The Reproductive System.docx 2580KB Apr 11 2010 - LUSUMA - Home

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The Reproductive System.docx 2580KB Apr 11 2010 - LUSUMA - Home

  1. 1. The Reproductive System Gametes– form fromdiploidgermcells –separatedfromsomaticcellsearlyinembryoniclife. Female –the ovum Male – the sperm Numberof female gametesproducedlimitedbynumberthatcan be supportedthroughgestation. Roughly12 – 14 a yearfor about40 years making400 intotal. A womenisonlyable toconceive ononly25 – 30 days a years.So malesproduce alot of sperm. Roughl7 700 a second. Gametesare producedinthe gonads (ovariesortestes).Internal &external genitalia Control of reproduction – coordinatedmainlybyhormones  Gonadotrophins –anteriorpituitary –LH & FSH (bothglycoproteins)  Gonadal steroids – female (oestrogen&progesterone) male (testosterone).  Posteriorpituitary –Oxytocin(functions: milk&others)  Anteriorpituitary –prolactin(milk&others) &TSH, GH, ACTH Development Germ cellsarise 3 weekspostconception.Geneticsex determinedby chromosomesof germcells. Germ cellsarise nearallantois&migrate togenital ridge formingthe primordialgonad.Gonadmade up of germ cellsplussomaticcellsfrom primordial gonad.Primordial gonadhascortex &medulla. Primordial gonadcanformeitherovaryor testis – whichdependsongeneticsex.Male germcells colonise the medulla,formingdefinitive sexcordswhichwill becomeseminiferoustubules connectedtothe urinarysystem. Testis:Germ cellsassociatedwithSertoli cells (secreteMIH) expressSRYgene whichinfluences subsequentmasculinisation.Leydigcellsdevelopbetweensex cords&secrete testosterone. Ovary: Female germcellscolonise the cortex of the primordial gonad.Germcellsbecome surroundedbymesenchymalcellseventuallyformingprimordial follicles.Cortexdevelopsevenif no germcellsarrive. Internal genitaliafoetushas2 duct systems:  The wolffianductformsmale internal genitalia o In the female regressesspontaneously o In the male stimulatedtoformepididymus,vasdeferens,seminal vesicles  The mullerianductformsfemale internal genitalia(Mformother) o In the female thisformsfallopiantubes,uterus,cervix &upperpartof vagina o In the male mullerianinhibitoryhormone secretedfromSertoli cellsisreleased whichcausesregression
  2. 2. Primordiaof external genitaliabipotential  Urethral folds  labiaminorain female &shaftof penisinmale  Genital swellings  Labiamajorainfemale &scrotuminmale  Genital tubercle  clitorisorthe glansof penis  Female versionsdevelopif noGonadal steroidssecretedbygonads(orotherendocrine glands)  Male external genitaliaproducedbytestosteronefromLeydigcellsintestis. The normal human conditionisfemale,the male isadistortion.Developmentmustbe affectedby MIH & testosterone toformamale. Origin of the Gametes Aftercolonisingthe gonad,germcellsgoontoproliferate bymitosisthenreshuffle genetically& reduce to haploidbymeiosis&cyto-differentiateintomature gametes. The female: Germ cellscolonisethe Gonadal cortex &become oogonia.These proliferate rapidlybymitosisto about7 millionmidgestation.Mostdie duringgestation&the remaining2millionall entermeiosis before birth. Entry to meiosisstimulatedbysurroundingcells,meiosisstopsatprophase.Formingaprimary oocyte,surroundedbysingle layerof granulosacellstoformthe primordial follicle The female hasdevelopedherentirestockof potential gametesbefore birth.Nonew folliclescan arise later,startingat pubertyfolliclesbegintodevelopfurther.A small proportionstartstodevelop at any one time. The cycle:Most developinggametesdie,eachmonthone ortwo complete development.The release of the resultingovum –ovulationisthatstart of a veryshort periodof fertility(about 36hrs).The ovumsitsin the ampullaatthispoint. Ovulation isprecededbyaperiodof preparation:where the ovumdevelops,reproductive tract preparedforspermtransport& implantationof conceptus,changesinrestof bodytomaximise chancesof conception. If the ovumisfertilisedthe conceptusisinitiallytoosmall tosignal itspresence.Furtherproduction of gametesissuspendeduntil pregnancycanbe confirmedbysecretionof placentalhormone.A periodof waiting(bodypreparesforpregnancy).The liningof the uterusisshedat the endof an unsuccessful cycle (menstruation).The humanreproductive cycle iscalledthe menstrual cycle. Thisis:  28 days long  Starts on firstdayof bleeding  Ovulation12-14  Preparatoryphase 0 -12 daysfollicularorproliferativephase  Waitingphase 14-28 (luteal orsecretoryphase)
  3. 3. At the beginningof the menstrual cycle asmall numberof gametesthathave alreadystarted developmentbegintodevelopfurther. Folliculardevelopment:primordial folliclesdeveloptopre-antral follicles –independentof hormonesthe zonapellucida,more granulosacell layers&a theca isformed.Anantrum(fluidfilled space) develops. Growth of follicles,afterthe beginningof the cycle,underinfluence of FSH& LH one or twofollicles grow to 20mm. Theca secretesincreasingamountof oestrogen,pre-ovulatoryfollicle whichis capable of rupture to release ovum,thenLHsurge triggersrupture. Ovulation:justbefore ovulationmeiosisrestarts.Firstdivisioncompletedmakesfirstpolarbody. Seconddivisionnottill afterfertilisation.Laststagesof meiosisoccurveryquickly. Afterovulationthe follicle reorganisedtoforma corpus luteum,whichgrowsunderthe influence of LH & secretesoestrogen&progesterone &diesafter14 days. The male Germ cellscolonisethe sex cords(medullaof primordialgonad) &before birthproliferatebymitosis, formingspermatogonia.Atpubertythe cordsfollow outtoformseminiferoustubules& spermatogoniaclusteraroundthe periphery. Spermatogoniamaintainedbymitosis –‘raw material’of spermatogenesisavailableforupto 70 years.A1 spermatogoniaarise &these divideafixednumberof timesbymitosiswhichforms256 clonesthese are primaryspermatocytes. Clone of primaryspermatocytesall linkedbycytoplasmMeiosisbegins:  Each spermatocytesforms4 haploidspermatids  Movingtowardsthe lumenasitdoes(thisforms1024) in total.
  4. 4. Spermatidsare released&remodel astheypassdownthe tubule throughthe rete testis,ducti efferentes&epididymistoformspermatozoa. Deliveryof spermtothe female Semen:  Secretionsof seminal vesicle (60%)  Secretionsof prostate (20%)  Sperm(viavasdeferens)  Secretionsof bulbo-urethral glands.  100ml containsfructose Mixedbyemission(sympatheticpathway);intovaginabyejaculation(parasympathetic) Functionsof semen:keepspermalive,motile&trapsthemin the cervix.Itexertsinfluenceonthe female tractto contact to helpsemenpropel up. Histology of the Male reproductive tract TheTestes Each testisissurroundedbya capsule (tunicaalbuginea),&consistsof anumberof seminiferous tubuleswhichdrain  rete testis  efferentductulesleadtothe epididymiswhichishighlycoiled. Belowthe tunicaalbugineathisisthe tunica vasculosa(whichisvascular).
  5. 5. Each seminiferoustubule issurroundedbyperilobularCT.Surroundingthe tubulesare Leydigcells, whichsecrete testosterone. The male germ cellsdeveloptoformspermatogonia whichdifferentiate intofirstlyspermatocytes, thenSpermatids&finallymature sperm.2typesof spermatogoniaexist(type A dark,type A pale & type B).Type A dark spermatogoniaare the stemcellswhose divisionresultsinthe formationof more type A dark & some type A pale.Mitoticdivisionof type A pale increasesthe pool of these cells whichthenmature intotype B cells  whichwill mature intospermatocytes. Seminiferoustubulesare linedbycellswithdifferingmorphologies;these are the developingmale gametes.The seminiferousepitheliumalsocontainsSertoli cells. Sertoli cellsextendthroughthe depthof the seminiferousepithelium&serve asupportingrole forgermcells. As the developinggermcellsmature theyare envelopedbyprocessesof Sertolicells.The membranesof these lattercells,atthe pointswhere theysurroundgermcellsare connectedbygap junctionsthatserve toform a blood/testisbarrier&protectthe germcellsfromsome materials carriedin the blood.Cellsproducedfromthe same spermatogoniummature spontaneously.Pre- pubertal developmentof SertolicellsrequiredFSH.The cellsalsocarry testosteronereceptors which are essential fornormal germcellsdevelopment. The rete testisconsistsare linedbya cuboidal epithelium;flow intoefferentductules. The epididymisis4-6mlong.The epididymisislinedbya pseudostratifiedcolumnarepitheliumwith stereocilia.The outside layercontainsincreasingamountsSMas it approachesthe vasdeferens The firstpart of the duct has an absorptive function&alsomaybe involvedindigestingthe residual bodieslostfromthe spermduringmaturation.The muscle layersinthe head&bodyof the epididymisshowsrhythmiccontractionsbutinthe tail isunderautonomiccontrol inthe tail region. The epithelialcellsalsohave asecretoryfunctionproducingarange of proteinswhichcontribute to spermmaturation. The vas deferenstransportsthe male germcells fromthe epididymistothe ejaculatoryductwhich isformedbythe unionof the duct of the seminal vesicle &the terminal partof the vas. 3 layersof structure.The luminal surface islinedby epitheliumsittingonthe laminapropria. Externally there isa thick muscularcoat consistingof 3 separate layersof SM. the inner& outerlayersare arrangedlongitudinally;the middleone circularly& contract powerfullyduringejaculation. Vashas Pseudostratifiedcolumnarepithelium, withonlya few stereocilia.The foldingof the mucosal layerisdue to the tone of circularlayerof SM. Aftervasectomyspermare phagocytosedby the epitheliaof boththe vas & epididymis.
  6. 6. The pairedseminal vesiclesdevelopas outgrowths of the vasdeferens.Eachare coiled tubulosaccularglands.The mucosaishighlyfolded&consistsof an epitheliumsittingonalamina propria.Each glandularelementissurroundedbyamuscularcoat whichisactivatedbysympathetic activityduringejaculation.There isa pseudostratifiedcolumnarepitheliumthese formasecretion rich infructose & alsocontaina numberof proteins&prostaglandins.Theydonotstore spermbut provide 60% of the ejaculate. The prostate consistsof a numberof tubuloalveolarglands;the mucosal,submucosal&mainglands. Each group drainsseparatelyintothe urethra. The prostate is surroundedbya fibromuscularcapsule fromwhichseptae dividethe glandinto lobules;the secretoryelementsalsositina fibromuscularCTstroma.The glandssecrete acid phosphatase &alsoPSA.The epitheliumisheterogeneous&may be cubiodal,columnar, pseudostratifiedorevensquamous. Inoldermen,prostaticconcretionsare commonlyseeninthe glandularelements.Theseare lamellatedbodiescontainingproteins,nucleic acids,cholesterol & calciumphosphate.Because of the contentof calciumtheymaycalcify. Most of the prostate glanddevelopsfromthe same primordial areaof the urogenital sinusthat formsthe vaginal plate inthe female,makingthe prostate ahomologue of the uppervagina. Mesenchyme inthis tissue differentiatesintothe peripheralzone of the prostate.The transition & central zonesof the adultprostate are fromthe Wolffian duct,whilstthe peripheralzone arisesfrom the urogenital sinus.These distinctembryological originsmayexplainwhyBPHoccurs withinthe transition &central zoneswhile prostaticAdenocarcinomaoriginateswithinthe peripheralzone. Histology ofFemale Reproductive System The ovary iscoveredbya squamousepithelium(AKA germinative epithelium);althoughithas nothingtodo withthe formationof germcells.Ratheritis a layerof peritoneum&all of the germ cellsare derivedfrom yolksacendoderm. The Ovary consistsof an outercortex & innermedulla.Atone pole of the organisthe hilum. The medullaof the ovarycontainsnerves,bloodvessels&CT & stromal cells.The cortex of the mature ovary containsnumerousgermcellsinvariousstagesof developmentcalledthe primordial follicle.The primordialfolliclesconsistof anoocytessurroundedbyasingle layerof squamous follicularorgranulose cells. At puberty,the productionof FSHstarts the maturationof these primordial follicles.Initially,the surroundinggranulosacellsbecome cuboidal&eachoocyte issurroundedbya single layerof cuboidal cells.Thisstage of developmentiscalledthe unilaminarprimaryfollicle.The granulosacells dived&become stratified soformingamultilaminarprimaryfollicle. At thisstage a layercalledthe zonapellucidadevelopsbetweenthe oocytes&the granulosacells. The zona pellucidaisrichinglycoproteinswhichare importantduringfertilisation.Atthe outer marginof the developingfollicle,the ovarianstromal cellsdifferentiate intothe thecafolliculi which will developtosecrete steroidhormones. Nextstage  fluidfilledspacesappearbetweenthe granulosacellsformingasecondaryfollicle.
