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Semester 4 Revision > Repro > Flashcards

Repro Flashcards

1
Q

What is sexual determination? (3)

A

A genetically controlled process dependent on the ‘switch’ on the Y chromosome
Chromosomal determination of M/F
Contiguous with sexual differentiation + consists of several stages

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2
Q

What is sexual differentiation? (2)

A

Process by which internal + external genitalia develop as male or female
Contiguous with sexual determination + consists of several stages

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3
Q

Stages of sexual differentiation (5)

A

Genotypic sex -> gonadal sex -> phenotypic sex -> legal sex -> gender identity

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4
Q

What is the SRY gene + what is its role? (3)

A

Sex-determining region Y gene

Switches on briefly on during embryo development (> week 7) + makes the gonad into a testis

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5
Q

What happens in the absence of the SRY gene? (1)

A

Ovaries develop

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6
Q

What important hormone does the testis produce and which cells are developed to produce them? (4)

A

Sertoli cells produce anti-Mullerian hormone (AMH)

Leydig cells produce testosterone

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7
Q

What do products of testis influence? (3)

A

Further gonadal + phenotypic sexual development e.g. regression of Mullerian duct + development of Wolffian duct

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8
Q

Straight after fertilisation, what are the pair of gonads said to be? (1)

A

Bipotential

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9
Q

Describe primordial germ cell migration (3)

A

~ 3wks, initially small cluster of cells in yolk sac epithelium expands by mitosis
Then migrate to connective tissue of hind gut, to the region of the developing kidney + on to genital ridge - completed by 6wks
Become sperm + oocytes

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10
Q

Generalised formation of the primitive sex chords (1)

A

Cells from germinal epithelium overlying the genital ridge mesenchyme migrate inwards as columns called the primitive sex cords

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11
Q

Describe the formation of the male primitive sex cords (3)

A

Expression of SRY
Penetrate the medullary mesenchyme + surround PGCs to form testis cords
Eventually become Sertoli cells which express AMH

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12
Q

Describe the formation of the female primitive sex cords (3)

A

No SRY expression
Sex cords are ill-defined + do not penetrate deeply but instead condense in the cortex as small clusters around PGCs
Eventually become Granulosa cells

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13
Q

Where do mesonephric cells originate? (1)

A

Originate in mesonephric primordium which are just lateral to the genital ridges

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14
Q

What do mesonephric cells form in males? (4)

A

Under influence of pre-Sertoli cells, expressing SRY
Vascular tissue
Leydig cells (synthesis testosterone, do not express SRY)
Basement membrane - contributing to formation of seminiferous tubules + rete-testis

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15
Q

What to mesonephric cells form in females? (3)

A

Without influence of SRY
Vascular tissue
Theca cells (synthesis androstenedione which is a substrate for estradiol production by the granulosa

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16
Q

Mullerian ducts? (2)

A

Most important in female

Inhibited by male AMH

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17
Q

Wolffian ducts? (3)

A

Most important in male
Stimulated by testosterone (Leydig cells)
AMH causes regression of Mullerian ducts (Sertoli)

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18
Q

What is DHT and what does it cause? (5)

A

Dihydrotestosterone, a more potent form of testosterone
Binds to testosterone receptor
Causes differentiation of male external genitalia
- clitoral area enlarges to penis
- labia fuse + become more ruggated to form scrotum
- prostate forms

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19
Q

How is testosterone converted to DHT? (2)

A

By the enzyme 5-α-reductase

Adds a hydrogen

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20
Q

What are some disorders of sexual differentiation? (3)

A

Gonadal dysgenesis
Sex reversal
Intersex

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21
Q

What is meant by gonadal dysgenesis? (2)

A

Incomplete sexual differentation

Usually missing SRY (in male), or partial/complete of second X (in female)

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22
Q

What is meant by sex reversal? (1)

A

Phenotype doesn’t match genotype

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23
Q

What is intersex? (2)

A

Some components of both tracts/ambiguous genitalia

Sex of infant difficult to determine

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24
Q

What is androgen insensitivity syndrome (AIS)? (3)

A

When XY individual makes testosterone but it has no effect (possibly due to problem with receptor signalling)
Wolffian + Mullerian duct absent (AMH but ineffective testosterone) so no internal genitalia
External genitalia appear female (as no DHT effect)

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25
Q

Presentation of complete AIS and diagnosis? (5)

A

Appear completely female at birth + assigned female gender despite being XY
Have undescended testes (ultrasound)
Usually present with primary amenorrhoea
Lack of body hair
Ultrasound scan + karyotype with male levels of androgens but no response to androgens

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26
Q

Presentation of partial AIS?

A

Varying degrees of penile + scrotal developments - from ambiguous genitalia to large clitoris

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27
Q

Treatment of AIS?

A

Surgery was universal but now considered optional/best delayed
Decisions made on potential
Very difficult for patients and parents

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28
Q

What is 5-α-reductase deficiency? (4)

A

Testosterone made by XY individual but not DHT
Working testosterone receptor so Wolffian ducts form (male internal genitalia)
But no DHT therefore female external genitalia/ambiguous
Testes form, AMH acts, testosterone acts

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29
Q

What is the presentation + incidence of 5-α-reductase deficiency? (2)

A

Incidence varies enormously - autosomal recessive + can depend on inter-related marriage
Degree of enzyme block varies, as does presentation

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30
Q

What happens at puberty in 5-α-reductase deficiency? (1)

A

Need to assess potential as high testosterone level, which occur at adrenarche + puberty may induce virilisation

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31
Q

What is Turner syndrome? (6)

A 
45XO
Failure of ovarian function
Ovaries form as no SRY
Mullerian ducts form as no AMH
No Wolffian ducts as no testosterone
External genitalia is female
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32
Q

What are features of Turner syndrome? (5)

A

Streak ovaries (ovarian dysgenesis) - shows we need 2 Xs for ovarian development
Uterus + tubes are present but small
Other defects in growth + development e.g. morphological/thyroid/kidney problems
May be fertile
Many have mosaicsm

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33
Q

What is the link between cholesterol and steroid structure? (2)

A

Cholesterol structure = 3x 6-sided rings, 1x 5-sided ring + tail
All steroids have some structure as cholesterol but with different tail lengths + sometimes groups on rings are moved around

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34
Q

What is congenital adrenal hyperplasia (CAH)? (2)

A

Most common cause of XX female being exposed to high levels of androgens in utero
In females, masculinisation of external genitalia occurs

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35
Q

What happens in CAH? (4)

A

Absence of 21-hydroxylase enzyme (pathway block)
Failure to synthesise cortisol + so reduced -ve feedback effect on ACTH
High levels of ACTH stimulate adrenal hyperplasia + excessive androgen production
Mimics DHT leading to masculinisation of ext. genitalia (wrongly gender-assigned at birth/ambiguous genitalia)

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36
Q

What else can occur as a result of CAH? (2)

A

‘Salt-wasting’ due to lack of aldosterone
Can be lethal
Rapid diagnosis required with infants

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37
Q

How is CAH treated? (1)

A

With glucocorticoids to correct feedback

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38
Q

What happens in the hypothalamic-pituitary-adrenal axis normally? (5)

A

Corticotropin releasing hormone (CRH) is released from the hypothalamus
Stimulates anterior pit. gland to secreted adrenocorticotropic hormone (ACTH) which:
- stimulates rapid uptake of cholesterol into the adrenal cortex
- upregulates cholesterol side-chain cleavage enzyme (P450scc)
- increased glucocortioid secretion

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39
Q

What is the importance of the HPG axis? (2)

A

Master controller of gonadal function + reproduction
Via hypothalamic + pituitary peptide hormones as well as gonadal steroid (+ peptide)
Coordinated gonadal function for viable gamete production (male) as well as growth + development (both)

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40
Q

Does the HPG axis work via +ve or -ve feedback? (2)

A

BOTH but primarily -ve feedback

Exception is mid cycle surge in oestrogen + LH = +ve feedback

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41
Q

What are the hormones of the HPG axis? (4)

A

Hypothalamus = gonadotrophin releasing hormone (GnRH), kisspeptin
Pituitary = follicle stimulating hormone (FSH), luteinising hormone (LH)
Female gonad = oestradiol (E2), progesterone (P4)
Male gonad = testosterone, (inhibin + activin)

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42
Q

What is kisspeptin? (1)

A

Hormone controlling GnRH synthesis + secretion

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43
Q

What happens in GnRH synthesis + secretion? (3)

A

Decapeptide (10aa) synthesised + secreted from GnRH neurones in hypothalamus
Co-secreted with GnRH associated peptide (GAP)
In a pulsatile fashion (intrinsic pulse generator within hypothalamus)

