Repro Flashcards
How is the development of secondary sex characteristics controlled?
Hormones: gonadotrophins + testosterone/oestrogen and progesterone
Describe the migration of germ cells that occurs embryologically.
The germ cells arise in the yolk sac then migrate along the dorsal mesentery to the urogenital ridge to reside within the primordial gonad.
How does development of the primordial gonad into the adult gonads differ according to genetic sex?
In males, germ cells colonise the medullary region and the cortex region atrophies. The germ cells allow rapid growth of the definitive sex cords which they subsequently invade. In the adult these give rise to the seminiferous tubules. The orignial mesodermal somatic cells form Sertoli cels, Leydig cells develop between the sex cords.
In females, germ cells colonise the cortex and so the medullary cords do not develop. The germ cells become surrounded by somatic mesenchymal cells which will eventually form primordial follicles.
Why can female genitalia be considered the “default”?
The cortex of the primordial gonad will develop even if no germ cells arrive.
How are the female internal genitalia formed?
The Mullerian / Paramesonephric ducts grow medially towards each other formining the uterus and its tubes, cervix, fornices and upper 2/3 of the vagina. The rest of the vagina is formed from the sinovaginal bulbs from the vaginal plate which grows from the urogenital sinus.
What is the function of Mullerian Inhibitory Hormone (MIH) and what is it secreted by?
MIH suppresses the growth of the Mullerian / Paramesonephric ducts in the male. It is secreted by Sertoli cells.
What is the genotype of an individual with true hermaphroditism?
Mosaicism of XY and XX or XO
Describe the important features of pseudo-hermaphroditism.
Occurs in individuals with XY genotypes but where foetal genitalia are insensitive to testosterone. The testis are undescended in the lumbosacral region, no internal genitalia will be produced and the external genitalia will be female. Undescended testes have an increased risk of developing germ cell tumours.
What genitalia (internal and external) will develop in an XX individual with congenital adrenal hyperplasia?
Female gonads but both male and female internal genitalia will develop. External genitalia will be male.
Describe the descent of the testes.
Testes start in the lumbosacral region, they then move caudally, crossing the inguinal canal obliquely and an invagination into the scrotum develops to form the processus vaginalis. Around 9 months gestation the testes migrate over the pubic bone to enter the scrotum.
What is the fate of the gubernaculum?
In females the guberaculum becomes the ovarian ligaments that join each ovary to the uterus.
In males the guberaculum becomes the scrotal ligament.
What is hypospadia and how does it develop? What is it associated with?
Hypospadias are where the urethral opening is on the ventral surface of the penis, they form due to incomplete fusion of the urethral folds. They are always associated with descended testes and sometimes with micropenis.
What is uterus bicornis? How does it develop? What are the consequences of it?
Uterus bicornis is where the uterus is “heart shaped” due to incomplete fusion of the paramesonephric ducts. It may cause menorrhagia but fertility is usually unaffected.
Describe the 4 main steps required for gametogenesis.
Colonisation of the gonad
Proliferation by mitosis
Introduction of genetic variation by meiosis
Cytodifferentiation
How does meiosis introduce genetic variation? MGD
Crossing over when pairs of chromosomes become bivalent
Random assortment as chromosomes line up at metaphase
Where does spermatogenesis occur?
In the seminiferous tubules
What is spermiogenesis?
Spermiogeneisis is the cytodifferentiation of spermatids into spermatozoa (mature sperm cells)
When do males start producing sperm?
At puberty
What is the spermatogenic cycle?
The spermatogenic cycle is the time taken for the reappearance of the same stage of spermatogenesis within a given segment of a seminiferous tubule.
What is the spermatogenic wave?
The spermatogenic wave is the distance along the seminiferous tubule between cells undergoing the same stage of spermatogenesis.
Where is the majority (by volume) of semen produced?
The seminal vesicle
What is the function of secretions from the bulbourethral (Cowper’s) glands?
To help lubricate the distal urethra and neutralise any acidic urine present
What is the source of the energy needed by sperm?
Fructose within semen is used to form ATP
What do the prostaglandins in semen do?
To increase sperm motility and to cause smooth muscle contraction within the female genital tract
What processes are involved in sperm capacitation?
Removal of glycoproteins and cholesterol from the cell membrane and the activation of sperm signalling pathways (atypical soluble adenylyl cylase and PKA involved)
What is the acrosome reaction?
The acrosome reaction is the process by which polyspermy is prevented at fertilisation. It is triggered by the binding of proteins on the head if the sperm to ZP3 proteins of the zona pellucida and involves at Ca2+ wave.
What are oogonia?
Diploid immature female reproductive cells produced by differentiation of the primordial germ cells which later form oocytes
When do oocytes complete meiosis I?
In utero - between 3 and 7 months gestation
What cells surround the oocyte once it has become part of a primordial follicle?
Flat epithelial cells of gonadal origin
What happens during the pre-antral stage of the maturation of the ovaries?
Follicular cells become cuboidal and proliferate to form a stratified epithelium of granulosa cells
What happens during the antral stage of maturation of the ovaries?
Fluid filled spaces appear between the granulosa cells and coalesce to form the antrum. The granulosa cells left surrounding the oocyte are then called the cumulus oophorus. The stromal cells form the theca folliculi: the theca externa (outer fibrous layer) and theca interna (inner secretory layer).
When do oocytes complete meiosis II?
At fertilisation
What is the polar body?
Either of two small cells produced during the first and second meiotic divisions in the development of an oocyte, containing little cytoplasm and eventually degenerating.
What stimulates the formation of the Graafian follicle?
The rise in FSH and LH before ovulation
How is the oocyte extruded from the ovary during ovulation?
LH surge increases collagenase activity
Prostaglandins increase the response to LH and cause local muscular contractions of the ovarian wall
What is the name of the cells which develop from the ovarian follicle and produce oestrogen and progesterone?
Lutein cells
What happens to the ovarian follicle if fertilisation does not occur after ovulation?
It degenerates and forms a mass of fibrotic scar tissue known as the corpus albicans
What is the function of human chorionic gonadotropin?
To prevent degeneration of the corpus luteum so that progesterone continues to be secreted to support the pregnancy until placental secretion becomes adequate
After ovulation, how is the oocyte transported to the uterus?
Fimbrae sweep over the surface of the ovary as the Fallopian tube begins to contract rhythmically. The oocyte is carried into the tube by these sweeping movements and the motion of cilia on the epithelial lining. It is then propelled along the tube by peristalsis and the mucosal cilia
How does the hypothalamus communicate with the posterior pituitary gland?
Via impulses that travel through the hypothalmic neurons in the neural stalk
How does the hypothalamus control the anterior pituitary gland?
Via the release of hypothalmic hypophysiotrophic releasing hormones (eg GnRH) which reach the ant pituitary via the hypophyseal portal system
What does the posterior pituitary gland produce?
ADH and oxytocin
What does the anterior pituitary gland produce?
Prolactin, Growth hormone, Thyroid stimulating hormone, Adrenocorticotrophic hormone, Follicle stimulating hormone and Luteinising hormone
How do gonadal cells detect FSH and LH?
Via Gs Protein Coupled Receptors
What is the effect of moderate oestrogen and progesterone on the Hypothalmic-Pituitary-Gonadal axis?
Oestrogen decreases amount of GnRH released per pulse released by the hypothalamus
while Progesterone decreases the frequency of GnRH pulses released by the hypothalamus
Under stimulation from FSH what do Sertoli cells produce, and what is the function of these products?
Androgen binding globulin - binds to testosterone and keeps it within the seminiferous tubules
Inhibin - helps support spermatogenesis and important inhibitory effects
Why is control of reproduction in females so much more complicated than in males?
Female reproductive tract needs to prepare for implantation of conceptus if fertilisation is achieved and also wait for a signal to develop from any conceptus formed, thus two phases (ie the follicular and luteal) are required.
Under stimulation from FSH what do the ovaries produce?
Inhibin
What is the effect of high [oestrogen] in the absence of progesterone?
Gives positive feedback to HPG axis leading to “LH surge”
Why does FSH rise at the beginning of the menstrual cycle?
Little inhibition to FSH secretion (as inhibin levels are low)
After ovulation, what part of the corpus luteum produces oestrogen? And which part produces progesterone?