  7. 7. The fluidfilledspacesincreaseinsize &start a processwherebythe granulosacellsare pushed towardsthe peripheryof the developingfollicle. The continuedcoalescence of spacesbetweenthe granulosacellsresultsinafollicle withanumber of fluidfilledspaceswhichwill ultimatelyform asingle large antrum. At thisstage the follicle is knownas the ternaryfollicle &the oocytesissurroundedbyafew layersof granulosacellsknownas the corona radiata.As the antrum becomeslarger,the oocytesare pushedtoone side of the follicle where itwill sitona pegof granulosacellscalledthe cumulus oophorus. Final stage producingthe mature orGraafianfollicle occurswhenthere isasingle large fluidfilled antrum.Just priorto ovulationthe cumulusoophorus startstobreakdown& the oocytestogether withitssurroundingcoronaradiatafloatsfree inthe follicularfluid.Atovulationthe tissue surroundingthe mature follicle thins&becomesischaemic.The follicle ruptures&the oocytesare releasedtobe capturedbythe fallopiantubes. The initial developmentof the primordial folliclesoccursunderthe influence of FSH.Once developed the theca stimulatesoestrogen &risingoestrogenlevelsleadtoareductioninthe levelsof FSH& a increasingsecretionof LH> The LH surge controlsthe final maturationof the follicle,stimulates ovulation &leadstothe formation&the corpus luteum fromthe remnantsof the follicle. The corpus luteum develops fromthe granulosa&thecainternacellsof the rupturedfollicle.The granulosacellsare transformedinto granulosaluteincells by LH whichsecretes progesterone.The thecainternacellsbecome thecaluteincells &secrete oestrogen. In the absence of fertilisation,the corpusluteumstartstodegenerate withintwoweeksof ovulation.Itbecomesfibroses&hyalinisedintoawhite connective tissue. Duringregressionof the corpusluteumthe erythrocytesinthe centre of the corpusluteumare normallyremovedby macrophages.If thisprocessisincomplete,cellscontainingbreak downproductsof erythrocyte phagocytosisremaininthe regressingcorpus luteum.Underthese conditionsthe degeneratingcorpusluteumcanforma pigmentedstructure calleda corpusnigricans. Fallopian tube These collectthe releasedova,provide asite fortheirfertilisation&thentransportthe zygote tothe uterusforimplantation.Tube splitinto3parts:  the fimbrial which capture the ovum  The infundibulum, a bell shaped portion to which the fimbrial are attached.  the ampulla the wide segment in which fertilisation normally occurs  The intramural part within the uterine wall. The wall of the fallopiantube consists of an inner mucosa, a muscular layer & an outermost serosal covering. Throughout the tube the mucosa consists of an epithelium & underlying lamina propria. Regional variations  in the cells found in the epithelial layer.
  8. 8. All of the epithelial cellsare columnarinshape.One varietyissuppliedwithnumerousciliawhile the other,alsocalledpegcells,are non-ciliated & secretes mucus. The structure of the tube wall varies along its length. In the ampulla the muscle coat consists of two layers. In the isthmus the muscle layer is much thicker & has 3 layers. There are alsoregional variationsinthe mucosal layer.Inthe ampullathe ciliatedcellspredominate. The relative number of peg cells increase as the tube approaches the uterus. The uterus Two layers.The innermostlayer  endometriumlinedby simple columnarepitheliumwhichrests on a laminapropria.The laminapropriacontainsglands&connective orstromal elements.The outer,thicker,layeristhe myometrium&consistof 4 poorlydefinedlayersof smoothmuscle. The uterusreceivesitsbloodsupplyfromthe paireduterine arterieswhichbranchtoform the arcuate arterieslocatedinthe myometrium.The arcuate arteriesgive rise totwosetsof braches:  Straightarterieswhichramifyinthe stratumbasalis  Coiledarterieswhichsupplythe stratumfunctionalis. The significance of the functional &basal layers(of the endometrium) liesinthe factthatthe former isshedcompletelyduringmenstruation.Inthe nextcycle anew functional layerdevelopsfromcells liningthe glandsinthe basal layer. The precise structure of the endometrial layervariesatdifferenttimesduringthe menstrual cycle. The menstrual cycle iscontrolledbythe levelsof oestradiol &progesterone.  Proliferative phaseprimarilyunderthe control of oestrogen  Secretoryphase primarilyunderthe control of progesterone  Menstrual phase causedbythe suddendropin progesterone levels
  9. 9. At eachof these stagesthe endometriumhasacharacteristicappearance. Duringthe proliferativephase the stratumfunctionalis regenerates fromcellsliningthe glandsinthe stratumbasaliswhichremainintactduring menstruation.The growthinthe depthof the s. functionalisleadstoincreasinglengthof the endometrialglandswhichare straight,unbranched& tubularat thisstage.Cellssurroundingthe developingglands,the stromal cells,proliferate &bythe endof thisstage the spacesbetweenthe endometrial glandsare lackedwiththesestromal cells. Increasinglevelsof Pleadtofurtherdevelopmentof the endometrium.The glandsgrow more than the surroundinglaminapropria&so become coiled.The degreeof coilingissogreatthatin section the glandsappearto have a sawtoothappearance.Towardsthe endof thisstage there are also changesinthe stromaor laminapropria. The stroma become oedematous &the stromal cellsstarttodevelopintodecidualcells.If fertilisationoccurs,thenthe decidualcellscontribute tothe formationof the placenta&alsosecrete prolactin. In the absence of a fertilisedovum,progesterone levelsstarttodecline.Ataboutday28, the endometriumbreaksdown&isshed.Falling levelsof progesteroneleadtospasmof the spiral arteries.The stratumfunctionalisis therefore deprived&dies.The spasmof the arteriesisbelievedtobe due tolocallyreleased prostaglandins.Atthe coiledarteriesdonotgo intospasmthe stratumbasalisremains& inthe nextcycle proliferatestoforma new stratum functionalis. Cervix & Vagina The cervix extendsbetweenthe internalos& external os;thisportionknownasthe cervical canal. Like the uterus,mostof the cervical canal islinedbya simple columnarepithelium.Justonthe inner aspectof the external os,however,the epitheliumabruptlychangesto non-keratinisedstratified squamous.The cervical canal containsmanymucoussecretingglandsunderlyingthe epithelium. The pointat whichthe change fromcervical to vaginal epitheliumoccurschangesduring reproductive life The vaginais a fibromusculartube connectedtothe cervix tothe exteriorconsistingof amucosa, submucosal &muscularlayerwhichcontainsbothsmooth& skeletal muscle.The epitheliumisnon- keratinisedstratifiedsquamous.The epithelial cellsaccumulate glycogenunderthe influence of oestrogen.Thisglycogenprovidesasubstrate forthe numerouslactobacillifoundwithinthe vagina. Its metabolismaccountsforthe normally acidpHof the vagina. The vaginal lacksglands;itis lubricatedbymucousproducedbythe cervical glands& alsobythe vestibularglandswhichopenintothe vestibule.
  10. 10. At pubertythe junctionbetweenthe cervical &vaginal epitheliaoccursat the external osthere isa gradual movementof thisjunctionfromthissite intothe cervical canal duringreproductive life. Histology of the Breast The breast isrudimentaryatbirthinboth sexes&consistsof predominantlyof the ductsystem& the nipple which issurroundedbythe pink areola.Atpubertyinthe female,underthe influence of O, the breastenlarges accumulationof adipose &the ductsystembecomesmuchenlarged. The breast,at puberty,the secretoryportionsof the glandare poorlydeveloped& surroundedby Myoepithelial cells.The ductsare linedbya cuboidalto columnarepitheliumwhichchangesto stratifiedsquamousatlevelof the lactiferoussinuses;the ductsare surroundedby Myoepithelial cells.The mammaryglandsare stimulatedfurther duringeachmenstrualcycle asthe O peakinduces duct proliferationwhichinturnleadstoenlargement&sometimesoedema&tenderness. DuringpregnancyO resultsinproliferationof the ductsystemwhilstPinfluencesdevelopmentof the secretorytissues. Gross Anatomy of the breast The female breastisa modifiedsebaceousglandwhich,initsactive form, secretesmilk.Mature breastsare of variable size &shape butoftenapproximatelyconical withbase extendingfromthe lateral borderof the sternumto the mid-axillaryline &overlyingthe secondtosixthribs. The major featuresare the nipple,the areolawhichsurroundsthe nipple&the axillarytail.Itisoften saidthat the nipple overliesthe fifthintercostalsspace &isa guide tothe positionof the apex.True inyoungnot inold Each breast consistsof 15-20 lobulesradiatingoutfromthe nipple.The ductfromeach lobule hasa dilatedlactiferoussinusjustpriortoitsopeningontothe surface of the nipple.Eachlobule of glandulartissue isdelineatedbyfibrousCTsepta(suspensoryligament) extendingfromthe skinto the underlyingdeepfascia. The skinof the areolaisnot smoothbut hasmany tubercles;these are producedbythe underlying areolarglands.The breastoverliesthe musclesof the chestwall;betweenthe breast&fascia overlyingthesemusclesisapotential space,the retromammaryspace or bursa. The existence of thisspace accounts for the mobility of the breast. Part of the examinationof the breastinvolvesobservingthe regularityof the structure &the nature of the surface skin.Tumourswithinthe breastcanleadto shorteningof the suspensoryligaments whichwill cause distortion of the breast.Tumoursmayalsoleadtooedemaof the breastwhichcan resultindimplingof the skin. Each breast receivesitsbloodsupplyfromthe internalthoracicartery,intercostalsartery,lateral thoracic & thoracoacromial arteries.The venousdrainageof the breastisto the axillaryvein,the posteriorintercostalsveins &the internal thoracicvein. Most lymphfromthe lateral quadrantsof the breastdrainsto the axillarylymphnodes.The medial quadrantsdrainto the parasternal nodesor tothe opposite breast.
  11. 11. Session2 – The Control of Reproduction Anteriorpituitary –arisesfromRathke’spouch,notnervoustissue &endocrine gland  Glycoproteinhormones o FSH & LH producedby gonadotrophs o Thyroidstimulatinghormone–thyrotrophs.  Polypeptide hormones o Growth hormone – somatotrophs o ACTH – corticotrophs o Prolactin – fromlactotrophs (control of milkproduction&sperminmale) The posteriorpituitary –nervoustissue &neurosecretoryglandsecretesADH&Oxytocin(peptides) Anteriorpituitarysecretioncontrolledbyhypothalamusviareleasinghormonestravellingin hypophyseal portal circulation.Veinconnected twocapillarybeds thismeans↑concentrationof releasinghormone reachesthe anteriorpituitary. Gonadotrophinreleasinghormone(smallpeptide) releasedundercontrol of several differentgroups of nerve cellsinthe medianeminence).Releaseispulsatile ataboutonce an hour.Thissecretion stimulatesthe gonadotrophstosecrete FSH& LH. Amountof LH & FSH secreteddependshow GnRH acts on gonadotrophs.Proportionsof FSH& LH influencedbyotherfactorsactingon gonadotrophs Neuronesinfluencedbyotherneurones(inhypothalamus) environmental effects,bodyweight& feedbackfromGonadal steroids. Male – testosterone reducesGnRHsecretion Female –moderate titresof oestrogenreduce GnRHsecretion(negativefeedback)buthightitresof oestrogenalone promote GnRHsecretion –positive feedbackcausingLHsurge. Progesterone increasesinhibitoryeffectsof moderate oestrogen,&preventspositive feedbackof high oestrogensostoppingLHsurge. O ↓GnRH perpulse,P ↓ frequencyofpulses. Control at anteriorpituitary:  Male – testosterone  ↓LH& ↓ FSH secretion  Female –Oat moderate titres↓LH& ↓ FSH secretionbutat hightitres↑LH& ↑ FSH.  In both– inhibinfromgonad↓FSHsecretion selectively;Soinhibinsecretionrelatedto developinggametes. The Male Hypothalamic Pituitary axis in the male the hormone levelsmustbe constantinthe medium&long term& thisisachievedbynegative feedbackcontrol. FSH bindstoSertoli cells(productionof sperm) LH bindsto Leydigcellswhichsecretetestosterone,
  12. 12. promote spermatogenesis&maintainsthe reproductive system.Inhibintherefore relatedtorate of spermatogenesis. LH ↑Tsecretionbuttestosterone↓GnRHsecretion. If testosterone levelsget↑,GnRH& therefore LH levels↓,bringingTlevelsbacktonormal range. If spermatogenesisspeedsup↑inhibinsecretion whichreducesFSH& bringsrate back to normal In the medium&longterm testosteronelevels constantbut it ishighestinthe morning&effectsof environmental stimulibothdrivenbybrain. Testosterone hasdeterminativeeffectsonsecondary sexual characteristicswhichare notreversible & regulatoryeffectsonthe adultreproductive system. The Menstrual cycle  Follicularor‘proliferativephase’: o Folliclesgrowinovary o Uterus preparedforsperm transport& implantationof conceptus o Changesto facilitate sexual interactions  Ovulation Briefperiodof fertility (36 hours) formationof corpus luteum(remainsinfollicles&grows)  ‘luteal orsecretoryphase’  Corpus luteuminovarychangesin preparationforpregnancy Highprimatesonly:ovulationsspontaneous, corpus luteumalsoformsspontaneously, preparatory& waitingphasessimilar duration& endedbysheddingof partof endometrium. FSH stimulates &LH maintains the growthof antral follicles Follicularphase:FSHbindstogranulosacells&LH to thecal.Stimulate developmentof follicle. Pre-ovulation –LH surge stimulatesovulation The LH surge has fourmajor effects
  13. 13. 1. the oocyte restartsmeiosiswithin3hrsof LH surge 2. The firstmeioticdivisioniscomplete-->formationof one daughtercell &a polarbody 3. 20 follicle entersmeiosisII &arrests3hrs prior to ovulation 4. The follicle size increase dramaticallydue tothe increase influidinthe antrum. LH stimulates the activityof collagenaseswhichcausesthe follicle toweaken &rupture Luteal phase – LH maintainscorpusluteum. Follicularphase oestrogensstimulate:  Fallopiantube function  Growth & motilityof myometrium(supportssperm)  Thinalkaline cervical mucus  Vaginal changes(secretions)  Changesinskin,hair& metabolism  Calciummetabolism. Luteal phase progesterone actsonoestrogenprimedcells(nevergetprogesterone onitsown)  Furtherthickeningof endometriuminto secretoryform  Thickeningof myometrium,butreductionof motility  Thick,acid cervical mucus(causesspermtobecome acid)  Changesinmammarytissue  Increasedbodytemperature  Metabolicchanges  Electrolyte changes Gonadotrophinssecretedbypituitarygonadotrophs.Stimulatedbypulsatile release of GnRHfrom hypothalamuswhichismodifiedbyfeedbackeffectsof Gonadal hormones. Cycle Corpusluteumabsent,folliclesonlypartdevelopedsecretionof steroidorinhibinverylow.O& P levelslow.Little inhibitionathypothalamusorpituitary.FSHlevelsrise. Effectsof FSH: FSH bindstogranulosacells,folliculardevelopmentcontinues, thecainterna develops,(stimulatedbyLH) secretesandrogenswhichare convertedbygranulosacellsinto oestrogen& so oestrogen&inhibinare secreted Mid follicularphase –Olevelsrising,inhibinlevelsrising –selective inhibitionof FSHnonew follicles can develop.Oexerts+’ve feedbackathypothalamus&pituitary.SoLHstarts to rise butnot FSH. Pre-ovulatoryphase–risingO increaseschange of LH surge (release of ovumoccurs) precise Humans– little evidenceforcircadianeffects,butsome evidence of effectsof copulation.Lotsof evidence foreffectsof stress(slowsitdown) soprecise timingof ovulationaffectedbythe environment. The windowof opportunity,risingoestrogenlevelscreate awindow of opportunityforovulation precise timingwithinitdependentonenvironment. Afterovulationinhumanscorpusluteumformsspontaneously,beginsto secrete P& O maintains suppressionof FSH.LH alsosuppressedbecausepositivefeedbackinhibitedbyP.
