months: If you have had treatment for cervical abnormalities called CIN
(cervical intraepithelial neoplasia), you will be screened again six months afterwards
...
•
Follow-‐up in the form of regular smears will be required e,g, every 3 years (20-‐60 year olds
Endometrial and ovarian disorders
Endometriosis
•
•
The uterine cavity is lined with endometrial cells, which are under the influence of female
hormones => cyclical symptoms
•
Endometrial cells in areas outside the uterus are also influenced by hormonal changes and
respond in a way that is similar to the cells found inside the uterus
...
•
The pain often is worse with the menstrual cycle and is the most common cause of
secondary dysmenorrhea
...
g
...
When blood touches these other organs, especially inside the abdomen, it can cause
inflammation and irritation, creating pain
...
This scar tissue can also contribute to
sub-‐fertility
•
Linked with retrograde mensruation
•
Defnitive Dx = laporoscopy
Clinical features
•
Pain: a major symptom of endometriosis is recurring pelvic pain
! Dysmenorrhea (secondary): painfull periods
! Dyspareunia: painful sex (coitus) – often deep
! Dysuria: painful voiding
•
Infertility
•
•
As endometriosis can lead to anatomical distortions and adhesions (the fibrous
bands that form between tissues and organs following recovery from an injury),
the causality may be easy to understand; however, the link between infertility
and endometriosis remains enigmatic when the extent of endometriosis is
limited
...
•
•
Many women with infertility may have endometriosis
...
Occurs during the
normal menstrual cycle because the endometriosis responds to hormones just like the
endometrium
...
Endometriosis of ovary
•
•
An endometrioma, endometrial cyst, or chocolate cyst of ovary is a condition related to
endometriosis => endometriosis of the ovary
Endometriomas usually cause the symptoms associated with endometriosis, including
dysmenorrhoea, dyspareunia, pelvic pain
...
•
There may also be an adnexal mass (RIF or LIF)
•
Ultrasound scan can be helpful in diagnosis, and CA125 may be slightly elevated
...
On pelvic
examination she has a 10 cm fixed smooth pelvic mass in her left adnexal region
...
•
Dx= Endometrioma (endometriosis of the ovary, endometrial cyst, or chocolate cyst)
...
Due to the adnexal
mass => suggestive of endometrioma
...
The malignant version of a
fibroid is extremely uncommon and termed a leiomyosarcoma
...
•
Ostrogen driven so regress post menopause
•
While most fibroids are asymptomatic, they can grow and cause heavy menstruation
(menorrhagia), painful menstruation (dysmenorrhoea), painful sexual intercourse, and
urinary frequency and urgency
...
Symptoms depend on the
location of the lesion and its size
...
g
...
A 35 year old woman complains of dysmenorrhoea and dyspareunia
...
A serum CA125 is mildly elevated
...
Ultrasound scan can be helpful in diagnosis, and
CA125 may be slightly elevated
...
A 68 year old present with vaginal bleeding 15 years after she had her last period e
...
PMB
...
•
Dx = Endometrial adenoCa usually presents as post-‐menopausal bleeding
...
Therefore the patients age is key for the formation of
the DD and a woman of 68 years presenting with postmenopausal bleeding => endometrial
cancer is right at the top of the DD
...
Example 3
3
...
On
examination she has a fixed irregular pelvic mass, measuring 8cm
...
•
Dx = Ovarian cancer commonly presents non-‐specific symptoms, such as anorexia, weight
loss and constipation
...
•
Commonest cause is (pappilary) serous cytadenocarcinoma
INFERTILITY, INFERTILITY SCREEN AND LABORATORY INVESTIGATION OF AMENORRHEA
DEFINITIONS
Primary amenorrhea: Failure to establish spontaneous periodic menstruation by the age of 16 years
regardless of whether secondary sex characteristics have developed (e
...
Turners sundrom 45 X)
...
g
...
Secondary amenorrhea: Absence of periodic menstruation for at least 6 months in women who have
previously experienced menses
...
g
pre-‐ovarian causes (hypothalamus and pituitary), pelvic causes, post-‐ovarian (obstructive)
•
Use endocrinology block lectures
ESTROGENS AND OVARIAN FUNCTION
•
The normal human ovary produces all 3 classes of sex steroids, estrogens, progestins and
androgens; however, estradiol (E2) and progesterone are its primary secretory products
...
