Reproductive System Flashcards
What is the urogenital ridge?
Region of intermediate mesoderm giving rise to the embryonic kidney and the gonad.
Where do the primordium germ cells originate?
Yolk sac.
What genes are expressed by the Y chromosome?
SRY genes.
What structural features of the gonad develop with an XY genotype?
Medullary cords develop but no cortical cords.
Thick tunica albuginea (outer capsule).
What structural features of the gonad develop with an XX genotype?
Medullary cords degenerate and cortical cords develop.
No outer capsule as the oocytes must be able to ovulate through the gonadal wall.
What is the urogenital sinus?
Region of the hindgut created by the urorectal septum that is continuous with the umbilicus.
What is the adult remnant of the urachus?
Median umbilical ligament.
Outline the process of the development of the internal male reproductive tract:
Mesonephric ducts sprout ureteric buds at the urogenital sinus and make independent openings.
Mesonephric ducts are maintained by dihydrotestosterone.
Paramesonephric ducts degenerate in males under the influence of Mullerian Inhibiting Substance (MIS).
Outline the process of the development of the internal female reproductive tract:
Mesonephric ducts regress due to lack of androgens.
Mullerian/paramesonephric ducts continue to develop and fuse to form the uterus, cervix and fornices.
The urogenital sinus expands and elongates to form the vagina.
What features of the external genitalia are found during the indifferent stage?
Genital tubercle
Genital folds
Genital swellings
How does the external genitalia of the male develop?
The genital tubercle elongates and the folds fuse to form the spongy urethra under the influence of androgens.
How does the external genitalia of the female develop?
There is no fusion of the genital folds and the urethra opens into the vestibule; the genital tubercle becomes the clitoris.
What is the processus vaginalis?
An invagination of the peritoneum that creates a path for the descent of both testis through the inguinal canal.
What is the gubernaculum?
Fibrous cord connecting the ovary to the labioscrotal folds via the uterus and the testis to scrotum.
How is genetic variation produced?
Crossing over
Random segregation
Independent assortment
What forms the blood-testis barrier?
Tight junctions between Sertoli cells within the seminiferous tubules separating the basal and adluminal compartments.
Outline the basic process of spermatogenesis:
Spermatogonia divide by mitosis to form the ad and ap spermatogonia.
Ap spermatogonia become primary spermatocytes.
Primary spermatocytes divide by meiosis to produce secondary spermatocytes and spermatids.
Haploid spermatids differentiate into spermatozoa by spermiogenesis.
What is the spermatogenic cycle?
Not all stages of spermatogenesis are visible in cross-section at once; the spermatogenic cycle is the time taken for the reappearance of the same stage of spermatogenesis within a given segment.
What is the spermatogenic wave?
The distance between the same stages of the cycle.
What is spermiation?
The release of sperm into the seminiferous tubules where they remodel to form spermatozoa.
What is the composition of semen?
Vas deferens (5%)- sperm Seminal vesicles (70%)- amino acids, citrate, fructose and prostaglandins Prostate (25%)- proteolytic enzymes and zinc
What is the purpose of Cowper’s glands?
Produce mucoproteins that help to lubricate the urethra and neuralise acidic urine in the distal urethra.
What is sperm capacitation?
The final maturation step that occurs in the female gential tract that includes removal of glycoproteins and cholesterol from the sperm cell membrane and activation of sperm signalling pathways.
Outline the basic process of oogenesis:
Germ cells differentiate into oogonia.
Oogonia proliferate by mitosis.
Primary oocytes enter meiosis and arrest in prophase.
Many oocytes/oogonia undergo atresia and the surviving primary oocytes form primordial follicles.
Cells remain arrested meiosis I until puberty.
What are the features of pre-antral follicle?
Production of stratified cuboidal epithelium of granulosa cells that secrete glycoproteins to form the zona pellucida.
What are the features of the antral follicle?
Theca externa and interna develop.
Granulosa cells surrounding the oocyte are known as the cumulus oophorus.
Antrum is formed by the coalescence of fluid filled spaces between granulosa cells.
What are the features of the pre-ovulatory follicle?
Meiosis I completes producing the oocyte and first polar body.
Cell enters meiosis II and arrests in metaphase.
How is the oocyte released from the ovary (ovulation)?
LH surge stimulates collagenase activity.
Prostaglandins respond to raised LH and cause local muscular contractions of the ovarian wall allowing the oocyte to be extruded.
What is the corpus luteum?
The remaining follicle after extrusion of the oocyte that secretes oestrogens and progesterone for 14 days after ovulation (unless fertilisation occurs).
What is the corpus albicans?
Fibrotic mass of scar tissue formed from the degeneration of the corpus luteum.
