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presented to you by: Cardiff University Cardiovascular Society in collaboration with chips & cuss S1/S2 secrets Case 4 Kate Bailey 2023-2024TODAYS SESSION WILL COVER Female pelvic anatomy and histology (some male) Hormones in the menstural cycle Puberty Contraception ANTIBIOTICS STI’s and UTIGeneral gross female anatomy Anatomy of the ovary Cortex: more peripheral, dense irregular connective tissue, numerous follicles Medulla: loose connective tissue, rich Hillum: where blood vessles, neurovascular network which enteres nerves, lymphatics enter and exit through hilum of ovaryAnatomy of uterine tubes Fimbriae = ciliated finger like projections that capture ovum. Epithelium = simple columnar Peg cells and cilaited cells for secretion Ampulla is the site of fertilisation!! Comparison ampulla and isthmus AMPULLA ISTHMUS 1.Wide and 1.Narrow and straight convoluted (coiled) 2.THICK wall 2.THIN wall 3.Less convoluted 3.Highly convoluted mucosal folds mucosal folds 4.Oocyte moves 4.Oocyte moves through SLOWLY through QUICKLY Question 1 reveals fibroids and the doctor explains that they are likely to be preventing embryo implantation. Where are they likely to be located? A Cervix B Uterus - submucosal C Uterus - suberosal D Vagina E Uterus - intermural Question 1 - Answer Uterus - submucosal B Fibroids causing difficulty conceiving are likely to be submucosal, as here they lie in the uterine cavity and disrupt the process of embryo implantation. Intramural and subserosal fibroids are unlikely to do so. However, subsersoal may cause mass effect symptoms such as increased urinary frequency (pressing on the bladder) and constipation (pressing on the bowels). Fibroids are not typically found outside the uterus. UTERUS ANATOMY The uterus is anteverted and anterlexed in majority of women If any internal bleeding e.g. ectopic pregnancy the bloiod collects in the rectouterine pouch MYOMETRIUM ENDOMETRIUM 1.Simple columnar epithelium 1. Smooth muscle + 2.Longitudinal folds, spiral connective tissue 2. 3 layers: spiral, arteries (site of implantation so needs to be vascularised circular, and glands) and endometrial longitudinal muscle glands 3.2 layers: stratum basalis present throughout and stratum functionalis (sheds) endometrium myometrium Question 2 a sensation of heaviness and 'dragging' consistent with prolapse.ast year. She reports A ligament that runs between the cervix and lateral pelvic wall has been damaged. What is the name of the affected ligament? A Ovarian ligament B Cardinal ligament C Broad Ligament D Round ligament E Suspensary ligament Question 2- Answer B Cardinal ligament The cardinal ligament runs between the cervix and the lateral pelvic wall. Weakness of this ligament and/or the uterosacral ligament is responsible for many cases of uterine prolapse.. in LIGAMENTS 1.Ovarian ligament - connects ovary to side of the uterus 2.Round ligament - connects the uterus to the labia majora via the inguinal canal. 3.Suspensory ligament - contains the ovarian vessels and nerves 4.Broad ligament - double fold of peritoneum that attacthes the uterus to the pelvic walls 5.Cardinal ligament - connects cervix to lateral pelvic wall, contains the uterine artery and veins in CERVIX ANATOMY Endocervix: simple columnar secretory epithelium Ectocervix: stratified squamous non-keratinised epithelium (stratified to be more durable as exposed to outside) Cervical metaplasia: Stratified squamous epithelium replacing preexisting mucin producing columnar epithelium (non-cancerous condition) Cervical dysplasia: Invasion of cervical basement membrane by dysplastic nonkeratinized squamous epithelium Ectocervix is visible via speculum Arrow shows os in PELVIC ARTERIAL BLOOD SUPPLY Left common iliac and right common iliac branch out at L5 External iliac - no branches Internal iliac - uterine, rectal and gluteal arteries Exception testicular and ovarian arteries come DIRECTLY from AORTAPELVIC VNEOUS BLOOD SUPPLY in LEFT testicular/ ovarian veins drain into the renal vein RIGHT testicular/ ovarain veins drain directly into vena cava Question 3 cycle?of the following is a correct description of the proliferative phase of the menstrual A