Oestrogen secreted by theca lutein cells
Progesterone secreted by granulosa lutein cells
How is menstruation initiated?
In absence of further stimulation from LH, the corpus luteum regresses, causing a rapid fall in oestrogen and progesterone. This, in turn, causes the spiral arteries of the endometrium to spasm leading to ischeamic sloughing and thus loss of endometrial tissue
In early pregnancy, what part of the conceptus produces hCG?
The placenta
Describe the cervical mucus produced after menstruation but before ovulation
Thin, watery and alkaline
Describe the cervical mucus produced after ovulation
Thick, sticky and acidic
Describe the main effects of oestrogen on the female genital tract during the follicular phase
Increases motility of Fallopian tubes
Thickening of endometrium and growth and increased motility of myometrium
Cervical mucus is thin and alkaline
Besides the effects on the genital tract, what effects does progesterone have on the female body during the luteal phase of the menstrual cycle?
Changes in mammary tissue (hypertrophy of ducts)
Increased body temperature
Metabolic changes
Electrolyte changes
What is the thelarche?
The beginning of breast development (first stage of female puberty)
How is the pubertal growth spurt controlled?
By the Hypothalmic-Pituitary-Gonadal axis
How are the hormonal changes of puberty initiated?
Increased Gonadotrophin Releasing Hormone secretion from the hypothalamus causing increased stimulation of HPG axis
How does the initiation of androgen secretion support the pubertal growth spurt (in males)?
Stimulates retention of minerals to support bone and muscle growth
What scale is used to assess pubertal development?
Tanner standard (also monitoring of growth spurt)
Below what age would starting puberty be considered precocious?
8 years old in girls and 9 years old in boys
onset occurring at least 2 standard deviations younger than average age
Why is precocious puberty with a gonadotropin independent cause considered pseudo puberty?
It occurs independently of the HPG axis
List some gonadotropin dependant causes of precious puberty
Tumours such as gliomas and pineal tumours
CNS trauma or injury
Hamartomas of hypothalamus
Congenital eg hydrocephalus and arachnoid cysts
(very rarely gonadotropin secreting tumours)
How does Turner’s syndrome cause delayed puberty?
An absent (or structurally abnormal) X chromosome -> gonadal dysgenesis -> hypergonadotropic hypogonadism
How is the menopause diagnosed?
Retrospectively - when cessation of menstrual cycles has been experienced for 12 months
What are “hot flushes” and why do they occur?
Transient increases in skin temperature associated with flushing, they occur due to vascular dilation brought on by the hormonal changes of menopause
Why can the menopause cause urinary incontinence?
Causes changes in pelvic and bladder tone
How can the menopause lead to osteoporosis?
Reduced circulating levels of oestrogens enhances osteoclast ability to reabsorb bone and thus bone mass reduces by 2.5% for several years
What are the risks of HRT?
Increased risk of breast cancer
Increased risk of DVT and VTE can cause strokes and BP effects
Small increased risk of ovarian cancer
Side effects including headaches, bloating, nausea and indigestion
Describe and explain the hormonal changes of menopause
Cessation of development of ovarian follicles causes a dramatic decrease in oestrogen levels which initially causes dramatic increased FSH and increased LH
What, besides problems in the outflow tract, can cause primary amenorrhea?
Gonadal dysgenesis including Turners syndrome
Andogen insensitivity syndrome
Receptor abnormalities for FSH or LH
Congenital adrenal hyperplasia
Or Kallman’s syndrome - problems in hypothalmic devlopment due to a chromosomal defect
What are the most common causes of secondary amenorrhea?
Pregnancy (most common cause), Menopause and Polycystic Ovarian syndrome
How may hypo- or hyperthyroidism affect menstruation?
They can affect the HPG axis and cause amenorrhea (and other menstrual disturbances such as oligomenorrhea or, in hypothyroidism, polymenorrhagia)
How is prolactin secretion regulated?
By Dopamine, Thryotropin releasing hormone (and some other mechanisms)
How can hyperprolactinaemia cause amenorrhea?
Inhibition of oestrogen production due to increased prolactin
What drugs can cause hyperprolactinaemia?
Any that inhibit dopamine: includes anaethesia, opiates and H2antagonists
What are the main hormonal changes in polycystic ovary syndrome (PCOS)?
Increased frequency of GnRH pulse causing an increase in LH pulses and thus increased androgen secretion
What is the linea terminalis?
The line around the pelvis made of the pubic crest, the pectineal line and the arcuate line
What is the “true pelvis”?
The part of the pelvis between the pelvic inlet and the pelvic outlet
How is the size of the pelvic girdle assessed clinically?
By assessing:
Anteroposterior diameter (pelvic inlet)
Bi-spinous diameter (mid-pelvis)
Infra-pubic angle & distance between ischial tuberosities (pelvic outlet)
Distance from the sacral prominence to the the inferior border of the pubic symphysis (diagonal conjugate), allowing an estimate of the true / obstetrical conjugate (the distance between the sacral prominence and the pubic symphysis)
What 2 ligaments are important which regards to the pelvic girdle?
Sacrotuberous ligament - between ischial tuberosity and posterioir ileum, lateral sacrum and coccyx
Sacrospinous ligament - divides sciatic foramen
Approximately what angle of supra-pubic arch provides a ‘good’ pelvis for childbirth?
> 90’
What symptoms can BPH (benign prostatic hyperplasia) cause and why?
Dysuria, Nocturia and Urgency
Due to compresssion of prostatic urethra by enlargement of the middle zone of the prostate
Where are the seminal vesicles located?
Lie above prostate between bladder and the rectum
Describe the course of the vas deferens
Ascends in spermatic cord, passes through inguinal canal, traverses around bladder, and passes on medial side of ureter to form a dilated ampulla
Describe the internal composition of the penis
A pair of corpus cavernosa dorsally
Corpus spongiosum ventrally
All surrounded by tunica albuginea
What is the arterial supply to the penis?
Branches of Internal Puodenal arteries which are themselves branches of anterior division of Internal Iliac artery
What is the function of the bulbous spongiosus muscle?
Helps expel urine or semen and also helps maintain erections
What is the function of the ischiocaverosus muscle?
Compresses veins to help maintain erections
Describe the innervation of the scrotal area
Anterior surface - lumbar plexus
Posterioir and inferioir surfaces - sacral plexus
What is the lymphatic drainage of the scrotum?
To the superficial inguinal nodes
What is the lymphatic drainage of the testes?
To the para-aortic nodes
What is the arterial blood supply to the testes?
Direct branches of the abdominal aorta
What is the venous drainage of the testes?
Left - L renal vein
Right - IVC
What is the function of the dartos muscle?
To wrinkle the scrotal skin to prevent heat loss in cold conditions
Where are the bulbourethral glands located?
Within the urogenital diaphragm between the bulb of the penis, the prostate and the rectum
Describe the course a sperm cell takes from production to ejaculation
Produced in seminiferous tubules then -> straight tubules / tubuli recti -> rete testes -> efferent ductules -> epididmis where it is stored.
Then on emission passes through vas deferens where it is joined by secretions of seminal vesicles just before entering urethra (prostatic -> membranous -> spongy), pooling in urethral bulb before exiting penis on ejaculation
Describe the contents of the spermatic cord
Genitofemoral nerve (genital branch) Testicular artery Cremasteric artery Artery to vas Paminiform plexus Vas deferens Lymphatics Processus vaginalis
Describe the coverings of the spermatic cord
Superficial fascia and skin
External spermatic fascia (derived from aponeurosis of external oblique muscle)
Cremasteric muscle and fascia (derived from transversalis and external oblique)
Internal spermatic fascia (derived from transversialis fascia)
What is a hydrocoele?
A usually painless accumulation of fluid in the tunica vaginalis - can be within spermatic cord or the testis
How can a haematocoele be distinguished from a hydrocoele?
Transillumination - shine torch through and haematocoele will be red, hydrocoele will be clear
What is the most common cause of epididymitis?
STI
What is a spermatocoele?
An epididymal cyst - generally painless accumulation of sperm and fluid that arises from the head of the epididymis
What would you be worried about in a patient with testicular torsion?
