Week 1 RNU Lectures Flashcards
What two substance pass through the urethra?
Sperm and urine
What does the urogenital tract originate from?
Intermediate mesoderm
What are the three sets of kidney structures during development?
Pronephros
Mesonephros
Metanephros
Where are the pronephros found?
Cervical region
Where are the mesonephros found?
Abdominal region
Where are the metanephros found?
Pelvic region
How are the three sets of kidney structures formed during development?
cranial to caudal and chronological sequence
What are the pronephros?
Rudimentary and non-functional structures that begin to regress by week 4
How do the pronephros form?
Intermediate mesoderm starts to thicken and forms 7-10 solid cell groups in the cervical region
What are the mesonephros derived from?
Intermediate mesoderm from the upper thoracic and upper lumbar segments
What is the mesonephros?
A solid rod of intermediate mesoderm in the future abdominal area. It has everything needed to be functional but is not. Contributes cells to the genital ridge and eventually starts to regress
What is the metanephros?
The definitive kidney
When does the metanephros develop?
In week 5 and is functional by week 11
How do the excretory units of the metanephros form?
Develop from the metanephric mesoderm.
Formed from 2 parts at the bottom of the developing structure:
- Ureteric bud
- Metanephric cap
How is the metanephric cap formed?
Mesoderm around the ureteric bud forms mesenchyme which is the metanephric cap
What sources does the definitive kidney form from?
- Metanephric mesoderm (forms the excretory units)
- Ureteric duct (collecting system for excreted stuff)
What is the cloaca?
Posterior orifice that serves as the only opening for the intestinal, reproductive and urinary tracts at early stages
What is the ureteric bud?
A protrusion of mesonephric duct that allows urine drainage from the developing kidney
What does the cloaca begin as?
Hindgut (endodermal lining)
What divides the cloaca?
The Urorectal septum by fusing with the cloacal membrane
What does the division of the cloaca form?
- Anterior urogenital sinus
- posterior rectal/anal canal
What does the bladder form from?
the urogenital sinus and caudal parts of the mesonephric duct
What lines the bladder?
Endoderm
When is genetic sex determined?
At fertilisation
When do the gonads acquire morphological characteristics?
Week 7 of development
What are the three steps of the development of the reproductive tract?
- Genital duct development
- Gonadal development
- External genitalia development
What is present during the indifferent stage (weeks 5-6)?
2 pairs of genital ducts
- paramesonephric ducts (Mullerian) FEMALE
- mesonephric (Wolffian) ducts MALE
What is the function of the mesonephric ducts?
- drain urine from the mesonephric kidney
- an essential role in the development of the male reproductive system
What happens to the mesonephric ducts under the influence of testosterone?
forms the ductus deferens and ejaculatory duct when mesonephros vanishes
What happens to the mesonephric ducts in females?
almost completely disappears, leave a few non-functional remnants
What happens to the paramesonephric ducts in males?
degenerate due to the action of anti-Mullerian hormone. This is a protein made by the Sertoli cells of the testis
What do the paramesonephric ducts form in females?
- Cranial portion forms uterine tubes
- Caudal portion fuses to form the uterovaginal primordium (uterus and superior vagina)
What do the gonads initially appear as?
A pair of longitudinal ridges (on top of the urogenital ridge)
Where do primordial germ cells originate?
The yolk sac
How do primordial germ cells move from the yolk sac and to where?
To the genital ridge via the dorsal mesentery
What happens if the primordial germ cells don’t arrive into the gonadal ridge by week 6?
The ridges develop no further and the gonads don’t develop
What type of structure do the primordial germ cells form in?
A cord like structure - primitive sex cords
What does the Y chromosome encode?
SRY - Sex determining Region of Y chromosome
What does SRY act on and cause?
Acts on somatic cells causing proliferation of the sex cells
What happens to the primitive sex cords in male development?
They become horseshoe shaped and break up into tubules
What do Leydig cells produce?
Testosterone
What do Sertoli cells produce?