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44
Q

How does GnRH secretion cause LH + FSH secretion? (5)

A

Binds to GnRHR on gonadotroph cells of ant. pituitary
Stimulates synthesis + secretion of LH + FSH
Increased gene transcription of LH + FSH subunits
Pulse of GnRH corresponds with pulse of LH
Extra-hypothalamic + -pituitary input invovled

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45
Q

What is the importance of pulsatile GnRH secretion? (3)

A

Used animal models + created hypothalamic lesion which lead to no pulses of LH as no endogenous GnRH pulses
Then infused pulsatile GnRH into animals leading to gradual increase in pulsatile release of LH (then could see how this related to oestradiol/progesterone release)
Administration of continuous GnRH stops HPG axis working - gradual down-regulation + inhibition of production of LH/FSH

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46
Q

How does GnRH secretion relate to LH/FSH secretion? (4)

A

GnRH secreted every 30-120mins
Stimulates a pulse of LH + FSH secretion
Slow frequency pulse favours FSH
Fast frequency pulse favours LH

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47
Q

What effect does synthetic GnRH have? (2)

A

Stimulatory

Same structure as GnRH

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48
Q

What effect do GnRH analogues have? (4)

A

Inhibitory
Modified GnRH peptide structure so loss of pulsatility
Either agonists/antagonists (competitive inhibitors
Might use in delayed puberty

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49
Q

What is the mechanism of action of synthetic GnRH? (5)

A

Binds to GnRHR
Activation of signalling
Stimulation of gonadotrophin synthesis + secretion
Dissociation from GnRHR
GnRHR is then responsive to next GnRH pulse

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50
Q

What is the mechanism of of action of a GnRH agonist analogue? (5)

A

Binds to GnRHR
Activation of signalling
Stimulation of gonadotrophin synthesis + secretion
Uncoupling of GnRHR from G-protein signalling (after ~2-3 weeks)
GnRHR non-responsive to GnRH

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51
Q

What is the mechanism of of action of a GnRH antagonist analogue? (3)

A

Binds to GnRHR
Blockage of receptor
No downstream effects

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52
Q

What are some clinical uses of GnRH analogues? (8)

A 
Ovulation induction + IVF
Prostate cancer
ER + breast cancer in pre-menopausal women
GnRHR/GnRH + ovarian endometrial cancers
Gonadal protection prior to chemotherapy (controversial)
Uterine fibroids
Endometriosis
PCOS (polycystic ovary syndrome)
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53
Q

What are the gonadotrophins? (2)

A

LH, FSH, human chorionic gonadotrophin (hCG)

hCG is produced during pregnancy to maintain the corpus luteum (so secretion of progesterone is maintained)

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54
Q

What is the structure of the gonadotrophins? (4)

A

Heterodimeric peptides with a common α-subunit + hormone specific β-subunit
All glycosalated
N-linked carbohydrate side chains (+ O-linked in hCG)
Microheterogeneity is required for biological function

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55
Q

How are the α- + β-subunits synthesised? (2)

A

α-subunits are synthesised in excess with β-subunit production limiting the hormone conc.
Free subunits have no biological action

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56
Q

Why can we administer the gonadotrophins be administered as daily injection? (2)

A

Because they are only secreted in a pulsatile fashion due to pulsatile GnRH release
+ their pulsatile secretion is not necessary to their biological activity

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57
Q

What are the functions of LH? (4)

A

Testis = stimulation of Leydig cell androgen synthesis
Ovary =
- Theca cell androgen synthesis
- ovulation
- progesterone production of corpus luteum

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58
Q

What are the functions of FSH? (3)

A

Testis = regulation of Sertoli cell metabolism
Ovary =
- follicular maturation
- Granulosa cell oestrogen synthesis

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59
Q

What is the nature of normal follicular phase gonadotrophin pulses? (2)

A

Pulses every ~90 mins, releasing LH

Smaller releases of FSH

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60
Q

What is the nature of gonadotrophin pulses in an underweight patient? (2)

A

Diminishing levels of LH + FSH

Down-regulation of HPG axis

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61
Q

What happens in Leydig cell steroid production? (2)

A

LHR expression leads to androgen production = testosterone

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62
Q

What happens in Sertoli cell steroid production? (3)

A

FSHR expression is involved in Sertoli cell metabolism + spermatogenesis

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63
Q

What happens in Theca cell steroid production? (2)

A

LHR expression leads to the production of androgens

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64
Q

What happens in Granulosa cell steroid production? (2)

A

FSHR expression leads to the production of oestrogen

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65
Q

How are androgens converted to oestrogens? (1)

A

By the aromatase enzyme

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66
Q

What do LHR (+ FSHR) expression lead the production of in the CL? (1)

A

Production of progesterone (+ oestrogen)

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67
Q

What happens during puberty? (5)

A

Transition from non-reproductive to reproductive
Secondary sexual characteristics develop (primary are present at birth)
Adolescent growth spurt
Profound physiological + psychological changes
Gonads produce mature gametes (spermatozoa + oocytes)

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68
Q

What are the 2 endocrine events of puberty? (2)

A

Adrenarche + gonadarche

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69
Q

What is adrenarche? (2)

A

Instigated by maturation of the cells in the adrenal cortex
Results in release of adrenal androgens
Growth of pubic hair (pubarche) + axillary hair
Growth in hair

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70
Q

What is gonadarche? (6)

A

Follows adrenarche
HPG drive
Synthesis + secretion of pituitary peptide hormones LH + FSH
Activate gonadal function
LH leads to steroid synthesis + secondary sex characterisics
FSH leads to steroid synthesis, growth of testis (male) + folliculogenesis (females)

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71
Q

What happens in adrenarche? (7)

A

Change in adrenal androgen secretion from zona reticularis
Dehydro-epiandrosterone (DHEA) + dehydro-epiandrosterone sulphate (DHEAS)
Gradual increase from 6-15yrs
20-fold increase peaking at ~20-25yrs
Decline in DHEA/DHEAS thereafter = adrenopause
No change in other adrenal androgens
No known mechanism for trigger of adrenarche

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72
Q

What happens in pubarche? (4)

A

Appearance of pubic (+ axillary) hair
Induced by adrenal androgen secretion
Associated with increased sebum production, infection + abnormal keratinisation = acne
If before 8yrs (girls) or 9yrs (boys) = precocious

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73
Q

When and why does gonadarche occur? (5)

A 
Several years after adrenarche, ~11yrs typically
Reactivation of hypothalamic GnRH
Activation of gonadal steorid production
Production of viable gametes
Ability to reproduce
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74
Q

When is HPG first activated? (2)

A

16th gestational week
Then occurs until 1-2wks postnatally
(Re-activation at ~11yrs)

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75
Q

What stimulates the onset of puberty? (7)

A

Maturational event in CNS

  • inherit (genetic) maturation of 1000-3000 GnRH synthesising neurones?
  • environmental/genetic factors?
  • body fat/nutrition?
  • leptin?
  • other gut hormones?
  • kisspeptin = critical in the initiation of puberty + reproductive function?
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76
Q

How does nutrition + body fat affect puberty onset? (6)

A

Link b/w fat metabolism + reproduction
Anorexia nervosa/intensive training can lead to:
- reduced response to GnRH
- decreased gonadotrophin levels
- amenorrhea
- restored when nourished/stopped exercise

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77
Q

What is the body fat hypothesis? (3)

A

Certain % fat : body necessary for:

  • menarche (= 1st menstrual cycle) = 17%
  • maintaining female reproductive ability = 22%
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78
Q

What is the evidence of kisspetin’s (metastin) role in puberty? (7)

A

Neurohormone found in hypothalamic neurones
Kisspeptine receptors expressed on GnRH neurones
Mutations of GPR54/gene coding for kisspeptin lead to:
- abnormal development of GnRH neurone (leads to hypogonadism)
- failure to enter puberty
- hypothalamic hypogonadism
- activating mutations of kisspeptin receptor (leading to precocious puberty)

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79
Q

What is consonance? (3)

A

Smooth, ordered progression of changes
Order of pubertal changes in uniform
Wide inter-individual differences in age of onset/pace + duration of change

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80
Q

What is menarche? (2)

A 
First menstrual period
Average age (UK) = 12.5yrs
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81
Q

Tanner stages of puberty

A

.

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82
Q

Development of secondary sexual characteristics

A

.