Necrosis
Describe the epithelium lining the epididymis
Pseudo-stratified columnar with sterocilia
Describe the cremasteric reflex
Elevation of testis on stroking superior medial thigh. This area is innervated by the ilioinguinal nerve whose genital branch innervates the cremaster muscle
Why can prostatic malignancies spread to the vertebrae and the brain?
Through the valveless internal venous plexus
Describe the structure and function of the epithelial cells lining the tubuli recti and rete testis
Columnar ciliated and simple cuboidal to absorb fluid and propel sperm along tube
What are the 4 layers of the vas deferens?
Epithelium + lamina propria
Inner and outer longitudinal smooth muscle
Middle circular smooth muscle
Describe the epidemiology of testicular tumours
High percentage of tumours seen in early life
Vast majority are germ cell tumours
What is the mesovarium?
A short peritoneal fold that suspends the ovaries
Where do the ovaries develop?
Within the mesonephric ridge on the posterior abdominal wall
What is the lymphatic drainage of the ovaries?
To the para-aortic nodes
What is the ovarian ligament?
The ligament attaching the ovary to the uterus, it is derived from the gubernaculum
What is the round ligament?
The ligament attaching the uterus to the labium majus, it is derived from the gubernaculum
Describe the blood supply to the ovaries.
From the ovarian arteries which are direct branches off the abdominal aorta
Describe the venous drainage of the ovaries
Left ovarian vein -> L renal vein
Right ovarian vein -> IVC
What is the suspensory ligament of the ovary?
The ligament that attaches the ovary to the wall of the pelvis and contains the ovarian vessels, lymphatics and nerves
Where would you find the Fallopian tubes?
Extending posterolaterally from the uterus to the pelvic walls before arching anteriorly and superiorly to the ovaries
Describe the parts of the Fallopian tubes
Fimbrae - finger like projections
Infundibulum - funnel shaped distal end of the tube that opens into peritoneal cavity
Ampulla - widest and longest part of the tube where fertilisation usually occurs
Isthmus - thick walled part of the tube that enters the uterus
Why is there a higher risk of peritonitis in females?
Because in females the peritoneal cavity is open via the ostium of the Fallopian tubes whereas in males the cavity is completely closed
Describe the blood supply to the Fallopian tubes
Anastomosis of the ovarian artery and the ascending branch of the uterine artery
Describe what happens to the endometrium at menstruation
Spiral arteries spasm, retract back into the deeper evoking ischeamia which leads to desquamation of the outer 2/3 and associated bleeding
What are the 3 layers of the endometrium in the secretory phase?
The compact superficial zone
Spongy middle zone
Inactive basal layer
What are the anterior and posterior relations to the uterus?
Anterior - uterovesical pouch
Posterior - rectouterine pouch (Pouch of Douglas)
How does the uterus develop?
The uterus is formed embryologically by the the Mullerian/paramesonephric ducts which grow to fuse in the midline
What are the 3 layers of the uterine wall?
Endometrium
Myometrium
Perimetrium
How is the uterus normally positioned?
Anteverted and anteplexed
What is the blood supply to the uterus?
Uterine artery from the internal iliac artery
With some anastomosing with the ovarian artery
Describe the venous drainage of the uterus
Uterine plexus draining into uterine veins
Where do the ureters run in relation to the uterus?
Laterally, under the uterine artery and vein (water under the bridge)
Describe the parts of the cervix
Internal os
Endocervical canal
External os
What type of epithelium lines the cervix?
Simple columnar with branched glandular cells
Stratified non-keratinised squamous on inner aspect of external os
How is cervical mucus different around the time of ovulation?
Has higher water content, is less acidic and higher in electrolytes, acellular clear and “stretchy”
What are Nabothian cysts?
Infected, blocked cervical glandular ducts
Explain the clinical consequence of Nabothian cysts
Can cause infertility by making vagina in hospitable to sperm
Where may pain likely to be felt by a patient with an ectopic pregnancy?
R or L iliac fossae
What ligaments support the uterus within the pelvic cavity?
The transverse cervical ligament (lateral stability)
The uterosacral ligaments (oppose anterior pull of round ligament)
Why can ectopic pregnancy often be misdiagnosed as appendicitis?
Resultant appendicitis
R iliac fossa pain
How would you examine the uterus?
Bimanual palpation - two fingers pressed superiorly into the vagina while the other hand is pressed inferoposterioirly in the pubic region anteriorly
What is endometriosis?
Presence of tissue resembling endometrial glands and stroma outside the uterine cavity, inducing a chronic inflammatory reaction
Where are the Bartholin glands located?
On each side of the vestibule near the vagina
When are the Bartholin glands palpable?
When they are infected
How does the presence of Lactobacillus protect the vagina from pathogens?
They utilise glycogen to produce which maintains a low pH
What is culdocentesis?
Medical procedure performed to extract accumulated fluid
Describe the innervation of the vagina
Inferior 1/5th somatic innervation from pudenal nerve
Superior 4/5ths uterovaginal plexus
What nerves supply the perineum?
Pudenal nerve (S2-4) and ilioinguinal nerve
Describe the anaesthetic options available for childbirth
Caudal epidural block - anaesthetic through indwelling cather in the spinal canal, affects S2-4, must be administered in advance of delivery
Pudenal nerve block - local anaesthesia for S2-4 dermatomes and inferior quarter of vagina
Spinal anaesthesia - Spinal needle of anaesthetic at L3-L4 level - complete motor and sensory anaesthesia below the waist so mother becomes totally reliant on electrical monitoring for sensation of uterine contractions
Describe and name the levator ani muscles
Puborectalis - from pubic symphysis looping around rectum
Pubococcygeus - from pubis to coccyx and sacrum
Iliococcygeus - ischial spine to sacrum and coccyx
Coccygeus - overlying sacrospinous ligament, ischial spines to lateral aspect of sacrum and coccyx
What is the clinical relevance of the superficial perineal pouch?
Site where urine collects if the urethra is ruptured below perineal membrane
Describe the layers of the urogenital triangle
Skin, Deep perineal fascia, Superficial perineal pouch, Perineal membrane, Transverse perineal muscle contained within Deep perineal pouch which also contains External urethral sphincter
What are the anatomical boundaries of the perineum?
Anterior – Pubic symphysis Laterally – Inferior pubic rami and inferior ischial rami, and the sacrotuberous ligament Posterior– The tip of the coccyx Roof – The pelvic floor Base – Skin and fascia
Describe the blood supply of the pelvic floor
Internal pudenal artery
What is the innervation of the pelvic floor and the spinal roots of this?
Pudenal nerve
S2,3&4 (keeps your guts off the floor)
What is the perineal body?
Fibromuscular node at the centre of the perineum at the junction of the anterior and posterior perineum that functions as a point of attachment for the muscle fibres of the pelvic floor
What is an episiotomy?
Surgical cut to the perineum
How can childbirth damage the pelvic floor?
Stretching of the pudenal nerve leading to neuropraxia and muscle weakness
Stretching and damage of pelvic floor and perineal muscles leading to muscle weakness
Stretching and damage of ligaments of pelvic floor leading to ineffective muscle action
What are the surgical treatments for incontinence?
Colposuspension
Tension free vaginal tape
Name the organism that causes genital chlamydia
Chlamydia trachomatis, generally serotypes D-K
Where would you look up up-to-date advice for STI management?
BASHH Guidelines
Which strains of HPV cause cutaneous mucosal and anogenital warts?
HPV 6 and 11
How would you treat cutaneous mucosal and/or anogenital warts?
Conservatively - majority resolve spontaneously
Otherwise topical podophyllin, cryrotherapy, intralesional interferon, imiquimod or surgery
Specifically, what type of organism causes chlamydia?
Obligate intracellular bacterium
What are the signs and symptoms of genital chlamydia?
Typically no symptoms!!
Urethritis
Prostatitis (men), procticitis (MSM)
Cervicitis, salpingitis, perihepatitis (women)
How is chlamydia diagnosed?
Endocervical or urethral swabs (if refused, first pass urine sample) subjected to nucleic acid amplification techniques
Consider dual testing with N. gonorrhoae
How would you treat chlamydia?
Azithromycin (single dose or few days course)
Which strain of herpes simplex virus is associated with genital herpes?
HSV2
How is genital herpes different from genital warts?
