Repro- Physiology Flashcards

Question

Describe the formation of male gametes/ sperm

Answer 1

Primordial germ cells colonise the seminiferous cords (which connect the epididymis to the vas deferens) in the medulla of the primordial gonad Post natal development of testis is slow - germ cells don't begin meiosis before puberty At puberty- hollow seminiferous tubules form from seminiferous cords Spermatazoa develop within the seminiferous tubules in association with Sertoli cells Seminiferous tubules are separated from the surrounding interstitial tissue by the blood testis barrier Leydig cells in interstitial tissue secrete testosterone Germ cells form spermatogonia stem cells- begins mitosis to maintain a population of self regenerating stem cells - remain available until ~70y/o; allows for continuous production of sperm cells at a high rate At intervals, groups of distinct cells- A1 spermatogonia emerge - marking the beginning of spermatogenesis in that part of the tubule - undergo differentiation - Type A - stem cells - Type B - committed to differentiation to spermatozoa --> Each type B spermatogonium then undergoes 4 mitotic divisions to produce a clone (64) of Primary spermatocytes all linked together by cytoplasmic bridges Primary spermatocytes push their way to the lumen of the tubule where they begin meiosis First meiosis division produces 2 haploid secondary spermatocytes which then divide again to produce 4 spermatids Spermatids are then remodelled to produce sperm Cytoplasmic bridges breakdown and sperm are released into the lumen to be washed down to the rete testis by fluid secreted by the Sertoli cells Sperm finally mature during the progression through the epididymis

Answer 2

Primordial germ cells colonise the cortex of the primordial gonad becoming oogonia Oogonia proliferate rapidly (7million by week 20 of gestation) majority of which die, leaving around 2 million which all begin meiosis before birth becoming primary oocytes Entry to meiosis 1 is stimulated by Mesonephric cells (follicular cells- flattened epithelia cells) which surround the primary oocyte to form primordial follicles Meiosis is then arrested at diplotene (resting) stage of prophase (due to ooctye maturation inhibitor OMI- released from follicular cells) At puberty--> until menopause- a small number of follicles begin further development each day until the follicle becomes a mature gamete 1) Primordial to Preantral - primary oocyte grows; does not restart meiosis - follicular cells change from flat to cuboidal cells and then proliferate to form multiple layered epithelium = granulosa cells - secrete glycoprotein glycoprotein which surrounds the primary oocyte with zona pellucida - surrounding stromal cells form the theca folliculi (inner theca interna- vascular and endocrine & outer theca externa- fibrous capsule) - theca and granulosa cells collaborate to secrete oestrogens 2) Antral transition - granulosa cells continue to proliferate - fluid appears between cells forming an Antrum - as more fluid forms - Graafian or secondary follicles expands dramatically (w/o hormones--> 2mm; w/FSH- binds to granulosa cells; w/LH- binds to thecal cells which secrete androgens which are converted to oestrogens under the influence of FSH via granulosa cells) - each cycle only one follicle becomes dominant and develops further 3) Preovulatory follicle - begins 37 hours before ovulation - under influence of oestrogen, LH receptors appear on outer granulosa cells - stimulated by LH surge --> rapid changes in follicle - within 3 hours of surge - oocyte restarts meiosis - first meiosis division is complete - asymmetric cytoplasm remains with one daughter - other forms a condensed polar body - secondary follicle enters meiosis II and then arrests again 3 hours prior to ovulation - follicle size increases due to increase in antral fluid volume - structure begins to weaken - LH stimulates collegenase activity - follicle rupture - ovum carried out into fluid and gathered up into Fallopian tube by fimbriae - meiosis not completed unless ovum is fertilised

Answer 3

Remains of the follicle rearranges itself into the corpus luteum - secretes progesterone and oestrogen under influence of LH In humans the corpus luteum lives for 14 days before spontaneously regressing (in the absence of a fertilised ovum) Early antral to corpus luteal stages- synchronised with reproductive cycle of female

Answer 4

Woman has all oocytes she will ever have at birth- none formed later All ova are produced from this stock - some of which remain arrested for 50 years before development - increases the chance of cell damage - eventual chromosomal abnormalities

Answer 5

Right number of gametes produced at the right time Male and female to get together at the same time Effective transfer of sperm from male to female Effective sperm transport Fertilisation Support of conceptus, embryo and foetus Birth at right time Support neonate

Answer 6

Releasing hormones Neuro secreted Direct from the median eminence Travel to the anterior pituitary is the hypophyseal portal system

Answer 7

``` Gonadotrophin releasing hormone (GnRH) Pulsatile release (1x/hr) ```

Answer 8

Other neurones Environmental effects and body weight Feedback from gonads and gonadal steroids

Answer 9

Trophic hormones Arise from Rathke's pouch - not nervous tissue/ it's an endocrine gland Gonadotrophs, thyrotrophs, lactotrophs, somatotrophs, corticotrophs

Answer 10

Follicle stimulating hormone FSH Luteinising hormone LH Act primarily on gonads (cells of gonadal origin not germ cell origin) Control gamete production and stimulate secretion of gonadal steroids

Answer 11

ADH | Oxytocin

Answer 12

GnRH stimulates gonadotrophs to secret LH and FSH | But the amount and proportion of LH and FSH secreted depends on OTHER FACTORS acting on gonadotrophs

Answer 13

Preparation/ follicular/ proliferative phase Ovulation Waiting/ Luteal/ Secretory phase

Answer 14

Oestrogen | Progesterone

Answer 15

Oestrogen, progesterone and inhibin levels are low as corpus luteum has broken down and LH and FSH levels are generally low GnRH secretion is released from inhibition due to less negative feedback from oestrogen and progesterone and levels increase LH and FSH tend to rise - FSH rises more than LH as there is no inhibition by oestrogen AND inhibit, whereas with LH there is just no inhibition by oestrogen ONLY FSH and LH cause the growth of the follicle Oestrogen and inhibin secretion from the ovaries then increases as a result FSH secretion is selectively inhibited by inhibin- so that only one follicle forms Oestrogen at low levels inhibits GnRH and LH secretion BUT rising oestrogen above a threshold leads to stimulation of GnRH and LH secretion and thus an LH surge results (positive feedback and influenced by environmental factors)

Answer 16

LH surge results in release of a follicle from the ovary into the fimbriae of the Fallopian tube- ovulation Oestrogen then instantaneously falls dramatically due to the release of the follicle and LH levels also fall The follicle then rearranges itself and the corpus luteum forms spontaneously

Answer 17

Initially LH promotes the secretion of oestrogen and progesterone from the corpus luteum As the corpus luteum grows more oestrogen and progesterone are secreted Rising oestrogen levels (above the threshold) do not cause another LH surge due to the rising levels of progesterone which stimulates the effects of oestrogen (as if at low levels) and prevents the positive feedback of high oestrogen Oestrogen and progesterone at high levels inhibit GnRH secretion and hence LH and FSH secretion- oestrogen reduces GnRH per pulse and progesterone reduces the frequency of the pulses

Answer 18

Corpus luteum regresses spontaneously (by apoptosis) Progesterone and oestrogen levels fall due to regression of corpus luteum This fall in progesterone (in particular) triggers the menstrual bleed as the endometrium is no longer maintained in preparation of pregnancy Low levels of oestrogen and progesterone again causes GnRH to be released from inhibition- back to beginning of cycle

Answer 19

Implanted embryo develops a placenta which secretes human chorionic gonadotrophin hormone (hCG) hCG prevents the regression of the corpus luteum Corpus luteum continues to secrete oestrogen and progesterone - supports the early weeks of pregnancy and maintains suppression of the menstrual cycle

Answer 20

In order to prepare/ increase the likelihood of Fertilisiation Fallopian tube function- motile, captures ovum, moves it to uterus Thickening of endometrium- secretes fluid adhesive to sperm Growth and fertility of myometrium- stimulates contraction- propels sperm to point of fertilisation Thin alkaline cervical mucus- attracts sperm which can move through it Vaginal changes- facilitates copulation Changes skin, hair and metabolism- body shape (anabolic) Calcium metabolism- affects bone

Answer 21

In order to prepare for pregnancy Acts on oestrogen primed cells Further thickening of endometrium into a secretory form - to sustain a conceptus and grow and maintain a placenta Thickening of myometrium- but reduction in motility Thick acid cervical mucus- inhibits spermatocytes transport so that not one sperm fertilised the egg Changes in mammary tissue Increased body temperature Metabolic changes- mildly catabolic Electrolyte changes- without oestrogen there is net sodium and water retention Reduced Fallopian tube motility, secretion and cilia activity

Answer 22

Ovary stops producing oestrogen and inhibin No longer any suppression of LH and FSH- negative feedback system breaks down Increased LH and FSH levels

Answer 23

Gonadotrophins secreted by pituitary gonadotrophs Stimulated by pulsatile releaseoif GnRH from hypothalamus Modified by feedback effects of gonadal hormones Environmental factors

Answer 24

Granulosa cells

Answer 25

Theca cells

Answer 26

Androgens which under the influence of FSH are then converted to oestrogen in the granulosa cells

Answer 27

Inhibin and oestrogen

Answer 28

Leydig cells

Answer 29

Testosterone

Answer 30

Sertoli cells

Answer 31

Testosterone is produced in the Leydig/ interstitial cells and is released into the spermatic tubules via the Sertoli cells- only cells permeable to testosterone- the rest have a spermatic barrier - promoting sperm production

Answer 32

Production of testosterone in the Leydig cells Secretion of testosterone via Sertoli cells Promotes spermatogenesis (via FSH) Maintains reproductive system (via testosterone)

Answer 33

FSH maintains Sertoli cells and makes them responsive to testosterone so that it can be released into spermatic tubules Stimulates Sertoli cells to secrete ABP and promotes spermatogenesis Inhibin release - levels rise if spermatogenesis proceeds too rapidly - reduces secretion of FSH by acting on gonadotrophs in the anterior pituitary

Answer 34

Circadian rhythm - highest early in the morning and is affected by environmental stimuli - light and dark, sex

Answer 35

Negative feedback control ensures that: - spermatogenesis occurs continuously - male reproductive tract is continuously ready for action - hormone levels are kept relatively constant in the medium to long term Testosterone inhibits GnRH secretion and so LH levels fall - brings testosterone levels back to normal

Answer 36

Not reversible/ only partly reversible | Secondary sexual characteristics

Answer 37

Maintains adult Repro system- maintenance of male internal genitalia (prostate, seminal vesicles, vas deferens, epididymis) Metabolic effects - anabolic action Behavioural effects- aggression and sexual activity

Answer 38

Before birth

Answer 39

Varies between sexes and between individuals, but in each sex there is a fixed sequence of events, which depend on the sex steroids secreted from the gonads and adrenal glands, that occur before the obvious signs of puberty become apparent: Boys- reach puberty at 9-14years Girls- reach puberty at 8-13 years

Answer 40

Starts later in boys (9-14years) - 10cm/year velocity ``` Genital development begins Pubic hair growth Spermatogenesis begins Growth spurts - Adult males end up larger because boys grow more before the growth spurt and slightly more during it - Growth spurt is terminated by epiphyseal fusion, at which point the adult height is virtually set Adult genitalia forms Adult pubic hair forms ```

Answer 41

Testicular androgens - testosterone

Answer 42

