1
Q
What is the precursor of all steroids?
A
Cholesterol
2
Q
What is the distribution of cholesterol?
A
- Membrane lipid
- In plasma associated with apoproteins, triacylglycerols & phospholipids in structures called lipoproteins
- Cytosolic lipid droplets as cholesterol esters
3
Q
What is the structure of Cholesterol?
A
- Cyclopentanoperhydrophenanthrene nucleus
- 8-carbon aliphatic side chain
4
Q
How is cholesterol synthesised?
A
From acetyl CoA in a multi-step process that occurs in the SER & cytosol
5
Q
What is the rate limiting step in cholesterol synthesis?
A
Conversion of 3-hydroxy-3-methylglutaryl (HMG-CoA) to Mevalonate by HMG-CoA reductase
6
Q
What are the 3 main physiological roles of cholesterol?
A
- Component of cell (plasma) membrane
- Precursor for the production of bile salts
- Precursor for all steroid hormones
7
Q
What does cholesterol do as a component of the cell (plasma) membrane?
A
- Decreases membrane fluidity
- Decreases physical permeability to charged/polar compounds
- Associated with formation of lipid rafts
8
Q
What does cholesterol do as a precursor for the production of bile salts?
A
Uptake of fats & fat-soluble vitamins in GI tract
9
Q
Give 3 examples of steroid hormones that cholesterol acts as a precursor to?
A
- Glucocorticoids
- Mineralocorticoids
- Sex steroids
10
Q
Give 5 examples of what pregnenolone (from cholesterol esters) form into?
A
- Aldosterone
- Cortisol
- Testosterone
- Estradiol
- Progesterone
11
Q
What are the 2 adrenal steroids?
A
- Mineralocorticoid aldosterone
2. Glucocorticoid cortisol
12
Q
Where are the enzymes associated with biosynthesis of adrenal steroids located (2)?
A
- Smooth endoplasmic reticulum (SER)
- Mitochondria
13
Q
What is the side-chain cleavage enzyme that produces pregnenolone also known as?
A
20,22 desmolase
14
Q
What happens if the synthesis of cortisol is prevented by any one of several dysfunctional enzymes?
A
Other steroid products might be produced in excess
15
Q
In the biosynthesis of what 2 things are certain pathways shared?
A
Androgens as well as estrogens
16
Q
What is the main cytochrome P-450 enzyme involved in steroidogenesis?
A
Cholesterol side chain cleavage (P-450SSC)
17
Q
What is the gene associated with Cholesterol side chain cleavage enzyme (P-450SSC)?
A
CYP11A1
18
Q
What does Aromatase enzyme (P-450arom) do?
A
Catalyzes a reaction essential for the production of estrogens
19
Q
How many different P-450 enzymes have been identified in the human genome?
A
57
20
Q
What are the 3 different structures making up the adrenal gland?
A
- Capsule
- Cortex
- Medulla
21
Q
What are the 3 different zones in the cortex of an adrenal gland?
A
- Zona glomerulosa
- Zona fasciculata
- Zona reticularis
22
Q
What hormone does the Zona Glomerulosa produce in the adrenal gland cortex?
A
Mineralocorticoid (aldosterone)
23
Q
What hormones does the Zona Fasciculata & Zona Reticularis produce in the adrenal gland cortex?
A
- Glucocorticoids (cortisol)
- Androgens (DHEA) / sex hormones
24
Q
Describe the course of the blood supply of the adrenal glands?
A
Enters cortex in subcapsular region & flows through anastomotic capillary beds while coursing through both cortex & medulla
25
What special cells does the adrenal medulla contain?
Chromaffin cells
26
What hormones does the chromaffin cells in the adrenal medulla secrete?
- Epinephrine
| - Small amount of norepinephrine
27
What does DHEA stand for?
Dehydroepiandrosterone
28
In a male human what is the preferred pathway for pregnenolone to from testosterone?
Pregnenolone --> DHEA --> Androstenediol --> oxidation of A ring --> Testosterone
29
What is the function of Leydig cells in testis?
They produce testosterone in the presence of luteinizing hormone (LH)
30
What is the function of Sertoli cells in testis?
- FSH stimulates the Sertoli cells to secrete androgen-binding protein into lumen of seminiferous tubules
- Binding of testosterone in lumen provides local testosterone supply for developing spermatogonia
31
What is the cross-link between Leydig cells and Sertoli cells?
- Leydig cells make testosterone, which acts on Sertoli cells
- Sertoli cells convert some of this to estradiol, which can act on Leydig cells
- Sertoli cells generate growth factors that act on the Leydig cells
32
How does the biosynthesis of ovarian steroids differ to testicular steroids?
Ovaries have aromatase, which converts androgens to estrogens
33
What is the major product of the ovary follicle in the follicular phase?
Estradiol
34
What is the major product of the corpus luteum in the ovary?
Progestins
35
What happens in the follicular phase of the ovary?
- LH primes the Theca cell to convert cholesterol to androstenedione
- Androstenedione diffuses to the granulosa cell, whose aromatase activity has been stimulated by FSH
- Aromatase converts androstenedione to estradiol
36
Why does Androstenedione have to diffuse from the Theca cell to the granolasa cell to be converted?
Theca cell lacks aromatase, it cannot generate estradiol from androstenedione
37
Where are the 2 places cholesterol is derived from?
1. Diet
| 2. Synthesised in Liver
38
Describe the movement of cholesterol?
Transported to steroidogenic tissue primarily in form of LDL, taken up by receptor- mediated endocytosis & stored esterified to fatty acids in cytosolic lipid droplets
39
What are the 2 major sites for steroid hormone biosynthesis?
1. Adrenal cortex
| 2. Gonads
40
What are the 5 major classes of plasma lipoproteins?
1. Chylomicrons
2. VLDL
3. IDL (intermediate density lipoproteins)
4. LDL
5. HDL
41
What enzyme breaks cholesterol esters into free cholesterol?
Cholester Hydrolase
42
What does free cholesterol give rise to?
Pregnenolone
43
What is the fundamental reproductive unit of the female?
Single ovarian follicle, composed of one germ cell (oocyte), surrounded by endocrine cells
44
What is Menarche?
- Beginning of menstrual cycles (average 11-13yr)
| - Maturation of GnRH pulsatility so primarily hypothalamic
45
What are the different things which determine age at puberty for a female?
- Genetics
- Nutrition
- Geographic location
- Exposure to light
- Body composition, fat deposition
- Exercise
46
What is the female sexual cycle/menstrual cycle controlled by?
- Gonadotropins
| - Gonadal hormones
47
Describe the 3 phases in the ovarian cycle?
1. Follicular phase (15days)
2. Ovulatory phase (1-3days)
3. Luteal phase (13day)
48
What are the 3 phases in the endometrial cycle?
- Menstruation
- Proliferative
- Secretory
49
What is oogenesis?
Production of gametes (eggs) during the foetal period
50
What are the 4 functions of the ovaries?
1. Oogenesis
2. Maturation of oocyte
3. Expulsion of mature oocyte (ovulation)
4. Secretion of female sex steroid hormones (oestrogen & progesterone) & peptide hormone inhibin
51
What are the 5 stages in the development ovarian follicle?
1. Primordial follicle
2. Primary follicle
3. Preantral follicle
4. Early astral follicle
5. Mature follicle
52
What is the mature version of an oocyte called?
Ovum
53
What does oogenesis involve?
Completion of meiosis which occurs at the time of fertilisation
54
How is oogonia produced?
In embryonic yolk sac by mitotic division (max 7 million) 3 weeks post conception
55
What happens to oogonia at 8-10weeks of gestation?
Prophase of 1st meiosis starts, becomes primary oocyte
56
What is the oogonia surrounded by?
Pre-granulosa cells
57
What is the oogonia also called?
Primordial follicle
58
Describe 1st phase of oogenesis occurring during foetal life?
- Migrate to ovary
- Colonise the cortex
- Undergo mitosis
- At 8-10weeks meiosis begins
59
What happens to the remaining oocytes which aren't degenerated?
Arrested in meiotic prophase until last oocytes are ovulated (upto 50years)
60
What are the 2 most common cytogenetic abnormality which increases with maternal age?
- Aneuploidy
| - Down Syndrome
61
What happens in the 2nd phase of oogenesis at ovulation?
- Meiosis resumes, 1st division is completed & haploid nuclei separated to form 2 cells
- Cytoplasma unequally shared
- Meiosis arrests again at metaphase II & secondary oocyte is ovulated
- 2nd division of meiosis is only completed in those oocytes that are fertilised
62
What stimulates meiosis resuming in 2nd phase of oogenesis?
Lutenizing Hormone (LH)
63
What does the cytoplasm being unequally shared in the 2nd phase of oogenesis form?
Large secondary oocyte & polar body (which has no further role)
64
What are the 3 differences between spermatogenesis & Oogenesis?
