Repro- Physiology Flashcards
Briefly describe structural development of humans
In utero
Start with one tissue, 2 pairs of ducts (mesonephric and paramesonephric duct)
2 possible development outcomes - under the influence of sex chromosomes- male or female
Briefly describe functional development of humans
Human babies are born physically immature
Childhood is followed by adolescence - sexual maturation and puberty
Secondary sexual characteristics
What are some male secondary characteristics?
Increased body height (relative to females) Body composition and fat distribution Hair and skin Facial hair, male pattern and baldness CNS effects Smell
Under influence of presence of male sex hormones
What are some female secondary characteristics?
Decreased body height relative it males Subcutaneous fat distribution Hair and skin Breast development CNS effects
Under influence of absence of male sex hormones; prepare female for support of gestation
List the male internal genitalia
Testis Duct system- epididymis, vas deferens, urethra Seminal vesicles Prostate gland Bulbourethral glands
List the male external genitalia
Penis
Scrotum
List the female internal genitalia
Ovaries
Duct system- Fallopian tube, uterus, cervix vagina (superior 1/3)
List the female external genitalia
Vagina (inferior 2/3) Vestibule Labia minora Labia majora Clitoris
What cells influence the formation of the gonad in a foetus, thus determining gender?
Primordial germ cells
When do primordial germ cells form in a foetus?
Very early
Differentiation that produces these cells happens well before folding
Where do primordial germ cells arise?
In the yolk sac
Where do primordial germ cells migrate to?
Migrate to peritoneum along the dorsal mesentery
Describe the formation of the gonad (testis) in a male foetus
Male gamete has a Y chromosome, so a XY concepts forms
Primordial germ cells in the yolk sac carry a Y chromosome- which has a SRY gene on it (44+XY)
Primordial germ cells migrate to peritoneum along the dorsal mesentery and occupy the urogenital ridge, stimulating the development of the indifferent gonad which has SRY gene receptors
Primordial germ cells set up population in the medullary cords of the indifferent gonad
Causes the development of testis - where gametes are produced in the medulla
Describe the formation of the gonad (ovary) in a female foetus
Male gamete has an X chromosome, so a XX concepts forms
Primordial germ cells in the yolk sac do not carry a Y chromosome- so there is no SRY gene on it (44+XX)
Primordial germ cells migrate to peritoneum along the dorsal mesentery and occupy the urogenital ridge, stimulating the development of the indifferent gonad which does not have the SRY gene receptors
Primordial germ cells set up population in the cortical cords of the indifferent gonad
Causes the development of ovary - where gametes are produced in the cortex
Describe the formation of the duct system (epididymis, vas deferens, urethra) in the male foetus
As the testis develops, male sex hormones/ androgens/ testosterone are released from the interstitial leydig cells
These hormones cause the Mesonephric ducts (Wolffian ducts) to be maintained
Sertoli cells release Müllerian inhibitory hormone which causes the Paramesonephric ducts (Müllerian ducts) to regress
Describe the formation of the duct system (Fallopian tube, uterus, cervix and superior 1/3 of vagina)
As the ovary develops, absence of male sex hormones/ androgens/ testosterone causes the Mesonephric ducts (Wolffian ducts) to regress
Absence of Sertoli cells means that Müllerian inhibitory hormone is not released and so the Paramesonephric ducts (Müllerian ducts) are maintained
Paramesonephric ducts grow out into the peritoneal cavity towards each other in the midline and fuse- the fused part enlarges and becomes patent -uterus and cervix
Describe the development of the external genitalia (penis and scrotum) in the male foetus
Urogenital sinus - endoderm
Under influence of male sex hormones/ androgens- in particular dihydrotestosterone
Genital swellings (labialscrotal) enlarges and becomes the scrotum
Genital folds fuse to form the spongy urethra forming the penile shaft
Genital tubercle becomes the glans penis
Describe the formation of the external genitalia (inferior 2/3 of vagina, labia minora, labia majora and clitoris)
PMD and UGS has an inductive effect on mesoderm and endoderm –> vagina
UGS develops into vestibule, labia majora, minora and clitoris
In absence of male sex hormones
Gneital folds do not fuse properly forming the labia minora
Genital swellings enlarge and form the labia majora
Genital tubercle forms the clitoris
Describe the descent of the testis in males
Testis arises in the upper lumbar region- tethered to genital folds (penile shaft) by the gubernaculum ligament
As the trunk elongates the gubernaculum shortens and the relative position of the testis becomes more caudal
Musculofascial layer evaginates into the scrotum as it develops, together with the peritoneal membrane - forming the processus vaginalis
Week 25-28 of gestation: testis migrates over the pubic bone behind the processus vaginalis
Week 34-40: testis reaches the scrotum and is surrounded by the processus vaginalis
Above testis- fascia and peritoneum become closely apposed
Fascial layers and obliterated stem of processus vaginalis and vas deferens and testicular vessels and nerves = spermatic cord- occupies inguinal canal in males
Scrotal ligament is the vestigial remnant of the gubernaculum in the male
Describe the descent of the ovaries in females
Ovaries undergo a less dramatic shift caudally in positions from their origin on the posterior abdominal wall
Gubernaculum connecting the ovary to the genital folds becomes the ovarian ligament (connecting the ovary to the uterus) and the round ligament of the uterus (connects the uterus to the labia majora)
Round ligament is the on,y structure occupying the inguinal canal in females
What happens to primordial germ cells once they colonise a gonad?
They proliferate by mitosis
They reshuffle genetically and reduce haploid by meiosis
They cytodifferentiate into mature gametes
How long is spermatogenesis in males?
70 days
How often does spermatogenesis occur in males?
Continuously as different sections along the length of the tubule begin process of spermatogenesis at different times - so some part always releases sperm
Roughly how many sperm are produced every day?
200 million per day
Describe the formation of male gametes/ sperm
Primordial germ cells colonise the seminiferous cords (which connect the epididymis to the vas deferens) in the medulla of the primordial gonad
Post natal development of testis is slow - germ cells don’t begin meiosis before puberty
At puberty- hollow seminiferous tubules form from seminiferous cords
Spermatazoa develop within the seminiferous tubules in association with Sertoli cells
Seminiferous tubules are separated from the surrounding interstitial tissue by the blood testis barrier
Leydig cells in interstitial tissue secrete testosterone
Germ cells form spermatogonia stem cells- begins mitosis to maintain a population of self regenerating stem cells - remain available until ~70y/o; allows for continuous production of sperm cells at a high rate
At intervals, groups of distinct cells- A1 spermatogonia emerge - marking the beginning of spermatogenesis in that part of the tubule - undergo differentiation
- Type A - stem cells
- Type B - committed to differentiation to spermatozoa
–> Each type B spermatogonium then undergoes 4 mitotic divisions to produce a clone (64) of Primary spermatocytes all linked together by cytoplasmic bridges
Primary spermatocytes push their way to the lumen of the tubule where they begin meiosis
First meiosis division produces 2 haploid secondary spermatocytes which then divide again to produce 4 spermatids
Spermatids are then remodelled to produce sperm
Cytoplasmic bridges breakdown and sperm are released into the lumen to be washed down to the rete testis by fluid secreted by the Sertoli cells
Sperm finally mature during the progression through the epididymis
Describe the formation of the female gametes/ eggs
Primordial germ cells colonise the cortex of the primordial gonad becoming oogonia
Oogonia proliferate rapidly (7million by week 20 of gestation) majority of which die, leaving around 2 million which all begin meiosis before birth becoming primary oocytes
Entry to meiosis 1 is stimulated by Mesonephric cells (follicular cells- flattened epithelia cells) which surround the primary oocyte to form primordial follicles
Meiosis is then arrested at diplotene (resting) stage of prophase (due to ooctye maturation inhibitor OMI- released from follicular cells)
At puberty–> until menopause- a small number of follicles begin further development each day until the follicle becomes a mature gamete
1) Primordial to Preantral
- primary oocyte grows; does not restart meiosis
- follicular cells change from flat to cuboidal cells and then proliferate to form multiple layered epithelium = granulosa cells - secrete glycoprotein glycoprotein which surrounds the primary oocyte with zona pellucida
- surrounding stromal cells form the theca folliculi (inner theca interna- vascular and endocrine & outer theca externa- fibrous capsule)
- theca and granulosa cells collaborate to secrete oestrogens
2) Antral transition
- granulosa cells continue to proliferate
- fluid appears between cells forming an Antrum
- as more fluid forms - Graafian or secondary follicles expands dramatically (w/o hormones–> 2mm; w/FSH- binds to granulosa cells; w/LH- binds to thecal cells which secrete androgens which are converted to oestrogens under the influence of FSH via granulosa cells)
- each cycle only one follicle becomes dominant and develops further
3) Preovulatory follicle
- begins 37 hours before ovulation
- under influence of oestrogen, LH receptors appear on outer granulosa cells - stimulated by LH surge –> rapid changes in follicle
- within 3 hours of surge - oocyte restarts meiosis - first meiosis division is complete - asymmetric cytoplasm remains with one daughter - other forms a condensed polar body
- secondary follicle enters meiosis II and then arrests again 3 hours prior to ovulation
- follicle size increases due to increase in antral fluid volume - structure begins to weaken
- LH stimulates collegenase activity - follicle rupture
- ovum carried out into fluid and gathered up into Fallopian tube by fimbriae
- meiosis not completed unless ovum is fertilised
Describe the formation of the corpus luteum
Remains of the follicle rearranges itself into the corpus luteum - secretes progesterone and oestrogen under influence of LH
In humans the corpus luteum lives for 14 days before spontaneously regressing (in the absence of a fertilised ovum)
Early antral to corpus luteal stages- synchronised with reproductive cycle of female
How many oocytes does a female have at birth? What is the clinical consequence of this?
Woman has all oocytes she will ever have at birth- none formed later
All ova are produced from this stock - some of which remain arrested for 50 years before development
- increases the chance of cell damage
- eventual chromosomal abnormalities
What does successful reproduction require?
Right number of gametes produced at the right time
Male and female to get together at the same time
Effective transfer of sperm from male to female
Effective sperm transport
Fertilisation
Support of conceptus, embryo and foetus
Birth at right time
Support neonate
What hormones are generally released from the hypothalamus?
Releasing hormones
Neuro secreted
Direct from the median eminence
Travel to the anterior pituitary is the hypophyseal portal system
Which hormone released from the hypothalamus is involved in reproduction?
