Repro Flashcards
1
Q
After colonising the gonad, what must germ cells do in order to complete gametogenesis?
A
Proliferate by mitosis
Reshuffle genetically and reduce to haploid by meiosis
Cytodifferentiate into mature gametes
2
Q
List some basic differences between the nature of oocyte production and spermatogenesis
A
Oocytes - very few gametes (about 400 in lifetime), intermittent production (about 1 a month)
Spermatogenesis - huge number, (about 200 million/day), continuous production, essentially ‘disposable’ cells
3
Q
What are the 2 main functions of meiosis?
A
Reduce the chromosome number in gamete to 23, and ensure every gamete is genetically unique
4
Q
When is meiosis used?
A
Only in the production of eggs and sperm
5
Q
Briefly outline the process of meiosis
A
Two successive cell divisions, meiosis 1 and meiosis 2, producing 4 daughter cells
6
Q
How does meiosis differ in females?
A
Only 1 daughter cell develops into a mature oocyte, others form polar bodies
7
Q
How do genetic variations arise?
A
Crossing over - exchange of regions of DNA between 2 homologous chromosomes
Random segregation - distribution of chromosome among 4
Independent assortment - 2 homologous chromosomes of a pair must go into separate gametes
8
Q
Why is there a blood-testes barrier?
A
There is different genetic material in sperm, so may be attacked by the immune system
9
Q
What do Sertoli cells do?
A
Nurse/nurture cells
10
Q
What is the Sertoli cell barrier also referred to as?
A
Blood testes barrier
11
Q
What are spermatogonia?
A
Male germ cells - the ‘raw material’ for spermatogenesis
12
Q
What can spermatogonia divide into?
A
Ad spermatogonium (maintain stock) Ap spermatogonium (give rise to primary spermatocytes)
13
Q
Describe the sequence of division by meiosis by primary spermatocytes
A
Primary spermatocytes - secondary spermatocytes - spermatids
14
Q
What is spermiogenesis?
A
The process by which a primary spermatocyte forms 4 haploid spermatids, which differentiate into spermatozoa
15
Q
List the sequence of cells produced in spermiogenesis
A
Spermatogonium - primary spermatocyte - secondary spermatocyte - spermatid - spermatozoa (sperm)
16
Q
How is the spermatogenic cycle defined?
A
The time taken for reappearance of the same stage within a given segment of tubule (approx 16 days in a human)
17
Q
What is the spermatogenic wave?
A
The distance between the same stage along a tubule.
Waves follow a corkscrew like spiral towards the inner part of the lumen
18
Q
How are sperm transported to the epididymis?
A
Non-motile - transport via Sertoli cell secretions, assisted by peristaltic contraction, until they reach the epididymis
19
Q
How do spermatids become spermatozoa?
A
Spermatids are released into lumen of seminiferous tubules (spermiation). They remodel as they pass down seminiferous tubule, through rete testes and ductuli efferentes and into the epididymis to finally form spermatozoa.
20
Q
Approximately how much fluid is in ejaculate?
A
2ml
21
Q
What are the seminal vehicle secretions constituted of?
A
Amino acids, citrate, fructose, prostaglandins
70%
22
Q
What proportion of ejaculate is seminal vesicle secretions?
A
Approx 70%
23
Q
What proportion of ejaculate is secretions of prostate?
A
Approx 25%
24
Q
What constitutes the prostatic portion of ejaculate?
A
Proteolytic enzymes, zinc
25
What proportion of ejaculate is sperm? (Via vas deferens)
2-5%
26
How many sperm are approximately in an ejaculate?
200-500 million per ejaculate
27
What proportion of ejaculate is bulbourethral gland secretions?
Less than 1% total volume
28
What constitutes bulbourethral gland secretions in ejaculate?
Mucoproteins, help to lubricate and neutralise acidic urine in distal urethra
29
What is sperm capacitation?
The final maturation step required for sperm to become fertile, stimulated by the conditions in the female genital tract.
30
What are the steps of capacitation, stimulated in spermatids by the conditions of the female genital tract?
Removal of glycoproteins and cholesterol from sperm membrane
Activation of sperm signalling pathways (atypical soluble adenylyl cyclise and PKA involved)
Allow sperm to bind to zona pellucida of oocyte and initiate acrosome reaction
31
What must first be done to sperm before it can be used for IVF?
Must be incubated in capacitation media
32
Where do germ cells arise from?
The yolk sac
33
Describe the migration of female germ cells embryologically
Germ cells arise from yolk sac, colonise the gonadal cortex and differentiate into oogonia (single oogonium). Oogonia then proliferate rapidly by mitosis. By end of 3rd month, oogonia arranged in clusters surrounded by flat epithelial cells. Majority continue to divide by mitosis, but some enter meiosis (arrest in prophase of meiosis 1 and are called primary oocytes)
34
Embryologically, what has happened to female gametes by the end of the 3rd month?
By end of 3rd month, oogonia arranged in clusters surrounded by flat epithelial cells. Majority continue to divide by mitosis, but some enter meiosis (arrest in prophase of meiosis 1 and are called primary oocytes).
35
When is the max number of germ cells reached in the female?
By mid gestation (approx 7 million)
| Cell death then begins, and many oogonia and primary oocytes degenerate (atresia)
36
What occurs after the max no. Of germ cells has been reached in the female, embryologically?
Cell death then begins, and many oogonia and primary oocytes degenerate (atresia)
37
What embryologically has occurred with regards to gametes in the female by 7 months?
The majority of oogonia have degenerated. All surviving (approx 2 million) primary oocytes have now entered meiosis 1 and are individually surrounded by layer of flat epithelial cells, called follicular cells - now called primordial follicle
38
When does maturation of oocytes continue in the female, post birth?
Puberty
39
Approximately how many oocytes remain in the female by puberty?
Approx 40,000
| Most undergo atresia during childhood
40
What are the 3 phases of oocyte maturation?
1 - preantral
2 - antral
3 - preovulatory
41
Approximately how many oocytes start to mature each month from puberty onwards?
Approx 15-20
42
Preantral stage - What changes occur to the surrounding follicular cells of primordial follicles, as they begin to grow?
Change from flat to cuboidal, and proliferate to produce a stratified epithelium of granulosa cells
43
Describe the antral stage
As development continues, fluid filled spaces appear between granulosa cells. These coalesce to form the Antrum. Several follicles begin to develop with each ovarian cycle. Usually one reaches maturity (rest become atretic)
44
What is the 1st polar body?
Meiosis 1 completes, producing 2 haploid daughter cells. One receives most of cytoplasm, the other receives practically none, and is a rememant (called the 1st polar body)
45
Describe the preovulatory phase?
Surge in LH induces preovulatory growth phase. Cell has now completed meiosis1 and enters meiosis 2, but arrests in metaphase approx 3hrs before ovulation. Meiosis 2 is only completed if oocyte is fertilised, otherwise cell degenerates approx 24hrs after ovulation.
46
Describe the ovulation stage
FSH and LH stimulate rapid growth of follicle several days before ovulation. Mature follicle now approx 2.5 cm in diameter and called gracfian follicle. LH surge increases collagenase activity. Prostaglandins increase response to LH and cause local muscular contraction in ovarian wall. Oocyte extruded and breaks free from ovary.
47
What is the corpus luteum ?
Remaining granulosa and theca interna cells become vascularised. Develop yellowish pigment and change into lutein cells, which form the corpus luteum.
48
What does the corpus luteum do?
Secretes oestrogens and progesterone
Stimulates uterine mucosa to enter secretory stage in preparation for embryo implantation.
Dies after 14 days if no fertilisation occurs
49
Describe oocyte transportation
Shortly before ovulation, fimbriae sweep over surface of ovary. Uterine tube begins to contract rhythmically. Oocyte carried into tube by sweeping movements of fimbriae and by motion of cilia on epithelial lining.
Oocyte then propelled by peristaltic muscular contractions of the tube and by cilia in the mucosa. If fertilised, oocyte reaches uterine lumen in 3-4 days
50
What happens to the corpus luteum if no fertilisation occurs?
Corpus luteum degenerates. Forms mass of fibrotic scar tissue, the corpus albicans. Progesterone production decreases, precipitating menstrual bleeding.
51
What happens to the corpus luteum if fertilisation does occur?
Degeneration of corpus luteum prevented by human chorionic gonadotropin, secreted by the developing embryo. The corpus luteum continues to grow and forms the corpus luteum of pregnancy (corpus luteum graviditatis). Cells continue to secrete progesterone until approx 4th month, secretion of progesterone by placenta then becomes adequate.
52
Briefly describe hormonal control of the ovarian cycle
Under influence of GnRH, anterior pituitary releases FSH and LH. Follicles stimulated to grow by FSH, and to mature by FSH and LH. Ovulation occurs on LH surge. LH also promotes development of corpus luteum.
53
Approximately how many sperm are formed a day?
Approx 200 million
54
How are sperm formed, very basically?
4 spermatids formed with no polar body formation and equal division of cytoplasm.
55
When does spermatogenesis begin?
Puberty, continues throughout adult life
56
Where does spermatogenesis occur?
All stages complete in testes
57
At what rate does oogenesis occur?
Usually 1 ovum per 28 day menstrual cycle.
58
Very briefly outline oogenesis
1 ovum produced with unequal division of cytoplasm and 3 polar bodies produced.
59
When does oogenesis occur?
Starts in foetus, ends at menopause.
60
Where does oogenesis occur?
Ovaries, last stage of meiosis 2 occurs in oviduct.
61
What effect does corticotropin releasing hormone CRH have on the pituitary?
Stimulates ACTH secretion
62
What effect does thyrotropin releasing hormone TRH have on the pituitary?
Stimulates TSH and prolactin secretion
63
What effect does growth hormone releasing hormone GHRH have on the pituitary?
Stimulates GH secretion
64
What effect does somatostatin have on the pituitary?
Inhibits GH (+ other hormones) secretion
65
What effect does gonadotropin releasing hormone GnRH have on the pituitary?
Stimulates LH and FSH secretion
66
What effect does prolactin releasing hormone PRH have on the pituitary?
Stimulates PRL secretion
67
What effect does prolactin inhibiting hormone (dopamine) have on the pituitary?
Inhibits PRL secretion
68
What type of tissue is the anterior pituitary?
Not nervous tissue, an amalgam of hormone producing glandular cells. Stains darker, arises from Rathke's pouch. Connected to the hypothalamus by the superior hypophyseal artery
69
What connects the anterior pituitary to the hypothalamus?
Connected to the hypothalamus by the superior hypophyseal artery
70
What 6 peptide hormones does the anterior pituitary produce?
Prolactin, GH, TSH, ACTH, FSH, LH
71
What constitutes the posterior pituitary?
Nervous tissue, stains lighter.
72
What is the anterior pituitary also called?
Pars distalis, adreno hypophysis
73
What is the posterior pituitary also called?
Pars nervosa, neuro hypophysis
74
What does the posterior pituitary secrete?
ADH (vasopressin - urinary) and oxytocin (important in reproduction)
75
What, essentially, is the posterior pituitary?
An overgrowth of the hypothalamus, composed of neural tissue. Hypothalamic neurons pass through the neural stalk and end in the posterior pituitary.
The upper portion of the neural stalk extends into the hypothalamus and is called the median eminence.
76
What does GnRH stimulate?
The anterior pituitary gland to secrete LH and FSH
77
Describe hypothalamic control of FSH and LH
One releasing hormone - GnRH
GnRH release is pulsatile, every 1-3 hrs. Intensity of GnRH stimulus is affected by frequency of release and intensity of release. GnRH travels to pituitary in hypophyseal portal system.
78
What size protein is GnRH
10 amino acids long
79
What controls the intensity of GnRH stimulus?
Intensity of GnRH stimulus is affected by frequency of release and intensity of release (pulsatile release every 1-3hrs)
80
What happens in the absence of GnRH?
Little or no FSH of LH release
81
What proportion of anterior pituitary cells secrete FSH and LH?
5-10% total anterior pituitary cells
82
What controls gonadotroph synthesis and release?
Positive and negative feedback by gonadal steroids and gonadal peptides. Controlled by gonadotroph cells in anterior pituitary.
83
How do gonadal hormones decrease gonadotrophin release?
Decrease GnRH release from hypothalamus and by affecting ability of GnRH to stimulate gonadotropin secreting from anterior pituitary
84
In the male, LH and FSH primarily work via which receptors?
GalphaS
| PCR to adenylyl cyclase
85
In the male, upon which cells do LH and FSH primarily act upon?
Testicular sertoli cells, leydig cells
86
What effects do LH and FSH have in the male?
Stimulate sex hormones synthesis (steroidgenesis) and control gamete production
87
Where does LH act in the male, and what effect does it have?
Leydig cells of the testis, causing secretion of testosterone
88
Describe negative feedback of LH in the male
Negative feedback control - testosterone reduces LH from AP and reduces GnRH secretion, thus anterior pituitary LH and FSH decrease
89
What stimulates spermatogenesis?
FSH receptor activation on Sertoli cells of seminiferous tubules
90
What effects does FSH have on Sertoli cells?
Causes them to grow and secrete spermatogenic substances, but needs testosterone, which diffuses in to seminiferous tubules
91
What does inhibit do in the male?
Reduces FSH secretion selectively - related to developing gametes
92
Describe briefly the male HPG axis
In median long term testosterone levels constant
| Circadian rhythm, highest early morning, and effects of environmental stimuli, driven by the brain
93
When are testosterone levels generally highest in the male?
Early morning
94
Via which receptors do FSH and LH act primarily on in the female?
GalphaS PCR (adenylyl cyclase)
95
Which cells do FSH and LH target in the female?
Ovarian granulosa cells, theca interna
96
What do FSH and LH stimulate in the female?
Stimulate sex hormone synthesis (steroidgenesis, oestrogen, progesterone, inhibin). Control gamete production (folliculogenesis and ovulation)
97
What does oestrogen do in the female?
Moderate titres of oestrogen reduce GnRH secretion (negative feedback)
High titres of oestrogen alone promote GnRH secretion (positive feedback, LH 'surge')
98
What effects does progesterone have in the female?
Increase inhibitory effects of moderate oestrogen
| Prevents positive feedback of high oestrogen (no LH surge)
99
What effect does oestrogen have upon the pulses of GnRH?
Reduces GnRH quantity in pulse
100
What effect does progesterone have upon the pulses of GnRH?
Decreases the frequency of pulses
101
What effect does inhibin have on FSH in the female?
Inhibits the secretion of FSH. Has a small inhibitory effect on LH also
102
Where is inhibin released from in the female?
From granulosa cells of corpus luteum
103
What does the menstrual cycle enable the preparation of?
```
The gamete (ovarian cycle)
The endometrium (uterine cycle)
```
104
What are the key points of the menstrual cycle?
```
Ovulation
Waiting (pause, maintaining endometrium until a signal is received to indicate that fertilisation has occurred)
```
105
What controls the menstrual cycle?
```
Gonadotrophins (acting on the ovary)
Ovarian steroids (acting on tissues of reproductive tract, to control the cycle)
```
106
Where do gonadotrophins act in the female?
Act on ovary, promoting follicular development and production of ovarian hormones (steroid hormones an inhibin). Controlled by effects of gonadal hormones (negative and positive feedback).
107
Describe the start of the menstrual cycle
No ovarian hormone production. Early development of follicles begins. Low steroid and inhibin levels. Little inhibition at the hypothalamus of anterior pituitary. Free from inhibition (FSH levels rising)
108
Describe the role of FSH at the start of the menstrual cycle
```
FSH binds to granulosa cells
Follicular development continues
Theca interna appears
Follicle now capable of oestrogen secretion
Inhibin secretion begins
```
109
Describe the mid follicular phase of the menstrual cycle
Need to nominate a dominant follicle, and prevent recruitment o any further follicles. 2 things happen.
Follicular oestrogen now at a concentration when it can exert POSITIVE feedback at the hypothalamus and anterior pituitary.
Gonadotrophin levels can rise - effect seen on LH only.
Follicular inhibin rising, selective inhibition on FSH production by anterior pituitary
110
What does inhibin do in the mid follicular phase in the female?
Follicular inhibin rising, selective inhibition on FSH production by anterior pituitary
111
Describe the preparation for ovulation phase of the menstrual cycle
Circulating oestradiol and inhibin rise rapidly - oestradiol production no longer dependent on FSH. Surge in LH production. Progesterone production begins (granulosa cells become responsive to LH). Modulation of GnRH pulse generator.
112
What effect does high oestradiol concentration have on the anterior pituitary?
Enhances sensitivity of anterior pituitary gonadotrophins to GnRH
113
Describe the ovulation phase of the menstrual cycle
Meiosis 1 completes and meiosis 2 starts.
Mature oocyte extruded through the capsule of the ovary.
After ovulation, the follicle is luteinised. Secreted oestrogen and progesterone in large quantities. Inhibin continues to be produced. LH is now suppressed because of negative feedback due to presence of progesterone. Further gamete development suspended - waiting phase established.
114
What inhibits LH production after ovulation?