Outline the basis of the hypothalamic-pituitary-gonadal (HPG) axis for both males and females:
Hypothalamus produces GnRH that acts on the pituitary gland to release LH and FSH.
LH and FSH act on the reproductive system and exert negative feedback onto the hypothalamus.
Specifically where to LH and FSH act in the male and what effects do they produce?
LH acts on Leydig cells to produce Testosterone.
FSH acts on Sertoli cells to produce Inhibin and ABG (binds testosterone to keep it in the seminiferous tubules)
What is the action of inhibin?
Specifically inhibits the release of FSH by feeding back negatively on the pituitary gland.
What are the products of ovarian stimulation by LH and FSH in females and where are they produced?
Oestrogen from granulosa cells (LH)
Progesterone from the corpus luteum
Inhibin from granulosa cells (FSH)
Explain the differences in oestrogen feedback over the course of the menstrual cycle:
Initially oestrogen feeds back negatively on the hypothalamus and pituitary.
Once oestrogen levels are high this changes to positive feedback resulting in the LH surge.
After ovulation progesterone production by the corpus luteum in combination with the high oestrogen levels results in negative feedback again to reset the axis.
What is meant by the waiting phase of the menstrual cycle?
Maintenance of the endometrium until a signal is recieved to indicate that fertilisation has/has not occurred.
If fertilisation occurs what signals alert the female reproductive tract?
The syncytiotrophoblast produces hCG which exerts a luteinising effect to maintain the corpus luteum.
What actions does oestrogen produce in the female reproductive tract?
Contributes to Fallopian tube function
Produces thickening of the endometrium
Contributes to growth and motility of the myometrium
Thin, alkaline cervical mucus
What actions does progesterone produce in the female reproductive tract?
Thickening of the endometrium and myometrium
Thick, acidic cervical mucus
Increased body temperature
How is variation in the length of menstrual cycles produced?
Variation in the follicular phase as the luteal phase is strictly controlled.
What is thelarche?
Development of breasts
What is puberache?
Development of axillary and pubic hair
What is meant by puberty?
The completion of sexual maturation and growth in humans, onset typically between the ages of 8-13 years.
What factors contribute to the onset of menarche?
First menstrual period usually occurs between 8-13 years and there is a critical weight of 47kg.
What are the first phenotypic changes observed that mark the beginning of puberty?
Breast development in girls
Testicular enlargement in boys
What effects do androgens have in both boys and girls?
Mineral retention to support bone and muscle growth
Growth of pubic hair
Sebaceous gland secretion
How do we measure what stage of puberty a child is at?
Tanner Standard staging
How do we define precocious puberty?
Onset occurring younger than 2 standard deviations before the average age i.e.
How do we define delayed puberty?
Initial physical changes not present before age 13 in girls or by age 14 in boys.
Alternatively this can also be considered with primary amenorrhoea at 16 years or if the interval between first signs and completion of genital growth in boys/menarche in girls is greater than 5 years.
What physiological features occur in pre-menopausal women?
The follicular phase shortens
Ovulation becomes earlier/absent due to decreased oestrogen production (and resulting increased LH and FSH)
Reduced feedback and reduced fertility
How do we define menopause?
12 clear months with no menstrual period.
What are some of the symptoms of the menopause?
Vascular changes causing ‘hot flushes’
Regression of the endometrium and shrinkage of the myometrium
Thinning of the cervix and decreased vaginal tone
Changes in skin
Involution of breast tissue
Decreased bladder and pelvic tone
What is dysfunctional uterine bleeding?
Uterine bleeding with no recognisable pelvic pathology, pregnancy or bleeding disorders.
What are fibroids?
Leiomyomas- benign tumours of the myometrium that may be subserous, intramural or submucous.
What is meant by menorrhagia?
Heavy vaginal/menstrual bleeding that may be described as “flooding”/passing clots etc.
What is the difference between primary and secondary amenorrhoea?
Primary amenorrhoea means that the woman has never had a menstrual period.
Secondary amenorrhoea indicates that the woman has previously had a menstrual period but has not had one for more than three cycles.
What are some of the advantages of HRT?
Relieves symptoms of menopause
Improves wellbeing
Limits osteoporosis
What are some disadvantages of HRT?
Increased risk of breast/ovarian/uterine cancer
Increased risk of stroke
What is the tunica vasculosa?
Vascular layer below the outer tunica albuginea and the seminiferous tubules.
What is the structural arrangement of the seminiferous tubules?
Each lobule of seminiferous tubules is surrounded by perilobular connective tissue.
What epithelium is found in the efferent ductules and how does this relate to its function?
Ciliated simple columnar/cuboidal cells that act to absorb excess fluid from the seminiferous tubules.
What epithelium is found in the epidydimis?