``` Starts earlier in girls- (8-13 years)- 9cm/year velocity Breast bud- thelarche Pubic hair growth begins- adenarche Growth spurt - Growth spurt is terminated by epiphyseal fusion, at which point the adult height is virtually set Onset of menstrual cycles Public hair adult Breast adult ```

Answer 43

Gonadal oestrogens- breast development and female genitalia development Androgens from adrenals- pubic and axillary hair development

Answer 44

Nocturnal erection and first ejaculation

Answer 45

First menstrual bleed- menarche

Answer 46

FSH and LH levels rise later, to reach the adult levels at 16 years, associated with steady rises in testosterone levels Weak androgens are released from the adrenal cortex

Answer 47

Plasma levels of FSH and LH rise gradually from about 7 years to reach adult levels soon after menarche Plasma oestrogen levels rise steadily until at the beginning of menstrual cycles - regular cyclical rises and falls are associated with the ovarian cycle Weak androgens are secreted from the adrenal cortex

Answer 48

Anterior pituitary gonadal axis is capable of responding to stimulation by GnRH long before puberty normally occurs but GnRH secretion is low Puberty occurs when the brain initiates pulsatile GnRH secretion - does not seem to depend on any signal from the gonads Once thought that the pre pubertal hypothalamus was very sensitive to the negative feedback by gonadal steroids - so very low circulating levels completely inhibited the secretion of GnRH - puberty would then arise from gradually decreasing hypothalamic sensitivity to feedback An alternative and now thought more likely explanation is that the hypothalamic mechanisms mature and steadily secrete more GnRH under other influences Either way- various factors influence the timing of puberty

Answer 49

Precocious puberty- signs of puberty before the age of 8 - mostly unknown cause - can be due to - neurological - early stimulation of central maturation (pineal tumours or meningitis) OR uncontrolled gonadotrophin or steroid secretion (hormone secreting tumours)

Answer 50

End of reproductive life in the female

Answer 51

Pre menopause Menopause Post menopause

Answer 52

~ age of 40 Changes in menstrual cycle - follicular phase shortens - ovulation is early or absent - less oestrogen is secreted - - LH and FSH levels rise, FSH more so - reduced feedback - reduced fertility

Answer 53

``` Cessation of menstrual cycles Age 49-50 but variable No more follicles develop Oestrogen levels fall dramatically LH and FSH levels rise, FSH dramatically (no inhibin as well as lower oestrogen) ```

Answer 54

Vascular changes- low oestrogen causes hot flushes and transient rises in temperature (relieved by oestrogen treatment) On oestrogen sensitive tissues - uterus - regression of endometrium and shrinkage of myometrium - thinning of cervix - vaginal rugae lost - involution of some breast tissue - changes in skin - changes in bladder Bone - bone mass reduces by 2.5%/year for several years - increased reabsorption relative to production - type 2 osteoporosis - much greater in some compared to others - major reason for fractures (e.g. Hip) in later life (limited by oestrogen therapy)

Answer 55

No obvious event Sperm production continues But incidence of loss of libido, impotence and inability to reach orgasm increases with age

Answer 56

Absence of menses by age 14 with absence of secondary sexual characteristics (e.g. Breast development) Absence of menses by age 16 with normal secondary sexual characteristics

Answer 57

Where an established menstruation has ceased for 3 months in a woman with a history of regular cyclical bleeding or 9 months in a woman with a history of irregular periods --> usually in women aged 40-55

Answer 58

Family history (age of menopause, thyroid dysfunction, diabetes, cancer), menstrual history, contraception, pregnancy, surgery, medication, weight change, chronic diseases/ stressors etc.

Answer 59

``` BMI Hair distribution Thyroid Visual fields Breast discharge Abdomen masses/ tenderness ```