1. Females, mitotic proliferation of oogonia occurs prior to birth. Males, spermatogonia proliferate after puberty
2. Females, meiotic divisions of oocyte produces only 1 mature ovum. Males, produce 4 mature spermatozoa
3. Females, 2nd meiotic division is completed only upon fertilisation. Males, products of meiosis (spermatids) undergo substantial differentiation in maturing process
65
Describe the male spermatogenesis?
- Continuous
- Lower temperature required
- Meiosis begins at puberty
- Results in production of infinite numbers of sperm (testis have stem cell population)
- Results in production of motile gametes
66
Describe the female oogenesis?
- Discontinous (periods of arrest)
- Normal body temperature
- Meiosis begins before birth
- Results in production of finite numbers of oocytes (no stem cells)
- Results in production of immotile gametes
67
What do the eggs in ovaries exist in?
Follicles
68
What is step 1 to follicular development?
Primordial follicle= single layer of granolas cells around oocyte
69
What is step 2 to follicular development?
Oocyte size increases, multiple layers of granulosa cells & separation of oocyte from granulosa cells by thick layer of material
70
What is step 3 to follicular development?
Cytoplamic processes cross the zona pelucida & form gap junctions with oocyte & nutrients & chemical messengers are passed to oocyte
71
What is step 4 to follicular development?
Follicle grows by mitosis of granulosa cells & some differentiate to become theca
72
What is step 5 to follicular development?
Antrum begins to form amongst granulosa cells from fluid they secrete
73
Describe Small Follicles (Primordial)?
- Most numerous
- Non-growing
- Oocyte nucleus is in meiotic prophase
- Single layer of follicular cells (granulosa cells)
- Secrete anti-Müllerian hormone (AMH)
74
What do anti-Müllerian hormone (AMH) levels tell us?
Reflect the ovarian follicular reserve & therefore can be measured to assess ovarian ageing
75
Describe Medium Follicles (Primary)?
- Follicular (granulosa) cells divide, forming 3 layers around the oocyte
- Growth is independent of hormones
- Takes 85days (3 cycles) to reach 3 layers of follicular cells
76
How many oocytes may a female lose?
~650 per cycle
77
Describe Large follicles (Secondary, antral, Graafian, preovulatory)?
- Zona pellucida (egg shell) develops & enclosing the oocyte & masking its antigens
- Rapid mitotic division in follicular cells forms many layers
- Antrum develops & fills with fluid
78
What does the FSH do to medium follicles?
Stimulates rapid development of medium follicles over 14days leading to either ovulation/atresia
79
Initial follicular growth is ________ of hormones and takes _______?
- Independent
| - 85 days
80
Final follicular growth is dependent on _____ and takes ________?
- FSH
| - 10-14 days
81
What effect does LH surge have on the chemical mechanics of ovulation?
Induces prostaglandin endoperoxide synthase in granulosa cells (sets up pseudoinflammatory response)
82
What effect does FSH (some LH) have on the chemical mechanics of ovulation?
Stimulates release of plasminogen activator from granulosa cells (converts plasminogen to plasmin)
83
What effect does Prostaglandins E & F have on the chemical mechanics of ovulation?
Release lysosomal enzymes that digest follicular wall
84
What effects does "stigma" have on the chemical mechanics of ovulation?
- Forms on surface of follicle, balloons out, forms vesicle and ruptures
- Oocyte expelled
85
What 2 things is the process of ovulation facilitated by?
- Intrafollicular pressure
| - Contraction of smooth muscle in theca
86
How is the corpus luteum formed?
- Mature follicle discharges its astral fluid & egg, collapses around antrum & undergoes rapid transformation
- Granulosa cells enlarge, & form gland-like corpus luteum
87
What 3 things does the Corpus luteum secrete?
- Oestrogen
- Progesterone
- Inhibin
88
What happens to the corpus luteum if no egg is fertilised?
Development reaches max within ~10 days & rapidly degenerates by apoptosis
89
What happens half way through the follicular phase?
One follicle becomes dominant and matures
90
What are the 2 anterior pituitary gonadotopins in a female?
- LH
| - FSH
91
What are the 2 gonadal sex hormones in a female ?
- Oestrogen
| - Progesterone
92
What is the hormonal pattern of FSH in a female?
Increases in early part of follicular phase, then steadily decreases throughout remainder of cycle EXCEPT small midcycle peak
93
What is the hormonal pattern of LH in a female?
- Constant during most of follicular phase, then large midcycle increase (LH surge) peaking ~18h before ovulation
- Then rapid decrease with further slow decline during the luteal phase
94
What is the hormonal pattern of Oestrogen in a female?
- Low & stable for 1st week, increases rapidly in 2nd weeks, starts to decline before LH peak
- Then 2nd increase due to corpus luteum in last few days of cycle.
95
What is the hormonal pattern of Progesterone in a female?
- Low level due to ovary release during follicular phase with small increase just before ovulation
- Soon after ovulation, large increase due to CL release, then similar pattern to oestrogen
96
What is the hormonal pattern of Inhibin in a female?
Similar pattern to oestrogen ie. increases in late follicular phase, remains high during luteal phase, decreases as corpus luteum degenerates
97
How does oestrogen have NEGATIVE feedback effects on ovarian hormones?
In low plasma conc, causes anterior pituitary to secrete less FSH & LH during early & middle follicular phase in response to GnRH & also may INHIBIT hypothalamic neurons that secrete GnRH
98
How does inhibin have NEGATIVE feedback effects on ovarian hormones?
Acts on pituitary to INHIBIT the secretion of FSH throughout cycle
99
How does oestrogen have a POSITIVE feedback effect on ovarian hormones?
- Increasing dramatically, causes anterior pituitary cells to secrete more LH & FSH in response to GnRH which triggers ovulation
- Can also STIMULATE hypothalamic neurons that secrete GnRH
100
How does progesterone have a NEGATIVE feedback effect on ovarian hormones?
High plasma conc, in presence of oestrogen, INHIBIT hypothalamic neurons that secrete GnRH, preventing LH surges during luteal phase & pregnancy
101
When is the concentration of FSH in the blood at its maximum?
During follicular phase of the menstrual cycle
102
In the 1st week of the follicular phase what does FSH stimulate?
Growth of medium sized follicles
103
During the follicular phase what do granulosa cells express?
FSH receptors
104
What are granulosa cells homologous with?
Sertoli cells of the testis
105
What does Luteinising hormone (LH) stimulate during the secretory phase?
Steroid hormone synthesis by the corpus luteum
106
What are Theca cells similar to?
Leydig cells in males
107
What diffuses from the Theca cells to the Granulosa cells during the early & middle follicular phases?
Androgen (androstenedione) through basement membrane
108
How is an LH surge formed?
Dominant follicle secretes large amounts of oestrogen which acts on anterior pituitary (& hypothalamus) to cause LH surge
109
What does LH surge trigger?
Ovulation & formation of corpus luteum
110
What is the action of LH mediated by?
Granulosa cells
111
What does oestrogen cause?
- Mid-cycle shift from negative to positive feedback
- Caused by up regulation of receptors (GnRH) when oestrogen levels increase
- Resulting in LH & FSH surge prior to ovulation
112
What are the 5 effects of LH surge on ovarian function?
1. Oocyte completes 1dt meiotic division & undergoes cytoplasmic changes that prepare the ovum for implantation
2. Antrum size & blood flow to follicle increase
3. Granulosa cells release progesterone & decrease release of oestrogen
4. Enzymes & prostaglandins breakdown follicular-ovarian membranes which rupture
5. Remaining granulosa cells of ruptured follicle are transformed into corpus luteum
113
What are the 7 functions of granulosa cells?
1. Nourish oocyte
2. Secrete chemical messengers
3. Secrete antral fluid
4. Site of action for oestrogen & FSH (early & middle follicular phase)
5. Express aromatase
6. Secrete inhibin
7. Site of action for LH induction of changes in oocyte & follicle culminating in ovulation & formation of corpus luteum
114
What does aromatase do?
Converts androgen (from theca cells) to oestrogen
115
What things happen if no implantation in the luteal phase?
- hCG does not appear in blood
- Corpus luteum dies
- Progesterone & oestrogen decreases
- Menstruation occurs & next menstrual cycle begins
116
What is the timeline of events which occur when there is enough oestrogen from ovary?
LH surge induced --> ovulation --> corpus luteum degenerates --> decrease (oestrogen/progesterone) secretion --> FSH & LH increase enough for new follicle growth
117
What happens if progesterone remains high?
Levels of LH & FSH will be suppressed & ovulation will NOT occur ie. in pregnancy
118
How does progesterone remain high in pregnancy?
Human chorionic gonadotrophin produced by placenta maintains corpus luteum which continues to secrete progesterone
119
What is used for oral contraceptive pills/why?