Pseudostratified columnar epithelium with stereocilia
Where is testosterone produced?
Islands of specialised Leydig cells found between the seminiferous tubules.
What is the role of the cytoplasmic bridges observed between developing gametes?
Ensures that the gametes mature simultaneously.
What are the seminal vesicles?
Outgrowths of the ductus deferens forming coiled tubulosaccular glands with pseudostratified columnar epithelium.
What does the prostate gland consist of?
Tubuloalveolar glands arranged in groups of three around the urethra.
How is the structure of the prostate gland organised?
The fibromuscular capsule has septae that divide the gland into lobules.
What are corpura amylacea?
Lamellated bodies found in older men that contain proteins, amino acids, cholesterol and calcium phosphate.
What is the scrotum?
A cutaneous sac developed from the labioscrotal folds under the influence of DHT.
How can you differentiate between a hydrocoele and haematocoele?
Transillumination (haematocoele produces red/pink light)
What is the arterial supply to the testis?
Direct testicular branches of the abdominal aorta.
What is the venous drainage of the testis?
Right testicular vein to the IVC
Left testicular vein to the left renal vein
What is the course of the spermatic cord?
From the deep inguinal ring to the posterior border of the testis via the inguinal canal and superficial inguinal ring.
What are the layers of skin/fascia surrounding the testis and from where do each of them originate?
Internal spermatic fascia (transversalis fascia) Cremasteric muscle (Internal oblique) External spermatic fascia (aponeurosis of external oblique)
What is the difference between indirect and direct hernias?
Indirect hernias pass through the deep inguinal ring and then along the inguinal canal and can pass down into the scrotum to affect the testis.
Direct hernias protrude directly through the posterior wall of the inguinal canal, medially to the epigastric vessels.
What is the function of the pampiniform plexus?
Acts as a heat exchanger to reduce the temperature of the scrotum and testis in order to find the optimum temperature for spermatogenesis.
What structures are found in the spermatic cord?
Vas deferens
Testicular artery
Genitofemoral nerve
Pampiniform plexus
What is the innervation to the scrotum?
Lumbar and sacral plexuses
Where is the lymphatic drainage of the testis to?
Para-aortic nodes
Where is the lymphatic drainage of the scrotum to?
Superficial inguinal nodes
Which arteries supply the penis?
Internal pudendal arteries
What is the role of the superficial perineal muscles in maintenance of erections?
Bulbospongiosus- helps expel last drops of urine and maintain erections
Ischiocavernosus- compresses veins to help maintain erections
What makes up the linea terminalis?
Arcuate line, pectineal line and pubic crest
What is the sacral promontory?
Prominence where the sacrum projects into the pelvic cavity
What are the features of the ideal gynaecoid pelvis?
Well curved sacrum Well rounded greater sciatic noth Straight side walls Small ischial spines Sub-pubic arch >90 degrees
What is the obstetric conjugate?
Measured from sacral promontory to the midpoint of the pubic symphysis
What is the diagonal conjugate?
Measured from the sacral promontory to the inferior border of the pubic symphysis
What makes up the pelvic outlet?
Infrapubic angle and the distance between ischial tuberosities
What ligaments support the pelvis?
Sacrospinous ligament
Sacrotuberous ligament
What is the anatomical structure of the ovary?
Outer cortex of germ cells with an inner medulla of nerves, blood vessels, stroma and connective tissue with a hilum found at one pole.
What are the features of the Graafian follicle?
Cumulus oophorus breacks down and the oocyte and corona radiata (layer of granulosa cells) float free in the follicular fluid
What type of epithelium is found in the Fallopian tubes?
Inner mucosa with columnar ciliated epithleium and peg cells (secretory cells that produce a nutrient-rich fluid for the gametes and that promotes capacitation)
What is the histological structure of the endometrium?
Columnar epithelium and lamina propria with glands and stroma
How many layers of smooth muscle make up the myometrium?
4
What is the blood supply to the uterus?
Paired uterine arteries that branch into the arcuate arteries of the myometrium
Straight arteries ramify the stratum basalis
Coiled arteries supply the stratum functionalis
What is shed during menses?
The functional layer of the endometrium (stratum functionalis)
What effects does progesterone have on the endometrium?
Growth and coiling of endometrial glands
Stromal oedema and production of decidual cells
What is the epithelium of the cervix?
Simple columnar epithelium transitions to non-keratinized stratified squamous epithelium
What epithelium is found in the sinuses of the breast?
Cuboidal to columnar epithelium in the ducts that changes to stratified squamous epithelium at the level of the lactiferous sinuses.
What is the course of the round ligament?
The ovarian ligament reflects off of the fundus of the uterus to become the round ligament of the uterus that travels through the inguinal canal to the labia majora.