Answer 60

``` Always rule out pregnancy!!! Ovarian axis problem- TSH prolactin LH FSH Hilsuitism- testosterone, OHEA's Chronic diseases- LFTs CNS - MRI ```

Answer 61

Yes so FSH levels are normal

Answer 62

Uterine- Müllerian agenesis (2nd most common cause) Vaginal- vaginal atresia, cryptomenorrhoea, imperforate hymen Turners syndrome- gonadal dysgenesis (most common cause) Androgen insensitivity syndrome Receptor abnormalities for FSH and LH Specific forms of congenital adrenal hyperplasia Hypothalamic- Kallman syndrome

Answer 63

Intrauterine adhesions - Asherman's syndrome Pregnancy (most common cause) Anovulation Menopause (and premature) Polycystic ovarian syndrome Drug induced Hypothalamic- exercise/ stress amenorrhoea, eating disorders Pituitary- Sheehan syndrome, prolactinaemia, haemochromatosis

Answer 64

Ovary/ gland does not respond to pituitary stimulation- due to gonadal dysgenesis or premature menopause for example Chromosome testing indicated in younger individuals with hypergonadotropic amenorrhoea Low oestrogen levels - may require treatment Tend to be linked to elevated FSH levels- typically in the menopausal range

Answer 65

Inadequate levels of FSH - Inadequately stimulated ovaries- fail to produce enough oestrogen to stimulate the endometrium --> amenorrhoea (low FSH levels- not usual with amenorrhoea)

Answer 66

Excessive (>80ml) uterine bleed OR prolonged (>7 days) | Heavy vaginal bleeding that is not DUB (dysfunctional uterine bleeding)

Answer 67

Usually secondary to distortions of the uterine cavity - heavy with or without prolongation Uterus unable to contract down on open venous sinuses in zona basalis Other causes: organic, endocrinologic, haemostatic and iatrogenic Usually ovulatory

Answer 68

Take history and full blood count 1) No structural or histological abnormality suspected, no exam required and treatment by GP with drugs: - tranexanic acid/ NSAIDs/ combined OCP - norethisterone (day 5-26 of MC) - levonorgestrel releasing ILS (12 months) 2) Structural or histological abnormality suspected. Physical examination- anaemia, obesity, androgen excess (Hilsuitism), acne, ecchymosis, purpura, thyroid, galactorrhoea, liver/ spleen, uterine, cervical and adnexal exam

Answer 69

Excessively heavy, prolonged, or frequent bleeding of uterine origin that is not due to pregnancy, pelvic or systemic disease Abnormal bleeding with no obvious organic cause - usually anovulatory Diagnosis of exclusion Usually at extremes of reproductive life and in patient with poly cystic ovaries

Answer 70

Disturbance in the HPO axis thus changes in length of menstrual cycle No progesterone withdrawal from an oestrogen primed endometrium Endometrium builds up with erratic building as it breaks down

Answer 71

HCG/ TSH Coagulation work up Ensure smear if appropriate > 35 or Cancer risk factors- tamoxifen use- sample the endometrium IV or IM conjugated oestrogen therapy acute DUB Usually followed by OCP or progesterone Cyclic progesterone for 10-12 days each cycle- consider mirnalUD OCP

Answer 72

Testicular

Answer 73

Pain during menstruation that interferes with daily activities

Answer 74

Regular menstrual cycles and premenstrual symptoms such sad dysmenorrhoea and mastalgia

Answer 75

Oligo or amenorrhoea +/- menorrhagia

Answer 76

Uterine bleeding occurring at intervals between 35 days and 6 months

Answer 77

Data from GUM services will underestimate the true incidence of STI's as patients may be seen in a variety of other settings such as GP Centres, family planning clinics etc. Additionally many symptoms are asymptomatic - e.g. With GP practices only 10% services attend GUM services

Answer 78

STI- both symptomatic and asymptomatic cases; sexual action is the principle mode of transmission STD- only symptomatic cases

Answer 79

HSV Syphylis Chancroid (haemophiliis ducreyi)

Answer 80

Transient manifestations of STI's Condylomata acumilata (anogenital warts) Umbilicated lesions of Molluscum Contagiosum virus

Answer 81

Gonococcal urethritis Non gonococcal urethritis - chlamidya trachomatis, ureaplasma, mycoplasma, trichomonas HSV Post gonococcal urethritis

Answer 82

Candiasis, trichomonasis, staphylococcal, foreign body, HSV

Answer 83

Chlamidya trachomatis, Neisseria gonorrhoea

Answer 84

Poly microbial infections with endogenous flora, rarely STI's

Answer 85

Overgrowth of normal flora - Gardnerella vaginalis Vaginal pH > 4.5 A pungent odour KOH Whiff test Presence of clue cells on a wet mount- lacking many PNMS

Answer 86

Pregnancy related infection- chorioamnionitis, post partum endometriosis, episiotomy infections, puerperal ovarian vein thrombophlebitis, osteomyelitis pubis Pelvic inflammatory disease

Answer 87

Acute bacterial prostatitis Chronic bacterial prostatitis Chronic pelvic pain syndrome

Answer 88

Non specific bacterial Epididymitis | Sexually transmitted Epididymitis

Answer 89

``` Viral orchitis (mumps, coxsackievirus B) Pyogenic bacterial orchitis ```

Answer 90

Obligate intracellular bacteria Does not grow routinely on lab media- implication for diagnostic methods Infective form is the elementary body which develops in the host cell into the reticulate body Reticulate body replicates until it eventually reverts back to the elementary body which then leaves the cell to infect other cells

Answer 91

Organism infects and replicates within cervix and urethra epithelium Urethritis Cervicitis Salpingitis Perihepatitis Most important cause of PID Ocular infection- common in sexually active individuals

Answer 92

Urethritis Epididymitis Prostatitis Proctitis Reiter's syndrome- urethritis, conjunctivitis and arthritis (triad) Ocular infection- common in sexually active individuals

Answer 93

Caused by cervical infection in a pregnant woman Inclusion conjunctivitis If untreated may progress to neonatal pneumonia

Answer 94

Urethral swab or first catch urine

Answer 95

Endo revival swab- any pus must be first removed from the cervix and a good quality cellular material must be obtained Urine may be used for molecular methods but is much less sensitive than an endo cervical swab

Answer 96

Population screening patients may provide a specimen whereas swab is time consuming, requires a trained staff member and is generally less acceptable to a patient

Answer 97

Eye swab- remove any pus, invert eyelid and scrape conjunctiva surface Pneumonia- serology is useful; differential on WCC may show eosinophilia

Answer 98

``` Chlamidya does not grow on lab media and tissue culture is too expensive So antibody detection: - Immunofluorescence - enzyme immunoassays - molecular methods: PCR ```

Answer 99

Macrolides (erithromycin, clarithromycin, azithromycin) or Tetracyclines (doxycycline) As conjunctivitis is part of a more widespread infection this should always be treated with systemic antibiotics

Answer 100

Member of Neisseriaceae family Gram negative bacteria diplococcus Only grow on an enriched media - chocolate agar

Answer 101

``` Gonococcal urethritis Epididymitis Prostatitis Proctitis Pharyngitis Disseminated gonococcal infections- pain in joints, tenosynovitis, rash ```

Answer 102

Asymptomatic May lead to endocervicitis, urethritis, PID, Bartholins abscess, infertility, disseminated gonococcal infection- pain in joints, tenosynovitis and rash (more likely in females)

Answer 103

Urethral, rectal and pharyngeal swabs

Answer 104

Endo cervical swab, urethral swab, rectal and pharyngeal swab

Answer 105

Neisseria gonorrhoea is a fragile organism that does not survive transportation well Ideally specimens taken should be placed on media directly at bed side Gram stain- gram negative diplococcus Culture/ sensitivities- more sensitive than microscopy, organisms resmbling neisseria gonorrhoea must be confirmed on the basis of a biochemical test to distinguish them Sensitivity testing is important as antibiotic resistance patterns are valuable in guiding future management guidelines

Answer 106

Initial therapy guided by severity of symptoms and local knowledge of sensitivity patterns Penicillin resistance is common

Answer 107

Human papilloma virus

Answer 108

Cutaneous mucosal and anogenital warts - benign and painless In penis, vulva, vagina, urethra, cervix, perianal skin High risk of becoming oncogenic -females aged 15-24 - cervical cancer

Answer 109

Clinical features Biopsy Genome analysis Hybrid capture

Answer 110

None Topical podophyllin cryotherapy Intralesional interferon surgery

Answer 111

Cervical Pap smear cytology | Cervical swab

Answer 112

Cervarix Gardasil (girls 12-13)

Answer 113

HSV1- cold sores | HSV2- genital herpes

Answer 114

Can be asymptomatic to moderate with symptoms | Infection can remain latent in the dorsal root ganglia

Answer 115

PCR of vesicle fluid and/or ulcer base

Answer 116

Prophylactic aciclovir

Answer 117

Barrier contraception

Answer 118

Extensive painful genotal ulceration Dysuria Inguinal lymphadenopathy Fever

Answer 119

Treponema pallidum

Answer 120

Mostly men and MSM

Answer 121

1- individual, painless ulcer (chancre) 2- 6-8 weeks later- fever, rash, lymphadenopathy, mucosal lesions 3- neurosyphylis, cardiovascular syphylis, gumma's

Answer 122

Organism can't be grown - dark friend microscopy

Answer 123

Initial screening with EIA antibody test then positives Rapid plasma reagin (RPR) time TPPA Interpret serological pattern (false positives)

Answer 124

Penicillin and test of cure 'follow up'

Answer 125

Flagellated protozoan

Answer 126

Trichomonas vaginitis Thin, frothy, offensive discharge Irritation, dysuria and vaginal inflammation

Answer 127

Vaginal wet prep +/- culture enhancement

Answer 128

Metronidazole

Answer 129

Can affect genitalia | Spreads sexually

Answer 130

``` Granuloma inguinale (Klebsiella) - genital nodules --> ulcers Chancroid- haemophilius ducreyi- painful genital ulcers Chlamidya trachomatis stereotypes- rapidly healing papule then inguinal bubo- LGV, MSM ```

Answer 131

Candida albicans Risk factors - antibiotics, oral contraceptive, pregnancy, obesity steroids, diabetes Presents with profuse, white, itchy, curd like discharge Diagnosis: High vaginal smear +/- culture Treat: Azores or nystatin oral fluconazole

Answer 132

Normal flora Gardnerella anaerobes, myocplasm Presents with scanty but offensive, fishy discharge Diagnosis- vaginal pH>5, KOH Whiff test, smear- clue cells (gram variable cocobacillus, reduced number of lactobacillus absence of pus cells)

Answer 133