The presence of progesterone, released by the follicle
115
Describe the luteal phase of the menstrual cycle
Corpus luteum produces progesterone and oestrogens from androgens. Produces inhibin (promotes production of progesterone). Regresses spontaneously in the absence of a further rise in LH
116
Describe the end of the menstrual cycle, in the absence of a pregnancy
In the absence of a further rise in LH, corpus luteum regresses. Dramatic fall in gonadal hormones. Relieving negative feedback. Resets to start again
117
Describe the end of the menstrual cycle, in the presence of a pregnancy
If fertilisation has occurred, syncytiotrophoblast produces human chorionic gonadotropin (approx same effect as LH). Exets luteinising effect
118
Describe what the corpus luteum does at the start of pregnancy to support it
Corpus luteum, supported by placental hCG, produces steroid hormones to support pregnancy. Eventually, the placenta is capable of production of sufficient quantities of steroid hormones to control the HPO axis throughout pregnancy
119
Describe the actions of oestrogen in the follicular phase
```
Fallopian tube function
Thickening of endometrium
Growth and motility of myometrium
Think alkaline cervical mucus
Vaginal changes
Changes in skin, hair and metabolism
```
120
Describe the actions of progesterone in the luteal phase
Further thickening of endometrium into secretory form
Thickening of myometrium, but reduction of motility
Thick, acid cervical mucus
Changes in mammary tissue
Increased body temperature
Metabolic changes
Electrolyte changes
121
What is the normal duration of the menstrual cycle?
21-35 days
122
What are variations in menstrual cycle length due to?
Variation in length of follicular phase
123
What is the length of the luteal phase?
Strictly controlled to 14 +/- 2 days
124
What factors affect the menstrual cycle?
Physiological factors (pregnancy/lactation)
Emotional stress
Low body weight
125
What is thelarche?
Development of breast
126
What is puberarche?
Development of axillary pubic hair
127
What is menarche?
The first menstrual period
128
What is adrenarche?
The onset of an increase in the secretion of androgens
129
What is puberty?
When sexual maturation and growth are completed and result in ability to reproduce. Primary sexual characteristics established before birth, but reproductive system inactive until puberty
130
Describe th basic sequences of events in puberty
Accelerated somatic growth
Maturation of primary sexual characteristics (gonads and genitals)
Appearance of secondary sexual characteristics (pubic and exillary hair, female breast development, male voice change)
Menstruation and spermatogenesis begin
131
How is puberty initiated?
By the brain. Onset of puberty associated with steady rise in FSH and LH secretion, due to a rise in GnRH secretion.
132
What is early onset puberty also termed?
Precocious puberty
133
Describe the growth spurt in puberty
Occurs in both sexes. Earlier and shorter in girls, males larger as growth spurt longer and faster. Depends on growth hormones and steroids in both sexes.
134
What does the growth spurt depend on?
Depends on growth hormones and steroids in both sexes.
135
Why are males bigger, with regards to the growth spurt?
Growth spurt longer and faster. Oestrogen closes the epiphyses earlier in girls.
136
What ends the growth spurt?
Closing of the epiphyseal growth plates. Epiphyseal fusion. Oestrogen closes the epiphyses earlier in girls
137
What generally determines when a girl will undergo menarche?
Critical weight (usually 47kg)
138
What is the critical weight, at which girls generally undergo menarche?
47kg
139
What factors might influence when a girl undergoes menarche?
Significant weight loss (reproductive cycle ceases)
Nutrition important
Leptins may be involved in signalling
Body weight most important factor
140
What kind of tumours may influence puberty in humans?
Pineal tumours
141
What are the first changes seen in puberty?
Hormonal changes
142
Describe the hormonal changes seen during puberty
Increased stimulation of hypothalamo-pituitary-gonadal axis
Gradual activation of GnRH
Increased frequency and amplitude of LH pulses
Gonadotrophins stimulate secretion of sexual steroids (oestrogen and androgens)
Extragonadal hormonal changes (elevation of IGF-1 and adrenal steroids)
143
Describe the effects of GH secretion from the pituitary during puberty
Increased TSH
Increased metabolic rate
Promotes tissue growth
Increased androgens - retention of minerals in body to support bone and muscle growth
144
What is the first phenotypic changes seen in the female?
Breast development
145
What is the first phenotypic changes seen in the male?
Testicular enlargement
146
What is the very first changes that occur in puberty (proceeding phenotypic changes by several years)
Nocturnal GnRH pulsatory LH secretion
| Sleep related LH increase, stimulates a nocturnal rise of testosterone/oestrogen
147
Why is there no gonadal function in young children?
Levels of LH and FSH are insufficient to initiate gonadal function
148
Describe the male hormonal changes that occur during puberty
LH and FSH increase at approx 10yrs
Adrenals also secrete androgens
Androgens initiate growth of sex accessory structures (e.g. Prostate), male secondary sex characteristics (facial hair growth of larynx)
149
Describe the female hormonal changes that occur during puberty
Oestrogen induces secondary ex characteristics (growth of pelvis, deposit of subcutaneous fat, maturation of internal reproductive organs, external genitalia)
Androgens release by adrenal glands increases growth of pubic hair, growth of bone, increased secretion from sabaceous glands
150
What initiates the first ovarian cycle?
LH surge. Usually not sufficient to cause ovulation during 1st cycle. Brain and endocrine system mature soon thereafter. Oestrogen levels increase due to growing follicles.
151
Describe the tanner classification system for pubertal development of girls
Breast B 1-5
Pubic hair PU 1-5
Axillary hair A 1-5
Menarche
152
Describe the tanner classification system for pubertal development of boys
```
Testicular volume over 4ml Te
Penis enlargement G 1-5
Pubic hair PU 1-5
Axillary hair A 1-5
Spermarche
```
153
At what approximate speed is the pubital growth spurt?
Growth velocity is 2-3 times greater than prepupertal.
154
What is the normal age for the start of pubertal development in boys?
10 to 14
155
What is the normal age for the start of pubertal development in girls?
9 to 13
156
What is usually the 1st sign of puberty in boys?
G2 (testicular volume up to 4ml)
157
What is usually the 1st sign of puberty in girls?
B2
158
What is usually the growth velocity during puberty in boys?
10.3 cm/yr
| Tanner 3-4
159
What is usually the growth velocity during puberty in girls?
9.0 cm/year
| Tanner 2-3
160
What is the normal duration of puberty (in years) in boys?
3.2 +/- 1.8
| Adult size of testes
161
What is the normal duration of puberty (in years) in girls?
2.4 +/- 1.1
| Menarche
162
What is precocious puberty?
Defined as occurring younger than 2 SD before the average age.
163
What is the prevalence of precocious puberty?
1 in 5000 to 1 in 10,00
| 5 to 10 times more common in girls
164
At what age, in girls, would onset of puberty be considered to be precocious?
Less than 8 yrs
165
At what age, in boys, would onset of puberty be considered to be precocious?
Less than 9yrs
166
What causes precocious puberty?
Majority unknown cause.
Could be:
Gonadotrophin dependant (central) - hormone secreting tumour.
Gonadotrophin independent (neurological) early stimulation of central maturation, pineal tumours, meningitis
167
What might cause gonadotrophin dependant precocious puberty?
Tumours
Gonadotrophin secreting tumour (rare)
Gliomas, astrocytomas, harnartomas, pineal tumours, HCG secreting germ cell tumours
CNS trauma or injury (infection, radiation, surgery)
Hamartomas of the hypothalamus
Congenital disorders e.g. Hydrocephalus and arachnoid cysts
168
What is precocious pseudopuberty?
Appearance of secondary sexual characteristics due to an increased producing of female/male hormones. Occurs independently to HPG axis. Gonads mature without GnRH stimulation - levels of testosterone/oestrogen raised whilst LH and FSH are suppressed
169
What might cause precocious pseudopuberty?
Congenital adrenal hyperplasia
Testotoxicosis (or familial male precocious puberty) - autosomal dominant condition. Rapid physical growth, sexual maturation and sexually aggressive behaviour in first 2/3 yrs of life.
Exogenous oestrogen or androgen exposure (therapeutic or accidental)
Tumours:
HCG secreting tumours in liver
Choriocarcinomas of gonads, pineal gland, mediastinum (ovarian tumours may cause either masculinisation or feminisation. Testicular leydig-cell tumours may cause early virilisation in males)
Adrenal tumours (rare)
170
What tumours may cause precocious pseudo puberty?
```
HCG secreting tumours in liver
Choriocarcinomas of gonads, pineal gland, mediastinum (ovarian tumours may cause either masculinisation or feminisation. Testicular leydig-cell tumours may cause early virilisation in males)
Adrenal tumours (rare)
```
171
At what age would delayed puberty be declared if initial physical changes of puberty are not present by in girls?
13
| Or primary amenorrhea by 15.5yrs
172
At what age would delayed puberty be declared if initial physical changes of puberty are not present by in boys?
14
173
How long should the interval between first signs of puberty and completion of genital growth/menarche be?
Less than 5yrs
174
What might cause gonadal failure? (Hypergonadotrophic hypogonadism)
Post malignancy chemo/radiotherapy/surgery
Polyglandular autoimmune syndromes
Hereditary e.g. Turner's syndrome
175
What might cause gonadal deficiency?
Congenital hypogonadotrophic hypogonadism (+anosmia)
Hypothalamic/pituitary elisions (tumours, post radiotherapy)
Rare gene mutations inactivating FSH/LH at their receptors
176
What are the symptoms of menopause?
Itchy, twitchy, sweaty, sleepy, bloated, moody, forgetful...
177
What happens pre-menopause?
Changes in menstrual cycle, follicular phase shortens. Ovulation early or absent, less oestrogen secreted. LH and FSH levels rise (FSH moreso).
Reduced feedback, reduced fertility
178
At what age does menopause generally occur from?
Approx 40 yrs
179
What is menopause?
Cessation of menstrual cycles. Average age 49-50, but variable. No more follicles develop.
12 months of no menstruation.
180
What happens to the hormones in menopause?
Oestrogen levels fall dramatically, FSH and LH levels rise. (FSH dramatically, no inhibin)
181
What are hot flushes?
Vascular changes seen in menopause, affect cerca 80% to some degree. Transient rises in skin temp and flushing.
182
What might relieve hot flushes?
Oestrogen trestment
183
What occurs to the up uterus during menopause?
Regression of endometrium. Shrinkage of myometrium
184
What occurs to the female reproductive tract during menopause?
Thinning of cervix
Vagina rugae lost
Uterus - Regression of endometrium. Shrinkage of myometrium
185
What changes outside of the female reproductive tract occur in menopause?
Changes in skin.
Involution of some breast tissue
Changes in bladder, loss of pelvic tone (urinary incontinence)
Bone - reduced in mass by 2.5% per year henceforth
186
What changes occur to bone structure in menopause? Why?
Bone - reduced in mass by 2.5% per year henceforth
Reduced oestrogen enhances osteoclasts ability to absorb bone. Osteoporosis (greater in some than others). Fractures later in life, can be limited by oestrogen therapy
187
Describe hormone replacement therapy in treatment of menopause
Relieves symptoms of menopause. Can improve well being. Oestrogen given orally of topically by patch or gel. Can limit osteoporosis, current advice no longer recommended as 1st line treatment. Not advices for cardioprotection
188
Is there a male menopause?
No obvious event. Sperm production continues
189
What is the menstrual cycle?
Th interaction of the CNS, namely hypothalamus and pituitary and the ovaries, resulting in the cyclic and ordered sloughing of the uterine endometrial lining
190
What are the key hormones of the menstrual cycle?
GnRH gonadotrophin releasing hormone
FSH follicle stimulating hormone
LH luteinising hormone
Estradiol and progesterone
191
What is the proliferative phase of the menstrual cycle?
Begins at the onset of menses until ovulation taken place
192
What takes place during the proliferative phase of the menstrual cycle?
Folliculogenesis. A dominant follicle is selected from a pool of growing follicles that are destined to ovulate. Growth of follicles at this stage depends on pituitary hormones. Growth of follicle leads to production of estradiol from the layers of granulosa cells surrounding it. Estradiol is responsible for the proliferation of the endometrial lining of the uterus.
193
What does growth of follicle lead to?
Growth of follicle leads to production of estradiol from the layers of granulosa cells surrounding it. Estradiol is responsible for the proliferation of the endometrial lining of the uterus.
194
What does estradiol do?
Estradiol is responsible for the proliferation of the endometrial lining of the uterus.
195
When does ovulation occur?
At the peak of follicular growth, in response to LH surge
196
Approx what size are follicles prior to ovulation?
Over 20mm in average diameter
197
Describe the ovulation phase of the menstrual cycle
LH is released in a positive feedback mechanism from the anterior pituitary due to prolonged exposure to estradiol. For this positive feedback to take place, levels of estradiol above 200 pg/ml for approx 50h are necessary
198
What is required to initiate the positive feedback response of LH release in the LH surge?
For this positive feedback to take place, levels of estradiol above 200 pg/ml for approx 50h are necessary
199
By what mechanism is the oocyte released from the follicle?
Several proteolytic enzymes and prostaglandins are activated, leading to digestion of the follicle wall collagen
200
Describe what happens during the secretory phase of the menstrual cycle?
The remaining granulosa cells that are not released with the oocyte during the ovulation process enlarge and acquire lutein (carotenoids), which is yellow.
These granulosa cells are now called the corpus luteum and predominantly secrete progesterone. Peak progesterone production is noted 1 week later after ovulation takes place.
201
What does the lifespan of the corpus luteum depend on?
Continued LH support from the anterior pituitary, or, if a pregnancy occurs then HCG of pregnancy would maintain corpus luteum
202
What does the corpus luteum predominantly secrete?
Progesterone
203
What will happen to the corpus luteum if no pregnancy occurs?
Luteolysis occurs and the corpus luteum is converted to a white scar called the carpus albicans
204
What happens to the remaining granulosa cells that are not released in ovulation?
Enlarge and acquire lutein (carotenoids), which is yellow. Now called the corpus lutein, and predominantly secrete progesterone.
205
Approximately how long is a menstural cycle?
24-32 days
206
When might the menstrual cycle be longer?
After menarche
207
When might the menstrual cycle be shorter?
In pre menopause
208
When is regularity of the menstrual cycle generally best?
Between the ages of 20-40 yrs
209
What is the median blood lost per cycle?
37-43ml/cycle. Mostly in the first 48hrs
210
What is most important with regards to menstrual cycles?
Pattern/amount. What is normal.
211
What is menorrhagia?
Heavy periods
212
What might cause menorrhagia?
Abnormal clotting, pathology, fibroids, IUCD, medical disorders, cancer, progesterone contraception
213
List 5 types of uterine fibroids
Intracavitary, pedunculated, subserosal, submucosal, intramural
214
What is DUB
Dysfunctional uterine bleeding
215
What is dysfunctional uterine bleeding DUB?
60% heavy bleeding. No recognisable pelvic pathology, pregnancy or general bleeding disorder
216
What might cause irregular bleeding?
Hormonal contraceptives
Missed combined pills/missed progesterone only pill
Vomiting/diarrhoea whilst on the COCP
Certain prescription medicines or St Johns wort (a herbal remedy) whilst using the pill, patch, ring or implant
217
Irregular bleeding is common during the 1st 3 months of starting hormonal contraception, such as?...
```
COCP
Progesterone only contraceptive pill
Contraceptive patch (transdermal patch)
Contraceptive implant or injection
Intrauterine system IUS
```
218
What types of amenorrhoea are there?
Prepubertal, pregnancy, menopause, uterine/endometrial, ovarian, pituitary, hypothalamic
219
What is the possible impact of menstrual disorders?
Physical - tiredness, anaemia
Psychological - depression, irritability, mood swings, anxiety
Social - impact on ability to socialise, swim, perform sports
220
What makes up the linea terminalis?
The arcuate line, pectineal line and pubic crest
221
What type of pelvis is good for childbirth?
Gynecoid
222
Describe the features of a gynecoid pelvis
```
Round inlet
Straight side walls
Ischial spines not too prominent
Well rounded greater sciatic notch
Well curved sacrum
Sub pubic arch over 90 degrees
```
223
What is the 'true' pelvis?
The lesser pelvis. Bony canal. Solid and immobile
224
What is the 'false' pelvis?
The greater pelvis. No obstetric relevance
225
What are the 4 pelvic planes?
Pelvic inlet
Plane of greatest diameter
Plane of least diameter
Pelvic outlet
226
How might you clinically assess the pelvic inlet?
Anteroposterior diameter
227
How might you clinically assess the mid pelvis?
Check for straight side walls. Bispinous diameter
228
How might you clinically assess the pelvic outlet?
Infrapubic angle. Distance between ischial tuberosities
229
Where is the obstetric conjugate measured from?
Measured from the sacral promontory to the midpoint of the pubic symphysis
230
Where do you measure the diagonal conjugate from?
Measured from the sacral promontory to the inferior border of the pubic symphisis
231
What are the ligaments of the pelvis?
Sacrospinous ligament
| Sacrotuberous ligament
232
Describe a gynecoid pelvis
Circular pelvic inlet
80-85 degrees
Well rounded greater sciatic notch
233
Describe an android pelvis
Heart shaped inlet
Prominent projecting promontory
Prominent medically projecting ischial spines
50-60 degrees
234
What is the scrotum?
Cutaneous sac developed from labioscrotal folds. Contains the testes, epididymis and first part of the spermatic cord.
235
What is the scrotum developed from?
labioscrotal folds.
236
What does the scrotum contain?
Contains the testes, epididymis and first part of the spermatic cord.
237
What surrounds the testes?
Tunica vaginalis. Enclosed by tunica albuginea
238
Are the testes enclosed in peritoneum?
No
239
What organises the testes into lobules?
Fibrous septae
240
Describe the descent of the testes
Gonads develop within the mesonephric ridge. Descend through the abdomen. Testes cross the inguinal canal. Testes exit the anterio lateral abdominal wall
241
Describe the arterial supply to the testes
Direct branches from the abdominal aorta
242
Describe the venous drainage of the testes
Right - right testicular vein to the IVC
| Left - left testicular vein to the left renal vein
243
What is the epididymis?
Connects the seminiferous tubules via efferent ductules and fete testes. Head, body and tail.
244
What is the spermatic cord?