Granulosa cells: conversion of androgens to estrogens (mainly estradiol E2) by
aromatisation, regulated by FSH
...
Effect on pituitary:
•
•
Slowly rising or sustained high levels of estrogen together with progesterone inhibit pituitary
gonadotrophin (LH and FSH) secretion by NEGATIVE FEEDBACK
...
PROGESTERONE
In nonpregnant women, progesterone is secreted mainly by the corpus luteum under the influence
of LH, during the luteal phase of the menstrual cycle
...
As estrogen concentrations rise, FSH secretion declines until regulatory mechanism take a
drastic change and high levels of estrogens E2 trigger a positive feedback mechanism,
causing an explosive release of LH (mid-‐cycle LH-‐surge) and to a lesser extent FSH
...
Inhibin (also produced by ovaries) also inhibits FSH secretion
...
Anatomical defects e
...
fibroids, endometriosis, fibrosis
B
...
g radiation, chemo, mumps, AI
C
...
Hypothalamic deficiency of GnRH (hypogonadotrophic hypogonadism): ↓ LH and
FSH => ↓ Estradiol E2)
• Organic causes: tumors, infection and other disorders
• Functional disorders: Stress, weight loss/diet (anorexia nervosa),
exercise, malnutrition, chronic debilitating diseases (eg end-‐stage
kidney disease, AIDS)
...
Pituitary:
• Deficiency of LH/FSH e
...
Sheehans syndrome or adenoma
(hypogonadotrophic hypogonadism): ↓ LH and FSH => ↓ Estradiol
E2)
• Inappropriate seceretion of prolactin: Drugs (e
...
anti-‐psychotics
and other dopamine blockers, metoclopramide and domperidone),
hypothyroidism, prolactinoma
...
Chronic anovulation with estrogen present:
1
...
Adrenal disease
• Cushing syndrome
• Adult-‐onset adrenal hyperplasia
3
...
Ovarian tumors
Note: classicaly hyperthyroidism is associated with amenorrhoea and hypothyroidism is associated
with menorrhagia
A good way to consier the causes of infertility is: pre-‐ovarian, gynae causes, and post ovarian
PRIMARY OVARIAN FAILURE (HYPERGONADOTROPHIC HYPOGONADISM)
Primary defect in the ovaries (absent/destruction):
•
•
•
↓ Estradiol-‐production (hypogonadism)
↓ Negative feedback => ↑ LH and FSH (hypergonadotrophic)
No withdrawal bleeding following progesterone challenge (as not enough oestrogen
present to cause proliferation of the endometrium)
Causes
•
Primary amenorrhea
•
! Androgen insensitivity syndrome – chrosomally male!
! 45 X: Turner syndrome
Secondary amenorrhea
! Premature ovarian failure (before age of 40): often idiopathic, many contributing
factors e
...
radio and chemo and AI
SECONDARY OVARIAN FAILURE (HYPOGONADOTROPHIC HYPOGONADISM)
Ovarian failure is secondary to organic or functional disorders of the CNS-‐hypothalamic-‐pituitary
axis:
•
•
•
↓ GnRH (hypothalamic disorder e
...
anorexia, severe illness) or ↓ (or inappropriately
normal) LH and FSH (pituitary disorder) => hypogonadotrophic
↓ Estradiol (hypogonadism)
No withdrawal bleeding following progesterone challenge (due to low oestrogen and
minimal/absent proliferation of endometrium)
Several disorders of the pituitary can lead to hypogonadism:
•
•
•
Space-‐occupying lesions that directly inhibit gonadotropin secretion by destruction of the
producing cells or by blocking delivery or secretion of GnRH
Necrosis of the pituitary (following postpartum hemorrhage: Sheehan syndrome)
Inappropriate secretion of prolactin (including drugs, other diseases eg hypothyroidism,
prolactinoma) => ↓ secretion of LH and FSH
...
g
...
5)
...
Obesity and ↑ androgens → ↑ peripheral aromatisation and ↑ acyclic estrogen production
→ anovulation/amenorrhea
...
5)
Normal estrogen and withdrawal bleeding following progesterone challenge
↑ testosterone and androstenedione
↓ SHBG (↓ synthesis due to ↑ androgens)
Insulin resistance and IGTT
LABORATORY TESTS AVAILABLE FOR EVALUATION OF PATIENTS WITH AMENORRHEA
A
...