``` Pediculosis pubis CRAB louse (Pthirius pubis)- distinct from other human body lice ```

Answer 134

The result of infection ascending from the endocervix causing endometritis, Salpingitis, parametritis, oophoritis, tubo ovarian abscess and or pelvic peritonitis

Answer 135

Endometritis Salpingitis Tubo ovarian abscess

Answer 136

Inflammation and infection of the endometrium (lining of the uterus)

Answer 137

Inflammation of the Fallopian tube

Answer 138

Pocket of pus that forms during infection of a Fallopian tube

Answer 139

Disease of sexually active women Incidence higher in urban areas Peak incidence 20/1000 Highest incidence in 20-24 years old

Answer 140

Majority of the time caused by polymicrobial infections Caused by gonorrhoea (14%) and chlamidya (10-25%) 40% risk of a concurrent infection Garderella, Mycoplasma and anaerobes (bacterial vaginosis) have also been implicated Tuberculosis and group A strep

Answer 141

Infection ascends from the endocervix and vagina into the uterus causing inflammation Inflammation causes adhesion formation and damage to tubule epithelium

Answer 142

``` Young age Sexual behaviour Type of contraception used - lack of use of barrier contraception; IUCD increases risk of PID in first few weeks of insertion; COCP is considered to be protective against symptomatic PID Alcohol/ drug use Cigarette behaviour/smoking Lower socioeconomical ```

Answer 143

``` Pyrexia Pain- bilateral lower abdominal tenderness, adnexal tenderness, cervical excitation, deep dyspareunia Abnormal vaginal/ cervical discharge Abnormal vaginal bleeding Sexual history and prior STI Contraceptive history ```

Answer 144

Pyrexia > 38 degree Celsius - fever Lower abdominal tenderness (bilateral) Bimanual examination- Adnexal tenderness, Cervical motion tenderness/excitation Speculum examination- purulent cervical discharge, Cervicitis, Discharge (vaginal and cervical)

Answer 145

Endocervical swab- gonorrhoea and chlamidya High vaginal swab- bacterial vaginosis, trichomonas vaginalis, candida *positive swabs support diagnosis *negative swabs don't exclude it

Answer 146

``` Surgical emergency can't be excluded Clinically severe disease PID in pregnancy Tubo ovarian abscess Lack of response/ intolerance to oral therapy ```

Answer 147

Analgesia Antibiotics - mild to moderate disease- oral antibiotics - severe- IV antibiotics

Answer 148

IM Ceftriaxone 500mg stat PO Doxycycline 100mg BD PO Metronidazole 400mg BD

Answer 149

``` IM Ceftriaxone 500mg stat PO Doxycycline 100mg BD PO Metronidazole 500mg BD ... PO Doxycycline 100mg BD PO Metronidazole 400mg BD ```

Answer 150

Laparoscopy / laparotomy may be considered if : no response to therapy, clinically sever disease, presence of tubo ovarian abscess US guided aspiration of pelvic fluid collections is less invasive

Answer 151

Ectopic pregnancy Infertility Adhesions and chronic pelvic pain Fitz Hugh Curtis syndrome

Answer 152

``` Gynaecological - ectopic pregnancy - endometriosis - complication of an ovarian cyst Gastrointestinal - irritable bowel syndrome - acute appendicitis Renal - urinary tract infection Other - functional pain ( pain of unknown physical origin) ```

Answer 153

RUQ pain and perihepatitis - following chlamydial PID (10-15%) Risks increase with repeat episodes Future use of barrier contraception will reduce the risk of PID Contact screening Severe disease= greater risk of complications Early treatment= lower risk of complications

Answer 154

Pelvic diaphragm- bowl or funnel shaped; coccygeus and levator ani muscles, fascia covering superior and inferior aspects of these muscles; between ischiopubic rami Superficial muscles and structures- anterior (urogenital) perineum and posterior (anal) perineum

Answer 155

Within the lesser pelvis separating the pelvic cavity from the perineum

Answer 156

Exerts a sphincteric actions on the rectum and vagina and can resist increases in intra abdominal pressure associated with coughing, defecation, heavy lifting etc.

Answer 157

Urogenital diaphragm fills the gap of the public arch stretching between converging ischiopubic rami Triangle sandwich with striated muscle fibres between 2 layers of fascia - superior fascia and inferior or superficial fascia - thickened (aka perineal membrane) sandwich the sphincter urethrae- striated muscle fibres

Answer 158

Superficial transverse perineal membrane Bulbospongiosus muscle Ischiocavernous muscle Superficial perineal pouch - site of urine collection if the urethra is ruptured below the perineal membrane

Answer 159

Superficial perineal pouch - site of urine collection if the urethra is ruptured below the perineal membrane

Answer 160

Forms a triangle between ischial tuberosities and coccyx Comprised of anus, levator ani, and ischiofemoral fossae (fatty fossa that may become infected spreading behind the anus) Pudendal nerve passes along lateral wall of the fossa

Answer 161

Paired muscles, form 3 slings of muscle extending from posterior aspect of the pubic bone, fascia over obturator internus and ischial spines Forms part of pelvic diaphragm Anterior fibres around the prostate/ vagina Intermediate fibres around the rectum (puborectalis) and into anococcygeal body (pubococcygeus) Posterior fibres to anococcygeal body and coccyx (iliococcygeus)

Answer 162

Lies to posterior, overlying the sacrospinous ligament | Forms part of pelvic diaphragm

Answer 163

Pyramidal fibromuscular mass found at the junction between urogenital and anal triangles (anterior and posterior perineum)

Answer 164

Found between bulb of penis and anus

Answer 165

Found between vagina and anus (~1.25cm in front of anus)

Answer 166

Essential for the integrity of the pelvic floor in females- anchoring perineal muscles and rectum Point of attachment for the anal sphincters, bulbospongiosus, superficial transverse perineal muscles and fibres of levator ani

Answer 167

Weakness of the pelvic floor Leading to prolapse of structures such as the vagina and uterus May be avoided by episiotomy (scissors)

Answer 168

Stretching of nerves (pudendal nerve - neuropraxia and muscle weakness), muscles (pelvic floor and perineal muscles- muscle weakness) and ligaments (supporting muscles - ineffective muscle action) Prolapse of organs and stress incontinence

Answer 169

Age, menopause (atrophy of tissues after oestrogen withdrawal), obesity, chronic cough, intrinsic CT laxity (defined conditions- constitutional)

Answer 170

Pelvic floor muscle exercises- easy, safe and effective (cure in 50-75% cases) Continence surgeries Prolapse procedures

Answer 171

Increase support of sphincter mechanism and prevent the descent of the bladder neck - colosuspension, tension free vaginal tape Effective- 85-90% cure rate Side effects- voiding difficulty / urinary retention; overactive bladder disease (obstruction)

Answer 172

Replace prolapsed organs Restore CT support Maintain function Side effects- recurrence, new incontinence, dyspareunia (painful sex)

Answer 173

74 days | 50 in the seminiferous tubules and 12-26 in the epididymis

Answer 174

6.5m/g/day

Answer 175

3.8m/g/day

Answer 176

Excitement phase Plateau phase Orgasmic phase Resolution phase (+/- refractory period)

Answer 177

Vaginal lubrication Swelling and engorgement of external genitalia- clitoris, vaginal mucosa, beast and nipples Internal enlargement of vagina Cervical mucus - oestrogen: abundant, clear, non viscous mucus - oestrogen and progesterone: thick and sticky mucus plug +/- Orgasm No physiological refractory period

Answer 178

Stimulants: psychogenic and tactile (sensory afferents of penis and perineum) --spinal reflex--> Efferents: somatic and autonomic efferents - pelvic nerve (PSNS) and pudendal nerve (Somatic) --> Haemodynamic changes --> Tumescence Haemodynamic changes: - inhibition of SNS arterial vasoconstriction nerves - activation to PSNS nerves; postganglionic PSNS nerves release ACh; ACh bonds to M3 receptors on endothelial cells, causing a rise in Ca2+ and activation of NOS and NO; NO then activates NANC upto omit nerves to the arteries causing increased NO release NO release: - increase in NO --> increase in cGMP - increased uptake of Ca2+ by intracellular stores - decrease in cytoplasmic calcium --> less actin myosin cross bridges - relaxation of smooth muscle Erection of penis - as a result of smooth muscle relaxation - corpora cavernosa central arteries straighten, enlarging their lumen and allowing blood to flow into and dilate the cavernous spaces in the corpora of the penis - corpus spongiosum also dilates but not very much as it would compress and close off to the urethra - bulbospongiosus and ischiocavernosus muscles compress veins egressing from the corpora cavernosa, so blood pools in the veins --> impeding the return of venous blood and the dilation of the helicline arteries causes the corpora cavernosa to become engorged with blood, near arterial pressure, causing erectile bodies to become turgid - enlarged

Answer 179

Psychological (descending inhibition of spinal reflexes) Tears in fibrous tissue of corpora cavernosa Vascular (arterial and venous) Drugs - factors blocking NO: alcohol, antihypertensives, diabetes - viagra: inhibits cGMP breakdown maintaining an erection

Answer 180

Emission is the movement of ejaculate into the prostatic urethra before ejaculation. This occurs due to peristalsis of the vas deferens and secretions from the seminal vesicles.

Answer 181

