Pregnancy Pathophysiology PDF

Advanced Physiology and Pathohysiology Pregnancy Pathophysiology Josh Watson, Ph.D. [email protected] Pregnancy Dating Gestational Period From conception to birth is normally 38 weeks (9 months) BUT we calculate gestation from the first day of the last menstrual period (2 weeks before ovula...

Advanced Physiology and Pathohysiology Pregnancy Pathophysiology Josh Watson, Ph.D. [email protected] Pregnancy Dating Gestational Period From conception to birth is normally 38 weeks (9 months) BUT we calculate gestation from the first day of the last menstrual period (2 weeks before ovulation/fertilization) 40 weeks (9.5 months or 280 days) Trimesters 1st – First 12-14 weeks 2nd – Week 12-14 to week 24-28 3rd – Week 24-28 to week 37-42 Delivery Preterm- any delivery before 37 weeks Term- delivery between 37-42 weeks Postterm- delivery after 42 weeks Pregnancy Terms Gravidity (G) Number of times a woman has been pregnant (including current pregnancy, if applicable) Parity (P) Describes the outcomes of those pregnancies Term deliveries, preterm deliveries, abortions (spontaneous or induced), number of living children A woman who comes to see you for her first prenatal visit has a son who was born at 35 weeks, a daughter who was born at 38 weeks, and had one abortion at age 15. G4P1112 A woman who comes to see you for her first prenatal visit has twins who were born at 39 weeks and has had two miscarriages in the past. G4P1022 Anatomic Changes in Pregnancy Almost every organ system is affected to accommodate the maternal/fetal environment and allow for delivery Bladder GI track Thorax IVC Lymphatics Spinal column Round ligament Breast Uterus Physiologic Changes in Pregnancy Cardiovascular System CO, SV, and HR Increase Blood volume increases – Dilution effect Plasma more than RBC count Reduced plasma oncotic pressure Pro-coagulable state Lungs Increase respiratory rate and ventilation Can be compressed due to displacement Kidneys Increased RBF and GFR Physiologic Changes in Pregnancy Cardiovascular System CO, SV, and HR Increase Pressure varies based on trimester Blood volume increases – Dilution effect Plasma more than RBC count Reduced plasma oncotic pressure Pro-coagulable state Lungs Increase respiratory rate and ventilation Can be compressed due to displacement Kidneys Increased RBF and GFR Physiologic Changes in Pregnancy Pregnancy is a hyperestrogenic state produced mainly by the placenta Necessary for fetal well being Increased estrogen = hypercoagulable state Increased risk of blood clots (DVT, PE) Pregnancy is diabetogenic Increased maternal blood sugar due to increased insulin resistance Progesterone causes smooth muscle relaxation Necessary to relax the uterus to prevent early delivery Miscarriage Spontaneous abortion – pregnancy loss < 20 weeks gestation 1st trimester spontaneous abortions are extremely common 2nd trimester rare Causes: Fetal chromosomal anomalies, Anembryonic Teratogen exposure Endocrine abnormalities (progesterone, thyroid), DM Space in issues uterus – Fibroids uterine malformation Risk factors Advanced maternal age Previous miscarriage – especially consecutive (do chromosomal analysis) Other: maternal smoking/drug/alcohol use, maternal disease (DM, autoimmune, endocrinopathies) Miscarriage Presentation Most spontaneous abortions are subclinical Happen frequently and most patients were unaware they were pregnant If clinical Vaginal bleeding Pelvic pain Positive hCG test May still retain fetal content May become septic if tissue is not removed Miscarriage Management Ultrasonography and B-hCG levels helpful to monitor fetal tissues if miscarriage uncertain Examination of expelled contents, difficult to distinguish complete from incomplete abortion Removal of retained tissue Expectant management Medical treatment: anti-progesterone and prostaglandin analog Pt follow up: follow u/s, hCG Dilatation and curettage (D&C) Ectopic Pregnancy Pregnancy with inappropriate implantation of developing embryo Majority happens in fallopian tube Not a viable pregnancy, must be removed Maternal life is in danger Risk factors are anything that causes scaring