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83
Q

What physical changes occur in girls during puberty? (12)

A

Breast enlargement (thelarche) = 1st sign of E2 activity
Pubic/axillary hair
Uterus enlarges, cytology changes, secretions in response to E2
Uterine tube
Vagina
Increase in height
- earlier than boys
- peak height velocity (PHV) = 9cm/yr, reached at 12yrs
Body shape
HPG axis
Menarche (not equated with onset of fertility)
- in 1st year ~80% menstrual cycles are anovulatory, irregular cycles

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84
Q

What physical changes occur in boys during puberty? (11)

A

Increase in testicular volume >4ml
Growth of penis + scrotum, scrotal skin changes
Vas deferens’ lumen increases
Seminal vesicles + prostate
Facial/body hair
Pubic/axillary hair
Androgens enlarge the larynx, projection of thyroid cartilage (Adam’s apple), voice deepens
Increase in height
- PHV = 10.3cm/yr, reached at 14yrs
Body shape
Onset of fertility:
- boys are fertile at beginning of puberty
- testosterone from Leydig cells stimulates meiosis + spermatogenesis in Sertoli cells

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85
Q

What does the prader orchidometer measure? (2)

A

Testicular volume in mms

Growth chart shows 10th, 50th + 90th percentiles

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86
Q

How does the growth spurt occur? (5)

A

Complex interaction b/w growth hormone + oestrogen (both M + F)
Earlier in girls (~2yrs)
Biphasic effect of oestrogen on epiphyseal growth
- low levels = linear growth + bone maturation
- high levels = epiphyseal fusion

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87
Q

How do androgens effect the differentiations of pilosebaceous units (PSUs)? (3)

A

Androgens stimulate sebum secretion (this + infection can cause acne)
Androgens can induce differentiation of vellus PSUs to terminal PSUs - encouarge moustache/beard growth
Androgens can induce differentiation of vellus hairs to apo-PSUs - encourage increased growth in areas of pubic + axillary hair

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88
Q

What psychological changes occur during puberty? (4)

A

Increasing need for independence
Increasing sexual awareness/interest
Development of sexual personality
Later maturation = better development

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89
Q

What is precocious sexual development/precocious puberty? (2)

A

Development of any secondary sexual characteristic before the age of 8 (girls) or 9-10 (boys)

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90
Q

What types of precocious puberty are there? (2)

A

Gonadotrophin-dependent (central) or gonadotrophin-independent

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91
Q

What happens in gonadotrophin-dependent precocious puberty? (3)

A

In consonance
Excess GnRH secretion (idiopathic or secondary)
Excess gonadotrophin secretion (pituitary tumour)

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92
Q

What happens in gonadotrophin-independent precocious puberty? (3)

A

Loss of cosonance
Testotoxicosis - activating mutation of LH receptor
McCune Albright syndrome = constitutive activation of adenyl cyclase, leading to hyperactivity of signalling pathways + overproduction of hormones
Sex steroid secreting tumour or exogenous steroids

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93
Q

What occurs in McCune Albright sydrome? (4)

A

Mutations of GNASI gene
Cafe au lait pigmentation
Autonomous endocrine function
Fibrous dysplasia

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94
Q

What happens in pseudo-precocious puberty? What happens in gonadotrophin-dependent precocious puberty? (6)

A

Premature adrenarche/pubarche
- also congenital adrenal hyperplasia (CAH)/Cushing’s
Premature thelarche
- can be unitlateral
- isolated ‘cylclical (2yrs) proceeding to precocious puberty

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95
Q

How do we investigate precocious sexual development? (7)

A

Auxology (science of human growth + dev.)
- accurate measure of height, including body proportions, + weight
Pubertal staging
Bone age estimation
LH, FSH, sex steroid measurements
MRI scans of H-P area
Ultrasound scans of pelvis (uterus + ovaries)

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96
Q

What is the LH investigation for precocious puberty? (3)

A

LH response to 100 micrograms GnRH

  • normal for stage of puberty in central precocious puberty
  • suppressed in testotoxicosis
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97
Q

How do we use adrenal steroids to investigate precocious puberty? (2)

A

High with tumours

Precursors high with CAH

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98
Q

How do we treat precocious sexual development? (4)

A

Anti-androgens
5-α-reductase inhibitor
Aromatase inhibitor
Long-acting GnRH analogue (central precocious puberty)

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99
Q

What is pubertal delay? (3)

A

Absence of secondary sexual maturation

  • by 13yr (girls)/absence of menarche by 18yrs
  • by 14yrs (boys)
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100
Q

What are the causes of pubertal delay? ()

A 
Constitutional delay
HypOgonadotrophic hypogonadism (low LH + FSH)
HypERgonadotrophic hypogonadism (high LH + FSH)
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101
Q

What is constitutional delay? (4)

A

Affects both growth + puberty
~90% of all pubertal delay cases
10x more common in boys
Secondary to chronic illness (e.g. diabetes, CF)

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102
Q

What happens in hypOgonadotrophic hypogonadism? (3)

A

Low LH + FSH
Kallman’s syndrome (X-linked Kal gene, GnRH migration)
Other genetic causes, hypopituitarism

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103
Q

What happens in hypERgonadotrophic hypogonadism? (5)

A

High LH + FSH
Gonadal dysgenesis, low sex steroid synthesis
Klinefelter’s syndrome (XXY) = 1:500 males (congenital)
Turner’s syndrome (XO) = 1:3000 females (congenital)
Gonadal dysgenesis with normal karyotype

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104
Q

What is Klinefelter’s syndrome? (5)

A 
XXY or variants
Breast development
Less body hair
Smaller testicular size
Wide hips etc.
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105
Q

What is Turner’s syndrome? (3)

A

XO
Shorter than normal
Underdeveloped or ‘streaked’ ovaries

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106
Q

How do we investigate delayed puberty? (7)

A

Family history, dysmorphic features, anosmia
Auxology
Pubertal staging
Bone age estimation
LH, FSH, sex steroid measurements
MRI scans of H-P area
Ultrasound scans of pelvis (uterus + ovaries)

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107
Q

How do we treat delayed puberty? (3)

A

Testosterone (M)
Oestrogens (F)
Oxandralone (synthetic steroid of DHT)

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108
Q

What are primordial germ cells (PGCs)? (1)

A

Cells that will become sperm + eggs

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109
Q

When are PGCs first identifiable? (1)

A

In yolk sac of developing foetus, 3wks after conception

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110
Q

What happens before the PGCs differentiate? (4)

A

Undergo many cycles of mitosis
Migrate to genital ridge in foetus
Genital ridge becomes gonad
Further differentiation of PGCs depends on development of gonad (testis or ovary)

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111
Q

How do PGCs become oocytes? (6)

A

If PGCs enter ovary they become oocytes
Oogonia (egg-precursors) are diploid + divide by mitosis
Once mitosis stops they enter meiosis + are known are primary oocytes
No more division occurs
All the eggs every women will have are made at this stage
Primary oocytes remain in 1st phase of meiosis until it is ovulated (or dies) - maybe for 52yrs

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112
Q

Where are the primary oocytes located? (1)

A

Outer layer of the ovary = the cortex

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113
Q

What surrounds the primary oocytes? (4)

A

Protective layers and protective cells
In foetal ovary the surrounding cells condense around the oocyte + differentiate into the granulosa cells
Granulosa cells then secrete an acellular layer = basal lamina
Whole structure = PRIMORDIAL FOLLICLE

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114
Q

What is folliculogenesis? (2)

A

The growth + development of follicles From the earliest ‘resting’ stages (as laid down in foetus) through to ovulation

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115
Q

After puberty, what proportion of follicles are growing? (1)

A

Only a few grow each day

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116
Q

What happens when the follicles grow? (4)

A

Granulosa cells multiple
Oocyte secretes another protective acellular layer = zona pellucida
ZP which stays attached after ovulation
2nd layer of cells then differentiated around basal lamina = theca cells

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117
Q

How is initiation + early stages of growth controlled? (3)

A

Largely unknown

FSH controls most of folliculogenesis but early growth is independent of FSH + driven by local factors

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118
Q

How do we know early growth of follicle is FSH independent? (2)

A

Apparent in FSH-deficient patients + those with mutations of FSHR
When FSH is suppressed (e.g. in combined oral contraceptive pill) follicles continue with early growth but then die

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119
Q

What happens to granulosa cells when follicles starts to grow? ()

A

Follicle rapidly increases in diameter
Granulosa cells’ division increases but gaps forms in the GC layers
Gaps consist of fluid filled spaces which form an antrum
2 main phases of follicle growth labelled by absence or presence of antrum
Follicles with antrum are known as

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120
Q

What are the 2 main phases of follicle growth labelled by? (2)

A

Absence or presence of antrum

Follicles with antrum = antral or secondary follicles

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121
Q

What are the aims of the menstrual cycle? (6)

A 
Selection of single oocyte
Regular spontaneous ovulation
Correct no. of chromosomes in eggs
Cyclical changes in vagina, cervix + fallopian tube
Preparation of uterus
Support of fertilised dividing egg
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122
Q