Oestrogen as it suppresses LH & FSH & prevents ovulation
120
What are the 11 other things oestrogen stimulates?
1. Growth of ovary & follicle
2. Growth of smooth muscle & proliferation of epithelial linings of reproductive tract
3. External genitalia growth, particularly during puberty
4. Breast growth, particularly ducts & fat deposition during puberty
5. Female body configuration development
6. Fluid secretion from lipid-producing skin glands
7. Bone growth & cessation of bone growth
8. Vascular effects
9. Feedback effects on hypothalamus & anterior pituitary
10. Prolactin secretion
11. Protects against atherosclerosis
121
What effect does oestrogen have on the Fallopian tubes?
Increases contractions & ciliary activity
122
What effect does oestrogen have on the uterus?
- Increase myometrial contraction & responsiveness to oxytocin
- Stimulates secretion of abundant, watery cervical mucus
- Prepares endometrium for progesterone's actions by inducing progesterone receptors
123
What effect does oestrogen have on the vagina?
Increases layering of epithelial cells
124
What are the 8 other effects of progesterone?
1. Converts oestrogen-primed endometrium to actively secreting tissue suitable for implantation of an embryo
2. Induces thick, sticky cervical mucus
3. Decreases contractions of fallopian tubes & endometrium
4. Decreases proliferation of vaginal epithelial cells.
5. Stimulates breast growth (glandular tissue)
6. Inhibits milk-inducing effects of prolactin.
7. Feedback effects on hypothalamus & anterior pituitary
8. Increases body temperature.
125
What inhibits the secretion of GnRH & gonadotropins during the luteal phase?
Combination of progesterone, oestrogen and inhibin
126
What is the mean length of the menstrual cycle?
Mean 28days (3/- 3.95) for about 40 years
127
What is Menopause?
- Occurs at ~45-55yrs (51yrs avg) & marks end of natural fertility
- Exhaustion of primordial follicles so primarily ovarian
128
When are human females sexually receptive to males?
Throughout their cycle
129
How long is the menstrual phase?
~3-5 days in a typical 28 day cycle
130
What happens during the 1. menstrual phase?
Epithelial lining of uterus (endometrium) degenerates which is part of ovarian follicular phase
131
What happens during the 2. proliferative phase
- Menstrual flow ceases
- Under influence of oestrogen, endometrium thickens
- Growth of underlying smooth muscle (myometrium)
- Synthesis of receptors for progesterone in endometrial cells
132
How long does the 2. proliferative phase last?
~10 days until ovulation
| part of follicular phase
133
What is the proliferative phase dominated by?
Estradiol 17β
134
Describe the proliferative phase histology?
- Repair of lining epithelium after menstruation
- Proliferation & thickening of stroma
- Simple test tube shaped glands
- Induction of synthesis of intracellular receptors for progesterone
- Contractility & excitability of myometrium increases
135
When does the 3. secretory phase occur/ how long does it last?
- Soon after ovulation
| - ~12 days long
136
What happens during the 3. secretory phase?
- Endometrium increases secretory activity under influence of progesterone acting on oestrogen-primed tissue
- Effect on endometrial glands
- Coincides with ovarian luteal phase
137
What effects does the 3. secretory phase have on the endometrial glands & why?
- Become coiled, filled with glycogen, blood vessels become more numerous, enzymes accumulate in glands & connective tissue
– Making endometrium hospital environment for implantation & nourishment of developing embryo
138
What is the secretory phase dominated by?
Progesterone
139
Describe the secretory phase histology?
- Proliferation/thickening of stroma
- Spiral arteries develop alongside complex,
hacksaw shaped glands
- Secretion in the glands is rich in glycoprotein sugars & amino acids
- Enlargement of myometrial cells but depressed overall excitability
140
What is lost during the ischaemic phase?
Steroid support
141
Describe the ischaemic phase histology?
- Constriction of spiral arteries
- Ischemia & collapse of endometrium
- Separation of basal & functional layers
- Functional layer is shed as menstrual bleeding
- Increase in neutrophils
142
How much blood is lost in each menstrual phase?
30-80mls normal
143
Describe the bleeding in the menstrual phase?
Bleeding without clotting, endogenous fibrinolytic activity
144
What happens to oestrogen & progesterone levels during the menstrual cycle days 1-5?
Low because the previous corpus luteum is regressing
145
What is the effect of LOW oestrogen & progesterone in the menstrual cycle?
- Endometrial lining sloughs
- Secretion of FSH & LH is released from inhibition & plasma conc increase
- Severe growing follicles are stimulated to mature
146
What is the major event which occurs at day 7 of the menstrual cycle?
Single follicle (usually) becomes dominant
147
What is the major events which occur during days 7-12 of the menstrual cycle?
- Plasma oestrogen increases due to secretion by dominant follicle so endometrium stimulated to proliferate
- LH & FSH decrease due to oestrogen & inhibin negative feedback so degeneration of non-dominant follicles
148
What are the major evens which occur at days 12-13 during the menstrual cycle?
- LH surge induced by increased plasma oestrogen
- Oocyte induced to complete 1st meiotic divisions & undergo cytoplasmic maturation
- Follicle stimulated to secrete digestive enzymes & prostoglandins
149
What are the major events at day 14 during menstrual cycle?
Ovulation is mediated by follicular enzymes & prostaglandins
150
What are the major events at days 15-25 of the menstrual cycle?
- Corpus luteym forms & under influence of low LH, secretes oestrogen & progesterone increasing plasma conc
- Secretory endometrium develops
- Secretion of LH & FSH inhibited
- No new follicles develop
151
What are the major events at days 25-28 of the menstrual cycle?
- Corpus luteum degenerates
- Plasma oestrogen & progesterone conc decrease
- Endometrium begins to slough at conclusion of day 28, new cycle begins
152
What is the ovarian follicular phase equivalent to?
Uterine menstrual & proliferative phases
153
What is the ovarian luteal phase equivalent to?
Uterine secretory phase
154
What is oligomenorrhoea?
Infrequent light periods
155
What is metrorrhagia?
Irregular bleeding
156
What is polymenorrhoea?
Frequent periods
157
What is amenorrhoea?
No periods
158
Describe the causes of dysmenorrhoea?
- Overproduction of prostaglandins produced by endometrium in response to decrease in plasma oestrogen & progesterone
- May account for systemic symptoms ie. nausea, vomiting, headache
159
How common is Premenstrual syndrome (PMS)?
3/4
160
How common is premenstrual dysphoric disorder (PMDD)?
3-8%
161
Describe symptoms of premenstrual dysphoric disorder (PMDD)?
- Anxiety
- Mood swings
- Headaches
- Bloated
- Change in appetite
- Joint pain
- Tender enlarged breasts
- Abdo pain
- Clumsiness
- Depression
162
What may be the cause of the symptoms associated with premenstrual dysphoric disorder (PMDD)?
Fall of progesterone (anxiolytic effects) at end of the cycle
163
What are the primary causes of amenorrhoea?
- Anatomical/congenital abnormality ie. underdevelopment or absence of uterus/vagina
- Genetic ie. Turner's syndrome
164
What are the secondary causes of amenorrhoea?
- Pregnancy
- Lactation
- Exercise/nutrition
- Menopause
- Polycystic ovarian syndrome
- Latrogenic (surgery, medication)
165
What are the effects of amenorrhoea?
- Estrogen deficiency can cause hot flushes, vaginal dryness
| - Loss of bone mineralisation causing reduction in peak bone mass & osteopenia/osteoporosis
166
What is "natural" breast feeding?
- Feeding ad lib & with baby sleeping with mother & feeding though the night
- Female may experience lactational amenorrhoea decreasing likelihood of pregnancy until weaning occurs
167
How common is polycystic ovary syndrome (PCOS)?
- 10% of reproductive age woman
| - Most common reproductive problem
168
What are the characteristics of polycystic ovary syndrome (PCOS)?
- Hyperandrogenemia
- Oligomenorrhea
- Obesity (ethnicity of women)
- Hirsutism (hairiness & acne)
- Infertility
- Enlarged cystic ovaries
169
What is the biochemical spectrum of polycystic ovary syndrome (PCOS)?
- Elevated oestrogen from peripheral armatase, or low from anovulation
- Elevated free testosterone
- Insulin resistance
- Elevated anti Müllerian hormone
170
What are the different types of Polycystic ovary syndrome (PCOS) therapies?
- Weight control (difficult)
- Cycle regulation (oral contraceptive pill)
- Anti androgen therapy (cyproterone acetate)
- Cosmetic hair removal
- Ovulation induction
171
Where is prolactin synthesised & released?
Anterior pituitary gland
172
What is prolactin production normally controlled by?
- Hypothalamic prolactin inhibitory factor (PIF), shown to be dopamine
- Stress inhibits dopamine release which allows prolactin levels to rise
173
How does dopamine have an effect on prolactin production?
