Repro Flashcards
Through which tube does sperm cells leave the testes?
Ductus deferens
What are the 3 areas of the epididymis?
Head
Body
Tail
What is the structure that connects the epididymis to the seminiferous tubule?
Rete testis in mediastinum testis
What is the structure that produces the sperm cells?
Seminiferous tubule
What is the function of the seminiferous tubule?
Germination, maturation and transportation of sperm cells
What is the serous membrane called that covers the testes?
Tunica vaginalis
What is the structure that covers the seminiferous tubules called?
Tunica albuginea
What is the basic function of the epididymis?
Absorption of fluid and concentration of the sperm cells
What is the structure that connects the tunica vaginalis to the peritoneum?
Ligamentous remnant of processus vaginalis
In what structure of the testis does a hydrocele develop?
Within the tunica vaginalis serous membrane - between the parietal layer and the visceral layer
What is the reason a hydrocele forms in the testis?
Excess fluid secreted from the tunica vaginalis that doesn’t drain correctly
What are the two main cells of the testis?
Sertoli and leydig cells
What is the function of the sertoli cells and what hormone activates it?
“Nurse” cell that is part of a seminiferous tubule and helps in the process of spermatogenesis
It is activated by follicle-stimulating hormone
What is the stem cell for producing sperm?
Spermatogonia
What is the function of the leydig cells?
Synthesis of sex steroid hormones e.g. testosterone,
in the presence of luteinizing hormone (LH)
What is the blood supply to and from the testis?
Right testis - testicular artery and vein direct to and from the abdominal aorta and IVC.
Left testis - testicular vein -> left renal vein -> IVC
Cremasteric artery also supplies the testes.
What is the pampiniform plexus?
The testicular vein wrapping around the testicular artery on its ascent to the IVC
It acts as a heat exchanger for the cooled venous blood to cool the arterial blood
What nodes do the R+L testes drain into?
Right testis -> lumbar nodes -> para-aortic nodes
Left testis -> lumbar nodes -> para-aortic nodes
What is the term used to describe a twisted testicle?
Torsion
What is the potential problem of testicular torsion and why?
Compression of the spermatic cord
Venous drainage gets occluded therefore increase capillary pressure and then the arteries get occluded too
Immune privilege can be compromised and then the other non-torted testicle can be attacked too
What nodes do the lymphatic drain into from the scrotum?
Right testis -> superficial inguinal lymph nodes -> deep inguinal lymph nodes -> external iliac lymph nodes -> common iliac lymph nodes
Left testis -> Internal iliac lymph nodes -> sacral lymph nodes ->
What is the structure that pulls the testes from the abdominal cavity to the scrotum?
Gubernaculum
What are the peritoneal layers that make the spermatic cord?
In -> out
Transversalis fascia -> internal oblique muscle -> External oblique aponeurosis
What are the spermatic cord layers?
External spermatic fascia
Cremasteric fascia
Internal spermatic fascia
In what layer of the scrotum is the muscle that pulls the testis up towards the body?
Muscle fibres from the cremaster muscle
In what layer(s) of the spermatic cord is the nervous supply?
Genital branch of the genitofemoral nerve lumbar plexus -> between the cremasteric and internal spermatic fascia
Ilioinguinal nerve - sympathetics -> vas deferens
What are the layers of the prostate?
Anterior region -> Transitional zone -> Peripheral zone -> Central zone is within the peripheral zone
Through which structures of the prostate does the ejaculatory duct pass through?
Central zone
Through which structures of the prostate does the urethera pass through?
Transitional zone
Convergence of what structures becomes the ejaculatory duct?
Seminal vesicle and ampulla of the ductus deferens
Which part of the prostate does BPH tend to affect?
Transitional zone
Which part of the prostate does prostate cancers affect?
Peripheral zone
Of the total volume of semen which parts of the ejaculatory system contributes to its production and in which approximate quantities?
Epididymis/ testicle ~ 5% Seminal vesicle ~ 70% Prostate gland ~ 25% Bulbourethral gland ~ 1% Periurethral glands ~ 1%
What is the function of the penis?
Expulsion of urine via urethra
Deposition of sperm in female genital tract
Removal of competitor’s sperm
Attraction of mates
What causes an erection in terms of blood?
Sinusoidal relaxation
Vasodilation of penile arterioles
Compression of veins
What ANS subcategory is responsible for erection?
PNS
What ANS subcategory is responsible for ejaculation?
SNS
What are the two tissues which engorge due to blood entry of the penis?
Corpus cavernosum
Corpus spongiosum
What is the urogenital triangle?
Attachment of the penis to the pelvic bone anterior to the perineal membrane
What is the fibrous sheath encases the corpus cavernosum and spongiosum?
Tunica albuginea
In what direction do the collagen fibres run in the tunica albuginea?
Circumferential
Parallel along axis
What is the blood supply to the penis?
Perineal arteries -> Dorsal arteries (run above the penis)
Cavernous artery -> runs inside the corpus cavernosum
Bulbouretheral artery -> runs inside the corpus spongiosum
What is the follicular development of an ovarian follicle from beginning to end if unfertilised?
1 - primordial follicles 2 - early primary follicle 3 - late primary follicle 4 - secondary (antral) follicle 5 - tertiary (Graafian follicle) 6 - ruptured follicle -> oocyte at ovulation leaves 7 - active corpus leuteum 8 - regressing corpus leuteum 9 - corpus albicans
During ovulation what is the reason for pain?
Rupturing of ovarian follicle
In which layer of the ovary are gametes formed?
Ovarian surface - germinal epithelium
What is an atretic follicle?
Follicular atresia
Breakdown of a follicle
Natural process - removal of old oocytes that would not be suitable for fertilisation
What is the superior part of the uterus?
Fundus
What is the structure of the uterus that leads out into the peritoneum?
Fimbriae
What is the suspensory ligament of the ovary and what is its function?
A fold of peritoneum that covers the ovarian artery, vein, ovarian nerve plexus and lymphatics
What is the round ligament?
Remnant of the gubernaculum
Originates at the uterine horns -> and attaches to the labia majora, passing through the inguinal canal
Keeps the uterus in the anteverted position
What are the two pouches found in the female?
Vesicouterine pouch
Rectouterine pouch
What is the term for the external hole of the cervix?
External OS
What is the gap between the cervix and the uterus called?
Fornices
What ligament stretches and potentially causes pain in the female reproductive tract?
Round ligament
Stretches from the uterine horns to the labia majora
Why during pregnancy does the woman suffer from urinary incontinence and urgency?
The gravid uterus pushes down on the bladder decreasing its volume
Why during pregnancy does the woman suffer from constipation?
The gravid uterus pushes against the rectum reducing its size
What is the term used to describe the oviduct portion that connects the isthmus and the infundibulum?
Ampulla
What is the infundibulum of the oviduct?
The distance between the opening of the uterine tube and the fimbriae
What is the first part of the fallopian tube called?
Isthmus
What is the ligament that connects the ovary to the uterus?
Ovarian ligament
What is the broad ligament made up of?
Round ligament + Ovarian ligament + Fallopian tube
What part of the female reproductive tract is intraperitoneal?
Ovary + fallopian tube (ampulla + infundibulum + fimbriae)
What are the remnants of the Gubernaculum in women?
Round ligament and the ligament of the ovary
What is the mesosalpinx?
Mesentery of fallopian tube
Wha is the mesovarian?
Mesentery of the ovary from peritoneum
What is the blood supply to the uterus?
Internal iliac artery -> uterine artery
What is the positioning of the uterus?
Anteverted and anteflexed
What is the histological appearance of the vagina?
Thick stratified squamous epithelium with lots of granules of glycogen
Why does the vaginal cells have lots of glycogen?
Lactobacilli convert the glycogen into lactic acid which helps keep other bacteria unable to survive in the area
What are the 3 germ layers?
Mesoderm, ectoderm and endoderm
In embryology what does the hindgut end in?
A dilated structure - the cloaca
What is the urogenital ridge?
An area in the embryonic body that contains the mesonephric duct + gonad + mesonephros
What part of the embryo gives rise to both the embryonic kidney and the gonad?