Gonadotrophin releasing hormone (GnRH) Pulsatile release (1x/hr)
What is GnRH release from the hypothalamus controlled by?
Other neurones
Environmental effects and body weight
Feedback from gonads and gonadal steroids
What enzymes are generally released from the anterior pituitary?
Trophic hormones
Arise from Rathke’s pouch - not nervous tissue/ it’s an endocrine gland
Gonadotrophs, thyrotrophs, lactotrophs, somatotrophs, corticotrophs
What two gonadotrophs are released from the anterior pituitary?
Follicle stimulating hormone FSH
Luteinising hormone LH
Act primarily on gonads (cells of gonadal origin not germ cell origin)
Control gamete production and stimulate secretion of gonadal steroids
What hormones are released from the posterior pituitary?
ADH
Oxytocin
What does the amount and proportion of LH and FSH produced depend on?
GnRH stimulates gonadotrophs to secret LH and FSH
But the amount and proportion of LH and FSH secreted depends on OTHER FACTORS acting on gonadotrophs
What are the three stages of the menstrual cycle?
Preparation/ follicular/ proliferative phase
Ovulation
Waiting/ Luteal/ Secretory phase
What are the two gonadotrophin hormones?
LH
FSH
What are the two gonadal steroids in females?
Oestrogen
Progesterone
What happens in the follicular phase of the menstrual cycle in females?
Oestrogen, progesterone and inhibin levels are low as corpus luteum has broken down and LH and FSH levels are generally low
GnRH secretion is released from inhibition due to less negative feedback from oestrogen and progesterone and levels increase
LH and FSH tend to rise - FSH rises more than LH as there is no inhibition by oestrogen AND inhibit, whereas with LH there is just no inhibition by oestrogen ONLY
FSH and LH cause the growth of the follicle
Oestrogen and inhibin secretion from the ovaries then increases as a result
FSH secretion is selectively inhibited by inhibin- so that only one follicle forms
Oestrogen at low levels inhibits GnRH and LH secretion BUT rising oestrogen above a threshold leads to stimulation of GnRH and LH secretion and thus an LH surge results (positive feedback and influenced by environmental factors)
What happens at ovulation of the menstrual cycle in females?
LH surge results in release of a follicle from the ovary into the fimbriae of the Fallopian tube- ovulation
Oestrogen then instantaneously falls dramatically due to the release of the follicle and LH levels also fall
The follicle then rearranges itself and the corpus luteum forms spontaneously
What happens in the luteal phase of the menstrual cycle in females?
Initially LH promotes the secretion of oestrogen and progesterone from the corpus luteum
As the corpus luteum grows more oestrogen and progesterone are secreted
Rising oestrogen levels (above the threshold) do not cause another LH surge due to the rising levels of progesterone which stimulates the effects of oestrogen (as if at low levels) and prevents the positive feedback of high oestrogen
Oestrogen and progesterone at high levels inhibit GnRH secretion and hence LH and FSH secretion- oestrogen reduces GnRH per pulse and progesterone reduces the frequency of the pulses
What happens in the menstrual cycle in the absence of fertilisation?
Corpus luteum regresses spontaneously (by apoptosis)
Progesterone and oestrogen levels fall due to regression of corpus luteum
This fall in progesterone (in particular) triggers the menstrual bleed as the endometrium is no longer maintained in preparation of pregnancy
Low levels of oestrogen and progesterone again causes GnRH to be released from inhibition- back to beginning of cycle
What happens in the menstrual cycle when fertilisation occurs?
Implanted embryo develops a placenta which secretes human chorionic gonadotrophin hormone (hCG)
hCG prevents the regression of the corpus luteum
Corpus luteum continues to secrete oestrogen and progesterone - supports the early weeks of pregnancy and maintains suppression of the menstrual cycle
In the follicular phase of the menstrual cycle, structurally what does oestrogen stimulate?
In order to prepare/ increase the likelihood of Fertilisiation
Fallopian tube function- motile, captures ovum, moves it to uterus
Thickening of endometrium- secretes fluid adhesive to sperm
Growth and fertility of myometrium- stimulates contraction- propels sperm to point of fertilisation
Thin alkaline cervical mucus- attracts sperm which can move through it
Vaginal changes- facilitates copulation
Changes skin, hair and metabolism- body shape (anabolic)
Calcium metabolism- affects bone
In the luteal phase of the menstrual cycle, structurally what does progesterone stimulate?
In order to prepare for pregnancy
Acts on oestrogen primed cells
Further thickening of endometrium into a secretory form - to sustain a conceptus and grow and maintain a placenta
Thickening of myometrium- but reduction in motility
Thick acid cervical mucus- inhibits spermatocytes transport so that not one sperm fertilised the egg
Changes in mammary tissue
Increased body temperature
Metabolic changes- mildly catabolic
Electrolyte changes- without oestrogen there is net sodium and water retention
Reduced Fallopian tube motility, secretion and cilia activity
What happens in menopause?
Ovary stops producing oestrogen and inhibin
No longer any suppression of LH and FSH- negative feedback system breaks down
Increased LH and FSH levels
How is the menstrual cycle coordinated and controlled?
Gonadotrophins secreted by pituitary gonadotrophs
Stimulated by pulsatile releaseoif GnRH from hypothalamus
Modified by feedback effects of gonadal hormones
Environmental factors
What cells does FSH act on in the ovaries?
Granulosa cells
What cells does LH act on in the ovaries?
Theca cells
What do theca cells in the ovary release?
Androgens which under the influence of FSH are then converted to oestrogen in the granulosa cells
What do granulosa cells in the ovary release?
Inhibin and oestrogen
What cells does LH bind to in the testis?
Leydig cells
What do Leydig/ interstitial cells in the testis produce?
Testosterone
What cells does FSH bind to in the testis?
Sertoli cells
What do sertoli cells in the testis directly secrete?
Inhibin
How is testosterone secreted into the spermatic tubules?
Testosterone is produced in the Leydig/ interstitial cells and is released into the spermatic tubules via the Sertoli cells- only cells permeable to testosterone- the rest have a spermatic barrier - promoting sperm production
What is the action of LH in males?
Production of testosterone in the Leydig cells
Secretion of testosterone via Sertoli cells
Promotes spermatogenesis (via FSH)
Maintains reproductive system (via testosterone)
What is the action of FSH in males?
FSH maintains Sertoli cells and makes them responsive to testosterone so that it can be released into spermatic tubules
Stimulates Sertoli cells to secrete ABP and promotes spermatogenesis
Inhibin release - levels rise if spermatogenesis proceeds too rapidly - reduces secretion of FSH by acting on gonadotrophs in the anterior pituitary
What type of rhythm does testosterone have?
Circadian rhythm - highest early in the morning and is affected by environmental stimuli - light and dark, sex
How is the HPG axis controlled in males?
Negative feedback control ensures that:
- spermatogenesis occurs continuously
- male reproductive tract is continuously ready for action
- hormone levels are kept relatively constant in the medium to long term
Testosterone inhibits GnRH secretion and so LH levels fall - brings testosterone levels back to normal
What are the determinative effects of testosterone in males?
Not reversible/ only partly reversible
Secondary sexual characteristics
What are the regulatory effects of testosterone in males?
Maintains adult Repro system- maintenance of male internal genitalia (prostate, seminal vesicles, vas deferens, epididymis)
Metabolic effects - anabolic action
Behavioural effects- aggression and sexual activity
When are primary sexual characteristics established by?
Before birth
Compare the timing of the initiation of puberty in males and females
Varies between sexes and between individuals, but in each sex there is a fixed sequence of events, which depend on the sex steroids secreted from the gonads and adrenal glands, that occur before the obvious signs of puberty become apparent:
Boys- reach puberty at 9-14years
Girls- reach puberty at 8-13 years
Describe puberty in males
Starts later in boys (9-14years) - 10cm/year velocity
Genital development begins Pubic hair growth Spermatogenesis begins Growth spurts - Adult males end up larger because boys grow more before the growth spurt and slightly more during it - Growth spurt is terminated by epiphyseal fusion, at which point the adult height is virtually set Adult genitalia forms Adult pubic hair forms
What hormones are involved in male puberty?
Testicular androgens - testosterone
Describe puberty in females
Starts earlier in girls- (8-13 years)- 9cm/year velocity Breast bud- thelarche Pubic hair growth begins- adenarche Growth spurt - Growth spurt is terminated by epiphyseal fusion, at which point the adult height is virtually set Onset of menstrual cycles Public hair adult Breast adult
What hormones are involved in female puberty?
Gonadal oestrogens- breast development and female genitalia development
Androgens from adrenals- pubic and axillary hair development
In males what is the defining pubertal event (that does not necessarily indicate onset of full fertility)?
Nocturnal erection and first ejaculation
In females what is the defining pubertal event (that does not necessarily indicate onset of full fertility)?
First menstrual bleed- menarche
What hormonal changes occur in males in puberty?
FSH and LH levels rise later, to reach the adult levels at 16 years, associated with steady rises in testosterone levels
Weak androgens are released from the adrenal cortex
What hormonal changes occur in females in puberty?
Plasma levels of FSH and LH rise gradually from about 7 years to reach adult levels soon after menarche
Plasma oestrogen levels rise steadily until at the beginning of menstrual cycles - regular cyclical rises and falls are associated with the ovarian cycle
Weak androgens are secreted from the adrenal cortex
Describe some theories behind the initiation of puberty
Anterior pituitary gonadal axis is capable of responding to stimulation by GnRH long before puberty normally occurs but GnRH secretion is low
Puberty occurs when the brain initiates pulsatile GnRH secretion - does not seem to depend on any signal from the gonads
Once thought that the pre pubertal hypothalamus was very sensitive to the negative feedback by gonadal steroids
- so very low circulating levels completely inhibited the secretion of GnRH
- puberty would then arise from gradually decreasing hypothalamic sensitivity to feedback
An alternative and now thought more likely explanation is that the hypothalamic mechanisms mature and steadily secrete more GnRH under other influences
Either way- various factors influence the timing of puberty
How can pineal tumours or meningitis influence puberty in humans?
Precocious puberty- signs of puberty before the age of 8
- mostly unknown cause
- can be due to - neurological - early stimulation of central maturation (pineal tumours or meningitis) OR uncontrolled gonadotrophin or steroid secretion (hormone secreting tumours)
What is menopause?
End of reproductive life in the female
What are the three stages of menopause?