How is the menstrual cycle controlled? (1)

A

Via the HPG axis

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123
Q

What are the two phases of the menstrual cycle? (2)

A

Follicular phase

Luteal phase

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124
Q

What are the two phase separated by? (1)

A

Ovulation (~day 14)

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125
Q

What day of the cycle does bleeding occur? (1)

A

Day 1

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126
Q

What happens in the 14 days before ovulation? (3)

A

Follicular phase
Growth of follicles
Dominated by oestradiol production from dominant follicle

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127
Q

What happens in the 14 days after ovulation? (4)

A

Luteal phase
Empty follicle becomes CL
Which produces progesterone

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128
Q

What happens after luteal phase? (1)

A

Menstruation occurs

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129
Q

How long does menstruation last? (1)

A

~3-8 days

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130
Q

What feedback occurs in the luteal phase? (1)

A

Progesterone = -ve feedback

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131
Q

What feedback occurs in follicular phase? (3)

A

Release of -ve feedback
-ve feedback then reinstated
Then switch form -ve to +ve

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132
Q

General summary of feedback in the menstrual cycle (11)

A

At end of cycle, CL is dying + prog. it was making falls
This high [prog] was exerting -ve feedback at HP level, thereby keeping LH + FSH low
As prog. levels fall, -ve feedback is lost causing FSH levels to increase preferentially
Stimulates follicles to grow + make E2
E2 feeds back to HP level + inhibits FSH release
FSH levels fall again
Meanwhile LH levels have been rising a little across the follicular phase
This allows a single follicle to grow + become the dominant follicle producing huge amounts of E2
After 2 days of E2, -ve feedback becomes +ve + there is a huge release of LH which causes egg to be released
Remaining follicle becomes CL which produces prog. (causing -ve feedback again)

133
Q

What happens at the inter-cycle rise in FSH? (4)

A

Allows selection of single follicle
Nothing wrong with non-selected follicles
(if we give FSH injections can pick them all up)
FSH levels increase + then decline causing other follicles to die
This occurs because selected follicles x2 in size every 24hrs making lots of E2 exerting -ve feedback at HP level to decrease FSH

134
Q

What is the FSH threshold hypothesis? (3)

A

1 follicle from group of antral (secondary) follicles is just at the right stage at the right time
Become dominant follicle which goes on to be ovulated
Can happen in either ovary

135
Q

How is further growth of the other follicles prevented? (1)

A

Oestradiol levels rise reinstating -ve feedback at pit. level

136
Q

How do most of the unselected follicles die? (2)

A

Due to atresia

= periodic process in which immature follicles degenerate + are subsequently reabsorbed

137
Q

How does the dominant follicle survive fall in FSH? (3)

A

As FSH falls, LH increases
Dominant follicle acquires LH receptors on granulosa cells
Others do not so lose their stimulant + die

138
Q

What receptors do Theca cells have? (2)

A

Always have LHR, never have FSHR

LH drives androgen + prog. production from theca cells

139
Q

What receptors do Granulosa cells have? (2)

A

FSHR, then LHR acquired from mid-follicular phase onwards

FSH + then LH drive oestrogen production in follicular phase

140
Q

What is required for the HPO axis to function? (2)

A

Important + calorific process requiring input from lots of other body systems
Detecting fitness to reproduce

141
Q

What happens in the selection + growth of the dominant antral follicle? (5)

A 
Dominant follicle selected
Grows rapidly (7mm to 14mm in week)
Needs lots of GFs, nutrients + steroids
Rapid neoangiogenesis
Oestrogen released from follicle into circulation
142
Q

How is LH surge caused? (2)

A

E2 feedback switches from -ve to +ve

Causes LH surge from pit. (exponential rise of LH in serum)

143
Q

What does the LH surge cause? (4)

A

Ovulation cascade:

  • egg released
  • follicle cell changes = luteinisation - formation of CL
  • E2 production falls, prog. is stimulated
144
Q

What happens during ovulation? (10)

A

Blood flow to follicle increases dramatically
Increase in vascular permeability causes increase in intra-follicular pressure
Appearence of apex/stigma on ovary wall
Local release of proteases
Enzymatic breakdown of protein of ovary wall
18hrs after LH peak, hole appears in follicle wall + ovulation occurs
Oocyte with cumulus cells is extruded from ovary under pressure
Follicular fluid may pour into Pouch of Douglas
Egg ‘collected’ by fimbria of Fallopian tube (due to signal from fluid)
Egg progresses down tube by peristalsis

145
Q

How does the patient know when they are going to ovulate? ()

A

Easy if cycles are regular
If irregular:
- if having intercourse 3 times/week probably ok but many will not be
Ultrasound monitoring if having induction of ovulation

146
Q

How does ovulation prediction work? (2)

A

Ovulation ‘sticks’ that detect LH surge
Home ovulation methods based on detection of these hormone products in urine/saliva or changes in body fluids e.g. cervical mucus in vagina

147
Q

What is the ‘pee on a stick’ ovulation kit? (3)

A

Detects LH surge in urine
Ovulation occurs ~12-14hrs after detection of LH surge in urine
Mostly, this is adequate + accurate

148
Q

What stage of meiosis is the oocyte in from its formation as a primary oocyte up until ovulation? (1)

A

Arrested in the first meiotic division

149
Q

Why does oocyte remain arrested in first meiotic division until ovulation? (1)

A

To retain all of the DNA + remain as large as possible

150
Q

What happens to oocyte in response to LH surge? (4)

A

Nucleus of oocyte in dominant follicle completes first meiotic division but does not divide
1/2 of chromosomes are packaged into part of the egg called the 1st polar body (plays no further part + doesn’t divide again)
Egg is now a secondary oocyte
Oocyte begins second meiotic division but arrests again

151
Q

What happens to the secondary oocyte when it is ovulated? ()

A

Has to support all early cell division of dividing embryo until it establishes attachment to placenta
Spends 2-3 day in uterine tujbe

152
Q

What happens to the follicle after ovulation? ()

A

Follicle collapses
CL forms (yellow body)
Prog. production increases greatly, also E2
CL contains large number of LHRs
CL supported by LH (hCG if pregnancy occurs)

153
Q

What are the roles of the secretions of the CL? (5)

A 
Progesterone:
- supports oocyte on its journey
- prepares endometirum
controls cells in fallopian tube
- alters secretions of cervix
Oestradiol:
- for endometrium
154
Q

What happens to CL if fertilisation does not occur? (3)

A

CL has finite lifespan of 14 days (if not fertilisation)
Removal of CL = essential to initiate new cycle
Cell death occurs -> vasculature breakdown -> CL shrinks

155
Q

Basic physiology of the uterus (2)

A

~6-8cm in adult woman

Mainly consists of muscle (myometrium) but inner lining is called endometrium

156
Q

What is the function of the endometrium? (2)

A

Site of implantation in pregnancy

Shed each month in absence of pregnancy

157
Q

Changes in uterus + cervix

A

Maternal steroids increases size of newborn uterus (oestrogen) which is larger that 4yr old uterus due to exposure of huge amount of maternal oestrogen in utero
Nulliparous (never given birth) uterus is smaller than parous uterus
Menopausal uterus decreases in size as exposed to much lower/negligible conc. of oestrogen
Grows with height during infancy
Corpus of uterus undergoes greater increase in size that cervix

158
Q

What changes can occur to the myometrium? (4)

A

Outer muscular myometrium grows gradually throughout childhood
Increases rapidly in size + config. during puberty
Changes in size throughout cycle
Capable of vast expansion during pregnancy

159
Q

What layers does the myometrium consist of? (3)

A

Inner layer of circular fibres
Middle layer of figure-of-8 fibres
Outer layer of longitudinal fibres

160
Q

What changes can occur to the endometrium? (6)

A

Very thin in childhood + begins to thicken at puberty
Dependent on steroids
Responds cyclically to hormone changes
Can be seen + measured on ultrasound scan
Good ‘bioassay of oestradiol level
Changes in glandular + epithelial cells throughout cycle

161
Q

What happens to endometrium during menstruation? (1)

A

Most of it is lost

162
Q

What happens to endometrium in fully receptive state? (2)

A

Arteries supplying it are v. convoluted to increase SA + so increase blood supply + nutrients to the tissue

163
Q

What happens during the endometrial proliferative phase? (5)

A

(Follicular phase of ovary)
Stimulated by oestradiol from dominant follicle
Stromal cell division, ciliated surface
Glands expand + become tortuous, increased vascularity, neoangiogenesis
Maximal cell division by days 12-14
When endometrium >4mm induction of prog. receptors + small muscular contractions of myometrium

164
Q

What happens during the endometrial secretory stage? ()