Contains the structures running to and from the testes, neurovascular structures and duct system.
From the deep inguinal ring, lateral to inferior epigastric vessels, via the inguinal canal and superficial inguinal ring, to the posterior border of the testis.
245
Describe the course of the spermatic cord
From the deep inguinal ring, lateral to inferior epigastric vessels, via the inguinal canal and superficial inguinal ring, to the posterior border of the testis.
246
Describe the contents of the spermatic cord
```
Lymphatic
Processes vaginalis
Vas deferens
Pampiniform plexus
Genital branch of genitofemoral nerve
3 arteries - testicular, cremasteric, artery to vas deferens
```
247
Describe the coverings of the spermatic cord
External spermatic fascia (aponeurosis of external oblique)
Cremasteric muscle and fascia (internal oblique and transversalis)
Internal spermatic fascia (transversalis fascia)
248
What is hydrocoele?
Serous fluid in vaginalis
249
What is haematocoele?
Blood in tunica vaginalis
250
What is varicocoele?
Varicosities of pampiniform plexus
251
What is spermatocoele?
AKA epididymal cyst
| Retention cyst within epididymis
252
What is epididymitis?
Inflammation of the epididymis
253
Why is transillumination important when analysing the scrotum?
Light passes through liquid but not solid
254
What is an indirect hernia?
Reopening of the processus vaginalis. Potential continuity between peritoneal cavity and the tunica vaginalis (between abdomen and scrotum). Via canal
255
What is testicular torsion?
Twisting normally occurs just above upper pole. Risks of necrosis of testis
256
Describe the innervation of the testis
Anterior surface - lumbar plexus
| Posterior and inferior surfaces - sacral plexus
257
Describe the lymphatic drainage of the testis
Drains to paraaortic nodes
258
Describe the lymphatic drainage of the scrotum
Drains to superficial inguinal nodes
259
Describe the course of the ductus vas deferens
Ascends in spermatic cord. Traverses inguinal canal. Tracks around pelvic side wall. Passes between bladder and ureter. Forms dilated ampulla. Opens into ejaculatory duct.
260
Where does the seminal vesicle lie?
Between the bladder and the rectum
261
Is the seminal vesicle a storage site?
No
262
What forms the ejaculatory duct?
Duct of seminal vesicle combine with the vas deferens to form ejaculatory duct
263
Approx how much of ejaculate comes from diverticulum of vas deferens? (Seminal vesicle)
70-80%
264
What is the important anatomical relationship of the prostate base?
Neck of bladder
265
What is the important anatomical relationship of the prostate apex?
Urethral sphincter and deep perineal muscles
266
What is the important anatomical relationship of the prostate muscular anterior surface?
Urethral sphincter
267
What is the important anatomical relationship of the prostate posterior?
Ampulla of rectum
268
What is the important anatomical relationship of the prostate infero lateral surface
Levator ani
269
What is benign prostatic hyperplasia?
Increased sized middle lobule. Obstruction of internal urethral orifice.
270
What are the symptoms of benign prostatic hyperplasia?
Dysuria, nocturia, urgency
271
How might prostatic malignancies metastasise?
```
Via lymphatic route (internal iliac and sacral nodes)
Venous routes (internal vertebral plexus to vertebrae and brain)
```
272
Describe the structure of the penis
Consists of a root, body and glands. Internal structure consists of a pair of corpora cavernosa dorsally, and a single corpus spongiosum ventrally
273
What arteries supply the penis?
Branches of internal pudendal arteries
274
Describe the blood supply to the male perineum
Internal pudendal artery is a branch of the anterior division of the internal iliac artery
275
What does bulbospongiosus do?
Helps expel last drops of urine, and maintain erection
276
What does ischiocavernosus do?
Compresses veins, therefore helping maintain erection
277
Describe the divisions of the male urethra
Pre prostatic, prostatic, membranous (pierces through peroneum), spongy
278
Which part of the male urethra pierces through the peroneum?
Membranous portion
279
What type of cells form the blood testis barrier ?
Sertoli cells. Also cells of germ cell lineage
280
What type of tumours are 90-95% of testicular neoplasms?
Germ cell tumours
281
How do seminiferous tubules converge on the rete testis?
Via the tubule recti
282
What type of cells form the exit duct system for male germ cells?
Simple cuboidal
283
What does the efferent duct of the male reproductive tract connect?
The rete testis with the head of the epididymis
284
What epithelium does the efferent duct of the male reproductive tract have?
Characteristic scalloped epithelium
285
How is sperm transported along the efferent duct of the male reproductive tract?
Combined ciliary action and myoid contraction
286
What is the epididymis?
Smooth muscle tube lined by pseudostratified epithelium. Characterised by the presence of stereocilia. Sperm maturation is completed (mobile)
287
What type of cells lines the epididymis?
Pseudostratified epithelium. Characterised by the presence of stereocilia
288
Describe the layers of the vas deferens
4 layers tube, epithelium and 3X smooth muscle
289
What is the function of the vas deferens?
Connects epididymis with ejaculatory duct. Smooth muscle contracts powerfully during ejaculation
290
What is the seminal vesicle?
Secretory epithelium, contributes 85% ejaculate volume. Smooth muscle layer. Sympathetic innervation enables discharge of contents into duct.
291
What proportion of ejaculate volume is from the seminal vesicle?
85%
292
What type of innervation enables discharge of seminal vesicle contents?
Sympathetic
293
What is the prostate?
Collection of 30-50 tubule-alveolar glands draining into prostatic urethra. Ejaculatory ducts merge with urethra within the prostate. Characteristic fibromuscular stroma.
294
Where does the ejaculatory duct merge with the urethra?
Within the prostate
295
In which zone does benign prostatic hyperplasia occur?
Transition zone
296
In which zone does adenocarcinoma of the male reproductive tract generally occur?
Peripheral zone
297
List the sequence of ovarian follicular development
Primordial, primary, pre-antral, early antral, mature, corpus luteum
298
What is a primordial follicle?
Small oocyte with flat follicular cells
299
What is a primary follicle?
Oocyte with maximum diameter with one or more layers of cuboidal granulosa cells. Zona pellucida develops.
300
Where does 90% of ovarian cancer arise?
Epithelium
301
What is stroma?
Theca and granulosa cells, may also give rise to tumours
302
What is the endometrium comprised of? (Layers)
Stratum basalis
Stratum functionalis, which is comprised of
Stratum spongiosum
Stratum compactum
303
Describe the histiological appearance of the uterus in the early proliferative phase of the menstrual cycle
Glands sparse, straight
304
Describe the histiological appearance of the uterus in the late proliferative phase of the menstrual cycle
Functionalis has doubled, glands now coiled
305
Describe the histiological appearance of the uterus in the early secretory phase of the menstrual cycle
Endometrium max thickness, very pronounced coiled glands
306
Describe the histiological appearance of the uterus in the late secretory phase of the menstrual cycle
Glands adopt characteristic 'saw tooth' appearance
307
Describe the histology of the cervix
Endocervical canal with mucus secreting, simple columnar epithelium. Ectocervix with stratified squamous non-keratinised epithelium. Squamocolumnar junction SCJ can be located at any point across the cervix
308
What is the transformation zone in the cervix? Why is it significant?
Adjacent to the SCJ (squamocolumnar junction). Absolute junction between one type of epithelium and another. Where the majority of neoplasms arise.
309
Describe the histology of the vagina
3 layered fibromuscular canal. Glycogen producing non keratinised squamous epithelium. Submucosa rich in elastin fibres and highly vascular. No glands.
310
Describe the histology of the breast
A single lactiferuos duct opens from each of multiple (15-20) lobes. Main duct branches repeatedly. Terminal ducts. Lobular unit, consisting of multiple acini.
Approx 70% breast malignancies are infiltrating ducts carcinoma
311
What's the most common type of breast malignancy?
Approx 70% breast malignancies are infiltrating ducts carcinoma
312
Describe the appearance of inactive breast tissue
Limited development of duct alveolar system. Relatively dense fibrous interlobar tissue
313
Describe the appearance of lactating breast tissue
Highly developed with milk secretions in alveolar lumen. Interlobular tissue reduced to thin septa
314
Describe the descent of the female gonads
Gonads develop in the mesonephric ridge. Descend through abdomen, but stop in the pelvis
315
What is the arterial supply to the ovary?
Direct branches from the abdominal aorta
316
Describe the venous drainage of the right ovary
Right ovarian vein to the IVC
317
Describe the venous drainage of the left ovary
Left ovarian vein to left renal vein
318
What is the top of the uterus called? (Palpable in pregnancy)
Fundus
319
What is the anterior peritoneal pouch called?
Uterovesical pouch
320
What is the posterior peritoneal pouch called in the female?
Rectouterine pouch AKA pouch of Douglas
| Posterior formix of the vagina
321
What is the posterior peritoneal pouch called in the male?
Rectovesical peritoneal recess
322
Describe the development of the peritoneal pouches
Paramesonephric ducts, a pair of ducts that are open cranially and connect to the urogenital sinus caudally. Persist in the absence of MIH. Fusion of the ducts in the midline creates a broad transverse fold draped by peritoneum.
323
What is the broad ligament?
Peritoneal fold in the female pelvis. Mesentery of the uterus, uterine tube and ovary.
324
What is the round ligament?
Attached to ovary and labium majus, travels through inguinal canal. Consequences for lymphatic drainage
325
What is the round ligament embryologically?
Gubernaculum
326
What is an anteverted uterus with respect to?
Vagina
327
What is an anteflexed uterus with respect to?
The cervix
328
What constitutes then uterine tube?
Abdominal ostium, fimbria, infundibulum, ampulla and isthmus
329
What is the function of the uterine tube?
To conduct the oocyte into the uterine cavity. Normally the site of fertilisation
330
Is the lining of the uterine tube similar to that of the uterine cavity?
No - consequences for ectopic implantation
331
How is the female peritoneal cavity open?
Via the ostium of the uterine tube
332
Describe the support of the pelvic viscera
Transverse cervical ligament - thickening at the base of broad ligament. Lateral stability of cervix. Uterosacral ligament opposes anterior pull of round ligament, assists in maintaining anteversion.
333
Describe the blood supply to the female internal genitalia
Ovarian artery - branches from abdominal aorta
Uterine artery - anterior division of internal iliac
Internal pudendal - anterior division of internal iliac
334
Describe the lymphatic drainage of the ovaries
Drains to paraaortic nodes
335
Describe the lymphatic drainage of the uterus
Fundus - to aortic nodes (and inguinal nodes)
Body - to external iliac nodes
Cervix - external and internal iliac nodes and sacral nodes
336
Where is the labia majora?
Enclosing the pudendal cleft
337
Where is the labia minora?
Enclosing the vestibule of the vagina (bulb of vestibule, clitoris)
338
What is enclosed in the vestibule?
Orifices of urethra, vagina, greater and lesser vestibular glands
339
What are the greater vestibular glands also called?
Bartholin glands (barthdinitis, bartholin gland cyst)
340
Describe the vagina orifice
Vagina orifice opens into the vestibule along with the external urethral orifice and the ducts of the greater and lesser vestibular glands.
Vaginal fornices - recesses if vagina around the cervix
341
What are Vaginal fornices?
recesses if vagina around the cervix
342
Describe the innervation of the vagina
Inferior 1/5 of vagina receives somatic innervation from pudendal nerve
Superior 4/5 of vagina and uterus receives innervation from uterovaginal plexus
343
Describe the pain afferents of the vagina
Vary depending on pelvic pain ripe thoracic lumbar spinal ganglia
S2 to S4 spinal ganglia
344
Describe the innervation of the perineum
Pudendal nerve, plus ilioinguinal nerve
345
Describe the course and distribution of the pudendal nerve
Exits pelvis via greater sciatic foramen. Enters perineum via lesser sciatic foramen. Travels through pudendal canal.
346
What is the pelvic floor?
Muscular and fibrous tissue diaphragm. Fills the lower part of the pelvic canal. Closes the abdominal cavity. Defines the upper border of the perineum. Supports the pelvic organs. Pierced by the urethra, vagina and rectum.
347
Describe the pelvic side wall
Ischium of pelvis, sacrospinous and sacrotuberous ligaments, obturator nerve and membrane, obturator internus. Piriform and coccygeus, branches of sacral plexus. Fascia (including tendineus), levator ani muscles. Internal iliac vessels and branches, ureters.
348
Describe the pelvic floor
Levator ani - puborectalis, pubococcygeus, iliocococcygeus.
349
What is attached to the pelvic side wall?
Ischial spine, arcus tendineus fascia pelvis, urogenital hiatus allows passage of urethra, vagina and rectum.
350
Describe the main blood vessels of the pelvis
Branches of posterior trunk of internal iliac artery (pudendal artery, vaginal artery, inferior rectal artery)
351
Describe the major nerves of the pelvis
Pudendal nerve S2,3,4 'keeps your guts off the floor'
352
What is the perineum?
Fibromuscular sheet which closes the pelvic outlet. Lower limit of perineal space. Perineal space continues with ischiorectal fossa. Perineal muscles. Perineal body.
353
What constitutes the perineum?
Urogenital diaphragm, transverse perineal muscles, ischiocavernosus, perineal body, bulbospongiosus
354
What is the perineal body?
Connective tissue mass in centre of perineum. Anchors the perineal muscles and rectum. Central fulcrum for pelvic support.
355
What does the pelvic floor do?
Supports the pelvic organs - retains uterus and bladder in correct positions
Contributes to continence - sphincter mechanism directly and indirectly
Contributes to the process of childbirth
Contributes to 'truncate stability'
356
Describe some of the possible effects of childbirth on the woman's anatomy
Stretch of pudendal nerve (neuropraxia and muscle weakness)
Stretch and damage of pelvic floor and perineal muscles (muscle weakness)
Stretch/rupture of ligaments support of muscles (ineffective muscle action)
357
Describe some consequences of the effects of childbirth on a women
Lack of support of pelvic organs - prolapse
| Contributions to continence - incontinence
358
What other factors affect the effects of childbirth on a women
Age, menopause (atrophy of tissues after oestrogen withdrawal), obesity, chronic cough, intrinsic connective tissue laxity (defined conditions, constitutional)
359
What are the treatment options for urinary incontinece?
Pelvic floor muscle exercise
| Surgery
360
Describe some continence procedures used to treat urinary incontinence
Increase support to sphincter mechanism and prevent descent of bladder neck (colposuspension, tension free vaginal tape). Effective. Side effects, voiding difficulty/retention, overactive bladder disease (obstruction)
361
Describe possible treatments for a vaginal prolapse
Remove prolapsed organs. Restore connective tissue supports. Maintain function. Side effects, recurrence, new incontinence, dysparenuria.
362
What is pelvic inflammatory disease PID?
The result of infection ascending from the endocervix, causing endometritis, salpingitis, parametritis, oophoritis, tube-ovarian abscess and/or pelvic peritonitis.
363
What is endometritis?
Inflammation and infection of the endometrium (lining of the uterus)
364
What is salpingitis?
Inflammation of Fallopian tube
365
Briefly outline the pathophysiology of pelvic inflammatory disease PID
Ascending infection from the endocervix and vagina. Infection causes inflammation, which causes damage. Therefore damaged tubal epithelium, adhesions form
366
List some complications of pelvic inflammatory disease PID
Ectopic pregnancy, infertility, chronic pelvic pain, fitz-hugh-curtis syndrome (RUQ pain and peri-hepatitis following chlamydia PID)
367
Briefly outline the aetiology (cause) of PID
Often polymicrobial. Sexually transmitted infections (c. Trachomatis, n. Gonorrhoea). Also gardnerella vaginalis, mycoplasma, anaerobes.
368
Briefly outline the epidemiology of PID
Understimated. Sexually active women, peak 20-30yrs old. Incidence rate in primary care approx. 280 per 100,000
369
What are the risk factors for PID?
As for STIs
| Young age, lack of use of barrier contraception, multiple sexual partners, low socioeconomic class
370
What are the clinical features of PID?
Pyrexia (fever), pain (lower abdominal, deep dysparaunia (pain when having sex), abnormal vaginal/cervical discharge, abnormal vaginal bleeding, sexual history, prior STIs, contraceptive history
371
What might be on a differential diagnosis for PID?
Gynaecological - ectopic pregnancy, endometriosis, ovarian cyst complication
GI - IBS, appendicitus
Urinary - UTI
Other - Functional pain
372
Describe the clinical features of PID
Fever, lower abdominal tenderness (usually bilateral).
Bimanual examination - adnexal (area around ovary) tenderness. Cervical motion tenderness.
Speculum examination - purulent cervical discharge. Cervicitis
373
What investigations might you do for PID?
Urinary and/or serum pregnancy test.
Endocervical and high vaginal swabs (presence of NG/CT supports diagnosis, but absence doesn't exclude it)
Blood tests - WBC and CRP
Screening for other STIs including HIV
Diagnostic laparoscopy is gold standard (bus risky) - could also perform adhesidysis and drain abscesses
374
What management would be done for PID?
Low threshold for empirical treatment - delayed treatment increases long term sequelae
Severe disease requires IV antibiotics and admission for observation and possible surgical intervention
375
Describe outpatient treatment of PID
Antibiotic therapy 14 days
IM ceftriaxone 500mg STAT + PO doxycycline 100mg BD + PO
Metronidazole 400mg BD
376
Describe inpatient treatment for PID
IV ceftriaxone 500mg STAT + IV/PO doxycycline 100mg BD + IV metroniadazole 400mg BD
Progresses to
PO doxycycline 100mg BD + PO metroniadazole 400mg BD
377
When would surgical treatment of PID be considered?