Pre menopause
Menopause
Post menopause
Describe pre menopause
~ age of 40
Changes in menstrual cycle
- follicular phase shortens - ovulation is early or absent
- less oestrogen is secreted -
- LH and FSH levels rise, FSH more so - reduced feedback
- reduced fertility
Describe menopause
Cessation of menstrual cycles Age 49-50 but variable No more follicles develop Oestrogen levels fall dramatically LH and FSH levels rise, FSH dramatically (no inhibin as well as lower oestrogen)
Describe the effects of menopause which become apparent in post menopause
Vascular changes- low oestrogen causes hot flushes and transient rises in temperature (relieved by oestrogen treatment)
On oestrogen sensitive tissues
- uterus - regression of endometrium and shrinkage of myometrium
- thinning of cervix
- vaginal rugae lost
- involution of some breast tissue
- changes in skin
- changes in bladder
Bone
- bone mass reduces by 2.5%/year for several years
- increased reabsorption relative to production
- type 2 osteoporosis - much greater in some compared to others
- major reason for fractures (e.g. Hip) in later life (limited by oestrogen therapy)
How does reproductive life end in males?
No obvious event
Sperm production continues
But incidence of loss of libido, impotence and inability to reach orgasm increases with age
What is primary amenorrhea?
Absence of menses by age 14 with absence of secondary sexual characteristics (e.g. Breast development)
Absence of menses by age 16 with normal secondary sexual characteristics
What is secondary amenorrhoea?
Where an established menstruation has ceased for 3 months in a woman with a history of regular cyclical bleeding or 9 months in a woman with a history of irregular periods –> usually in women aged 40-55
How would you evaluate a patient with suspected amenorrhoea?
Family history (age of menopause, thyroid dysfunction, diabetes, cancer), menstrual history, contraception, pregnancy, surgery, medication, weight change, chronic diseases/ stressors etc.
What physical examination would be carried out on an individual with suspected amenorrhoea?
BMI Hair distribution Thyroid Visual fields Breast discharge Abdomen masses/ tenderness
How would you investigate suspected amenorrhoea?
Always rule out pregnancy!!! Ovarian axis problem- TSH prolactin LH FSH Hilsuitism- testosterone, OHEA's Chronic diseases- LFTs CNS - MRI
Is the HPO axis functional in amenorrhoea?
Yes so FSH levels are normal
What are some causes of primary amenorrhoea?
Uterine- Müllerian agenesis (2nd most common cause)
Vaginal- vaginal atresia, cryptomenorrhoea, imperforate hymen
Turners syndrome- gonadal dysgenesis (most common cause)
Androgen insensitivity syndrome
Receptor abnormalities for FSH and LH
Specific forms of congenital adrenal hyperplasia
Hypothalamic- Kallman syndrome
What are some causes of secondary amenorrhoea?
Intrauterine adhesions - Asherman’s syndrome
Pregnancy (most common cause)
Anovulation
Menopause (and premature)
Polycystic ovarian syndrome
Drug induced
Hypothalamic- exercise/ stress amenorrhoea, eating disorders
Pituitary- Sheehan syndrome, prolactinaemia, haemochromatosis
How may gonadal/ end organ disorder result in primary or secondary amenorrhoea?
Ovary/ gland does not respond to pituitary stimulation- due to gonadal dysgenesis or premature menopause for example
Chromosome testing indicated in younger individuals with hypergonadotropic amenorrhoea
Low oestrogen levels - may require treatment
Tend to be linked to elevated FSH levels- typically in the menopausal range
How may pituitary and hypothalamic/ central regulatory disorders result in primary or secondary amenorrhoea?
Inadequate levels of FSH - Inadequately stimulated ovaries- fail to produce enough oestrogen to stimulate the endometrium –> amenorrhoea (low FSH levels- not usual with amenorrhoea)
What is menorrhagia?
Excessive (>80ml) uterine bleed OR prolonged (>7 days)
Heavy vaginal bleeding that is not DUB (dysfunctional uterine bleeding)
What are some causes of menorrhagia?
Usually secondary to distortions of the uterine cavity - heavy with or without prolongation
Uterus unable to contract down on open venous sinuses in zona basalis
Other causes: organic, endocrinologic, haemostatic and iatrogenic
Usually ovulatory
How would you manage a patient with suspected menorrhagia?
Take history and full blood count
1)
No structural or histological abnormality suspected, no exam required and treatment by GP with drugs:
- tranexanic acid/ NSAIDs/ combined OCP
- norethisterone (day 5-26 of MC)
- levonorgestrel releasing ILS (12 months)
2)
Structural or histological abnormality suspected.
Physical examination- anaemia, obesity, androgen excess (Hilsuitism), acne, ecchymosis, purpura, thyroid, galactorrhoea, liver/ spleen, uterine, cervical and adnexal exam
What is dysfunctional uterine bleeding? (DUB)
Excessively heavy, prolonged, or frequent bleeding of uterine origin that is not due to pregnancy, pelvic or systemic disease
Abnormal bleeding with no obvious organic cause - usually anovulatory
Diagnosis of exclusion
Usually at extremes of reproductive life and in patient with poly cystic ovaries
What is the pathophysiology of DUB?
Disturbance in the HPO axis thus changes in length of menstrual cycle
No progesterone withdrawal from an oestrogen primed endometrium
Endometrium builds up with erratic building as it breaks down
How would you manage DUB?
HCG/ TSH
Coagulation work up
Ensure smear if appropriate
> 35 or Cancer risk factors- tamoxifen use- sample the endometrium
IV or IM conjugated oestrogen therapy acute DUB
Usually followed by OCP or progesterone
Cyclic progesterone for 10-12 days each cycle- consider mirnalUD
OCP
In what cancer is high hCG commonly present?
Testicular
What is dysmenorrhea?
Pain during menstruation that interferes with daily activities
What does an ovulatory cycle refer to?
Regular menstrual cycles and premenstrual symptoms such sad dysmenorrhoea and mastalgia
What does an anovulatory cycle refer to?
Oligo or amenorrhoea +/- menorrhagia
What does oligomenorrhoea refer to?
Uterine bleeding occurring at intervals between 35 days and 6 months
What is the problem with gaining information about STI’s and STD’s from GUM services?
Data from GUM services will underestimate the true incidence of STI’s as patients may be seen in a variety of other settings such as GP Centres, family planning clinics etc.
Additionally many symptoms are asymptomatic - e.g. With GP practices only 10% services attend GUM services
What is the difference between an STI and an STD?
STI- both symptomatic and asymptomatic cases; sexual action is the principle mode of transmission
STD- only symptomatic cases
What are the major causative organisms of a genital ulcer?
HSV
Syphylis
Chancroid (haemophiliis ducreyi)
What is the major causative organism of vesicles of bullae?
HSV
What are the major causative organisms of genital papules?
Transient manifestations of STI’s
Condylomata acumilata (anogenital warts)
Umbilicated lesions of Molluscum Contagiosum virus
What are three types of urethritis? And their causative organisms?
Gonococcal urethritis
Non gonococcal urethritis - chlamidya trachomatis, ureaplasma, mycoplasma, trichomonas HSV
Post gonococcal urethritis
What are the major causative organisms of vulvovaginitis?
Candiasis, trichomonasis, staphylococcal, foreign body, HSV
What are the major causative organisms of cervicitis
Chlamidya trachomatis, Neisseria gonorrhoea
What are the major causative organisms of batholinitis
Poly microbial infections with endogenous flora, rarely STI’s
What are the major causative organisms of bacterial vaginosis?
Overgrowth of normal flora - Gardnerella vaginalis
Vaginal pH > 4.5
A pungent odour
KOH Whiff test
Presence of clue cells on a wet mount- lacking many PNMS
What at the main infections of the the female pelvis?
Pregnancy related infection- chorioamnionitis, post partum endometriosis, episiotomy infections, puerperal ovarian vein thrombophlebitis, osteomyelitis pubis
Pelvic inflammatory disease
What are the major causative organisms of prostatitis?
Acute bacterial prostatitis
Chronic bacterial prostatitis
Chronic pelvic pain syndrome
What are the major causative organisms of Epididymitis?
Non specific bacterial Epididymitis
Sexually transmitted Epididymitis
What are the major causative organisms of orchitis?
Viral orchitis (mumps, coxsackievirus B) Pyogenic bacterial orchitis
Describe the organism chlamidya trachomatis
Obligate intracellular bacteria
Does not grow routinely on lab media- implication for diagnostic methods
Infective form is the elementary body which develops in the host cell into the reticulate body
Reticulate body replicates until it eventually reverts back to the elementary body which then leaves the cell to infect other cells
How does infection by chlamidya trachomatis present in females?
Organism infects and replicates within cervix and urethra epithelium Urethritis
Cervicitis
Salpingitis
Perihepatitis
Most important cause of PID
Ocular infection- common in sexually active individuals
How does infection by chlamidya trachomatis present in males?
Urethritis
Epididymitis
Prostatitis
Proctitis
Reiter’s syndrome- urethritis, conjunctivitis and arthritis (triad)
Ocular infection- common in sexually active individuals
How does infection by chlamidya trachomatis present in neonates?
Caused by cervical infection in a pregnant woman
Inclusion conjunctivitis
If untreated may progress to neonatal pneumonia
How would you collect a specimen when suspecting infection by chlamidya trachomatis in males?
Urethral swab or first catch urine
How would you collect a specimen when suspecting infection by chlamidya trachomatis in females?
Endo revival swab- any pus must be first removed from the cervix and a good quality cellular material must be obtained
Urine may be used for molecular methods but is much less sensitive than an endo cervical swab
What are some advantages of using urine samples over swabs for specimen collection?
Population screening patients may provide a specimen whereas swab is time consuming, requires a trained staff member and is generally less acceptable to a patient
How would you collect a specimen when suspecting infection by chlamidya trachomatis in neonates?
Eye swab- remove any pus, invert eyelid and scrape conjunctiva surface
Pneumonia- serology is useful; differential on WCC may show eosinophilia
How is infection by chlamidya trachomatis generally diagnosed?
Chlamidya does not grow on lab media and tissue culture is too expensive So antibody detection: - Immunofluorescence - enzyme immunoassays - molecular methods: PCR
How is infection by chlamidya trachomatis treated?
Macrolides (erithromycin, clarithromycin, azithromycin) or
Tetracyclines (doxycycline)
As conjunctivitis is part of a more widespread infection this should always be treated with systemic antibiotics
Describe the organism neisseria gonorrhoea
Member of Neisseriaceae family
Gram negative bacteria diplococcus
Only grow on an enriched media - chocolate agar
How does infection by neisseria gonorrhoea present in males?