What is found within the suspensory ligament of the ovary?
Contains an arterial supply, venous and lymphatic drainage of the ovary.
What are the three components of the broad ligament?
Mesovarium
Mesosalpinx
Mesometrium
How is the broad ligament formed?
It is a peritoneal reflection/mesentery.
What is the clinical significance of the posterior fornix of the cervix?
Provides access to the Pouch of Douglas for culdocentesis.
What is the arterial supply to the ovary?
Direct branches of the abdominal aorta
What is the venous supply to the ovary?
IVC on the right and the left renal vein
How would you describe the orientation of the uterus within the pelvic cavity?
Anteverted with respect to the vagina
Anteflexed with respect to the cervix
How is the pelvic viscera supported?
Transverse cervical ligament
Uterosacral ligament
Round ligament
What is meant by redundancy of supply?
There are numerous anastomoses of the arterial supply to the female reproductive tract so the loss of one artery will not result in ischaemia of any one part of the tract.
Where is the lymphatic drainage of the fundus to?
Para-aortic and inguinal nodes
Where is the lymphatic drainage of the body of the uterus to?
External iliac nodes
Where is the lymphatic drainage of the cervix to?
Iliac and sacral nodes
What is found within the vestibule?
Orifices of the urethra, vagina and the greater and lesser vestibular glands
What is the innervation to the vagina?
Inferior 1/5- somatic innervation via the pudendal nerve
Superior 4/5- uterovaginal plexus
What is the course of the pudendal nerve?
Exits the pelvis via the greater sciatic foramen and then enters the perineum through the lesser sciatic foramen.
What is the pelvic floor?
Muscular and fibrous tissue diaphragm that fills the lower part of the pelvic canal, closes the abdominal cavity and supports pelvic organs.
What three muscles make up the levator ani muscle?
Iliococcygeus
Pubococcygeus
Puborectalis
Which muscles are found within the pelvic side wall?
Obturator internus
Piriformis
What makes up the deep layer of the perineum?
Deep transverse perineal muscle
External urethral sphincter
What makes up the superficial layer of the perineum?
Bulbospongiosus
Ischiocavernosus
External anal sphincter
What is the perineal body?
Fibrous insertion found in the perineum that acts as an anchor and site of attachment for perineal muscles and contributes to the integrity of the pelvic floor.
What nerve roots supply the perineum?
S2, 3 and 4
What consequences could occur following damage to the ureters during pelvic surgery?
Renal obstruction
Retroperitoneal urine collection
What role do the pelvic floor muscles play in maintenance of fecal continence?
Puborectalis hooks around the rectum to form the anorectal flexure
What effects of childbirth can result in a weakened pelvic floor?
Stretch of the pudendal nerve resulting in neuropraxia and muscle weakness
Stretch or direct damage to the perineal muscles
Stretch or rupture of ligaments resulting in ineffective muscle action
What are the symptoms of HPV infection?
Cutaneous, mucosal and anogenital warts that are benign and painless.
What are the high-risk oncogenic types of HPV?
16 and 18
How do we treat HPV infection?
Spontaneous resolution
Topical podophyllin
Cryotherapy
Surgery
What type of organism is Chlamydia Trachomatis?
Obligate intracellular bacterium
How do we test for chlamydia?
Endocervical and urethral swabs
First void urine
How do we treat chlamydia?
Doxycycline/azithromycin
What are the symptoms of herpes?
Painful genital ulceration, dysuria, inguinal lymphadenopathy and fever
What do we use to treat herpes simplex virus infection?
Acciclovir
How do we treat gonorrhoea?
IM Ceftriaxone
What organism is reponsible for gonorrhoeal infection?
Neisseria gonorrhoea
What type of organism is responsible for syphilis?
Spirochaete (Treponema pallidum)
Outline the symptom progression of syphilis?
Begins with an indurated painless ulcer
6-8 weeks later flu-like symptoms
Latent period
Neurosyphilis- locally destructive lesions
How do we treat syphilis?
Penicillin
What is chancroid?
Painful genital ulcers caused by Haemophilius ducreyi
What is granuloma inguinale?
Genital nodules and ulcers caused by Kleibsella granulomatis
What are the symptoms of trichomonas vaginalis?
Thin, frothy and offensive discharge
Irritation
Dysuria
Vaginal inflammation
How do we treat trichomonas vaginalis?
Metronidazole
What organisms can cause BV?
Gardnella vaginalis, anaerobes and mycoplasmas
What test do we use to diagnose BV?
Potassium hydroxide “whiff” test
What are clue cells?
Epithelial cells studded with gram variable coccobacilli, often seen in BV
How do we treat BV?
Metronidazole
What is PID?