Herpes, unlike warts is typically painful, can cause genital ulceration and inguinal lymphadenopathy
Explain why recurrent herpes infections can occur
Latent infection in dorsal root ganglia
How would you diagnose herpes?
PCR of vesicle fluid and/or ulcer base
How would you treat herpes?
Aciclovir and advice on barrier contraception to reduce transmission risk
Which strains of HPV are strongly associated with cervical and anogenital cancer?
16 and 18
What are the symptoms of gonorrhoea?
Men: Urethritis, often with purulent discharge, epididimytis, prostatitis (also procitis and pharyngitis in MSM)
Women: Often none! Urethritis, Endocervitis, PID
Also, in disseminated infections - skin and joint lesions
Describe the causative organism in genital gonorrhoea
Neisseria gonorroeae - a gram negative intracellular diplococcus
How would you diagnose gonorrhoea?
Swab from urethra or cervix and gram stain
Or urine sample subjected to nucleic acid amplification techniques
How would you treat gonorrhoea?
Ceftriaxone IM plus testing and/or treatment for chlamydia with azithromycin
What is the causative organism in syphilis?
Treponema pallidum
Describe the 4 stages of syphilis
Primary - indurated, painless ulcer
Secondary - rash, fever, lymphadenopathy, mucosal lesions 6-8 wks later
Latent - symptom free years
Tertiatry - neurosyphilis, cardovascular syphilis, gummas (local destruction, often on face)
How would you diagnose syphilis?
Serology - dark field microscopy
How would you treat syphilis?
Penicillin and test-of-cure follow up
What are the potential sexually transmitted causes of inguinal lymphadenopathy?
Genital herpes, secondary stage syphilis
LGV (chlamydia trachomatis serotypes L1,2&3)
Chancroid (Heamophilus ducreyi)
Granuloma inguinale (Klebsiella granulomatis
What are the risk factors for vulvovaginal candidiasis?
Antibiotics
Oestrogen: pregnancy, obesity, oral contraceptive pill
Diabetes
How would you diagnose vulvovaginal candidiasis?
High vaginal smear and microscopy +/- culture
What are the treatment options for vulvovaginal candidiasis?
Topical azoles or nystatin
Oral fluconazole for more problematic cases
And control risk factors!
What are the symptoms of BV?
Offensive, fishy discharge
What are the potential causative organisms in BV?
Gardenerella vaginalis, other anaerobes, mycoplasmas
How would you treat BV?
Metrionidazole
What are the symptoms of trichomonas vaginitis?
Thin, frothy and offensive discharge
Irritation, dysuria and vaginal inflammation
What is the treatment for trichomonas vaginitis?
Metronidazole
What is the causative organism in trichomonas vaginitis?
Trichomonas vaginalis - a flagellated protozoan
What are the risk factors for pelvic inflammatory disease?
STI risk factors
IUD insertion and removal
Describe the aetiology of PID
Often polymicrobial, commonly C. trachomatis and N. gonorrhoea but can be gardenerella vaginalis, myoplasma hominis or various anaerobes
Actinomycosis is associated with IUDs
Who is PID most common in?
Sexually active women in their 20s
What are the symptoms of PID?
Pyrexia +/- rigors
Lower abdo pain and deep dysparenunia
Abnormal vaginal discharge or bleeding
What findings may you illicit on bimanual examination of a patient with (suspected) PID?
Adenexal tenderness
Cervical motion tenderness
What could you expect to see on speculum examination of a patient with PID?
Purulent cervical discharge
Cervicitis
Give a differential diagnosis for lower abdominal pain
Ectopic pregnancy, endometriosis, ovarian cyst complications,
IBS, Appendictis, IBD,
UTI, bladder or kidney stones,
Functional pain
What investigations are implicated in a case of suspected PID?
Diagnostic laproscopy Pregnancy test Endocervical and high vaginal swabs - for chlamydia and gonorrhoea WBC and CRP Screening for other STIs
Why is there a low threshold for treatment in PID?
Delayed treatment increases risk of long term sequalae
When would you admit a patient with PID?
Severe cases or if patient is pregnant
What signs would indicate a case of PID is severe?
Pyrexia > 38’c
Signs or tubo-ovarian abscess or pelvic peritonitis
No response to oral therapy
What is the UHL regimen for treatment of PID in out-patients?
IM Ceftriaxone
With Doxycyclin and Metronidazole tablets
Follow up in 72 hrs
How does the UHL regimen for treatment of PID differ for inpatients?
Metronidazole IV not PO and give another dose of IM Ceftriaxone
Describe Fitz-Hugh-Curtis syndrome
RUQ pain and peri-hepatitis, commonly caused by chamydial PID
Describe Reiter syndrome
(Can’t pee, can’t see, can’t bend at the knee)
Urethritis, Conjunctivitis, Arthritis due to disseminated infection following PID
What are the long term sequelae for PID?
Ectopic pregnancy Infertility Chronic abdo pain Fitz-Hugh-Curtis syndrome Reiter syndrome
List the main constituents of semen and their origins
Secretions from seminal vesicle (70%) - contains amino acids, fructose, prostaglandins, clotting factors
Secretions from prostate (25%) - contains proteolytic enzymes (to break down clotting factors and reliquify semen), zinc, acid phosphatase
Secretions of Cowper’s glands (
Describe the stages involved in the remodelling of spermatids into spermatozoa
Nuclear condensation within head
Acrosome formation - Golgi apparatus produces lyosome-like hydrolytic enzymes which enable sperm to penetrate ovum
Packing of mitochondria around contractile filaments in the midpiece
Production of flagellum from microtubules, growing from centriole to form axoneme
Briefly describe the sexual response cycle
Excitement phase -> plateau phase -> orgasmic phase -> resolution phase (followed by refractory period in males)
Which neurons are inhibited during the excitement phase of the sexual response cycle?
Thoracolumbar sympathetic neurons
How does activation of the limbic system and the sacral parasympathetic neurons lead to the initiation of penile erection?
M3 receptors on endothelial cells activated -> stimulates increase in intracellular Ca2+ -> activates eNO synthase -> Nitric oxide produced -> arteriolar vasodilation in corpora cavernosa -> increases penile flow so causing penile filling and tumescence
What neural reflex is activated in the plateau stage of the sexual response cycle?
Sacrospinous reflex
What is the difference between seminal emission and ejaculation (males)?
Emission is release of semen into the penis where it pools in the urethral bulb, controlled by thoracolumbar reflex
Ejaculation is explusion of semen from penis, controlled by spinal reflex L1&2
What neural reflex is responsible for seminal emission?
Spinal reflex L1&2
Filling of urethra stimulates pudenal nerve
When is secretion from the Cowper’s and Littre’s glands stimulated?
The plateau phase
How is penile erection maintained during the plateau stage of the sexual response cycle?
Contraction of ischiocavernosus which compresses penis and impedes venous return
(while pressure within corpus caverosa increases above systemic blood pressure decreasing arterial inflow)
What neural pathway controls the resolution stage of the sexual response cycle?
Activation of Thoracolumar sympathetic pathway
What systemic changes occur in the excitement phase of sexual response in females?
Increase muscle tone, heart rate and blood pressure
By what physiological mechanism is vaginal lubrication achieved?
Vasocongestion
List some causes of sexual impotence
Drugs - alcohol, antihypertensives
Psycological
Vascular - atherosclerosis, diabetic microvascular disease
Trauma - tears in fibrous tissue of corpora cavernosa
How does Viagra work?
Decreases cyclic GMP breakdown which increases action of nitric oxide
When does the fertile period occur?
Day of ovulation and 5 days prior
Describe the stages of capacitation of sperm
Occurs within female genital tract
Protein coat removed from cell membrane to expose acrosomal enzymes
Tail movement changes from beat to whiplike
-> allowing sperm to penetrate corona radiata and zona pellucida and fuse with oocyte cell membrane
How is the acrosome reaction triggered?
When proteins on sperm head bind to Zp3 proteins of zona pellucida
How is polyspermy prevented?