Gonococcal urethritis Epididymitis Prostatitis Proctitis Pharyngitis Disseminated gonococcal infections- pain in joints, tenosynovitis, rash
How does infection by neisseria gonorrhoea present in females?
Asymptomatic
May lead to endocervicitis, urethritis, PID, Bartholins abscess, infertility, disseminated gonococcal infection- pain in joints, tenosynovitis and rash (more likely in females)
How would you collect a specimen when suspecting infection by neisseria gonorrhoea in males?
Urethral, rectal and pharyngeal swabs
How would you collect a specimen when suspecting infection by neisseria gonorrhoea in females?
Endo cervical swab, urethral swab, rectal and pharyngeal swab
How is infection by neisseria gonorrhoea diagnosed?
Neisseria gonorrhoea is a fragile organism that does not survive transportation well
Ideally specimens taken should be placed on media directly at bed side
Gram stain- gram negative diplococcus
Culture/ sensitivities- more sensitive than microscopy, organisms resmbling neisseria gonorrhoea must be confirmed on the basis of a biochemical test to distinguish them
Sensitivity testing is important as antibiotic resistance patterns are valuable in guiding future management guidelines
How is infection by neisseria gonorrhoea treated?
Initial therapy guided by severity of symptoms and local knowledge of sensitivity patterns
Penicillin resistance is common
What is the most common viral STI?
Human papilloma virus
How does infection by HPV present?
Cutaneous mucosal and anogenital warts - benign and painless
In penis, vulva, vagina, urethra, cervix, perianal skin
High risk of becoming oncogenic -females aged 15-24 - cervical cancer
How is HPV infection diagnosed?
Clinical features
Biopsy
Genome analysis
Hybrid capture
How is HPV infection treated?
None
Topical podophyllin cryotherapy
Intralesional interferon surgery
How is HPV infection screened?
Cervical Pap smear cytology
Cervical swab
What is the vaccine for HPV infection and hence cervical cancer?
Cervarix
Gardasil
(girls 12-13)
Herpes simplex virus Treponema pallium Trichomonas vaginalis Inguinal lymphadenopathy Scabies Vulvovaginal candiasis Bacterial vaginosis Pubic life
X
What are the two types of herpes simplex virus and what do these strains cause?
HSV1- cold sores
HSV2- genital herpes
Why can herpes simplex virus cause recurrent genital herpes?
Can be asymptomatic to moderate with symptoms
Infection can remain latent in the dorsal root ganglia
How would you diagnose herpes simplex virus infection?
PCR of vesicle fluid and/or ulcer base
How would you treat infection by herpes simplex virus?
Aciclovor
What prophylaxis could you give for recurrent infection by herpes simplex virus?
Prophylactic aciclovir
How could you reduce the risk of transmission of herpes simplex virus?
Barrier contraception
How does primary general herpes usually present?
Extensive painful genotal ulceration
Dysuria
Inguinal lymphadenopathy
Fever
What is the causative organism of syphilis?
Treponema pallidum
What type of people does syphylis usually affect?
Mostly men and MSM
Describe the three stages of syphylis
1- individual, painless ulcer (chancre)
2- 6-8 weeks later- fever, rash, lymphadenopathy, mucosal lesions
3- neurosyphylis, cardiovascular syphylis, gumma’s
How can syphylis be diagnosed?
Organism can’t be grown - dark friend microscopy
Describe the serology of treponema pallidum in syphylis
Initial screening with EIA antibody test then positives
Rapid plasma reagin (RPR) time
TPPA
Interpret serological pattern (false positives)
How would you treat syphylis?
Penicillin and test of cure ‘follow up’
Describe the organism, trichomonas vaginalis
Flagellated protozoan
How does a patient with infection by trichomonas vaginalis present?
Trichomonas vaginitis
Thin, frothy, offensive discharge
Irritation, dysuria and vaginal inflammation
How would you diagnose a patient with infection by trichomonas vaginalis?
Vaginal wet prep +/- culture enhancement
How would you treat infection by trichomonas vaginalis?
Metronidazole
Describe scabies
Can affect genitalia
Spreads sexually
Describe inguinal lymphadenopathy
Granuloma inguinale (Klebsiella) - genital nodules --> ulcers Chancroid- haemophilius ducreyi- painful genital ulcers Chlamidya trachomatis stereotypes- rapidly healing papule then inguinal bubo- LGV, MSM
Describe Vulvovaginal Candiasis
Candida albicans
Risk factors - antibiotics, oral contraceptive, pregnancy, obesity steroids, diabetes
Presents with profuse, white, itchy, curd like discharge
Diagnosis: High vaginal smear +/- culture
Treat: Azores or nystatin oral fluconazole
Describe bacterial vaginosis
Normal flora
Gardnerella anaerobes, myocplasm
Presents with scanty but offensive, fishy discharge
Diagnosis- vaginal pH>5, KOH Whiff test, smear- clue cells (gram variable cocobacillus, reduced number of lactobacillus absence of pus cells)
Describe pubic lice
Pediculosis pubis CRAB louse (Pthirius pubis)- distinct from other human body lice
What is pelvic inflammatory disease?
The result of infection ascending from the endocervix causing endometritis, Salpingitis, parametritis, oophoritis, tubo ovarian abscess and or pelvic peritonitis
What are the main 3 sequelae of PID?
Endometritis
Salpingitis
Tubo ovarian abscess
What is endometritis?
Inflammation and infection of the endometrium (lining of the uterus)
What is Salpingitis?
Inflammation of the Fallopian tube
What is a tubo ovarian abscess?
Pocket of pus that forms during infection of a Fallopian tube
Which people does PID usually affect?
Disease of sexually active women
Incidence higher in urban areas
Peak incidence 20/1000
Highest incidence in 20-24 years old
What infections does PID usually arise in?
Majority of the time caused by polymicrobial infections
Caused by gonorrhoea (14%) and chlamidya (10-25%)
40% risk of a concurrent infection
Garderella, Mycoplasma and anaerobes (bacterial vaginosis) have also been implicated
Tuberculosis and group A strep
Describe the pathophysiology of pelvic inflammatory disease
Infection ascends from the endocervix and vagina into the uterus causing inflammation
Inflammation causes adhesion formation and damage to tubule epithelium
What are some behavioural risk factors for PID?
Young age Sexual behaviour Type of contraception used - lack of use of barrier contraception; IUCD increases risk of PID in first few weeks of insertion; COCP is considered to be protective against symptomatic PID Alcohol/ drug use Cigarette behaviour/smoking Lower socioeconomical
What are the main clinical features in the history of patient with PID?
Pyrexia Pain- bilateral lower abdominal tenderness, adnexal tenderness, cervical excitation, deep dyspareunia Abnormal vaginal/ cervical discharge Abnormal vaginal bleeding Sexual history and prior STI Contraceptive history
What are the main clinical features upon examination of a patient with PID?
Pyrexia > 38 degree Celsius - fever
Lower abdominal tenderness (bilateral)
Bimanual examination- Adnexal tenderness, Cervical motion tenderness/excitation
Speculum examination- purulent cervical discharge, Cervicitis, Discharge (vaginal and cervical)
What investigations should be carried out in PID?
Endocervical swab- gonorrhoea and chlamidya
High vaginal swab- bacterial vaginosis, trichomonas vaginalis, candida
*positive swabs support diagnosis
*negative swabs don’t exclude it
When would you admit a patient with PID to hospital?
Surgical emergency can't be excluded Clinically severe disease PID in pregnancy Tubo ovarian abscess Lack of response/ intolerance to oral therapy
What are the two main methods of medical management in a patient with PID?
Analgesia
Antibiotics
- mild to moderate disease- oral antibiotics
- severe- IV antibiotics
What specific antibiotics would you give in outpatient treatment of PID?
IM Ceftriaxone 500mg stat
PO Doxycycline 100mg BD
PO Metronidazole 400mg BD
What specific antibiotics would you give in inpatient treatment of PID?
IM Ceftriaxone 500mg stat PO Doxycycline 100mg BD PO Metronidazole 500mg BD ... PO Doxycycline 100mg BD PO Metronidazole 400mg BD
What surgical treatments are available for PID?
Laparoscopy / laparotomy may be considered if : no response to therapy, clinically sever disease, presence of tubo ovarian abscess
US guided aspiration of pelvic fluid collections is less invasive
What are the potential complications of PID?
Ectopic pregnancy
Infertility
Adhesions and chronic pelvic pain
Fitz Hugh Curtis syndrome
What are some potential differential diagnoses for PID?
Gynaecological - ectopic pregnancy - endometriosis - complication of an ovarian cyst Gastrointestinal - irritable bowel syndrome - acute appendicitis Renal - urinary tract infection Other - functional pain ( pain of unknown physical origin)
What is Fitz Hugh Curtis syndrome?
RUQ pain and perihepatitis - following chlamydial PID (10-15%)
Risks increase with repeat episodes
Future use of barrier contraception will reduce the risk of PID
Contact screening
Severe disease= greater risk of complications
Early treatment= lower risk of complications
What is the pelvic floor formed by?
Pelvic diaphragm- bowl or funnel shaped; coccygeus and levator ani muscles, fascia covering superior and inferior aspects of these muscles; between ischiopubic rami
Superficial muscles and structures- anterior (urogenital) perineum and posterior (anal) perineum
Where does the pelvic diaphragm lie?
Within the lesser pelvis separating the pelvic cavity from the perineum
How does the pelvic floor support the pelvic viscera?
Exerts a sphincteric actions on the rectum and vagina and can resist increases in intra abdominal pressure associated with coughing, defecation, heavy lifting etc.
What makes up the anterior (urogenital) perineum?
Urogenital diaphragm fills the gap of the public arch stretching between converging ischiopubic rami
Triangle sandwich with striated muscle fibres between 2 layers of fascia - superior fascia and inferior or superficial fascia - thickened (aka perineal membrane) sandwich the sphincter urethrae- striated muscle fibres
What is found below the perineal membrane in males?
Superficial transverse perineal membrane
Bulbospongiosus muscle
Ischiocavernous muscle
Superficial perineal pouch - site of urine collection if the urethra is ruptured below the perineal membrane
What is found below the perineal membrane in females? And how is it clinically relevant?
Superficial perineal pouch - site of urine collection if the urethra is ruptured below the perineal membrane
What makes up the posterior (anal) perineum?