Laparoscopy/laparotomy may be considered if
- no response to therapy
- clinically severe disease
- presence of a tube-ovarian abscess
Ultrasound guided aspiration of pelvic collections is less invasive
378
Define sexually transmitted infection STI
Includes both symptomatic and asymptomatic cases. Sexual activity is the principal mode of transmission
379
Define sexually transmitted disease STD
Symptomatic cases only
380
What groups of people are particularly at risk of STIs?
Young people, certain ethnic groups, low socioeconomic status, specific aspects of sexual behaviour (age at 1st sexual intercourse, number of partners, orientation, unsafe activity)
381
Why is there an increasing incidence of STIs?
Increased transmission - changing sexual and social behaviour, increasing density and mobility of populations, increased GUM attendance. Greater public, medical and national awareness (elgl campaigns). Improved diagnostic methods, including screening programs.
382
What is the possible effects of stigma associated with STIs?
Impact on diagnosis and tracing contacts
383
How may patients with STIs present?
Patient presentation with genital lesions/problems to GP or GUPI clinic (ulcers, vesicles, warts, urethral discharge, pain, vaginal discharge, clinician notes of features suggestive of an STI). Detection of asymptomatic case (contact tracing/screening)
384
Outline general management of STIs
Treatment preferably single dose/short course. Co-infections are common, screen and consider empiric treatment for other STIs
Contact training. Patient and public health management. Sexual health education, advice and instruction on safe sex.
385
What is the most common viral STI?
Human papillomavirus. Over 100 HPV types of this DNA virus.
386
Describe presentation of HPV infection
Cutaneous, mucosal and anogenital warts (mainly HPV 6 and 11). Benign, painless, varrucous epithelial or mucosal outgrowths
387
What are the high risk types of HPV?
HPV16 and HPV18. Oncogenic. Associated with cervical and anogenital cancer
Cervical cancer most common cancer in woman aged 15-34, associated with over 70% of cases
388
Describe diagnosis of HPV infection
Clinical. Biopsy and genome analysis, hybrid capture.
389
Describe the treatment of HPV infection
```
None
Spontaneous resolution (70% 1yr, 90% 2yrs).
```
390
How is screening for HoV carried out?
Cervical pap smeer cytology. Colposcopy + acetowhite test. Cervical swab, HPV hybrid capture (40% 20-24yr olds +ve)
391
What is the HPV vaccine used in the UK, and against what strains is it effective?
Gardasil, HPV 6, 11, 16 and 18
392
Describe the nature of the causative organism of chlamydia
Obligate intra-cellular bacterium. Non specific genital chlamydia infections (serotype D-K)
393
Describe symptoms of chlamydia in males
Urethritis, epididymitis, prostatitis, proctitis
394
Describe symptoms of chlamydia in females
Urethritis, cervicitis, salpingitis, perihepatitis
395
How is chlamydia diagnosed?
Endocervical and urethral swabs NAAT. 1st void urine.
| Neonatal infection, conjunctival swab.
396
What is the treatment for chlamydia?
Doxycycline or azithromycin. Erythromycin in children
397
Describe the symptoms of herpes simplex virus
Primarily genital herpes - extensive painful genital ulceration, dysuria, inguinal lymphadenopathy, fever
398
Which herpes simplex virus causes genital herpes, and which causes cold sores?
HSV1 - cold sores
| HSV2 - genital herpes
399
Why is herpes recurrent?
Asymptomatic to moderate recurrent genital herpes. Latent infection in dorsal root ganglion.
400
How is herpes diagnosed?
PCR of vesicle fluid and/or ulcer base
401
What is the treatment for herpes?
Aciclovir (primary and severe disease).
| Aciclovir prophylaxis for frequent recurrences
402
What sort of orangish causes gonorrhoeae?
Neisseria gonorrhoeae. Gram negative intracellular diplococcus
403
What are the symptoms of gonorrhoeae in males?
Urethritis, epididymitis, prostatitis, prodtitis, pharyngitis
404
What are the symptoms of gonorrhoeae in females?
Asymptomatic, endocervicitis, urethritis, PID which may lead to infertility
405
What might be a result of disseminated gonococcal infection?
Bacteraemia, skin and joint lesions
406
How is gonorrhoea diagnosed?
Swab from urethra, cervix (threat, rectum), or urine (NAAT). Gram stain (pus or normally sterile site). Fastidious organism requiring special media.
407
What is the treatment of gonorrhoea?
Ceftriaxone (IM), increasing resistance to many other agents. All patients tested and tested for chlamydia with azithromycin, which may also prevent emergence of resistance to cephalosporins
408
What is the aetiological agent of syphilis?
Treponema pallidum - spirochaet
409
In which group is there the highest incidence of syphilis?
MSM
| Men generally
410
Describe the stages of syphilis
Primary - indurated, painless ulcer (chancre)
Secondary - 6 to 8 weeks later fever, rash, lymphadenopathy, mucosal lesions.
Latent, symptom free years
Tertiary - Neurosyphilis (GPI tabes dear salis). Cardiovascular syphilis, gummas (local destruction)
411
How is syphilis diagnosed?
Serology. Dark field microscopy. Organism can't be grown
412
Describe the serology of syphilis
Initial screening with EI antibody test then +ves
- Rapid plasma region RPR titre (cross reacting antigen)
- TP particle agglutination TPPA
- Serologic pattern interpreted (false +ves, response to treatment ect)
413
What is the treatment of syphilis?
Penicillin and 'test of cure' follow up
414
What might cause inguinal lymphadenopathy?
```
LGV (lymphogranuloma venereum)
- C. Trachoma serotypes L1, L2, L3
- Rapidly healing papule then inguinal bubo (abscess/lump in groin)
- Recent clusters in Europe in MSM
Chancroid (Haemophilus ducreyi)
- Painful genital ulcers
Granulosa inguinale/donovanosis (klebsiella granulomatis
- Genital nodules - ulcers
```
415
What is trichomonas vaginalis?
Flagellated protozoan, Trichomonas vaginitis. Thin, frothy, offensive discharge. Irritation, dysuria, vaginal inflammation.
416
How is trichomonas vaginalis diagnosed?
Vaginal wet preparation +/- culture enhancement
417
What is the treatment of trichomonas vaginalis?
Metroniadazole
418
Briefly outline the stages of sperm production
Spermatozoa are produced in the siminiferous tubules of the testis
Spermatogonia to mature spermatozoa - up to 74 days (50 days in testis, 12-24 days in epididymis)
419
When does sperm production begin?
Starts at puberty and continues till death
420
Approx how many sperm are produced a day?
200-300 million a day (only half become viable sperm)
421
What is the effect of age on sperm production?
Slight decrease in quantity and quality with age.
422
Describe the hormonal control of spermatogenesis
LH - (anterior pituitary) to leydig cells (testis) - testosterone - spermatogenesis
FSH - androgen binding protein (Sertoli cells) - formation of blood testis barrier (increasing testosterone conc) - spermatogenesis
Oestrogen (leydig cells) - increases sperm viability
Negative feedback loop - inhibin (Sertoli cells) decreases FSH
423
Describe LHs role in spermatogenesis
LH - (anterior pituitary) to leydig cells (testis) - testosterone - spermatogenesis
424
Describe FSHs role in spermatogenesis
FSH - androgen binding protein (Sertoli cells) - formation of blood testis barrier (increasing testosterone conc) - spermatogenesis
Negative feedback loop - inhibin (Sertoli cells) decreases FSH
425
Describe oestrogens role in spermatogenesis
Oestrogen (leydig cells) - increases sperm viability
426
If pituitary gland is removed, can spermatogenesis still occur?
Yes, can be initiated by FSH and testosterone alone
427
Briefly describe the composition of a spermatid
Head - nuclear condensation
Acrosome - Golgi apparatus. Lysosomes like (hydrolytic enzymes). Enable sperm to penetrate ovum
Midpiece - mitochondria packed around contractile filaments
Tail - flagellum produced by microtubules growing from centriole to form axoneme
428
Describe the final step of spermatogenesis, formation of spermatozoa
Cytoplasm and organelles stripped under influence of testosterone. Spermatozoa now mature, but lack mobility (infertile). Released from Sertoli cells into lumen of seminiferous tubule (spermation). Transported into epididymis in testicular fluid (produced by Sertoli cells) by peristaltic contraction. Gain mobility and become fertile in epididymis
429
How long can spermatozoa be stored in the epidiymis?
Several months, no loss of fertility.
430
Hoe do sperm leave the epididymis?
Sexual arousal - contraction of epididymal wall muscle - expels spermatozoa into ductus (vas) deferens
431
What happens to spermatozoa if they're not expelled?
Eventually phagocytosis by epididymal epithelial cells (after several months)
432
Describe the male sexual response - excitement phase
Sensory and psychological stimulation - limbic system
Activation of sacral parasympathetic neurons
Inhibition of thoracolumbar sympathetic neurons
ACh - M3 receptors on endothelial cells - increase Ca2+ - activation of eNOS - NO production
Arterial vasodilation on corpora cavernosa
Increased penile blood flow. Penile filling (latency). Penile tumescence (erection)
433
Describe the male sexual response - plateau
Activation of sacrospinous reflex
Contraction of ischiocavernosus (compresses crus penis and impedes venous return) - venous engorgement
Rise in intercavernosus pressure - decreased arterial inflow
Simulation of secretion from accessory glands - cowpers and littres glands
- lubricate distal urethra
- neutralise acidic urine in urethra
- 5% of ejaculate
434
How is the male sexual response - emission, divided?
Orgasm is subdivided into emission and ejacualtion
435
Describe the male sexual response - emission
Stimulation of thoracolumbar sympathetic reflex
Contraction of smooth muscle in ductus deferens, ampulla, seminal vesicle and prostate
Internal and external urethral sphincters contract
Semen is pooled in urethral bulb
436
Describe the male sexual response - ejaculation
Spinal reflex (with cortical control)
Sympathetic nervous system (L1, L2)
- contraction of glands and ducts (smooth muscle)
- internal urethral sphincter contracts
Filling of the internal urethra stimulates pudendal nerve - contractions of the genital organs, the ischiocavernosus and bulbocavernosus muscles - expulsion of semen
437
Describe the male sexual response - resolution
Activation of the thoracolumbar sympathetic pathway
Contraction of the arteriolar smooth muscle in corpora cavernosa
Increased venous return
Detumescence and flaccidity
Refractory period
438
Describe the female sexual response - excitement
```
Same neuronal response as the male
Vaginal lubrication begins (due to vasocongestion)
Clitoris engorges with blood
Uterus elevates
Increase in muscle tone, HR and BP
```
439
Describe the female sexual response - plateau
Further increase in muscle tone, HR and BP
Labia minora deepens in colour
Clitoris withdraws under its hood
Bartholin gland secretion lubricates vestibule for entry of penis
Orgasmic platform in lower 1/3 of vagina
Uterus is fully elevated
440
Describe the female sexual response - orgasm
Orgasmic platform (outer 1/3 of vagina) contracts rhythmically 3 - 15 times
Uterus contacts, anal sphincter contracts
Clitoris remains retracted under hood
No refractory period - multiple orgasms possible
441
Describe the Female sexual response - resolution
Clitoris descends and engagement subsides
Labia return to unaroused size and colour
Uterus descends to unaroused position
Vagina shortens and narrows back to unaroused state
442
Describe the changes in breasts during sexual response
Excitement phase - breast size increases, nipple becomes erect, veins become more distinct
Plateau and orgasm phase - greater size increase, areola increases in size and causes nipple to appear less erect. Sex flush may appear on breasts and upper abdomen
Resolution phase - return to unaroused size, detumescence of areola- nipple appears more erect, disappearance of sex flush
443
What is the anatomical G spot?
An area of erotic sensitivity located along the anterior wall of the vagina. Some women are able to experience orgasm and possibly ejaculation from G spot stimulation. Tissue similar to male prostate, therefore fluid may be similar to prostatic component of semen
444
Describe the effect of ageing on the female sexual response
Some women report reduced desire. Reduced vasocongestion response, causing reduced vaginal lubrication. Vaginal and urethral tissue lose elasticity. Length and width of vagina decreases, reduced expansion ability of inner vagina during arousal. Number of orgasmic contractions often reduced. More rapid resolution
445
Describe lack of sexual desire
Hypoactive, little or no interest in sex (for age). Most common sexual dysfunction.
446
What is sexual aversion?
Revulsion or fear of one or all aspects of sex, often as a result of abuse or assault.
447
What is klümer-bucci syndrome?
Bilateral medial temporal bone lesions. Hyperphagia, hypersexuality, hyperorality, visual agnosia and docility
448
List some common psychological sexual dysfunctions
Hypoactive
Hyperactive
Nymphomaniac
Aversion
449
What is failure of sexual arousal in the female?
Persistent, recurrent, inability to attain or maintain lubrication. Swelling response = lack of lubrication (especially in menopause)
450
What might cause male impotence?
Psychological (descending inhibition of spinal reflexes)
Tears in fibrous tissue of corpora cavernosa
Vascular - atherosclerosis, diabetics
Drugs - alcohol, antihypertensives (beta blockers, diuretics)
451
How does viagra work?
Inhibits cGMP breakdown in corpus cavernosum
Therefore increase in nitric oxide stimulated vasodilation
Therefore increase in penile blood flow - erection
452
How much in volume is normally in ejaculate?
2-4ml
453
How many sperm per ml is there normally in ejaculate?
20-200 X 10^6 sperm per ml
454
Approx how many sperm is there in an ejaculate?
Over 40 X 10^6
455
What is the composition of most sperm in ejaculate?
Over 60% swimming forwards vigorously
| Less than 30% abnormal morphology
456
List some common ejaculate abnormalities
Liquefaction should take place within 1hr
| Oligozoospermia - Less than 20 X 10^6 sperm per ml
457
Describe the bulbourethral/cowpers glandular component of semen
5% volume
Alkaline fluid
Mucous lubricates the tip of the penis and urethral lining
458
Describe the seminal vesicles component of semen
60% volume
Alkaline fluid (neutralises the acid in male urethra and female reproductive tract)
Fructose (ATP production), prostaglandins (increase sperm motility and increase female genital smooth muscle contraction), clotting factors (particularly semenogelin)
459
Describe the prostate glandular component of semen
25% volume
Milky, slightly acidic fluid
Proteolytic enzymes (e.g. PSA, pepsinogen break down clotting factors, from seminal vesicles, re-liquiefying semen in 10-20mins)
Citric acid (ATP production), acid phosphate
460
What typically happens in menstrual cycle, days 7-14?
Endometrial proliferation
| Ovulation approx day 14
461
What typically happens during days 14-28 of the menstrual cycle?
Uterine secretory phase. Oestrogen and progesterone (corpus luteum). Hospitable environment for fertilisation and implantation
462
Describe oocyte maturation (nuclear maturation)
Oocyte undergoes meiosis 1
Nuclear membrane of oocyte disappears
First polar body separates and enters the perivitelline space
Second meiotic division takes place and stops metaphase 2
This process is know as maturation of oocyte nucleus
463
Describe oocyte maturation (cytoplasmic maturation)
Mitochondria dispersed throughout cytoplasm
Endoplasmic reticulum accumulates in oocyte cortex.
Proteins and lipid synthesis - cortical granules
Immature oocyte - corti for granules displaced throughout cytoplasm. Become cortical during maturation.
Cytoskeleton microfilaments migrate toward oocyte cortex
464
What provides the energy for an oocyte?
Lipid droplets provide energy (meiosis, maturation, fertilisation and early embryo development).
465
How many sperm does it take to fertilise an egg?
Approx 300 reach site of fertilisation
| 299 sacrificed to disperse the zona pellucida
466
How long can sperm survive in the female genital tract?
Up to 5 days
467
How long do oocytes survive before phagocytosis?
6-24hrs
468
When is the fertile period?
Sperm deposition up to 3 days prior to ovulation or on day of ovulation
469
How long does it take oocyte to travel from ovary to body of uterus?
3-4 days
470
How does the oocyte travel from the ovary to the body of the uterus?
Cilia and Fallopian tube peristalsis
471
Describe the layers through sperm penetration of the oocyte must occur
Sperm needs to penetrate corona radiata (follicular cells) and zona pellucida (glycoprotein membrane). Undergoes capacitation
472
Describe capacitation of sperm
Further maturation of sperm in female reproductive tract 6-8hrs. Sperm cell membrane changes to allow fusion with oocyte cell surface (removal of protein coat of sperm and acrosomal enzymes are exposed).
Tail movement changes from beat to whip like action (3mm/hr)
473
What is the most movement of sperm due to?
Contraction of the female genital tract
474
At what rate can sperm move?
3mm an hour
475
What initiates the acrosome reaction of sperm
When sperm contacts corona radiata, it has an intact acrosome. Sperm pushes through granulosa cells of corona radiata. Proteins on sperm head bind it to ZP3 proteins of zona pellucida ZP. Binding triggers acrosome reaction
476
Describe the acrosome reaction of sperm
Binding to corona radiata triggered
- Key signalling mechanism involves intracellular Ca2+
- Acrosome enzymes digest path through zona pellucida
- One sperm penetrates, fusion of plasma membranes of egg and sperm
- Sperm moves into cytoplasm, oocyte and sperm together become zygote
- Polyspermy blocked via cortical reaction
477
Describe the oocyte plasma membrane
Can be divided into 2 parts:
- Part of membrane directly overlying the metaphase chromosomes, has a smooth surface devoid of microvilli
- Remainder of the oocyte is rich in microvillar protrusions. This is the region of the oocyte where sperm bind and fuse
478
Describe the block to polyspermy, fast block
Electric change in oocyte membrane. Sodium channels open (resting potential from -75 to +20 mV). Wave of depolarisation starts at the site of entry of sperm and propagates across cytoplasm
479
Describe the block to polyspermy: slow block
Ca2+ released from ER, induces local exocytosis of cortical granules. Granules release enzymes to stimulate adjacent cortical granules to undergo exocytosis. Wave of exocytosis occurs around oocyte in 3 dimensions from original site of sperm entry
480
What is syngamy?