Pelvic inflammatory disease results from an ascending infection from the endocervix resulting in inflammation of the pelvic viscera.
What are the complications of PID?
Ectopic pregnancy
Chronic pelvic pain
Infertility
What organisms are often responsible for PID?
Chlamydia trachomatis
Neisseria gonorrhoeae
Gardnella vaginalis
What signs would you find on examination in a women with PID?
Fever Abdominal tenderness Adnexal and cervical motion tenderness Purulent cervical discharge Cervicitis
How would you manage a patient with PID?
IV antibiotics - Ceftriaxone 500mg, Doxycycline 100mg, Metronidazole 400mg
What physiological changes occur in the male during the excitement phase of the sexual arousal cycle?
Stimulation of limbic system Activation of parasympathetic neurones Production of NO using eNOS Arteriolar vasodilation in corpora cavernosa Elevation and enlargement of the testis
What is the result of the sacrospinous reflex in men?
Contraction of the ischiocavernosus increasing pressure within the copora cavernosa of the penis in order to maintain erection
How is semen expelled?
Stimulation of the sympathetic neurones results in contraction of the muscles of reproduction
Urethral filling stimulates the pudendal nerve resulting in muscular contraction to expel the semen
What physiological changes take place in the female prior to sexual intercourse?
Vasocongestion increases vaginal lubrication
Increase in HR and BP
The vagina lengthens and increases in tone
Breasts become larger and the areola increase in size
Bartholin’s glands lubricate the vestibule
Clitoris engorges
What is the G spot?
Area of erotic sensitivity located on the anterior wall of the vagina
What are the effects of ageing in females on the reproductive tract?
Menopause Decreased sexual desire Decreased vasocongestion resulting in dryness Loss of elasticity Rapid resolution
What specifications is semen supposed to meet when undergoing fertility testing?
Between 20-200 x 10^6 sperm per ml
Liquefaction within one hour
How long can sperm survive in the female reproductive tract?
5-7 days
Outline the process of the acrosome reaction:
Head proteins bind to ZP3
There is increased intracellular calcium concentration and enzymatic digestion of the zona pellucida
What are the two methods of preventing polyspermy?
Fast-block: open sodium channels to initiate wave of depolarisation
Slow-block: calcium release from the ER induces exocytosis of cortical granules
What is meant by syngamy?
Fusion of the male and female pronuclei to form a diploid zygote.
What cellular changes occur during cleavage?
Increased nuclear:cytoplasmic ratio
No G1 or G2 stages (skipped)
Process is asynchronous
Give examples of some natural methods of contraception:
Abstinence
Coitus interruptus
Rhythm method
Give examples of some barrier methods of contraception:
Condoms
Diaphragm
Cap
Spermicides
What is the IUD?
Intra-uterine device that may be inert or copper and may be impregnated with progesterone. (Copper induces a foreign body reaction that interferes with endometrial enzymes and sperm transport)
Give examples of some hormonal methods of contraception:
Combined OCP
Progesterone-only pill
Progesterone implant
Progesterone injection
What are the effects of oestrogenic contraception?
Inhibits FSH and prevents the LH surge thus inhibits ovulation
What are the effects of progesterone contraception?
Thick hostile mucus
Reduced receptivity of the endometrium
What is used for post-coital contraception?
High-dose oestrogen and progesterone (or may be progesterone only) that acts to block implantation. Can only be used up to 72 hours after sex.
How do we define infertility?
Failure to conceive within one year.
How can we induce ovulation?
Anti-oestrogens
Exogenous FSH
GnRH agonists
What is the role of the villi in the placenta?
Acts as an anchor for the placenta to the outer cytotrophoblast shell
Establishes maternal blood flow within the placenta
What is decidualisation?
Production of decidual cells within the endometrium that act as a balancing force against the invasive trophoblast i.e. prevents conditions such as placenta acreta.
What is the placental structure within the first trimester?
There is a complete cytotrophoblast layer beneath the syncytiotrophoblast
What is the structure of the placenta at term?
Placental surface area is increased
Placental barrier is now thin and the cytotrophoblast layer is gone
What are the functions of the placenta?
Synthesis of glycogen, cholesterol and fatty acids Steroid synthesis (Oestrogen and progesterone) Protein synthesis (hCG, HPL, thyrotropin, corticotropin).
What substances pass across the placenta by simple diffusion?
Water
Electrolytes
Urea
Blood gases
What substances pass across the placenta by fascilitated diffusion?
Glucose
What substances pass across the placenta by active transport?
Iron
Vitamins
IgG immunoglobulins (passive immunity)
Give examples of some infectious agents that can pass across the placenta:
Varicella Zoster Rubella Chlamydia Treponema pallidum HIV
What physiological changes occur to the cardiovascular system during pregnancy?