Forms a triangle between ischial tuberosities and coccyx
Comprised of anus, levator ani, and ischiofemoral fossae (fatty fossa that may become infected spreading behind the anus)
Pudendal nerve passes along lateral wall of the fossa
What are the levator ani muscles?
Paired muscles, form 3 slings of muscle extending from posterior aspect of the pubic bone, fascia over obturator internus and ischial spines
Forms part of pelvic diaphragm
Anterior fibres around the prostate/ vagina
Intermediate fibres around the rectum (puborectalis) and into anococcygeal body (pubococcygeus)
Posterior fibres to anococcygeal body and coccyx (iliococcygeus)
What is the coccygeus?
Lies to posterior, overlying the sacrospinous ligament
Forms part of pelvic diaphragm
What is the perineal body?
Pyramidal fibromuscular mass found at the junction between urogenital and anal triangles (anterior and posterior perineum)
Where is the perineal body found in males?
Found between bulb of penis and anus
Where is the perineal body found in females?
Found between vagina and anus (~1.25cm in front of anus)
Why is the perineal body important?
Essential for the integrity of the pelvic floor in females- anchoring perineal muscles and rectum
Point of attachment for the anal sphincters, bulbospongiosus, superficial transverse perineal muscles and fibres of levator ani
A rupture of the perineal body in childbirth may lead to what?
Weakness of the pelvic floor
Leading to prolapse of structures such as the vagina and uterus
May be avoided by episiotomy (scissors)
What may damage to the pelvic floor cause?
Stretching of nerves (pudendal nerve - neuropraxia and muscle weakness), muscles (pelvic floor and perineal muscles- muscle weakness) and ligaments (supporting muscles - ineffective muscle action)
Prolapse of organs and stress incontinence
What are some risk factors for pelvic dysfunction?
Age, menopause (atrophy of tissues after oestrogen withdrawal), obesity, chronic cough, intrinsic CT laxity (defined conditions- constitutional)
What are some possible treatments for pelvic wall damage?
Pelvic floor muscle exercises- easy, safe and effective (cure in 50-75% cases)
Continence surgeries
Prolapse procedures
What are some continence surgeries? And their side effects?
Increase support of sphincter mechanism and prevent the descent of the bladder neck - colosuspension, tension free vaginal tape
Effective- 85-90% cure rate
Side effects- voiding difficulty / urinary retention; overactive bladder disease (obstruction)
What are some prolapse procedures? And their side effects?
Replace prolapsed organs
Restore CT support
Maintain function
Side effects- recurrence, new incontinence, dyspareunia (painful sex)
How long does it take for spermatogonia to become mature spermatozoa?
74 days
50 in the seminiferous tubules and 12-26 in the epididymis
What is the rate of production of mature spermatozoa in a 20 year old male?
6.5m/g/day
What is the rate of production of mature spermatozoa in a >50 year old male?
3.8m/g/day
What are the 4 broad stages of coitus?
Excitement phase
Plateau phase
Orgasmic phase
Resolution phase (+/- refractory period)
What is the female sexual response in coitus?
Vaginal lubrication
Swelling and engorgement of external genitalia- clitoris, vaginal mucosa, beast and nipples
Internal enlargement of vagina
Cervical mucus
- oestrogen: abundant, clear, non viscous mucus
- oestrogen and progesterone: thick and sticky mucus plug
+/- Orgasm
No physiological refractory period
Describe the mechanism of penile erection
Stimulants: psychogenic and tactile (sensory afferents of penis and perineum) –spinal reflex–> Efferents: somatic and autonomic efferents - pelvic nerve (PSNS) and pudendal nerve (Somatic) –> Haemodynamic changes –> Tumescence
Haemodynamic changes:
- inhibition of SNS arterial vasoconstriction nerves
- activation to PSNS nerves; postganglionic PSNS nerves release ACh; ACh bonds to M3 receptors on endothelial cells, causing a rise in Ca2+ and activation of NOS and NO; NO then activates NANC upto omit nerves to the arteries causing increased NO release
NO release:
- increase in NO –> increase in cGMP
- increased uptake of Ca2+ by intracellular stores
- decrease in cytoplasmic calcium –> less actin myosin cross bridges
- relaxation of smooth muscle
Erection of penis
- as a result of smooth muscle relaxation
- corpora cavernosa central arteries straighten, enlarging their lumen and allowing blood to flow into and dilate the cavernous spaces in the corpora of the penis
- corpus spongiosum also dilates but not very much as it would compress and close off to the urethra
- bulbospongiosus and ischiocavernosus muscles compress veins egressing from the corpora cavernosa, so blood pools in the veins
–> impeding the return of venous blood and the dilation of the helicline arteries causes the corpora cavernosa to become engorged with blood, near arterial pressure, causing erectile bodies to become turgid - enlarged
What is erectile dysfunction?
Psychological (descending inhibition of spinal reflexes)
Tears in fibrous tissue of corpora cavernosa
Vascular (arterial and venous)
Drugs
- factors blocking NO: alcohol, antihypertensives, diabetes
- viagra: inhibits cGMP breakdown maintaining an erection
What is emission?
Emission is the movement of ejaculate into the prostatic urethra before ejaculation. This occurs due to peristalsis of the vas deferens and secretions from the seminal vesicles.
Describe the mechanism of ejaculation?
o Spinal reflex o Sympathetic Nervous System Control (L1, L2) 1. Contraction of glands and ducts • Smooth muscle 2. Bladder internal sphincter contracts • Prevents entry of semen into the bladder 3. Rhythmic striatal muscle contractions • Pelvic floor • Ischiocavernosus – Pudendal (S2-S4) • Bulbospongiosus – Pudendal (S2-S4) • Hip and anal muscles
What is normal ejaculate fluid like?
2-4ml 20-200x10^6 sperm/ ml Total sperm/ ejaculate >40/10^6 >60% sperm swimming forward vigorously <30% abnormal morphology
What are the glandular components of semen?
Seminal vesicles- 60% of volume, alkaline fluid (neutralises acid; male urethra and female reproductive tract), fructose/PGs/clotting factors (semenogelin) Prostate- 25% of volume, milky/ slightly acidic fluid, proteolytic enzymes (breakdown clotting proteins reliquifying the semen in 19-20 minutes), citric acid and acid phosphatase Bulbourethral glands (Cowpers), very small volume, alkaline fluid, a mucus that lubricates end of penis and urethral lining
Briefly describe the ovarian and uterine cycles
Typically
Day 7-14 - uterine proliferation (oestrogen)
Day 14 - ovulation
Day 14-28 - uterine secretory phase, corpus luteum (progesterone and oestrogen)
How do sperm travel through the cervix and uterus?
Immediately after ejaculation, the semen first coagulates due to the action of clotting factors (fibrinogen). This is to prevent sperm being physically lost from the vagina. 10 – 20 minutes later the semen re-liquefies by the action of enzymes found in prostatic secretions.
The vast majority of sperm do not enter the cervix of the uterus and are lost by leakage from the vagina. Those that do enter the uterus have to travel 15 – 20cm to reach the uterine tube, a journey that may last a few hours.
Transport of sperm is as a result of their own propulsive capacity and the fluid currents caused by the action of ciliated cells in the uterine tract.
What two maturational changes does sperm undergo as it passes through the uterus?
Capacitation and Acrosomal reaction
What causes the maturational changes to sperm in the uterus to happen?
Both capacitation and the acrosomal reaction are induced by an influx of calcium and a rise in cAMP in spermatozoa.
What is Capacitation?
Capacitation
o Further maturation of sperm in female reproductive tract (6 – 8 hours)
o Sperm cell membrane changes to allow fusion with oocyte cell surface
• Removal of glycoprotein coat
o Tail movement changes
• Beat –> Whip-like action
o Sperm become responsive to signals from the oocyte
What is the Acrosomal reaction?
Capacitated sperm comes into contact with the oocyte zona pellucida
o Sperm pushes through granulosa cells
o Proteins on sperm head bind to ZP3 proteins on zona pellucida
o Binding –> Start of reaction
o Acrosome swells and liberates its contents by exocytosis
o Proteolytic enzymes digest path through zona pellucida and facilitate penetration of the zona pellucida by the sperm (takes about 15 minutes)
o One sperm penetrates- and membrane of sperm and egg fuse: sperm moves into cytoplasm of egg = ZYGOTE
o Polyspermy is blocked by cortical reaction
How does the ovum come to be in the ampulla of the Fallopian tube, ready for fertilisation?
By the time of ovulation, the ovum (primary oocyte) in the ovulatory follicle has completed its first meiotic division to form a secondary oocyte.
o Secondary Oocyte
• Haploid number of chromosomes and bulk of cytoplasm
o First Polar Body
• Remaining haploid number of chromosomes
The secondary oocyte, surrounded by follicular cells (cumulus) embedded in a gelatinous matrix, is released from an ovulatory follicle and picked up by the fimbria of the uterine tube and guided into its lumen by the ciliary movements of epithelial cells towards the ampulla, the site of fertilisation, where the oocyte and sperms come together.
What happens after fertilisation has occured?
Only one sperm penetrates the cytoplasm of the ovum and its nucleus fuses with the nucleus of the ovum. This forms the zygote.
Within a few hours the zygote begins to divide by a series of mitotic cell divisions known as cleavage to form a ball of cells called the morula and then a hollow structure, the blastocyst. During this transformation process it is gradually transported along the uterine tube towards the uterus.
By the time the blastocyst enters the uterine cavity (4 – 5 days after fertilisation), the endometrium is ready to receive it for pregnancy to be established. After a day or so in the uterine cavity the blastocyst attaches itself to the uterine endometrium – implantation.
What is an ectopic pregnancy?
Ectopic Pregnancy o Failure of transport of egg o Embeds in Fallopian tube, ovary or abdomen o Embryo dies o Severe risk of maternal haemorrhage
Why does the blastocyst take 4/5 days to enter the uterus after fertilisation?
It awaits the rise in progesterone - smooth muscle relaxation
Describe the blastocyst
Not totipitent like zygote
Outer layer - trophoblast becomes supporting structures
Inner layer - embryoblast becomes the embryo
Describe the conceptus in the uterus
Zygote to blastocyst in days 14-21 in the uterine cycle Progesterone primes the endometrium Conceptus is nourished in intrauterine fluid, 3 days floating Sticky trophoblasts over inner cell mass, adheres to endometrium (hCG) Implantation commences (6 days after ovulation)
When specifically does ovulation occur?
Always - 14 days before the first day of menstruation
What hormone tells us that ovulation has occurred and on what day is it highest?
Progesterone day 21
What is contraception?