Union of male and female pronuclei to form diploid zygote (46 chromosomes) = syngamy
Oocyte completes meiosis 2. Expels second polar body. Male and female pronuclei migrate towards each other (23+23 chromosomes).
481
What is polyploidy?
Embryos containing 3 or more pronuclei are polyploidy - entry of more than 1 sperm, or failure of extrusion of second polar body.
482
Describe cleavage
A series of rapid mitotic divisions and metabolic changes. Increased number of cells (16-32 blastomeres) of decreasing size, without increase in size of fertilised ovum. Cells are totipotent. Generation of a large number of cells that can undergo differentiation and gastrulation to form organs. Increase in the number/cytoplasmic ratio. One nucleus can't transcribe sufficient RNA to support the enormous cytoplasm of the zygote.
483
What is totipotency?
Cell has the capacity to develop into entire individual
484
What results in monozygotic twins?
In cleavage, totipotent cells become divided into 2 separate independent cell masses
485
What causes dizygotic/non identical twins?
2 eggs ovulate, 2 eggs fertilised.
486
Describe the mechanics of cleavage
No G1 (duplication of organelles and cytosol) or G2 (synthesis of enzymes and proteins) stages in cell cycle during cleavage
With each mitotic division during cleavage, the nuclear cytoplasmic ratio increases
Cleavage is asynchronous (not all blastomeres divide at the same time)
487
Describe compaction
At the 8 cell stage, blastomeres undergo polarisation and form tight junctions to create 'inner embryo environment'
488
What is the morula?
16 blastomeres stage. 3-4 days after fertilisation embryo passes from oviduct into uterus.
489
What is key about oestrogens feedback role?
Oestrogen has different feedback roles at different stages of the menstrual cycle
490
What feedback effects does progesterone have at moderate/high doses?
Enhances the negative feedback of natural oestrogen, thus reducing LH and FSH secretion
491
What feedback effects does progesterone have at moderate/high doses with regards to fertility?
Inhibits the positive feedback of oestrogen, no LH surge, so no ovulation
492
What feedback effects does progesterone have at relatively low doses?
Does not inhibit LH surge, so ovulation still likely. Lower doses of progesterone will thicken cervical mucus
493
Describe the natural contraceptive method of fertility awareness
Use of fertility indicators to identify fertile and infertile periods of the menstrual cycle - cervical secretions, basal body temperature, length of menstrual cycle.
494
Describe the natural contraceptive method of lactational amenorrhoea
Breastfeeding delays the return of ovulation after childbirth. Only effective up to 6months after giving birth
495
List some advantages of natural methods of contraception
No hormones
| No contraindications
496
List some disadvantages of natural methods of contraception
Unreliable
| Not as effective
497
What is barrier contraception?
Physical barrier. Prevents entrance of sperm into the cervix. Diaphragm/cap also used with spermicide so additional chemical barrier
498
List positive of male/female condoms
Can help prevent against STIs
499
Give a disadvantage of male condoms
Sensitivity/allergy to latex
500
Give a disadvantage of female condoms
Not as widely available
501
Give an advantage and disadvantage of a female diaphragm/cap
Can be inserted anytime before intercourse
BUT...
Needs to be used with spermicide (can cause a local reaction)
502
What is the principle action of the COCP?
Prevents ovulation
503
What are the secondary actions of the COCP?
Reduces endometrial receptivity to inhibit implantation. Thickens cervical mucus to inhibit penetration of sperm.
504
Give some advantages of the COCP
Can relieve menstrual disorders
| Reduces risk of ovarian cysts and cancer
505
Give some disadvantages of the COCP
User dependent
Side effects - breakthrough bleeding, breast tenderness, mood disturbances
Increased risk of venous thromboembolism, myocardial infarction
Many contraindications
506
What is the principle action of the progesterone depot (injection) method of contraception?
Prevents ovulation
507
What is the secondary action of the progesterone depot (injection) method of contraception?
Reduces endometrial receptivity to inhibit implantation. Thickens cervical mucus to inhibit penetration of sperm
508
Give some advantages of the progesterone depot (injection) method of contraception?
Can also relieve menstrual disorders
| Convenient
509
Give some disadvantages of the progesterone depot (injection) method of contraception?
Altered and irregular bleeding is common
Delayed return of fertility for up to 1yr after stopping
Not quickly reversible
Small loss of bone mineral density and possible increase in fracture risk
510
What is the principle action of the progesterone implant method of contraception?
Prevents ovulation
511
What is the secondary action of the progesterone implant method of contraception?
Reduces endometrial receptivity to inhibit implantation. Thickens cervical mucus to inhibit penetration of sperm.
512
Give some advantages of the progesterone implant method of contraception
Long duration of action
Convenient
Can also relieve menstrual disorders
513
Give some disadvantages of the progesterone implant method of contraception
Small procedure required to fit and remove the implant
Local adverse effects can occur
Can cause changes in bleeding pattern
514
What is the principle action of the progesterone only pill method of contraception?
Thickens cervical mucus, making it impenetrable to sperm. Ovulation usually not prevented.
515
List some advantages of the progesterone only pill method of contraception
Can be used where the COCP is contraindicated
516
Give some disadvantages of the progesterone only pill method of contraception
Menstrual problems are common
| Must be taken at the same time each day (error for forgotten pill is only 3hrs late)
517
What are the main mechanisms of contraception?
```
Natural
Barrier
Prevention of ovulation
Inhibition of sperm transport
Inhibition of implantation
Sterilisation
```
518
What is the principle action of intrauterine system IUS (coils)?
Progesterone reduces endometrial proliferation and prevents implantation
519
What is the secondary action of intrauterine system IUS (coils)?
Thickens cervical mucus. Ovulation usually not prevented
520
Give some advantages of the intrauterine system IUS (coils)
Convenient
Long duration of action
Can also relieve menstrual disorders
521
Give some disadvantages of the intrauterine system IUS (coils)
Insertion may be unpleasant
IUS displacement/expulsion may occur
Menstrual irregularity common in 1st 6 months
Risk of uterine perforation (2/1000 insertions)
522
What is the intrauterine system IUS?
Coils, small device of plastic which added slow release progesterone that is placed in the uterus, can last between 3-5 yrs
523
How long would a coil last?
Between 3-5yrs
524
What is a intrauterine device IUD?
Contains copper. Small device made of plastic with added copper that is placed into the uterus, can last between 5-10yrs
525
How long can a intrauterine device last? IUD copper
Between 5-10 yrs
526
What is the principle action of a intrauterine device IUD?
Copper is toxic to sperm and ovum, so prevents fertilisation.
527
What is the secondary action of a intrauterine device IUD?
Copper causes endometrial inflammatory reaction, prevents implantation. Reduces penetration by sperm due to effect of copper on cervical mucus
528
Give some advantages of an intrauterine device IUD? Copper
Convenient
Long duration of action
Can also be used as emergency contraception (up to 5 days after unprotected intercourse)
529
Give some disadvantages of an intrauterine device IUD? Copper
Insertion may be unpleasant
IUD displacement/expulsion may occur
Periods may be heavier, longer or more painful
Risk of uterine perforation (2/1000 insertions)
530
Describe a vasectomy
Vas deferens interrupted to prevent sperm entering ejaculate. Performed under local anaesthetic. Must confirm success by post operative semen analysis to confirm no sperm (approx 12-16wks after surgery)
531
Describe female sterilisation
Tubal ligation/clipping
Fallopian tubes cut or blocked to stop ovum travelling from the ovary to the uterus. Can be done under local or general anaesthetic.
532
Give some advantages of sterilisation
Permanent
| No hormonal side effects
533
Give some disadvantages of sterilisation
Male failure rate 1/2000
Female failure rate 2-5/1000
Should not be chosen if in any doubt about having children in the future
534
Define infertility
Failure of contraception in a couple having regular unprotected coitus for one year
535
What is the general fertility rate?
80% of couples will be pregnant after 12 cycles with regular unprotected coitus
536
What is primary infertility?
No previous pregnancy
537
What is secondary infertility?
Previous pregnancy, successful or not
538
What is the rate of infertility?
Approx 1 in 7 couples may have difficulty in conceiving
| Approx 3.5 million people in the U.K.
539
What is important in the history of a female with infertility?
Age, duration of infertility, menstrual cycle (length and predictability of cycle), age of menarche. Tubal or pelvic surgery, PID, menorrhagia, pelvic pain, sexual history (STI)
540
What is important in the history of a male with infertility?
General health, alcohol/smoking, previous surgery to testis, drug history, previous infections, sexual dysfunction
541
What would be important in the examination of someone with infertility?
BMI, signs of secondary sexual characteristics, galactorrhoea, pelvic examination - feel for structural abnormalities.
Don't usually perform a male examination in the absence of relevant history. Potentially look at testicular size and check for descent.
542
How often do male factors cause infertility?
Approx 30%
543
How often do ovulatory disorders cause infertility?
Approx 25%
544
How often does tubal damage cause infertility?
Approx 20%
545
How often does uterine or peritoneal disease cause infertility?
Approx 10%
546
How often is infertility unexplained/other things?
Approx 25%
547
What male factors might cause infertility?
Varicocele
Abnormal sperm production (e.g. Testicular disease)
Hypothalamic/pituitary dysfunction
Ductal obstruction (post infective epididymitis, post vasectomy, scarring)
Failure to deliver sperm to vagina (hypospadias, impotence)
Idiopathic digospermia (not enough sperm, most common)
548
What are the 3 groups into which ovulatory disorders can be classed?
Hypothalamic pituitary failure
Hypothalimic pituitary ovarian dysfunction
Ovarian failure
549
What is polycystic ovary syndrome?
Syndrome consisting of polycystic ovaries and systemic features resulting from elevated androgens. Unknown pathophysiology, but appears to have a genetic component.
Increased androgen secretion
Raised LH/FSH ratio
Insulin resistance
Multiple small ovarian cysts
Anovulation - amenorrhoea or oligomenorrhoea
550
What are the clinical features of polycystic ovarian syndrome?
```
Hirsuitism (abnormal hair growth)
Acne
Obesity
Male pattern baldness
Oligomenorrhoea
Psychological Sx e.g. Mood swings, depression, anxiety
```
551
What are the Rotterdam diagnostic criteria for polycystic ovarian syndrome?
2/3 of the following
- Polycystic ovaries (12 or more follicles on ultrasound)
- Oligo-ovulation of anovulation
- Clinical and/of biochemical signs of hyperandrogenism
- Exclusion of other causes of androgen excess
552
What might cause tubal damage (resulting in infertility)?
Past pelvic infection e.g. Chlamydia, previous pregnancies, pelvic surgery, endometriosis, müllerian developmental anomaly
553
What might cause uterine or peritoneal disease resulting in infertility?
Endometriosis, Ashermans syndrome, uterine fibroids (impacts implantation), cervical stenosis, cervical hostility due to infection or female sperm antibodies
554
What is endometriosis?
The presence of endometrial tissue in sites other than the uterine cavity. Most commonly the pelvic cavity. 10-15% of women.
555
What are the clinical features of endometriosis?
Dysmenorrhoea, dyspaurenumia, chronic pelvic pain, infertility
556
What other factors might contribute to female infertility?
Idiopathic, poorly controlled diabetes, coital problems, multifactorial in 5-10% of cases
557
When would you refer a woman for further investigations about infertility?
A woman of reproductive age who has not conceived after 1 yr of unprotected vaginal sex, in the absence of any known cause of infertility.
A woman of reproductive age who is using artificial insemination to conceive who has not conceived after 6 cycles of treatment, in the absence of any known cause of infertility.
Early referral for woman over 36yrs, or a known clinical cause of infertility, or a history of predisposing factors for infertility.
558
What investigations might you do for an infertile woman?
```
Follicular phase LH, FSH (day 2)
Luteal phase progesterone (day 21) if ovulating regularly
Prolactin, androgens, TFTs
Cervical smear
Pelvic USS
Tests of tubal patency
```
559
What investigations might you do for an infertile male?
```
Sperm analysis, sperm count, motility ect
Antisperm antibodies
FSH/LH/testosterone
USS
Karyotype
Cystic fibrosis
Testicular biopsy
```
560
Describe a normal semen analysis
```
Volume: over 2ml
pH: 7.2-7.8
Sperm count: over 20 million
Motility: over 50%
Morphology: over 50%
```
561
What management might you do for infertility cause by lack of ovulation?
Induction of ovulation, clonifene citrate, gonadotrophins, GnRH agonists, weight loss/gain, dopamine agonists, ovum donation
562
What management might you do for infertility caused by tubal occlusion?
Surgery (re-anastomosis), assisted conception
563
What management might you do for infertility caused by male factors?
Artificial insemination by donor, intracytoplasmic sperm, injection, GnRH agonists, dopamine agonists
564
What takes precendence in very early embryonic development?
Development of the placenta
565
What occurs in the 2nd embryologically week (the week of 2s)?
Outer cell mass to cytotrophoblast and syncytiotrophoblast
| Inner cell mass to hypoblast and epiblast
566
What are the 2 cavities of the embryo at the end of the second week?
Amniotic cavity and yolk sac
567
Describe implantation
Is interstitial. The uterine epithelium is breached and the conceptus implants within the stroma. The placental membrane becomes progressively thinner as the needs of the foetus increase. The human placenta is haemomonochorial - one layer of trophoblast ultimately separates maternal blood from feral capillary wall
568
What are the aims of embryonic implantation?
Anchor the placenta - establishment of the outermost cytotrophoblast shell
Establish maternal blood flow within the placenta
Establish the basic unit of exchange
- Primary villi: early finger like projections of trophoblast
- Secondary villi: invasion of mesenchyme into cord
- Tertiary villi: invasion of mesenchyme core. By foetal vessels
569
Describe the basic unit of exchange established prior to the placenta
Establish the basic unit of exchange
- Primary villi: early finger like projections of trophoblast
- Secondary villi: invasion of mesenchyme into cord
- Tertiary villi: invasion of mesenchyme core. By foetal vessels
570
Describe the histology of the endometrium at the very start of pregnancy
The endometrium is prepared for implantation 'pre-decidual' cells. Elaboration of spiral arterial blood supply.
571
What does decidualisation do?
The decidual reaction provides the balancing force for the invasive force of the trophoblast
572
When is there errors in decidualisation?
Ectopic pregnancy
| Condition characterised by excessive invasion
573
Describe the purpose of the remodelling of the spiral arteries during implantation
Creation of new low resistance vascular bed. Maintains high flow required to meet feral demand - particularly late in. Gestation
574
List some implantation defects
Invasion incomplete, placental insufficiency, pre-eclampsia
575
When is the final disc shape of the placenta achieved?
Week 12
576
Describe how the degree to which membranes are share in monozygotic twins can vary
2 amnions and 2 chorion
2 amnions, but the same choirion
Amnions and chorion are both shared
577
Describe the 1st trimester placenta
Placenta is established
Placental 'barrier' is still relatively thick
Complete cytotrophoblast layer beneath syncytiotrophoblast
578
Describe the term placenta
Surface area for exchange dramatically increased. Placental 'barrier' is now thin. Cytotrophoblast layer beneath syncytiotrophoblast lost.
579
What occurs to the placenta during pregnancy?
Thinning of the 'placental barrier'
580
Describe the umbilical blood supply
2 umbilical arteries - deoxygenated blood from fetes to placenta
1 umbilical vein - oxygenated blood from placenta to to foetus
581
What is the function of the placenta?
Metabolic, endocrine, exchange of substances
582
Describe the placentas metabolic role
Placental synthesis of glycogen, cholesterol, and fatty acids
583
Describe the placentas endocrine role
Placental production of hormones
Steroid - progesterone, oestrogen
Protein - human chorionic gonadotrophin, hCG, human chorionic somatomammotrophin, human chorionic thyrotrophin, human chorionic corticotrophin
584
When is HCG produced?
During the first 2 months of pregnancy
585
What does hCG do?
Supports the secretory function of the corpus luteum.
586
What produces hCG?
The syncytiotrophoblast, therefore is pregnancy specific
587
What is the basis for urine pregnancy testing?
hCG, produced by the syncytiotrophoblast, therefore is pregnancy specific, and is excreted in maternal urine.
588
What might cause trophoblast disease?
```
Molar pregnancy (hydatidiform mole)
Choriocarcinoma
```
589
What is the function of the placental steroid hormones?
Progesterone and oestrogen. Responsible for maintaining the pregnant state.
590
When does placental production of steroid hormones take over form the corpus luteum?
By the 11th week
591
What effect does placental progesterone have on maternal metabolism?
Increases appetite
592
What effect does placental hCS/hPL have on maternal metabolism?
Increases glucose availability to foetus
593
How does transport take place in the placenta?
Simple diffusion - molecules moving down a conc gradient (waters electrolytes, urea and uric acid, gases)
Facilitated diffusion - applies to glucose transport
594
Describe gas exchange in the placenta
Simple diffusion. Flow-limited, not diffusion limited. Fatal O2 stores small, so maintenance of adequate flow essential. Adequate uteroplacental circulation required.
595
Describe active transport within the placenta
Specific 'transporters' expressed by the syncytiotrophoblast- iron, amino acids, vitamins
596
Describe passive immunity in the fetus
Feral immune system is immature, receptor-mediated process, maturing as pregnancy progresses. Immunoglobulin class-specific , IgG only. IgG concentrations in foetal plasma exceed those in maternal circulation
597
What things might go wrong with regards to transport across the placenta?