A

(Luteal phase of ovary)
2-3 days after ovulation, the gradual rise in progesterone (due to CL production) causes reduction in cell division
Glands increase in tortuosity + distend - secretion of glycoproteins + lipids commences
Oedema -> increased vascular permeability -> arterioles contract + grow tightly wound
Myometrial cells enlarge + movement is suppressed, blood supply increases

165
Q

What happens to the the CL if fertilisation occurs? (2)

A

The fertilised ocyte becomes a blastocyst + produces hCG which acts like LH (i.e. acts on LH receptor) + ‘rescues’ the CL

166
Q

What does regression of the CL cause (when fertilisation does not occur)? (1)

A

Falling levels of the steroid from the CL results in menstruation

167
Q

What happens during menstruation? (8)

A

Prostaglandin release causes contraction of spiral arterioles
Hypoxia causes necrosis
Vessels then dilate + bleeding ensues
Proteolytic enzymes released from dying tissue
Outer layer of endometrium shed ,50% lost in 24hrs (up to 80ml is considered normal)
Bleeding normally last 4+ days
Basal layer remains + is then covered by extension of glandular epithelium
Oestrogen from follicle in next follicular phase starts cycle off again

168
Q

What happens in the uterine tubes? (3)

A

Site of fertilisation
Where early embryonic divisions occur
Critical secretions

169
Q

What are the layers of the uterine tube? (3)

A 
Serosa = outer layer
Muscularis = inner circular + outer longitudinal layers - blood vessels + lymphatics
Mucosa = innermost layer
170
Q

What does the mucosa layer consist of? (3)

A 
Secretor cells (secreting nutrients for early embryo + fertilisation)
Columnar ciliated epithelial cells (waft egg down tube)
Non-ciliated peg cells
171
Q

What is the histological difference b/w intramural region + isthmus region? (1)

A

Isthmus region contains more secretory ciliated mucosa

172
Q

What is the histological difference b/w isthmus region + ampullary region? (1)

A

When we reach ampullary region (site of fertilisation) the secretory ciliated mucosa becomes convoluted to increase SA

173
Q

How do oestrogen + progesterone cause differentiation of cells in uterine tubes? (4)

A

At start of cycle, oestrogen causes differentiation of cells in uterine tubes:
- cilia start wafting, sec. cells start secreting
- in prep. for ovulation
If sperm + egg don’t meet in first few days after ovulation, the secretion + wafting ceases due to rising levels of prog. (un-differentiates cells of uterine tubes)

174
Q

Comparison of oocyte size to cells lining uterine tube (2)

A

Cilia =~7-8µm

Oocyte =~100µm

175
Q

How does the ovulated egg reach the uterine tube? (1)

A

Fimbrial end of uterine tube picks up ovulated oocyte from ovary

176
Q

How is the egg transported along the uterine tube? (2)

A

Beating of cilia (stim. to grow by oestrogen)

Rapid contraction of muscular layer (caused by oestrogen)

177
Q

Why do the cilia stop beating? (3)

A

High number of oestrogen receptors present in follicular phase
Oestrogen receptors suppressed by progesterone
All stops by mid-luteal phase (even if egg was released it would be unable to pass)

178
Q

How long does the egg remain in the uterine tube for? (1)

A

~5 days

179
Q

Where does fertilisation occur most often? (1)

A

In the ampulla

180
Q

What are causes of damage/blockage to the uterine tube lining? (4)

A

Infection e.g. chlamydia
Endometriosis (where tissue that behaves endometrium is found outside womb)
Surgery
Adhesions

181
Q

What can damage to the uterine tubes result in? (3)

A

Pain
Infertility
Ectopic pregnancy

182
Q

What are the main methods of checking if uterine tubes are blocked? (2)

A

Laparoscopy + dye

HyCoSy

183
Q

What happens in laparoscopy + dye? (3)

A

Uterine cannula passes up through cervix + intros coloured dye to uterus
Insert laparoscope through abdominal wall into pelvis + look for dye emerging in fimbrial end of both uterine tubes
If there is no dye visible here we know the tube is blocked

184
Q

Benefit of laparoscopy + dye over HyCoSy (1)

A

Allows visual inspection of inside of pelvis e.g. to look for evidence of endometriosis
(but INVASIVE)

185
Q

What happens in Hystero Salpingo-contrast somography (HyCoSy)? (3)

A

Introduce cannula up vagina, through cervix + fill uterus with dye
The dye is opaque + visible on ultrasound
Use ultrasound to detect if dye is present at fimbrial ends

186
Q

Benefit of HyCoSy over laparoscopy + dye (1)

A

Non-invasive

187
Q

Basic physiology of cervix (5)

A

Muscular structure capable of great expansion
Mucosa 2-3mm thick
Many secretory glands producing mucous
- protective barrier to infusion
- but has to allow passage of motile sperm

188
Q

What happens in the follicular phase of the cervix? (5)

A

Oestrogen in follicular phase causes change in vascularity of cervix oedema
Mid-cycle oestrogen levels cause change in mucous to become less viscous:
- changes in mucous composition
- contains glycoproteins
- glycoproteins become aligned + form microscopic channels which sperm can swim up

189
Q

What happens in the luteal phase of the cervix? ()

A

Prog. in the luteal phase causes:

  • reduced secretion + viscous mucous (reduced water content)
  • glycoproteins form mesh-like structures + act as barrier
  • one mechanism of action of oral contraceptive
190
Q

Basic physiology of vagina (4)

A

Thick-walled tube, ~10cm
Lined by specialised ‘squamous epithelial’ cells
Warm damp environment containing glycoprotein
Susceptible to infection

191
Q

How does the physiology of the vagina prevent infection? (3)

A

Layers of epithelial cells shed constantly ‘flow’ downwards with the secretions
Secretions are from cervix + transudation from vaginal epithelium
Secretions change with cycle + are generally acidic providing anti-microbial protection

192
Q

Basic physiology + function of testes (5)

A 
Lie in scrotum outside body cavity
Well-vascularised, well-innervated
Normal volume of testes = ~15-25ml
Produce sperm + store it
Produce hormones which regulate spermatogenesis
193
Q

How do you measure testes volume? (1)

A

Orchidometer

194
Q

Why do testes lie outside body cavity? (2)

A

Optimum temp. for sperm production = 1.5-2.5°C below body temp.
Overheating of testes reduces sperm count

195
Q

Describe the structure of the testicles (3)

A

Tubules lead to an area on one side called rete
Rete leads to epididymis + vas deferens
90% seminiferous tubules = site of spermatogenesis (600m long in each testis but tightly coiled)

196
Q

What cells make up the seminiferous tubules? (3)

A

Walls of tubule made up of tall columnar endothelial cells = SERTOLI cells
B/w these lying on the basement membrane are PGCs/SPERMATOGONIA
Spaces b/w tubules are filled with blood + lymphatic vessels, LEYDIG cells + interstitial fluid

197
Q

Tight junctions of the seminiferous tubules (4)

A

Open to allow passage of spermatagonia prior to completion of meiosis
Divides into luminal + adluminal
Protects spermatogonia from immune attack
Alllows specific enclosed environment for spermatogenesis which is filled with secretion from Sertoli cells

198
Q

What are the differences b/w oogonia + spermatogonia? ()

A

Both oogonia/spermatogonia go through meiosis to make oocytes/spermatocytes
but only spermatocytes can divide mitotically to make more spermatogonia
Therefore infinite supply of spermatogonia + only finite supply of oogonia

199
Q

What are the sperm stages of spermatogenesis? (5)

A

Spermatogonia -> primary spermatocyte -> secondary spermatocyte -> spermatids -> spermatozoa

200
Q

What are spermatogonia? (3)

A

Germ cell on basement membrane, Capable of meiotic + mitotic division to produce primary spermatocytes (or more spermatogonia by mitosis)
Diploid

201
Q

What are primary spermatocytes? (2)

A

Cell committed to differentiated pathway
46XY diploid
Move into adluminal compartment + duplicate their DNA to produce sister chromatids which exchange genetic material + enter meoisis I

202
Q

What are secondary spermatocytes? (2)

A

Have undergone meiosis I to give 23X + 23Y haploid number of chromosomes
Arranged as sister chromatids

203
Q

What are spermatids? (2)

A

Meiosis II occurs to give 4 haploid spermatids

Round spermatid to elongated spermatid differentiation

204
Q

What are spermatozoa? (1)

A

Mature sperm extruded into the lumen

205
Q

What happens in spermatogenesis? (7)

A

New cycle every 16 days
Entire process take ~74 days
Mitotic proliferation of spermatogonia
Meiosis + development of spermatocytes
Spermiogenesis, elongation, loss of cytoplasm, movement of cellular contents
Movement into lumen controlled by Sertoli cell secretions
Factors produced by Sertoli cells are required for development

206
Q

What type of receptors do Leydig cells contain + what do they do? (2)

A

LH receptors

Primarily convert cholesterol into androgens

207
Q

How do intra-testicular testosterone levels compare to plasma levels? (1)

A

100x greater than in plasma

208
Q

What do the androgens produced in the Leydig cells stimulate? ()

A

Cross over + stimulate Sertoli cell function

Thereby control spermatogenesis

209
Q

What type of receptors do Sertoli cells contain + what do they do? (2)

A

FSH receptors

Convert androgens to oestrogen

210
Q

What role do FSH + androgens have in Sertoli cells? (2)

A

FSH establishes quantitatively normal Sertoli cell pop.

