Hypertansive disorders in pregnancy

1. Hypertansive disorders in pregnancy Zehra Eren,M.D.

2. LEARNING OBJECTIVES • recall hemodynamic and biochemical changes in normal pregnancy • describe preeclampsia-eclampsia • describe chronic (preexiting ) hypertension • describe preeclampsia-eclampsia superimposed upon chronic hypertension • describe gestational hypertension • explain HELLP Syndrome • manage hypertensive disorders during pregnancy

3. Hemodynamic and biochemical changes in normal pregnancy

4. Cardiovascular and Renal Physiology BloodPresure (BP) Regulation: • BP fallshortlyafterconceptionandreturnto normal at term - peripheralvasodilatationandresistancetoangiotensin II (prostacyclinandprolactinlevels↑) -Nitricoxidesynthesis↑ • Renin-angiotensin-aldosteronesystem(RAAS) is stimulated, aldosterone is critical in maintainingsodiumbalance

5. Volume Regulation • Circulatingbloodvolume↑ 50% • Redbloodcellmass↑20-30% • Cumulativesodiumretention (500-900mEq) → extrasellularfluidvolume↑ → weightgain → ‘’benign ‘’ edema of lowerextremities

6. Renal Hemodynamics • GFR: secondtrimester↑ 50% lasttrimester↑20% returntoprepartumlevelswithin 3 monts • Normal plasmacreatininefallto 0.5 mg/dl >0.8 mg/dl shoud be consideredabnormal • Renalbloodflow↑85% ↑cardiacoutput (30-40%max) ↑renalvasodilatation (afferentandefferent)

7. Hypertensive disorders • Systolic BP >140 mm Hg /125mmHg Diastolic BP >90 mm Hg /75mmHg • Mostcommon (10% of pregnancies) • ↑maternalandfetalmortalityandmorbidity • Leadingtoprematurebirth

9. Causes of Hypertansion in pregnancy

10. Chronic Hypertention • HT presentbeforepregnancyordiagnosedbeforetwentiethweek of gestation • May include HT diagnosedduringpregnancythatdoes not resolveafterdelivery • May be associatedwithnephrosclerosiswith minimal proteinuria • İncreased risk of preeclampsia, abruptioplacentae, intrauteringrowthretardationandsecondtrimesterfetaldeath

11. Treatment

12. Treatment • Methyldopa and labetalolarepreferredagentfortreatment • A long-acting calcium channel blocker (eg, nifedipine) can be added if needed • İn womenwhoenterpregnancywithwell-controlled BP, sameregimen can be continued • ACE inhibitors, ARBs anddirect renin inhibitorsarecontraindicated

13. Gestational Hypertantion Essentials of Diagnosis • Maternal blood pressure elevation of ≥140 mm Hg systolic or ≥90 mm Hg diastolic on 2 occasions 6 hours apart in a previously normotensive woman ≥20 weeks' gestation • No evidence of proteinuria • Resolved after delivery ( women are at risk for chronic HT) • Risk factors: multiparity, obesity, positive family history

14. Preeclampsia-Eclampsia • Systemic syndrome unique to pregnancy • Essentials of Diagnosis • Maternal blood pressure elevation of ≥140 mm Hg systolic or ≥90 mm Hg diastolic on 2 occasions 6 hours apart • Proteinuria ≥300 mg in a 24-hour urine specimen • Resolving with delivery • Eclapsia: occurrence of sezures

15. Preeclampsia-Eclampsia Hypertension in pregnancy: Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013; 122:1122

16. Pathogenesis of preeclampsia

17. Risk factors

18. Renal abnormalities in preeclampsia

19. Renal Abnormalities • Renalbloodflowand GFR fall • Decreasedurateclearenceandincreasedcalciumreabsorption→hyperuricemiaandhypocalciuria • GFR can decreaseby 30-40%→creatininelevelsincreased (1.0-1.5mg/dL) • Hyperuricemiamaycorrelatewithclinicalseverity of preeclampsia (>4.5mg/dL)

20. Clinical features • Usuallybeginsafterthethirty-secondweekandmayseenpostpartumwithin 24-48 h afterdelivery • Usuallyresolveswithin 10 daysafterdelivery • Diastolic HT is prominent, with SP<160mmHg • SBP>200mmHg suggestpreeclampsiasuperimposed on chronic HT • When HT andproteinuriaoccurbefore 20 w, etiologiesotherthanpreeclampsiashould be sought