Dopamine carried from neurosecretory cells in arcuate nucleus via hypophyseal portal system to anterior lobe of pituitary where it modulates secretion of prolactin
174
What does Hyperprolactinaemia cause?
- Inhibit FSH & LH leading to amenorrhea
| - Inappropriate lactation, libido loss
175
What can pituitary tumours (macro adenoma) cause?
Constrict blood supply to pituitary, preventing PIF from reaching anterior pituitary causing prolactin levels to rise = hyperprolactinaemia
176
What is the surgical approach to pituitary tumour?
Via nasal cavity & sphenoid air sinus
177
How are prolactinomas treated?
Dopamine agonist- Bromocriptine or Cabergoline
178
What is premature ovarian failure (POF)?
Menopause in women <40yrs (idiopathic, autoimmune disorders, genetic disorders such as fragile X, chemotherapy, radiation)
179
How can symptoms of menopause be treated?
Oestrogen replacement (hormone replacement therapy - HRT)
180
What is the definition of infertility according to OED in 2012?
Not fertile; unfruitful, unproductive, barren, sterile
181
What is the definition of infertility in a medical sense?
People who have difficulties (of may find it impossible) to have children naturally
182
What 3 ways is infertility described as being?
- Dysfunction (not a disease)
- Socially constructed disease
- "Terrible disease affecting our sexuality & well being"
183
What are the 3 steps to parenthood?
1. Begetting- bring child into existence through reproduction
2. Gestating- child grows inside the woman
3. Caring- post-birth role
184
What are the different types of parents?
- Intentional parents
- Genetic parents
- Gestational mother
- Nurturing parents
185
How many couples may have difficulty conceiving?
~1/6 couples
| ~3.5 million people
186
What is the % for number of couples who are infertile?
~5%
187
After 3 years of trying to conceive without success, what is the % chance of pregnancy occurring within the next year?
25% or less
188
What are the 3 factors affecting a woman fertility?
- Abnormal ovulation (polycystic ovary syndrome, early menopause)
- Blockage of Fallopian tubes
- Age
189
What are the 3 factors affecting a mans fertility?
- Low sperm count/quality
| - Damage to testicle and/or failure to ejaculate
190
What are the different methods to treat infertility/ assisted reproductive technologies?
- Intrauterine insemination (IUI)
- In vitro fertilisation (IVF)
- IVF with intracytoplasmic sperm injection (ICSI)
- Use of donor sperm/eggs
- Surrogacy
191
What are the 5 steps to in vitro fertilisation?
1. SUPPRESS (GnRH agonist)
2. STIMULATE (FSH)
3. MATURATION (hCG)
4. EGG COLLECTION (ultrasound transvaginal aspiration/laparoscopy)
5. TRANSFER after 2-6days , use ultrasound, use progesterone for luteal phase support
192
What are the risks associated with IVF?
- Ovarian hyperstimulation syndrome (can occur due to super ovulation in response to drugs)
- Transferral of several embryos (multiple births)
- Welfare of the child (1990: need for father. 2008: need for supportive parenting)
193
What is the definition of "supportive parenting"?
Woman shall not be provided with treatment services unless account has been taken of WELFARE of any child born of the treatment & any other child who may be affected by the birth
194
What are the guidelines for IVF in Scotland for <40 years old?
- 3 cycles if:
- Infertility with an appropriate cause of any duration
- Unexplained infertility of 2yrs (heterosexual)
- Unexplained infertility following 6-8 cycles of donor insemination (same sex)
195
What are the guidelines for IVF in Scotland for 40-42yrs old?
- 1 cycle if:
- No IVF before
- No evidence of low ovarian reserve
- Discussion of implications of IVF & pregnancy at this age
196
What is the HFEA statistic (%) for successful IVF in UK (2014)?
26.5% of IVF treatments, using own fresh eggs
197
How much does 1 IVF cycle cost?
~£3500
198
Who/when was the 1st test tube baby?
1978 - Louise Brown
199
What 2 things do the Human fertilisation & embryology authority (HFEA) regulate?
- Treatment (inspect & license clinics)
| - Research (licenses for human embryo research)
200
What was the case regarding homosexual couples using IVF?
NHS Greater Glasgow & Clyde (2009)- NHS said no, but then overturned that decision
201
What was the case regarding single women using IVF?
Elizabeth Pearce (Ealing PCT)- using sperm bought from the uS, and IVF funded by NHS
202
What are the ethical issues surrounding Gametes in IVF?
- Frozen: must state for how long & what happens in event of death
- Donated: is it ok to pay donors? Limit to number of children created? Should children be able to find out biological parents?
203
What is the UK limit of how many children a person can create via IVF?
10 families
204
What are the ethical issues surrounding embryos in IVF?
- Use immediately, freeze, discard, research
- How many should be made?
- How many should be implanted?
- What do we do with spares?
205
What are the ethical issues surrounding reproductive tourism?
- Cost
- Waiting lists
- Avoid legal restrictions
206
What is "3 parent IVF"?
IVF with mitochondrial replacement
207
What is IVF with mitochondrial replacement?
- Allows those at risk of passing on certain mitochondrial conditions to avoid risk
- Pro-nuclear transfer or maternal spindle transfer
208
What are the 4 considerations regarding IVF with mitochondrial replacement?
1. Modification of embryos & changing germline
2. Implications for identity & status of mitochondrial donor
3. General views on permissibility of techniques
4. Licensing models & further regulatory issues
209
What is the main difference between pronuclear & maternal spindle transfer?
- Pronuclear transfer repair is done AFTER fertilisation
| - Maternal spindle transfer repair is done BEFORE fertilisation
210
What did the "House of Commons" say regarding IVF with mitochondria replacement?
Tuesday 3 February 2015 MPs voted by 382-128 to amend the Human Fertilisation & Embryology Act 2008 & ALLOW mitochondrial donation
211
What did the "House of Lords" say regarding IVF with mitochondria replacement?
Tuesday 24 February 2015 peers voted by 280-48 to ALLOW mitochondrial donation to be licensed for use
212
What did the HFEA say regarding IVF with mitochondria replacement?
15th December 2016, APPROVED use of mitochondrial donation in certain, specific cases
213
When/where was the 1st approved clinic application of mitochondrial replacement?
16th March 2017 in Newcastle HFEA approved
214
What is Partial surrogacy?
Surrogate mother inseminates herself with commissioning father's sperm
215
What is full surrogacy?
IVF (commissioning couple's egg & sperm mixed in vitro then transferred
216
What does the Surrogacy Act 1985 say?
Surrogacy agreements are not unlawful but they are unenforceable
217
Who is the legal mother from birth in the UK?
The surrogate mother
218
What are 2 key reports regarding surrogacy?
1. Brazier Report
| 2. Warnock Report
219
What is sexual differentiation?
Male & females become structurally & functionally dissimilar
220
What is sex determination?
Initiation of the male differentiation pathway by SRY gene
221
Describe the human somatic cells?
- 22 pairs of autosomes
| - 1 pair of sex chromosomes (XX or XY)
222
Describe the female somatic cells?
- 46, XX
| - HOMOgametic
223
Describe the male somatic cells?
- 46, XY
| - HETEROgametic
224
Describe the oocyte somatic cells?
- 23
| - X
225
Describe the spermatozoa somatic cells?
- 23, X or...
| - 23, Y
226
What do not normally influence gonad differentiation?
Autosomes or "X" chromosomes
227
What is in control of the genetic determinant of sex?
Presence or absence of Y chromosome
228
What happens once gonadal differentiation is initiated?
Developing gonad releases gonadal hormones that trigger cascades producing sexual dimorphism of reproductive tract
229
Describe the Y chromosome?
- Small
- DNA condesned
- Encodes ~48genes involved in skeletal growth, tooth development
- Few genes involved with testis development
- Has regulatory gene which indirectly controls formation of testes
230
Where are many of the genes required for testis development?
Autosomes or X chromosome
231
What happens to the chromosomes in XY females?
Part of short arm of Y chromosome is missing or mutated
232
What happens to the chromosomes in XX males?
Section of Y chromosome translocated to autosome or X chromosome
233
What is the SRY gene?
Sex-determining region of the Y chromosome which encodes a DNA binding protein (transcription factor) that regulates expression of genes on other chromosomes responsible for testes differentiation
234
What are the 2 distinct cell types that the testes & ovaries are formed by?
1. Somatic mesenchyme
| 2. Primordial germ cells
235
How is the genital ridge formed?
Proliferation of surface epithelium & condensation of mesenchyme forming sex cords
236
Gonads are identical in both sexes until the _____ of development?
7th week
237
Where do the primordial germ cells (PGCs) originate?
Epiblast & 1st identifiable in wall of yolk sac (~2 weeks)
238
What is the movement of primordial germ cells?
Migrate into genital ridge (by week 6) driven by chemotaxis & become surrounded by primitive medullary sex cords
239
What happens if the migration of Primordial germ cells (PGCs) fails to enter the genital ridge?