``` o Spinal reflex o Sympathetic Nervous System Control (L1, L2) 1. Contraction of glands and ducts • Smooth muscle 2. Bladder internal sphincter contracts • Prevents entry of semen into the bladder 3. Rhythmic striatal muscle contractions • Pelvic floor • Ischiocavernosus – Pudendal (S2-S4) • Bulbospongiosus – Pudendal (S2-S4) • Hip and anal muscles ```

Answer 182

``` 2-4ml 20-200x10^6 sperm/ ml Total sperm/ ejaculate >40/10^6 >60% sperm swimming forward vigorously <30% abnormal morphology ```

Answer 183

``` Seminal vesicles- 60% of volume, alkaline fluid (neutralises acid; male urethra and female reproductive tract), fructose/PGs/clotting factors (semenogelin) Prostate- 25% of volume, milky/ slightly acidic fluid, proteolytic enzymes (breakdown clotting proteins reliquifying the semen in 19-20 minutes), citric acid and acid phosphatase Bulbourethral glands (Cowpers), very small volume, alkaline fluid, a mucus that lubricates end of penis and urethral lining ```

Answer 184

Typically Day 7-14 - uterine proliferation (oestrogen) Day 14 - ovulation Day 14-28 - uterine secretory phase, corpus luteum (progesterone and oestrogen)

Answer 185

Immediately after ejaculation, the semen first coagulates due to the action of clotting factors (fibrinogen). This is to prevent sperm being physically lost from the vagina. 10 – 20 minutes later the semen re-liquefies by the action of enzymes found in prostatic secretions. The vast majority of sperm do not enter the cervix of the uterus and are lost by leakage from the vagina. Those that do enter the uterus have to travel 15 – 20cm to reach the uterine tube, a journey that may last a few hours. Transport of sperm is as a result of their own propulsive capacity and the fluid currents caused by the action of ciliated cells in the uterine tract.

Answer 186

Capacitation and Acrosomal reaction

Answer 187

Both capacitation and the acrosomal reaction are induced by an influx of calcium and a rise in cAMP in spermatozoa.

Answer 188

Capacitation o Further maturation of sperm in female reproductive tract (6 – 8 hours) o Sperm cell membrane changes to allow fusion with oocyte cell surface • Removal of glycoprotein coat o Tail movement changes • Beat --> Whip-like action o Sperm become responsive to signals from the oocyte

Answer 189

Capacitated sperm comes into contact with the oocyte zona pellucida o Sperm pushes through granulosa cells o Proteins on sperm head bind to ZP3 proteins on zona pellucida o Binding --> Start of reaction o Acrosome swells and liberates its contents by exocytosis o Proteolytic enzymes digest path through zona pellucida and facilitate penetration of the zona pellucida by the sperm (takes about 15 minutes) o One sperm penetrates- and membrane of sperm and egg fuse: sperm moves into cytoplasm of egg = ZYGOTE o Polyspermy is blocked by cortical reaction

Answer 190

By the time of ovulation, the ovum (primary oocyte) in the ovulatory follicle has completed its first meiotic division to form a secondary oocyte. o Secondary Oocyte • Haploid number of chromosomes and bulk of cytoplasm o First Polar Body • Remaining haploid number of chromosomes The secondary oocyte, surrounded by follicular cells (cumulus) embedded in a gelatinous matrix, is released from an ovulatory follicle and picked up by the fimbria of the uterine tube and guided into its lumen by the ciliary movements of epithelial cells towards the ampulla, the site of fertilisation, where the oocyte and sperms come together.

Answer 191

Only one sperm penetrates the cytoplasm of the ovum and its nucleus fuses with the nucleus of the ovum. This forms the zygote. Within a few hours the zygote begins to divide by a series of mitotic cell divisions known as cleavage to form a ball of cells called the morula and then a hollow structure, the blastocyst. During this transformation process it is gradually transported along the uterine tube towards the uterus. By the time the blastocyst enters the uterine cavity (4 – 5 days after fertilisation), the endometrium is ready to receive it for pregnancy to be established. After a day or so in the uterine cavity the blastocyst attaches itself to the uterine endometrium – implantation.

Answer 192

``` Ectopic Pregnancy o Failure of transport of egg o Embeds in Fallopian tube, ovary or abdomen o Embryo dies o Severe risk of maternal haemorrhage ```

Answer 193

It awaits the rise in progesterone - smooth muscle relaxation

Answer 194

Not totipitent like zygote Outer layer - trophoblast becomes supporting structures Inner layer - embryoblast becomes the embryo

Answer 195

``` Zygote to blastocyst in days 14-21 in the uterine cycle Progesterone primes the endometrium Conceptus is nourished in intrauterine fluid, 3 days floating Sticky trophoblasts over inner cell mass, adheres to endometrium (hCG) Implantation commences (6 days after ovulation) ```

Answer 196

Always - 14 days before the first day of menstruation

Answer 197

Progesterone day 21

Answer 198

Methods of modifying conception to prevent its occurrence

Answer 199

1. Natural contraception 2. Preventing sperm from entering the ejaculate 3. Prevent/ inhibit sperm from reaching the cervix 4. Prevent ovulation 5. Inhibit transport of sperm along Fallopian tube 6. Inhibit implantation

Answer 200

- Abstinence - Coitus interuptus- but sperm can still be present in preejaculate (bulbourethral glands) - Rhythm method (not having sex whilst ovulating) - only works with regular cycles- assume maximum spermatozoa survival of 7 days (average 3-4 days) and ovum survival of 1 day--> so for a regular 28 day cycle, with ovulation on day 14 or 15; fertile period is day 7-16 of cycle

Answer 201

Vasectomy- divide the vas deferens bilaterally, ensure ejaculate is free of sperm before relying on contraception Needs to be checked a few months later

Answer 202

1- Barrier contraception- condoms (readily available, protects against STI's, effective if correctly used), diaphragm (lies diagonally across cervix, needs correct fitting, does not completely occlude passage of sperm, holds sperm in acidic environment of vagina and reduces survival time), cap (fits across cervix, physical barrier) 2- Spermicide - most effective in conjunction with barrier methods 3- Hormone interruption with drugs - combined OCP, depot progesterone, progesterone implant, progesterone only pill (POP) - main mode of action of POP and implant- affects cervical mucus creating a thick hostile mucus, progesterone mediated environment

Answer 203

Altering hormone levels with drugs 1. Combined OCP- oestrogen and progesterone; negative feedback to hypothalamus and pituitary - inhibits follicular development; oestrogen causes loss of positive feedback mid cycle and so no LH surge 2. Depot progesterone- 3 monthly injections of progesterone, negative feedback effect to inhibit ovulation 3. Progesterone only pill- low dose progesterone only, may inhibit ovulation 4. Progesterone implants- may inhibit ovulation

Answer 204

1. Sterilisation - occlude the Fallopian tubes (may (but rarely do) recanalise) - Clips, Rings, Ligation

Answer 205

1. Altering hormones with drugs- affect receptivity of endometrium, direct effect, plus absence of corpus luteum prevents preparation of endometrium for implantation - OCP, progesterone implant, POP, depot progesterone 2. Post Coital contraception - combined oestrogen/ progesterone high dose or POP; upto 72 hours after intercourse, may disrupt ovulation/ blocks implantation/ may also impair luteal function 3. Intrauterine device - may also be used as post coital contraception up to 5 days after ovulation; inert copper containing or progesterone impregnated; copper interferes with endometrium enzymes and may also interfere with sperm transport into Fallopian tubes; interferes with implantation

