MD210 Physiology Lecture 5: Egg Activation, Embryonic Development & Multi-foetal Pregnancies PDF

MD210 Physiology Lecture 5 Egg Activation Role of PLC-zeta Pronuclei Fusion - Haploid sperm nucleus enters egg - Becomes the sperm nucleus - Sperm pronucleus swells, migrates towards egg pronucleus (Pronuclei fusion is necessary for a fertilised zygote. The nuclear envelope needs to dissolve for it...

MD210 Physiology Lecture 5 Egg Activation Role of PLC-zeta Pronuclei Fusion - Haploid sperm nucleus enters egg - Becomes the sperm nucleus - Sperm pronucleus swells, migrates towards egg pronucleus (Pronuclei fusion is necessary for a fertilised zygote. The nuclear envelope needs to dissolve for it to occur. Geminal-vesical breakdown.) - When in close proximity the pronuclear envelopes vesiculate o Nuclear membranes break up to form a circle of small vesilces ▪ Surround the chromatin of each nucleus - Chromatin from each pronucleus intermixes o Form the diploid zygote nucleus - Nuclear envelope reforms around the zygote nucleus o Embryonic development begins The nuclei fuse together What happens now? - Development of the zygote, the study of which is known as embryology or developmental biology - The zygote undergoes a series of mitotic cell divisions called cleavage - The stages of development are: Fertilised ovum (zygote) -> 2-cell stage -> 4-cell stage -> 8-cell stage -> Morula -> blastula -> early gastrula -> late gastrula Early Embryonic development (Implantation in fallopian tube – ectopic - non-viable) (Fertilisation in ampulla of fallopian tube) (Placenta Previa – implantation low down in uterus – blocks birth canal – need C-section) Embryonic Development Cleavage - Begins ~ 12 hours post-fertilization - Zygote divides into 2 cells (mitosis) - 2 cell into 4 cell stage (24 – 36 hours) - 4 cell into 8 cell stage (36 – 72 hours) - 16 cell stage - Morula - Blastocyst Morula - Develops 72 hours (3 days) from fertilisation - Morula enters the uterus ~ after 3 days in oviduct - Solid Sphere of Cells o Zona Pellucida o No Enlargement - Totipotency (can give rise to any cell type) - Compaction o Desmosomes and gap junctions (uncompacted embryo – identical, compacted embryo – unidentical, first stage necessary to get differentiation – begin to lose individual shape ?) Post Compaction changes in Morula Pre-compaction - Low Biosynthetic Activity - Quiescent (Low QO2) - Oovid Mitochondria - Pyruvate as energy Source - Maternal Genome Active - Pluripotent Post-compaction - High Biosynthetic Activity - Highly Active (High QO2) - Elongated Mitochondria - Glucose as energy Source - Embryonic Genome Active - Transporting Epithelia - Cell Differentiation Blastocyst - Morula enters the uterine cavity, floats freely o Transporting Epithelia Result in Fluid Accumultation o Fluid Filled Cavity Formed - Once cavity appears, it is now called a blastocyst. - Loss of Totipotency o Trophectoderm, Inner Cell Mass, Blastocoele Cavity - Trophoblasts – will form the invading placenta - Inner cell mass cells – will form the embryo Blastocyst Expands and Hatches (Human blastocysts hatch at day 6 – if earlier issues with implanatation) Multi-foetal pregnancies - IVF Incidence (naturally, not IVF) - Twins – 1 in 100 births o African Americans: 1 in 70 o Caucasians: 1 in 88 o Japanese: 1 in 150 o Chinese: 1 in 300 - Triplets are about 1 in 7,500 births - Quadruplets are about 1 in 650,00 births Multiple Foetal Pregnancy – complications Early Delivery with Multiples - (Full term delivery is 37+ weeks) Twins - defined as those born at the same time or of the same pregnancy (don’t have to be born the same day) - may be Dizygotic, Monozygotic or Conjoined Monozygotic twins - Single fertilized zygote splits into two separate individuals - Unstable Epigenome o Including various DNA modifications such as DNA methylation, is dynamic and interchangeable in response to various environmental and random events - DNA Differences o Using ultra-deep, whole-genome DNA sequencing (WGS) -specific, extremely rare, somatic mutations - single-nucleotide polymorphisms (SNPs) during early development in one, but not the other, MZ twin Monozygotic Twins – Dichorionic Diamniotic (When morula splits – least complicated) - Embryo splits before Day 4 - Monozygotic twins will implant as 2 separate blastocysts. - Separate chorion and Separate amnion (each have their own placenta and amniotic sac so it is possible to delay the birth of one longer that the other) - Dichorionic Diamniotic - (NOTE that in this case, they are traveling through the oviduct when they separate.) - This occurs in 1 of every 4 twin sets. Dichorionic Diamniotic - Twins develop in their own amniotic sac and placenta. Decreased risk of entanglement and twintwin syndrome that occurs with greater frequency in monochorionic twinning Monozygotic Twins – Monochorionic Diamniotic - Embryo Splits between days 4-8 - share a chorion - separate amniotic sacs - 70% of Twins Late and rare – monochorionic and monoamniotic - Embryo Split between Day 8 -13 - Share chorion AND amnion - (Keep in mind: they were implanted in the endometrium as one, THEN split.) - Only 1-2% of monozygotic twins occur this way. Mo-Mo's - Increased risk of entanglement of umbilical cords. - The fetal heart rate is often tested daily to check for entanglement - This risk decreases as the twins mature, there is less room and less movement. Monochorionic Complications -Twin Twin Syndrome - Shared placenta, so blood vessels often go between the two - Can lead to imbalance of blood flow through vascular channels that connect the circulatory systems of each twin via the common placenta - One twin getting less blood and produces less urine. This twin is often much smaller than the other - Extra blood flow to the other, however, may result in heart failure. - Untreated, TTS may terminate the pregnancy Conjoined Twins - On day 13, the embryonic disk (bilayer of epiblast and endoderm) begins to differentiate. - If the split occurs after day 13, the twins will share a chorion and amnion. - They will also share body parts. They will be conjoined (Siamese) twins - Only monozygotic twins can be conjoined. Dizygotic (Fraternal) Twins - Where multiple sperm fertilize multiple eggs - Each offspring is unique in their genetic make up (no more closely related than any other 2 siblings) (always implant separately – dichoriotic diamniotic) Multiple Foetal Pregnancy – Complications Pre-eclampsia can occur in any pregnancy but increased risk with multi-foetal pregnancies Pre-eclampsia – The WHO - Pre-eclampsia stands out among the hypertensive disorders for its impact on maternal and neonatal health. - One of the leading causes of maternal and perinatal mortality and morbidity - The pathogenesis of pre-eclampsia is only partially understood, it is related to disturbances in placentation at the beginning of pregnancy, followed by generalized inflammation and progressive endothelial damage. (Risk of both foetal and maternal death. Preeclampsia present at beginning of pregnancy but gets worse during/after trimester 2) - It is generally accepted that the onset of a new episode of hypertension during pregnancy (persistent diastolic blood pressure >90 mm Hg) with the occurrence of substantial proteinuria (>0.3 g/24 h) can be used as criteria for identifying pre-eclampsia - Although pathophysiological changes (e.g. inadequate placentation) exist from very early