The placenta is not a true 'barrier'
Teratogens access the fetus via the placenta
Unintentional outcomes from physiological process
598
What is a teratogenic substance?
One which can disturbs the development of the fetus
599
What antibody transport dysfunction may occur across the placenta?
Haemolytic disease of the newborn. Rhesus blood group incompatibility of mother an fetus. Uncommon now due to prophylactic treatment.
600
List some infectious agents which might effect the placenta/fetus
```
Varicella zoster
Cytomegalovirus
Treponema pallidum
Toxoplasma gondii
Rubella
```
601
What is being looked for in antenatal screening?
History and examination. Risk factors e.g. For gestational diabetes. Blood test - blood group, haemoglobin, infection. Urinalysis - protein
602
Describe the physiological cardiovascular changes seen in pregnancy
Blood volume increases, CO, SV and HR all increase. BP is never normally increased, hypotension can occur in T1 and T2
603
What happens to CO during pregnancy?
Increases by approx 40% from T1
604
What happens to SV during pregnancy?
Increases by approx 35% from T1
605
What happens to HR during pregnancy?
Increases by approx 15% from T1
606
What happens to systemic vascular resistance during pregnancy?
Decreases by approx 25-30% from T1
607
What happens to BP during pregnancy?
Decreases in T1 and T2. Returns to normal in T3
608
Describe changes to BP during pregnancy
Systolic BP is never normally increased in pregnancy. Hypotension in T1 and T2 (progesterone effects on SVR). In T3 aortocaval compression by gravid uterus
609
Describe changes to endothelium in pregnancy
Controls vascular permeability. Contributes to the control of vascular tone. Vasodilation of pregnancy.
610
What is pre-eclampsia?
In a normal pregnancy, vasodilated, plasma-expanded. In pre-eclampsia pregnancy vasoconstricted, plasma contracted. Defect in placentation poor uteroplacental circulation. Wide spread endothelial dysfunction
611
Outline urinary system changes in pregnancy
Glomerular filtration rate increases. Renal plasma flow increases. Filtration capacity intact. Functional renal reserve decreases as GFR increases.
612
Describe what happens to urinary RPF in pregnancy
Increases by 60-80%
613
Describe what happens to urinary GFR in pregnancy
Increases by 55%
614
Describe what happens to urinary creatinine clearance in pregnancy
Increases by 40-50%
615
Describe what happens to urinary protein excretion in pregnancy
Increases by up to 300mg/24hrs
616
Describe what happens to urinary urea values in pregnancy
Decreases by 50% (approx 3.1mmol/l)
617
Describe what happens to urinary uric acid in pregnancy
Decreases by 33%, but rises with gestation
618
Describe what happens to urinary bicarbonate in pregnancy
Decreases by 18-22mmol/l
619
Describe what happens to urinary creatinine in pregnancy
Decreases by 25-75 umol/l
620
What are the possible consequences of the changes to the urinary system during pregnancy?
Urinary stasis - progesterone effect on urinary collecting system (hydroureter). Obstruction
UTI - pyelonephritis - pre term labour
621
What effect can progesterone have on the urinary collecting system?
Urinary stasis - progesterone effect on urinary collecting system (hydroureter). Obstruction
622
Outline the changes to the respiratory system during pregnancy
Anatomical. Diaphragm displaced. AP and transverse diameters of thorax increase. Physiological changes.
623
What are the consequences of the changes to the respiratory system during pregnancy?
Decreased functional capacity
Vital capacity unchanged, total lung capacity approx unchanged
Increased minute and alveolar ventilation
Increased tidal volume, RR unchanged
624
Describe the overall respiratory changes that occur in pregnancy
Physiological hyperventilation
- Increased respiratory drive effect of progesterone
- Increased metabolic CO2 production
- Resulting in respiratory alkalosis, compensated by increased renal bicarbonate excretion.
Physiological dyspnoea - due to progesterone, driven by hyperventilation
625
What happens to O2 consumption during pregnancy?
Increases by 20%
626
What happens to testing minute ventilation during pregnancy?
Increases by 15%
627
What happens to tidal volume during pregnancy?
Increases
628
What happens to respiratory rate during pregnancy?
Unchanged
629
What happens to functional residual capacity during pregnancy?
Decreases in T3
630
What happens to vital capacity in pregnancy?
Unchanged
631
What happens to FEV1 during pregnancy?
Unchanged
632
What happens to PaO2 during pregnancy?
Increases
633
What happens to PaCO2 during pregnancy?
Decreases
634
Describe what happens to carbohydrate metabolism during pregnancy
Placental transport of glucose - facilitated diffusion. Pregnacny increases maternal peripheral insulin resistance. Switches to gluconeogenesis and alternative fuels. Achieved by human placental lactogen. Also prolactin, oestrogen/progesterone, cortisol.
635
What happens to blood glucose during pregnancy?
Decrease in fasting blood glucose. Increase in post-prandial blood glucose.
636
What is in gestational diabetes?
Carbohydrate intolerance first recognised in pregnancy and not persisting after delivery. Risks associated with poor control - macrosomic fetus, stillbirth, increased rate of congenital defects. Oral glucose tolerance test required.
637
What are the risks associated with poorly controlled gestational diabetes?
Risks associated with poor control - macrosomic fetus, stillbirth, increased rate of congenital defects. Oral glucose tolerance test required.
638
What happens to lipid metabolism during pregnancy?
Increase in lipolysis from T2. Increase in plasma free fatty acids on fasting. Free fatty acids provide substrate for maternal metabolism leaving glucose for fetus.
639
What happens to the thyroid during pregnancy?
Thyroid binding globulin production increased. T3 and T4 increased. Free T4 in normal range. hCG direct effect on thyroid stimulating thyroid hormone production. TSH can be decreased in normal pregnancies.
640
What anatomically happens to the GI system during pregnancy?
Alterations in the disposition of the viscera, e.g. The appendix moves to the RUQ as uterus enlarges
641
What physiologically happens to the GI system during pregnancy?
Smooth muscle relaxation by progesterone. GI delayed emptying. Biliary tract stasis. Pancreas increased risk of pancreatitis.
642
Describe the changes in haematology which occur in pregnancy
Pregnancy is a pro thrombotic state. ++ fibrin deposition at the implantation site. Increased fibrinogen and clotting factors. Reduced fibrinolysis. Added to this, stasis, venodilation.
643
What are the consequences of the haematological changes which occur in pregnancy?
Thromboembolic disease in pregnancy, but warfarin crosses the placenta and is teratogenic (disturbs development of fetus)
644
Discuss anaemia in pregnancy
Plasma volume increases, red cell mass increases, but not by as much. Psyiological anaemia. However, anaemia due to Fe- and folate deficiency can occur. Also haemoglobinopathies
645
What happens to the immune system during pregnancy?
Fetus is an allograft. Non specific suppression of the local immune response at the maternal feral interface. Transfer of antibodies, haemolytic disease. Graves' disease and Hashimoto's thyroiditis.
646
What is bypassed in feral circulation?
Right ventricle and lungs
| Liver
647
What happens again the placenta?
Maternal feral exchange
648
What blood vessels ar associated with the placenta?
Umbilical arteries, umbilical veins, gets lost capillaries, (within chorionic villi), uterine arteries, uterine veins,
649
What blood vessel carries the oxygenated blood from the placenta to the fetus?
Umbilical vein
650
What blood vessel carries the deoxygenated blood from the placenta to the fetus?
Umbilical arteries
651
What happens to the diffusion barrier in the placenta as the pregnancy proceeds?
Decreases as pregnancy proceeds
652
Approx what value is feral pO2?
Low, approx 4kPa compared to normal adult value of 11-13 kPa
653
What factors increase fetal O2 content?
Fetal haemaglobin variant
Fetal haematocrit is increased over that in the adult
Double Bohr effect
Increase maternal production of 2,3 DPG (secondary to physiological respiratory alkalosis of pregnancy)
654
What causes maternal Increase maternal production of 2,3 DPG during pregnancy ?
Secondary to physiological respiratory alkalosis of pregnancy
655
Describe the composition of fetal haemoglobin
HbF
2 alphas subunits + 2 gamma subunits
Greater affinity for O2 as it doesn't bind 2,3 DPG as effectively as HbA
656
What is the benefit of fetal haemoglobin HbF?
Greater affinity for O2 as it doesn't bind 2,3 DPG as effectively as HbA
657
When does fetal haemoglobin HbF form ?
Predominant form from weeks 12-term is HbF
658
What is the double Bohr effect in the placenta?
Speeds up the process of O2 transfer. As CO2 passes into intervillous blood, pH decreases (Bohr effect), so decreasing maternal affinity for O2. At the same time, as CO2 is lost, pH rises (Bohr effect), so increasing affinity of fetal Hb for O2.
659
What causes maternal hyperventilation in pregnancy?
Progesterone driven. Maternal physiological adaptation to pregnancy.
660
What is the benefit of hyperventilation in pregnancy?
Lower pCO2 in maternal blood, aiding concentration gradient with fetus. As Hb gives up O2, it can accept increasing amounts of CO2. Fetus gives up CO2 as O2 is accepted. No alterations in local pCO2.
661
What is the double Haldane effect?
As Hb gives up O2, it can accept increasing amounts of CO2. Fetus gives up CO2 as O2 is accepted. No alterations in local pCO2.
662
What are the major fetal circulatory shunts?
Ductus venosus - bypasses liver
Ductus arteriosus - bypasses lungs
Foramen ovale - bypasses right ventricle and lungs
663
What does the ductus venosus do?
Connects umbilical vein carrying oxygenated blood to IVC. Blood enters right atrium. By ensuring shunting of blood around liver, saturation is mostly maintained (drops from 70% to 65%)
664
Describe the function of the free border of the septum secundum in the foramen ovale
Forms a crest (cresta dividens). This creates streams of blood flow, the majority of which flows into left atrium (minor proportion flows to right ventricle, mixing with deoxygenated blood from SVC)
665
Why is the foramen ovale open in the fetus?
Right atrial pressure is greater than left atrial pressure. Forces leaves of FO apart, so blood flows into left atrium.
666
What are the features of the fetal left atrium?
Small amount of pulmonary venous return (deoxygenated). Blood reaching left atrium has saturation of approx 60%. Pumped by LV to aorta. Heart and brain get lions share of O2.
667
What does the ductus arteriosus do?
Shunts blood from RV and PT to aorta. Joins aorta distal to supply to head and heart. Minimises drop in O2 saturation.
668
Describe the fetal adaptations to manage transient decreases in oxygen
HbF and increased Hb conc
Redistribution of flow to protect supply to heart and brain (reducing supply to GIT, kidneys, limbs)
Fetal heart rate slows in response to hypoxia to reduce O2 demand
Fetal chemoreceptors detecting decreased pO2 or increased pCO2 (vagal stimulation leading to bradycardia, opposite of adult where vagal stimulation leads to tachycardia)
669
What can chronic hypoxia cause in a fetus?
```
Growth restriction
Behavioural changes (impact on development)
```
670
What are the hormones necessary for fetal growth?
Insulin
IGF1 and 2
IGF1 nutrient independent, dominant in 1st trimester
IGF2 nutrient dependent, dominates in T2 and T3
Leptin
EGF, TGFalpha
671
When do the different IGFs appear in pregnancy?
IGF1 nutrient independent, dominant in 1st trimester
| IGF2 nutrient dependent, dominates in T2 and T3
672
What effects can malnutrition have on fetal growth?
Malnutrition can cause symmetrical or asymmetrical growth restriction. Nutrition and hormonal status during fetal life can influence health later in life, mechanisms not well understood
673
What are the dominant cellular growth mechanisms in fetal growth, when?
Hyperplasia 0-20wks
Hyperplasia and hypertrophy 20-28wks
Hypertrophy 28wks-term
674
Approx what volume of amniotic fluid is there at 8wks?
Approx 10ml
675
Approx what volume of amniotic fluid is there at 38wks?
1 litre
676
What does amniotic fluid do?
Protects fetus and contributes to development of lungs and GI tract
677
What primarily produces amniotic fluid?
Fetal urinary tract. Urine production by 9wks. Up to 800ml/day in T3. Effects lungs, GI tract, and also placenta and fetal membranes (intramembranous pathway)
678
What is amniotic fluid constituted of?
98% water
| Also electrolytes, creatinine, urea, bile pigments, renin, glucose, hormones, fetal cells, lanugo, and vernix caseosa
679
What is meconium?
First opening of bowls. Contains debris from amniotic fluid (that which is not reabsorbed) plus intestinal secretions, including bile (GREEN)
680
What is amniocentesis?
Sampling of amniotic fluid. Allows for collection of fetal cells, useful diagnostic test e.g. Fetal karyotyping. BUT is invasive, so poses risk.
681
How is fetal bilirubin metabolism managed?
During gestation, clearance of fetal bilirubin is handled efficiently by the placenta. Fetus can't conjugate bilirubin. Immaturity of liver and intestinal processes for metabolism, conjugation and excretion. Physiological jaundice common.
682
Why are germ cells separated from the somatic cell line so early in development?
Germ cells need to remain undifferentiated and protected from influences arising during development of the rest of the body.
683
What tissue forms the matrix of the gonads into which the primordial germ cells migrate?
Somatic mesenchymal tissue
684
Which gene on the short arm of the Y chromosome determines the formation of the testis?
SRY
685
What is true/primary hermaphroditism?
Both ovarian and testicular tissue present at birth
686
Where does mullerian inhibitory substance come from?
Secreted by Sertoli cells
687
What structures do the Müllerian ducts develop into?
Uterine tubes, uterus, cervix, upper vagina
688
What structures do the Wolffian ducts develop into?
Epididymis, vas deferens, seminal vesicles
689
What does the urogenital sinus form in the male?
Prostate
690
What does the urogenital sinus form in the female?
Lower part of the vagina
691
What is parturition?
The scientific term used to describe the transition from the pregnant state to the non-pregnant state at the end of gestation (I.e. Birth). Expulsion of the products of conception after 24 weeks.
692
What is labour?
The non-scientific term used to describe parturition when both the cervix and uterus have been remodelled. Often used instead of 'parturition' because lay people also use it, however labour is only a part of parturition.
693
When should parturition occur?
Expulsion of the products of conception after 24 weeks.
694
When might 'labour' be classed as 'spontaneous abortion'
Before 24 weeks
695
When might delivery be considered pre-term?
Before 36 completed weeks
696
When is delivery considered to be 'term'
Between 37 and 42 weeks
697
When is delivery considered post-term?
More than 42 weeks
698
Outline the stages of labour
1st stage - creation of the birth canal
2nd stage - expulsion of fetus
3rd stage - expulsion of placenta. Contraction of uterus.
699
By when is the uterus palpable?
Approx 12 weeks
700
When does the uterus reach the umbilicus in the pregnant woman?
Approx 20wks
701
When does the uterus reach the xiphisternum in the pregnant woman?
Approx 36wks
702
What is the 'lie' of a fetus, as assessed towards the end of pregnancy?
The relationship to long axis of uterus. Normally longitudinal. Fetus normally flexed.
703
What is the 'presentation' of a fetus, as assessed towards the end of pregnancy?
Which part of fetus is adjacent to pelvic inlet. Normally the head (cephalic), but sometimes buttocks (podalic).
704
What is the 'vertex' of a fetus, as assessed towards the end of pregnancy?
The relationship of the fetus along axis (orientation of presenting part). Most commonly longitudinal lie, cephalic presentation. Vertex to pelvic inlet at minimum diameter.
705
What determines the maximum size of the birth canal?
The pelvis
706
What is required to create the birth canal?
Structural changes and a lot of force.
707
How does cervical ripening occur?
Cervix collagen in proteoglycan matrix. Ripening involves reduction in collagen, increase in glycosaminoglycans. Increases in hyaluronic acid. Reduced aggregation of collagen fibres. Triggered by prostaglandins PGE2 and PGF2a.
Enzymatic degradation, hormonal influences.
708
How is myometrium triggered to contract?
Spontaneously by 'pacemaker' cells. Force when intracellular Ca2+ conc rises due to action potentials.
709
Describe uterine contractions in early pregnancy
Low amplitude, approx every 30 min
710
Describe uterine contractions in mid pregnancy
Less frequent than 'real' contractions. Higher amplitude. 'Braxon-Hicks' contractions.
711
Describe uterine contractions in early labour
Variable but higher amplitude
712
Describe uterine contractions in late pregnancy
More frequent and higher amplitude
713
What effect does prostaglandins have on contractions in parturition?
More Ca2+ per action potential
714
What effect does oxytocin have on contractions in parturition?
More action potentials (lower threshold)
715
What are prostaglandins?
Biologically active lipids. 'Local hormones'. Produced mainly in myometrium and decidua. Production controlled by oestrogen progesterone ratio.
716
What conc of prostaglandins are there if there is low (progesterone > oestrogen) ratio?
Low prostaglandins
717
What conc of prostaglandins are there if there is high (progesterone < oestrogen) ratio?
Increased prostaglandins
718
What is the result of a relative fall in progesterone in a pregnant lady?
Increases prostaglandins, ripens cervix, promotes uterine contractions
719
Where is oxytocin secreted from?
Posterior pituitary. Controlled by hypothalamus. Increased by afferent impulses from cervix and vagina - 'ferguson reflex'. Acts on smooth muscle receptors. More receptors if oestrogen : progesterone ratio is high
720
What controls oxytocin release?
Controlled by hypothalamus. Increased by afferent impulses from cervix and vagina - 'ferguson reflex'.
721
Where does oxytocin act?