of tube or decreased peristalsis Pelvic inflammatory disease Prior tubal surgeries Endometriosis Intrauterine device Smoking In vitro fertilization Ectopic Pregnancy Presentation Symptoms Abdominal/pelvic pain Missed menses (or known pregnancy) Vaginal bleeding If tube ruptures with significant bleeding May quickly develop hypovolemic shock Exam Abdominal/pelvic tenderness Palpable adnexal mass Ectopic Pregnancy Diagnosis Any female of reproductive age complaining of acute onset abdominal pain needs a pregnancy test β-hCG should double every 48 hours in an early, normal pregnancy β-hCG levels of 15 IU/ml is the threshold for embryo visualization via ultrasound If β-hCG is positive and does not increase appropriately over time, then abnormal pregnancy is likely (including ectopic) If miscarriage is suspected, β-hCG should decrease with time Ectopic Pregnancy Diagnosis Above threshold levels: If pregnancy not in uterus, then likely ectopic If uterine pregnancy confirmed, can exclude ectopic Below threshold: Lack of visualization is inconclusive, repeat hCG and u/s in 2-3 days Ultrasound to visualize gestational content and confirm location Transvaginal (TV) ultrasound looking for intrauterine pregnancy, adnexal mass Should see intrauterine pregnancy at threshold β-hCG level (10-15 IU/ml) Ectopic Pregnancy Management Can be treated surgically or medically Depends on patient stability Stable patients are candidates for either treatment If hemodynamically unstable or if rupture is likely surgery is needed Salpingectomy for severe tubal damage Used if repeated ectopics no future pregnancy planned IVF Salpingostomy will spare the tube May increase risk for future ectopics Salpingostomy Salpingectomy Ectopic Pregnancy Management Methotrexate is used to medically manage ectopic pregnancy Folic acid antagonist anticancer drug which inhibits DNA synthesis Targets rapidly dividing cells Low dose given to terminate pregnancy, can be given in combination with other therapies Can be given as single or multi-dose regimen depending on decline of hCG levels Must follow hCG decline post-treatment to confirm treatment Patient must be willing to comply with follow up or NOT a candidate for medical management Hypertension in Pregnancy Blood pressure decreases during 1st and 2nd trimester and return to pre-pregnancy levels in 3rd trimester 5-10% of pregnancies will develop hypertension 2nd leading cause of maternal death in pregnancy worldwide Gestational hypertension - BP > 140/90 mmHg or significantly elevated above pre-pregnancy levels after 20 weeks gestation Classically problems arise during the 3rd trimester Blood pressure should normalize after delivery Must monitor patient and assess for preeclampsia, worsening disease, fetal wellbeing etc. Preeclampsia Preeclampsia BP changes of gestational hypertension Proteinuria (>300 mg/24hrs, >1+ dipstick) Severe Preeclampsia BP >160/110 mmHg Severe proteinuria (>5g/day), edema End organ damage: neurological symptoms (severe headache, visual change), renal failure, liver dysfunction, pulmonary edema HELLP syndrome associated with hypertensive states (10-20% of pts in this category) Eclampsia All of the above plus seizures Stroke risk 2-3% of pts with severe preeclampsia Preeclampsia Pathophysiology Normal placentation involves invasion of cytotrophoblast tissue into maternal spiral arteries Allows for remodeling of arteries to increase blood flow Occurs by 20 weeks gestation Preeclampsia Cytorophoblasts fail to fully invade spiral arteries Shallow placental implantation and narrow vessels Low perfusion and placental hypoxia Placenta will release vasoactive substances to help alleviate hypoxia Vasoconstrictors and other products that damage vessels and other organs Preeclampsia Pathophysiology Preeclampsia Pathophysiology Why is placental remodeling affected? Failure of trophoblasts to express CAMs Disordered vessel growth Maternal inflammation Genetic Risks Personal or family history Immunogenic More common in first pregnancy or with new partner Short cohabitation with partner or use of barrier contraception Exposure to paternal antigens are protective History of