Gonads do NOT develop as PGCs have inductive influence but no role during sexual dimorphism
240
Describe the gonadal differentiation of a MALE?
- SRY gene = primitive sex cords proliferate & penetrate medulla = TESTIS CORDS
- Testis cords become looped, contract with ingrowing mesonephric tubule called Rete testis
- Primordial germ cells come to reside within developing testis cords
241
What do mesodermal cells differentiate into in the cords of a male gonad?
Sertoli cells
242
What does mesenchyme tissue in interstitial spaces develop into in a male?
Leydig cells & start to secrete testosterone by 8th week
243
What do the male gonads appear like by the 20th week?
Testis cords are horseshoe-shaped, composed of germ cells & Sertoli cells
244
Describe the gonadal differentiation of a female?
- Absence of Y = degeneration of primitive sex cords
- 2nd set of cords form from mesenchyme (cortical cords) & by 12weeks these form distinct cell clusters around the germ cells
245
How are primordial follicles formed in the female gonads?
Cells proliferative & surround each oogonium (germ cell) with epithelial layer of follicular cells
246
What happens to the genital ducts in embryo at 7-8 weeks?
Dual ductal systems that are precursors to male & female internal genitalia
247
What do Wolffian (mesonephric) ducts give rise to?
Male genital ductal system
248
What do the Müllerian (paramesonephric) ducts give rise to?
Female genital ductal system
249
Does the developmental path depend on hormones secreted by developing ovary?
NO
250
In males, what does the SRY act in conjunction with?
Other transcription factors such as SOX9 & SF-1 (steroidogenic factor-1) to stimulate differentiation of Sertoli & Leydig cells
251
What do the Sertoli cells express & why?
Anti-Müllerian hormone (AMH) which leads to regression of Müllerian ducts & prevents female structures
252
What does Leydig cells start secreting/ what does this do?
Testosterone which supports development of Wolffian ducts & leads to virilisation
253
What happens in absence of any hormones?
Wolffian ducts degenerate & Müllerian ducts develop forming fallopian tubes
254
What does WNT4 (ovary-determining gene) do?
- Up-regulates DAX1= inhibits function of SOX9, preventing male program
- Regulates expression of other genes responsible for ovarian differentiation
255
What forms the lower vagina?
Paramesonephric tubercle (region called sinovaginal bulbs)
256
When is the vaginal outgrowth complete?
20 weeks
257
Like gonads, external genitalia are initially ______?
Bipotential
258
What does the developmental path for external genitalia depend on?
Presence or absence of androgens
| present in male, absent in female
259
Describe Turner's Syndrome?
- 45, XO
- Deficiency in ovarian steroids
- Lack of secondary sex characteristics (pubic hair, breasts) & infertility
- Short stature, webbed neck, skeletal deformities
260
Describe Triple X syndrome?
- 47, XXX
- "Super female"
- Undiagnosed due to few symptoms apart from being very tall
261
Describe Klinefelter syndrome?
- 47, XXY
- Small testis with decreased spermatogonia
- Male phenotype
- Incomplete virilization & breast enlargement after puberty
262
Describe XYY syndrome?
- 47, XYY
- "Super males"
- Undiagnosed due to few symptoms apart from being taller
263
Describe Sex reversed syndrome ?
- 46, XXSXR
- Testis
- Have female genes
264
Describe (DSD) Pseudohermaphroditism?
Individual with gonads appropriate to genotype but external genitalia of opposite sex
265
Give an example of a DSD syndrome due to endocrine signalling between gonads & developing tissues?
- Androgen-insensitivity syndrome
| - 46, XY karyotype
266
Describe (DSD) Androgen-Insensitivity syndrome?
- Testis initially normal but tissues lack androgen receptor so unresponsive to testosterone
- Wolffian ducts degenerate without support of androgens
- Testes secrete normal AMH, female ducts degenerate
- Female external genitalia develops but have undescended testes
267
Describe (DSD) Congential Adrenal Hyperplasia?
- XX with ovaries
- Fetal adrenals are over-active & secrete large amounts of steroid hormones, some have androgenic action
- Development of Wolffian ducts & formation of male external genitalia
- No AMH secreted so female ducts persist
- 2 DUCTAL SYSTEMS!
268
What are the 2 different compartments in the cross section of seminiferous tubules?
- Intratubular compartment
| - Peritubular compartment
269
What are the 2 major compartments in the testes?
1. Semiinferous tubules
| 2. Interstitial spaces
270
Describe the seminiferous tubules of the testes?
- ~250m total length
- Developing germ cells
- Sertoli (sustentacular) cells
271
Describe the interstitial spaces of the testes?
- Leydig cells (synthesize androgens)
| - Blood & lymph vessels
272
What is the function of having 2 separate compartments in the testes?
- Separate "blood-testis barrier"
- Prevents immune reaction to spermatozoa
- Separates fluids of different composition
273
What is spermatogenesis?
Production of mature spermatozoa from undifferentiated germ cells (primordial germ cell)
274
What are the 3 stages of spermatogenesis?
1. Mitotic proliferation
2. Meiotic (reduction) division
3. Cell modelling (spermiogenesis)
275
What is the different types of cells which lead up to the production of spermatozoa?
Primordial germ cell --> Spermatogonia --> Primary spermatocyte --> Secondary spermatocyte --> Spermatids --> SPERMATOZOA
276
How long is the gap between 1st mitotic division & release of spermatozoa?
74 days
277
Spermatogenesis occurs in _____, initiated every ______>
- Waves (4-5 cells at different stages of development)
| - 16 Days
278
How often does spermiogenesis occur?
~200 million/day
| 2300/second
279
What are the 4 different parts to a sperm?
1. End piece
2. Principle piece
3. Middle piece
4. Head
280
What happens at the end of differentiation?
- Cytoplasmic links broken
- Spermatozoa released into tubule lumen
- Sperm virtually immobile
281
What does the large amounts of fluid secreted by Sertoli cells help the movement of?
Flushes developing spermatozoa from seminiferous tubules, through the rete testis into epididymis
282
How is motility of spermatids suppressed?
Epididymal fluid
283
If ejaculated spermatozoa are placed with oocytes in vitro fertilization _____ occur immediately. They need to undergo _______?
- Doesn't
| - Capacitation (normally occurs in female reproductive tract 2-6hrs)
284
What 2 changes happen to the sperm due to female reproductive tract (2-5hr)?
- Hyperactivation by progesterone (increased flagellar beats)
- Head acquires capacity to initiate acrosome reaction
285
What % of sperm in humans show morphological abnormalities?
Upto 30% (sperm quality poor)
286
What is a normal sperm count?
50-150 x 10*6/ml
287
What is sub fertility?
< 20 x 10*6/ml
| oligozoospermia
288
What is Azoospermia?
Absence of sperm in the ejaculate
289
What is Asthenozoospermia?
Low sperm motility (<50% moving)
290
What is Teratozoospermia?
High proportion of abnormally-shaped sperm
291
What is Antiserum antibodies?
Abnormal immune response to sperm
292
What are the 4 different types of hormones the testes synthesis?
1. Testosterone (steroid) by Leydig cells
2. Estrogens (steroid) but Sertoli & Leydig cells
3. Inhibins (polypeptides) by Sertoli cells
4. Oxytocin (polypeptide) by Leydig cells
293
What is the steroid hormone biosynthesis in the testis?
Acetate --> Cholesterol --> Progesterone --> Testosterone --> Estrogens
294
When/What happens if testosterone production is prevented?
- Spermatogenesis ceases
| - Blocked when primary spermatocyte enters meiotic prophase
295
What happens if blood testosterone is low?
Few stem cells with begin cell division but the whole process will still take 74 days
296
How does the pituitary gland & hypothalamus have a role in testicular function?
Hypothalamus secretes gonadotrophin-releasing hormone (GnRH) which causes anterior pituitary to secrete gonadotrophins from the gonadotroph cells
297
What hormones does the anterior pituitary/Adenohypophysis produce?
1. GONADOTROPHS- basophilic cells, secrete LH & FSH (glycoproteins). Most secrete 1, some both
2. LACTOTROPHS- acidophilic cells, secrete prolactin (polypeptide)
298
What hormones does the posterior pituitary/Neurohypophysis produce?
NEUROSECRETORY NEURONES- secrete arginine vasopressin (AVP) & oxytocin (peptides)
299
What must GnRH be for it to be effective?
Released into portal blood in PULSES every hr
300
What does high and low GnRH amplitiude & frequency each synthesis and secrete?
- HIGH: LH
| - LOW: FSH
301
What happens if LH secretion is too low?
Testosterone is low, spermatogenesis halts
302
What is the function of FSH?
Required for maximum sperm production, acts of Sertoli cells
303
What does FSH, binding to Sertoli cells FSH receptors, cause in increase in?