Answer 206

Failure to conceive within one year

Answer 207

Primary- no previous pregnancy | Secondary- previous pregnancy - successful or not

Answer 208

Female - 45-60% Male - 20-25% Unexplained - 20-30%

Answer 209

1. Coital problems (20-30%) 2. Anovulation (15-20%) 3. Tubal occlusion (15-40%) 4. Abnormal/ absent sperm production

Answer 210

(15-20%) Menstrual cycle, during which the ovaries don't release an egg so ovulation does not occur, so usually have very irregular periods Occasional anovulatory cycles normal- especially in extremes of reproductive life Causes : hypothalamus (hyperprolactinaemia, weight loss, exercise, stress), pituitary (tumours, necrosis) and ovaries (ovarian failure, menopause, radiotherapy, chemotherapy) and Polycystic ovarian syndrome

Answer 211

Uncertain pathogenesis- originates at pituitary or ovarian level Increased androgen secretion Raised LH/FSH ratio Insulin resistance Multiple small ovarian cysts Anovulation- often amenorrhoea or oligomenorrhoea

Answer 212

Serum progesterone level in mid luteal phase ( ~ day 21)

Answer 213

Differentiate causes by looking at hormone levels Menopause and ovarian failure - high LH and FSH and low Oestrogen Hypothalamus/ Pituitary failure - low LH, FSH and Oestrogen PCOS - increased LH:FSH ratio, normal Oestrogen

Answer 214

Anti oestrogen- reduce negative feedback to hypothalamus/ pituitary; increase GnRH and FSH Gonadotrophins- FSH administration GnRH agonists- pulsatile to mimic normal secretion

Answer 215

Sterilisation | Scarring from infection, endometriosis

Answer 216

Laprascopy and dye insufflation | Hysterosalpingogram

Answer 217

Tubal surgery- reanastamoses | Assisted conception

Answer 218

``` Abnormal production (e.g. Testicular disease) Obstruction of ducts (e.g. Infection, vasectomy) Hypothalamic/ pituitary dysfunction ```

Answer 219

Volume: >2ml Sperm count: > 20mill/ml Motility: >50% Morphology: >50%

Answer 220

``` o Regular, unprotected intercourse? o Ovulating? • Regular menstrual cycle? • Day 21 Progesterone? o Patent Tubes • History of infection / sterilisation • Hysterosalpingogram o Adequate sperm count? ```

Answer 221

o Induce ovulation- anti oestrogen, Gonadotrophins, GnRH agonists o Overcome tubal occlusion by surgery or IVF o If inadequate sperm then • Artificial insemination by donor • Intra-cytoplasmic sperm injection

Answer 222

By the time the blastocyst enters the uterine cavity (4-5 days after fertilisation) the endometrium is ready to receive it for pregnancy to be established After a day or so in the uterine cavity the blastocyst implants into the endometrium Implantation involves the interaction between the trophoblast cells and epithelium of the uterus Further embedding of the blastocyst into the endometrium is dependent on the invasive property of the trophoblasts, which by now have an outer layer- syncytiotrophoblast differentiated from the underlying cytotrophoblast By the 10th day after fertilisation the blastocyst is fully embedded within the endometrium

Answer 223

Epithelia of the uterus | Trophoblast cells --> syncytiotrophoblast and cytotrophoblast

Answer 224

The stroma of the endometrium

Answer 225

Placental membrane becomes progressively thinner as the needs of the fetus increase

Answer 226

One layer of trophoblast ultimately separates maternal blood from fetal capillary wall

Answer 227

Establish the basic unit of exchange (primary, secondary and tertiary villi) Anchor the placenta (establishment of outermost cytotrophoblast layer which anchors it) Establish maternal blood flow with placenta

Answer 228

Primary villi- early finger like projections of trophoblast Secondary villi- invasion of mesenchyme into core Tertiary villi- invasion of mesenchyme core by fetal vessels

Answer 229

Decidualisation | Remodelling of the spiral arteries

Answer 230

Decidual reaction provides the balancing force for the invasive force of the trophoblast, without which haemorrhage and ectopic pregnancy can occur Progesterone stimulates the endometrial epithelial cells to be changed into decidual cells - process consists of modifying stromal cells, uterine glands and vessels and uterine immune cells, by altering their expression of regulatory factors such as metalloproteinases, cytokines, surface integrity and MHC * Decidualisation occurs independently of the blastocysts presence in the uterine cavity and in fact happens any way in the late secretory phase of the menstrual cycle Stromal cells become round and show ultra structural similarities to Myofibroblasts and epithelial cells --> release factors: prolactin, relaxin, renin, insulin growth, factor BP and ECM proteins- laminin and fibronectin

Answer 231

Creation of low resistance vascular bed | Maintains the high flow required to meet fetal demand, particularly late in gestation

Answer 232

Ectopic pregnancy Placenta praevia Incomplete invasion

Answer 233

Implantation at a site other than the uterine body Most commonly in the Fallopian tube (can be peritoneal or ovarian) Can very quickly become a life threatening emergency

Answer 234

Implantation in lower uterine segment Can cause haemorrhage in pregnancy Requires c section delivery

Answer 235

Placental insufficiency | Pre eclampsia

Answer 236

1. A fetal portion - formed by chorion frondsum, bordered by chorionic plate 2. A maternal portion - formed by decidua basalis, decidual plate is most intimately incorporated into the placenta

Answer 237

Beginning of 4th month: -1. A fetal portion - formed by chorion frondsum, bordered by chorionic plate -2. A maternal portion - formed by decidua basalis, decidual plate is most intimately incorporated into the placenta Between the chorionic and decidual plates are the intervillous spaces which are filled with maternal blood During the 4th and 5th months: - decidua forms a number of decidual septa which project into the intervillous spaces but do not reach the chorionic plate - these septa divide the placenta into a number of compartments or cotyledons - as a result of the continuous growth of the fetus and expansion of the uterus, the placenta also enlarges - throughout pregnancy it covers approximately 15-30% of the internal surface of the uterus

Answer 238

First trimester placenta - placenta established - placental barrier to diffusion still relatively thick - complete cytotrophoblast layer beneath syncytiotrophoblast Term placenta - surface area for exchange dramatically increased - placental barrier now thin - cytotrophoblast layer beneath syncytiotrophoblast lost

Answer 239

The umbilical arteries and veins project into the tertiary villi which are bathed in oxygenated maternal blood - two umbilical arteries take deoxygenated blood from the fetus to the placenta - one umbilical vein takes oxygenated blood from the placenta to the fetus Cotyledons: - receive their blood through 80-100 spiral arteries that pierce the decidual plate - pressure in these arteries forces oxygenated blood deep into the intervillous spaces and bathes the numerous small villi of the villious tree in oxygenated blood - as the pressure decreases, blood flows back from the chorionic plate towards the decidua where it enters the endometrial veins

Answer 240

Concentration gradient - steeper the gradient, the more diffusion Barrier to diffusion - placental membrane (single layer of trophoblasts) gradually thins throughout pregnancy as the em and of the fetus increases Diffusion distance- haemomonochorial - one layer of trophoblasts ultimately separates maternal blood from fetal capillary walls

Answer 241

Simple diffusion- water, electrolytes, urea and uric acid, gases (flow limited, not diffusion limited; fetal O2 stores are small - maintenance of adequate flow is important) Facilitated diffusion- glucose Active transport- specific transporters are expressed by the syncytiotrophoblast; amino acids, iron and vitamins

Answer 242

Placenta is not a true barrier and so harmful substances, teratogens, can access the fetus via the placenta and guns give physiological consequences (these are particularly damaging during critical stages of development) - thalidomide - alcohol - therapeutic drugs - drugs of abuse - maternal smoking