Androgens initiate + maintain sperm production

211
Q

Effects of anabolic steroids (3)

A

Interfere with -ve feedback
Aromatise androgens to oestrogens
Reduce FSH from pit. leading to testicular atrophy

212
Q

What happens in erection/ejaculation? (4)

A

Vasodilation of the corpus cavernosum
Partial constriction of venous return
Autonomous NS causes coordinated contractions of vas deferens + glands
Symp. NS control + parasymp. NS control

213
Q

What is under sympathetic NS control of erection + ejaculation? (2)

A

Movement of sperm into epididymis, vas deferens, penile urethra
Expulsion of glandular excretions

214
Q

What is under parasympathetic NS control of erection + ejaculation? (2)

A

Erection + evacuation of urethra

215
Q

How many sperm are produced per day? (2)

A

~300mil/day

~3500/sec

216
Q

How many sperm are in average ejaculate + what is the average volume? (1)

A

~120mil

1.5-6.0ml (~1/3 teaspoon)

217
Q

What portion of the ejaculate is most sperm rich + what proportion of sperm get near egg? (3)

A

Initial portion
99.9% lost before reaching ampulla of uterine tube
~120,000 sperm get near egg, only 1 enters

218
Q

Seminal fluid consists of secretions from which structures? (4)

A

Seminal vesicles
Prostate
Bulbo-urethral gland
Combined with epididymal fluid

219
Q

What does the seminal vesicle secretion of seminal fluid consist of? (4)

A

Secretion comprises ~50-70% of ejaculate
Contains proteins, enzymes, mucous, vit. C + prostaglandins
Also high fructose conc. = energy source
High pH protects against acidic environment in vagina

220
Q

What does the prostate secretion of seminal fluid consist of? (5)

A

Secretes milky white fluid
~30% of seminal fluid
Protein content

221
Q

What does the bulbo-urethral secretion of seminal fluid consist of? (4)

A

Clear viscous secretion, high in salt
Known as pre-ejaculate
This fluid helps lubricate the urethra for spermatozoa to pass through, neutralising traces of acidic urine

222
Q

Semen analysis (9)

A 
Vol = 1.5-6.0ml
Sperm conc. >15million/ml
Liquefaction 40%
Progressive motility >32%
Vitality (live) >58%
Morphology (normal forms) >4%
pH > 7.2%
Leucocytes
223
Q

Structure of spermatozoa (2)

A

Head

Tail (mid-piece, principal piece, end piece)

224
Q

What causes the maternal changes in pregnancy? (3)

A

High levels of steroids
Mechanical displacement (new large mass in abdomen)
Foetal requirements

225
Q

How do we diagnose abnormality in pregnancy? (2)

A

Need to detect changes in the changes

Often changes overlooked + put down to women being pregnant

226
Q

What can pregnancy do to an existing condition? (2)

A

Exacerbate pre-existing condition (e.g. hypertension)

Uncover ‘hidden’/mild condition (e.g. diabetes)

227
Q

What are some main events which cause maternal changes? (6)

A

Increase in uterus size
Increased metabolic requirements of uterus
Structural + metabolic requirements of foetus
Removal of foetal waste products
Provision of amniotic fluid (~1L per term)
Preparation for delivery + puerperium

228
Q

What is puerperium? (2)

A

Period following birth

Where the various changes during pregnancy revert to non-pregnant state

229
Q

Which hormones cause system changes in pregnancy? (10)

A 
Maternal steroids
- placenta takes over steroidogenesis, previously done by CL ~week7
Placental peptides
- hCG, hPL, GH
Placental + foetal steroids
- prog., oestradiol, oestriol
Maternal + foetal pit. hormones
- GH thyroid homrones (increased thyroid function to increase met. rate)
- prolactin (involved in breast dev)
- CRF
230
Q

Weight gain in pregnancy (7)

A 
Total weight gain = 12.5-13.0kg
Foetus + placenta = 5kg
Fat + protein = 4.5kg
Body water (excluding that in other listed structures) = 1.5kg
- intravascular, interstitial, intracellular
Breast hypertropy = 1kg
Uterus = 0.5kg-1kg
Failure to gain/sudden change needs monitoring
231
Q

Why do we need to increase energy output + storage during pregancy? (2)

A 
Output = to cope with increased resp. + cardiac output
Storage = for foetus + labour/puerperium
232
Q

By what amount to fat/protein stores increase by in pregnancy + why? (4)

A

4-5kg
Increased consumption + reduced use
Utilised later in pregnancy + puerperium
Mainly laid down in ant. abdominal wall

233
Q

What does basic metabolic raise by during pregnancy? (3)

A

350kcal/day mid gestation
350kcal/day late gestation
(75% foetus + uterus, 25% respiration)

234
Q

Glucose levels during pregnancy (5)

A

Need increased levels in blood in 2nd trimester
Active transport across placenta as foetal energy source (doesn’t diffuse easily across placenta)
Foetus only functions well on glucose (needs aerobic resp.)
Foetus stores some in liver
Normal for mother to become insulin resistant when pregnant
(Can get gestational diabetes if already susceptible to diabetes)

235
Q

Maternal glucose reserves in 1st trimester (3)

A

Pancreatic β cells increase in number causing plasma insulin to increase
Therefore more glucose into tissue (laid down as stores + used by muscle)
Fasting serum glucose decreases

236
Q

Foetal glucose reserves in 2nd trimester (3)

A

hPL causes insulin resistance i.e. less glucose into stores
Increase in serum glucose
More crosses placenta (but can cause diabetes)

237
Q

Water gain in pregnancy (3)

A

Sodium retention in kidneys brings in extra fluid (E2 + P act on RAAS system)
Oedema is normal in pregnancy
80-90% pregnant women get swollen ankles

238
Q

Why does O2 consumption increase during pregnancy? (5)

A

Increased respiratory centre sensitivity to CO2
Thoracic anatomy changes - ribcage displaced upward + ribs flare outwards
Therefore breathe more deeply
Arterial PO2 increases ~10%, PCO2 decreases 15-20%
Facilitates placental gas transfer

239
Q

What happens to maternal blood during pregnancy? (9)

A

Maternal plasma volume = 45%
Red cell mass = 18%
Increased efficiency of iron absorption from gut
Haemodilation - apparent anaemia as conc. of Hb falls
- reference range for anaemia changes in pregnancy
Increase in WBCs
Increase in clotting factors (esp. 2, 7, 9 + 10 due to increased oestrogen)
Blood becomes hypercoagulable

240
Q

What are the effects of maternal blood becoming hypercoagulable? (2)

A

Increased fibrinogen for placental separation

BUT increased risk of thrombosis

241
Q

What effect does smoking have on foetal blood? (3)

A

Increases maternal carboxy-Hb which is more permanent
Reduces the increased O2 binding
Foetal hypoxia

242
Q

What might pregnancy do to mother with underlying cardiovascular disease? (2)

A

Uncover the disease

As woman may struggle with the CVS changes

243
Q

Maternal cardiovascular system - heart (5)

A

High volume, low pressure system
Expanding uterus pushes heart round + changes ECG/heart sounds
Increased cardiac output for maternal muscle + foetal supply
- due to increased HR/SV
- begins as early as 3wks to max 40% at 28wks

244
Q

Maternal cardiovascular system - vessels (4)

A

Increased CO + vasodilation by steroids (principally prog.)
Reduced peripheral resistance
Increased flow to uterus, placenta, muscles, kidney, skin
Neoangiogenesis includng extra capillaries in skin (spider naevi) to assist heatloss

245
Q

What happen to the GI tract during pregnancy? (5)

A 
In response to increased steroid levels
Increased appetite + thirst
Reduced GI motility (-> constipation)
Acid reflux:
- relaxed lower oesophageal sphincter (due to steroids)
- large uterus (small frequent meals)
80-90% experience heartburn
246
Q

Why is folic acid used as dietary supplementation during pregnancy? (4)