- RNA & Protein synthesis
- Energy metabolism
- cAMP
- Inhibin secretion
- ABP secretion
- Fluid secretion
- Androgen & FSH receptors
304
What are the contents of the spermatic cord?
- Testicular artery (from Ao L2) & pampiniform plexus
- Artery to vas
- Cremasteric artery (from inferior epigastric)
- Vas
- Lymph from testis (to para-aortic nodes)
- Closed remnant of processus vaginalis
- Genital branch of genitofemoral nerve
- Sympathetic (efferent & afferent to testis)
- Ilio-inguinal nerve (L1)
305
What could happen if the processus vaginalis did not close off?
Lead to cysts and/or hydrocele
306
How does the spermatic cord begin & end?
Begins at deep ring, completed as it picks up external spermatic fascia from external oblique at superficial ring
307
What is the L1 cremaster reflex?
Ipsilateral testicular retraction on stroking upper, medial thigh due to cremaster muscle supply by genital branch of genitofemoral nerve
308
Where does the referred pain go from the testis and why?
- Peri-umbilical region
| - Sympathetic nerves derived from lesser splanchnic nerve T10 & 11
309
What makes up the cremasteric (middle layer) fascia & muscle?
Transversus abdominis & internal oblique
310
What does the external oblique form?
External spermatic fascia
311
What does the transversalis fascia form?
Internal spermatic fascia
312
What does the parietal peritoneum form?
Loops down developing spermatic cord as processes & tunica vaginalis
313
Where is the scrotum & testis suspended?
Inferior to urogenital triangle, outside the body
314
What testis is lower than the other?
Left lower than right
315
Describe the skin of the scrotum?
- Rugose
- No fat
- Dartos muscle (smooth, sympathetic genital branch of genitofemoral)
- Midline raphe divided by septum
316
Name the different scrotal fascia layers?
- Tunica vaginalis (visceral & parietal)
- Internal cremasteric fascia
- External spermatic fascia
- Dartos fascia
317
What makes up Dartos fascia?
Colles' perineal fascia (continuous with Scarpa's) & Dartos muscle (camper's)
318
What 2 things does the Scarpa's fascia fuse with in the thigh below the inguinal ligament?
- Fascia lata
| - Perineal body
319
What are "blue swimming trunks, but front only" a sign of?
Bruising trapped under Scarpa's & Colles'
320
What are the 2 different nerve supplies of the scrotum?
- ANTERIOR 1/3: L1, ilio-inguinal, genitofemoral
| - POSTERIOR 2/3: S2 & S3 via scrotal branches of perineal branches of Pudendal nerve
321
What are the 2 different blood supplies of the scrotum?
- ANTERIOR 1/3: deep & superficial external pudendeal branches of femoral
- POSTERIOR 2/3: internal pudendal branch of internal iliac
322
What are the 2 different venous supplies of the scrotum?
- ANTERIOR 1/3: deep & superficial external pudendal veins to great saphenous
- POSTERIOR 2/3: internal pudendal
323
What is the lymph drainage of the scrotum?
Superficial inguinal nodes
324
Describe the movement of sperm in the testis?
Seminiferous Tubules --> Rete testis in mediastinum --> via efferent ductules --> Epididymis
325
What are the 3 different parts of the epididymis (post-lat)?
1. Head
2. Body
3. Tail becoming vas
326
What is the function of the tough capsule of tunica albuginea?
Maintains internal pressure to help transport of sperm
327
What can be the clinical problem of the epididymis & testis?
Testicular torsion, rotate on pedicle = necrosis
328
What is the appendix epididymis?
Remnant of the proximal end of mesonephric duct
329
What is the Appendix testis & Prostatic utricle?
Remnants of the paramesonephric duct
330
Describe the 3 different tunics/coats of the testis?
1. VAGINALIS (visceral & parietal), potential space for movement, sinus of epididymis
2. ALBUGINEA, fibrous, forms mediastinum & septae
3. VASCULOSA with branches of testicular vessels
331
What does the left & right testicular veins (from pampiniform plexus) drain into?
- LEFT: left renal vein
| - RIGHT: IVC
332
What is Varicocele?
Visible/Palpable in the scrotal skin, mass of varicose veins in the spermatic cord
333
Where does the vas deferens emerge into the abdomen?
Lateral to inferior epigastric artery, then lies on lateral wall of pelvis
334
Vas deferens leaves scrotum, ______ to epididymis?
Medial
335
What part of the vas deferens unites with the duct from seminal vesicle to form ejaculatory duct?
Dilated ampullary end of vas
336
What 3 things in the male urethra prevent compression?
1. Bulbo-urethral
2. Mucous glands
3. Corpus spongiosum
337
What happens to the internal sphincter during ejaculation?
Contracts (sympathetic) to prevent back flow of semen
338
Where does the ejaculatory duct enter the urethra?
Veru montanum
339
What is the "false pelvis"?
Posterior abdominal wall, iliacus covering the iliac bones
340
Obturatory internus lines _______, Levator ani forms _______?
- Pelvic lateral wall
| - Muscular pelvic floor
341
What does the diamond-shaped perineum contain anteriorly & posteriorly?
- ANTERIOR: genitalia & urethra
| - POSTERIOR: anal canal & ischia-anal fossae
342
What divides the perineum (pudendal region) into deep & superficial compartments?
Perineal membrane
343
What 2 things enclose the greater & lesser sciatic foramina?
- Sacrospinous ligament
| - Sacrotuberous ligament
344
Describe the piriformis muscle?
- From sacrum to greater trochanter
- Forms posterior pelvic wall
- Divides greater sciatic foramen
345
Describe the obturator internus muscle?
- From obturator membrane & adjacent bone to greater trochanter
- Forms lateral pelvic wall
- Overlying obturator fascia, giving origin to pelvic levator ani
346
What is the tendinous arch?
Thickening of obturator fascia for attachment of levator ani
347
What passes out of the greater sciatic foramen into the buttock and what happens to it next?
- Pudendal nerve
- Then curves posterior to ischial spine, sacrospinous ligament & coccygeus to run forward into perineum below levator ani
348
What 2 muscles makes up the pelvic floor/pelvic diaphragm?
1. Coccygeus
| 2. Levator ani
349
Describe the 2 divisions of levator ani muscle?
1. Iliococcygeus (S3, 4)
| 2. Pubo-coccygeus: divided into pubo -rectalis, -vaginalis/prostaticus, -urethralis (S3, 4)
350
What is the function of the pelvic floor/ "bowl" structure?
- Support of viscera
- Maintenance of urinary & faecal continence
- Augments external anal & urethral sphincters
- Forms vaginal sphincter
351
What does each side of the levator ani muscle meet in the midline to form?
Anococcygeal raphe & perineal body/central tendon of perineaum just anterior to anal canal & posterior to vagina in female
352
What is the nerve supply of puboprostaticus muscle?
Direct branches from S3, 4
353
Where may the obturator lymph nodes be located?
Lateral pelvic walls, alongside Obturator Neurovascular bundle
354
What are the somatic, conscious, voluntary pelvic nerves?
- Ventral rami of L4,5 & S1,2,3,4 from anterior sacral foramina --> lumbosacral plexus
- Pudendal nerve S2,3,4 to pelvic floor & voluntary sphincters
- Direct branches from S3,4 to pelvic floor muscles
355
Describe the sympathetic trunks (autonomic) which supply the pelvis?
- Bilateral
| - Give sacral splanchnics, superior hypogastric plexus sending left & right branches to pelvic plexuses
356
What are the nerve roots of parasympathetic pelvic splanchnics (autonomic)?
S2,3,4
357
What does the thoracic sympathetic trunk give off?
1. Greater splanchnic nerve T5-9 (foregut)
2. Lesser splanchnic nerve T10-11 (midgut)
3. Least splanchnic nerve T12 (hindgut)
358
What do the splanchnic nerves from?
Pre-aortic plexus & synapse in ganglia at coeliac trunk, SMA & IMA
359
Describe the sympathetic trunks?
- Anterior to sacrum & duse as ganglion impar opposite coccyx
- Carry pre-ganglionic nerves T10-L2 and emerge as white rami communicates to sympathetic trunks
- Then give sacral splanchnic nerves to pelvic plexus
360
Describe the Pelvic (inferior hypogastric) plexus?
- From superior hypogastric plexus
- Carrying fibres from lesser & least splanchnic nerves T10,11,12
- "Boosted" bu sacral splanchnics
- Afferent & efferent
361
Describe Pelvic Splanchnics?
- Afferent & efferent parasympathetic fibres S2,3,4
- Join pelvic plexus
- Splanchnic & somatic nerves (pudendal) carry both motor & sensory fibres
362
Where is the pelvic plexus located?
In fascia lateral to rectum, seminal vesicles & prostate (cervix & vaginal fornices) & posterior aspect bladder. In angle between internal iliac & inferior vesical arteries
363
What sends branches to control recto-anal, urinary & reproductive/sexual function?