stages of the pregnancy, hypertension and proteinuria usually become apparent in the second half of pregnancy (Pre-eclampsia – should get peripheral vasodilation during pregnancy but instead get vasoconstriction. Need to monitor BP changes in mother very carefully) (Shallow placentation – shallow implantation – reduced depth of implantation = decreased blood flow – oxidative stress, reduction in growth of foetus (decreased nutrients) Only treatment of preeclampsia is delivery – placenta causing issue, must get rid of it Gets serious during 3rd trimester) (Normally factors ensure there isnt an overgrowth of blood vessels – in preeclampsia have too much of these factors? – no growth) Multi-foetal Pregnancy and Preeclampsia MD210 Physiology Lecture 6 – Foetal functional development and neonatal changes at birth Circulatory System Development One of the first organ systems necessary to sustain viable Embryo Critical Period For its Development Day 20-Day 50 Post Fertilisation ➢Week 3 Begins Development (very early – mother may not know she's pregnant – if mother exposed to toxin, whichever system is being developed at that time is most affected) ➢Week 4 Functioning Heartbeat Ductus Venosus - Links Umbilical Vein with Inferior Vena Cava o Allows Blood to Bypass Foetal Liver - Flow Regulated by Sphincter o 50-80% of Blood flow can Avoid Hepatic Sinuses - Prevents Overloading of Heart o High Venous Return e.g.Uterine Contraction Foramen Ovale - Links Right Atrium with Left Atrium o Avoids Oxygen Rich Blood Going to Pulmonary Circulation - More Direct Route To Ascending Aorta o Upwards to Brain Ductus Arteriosus - Links Pulmonary Artery with Descending Aorta Decrease Blood Flow to Non-Functioning Lungs - 10% of Foetal Blood Travels via Lungs o Growth, Development of Lungs (Placenta – most oxygenated Liver – very immature Enzyme's necessary to breakdown foetal RBCs not found in foetal liver → delivered to mother to be detoxified First shunt allows 80% of blood to bypass liver. Shunt can be opened in times of increased venous return → when baby goes through birth canal – squeezing – increased venous return – open shunt to prevent too much blood returning to heart) Foramen Ovale at Birth These events occur when umbilical cord cut Childbirth – removal of placenta – removal of O2 source – need change of systems Foetus lungs are either full of fluid or collapsed Patent Foramen Ovale - Most Common Atrial Septal Defect - Patent Foramen Ovale Alone o No Haemodynamic Importance o Pressure in LHS > Pressure RHS o Sufficient To Close FO - With Other Defects o Cyanosis of Skin and Mucus Membrane Ductus arteriosus at birth (Prevent blood flow to non-functioning lungs – they start to function – it should close) - Closure is Dependent on Oxygen o PO2 in Foetal D.A. ≈ 15-20mmHg o PO2 in Neonatal D.A. increased ≈ 100mmHg - Critical Point PO2 ≈ 50mmHg o Bradykinin From Lungs and Prostaglandin E2/F2 ▪ Vasoconstriction - Patent Ductus Arteriosus (1in 5500) o Infant - Few Problems o Adults ▪ Increased Re-circulation, Increased Cardiac Output ▪ Decreased Cardiac and Respiratory Reserves Ductus Venosus - Closes within 1-3 Hours - Pressure in Portal System 6-10mmHg - Forces Blood Through Liver Neonatal Cardiac Functions Have to monitor foetus movement and HR closely Foetal heart so small, need to increase HR to ensure systolic BP is enough – drop => hypoxia Diastolic controlled by peripheral resistance Foetal Respiratory System - Respiratory Movements Through Pregnancy (lungs do open and close but movements tend to slow closer to pregnancy) - Decrease in Third Trimester - Protective Mechanism - Increased Foetal Growth - Increased Foetal waste in Amniotic Fluid - Decreased Respiratory Movements - Decreased Swallowing Waste Gas exchange in Foetus - Placenta is Feto-Maternal Organ o Maternal Sinuses ▪ Blood Flow - Uterine Arteries to Uterine Vein - Foetal Capillaries o Chorionic Villi, Dip into Maternal Sinuses - Gas Exchange Across Capillary Wall Separate Distinct Circulations Gas Pressure in Foetal Blood How does foetus survive at low PO2? Foetal haemoglobin 2,3-DPG is a metabolite of glycolysis that normally affects O2 dissociation curve – doesn’t affect foetal Hb – O2 curve shifted to LHS Oxygen-Dissociation Curve Blood supply to uterus - Uterine Blood Flow o Internal Maternal Cardiac Output o Increased to 500ml/min to Uterus (20x) - Re-Distribution of Blood Flow o Oestrogens Increased Uterine Vasodilatation o Progesterone Increased Uterine Venoconstriction o Local Placental Hormones Double Bohr Effect - Bohr Effect - Increased pH Shifts O2 Dissociation Curve To LHS Alkaline Conditions - Binds More Oxygen At Any Given PO2 Acidic Conditions - Binds Less Oxygen At Any Given PO2 (PCO2 foetal side – 46 – gives up PCO2 – becomes more alkaline – more O2 Maternal side acidic – gives up more O2) Bohr Effect: Foetal side of circulation - Foetal PCO2 = 46mmHg; Maternal PCO2 = 45mmHg - CO2 Dissolves to Maternal Circulation o Localised decreased Foetal PCO2 and increased pH - Foetal O2Dissociation Curve Shifted to LHS o At Any PO2 Foetus Binds More O2 Than Mother Bohr Effect: Maternal side of circulation - CO2 Dissolves to Maternal Circulation o Localised increased Maternal PCO2 and decreased pH - Maternal O2Dissociation Curve Shifted to RHS o At Any PO2 Mother Binds Less O2 Than Foetus Pressure/Volume Curve In adult – atm pressure = 760mmHg, Pressure in thoracic cavity = 759mmHg. 500ml air in, pressure increases to 761mmHg in thoracic cavity, 500 ml air out In foetus – line at 0 – either lungs closer or filled with fluid – smaller change. No 1 cause of morality in neonate – respiratory distress Respiratory Values of Neonate Neonate prone to hypoxia/hypercapnia Pulmonary Surfactant (helps neonate to open airway) - Surface tension arises from the difference between the attractive forces on molecules at an airliquid interface - Results in a tension on the surface film that resists expansion - Surfactant - Complex mixture of phospholipids and proteins - Reduce surface tension at the air-liquid interface of the alveolus, thus preventing its collapse during end-exhalation - Also participates in innate defence against inhaled pathogens - Synthesized and secreted by Type II pneumocytes - Differentiate between 24 and 34 weeks of gestation - Composed of o 70% to 80% phospholipids –dipalmitoylphosphatidylcholine o 10% protein - SP-A, SP-B, SP-C, SP-D o 10% neutral lipids – cholesterol Pulmonary Surfactant Production - Production Increased By: o Cortisol, Estrogen, Prolactin, T3/T4 o Hypoxia o Prostaglandins - Production Decreased or Composition Altered by: o Ozone – Decreased SP-A o NO2 – Alters Lipid Composition o TNFα – Decreases Production Effects of Insulin on Surfactant Well controlled levels of insulin stimulate it MD210 Physiology Lecture 7 – Endocrine Function Endocrine Function - Fetal, placental & maternal compartments form an integrated hormonal unit - The feto-placental-maternal (FPM) unit creates the Endocrine Environment that maintains and drives the processes of pregnancy and pre-natal development. Human Chorionic Gonadotrophin (HCG) - Protein mw = 30,000 Glycoprotein - Produced By Trophoblastic Cells - α Subunit = Common (with FSH, TSH, LH) (binding to receptor) - β = Hormone Specific (activity) - Secretion Rate o Begins with Implantation o Detected in Blood Day 8 (post fertilisation) o Detected in Urine Day 14 o Peaks Approx. Two Months of Gestation (drops after trimester 1) HCG – very important – activity similar to LH Corpus luteum at day 14 produces progesterone, stays for 12 weeks, not sufficient on its own – HCG Functions of HCG Basis of pregnancy test – fairly accurate from day 10 onwards Human Chorionic Somatomammotrophin (HCS also called human placental lactogen – because it increases milk production but that’s not its primary function so not as accurate. HCS also causes mammillary growth and involved in metabolism) - Protein o MW = 38,000 o Similar to Growth Hormone and Prolactin o Common Progenitor - Synthesis o Placental Secretion ▪ Week 5 Post Fertilisation ▪ Directly Proportional To Placental Size ▪ Low levels indicative of placental insufficiency HCS Mother – increase IGF – peripheral insulin resistance (normal response) – glucose inhibition – glucose to foetus – increase in maternal lipolysis – sufficient nutrition for foetus – switches metabolism in mother Steroid Hormones Steroid hormone levels Estriol nb in pregnancy Steroid levels during pregnancy much higher Corpus luteum and mother can't maintain levels alone – placenta and foetus involved Steroids in Pregnancy - Progesterone and Oestrogen Levels > during menstrual cycle - Elevated levels are necessary for maintaining pregnancy - In first trimester, hCG maintains the CL - source of steroids - CL cannot secrete high enough steroid levels for late pregnancy - Placenta takes over as major site production of steroids - Placenta is major site by week 8 - the luteal-placental shift o Removal of the ovaries (with CL) before the luteal-placental shift leads to miscarriage o Pregnancy continues normally if the ovaries are removed after the luteal-placental shift Steroid Production Fetal maternal placental unit – specific foetal organs need to be functioning – adrenal glands and liver – liver very immature – doesn’t fully function but produces hormones Progesterone - Source of Progesterone o First Trimester - Corpus Luteum Origin o Second and Third Trimesters - Placental Origin - Formed From Maternal Precursors - Levels Increase Significantly Throughout Pregnancy - 80-90% Produced by Placenta o Secreted to Both Fetus and Mother Maternal functions of Progesterone - Decreases Uterine Contractility (decreased progesterone is a signal for start of labour) - Inhibits Ovulation (basis of contraceptive pill) o Acting on GnRH, FSH and LH - Maintain Uterine Function o Placental Secretion and Function - Embryo Nutrition o Increases Decidual Cells o Increases Uterine Secretion Embryonic Functions of Progesterone - Precursor for other Hormones - Adrenal Hormones o Weak Androgen ▪ Oestrogen - Cortisol o Surfactant Production - Testicular Hormones o Testosterone ▪ Foetal Differentiation Oestrogens of Pregnancy - Oestrone, Oestriol, 17b-Oestradiol - Oestriol - Weak Oestrogen o Not important in nonpregnant women o Major oestrogen of pregnancy - based on circulating levels - From Precursor Weak Androgens o Maternal and Foetal Origin ▪ C-19 Steroids Adrenal Glands • Dehydroepiandrostenedione (DHEA), 17-OH -DHEA - Placental Produced Oestrogens Transfer to Maternal and Fetal Compartments Importance of Oestrogens in Pregnancy - Essential For Foetal Survival - Urinary Oestrogens Decreased with Foetal Death - Myometrial Hypertrophy and Gap Junctions - Lacterous Duct development - Increase Uterine Size (2oz to 2lb, plus increased myometrium growth) - Increase External Genitalia Size - Relaxes Pelvic Ligament (otherwise wouldn’t allow movement of baby’s head into birth canal) - Increase Oxytocin Receptors (causes uterine contractions) (Mother with a recurrent history of unplanned miscarriage – monitor hormones – decreased oestrogen indicated foetal distress.) (Don’t know exact trigger of labour but have decreased progesterone and increased oestrogen) Parturition: Initiation of Labour - Estrogen reaches a peak during the last weeks of pregnancy causing myometrial weakness and irritability - Weak Braxton Hicks contractions may take place - As birth nears, oxytocin and prostaglandins cause uterine ontractions - Emotional and physical stress: o Activates the hypothalamus o Sets up a positive feedback mechanism, releasing more oxytocin (Decreased cortisol linked to prolonged labour) Getting ready for delivery Myometrial Activation Infiltration of leukocytes into the uterine tissues is an essential step in term parturition. Manifested by multiple leukocyte subpopulations (monocytes, granulocytes, lymphocytes) migrating into various reproductive tissues such as the cervix, decidua, myometrium and fetal membranes prior to and during human labour. This mechanism is initiated by the upregulation of pro-inflammatory cytokine and chemokine secretion by the uterine tissues. An increase in the ratio of PRA/PRB, effecting myometrial responsiveness to Progesterone Inflammatory stimuli increase the local expression of 20α-HSD in the myometrium, resulting in higher P4 metabolism and the local P4 withdrawal Joint action of PRA and ERα - myometrial expression of Contraction Associated Proteins Connexin-43, PGF2α receptor, oxytocin receptor and COX-2 CAP protein (via activator protein-1 pathway) Inflammatory proteins (via NFkB pathway) Uterus is converted from quiescent organ to a contractile muscle Forceful synchronous contractions to expel the mature fetus Cortisol – foetus produces the stress hormone it needs to survive stress of being born MD210 Physiology Lecture 8 – Maternal physiology Maternal physiology Physiology changes that occur to ensure a successful pregnancy Almost all organ system affected – “normal”” changes (2 major changes: fluid volume overload, hypercoagulability) Maternal physiology weight gain Weight gain should be monitored closely Weight gain - Obesity and excessive weight gain in pregnancy are associated with: o Gestational diabetes o Macrosomia o pre-eclampsia o caesarean section o post-operative complications Distribution of weight - 6kg maternal tissue 5kg foetal tissues 7kg water, 3kg fat, 1kg protein (Mother becomes less sensitive to insulin so uses fat more for energy? Mother doesn’t need to put on fat reserves unless very underweight) Mother gains more weight at end of pregnancy Maternal Physiology Total Body Water - TBW increases over pregnancy o At term water content of: fetus + placenta + AF - 3.5L o Increased Volume of Blood, Plasma, RBC - Increases from week 6/8 - Max vol 32 weeks (45% increase) o Estrogen action on renin/angiotensin/ aldosterone (oestrogen increases renin/angiotensin system – promotes water retention) - Pregnancy is a condition of Chronic Volume Overload (Physiological response for large water intake is urination – decreased ADH due to decreased osmolality – heightened response in mother – increased urination) Hematologic changes - Red blood cell o Increased production by 33% o Possibly hormonally mediated (increased oestrogen and EPO) - Increase the O2 carrying capacity of blood (more O2 to foetus) - The increase in plasma is greater and faster than RBC - Hb concentration falls from 14gm/dl to 12gm/dl - Dilution anemia (true anaemia = Hgb<12g/dl; Htc<32%) (increased plasma due to retaining water, takes time for levels of RBCs to rise so more plasma than red blood cells – dilution anaemia – not “really” anaemia – eventually balances out) - - - - Leukocytes (Bone marrow is hyperplastic) o Peripheral WBC rises progressively during pregnancy (Normally have 4,000-10,000 ▪ 1st ∆ – mean 9500/mm3 (higher level of normal) ▪ 2nd and 3rd ∆ – mean 10,500 (slightly higher than normal) ▪ Labour – may rise to 20-30,000 (2 or 3 times normal – labour is a hyper-immune response?) o Rise is due to increase in PMNs Platelets o Platelets progressive decline but remain within normal range o Likely due to increased destruction (Pregnancy is a hyperimmune response) (Increase risk of clotting in pregnancy – hypercoagulability – clotting factors) Coagulation Factors o Increased levels ▪ Fibrinogen (Factor I) ▪ Factors VII through X o No change in prothrombin (Factor II), Factors V and XII o Decline in platelet count, Factors XI and XIII ▪ Bleeding time and clotting time are unchanged in normal pregnancy Pregnancy is a hyper-coaguable state Clinical implications 1. Increased circulatory need of the enlarging uterus and the feto/placental unit 2. Fills the ever-increasing venous reservoir 3. Protects the parturient from the bleeding at the time of delivery 4. Parturients become hypercoaguable as the gestation progresses. It takes about 8 weeks after delivery for the blood volume to return to normal. Cardiovascular Changes 1. Increased metabolic demands 2. Expansion of vascular channels 3. Increase in steroid hormone Hematologic changes Hemodynamic changes Cardiovascular System: CO CO = HR x SV - Maternal cardiac output increases about 30-40% - During pregnancy maximum CO is 6-7 L/min o CO remains maximal until delivery/Labor - Caused by hormones estrogen and progesterone - Maintained until 4 days post-partum Cardiac output can vary depending on the uterine size as well as on the maternal position Cardiovascular System: Cardiac Output – Increased – why? - First, it facilitates maternal and fetal exchanges of respiratory gases, nutrients and metabolites. - Second, it reduces the impact of maternal blood loss at delivery. Pulse – Heart rate - 1st trimester resting pulse increases by 8 beats/min - By term increased by 15-20 beats (BPM) Blood - Pressure Systemic blood pressure overall decreased Systolic Pressure changes little Diastolic reduced (5-10 mmHg) Venous pressure upper body unchanged Venous pressure in the lower body increased BP affected by position of mother Hemodynamic changes – Why? Increase O2 demand - Increased CO - Vasodilation at placenta and increased Vascularisation o Increased blood flow to the Feto-Placental unit o Decreased SVR - Diastolic BP decreases Cardiovascular changes - Apex displaced upwards and to the left - Heart size increased 12% - Left axis deviation of (approx. 15%) - Changes in ECG o benign dysrhythmia o reversal of ST, T, and Q waves o left axis deviation Heart Sounds - Split First heart sound - early closure of mitral valve - Intensity of the second sound may become louder - Systolic functional murmurs may develop due to tricuspid regurgitation Peripheral Vasodilation - Increased blood flow to the skin especially hands & feet lead to a feeling of warmth - Increased congestion of nasal mucosa leading to nasal congestion (nose bleeds more common during pregnancy) - Epistaxis common Supine Hypotension Compression of the inferior vena cava (by foetus) - Decreased venous return - Decreased cardiac output - Lowered blood pressure Respiratory changes - At term diaphragm can be elevated up to 4 cm (if diaphragm raised - Tidal volume not affected due to large reservoir - FRC decreased – FRC = functional residual capacity – vol air in lungs after normal respiration – keeps lungs open) Diaphragm - Diaphragm movement reduces thoracic cavity volume - Mobility reduced - Respiration becomes mainly thoracic - Widened subcostal angle increasing transverse diameter of the chest Changes in position of heart, lungs and thoracic cage in pregnancy Respiratory Changes Lung volume and pulmonary function - Tidal Volume increased 30 – 40% - Respiration Rate increased by 15% at term - Minute ventilation is increased at term by about 50% - Expiratory Reserve Volume decreased by 20% - Vital capacity and inspiratory reserve volume unchanged - Alveolar ventilation is greatly increased as the tidal volume increases - Due to elevation of the diaphragm o Total lung volume decreases (diaphragm) by 5% o Residual volume decreases (RV) by 20% o FRC is reduced 20% - No change in FEV1 or the ratio of FEV1 to forced vital capacity - Gas exchange o Minute ventilation rises 30-40% by late pregnancy o O2 consumption increases only 15- 30% o Results in higher PAO2 (alveolar) and PaO2 (arterial) (increased alveolar ventilation (because increased tidal volume but dead space unchanged)) o Fall in PACO2 and PaCO2 levels o Arterial pH remains unchanged ▪ Increased bicarbonate excretion via kidneys - Dyspnea of pregnancy o Common complaint ▪ 60-70% of patients ▪ late first or early second trimester o Likely due to various factors ▪ reduced PaCO2 levels ▪ awareness of increased tidal volume of pregnancy MD210 Anatomy Lecture 4 – Implanta on Embryology - Fer lisa on - Implanta on - Placenta on Fer lisa on - Begins with contact of sperm with secondary oocyte (cell formed in meiosis I) - ends forma on of Zygote (zygote = 1 cell embryo) - Semen deposited in vagina - 1990’s 182 million 300 million -1940’s (there’s a decline in the number of sperm men are producing) - Products of male accessory sex glands Human Semen - Creamy texture – grey to yellow - Average volume 2.5-3.5 ml a er 3 days abs nence (2-6ml) - Fer lity index o at least 20 million sperm/ml o 40% sperm show vigorous swimming o 60% normal shape (abnormal shape means they are immature?) o pH 7.35-7.5 - Epididymis o Water, nutrients o (70 days to grow sperm – majority of me in epididymis) - Seminal Vesicles (2/3) o Water, fructose fibrinogen Vit C Prostaglandins - Prostate (1/3) o Water Buffers, fibrinogenase (clo ng) Fibrinoly c enzyme (liquefac on) citric acid prostaglandins o (Semen coagulates to stay in female) - Bulbourethral (expels spent urine during erec on, route where many microorganisms that cause STDs enter into penis) o water buffers mucous Fer lisa on - ‘Vaginal’ Sperm - 1min - semen coagula on fibrinogenase - 20min - semen liquefac on fibrinoly c enzyme in seminal plasma - Vagina acidic inhibits mo lity basic content of semen makes pH 7.2 (rela on between bacteria and glycogen lowers pH to keep out microorganisms) - Pass through cervical canal - Thick mucus prevents entry (nature of cervical mucus changes – oestrogen dominant – thin & watery, progesterone dominant – thick & s cky – other things also affect hydra on of bodily secre ons) - Preovulatory rise is oestrogen - Thin watery - Swim through 1.2-3mm/min (only have ~3mm to swim) (reverse peristal c mo on on endometrium that selec vely pulls sperm towards the ovary containing the egg) - Uterine cavity - Ampulla of Fallopian tube – site of fer lisa on - Life span around 3-6 days - Capacita on – con nues in female tract - Secondary oocyte (1st polar body) surrounded by granulosa cells, zona pellucida - Acrosome reac on - Hyaluronidase - loss of corona - Acrosin and neuaminidase facilitate passage through zona pellucida - On contact with plasmallema of oocyte Zona reac on prevents polyspermy-release of cor cal granules (as soon as sperm head touches membrane of secondary oocyte, cor cal granules released – barrier against polyspermy) - Contact induces secondary oocyte to divide to become oo d (ovum) and second polar bodynucleus known as the female pronucleus - Tail of sperm degenerates - Head and