A

DNA production, growth, blood cells (in uterus, placenta + foetus)
400μg/day up to a week
Deficiency linked to spina bifida (neural tube defect)
Advise those trying to get pregnant to take folic acid supplements to increase chances (if poss. at least 3 months before start trying)

247
Q

What happens to to the urinary tract during pregnancy? (2)

A

Dilates/relaxes

Increased UTI risk due to stasis in system i.e. static urine

248
Q

What happens to kidney during pregnancy? (3)

A

Increased blood flow
Increased filtration
Increased clearance of creatinine, urea + uric acid

249
Q

Is it normal to have low levels of creatinine, urea + uric acid during pregnancy? (2)

A

Yes

Renal impairment if pregnant values match non-pregnant values

250
Q

What happens to the bladder during pregnancy? (5)

A

Uterus enlarges with pelvis compressing bladder as it comes forward
Relief at later point as uterus expands upwards
Baby’s head descends onto bladder as it comes forward
Baby’s head descends onto bladder again reducing volume + compressing bladder
Bladder cannot differentiated b/w high vol. of urine or expanded uterus

251
Q

What happens to uterine size? (6)

A

20x increase in muscle mass
Hypertrophy of smooth uterine muscle (not more cells)
Spiral network of muscle fibres
As vol. increases these muscle fibres push down
Lower uterine segment formed from isthmus
Upper part of cervix incorporated from 34wks

252
Q

What is the primary function of the cervix in pregnancy? ()

A

Retain pregnancy

Keeps uterus closed + foetus in

253
Q

What is the difference b/w cervix + myometrium during pregnancy + during parturition? (2)

A 
Pregnancy = quiescent uterine myometrium + doesn't contract, closed cervix
Parturition = active uterine myometrium, open cervix
254
Q

What changes occur in the cervix during pregnancy? (9)

A 
Increase in vascularity
Tissue softens + turns bluer from 8wks
Changes in connective tissue
Begins gradual preparation for expansion
Proliferation of glands
- mucosal layer becomes half of mass
- greater increases in mucus production
Protective i.e. anti-infective
Prog. involved in production of thick mucus plug
255
Q

How does the body return to normal after pregnancy? (5)

A

Dramatic, rapid fall in steroids on delivery of placenta
Most endocrine-driven changes return to normal rapidly
Within 6wks back to normal
Uterine muscle rapidly loses oedema but contracts slowly (never returns to pre-pregnancy size)
Removal of steroids permits action of raised prolactin on breast

256
Q

What happens in further pregnancies/labours if the first are successful? (1)

A

More likely to be successful

Improved function of uterine receptors by 2nd/3rd labours means labour becomes easier

257
Q

What is the trophoblast + what does it secrete? (2)

A

Cells of blastocyst that invade endometrium + myometrium

Secrete βhCG

258
Q

What is the chorion? (1)

A

That which becomes the placenta

259
Q

What is the amnion? (1)

A

Layer that becomes amniotic sac

260
Q

Where do sperm + egg typically meet? (1)

A

In ampullary region of Fallopian tube

261
Q

What nutrition is the free-living blastocyst reliant on? (1)

A

Cytoplasm inherited from the oocyte (maternal)

262
Q

After implantation what sort of nutrition does the embryo rely on? (2)

A

Initially HISTIOTROPHIC = blastocyst is bathed in uterine secretions
Later on HAEMOTROPHIC = vascular contact b/w mother + foetus

263
Q

Define the term ‘maternal recognition of pregnancy’ + describe how the embryo signals its presence to the maternal system (3)

A

Conc. of progesterone needs to be sustained at high level in maternal blood in order that endometrium is maintained for embryonic survival
The embryo signals its presence by the trophoblast producing βhCG (~day 10)

264
Q

What hormone’s structure is βhCG almost identical to + what does it do? (2)

A

LH

So binds to + maintains the CL

265
Q

Why must the corpus luteum be maintained? (3)

A

For prog. production
Decidulisation under prog.
Vital until placental steroidogeneis (e.g. for first 7wks of pregnancy)

266
Q

Define the term ‘window of implantation’ (5)

A

~day 6 for ~24-36hrs
Narrow window of time when endometrium receptive to the embryo
Complex molecular cross stalk b/w embryo + endometrium
Key balance of oestrogen + progesterone
LIF/EGF/IL 11 (come hither)
Muc1 (go away)

267
Q

What hormone is the basis of urinary pregnancy tests? (3)

A

βhCG
β-subunit is qualitative
Use Ab unique to βhCG (won’t bind to LH/FSH)

268
Q

What is a serum βhCG (quantitative) test used for? (1)

A

Useful for monitoring early pregnancy complications e.g. miscarriage, ectopic pregnancy

269
Q

What is the difference in βhCG serum levels in a normal + ectopic pregnancy? ()

A

Normally:
- (b/w 4-8 weeks after last menstrual period) plasma βhCG almost doubles ever day + is maximal by 9-11wks
- then production slows until pregnancy has ended, not reaching zero til post-pregnancy
Ectopic:
- βhCG plasma levels are slow-rising

270
Q

What are the functions of the placenta? ()

A

Steroidogenesis (oestrogen, progesterone, HPL, cortisol)
Nutrition (oxygen, CHO, fats, AAs, Abs, vitamins minerals)
Removal of waste (CO2, urea, NH4, minerals e.g. potassium)
Barrier (bacteria, viruses, drugs)
IgG is the only Ab that can cross the placenta

271
Q

How is the placenta adapted to its roles? (4)

A

Huge maternal uterine blood supply (low pressure)
Huge reserve in function
Huge SA in contact with maternal blood
Highly adapted + efficient transfer system

272
Q

How does the placenta develop? (4)

A

Differentiation of the trophoblast
Trophoblastic invasion of decidua + myometrium
Remodelling of maternal vasculature in the utero-placental circulation
Development of foetal vasculature within villi

273
Q

What is decidua? (1)

A

Term for uterine lining (endometrium) during pregnancy

274
Q

What does the connecting stalk become? (1)

A

The umbilical cord

275
Q

What is the menopausal transition? (1)

A

Period of time from change in menstrual pattern to menopause ~4yrs

276
Q

What is the menopause? (2)

A

Permanent cessation of menstruation due to loss of ovarian function (amenorrhoea for 12 months)

277
Q

Why is the menopause a retrospective diagnosis? (1)

A

Cannot predict at which age someone will become infertile

278
Q

What is perimenopause? (2)

A

Period of changing ovarian function

Preceding menopause by ~2-8yrs

279
Q

What is the average age of menopause? (1)

A

51

280
Q

What age is premature ovarian failure diagnosed at? (1)

A

40 or below

281
Q

What factors affect the age of menopause? (6)

A 
Smoking
Hysterectomy
Endometriosis
Chemo/radiotherapy
Genetic determinants e.g. maternal age
Ethnicity
282
Q

What are the symptoms of menopause? (4)

A

Hot flushes (vasomotor symptoms)
Declining fertility
Vaginal dryness
(Mood changes)

283
Q

What menstrual cycle changes occur prior to menopause? (4)

A

Very variable
Some women have no prior menstrual irregularity
Others have initially reduced cycle length (due to reduced follicular phase)
~4yrs prior to FMP some women experience irregular periods with episodes of amenorrhoea

284
Q

What is the symptom of vaginal dryness in menopause attributed to? (1)

A

Urogenital atrophy

285
Q

What are hot flushes? (5)

A

Occur in 50% of menopausal women
Often lead to sleep disturbance
Narrowing of normal temperature range that your body tolerates
Triggering sweating + vasodilation at lower temp. than normal
Very distressing in ~10-20%

286
Q

How long do hot flushes take to resolve? (1)

A

Can take months for most but years for some

287
Q

What are the physiological observation of the menopause? (3)

A

Decline in no. of primordial follicles
Fewer granulosa cells + reduced functionality
Decline in oocyte function + development

288
Q

Why is there a decline in no. of primordial follicles in menopause? (4)

A

Accelerated decline in no. of ova begins at critical threshold = ~25,000 ova, 12-14yrs before FMP
Increased follicular death - apoptosis
Ovarian environment e.g. smoking reduces age of menopause by ~2yrs + shortens menopausal transition
Ability of granulos cells to produce AMH decline -> FSH increses -> increased follicular recruitment + depletion

289
Q

How does AMH interact with FSH in reproductive years? (2)

A

AMH inhibits FSH

Inhibiting excessive follicular recruitment

290
Q

How does granulosa cell number in older women compare to younger women? (1)

A

30% decrease

291
Q

What factors lead to decline in granulosa number + function? (6)

A

Decreasing number of granulosa cells per follicle leads to decreasing levels of inhibin B
Decreased inhibin B production allows higher FSH levels
When FSH elevated there is fourfold increased rate of apoptosis in granulosa cells
Anovulatory cycles lead to decrease in inhibin A (normally produced in luteal phase) allowing higher FSH
Decreased FSH receptors + sensitivity impairs recruitment of dominant follicle
Impaired secretion of GFs + other signalling pathways, survival factors, prog. + oest.

