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