vascular diseases Lupus, hypertension, renal disease, Diabetes, etc. Preeclampsia Pathophysiology Placental Dysfunction Placenta releases mediators that damage vessels and inhibit vessel growth and cause endothelial damage Immune component Anti-AngII receptor antibodies will activate receptors Vascular Dysfunction causes other issues Hypertension, edema, poteinurea Increased clotting and DIC End organ damage in liver and brain Placental abruption, loss of pregnancy, and slower fetal growth Preeclampsia Management Only “cure” is delivery and removal of placenta Depends on fetal age and maternal condition Balancing act Mild/Stable Presentation Usually inpatient to monitor the patient for signs of maternal or fetal distress Changes in BP, Cr, AST, fetal heart rate, etc. Magnesium sulfate is seizure prophylaxis Control maternal blood pressure if possible Provide corticosteroids to aid fetal lung development Severe Disease or Fetal Distress Immediate Delivery Gestational Diabetes Maternal insulin resistance is normal in pregnancy Increases available glucose for fetus GDM occurs when maternal system can’t compensate 10-15% of pregnancies and rising Can be thought of as a preview of how body deals with carbohydrate stress GDM increases likelihood of maternal DM and CVD up to 10X. Gestational Diabetes Risks Previous GDM, family history of DM, insulin resistance, advanced age Obesity, PCOS, metabolic syndrome Increased in populations with increased DM risks: Hispanic, Native Americans, African Americans Screening involves a glucose tolerance test Drink sugar and monitor BG afterwards >130mg/dl after one hour is bad or multiple elevations if followed longer Gestational Diabetes Management Pre-pregnancy Lifestyle modifications At diagnosis Lifestyle modifications Glucose monitoring and medication if persistently high Maternal Complications Hypertension, preterm birth, C-section delivery Increased risk of future DM Infant Complications High birth weight can lead to injury Neonatal hypoglycemia Neonatal death Increased risk of future DM and obesity Abnormal Placental Conditions Normally placenta implants high on uterus and remains attached until after delivery Only invades the myometrial layer Placental Abruption Premature separation of placenta from uterus after 20 weeks Presents with painful bleeding Placenta Previa Placenta is located at or near the cervical os Presents with painless bleeding after 20 weeks Placental Accreta Placenta invades too deeply Usually asymptomatic, found on routine screens Placental Abruption Premature separation of maternal vasculature from uteroplacental attachement Risk of fetal mortality Risks Hypertention/preeclampsia Cocaine use Trauma Previous abruption Advanced maternal age Multiple gestations Smoking Placental Abruption Diagnosis is difficult Usually diagnosed after other conditions are ruled out Sometimes can see hematoma on ultrasound Requires constant monitoring Support mother and monitor fetal health Prepare for delivery, possibly preterm If abruption is severe or if >36 weeks immediate delivery/C-section Can have sever blood loss Placenta Previa Diagnosis is easy via ultrasound Pathology is unknown Usually found prior to symptoms during routine checkup Risks Uterine scarring from prior C-section or any uterine surgery Previa history Multiple gestations Multiparity (twins, etc.) Smoking Advanced age IVF Placenta Previa Diagnosis is easy via ultrasound Usually found prior to symptoms during routine checkup If found in 2nd trimester, can resolve on own Management If stable “Pelvic rest” – bed rest with no intercourse Must deliver by C-section If unstable, possible pre-term delivery Large hemorrhage risk Abnormal Placental Attachment Identified via ultrasound on routine screens Increased maternal hemrohhage during delivery when placenta detaches Can require C-section and surgical removal of placenta Hysterectomy is sometimes required to manage bleeds Usually due to uterine scarring from surgery Weakened walls allow for deeper invasion Accreta – attached through endometrium to myometrium Increta – attached into myometrium Percreta – attached through myometrium to serosa