Intermediate mesoderm
What cells is the gonad derived from in embryology?
Intermediate mesoderm plus primordial germ cells
What duct is known as the paramesonephric duct?
Mullerian duct
What duct is known as the mesonephric duct?
Wolffian duct
Which duct leads to the developing gonad in the embryo?
Mesonephric duct
Which duct leads to the developing kidney in the embryo?
Wolffian duct
Where do the paramesonephric and mesonephric duct end?
Urogenital sinus
What causes the gonad to differentiate into the epididymis or the uterus
Epididymis - Y gene on the SRY chromosome
Uterus - the lack of a Y chromosome and also presence of a X chromosome (in monosomy)
What happens to the Mullerian (paramesonephric) duct and the Wolffian (mesonephric) duct in a normal male with XY?
Testis produce Mullerian Inhibiting Hormone -> suppresses Mullerian (paramesonephric) duct development
Testis also produce androgens -> supporting mesonephric duct development
What happens to the Mullerian (paramesonephric) duct and the Wolffian (mesonephric) duct in a normal female with XX?
No testis -> no production of mullerian inhibiting hormone -> Mullerian duct develops
No testis -> no production of androgens -> no support for development of Wolffian duct -> Wolffian duct degenerates
What happens to the Mullerian (paramesonephric) duct and the Wolffian (mesonephric) duct if there is exogenous androgens in a female?
Support for Wolffian duct -> Wolffian duct develops
No MIH from testis -> development of the paramesonephric duct
What happens to the Mullerian (paramesonephric) duct and the Wolffian (mesonephric) duct in Androgen Insensitivity Syndrome?
Receptors for testosterone don’t work -> Wolffian ducts don’t survive as no response from adrogens
Testis present -> MIH produced -> Paramesonephric duct (Mullerian) duct don’t develop
What duct is the first duct for the embryonic kidney?
Mesonephric duct
What becomes the urinary bladder in the embryo?
Urogenital sinus
What does the mesonephric duct develop into in a normal male?
Androgen production -> in a male the Vas deferens and epididymis are required -> they develop
From what area of the urogenital sinus does the vagina develop from?
Sinovaginal bulbs
What are the basic components of the external genitalia in the embryo?
Genital tubercle
Genital folds
Genital swellings
What does the genital tubercle and folds develop into in males?
Spongy urethra
Specifically what does the genital tubercle develop into?
Glans penis
At what age can the gender of the foetus be differentiated?
At week 12
In females what does the genital tubercle develop into?
Clitoris
In the female embryo what does the genital swelling develop into?
Labia majora
In the female embryo what does the genital fold develop into?
Labia minora
In the female embryo what does the urogenital sinus develop into?
Vaginal orifice
Urethral orifice
At what age of gestation does the genitalia differentiate?
Week 9-12
What prevents further descent of the ovaries into the pelvis?
Growth of the uterus + round ligament of the uterus
Approximately how many sperm cells are made /day?
200 million
How many daughter cells are produced after meiosis?
4
What is different in meiosis in females compared to males?
There are polar bodies formed in the females which are essentially useless
Only one develops into a mature oocyte
Males - all sperm cells are created in equal size just the X and Y chromosome will inevitably be different
What are the 3 methods of getting genetic variation in meiosis?
Crossing over - between two homologous chromosomes
Independent assortment - random orientation of each bivalent along he metaphase plate
Random segregation - random distribution of alleles among the four gametes
What forms the blood-testis barrier?
Sertoli cells held tightly together with tight junctions
What is the name of the process that produces sperm cells called?
Spermatogenesis
What is the spermatogenesis process from germ cell to sperm cell?
Sptermatogonium -mitosis-> Primary spermatocyte -meiosis 1-> Secondary spermatocyte -meiosis 2-> Spermatid -spermiogenesis-> Spermatozoa
What are the two types of spermatogonium produced before mitosis?
Ad spermatogonium -> resting: reserve stock
Ap spermatogonium -> active: maintain stock and from puberty onwards produce type B spermatogonia giving rise to primary spermatocytes
What happens in the process of spermiogenesis?
Each primary spermatocyte forms 4 haploid spermatids which differentiate (spermiogenesis) into spermatozoa
Remodelling as passing down seminiferous tubule, through rete testis and ductile efferentes and into the epididymis to finally form spermatozoa
What is the spermatogenic cycle?
Time taken for reappearance of the same stage within a given segment of tubule
~16 days in human
What is the spermatogenic wave?
The distance between the same stage in the seminiferous tubule within the wave of corkscrew
How are spermatids able to move through the seminiferous tubules?
They are non-motile
Transport via sertoli cell secretions
Assisted by peristaltic contraction
Within the sperm cell where are the mitochondria situated?
Within the mid (connecting) piece
Within the sperm cell what connects the head of the sperm and the mid (connecting) piece of the tail together
Centriole
What are the main constituents of the seminal vesicle secretions?
Alkaline fluid Amino acids Citrate Fructose Prostaglandins Clotting factors - semenogelin
What are the main constituents of the secretions of the prostate?
Milky, slightly acidic fluidProteolytic enzymes, zinc
Citric acid
Acid phosphatase
What are the main constituents of the secretions of the bulbourethral glands (Cowper gland)?
Alkaline fluid
Mucoproteins
Lubricate and neutralise acidic urine in distal urethra
What is sperm capacitation?
Final maturation step in female genital tract prior to becoming fertile - 6-8hours long
Removal of glycoproteins and cholesterol from sperm membrane
Tail moves from beat to whip like
Activation of sperm signalling pathways (atypical soluble adenylyl cyclase and PKA involved)
Allows sperm to bind to zona pellucida of oocyte and initiate acrosome reaction
At how many months gestation are the oocytes ready?
4 months gestation
During development of the oogonia to primary oocytes what stage of meiosis do they stop in?
Prophase of meiosis 1
When does the maturation of the oocytes begin?
Before birth at approx month 7 majority of oogonia have degenerated
All surviving primary oocytes have entered meiosis 1
What is the structure called where the matured oocytes are formed and surrounded by a layer of cells?
Primordial follicle
Surrounded by follicular cells
What are the 3 stages of maturation of oocytes from puberty onwards?
Preantral
Antra
Preovulatory
What happens in the preantral stage?
Primordial follicles begin to grow -> follicular cells change from flat -> cuboidal -> proliferate to produce stratified epithelium of granulosa cells
What do the granulosa cells do in the preantral stage?
Secrete a layer of glycoprotein on oocyte forming the zona pellucida
What happens in the antral stage of oocyte development?
Development of the granulosa cells furthers -> fluid filled spaces coalesce = Antrum -> Secondary follicle
What are the theca cells?
Two types Theca interna and Theca externa
As the oocyte grows during 4 to 7 months of gestation what do the flat epithelial cells become?
Follicular cells
During ovulation what is the name of the cells also being released at the same surrounding the oocyte?
Granulosa cells -> Cumulus oophorus
What stimulates theca interna cells?
Leutenising hormone
What do theca interna cells release?
Androstenedione
What does androstenedione act on during follicular development?
Granulosa cells
How do granulosa cells respond to androstenedione?
By the action of aromatase they convert androstenedione into estradiol
What occurs in the preovulatory stage of follicular development?
LH surge -> induces preovulatory growth phase
Meiosis 1 complete -> 2 haploid cells produced -> meiosis 2 -> arrest in metaphase -> 3hours prior to ovulation
When does meiosis 2 complete?
If the oocyte becomes fertilised then the cell will complete Meiosis 2 otherwise cell degenerates 24hrs after ovulation
What occurs during ovulation in terms of LH and FSH and the follicle?
LH and FSH stimulate rapid follicular growth 2-4days prior to ovulation
What is the term used to describe a mature follicle?
Graafian follicle
What is a corpus luteum?
Post ovulation remaining granulosa and theca interna cells becomes vascularised -> develop a yellowish pigment and change into lutein cells -> corpus luteum
How does the corpus luteum function help the oocyte/ fertilisation?