Methods of modifying conception to prevent its occurrence
In what 6 broad ways can conception be altered as a form of contraception?
- Natural contraception
- Preventing sperm from entering the ejaculate
- Prevent/ inhibit sperm from reaching the cervix
- Prevent ovulation
- Inhibit transport of sperm along Fallopian tube
- Inhibit implantation
What are the three main methods of natural contraception?
- Abstinence
- Coitus interuptus- but sperm can still be present in preejaculate (bulbourethral glands)
- Rhythm method (not having sex whilst ovulating) - only works with regular cycles- assume maximum spermatozoa survival of 7 days (average 3-4 days) and ovum survival of 1 day–> so for a regular 28 day cycle, with ovulation on day 14 or 15; fertile period is day 7-16 of cycle
What method of contraception can be done to prevent sperm from entering the ejaculate?
Vasectomy- divide the vas deferens bilaterally, ensure ejaculate is free of sperm before relying on contraception
Needs to be checked a few months later
What 3 methods of contraception can be done to prevent sperm from reaching the cervix?
1- Barrier contraception- condoms (readily available, protects against STI’s, effective if correctly used), diaphragm (lies diagonally across cervix, needs correct fitting, does not completely occlude passage of sperm, holds sperm in acidic environment of vagina and reduces survival time), cap (fits across cervix, physical barrier)
2- Spermicide - most effective in conjunction with barrier methods
3- Hormone interruption with drugs - combined OCP, depot progesterone, progesterone implant, progesterone only pill (POP) - main mode of action of POP and implant- affects cervical mucus creating a thick hostile mucus, progesterone mediated environment
What method of contraception can be done to prevent ovulation?
Altering hormone levels with drugs
- Combined OCP- oestrogen and progesterone; negative feedback to hypothalamus and pituitary - inhibits follicular development; oestrogen causes loss of positive feedback mid cycle and so no LH surge
- Depot progesterone- 3 monthly injections of progesterone, negative feedback effect to inhibit ovulation
- Progesterone only pill- low dose progesterone only, may inhibit ovulation
- Progesterone implants- may inhibit ovulation
What method of contraception can be done to inhibit sperm transport along the Fallopian tube?
- Sterilisation - occlude the Fallopian tubes (may (but rarely do) recanalise) - Clips, Rings, Ligation
What 3 methods of contraception can be done to inhibit implantation?
- Altering hormones with drugs- affect receptivity of endometrium, direct effect, plus absence of corpus luteum prevents preparation of endometrium for implantation - OCP, progesterone implant, POP, depot progesterone
- Post Coital contraception - combined oestrogen/ progesterone high dose or POP; upto 72 hours after intercourse, may disrupt ovulation/ blocks implantation/ may also impair luteal function
- Intrauterine device - may also be used as post coital contraception up to 5 days after ovulation; inert copper containing or progesterone impregnated; copper interferes with endometrium enzymes and may also interfere with sperm transport into Fallopian tubes; interferes with implantation
What is the definition of infertility?
Failure to conceive within one year
What does primary and secondary infertility mean?
Primary- no previous pregnancy
Secondary- previous pregnancy - successful or not
What percentage of infertility problems are due to the female, male and unexplained?
Female - 45-60%
Male - 20-25%
Unexplained - 20-30%
What 4 main causes of infertility are there?
- Coital problems (20-30%)
- Anovulation (15-20%)
- Tubal occlusion (15-40%)
- Abnormal/ absent sperm production
Describe Anovulation as a cause of infertility
(15-20%)
Menstrual cycle, during which the ovaries don’t release an egg so ovulation does not occur, so usually have very irregular periods
Occasional anovulatory cycles normal- especially in extremes of reproductive life
Causes : hypothalamus (hyperprolactinaemia, weight loss, exercise, stress), pituitary (tumours, necrosis) and ovaries (ovarian failure, menopause, radiotherapy, chemotherapy) and Polycystic ovarian syndrome
What is Polycystic ovarian syndrome (POS)?
Uncertain pathogenesis- originates at pituitary or ovarian level
Increased androgen secretion
Raised LH/FSH ratio
Insulin resistance
Multiple small ovarian cysts
Anovulation- often amenorrhoea or oligomenorrhoea
How would you diagnose Anovulation?
Serum progesterone level in mid luteal phase ( ~ day 21)
How would you differentiate between different causes of Anovulation?
Differentiate causes by looking at hormone levels
Menopause and ovarian failure - high LH and FSH and low Oestrogen
Hypothalamus/ Pituitary failure - low LH, FSH and Oestrogen
PCOS - increased LH:FSH ratio, normal Oestrogen
How can you induce ovulation?
Anti oestrogen- reduce negative feedback to hypothalamus/ pituitary; increase GnRH and FSH
Gonadotrophins- FSH administration
GnRH agonists- pulsatile to mimic normal secretion
What can cause tubal occlusion?
Sterilisation
Scarring from infection, endometriosis
How is tubal occlusion diagnosed?
Laprascopy and dye insufflation
Hysterosalpingogram
How can tubal occlusion be treated?
Tubal surgery- reanastamoses
Assisted conception
What can cause abnormal sperm production as a cause of infertility?
Abnormal production (e.g. Testicular disease) Obstruction of ducts (e.g. Infection, vasectomy) Hypothalamic/ pituitary dysfunction
Describe normal semen analysis
Volume: >2ml
Sperm count: > 20mill/ml
Motility: >50%
Morphology: >50%
How would you investigate infertility?
o Regular, unprotected intercourse? o Ovulating? • Regular menstrual cycle? • Day 21 Progesterone? o Patent Tubes • History of infection / sterilisation • Hysterosalpingogram o Adequate sperm count?
How would you generally treat infertility?
o Induce ovulation- anti oestrogen, Gonadotrophins, GnRH agonists
o Overcome tubal occlusion by surgery or IVF
o If inadequate sperm then
• Artificial insemination by donor
• Intra-cytoplasmic sperm injection
Briefly, Describe how the conceptus implants into the endometrium
By the time the blastocyst enters the uterine cavity (4-5 days after fertilisation) the endometrium is ready to receive it for pregnancy to be established
After a day or so in the uterine cavity the blastocyst implants into the endometrium
Implantation involves the interaction between the trophoblast cells and epithelium of the uterus
Further embedding of the blastocyst into the endometrium is dependent on the invasive property of the trophoblasts, which by now have an outer layer- syncytiotrophoblast differentiated from the underlying cytotrophoblast
By the 10th day after fertilisation the blastocyst is fully embedded within the endometrium
What cells interact when a blastocyst implants in the endometrium of a uterus?
Epithelia of the uterus
Trophoblast cells –> syncytiotrophoblast and cytotrophoblast
Which part of the endometrium is a conceptus embedded in?
The stroma of the endometrium
How does the placental membrane change and the needs of the fetus change?
Placental membrane becomes progressively thinner as the needs of the fetus increase
The placenta is described as haemomonochorial - what does this mean?
One layer of trophoblast ultimately separates maternal blood from fetal capillary wall
What are the three main aims of implantation of a conceptus?
Establish the basic unit of exchange (primary, secondary and tertiary villi)
Anchor the placenta (establishment of outermost cytotrophoblast layer which anchors it)
Establish maternal blood flow with placenta
What is the difference between the primary, secondary and tertiary villi on the conceptus?
Primary villi- early finger like projections of trophoblast
Secondary villi- invasion of mesenchyme into core
Tertiary villi- invasion of mesenchyme core by fetal vessels
What two histological changes occur in order for a conceptus implants into the endometrium?
Decidualisation
Remodelling of the spiral arteries
What is decidualisation and how does it occur to help implantation?
Decidual reaction provides the balancing force for the invasive force of the trophoblast, without which haemorrhage and ectopic pregnancy can occur
Progesterone stimulates the endometrial epithelial cells to be changed into decidual cells
- process consists of modifying stromal cells, uterine glands and vessels and uterine immune cells, by altering their expression of regulatory factors such as metalloproteinases, cytokines, surface integrity and MHC
* Decidualisation occurs independently of the blastocysts presence in the uterine cavity and in fact happens any way in the late secretory phase of the menstrual cycle
Stromal cells become round and show ultra structural similarities to Myofibroblasts and epithelial cells –> release factors: prolactin, relaxin, renin, insulin growth, factor BP and ECM proteins- laminin and fibronectin
What is remodelling of spiral arteries and how does it occur to help implantation?
Creation of low resistance vascular bed
Maintains the high flow required to meet fetal demand, particularly late in gestation
What are three potential implantation defects that may occur?
Ectopic pregnancy
Placenta praevia
Incomplete invasion
Describe ectopic pregnancy as an implantation defect
Implantation at a site other than the uterine body
Most commonly in the Fallopian tube (can be peritoneal or ovarian)
Can very quickly become a life threatening emergency
Describe placenta praevia as an implantation defect
Implantation in lower uterine segment
Can cause haemorrhage in pregnancy
Requires c section delivery
Describe incomplete invasion as an implantation defect
Placental insufficiency
Pre eclampsia
What are the two components of the placenta at the beginning of the 4th month of pregnancy?
- A fetal portion - formed by chorion frondsum, bordered by chorionic plate
- A maternal portion - formed by decidua basalis, decidual plate is most intimately incorporated into the placenta
Describe the structure of the placenta
Beginning of 4th month:
-1. A fetal portion - formed by chorion frondsum, bordered by chorionic plate
-2. A maternal portion - formed by decidua basalis, decidual plate is most intimately incorporated into the placenta
Between the chorionic and decidual plates are the intervillous spaces which are filled with maternal blood
During the 4th and 5th months:
- decidua forms a number of decidual septa which project into the intervillous spaces but do not reach the chorionic plate
- these septa divide the placenta into a number of compartments or cotyledons
- as a result of the continuous growth of the fetus and expansion of the uterus, the placenta also enlarges
- throughout pregnancy it covers approximately 15-30% of the internal surface of the uterus
Compare the first trimester placenta and the term placenta
First trimester placenta
- placenta established
- placental barrier to diffusion still relatively thick
- complete cytotrophoblast layer beneath syncytiotrophoblast
Term placenta
- surface area for exchange dramatically increased
- placental barrier now thin
- cytotrophoblast layer beneath syncytiotrophoblast lost
Describe the fetal blood vessels in the placenta
The umbilical arteries and veins project into the tertiary villi which are bathed in oxygenated maternal blood
- two umbilical arteries take deoxygenated blood from the fetus to the placenta
- one umbilical vein takes oxygenated blood from the placenta to the fetus
Cotyledons:
- receive their blood through 80-100 spiral arteries that pierce the decidual plate
- pressure in these arteries forces oxygenated blood deep into the intervillous spaces and bathes the numerous small villi of the villious tree in oxygenated blood
- as the pressure decreases, blood flows back from the chorionic plate towards the decidua where it enters the endometrial veins
What three factors affect the passive diffusion of substances across the placenta?