Increased blood volume so increased SV and CO
Pre-load is increased and after-load is decreased
Progesterone-induced vasodilation reduces TPR
Therefore systolic BP should NOT increase
What physiological changes occur to the urinary system during pregnancy?
Increased GFR due to increased plasma volume
Progesterone induced vasodilation of afferent and efferent arterioles further increases GFR
Functional reserve decreases
Proteinuria
Creatinine and urine concentration should decrease
What physiological changes occur to the respiratory system during pregnancy?
Displacement of the diaphragm
Reduced functional residual capacity
Increased tidal volume
Progesterone-driven physiological hyperventilation
Why are pregnant women at greater risk of metabolic acidosis?
Progesterone-driven physiological hyperventilation can result in respiratory alkalosis that is compensated for with increased renal bicarbonate excretion so the body is less able to cope with metabolic acidosis
What physiological changes occur to carbohydrate metabolism during pregnancy?
Maternal peripheral insulin resistance
Gluconeogenesis and alternative fuels
Fasting hypoglycaemia and hyperglycaemia following meals
What physiological changes to lipid metabolism occur during pregnancy?
Increased lipolysis
Ketone production is increased
What GI tract conditions are common in pregnancy and why?
Constipation results from progesterone-induced smooth muscle relaxation
Increased risk of pancreatitis due to stasis of the biliary tract.
What is meant by physiological anaemia in pregnancy?
Plasma volume increases but red blood cell production does not increase enough to match the increased volume, producing a normocytic anaemia
Why is pregnancy a pro-thrombotic state?
Increased production of clotting factors
Decreased fibrinolysis
Venodilation results in stasis of blood
What is meant by the double Bohr effect?
Transfer of oxygen from the maternal blood to the fetus decreases pH resulting in a Bohr effect that reduces Hb’s affinity for oxygen
Simultaneously the transfer of carbon dioxide from the fetus to the mother increases the pH resulting in a Bohr effect that increases affinity of Hb for oxygen.
What is meant by the double Haldane effect?
As maternal Hb gives up oxygen it is more able to accept carbon dioxide from the fetus resulting in no overall change in local partial pressures of carbon dioxide that could affect the placental concentration gradient.
What is the crista dividends?
The free border of the septum secundum that creates separate streams of oxygenated and deoxygenated blood flow within the heart.
What mechanisms does the fetus use to manage transient decreases in blood flow?
HbF
Increased Hb
Redistribution of blood supply to the heart and brain
Why is bradycardia a worrying sign in a fetus?
It is indicative of prolonged hypoxia which can result in growth restriction and behavioural changes
Which growth factor dominates the first trimester?
IGF-II (nutrient independent)
Which growth factor dominates the second and third trimesters?
IGF-I (nutrient dependent)
What are the features of symmetrical growth restriction?
Restriction is generalised and proportional
What are the features of asymmetrical growth restriction?
Head-sparing
Abdominal growth lags
What is the dominant form of cellular growth from 0-20 weeks of pregnancy?
Hyperplasia
What is the dominant forms of cellular growth from 20-28 weeks?
Hyperplasia and hypertrophy
What is the dominant form of cellular growth from 28 weeks to term?
Hypertrophy
What are the functions of the amniotic fluid?
Protects the fetus
Moistens the skin
Contributes to development of the lungs
How much amniotic fluid is produced at 8 weeks and then at 38 weeks?
10 ml at 8 weeks
1L at 38 weeks
What makes up amniotic fluid?
Water Electrolytes Creatinine, urea, bile pigments Glucose Hormones Fetal cells
What is lanugo?
Fine hair that coats the fetus during development
What is meconium?
Debris that accumulates in the GIT throughout development; usually the first stool passed by the fetus after birth
Why is physiological jaundice reasonably common in the newborn?
The fetal liver is too immature to conjugate bilirubin so this is dealt with by the placenta.
What techniques do we use for antenatal assessment?
Symphysis-fundal height USS Crown-Rump Length Biparietal diameter Abdominal circumference
Outline the development of the respiratory system during the fetal period:
Respiratory diverticulum branches from the primitive gut tube to form the tracheoesophageal septum
Pseudoglandular stage forms the duct system (8-16)
Canalicular stage- budding forms the respiratory bronchioles (16-26)
Terminal sac stage (26-term) and differentiation of type I and type II pneumocytes
How can we help prevent respiratory distress syndrome of the newborn?
Maternal glucocorticoid treatment can stimulate surfactant production in the fetus.
When is “quickening” typically felt?
17 weeks
When do the corticospinal tracts required for coordinated voluntary movement begin development?
The 4th month
What is meant by parturition?