Anti-Mullerian hormone
What forms to separate cords from the surface epithelium (male gonadal development)
Dense connective tissue
- tunica albuginea
What happens to the testis cords in puberty?
- They acquire a lumen
- join with the rete testis
- join with efferent ductules
- rete testis and mesonephric duct link to form the ductus deferens
What does WNT4 do?
“ovary determining gene”
What happens to the primordial germ cells in female development?
They divide by mitosis creating a pool of oogonia
What happens to the oogonia at the beginning of the 4th month of gestation?
They enter meiotic arrest and are now oocytes
How are the external genitalia formed?
- a pair of cloacal folds develop around cloacal membrane
- join to form the genital tubercle at the cranial end – this will form the penis and the clitoris
- caudally the cloacal folds are subdivided:
• urethral folds in front - form labia minora in female
• anal folds behind
• genital swellings then appear on either side of the urethral folds
• form scrotal swellings in male, labia majora in the female
How is the urethra formed?
- From middle pelvic part of urogenital sinus
- In males, androgens from fetal testis cause genital tubercle to elongate into phallus
• phallus pulls urethral folds forward
• they form lateral walls of urethral groove and close over urethral plate to form penile urethra
• terminal part of male urethra (external urethral meatus) from surface ectoderm
What is hypospadias?
The urethra is open on the underside of the penis
How does the prostate gland form?
develops as outgrowths from the prostatic urethra
How do the bulbourethral glands form?
develop as outgrowths from penile urethra
How does the lower part of the vagina develop?
two outgrowths from urogenital sinus – sinovaginal bulbs – fuse to form a vaginal plate, hollows to form a cavity
How does the penis form?
androgens from fetal testis cause genital tubercle to elongate into phallus
o phallus pulls urethral folds forward
o they form lateral walls of urethral groove and close over urethral plate to form penile urethra
o terminal part of male urethra (external urethral meatus) from surface ectoderm
What are circulating oestrogens a mixture of?
Oestrone and oestradiol
Where is oestrone secreted from?
directly from the ovary or converted from androstenedione (via aromatase)
Where does oestradiol come from?
Produced by the ovary, derived by direct synthesis in developing follicles or through conversion of oestrone
What are oestrogens involved in?
Development of female secondary sex characteristics
What could happen if someone had issues with aromatase?
They could have issues with sexual development
What hormones do the ovaries produce?
androstenediol, dehydroepiandrosterone (DHEA) and small amounts of testosterone
Where does half of the daily production of androstenediol and DHEA and essentially all of the sulphated form of DHEA (DHEAs) come from?
The adrenal gland
What is DHEA?
An abundant circulating steroid hormone in humans and is a metabolic intermediate in the biosynthesis of androgens and oestrogens
What is DHEAs?
The sulfate ester of DHEA, catalysed by sulfotransferase in the adrenal, liver and small intestine.
In the blood, levels of DHEAs are 300x higher than DHEA and is more stable for measuring
When in the menstrual cycle are progestogens particularly important?
In the 2nd half
How are progestogens made?
From cholesterol via pregnenolone
Where are progestogens made?
Primarily in the corpus luteum, the adrenal glands, and, during pregnancy, the placenta
What are the roles of progestogens?
- Endometrial development
- smooth muscle control
- Maintenance of pregnancy - placenta (establishing and keeping pregnancy)
- Mammary gland development especially preparing breasts for lactation
What are some disorders relating to steroidogenesis?
- Congenital adrenal hyperplasia
- aromatase deficiency
- Aromatase excess
What causes congenital adrenal hyperplasia?
- 21-hydroxylase deficiency
- Deficiency in 11B- hydroxylase activity
What are the symptoms of Congenital adrenal hyperplasia?
- Ambiguous genitalia
- precocious puberty
- anovulation
- Hirsutism (excess hair)
- Steroid crisis
What happens in aromatase deficiency?
Prevents oestrogen synthesis
can lead to ambiguous genitalia
What happens in aromatase excess?
There is excessive conversion of androgens to oestrogens which can lead to the feminisation of male genitalia
What is the axis that regulates female reproduction?