Secretes oestrogenen and prosterone
Stimulates uterine mucosa to enter secretory stage in prep for embryo implantation
Dies after 14 days if no fertilisation occurs
How is an oocyte transported once secreted?
Fimbriae sweep over ovary -> uterine tube contracts rhythmically -> oocyte carried into tube by fimbriae and motion of cilia on epithelial lining
Oocyte propelled by peristaltic muscular contractions of the tube and by cilia in mucosa
If fertilised then reaches uterine lumen in 3-4 days
What is the corpus albicans?
If no fertilisation of occyte -> corpus luteum degenerates
Forms fibrous scar -> corpus albicans
Progesterone production decreases
What happens to the corpus luteum if fertilisation occurs?
Corpus luteum degeneration is prevented by human chorionic gonadotropin secreted by the developing embryo
Corpus luteum contines to grow and forms the corpus luteum of pregnancy
Progesterone secreted until 4th month
Secretion of placenta then becomes adequate - corpus luteum then dies
What is the latin name for the corpus luteum of pregnancy?
Corpus luteum graviditatis
What is the difference between when spermatogenesis and oogenesis start?
spermatogenesis - puberty
oogenesis - when a foetus
What is the difference between when spermatogenesis and oogenesis are complete?
Spermatogenesis - all stages complete in testis
Oogenesis - last stage of meiosis 2 occurs in oviduct
What are the 6 functions of the pelvic floor in women?
1 - Pelvic organ support 2 - Bladder and bowel control 3 - Passing of urine and faeces 4 - Sexual function 5 - Breathing 6 - Pregnancy and childbirth
What are the mechanisms of the supportive function of the pelvic floor?
Suspension
Attachment
Fusion
To what two bones (ant and post) are the pelvic floor muscles attached to?
Pubic bone - ant
Spine - post
How is the suspension function of the pelvic floor achieved?
Cardinal ligaments - hold cervix and upper vagina in place
Uterosacral ligaments - hold the back of the cervix and upper vaginal laterally
Round ligament - maintain anteverted position of the uterus
How is the attachment function of the pelvic floor possible in women?
Arcus tendinosus fascia pelvis - white line
Endopelvic fascia - stretches like a hammock from white line laterally to the vaginal wall medially
How does increased abdo pressure help maintain urinary continence in women?
Urethra lies anterior and superior to the endopelvic fascia - gets compressed during inc abdo pressure
How is the fusion function of the pelvic floor possible in women?
Urogenital diaphragm and perineal body
Lower half of the vagina is supported by fusion of vaginal endopelvic fascia to the perineal body posteriorly and levator ani laterally and to the urethra anteriorly
What are the 4 components of the pelvic floor in simple terms
Levator ani muscles
Urogenital diaphragm/ perineal membrane
Perineal body
Perineal muscles
What are the muscles of the pelvic diaphragm?
Coccygeus muscle
Levator ani muscles
What are the levator ani muscles?
Iliococcygeus
Pubococcygeus
Puborectalis
What is the area called where the vagina and urethra pass through the internal pelvic floor muscles?
Genital hiatus
What makes up the urogenital diaphragm?
The Levator ani muscles:
Iliococcygeus
Pubococcygeus
Puborectalis
What structures do the levator ani muscles contain?
Urethra
Vagina
Rectum
What is the origin and insertion of the levator ani?
Origin:
Back of the body of the pubic bone, the white line over the obturator internus muscle and medial aspect of the ischial spines
Insertion: Rectum + lower part of coccyx and ano-coccygeal raphe
What are the perineal muscles?
External anal sphincter
Bulbospongiosus aka bulbocavernous
Superficial and deep transverse perineal muscles
What is the urogenital diaphragm?
Spans the anterior half of the pelvic outlet
Arises from the inferior ischiopubic ramus
Attaches medially to the urethra, vagina and perineal body
What is the perineal body?
The centre point of the perineum
Muscular attachment point
What is the blood supply to and from the vagina?
To - internal and external pudendal arteries
From - internal and external pudendal veins
What is the lymphatic drainage from the vagina?
Inguinal lymph nodes
What is the nerve supply to the vagina?
S2-4 -> Branches of the pudendal nerve
What pelvic floor muscles encircle the anus?
Pubococcygeus
External sphincter ani
What is a pelvic organ prolapse?
Loss of support for the uterus, bladder, colon or rectum - leading to prolapse of one or more of these organs into the vagina
What is the term used to describe a prolapsed bladder into the vagina?
Cystocele
What is the term used to describe a prolapsed urethra into the vagina?
Urethrocele
What are the middle compartment prolapses?
Uterine prolapse
What is the term used to describe the whole uterus prolapsing out of the vagina?
Procidentia
What is a vaginal vault prolapse?
Prolapse of the vaginal apex through the vagina post hysterectomy only
What are posterior compartment prolapses?
Rectum prolapse into the vagina
Loops of bowel may prolapse into the rectovaginal space - (Pouch of douglas) -> enterocele
What are the risk factors for pelvic organ prolapses?
Age
Parity
Vaginal delivery - 4x increased risk after 1st child 11x increased risk after ≥4 deliveries
Obesity and causes of chronic raised intra-abdominal pressure
Postmenopausal oestrogen deficiency
Neurological - spina bifida
Genetic connective tissue disorder - Marfan’s, Ehlers’ Danlos
What is an obstetric anal sphincter injury?
Perineal tears involving the anal sphincter complex
Episiotomy performed to reduce risk of occurrence during crowning of baby
What is the main stay of treatment for urinary incontinence?
Pelvic floor muscle exercises to strengthen
Define FGM
all procedures involving partial or total removal of the external female genitalia or other injury to the female genital organs, whether for cultural or other non-therapeutic reasons
What is the term used to describe the breast bud growth starting?
Thelarche
What is the term used to describe the growth of secondary sexual characteristics such as hairs?
Adrenarche
What is the term used to describe the first menstruation?
Menarche
What is the tanner scale of development of secondary sexual characteristics?
1-5
1 - least developed
5 - most developed
Why are women shorter than men in general?
Androgens plus a longer and faster growth spurt in men gives them the height increase.
Oestrogen fuses the epiphyseal plates quicker and sooner + shorter growth spurt.
What is the critical weight for girls to start menarche?
47kg
What about GnRH is important in development?
Secretion in pulses tied to internal biological clock - synchronised external signals i.e. by light
Pulsatile release -> allows sensitisation of the GnRH receptors to remain -> if constant production of GnRH -> FSH and LH production stops -> Gonadal steroid production stops
Why can pineal tumours affect puberty?
Pineal gland -> melatonin released -> required for GnRH pulse release
Pineal gland tumour -> more melatonin released -> less GnRH released as body thinks awake -> puberty and growth occurs sooner -> precocious puberty
How often does GnRH release (pulsatile)?
Every 1-3 hours
What is the effect of GnRH being released in a pulsatile fashion?
LH and FSH would also be released in a pulsatile manner
When is GnRH released the most?
During sleep - amplitude of pulses increases significantly
High levels of LH and FSH initiate gonadal development
What cells in the testis does LH act on?
Leydig cells
What hormone do Sertoli cells produce as part of negative feedback on the HPG axis?
Inhibin - acts to negatively feedback onto the hypothalamus to release LH/FSH
What cells of the ovary respond to LH and FSH?
LH - theca interna
FSH - granulosa
What is the difference between high and low titres of oestrogen on the HPG axis?
Low titre - negative feedback to reduce GnRH secretion
High titre - positive feedback to increase GnRH secretion -> LH surge
How does oestrogen and progesterone affect FHS and LH?
Progesterone inc inhibitory effects of moderate oestrogen
Progesterone prevents positive feedback of high oestrogen -> no LH surge
Oestrogen reduces GnRH per pulse
What cells in the ovary release inhibin?
Granulosa cells of the corpus luteum
What is the function of leptin in puberty?
Leptin released from adipocytes
Reproductive dysfunction associated with leptin deficiency
Leptin has pulsatile release pattern significantly associated with the variations in LH
Leptin can regulate GnRH levels
What is the purpose of the menstrual cycle being a cycle and not a continuous process?