Acts on smooth muscle receptors of uterine smooth muscle. More receptors if oestrogen : progesterone ratio is high
722
What is the onset of labour?
More prostaglandins, cervix ripens. Uterus contractions more forceful.
723
Describe the onset of labour, brachystasis
Uterus relaxes less than it contracts. Fibres shorten in body of uterus, drives presenting part to cervix. A 'ratcheting' system is created.
724
Describe the changes in the cervix at the end stages of pregnancy
Cervix thins and flattens, 'effacement'. Ferguson reflex stimulates oxytocin release (contractions more forceful and more frequent). Cervix begins to dilate. Rupture of the amnion 'breaking of the waters'
725
What has occurred by the end of stage 1 of labour?
Cervix dilated to 10cm, may take several hours.
726
Describe the initiation of labour
Prostaglandins promote labour, but mechanisms unclear. Evidence surfactant protein A by fetal lungs causes prostaglandins production in the myometrium
727
How long does the second stage of labour generally last?
Up to 1hr
728
What occurs in the second stage of labour?
Urge to 'bear down' and 'push' initiated. Presenting part appears in the birth canal.
729
If presenting part in the birth canal is the top of the head, what is the correct term?
'Crowning'
730
If presenting part in the birth canal is the buttocks, shoulder, or knee what is the correct term?
'Breech position'
731
If presenting part in the birth canal is the foot, what is the correct term?
'Footling breach'
732
Describe the motion of the head during birth
Initially head flexes and rotates internally. Stretches vagina and perineum (risk of tearing). Once head is delivered, head rotates and extends
733
When is the second stage of labour complete?
Shoulders rotate and deliver. Followed rapidly by rest of the neonate.
734
What occurs in the third stage of labour?
Effect of uterine contractions dramatically increased by expulsion of fetus. Uterus contracts down hard. Shears off placenta and expels it. Normally occurs within 10 mins.
735
Why is underline contractions post birth important?
Compresses blood vessels to reduce haemorrhage. Enhanced by giving oxytocic drug (also manual fundal massage if needed)
736
What occurs during stage 0 of labour?
Braxon-Hicks contractions
Oestrogen : progesterone ratio changes, produces increased prostaglandins. Fetus moves and causes local uterine stretch. Myometrium contracts slightly.
737
What happens during stage 1 of labour?
Ferguson reflex initiated
Produces increased local prostaglandins. Myometrium
contracts slightly more. Fetal head positions over internal os of cervix, and causes local stretch. Ferguson reflex gains pace. Oestrogen : progesterone changes continue. Produces local increase in collagenases, cervical ripening. More prostaglandins. Myometrium contracts slightly more. Fetal head pushes on cervix and causes dilation and effacement.
738
Describe what happens during stage 2 of labour
'True' contractions start. Myometrium contracts harder. More forceful and frequent. Fetal membranes rupture. Mother has urge to 'bear down' and 'push'. Fetal head enters birth canal and rotates, shoulders then rotate. Fetus is delivered
739
Describe what occurs in stage 3 of labour
Oestrogen : progesterone changes continue
Ferguson reflex produces even more oxytocin. Myometrium contracts really hard, reducing blood to uterus. Neonate has umbilical cord clamped. Placenta and fetal membranes delivered. Spiral arteries in the myometrium are clamped shut. Prevents post-natal haemorrhage.
740
What stimulates neonate to take 1st breath?
Many things, trauma, cold, light, noise.
741
What does clamping the umbilical cord cause?
Closure of the ductus venosus
742
What does taking the first breath cause?
Reduced pulmonary vascular resistance, increase arterial pO2. Blood flows into lungs and becomes oxygenated. Net drop in pressure on the right side of the heart, higher pressure in left atrium closes foramen ovale.
Pressure imbalance results in a temporary reversal of flow through the ductus arteriosus and its muscle wall contracts in response to increased pO2, closing it.
743
What closes the ductus arteriosus?
Pressure imbalance as a result of first breath results in a temporary reversal of flow through the ductus arteriosus and its muscle wall contracts in response to increased pO2, closing it.
744
What are the main points in the establishment of independent life?
Placenta cut or clamped, ductus venosus closes
Left atrial pressure exceeds right, foramen ovale closes
Ductus arteriosus contracts in response to raised pO2 (normally closes)
Fetal circulation converts to adult circulation
745
What are the 3Ps for parturition?
Power, passage, passenger
746
What effect does progesterone have upon contraction in parturition?
Inhibits contraction
747
What effect does oxytocin have on muscles of parturition?
Increases excitability
748
What hormones does the fetus produce during labour?
Glucocorticoids - to placenta, inhibit progesterone
| Also produce oxytocin
749
What effects do prostaglandins have during parturition?
Powerful contractors of smooth muscle and are also involved in cervical softening
Increased oestrogen : progesterone ratio and mechanical damage stimulates prostaglandin synthesis
Placenta, decidua, myometrium and membranes can all synthesise prostaglandins
Increased synthesis of prostaglandins by amnion in 3rd trimester.
Levels of prostaglandins is amniotic fluid rise very early in labour
750
What causes cervical ripening?
Cervical ripening is due to oestrogen, relaxin and prostaglandins breaking down connective tissue
751
What effects does oxytocin have during parturition?
Initiates uterine contractions
Action inhibited in pregnancy by progesterone, relaxin and low number of oxytocin receptors
Pregnancy increases the number of gap junctions to aid communication between muscle cells (coordinates effective uterine activity)
Approx 36 wks, increase in number of oxytocin receptors in myometrium, therefore uterus can respond to pulsatile release of oxytocin from posterior pituitary gland.
752
Describe the special properties of myometrial muscle
Myometrial muscle does not return to its original size. Permanent partial shortening of the muscle fibres. Contraction and retention.
753
Describe the changes in the cervix as pregnancy progresses
Increasing levels of relaxin during pregnancy causes changes in cervix, collagen : ground substance ratio. Enzymes degrade collagen. Occurs over a period of weeks, evident from weeks 36-40. In labour cervix offers less resistance to presenting part. Known as effacement and dilatation.
754
Describe the changes to the pelvic floor, vagina and perineum in the latter stages of pregnancy
Stretching of the fibres of the levator ani and the thinning of the central portion of the perineum transforms to almost transparent mucous structure
755
Describe the 1st stage of labour
Interval between the onset of labour and full cervical dilation.
Latent phase - onset of labour with slow cervical dilation to approx 4 cm and variable duration
Active phase - faster rate of cervical change, 1-1.2 cm/hr. regular uterine contractions
756
What occurs to the placenta once the baby has been born?
Marked reduction on size of uterus due to powerful contraction and retraction. Size of placental site therefore reduced (up to half before separation begins). Inelastic placenta is squeezed by contraction.
757
Describe what happens to the placental bloodflow once the fetus has been delivered
Blood in intervillous space forced back into veins of spongy layer of decidua basilis. Veins become tense and congested, and kept under pressure by underlying muscle layer of uterus. Blood can't drain back into maternal bloodstream as uterus has retracted and doesn't allow it.
758
Describe the main factors controlling bleeding post partum
Powerful contraction/retraction of uterus, espicially action of interlacing muscle fibres ('living ligature') which constrict blood vessels running through the myometrium.
Pressure exerted on placental site by walls of contracted uterus (apposition - once placenta and membranes delivered)
Blood clotting mechanism (sinuses and torn vessels)
759
What are mammary glands?
Glands embedded in breast tissue. 15-24 lobulated masses of tissue, with fibrous and adipose tissue in between.
760
Describe how breasts appear
At birth, only a few ducts present. At puberty, ducts sprout and branch (in males this is prevented by androgen excess and testosterone). Alveoli being development.
761
What is mammogenesis?
Preparation of breasts
762
What is lactogenesis?
Synthesis and secretion from the breast alveoli
763
What is galactokinesis?
Ejection of milk
764
What is galactopoiesis?
Maintenance of lactation
765
Describe the changes in breasts during pregnancy (mammogenesis)
Substantial further development. Hypertrophy of the ductular-lobular-alveolar system. Prominent lobules form. Alveolar cells differentiate. Capable of milk production from mid gestation (2nd trimester).
Towards end of pregnancy, nipple becomes erect. Areola enlarges. Montgomery tubercles form. Breast becomes more sensitive.
During pregnancy, little milk is secreted, favours growth not secretion. High progesterone/oestrogen ratio
766
Outline how lactogenesis occurs
In alveolar cells. Fat in smooth ER. Protein secreted via Golgi apparatus. Sugars synthesised and secreted. Neutrophils and macrophages can also enter alveolar space (lumen), and so protect against bacterial infections.
767
What is the product of lactogenesis called soon after birth?
Colostrum
768
What is colostrum constituted of?
Less water, fat and sugar than milk produced later. More protein, particularly immunoglobulins (IgA, IgM, IgG) that coat intestinal mucosa, preventing bacteria from entering intestinal cells. WBC that kill microorganisms
769
What is in 'intermediate milk' (approx 2 weeks after birth)
90% water, 7% sugar, 3% fat, proteins (lactalbumin, lactoglobulin, lactoferrin). Minerals and vitamins, endocannabinoids
770
How is milk secretion controlled?
High progesterone and oestrogen in pregnancy stimulates breast tissue growth. Secretions allowed by fall in steroids. Promoted by prolactin.
771
Outline the role of prolactin?
Secreted during and after feed to produce next feed (sensory impulse from nipples stimulated). More prolactin secreted at night, suppresses ovulation.
Polypeptide hormone, secreted by anterior pituitary gland. Controlled by dopamine from hypothalamus (inhibits). Factors promoting secretion of prolactin reduce dopamine secretion.
772
Where is prolactin produced?
Polypeptide hormone, secreted by anterior pituitary gland. Controlled by dopamine from hypothalamus (inhibits). Factors promoting secretion of prolactin reduce dopamine secretion.
773
How is secretion of prolactin stimulated?
Promoted by suckling, potent neuro-endocrine reflex. Suckling at one feed promotes prolactin release, which causes production of the next feed, which accumulates in alveoli and ducts
774
When does milk production cease?
Ceases gradually if no suckling, tugor induced damage to secretory cells. Free feeding every 1-3hrs recommended. Ensure sufficient suckling at each feed.
775
Describe galactokinesis (milk let down)
Milk is not sucked out, it is ejected out by a let down reflex. Myoepithelial cells curling alveoli. Contracted by oxytocin to squeeze milk out of the breast. Oxytocin released from posterior pituitary.
776
Outline how glactopoeisis occurs
Oxytocin release a neuro-endocrine reflex, from suckling/expressing systems (anticipation of feeding)
777
List some mechanisms that cause lactation to cease
Lost feedback - not enough suckling
Pain - increased turf or from non suckling infant or infection (mastitis)
Menstruation - changes in breast texture, breasts feel particularly 'lumpy'
Suppression of prolactin - ergot preparation, diuretics, or retained placenta
Age - a gradual shrinking of the mammary glands (involution), typically begins around the age of 35
778
List some reasons why breast feeding is good
```
Babies have fewer infections
Bonding (through release of oxytocin)
Reduced risk of breast and ovarian cancer later in life
Further contraction of uterus
Aids loss of weight induced by pregnancy
```
779
What essentially is normal breast tissue?
Modified sweat glands. Non functional except during lactation
780
What constitutes the prepubertal breast?
Few lobules (before puberty male and female breasts are identical)
781
What constitutes the pubertal/menarche breast?
Increase in number of lobules, increased volume of interlobular stroma
782
What occurs in the breast during the menstrual cycle?
Follicular phase lobules quiescent, after ovulation cell proliferation and stromal oedema, with menstruation see decrease in size of lobules
783
What occurs in the breast during pregnancy?
Increase in size and number of lobules, decrease in stroma, secretory changes
784
What occurs in the breast at cessation of lactation?
Atrophy of lobules, but not to former levels.
785
What occurs in the breast with increasing age?
Terminal duct lobular units (TDLUs) decrease in number and size, interlobular stroma replaced by adipose tissue (mammograms easier to interpret)
786
How might breast conditions present clinically?
Pain, palpable mass, nipple discharge, skin changes, lumpiness, mammographic abnormalities
787
What might cyclical and diffuse pain suggest, as a presenting composing of breast conditions?
Often physiological
788
List some possible causes of a palpable mass in the breast
Invasive carcinoma, fibroadenoma, cysts...
| Most worrying if hard, craggy and fixed
789
What could a milky discharge from the breast indicate?
Endocrine disorders e.g. Pituitary adenoma. Side effect of medication
790
What might a bloody or serous discharge from the breast indicate?
Benign lesions e.g. Papilloma, duct ectasia, occasionally malignant lesions
791
Who is legible for mammographic screening?
Older woman, 47-73yrs, invited every 3yrs. Worrying findings include densities and calcifications.
792
What might mammographic densities be?
Invasive carcinomas, fibroadenoma cysts
793
What might mammographic calcifications be?
Ductal carcinoma in situ DCIS, benign changes
794
When do fibroadenomas generally present?
Can occur at any age during reproductive period. Most present over 30yrs. Most common benign tumour.
795
When do phyllodes tumours generally present?
Most present in 6th decade
796
When does breast cancer generally present?
Rare before 25yrs. Incidence increases with age.
797
List some possible disorders of breast development
Milk line remnants, polythelia, accessory axillary breast tissue
798
When might acute mastitis occur? What is it?
Almost always occurs during lactation. Usually staphylococcus aureus infection from nipple cracks and fissures. Erythematous painful breast, often pyrexia. May produce breast abscesses. Usually treated by expressing milk and antibiotics.
799
How might fat necrosis of the breast present?
Presents as a mass, skin changes of mammographic abnormality. Often history of trauma or surgery. Can mimic carcinoma clinically and mammographically
800
Describe fibrocystic change, benign epithelial lesion of the breast
Commonest breast lesion. May present as a mass or mammographic abnormality. Mass often disappears after fine needle aspiration FNA. Histology - cyst formation, fibrosis and apocrine metaplasia. Can mimic carcinoma clinically and mammographically
801
List some stroma tumours of the breast
Fibroadenoma, phyllodes tumour, lipoma, leiomyoma, hamartoma
802
How might fibroadenoma present?
Present with a mass (usually mobile), or mammographic abnormality (breast mouse - mobile and elusive). Macroscopically - well circumscribed, rubbery, greyish/white. Histology - composed of mixture of stroma and epithelial elements. Localised hyperplasia rather than a true neoplasm
803
What is a 'breast mouse'?
Fibroadenoma
804
How might phyllodes tumour present?
Present as masses of mammographic abnormalities. Rare before 40yrs. Benign, borderline and malignant types (most are benign).
Histology - nodules of proliferating stroma covered by epithelium (phullon = leaf). Stroma more cellular and atypical than that in fibroadenomas
Need to be excised with wide margin or will reappear. Malignant type aggressive
805
What is gynaecomastia?
Enlargement of male breast
806
What causes gynaecomastia?
Caused by a relative decrease in androgen effect of increase in oestrogen effect.
807
Why might gynaecomastia occur in neonates?
Secondary to circulating maternal and placental oestrogens and progesterones
808
Why might transient gynaecomastia occur in boys in puberty?
Oestrogen production peaks earlier than that of testosterone
809
Why might gynaecomastia occur in liver cirrhosis?
Oestrogen is not metabolised effectively, oestrogen excess
810
Why might gynaecomastia occur due to gonadotrophin excess?
Functioning testicular tumour e.g. Leydig and Sertoli cell tumours, testicular germ cell tumours
811
List some drugs that may cause gynaecomastia
Spironolactone, heroine, anabolic steroids, marijuana, alcohol....
812
When is there an increased risk of breast cancer in males?
Male to female transsexuals, klinefelters syndrome, males treated with oestrogen for prostate cancer
813
What are the majority of breast cancers?
Adenocarcinomas 95%
814
Where do most breast cancer occur?
In the upper outer quadrant
815
What genes are linked to an increased risk of breast cancer?
BRCA 1, BRCA 2, p53
816
How are breast cancers classified, broadly speaking?
In situ, invasive. Ductal of lobular
817
What is an in situ breast carcinoma ?
Neoplasm population of cells limited to ducts and lobules by basement membrane BM, myoepithelial cells are preserved. Does not invade into vessels and therefore cannot metastasise
818
Describe a breast ductal carcinoma in situ DCIS
Most often presents as mammographic calcifications (clutters or linear and branching), but can present as a mass. Can spread through ducts and lobules and be very extensive. Histiologically often shows central (comedo) necrosis with calcification. Non obligate precursor of invasive carcinoma
819
What is Paget's disease?
Cells can extend to nipple skin, without crossing BM. Unilateral red and crusting nipple. Eczematous or inflammatory conditions of the nipple should be regarded as suspicious and biopsy performed to exclude Paget's disease.
820
Describe a breast invasive carcinoma
Invaded beyond BM into stroma. Can invade into vessels and can therefore metastasise to lymph nodes and other sites. Usually presents as a mass, or a mammographic abnormality. By the time a cancer is palpable, more than half of the patients will have axillary lymph node metastasises.
821
What is a peau d'orange ?
When lymphatic drainage of skin is involved with breast carcinoma
822
What are the common types of invasive carcinoma in the breast?
Invasive ductal carcinoma - (no special type, IDC NST). 70-80%. Well differentiated type, tubules lined by atypical cells. Poorly differentiated type, sheets of pleomorphic cells
Invasive lobular carcinoma - infiltrating cells in a single file, cells lack cohesion. 5-15%. Similar prognosis to IDC NST
Other - e.g. Tubular, mucinous
823
What is the pattern of breast cancer?
Lymph nodes via lymphatics - usually in the ipsilateral axilla. Distant metastasises via blood vessels - bones, lungs, liver, brain.