Interactions between the Hypothalamic-pituitary-ovarian axis and the uterus
What happens when the hypothalamus secretes gonadotrophin releasing hormone (GnRH)?
GnRH –> anterior pituitary releases gonadotrophins (FSH and LH) –> target the gonads
What is the 2nd level of hormonal control of female reproduction?
The pituitary gland
What hormones does the anterior pituitary secrete?
FSH, LH
What does the posterior pituitary gland secrete?
Oxytocin
What is oxytocin involved in?
childbirth and lactation
What is the 3rd level of hormonal control of female sexual reproduction?
The ovaries and the placenta
What triggers follicle maturation and regulate steroid hormone production in the ovary
Levels of FSH and LH
What is the principle secretory product of the ovarian follicle after ovulation?
Progesterone
What does the placenta produce?
Oestrogens, progesterone and HcG
What is the function of FSH?
- Initiates the recruitment of follicles
- supports the growth of the follicle, especially the granulosa cells
What is the function of LH?
- supports theca cells - a shell that forms around the follicle (theca interna and externa)
- LH surge triggers ovulation
What are the stages of the menstrual cycle in terms of the ovary?
follicular (preovulatory) phase and luteal (postovulatory) phase
What are the stages of the menstrual cycle in terms of the endometrium?
The proliferative phase and the secretory phase
When is there the highest level of LH?
Ovulation
When is the highest level of oestrogens?
Ovulation
When is the highest level of progesterone?
the middle of the secretory/luteal phase (postovulatory)
This is at day 21 of the cycle (if ovulation has occurred)
What happens during the follicular phase?
- the growth of a dominant follicle
- Progesterone production is low but oestrogen is rising
What are the stages of the development of the follicle?
Primordial follicle –> primary follicle –> secondary follicle –> Graafian/ tertiary follicle
What are the layers of the late primary follicle?
Granulosa cells, theca cells, stromal cells
What happens during development of the secondary follicle?
- FSH secretion increases slightly, stimulating further growth of recruited follicles.
- Circulating LH levels increase slowly, beginning 1 to 2 days after the increase in FSH.
- Theca develops – follicle gains an independent blood supply
- Granulosa cells develop FSH, oestrogen and androgen receptors
What hormone do developing follicles produce?
inhibin
What does inhibin do during follicle development?
Inhibits FSH secretion but not LH secretion
What are the uterine changes in the proliferative phase?
Oestrogens from the ovary act on the endometrium
- thickening of the stroma
- elongation of the uterine glands
- growth of the spiral arteries
What happens around the time of ovulation?
Towards the end of the proliferative phase, rising oestrogens;
- Increase responsiveness of the pituitary to GnRH
- surge in hypothalamic secretion of GnRH
High levels of oestradiol trigger LH secretion and there is a surge of LH
What happens during the luteal/ secretory phase?
- Formation of the corpus luteum (yellow body) from the follicle
- The corpus luteum secretes primarily progesterone in increasing quantities, peaking at about 6 to 8 days after ovulation
- Progesterone stimulates development of the secretory endometrium
Why does the endometrium become spongy?
To encourage implantation
What does the corpus luteum eventually form?
The corpus albicans
What causes the corpus luteum to change into the corpus albicans?
Rising progesterone levels inhibit LH production
What causes menstruation?
When the corpus luteum becomes the corpus albicans the secretion of oestrogen and progesterone stop and the endometrial lining is no longer maintained.
What happens during menstruation?
- Leukocyte infiltration of endometrium – cells start to die and when blood supply gets cut off get massive ischaemia
- Constriction and breakdown of spiral arteries – ischemia
- Menstruation begins
What are the hormonal effects on the vagina through the menstrual cycle?
Early follicular phase - oestrogen is low - vaginal epithelium is thin and pale
Late follicular phase - oestrogen increases - Squamous cells mature causing the epithelium to thicken
Luteal phase - mature squamous cells shed as cellular debris
What are the hormonal effects on the cervix through the menstrual cycle?