centriole enter - Head forms male pronucleus - Pronuclei fuse - to form Zygote (Mitochondria from father tagged for destruc on so all mitochondria from mother) Results of fer lisa on - restora on of diploid number (46) - determina on of chromosomal sex of embryo - varia on of human species new combina on of chromosomes - ini a on of cleavage - mito c division of zygote into blastomeres (cell division – cleavage – each cell smaller than 1 before – filled & hatched – enzyma c breakdown of egg cell) The first week of human life - As zygote passes along fallopian tube undergoes cleavage daughter cells-blastomeres (fer lisa on in ampulla of fallopian tube) - new cells smaller a er each division - 16 cell embryo - Morula - blastocyst with blastocyst cavity - 4days - Outer fla ened cells -Trophoblast - Inner cells inside -Inner cell mass - Trophoblast - embryonic part of the placenta - Inner cell mass - primordium of the embryo - Zona pellucida disappears ~ 5-6 days a er fer lisa on - Process of implanta on begins - Part that touches uterus has inner cells Hatches & forms blastocyst – fla ened outside cells (trophoblast) – give rise to embryonic por on of placenta Inside inner cell mass – give rise to ssues of body – contain primordial stem cells Implanta on - Trophoblast differen ates into outer syncy otrophoblast, inner cytotrophoblast - Uterine stroma decidual (shedding) response - Co-ordinated sequence of complex interac ons between gene cally different cell types of embryonic and maternal ssues. - Success requires trophoblast penetra on of several ssue components to reach maternal blood supply. o Epithelial lining of the uterus, o the basal lamina - o underlying stroma. This sequence of events resembles invasion of malignant tumours. The invasive cells must a ach to ECM proteins; secrete proteases capable of degrading these proteins; and migrate through the degraded ECM. During implanta on and subsequent placenta on in the human, popula ons of trophoblast cells invade the endometrium and maternal vasculature within the uterus. Once reaching spiral arteries within the myometrium, trophoblast invasiveness ceases. (stops growing) Unlike tumour cells, which typically exhibit uncontrolled invasion, trophoblast invasion is ghtly regulated. Sub-op mal trophoblast invasion has been shown to occur in the pregnancy disease states of pre-eclampsia and intrauterine growth retarda on. (preeclampsia common in 1st pregnancy – not enough nutri on for foetus – low birth weight) Non-pregnant cycle Pregnant cycle Menstrual cycle is changes in lining of uterus, ovarian cycle is changes in ovary Message produced by embryo - Human chorionic gonadotropin (HCG) – “rescues” corpus luteum Corpus luteum – larger than ovary – first trimester produc on of progesterone from corpus luteum maintains lining of uterus – not enough progesterone = spontaneous abor on Day 7.5 (amnio c cavity – within inner cell mass – where baby will grow) - Trophoblast : cytotrophoblast, syncy otrophoblast End of second week - uteroplacental circula on Inner cell mass - bilaminar disc - amnio c cavity Chorionic cavity Day 9 (spaces begin to appear within synch otrophoblast) (organism starts to grow very quickly – 8 weeks from single cell to a basic plan with discernible organs) (trophoblas c villi – finger-like projec ons gaining nutrients) The only one of these sites that’s compa ble with life is the internal os of uterus but it s ll has complica ons Zona pallucida – barrier to polyspermy but also only to hatch in uterus – not perineal cavity – ectopic pregnancy The Haemochorial Placenta - The chorionic villi cons tute the major fetal component of the placenta. - They consist of a mesenchymal core containing matrix, cells and foetal blood vessels. - During the first trimester the villi are covered by the two-layered epithelium of Trophoblast - The cellular, non-invasive, villous cytotrophoblast and an outer layer of mul nucleated syncy otrophoblast which is bathed in maternal blood. - As gesta on con nues the cytotrophoblast becomes discon nuous and syncy otrophoblast thinner. - Nutrients from maternal blood transported across compartments to reach the foetal vessels. - Some chorionic villi - free others a ached to decidua at site of invasion- anchoring villi. - At these sites villous cytotrophoblast cells proliferate and break through the syncy otrophoblast to form cytotrophoblast columns and invade the decidua basalis. - Some extravillous cytotrophoblast cells also invade uterine spiral arteries becoming endovascular trophoblast. - These cells seem to augment vessel walls. - The maternal components of the placenta o Intervillous blood o Decidua basalis :decidualised endometrial cells and several kinds of immune cells including macrophages and Large Granular Lymphocytes. Evolu on of trophoblas c villi (mesoderm – primi ve connec ve ssue) (1 cell thick – very efficient barrier) Foetal side Maternal side Embryology Basic Embryology Carnegie stages are named after the famous Institute which began collecting and classifying embryos in the early 1900's. Stages are based on the external and/or internal morphological development of the embryo, and are not directly dependent on either age or size. The human embryonic period proper is divided into 23 Carnegie stages. Criteria beyond morphological features include age in days, number of somites present, and embryonic length Normal plate by the anatomist Wilhelm His. For this ‘normal plate’ from the founding work of modern human embryology, His had his artist draw embryos from about the end of the second week to the end of the second month. The plate almost creates the impression of a single embryo at a succession of stages, but in fact brought together specimens from diverse medical encounters. Many would be considered abnormal today. Embryology - The study of the origin and development of an organism - Prenatal period: before birth 38 weeks from conception to birth (average) “fetal” age Gynecologic timing has been from LMP therefore refers to 40 weeks “gestational” age LMP (last menstrual period) is on average two weeks before ovulation Traditional (artificial) division: - Embryonic period: first 8 weeks after conception o All major organs formed (but embryo wouldn't survive outside of mother) - Fetal period: remaining 30 weeks o Organs grow larger and become more complex Fertilisation to Implantation Ectopic pregnancy- vascular supplying it can rupture – blood loss & potential death for mother - Ovulation: egg released into the peritoneal cavity Travels down fallopian tube in which fertilization occurs At conception in fallopian tube, maternal and paternal genetic material join to form a new human life (zygote) Cell division occurs with travel down the tube and into the uterus Week 1 post conception - Zygote divides repeatedly moving down tube toward uterus (cleavage) The daughter cells are called blastomeres - Morula: the solid cluster of 12-16 blastomeres at about 72 hours - Day 4: late 60 cell morula enters uterus, taking up fluid becoming blastocyst Blastocyst - Two distinct types of cells o Inner cell mass: forms the embryo o Trophoblast: layer of cells surrounding the cavity which helps form the placenta - Floats for about 3 days - Implantation on about day 6 post conception o Trophoblast erodes uterine wall o Takes 1 week to complete - If inner cell mass of a single blastocyst divides: monozygotic (identical) twins