By the fast block and cortical reaction of the acrosome reaction
Fast block - Na+ channels in oocyte membrane open causing a wave of depolarisation propagating from site of sperm’s entry
Cortical reaction - Ca2+ released from ER induces local exocytosis of cortical granules -> release enzymes which stimulate the adjacent cortical granules to also undergo exocytosis -> wave of exocytosis from sperm’s entry site
ToB Describe the stages of the early embryonic period
Cleavage - increased number of cells, size stays same thus increasing nuclear:cytoplasm
Compaction - at 8 cell stage cells form tight junctions
Morula - 16 cell stage at which conceptus passes into uterus
Blastocyst stage - loss of totipotency as conceptus separates into embryoblast and trophoblast
Hatching - local digestion of zona pellucida by enzyme produced in trophoblast
Implantation - trophoblast overlying inner cell mass adheres to endothelium
ToB Describe the conceptus at the beginning of week 2
Embryoblast has formed bilaminar disc consisting of epiblast and hypoblast
Trophoblast has become cytotrophoblast which is mononucleated and synctiotrophoblast which is multinucleated
Describe the placental changes that occur after implantation of the conceptus
Placental membrane thins to become haemomonochorial
Chorion establishes basic unit of exchange by forming primary villi which are finger-like projections of trophoblast, these later develop a mesenchyme core at which point they are called secondary villi. The final stage of villi development, after which villi are known as tertiary villi, involves the invasion of this mesenchyme core by foetal vessels.
How is the trophoblast prevented from penetrating too far into the endometrium?
By the presence of “pre-decidual” cells within the endometrium
How is the endometrium prepared for implantation after ovulation?
Growth of pre-decidual cells
Elaboration of spiral arterial blood supply
What is placenta praevia?
A pregancy where the site of implanation is in the lower uterine segment
What type of monozygotic twins has the greatest risk of unequal blood supply?
Those that share an amnion and a chorion
Describe the blood supply to the foetus
1 umbilical vein within umbilical cord provides oxygenated blood from placenta to the foetus
2 umbilical arteries within umbilical cord pass deoxygenated blood from the foetus to the placenta
Placenta receives oxygen, water, electrolytes, glucose, amino acids etc. and gives up waste products such as urea by a counter-current exchange mechanism with maternal blood
What does the placenta produce?
Glycogen Fatty acids Cholesterol -> some of which is used to produce the steroid hormones progesterone and oestrogen Also produces polypetide hormones: human chorionic gonadotropin human chorionic somatotrophin human chorionic thyrotropin human chorionic corticotrop
What is hCG and what is its function?
Human chorionic gonadotropin
Supports corpus luteum to continue producing oetrogen and progesterone to support early pregnancy before placenta can produce its own steroid hormones
How does the foetus develop passive immunity to pathogens?
Receptor mediated endocytosis of IgG from mother to placenta which then supplies foetus
Describe how haemolytic disease of the newborn can develop
If baby is Rh positive and mother is Rh negative, during the pregnancy maternal antibodies against the Rh antigen (formed in past pregnancy that was also rhesus incompatible) pass to the foetus through the placenta after which they attack the foetal red blood cells, causing haemolysis.
List 6 infectious agents that can pass to the foetus
Varicella zoster Cytomegalovirus Treponema pallidum (syphillis) Toxoplasma gondii Rubella HIV
What is Rubella syndrome?
Range of foetal defects that occur when the mother has contracted Rubella: Microcephaly, patent ductus arteriosus and other CVS defects, cataracts
Describe the normal components of ante-natal screening
History and examination - identification of risk factors for and signs of gestational diabetes and pre-eclampsia etc
Blood test - for Rhesus status, haemoglobin levels, HIV
Urinanalysis - for proteinuria
When does the maternal CVS start to adapt to pregnancy?
From the 1st trimester (anticipatory changes)
What changes occur in the mother’s CVS during pregnancy?
Increased blood volume
40% increased cardiac output due to increased stroke volume and heart rate
30% decrease in systemic vascular resistance
Decrease in blood pressure in early pregnancy, returning to normal in 3rd trimester
Why does the maternal blood pressure usually return to normal in the 3rd trimester?
Due to compression of abdominal aorta and IVC by gravid uterus
What is the pathogenesis and aetiology of pre-eclampsia?
Vasoconstriction and plasma contraction due to secretion of unidentified circulating factor in response to foetal hypoxia due to a defect in placentation
What is the diagnostic criteria for pre-eclampsia?
New onset hypertension
+ Proteinuria >300mg/24hrs in absence of UTI
What signs and symptoms may develop in severe pre-eclampsia?
Those of CNS dysfunction such as headaches, visual distirbances
Those of liver capsule distention, such as liver tenderness
Pulmonary oedema
Papilloedma
Severe pain just below ribs or vomiting
What are the risk factors for pre-eclampsia?
1st time pregnancy Multiple gestation Chronic hypertension or renal disease Race - black Extremes of age Positive family history
What is eclampsia?
Onset of convulsions in a pregnancy complicated by pre-eclampsia
How would you manage eclampsia?
Maintain airway, O2, place mother on her left side
IV Magnesium sulphate
Delivery is definitive treatment for eclampsia
How does the maternal GFR change during pregnancy?
55% increase in GFR
What is the consequence of the change in maternal GFR during pregnancy?
Decreased functional renal reserve thus limited capacity for compensation
Describe how the urinalysis ranges for pregnant women are different from normal
50% decrease in urea
Increasingly decreasing uric acid
Decreased bicarbonate
Decreased creatinine
How does the raised levels of progesterone during pregnancy contribute to an increased risk of UTI, hydroureter and obstruction?
Progesterone causes dilation leading to urinary stasis
How and why is the maternal functional residual capacity changed during pregnancy?
It decreases in 3rd trimester due to displacement of diaphragm by gravid uterus
Describe the cause and effects of physiological hyperventilation in pregnancy
Due to increased respiratory drive due to increased progesterone
Causes respiratory alkalosis which is compensated by increased renal bicarbonate excretion and 20% increase in oxygen consumption
Describe the physiological changes to carbohydrate metabolism in pregnancy
Increased peripheral insulin resistance
Increased gluconeogenesis
Decreased fasting blood glucose
Increased post-pranial blood glucose
What is gestational diabetes?
Carbohydrate intolerance first recognised in pregnancy and not persisting after the pregnancy
What are the risk factors for gestational diabetes?
BMI over 30 Previous macrosomic birth History of gestational diabetes Family history of diabetes South Asian, black Caribbean or Middle eastern
What are the potential consequences of gestational diabetes?
Macrosomic baby
Stillbirth
Congenital defects such as cardiac and neural tube defects
Premature birth and associated Respiratory Distress Syndrome of newborn
Diabetic ketoacidosis
Pre-eclampsia
Why is there an increased risk of ketoacidosis in pregnancy?
Increased lipolysis from 2nd trimester leads to increased plasma free fatty acids on fasting
Describe the effects on the thyroid gland in pregnancy
Increased thyroid binding globulin production
Increased T3&4
Which can cause TSH to decrease
Due to stimulatory effects of hCG on thryoid
Why is there an increased risk of pancreatitis in pregnancy?
Progesterone causes relaxation of smooth muscle, causing stasis
What factors contribute to pregnancy being a pro-thrombotic state?
Increased fibrin deposition at implantation site
Increased fibrinogen and clotting factors
Decreased fibrolysis
Stasis and venodilation
Why does “physiological” anaemia occur in pregnancy?
Dilutional - red cell volume doesn’t increase to same degree as plasma volume
Why is anaemia more common in pregnant women?
Increased iron and folate requirements due to foetus
Why is it recommended that pregnant women take folate supplements?
Prevent neural tube defects such as spina bifida
Why are pregnant women slightly more susceptible to infections?
Non-specific immunosuppression of local immune response at materno-foetal interface to prevent rejection of allograffic foetus
Describe how oxygen transfer to the foetus is facilitated
Low foetal pO2
Increased maternal production of 2,3 DPG
Effects of Foetal haemoglobin - greater affinity for O2
Double Bohr effect - shift of O2 dissociation curve in opposite directions in mother and foetus
Describe the double Bohr effect
In mother, blood pH falls as CO2 enters into intervillous blood, decreasing affinity of Hb for O2.
While in the foetus, blood pH increases as CO2 is lost, increasing affinity of Hb for O2.
This effect maximises oxygen transfer from materal to foetal blood.
How is the transfer of CO2 from foetus to mother facilitated?