  14. 14. The luteal phase – corpusluteumgrows& secretesmore steroidsafter14 dayspreciselyitdiesby secretingprostaglandinswhichshutsoff itsblood supply&steroidlevelsdrop. Start of the newcycle – deathof corpusluteum, leadstorapidfall insteroidlevelswhichstimulate mensesrelievesinhibitiononFSH& off we go again. Timingsthe interval fromovulationtomensesisveryconstant14 daysvariationincycle lengthis due onlyto variationintimingof ovulation. The pelvicclose – The eventsof the ovariancycle provide atimingsignal viathe effectsof steroids on the hypothalamus&pituitarybasisof the control of reproductive cycles. Pregnancy – if conceptionoccurs,conceptusimplants&developingplacentasecreteshuman chorionicgonadotrophinwhichpreservescorpusluteum. The corpus luteumsecretes↑amountsof steroidscausingmanyphysiological changesbutplacenta soonsecretesevenmore &by about12-14 weekscorpusluteumnolongersupportspregnancy. Session3 – Puberty & the Menopause Pubertygirls8 -13 years  Breastbud (thelarche) 8– 11  1st definingeffect  Pubichairgrowth begins(adrenarchea) 11-12  Growth spurt10-14  Onsetof menstrual cycles(menarche) 11-15  Pubichairadult  Breastsadult The growth spurt,earlier&9cm/yr in girls,men10cm/yr because growthspurtlonger&slightly faster,endedinbothsexesbyepiphyseal fusion Most parts of the reproductive systemcanworkbefore normal age of puberty – precociouspuberty, but don’tbecause hormone levelslowdue tolow GnRH secretion.Manyof these systemscanoccur earlier.Butusuallyswitchedoff LH& FSH at verylow concentration,asGnRH low Hormonal control of puberty – onsetof pubertyassociatedwithsteadyrise inFSH&LH secretion, due to rise in GnRH secretion,pubertyinitiatedbythe brain. Pubic& axillaryhair(adrenarche) – dependsonandrogensinbothsexes,fromadrenalsingirls. Breastdevelopmentdependsonoestrogens,breastsnotmammary,oestrogensensitivetoadipose tissue. Growth spurt– dependsonGH & steroidsinbothsexes,oestrogenclosesepiphysesearlieringirls. Genital developmentinboysdependsontestosterone.Internalfemale oestrogen&progesterone Puberty – timing– controlledbythe brain,couldbe reductionin sensitivitytonegativefeedbackby steroidsordue to maturationof central mechanisms/Pubertystartswhenthe inhibitoryprocesses are switchedoff. Puberty – Boys9 – 14 years  Genital developmentbegins  Pubichairgrowth  Spermatogenesisbegins  Growth spurt  Genitaliaadult  Pubichairadult
  15. 15. The main determiningfactorinfluencingpubertyisbodyweight.The bodyweightatmenarche is about47Kg & that at the beginningof the growthspurt30kg. In boysthe critical weightisabout 55kg. The plasmaconcentrationof leptin –mayindicate tothe hypothalamusthe attainmentof the initial bodyweight. Pineal tumours caninfluencepubertyinhumans.Disturbstimingof puberty Precociouspuberty –signsof pubertybefore age of 8, or menstruationbefore 10majorityunknown cause but can be due to neurologicalreasons –earlystimulationof central maturationcausedby pineal tumoursormeningitis causingirritationof the meningesaffectingthe hypothalamus&early release of GnRH.Uncontrolledgonadotrophinorsteroidsecretion,hormonesecretingtumours. Menopause The climacteric– the last fewyearsof a women’sreproductivelife Pre-menopause –typicallyfromc40 yearschangesinmenstrual cycle occur – follicularphase shortens& ovulationearlyorabsent.LessOsecreted,LH& FSH levels↑,FSHmore – reduced inhibin&subsequently↓fertility. Menopause – cessationof menstrual cyclesaverage age 49-50,no more folliclestodevelop.Olevels ↓dramatically,LHlevels↑,FSH↑ dramaticallyasthere isno inhibin Effectsof the menopause  Vascularchanges – hot flushes(in80% transientrisesinskintemperature &flushing, relievedbyoestrogentreatment  On oestrogensensitive tissues o Uterus – regressionof endometrium&shrinkage of myometrium o Thinningof cervix o Vaginal rugae lost o Involutionof some breast tissue o Changesinskin o Changesinbladder  Bone o Bone mass reducedby2.5% peryear for several years o Increasedreabsorptionrelative toproduction o Osteoporosis– much greaterinsome than others  major cause of fracturesin laterlife,canbe limitedbyoestrogentherapy  Heightchange  Loss of libido  Increase CVD– due to changingcholesterol/lipidprofile  Poorsleep  Mood change/depression Hormone replacementtherapy –relievessymptomsof the menopause,Ogivenorallyortopicallyby patch or gel – can limitosteoporosis –currentadvice nolongerfirstline protection.HRTis comprisedusuallyof amix of O & P
  16. 16. O isa mildanaboliccausingNa& H2O retention,raisingHDL& lowersLDL’s,decrease bone resorption,impairsglucose tolerance &increasesblood coagubility,doesreduce Alzheimer’s diseases.Sideeffects:breasttenderness,breastcancer,nausea,hypertension,thrombosis, endometrial hyperplasia. The end of reproductive life –the male – no obviousevent,spermproductioncontinues. Womenwhohave still gota uterus – unopposedoestrogenscause proliferationof uterine liningwith a risk of endometrial cancer. Progesterone inhibits this. Menstrual Dysfunction  Activin– stimulatesFSHreleasefromthe pituitary&potentiatesitsactioninthe ovary. The normal cycle – length(24-32 days regularity(bestbetween20-40 yearslongeraftermenarche, shortedinpre menopause.MBL(37-43 ml/cycle) infirst48 hours Although9-14%lose >80 ml/cycle & 60-70% of these are anaemic. Menorrhagia– excessive amountof loss Heavy periods–  abnormal clottingPathology:fibroids,adenomyosis,polyps,endometriosis,endometrial carcinoma o Most fibroidsare asymptomatic.Large fibroidsmaybe palpableonbimanual clinical examination(irregularlyshapeduterus)examination &confirmedbyU/Sscan ultrasoundmayshowthe presence of a massit can distinguishfromovariancysts but itmay be difficulttodistinguishthe lesscommonsolidovariantumours. o Adenomyosis –conditionwhere ectopicendometrial tissuewithinthe myometrium o Endometriosis –ectopicendometrial tissue outside the uterus.  Iatrogenic:IUCD  Medical disorders:hypothyroidism DUB – 60% - heavybleedingnorecognisable pelvicpathology,pregnancyorgeneral bleeding disorders. MenorrhagiaTreatment Treatmentoptions<35-dependsonsize/symptoms/desire forfertility.Wait&see withmonitoringof bloodloss& medical treatmentstoreduce loss(e.g.contraceptivepill,mefanamicacid).Surgery withendometrialablationorabdominalmyomectomyorhysterectomy. The same optionsare suitable forperi-menopausal patientsbutkeepinmindthatsymptomswill resolve aftermenopause Irregular periods– Anovulation  Local pathology – cancer.  Iatrogenic– progesterone onlycontraceptives,depotprovera,irregularintakeof steroids.