•
Any woman of reproductive age with amenorrhea is assumed to be pregnant until proved
otherwise
...
B
...
g
...
g
...
Thyroid function tests:
•
•
•
TSH and free T4/T3
Primary hyperthyroidism: ↓ TSH, ↑ free T4 – associated with amenorroheea
Primary hypothyroidism: ↑ TSH, ↓ free T4 – associated with menorrhagia
D
...
Progesterone challenge test (to assess for oestrogen status)
•
•
•
•
Determination of relative estrogen status (not commonly used due to eoestrogen assays)
Give additional information regarding the outflow tract
...
If withdrawal bleeding occurs 5-‐7 days
later then the endometrium must have been previously exposed to adequate levels of
oestrogen, and the endometrium is able to proliferate in response to oestrogen +
progesterone
...
25 mg/day for 21 days) followed by another
progesterone challenge:
! If bleeding: normal outflow tract, but estrogen deficiency corrected by administered
estrogen: primary or secondary gonadal failure
...
This may be due to ovarian failure, indicated by raised
FSH, or hypothalamic-‐pituitary failure
...
g
...
Clinical examination found a euthyroid woman with some findings suggestive of low estrogen
production
...
3 U/l (1
...
5) => innapropriately normal (E2 is low so we would
expect FSH and LH to be raised)
LH 3
...
5-‐9
...
Lab results:
B-‐HCG Negative
Prolactin 7
...
6 U/l (0
...
0)
Bleeding following progesterone challenge
FSH 2
...
0-‐6
...
0 U/l (1
...
0)
Testosterone 2
...
6-‐2
...
0 nmol/l (15-‐90)
•
Dx= PCOS
! LH/FSH ratio is high
! Hirsutism and amenorrhoea and obesity are key clinical features
! Bleeding occurs on progesterone challenge test
Small Group Work: Intrapartum Care
You will be working in a small group to examine this clinical case and to go over your
answers
...
Scenario
Julie Evans, a primigravida (first pregnancy), is admitted in spontaneous labour at 41
weeks gestation
...
On admission, she is
experiencing uterine activity with mild to moderate uterine contractions occurring
every 5 minutes
...
The fetal heart rate is regular and within normal limits
...
The vertex is found to be 2 cms above the ischial spines (-2 foetal
station) and the pelvis is clinically adequate
...
She is accompanied by her husband
...
Most of the discussion concentrated upon Julie’s choice of pain relief
during labour
...
However, Julie also indicated that she
would consider Epidural Analgesia as a ‘last option’
...
Questions
A
Pain relief in labour
Following discussion, Julie opts for intramuscular injection of Diamorphine, 10 mgs
...
Strong in nature
...
Inhibit GABA inhibitory interneurons to reduce descending pain pathway
signals → increased tolerance for pain
...
3
Are there any effects on the fetus from Diamorphine?
Fetal respiratory depression
...
Following discussion,
Julie requests an Epidural to be sited and the obstetric anaesthetist is called
...
4
What is an Epidural and how does it relieve pain?
Epidural anaesthesia is inserted to the epidural spaces between L3 and L4
...
Monitor BP (can cause hypotension)
...
Catheter
...
Helps with
managing exhaustion and distress
...
This also avoids the
risks associated with GA and there is less nausea associated
...
Can cause
fetal bradycardia
Loss of Bladder Control (unable to tell it is full)
Itchy Skin, Sickness, Backache
...
Nerve damage
...
Progress of labour
To assess the progress of labour, a number of observations/assessments are made with
regard to the mother and fetus
...
8
What observations/assessments are made to assess the progress of labour?
•
Fetal Heart and CTG
•
Amniotic Fluid
•
Bishops score: Cervical Dilatation, cervical effacement, cervical consistency, cervical
position and foetal station
•
Contractions: length, frequency, strength (intrauterine)
•
Obstruction -‐ Moulding
•
Maternal Observations
9
Using the partogram, discuss the various observations/assessments recorded
...
If meconium present => label M
...
Positive caput and moulding
Dilated 7cm
1/5 palpable
Frequent but weak contractions
ROP
Dimorphine and epidural
BP fine
Urinalysis fine
10
From the partogram, it can be seen that by 1800 hours Julie is not progressing in
labour
...
The three P’s: Power, passage and passenger
Pow er is the problem s – as w eak contractions
...