Preparation of the gamete for fertilisation
Preparation of the endometrium for good implantation
A period of time with no menstruation to wait for fertilisation and implantation
What happens at the start of the menstrual cycle?
FSH levels are slightly rising
No ovarian hormone development
Little inhibition at the hypothalamus or anterior pituitary
Low steroid and inhibin levels produced
What is the effect of FSH?
Binds to granulosa cells
Follicular development
How long is the follicular phase of ovarian cycle?
day 0 till 14
14 days
How long is the luteal phase of the ovarian cycle?
day 15-28
14 days
What occurs in the mid-follicular phase for all hormones involved in the menstrual cycle?
Follicular oestrogen now at at conc -> positive feedback -> gonadotrophin levels rise -> Effects seen on LH only
Follicular inhibin rising - selective inhibition on FSH production by ant pituitary
What is the function of inhibin on the menstrual cycle?
Acts to inhibit the production of FSH from the ant pituitary
In preparation of ovulation what happens to the hormones?
Circulating oestradiol and inhibin rise rapidly
Oestradiol production no longer dependent on FSH
LH surge
Progesterone production begins -> Granulosa cells become responsive to LH
What is the LH surge?
High levels of oestradiol -> positive feedback onto pituitary -> LH/FSH produced more and more
How does oestrogen increases its release in positive feedback?
High levels enhance the sensitivity of the ant pituitary to gonadotropins to GnRH
Immediately after ovulation what happens to the hormones involved in the menstrual cycle?
After ovulation - follicle is leutenised Secretes oestrogen and progesterone Inhibin continues to be produced LH is now also suppressed due to negative feedback due to progesterone Further gamete development suspended
What happens in the luteal phase of the menstrual cycle?
Corpus luteum continues for 14 days
Produces progesterone and oestrogen form androgens
produces inhibin
Promotes production of progesterone
Regresses spontaneously in absence of a further rise in LH
How does the uterine lining respond to oestrogen and progesterone?
Oestrogen - proliferation + secretion
Progesterone - secretion
What are the two layers of the uterus?
Myometrium
Endometrium
What are the two layers of the endometrium?
Functional layer - hormone responsive - shed if no pregnancy
Basal layer - source of new functional cells (stem cell layer)
What happens to the histology of the uterus during the menstrual cycle?
Early proliferative phase - glands are sparse, straight
Late proliferative phase - functional layer doubles in size, glands now coiled
Early secretory phase - endometrium max thickness, very pronounced coiled glands
Late secretory phase - glands adopt a saw-tooth appearance
What happens at the end of the menstrual cycle?
Absence of a further rise in LH - corpus luteum regresses
Dramatic fall in gonadal hormones
Relieving negative feedback
What layer of the embryo produces the human chorionic gonadotrophin?
Syncytiotrophoblast layer
Exerts a luteinising effect
How does the corpus luteum support a pregnancy?
Placental HCG -> supports corpus luteum -> produces steroid hormones to support pregnancy
How are the uterine and ovarian cycles similar and different?
They are both 28 days long
Ovarian cycle - Follicular phase (14d) -> luteal phase (14d)
Uterine cycle - Menses (4d) -> Proliferative phase (10d) -> Secretory phase (14d)
What happens to the ovary during the ovarian cycle?
Day 0-4- menses Day 4-9 - Follicular development Day 9-13 - Graafian follicle Day 14- ovulation Day 15-28 - corpus luteum
What happens to basal body temp during the menstrual cycle?
Day 1-3 Temperature steady Day 13-14 - temperature decreases Day 14-15- Temperature rapidly increases Day 15-25 - Temp remains constant Day 25-28 - Temp decreases back to normal levels
What does oestrogen do during the follicular stage?
Fallopian tube function Thickening of endometrium Growth and motility of myometrium Thin alkaline cervical mucous Vaginal changes Changes in skin, hair, metabolism
What does progesterone do during the luteal phase?
Thickening of endometrium into secretory form
Thinking of myometrium, reduction in motility
Thick, acid cervical mucous
Changes in mammary tissue
Increased body temp
Metabolic changes
Electrolyte changes
What is a normal cycle length?
21-35 days (28 days +/- 7 days)
What gives a variation in the cycle length?
Follicular phase
Luteal phase is strictly controlled 14 +/-2 days
What are 3 main factors affecting the menstrual cycle?
Physiological factors - pregnancy and lactation
Emotional stress
Low body weight
Define menopause
Permanent cessation of menstruation at the end of reproductive life due to loss of ovarian follicular activity
No menstrual periods of 12 consecutive months and no other biological or physiological cause can be identified
What is physiologic menopause?
Normal decline of ovarian function due to ageing begins in women between ages 45 and 55
Results in infrequent ovulation
Decreased menstrual function and eventually cessation of menstruation
What is pathologic menopause?
Gradual or abrupt cessation of menstruation before 40 years occurs idiopathically
What are the 4 categories of menopause?
Pre-menopause
Peri-menopause
Menopause
Post-menopause
What happens in pre-menopause?
Typically from age circa 40 years
Less oestrogen is secreted
LH and FSH levels rise (FSH more) - may be reduced negative feedback
Could result in reduced fertility- cycles unchanged
What happens in peri-menopause?
Characterised by physiological changes associated with the end of reproduction capacity - follicular phase shortens and ovulation early or absent
Terminating with the completion of menopause
What are the phases of menopause?
Permanent cessation of menstruation causes by ovarian follicular development failure
What is post-menopause?
Defined formally as the time after which a women has experienced 12 consecutive months of amenorrhoea
What happens to FSH and LH levels during menopause?
Rising to try and produce more oestrogen and progesterone as there is no more feedback loop
What are 7 important signs and symptoms of menopause?
Itchy, twitchy, sweaty, sleepy, bloated, moody and forgetful
What are 5 important consequences of early oestrogen deficiency in menopause?
Hot flushes, sweating, insomnia, menstrual irregularity, psychological symptoms
What are 4 important consequences of intermediate oestrogen deficiency in menopause?
Vaginal atrophy
Dyspareunia
Skin atrophy
Urge-stress incontinence
What are 5 important consequences of late oestrogen deficiency in menopause?
Osteoporosis
Atherosclerosis - CHD, CVD
Alzheimers
How can hot flushes be relieved?
Oestrogen replacement therapy (HRT)
Why do women get blacker hairs after menopause?
Increased levels of gonadotropins -> increased amount of androgens produced -> aromatase function decreases -> ovarian androgen secretion increases despite substantial oestrogen demise
What happens the skin, weight, hair and voice of menopausal women?
Skin: loss of elasticity, thin and fine
Weight: weight increase - mood swings -> irregular food habit -> more deposition of fat around hips, waist, buttocks
Hair: Dry and coarse + hair loss
Voice: deeper due to vocal cord thickening
What happens to the uterus during and after menopause?
Small and fibrotic due to atrophy of muscles
Regression of endometrium and shrinkage of myometrium
Cx smaller and appears to flush with vagina (older women impossible to identify vagina from Cx.
What happens to the vulva and breast during and after menopause?
Vulva - fat in labia majora and mons pubis decreases and pub hair becomes spare
Breast - thin built - flat and shrivelled, heavy built - flabby, pendulous
What happens to the bone during and after menopause?
Calcium loss form bone is increased for 5 years post menopause -> reduced bone mineral density
Bone mass reduces by 2.5% per year
Reduced oestrogen -> enhanced osteoclast activity -> osteoporosis -> increased risk of fracture
What happens to the cardiovascular system after menopause?
Total cholesterol increases: LDL, VLDL, Lipoprotein A, LDL-cholesterol oxidation enhanced, triglycerides increased
HDL cholesterol decreases
Gradual rise in risk of heart disease and stroke after menopause
BP increases
Body weight increases
Carbohydrate tolerance decreases i.e. insulin sensitivity decreases
What are hormonal treatments of menopause?
HRT - pill form, vaginal oestrogen cream, transdermal path
Improves well-being, limits osteoporosis
What does amenorrhoea mean?