  17. 17. Amenorrhoea–causes – prepubertal,pregnancymenopause Pathological causes  Cryptomenorrhoea–menstruationoccursbutisnot visible due toanobstructionof the outflowtract.Specificallythe endometriumisshed,but acongenital obstructionsuchasa vaginal septumoron part of the hymenretainsthe menstrual flow.A patientwith Cryptomenorrhoeawill appeartohave amenorrheabutwill experiencecyclicmenstrual pain.The conditionissurgicallycorrectable.  PCOS, weightloss,hyperproteinlactemia,stress Dysmenorrhoea– acute,chronicor cyclical (recurrent) pain. Recurrentpelvicpainindicates –mittelschmerz(midcycle pain)orprimarydysmenorrhoeaor secondarydysmenorrhoea. The pain of primarydysmenorrhoea usuallybeginsafew hoursbefore orjustafterthe onsetof a menstrual period&maylast 48- 72 hours Seconddysmenorrhoeaoccursinassociationwithunder-lyingpelvicpathology.The painof secondarydysmenorrhoeaoftenbegins1to 2 weeksbefore menstrual flow&persistsuntil afew daysafter the cessationof bleeding. PrimaryAmenorrhoea–failure tomenstruate by16 SecondaryAmenorrhoea–absence of 3 menstrual cyclesorabsence of bleedingforsix (or3) months Session4 – The male reproductive system Scrotal Sac Cutaneoussacconsistingof pigmentedskin&dartosfascia(a fat free layercontainingsmooth muscle fibresof the dartosmuscle).Dartosmuscle causeswrinklingappearance of the scrotum – attachedto the skin> contractioncauseswrinklingwhencold. Cremastermuscle fibres (frominternaloblique) retracttestesclosertothe bodywall (reducesheat loss);one of the heatregulatorymechanisms>optimal conditionsforspermatogenesis. Scrotumdevelopsfromtwooutpouchingsof the anteriorabdominal wall;inthe foetal period,the testes& spermaticcordsenterit;closelyrelatedtothe formationof the inguinalcanal. Nerve supplyfromlumbar&sacral plexus>Ilioinguinal nerve L1,genitofermoral nerve L1/2perineal branchesof the pudendal nerve (S2-3).Rubbingthe inside thighwill cause the reflextohappen Testes The testisisa compoundtubulargland,enclosedthe tunicaalbuginea.Deeptothe tunicaalbuginea, strongCT septaextendsintothe testisdividingitintoabout250 pyramid-shapedlobules.Each lobule containsbetween1-4highlyconvolutedseminiferoustubules,inwhichspermatozoaare produced. Sertoli cells are fixedtothe BMof the seminiferoustubules,&are lessnumerousthanthe
  18. 18. spermatogeniccells.The cytoplasmof eachcell formsanelaborate systemof processesthatextend upwardto the luminal surface,surroundthe spermatogeniccells&fill all the spacesbetweenthem. The most primitive spermatogeniccells,the spermatogonia,restonthe BM. While the laterstages are locatedat successivelyhigherlevelsinthe epithelium. Primaryspermatocyteslineadjacentto the spermatogoniabutnearerthe lumen. Secondaryspermatocytes(short½life) dividerapidly(2nd meioticdivision)toformspermatids.The spermatidsmature intospermatozoathe deeplystaining headsof whichappearto be embeddedinthe cytoplasmof the Sertoli cells&theirtailshanginto the lumenof the seminiferoustubule. Betweenthe seminiferoustubules,thereisloose CTcontaininginterstitial Leydigcells whichare seeninisolatedclusters.The cellshave alargerspherical nuclei.Althoughspermatogenesis& steroidgenesis(inLeydig) occurinseparate compartmentswithinthe testis,the compartmentsare functionally&physiologicallyinteractive. Developinthe posteriorabdominal wall(7wks) processusvaginalisdecendsintothe labioscrotal swellings&passingthroughthe abdominal wall carriesthe fascial layersof the abdominal wall (external spermatic,cremasteic&internal spermaticfascia). Testesdescendbehindthe processusvaginalis&reachthe scrotumat 28 wks.Shortlyafterbitchthe processusvaginalisis obliterated;tunicavaginalisremnantof the processusvaginalisallows movementof the testeswithinthe scrotum. Persistentprocessusvaginalismayleadtothe developmentof acongenital hydrocoele inthe scrotumor provide apathwayforthe developmentof indirectinguinalhernia. Hydrocoeleisfluid withinthe tunicavaginalisdue to inflammationof the testis(orchitis) Testicularmalignancy –metastasesinretroperitoneal lumbar(paraaorticlymphnodes;scrotum – metastasesinsuperficial inguinallymphnodes,mainlyfromgermcells Undescendedtestes (cryptorchid) maybe foundatthe level of the inguinal canal;usuallydescend within12 months,otherwise surgical interventiontoensure correctlocationbefore 5yearsto preventinfertility,torsion&riskof malignancy.Due toincreasedtemperature germcellsare absent, while the Sertoli &Leydigcellssecrete male sexhormones. Orchitis(inflammationof the testis) occursinsome individualswhosuffermumpsafterpuberty  impairedspermatogenesis,occasionallyleadingtoSTdegenerationorattimes,infertility. Imperfect/incomplete descentmayresultinthe testistobe foundwithinthe abdomen,inguinal canal,at the superficial inguinal ringorhighupin the scrotum. Maldescent– testistravelsdownanabnormal path& failsto reachthe scrotum; may be found inthe superficial fasciaof the anteriorabdominal wall abovethe inguinal ligament,infrontof the pubic,in the perineum,orinthe thigh. Inversion –anterior(epididymisliesanteriorly&testis&tunicavaginialisposteriorly) Polarinversion –testis&epididymisare completelyinverted. Epididymis
  19. 19. Locatedon the superior& posterolateral surfaceof the testis:duringtheirpassage throughthe epididymis,the spermsundergostructural maturation&become motile,&theyare thenstoredin the tail segmentuntil ejaculation. Spermatic cord Collectionof structuresthatpassthroughthe inguinal canal to& from the testis;beginsatthe deep inguinal ring&endsat the testis The epitheliumliningthe lumenis pseudostratifed,columnar&the cellsusuallyhave stereocilia.The epitheliumliesonathinlaminapropriacontainingalarge numberof elasticfibres. contains3 fascial coverings(external spermaticfascia (externaloblique),cremastericmuscle fibres& fascia(internal oblique) &internal spermaticfascia(transversalisfascia)),3arteries(testicular, cremasteric,arterytovas deferens),testicularveins(pamininiformplexus),lymphvessels,vas deferens,remainsof the processusvaginalis,genital branchof the genitofermoral nerve& autonomicnerves;ilioinguinal nerveliesonthe outside of the cord. Encystedhydrocoele –upper& lowerendsof the processusvaginalismaybecome obliterated, leavingasmall intermediate cysticarea. Torsionof the spermaticcord- surgical emergency(testismaydie);torsionmayobstructvenous drainage > oedema& haemorrhage >arterial obstruction Varicocoele –varicositiesof the pampiniformplexusof veinsdue tovenousobstruction;onthe left side couldresultdue todisturbance of drainage of the leftrenal vein. The lefttesticularveinemptiesverticallyintothe renal vein.muchhigherthanthe rightdrainage. The varicositiesformwhenthe valve systembetweenthesetwoveinsfails & bloodfallsbackwards underthe pull of gravity.The right testicularveindrainsdirectlyintothe IVCatan oblique angle, furtherdown.Itsvalvesdonothave to supportthe same weightof bloodasthose inthe left testicularvein &are therefore muchlesslikelytofail.A rightsidedvaricocoele is veryuncommon & issuggestive of other,potentiallymore seriousproblemssuchraisedIVCpressure - e.g.due to obstruction. Vasectomy – easilypalpated(thickmuscularwall) inthe cordbetweenthe epididymis&superficial inguinal ring;accessedthrough skin&superficialfascia>surgical dissection&division(vasectomy) bilateral =sterilisation. Infections of the epididymis,vasdeferens,seminalvesiclesorurethrabybacteriamay resultin obstructionof the ducts,pain& general swellingof the structures;the ejaculate  few/nosperm. Bloodsupply  Testiculararteryfromthe AA  Pampiniformplexusof veinsfromthe testis  Testicularvesselsruninthe spermaticcord  RighttesticularveindrainsintoIVC;lefttesticularveindrainsintoLrenal vein  Bloodsupplytothe epididymisfromthe testicularartery
  20. 20.  Arteryto the vas deferensfromthe inferiorvesicleartery(br.internal iliac)  Bloodinthe testiculararteryisat bodytemp – so cooleddownbypampiniformplexus Vas/Ductus Deferens It isapproximately35cmlong. Ascendsinthe spermaticcord,entersthe inguinal canal throughthe superficial inguinal ring, transversesthe inguinalcanal &entersthe pelviccavityviadeepring.Tracksacross the lateral pelvic wall & passesbetweenthe urinarybladder&ureter.Formsa dilatedampullabehindthe bladder  opensintothe ejaculatoryduct(withthe ductof the seminal vesicle) withinthe prostate gland. It transportsspermrapidlyintothe prostaticurethra.Rich autonomic innervationof the SMfibres of the ductusdeferenspermitsrapidcontractionswhichpropelthe tubescontentstowardsthe ejaculatoryducts.Duringejaculationthe ejaculatoryduct&the duct of the seminal vesicledilate to facilitate the entryof sperms&seminal glandsecretionsintothe prostaticurethra. TheAccessoryglands Duringsexual arousal &ejaculation,the secretionsare emittedinacontrolledsequence commencingwiththe bulbourethral glands,then prostate,followedby spermatozoa,lastlythe seminal vesicles. Seminal Vesicles – highlyconvolutedtubulardiverticulumof the vasdeferens,itssecretions accounts for70-80% of ejaculate,secretionrichinfructose,AA,proteins,ascorbicacid& prostaglandins.The large lumenof the glandcontainscoagulatedsecretion.The epitheliumlining the mucousmembrane variesfromsimple columnartopseudostratifed.The laminapropriais surroundedbya SMcoat dividedintoaninnercircular&a verythinouterlongitudinal layer Prostate gland walnutsizedglandwithafibromuscularcapsule,lyinginferiortothe bladder, surroundsthe pelvicportionof the urethra(prostaticurethra).Consistsof 30-40 glandsthat open intothe prostaticsinuses.Ejaculatoryductsopenintothe seminal colliculus.Secretionsfromthe prostate,seminal vesicles&the ejaculate are dischargedintothe prostaticurethra&comprise the semen.Bloodsupplyfromthe branchesof the internal iliacartery.Venousdrainage intoaprostatic plexuswhichdrainsintothe internaliliacvein &alsointothe vertebral plexus.Lymphaticdrainage intothe internal iliac&sacral nodes – metastases Prostaticcarcinoma– typicallyoccursinthe peripheral zone,relativelyasymptomatic,diagnosedby DRE, & PSA,tumoursfeel rockhard BPH –oldage, occurs inthe transitional zone,because of thisthe urethragetscompressed>urinary outflowobstructed&bladderhypertrophy,TURPnecessary. Bulbourethral gland is locatedwithinthe urogenital diaphragm&containstubular& alveolar type glands.Just priorto ejaculation,theseglandsproduce aclearwaterysecretionthatlubricate the urethra. Penis composedof erectilestructuresthe corporacavernosa& a single corpusspongiosum which containsthe urethra& expandstoformthe headof penis(glans) distally.
  21. 21. Bloodsupplytothe penisisviathe cavernousarteries &branchesof the internal pudendalartery. Venousdrainage isviathe superficial &deepdorsal veins.The corporaare network-liketrabeculae of fibromusculartissue ramifiedbyspaces whichbecome filledwithbloodduringerection.The corpora are surroundedbythickbandsof CT. Root of penisconsistsof twocrura attachedto the pubicarch; bulbof penisisthe proximal partof the corpus spongiosum, anchored tothe perineal membrane. Base of the bodyof penisissupportedbysuspensoryligamentof penisattachedsuperiorlytothe pubicsymphysis&anotherligament(fundiformligamentof penis) attachedtothe lineaAlbaabove & splittingintotwobandsthatunite inferiorly The two crura coveredbythe ischiocavernosus muscle&attachedto the ischial rami. Bulbospongiosusmuscleformsasingle muscle envelopingthe bulb.Ischiocavernosusmuscle helps to maintainerectionbycompressingoutflow veins&pushingbloodintopenis. Bulbospongiosus muscle helpstoexpel lastdropsof urine &assistsinmaintainingerection. Urethral damage – fracture of the bonypelvismayleadtorupture of the membranousurethra> extravasationof urine &blood. Trauma to the perineumcanrupture the membranousorthe spongyurethra> extravasationof urine & blood. Session5 – Female Reproductive system Internal genitalia–ovary,fallopiantube,uterus,vagina, External – clitoris,blubof vestibulegreatvestibulargland,labiamajora&minora. Uterus – is usually anteverted &anteflexed &liesoverthe bladder.Peritoneumcoversthe uterus anteriorly&superiorly(exceptthe cervix;anteriorreflectionontothe bladder&posterioroverthe posteriorfornix of the vaginatothe rectum;uterovesiclepouchanteriorly&rectouterine pouch posteriorly. It isa slit-like uterinecavity;continuesasthe cervical canal extendingfromthe internal os& communicatingwiththe vaginal lumenviathe external os.The wall of the bodyconsistsof the perimetrium,the myometrium&the endometrium Lymphaticdrainage – fundus& upperbody  alongovarianvessels&lumbarnodes.Body& cervix > Internal iliacnodes. Bloodsupply – uterine arteriesfromthe IIA fromthe ovarian&vaginal arteries Uterine veinsformavenousplexus oneitherside of the cervix intothe IIV.Vesselsinthe broad ligament How the epitheliumchanges: mensesdays1 – 4 : desquamationof 2/3,bleeding days5 – 7 : rapidre-growthfromremainingepithelialcells
  22. 22. days7 – 14 : endometrial re-growthiscompleted Thisconcludesthe proliferativephase days14 – 28 : Secretaryphase includesendometrial thickening,enlargementof glandular cells,oedematous,proliferationof white cells. 3 layers: compact superficial zone spongy middle zone (glandules) inactive basal layer Typical amounts35 ml with10-80 reference range >80ml abnormal. As mensesapproachthe arteriesgointo spasm, retractingbackto the deeperlayersevoking ischaemia. Cervical cancer– inspectionof the cervix byvaginal distensionwithavaginal speculum;cellular material scrapedfromthe vaginal cervix &supravaginal cervix. Bimanual palpationof the uterus –to determine:  size & normal antevertedposition  2 fingersinsidethe vaginaotherhandpressed inferior-posteriorlyonthe antabdominal wall  Softeningof the isthmus –earlysignof pregnancy Intra-abdominal pressure  uteruspressingonbladdermaycause retroversion &increasesriskof uterine prolapse –higherriskinpregnancy Hysterectomy –relativelycommonprocedure followinguterine&cervical cancer Endometritis –inflammationof the endometrium Endometriosis (ectopicpresence of the endometrial tissue inthe peritoneum,pelvis&guy> leadsto painful menstruation&pelvicpain(menorrhagia–over productionof menstrual discharge & dyspareunia Roundligamentdevelopsfromthe gubernaculumof the gonad.Itpassesthroughthe inguinal canal. Attachedto the pole of the ovary& uterus(roundligamentof ovary containedinpartbythe broad ligament) &fromthe uterusto the labiummajora(roundligamentof uterus. Functions – maintainsthe anatomical positionof the uterus(anteversion)Stretches&becomestaut inpregnancy. Uterine fibroids – a fibroidisa benigngrowthof the uterus. Theycan varyfrom pea-sizedtothe size of a melon&occur anywhere inthe uterus.Atleast1/5 womendevelopthem.30-50years An overgrowthof SMC,like the uterus,fibroidsare sensitive toO.Fibroidstendtoswell whenlevels of O are high(e.g.pregnancy) theyalsoshrinkwhenOlevelsare low (menopause).DetectedbyUS Symptoms – heavyor more painful periods.If afibroidislarge – discomfortinL abdo.Occasionally,a fibroidmaypressonthe bladder  more pee.Rarelypressure onthe rectummaycause constipation.Repeatedmiscarriage orinfertilityisuncommon,&uncommontoeffectpregnancy. The Uterine Tubes The tubeslie inthe free edge of the board ligament(mesosalphinx) responsible forthe transportof the ovumdischargedfromthe ovary.4 anatomical parts; infundibulum(funnel-shapeddistal end