Concentration gradient - steeper the gradient, the more diffusion
Barrier to diffusion - placental membrane (single layer of trophoblasts) gradually thins throughout pregnancy as the em and of the fetus increases
Diffusion distance- haemomonochorial - one layer of trophoblasts ultimately separates maternal blood from fetal capillary walls
What substances move across the placenta by simple diffusion, facilitated diffusion and active transport?
Simple diffusion- water, electrolytes, urea and uric acid, gases (flow limited, not diffusion limited; fetal O2 stores are small - maintenance of adequate flow is important)
Facilitated diffusion- glucose
Active transport- specific transporters are expressed by the syncytiotrophoblast; amino acids, iron and vitamins
What are teratogens and how do they exploit the placenta?
Placenta is not a true barrier and so harmful substances, teratogens, can access the fetus via the placenta and guns give physiological consequences (these are particularly damaging during critical stages of development)
- thalidomide
- alcohol
- therapeutic drugs
- drugs of abuse
- maternal smoking
What are some pathogens which are capable of crossing the placenta?
Varicella zoster Cytomegalovirus Treponema pallidum Toxoplasma Gondii Rubella
How does the placenta act like an endocrine organ supporting pregnancy?
Releases protein hormones:
- Human Chorionic Gonadotrophin (hCG)- produced in first 2 months of pregnancy, supports the secretory function of corpus luteum, produced by syncytiotrophoblast, therefore is pregnancy specific
- Human Chorionic Somatommotrophin (hCS)- influences maternal metabolism, increasing the availability of glucose to the fetus
- Human Chorionic Thryotrophin
- Human Chorionic Cortiotrophin
Releases steroid hormones (responsible for maintaining the pregnant state)
- Progesterone- placenta takes over production from the corpus luteum (week 11); influences maternal metabolism by increasing appetite
- Oestrogen- placenta also synthesises glycogen,cholesterol and fatty acids
-
Which pathological state is hCG present in?
Testicular cancer
What is the hormonal basis of testing for pregnancy?
Human Chorionic Gonadotrophin? (hCG)
- produced in first two months of pregnancy
- supports the secretory function of the corpus luteum
- produced by syncytiotrophoblast, therefore is pregnancy specific
- excreted in maternal urine, therefore is used as the basis for pregnancy testing
How is passive immunity transferred from the mother to the neonate via the placenta?
Immunological competence begins to develop late in the first trimester, by which time the fetus makes all the components of complement
Fetal immunoglobulins consist almost entirely of maternal immunoglobulin (IgG) which begins tone transported from mother to fetus at about 14 weeks
The IgG is transported via Receptor Mediated Pinocytosis
Eventually the concentration of IgG in fetal plasma exceeds that of maternal plasma
In this way the fetus gains passive immunity against various infectious diseases
Newborns produce their own IgG, but adult levels are not attained until the age of 3
How can haemolytic diseases of the newborn form?
Rhesus blood group in compatibility of mother and fetus
Mother previously sensitised to Rhesus antigen ( e.g. Previous pregnancy)
IgG against Rhesus cross the placenta and attacks fetal RBC’s
Now uncommon because of the prophylactic treatment - Rhesus negative mothers pregnant with Rhesus positive fetus are given Rhesus specific IgG throughout pregnancy to prevent sensitisation in the event of exposure to the antigen (given IgG will bind to antigen before the mothers immune system can mount a response)
What are the three components of antenatal screening?
History and examination: risk factors- e.g. For gestational diabetes
Blood test: blood group, haemoglobin, infection
Urinalysis: protein
Describe the physiological changes that occur in the CVS of the mother in pregnancy?
- Blood volume increases –> CO = SV (increased 35%) x HR (increased 15%)
- RBC number increases but not as much as blood volume (ANAEMIA)
- Decreased BP in pregnancy –> BP = CO (increased by 40%) x TPR (decreased by 25-30%; systemic vascular resistance)
- T1 and T2- progesterone –> decreased SVR
- T3- aortocaval compression by gravid uterus - Endothelium - vasodilation of pregnancy
Describe the physiological changes that occur in the RESP system of the mother in pregnancy?
- Diaphragm displaced upwards
- A-P diameter (transverse) of thorax increases –> lower ribs expand
- Hyperventilation: progesterone –> increased respiratory drive and increased metabolic CO2 production (inc paO2 and dec paCO2)- RESP ALKALOSIS * compensated by increase in bicarbonate excretion –> SOB
- increase in TV, RR the same, decrease in FRC, VC the same, TLC roughly the same, FEV1 the same
Describe the physiological changes that occur in the GI system of the mother in pregnancy?
- Viscera move around –> appendix to RUQ
- Progesterone –> Smooth muscle relaxes:
- GI- delayed emptying
- Biliary tract- stasis
- Pancreas- increased risk of pancreatitis
Describe the physiological changes that occur in the IMMUNE system of the mother in pregnancy?
- Fetus is an allograft (foreign body) –> non specific suppression of local immune respons at materno-fetal interface
- Transfer of antibiotics –> haemolytic disease and Graves and Hashimoto’s thyroiditis
Describe the physiological changes that occur in the URINARY system of the mother in pregnancy?
- Increased GFR
- Increased RPF
- Increased creatinine clearance, increased protein excretion, decreased urea, uric acid bicarbonate and creatinine
- Progesterone –> relaxes smooth muscle in the walls of the ureters –> STASIS, HYDROURETER, UTI’s, PYELONEPHRITIS
Describe the physiological changes that occur in the metabolic system of the mother in pregnancy?
FATS AND GLUCOSE
1st half of pregnancy
- progesterone stimulates appetite - diverts glucose into fat synthesis in the mother
- increase in lipolysis from T2 –> increase in PFFA’s (fasting) - FFA’s substrate for maternal metabolism, sparing glucose for fetus
2nd half of pregnancy
- oestrogen stimulates prolactin (and human placental lactogen and oestrogen, progesterone and cortisol release) –> generates a maternal resistance to insulin –> maternal glucose usage declines and gluconeogenesis increases –> maximising the availability of glucose to the fetus
- blood glucose in pregnancy- decrease in fasting blood glucose and increase in post prandial (meal) blood glucose (placental transport of glucose is by facilitated diffusion)
KETOACIDOSIS AND GESTATIONAL DIABETES
THYROID
Increase on TBG –> decrease in free T4 and T3 in blood –> positive feedback to increased T3 and T4 secretion
Free T4 normally in normal range (has higher affinity for TBG that T3)
T3 (more metabolically active) usually in higher concentrations
hCG –> decreased TSH
Describe the physiological changes that occur in the HAEMATOLOGICAL system of the mother in pregnancy?
Increased fibrin deposition at site Increased fibrinogen and clotting factors Reduced fibrinolysis Added to stasis and venodilation PROTHROMBOTIC STATE, THROMBOEMBOLISM *Warfarin is teratogenic
Summarise the fetal circulation
Placenta –> umbilical vein –> ductus venosus (around liver) –> + ascending vena cava (gut and lower body; deoxygenated but only small amounts as lower body is small) –> RA –> crista dividens –> foramen ovale –> LA –> LV –> Aorta –> Brain (oxygenated with some deoxygenated)–> + ductus arteriosus to rest (highly deoxygenated from brain) –> mixed oxygenated and deoxygenated blood –> gut and lower body
Brain –> descending vena cava (highly deoxygenated blood) –> RA –> RV –> pulmonary artery –> some to collapsed lungs via high resistance vessels but most forced into ductus arteriosus –> Aorta (after branch supplying mostly oxygenated blood to brain has branched off the aorta)
Describe fetal oxygen supply
pO2 in the fetus is 4kPa (compared to adult at 13.3kPa) despite even the increased pO2 in pregnant women due to progesterone induced hyperventilation
- fetus adapted to degree of hypoxia that would be fatal in a normal adult
Fetal Hb - much higher affinity for O2 and will carry more O2 at a lower pO2 (70% saturated at 4kPa); has no B chains and so does not readily bind 2,3 DPG; present at higher levels (neonate at least 18g/dl compared to 12-14g/dl in adult)
Oxygen transfer across the placenta - O2 transport rate is determined by umbilical artery pO2; fetus gets O2 it needs via constant supply from placenta - which is good because fetal O2 stores are very LOW (about 2 mins worth)
Describe fetal CO2 drainage
Maternal CO2 levels are lowered by hyperventilation stimulated by progesterone- enables fetus to have relatively normal pO2
Fetus cannot tolerate higher pCO2 levels than its mother –> acid base problems
Progesterone stimulates progesterone, which allows for the placental transfer of CO2 facilitated by lower maternal pCO2
Describe fetal lungs
Fetus makes breathing movements (1-4 hrs a day) which draw amniotic fluid into and out of the lungs
Surfactant is produced by type 2 pneumocystes from around week 20
- surfactant production is significantly increased after week 30 when the alveoli open in significant number and the surface area dramatically increases
- surfactant lowers the alveolar surface tension such that inspiration is made with less effort post natally
* deficiency in pre term infants can lead to respiratory distress syndrome of the newborn
Describe fetal glucose
Fetus relies on relatively high maternal blood glucose to drive glucose across the placenta and support fetal growth and development
Fetal insulin secretion begins at week 10
Describe fetal bilirubin
Fetus cannot excrete bilirubin via its gut
Bilirubin is therefore not conjugated and so passes across to the maternal circulation
Neonate may not immediately become able to deal with bilirubin and so neonate jaundice is common
Describe fetal gut and kidneys
Fetal kidneys produce urine (25 weeks- 100ml hypotonic urine/ day –> Term- 500ml urine/ day) which forms a major part of amniotic fluid particularly late in gestation
This fluid is constantly swallowed so that the gut absorbs water and electrolytes, leaving debris to accumulate, together with debris from the developing gut in the fetal large bowel =meconium- only excreted by a fetus in severe distress (hypoxia)
Describe the amniotic fluid
Fluid that surrounds the fetus and provides mechanical protection and a moist environment
8 weeks - 10ml –> 42 weeks - 300ml
Reaches a maximum of 1l at about 38 weeks - may fall as labour nears
Cells within the amniotic fluid are derived from amnion of fetus
Biochemical, and cytological studies of the fluid are made by amniocentesis and can be used to assess the presence of neural tube defects, chromosomal abnormalities ( Down’s syndrome) etc.
