MD210 Physiology Lecture 5 - Egg Activation 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