  23. 23. that opensintothe peritoneal cavity) –has finger- likeprocesses(Fimbriae–facilitatescollectionof the ovum) that spreadof the surface of the ovary;ampulla (widest) site of fertilisation; isthmus (thick);intra-uterine passesthroughthe wall of the uterustoenterthe uterine cavity. Muscular tube witha mucosacontainingciliated&secretorycolumnarepithelium Bloodsupply – tubal branch of the uterine artery (branchof internal iliac) Peritonitis - infectionfromthe vagina,uterus&tubesmayspreadintothe peritoneal cavitybecause of communicationbetweenthe female tract& peritonealcavityviathe tube ostium Salpingitis(inflammationof the tube) –Spreadof infectionfromthe peritonealcavity Hysterosalpingography –radiographicimagingtoinvestigatethe patencyof the tube;hysteroscopy – endoscopyof the uterine tube Abdominal orlaproscopictubal ligation–surgical sterilisation Ectopic tubal pregnancy – blockage of the tube or disturbedtransportmechanism  implantationof the blastocystinthe tube  tubal pregnancy(mostcommon);small calibre of the tube leadstoits rupture as pregnancyadvances  severe haemorrhage intothe peritoneal cavity Rupturedtubal pregnancymaybe confusedwithappendicitisonthe RHS because of the closeness. Both have parietal peritoneuminflammation>painreferredtothe RLQ OVARY Posteriortobroad ligamentof the uterussuspendedbythe mesovarium&fromthe lateral wall of the pelvisbythe suspensoryligament;one pole isattachedtothe uterusbythe ligamentof the ovary.Ovarianvessels&lymphaticspassto& fromthe ovarywithinthe suspensoryligament Ovariancysts– may resultininflammationof the pelvicperitoneum;the ovaryliesinthe ovarian fossalinedbyperitoneum;liesinproximitytothe obturatornerve runningthroughthe pelvisbehind the ovary  pain onthe medial side of the thigh&knee joint. CERVIX – narrow inferiorthirdof uterus –supravaginal &vaginal parts Vaginal partprotrudesintothe vagina& surroundsthe external osof the uterus& is itself surroundedbyvaginal fornices(ant,post,lats) Nabothiancysts developfromthe cervical glandularducts –infectionsof the endocervical glands(as inchronic cervicitis) canresultinblockage of the ducts& hence cystformation(between2mmto 1cm). There presence,especiallyif infected,canreduce fertility  cervix inhospitabletosperm. VAGINA Musculomembranoustube;extendsfromthe cervix tothe vestibule (cleftbetweenthe labia minora).Relations –anteriorurethra&bladder;post – anal canal & rectum;lateral levatorani muscles,pelvisfascia&ureters Posteriorfornix –deepestpart&closelyrelatedtothe rectouterinepouch
  24. 24. Vaginal fistulae–obstetrical trauma– resultinweakness,necrosis&tearingof the vaginal wall  formationof fistulae betweenthe vaginal lumen&bladder,orurethraorrectum or perineum/ Lymphaticdrainage of the lower1/3 of the vaginaisto the superficialinguinal nodes Osteology of the Pelvis Made up of the innominate bones,the sacrum& the coccyx The superioraperture (the pelvicinlet) leadingintothe pelvisiswiderthanthe inferioraperture (pelvicoutlet).  Pelvicinletisdemarcatedbythe broadwingsof the iliacbones,the sacrum& the pubic symphysis  The outletisdemarcatedbythe pairedinferiorpubicrami,the ischial bones,ischialspines& the coccyx. In the erectposition,the pelvisistiltedsothatthe plane of its inletisatan angle of 60o to the horizontal.  The greater(false) pelviswhichisthe space surroundedbythe upperportionsof the iliac bones& the upperpart of the sacrum posteriorlyactuallylowerportionof the abdominal cavity  The lesser(true) pelvisisplacedmore deeply&surroundedbythe marginsof the obturator foramen,the ischial spines&the lowerportionof the sacrum. The Urogenital & pelvicdiaphragmsinthe lowerpartof the pelvicclose off the pelvicoutlet&form a barrier(withappropriate perforations)betweenthe visceral contents(i.e.bladder,urethra,vagina & anus) of the pelvis&the exterior. SexdifferencesinPelvicShape Sex differencesare associatedmainlywithtwofeatures: 1. The heavierthe build&strongermusclesinthe male accountfor the strongerbone structure & better- definedmuscle markings 2. The comparativelywider&shallowerpelviccavityinthe female iscorrelatedwith specialisationtoaccommodate the passage of the infant’shead. Alsodifferencesshow uponx-rays:  The pelvicinletisheart-shapedinthe male &oval inthe female  the subpubicangle (angle betweenthe inferiorpubicrami) isnarrow inthe male & wide in the female  The soft tissue shadowof the penis &scrotum(if notblockedbylead) Obstetricconjugate – ismeasuredfromthe midpointpart of the pubistothe sacral promontory. Thisis obstetricallyimportantasthe APdiameteristhe narrowestAPdiameterthe foetuspasses through& is usuallyabout10cm. Thisdiametercanonlybe assessedby imagingthereforeclinicians use the diagonal conjugate
  25. 25. The diagonal conjugate ismeasuredfromthe inferiorborderof pelvistosacral promontoryasa guideline tool.Itismeasuredbydigital insertionintothe vagina& palpationto sacral promontory needstobe about 11.5cm. Session5 – The Pelvic Floor The pelvicfloorisa muscular& fibroustissue diaphragmwhichfillsthe lowerpartof the pelvic cavity.It definesthe upperborderof the perineum,supportsthe pelvicorgans.Itispiercedbythe urethra,vagina& rectum. The pelvicside wall consistsof:  Ischiumof pelvis  Sacrospinous&sacrotuberousligaments  Obturatormembrane  Obturatornerve  Obturatorinternus Pelvicfloor  Levatorani are pairedmusclesforming3slingsof muscle extendingfromthe posterior aspectof the pubicbone,the fasciaoverObturatorinternus&Ischial spines: o Consistsof Puborectalis,pubococcygeus&iliococcygeus(+coccygeus= PF muscles) o Anteriorfibresaroundprostate orvagina o Posteriorfibrestoanococcygeal body&coccyx.Posteriorlycoccygeusliesoverthe Sacrospinousligament.  Attachedto pelvic side wall o Ischial spine o Arcus tendineusfasciapelvis.  Urogenital hiatusallowpassage of urethra,vagina&rectum Suppliedby branches of the posteriortrunkof the internal iliacartery these are pudendal artery, vaginal artery,& inferiorrectal artery.Nervoussupply pudendalnerve (S2,3& 4 keepsyourgetsoff the floor) The perineumisa fibromuscularsheetwhichclosesthe pelvicoutlet.Lowerlimitof perinealspace whichiscontinuouswith ischiorectal fossa The perineal body –is a connective tissue mass incentre of perineum, anchorsthe perineal muscles & rectum.Central fulcrumforpelvicsupport,canbe damagedat duringbirththat’s why episiotomies are performed Anterior(Urogenital) perineum:the urogenital diaphragmfillsthe gapof the pubicarch stretching betweenthe convergingischiopubicrami.Itisa triangularsandwichwithstriatedmuscle fibres between2layersof fascia:  Superiorfascia  Sphincterurethrae –striatedmuscle fibres  Interiororsuperficial fascia –thickened&knownasperineal membrane. The Urogenital diaphragmalsocontainsthe bulbourethral glands. Belowinthe perineal membrane:  Piriformis&coccygeus  Branchesof the sacral plexus  Fascia;includes arcus tendineus  Levatorani muscles  Internal iliacvessels& branches  Ureters.
  26. 26. Male – superficial transverse perineal membrane,bulbospongiosusmuscle,ischiocaveronosus muscle Both sexes –isthe superficialperineal pouch,whichisthe site of collectionof urine if the urethrais rupturedbelowperineal membrane. Functionsof pelvicfloor – supportspelvicorgans,aidscontinence,childbirth&truncal stability. Movesin concertwithabdominal muscles. Pelvicfloorrelaxesindefecation.Afterpregnancythe bladdercanfall throughthe Urogenital hiatus. PelvicFloordamage Duringvaginal childbirththe nerve supplycanbe stretched&damaged. Effectsof childbirth  Stretchof the pudendal nerve –neuropraxia&muscle weakness  Stretch& damage of the pelvicfloor& perineal muscles  Stretch/rupture of ligamentssupportsof muscles –ineffective muscle action. Consequencesof damage - prolapsed&incontinence Otherfactors whichmaydamage the pelvicfloor – age,menopause (atrophyof tissuesafterO withdrawal),obesity(load),chroniccough(load),intrinsicCTlaxity(marfans…) Prevalence of incontinence –50% of womenover40 will have urinaryincontinence problems, surgeryforprolapsediscommonprocedure ingynaecology,recurrence of prolapsedoccursin10- 15% of women. Episiotomy - A surgical cut inthe perineumduringchildbirthtoavoidtearing &damage to the perineal body (A medianepisiotomydividesorpartlydividesthe perineal body,which‘encourages’perineal tearingposteriorlyintothe anal sphincter.Itwasabandonedinfavourof a postero-lateral episiotomythatpassestothe lateral side of the body &anal sphinctertube.) Treatment Pelvicfloormuscle exercise,whichare easysafe &effective will cure incontinence in50-75% of patients&will preventordelayworseningof prolapsed. Or Surgery – continence procedures&prolapsedprocedures  Continence procedure,increase supportto sphinctermechanism&preventdescentof bladderneck o Colposuspension o Tension-free vaginal tape o Cure rate 85-90%, side effects:voidingdifficulty,overactivebladderdisease  Prolapse procedure o Remove prolapsedorgans o Restore CT supports,maintainfunction
  27. 27. o Side effects –recurrence,new incontinence,dyspareunia NB: pelvicfloorhasfast& slowfibres,sodifferentexercisestobuildupboth. Session6 – Genital tract Infections Communicable diseasesurveillancecentres –notifiedof aggregate dataviaregularreturnsfrom GUM clinics&receive dataongonorrhoea,genital Chlamydia,genital herpes&syphilisthrough reporting.Underestimationassome people presenttoGPs or familyplanningcentres,ahuge burdenof infectionremainsasymptomatic. Increasedincidence of STIS,due toincreasedtransmission,increasedGUMattendance,greater awareness,improveddiagnosticmethods,increasedscreening At-riskgroups:young,minorityethnicities,poverty,pooreducation,unemployed,individualsbornto teenage mums. Influence of aspectsof sexual behaviour  Age at firstsexual intercourse  Total numberof sexual partners  Frequencyof partnerchange  Concurrentpartners  Sexual orientation  Practice of unsafe sex o Inconsistentuse of barriercontraception o High-risksexual activity  Lack of skills&confidence tonegotiatesafersex MorbidityassociatedwithSTIs  Acute symptomaticinfection –gonorrhoea  Chronicsymptomaticinfection –warts  Recurrentsymptomaticmanifestations –herpes  Social & psychological stigma  Riskof lifelonginfection&problemsassociatedwithpotential transmissiontoothers.  Pelvicinflammatorydisease  Impairedfertility  Reproductive tractcancers  Riskof infectionwithblood-bornevirusesHBV,HIV  Riskof congenital orperipartuminfectionof neonate. Treatmentof STIs  Co-infectionsare common –screenfor otherSTIs  Antibioticorantiviral therapy –fromfirstvisit  Treat withanti-chlamydial agent o Highincidence of asymptomaticinfections o Reduce transmissionvolume o Reduce longterminfection-associatedmorbidity.  Cancer tracing– patient&publichealthmanagement  GUM clinicsundertake contracttracing,contactscreening&symptomaticorepidemiological treatment.  Advice onneedforabstinence duringcurrentactive episode&riskof reinfectionif partners untreated
  28. 28.  Opportunisticscreening,sexualhealtheducation,advice oncontraception,&detailed instructiononthe practice & needforsafersex. Viruses –HPV,HSV,HBV, HIV,HCV,molluscumcontagiosumvirus Bacteria– C. trachomatis,N.gonorrhoeae,ureaplasmaurealyticum,mycoplasmahominis,T. pallidum(syphilis),Haemophilusducreyi Fungi – candidaspp. Protozoa– Trichomonasvaginalis Arthropods – scabiesmite,pubiclouse. Clinical syndromes 1. Genital skin&mucous membrane lesionsc a. Genital ulcers – HSV,syphilis,chanchroid(Haemophilusducreyi) b. Vesiclesof Bullae–HSV c. Genital papules –transientmanifestationsof STIs,condylomataacuminate, umbilicatedlesionsof Molluscumcontagiosumvirus 2. Urethritis –discharge, dysuria,frequency a. Gonococcal Urethritis b. Non-gonococcal Urethritis –ChlamydialTrachomatis,ureaplasma,mycoplasma, trichomonasHSV c. Post-gonococcal Urethritis 3. Vulvo-vaginitis&Cervicitis –vaginal discharge,odour,itch,dyspareunia,soreness a. Vulvo-vaginitis–candiasis,trichomoniasis,staphylococcal,foreignbody,HSV b. Cervicitis –C.Trachomatis,N.gonorrhoeae, HSV,HPV c. Bartholinitis –Polymicrobial infectionswithendogenousfloraorrarelySTI d. Bacterial Vaginosis –commoncause of above symptoms. 4. Infectionsof femalepelviseitherpregnancyrelatedorPID a. Pregnancyrelated –chorioamnionitis,post-partumendometriosis,episiotomy infections,puerperal ovarianveinthrombophlebitis,Osteomyelitispubis 5. Prostatitis,epididymitis&orchitis a. Prostatitis –acute bacterial Prostatitis,chronicbacterial Prostatitis,chronicpelvic painsyndrome b. Epididymitis –non-specificbacterialepididymitis,sexuallytransmittedepididymitis c. Orchitis – viral (mumps,CoxsackieB) orchitis,pyogenicbacterial orchitis CommonSTI pathogens –HPV,HSV (1 &2), C. Trachomatis,N.gonorrhoeae,T.vaginalis,syphilis(t. pallidum), HIV? HPV Genital wartscausedby HPV are the commonestSTIdiagnosed atGUM clinicsinUK. More than 100 HPV typeshave beendescribed,howeverthe vastmajorityof infectedindividualsfail todevelop warts. Cutaneous,mucosal, &anogential warts,
  29. 29. Theycan be benign,painless,verrucousepithelial ormucosal outgrowths whichcanaffectthe penis, vulva,vagina,urethra,cervix,Perianal skin,. Highrisk types & HPV16 & 18 – associatedwithcervical &anogential (relatingtoanusor genital) cancers, Diagnosis – clinical,biopsy+genome analysis,hybridcapture Treatment– none- frequentspontaneousresolution Or – topical podophyllin,cryotherapy,intralesionalinterferon,imiquimod,surgery. Screening- cervical papsmearcytology,colposcopy+acetowhite test.Cervical swabwithHPV hybridcapture Herpessimplex Virus Primarygenital herpes –extensive painfulgenital ulceration,dysuria,inguinallymphadenopathy, fever Recurrentgenital herpes –asymptomatictomoderate Diagnosis – smear& swabof vesicle fluid &/orulcerbase Treatment– acyclovir(primary & severe disease) Acyclovirprophylaxisforfrequentrecurrences,barriercontraception! ChlamydiaTrachomatis Obligate intra-cellularbacterium,non-specificgenitalchlamydial infections(serotype D-K).Donot grow onroutine laboratorymedia.The infective formisthe elementarybody,whichdevelopswithin the host cell intothe reticulate body.The reticulate bodyreplicateseventuallyrevertingbackto elementarybodies,whichleave the cell toinfectothercells. Rarer, tropic,lymphogranulomavenereum serotypes(L1,L2,L3) Males– Urethritis,epididymitis,Prostatitis,proctitis(inflammationof anus) UsuallyUrethritisbutcommoncomplicationisacute Epididymitis. Reiterssyndrome – Urethritis,conjunctivitis&arthritisare the classical triadof clinical manifestationsassociated withthissyndrome. Females –Urethritis,cervicitis (usuallymucopurulent),salpingitis,perihepatitis,mostly asymptomatic complications –PIDmost importantcause inwesternworld (in10-40% of patients)  tubal damage & ectopicP’s Ocularinoculation –conjunctivitis Neonatal infection –inclusionconjunctivitis, complication  pneumonia Diagnosis – endocervical &urethral swabs –culture or othertest1st voidurine – NAA Neonatal infection –conjuctival swab,serologyif pneumonia(eosinophiliaonWCC) Antigendetectionbyimmunofluorescene (rarelyused) OR enzyme immunoassaysORPCR LGV – serology,buboaspirate forculture &histology Treatment– The organismscontainsrelativelylittle peptidoglycan,the targetforB lactam antibiotics.Somaintreatmentmacrolides(erythromycin,clarithromycin,azithromycin) & tetracycline (doxycycline).Asconjunctivitisispartof a more widespreadinfection,systemic antibioticsshouldbe used. NeisseriaGonorrhoeae Gram negative intracellulardiplococcus onlygrow onenrichedmediasuchaschocolate agar.