292
Q

Which factors account for decline in oocyte function + development? (5)

A

Consequence of impaired production of GFs/survival factors from granulosa cells
Impaired microtubule + spind formation in meiosis
Increased aneuploidy
Increased oocyte abnormality impairs follicle recruitment even with clomiphene (stimulates ovulation)
Results in anovulatory cycle + increased miscarriage rate

293
Q

What can cause a shortened cycle (linked to menopausal transition)? (5)

A

FSH normally rises in follicular phase (due to declining prog + oest @ end of luteal phase)
Inhibin B exerts -ve feedback on FSH production (ant. pit.)
Reduced inhibin B production leads to increased FSH
Higher levels of FSH stimulate higher oestrogen levels + formation of LH receptors
Earlier LH surge + earlier ovulation

294
Q

What can cause delayed/absent ovulation (linked to menopausal transition)? (5)

A

Oestrogen production is stimulated earlier in cycle by elevated FSH but may not reach levels high enough to induce GnRH surge
Consequentially ovulation is delayed/doesn’t occur
Also relative FSH insensitivity due to fewer receptors in granulosa cells
Fewer follicles to recruit
No inhibin A so FSH rises

295
Q

What can cause heavier periods (linked to menopausal transition)? (2)

A

Anovulation/delayed ovulation Leading to higher levels of oestrogen are around for longer leading to a thicker endometrium

296
Q

What can cause breast tenderness (linked to menopausal transition)? (1)

A

Transitory increases in oestrogen

297
Q

What can cause hot flushes (linked to menopausal transition)? (2)

A

Declining oest levels distrub serotonin levels

Resets thermoregulatory nucleus + leads to heat loss

298
Q

What happens to AMH levels during the menopausal transition? (3)

A

Decline well before inhibin B + before FSH levels/menstrual pattern change
First sign of ovarian function decline
May be a useful marker for declining fertility (but not used clinically)

299
Q

What happens to inhibin B levels during the menopausal transition? (1)

A

Declines ~2yrs before FMP

Not used clinically

300
Q

What happens to FSH levels during the menopausal transition? (1)

A

FSH levels are variable each cycle but increase towards menopause

301
Q

What happens to LH levels during the menopausal transition? (1)

A

Nothing during transition but increase later during menopause

302
Q

What happens to oestrogen levels during the menopausal transition? (1)

A

Decline close to (+ after) the menopause

303
Q

Are changes in ovarian + adrenal androgen levels related to menopause? (2)

A

No

Experience a gentle decline with age from 20s but not related to menopause

304
Q

What are marker for declining fertility? (3)

A 
Ovarian volume as a proxy for number of follicles (or antral follicle count)
Response to ovarian stimulation
AMH levels (useful for family planning + IVF in older women)
305
Q

What is black cohosh? (2)

A

Herbal medicine for reducing menopausal symptoms

Associated with liver problems in rats so concern over patients with liver problems

306
Q

What therapy was found to be most successful in the meta-analysis trial for hot flush treatment? (2)

A

Oestrogen

Reduced hot flushes by 2 a day compared to placebo

307
Q

What treatment is there for urogenital symptoms associated with menopause? (2)

A 
Moisturisers + lubricants
Topical oestrogen (women should report unscheduled bleeding to GP)
308
Q

What treatment is there for the low mood associated with menopause? (2)

A

HRT (but no strong evidence for efficacy)
CBT + SSRI indicated if woman diagnosed with depression
(SSRIs also prescribed as 2nd line for vasomotor symptoms)

309
Q

What is the effectiveness of oestrogen in HRT to treat hot flushes? (2)

A

80% reduction in hot flush severity + frequency

60% efficacy at lower dose

310
Q

Ideally how should HRT be taken? (4)

A

At as low a dose + for as short a period as possible
Minimises unwanted effects e.g. mastalgia + nausea
With attempts to stop treatment every 6 months
Consider individual risks
Women themselves should be clear about indication, risks/benefits + have a plan for review

311
Q

What happens when prescribing HRT to a women with a uterus? (5)

A

Progesterone must also be given to avoid endometrial hyperplasia (~56% of women using unopposed oestrogens)/cancer (3% go on to develop carcinoma)
From unopposed oestrogen
Give progesterone for 13 days

312
Q

How high are the risks of ST use of HRT? (2)

A

Relatively low

Low risk of thrombosis

313
Q

How can HRT be prescribed? (3)

A 
Combined oest + prog:
- continuous combined
- cyclical progesterone
Oestrogen alone:
- continuous oestrogen for women without uterus
314
Q

In which forms can HRT be administered? (3)

A

Oestrogen - tablets, patches, subcutaneous implants, gel
Progesterone - tablets, intrauterine device, patches (comb. with oest.), gel
Vaginal oestrogen creams/rings for vaginal dryness

315
Q

HRT usage 1970s-2002? (4)

A

60% of women used it for variable durations
Supposedly prevented Alzheimer’s
Endorsed by O+G/primary care despite lack of license

316
Q

What were the main conclusions of the 2002 WHI RCT? (3)

A

Placebo vs oest + prog
Excess of 20 events per 10,000 women after 5yrs of combined oest. + prog. HRT compared to non-users
No increase in mortality
Oestrogen alone showed no overall benefit or hazard but is associated with significant increased risk of stroke events

317
Q

What are the risks of HRT + venous thromboembolism? (3)

A

Increased risk for oral formulations/high dose transdermal preparation
But no increased risk for standard dose of transdermal preparation
Consider transdermal for women with BMI>30 + increased risk

318
Q

What are the risks of HRT + osteoporosis? (3)

A

Effective treatment but overall HRT risks outweighed benefits
Also only prevents fractures whilst its being taken
(Other treatments include bisphosphonates, calcium + vit. D, strontium, raloxifene)

319
Q

What are the risks of HRT + breast cancer? (3)

A

In women of around menopausal age combined HRT increased risk of breast cancer whilst being take + reduces when stopped
Oestrogen only is associated with little/no risk
Breast cancer risk increases with age + so estimated that in last decade use of HRT by women aged 50-64 has resulted in ~20,000 extra breast cancers in UK

320
Q

What are the risks of HRT + endometrial cancer? (3)

A

EH found in 56% of women using unopposed oestrogen after ~1yr
Risk declines slowly after stopping use
Almost complete protection from EH obtained by 10-13 days of prog. per cycle

321
Q

How is protection from endometrial hyperplasia (EH) obtained from combined HRT? (3)

A

10-13 days of prog. per cycle

Decreases oestrogen receptors + promotes formation of less potent oestrone from oestradiol

322
Q

What are the risks of HRT + ovarian cancer? (2)

A

Non-significant 58% increase in ovarian cancer for combined HRT
Excess risk of 1 extra ovarian cancer/2500 women (1 extra death/3500) indicated

323
Q

Are there benefits of HRT on colorectal cancer? (3)

A

WHI study showed beneficial effect of HRT on colorectal cancer incidence
Agrees with many observational study findings
Underlying mechanism unknown

324
Q

What are the risks of HRT + cardiovascular disease? (3)

A

WHI study showed excess risk (29%) of combined CV events with combined HRT (mostly non-fatal MI)
Stroke, PE + DVT rates higher
Oestrogen only HRT only showed increased risk of stroke
No significant risk of IHD in women aged 50-59/within 10yrs of menopause
Stroke risk remains significantly raised for all age groups

325
Q

For what conditions have some groups hypothesised a ‘critical period’ for peri-menopausal administration of oestrogen? (2)

A

IHD (cardio-protective)

Alzheimer’s disease (protecting memory)

326
Q

What are the risks of HRT + Alzheimer’s disease? (3)

A

Observational studies suggest benefit of HRT on cognition in older women
But not confirmed by RCTs - actually found a 2x increase of dementia incidence

327
Q

What are the risks of HRT + urinary incontinence? (1)

A

WHI study showed combined HRT significantly increase risk of UI + worsens existing symptoms

328
Q

How does HRT impact on quality of life? (2)

A

WHI showed no improvement of quality of life

But improvement in sleep due to effective treatment for hot flushes

329
Q

What doe post-menopausal bleeding indicate? (3)

A

Not associated pattern of menopause
All post-menopausal bleeding is due to cancer until proven otherwise
Bleeding after 6 months amenorrhoea - need a biopsy to see whether or not women has cancer

Semester 4 Revision (15 decks)

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