Week 2 - Inner cell mass divides into epiblast and hypoblast - 2 fluid filled sacs o Amniotic sac from epiblast o Yolk sac from hypoblast - Bilaminar embryonic disc: area of contact (gives rise to the whole body) Week 3 - Bilaminar to trilaminar disc - Three primary “germ” layers: all body tissues develop from these o Ectoderm o Endoderm o Mesoderm Formation of the 3 “germ” layer - Primitive streak (groove) on dorsal surface of epiblast - Grastrulation: invagination of epiblast cells - Days 14-15: they replace hypoblast becoming endoderm - Day 16: mesoderm (a new third layer) formed in between - Epiblast cells remaining on surface: ectoderm The three “germ” tissues - Early specialization of cells - ectoderm and endoderm are epithelial tissue (form sheets of tissue) - Mesoderm is a mesenchyme tissue o Mesenchyme cells are star shaped and do not attach to one another, therefore migrate freely Notochord (organised bundle of cells growing towards the front of embryo – long axis of embryo – signals change in other cells) - Days 16-18 - Primitive node epiblast cells invaginate and migrate anteriorly with some endoderm cells - Rod defining the body axis is formed - Future site of the vertebral column Neurulation - Notochord signals overlying ectoderm - Formation begins of spinal cord and brain (neurulation) - Neural plate to neural groove to neural tube: pinched off into body - Closure of neural tube: begins at end of week 3; complete by end of week 4 (folic acid important for this step) Extends cranially (eventually brain) and caudally (spinal cord) - Neural crest, lateral ectodermal cells, pulled along and form sensory nerve cells and other structures - Mesoderm begins to differentiate o Lateral to notochord, week 3 o Extends cranially and caudally (from head to tail or crown to rump) Division of mesoderm into three regions o Somites: 40 pairs of body segments (repeating units, like building blocks) by end week 4 o Intermediate mesoderm: just lateral to somites o Lateral plate: splits to form coelom (“cavity”) (Gastrulation – formation of 3 layered embryo from 2 layered embryo) - Divisions of the mesodermal lateral plate - Somatic mesoderm: apposed to the ectoderm - Splanchnic mesoderm: apposed to the endoderm - Coelom in between will become the serous cavities of the ventral body cavity: – Peritoneal – Pericardial – Pleural Folding begins at week 4 (main difference between the 3 week embryo and the adult body is that the embryo is still a flat disc) Lateral folding + degree of longitudinal folding Major derivatives of the embryonic germ layers 29 day embryo (this is when the heart starts pumping, about 4 weeks or 1 month, ½ cm size) By 8 weeks, about 2 months, all major organs are in place in at least a rudimentary form; this is why drugs early in pregnancy are so important to avoid – many cause birth defects; baby is a little over 2.5cm long There are many different ways that developmental abnormalities can occur the 2 major types are 1. Congenital (inherited or genetic) and 2. Maternal/environmental derived abnormalities. Congenital abnormalities These developmental abnormalities usually involve only small DNA mutations affecting individual or a few genes, two exceptions are the major chromosomal abnormalities usually trisomy; trisomy 21 (Down syndrome) and trisomy 18 (Edwards syndrome) (also trisomy 9, 13, 15). Note that the occurance of chromosomal abnormalities also increases with increasing maternal age Maternal derived abnormalities: Relate to lifestyle, environment and nutrition. Some examples of this form of abnormality are the impact of excess alcohol on neural development (Fetal alcohol syndrome), viral infection (rubella) at a critical stage of development, inadequate dietry folate intake (neural tube defects), effects of prescription drugs (Thalidomide- limb development) and even maternal endocrine function (thyroid development). In addition to these obvious maternally-derived abnormalities, there is growing evidence that the interuterine environment has a strong influence on later postnatal health. This theory is based on the early statistical analysis of disease/longevity in babies with low birth weights in England by Barker, and has been called the "Barker Hypothesis". Teratogen - any agent that causes a structural abnormality following fetal exposure during pregnancy. The overall effect depends on dosage and time of exposure. Absolute risk - the rate of occurrence of an abnormal phenotype among individuals exposed to the agent. (e.g. fetal alcohol syndrome) Relative risk - the ratio of the rate of the condition among the exposed and the nonexposed. (e.g. smokers risk of having a low birth weight baby compared to non-smokers) A high relative risk may indicate a low absolute risk if the condition is rare. Assisted reproductive technologies Assisted Conception Objective - To bring sperm and oocyte close to each other to promote chances of fertilization and, ultimately, achieve a pregnancy Assisted Conception - IUI: intrauterine insemination* - IVF: in vitro fertilization * - ICSI: intracytoplasmic sperm injection * - GIFT: gamete intrafallopian transfer - ZIFT: zygote intrafallopian transfer - PESA: percutaneous epididymal sperm aspiration - ET: embryo transfer - TESE: testicular sperm extraction - SUZI: subzonal sperm injection - PGD: preimplantation genetic diagnosis *main types - - - Required procedures • Superovulation (Hormonal manipulation to enhance ovulation and release multiple oocytes during ovulatory cycle) (increases chances but uncontrolled overstimulation is risky – twins, triplets, etc.) • Sperm preparation • Assisted fertilization Human menopausal gonadotropin • Taken from urine of postmenopausal women • Follicle stimulating hormone (FSH) and luteinizing hormone (LH) activity Recombinant FSH Recombinant LH Sperm Preparation - Select PMNS (progressively motile normal sperm) - Remove seminal plasma, WBC, and bacteria - Sperm capacitation (ability of sperm to fertilise egg) • Coating of sperm with seminal plasma proteins • Allow sperm to become fertile • In vivo or in test tube Intrauterine insemination - Sperm sample deposited in uterus just before release of an oocyte (s) in a natural or stimulated cycle - Soft catheter - Give hCG at injection or up to 24 hrs later - Sperm volume: 0.2-0.3 ml - Pregnancy rates • Around 15% per cycle Gamete intrafallopian transfer - Laparoscopic technique in which oocyte and sperm placed in fallopian tube, allowing in vivo fertilization - Procedure • Superovulation • US guided transvaginal oocyte retrieval - 0.1-0.2 mil sperm with 2-3 oocytes In vitro fertilisation – IVF - Taking oocytes from woman - Fertilizing them in lab with her partner's sperm - Transferring resulting embryos back to her uterus 3 or 5 days later - Procedure • Superovulation • Insemination • Embryo transfer • Luteal support (giving HCG to maintain corpus luteum) IVF – Superovulation - Gonadotropin stimulation - Monitoring follicular development - US guided transvaginal oocyte retrieval - Oocyte fertilization with sperm IVF – Insemination - Containers used • Test tubes, Petri dishes, multi-well dishes - Each oocyte inseminated with 0.5-1.0 mil PMNS - Fertilization detected 12-20 hrs later by presence of • 2 pronuclei in oocyte cytoplasm • 2 polar bodies in perivitelline space - Syngamy (combination of maternal and paternal pronuclei 24 hrs after insemination Further cleavages