The Double Haldane effect which is unique to placenta - as Hb gives up O2 it can accept increasing amounts of CO2, foetus gives up CO2 as O2 is accepted so there are no alterations in local pCO2 so CO2 concentration gradient is unaffected.
Describe the foetal circulation
Liver bypassed by ductus venosus.
Lungs as bypassed by foramen ovale which shunts blood from R to L atrium of the heart, and the ductus artiosus which shunts blood from the R ventricle and pulmonary trunk to the aorta, distal to supply for head and heart.
How is the foetus adapted to manage transient hypoxia?
Foetal heamoglobin has greater affinty for oxygen and presnet at higher concentration than Hb in an adult.
Can redistriubte flow to protect supply to heart and brain
Vagal stimulation by chemoreceptors detecting low pO2 or high pCo2 stimulates bradycardia
What are the potential consequences of chronic foetal hypoxia?
Growth restriction
Developmental disorders due to foetal behavioural changes
Risk of cerebral palsy and other consequences of ischaemic injury to the brain
Name the hormones necessary for foetal growth
IGFI - dominant in 1st trimester IGFII - dominant in 2nd and 3rd trimester Insulin Leptin EGF TGFalpha
Why is foetal growth typically unaffected by maternal “morning sickness”?
IGFI has large role in controlling foetal growth in 1st trimester, when morning sickness usually occurs. This hormone is “nutrient independent” so is unaffected by the maternal nutritional status, lessening the effect on foetal growth.
What factors can affect foetal growth?
Maternal nutritional status Maternal smoking or alcohol use Efficiency of placenta Utero-placental blood flow Maternal parity Genetic factors Race, maternal height and weight
What is asymmetrical growth restriction and why might it occur?
Intra-uterine growth restriction where admonial fat and glycogen is diminshed but the head and brain are “spared”, may occur due to maternal malnutrition, typically in 3rd trimester
What are the functions of amniotic fluid?
Provide mechanical protection to foetus and a moist environment for developing skin
Contributes to lung development
How is amniotic fluid produced in early gestation?
Transudation - passage of fluid across amnion and foetal skin
How is amniotic fluid produced for the majority of gestation?
Mostly from urine production by foetal kidneys, some contribution from lung fluid and fluid from head.
What happens to amniotic fluid after it has been produced?
Recycled - Swallowed by foetus and water and electrolytes absorbed, with debris accumulating the the gut
What is meconium and what does its presence in the amniotic fluid indicate?
1st bowel movement, usually passed after birth.
Consists of accumulated debris from amniotic fluid, intestinal secretions and bile.
If present in amniotic fluid indicates foetus has experienced distress.
Is a jaundiced appearance of a neonate alarming and why?
No, physiological jaundice of newborn is common as foetus cannot conjugate bilirubin due to immaturity of liver and intestinal processes.
Describe the differences in the pattern of growth in the embryonic stage and the foetal stage
Embryonic - development of organ systems; absolute growth, besides that of placenta, is very small
Foetal - acceleration of growth and weight gain causing change in body proportion; protein and adipose deposition in mid and late foetal periods respectively
Describe how ante-natal foetal well-being is assessed
Ask mother about foetal movements
Regularly measure symphysis-fundal height
Ultrasound scan - typically at 20 weeks to assess foetal growth and detect foetal abnormalities
When would you perform a non-stress test in a low risk pregnancy?
If foetal movements are decreased
In what circumstances may a pregnancy be considered “high risk”?
Maternal hypertension, renal disease, cardiovascular disease, diabetes or anaemia
Post-term
Multiple pregnancy
Evidence of intra-uterine growth restriction
Suspected oligohydraminios
Placenta abnormality
How is foetal well-being monitored in “high risk” pregnancies?
Foetal movement charts (“kickcharts”) from 28-32 weeks
Weekly non-stress test and potentially amniotic fluid estimations from 28-32 weeks
Potentially biophysical profiling
Describe how you can make an estimation of foetal age
Count from last menstrual period, being aware of potential inaccuracy
Assessment of developmental criteria at ultrasound- crown rump length if early in pregnancy or biparietal diameter, abdominal circumference and femur length if later on
What is the exact definition of macrosomia?
Birth weight over 4500g
Describe the foetal development of the respiratory system
Pseudoglandular stage at 8-16 wks, where duct system begins to form within the broncho-pulmonary segments created during embryonic period.
Canalicular stage at 16-26 wks, where respiratory bronchioles form via budding from bronchioles formed in pseudo-glandular stage. Epithelium becomes ciliated.
Terminal sac stage at 26 wks - term, where terminal saces begin to form from respiratory bronchioles, and type 1 & 2 alveolar cells /pneumocytes differentiate and surfactant production begins by type 2 alveolar cells.
*Describe the initiation of surfactant production
In Terminal sac stage of lung development, type 1 & 2 alveolar cells /pneumocytes differentiate. At 20 wks surfactant production begins by type 2 alveolar cells, rapidly increasing at 30 wks and reaching significant levels around 34 weeks
What is the function of foetal breathing movements?
Conditioning of the respiratory musculature
Drawing of amniotic fluid into lungs, promoting differentiation of pneumocytes / alveolar cells
If a pre-term delivery is unavoidable how can you limit the probability of respiratory distress syndrome?
Glucocorticoid treatment of the mother - reduces risk by 50%
What does foetal bradycardia suggest?
Foetal hypoxia and demise
When can the foetal heart beat be identified?
By transvaginal ultrasound at 5-6 weeks
Doppler stethoscope at 10-12 weeks
Plain stethoscope at 18-20 weeks
What would be a typical foetal heart rate at term?
140-160 bpm
When do the foetal kidneys become functional?
Around week 10 gestation
What are the potential causes of oligohydramnios?
Problems with foetal kidney function including obstruction
Maternal hypertensive disorders incl. pre-eclampsia
Premature rupture of membranes or leakage of amniotic fluid
What are the potential causes of polyhydramnios?
Problems with foetal swallowing such as oesophageal or atresia or duodenal atresia
Why do we measure the levels of alpha fetoprotein in maternal blood?
Levels are elevated in open neural tube defects (and also multiple pregnancies)
When do foetal movements begin?
8th week of gestation
What is quickening and when does it occur?
Maternal awareness of foetal movements
Typically 17 weeks onwards
What is parturition?
The process of the explusion of the products of conceptus, includes labour
During which weeks of gestation would birth be considered to be at term?
37 to 42 weeks
What are the 3 stages of labour?
Creation of birth canal
Expulsion of foetus
Expulsion of placenta and contraction of uterus
Describe how symphysis-fundal height increases over pregnancy, including key anatomical landmarks
Distance in cm roughly same as number of weeks gestation, decreasing slightly at term (as baby’s head engages)
Reaches umbilicus around 20 weeks
Reaches xiphisterum by 36 weeks
How is the normal positing of the foetus at the beginning of parturition described?
Longitudinal lie
Cephalic presentation
Vertex to pelvic inlet at minimum diameter
Describe the process of cervical ripening
Softening of cervix due to reduction in collagen due to action of collegenases, and
Increased glycosaminoglycans, decorin and hyaluronic acid resulting in reduced aggregation of collagen fibres.
How is cervical ripening triggered?
By prostaglandins PGE2 and PGF2alpha
Also oestrogen and relaxin
How are contractions of the myometrium triggered?
Spontaneously triggered action potentials from pacemakers at top of fundus
How are contractions of the myometrium controlled?
Prostaglandins and oxytocin and oestrogen via the Ferguson reflex
Describe the Ferguson reflex
Oestrogen induces oxytocin receptors on the uterus.
Oxytocin stimulates uterus to contract and stimulates placenta to make prostaglandins. These prostaglandins stimulate further contractions of the uterus which have a positive feedback effect, stimulating further oxytocin and prostaglandin production / release.
When do contractions occur?
Throughout pregnancy, increasing in amplitude over time
What are Braxton-Hicks and what is their function?
Contractions of myometrium starting in middle gestation, often referred to as “practice contractions”.
They pull cells of myometrium closer together to produce a synctium.
How can you tell if a women has entered the late stages of labour?
Contractions occur every 10 minutes, each lasting 1 minute
How does the cervix change during the onset of labour?
It undergoes “effacement” where it thins and flattens, it also begins to dilate
How can you tell that the 1st stage of labour has been completed?