If the cervix was poorly
dilated and unfavourable could sue vaginal PGs
...
2 nd stage C - section is very dangerous
...
individually
...
Gravidity and Parity
•
•
Gravida (Grava or G) is the number of times a woman has been pregnant
...
•
Parity (Para or P) is the number of completed pregnancies beyond 24 weeks gestation,
whether viable or stillborn
...
•
For example a woman who has been pregnant 3 times (where one pregnancy was a set of
triplets) has one term delivery, one preterm delivery (of her triplets), and one termination at
16 weeks would be described as: G3, P2
•
For example, a woman who is described as 'gravida 2, para 2 (sometimes abbreviated to G2
P2) has had two pregnancies and two deliveries after 24 weeks, and a woman who is
described as 'gravida 2, para 0' (G2 P0) has had two pregnancies, neither of which survived
to a gestational age of 24 weeks
...
•
In an obstetrical history the gravida (G) and para (P) status of a woman is often written in
abbreviated form
...
In a survey, only 20% of British midwives and obstetricians recognised a twin
delivery as a single parous event -‐ G1 P1 rather than G1 P2, revealing the potential lack of
standardisation in our documentation
...
A woman does
not become primiparous until she has delivered her baby/stillborn
...
•
A primagravida is in her first pregnancy
•
A multigravida has been pregnant more than once
...
Relationship of gravidity and parity to risk in pregnancy
•
Obstetric histories should always record parity, gravidity and outcomes of all previous
pregnancies, as:
! Outcomes of previous pregnancies give some indication of the likely outcome
and degree of risk with the current pregnancy
...
•
•
Normal labour in a primagravida is significantly different to normal labour in multiparous
women, as physiologically the uterus is a less efficient organ, contractions may be poorly
coordinated or hypotonic
...
Therefore,
progress is expected to be slower but delay longer than expected should prompt
augmentation in managed labour
...
After 6 cm dilation,
partogram curves for lower parity multips and grand multips are indistinguishable
...
[5]
Risks associated with nulliparity/primagravidae
•
Higher risk of developing pre-‐eclampsia
•
Delayed first stage of labour, though this could be considered normal in a primagravida
...
• HPV is a DNA virus which infects immature/metaplastic squamous epithelium as found at
the cervical transformation zone
...
The virus therefore
alters the host cell's signaling to stimulate proliferation
...
• High risk HPV – 16 and 18, increased risk of in-‐situ neoplasia (CIN) and invasive malignancy
•
•
•
•
•
•
•
•
•
•
(cervical carcinoma)
...
Cervical intraepithelial neoplasia (CIN) is dysplasia (altered growth and maturation) of the
cervical stratified squamous epithelium
...
CIN 2 and 3 = high grade, pre-‐cursor lesions to invasive carcinoma
...
The cervical screening programme aims to detect CIN using cytology (cervical smear) and
enables early treatment of CIN to prevent progression to carcinoma
...
Low grade dyskaryosis correlates with CIN 1 (low grade)
Moderate dyskaryosis correlates with CIN 2 (high grade)
Severe dyskaryosis correlates with CIN 3 (high grade)
The HPV vaccine aims to prevent HPV infection and we hope that over coming years we will
see a further decrease in CIN and cervical carcinoma
...
• Oestrogen causes proliferation of the endometrium
...
• Obesity is a risk factor
...
• Tamoxifen increases the risk of endometrial cancer
...
• Diagnosis is usually made on pipelle endometrial biopsy or hysteroscopy and
endometrial curettings (D&C)
• Most endometrial carcinoma is adenocarcinoma
...
These are graded 1-‐3 based on
percentage of solid growth and nuclear atypia
...
These are all by
definition high grade (grade 3) and show more aggressive behaviour
...
• High grade (grade 3) carcinomas are more likely to show advanced local invasion and
metastases
...
• Tumour stage (TNM system) is based on depth of myometrial invasion and involvement of
cervix, vagina, parametrial tissue and adnexae
...
Other uterine
tumours to be aware of:
Fibroids
• Leiomyoma – benign smooth muscle tumour of myometrium (fibroids)
...
Ovarian tumours
Tumour Origin
Name
Behaviour
Description
Epithelial (60-‐70%)
Serous cystadenoma
Benign
Cystic tumour lined by benign (single
layer) serous epithelium
...