occur at 24 hr intervals IVF - Embryo transfer - Embryos transferred to uterus on 2nd or 3rd day after in vitro insemination - 4-8 cells embryos - 2-3 embryos transferred in 20 µl of culture fluid - Transabdominal US to see fluid placed in uterus - Cryopreserve excess embryos IVF - Luteal support - Progesterone (P4) necessary for pregnancy maintenance - Premature luteolysis in some superovulatory regimens - P4 supplementation until menses occur or woman has positive pregnancy test Intracytoplasmic sperm injection – ICSI - Injection of single sperm into single oocyte in order to get fertilization - Procedure • Superovulation • US guided transvaginal oocyte retrieval • IVF ▪ Oocytes injected with sperm using special microscopes, needles and micromanipulation equipment ICSI – Indications - Low sperm concentration, motility, abnormal morphology - Antisperm antibodies - Fertilization failure after conventional IVF - Ejaculatory disorders - absence of vas deferens or obstruction of ejaculatory ducts Assisted Hatching - Indications • Couples having IVF with ▪ Female partner's age over 37 ▪ Poor quality embryos • Excessive fragmentation • Slow rates of cell division (Hatching of zona pallucida –tricky – not as successful as other procedures) Assisted Hatching – Procedure - Embryo held with a specialized holding pipette - A needle used to expel an acidic solution against ZP - A small hole made in ZP - Embryo washed and put back in culture in incubator - ET shortly after hatching procedure • Hope for the best Further Advances And Uses Of Assisted Conception Technology - Cryopreservation of • Sperm • Embryo • Oocyte • Ovarian tissue - Growth of human follicles and oocytes in vitro - In vitro maturation and transplantation of human spermatozoa Assisted Reproductive Technology (ART) - - - - Infertility • Inability to conceive after 1 year of unprotected and regular sexual intercourse Primary infertility • Couples have never had children Secondary infertility • Couples initiated conception in the past and then had difficulty Infertility • Female partner: 35% • Male partner: 35% • Both partners: 20% • Unknown cause: 10% Infertility more common with increasing age USA women infertility rate • Ages 20-24: 4.1% • Ages 25-29: 5.5% • Ages 30-34: 9.4% • Ages 35-39: 19.7% 80% of infertility cases can be diagnosed 85% of cases can be successfully treated - Female infertility • Disorders of ovulation: 27% • Fallopian tube disorders: 22% • Pelvic adhesions: 12% • Endometriosis: 5% to 15% • Hyperprolactinemia: 7% (Patches of tissues that behave like endometrial tissue – clumps of tissues – patches not inside uterus – bleeding – outside ovary, mesentery, broad ligament – bleeding in “wrong” place – more discomfort/pain in menstrual cycle, can still get pregnant) - Male infertility • Abnormal semen parameters ▪ Count, motility, morphology Infertility treatment • Correcting underlying abnormality • ART - - Main techniques • IUI • IVF - embryo transfer • ICSI • Assisted hatching Preimplantation Genetic Diagnosis (PGD) - Identify genetic conditions in embryo before ET - Hemophilia - Cystic fibrosis - Aneuploidy - Performed with IVF 8-cell stage (3 days old) embryo biopsy Obtain 1-2 blastomeres for genetic PGD - Genetic analysis - Multicolor fluorescence in situ hybridization (FISH) - Polymerase chain reaction (PCR) MD210 Anatomy Lecture 7 - Anatomy of Pregnancy The uterus Muscle and Connective Tissue - The myometrium, grows very markedly during pregnancy. - Muscle fibres hypertrophy and increase in number. - Muscle - three layers; outer longitudinal, middle interlacing and inner circular - The connective tissue becomes more vascular. The uterus - The peritoneum intimately attached to the upper uterine segment - Loose and mobile over the lower segment. - The uterine supports hypertrophy. (has to grow to accommodate foetus – tissue would tear otherwise) - The broad ligaments show hypertrophy of all their content. - Levatores anii muscles hypertrophy and become softer. - As a result the pelvic floor becomes progressively more distensible, thereby facilitating passage of the fetus. (process of maturation and softening of tissues to prepare for labour) Uterus - The uterine bloody supply increases - uterine and ovarian arteries become larger and very tortuous. Protective function. - The lymphatics, like the blood vessels, increase in size and number, - Large lymph spaces beneath the decidua and a well-developed plexus under the enveloping peritoneum. - From the 2nd month onwards, hypertrophy of blood vessels and lymphatics produces progressive softening of whole of the body. By 9th month: - The whole of uterus and outer pelvic viscera are so engorged with the blood and lymph that the outlines of the various organs become vague and difficult to define. Size and Position - The non-pregnant uterus measured approximately 2.5x5x7.5cm - At full term the corresponding measurements are 23x25x30cm - The uterus lies in the true pelvis at first but by week 12 the fundus is level with the top of the symphysis pubis. - By week 16 it lies mid-way between the symphysis pubis and the umbilicus - 20 weeks below umbilicus - 24 weeks it is just above it. - Thereafter the fundus rises two fingerbreadths every 4 weeks until 36 weeks when it lies at the xiphisternum. Between 36 and 40 weeks it drops by 1 fingerbreadth per week and at week 40 it lies at the same level that it had reached at week 32. The drop which occurs during the last month( lightening), is due to the descent of the foetal head into the cavity of the true pelvis. Although the woman may feel more comfortable and may breathe more easily after lightening has occurred, she may notice frequency of micturition (urination) due to lack of space in the pelvis. Cervix - Unlike the body, which adapts to the accommodation and expulsion of the foetus, the cervix plays a relatively passive role. - Cervical blood vessels and lymphatics hypertrophy, thereby causing progressive softening which may be detected very early in pregnancy. - The connective and muscular tissues, although they both become more vascular and softer, do not undergo hyperplasia. - The cervical mucosa hypertrophies markedly until it constitutes nearly half the cervix at full term. Eventually, the complex of glands resembles a honeycomb full of sticky tenacious mucus. When this protective mucus plug is expelled at the onset of labour, it carries most of the honeycombed mucosa with it. The external os comes to have anterior and posterior lips, especially in multiparae (has had more than one pregnancy). Isthmus and lower uterine segment - Approximately upper 1/3 of cervix constitutes the isthmus. - Unaffected in 1st month of pregnancy, - Dilates and is taken up into the body of the uterus, to form the lower uterine segment. - The fetal membranes are less firmly blended with the mucosa in the isthmus than elsewhere. - The endometrium lining the lower segment does not undergo a full decidual change. Extra-uterine structures Vagina - Changes are similar to those which occur in uterus. - The blood supply increases enormously (deep violet colour is typical of pregnancy). - Hypertrophy of wall increase both length and width of vaginal canal. Vulva - The vulva undergoes similar changes increased blood and lymphatic supply - causes progressive softening. Breasts - During the first six months of pregnancy the duct system proliferates. - During the last