Occurs between day 15-28 Progesterone from the corpus luteum acts upon the endometrium to B stimulate endometrial glands Falls in oestrogen and progesterone cause degeneration of the C endometrium Oestrogen produced by the follicle results in thickening of the D endometrium and formation of spiral arteries and glands E FSH and LH cause the follicle to grow and mature Question 3 - Answer Oestrogen produced by the follicle results in thickening of the D endometrium and formation of spiral arteries and glands During the proliferative phase, the endometrium is exposed to increased oestrogen levels. The endometrium proliferates and becomes thickened, tubular glands extend and spiral arteries form (increased vascularity). Oestrogen also stimulates progesterone receptors on endometrial cells.Menstrual cycle The Hypothalamic-Pituatry-Gonadlal (HPG) Axis The hypothalamus, anterior pituitary glands and ovaries regulate the menstrual cycle. GnRH is released from the hypothalamus stimulates LH and FSH release from pituitary gland. FSH binds to granulosa cells to stimulate follicle growth, permit the conversion of androgens (from theca cells) to oestrogens and stimulate inhibin secretion. LH acts on theca cells to stimulate the production and secretion of androgens, triggers ovulation Oestrogen is produced by the ovaries, particularly the developing follicles. Thickens the endometrium in preparation for potential implantation. Moderate oestrogen levels exert negative feedback on HPG axis and high oestrogen levels (in absence of progesterone) positively feedback on the HPG axis. Progesterone produced mainly by the corpus luteum which forms the follicle after ovulation. Prepares uterine lining for implantation. If fertilization does not occur drop in progesterone levels lead to menstruation. The Ovarian Cycle The Ovarian Cycle Follicular phase day 1-13 Pulsatile release of GnRH from hypothalamus --> LH and FSH secreted from anterior pituitary. As there is little negative feedback due to low inhibin and steroid levels, resulting in an increase of LH and FSH stimulating follicle growth and oestrogen production. Only one dominant follicle can continue to mature, oestrogen levels rise and negative feedback reduced FSH levels. Follicular oestrogen eventually becomes high enough for positive feedback at HPG axis, increasing GnRH causing an LH surge (inhibin selectively inhibits FSH at anterior pituitary). Granulosa cells become luteinsied and express receptors for LH. Ovulation day 14 of cycle In response to the LH surge, the follicle ruptures and the mature oocyte is released and remains viable for fertilization for 24 hours. Following ovulation the follicle secretes oestrogen and progesterone reverting it back to negative feedback on HPG axis, inhibiting FSH in anticipation of fertilisation. Luteal phase day 15-28 The corpus luteum forms at the site of the ruptured follicle following ovulation. It produces oestrogens, progesterone and inhibin to maintain conditions for fertilization and implantation. At the end of this cycle in the absence of fertilization the corpus luteum spontaneously regresses after 14 days. The significant fall in hormones reboots the negative feedback and resets the HPG axis for the cycle to begin again. If fertilization occurs the embryo produces HCG which maintains the corpus luteum. The Uterine Cycle Proliferative phase Following menses the proliferative phase runs alongside the follicular phase preparing the reproductive tract for fertilisation. Oestrogen initiates fallopian tube formation, thickening of endometrium, increased growth and motility of the myometrium. Secretory phase Runs alongside the luteal phase. Progesterone stimulates further thickening of the endometrium, reduction of motility of the myometrium, thick acidic cervical mucus (prevents polyspermy). Menses Menses marks the beginning of a new menstrual cycle. Occurs in the absence of fertilization once the corpus luteum has broken down and internal lining of uterus is shed. Question 4 Which of the conditions listed below would cause hypergonadtropicve. hypogonadism? Turner syndrome A Adrenal hyperplasia B C Hyperprolactinamia D Pituatry tumour E Cystic fibrosis Question 4 - Answer Turner