Absence of menstruation
What are the classifications of amenorrhoea?
Primary and secondary
What is primary amenorrhoea?
No periods by age 16
What is secondary amenorrhoea?
No periods for >6months
Through which organs could be implicated in primary amenorrhoea and secondary amenorrhoea?
Primary - HPG axis including uterus and genitalia
Secondary HPG axis + uterus only.
What is the most common cause of amenorrhoea in young adults and what happens?
Turner’s syndrome
45XO chromosomal defect
Ovary does not complete its normal development
What lab values would be reduced in turners syndrome?
Low oestradiol
High FSH and LH
What are the anatomical causes of primary amenorrhoea?
Imperforate hymen
Transverse vaginal septum
Mullerian agenesis - congenital absence of vagina with variable uterine development
What is the result of complete androgen insensitivity syndrome?
XY -> testes formed -> AMH and testosterone produced -> regression of Mullerian structures -> failure of androgen receptor -> absence of virilization -> testosterone converts to oestrogen -> female phenotype
What hypothalamic and pituitary causes are there for primary amenorrhoea?
Isolated GnRH deficiency - idiopathic hypogonadotrophic hypogonadism - with anosmia = Kallman syndrome
Constitutional delay of puberty
What are anatomical causes of secondary amenorrhoea?
Cervical stenosis
Asherman syndrome - intrauterine adhesions
Ovarian disorders: Primary ovarian insufficiency - depletion of oocytes before age 40. No oestrogen, no inhibin -> high FSH
What is PCOS in relation to amenorrhoea?
Elevated LH
Insulin resistance
Triad of symptoms to diagnose: Androgen excess (hirsutism, acne) + Menstrual irregularity + Obesity
What are 4 endocrine disorders that lead to secondary amenorrhoea?
(1) Thyroid disease: hyper and hypothyroidism - severe hypothyroidism classically associated with amenorrhoea.
(2) Hyperprolactinaemia: high PRL levels >800 -> Negative feedback onto HPT -> decreased dopamine production + reduced GnRH -> decreased FSH/LH -> decreased oestrogen and progesterone
(3) Sheehan syndrome -> pituitary necrosis
(4) Functional hypothalamic amenorrhoea -> weight loss, excessive exercise, emotional stress and stress induced by illness
What are 2 main causes of physiological amenorrhoea?
Pregnancy
Menopause
What features of abnormal uterine bleeding is important to notes?
Frequency (days) Regularity (variation) Duration of flow (days) Volume (objective) Volume (subjective)
How many days of a menstrual cycle constitutes a infrequent and absent cycle?
> 38 days
What does metrorrhagia mean?
Abnormal bleeding from the uterus
What would be classed as irregular menstrual cycle in days?
> 7-9days difference between cycles
What would be classed as a prolonged period in the menstrual cycle?
> 8 days
What volume (Objective) would be classed as heavy and light in the menstrual cycle?
> 80mls heavy
<5ml light
What is classed as acute and chronic on duration of symptoms of abnormal uterine bleeding?
Acute - episode of heavy bleeding that is sufficient quantity to require immediate clinical intervention
Chronic - abnormal bleeding volume, duration, regularity, frequency that as persisted for ≥6months
What is the mnemonic that describes abnormal bleeding’s underlying causes?
PALM-COEIN Polyps Adenomyosis Leiomyoma Malignancy/hyperplasia Coagulopathy Ovulatory dysfunction (includes thyroid) Endometrial Iatrogenic Not yet classified
Why does a fibroid get worse in pregnancy but then disappears after?
Oestrogen dependent
How do you subdivide dysfunctional uterine bleeding?
Anovulatory - inadequate signal -> impaired positive feedback
Ovulatory - secondary to increased prostaglandins and reduced endothelins
What is dysmenorrhoea?
Painful menstruation - crampy and intermittent intense of continuous dull ache
Presents 1-2 days before with onset of menses
Improved 12-72 hours
Lower abdomen and suprapubic area - radiating to back
Primary - since menarche
Secondary - developed over time
What is endometriosis?
Endometrial glands and stroma that occur outside the uterine cavity
Oestrogen dependent, benign, inflammatory disease - responding to cyclical hormonal changes (every time a woman has a period)
Can cause dysmenorrhoea, dyspareunia, chronic pain, infertility
What are the most common sites of endometriosis?
Ovaries - endometrioma
Bladder
Rectum
Peritoneal lining and pelvic side walls
How is dysmenorrhoea managed?
NSAIDS
Hormonal contraceptives
GnRH analogues
Surgery - adhesiolysis, treatment to endometriosis, hysterectomy
What are risk factors for developing an STI?
Risky sexual behaviour - multiple sexual partners, not using barrier contraception, early age first intercourse
Low socio-economic status
Race/ethnicity
Lack of immunisation
What are 2 potential causative organisms for male urethral discharge?
Chlamydia trachomatis,
Neisseria gonorrhoeae
What is Non-gonococcal urethritis?
Inflammation of the urethra with associated discharge
Can be STI - chlamydia trichomatis, Mycoplasma genitialium, Trichomonas vaginalis
‘Pathogen negative’ too
What are the signs and symptoms of a chlamydia trachomatis infection?
Testicular pain
Dysuria
May have discharge
What are the signs and symptoms of a Neisseria gonorrhoeae infection?
90% of men are symptomatic
Thick, yellow discharge +/- dysuria
What investigations can be done in male urethral discharge symptoms?
Urethral sample - first catch not mid stream urine:
Gonorrhoea - microscopy and culture, NAATs
Chlamydia - NAATs
Urethritis - NAATs
Urethral swab - Gonorrhoea
Name 3 potential causative organisms that cause sexually transmitted urethral discharge in women?
N. gonorrhoea
Chlamydia trachomatis
Trichomonas vaginalis
How does Chlamydia trachomatis usually present in women?
Discharge
Postcoital/ intermenstrual bleeding
Dyspareunia
How does Trichomonas vaginalis infection usually present?
Protozoal infection
Copious yellow malodorous discharge
Name 2 potential causative organisms that cause non-sexually transmitted urethral discharge?
Candida albicans
Gardnerella sp
What type of discharge is seen in a candida albicans infection in females?
White discharge
Very itchy
Typically non-offensive odour
What is the name of the condition caused by Gardnerella sp in females?
Bacterial vaginosis
What type of discharge is seen in bacterial vaginosis?
Offensive smelling, white discharge
What is the risk in females with STI’s?
Pelvic inflammatory disease
How would you investigate STI/Non-STI related vaginal discharge?
Chlamydia - Vulvo-vaginal swabs (VVS), Endocervical swab
Gonorrhoea - VVS, endocervical
Trichomoniasis: High Vaginal Swab - posterior fornix
BV: Gram staining, KOH test - fishy smell recreated when added to KOH
Candida: HVS, Microscopy>culture
Describe a HPV infection in men and women
Genital or cutaneous warts
HPV 6 and 11 cause 90% of genital infections
HPV 16 and 18 highest association with cervical cancer
PCR, swab/biopsy in high risk patients
Vaccinations: Gardasil HPV 6,11,16,18
Cervarix HPV 16,18 only
Describe a Herpes Simplex Virus 1 and 2 in men and women
Lifelong infection = lays dormant and reoccurs
Can be asymptomatic initially or present with painful ulcers/ blisters
HSV-1 - cold sores
HSV 2 - more likely to become infected with HIV
Check all areas: Genitals, Mouth, Anus
Swabs: PCR, NAATs
Manage- topical antivirals
Describe a Syphilis infection
Bacteria - Treponema pallidum
Transmission: Direct contact, Vertical transmission
Primary syphilis: Painless ulcers
Secondary syphilis: 4-10weeks after initial infection, multi-system effects (skin, kidneys), can enter a latent phase
Swabs: Microscopy/ PCR, serology
Manage: Penicillin ABx = Benzathine penicillin
Define Pelvic Inflammatory Disease
Infection of the uterus, fallopian tubes and ovaries
What usually causes PID?