three months of pregnancy the alveoli proliferate. Accompanying these changes in the alveoli, there is hypertrophy of the blood vessels and lymphatics which supply them. - About week 8, Montgomery’s tubercles (raised bumps around aerola that produce a waxy secretion which protects the skin during breatfeeding), which are the mouths of enlarged sebaceous glands, become prominent in the areola. - By week 12, darkening of the primary areola occurs. - From week 16 a paler, secondary areola forms, which is most noticeable in dark-haired women. Abdominal Viscera - The stomach is displaced upwards during the second half of pregnancy. - Diaphragmatic herniation is a fairly common complication of pregnancy. Pelvis - The symphyseal, sacroilac and sacrococcygeal joint capsules soften and relax. - This reaches a maximum about week 28 and may cause sacroiliac backache, - May be accompanied by pain and tenderness in the symphysis. Skin - Skin Pigmentation. Deposition of melanin occurs in certain areas in the body, particularly in dark haired women. - In the face, staining occurs on the forehead and cheeks which is known as the chloasma uterinum. - Increased pigmentation also occurs in the midline of the abdominal wall to form the linea nigra. The Obstetric Pelvis - Dimensions and shape of the maternal pelvis must facilitate passage of the fetal head without injury to it. - The fetal cranium is relatively deformable: the bones of the calvaria are thin and elastic and can alter their shape to some extent. - In addition, they are attached to one another by relatively loose fibrous sutures. - Accordingly, they can override one another somewhat in response to compression forces as the head is squeezed down through the pelvis. - This is known as moulding. - There is, of course, a limit to the amount of moulding which can take place without damage, most significantly to the brain. Moulding is thus something of a fine adjustment. There must be sufficient prior congruity to permit first engagement and then passage of the fetus through the pelvic cavity. Pelvic Measurements The pelvic inlet - The inlet is heart-shaped and is bounded posteriorly by the sacral promontory, laterally by the iliopectineal line and anteriorly by the symphysis pubis. - The plane of the pelvic inlet makes an angle of about 60 degrees with that of the floor. Diameters - The true conjugate. This is measured from the top of the symphysis pubis to the sacral promontory and averages about 4.5 in. - The oblique diameter. This is measured from the sacroiliac joint to the obturator foramen of the opposite side and averages 4.75in. - The transverse diameter. This is the widest measurement from side to side and averages 5.25in. The Pelvic Cavity - This is bounded anteriorly by the symphysis pubis and posteriorly by the sacrum and coccyx. - Its diameters are usually taken at the level of the junction of the second and third sacral vertebrae posteriorly and the middle of the symphysis anteriorly. - Here the anteroposterior, oblique and transverse diameters all measure ca 12cm The Pelvic Outlet - The outlet is bounded by the pubic arch anteriorly, by the ischial tuberosities and sacroiliac ligaments laterally and by the tip of the coccyx posteriorly. Diameters - Anteroposterior. This is measured from the lower border of the symphysis pubis to the sacroiliac joint, and averages 5.25 in. - Transverse (bituberous) diameter. This is taken between the lower borders of the ischial tuberosities and averages 4.25 in. - The subpubic angle. This is bounded buy the pubic rami and symphysis and averages 86 degrees. Method of Pelvic Analysis The Inlet is divided into the forepelvis and the hindpelvis by the widest transverse diameter. - The walls of the hindpelvis include that portion of the ilium overlying the sacroiliac notch. - This is one of the most variable sections in the pelvis and this region is most affected most by sexual and evolutionary differences. The Outlet is divided into anterior and posterior segments by the intertuberous diameter. Three factors influence the capacity of the anterior segment: - (a) The subpubic arch. The arch may be wide, moderate or narrow. - Its shape depends the curve of the inferior pubic rami and is usually well curved in the female pelvis and straight-edged in male pelvis. - (b) The side walls which may incline toward or away from one another, or may be parallel, as they pass downward. - (c) The depth of the pelvis, which is taken from the iliopectineal line along the back of the obturator foramen to the ischial tuberosity. - The posterior segment is mainly influenced by the following factors: The width of the greater sciatic notch; The sacral curve and inclination. The greater the upward and backward tilt of the lower end of the sacrum, the more room there is in the lower pelvis for passage of the fetal head; The degree to which the ischial spines project inward. Anatomical changes during normal labour - In a primigravida (first pregnancy) the head normally becomes engaged in the pelvic inlet by week 37 or 38 of pregnancy. - In a multipara, engagement may not occur until the membranes rupture at the end of the first stage of labour. - Although labour is continuous, for descriptive convenience it is divided into three stages. (First labour usually longer than subsequent deliveries) Stage 1 - During labour, rhythmic uterine contractions increase markedly in strength, frequency and duration. - These are typically experience as pain, beginning in the sacral region and passing round to the front of the abdomen, rising to a climax and then fading away. - Associated with the successive contraction and retraction of the upper uterine segment, the lower uterine segment becomes progressively thinner and the cervix dilates. - This leads to detachment of the mucosa lining the lower uterine segment, with rupture of the small blood vessels attaching it to the uterine wall. In this manner the forewaters are formed. - The blood that has been shed mixes with the mucous of the cervical plug, which separates at the same time, to form the blood-stained mucous discharge known as the show. - Cervical dilation is termed effacement. The internal os of the cervix and the cervical canal are gradually “taken up”: they merge with the cavity of the lower uterine segment. - This process is completed by the dilation of the external os. - There are two pacemakers, one on each side, at the uterine end of each uterine tube, which drive uterine contractions. - Uterine contractions have the following sequence: increasing strength, a maximum, a quick decline and a period of rest. Some of the shortening of a muscular contraction is permanently maintained. - - - This progressive process is known as retraction. Retraction occurs throughout the upper uterine segment but manly at the fundus. With each contraction, traction is applied to the relatively passive lower segments and through it to the cervix. At the same time the forewaters and the presenting part are forced downwards. Retraction causes the upper segment to progressively thicken and the lower segment to stretch. The junction of the two parts is known as Bandl’s ring. The stretching and expansion of the lower segment, combined with effacement and dilation of the cervix, ultimately converts the cavities of the uterus, cervix and vagina into a single unit – the birth canal. This is a low resistance pathway down which th