The scientific term used to describe the transition from the pregnant state to the non-pregnant state at the end of gestation
What is meant by labour?
The non-scientific term used to describe parturition when both the cervix and the uterus have been remodelled
What are the three stages of labour?
1) Creation of the birth canal
2) Expulsion of the fetus
3) Expulsion of the placenta and contraction of the uterus
What is the lie of the fetus?
The relationship of the fetus to the long axis of the uterus, usually longitudinal
What is the presentation of the fetus?
Which part of the fetus is adjacent to the pelvic inlet, usually cephalic.
What is meant by ‘vertex’?
The relationship of the fetus along its axis e.g. the orientation of the presenting part
What is the maximum size of the birth canal typically?
11 cm
What is meant by cervical ripening?
The effacement and dilation of the cervix
What changes happen in the cervix to bring about cervical ripening?
Reduction in collagen due to enzymatic degradation
Increased glycosaminoglycans
Increased hyaluronic acid produced from friction of the baby’s head leading to blisters
Decreased aggregation of collagen fibres
How is labour triggered?
Prostaglandins PGE2 and PGF2-alpha
How does the uterus contract?
Spontaneous action potential generation by specialised pacemaker cells at the top of the fundus
What are Braxton-Hicks contractions?
Uterine contractions occur throughout pregnancy, during the middle of pregnancy these contractions are less frequent and are known as Braxton-Hicks contractions, but do not mark the onset of labour
How is contractility of the uterus controlled?
Prostaglandins (increase calcium released per AP)
Oxytocin (lowers the threshold so more APs can be generated)
What are prostaglandins?
Biologically active lipids that act as local hormones; in pregnancy are produced in the myometrium and decidua under the control of the oestrogen:progesterone ratio
What is the ‘Ferguson reflex’?
Oxytocin is produced from the posterior pituitary gland and stimulates uterine contractions and the production of prostaglandins.
The prostaglandins positively feedback on the pituitary gland to increase oxytocin production and on the uterus to increase the strength and frequency of contractions.
This pushes the baby’s head against the cervix producing afferent impulses that further stimulate oxytocin release.
What is meant by brachystasis?
Uterus relaxes less than it contracts resulting in the fibres shortening in the body of the uterus to drive the presenting part to the cervix.
When is the urge to ‘bear down’ and ‘push’ felt?
Second stage of labour
How is the placenta expelled in the third stage of labour?
Uterine contractions increase to shear the placenta
Blood in the intervillous spaces is forced back into veins which become congested
Living ligatures retract to seal the vessels
How can we enhance uterine contractions to prevent postpartum haemorrhage?
Administration of oxytocin
Manual fundal massage
What is the basic structure of the breast?
Mammary glands are embedded- lobulated masses of tissue interspersed with fibrous and adipose tissue inbetween
Lactiferous ducts form lactiferous sinuses
How are the breasts held up on the chest?
Suspensory ligaments of Cooper
What changes occur in the breasts at puberty?
Ducts develop and branch
Acini develop
What is mammogenesis?
Preparation of the breasts for lactation
What occurs within the breast during mammogenesis?
Hypertrophy of the ductular-lobular-alveolar system
Milk production from mid-gestation
Formation of Montgomery tubercles
Increased sensitivity due to intercostal nerves III-V
Fusion of mammary and sebaceous glands
What is lactogenesis?
Synthesis and secretion of milk from the breast
What is the purpose of the hemidesmosome within the lactiferous sinuses?
Allows immune cells to move between adjacent epithelial cells in order to protect against infection (pass to the baby)
What is colostrum?
The first form of milk produced from the breast that is higher in proteins and immunoglobulins than normal milk?
What causes cessation of lactation?
Age Loss of feedback Pain e.g. mastitis Menstruation Prolactin suppression e.g. ergot/diuretics/retained placenta
What is the feedback mechanism of lactation?
The baby suckling the breast stimulates mechanoreceptors that inhibits dopamine and GnRH release from the hypothalamus.
This results in increased prolactin and oxytocin production.
The breast produces a feed under stimulation from prolactin and milk is ejected under the influence of oxytocin.
What is the ‘let-down reflex’?
Otherwise known as galactokinesis the let-down reflex is when oxytocin release stimulates contraction of myoepithelial cells to squeeze milk from the breast.
What is galactopoeisis?
Maintenance of lactation- recommended to feed every 1-3 hours
What are the advantages of breast feeding?
Babies get fewer infections due to passive immunity
Bonding due to oxytocin release
Reduced risk of breast and ovarian cancer
Further contraction of the uterus
Aids loss of weight gained during pregnancy
What physiological changes occur in the breast throughout the menstrual cycle?
After ovulation there is cell proliferation and stromal oedema and then menstruation decreases lobule size
What is the clinical significance of the milk lines?