Late follicular phase - oestrogen levels increasing - Increased cervical vascularity and water mucus
Luteal phase - progesterone levels increasing - Thicker cervical mucus reduces elasticity
What is PCOS?
A common endocrine abnormality that often presents clinically with infertility, Amenorrhea and weight gain
What causes PCOS?
The LH and FSH secretion is out of balance and there is no negative feedback. Increased LH leads to increased androgen production
What is the management of PCOS?
- weight loss - loss of 5% of body weight can cause significant improvement of the condition
- Contraceptive pill - can induce regular periods
- metformin - can lower insulin levels
- fertility treatment (if needed)
What is the female reproductive tract made up of?
- Paired gonads - Ovaries
- duct system - uterine tubes, uterus, vagina
What is the function of the ovaries?
Produces gametes and hormones
What is the blood supply to the ovaries?
Ovarian artery - arises from the aorta at level of the renal artery
What is the venous drainage of the ovaries?
Ovarian vein - drains to IVC on right and to the left renal vein on the left
What ligaments support the ovaries?
- Broad ligament
- Ovarian ligament
- Suspensory ligament of the ovary
What is the broad ligament?
A peritoneal sheet draped over the uterus and uterine tubes.
The ovaries attach to the posterior layer by short mesentery ‘the mesovarium’
What is the ovarian ligament?
A fibrous cord that links the ovary to the uterus
What is the suspensory ligament of the ovary?
Connects the lateral wall of the pelvis to the ovary and carries the ovarian artery and vein
Where are the fallopian tubes found?
In the free margin of the broad ligament.
They are not connected directly to the ovary
How does the egg get from the ovary to the tube?
the egg is released and is sucked into the tube by the fimbriae
What are the parts of the fallopian tube?
- infundibulum
- ampulla
- isthmus
- interstitial/uterine section
What is the infundibulum of the fallopian tube?
A funnel shaped opening to the peritoneal cavity, fringed by finger like fimbriae
What is the ampulla of the fallopian tube?
The middle section where fertilisation occurs
What is the isthmus of the fallopian tube?
A short narrowed section that is connected to the uterine wall
What are the parts of the uterus?
- Body
- Cervix
- Fundus
- Isthmus
What is the fundus of the uterus?
The rounded part that projects up above the level of the uterine tubes
What is the isthmus of the uterus?
The narrowing between the body and cervix
What separates the parts of the cervix?
Internal and external os
What are the parts of the cervix?
Endocervical canal and ectocervix
What is a bicornuate uterus?
Failure of fusion of the uterus when it is forming. People with this condition can get pregnant and have a healthy pregnancy but it can be harder.
What is the term to describe the position where the body of the uterus is bent forwards on the cervix?
Anteflexion
What is the term to describe the position of the uterus bent forward at a right angle to the vagina?
Anteversion
What is the normal position of the uterus in relation to other organs?
Anteverted, anteflexed
What is it known as if the uterus is in the opposite position to normal?
retroflexion and retroversion
What is the blood supply to the uterus?
Uterine artery - branch of the internal iliac artery
What is the venous drainage of the uterus?
Uterine vein - drains to the internal iliac vein
What is the male reproductive tract made up of?
- paired gonads - testes
- Duct system - closely associated with the urinary system
- accessory glands - prostate, seminal vesicles, bulbourethral glands
What makes up the wall of the scrotum?
Skin Dartos muscle External spermatic fascia Cremasteric fascia Internal spermatic fascia Tunica vaginalis
What is the function of the dartos muscle?
It is smooth muscle that gives the scrotum its crinkle
What is the function of the cremaster muscle?
skeletal muscle that contracts to raise the testis in cold weather (cremasteric reflex)
What is the tunica vaginalis?
A closed sac of peritoneum that has visceral and parietal layers that cover the testes
What is in between the two layers of the tunica vaginalis?
A film of peritoneal fluid
What is the duct system of the testes made up of?
Seminiferous tubule –> straight tubule –> rete testis –> efferent ductules –> epididymis –> ductus deferens
What is the epididymis?