824
What are the factors determining the prognosis of breast cancer?
In situ disease or invasive carcinoma. Histologic subtype (IDC NST has poorer prognosis). Tumour grade. Gene expression profile. Tumour stage.
825
Outline the 'triple approach' to investigation and diagnosis of breast cancer
Clinical - history, family history, examination
Radiographic imaging - mammogram, USS
Pathology - fine needle aspiration cytology FNAC and core biopsy
826
What might the decision between mastectomy or breast conserving surgery depend on?
Patient choice, size and site of tumour, number of tumours, size of breast
827
What is a sentinel lymph node biopsy, with regards to breast cancer
Reduces risk of postoperative morbidity. Intraoperative lymphatic mapping with dye and/or radioactivity of the draining or 'sentinel' lymph nodes - the one most likely to contain cancer metastases. If the sentinel node/s is negative, axillary dissection can be avoided.
828
What does hormonal treatment of breast cancer depend upon?
Oestrogen receptor status (approx 80% of cancers are ER +ve). Tamoxifen
829
What does treatment wait Herceptin depend on for breast cancer?
Her2 receptor status (approx 20% of cancer are are Her2 +ve).
830
Where might gynaecological tumours arise?
In the vulva, cervix, endometrium, myometrium, ovary
831
What are almost all cervical cancer cases related to?
High risk HPVs (16 and 18)
832
How do high risk HPVs cause cancer?
Infect immature metaplastic squamous cells in transformation zone. Produce viral proteins E6 and E7, which interfere with activity of tumour suppressor proteins (e.g. P53, RB), to cause inability to repair damaged DNA and increased proliferation of cells.
833
Why is cervical screening so successful?
Worldwide, 3rd most common cancer in women. Cervix is relatively accessible to examination (coloposcopy) and sampling. Papanicolau (pap) test detects precursor lesions and low stage cancers. Allows early diagnosis and therapy.
834
What does cervical screening involve?
Cells from the transformation zone are scraped off, stained with papanicolaou stain and examined microscopically. Can also test for HPV DNA in cervical cells, molecular method of screening. If abnormal referred for colposcopy and biopsy
835
When does cervical screening take place?
Starts age 25, then every 3yrs till 50. Thereafter every 5yrs till 65yrs.
836
How long does gardasil, the HPV vaccine given to girls, protect for?
Up to 10 yrs, the 'critical time'
837
What is cervical intraepithelial neoplasia CIN?
Dysphasia of squamous cells within the cervical epithelium, induced by infection with high risk HPVs. CIN 1, CIN 2, and CIN 3 (carcinoma in situ)
838
What is the treatment for CIN 1?
Follow up cryotherapy
839
What is the treatment for CIN 2 and 3?
Superficial excision (cone, large loop excision of the transformation zone LLETZ)
840
What sort of cancer is invasive cervical carcinoma usually?
80% squamous cell carcinoma
| 15% adenocarcinoma
841
How may invasive cervical carcinoma look?
Exophytic (stick out) or infiltrative (infiltrate into body)
842
How might invasive cervical carcinoma present?
Screening abnormality, postcoital, intermenstrual, of post menopausal bleeding.
843
What would the treatment for microinvasive cervical carcinoma be?
Treated with cervical cone excision. 5yr survival 100%
844
What is the treatment for invasive cervical carcinoma ?
Treated with hysterectomy, lymph node dissection, and, if advanced, radiation and chemotherapy. Overall 62% 10yr survival
845
What is the endometrium?
Liners internal cavity of uterus, glands within a cervical stroma
846
What is endometrial hyperplasia often a precursor to?
Endometrial carcinoma, increased gland to stroma ratio
847
What is endometrial hyperplasia associated with?
Prolonged oestrogenic stimulation (anovulation, increased oestrogen from endogenous sources e.g. Adipose tissue)
848
What is the usual presentation of endometrial carcinoma?
Irregular or postmenopausal vaginal bleeding, early detection and cure often possible.
Can be polyploid or infiltrative.
849
Where might gynaecological tumours arise?
In the vulva, cervix, endometrium, myometrium, ovary
850
What are almost all cervical cancer cases related to?
High risk HPVs (16 and 18)
851
How do high risk HPVs cause cancer?
Infect immature metaplastic squamous cells in transformation zone. Produce viral proteins E6 and E7, which interfere with activity of tumour suppressor proteins (e.g. P53, RB), to cause inability to repair damaged DNA and increased proliferation of cells.
852
Why is cervical screening so successful?
Worldwide, 3rd most common cancer in women. Cervix is relatively accessible to examination (coloposcopy) and sampling. Papanicolau (pap) test detects precursor lesions and low stage cancers. Allows early diagnosis and therapy.
853
What does cervical screening involve?
Cells from the transformation zone are scraped off, stained with papanicolaou stain and examined microscopically. Can also test for HPV DNA in cervical cells, molecular method of screening. If abnormal referred for colposcopy and biopsy
854
When does cervical screening take place?
Starts age 25, then every 3yrs till 50. Thereafter every 5yrs till 65yrs.
855
How long does gardasil, the HPV vaccine given to girls, protect for?
Up to 10 yrs, the 'critical time'
856
What is cervical intraepithelial neoplasia CIN?
Dysphasia of squamous cells within the cervical epithelium, induced by infection with high risk HPVs. CIN 1, CIN 2, and CIN 3 (carcinoma in situ)
857
What is the treatment for CIN 1?
Follow up cryotherapy
858
What is the treatment for CIN 2 and 3?
Superficial excision (cone, large loop excision of the transformation zone LLETZ)
859
What sort of cancer is invasive cervical carcinoma usually?
80% squamous cell carcinoma
| 15% adenocarcinoma
860
How may invasive cervical carcinoma look?
Exophytic (stick out) or infiltrative (infiltrate into body)
861
How might invasive cervical carcinoma present?
Screening abnormality, postcoital, intermenstrual, of post menopausal bleeding.
862
What would the treatment for microinvasive cervical carcinoma be?
Treated with cervical cone excision. 5yr survival 100%
863
What is the treatment for invasive cervical carcinoma ?
Treated with hysterectomy, lymph node dissection, and, if advanced, radiation and chemotherapy. Overall 62% 10yr survival
864
What is the endometrium?
Liners internal cavity of uterus, glands within a cervical stroma
865
What is endometrial hyperplasia often a precursor to?
Endometrial carcinoma, increased gland to stroma ratio
866
What is endometrial hyperplasia associated with?
Prolonged oestrogenic stimulation (anovulation, increased oestrogen from endogenous sources e.g. Adipose tissue)
867
What is the usual presentation of endometrial carcinoma?
Irregular or postmenopausal vaginal bleeding, early detection and cure often possible.
Can be polyploid or infiltrative.
868
What are the types of adenocarcinoma?
Endometrioid and serous
869
Describe endometrioid endometrial carcinoma
More common, mimics proliferative glands. Typically arises in setting of endometrial hyperplasia. Associated with unopposed oestrogen and obesity. Spreads by myometrial invasion and direct extension to adjacent structures to local lymph nodes and distant sites.
870
Describe serous endometrial carcinoma
Poorly differentiated, aggressive, worse prognosis. Exfoliates, travels through Fallopian tubes, implants on peritoneal surfaces.
871
What is the most common tumour of the myometrium?
Leiomyoma (fibroid)
| Benign tumour of uterine smooth muscle
872
Describe leiomyomas
Benign tumour of uterine smooth muscle. Often multiple. Range from tiny to massive (filling the pelvis). May be asymptomatic, or can cause heavy/painful periods, urinary frequency, infertility. Malignant transformation very rare. Well circumscribed, round, firm, and whitish in colour. Bundles of smooth muscle, rambles normal myometrium.
873
Describe a malignant tumour of the myometrium
Leiomyosarcoma
| Uncommon, peak incidence 40-60yrs. Highly malignant. Arises de novo, not from leiomyomas. Metastasises to lungs.
874
Outline ovarian tumours
Approx 80% are benign. Generally occur 20-40yrs. Malignant tumours generally occur at 45-60yrs. Have often spread beyond the ovary by the time of presentation and therefore the prognosis is often poor. Many are bilateral.
Most are non-functional, so produce symptoms when they become large, invade adjacent structures and metastasize. Mass effects - abdominal pain, abdominal distension, urinary and GI symptoms, ascites.
875
Describe the features of malignant ovarian tumours
Approx 50% spread to other ovary. Spread to regional nodes and elsewhere e.g. Liver, lungs
CA-125 used in diagnosis and to monitor disease recurrence and progression
Some association with BRCA mutations - carriers can be treated with prophylactic salpingo-oophrectomy
876
What is the cancer marker used in ovarian cancer?
CA-125
877
Outline the classification of ovarian tumours
Dependent upon the tissue from which they have arisen
- Müllerian epithelium (including endometriosis)
- Germ cells (pluripotent)
- Sex cord-stroma cells (from the endocrine apparatus of the ovary)
- Metastases (from other primary sites)
All others won't produce sex hormones
878
What are the 3 main histological types of ovarian epithelial tumours
Serous
Mucinous
Endometrioid
All can then be classified as benign/malignant/borderline. Many are cystic.
879
What are the risk factors for ovarian epithelial tumours?
Nulliparity or low parity, OCP protective (no ovulation, therefore no breaking of epithelium and subsequent healing), heritable mutations e.g. BRCA 1 - and BRCA2, smoking, endometriosis
880
Why are serous ovarian tumours often associated with ascites?
Often spread to peritoneal surfaces and omentum
881
Describe mucinous ovarian tumours
Often large, cystic, masses. Filled with sticky, thick fluid. Usually benign or borderline.
Pseudomyxoma peritonei - extensive mucinous ascites, epithelial implants on peritoneal surfaces, frequent involvement of ovaries, can cause intestinal obstruction. Most likely primary is extra-ovarian, usually appendix.
882
Describe endometrioid ovarian tumours
Contain tubular glands resembling endometrial glands. Can arise in endometriosis. Some have associated endometrial endometrioid adenocarcinoma, probably arising separately.
883
Describe germ call tumours
20% of all ovarian neoplasms. Most are teratomas, usually benign. Other types are malignant and include non-gestational choiriocarcinoma (which produces HCG, unlike gestational type)
884
What are the 3 groups of ovarian teratomas?
Mature (benign) - most common
Immature (malignant) - rare, composed of tissues that resemble immature foetal tissue
Monodermal (highly specialised) - only 1 type of tissue present
885
Describe the clinical features of a mature ovarian teratoma
Most are cystic. Also called dermoid cysts as they almost always contain skin-like structures. Usually occur in young women. Bilateral in 10-15% of cases. Usually contain hair and sebaceous material, can contain tooth structures. Often tissue from other germ layers also present e.g. Bone, cartilage, thyroid.
886
Describe monodermal ovarian teratomas
Most common in struma ovarii. Benign, composed entirely of mature thyroid tissue. May be functional and cause hyperthyroidism.
887
Describe ovarian secondary chord stromal tumours
Derived from ovarian stroma (which is derived from sex cords of the embryonic gonad). Sex cord produces Sertoli and leydig cells in testes, and theca and granulosa cells in ovaries. Tumours resembling all of these 4 cell types can be found in the ovary. Can be feminising or masculinising.
888
Describe the clinical features of granulosa cell tumours
Occur mostly in post-menopausal women. May produce large amounts of oestrogen in pre-pubertal girls may produce precocious puberty. In adult women may be associated with endometrial hyperplasia, endometrial carcinoma and breast disease.
889
Scribe the clinical features of ovarian Sertoli-Leydig cell tumours
Often functional - in children may block normal female sexual development. In women can cause defeminisation and masculinisation (breast atrophy, amenorrhoea, sterility, hair loss, hiruitism with male hair distribution, clitoral hypertrophy, voice changes). Peak incidence in teens/20s.
Distressing, so often present early
890
Describe the features of metastasis to the ovaries
Most commonly Müllerian tumours - uterus, Fallopian tubes, contralateral ovary, pelvic peritoneum. Also GI tumours and breast.
891
What is a krukenberg tumour?
Metastatic tumour to the ovary of GI origin. Often bilateral, usually from stomach
892
Describe vulva carcinomas
Uncommon. Usually in over 60s. Usually squamous cell carcinoma. Longstanding inflammatory and hyperplastic conditions of the vulva e.g. Lichen sclerosis
893
Are vulva carcinomas related to HPV?
Approx 30% are, 70% aren't (often these are in older women, 80s as opposed to 60s)
894
What is vulvar intraepithelial neoplasia?
Atypical squamous cells within the epidermis (no invasion). In situ precursor of vulval squamous cell carcinoma
895
Describe vulval squamous cell carcinoma spread
Spreads initially to inguinal, pelvic, iliac, and para-aortic lymph nodes. Also to lungs and liver. Lesions less than 2cm. 90% 5yr survival following vulvectomy and lymphadenectomy.
896
What are gestational tumours?
Gestational trophoblast disease - tumours and tumour like conditions which show proliferation of placental tissue. Villus and/or trophoblastic
897
What are the major types of gestational tumour?
Hydatidiform mole (complete and partial)
Invasive mole
Choriocarcinoma
898
Describe a hydatidiform mole
1-3/1000 pregnancies. Associated with choriocarcinoma, can become malignant. Cystic swelling of chorionic villi and trophoblast proliferation. Usually diagnosed in early pregnancy by USS, can present with miscarriage. Highest risk groups are teenagers and 40-50yrs. Two types, complete or partial. Abnormal DNA (no maternal DNA or 2 sperm).
899
How is a hydatidiform mole usually diagnosed?
Early in pregnancy by USS or can present with miscarriage
900
What is the appearance of a hydatidiform mole?
Friable mass of thin walled, translucent, grape like structures. Swollen oedematous villi.
901
What is the treatment for a hydatidiform mole?
Treated with curettage followed by HCG monitoring. If HCG levels don't fall, may indicate invasive mole.
902
Describe a gestational choriocarcinoma
Malignant neoplasm of trophoblastic cells derived from previously normal, or abnormal pregnancy (no villi present), just trophoblast.
Rapidly invasive, metastasises widely but responds well to chemotherapy.
Non gestational choriocarcinoma arise from germ cells in the ovary of in the mediastinum
903
When does gestation choriocarcinoma generally occur
50% in association with complete moles.
| Others following abortion, following normal pregnancy, or in ectopic pregnancies.
904
How might gestational choriocarcinoma present?
Usually with vaginal spotting. HCG levels are high (blood test, indicating placental tissue is still present).
905
What is the treatment for gestational choriocarcinoma?
Treated with uterine evacuation and chemotherapy. Very high cure rate.
Same for non-gestational choriocarcinomas
906
Describe mucinous ovarian tumours
Often large, cystic, masses. Filled with sticky, thick fluid. Usually benign or borderline.
Pseudomyxoma peritonei - extensive mucinous ascites, epithelial implants on peritoneal surfaces, frequent involvement of ovaries, can cause intestinal obstruction. Most likely primary is extra-ovarian, usually appendix.
907
Describe endometrioid ovarian tumours
Contain tubular glands resembling endometrial glands. Can arise in endometriosis. Some have associated endometrial endometrioid adenocarcinoma, probably arising separately.
908
Describe germ call tumours
20% of all ovarian neoplasms. Most are teratomas, usually benign. Other types are malignant and include non-gestational choiriocarcinoma (which produces HCG, unlike gestational type)
909
What are the 3 groups of ovarian teratomas?
Mature (benign) - most common
Immature (malignant) - rare, composed of tissues that resemble immature foetal tissue
Monodermal (highly specialised) - only 1 type of tissue present
910
Describe the clinical features of a mature ovarian teratoma
Most are cystic. Also called dermoid cysts as they almost always contain skin-like structures. Usually occur in young women. Bilateral in 10-15% of cases. Usually contain hair and sebaceous material, can contain tooth structures. Often tissue from other germ layers also present e.g. Bone, cartilage, thyroid.
911
Describe monodermal ovarian teratomas
Most common in struma ovarii. Benign, composed entirely of mature thyroid tissue. May be functional and cause hyperthyroidism.
912
Describe ovarian secondary chord stromal tumours
Derived from ovarian stroma (which is derived from sex cords of the embryonic gonad). Sex cord produces Sertoli and leydig cells in testes, and theca and granulosa cells in ovaries. Tumours resembling all of these 4 cell types can be found in the ovary. Can be feminising or masculinising.
913
Describe the clinical features of granulosa cell tumours
Occur mostly in post-menopausal women. May produce large amounts of oestrogen in pre-pubertal girls may produce precocious puberty. In adult women may be associated with endometrial hyperplasia, endometrial carcinoma and breast disease.
914
Scribe the clinical features of ovarian Sertoli-Leydig cell tumours
Often functional - in children may block normal female sexual development. In women can cause defeminisation and masculinisation (breast atrophy, amenorrhoea, sterility, hair loss, hiruitism with male hair distribution, clitoral hypertrophy, voice changes). Peak incidence in teens/20s.
Distressing, so often present early
915
Describe the features of metastasis to the ovaries
Most commonly Müllerian tumours - uterus, Fallopian tubes, contralateral ovary, pelvic peritoneum. Also GI tumours and breast.
916
What is a krukenberg tumour?
Metastatic tumour to the ovary of GI origin. Often bilateral, usually from stomach
917
Describe vulva carcinomas
Uncommon. Usually in over 60s. Usually squamous cell carcinoma. Longstanding inflammatory and hyperplastic conditions of the vulva e.g. Lichen sclerosis
918
Are vulva carcinomas related to HPV?
Approx 30% are, 70% aren't (often these are in older women, 80s as opposed to 60s)