syndrome A Adrenal hyperplasia = precious Turner’s syndrome: puberty, GnRH independent Lack of second X chromosome in Hyperprolactinaemia = prolactin females (mosonomy). directly inhibits GnRH so this is a Ovaries fail to develop or are secondary cause of hypogonadism damaged and do not respond to and hypogonadotropic hypogonadism hormones. Pituatry tumour = precocious puberty, Therefore this is primary hypogonadism or GnRH dependent hypergonadotropic gypogonadism Cystic fibrosis = cause of as the HPA axis IS SWITCHED ON. hypogonadotropic hypogonadism in men PUBERTY PRECOCIOUS NORMAL DELAYED Development of secondary sexual Males: 10-15 Development that occurs at a characteristics before 8 y/o in First sign is testicular growth LATER age than normal females and 9y/o in males. Females: 9-13 2 types: 1.HYPOgonadotropic( or 1. Gonadotropin dependent First sign is breast development. SECONDARY) hypogonadism due to premature activation of the Growth hormone (GH) increases - HPG axis does NOT get hypothalamic-pituatry-gonodal axis. switched on FSH and LH raised, high GnRH initially causing a growth spurt. panhypopituitarism, usually idiopathic or CNS lesion Kallmann syndrome, cystic (usually follows normal puberty) HPG (hypothalamus-pituitary- fibrosis gonadal) axis activated --> FSH 2. HYPERgonadotropic ( or 2. Gonadotropin independent AND LH released. PRIMARY) hypogonadism due to excess sex hormones -HPG axis is switched on but FSH and LH low, normal GnRH gonads do not respond to it adrenal hyperplasia or leydig FSH stimulates eostrogen. LH stimulates androgen -Direct testicular cell tumour damage/ovarian damage, mumps production. Question 5 She has suffered from migarines with aura for 4 years. Which of the following methods? contraceptive methods is classed as having no caution or contraindications to use with this condition? A Combined oral contraceptive pill B Progesterone only impant C Progesterone only pill D Copper intrauterine device E Levongesterel-releasing intrauterine device Question 5 - Answer D Copper intrauterine device Migarine with aura is a COMPLETE contraindication to the COCP. Progesterone based methods of contraception are classed as ‘advantages outweighing risks’ in patients with migraine with aura The COPPER IUD is the only form of contraception with NO RISKS for MIGRAINE WITH AURA also patches and ring which release oestrogen and progesterone risk of breast + Combined oral contraceptive pill cervical cancer reduced risk of ovarian + Mechanism of action endometrial cancer Oestrogen and progesterone provide negative feedback to the hypothalamus and inhibiting the production of GnRH. --> GnRH promotes release of LH and FSH from pituitary gland. Therefore preventing ovulation. Progestrone thickens cervival mucus and inhibits proliferation of the endometrium. Contraindications UK medical eligibility criteria states that UKMEC 1 = no risk, UKMEC 2 = advantages outweigh disadvatages, UKMEC 3 = disadvantages outweigh advantages, UKMEC 4 = unacceptable health risk Examples of UKMEC 3 conditions: >35 years old and smoking less than 15 cigarettes per day, BMI >35, FHx of thromboembolic disease, carrier of genes asscoiated with breast cancer UKMEC 4 = 35 years + and smoking more than 15 cigarettes per day, Hx of thromoembelic disease, migraine with aura Other Progesterone only pill is Pill taken every day - people can have withdrawal bleed to mimic periods if wanted <1 in 100 pregnancy if taken correctly - does not protect against STIs alternative must be taken at the same time every day Long-acting reversible contraceptive methods (LARCs) most effective form of contraception Intrauterine contraceptive devices Injectable and implantable Both are over 99% effecrive!! Depo Provera is the main injection in UK Intrauterine device --> prevents fertilization by causing decreased sperm mobility (copper contains medroxyprogesterone -> inhibits ovulation and thickens cervical mucus ions) IM injection every 12 weeks Immediately effective and effective for 5 Injection cannot be reversed once given and years can make periods heavier longer and more potential delayed return to fertility Nexplanon is a subdermal contraceptive impant painful contains the progesterone