A very coiled tube that is coiled so tightly you can see it clearly.
It has a head body and tail
What epithelium lines the epididymis?
Pseudostratified columnar epithelium with stereocilia
What is the function of the stereocilia in the epididymis?
They increase the area for fluid absorption and can monitor and adjust the fluid composition
What is the blood supply to the testes?
Testicular artery
What is the venous drainage of the testes?
Pampiniform plexus –> testicular vein –> IVC (on right) Renal vein (on left)
What is the structure of the ductus deferens?
Thick walled with smooth muscle in the wall which contracts by peristalsis at emission.
It is 45cm long
Where does the ductus deferens run?
The spermatic cord through the inguinal canal
What are the seminal vesicles?
Coiled tubes that secrete an alkaline viscous fluid which helps them to neutralise the acid in the female tract
What does the fluid in the seminal vesicle contain?
- fructose - used for ATP production by sperm
- Prostaglandins which aid sperm motility and may also stimulate muscle contraction in the female tract
Where is the prostate gland found?
Surrounds the beginning of the urethra
What is the function of the prostate gland?
secretes a slightly acidic fluid containing citrate (used by sperm for ATP production), acid phosphatase and proteolytic enzymes which liquefy coagulated semen
What are the bulbourethral glands?
Pea sized glands that produce a mucus like secretion
What does the trophoblast become?
Extraembryonic membranes
What two layers does the trophoblast differentiate into?
- The proliferating inner villous cytotrophoblast (vCTB)
- The non-dividing outer multinucleate layer called the syncytiotrophoblast
When do the lacunae develop?
By day 8 post conception
What are lacunae?
Fluid filled spaces
What happens when they cytotrophoblast cells migrate?
The form villous projections that extend towards the maternal basal plate
When do tertiary villi form?
By the third week of gestation
What do the tertiary villi consist of?
An outer monolayer of syncytiotrophoblast, invaded by an inner layer of cytotrophoblast cells and vascularised with foetal capillaries
What is the chorionic plate?
The foetal side of the placenta
What is the basal plate?
The maternal side of the placenta
What is decidua?
A shiny surface on the basal plate that is the endometrium during pregnancy
What is pregnancy induced hypertension?
Hypertension that generally occurs in the 2nd half of pregnancy in the absence of proteinuria
What is pre-eclampsia?
Hypertension occurring typically after 20 weeks with associated oedema and proteinuria
How common is pre-eclampsia?
It effects up to 6% of UK pregnancies
What happens if pre-eclampsia develops further?
It can turn into eclampsia
What is eclampsia?
Fits or convulsions associated with the features of pre-eclampsia if severe can lead to maternal and/or foetal death
How common is eclampsia?
Occurs in 1-2% of pregnancies
What is pre-term birth?
Delivery at <37 weeks of gestation
What is are the different levels of pre-term birth?
Extreme preterm = <28 weeks
Very preterm = 28-32 weeks moderate to late preterm = 32-37 weeks
What percentage of pregnancies are preterm?
7-8% of pregnancies
What is foetal growth restriction (FGR)?
The failure of the foetus to reach its ‘genetically predetermined growth potential’
What is the outcome of foetal growth restriction?
Results in birthweight below 5th centile of individualised birthweight ratio (IBR) charts
What may be associated with foetal growth restriction?
- abnormal umbilical artery blood flow on doppler ultrasound and/or oligohydramnios
- Pre-eclampsia and other complications of pregnancy
What is foetal growth restriction a risk factor for?
- still birth
Survivors are also at increased risk of neonatal and adulthood diseases
What is the definition of pre-eclampsia?
new onset hypertension (systolic >140 or diastolic >90 mmHg) occurring after 20 weeks’ gestation with new proteinuria (protein: creatinine ratio >30mg/mmol)
How is pre-eclampsia treated?
There is not a cure but there are aspects of the condition that can be treated
What are factors thought to have a role in pre-eclampsia?