Cervix becomes fully dilated - 10 cm or 4 fingers wide
What is brachystasis?
The contraction and retraction of myometrium that occurs during labour that causes the myometrial fibres to shorten and drives presenting part of the foetus towards the cervix
What is thought to trigger the initiation of labour?
Increase in prostaglandins
How does the positioning of the baby’s head change as it is delivered in labour?
It flexes and rotates internally, then after it is delivered it rotates and extends
How long does the 2nd stage of labour last?
Up to an hour, but can be very fast in multparous women
How is the risk of post-partum haemorrhage reduced in the 3rd stage of labour, physiologically and clinically?
Contractions become much stronger and compress blood vessels. Spiral arteries clamped shut by “living ligatures” of myometerial cells.
Clinically this is enhanced by administration of oxytocic drug and manual fundal massage.
Explain how the circulatory system of the neonate changes after birth
Clamping of umbilical cord results in closure of ductus venosus.
As neonate takes first breath, pulmonary vascular resistance is decreased and blood flows to the lungs, causing a net drop in pressure on the R side of the heart, closing the foramen ovale which causes ductus arteriosus to close.
What is “operative delivery” and when is it indicated?
When delivery is assisted by forceps or vacuum extraction
Indicated if foetal distress, maternal exhaustion or inadequate maternal explusive efforts due to neuromuscular disease etc
How can labour be induced?
Membrane sweep - though not technically an induction Vaginal PGE2 (prostaglandin)
What is a disadvantage of inducing labour?
Labour likely to be more painful
How can the physiological state of the foetus be assessed during labour?
Monitoring of foetal heart rate:
Either by auscultation > 1 minute after a contraction, while maternal pulse is palpated to differentiate
or by foetal scalp electrode if continuous monitoring needed
Describe the structure of the breasts
Lobulated masses of tissue - the mammary glands, embedded in fibrous and adipose tissue, suspended by Cooper’s ligaments
How do oestrogen and progesterone affect breast tissue?
Oestrogen stimulates sprouting and hypertrophy of lactiferous ducts and progesterone stimulates hypertrophy of ducts also.
Name the physiological stages of lactation
Mammogensis
Lactogenesis
Galactokinesis
Galactopoesis
How does the breast tissue change in preparation for milk production?
Hypertrophy of ductular-lobular-alveolar system
Prominent lobules form
Alveolar cells differentiate from squamous to cuboidal
How is mammogenesis controlled?
By oestrogen, progesterone, EGF and TGFalpha
How is breast milk produced?
Within alveolar cells, various cell organelles produce the components of breast milk:
Smooth ER produces fat
Golgi body secretes protein
Sugars are synthesied and secreted
Why do neutrophils and macrophages enter the alveolar space during lactation?
To protect against from bacterial infections eg E.coli which may ascend into the lobules of the breast via the lactiferous ducts
How does colostrum compare to mature breast milk?
More protein, fat soluble vitamins, and immunoglobulins especially IgA
Contains maternal neutrophils and macrophages
Less water-soluble vitamins, fat and sugar
What is the main source of energy in breast milk?
Lactose
How is milk secretion stimulated, and how is this controlled?
By the fall in progesterone and oestrogen promoted by prolactin which inhibits HPG axis. Prolactin secretion is promoted during suckling to stimulate secretion of milk for the next feed. Prolactin is controlled by the inhibitory action of dopamine.
What is the let-down reflex?
Mechanism controlling ejection of breast milk where receptors in nipples are stimulated by the baby’s mouth, stimulating oxytocin release form the posterior pituitary. This causes myoepithelial cells around the lactiferous ducts to contract which then squeezes milk out of the breast.
Why does milk production cease if suckling does not occur?
Prolactin secretion which stimulates milk secretion is promoted by suckling, also if suckling doesn’t occur the breast fills with milk causing turgor induced damage.
What can cause lactation to cease (5 points)?
Insufficient suckling
Pain from increased turgor due to non-suckling infant or mastoiditis
Menstruation
Supression of prolactin - ergot, diuretics, retained placenta etc
Age - due to gradual shrinking of mammary glands
How is the maintenance of lactation achieved?
By the neuroendocrine reflex of suckling or anticipation of feed stimulating oxytocin release
What type of secretion do breast alveoli (acini) have?
Apocrine
ToB Describe the 3 types of cellular secretion
Apocrine - part of cell pinches off
Holocrine - cell dies
Merocrine - products released in vesicles
Describe the changes in breast tissue that occur during the menstrual cycle
In follicular phase: lobules are quiescent
After ovulation: proliferation of cells and stromal oedema
At menstruation: decreased size of lobules
How does the breast tissue change in pregnancy?
Increased size and number of lobules
Decreased volume of stroma
Acini distend and increase in number
Why are mammograms easier to interpret in older women?
During aging interlobular stroma of breasts replaced by adipose tissue
How does the breast tissue change a menarche?
Increased number of lobules
Increased volume of interlobular stroma
What type of breast pain is concerning? What may it be due to?
Focal and non-cyclical
Ruptured cyst, injury, inflammation, or less commonly breast cancer
Give a differential diagnosis for a palpable breast mass
Cyst
Fibroadenoma
Invasive carcinoma
What features of a breast mass would be concerning?
Hard, craggy, fixed
What questions would be important to ask a patient with spontaneous nipple discharge?
Nature of discharge - milky, bloody, serous?
Bilateral or unilateral?
Medications, history or family history of breast cancer, general health
List some causes of nipple discharge and describe how they would present
Papilloma - bloody discharge
Pituitary adenoma - milky, often bilateral
Medication side effect - milky, often bilateral
What do densities and calcifications on a mammogram suggest?
Densities - invasive carcinomas, fibroadenomas, cysts
Calcifications - ductal carcinoma in-situ, benign changes
Why can breast pathology sometimes be seen in the axilla or groin (for example)?
Accessory breast tissue can be found anywhere along milk line
What is polythelia?
Accessory nipple
Describe the aetiology, presentation and treatment of acute mastitis
Bacterial, often Staphlococcus aureus, infection from cracked nipple during breast feeding
Erythematous painful breast, pyrexia
Antibiotics and express milk (discard milk)
If there is a history of trauma to the breast, what cause of a mass would you consider?
Fat necrosis
What benign breast changes can mimic carcinoma clinically and mammographically?
Fat necrosis
Fibrocystic change
Finroadenoma
What is a mobile breast mass, particularly in a young woman, likely to be?
Fibroadenoma
Describe the histology of a Phyllodes tumour
Nodules of proliferating stroma covered by epithelium
Stroma more cellular and atypical than in fbroadenoma
Can a Phyllodes tumour be malignant?
Yes but only
How common is fibrocystic change?
Very!
Most common breast lesion
Almost invariablely present in older women
Describe the histology and macroscopic appearance of a fibroadenoma
Mixture of stromal and epithelial elements, smooth outline
Well circumscribed, rubbery, greyish white
Describe 5 causes of gynecomastia
Puberty - oestrogen peaks earlier than testosterone
Klinefelter’s syndrome - XXY
Liver cirrhosis - oestrogen excess as not metabolised
Testicular tumor - gonadotropin excess
Drugs such as spironolactone, digitalis, alcohol, marijuana, anabolic steroids, heroin
Which histological classification of breast cancer is the most common?
Adenocarcinoma
In what area of the breast do most cancers develop?
Upper outer quadrant
What are the risk factors for breast cancer?
Gender Obesity and high fat diet Uninterrupted menses Breast feeding Early menarche and/or late menopause HRT BRCA mutation Radiation eg for Hodgkin's lymphoma
If a woman carries the BRCA1 or BRCA2 genes, what is her lifetime risk of breast cancer?
60-85%
Describe the histology of ductal carcinoma in situ (DCIS)
Central necrosis (comedo) with calcification
How is ductal carcinoma in situ (DCIS) likely to present?
Calcifications on mammography
Describe the presentation of Paget’s disease of the breast
Red, crusting nipple, unilateral
What is the most common type of invasive carcinoma of the breast?
Invasive Ductal Carcinoma, No Special Type
Describe the histology of invasive lobular carcinoma
Infiltrating cells in single file, cells often lack cohesion
Describe the signs of invasive carcinoma
Peau d’orange
Newly inverted or retracted nipple
Why is it much better to detect invasive carcinoma by mammography than palpation?