Chlamydia trachomatis
Neusseria gonorrhoeae
Gardnerella sp
Mycoplasma genitalium
Source of infection: intrauterine contraceptives, intrauterine surgery/ interventions
What are signs and symptoms of PID?
Symptoms: Lower abdo pain, Dyspareunia, Purulent discharge, Abnormal uterine bleeding - intramenstrual or postcoital
Signs: Pyrexia, Pain on palpation (abdo/ bimanual vaginal exam), Evidence of discharge/ cervicitis
What are complications of PID?
Chronic pelvic pain
Pelvic access
Can lead to sub fertility - adhesions, inc risk of ectopic pregnancy
Peritonitis
Fitz-Hugh Curtis syndrome (peri-hepatitis)
How is PID managed?
Broad spectrum antibiotics
Analgesia
Sexual partner screening
When are sperm cells able to move?
Tail of epididymis
What is the function of semen?
Transport medium
Nutrition
Buffering capacity
Role of prostaglandins in stimulating muscular activity in female tract
What is a normal ejaculate volume?
2-6ml
How many sperm cells are usually found in semen?
20million per mL
What is the normal motility level of semen?
> 50% motile
What is the normal fertilisation site?
Ampulla of uterine tube
What are the 4 human sexual responses?
Excitement phase Plateau phase Orgasm phase Resolution phase Males: final step - refractory phase
What are the 2 responses to cause an erection?
1 - psychogenic
2 - Tactile (sensory afferents of penis and perineum)
What are the somatic efferents of an erection?
1 - Pelvic nerve (PNS)
2 - Pudendal nerve (somatic)
What is the PNS innervation to the penis?
Fibres - Lumbar and sacral spinal levels
Pelvic nerve and pelvic plexus
Cavernous nerve to corpora and vasculature
What do the parasympathetic nerves release and what type of nerves are they that cause erection?
Activation of non-adrenergic non-cholinergic autonomic nerves to arteries releasing Nitric Oxide
From what two areas does NO get released to cause an erection?
NO released from endothelial cells and directly from nerves
What are 4 main categories of causes of erectile dysfunction?
Psychological (descending inhibition of spinal reflexes)
Tears in fibrous tissue of corpus cavernosa
Vascular causes
Drugs
How is emission of semen controlled?
Sympathetic control
It is movement of semen into prostatic urethra
Contraction of SM in prostate, vas deferens and seminal vesicles
How is ejaculation controlled?
Contraction of glands and ducts (smooth muscle)
Bladder internal sphincter contracts - preventing retrograde ejaculation
Rhythmic striatal muscle contractions (pelvic floor, perineal muscle ischiocavernosus, bulbospongiosus
Which spinal roots are part of the psychogenic pathway and reflexogenic pathway of erection and ejaculation?
Psychogenic pathway - T10-L2
Refelxogenic - S2-S4
What is the fertile time period of sperm and oocyte?
Sperm - 48-72hours
Oocyte - 6-24hours max
Period: Sperm deposition max 3days prior to ovulation - or on day of ovulation
What is the acrosome reaction?
Removal of the sperm outer coating to allow fusion with the oocyte
Sperm pushing through corona radiata
Binding of sperm surface receptor to ZP3 glycoprotein of zona pellucida
Triggers acrosome reaction
Digestion of zona pellucida
What is the acrosome?
Derived from golgi region of developing spermatid
Contains enzymes
Necessary for fertilisation
Release of what ion occurs following fusion of oocyte and sperm membranes
Calcium
What is blastocyst hatching?
Blastocyst hatches from zona pellucida
How many days post fertilisation is implantation complete?
12 days
What part of the uterus controls degree of invasion of the blastocyst?
Endometrium
What is the term used to describe implantation at a lower uterine segment?
Placenta praevia
Which part of the gonad develops in women and men?
Women - Cortex
Men - Medulla
What is congenital adrenal hyperplasia?
Autosomal recessive disorder
Adrenals produce androgens from cholesterol
CAH = 21 hydroxylase deficiency which is used in the process of cholesterol to androgen conversion
What happens with oestrogen levels in the ovaries during the ovarian cycle??
Day 1 - [GnRH] inc -> [FSH+LH] inc slightly -> Oestrogen released -> oestrogen -ve feedback on HPT -> inc [Inhibin] as more [oestrogen] -> inhibiting FSH release -> [oestrogen] continues to rise
Day 10-12 - Oestrogen becomes positive feedback -> inc [Oestrogen] -> inc [GnRH] -> inc [LH] dec [FSH] -> inc [Inhibin]
Day 14 - [Oestrogen] highest + [LH] surge (highest conc) + ovulation.
Day 14-16- [Oestrogen} rapidly declines to normal levels
Day 16-28 - [Oestrogen] remains level
What happens to progesterone levels during the ovarian cycle?
Stays level till day 12 when levels rise rapidly to maximal levels on day 22
They rapidly decline from day 22 to 28 if no fertilisation occurs and the corpus luteum does not maintain levels.
What are 6 important functions of progesterone on oestrogen-primed cells?
Basal body temp rises
Change in salt and water excretion -> salt and water retention when combined with oestrogen
Thickening of endometrium and development of spiral arteries
Thickening and acidification of cervical mucous to inhibit sperm transport
Thickening of myometrium but reduces its motility
Reduces fallopian tube motility, secretion and cilia activity
What blood test would be done to find out causes of primary amenorrhoea?
FSH
If high - problem at ovary
If low - problem at HPT/Pituitary
After giving birth how long can the lactation amenorrhoea method of birth control potentially work for?
6 months if amenorrheic
Can technically get pregnant within 21 days if the cycle starts right away
How does progesterone work as a hormonal contraceptive?
High dose -> enhances oestrogen -ve feedback on HPT -> dec LH and FSH
High dose -> inhibits +ve feedback of oestrogen -> no LH surge -> no ovulation
Low dose -> not inhibiting LH surge -> ovulation likely -> thicken cervical mucous
What are important contraindications to COCP?
Age
BMI
Migraine
Breast cancer Hx
How often does injectable progesterone only need to be done?
12 weekly - Progestogen injection - Depo provera
3 years - Progestogen implant
What is the difference between intrauterine system and intrauterine device?
IUS - progestogen releasing, 3-5year life
IUD - copper device, 5-10year life
How do you confirm if a vasectomy has been successful?
12-16weeks post surgery - check ejaculate for sperm
What are emergency contraception methods?
Emergency IUD
Pill - Ulipristal or levonorgesterel
What are the main differences between Ulipristal acetate and levonorgestrel?
Ulipristal - used within 5 days
Levonorgestrel - used within 3 days
What is the criteria method for contraceptive use?
UKMEC - UK medical eligibility criteria
Depends on Cervical cancer risk, cervical ectropion, or cervical intraepithelial neoplasia, Breast conditions - cancer, FMHx, BRCA1/2, Endometrial cancer, Ovarian cancer
What is the difference between primary and secondary sub fertility?
Primary - someone who’s never conceived a child in the past
Secondary - someone has had previous pregnancy but is finding it difficult to conceive again (includes abortion and ectopic)
What are the 5 main causes sub fertility?
Factors in the male - 30% Unexplained infertility - 25% Ovulatory disorders - 25% Tubal damage - 20% Uterine or peritoneal disorders - 10% Other - coital problems, concurrent health problems
What are the categories of ovulatory disorders that result in sub-fertility?
Group 1 - hypothalamic-pituitary failure -10%
Group 2 - hypothalamic-pituitary-ovarian dysfunction - 85%
Group 3 - ovarian failure - 5%
When would women be referred to fertility clinic?
Women of reproductive age not conceived after 1 year of unprotected vaginal sexual intercourse in the absence of any known cause of infertility
Early referral for women >36years old, known clinical cause of infertility or Hx of predisposed factors
What are the 5 areas in which the body needs to adapt for pregnancy
1 - volume support 2 - nutritional support 3 - waste clearance 4 - pregnancy maintenance 5 - childbirth
How does the body deal with volume support during pregnancy?
Volume expansion
Vasodilation
How does the body deal with nutritional support during pregnancy?