hormone Intra uterine systems - levongestrel prevents etonogestrel endometrial proliferation and causes cervical Most effective form of contraceptive 0.07/100 mucous thickening lasts for 3 years effective for 5 years does not contain oestrogen: can be used for women experience light periods and some migraines and thromboembolism women have no period can cause heavy/irregular bleeding Emergency contraception Levongestrel Ulipristal IUD Must be fitted within Must be taken within Must be taken within 120 hours of 72 hours of 120 hours of unprotected sexual unprotected sexual unprotected sexual intercourse or 5 days intercourse intercourse before ovulation stops ovulation and Selective Most effective inhibit implantation single dose of progesterone method of levonorgestrel 1.5mg receptor modulator - emergency -> inhibits ovulation. contraception (progesterone analogue) Abortion Abortion can be performed up to 24 weeks, two registered practioners must sign a legal document and only a registered medical practitioner can perform an abortion. 1.Mifepristone Blocks the action of progesterone halting the pregnancy and relaxing the cervix 2. Misoprostol Prostaglandin analogue taken 48 hours after mifepristone. Prostaglandins soften the cervix and stimulate uterine contractions 3. Oxytocin IV Induces regular waves of myomeytrial contractions.ANTIBIOTICS Difficult places for antibiotics to reach: blood brain barrier prostate eye intracellular bacteria Antibiotic resistance is an issue due to overuse and inapropiatre drug use Question 6 urgent chest X-ray is arranged. Sputum cultures reveal that he has pneumonia. He is started on erythromycin. What is the mechanism of action of erythromycin? A Inhibits RNA synthesis B Inhibits protein wall syntheis C Binds to 50S subunit of ribosomes D Binds to 30S subunit of ribosomes E Inhibits DNA syntheis Question 6 - Answer C Inhibits 50S subunit of ribsomes High Yield !! Erythromycin is a macrolide, which works by inhibiting the 50S subunit of ribosomes. This prevents the production of proteins from bacteria.Inhibits cell wall synthesis Beta-lactams MOA: binds transpeptidase blocking cross- linking of peptidoglycan cell walls Used for mostly gram positive Examples: infections penicillins - icillin suffix staphylococcus cephalosporins - cef or ceph prefix streptococcus Co-amoxiclav= amoxicillin+ clavulanic acid Penicillin and ceftriaxone can cross Side effects: hypersensitivty reactions (skin blood brain barrier so used for rashes), GI disturbances meningitis - inflammation of meningies in brain.Protein syntheis inhibitors block initiation of bacterial protein by binding to the 30S ribosomal subunit Aminoglycosides Tetracyclines Example: Gentamicin Example: Doxycycline - suffix cycline Treats: gram negative infections - campylobacter and Treats: broad spectrum e.g. staphylococcus neisseria, pseudomonas. chlamydia and malaria. Side effects: otoxicity (hearing and balance), Side effects: oral thrush, increased chance of optic nephrotoxocity, neuromuscular efffects. disk swelling, photosensitivity. Contraindicated in ELDERLY patients and patients Contraindicated in children under 12 as discolours with renal toxicity. teeth and pregnancy. block initiation of bacterial protein by binding to the 50S ribosomal subunit Macrolides Chloramphenicol Example: Azithromycin - suffix ‘mycin’ Treats conjunctivitis. Side effects: GI disturbances, increases QT interval. Not commonly used as can cause aplastic anemia. Can raise INR so monitor patients on warfarin. Can go into cell = treat intracellular infection.DNA synthesis inhibitor RNA synthesis inhibitor Fluoroquinolones Rifampicin Example: ciprofloxacin - contains ‘flo‘ Used to treat several types of mycobacterium infections in MOA: inhibit topoisomerase II (DNA gyrase) and topoisomerase IV. combination with other Topoisomerase II cuts DNA in DNA antimicrobials replication so quinolones prevent this. side effects: lower seizure threshold, tendon rupture, lengthens QT interval. Nitrofurantoin used to treat UTIs. MetronidazoleFolate synthesis inhibitor Not effective in the presence of pus!! As pus contains dead neutrophils 1.Sulfonamides e.g. Sulfamethoxazole and bacteria which the bacteria 