By the time masses become palpable >50% of patients will have lymph node metastatis
Where does breast cancer tend to metastasise to?
(thinking, drinking, boning, breathing)
Brain, liver, bone, lungs
What factors affect the prognosis in breast cancer?
Type and subtype
Tumour grade and stage
Gene expression profile
Describe how you would investigate a case of suspected breast cancer
Triple approach:
Clinical - history, family history, examination
Radiographic imaging - mammogram and ultra-sound
Pathology - fine needle aspiration cytology, core biopsy
What therapeutic approaches are available for breast cancer?
Breast surgery - mastectomy or breast conserving
Axillary surgery- sentienal node sampling, then may need axillary dissection
Radiotherapy
Chemotherapy
Hormonal treatments -depending on receptor status - oestrogen on Her2
Why has the survival rate for breast cancer improved in recent decades?
Early detection Neoadjuvant chemo Use of newer therapies eg herceptin Gene expression profiles Prevention in familial cases
Why is having a partner with carcinoma of the penis a risk factor for cervical carcinoma?
Associated with HPV
How does HPV cause cervical intraepithelial neoplasm (CIN) or cervical carcinoma?
Infects immature metaplastic squamous cells in transformation zone of cervix ->
Produce viral proteins E6 & E7 ->
These interfere with tumour suppressor protein activity ->
Cells become unable to repair DNA and cellproliferation results
How may cervical carcinoma present?
Screening abnormality
Post-coital, intermenstual or post-menopausal bleeding
Which lymph nodes may be affected in cervical carcinoma?
Para-cervical
Pelvic
Para-aortic
Describe the grading and corresponding treatment of cervical intraepithelial neoplasm
CIN I - follow up or cryrotherapy
CIN II - superficial excision - cone or LLETZ
CIN III - “
How likely is it that cervical intraepithelial neoplasm will lead to invasive carcinoma?
10% progress to invasive carcinoma in 2-10 years
What histological classification of cervical cancer is most common?
80% squamous cell carcinoma
What is an exophytic cervical carcinoma & what other type of cervical carcinoma is there?
One that protrudes
Other type is infiltrative
Why is cervical carcinoma suitable for screening?
Cervix visible and accessable for sampling
Slow progression
Papanicolaou (pap) test can detect precursor lesions and low stage cancers
How can the presence of carcinoma in a cervical scrape sample be identified?
Microscopic examination with papanicolaou stain
Why is it still important for HPV vaccinated women to be screened for cervical cancer?
Vaccine doesn’t protect against all high risk strains (only 16 and 18)
MGD Describe a molecular method of testing for HPV
Southern blotting:
Digestion with restriction enzymes
Separation with DNA gel electrophoresis
Transfer onto common nylon or nitrocellulose filter with capillary action of paper towels or electrophorectic transfer
Hybridise filter with labelled DNA probes
Detection of hybridisationusing Xray film
What are the risk factors for endometrial hyperplasia?
Prolonged oestrogen stimulation: anovulation, excess adipose tissue, HRT
Does endometrial hyperplasia lead to endometrial carcinoma?
Yes, it is a frequent precursor to endometrial carcinoma
Describe the histological features of endometrial hyperplasia
Increased gland-stroma ratio
Glands can be atypical in appearence
Describe the epidemiology of endometrial adenocarcinoma
Usually 55-75 year old women, unusual before 40
Why does endometrial carcinoma generally have a good prognosis?
Generally detected early as symptoms are irregular or post menopausal bleeding which women will tend to present to dr early with
Describe the histological appearance of endometrioid endometrial adenocarcinoma
Mimics proliferative glands
Describe the histological appearance of serous endometrial adenocarcinoma
Poorly differentiated
Exfoliating cells
What are the risk factors for endometrioid endometrial adenocarcinoma?
Exogenous oestrogen (as typically arises from endometrial hyperplasia)
Why does serous endometrial adenocarcinoma have a worse prognosis that endometrioid?
It is aggressive
Cells tend to exfoliate, travel through Fallopian tubes and implant on peritoneal surfaces
What symptoms can leiomyomas (fibroids) cause?
Heavy / painful peroids
Urinary frequency
Infertility
Describe the histological and macroscopic appearance of leiomyomas
Bundles of smooth muscle (identical to normal myometrium)
Well-circumscribed, round, firm and whiteish
Are uterine fibroids (leiomyomas) likely to become malignant?
No - malignant transformation probably doesn’t occur
Describe the behaviour of leiosarcomas
Highly maligant
Metastatise early to lungs
How likely is it that an ovarian tumour is malignant?
Unlikely, 80% are benign
What is the serum CA125 test used for?
For diagnosis and monitoring of maligant ovarian tumours
What symptoms may ovarian tumours present with?
Abdo pain and/or distension
Urinary and GI symptoms
Ascites if malignant
Can cause hormonal problems such as mentsrual distirbances
Why is the prognosis for ovarian cancer poor?
Tends to present late as symptoms are very vague, by this point often have spread to regional lymph nodes and elsewhere
Where may ovarian tumours have metastasised from?
Most commonly Mullerian tumours (uterus etc)
GI system
Breast
What are the 4 main categories of ovarian tumours?
(MEGS) Metastatic Epithelial Germ cell Sex-cord stromal tumours
What are the risk factors for epithelial ovarian tumours?
Nulliparity or low parity (maligancy thought to arise after breaching and repair of ovarian epithelium on ovulation)
Smoking
Endometriosis
BRCA1&2 and other heritable mutations
Describe the 2 most common types of monodermal ovarian teratomas
Struma ovarii - benign thyroid tissue which can be functional and cause hyperthyroidism
Carcinoid - can produce 5HT leading to carcinoid syndrome (diarrhoea, abdo pain, increase HR, anorexia, skin flushing, breathlessness and wheeziness)
Describe the 3 types of epithelial ovarian tumours
Serous - friable and delicate, often spread to peritoneum
Mucinous - often large cystic masses, usually benign or borderline
Endometroid - contain tubular glands resembling those of the endometrium
Why may the presence of endometrioid epithelial ovarian tumours be concerning?
Significant % associated with endometrial adenocarcioma (probably arising separately)
What abnormal blood test finding would you expect in non-gestational choriocarcinoma?
Raised hCG
What abnormal blood test finding would you expect in a patient with yolk sac tumours?
Raised alpha fetoprotein
What type of ovarian teratoma is malignant?
Immature teratoma (fortunately this is rare)
What is the most common type of ovarian teratoma?
Mature (benign) teratoma
What signs and symptoms may Sertoli-Leydig cell tumours present with?
Breast atrophy Amenorrhoea Hair loss in male pattern Hirsuitism Clitoral hypertrophy Voice changes Sterility
Which age group has the highest incidence of Sertoli-Leydig cell tumours?
Teenage girls and women in their 20s
What do granulosa cell tumours cause?
Precious puberty
Endometrial hyperplasia and carcinoma
Breast disease
What would teeth and/or hair in the ovary indicate?
A mature ovarian germ cell teratoma - also called a dermoid cyst
What is the most common type of vulval cancer?
Squamous cell carcinoma
What is the most likely cause of vulval cancer in a women in her 8th decade?
Longstanding inflammatory or hyperplastic conditions of the vulva such as lichen sclerosis
Describe the aetiology of squamous cell carcinoma of the vulva
Around 30% arise from VIN, caused by HPV
Around 70% unrelated to HPV, often occur in longstanding inflammatory or hyperplastic conditions of the vulva such as lichen sclerosis
Where does vulval cancer tend to spread to?
Inguinal, pelvic, iliac and para-aortic lymph nodes
then Lungs and liver
Describe the prognosis for choriocarcinoma (gestational)
Good if diagnosed and treated - rapidly invasive and metastatises widely but responds well to chemo which very high cure rate
What are the symptoms and signs of an invasive mole in the trophoblast?
Vaginal bleeding
Uterine enlargement
What is a hyatidiform mole?
A cystic swelling of chorionic villi and trophoblastic proliferation
Why might an invasive mole require hysterectomy?
Can cause uterine rupture
What are the potential causes of elevated hCG?
Pregnancy
Choriocarcinoma - gestational or non-gestational
Invasive mole of uterus