Inc respiration
Insulin resistance
Inc absorption
How does the body deal with waste clearance during pregnancy?
Inc GFR
Hepatocellular stimulation
How does the body deal with pregnancy maintenance during pregnancy?
Uterine quiescence
Immunologic sequestration
How does the body deal with child birth during pregnancy?
MSK
Clotting
What hormones drive the adaptations needed during pregnancy in the mother?
hCG Oestrogen Progesterone Relaxin hPL
What are immunological changes made during pregnancy?
Immunosuppressed state -
Higher attack rate and severity of certain viral pathogens i.e. varicella
May improve certain autoimmune conditions too e.g. psoriasis which is TH1 mediated
What are the respiratory changes during pregnancy?
Tidal volume increases by 30-40%
Increased in minute ventilation then by 40-50%
Increase in PaO2 and decrease in PCO2 ->
pH increases
Expiratory reserve volume decreases -20% as TV increases
Total lung capacity decreases by 5% as the diaphragm elevates to allow growth of foetus
What are cardiovascular changes seen in pregnancy?
Early pregnancy -> increased volume
Late pregnancy -> increase HR
Progesterone: smooth muscle relaxation -> Decreased SVR -> BP drops
Clotting: Increased pro-coagulants, decreased anticoagulants, reduced fibrinolysis
How does oestrogen increased stroke volume?
Oestrogen -> stimulates angiotensinogen from liver -renin-> angiotensin 1 -ACE-> adrenals to release aldosterone -> NaCl and H20 resorption from nephrons
Why do pregnant mothers seem anaemic in blood tests?
Dilutional anaemia
Changes in blood volume
Could also be iron/folate deficiency -> need to investigate
What are the renal and urinary tract changes seen in pregnancy?
Systemic vasodilation:
Increased GFR 50%
Decreased serum urea and creatinine by 25%
Decreased PCT absorption:
Glucosuria/ proteinuria
Structural:
Smooth muscle relaxation + obstruction= Increased size of kidneys and ureters, decreased urine speed through ureters
What are GI changes seen in pregnancy?
Decreased LOS tone: GORD, aspiration
Decreased gallbladder contractility: Gallstones,
Decreased small bowel movement :Mineral absorption, Constipation
Decreased large bowel movement: Water absorption
What are thyroid changes seen in pregnancy?
Overall pregnancy = euthyroid - imbalanced can affect foetal development
Oestrogen stimulates thyroid binding globulin hepatic production -> need to inc thyroxine production
hCG similar alpha-subunit to TSH -> weak stimulating effect at TSH
What are PTH and Ca2+ changes seen in pregnancy?
PTH levels rise despite slight drop in Ca2+
Placenta produces extra hydroxylase -> inc intestinal absorption
What happens to glucose metabolism in pregnancy?
Pregnancy = diabetogenic
Insulin resistance + increased insulin secretion
What hormones released by the placenta cause insulin resistance during pregnancy?
Placental lactogen, placental growth hormone, oestrogen, progesterone, cortisol
What 5 factors can cause impaired glucose metabolism during pregnancy?
Ethnicity Physical inactivity Obesity Dietary composition PCOS HTN
What is a risk with GDM of the foetus?
Foetal macrosomia
What are MSK changes seen in pregnancy?
Increased lordosis, kyphosis
Forward flexion of neck
Stretching of abdo muscles: impede posture, strain paraspinal muscles
Increased mobility of sacroiliac joints and pubic symphysis, anterior tilt of pelvis
What are the skin changes seen in pregnancy?
Melasma
Palmar erythema
Vascular spiders
Linea nigra
What is pre-eclampsia?
Hypertension + proteinuria
Usually presents in 3rd trimester
What are risk factors for pre-eclampsia?
Chronic or gestational HTN, pre-existing renal disease, diabetes, obesity, FMHx, first pregnancy, extremes of age, multiple gestation, IVF, pre-eclampsia in prior pregnancy
What is the pathogenesis of pre-eclampsia?
Impaired invasion of trophoblast leading to shallow invasion of spiral arteries - remains small caliber and of high resistance
Leads to hypo perfusion and ischaemia - systemic endothelial dysfunction
What are maternal complications of pre-eclampsia?
Seizure Cerebral haemorrhage Renal failure Pulmonary oedema DIC, thrombocytopenia Hepatic failure or rupture
What are foetal complications of pre-eclampsia?
Growth restriction Oligohydroamnios Placental infarct or abruption Foetal distress Premature delivery Stillbirth
How do you treat pre-eclampsia?
Stablise BP Monitor blood results Monitor baby MgSO4 for neuroprotection and seizure prevention Fluid restrict and monitor output Delivery of the baby
What is the placenta?
Flattened circular organ that nourishes and maintains the foetus through the umbilical cord
What is the week of 2’s in embryonic development
Outer cell mass= 2 distinct layers -> syncytiotrophoblast, cytotrophoblast
Inner cell mass= epiblast, hypoblast
Week 2
Of the 3 sacs during embryonic development what do they become?
Yolk sac - disappears
Amniotic sac enlarges
Chorionic sac (cavity) - occupied by the amniotic sac
What does implantation of the embryo achieve?
Basic unit of exchange: vili project into the mesenchyme
Anchor the placenta
Establish maternal blood flow within the placenta
What is a chorionic villus?
Placenta is a specialisation of the chorionic membrane
Finger like projections from the trophoblast layer enter the endometrium
Essentially one cell layer thick to allow maximal transport of substances but not mixing the blood circulations
What are potential implantation defects?
Implantation in wrong place: Placenta praevia Ectopic pregnancy Incomplete invasion: Placental insufficiency Pre-eclampsia
What controls the invasion of the embryo in implantation?
Transformation of the endometrium to the decidua (mucous membrane)
If no decidua -> ectopic pregnancy
If decidua too much -> implantation is not enough
What is a cotyledon?
This is the villus that leads to blood nutrient exchange
How many umbilical veins and arteries are there?
2 umbilical arteries and 1 umbilical vein
What are the endocrine hormones produced by the placenta?
Human: chorionic gonadotrophin, somatomammotrophin (human placental lactogen), thyrotrophin, corticotrophin
Progesterone, oestrogen
From what week of pregnancy does the placenta produce its own steroid hormones?
11th week
Why do contractions during labour sometimes cause foetal distress?
Contractions can prevent uterofoetal circulation by clamping down on spiral arteries and veins + umbilical vein and arteries.
What substances are actively transported across the placenta?
Amino acids
Iron
Vitamins
What immunoglobulin is transferred through the placenta and through which simple process?
IgG
Receptor-mediated endocytosis
During which embryonic periods is the embryo most susceptible to teratogenic insult?
Pre-embryonic - lethal effects
Embryonic - ++sensitive due to narrow windows of development of some systems
Foetal - +/- sensitive
After embryonic period risk of structural defects is low except the CNS
How does the foetus deal with a hypoxic environment in general?
Maintaining a large PO2 gradient from the maternal circulation and the foetal blood
Foetal Hb variant - lower PO2 more O2 is bound
Foetal haematocrit - higher therefore more Hb to carry more O2
Increased maternal production of 2,3DPG - secondary to resp alkalosis
Double bohr effect
Foetal HR slows to reduce O2 demand - Vagal stimulation leads to BRADYCARDIA
What is the duct that allows foetal blood to bypass the liver?
Ductus venous
At what point in the aorta does the ductus arteriosus join it?
After the right brachiocephalic artery + left common carotid artery + left subclavian artery
What hormones are necessary for foetal growth?
Insulin IGF1 and 2 Leptin EGF TGF-alpha
What are the problems with maternal malnutrition?
Symmetrical and asymmetrical growth restriction
CVD risk factor later in life
Why is a delayed birth bad for the foetus?
Affects lung growth >38weeks
The amniotic fluid is not needed after this time period and so starts to decrease in volume which affects lung growth
When does a foetus start producing urine?
9 weeks
What is the intramembranous pathway in the foetus?
Pathway that maintains the volume of amniotic fluid at a relatively constant amount
What is the name of the foetus’s first bowel movement?