2.Trimethoprim can take building blocks needed for folate synthesis. These two antibiotics are taken together to form + co-trimoxazole - side effects: hyperkalaemia, headache, rash (including Steven Johnson syndrome) Folate is needed by bacteria to syntheise DNA(nucleic acid) and help them grow. Question 7 new relationship.e requests screening for sexually transmitted infections after starting a What is the most commonly diagnosed sexually transmitted infection in the UK? A Gonnorhea B Genital herpes C Genital warts D Chlamidya E Syphylis Question 7 - Answer D Chlamidya High Yield !! Chlamydia is the most prevalent STI in the UK and 7/10 cases are Other common STIs asymptomatic in women and include genital 5/10 in men. warts, gonorrhea and genital herpes. SYMPTOMS CAUSE TREATMENT Chlamydia Asymptomatic in 7/10 women and Chlamydia Trachomatis, Doxycycline (7 day course) first line 5/10 men gram negative Or Azithromycin Most common STI If not treated can lead to pelvic Females: cervicitis, unusual discharge, bleeding, dysuria inflammatory disease. Males: urethral discharge, dysuria Females: dysuria, yellow or green IM injection ceftriaxone or single Gonorrhoea vaginal discharge, lower abdominal Neisseria gonorrhoeae, dose of oral ciprofloxacin pain, abnormal vaginal bleeding intermenstrual or poscoital gram-negative If not treated can lead to PID or diplococcus Males: dysuria, yellow or green prostate infection discharge, increased freuqnecy of urination, testicular pain or swelling human papillomavirus HPV Types 6 and 11 = genital warts small non-enveloped For warts topical creams podophyllum or imiquimod. Types 16 and 18 = cervical cancer DNA virus Cryotherapy is also considered. Primary features: chancre (painless sore) at site of Syphilis sexual contact, local lymphadenopathy. Secondary features, 6-10 weeks after infection: rash on trunk, palms and sole, fever, lymphadenopathy, Treponema IM injection of penicillin fever, alopecia, condylomata lata (grey wart-like pallidum, gram- is the first-line lesions around the genitals and anus). negative spirochaete management Tertiary features: can affect any organ important is (spiral bacteria) neurosyphilis = paralysis, blindness, difficuties in movement and coordiantion Trichomonas Females: white/yellow/green discharge with fishy Trichomonas smell, pH > 4.5, strawberry cervix vaginalis, flagellated oral metronidazole Males: usually asymptomatic protozoan parasite, highly mobile Herpes simplex virus primary infection: may present with : may present HSV 1 = oral lesions HSV with a severe gingivostomatitis HSV 2 = genital topical aciclover for sold cold sores herpes cores oral aciclover for genital painful genital ulceration however now herpes considerable overlap UTI’s Causes Treatment Most common: Escherichia coli, gram-negative, anaerobic, rod- Non-pregnant women and men: shaped bacteria. nitrofurantoin or trimethoprim Easily spread from faeces to bladder. Other gram negative causes: Klebsiella pneumoniae Pregnant women: nitrofurantoin or amoxicillin (trimethoprim is Gram positive causes: Pseudomonas aeruginosa and teratogenic = harm foetus) Staphylococcus saprophyticus Symptoms Dysuria (pain, stinging when peeing) Upper UTI e.g. acute Suprapubic pain or discomfort pyelonephritis increased frequency Symptoms = fever, back increased urgency pain (can lead to sepsis) fever haematuria Lower UTI e.g. cystitis confusion is commonly the only symptom in elderly patients Prevention of UTI 1.There is one way flow of urine in ureter 2.Cysto-uretic valve prevents backflow of urine to kidneys 3.Regular micturition flushes out the bladder and urethra Micturition - contraction of the detrouser muscle in the bladder to pass urine The longer the catheter is in place the more likely bacteria will grow in urine Risk Factors All pregnant people offered Catheterisation regular testing for UTI Pregnancy During menopause the microflora Female Age and hormonal change makes people more susceptible to UTI Sexual activity Male urethra = 16-22 cm Female urethra = 3-5cm Females are more susceptible to UTI due to proximity Thank you QR code instagram: @cu_cardiosoc this is a fake one facebook: Cardiff university cardiovascular society use a real one