  30. 30. Males– Urethritisleadingto proctitis,pharyngitis,Prostatitis,epidymitis, Females –asymptomatic, endocervicitis,Urethritis (causingurethral syndrome),PID can complicate toPID(in10-40% of patients) with/withouttubo-ovarianabscess,Bartholinsabscess, DisseminatedGonococcal infection (rare complicationbothM/F) –bacteraemia,skin &jointlesions Diagnosis – smear& culture Lab – gram stain– can be enoughOr culture Treatment– Ciprofloxacin(single large oral dose)because of frequentpenicillinresistantNeisseria gonorrhoeae ORCeftriaxone250 mg IMsingle dose inregionswhere ciprofloxacinresistance is prevalent(>5%) orwithlikelyexposure toCipRN.gonorrhoeae (overseastravel,partner’sdiagnosis) PLUS Doxycycline for7 dayfor possible Chlamydiatrachomatisco-infection ORAzithromycin(single large oral dose) if pregnantorunlikelytobe compliant Trichomonas vaginalis Flagellatedprotozoancausesathin,frothyoffensivedischarge, irritation,dysuria&vaginitis. Diagnosis – vaginal wetpreparation &culture enhancement Treatment– metronidazole TreponemaPallidum– syphilis Multi stage disease – ‘the greatpretender’ Primary – indurated (hard),painlessulcer Secondary – 6 to 8 weeks –fever,rash,lymphadenopathy,mucosal lesions Latent– symptomfree years Tertiary – chronicgranulomatouslesions Quaternary – cardiovascular& CNSpathology Congenital syphilis Diagnosis –serology,dark-fieldmicroscopy Treatment– penicillin &testof cure follow uo Common non-sexually transmitted infections Vulvovaginal candidiasis– candida spp.Normal gastrointestinalflora. Riskfactors – antibiotics,oral contraceptives,pregnancy,obesity,steroids,diabetes Profuse,white,curd-like discharge withavaginal itch,discomfort&erythema Diagnosis – highvaginal smear&culture Treatment– topical azoles&nystatin,or oral fluconazole Bacterial vaginosis Perturbednormal flora–Gardnerella,anaerobes,mycoplasmas.Scantybutoffensivefishydischarge Clinical diagnosis –vaginal pH>5, KOH whiff test. Lab diagnosis –HVS smear  Clue cells –epithelial cellsstuddedwithGramvariable coccobacilli
  31. 31.  Reducednumbersof lactobacilli  Absence of PMNs Treatment- Metronidazole. Pelvic Inflammatory Disease PID isthe clinical syndrome infemales,unrelatedtopregnancyorsurgery,wherebyorganisms ascendfromthe cervix,viathe uterus,tothe uterine tubes&contiguouspelvicstructure toproduce inflammatoryconditionssuchassalpingitis,pelvicperitonitis&/ortubo-ovarianabscess. Causative Organisms:  N.Gonorrhoea:gram negative intracellulardiplococcic  C. Trachomatis – Gram negative extracellular(infective)&intracellular(vegetative) organism  B. Vaginosis(G.Vaginalis,Bacteroidessp)  Streptococci  Mycoplasmahominis Bacterial Vaginosissyndrome maybe antecedentto lowerGTIassociatedwithpolymicrobialacute PID.The organismsof B. V are similartothe non-gonococcal,non-chlamydial bacteriaof the upper GT inwomenwithPID. Unlikelytoculture cause in55% of patients. Differential diagnosis:ectopicP,acute appendicitis,IBS,ovariancysts,UTI,functional pelvicpain. Risk factors – the rate of PIDis inverselyrelatedtoage,& alongwiththissexual experience,the numberof partners& increasedfreq.STIall add to the likelihoodof developingPID.Contraception alsoinfluencesthe disease.Barrierreducesrisk,oral variable risk,IUCDincreasesriskespeciallyon the firstfew weeksof insertion. Othervariables  Vaginal douching(insufficientevidence)  Menses(within7days,proliferative phase)  Alcohol/druguse (especiallygonococcal PID  Cigarette smoking(2timesincreasedrisk:thisisabehavioural riskfactor)  Instrumentatione.g.cervical dilatation,coil insertion  Hormonal changesassociatedwithmenstruationmaylowerbarriertoascentof organisms fromthe cervix aswell asbacteriostaticeffectof the cervical secretion.Retrograde menstruation:infectionismore commonaftera period.Virulence of the organismsinacute Chlamydial &gonococcal PID Pathogenesis NG & CT cause endocervicitis –10%-40% untreatedwill have acute PID.Spread –director lymphatic to the endometrium, tubes(salpinges),ovaries &the pelvicperitoneum.Inmilddisease,the tubes are hyperaemic&oedematous.Pusmaybe present.The tubesremainmotile &the ostiaare patent
  32. 32. In moderate tosevere disease,the markedinflammation &oedemareduce tubal motility.Fibrin deposition &fibrosisadhere the serosal surfaceof the tubestootherpelvic &abdominal viscera. The ostia can be obstructed. The markedinflammationcanleadtothe developmentof atubo- ovarianabscess.The consequencesof chronicinflammationare infertility,ectopicP & chronic pain. Two typeschronicor acute Acute PID APID– symptoms</= 6 monthduration Ascendinginfectionfromthe endocervix causingeither:Endometritis,Salpingitis,oophoritis,pelvic peritonitiswithorwithouttuboovarianabscess. Diagnose itquicklyneedtotreataggressivelytostopinfertilityoccurring. Factors associatedwith ascentof bacteria: Complications(in15-20%of womenwithPID) Minimumdiagnosticcriteria:  Uterine/adnexal tendernessorcervical motiontenderness  Lowerabdominal pain&tenderness  Dyspareunia  Abnormal bleeding Others  Oral temp> 38.3  Endocervical CTor GC  RaisedWBCs  Vaginal/cervical discharged  RaisedESR or CRP Chronic PID Olderage groups,withpreviousacute PIDor historyof chronicinfectionsuchasTB Symptoms> 6 monthsduration Features  chronicpelvicpain,secondarydysmenorrhoea,deepdyspareunia,menstrual disturbance,recurrentexacerbations. Causes:Non-specificorganismsorVaginosisorganisms,orTB Consequences  infertility,ectopicP,chronicpelvicpain,pelvicadhesions,abnormal periods Lab tests  pregtest,urethral swabs,MSU, CRP, Enzyme immune-assayonEndocervical swabsforCTor GC. ThenDNA tests(PCRetc.)
  33. 33. Diagnosticcriteria– laparoscopicabnormalities,transvaginal sonographyor MRI showingthickfluid-filledtubes Treatment – Oral ofloxacin&Metronidazole for14days. Hospitalisationmayoccurdue to pregnancy,clinical failure of antibiotics,inabilitytotolerate regime,severe illness,tubo- ovarianabscess. furthermanagement  male sex partnersof womenwith PID shouldbe examined&treated,aswell asanysexual contacts inthe 60 daysbefore. Sex partnersshouldbe treatedempiricallywithregimens effectiveagainstCT& GC. Sendto GUM. Session7 – Coitus & Conception Spermatogoniatake upto74 days to mature (50n in seminiferous,12-26 inepididymis).1000 Spermatozoapersecond.20 yo 6.5m/g/Day,over50 yo 3.8m/g/day(due to damage of spermatogonia. Phasesof coitus  Excitement–engorgementof erectile tissue  Plateauphase – Gonadal excitation  Orgasmicphase  Resolutionphase - +/- refractoryperiod) alwaysinmale can’tgetexcitedduringthisperiod. Questionablyresolutionphase infemales. Female sexual response – bloodengorgement&erection:clitoris,vaginal mucosa,breast&nipples. Glandularactivity,sexualexcitementssinmale with/withoutorgasm.Nophysiological refractory period. Mechanismof penile erection  stimulants –psychogenic,&tactile (spinal reflex)  Cause somatic& autonomicefferent,viapelvic(PNS) &pudendalnerve (somatic)  these resultinhaemodynamicchanges o Causingtumescence: o Inhibitionof sympatheticarterial vasoconstrictornerve o Activationof PNS,activationof NANCautonomicnervestoarteriesreleasingNO. Nitric oxide:post-ganglionicPNSreleaseAch,AchbondstoM3 receptoronendothelial cells.A rise inCa2+ activationof NOS& formationof NO.NO diffusesintoSM& causes relaxation(vasodilation). NO alsoreleaseddirectlyfromnerves. Vasodilationcausedbyuptake of Cainto ER causingthe myosinheadtodetach fromactin& come more relaxed.