Most common ovarian tumour
Mucinous cystadenoma
Benign
Cystic tumour lined by benign (single
layer) of mucinous epithelium
...
Borderline tumour (serous
or mucinous)
Some cystic tumours can show
borderline change
...
Rarely can metastasise
...
Ca125
Peritoneal
metastases common
...
Peritoneal involvement results in
mucinous ascites (Pseudomyxoma peritonei)
Germ Cell
Mature teratoma (dermoid
cyst)
Benign
Usually a mixture of differentiated
tissue types e
...
skin, hair, cartilage,
teeth, fat and thyroid
...
Metastases
Metastases
(type Malignant
depends on
primary tumour)
Often bilateral
...
A Krukenberg tumor refers to a malignancy in the
ovary that metastasized from a primary site,
classically the gastrointestinal tract, although it can
arise in other tissues such as the breast
...
• Recent research suggests that ovarian epithelial carcinomas actually arise from the
epithelium lining the fimbrial end of the fallopian tube not the ovarian surface epithelium
...
It is usually not diagnosed until an advanced
stage (stage 3 or 4)
...
• The tumour marker Ca125 is usually elevated
...
• 5 year survival rates; stage 1, 76%, stage 2, 56% , stage 3, 25% and stage 4 <10%
...
The tumour is high grade
(high rate of proliferation) and therefore tends to be chemo-‐sensitive
...
Women under 60 at
diagnosis are often tested for BRCA mutations as this can have an effect on novel treatments
(PARP inhibitors) and has consequences for female relatives
...
This is when the baby's head is even with the
ischial spines
...
• Key points
! -‐3 => 3/5th palpable => 2/5th engaged
! -‐2 => 2/5th palpapble => 3/5th engaged
! -‐1 => 1/5th palpable => 4/5th engaged
! 0 => 0/5th palpable => 5/5th engaged or fully engaged
! +1: nearly there
! +2: starting to crown (extend neck)
Questions
Scenario 1
A 32 year old woman attends for her routine smear test
...
At colposcopy the
gynaecologist sees an abnormal acetowhite area on the cervix and decides to take a punch biopsy
...
• What is the aetiology of this patient's disease? HPV 16 and 18
• What is the relevant pathology in this case? CIN III (high grade severe dyskaryosis)
• What further treatment or management does this patient need and why? Cold coagulation
or LLETZ electrowire technique (as significant risk of preogressing to cervical squamous cell
carcinoma)
• Combined test of cure (smear + HPV test) in 6 months
• How do you think the HPV vaccination programme will affect this disease over coming
years? Incidence will decrease
Scenario 2
A 59 year old obese lady is referred to the gynaecology clinic with persistent, heavy postmenopausal
bleeding
...
Ultrasound scan shows an abnormally thickened endometrium
...
• What is the likely diagnosis? Endometrial cancer (adenoCa)
• What are the risk factors? High levels of endogenous or exogenous oestrogens (unopposed),
DM, obesity, PCOS
• What is the relevant pathology? Adenocarcnioma in majority of cases
• What is the prognosis for this patient? Nornally very good
...
Her Ca125 is elevated at 331
...
The patient
also has a family history of breast cancer
...
Why? Risk of BRCA1/2 mutation
Para note
• Some teminology uses: Para = X +Y (e
...
two numbers assigned to Para)
• X = number of pregnancies exceeding 24 weeks gestation (with a delivery of live or stillborn
baby)
• Y = number of pregnancies ending before 24 weeks gestation
Example 1
•
A woman at 8 weeks into her first pregnancy = para 0+0
•
Parity does not become 1 until after delivery
•
Para 1+0 = single pregnancy with delivery of baby(s) born after 24 weeks gestation (alive or
still born)
•
Para 0+1 = single pregnancy with loss of baby(s) before 24 weeks
Example 2
•
•
A woman who has had a previously still birth at 32 weeks and a previous live birth at 40
weeks = para 2+0
Remember that the first figure = deliveries beyond 24 weeks (live or stillborn)
Title: Obstetrics and Gynaecology lecture notes
Description: A very comprehensive and detailed set of notes covering all aspects of Obstetrics and Gynaecology. Complete with a nice set of diagrams to aid learning. Useful for medical students.
Description: A very comprehensive and detailed set of notes covering all aspects of Obstetrics and Gynaecology. Complete with a nice set of diagrams to aid learning. Useful for medical students.