Meconium
What is the name of the white waxy substance over the baby body after birth?
Vernix caseosa
What is the term used to describe removal of amniotic fluid for diagnostic testing?
Amniocentesis
Why is it normal for foetuses to have jaundice?
Foetal liver can not conjugate bilirubin due to immaturity of the liver and intestinal processes for metabolism, conjugation and excretion of bilirubin
What are the embryonic periods and how long do they last?
Pre-embryonic - 1-2weeks
Embryonic - 3-8 weeks
Foetal 9-38 weeks
How is pregnancy calculated?
Date of LMP
Conception weeks +2 weeks
Therefore term is 40 weeks
When does the embryo/foetus grow the most during gestation?
Foetal period - 9-38weeks is fastest growth
0-9 weeks there is small amount of growth but mainly placental growth
What is the crown-rump length and when is it used?
The distance from the top of the head to the bottom
Measured between 7 and 13 weeks to date the pregnancy and estimated date of delivery
How do the body proportions change during the foetal period?
9 weeks= head is approx half crown-rump length thereafter the body length, lower limb growth accelerates
How do you check for uterine expansion in a low tech method?
Symphysis-fundal height
What method of measurement of the foetus is used in the second and third trimesters?
Biparietal diameter
Abdominal circumference and femur length
What birth weights are normal and abnormal?
<2500grams = growth restriction 3500grams = average weight >4500grams = macrosomia
What are the 3 main reasons for low birth weight?
Premature
Constitutionally small
Intra-uterine growth restriction
What are the stages of lung development and during which weeks?
weeks 8-16= pseudoglandular stage - bronchioles form
weeks 16-26 = canalicular stage - budding of bronchioles to form respiratory bronchioles
weeks 26-term= terminal sac stage - differentiation of type 1 and 2 pneumocytes
What ways are the foetuses pulmonary system conditioned for development?
Breathing movements = practice breathing to improve the musculature for when it needs to breath
Fluid filled = amniotic fluid provides the right mediators to drive lung development
What is the threshold of viability of a foetus?
Limit beyond which the lungs will not be sufficiently developed to sustain life
It is only a possibility once the lungs have entered the terminal sac stage of development i.e. >24weeks
What is RDS?
Insufficient surfactant production
Pre-term delivery
What drug can be given to the mother if delivery of the foetus is unavoidable/ inevitable to help the lungs?
Glucocorticoid treatment
Hydrocortisone IV - increases surfactant production in the foetus
When is the definitive foetal HR achieved?
15 weeks
What are the terms used to describe too much or too little amniotic fluid and what are their implications?
Oligohydramnios = too little - placental insufficiency, foetal renal impairment cause Polyhydramnios = too much - foetal abnormality - unable to swallow - blind ending oesophagus or neurological problem etc
After how many weeks postpartum should the body return to normal and what is this period of time called?
6 weeks
Puerperium
How does oxytocin work in the breast?
Contraction of my-epithelial cells situated around the alveolae -> expel milk -> milk collecting ducts -> longitudinal muscle cells -> dilate -> larger flow of milk towards nipple
Why is there a 90minute milk ‘let down’?
Oxytocin is released in a pulsatile manner from the pituitary
What are the protective aspects of breast milk?
Lactoferring - binds iron preventing proliferation of E. coli
Bacteriocidal enzymes
Lymphocytes, polymorphs, plasma cells
IgA
What are the layers of muscle of the uterus?
Longitudinal - outermost
Interlacing - middle
Circular - innermost
Define labour
Process where the foetus, placenta and membranes are expelled through the birth canal
When does labour spontaneously start and how long will it be?
37-42 weeks
Within 18hours assuming no complications
What are the stages of labour?
1st stage - onset of regular contractions until the cervix is fulled dilated (latent and active)
2nd stage - cervix is fully dilated -> birth of baby
3rd stage - birth of the baby -> delivery of placenta and membrane
What are the latent, active and transition stages of labour?
latent - painful contractions + cervical effacement and dilation up to 4cms
Active - regular painful contractions and progressive dilation from 4cms
Transition - 8-10cm cervix dilation
What is the difference between Braxton Hicks contractions and the Ferguson reflex?
Braxton Hicks - practice sporadic uterine contractions
Ferguson - positive feedback loop of pressure on the cervix and vaginal walls causing contractions
What is the mechanical initiation of labour?
Uterus grows and stretches -> stretch detected in wall of uterus -> critical degree of stretch -> contractions
What is the hormonal initiation of labour?
Just before labour level of [progesterone] decreases and [oestrogen] rises
Prostaglandins released from placenta, decidua
Oxytocin released from posterior pituitary
Prostaglandins -> activate collagenases -> digest collagen in cervix -> cervix softens
What hormones are important in labour?
Progesterone, oestrogen Prostaglandins Oxytocin Endorphins Adrenaline - acts against oxytocin effects
Where do uterine contractions begin?
Cornua of the uterus
Entry of the fallopian tube into the uterus
What is effacement of the cervix?
The cervix shortens and widens to go from a structure of support to a birth canal
What is the plug of mucous that comes away as the cervix dilates called?
Operculum
What are the 4 stages of the second stage of labour?
Transition from 4cm cervix to >4cm
Active phase - contractions stronger and longer but less frequent - spontaneous rupture of operculum
Latent phase - period of calm - 10cm cervix dilation and contractions stop temporarily
Perineal phase - descending foetus
How long is the second stage of labour usually?
Nulliparous women - 3 hours
Multiparous women - 2 hours
More than these figures - referral to obstetrician
Are vulval cancers related to HPV?
70% not but 30% yes
Usually HPV 16 if yes
IF not usually to do with longstanding inflammatory conditions
How do vulval cancers spread?
Direct extension - anus, vagina, bladder
Lymph nodes - inguinal, iliac, para-aortic
Distant mets - Lungs, liver
What is cervical intraepithelial neoplasia?
Dysplastic changes to the cells
Confined to the cervical epithelium
Caused by HPV infection
Divided into CIN 1/2/3
How does CIN staging develop?
CIN1 - mild dysplasia a few cell layers thick
CIN2 - moderate dysplasia More than a few cell layers thick but not full thickness
CIN3 - severe dysplasia with full thickness
SCC - Invasive carcinoma - full thickness plus breach of basement membrane
How do you treat CIN?
CIN1 - often regresses spotaneously
CIN2+3 - needs treatment - Large loop excision of transformation zone
What are the 2 main types of cervical cancer?
Squamous cell carcinoma - most common
Adenocarcinoma - rarer from endocervical glandular cells
What are causes of endometrial hyperplasia?
Excessive oestrogen
Endogenous - obesity + early menarche + oestrogen secreting tumours
Exogenous - unopposed oestrogen replacement therapy + tamoxifen
Irregular cycles - PCOS
What are the 2 main forms of endometrial cancers?
Endometrioid adenocarcinoma - most common, arises from hyperplasia
Serous adenocarcinoma - less common, more aggressive, poorly differentiated cells
What are the stages of endometrial cancer?
Stage 1A- endometrium Stage 1B - endometrium + myometrium
Stage 2 - cancer grown into cervix
Stage 3A - spread to ovary, Stage 3B - spread to vagina
Stage 3C - spread to lymph nodes
Stage 4 - in bladder/ bowel wall, Stage 4B - in other organs elsewhere
How does serous adenocarcinoma of the endometrium spread to other organs?
Transcoelomic
Exfoliates -> fallopian tubes -> peritoneal surface
How are endometrial cancers treated?
Hysterectomy
Bilateral salpingo-oophorectomy
+/- lymph nodes
+/- chemo/ radiotherapy
How do leiomyoma’s present?
Asymptomatic
Pelvic pain
Heavy periods
Urinary frequency
What are the serum markers for ovarian cancer?
CA-125
BRCA1/2 - tumour suppressor genes, high grade serous cancers
What is a teratoma?
Germ cell tumour
Mature - benign
Immature - malignant
Monodermal - highly specialised
What are testicular cancer tumour markers?
beta-HCG - choriocarcinoma
Alpha fetoprotein - yolk sac tumour