  34. 34. Viagraworksby inhibitingcGMPbreakdown Erectile Dysfunction  Psychological causes(descendinginhibitionof spinalreflexes)  Tears infibroustissue of corporacavernosa  Vascularchanges(arterial &venous)  Drugs – factors blockingNO – alcohol,anti-hypertensive’s,diabetes,antihistamines, antidepressants. Emission –movementof ejaculate intoprostaticurethra(leakage) ,vasdeferensdue thisby peristalsis,accessoryglandsecretionmix now. Ejaculation is a spinal &cerebral reflex Sympatheticnervouscontrol (L1,L2) 1. contractionof glands& ducts(SM) 2. Bladderinternal sphinctercontracts 3. Rhythmicstriatal muscle contractions(pelvicfloor,ischiocavernosus,Bulbospongiosus,hip& anal muscles) So erectionSNS  inhibitionof arterioles(erection),PSN:active Ejaculation SNS:active (ducts) So Point& Shoot. Ejaculate – normally – 2-4ml,.20-200 X 106 spermperml,total sperm>40 X 106 > 60% of sperm swimmingforwardvigorously,<30%abnormal morphology. (Abnormaloligozoospermia<20 X 106 spermperml) Immediatelyafterejaculation,the semenfirstcoagulatesdue tothe actionof clottingfactors, namelyfibrinogen&vesiculae (stopsspermfrombeingphysicallylostfromVJ) &thenliquefiesby the action of enzymesderivedfromprostaticsecretions(fibrinolysis).The vastmajorityof the sperm do notenterthe cervix of the uterus& are lostby leakage fromthe vagina. Those that enterthe uterushave to travel a distance of some 15 to 20cm to reach the uterine tube,ajourney that may lasta fewhours.Duringthistravel they undergoCapacitation&Acrosomal reaction. Capacitationof sperm – removal of a glycoproteincoat promoteschangesinthe spermcellsmembrane. Furthermaturationof sperminfemale reproductive tract (6-8 ours)  spermcell membrane changesto allowfusionwithoocyte cell surface,tail movementchangesfrombeattowhip-like action (3mm/hour)
  35. 35. Spermatozoa– 48- 72 hoursof life intract oocytes – 6 – 24 hours Fertile period:spermdepositionupto3 dayspriorto ovulationorday of ovulation Oocyte transport:beatingcilia. Fertilization Shouldoccur inthe ampullaof fallopiantubes,requiteslossof spermoutershell(acrosome). Spermpushesthroughgranulosacells –proteinsonspermheadbindstoZP3 proteinsof zona pellucida Bindingtriggersacrosome reaction: 1. Acrosomal enzymes exposedtozona pellucida 2. hydrolysingenzymes digestpaththroughZP 3. One spermpenetrates: fusionof plasma membranes 4. Spermmovesinto cytoplasm:zygote 5. Polyspermyblockedby the cortical reaction (AKA zonareaction), cortical cell degranulation. Egg thencompletesmeiosis2 pronuclei (2setsof chromosomes),pronuclei fusionintothe diploidzygote&thenmitosis begins. Both Capacitation&the Acrosomal reaction are inducedbyan influx of Ca& rise incAMP inthe spermatozoa. Zygote –cleavage--  Morula – compaction  blastocyst trophoblast(outercell mass) Cleavage – seriesof metabolicchanges&rapidmitoticdivision(cleavage) increasednumberof cells 16-32 withoutgrowth,totipotency,thisiswhenidentical twinscanoccur.
  36. 36. Conceptusinuterine tube,waitsfor3days awaitingrise inprogesterone (smoothmuscle relaxation),periodof cell divisiontoblastocyststage.Inthe blastocystthere isalossof totipotency, outerlayer(trophoblastsurroundsembryo),innercell mass(becomesembryo) &afluidfilledcavity. Zygote to blastocyst:days14 to 21 of uterine cycle.Progesteroneprimingof endometrium. Conceptusnourishedinintrauterine fluid,3days floating.Stickytrophoblastoverinnercell mass, adherestoendometrium(hCG) implantationcommences(6daysafterovulation).Bythe 10th day afterfertilisation,the blastocystisfullyembeddedwithinthe endometrium. Infertility & contraception Contraception –howthe processof conceptionmaybe modifiedtopreventitsoccurrence Infertility –possible abnormalitiesof the processof conceptionthatmaypreventitsoccurrence Natural Contraception  Abstinence  Coitusinterruptus –but sperminpre-ejaculate  Rhythmmethod - needregularcycle.Assumemaximumspermsurvivalof 7 days(av3-4), ovumsurvival of 1 day. So fora regular28 daycycle,withan ovulationnday14 or 15, the fertile periodisday7-16 of cycle. Vasectomy– divide vasdeferensbilaterally –ensure ejaculatefree of spermbefore relyingonfor contraception.The spermwill be broken downinthe tube. Barrier methods ofcontraception  Condoms – readilyavailable,alsoprotectsagainstSTI’seffective if usedcorrectly  Diaphragm– liesdiagonallyacrosscervix,needscorrectfitting.Doesnotcompletelyocclude passage of sperm.Holdssperminacid environmentof vagina&reducessurvival time  Cap – fitsacrosscervix – physical barrier  Spermacides –mosteffective usedinconjunctionwithbarriermethods Hormonal contraception
  37. 37.  Combinedoral contraceptivepill –oestrogen&progesterone–negative feedbacktothe hypothalamus&pituitary –inhibitsfolliculardevelopment –oestrogen –lossof positive feedbackmidcycle,sonoLH surge,oestrogeninhibitsFSHrelease o DecreasedriskforPID,benignbreastdisease,anaemia&endometrial &ovarian carcinoma o Increasedriskof thromboembolismdisease,non-thromboticstroke,gallbladder disease  Depotprogesterone –3 monthlyinjectionsof progesterone.Negative feedbackeffectto inhibitovulation  Progesterone-onlypill –low-doseprogesteroneonly,mayinhibitovulation,fillsthe cervix withstickyacidicmucous.  Progesterone implants –mayinhibitovulation. Rodsinsertedunderthe skinof the forearm, lastfor 5 years. Progesterone onlyinhibitsovulationvianegative feedbackinhighdoses - asindepot In lowdosesitmayinhibitovulation - inPOP & implant,butnotthe mainmode of action Sterilisation– occlude fallopiantubes –clipsrings,ligation,mayrarelyrecanalise &thisworksto inhibittransportof oocyte alongfallopiantube. Inhibitsperm through cervix – affectcervical mucous – thickhostile mucous,progesterone mediated.CombinedOCP,depotprogesterone,progesterone implant&progesterone onlypill. Inhibitimplantation– hormonal conception(all listedpreviously) affect receptivityof endometrium. Directeffect.Plusabsence of corpusluteumpreventspreparationof endometriumforimplantation. Post-coital contraception – combinedoestrogen/progesterone highdose orprogesterone only. Combinedoestrogen&progesteroneinhighndose,orprogesterone only. Intra-uterine device – (these alsomaybe usedas post-coital contraceptionupto5 daysafter ovulation) –needtobe changedeveryfew yearsmaycause perforation.Maycause infectionwhen inserted&changed.  Inertcoppercontainingorprogesterone impregnated  Copperinterfereswithendometrial enzymes,&mayalsointerfere withspermtransportinto fallopiantubes,interfereswithimplantation. Inhibit ovulation Cervical mucus Endometrium Combined OCP +++ Y Y POP + Y Y Progesterone implant ++ Y Y Depot progesterone +++ Y Y Post-coital contraception Y Infertility A youngcouple havingunprotectedsex 2-3timesa weekwill have a75% chance of conception withinayear.
  38. 38. Definedasfailure toconceive within1year.Affectsapprox.15% of couple.Primary(noprevious pregnancy) orsecondary(previouspregnancy,successful ornot)  Male – 20-25%  Female –45 – 60% o Failure toovulate – 28% o Fallopiantube problems22% o Uterine problems11% o Cervical problems3%  Unexplained–20 – 30% Reasons: Coital problems Anovulation(15-20%)  occasional anovulatorycyclesnormal,especiallyatthe extremesof reproductive life.  Hyperprolactinaemia,weightloss&stressmayall affectthe hypothalamussecretionsof GnRH.  treatmentBromocryptine –Dopamine agonist –mimicseffectsof prolactin inhibitoryhormone.  Pituitarytumours – affectonLH & FSH  Ovarianfailure,menopause,radiotherapy,chemotherapy,mayall affectthe ovary&its secretionof oestrogen&progesterone. Polycysticovariansyndrome –uncertainpathogenesis –originatesatpituitaryorovarianlevel Increasedandrogensecretion,raisedLH/FSH,insulinresistance,multiple smallovariancysts. Anovulation –oftenamenorrhoeaoroligomenorrhoea Diagnosisof Anovulation:serumprogesterone levelinmid-luteal phase (day21) itshouldat maximum. Differentiate causesbylookingathormone levels: LH FSH Oestrogen Menopause High High Low Ovarian failure High High Low hypothalamic/pituitary failure Low Low low PCOS LH:FSH ratio increased Normal or increased Treatment  Anti-oestrogen(clomiphene) –reduce negative feedbacktohypothalamus/pituitary, increase GnRH,increase FSH  FSH administration  GnRH agonists – pulsatile tomimicnormal secretion. Tubal occlusion(15-40%) Causes:sterilisation,scarringfrominfection,endometriosis
  39. 39. Diagnosedbylaparoscopy&dye insufflations,hysterosalpingogram Treatment– tubal surgery.assistedconception. Abnormal Sperm production  Abnormal production(testiculardisease)  Obstructionof ducts(infection,vasectomy)  Hypothalamic/pituitarydysfunction Analysisnormal:Volume (>2ml) spermcount(>20 mil perml),Motility(>50%) morphology(>50%) Cervical mucus – shouldbe alkaline,withloweredviscosity –to testcollectcervical mucussoon aftercopulation Management of infertility Investigation:  Couplesshouldbe havingsex 2-3timesaweek  Ovulation –check regularity,day21 progesterone levels  Patenttubes – Hx of infection/sterilisation,dye insufflationsor HSG  Adequate spermcount Treatment:  Induce ovulation  Overcome tubal occlusionbysurgeryorIVF  If inadequate spermthen –artificial inseminationbydonororintracytoplasmicsperm injection(assistedconception). Session8- The placenta function & dysfunction The placentahas a metabolicrole,endocrine role,transportpathways(simplediffusion,active transport& Pinocytosis). Dysfunction –of implantation(keyprocess),problemswithtransport –teratogenesis(mother exposedtoacompoundwhichishostile tothe foetus,&infectiousagents Early embryonicdevelopmentestablishmentof the placentatakes precedence,makessense asthis ensuressupportforthe pregnancy. Week2 – weekof twos Differentiation –to create twolayers  Outercell mass(trophoblast) differentiatesinto o Syncytiotrophoblast o Cytotrophoblast  Innercell massbecomesthe bilaminardisk o Epiblast
  40. 40. o Hypoblast o Amnioticcavityoccurswithinthe innercell mass Implantationday6 – cytotrophoblastmakescontactwiththe endometrium(cuboidal epithelium) makescontact & the syncytiotrophoblastdigestsitswayintothislayer. By day 9 the burrowingof the blastocysthasbeenachieved.The blastocystisnow embeddedinthe endometriumprecedingovulationinthe proliferativestage of the endometriumreadytofeedthe blastocyst.Lotsof glandsdeveloptodothis.The endometriumgrows&coversthe embryowitha fibrinplug.Canget breakthroughbleeding asaresultthiscan confuse the date at whichpregnancy occurred,whichiswhydatingscans are now done routinely. By the end ofweek two – there isan implantedembryo&itstwocavitiesthe amnioticcavity&yolk sac; these are suspendedbythe connectingstalk(eventuallyumbilical cord) withinasupportingsac (chorioniccavity). The embryonicspaces  the yolksac disappears,the amnioticsacenlarges(withembryo),the chorionicsac isoccupiedbythe expandingamnioticsac(the amnionmembrane &chorionic membrane fuse &thisiswhat ruptureswhenthe watersbreak).Earlystagesof developmentthere are little fluffyvilliaroundthe blastocystthesevilli onlyremaininone regiontheyconstitute the placentaproper.We make a definitive placentabythe endof the firsttrimester.Ultimatelythe placentaisderivedfromthe outercell mass. Implantation –isinterstitial,the uterineepitheliumisbreached&the conceptusimplantswithinthe stroma - it producesproteolyticenzyme –& implantswithinthe stroma.The placental membrane becomesprogressivelythinnerasthe needs of the foetusincreases. The human placentais haemomonochorial  one layerof trophoblastultimatelyseparates maternal bloodfromfoetal capillarywall. Justone tissue layer. Aimsof implantation:  Establishthe basicunitof exchange o Primaryvilli –earlyfiner-likeprojectionsof trophoblast o Secondaryvilli –invasionof mesenchymeintocord o Tertiaryvilli –invasionof mesenchyme by foetal vessels  Anchorthe placenta– establishmentof the outermostcytotrophoblastshell  Establishmaternal bloodflow withinthe placentasogetnutrientsintothe foetus. Foetal vesselsderivefromthe mesenchyme core. Implantation defects – Ectopicpregnancy – implantationatsite otherthanuterine body(most commonly fallopiantube (ampullaof FT55%), can be peritoneal orovarian,canveryquicklybecome life-threateningcrisis In ectopicpregnancy – the fallopiantube lacksthe pre-decidual cellssoinvasiongoesonun- checked,soyoucan getmassive haemorrhage. Commonsites – fimbrial,ampullary,isthmicorinterstitial (of the uterinetubes);ovary