Answer 243

``` Varicella zoster Cytomegalovirus Treponema pallidum Toxoplasma Gondii Rubella ```

Answer 244

Releases protein hormones: - Human Chorionic Gonadotrophin (hCG)- produced in first 2 months of pregnancy, supports the secretory function of corpus luteum, produced by syncytiotrophoblast, therefore is pregnancy specific - Human Chorionic Somatommotrophin (hCS)- influences maternal metabolism, increasing the availability of glucose to the fetus - Human Chorionic Thryotrophin - Human Chorionic Cortiotrophin Releases steroid hormones (responsible for maintaining the pregnant state) - Progesterone- placenta takes over production from the corpus luteum (week 11); influences maternal metabolism by increasing appetite - Oestrogen- placenta also synthesises glycogen,cholesterol and fatty acids -

Answer 245

Testicular cancer

Answer 246

Human Chorionic Gonadotrophin? (hCG) - produced in first two months of pregnancy - supports the secretory function of the corpus luteum - produced by syncytiotrophoblast, therefore is pregnancy specific - excreted in maternal urine, therefore is used as the basis for pregnancy testing

Answer 247

Immunological competence begins to develop late in the first trimester, by which time the fetus makes all the components of complement Fetal immunoglobulins consist almost entirely of maternal immunoglobulin (IgG) which begins tone transported from mother to fetus at about 14 weeks The IgG is transported via Receptor Mediated Pinocytosis Eventually the concentration of IgG in fetal plasma exceeds that of maternal plasma In this way the fetus gains passive immunity against various infectious diseases Newborns produce their own IgG, but adult levels are not attained until the age of 3

Answer 248

Rhesus blood group in compatibility of mother and fetus Mother previously sensitised to Rhesus antigen ( e.g. Previous pregnancy) IgG against Rhesus cross the placenta and attacks fetal RBC's Now uncommon because of the prophylactic treatment - Rhesus negative mothers pregnant with Rhesus positive fetus are given Rhesus specific IgG throughout pregnancy to prevent sensitisation in the event of exposure to the antigen (given IgG will bind to antigen before the mothers immune system can mount a response)

Answer 249

History and examination: risk factors- e.g. For gestational diabetes Blood test: blood group, haemoglobin, infection Urinalysis: protein

Answer 250

1. Blood volume increases --> CO = SV (increased 35%) x HR (increased 15%) 2. RBC number increases but not as much as blood volume (ANAEMIA) 3. Decreased BP in pregnancy --> BP = CO (increased by 40%) x TPR (decreased by 25-30%; systemic vascular resistance) - T1 and T2- progesterone --> decreased SVR - T3- aortocaval compression by gravid uterus 4. Endothelium - vasodilation of pregnancy

Answer 251

1. Diaphragm displaced upwards 2. A-P diameter (transverse) of thorax increases --> lower ribs expand 3. Hyperventilation: progesterone --> increased respiratory drive and increased metabolic CO2 production (inc paO2 and dec paCO2)- RESP ALKALOSIS * compensated by increase in bicarbonate excretion --> SOB 4. increase in TV, RR the same, decrease in FRC, VC the same, TLC roughly the same, FEV1 the same

Answer 252

1. Viscera move around --> appendix to RUQ 2. Progesterone --> Smooth muscle relaxes: - GI- delayed emptying - Biliary tract- stasis - Pancreas- increased risk of pancreatitis

Answer 253

1. Fetus is an allograft (foreign body) --> non specific suppression of local immune respons at materno-fetal interface 2. Transfer of antibiotics --> haemolytic disease and Graves and Hashimoto's thyroiditis

Answer 254

1. Increased GFR 2. Increased RPF 3. Increased creatinine clearance, increased protein excretion, decreased urea, uric acid bicarbonate and creatinine 4. Progesterone --> relaxes smooth muscle in the walls of the ureters --> STASIS, HYDROURETER, UTI's, PYELONEPHRITIS

Answer 255

FATS AND GLUCOSE 1st half of pregnancy - progesterone stimulates appetite - diverts glucose into fat synthesis in the mother - increase in lipolysis from T2 --> increase in PFFA's (fasting) - FFA's substrate for maternal metabolism, sparing glucose for fetus 2nd half of pregnancy - oestrogen stimulates prolactin (and human placental lactogen and oestrogen, progesterone and cortisol release) --> generates a maternal resistance to insulin --> maternal glucose usage declines and gluconeogenesis increases --> maximising the availability of glucose to the fetus - blood glucose in pregnancy- decrease in fasting blood glucose and increase in post prandial (meal) blood glucose (placental transport of glucose is by facilitated diffusion) KETOACIDOSIS AND GESTATIONAL DIABETES THYROID Increase on TBG --> decrease in free T4 and T3 in blood --> positive feedback to increased T3 and T4 secretion Free T4 normally in normal range (has higher affinity for TBG that T3) T3 (more metabolically active) usually in higher concentrations hCG --> decreased TSH

Answer 256

``` Increased fibrin deposition at site Increased fibrinogen and clotting factors Reduced fibrinolysis Added to stasis and venodilation PROTHROMBOTIC STATE, THROMBOEMBOLISM *Warfarin is teratogenic ```

Answer 257

Placenta --> umbilical vein --> ductus venosus (around liver) --> + ascending vena cava (gut and lower body; deoxygenated but only small amounts as lower body is small) --> RA --> crista dividens --> foramen ovale --> LA --> LV --> Aorta --> Brain (oxygenated with some deoxygenated)--> + ductus arteriosus to rest (highly deoxygenated from brain) --> mixed oxygenated and deoxygenated blood --> gut and lower body Brain --> descending vena cava (highly deoxygenated blood) --> RA --> RV --> pulmonary artery --> some to collapsed lungs via high resistance vessels but most forced into ductus arteriosus --> Aorta (after branch supplying mostly oxygenated blood to brain has branched off the aorta)

Answer 258

pO2 in the fetus is 4kPa (compared to adult at 13.3kPa) despite even the increased pO2 in pregnant women due to progesterone induced hyperventilation - fetus adapted to degree of hypoxia that would be fatal in a normal adult Fetal Hb - much higher affinity for O2 and will carry more O2 at a lower pO2 (70% saturated at 4kPa); has no B chains and so does not readily bind 2,3 DPG; present at higher levels (neonate at least 18g/dl compared to 12-14g/dl in adult) Oxygen transfer across the placenta - O2 transport rate is determined by umbilical artery pO2; fetus gets O2 it needs via constant supply from placenta - which is good because fetal O2 stores are very LOW (about 2 mins worth)

Answer 259

Maternal CO2 levels are lowered by hyperventilation stimulated by progesterone- enables fetus to have relatively normal pO2 Fetus cannot tolerate higher pCO2 levels than its mother --> acid base problems Progesterone stimulates progesterone, which allows for the placental transfer of CO2 facilitated by lower maternal pCO2

Answer 260

Fetus makes breathing movements (1-4 hrs a day) which draw amniotic fluid into and out of the lungs Surfactant is produced by type 2 pneumocystes from around week 20 - surfactant production is significantly increased after week 30 when the alveoli open in significant number and the surface area dramatically increases - surfactant lowers the alveolar surface tension such that inspiration is made with less effort post natally * deficiency in pre term infants can lead to respiratory distress syndrome of the newborn

Answer 261

Fetus relies on relatively high maternal blood glucose to drive glucose across the placenta and support fetal growth and development Fetal insulin secretion begins at week 10

Answer 262

Fetus cannot excrete bilirubin via its gut Bilirubin is therefore not conjugated and so passes across to the maternal circulation Neonate may not immediately become able to deal with bilirubin and so neonate jaundice is common

Answer 263

Fetal kidneys produce urine (25 weeks- 100ml hypotonic urine/ day --> Term- 500ml urine/ day) which forms a major part of amniotic fluid particularly late in gestation This fluid is constantly swallowed so that the gut absorbs water and electrolytes, leaving debris to accumulate, together with debris from the developing gut in the fetal large bowel =meconium- only excreted by a fetus in severe distress (hypoxia)

Answer 264

Fluid that surrounds the fetus and provides mechanical protection and a moist environment 8 weeks - 10ml --> 42 weeks - 300ml Reaches a maximum of 1l at about 38 weeks - may fall as labour nears Cells within the amniotic fluid are derived from amnion of fetus Biochemical, and cytological studies of the fluid are made by amniocentesis and can be used to assess the presence of neural tube defects, chromosomal abnormalities ( Down's syndrome) etc. In early pregnancy amniotic fluid is derived probably by dialysis of fetal and maternal extracellular compartments with some exchange occurring across the fetal skin --> With functional maturation of the fetal kidneys, fetal urine contributes a lot to volume in later pregnancy; fetus also swallows amniotic fluid that is processed by fetal kidneys and gut Amniotic fluid volumes are assessed by ultrasound - excess (polyhyramnios - oesophageal and duodenal atresia/ CNS abnormalities) or deficiency (oligohydramnios - poor or absent renal function / reduced placental function - pre eclampsia