These are lines that occur in all mammals along which breast pathology can arise at any point, commonly in the axilla e.g. accessory breast tissue
What is acute mastitis?
Staphylococcus aureus infection of nipple cracks/fissures causing an erythematous and painful breast
How can fat necrosis present?
A mass, skin change or mammographic abnormality
What are the histological features of fibrocystic change?
Cysts
Fibrosis
Apocrine metaplasia
What is a fibroadenoma?
A benign mobile mass (may be multiple or bilateral) that is a localised hyperplasia (not a true neoplasm)
In what conditions can you get gynaecomastia?
Puberty/elderly Neonates Cirrhosis of the liver Gonadotropin excess e.g. Sertoli/Leydig cell tumours Drug-related e.g. spironolactone
What is a Phyllodes tumour?
Nodules of epithelium-covered proliferating stroma that present as masses of the breast. Has benign and malignant types and can grow very large.
What is the most common form of breast cancer?
Adenocarcinoma of the upper outer quadrant
List some of the risk factors associated with breast cancer:
Obesity Late pregnancy Exogenous oestrogens Uninterrupted menses/early menarche Radiation e.g. for Hodgkin's lymphoma BRCA1/2 tumour suppressor genes
What is Paget’s disease?
Extension of metaplastic cells into the nipple without crossing the basement membrane resulting in a unilateral red and crusting nipple.
What causes the appearance of the breast known as peau d’orange?
Involvement of the lymphatic drainage system of the skin of the breast in breast carcinoma resulting in oedema of the breast and sunken hair follicles.
Name some of the common sites of metastasis of breast carcinoma:
The ipsilateral axilla Bone Lungs Liver Brain Ovaries GIT
Why do we use gene expression profiles?
Microarrays of 17 marker genes can correctly identify approximately 90% of women who will eventually develop metastases
What is Tamoxifen?
An oestrogen-receptor blocker
What is Herceptin?
A monoclonal antibody that interferes with the Her2 protein
How does HPV result in cancerous changes in the cervix?
Production of viral proteins E6 and E7 that interfere with tumour suppressor proteins
What is CIN?
Cervical intraepithelial neoplasia- dysplasia of squamous cells in the cervix that predisposes to cervical carcinoma
How is cervical carcinoma treated?
Large loop excision of the transformation zone (LLETZ)
Cryotherapy
Hysterectomy and lymph node dissection
Approximately how long does it take for CIN I to progress to carcinoma in situ?
7 years
What is endometrial hyperplasia?
Precursor to endometrial carcinoma, abnormal proliferation of the endometrium with an increased gland:stroma ratio associated with prolonged oestrogenic stimulation
What are the two types of endometrial adenocarcionma and the differences between them?
Endometrioid- mimics proliferative glands, spreads by myometrial invasion
Serous carcinoma- poorly differentiated and aggressive, spreads by exfoliation and implantation on peritoneal surfaces
What symptoms may a patient with ovarian cancer present with?
Abdominal pain Abdominal distention Ascites Menstrual disturbances GI/Urinary symptoms
What are the three types of epithelial ovarian tumour?
Serous
Endometrioid
Mucinous
What are the three types of teratoma?
Dermoid cysts (benign) Immature teratomas (immature fetal tissue) Monodermal teratoma (highly specialised)
Name two common monodermal teratomas:
Struma ovarii (mature thyroid tissue) Carcinoid teratoma (neuroendocrine)
What are the two types of sex-cord-stromal tumours?
Sertoli/Leydig cell tumours
Granulosa/Thecal cell tumours
What is a Krukenberg tumour?
Metastatic GI tumour within the ovary, often bilateral and originating from the stomach
What two conditions are associated with vulval carcinoma?
HPV 16 infection
Longstanding inflammatory/hyperplastic conditions such as lichen sclerosis
What is vulvar intraepithlial neoplasia?
In situ precursor to vulval carcinoma.
What is gestational trophoblastic disease?
Abnormal proliferation of placental tissue (may be villous or trophoblastic)
What is a hydatidiform mole?
Cystic swlling of chorionic villi and trophoblastic proliferation; may be complete or partial
What is an invasive mole?
Penetrates/perforates the uterine wall resulting in rupture, characterized by persistently high hCG.
What is gestational choriocarcinoma?
Malignant neoplasm of trophoblastic cells derived from an abnormal or normal pregnancy, arising from the germ cells in the ovary or the mediastinum.
How is gestational choriocarcinoma different to non-gestational choriocarcinoma?
Gestational choriocarcinoma, although it metastases widely, is less aggressive and responds well to chemotherapy.
Non-gestational choriocarcinoma is very aggressive and much rarer.