  41. 41. Rare: Pouchof Douglas,abdominal viscera. Commonpain(due toit beinginthe ampulla) - Painfroman ectopicpregnancyisfeltinthe lower abdominal quadrants If lyingdownbloodinthe peritoneal cavitymaycollectbeneaththe diaphragmirritatingthe phrenic nerve.Since thisnerve originateswithcutaneousnervesfromC3,4 & 5, painmay be referredtothe dermatomesforthese segments;i.e.shoulders.Painfeltinthe lowerquadrantsisdue tostretching & tearingof the peritoneum. Bloodpassingfromthe vaginaisusuallywithdrawal bleeding(notaresultof bleedingatthe site of the rupture),causedbyreductioninthe hormone hCGwhichmaintainsthe corpusluteum & hence preparesthe endometriumforimplantation. Placentapraevia– where the blastocystbeginstoimplantinthe loweruterinesegment,&cancause haemorrhage inpregnancy,asthe placentagrowsoverthe external ossoblocksthe way out& gives a highrisk of bleedingduringpregnancyrequiresC.section. Can geta defectinthe processof implantation Histologyof the endometrium –the endometriumispreparedforimplantation.A populationof pre- decidual cellsgrow,& an elaborationof spiral arterial bloodsupply.Pre-decidual cellshelpto balance the invasive characterof the trophoblast Decidualisation –the decidual reactionprovidesthe balancingforce forthe invasive force of the trophoblast Otherconditionscharacterisedbyexcessive invasiontheseare called placentaacreta,here the trophoblastinvadesall the wayintothe myometrium.Atdeliverythe placentadoesn’tcome out & get a massive post-partumhaemorrhage. If the pre-decidual cellsare toorigorous&stops the invasiontoosoon.Usuallycreationof low resistance vascularbedoccurs& maintainsthe highflow requiredtomeetfoetal demandneeded for late ingestation.The trophoblastmovesouttoendometriumproperinvadestoendotheliumof the spiral artery,the large pale decidual cells,the trophoblastinvadesthe endotheliumof the spiral arteriole &changesitintotrophoblastcells,&thisiswhat ensureshighflow low resistance blood supply.Absolutelyessential formaintainingastrongpregnancy.Inpre-eclampsia,verycommon, affectpregnantwomen,itisa defectinthisprocess,some womenare unaffectedbutsome women the arteriolesmaintainthe standard endotheliallining & these can’tcope withthe demandsof pregnancy.Thisisan example of animplantationdefect.The motherwill have Proteinuria&high bloodpressure Placental insufficiency –describessmall foetus’nomaternal symptoms.(Similartopre-eclampsiain pathology). Definitive placentabyweek22thisoccurs due to fusionof amnion& chorionicbecome acomposite membrane
  42. 42. Twinning–the degree towhichmembranesare sharedinmonozygotictwinscanvary.Each can own placenta,amnion&chorion.Due to splittingof the morulaveryearlierbefore implantation.Later the splittingoccursmore of the membranesare shared.Increasingsharingadditional risksbecause single placentafeedsbothbabieswhere the amnioticsacissharedrisktwinintotwintransfusion syndrome where onlyone getsthe bloodsupply.Anevaluationof foetalmembranesmustoccur. On the foetal side,we see the amnion&umbilical cord,lotsof large vesselsfull of blood. The villi,branchcontinuously,togetbetterexchange the core of the villi isfoetalvessels&veins. The structure isanchoredat stemvilli atstemvilli the cytotrophoblastspillsout&populatesthe area,so here it isnot underneaththe syncytiotrophoblast.The villi are bathedinmaternal blood (lake). 1st trimesterplacenta – placentaestablished, placental ‘barrier’isstill relativelythick,complete cytotrophoblastlayer beneath syncytiotrophoblast. Term placenta surface area forexchange dramaticallyincreased, placental ‘barrier’isnow thin,cytotrophoblast(not complete broken) layerbeneathsyncytiotrophoblast.Don’tneedthe stempropertiesof cytotrophoblastneedafewtorepairholesif theyoccur.There isalsoincreasingbranchingof the villi. The interhaemal distance asbeendecreased.Achievedbythinningof the trophoblastlayer, marginationof the foetal capillariesof the core of the villi &increasingthe surface areaforexchange throughincreasedbranchingof the villustree. Smokingorlivingathighaltitude have reduced interhaemal distancestocompensate. Althoughthishasa limit.Placental defectsare amongthe majorrisk factors forintrauterine growthrestriction,&impairedfoetal growth has beenlinkedtolong-termadulthealth problemscalled the Barkerhypothesis – foetal originsof adultdisease. Placentabarriernota true barriersome unwantedthingscanstill passthroughitcan be breachedwitherbysimple ‘leakage’of a numberof infectiousagentsmayutilise
  43. 43. existingtransportsystems(e.g.HIV),activelypenetrate (e.g.Treponema) oropportunisticallyexploit gaps inthe epithelium(e.g.Toxoplasma) Umbilical cord vessels& the foetal circulation Two umbilical arteries –deoxygenatedbloodfromfoetusintoplacenta One umbilical vein –oxygenatedbloodfromthe placentatofoetus Functions:  Metabolicrole – placental synthesisof glycogen,cholesterol,fattyacidsthese are mainlyfor itsown demands  Endocrine role – hCG, HC somatomammotrophin,hCThyrotrophin,hCcorticotrophin (proteinhormones) &progesterone&oestrogen(takesof corpusluteumbothsteroid hormones o HCG – producedduringthe first8 weekssupportscorpusluteum, producedby syncytiotrophoblast (normally) therefore ispregnancyspecific.Itisexcretedin maternal urine thereforeusedasthe basisforpregnancytestingcanbe detected from6 days ina serumtest.Levelsshoulddropin2nd trimesterwillremainhighif:  Trophoblastdisease –molarpregnancy(apregnancywhere there isonly trophoblasttissue veryhighlevelsof hCG) & choriocarcinoma(metastatic disease) o Progesterone &oestrogen –responsible formaintainingthe pregnant, placental productiontakesoverfromcorpusluteumbythe 11th week.Theymodulate maternal physiology,progesterone  increasedappetite. hCSincreases glucose availabilitytothe foetusbymakingthe motherslightlydiabetic.  Transport o Simple diffusion –moleculesmovingdownaconc.grad  water,electrolytes,urea & uric acid,gases o Facilitateddiffusion - appliestoglucose transportneededforfoetal brain o Gas exchange – flow-limitednotdiffusion-limited,foetal O2 storesare small therefore maintenance of adequateflow essential adequate uteroplacental circulation.Soif the spiral arteriolesdon’tdevelopproperlythere will be aproblem o Active transport – specifictransportersexpressedbythe syncytiotrophoblast  AA iron,vitamins. o Passive immunity –foetal immune systemisimmature,receptor-mediatedprocess, maturingas pregnancyprogresses.Igclass-specificIgGonly, IgG concentrationsin foetal plasmaexceedthoseinmaternal circulation.Activeprocessagainsta concentrationgradienttoppedupbybreastfeeding  Transport goeswrong,the placentaisnota true barrierteratogensaccess the foetusviathe placenta,unintentional outcomesfromthe physiological process  Thalidomide,alcohol,therapeuticdrugs,drugsof abuse,maternal smoking (notterratogenicbutbabiesmuchsmaller)  Antibodytransport – haemolyticdiseaseof the newborn,rhesusblood groupincompatibilityof mother&foetus,now uncommonbecause of
  44. 44. prophylactictreatment.Routine screening.All IgGmove acrossincluding those forbloodtypes,a Rhesusnegative motherwillmake antibodies againstpositive Rhesusif the babyisRhesuspositive,sowill make antibodiesagainsttheirbabiesredbloodcells.  Infectiousagents  varicellazoster,cytomegalovirus, treponema pallidum, toxoplsma gondii, Rubella Maternal problems in pregnancy BP changesinpregnancy:BP α TPR X cardiac output. Vasodilation isprimarychange inpregnancy(so BP falls),Phase V Korotakoffsoundusedasmore reproducible.Over160 systolichave toadmit to hospital.Will getaorto-caval compressionasa resultof foetus Bloodpressure isnottakensupine inlate 2nd or 3rd trimesterasdecreasedvenousreturntothe heartfrom graviduterus. Clinical effects  Vaso-vagal episodes - isa malaise mediatedbythe vagusnerve.  Pre-eclampsia–HT withProteinuria significantmorbidity&mortality associatedwithit  Nausea& sicknessinsupine  Compromise of utero-placental perfusioninsupine  Postural hypotension  Maskingof pre-existingHT Coagulationinpregnancy,motherbecomesin pro-thromboticstate due toincreased fibrinogen,increasedfactors(V,VII,IX,X) reducedfibrinolysis,stasis,co-existingriskfactors – esp operative delivery. ThromboembolismDisease –maincause of maternal mortalityinUK Pregnancyincreasedthe riskof vascularthromboembolism of 6X.C-sectionincreasesrisk10-20 fold Therapeuticconsiderations:Warfarin(unlikely),heparin,low molecularweight heparin (mostused) Clinical Effects  Pulse – full +/- collapsing  Oedema  Apex beatdisplacedoutwards  S3, murmurs-ejectionsystolicmurmursinover90% of pregnancywomen.Loud,all over precordium  Relative sinustachycardia  ECG – L axisdeviation,QIII,TIII,ST& T wave changes,atrial/ventricularextrasystoles,SVT
  45. 45. Heart disease inpregnancy –hyperkineticcirculationaccentuatesmurmurswithstenoticvalvular disease normal hearts –cardiac disease.Gradingof symptomsoftenunhelpful(how itaffectsthe patient).Prompttreatmentof infection&anaemia. Valvulardisease&bacterial endocarditis –(no longerneedantibioticprophylaxisNICEonlywithvalve replacements).Anticoagulationpost-valve replacement.DuringaC.sectionwomencanlose 1.5L of blood. Respiratoryclinical effects:  CXR – increased lungmarkings  Mildrespiratoryalkalosis(compensatorymetabolicacidosis)  SOB in70% of pregnancies  Asthma,chronicLD, Sarcoidosisnoconsistenteffect  TB – riskreactivationinpregnancy. Renal clinical effects –(RFP – renal perfusionflow) Stasis– bacteruria& UTI’s Asymptomatic–20-40% acute pyleonephritis,10-15% chronicPN, premature labour Glycosuria,Proteinuria(either idiopathicornephroticsyndrome – pre-eclampsiaorRD) Endocrine changes in pregnancy  placental lactogenT1– increasedhepaticsynthesisof thyroidbindingglobulin  Total T4 & T3 increasedto compensate  Free T4 levelsfallin2nd & 3rd T  Renal thresholdiodine reduced –lostinurine  Glandhyperplasia especiallyif alreadydietaryinsufficiency – pregnancygoitre  Total T3/T4 thyrotoxicrange  Free T4 or FTI betterbutall difficult to interpret. Effects  Normal pregnancymaymimic thyrotoxicosis –heatintolerance, goitre,sweating,appetite,fatigue, palpitations  Hypothyroidism maskedbynormal weightgainof pregnancy  Untreatedthyrotoxicosis –increasedfoetal loss
  46. 46.  Neonatal thyrotoxicosis –Transplacental passage of thyroidstimulatingantibodiescauses delayedeffects. Carbohydrate metabolismchangespregnancyisastate of insulinresistance,normal glucose homeostasismaintainedbyincreasedinsulinsecretion.Fastingbloodsugarlevelslowerin pregnancywitha slightincrease inpost-prandial bloodglucoselevels. So the foetal energyrequirementsmetbyfacilitateddiffusionglucose acrossthe placenta.Diabetic mothers– hyperglycaemia–pancreaticisletsinhyperplasiainfoetus –increasedfoetalinsulin production – hypoglycaemia–increasedlipogenesis –macrosomia(large babies) Complicationsof IDDMinpregnancy  increased foetal mortality:congenitalabnormalities, prematuritystill birth,neonatal respiratoryproblems&hypoglycaemia.Increasedmaternal morbidity  hypo’s, polyhydramnios (toomuchamnioticfluid),labour,pre-eclampsia,infection, lossof control esp.T3, postnatal dropinsugars GI problemsinpregnancy –generalisedrelaxationof tone &reducedsmoothmuscle motility – changesinintra-abdominal pressure &physical effectsof enlarginguterus AlsoGORD & constipationverycommoninpregnancy --?O& reducedgastricsecretioninpregnancy – pepticulcerdisease actuallyimprovesinpregnancydue tolessgastricsecretion. Acute abdomencanoccur inpregnancythere isusuallyadelay& confoundingof diagnosisdue to alteredclinical presentation,reluctance tolaparoscope inpregnancy. For example appendicitis(1/3000) increasedmorbidity&mortalitydue todelayindiagnosis, there isdisplacedanatomy,uterusinterposedwill maskingguarding,PRunhelpful Direct complicationsof pregnancy – ectopicpregnancy,miscarriage,retrovertedgravid uterus (causesurinaryretention),placental abruption,labour,UTI,reddegenerationof fibroids(outstrip bloodsupply&necrosisoccursnot common),separationof symphysispubis. Haematological problemsin pregnancy – increasedplasmavolume (1L) Vs increasedcell mass – relative haemodilutionwithreducedhaemocrit&haemoglobin –physiological anaemiaof pregnancy Iron deficiencyanaemia–250- 300mg to foetus,150mg inplacenta& some inbreastmilk Inadequate ironstoresatentrywill resultin pregnancy-precipitatedanaemia. Folicaciddeficiency –2-4% of innercitypopulationpregnantwomen –linkwith neural tube defect & preconceptual folicacid  Folicacidnow givenduringpregnancy Psychiatric & related disorders: AnxietyinT1common due to miscarriage threat,singlemotherpregnancy,&unwantedpregnancy (mayresultindepression&attemptedsuicide) Anxiety&depressioninT3– physical changes,disturbedsleep&anxietyrelatedtonormal baby expectations Postpartum– lossof independence &parentingskills –furtheremotionalstress

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