In early pregnancy amniotic fluid is derived probably by dialysis of fetal and maternal extracellular compartments with some exchange occurring across the fetal skin –> With functional maturation of the fetal kidneys, fetal urine contributes a lot to volume in later pregnancy; fetus also swallows amniotic fluid that is processed by fetal kidneys and gut
Amniotic fluid volumes are assessed by ultrasound - excess (polyhyramnios - oesophageal and duodenal atresia/ CNS abnormalities) or deficiency (oligohydramnios - poor or absent renal function / reduced placental function - pre eclampsia
Describe fetal nervous system
Whilst withdrawal from pain can be limited at 15 weeks, thalamocortical projections do not reach maturity until week 29
Completion of myelination in corticospinal tracts is not complete until post natal period but musculoskeletal movements are essential for fetal growth
Describe the fetal endocrine system
Placental progesterone promotes fetal corticosteroid production especially near term and is also vital for fetal physiology (esp. CVS function) Thyroid hormones (active from week12) are all vital for nervous system development, bone and hair growth
Describe the fetal liver
Liver stores large amounts of glycogen which is reflected in changes in fetal abdominal circumference
How do the three fetal shunts close at birth?
At birth, physical trauma and cold temperature induces neonate to take its first breath - dramatic reduction In pulmonary vascular resistance and a dramatic rise in arterial pO2
- causes left atrial pressure to rise respect to right atrial pressure so closing the foramen ovale
- smooth muscle sensitive to high pO2 in the wall of the ductus arteriosus contracts to close the ductus, so both fetal shunts are rapidly closed just by taking its first breaths
- both shunts close off completely in a few weeks
- ductus venosus variably remains open for several days after birth but closes within two or three months - a sphincter in the vessel constricts shortly after birth redirecting all blood through the liver sinusoids - again regulated by pO2 levels
What are the three periods of fetal growth and development?
Pre embryonic - fertilisation –> 3 weeks
Embryonic - 3 –> 8 weeks
Fetal - 8 –> 38 weeks
What is the function of the fetal period?
Growth and physiological maturation of the structures created during the (very much shorter) embryonic period
How are pregnancy weeks calculated?
From date of LMP (i.e. Conception weeks + 2)
So term is 40 pregnancy weeks
How does fetal growth change over pregnancy?
Growth and weight gain accelerate in pregnancy
What is crown rump length and how does it and weight gain change over pregnancy?
Crown Rump Length (CRL) is the measurement of the length of human embryos and fetuses from the top of the head (crown) to the bottom of the buttocks (rump)- increases rapidly in the pre-embryonic, embryonic and early fetal periods.
Weight gain is slow at first, but increases rapidly in the mid and late fetal periods. o Embryo • Intense morphogenesis and differentiation • Little weight gain • Placental growth most significant o Early fetus • Protein deposition o Late fetus • Adipose deposition
How does body proportion change over pregnancy?
Body proportions change dramatically during the fetal period.
o At week 9, the head is approximately half of the crown rump length
o Thereafter, body length and lower limb growth accelerates. At birth the health is approximately one quarter of the crown rump length
What are the 4 major stages of change in the respiratory system in the fetus in the fetal period?
Pseudoglandular Stage
o Weeks 8 – 16
Canalicular Stage
o Weeks 16 – 26
Terminal Sac Stage
o Week 26 – Term
Alveolar Period
o Late fetal to 8 years
What happens to the respiratory system in the embryonic period and hence why is the fetal period so important?
The lungs develop relatively late, as they are not needed until birth.
o Embryonic development creates only the bronchopumonary tree
• Airways, no gas exchanging parts
o Functional specialisation occurs in the fetal period
o Major implications for pre-term survival
• Threshold of Viability
• Viability is only a possibility after 24 weeks
What happens in the Pseudoglandular Stage of the fetal period?
o Weeks 8 – 16
o Duct systems begin to form within the bronchopulmonary segments created during the embryonic period
• Bronchioles
What happens in the Canalicular Stage of the fetal period?
o Weeks 16 – 26 o Formation of respiratory bronchioles • Budding from bronchioles formed during the pseudoglandular stage o May be viable at the end o More vascular o Some terminal sacs
What happens in the Terminal Sac Stage of the fetal period?
o Week 26 – Term
o Terminal sacs begin to bud from the respiratory bronchioles
o Some primitive alveoli
o Differentiation of pneumocytes
• Type 1 – Gas exchange
• Type 2 – Surfactant production from week 20
What happens in the Alveolar period of the fetal period?
o Late fetal to 8 years
• 95% of Alveoli are formed post-natally
How are the lungs conditioned in T2 and T3 to allow the lungs to take over from placental gas exchange when the baby is born?
During T2 and T3 gas exchange occurs at the placenta. However, the lungs must be prepared to assume the full burden immediately after birth.
o ‘Breathing’ movement
• Conditioning of the respiratory musculature
o Fluid filled
• Crucial for normal lung development
What are the changes that occur in the nervous system in the fetal period?
The nervous system is the first to begin development and the last to finish.
o Corticospinal tracts required for coordinated voluntary movements begin to form in the 4th month
o Myelination of the brain only beings in the 9th month
• Corticospinal tract myelination incomplete at birth, as evidence by increased infant mobility in the 1st year
o No movement until Week 8
o After week 8 a large repertoire of movements develop
• ‘Practicing’ for post-natal life
• E.g. suckling, breathing
The brain is the fastest developing organ in the fetus and infant. On average it accounts for 12% of body weight at birth, falling to about 2% in adults. During the fetal period important changes occur, structurally and functionally.
o Cerebral hemisphere becomes the largest part of the brain
• Gyri and sulci form after 5 months as the brain grows faster than the head
o Histological differentiation of cortex in the cerebrum and cerebellum
o Formation and myelination of nuclei and tracts
o Relative growth of the spinal cord and vertebral column
What are the changes that occur in the sensory and motor systems in the fetal period?
Hearing and taste mature before vision. The organ of corti in the inner ear is well developed in the fetus at 5 months, but the retina is immature at birth.
What is quickening and when can it be felt?
Maternal awareness of fetal movements
o Fetal movements can be seen by USS at Week 8
o Maternal awareness of fetal movements from Week 17 onwards
o Low cost, simple method of ante-partum fetal surveillance
o Reveals fetuses that require follow-up
What changes occur in the CVS in the fetal period?
The fetal cardiovascular system is arranged to ensure oxygenated blood collected by the umbilical vein at the placenta is circulated around the fetus.
The definitive fetal heart rate is achieved around 15 weeks
o Fetal bradycardia is associated with fetal demise
What changes occur in the urinary system in the fetal period?
Kidneys
o Ascent of kidneys complete at week 10
o Fetal kidney function begins in week 10
• Functional embryonic kidney is the Metanephros
o Renal pelvis, calyces etc present by week 23
o Histological differentiation of cortex and medulla almost complete by 8 months
o Fetal urine is a major contributor to amniotic fluid volume
o Fetal kidney function is not necessary for survival during pregnancy, but without it there is oligohydramnios.
Bladder
o Lies in the abdominal cavity in the fetus and infant
o Urine is emptied into the amniotic fluid, to be swallowed by the fetus.
o Bladder fills and empties every 40 – 60 minutes in the fetus (seen on USS)
What factors affect the viability of a pre-term/ premature neonate?
Threshold of Viability
Viability is only a possibility once the lungs have entered the terminal sac stage of development (after 24 weeks).
Brain Development
Viability is only possible if the brain is sufficiently mature to control body functions, e.g. breathing.
Respiratory Distress Syndrome
o Often affects infants born prematurely
o Insufficient surfactant production
o If pre-term delivery is unavoidable or inevitable
• Glucocorticoid treatment (of the mother)
• Increases surfactant production in the fetus
What are the broad techniques used to assess fetal development and growth?
Ultrasounds- Doppler (blood vessels); Non stress tests (heart rate changes associated with fetal movements); biophysical profiles (5 measured variables); fetal movement kick charts
Developmental criteria- crown rump length; foot length; biparietal diameter of head; abdominal circumference; femur length; weight and appearance after delivery; Symphysis – Fundal height
Daily rhythms
Duration of pregnancy- fertilisation age; age since mother’s last menstrual period
Amniotic fluid volume
Quickening
What is growth restriction and the meaning of it’s two types?
A fetus is regarded as having ‘growth restriction’ if weight is below the 10th percentile for gestational age. Depending on the cause a fetus with growth restriction may be compromised in the uterine environment and require closer monitoring in order to allow the continuation of the pregnancy to term.
o Symmetrical Growth Restriction
• Growth restriction is generalised and proportional
o Asymmetrical Growth Restriction
• Abdominal growth lags
• Relative sparing of head growth
• Tends to occur with deprivation of nutritional and oxygen supply to fetus
What is symphysis fundal height, how is it measured and what are some potential difficulties with it?
o Distance between symphysis pubis to top of uterus (fundus)
o Measured with a tape measure
• Number of fetuses can cause variation
• Volume of amniotic fluid can cause variation
• The lie of the fetus can cause variation
What is oligohydramnios and some causes?
Oligohydramnios o Too little o Placental insufficiency o Fetal renal impairment o Pre-eclampsia
What is polyhydramnios and some causes?
Polyhydramnois o Too much o Fetal abnormality • E.g. inability to swallow • Structural – blind-ended oesophagus • Neurological – unable to coordinate swallowing movements
When testing fetal movement what systems are assessed?
Nervous
MSK
When testing fetal breathing movement what systems are assessed?
Respiratory
Nervous
MSK
When testing fetal tone what systems are assessed?
Nervous
MSK
When testing amniotic fluid volume what systems are assessed?
Urinary
GI
Utero placental
When doing non stress tests what systems are assessed?
CVS
Autonomic
Nervous
What are the general classification of birth weights?
Classification of Birth Weights o < 2,500g = Growth Restriction o 3,500g = Average o > 4,500g = Macrosomia o Maternal diabetes
What may happen as a result of nutrition imbalances in early and late pregnancy?
Poor Nutrition in Early Pregnancy
o Neural tube defects
• E.g. DiGeorge Syndrome
Poor Nutrition in Late Pregnancy
o Asymmetrical Growth Restriction
• Subsequent oligohydramnios