Pelvic plexuses & Pudendal nerves
364
Where does the internal iliac artery originate from?
Common iliac opposite SI joint at level of L5 disc
365
What does the internal iliac artery supply?
- Buttock & medial thigh, posterior pelvic & abdominal walls, pelvic viscera & perineum
- Gluteal branches contribute to anastomoses around hip = collateral circulation for lower limb
366
Describe the internal iliac vein?
- Joins external iliac to form common iliac, forming IVC
367
What is the anal canal a site of?
Porto-systemic anastomosis
368
What is the head of the spermatozoon made of?
- Nucleus
| - Acrosome
369
What happens is vasa efferentia is blocked?
Seminiferous tubules & testis swell
370
How long does it take sperm & fluid to travel through vasa efferentia & epididymis?
6-12 days
371
What are the concentration changes to spermatozoa in epididymis?
100-fold
| 5x10*7/ml entering & 5x10*9/ml leaving
372
What are the sperm modelling changes to spermatozoa in epididymis?
- Nuclear condensation & acrosome shaping completed
| - Cytoplasmic droplet shed
373
What are the metabolism changes to spermatozoa in the epididymis?
- Increase dependence on external fructose for glycolytic energy
- Little oxidative metabolism
- Increase intracellular pH (due to NA+/H+ exchange)
374
What are the motility changes to spermatozoa in the epididymis?
- Increase disulphide bridges between proteins in outer dense fibres of tail
- [cAMP] rises in the tail
- Acquires capacity for forward movement
375
What are the membrane changes to spermatozoa in the epididymis?
Composition of various components change
376
Where is the seminal fluid mainly formed?
Accessory glands
377
What is exploited by infectious agents (ie. Hep B, HIV)?
Seminal fluid
378
What are the different glands in the male and describe the type of seminal fluid they produce?
1. TESTES: 0.1-0.2ml, contains spermatozoa
2. SEMINAL VESICLE: 1-3ml, alkaline, gelantinous
3. PROSTATE: 0.5-1ml, acidic, watery
4. BULBOURETHRAL GLANDS: 0.1-0.2ml, viscous, clear
379
What are the 6 major constituents of male ejaculate & where are they produced?
1. Spermatozoa (testes)
2. Fructose (seminal vesicle & ampulla)
3. Inositol (testes & epididymis)
4. Citric acid (prostate)
5. Glycerlyphosphorylcholine (epididymis)
6. Acid phosphatase (prostate)
380
What is the function of fructose in the male ejaculate?
Anaerobic energy metabolism
381
What is the function of inositol in the male ejaculate?
Osmotic ballast
382
What is the function of citric acid in the male ejaculate?
Ca2+ chelater- depresses semen coagulation
383
What is the function of glycerlyphosphorylcholine in the male ejaculate?
Source of choline in phospholipid metabolism
384
What is the function of acid phosphatase in the male ejaculate?
Cleaves choline from glycerophosphorylcholine
385
What causes the penis to become turgid so to allow semen to be introduced into female genital tract?
- Haemodynamic changes involving the corpora cavernosa (singular=corpus cavernosum)
- Sinuses along most of the length of the penis
386
What 3 things can produce arousal in the male reproductive system?
1. Erotic psychological stimulio (visual, olfactory)
2. Tactile stimuli at level of brain
3. Tactile stimuli can also mediate local spinal reflexes
387
What is the sympathetic role in the male reproductive system?
- Lower thoracic & lumbar spinal segments
| - Maintains flaccidity
388
What is the parasympathetic role in the male reproductive system?
- Control centre in sacral spinal segments
| - Increased activity produces turgidity
389
Describe how the Erection Centre in the sacral spinal cord mediated the erection reflex in the male reproductive system?
- Dilatation of arterioles to c. cavernosa & c. spongiosum
- Closing of arteriovenous shunts that normally bypass the c. cavernosa
- Probably also occupation of veins draining penis
390
Describe the parasympathetic relaxation of vascular smooth muscle in the male penis?
- Involves ACh acting on vascular endothelial cells
- Indirectly triggers release nitric oxide (NO)
- NO causes relaxation of vascular smooth muscle
391
What can result in the failure to obtain an erection in the male penis?
- Mechanical damage to the c. cavernosa
- Obstruction of arteries to penis
- Drugs that block parasympathetic actions
- Psychological factors
392
How is stress associated with high sympathetic activity preventing a male erection?
NA causes vasoconstriction of penile arterioles & so inhibits erection
393
How does the sympathetic nervous system mediate male ejaculation?
- Ejaculation centre in lower thoracic & lumbar spinal cord
- Signals to ducts of genital tract & bulbocavernosus muscle at base of penis
394
What is the emission phase in male ejaculation?
- Smooth muscle contraction in walls of genital tract
| - Expels semen into urethral bulb
395
What is the expulsion phase in male ejaculation?
- Rhythmic contractions of penis & bulbocavernosus muscle
- Ejects semen in spurts
396
What is male ejaculation normally followed by?
Refractory phase of 10mins - 1hr
397
Describe the 3 different compositions of the male ejaculate (not uniform)?
1st- PROSTATE: rich in acid phosphatase & citric acid
2nd- VAS DEFERENS: rich in spermatozoa
3rd- SEMINAL VESICLE: rich in fructose
398
What happens to the male ejaculate if it lingers somewhere?
Coagulation followed by liquefaction
399
What does tumescence mean?
Swollen/becoming swollen, due to sexual arousal
400
What does a PDE V inhibitor?
| phosphodiesterase 5
It stops cGMP from being degraded by PDE V which allows the penile erection to last longer
401
What are the different surfaces of the bladder?
- Superior
- Infero-lateral x2
- Base (trigone between ureteric orifices & neck)
402
Describe the apex of the bladder?
- Upper aspect of pubic symphysis
403
What is the distance of the 2 ureters in an empty and full bladder?
EMPTY: 2.5cm
FULL: 5cm
404
What is the median umbilical ligament?
Remnant of embryonic urachus, extends from apex
405
Describe the mucous membrane of the different parts of the bladder?
- Over the DETRUSOR: loose & "ruckled"
| - Over TRIGONE: smooth, fixed
406
Where is the bladder neck in the female?
Above pelvic floor so pressure of pelvic organs & levator ani contribute to urinary continence
407
What are the different ligaments in the male & female that support the bladder?
- Puboprostatic (male)
| - Pubovesical (female)
408
What forms the puboprostatic & pubovesical ligaments in the pelvis?
Fibromuscular & fascial condensations from pelvic floor
409
What part of the bladder has NO peritoneum?
Apex
410
What are the different pouches which support the bladder?
- Rectovesical
| - Vesico-uterine & Recto-uterine in female
411
What are the bladder relations in the male?
- Superior: peritoneum, ilium, sigmoid
| - Base: rectovesical pouch, septum, rectum, vas deferens, seminal vesicle
412
What is the arterial supply of the bladder?
- Internal iliac, anterior trunk
- Superior vesical
- Inferior vesical (replaced by vaginal in female)
413
What is the main principle with the arterial supply of the bladder?
Pelvic organs are supplied by arteries to adjacent organs
414
What are the veins draining the bladder?
- Plexus on inferolateral surface of bladder
- Drain directly into internal iliac veins
- Male drain to prostatic plexus --> internal iliac
415
What may the male prostatic plexus/veins communicate with?
Valveless veins of the vertebral plexuses (Batson) facilitating potential prostatic tumour spread
416
What are the 3 lymph plexuses of the bladder?
1. Mucosa
2. Muscle
3. Serosa
417
What is the main lymph drainage of the bladder?
Nodes on external iliac artery
418
What are the different nerve supplies of the bladder?
- Anterior part of pelvic plexus that passes the rectum
- Detrusor parasympathetic (afferent & efferent) from pelvic splanchnic S2,3,4 via pelvic plexus
- Sympathetic to preprostatic sphincter & some detrusor from T12, L1,2 via pelvic plexus
- Parasympathetic in female bladder neck
419
Whats at surgical risk around the rectum?
Pelvic plexus
420
Describe the urethra in a male?
- Bladder neck, preprostatic urethra with internal sphincter
- Prostatic urethra receiving ejaculatory duct
- External sphincter surrounding membranous urethra
- Spongy urethra in bulb of penus & then corpus spongiosum
421
Describe the preprostatic part of the male urethra?
- From bladder neck to upper aspect of verumontanum (colliculus seminalis)
- Surrounded by genital, preprostatic/internal sphincter & smooth muscle from bladder wall passing into urethra & prostate
422
Describe the prostatic part of the male urethra?
- Closer to anterior aspect prostate
- Emerges anterior to apex
- Urethral crest causes crescentic section with sinuses each side
- Verumontanum with utricle & ejaculatory ducts each side
423
How many ducts open into the prostatic sinuses?