Answer 265

Whilst withdrawal from pain can be limited at 15 weeks, thalamocortical projections do not reach maturity until week 29 Completion of myelination in corticospinal tracts is not complete until post natal period but musculoskeletal movements are essential for fetal growth

Answer 266

``` Placental progesterone promotes fetal corticosteroid production especially near term and is also vital for fetal physiology (esp. CVS function) Thyroid hormones (active from week12) are all vital for nervous system development, bone and hair growth ```

Answer 267

Liver stores large amounts of glycogen which is reflected in changes in fetal abdominal circumference

Answer 268

At birth, physical trauma and cold temperature induces neonate to take its first breath - dramatic reduction In pulmonary vascular resistance and a dramatic rise in arterial pO2 - causes left atrial pressure to rise respect to right atrial pressure so closing the foramen ovale - smooth muscle sensitive to high pO2 in the wall of the ductus arteriosus contracts to close the ductus, so both fetal shunts are rapidly closed just by taking its first breaths * both shunts close off completely in a few weeks - ductus venosus variably remains open for several days after birth but closes within two or three months - a sphincter in the vessel constricts shortly after birth redirecting all blood through the liver sinusoids - again regulated by pO2 levels

Answer 269

Pre embryonic - fertilisation --> 3 weeks Embryonic - 3 --> 8 weeks Fetal - 8 --> 38 weeks

Answer 270

Growth and physiological maturation of the structures created during the (very much shorter) embryonic period

Answer 271

From date of LMP (i.e. Conception weeks + 2) | So term is 40 pregnancy weeks

Answer 272

Growth and weight gain accelerate in pregnancy

Answer 273

Crown Rump Length (CRL) is the measurement of the length of human embryos and fetuses from the top of the head (crown) to the bottom of the buttocks (rump)- increases rapidly in the pre-embryonic, embryonic and early fetal periods. ``` Weight gain is slow at first, but increases rapidly in the mid and late fetal periods. o Embryo • Intense morphogenesis and differentiation • Little weight gain • Placental growth most significant o Early fetus • Protein deposition o Late fetus • Adipose deposition ```

Answer 274

Body proportions change dramatically during the fetal period. o At week 9, the head is approximately half of the crown rump length o Thereafter, body length and lower limb growth accelerates. At birth the health is approximately one quarter of the crown rump length

Answer 275

Pseudoglandular Stage o Weeks 8 – 16 Canalicular Stage o Weeks 16 – 26 Terminal Sac Stage o Week 26 – Term Alveolar Period o Late fetal to 8 years

Answer 276

The lungs develop relatively late, as they are not needed until birth. o Embryonic development creates only the bronchopumonary tree • Airways, no gas exchanging parts o Functional specialisation occurs in the fetal period o Major implications for pre-term survival • Threshold of Viability • Viability is only a possibility after 24 weeks

Answer 277

o Weeks 8 – 16 o Duct systems begin to form within the bronchopulmonary segments created during the embryonic period • Bronchioles

Answer 278

``` o Weeks 16 – 26 o Formation of respiratory bronchioles • Budding from bronchioles formed during the pseudoglandular stage o May be viable at the end o More vascular o Some terminal sacs ```

Answer 279

o Week 26 – Term o Terminal sacs begin to bud from the respiratory bronchioles o Some primitive alveoli o Differentiation of pneumocytes • Type 1 – Gas exchange • Type 2 – Surfactant production from week 20

Answer 280

o Late fetal to 8 years | • 95% of Alveoli are formed post-natally

Answer 281

During T2 and T3 gas exchange occurs at the placenta. However, the lungs must be prepared to assume the full burden immediately after birth. o ‘Breathing’ movement • Conditioning of the respiratory musculature o Fluid filled • Crucial for normal lung development

Answer 282

The nervous system is the first to begin development and the last to finish. o Corticospinal tracts required for coordinated voluntary movements begin to form in the 4th month o Myelination of the brain only beings in the 9th month • Corticospinal tract myelination incomplete at birth, as evidence by increased infant mobility in the 1st year o No movement until Week 8 o After week 8 a large repertoire of movements develop • ‘Practicing’ for post-natal life • E.g. suckling, breathing The brain is the fastest developing organ in the fetus and infant. On average it accounts for 12% of body weight at birth, falling to about 2% in adults. During the fetal period important changes occur, structurally and functionally. o Cerebral hemisphere becomes the largest part of the brain • Gyri and sulci form after 5 months as the brain grows faster than the head o Histological differentiation of cortex in the cerebrum and cerebellum o Formation and myelination of nuclei and tracts o Relative growth of the spinal cord and vertebral column

Answer 283

Hearing and taste mature before vision. The organ of corti in the inner ear is well developed in the fetus at 5 months, but the retina is immature at birth.

Answer 284

Maternal awareness of fetal movements o Fetal movements can be seen by USS at Week 8 o Maternal awareness of fetal movements from Week 17 onwards o Low cost, simple method of ante-partum fetal surveillance o Reveals fetuses that require follow-up

Answer 285

The fetal cardiovascular system is arranged to ensure oxygenated blood collected by the umbilical vein at the placenta is circulated around the fetus. The definitive fetal heart rate is achieved around 15 weeks o Fetal bradycardia is associated with fetal demise

Answer 286

Kidneys o Ascent of kidneys complete at week 10 o Fetal kidney function begins in week 10 • Functional embryonic kidney is the Metanephros o Renal pelvis, calyces etc present by week 23 o Histological differentiation of cortex and medulla almost complete by 8 months o Fetal urine is a major contributor to amniotic fluid volume o Fetal kidney function is not necessary for survival during pregnancy, but without it there is oligohydramnios. Bladder o Lies in the abdominal cavity in the fetus and infant o Urine is emptied into the amniotic fluid, to be swallowed by the fetus. o Bladder fills and empties every 40 – 60 minutes in the fetus (seen on USS)

Answer 287

Threshold of Viability Viability is only a possibility once the lungs have entered the terminal sac stage of development (after 24 weeks). Brain Development Viability is only possible if the brain is sufficiently mature to control body functions, e.g. breathing. Respiratory Distress Syndrome o Often affects infants born prematurely o Insufficient surfactant production o If pre-term delivery is unavoidable or inevitable • Glucocorticoid treatment (of the mother) • Increases surfactant production in the fetus

Answer 288

Ultrasounds- Doppler (blood vessels); Non stress tests (heart rate changes associated with fetal movements); biophysical profiles (5 measured variables); fetal movement kick charts Developmental criteria- crown rump length; foot length; biparietal diameter of head; abdominal circumference; femur length; weight and appearance after delivery; Symphysis – Fundal height Daily rhythms Duration of pregnancy- fertilisation age; age since mother's last menstrual period Amniotic fluid volume Quickening

Answer 289

A fetus is regarded as having ‘growth restriction’ if weight is below the 10th percentile for gestational age. Depending on the cause a fetus with growth restriction may be compromised in the uterine environment and require closer monitoring in order to allow the continuation of the pregnancy to term. o Symmetrical Growth Restriction • Growth restriction is generalised and proportional o Asymmetrical Growth Restriction • Abdominal growth lags • Relative sparing of head growth • Tends to occur with deprivation of nutritional and oxygen supply to fetus

Answer 290

o Distance between symphysis pubis to top of uterus (fundus) o Measured with a tape measure • Number of fetuses can cause variation • Volume of amniotic fluid can cause variation • The lie of the fetus can cause variation

Answer 291

``` Oligohydramnios o Too little o Placental insufficiency o Fetal renal impairment o Pre-eclampsia ```

Answer 292

``` Polyhydramnois o Too much o Fetal abnormality • E.g. inability to swallow • Structural – blind-ended oesophagus • Neurological – unable to coordinate swallowing movements ```

Answer 293

Nervous | MSK

Answer 294

Respiratory Nervous MSK

Answer 295

Nervous | MSK

Answer 296

Urinary GI Utero placental

Answer 297

CVS Autonomic Nervous

Answer 298

``` Classification of Birth Weights o < 2,500g = Growth Restriction o 3,500g = Average o > 4,500g = Macrosomia o Maternal diabetes ```

Answer 299

Poor Nutrition in Early Pregnancy o Neural tube defects • E.g. DiGeorge Syndrome Poor Nutrition in Late Pregnancy o Asymmetrical Growth Restriction • Subsequent oligohydramnios