- Genes
- The placenta
- The immune response
- Maternal vascular disease
What does Iatrogenic mean?
illness caused by medical treatment or examination
Why is Pre-eclampsia a major cause of pre-term birth?
Delivering the baby and the placenta is the only ‘cure’ for pre-eclampsia
What are the symptoms of pre-eclampsia?
- Hypertension
- proteinuria
- Oedema - hands feet face
Severe pre-eclampsia: - Headaches
- blurred/flashing vision
- Pain in upper right abdomen
- Nausea/vomiting
- Heartburn (that doesn’t go away with antacids)
- rapid oedema
What are risk factors for pre-eclampsia?
- First pregnancy (/first with new partner/ first in 10 years) - immunological hypothesis for pre-eclampsia
- a relative has already had pre-eclampsia
- high maternal age (>40)
- High maternal BMI/ weight (BMI >35 or weight >90kg)
- Multiple pregnancy
- Existing hypertension
- some evidence suggests that women who are pregnant from egg donation are more susceptible
What are the three step hypotheses for pre-eclampsia?
- Abnormal placentation
- abnormal maternal response to placental trigger
- Organ / systems failure
What is abnormal about placentation in pre-eclampsia?
Normally extra villous trophoblast cells invade into the maternal endometrium, myometrium then spiral arteries
Remodel the coiled vessels: from low flow, high resistance to become wider, high flow, low resistance channels
In pre-eclampsia this doesn’t happen
What is ART?
Assisted reproductive technology
What is the abnormal maternal response that occurs in pre-eclampsia?
- maternal response to placental dysfunction
- Hypoxia and/or ischaemia-reperfusion injury causes increased free radicals and inflammatory mediators = syncytiotrophoblast cellular stress
- excess release of placental factors (soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sENG) which sequester circulating vascular endothelial growth factor (VEGF) and placental growth factor (PlGF)
- Maternal circulation = inflammatory response and endothelial dysfunction – lipid, insulin resistance, coagulation
What is the endothelial dysfunction in pre-eclampsia?
- Excessive maternal systemic inflammatory response to pregnancy has been suggested to be responsible for endothelial dysfunction leading to cellular activation and/or damage
- endothelial dysfunction is considered to be central in the pathogenesis of pre-eclampsia
Why is it suggested that pre-eclampsia could be more than one disease?
- early onset vs late
- rapid onset vs slow
- with and without growth restriction
What are the treatment options for pre-eclampsia?
- Offer labetalol to treat hypertension in pregnant women with PE
- Offer nifedipine for women in whom labetalol is not suitable, and methyldopa if labetalol or nifedipine are not suitable.
- Base the choice on any pre-existing treatment, side-effect profiles, risks (including foetal effects) and the woman’s preference.
What foetal monitoring should be carried out in women with pre-eclampsia?
repeat ultrasound for foetal growth and amniotic fluid volume assessment or umbilical artery Doppler velocimetry every 2 weeks, with subsequent surveillance and monitoring determined by the findings of these scans
What are some concerns in mothers with pre-eclampsia that could cause admission to hospital?
• sustained systolic blood pressure of 160 mmHg or higher
• any maternal biochemical or haematological investigations that cause concern, for example a new and persistent:
o rise in creatinine (90 micromol/litre or more, 1 mg/100 ml or more) or
o rise in alanine transaminase (over 70 IU/litre, or twice upper limit of normal range) or
o fall in platelet count (under 150,000 cells/microlitre)
• signs of impending eclampsia
• signs of impending pulmonary oedema
• other signs of severe pre-eclampsia
• suspected foetal compromise
• any other clinical signs that cause concern
What could cause an early birth to be considered in PE cases?
- inability to control maternal BP despite using 3 or more classes of antihypertensives in appropriate doses
- maternal pulse oximetry less than 90%
- progressive deterioration in liver function, renal function, haemolysis, or platelet count
- ongoing neurological features, such as severe intractable headache, repeated visual scotomata, or eclampsia
- placental abruption
- reversed end-diastolic flow in the umbilical artery doppler velocimetry, a non-reassuring cardiotocograph, or stillbirth