15-20
424
Describe the prostate & its function?
- Acid seminal secretion
- Fibromuscular & glandular
- In tough capsule & supported by puboprostatic ligaments
- Has base, apex, posterior, inferiolateral x2 sufaces
425
What is in the slightly acid seminal secretion of the prostate?
- Acid phosphatase
- Amylase
- Prostate specific antigen (PSA)
- Fibrinolysin
426
What lies posterior to the prostate?
- Denonvillier's fascia
| - Rectum
427
When would you describe the prostate as having lobes?
Only in foetus
| 2 lateral & a median
428
What are the 3 different zones of the prostate?
1. Transition 5%, around urethra anterior to ejaculatory ducts
2. Central 25%, behind transition, contains ejaculatory ducts
3. Peripheral 70%, around transition & central
429
What abnormality can commonly occur in the Transition zone of the prostate?
Benign prostatic hypertrophy (BPH)
430
What abnormality can commonly occur in the Peripheral zone of the prostate?
Carcinoma
431
How much does the normal & BPH prostate weight?
- Normal: 8-40g
| - BPH: 150g+
432
What resides in the superior surface of the bladder?
Loops of ileum & sigmoid colon
433
What is the arterial supply of the prostate & urethra?
- Prostate & Proximal male urethra: inferior vesical
| - Female Urethra: vaginal & internal pudendal
434
What is the venous drainage of the prostate & urethra?
- Prostate & Male Urethra: vesical & prostatic plexuses --> internal iliac vein
- Female Urethra: vaginal & internal pudendal veins
435
What is the main lymph drainage of the prostate and proximal urethra in the male?
Internal iliac nodes
436
What 3 types of nerve supply does the urethra & prostate require?
1. Somatic motor for control of striated muscle (external sphincter)
2. Autonomic (sympathetic & parasympathetic)
3. Sensation
437
Whats the nerve supply of the urethra & prostate?
- S2,3,4 Pudendal nerve (somatic motor & sensory)
- Parasympathetic pelvic splanchnics to pelvic plexus
- Sympathetic L1,2 via superior hypogastric plexus to pelvic plexus
438
Describe the 1. Storage part of Micturition (urination)?
- Detrusor parasympathetic control, counteracted via sympathetics = bladder relax & fill without increase in tension
- Stretch receptors send signals via parasympathetic pelvic splanchnics to cord S2,3,4 & trigger reflexes in parasympathetic efferents to cause detrusor contraction = AUTONOMIC STRETCH REFLEX
439
When does the Autonomic stretch reflex prevail?
Untrained infant so the bladder empties automatically when full
440
Describe the 2. "Full" causing desire to micturate (urinate)?
- With training, afferents ascend up spinal cord trigger cortical inhibition in frontal lobe
- Superimposes cortical control on "M" centre in pons that in turn (reticulospinal & corticospinal pathways) controls/stimulates preganglionic parasympathetic neurones S2,3,4 cord = VOID
441
What does the "M" centre stand for?
Micturition centre in the pons
442
Describe the 3. Void part of Micturition (urination)?
- 1y neurones stimulate 2y neurones in bladder wall ganglia, causing detrusor contraction
- Simultaneous relaxation of external urethral sphincter (striated) by pudendal nerve & contraction of abdominal wall
- Sensation of urine in urethra maintains reflex
443
What happens if you transect the spinal cord above S2 (after stroke)?
Loss of cortical control cause return to automatic infant reflex of the bladder emptying when full
444
What happens if the sacral segments S2,3,4 are destroyed?
Detrusor is paralysed & bladder distends until there is overflow incontinence
445
What are the 3 frequent disorders of the prostate?
1. Benign prostatic hyperplasia
2. Carcinoma
3. Prostatitis
446
Describe Benign Nodular Hyperplasia?
- Common
- Non-neoplastic (hormonal imbalance)
- Nodular hyperplasia of glands & storm
- Not premalignant
- Obstructs urine flow
- Infection
- Treatable
447
Describe Benign Prostatic Hyperplasia?
- Transition zone & peri-urethral glands
- Nodules of glands & stroma
- Compress & elongate urethra
- Interferes with urethral sphincter
- Urinary retention
448
Describe acute & chronic urinary retention?
- ACUTE: painful
| - CHRONIC: painless, more gradual
449
Describe Prostate Carcinoma?
- Prostatic intraepithelial neoplasia precursor
- Adenocarcinoma usually >50yrs
- Latent or indolent (incidental) carcinoma
450
Describe Adenocarcinoma of the prostate?
- Posterior subcapsular area
- Asymmetric firm enlargement
- Metastasises (esp to bone)
451
Describe Latent or indolent (incidental) carcinoma of the prostate?
- Microscopic incidental focus
- Common, incidence high in old age
- Lesions dormant, metastases in 30% after 10yrs
452
What does the Gleason score of a prostate cancer show?
- Differentiation
| - Distribution
453
What is the different stage TN of prostate cancer?
- Direct
- Via lymphatics
- Via blood
454
How does prostate cancer present?
- Urinary symptoms
- Incidental finding on rectal examination
- Bone metastases
- Lymph node metastases
455
How do you diagnose prostate cancer?
- Imaging: ultrasound, MRI, isotope bone scan
- Cystoscopy
- Biochemistry PSA
- Haematology: bone marrow involvement
- Biopsy
456
How do you treat prostate cancer?
- Oestrogen
- GnRH analogues
- Orcidectomy
- Radiotherapy
- Radical prostatectomy
457
What are the different penis & scrotum abnormalities?
- Venereal infection
- Hypospadias: urethral opening on inferior aspect
- Epispadias: often accompanied by abnormal development of bladder
- Phimosis: narrowing of foreskin
- Paraphimosis: retracted foreskin of male cannot be returned to normal
- Bowen's disease (non-invasive)
- Invasive squamous cell carcinoma
- Peyronie's disease: scar tissue causing penis to bend during erection
458
Describe Intraepithelial carcinoma of the penis?
- Bowen's disease
- Occur anywhere on penis erythematous patch Kerototic surface
- Raised red plaque
459
Describe Invasive squamous carcinoma of the penis?
- Rare in UK
- HPV
- Glans penis or inner aspect of prepuce
- Nodule or plaque
- Metastasises to inguinal lymph nodes
460
Describe carcinoma of the scrotum?
- Chimney sweeps & arsenic workers
- Nodular ulcerated mass
- Squamous carcinoma
- Inguinal nodes
- Possible ulceration
461
What are the different urethral abnormalities?
- Congenital valves
- Rupture
- Stricture
- Gonococcal
- Non-gonococcal (non-specific)
- Warts
- Transitional cell carcinoma
462
What are the different developmental & cystic lesions of the testicles?
- Undescended testis (cryptorchidism)
- Hydrocoele
- Haematocoele
463
What are the different orchitis/inflammations of the testis?
- Mumps orchitis
- Idiopathic granulomatous orchitis
- Syphilitic orchitis
464
Describe testicular tumours?
- Uncommon but treatable
- Young & old men
- Aetiology unknown but undescended tests is predisposing factor (x10 risk)
- In situ neoplasia does occur & is precursor
465
What are the 2 most common testicular tumours?
- Seminoma 40%
| - Teratoma 32%
466
What is the presentation of testicular tumours?
- Painless unilateral enlargement of testis
- Secondary hydrocele
- Symptoms from metastases
- Retroperitoneal mass
- Gynaecomastia
467
Describe Seminoma?
- Commonest
- Germ cell origin
- 30-50yrs
- Classical type
- Spermatocytic type
- Anaplastic type: with syncytiotrophoblast giant cells (gynaecomastia)
- Combined type
- Produce hCG
468
Describe Teratoma?
- Germ cell origin
- 20-30yrs
- More aggressive
- Differentiated type
- Intermediate type
- Undifferentiated type
- Trophoblastic type
- beta-hCG & alpha-fetoprotein useful markers
469
What are different non-germ cell tumours?
- Malignant lymphoma: elderly men
- Leydig cell tumour: may produce androgens
- Sertoli cell tumour
- Metastatic tumours
470
What the 4 different stages of testicular tumours?
- Stage I: confined to testis & its coverings
- Stage II: involves testis & para-aortic lymph nodes
- Stage III: involves lymph nodes in mediastinum &/or supraclavicular region
- Stage IV: visceral metastases
471
What are the different causes of male infertility?
- Endocrine disorders: GnRH deficiency, oestrogen excess
- Testicular lesions: cryptorchidism, abnormal spermatogenesis
- Post-testicular lesions: obstruction of efferent ducts
472
What are the different abnormalities of the epididymis & spermatic cord?
- Congenital
- Epididymal cysts & spermatocoeles
- Varicocoele
- Torsion of spermatic cord & testis
- Inflammatory lesions: epididymo-orchitis
- Tumours: rare
MD3002
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