22. Clinical features • Pulmonaryedemacan occurduetochanges in pulmonarycapillarypermeability • Hyperreflexiasecondarytocentralnervoussystemexcitabilityreflects of neurologicinvolvement

23. Classification of Preeclampsia

25. HELLP Syndrome • Hemolysis • ElevatedLiverFunctionTests • LowPlatelets

26. HELLP Syndrome • Commonlyassociatedwith severe HT andvariabledegrees of renalfailure • May be associatedwith -pulmonaryedema -ascites -acuterenalfailure -disseminatedintravascularcoagulation

28. Treatment of Preeclampsia • Prophylacticlow-doze aspirin orcalcium→ noevidence of significantreductionorimprovedoutcomes • Bed rest→ therapy of choiceformilddisease (BP<140/90 mmHg, proteinuria<500mg/24h, normal renalfonction,uratelevels<4.5mg, normal PLT, andnoevidence of hemolysisorhepaticdysfunction) • Optimal levels has not be defined

29. Treatment of Preeclampsia 2

31. Target blood pressure • 130 to 150 mm Hg systolic and 80 to 100 mm Hg diastolic • The rapidity with which blood pressure should be brought to safe levels is controversial • Cerebral or myocardial ischemia or infarction can be induced by aggressive antihypertensive therapy if the blood pressure falls below the range at which tissue perfusion can be maintained by autoregulation • Reducing mean arterial pressure by no more than 25 percent over 2 hours and achieving a target of 130 to 150 mmHg systolic and 80 to 100 mmHg diastolic seems reasonable

32. Preeclampsia superimposed upon chronic hypertension • Difficulttodistinguishfromworseninghypertansion • Suspect in womenwith HT before 20 week of gestationwhodeveloptproteinuriaorsuddenincrease in BP • Morelikelytooccur in olderpatients • Hyperuricemia, proteiuria, orrise in serum creatininesuggestspreeclampsia • Risk in womenwithsome form of renaldisease is between 20-40%

33. Acute Renal Failure in Pregnancy • Earlypregnancy 1.Prerenalazotemia→ hyperemesis, hemorrage of spontaneusabortion 2. Acutetubularnecrosis→ volumedepletionsecondarytohyperemesis, hemorrage of spontaneusabortion, septicabortus, Gram-negativesepsis, myoglobulinuriasecondarytoClostridiuminducedmyonecrosis of uterus 3.Renalcorticalnecrosis

34. Renal Cortical Necrosis • Frequentlyseen in olderwomen, multigravidas, multiplgestations • Causes: abruptioplacentae, septicabortion, severe preeclampsia, amnioticfluidembolism, retainedfetus • Presentswithgrosshematuria, flankpain, severe oliguriaoranuria • Renalfunctionalrecoveryrequiresmontsand is incomplete, mayleadto ESRD

35. Acute Renal Failure in Pregnancy • Latepregnancy 1. Acutetubularnecrosis→ preeclampsia, HELLP syndrome, bleeding in abruptioplacentae 2. Acutefattyliver of pregnancy→ presentafter 34 weekwithjaundiceandabdminalpain; associatedwith ARF

36. Acute Renal Failure in Pregnancy 3.Postpartum acute renal failure and thrombotic thrombocytopenic purpura- hemolytic uremic syndrome -presents with severe HT, microangiopathic hemolytic anemia, thrombocytopenia and ARF days to weeks after normal pregnancy -patients can have severe deficiency of ADAMSTS-13 activity

37. Acute Renal Failure in Pregnancy 3.Postpartum acute renal failure and thrombotic thrombocytopenic purpura- hemolytic uremic syndrome -Retained placental fragments may play a role -major clinical issue is to differantiate from preeclampsia and HELLP syndrome -Treatment: plasma exchange or plasmapheresis

39. What Did We Learn? • - Cardiovascularandrenalhemodynamicchanges in normal pregnancy • Preaclampsia-eclampsia • Chronichypertension • Preeclampsia-eclampsiasuperimposedchronichypertension • Gestationalhypertension • Maternalevaluation • Indicationfortreatment of hypertensivedisorders • Acutetherapy • Long-term oral therapy