Hypertansive disorders in pregnancy Zehra Eren,M.D.

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 HEELP Syndrome manage hypertensive disorders during pregnancy

Hemodynamic and biochemical changes in normal pregnancy

Cardiovascular and Renal Physiology Blood Presure (BP) Regulation: BP fall shortly after conception and return to normal at term - peripheral vasodilatation and resistance to angiotensin II (prostacyclin and prolactin levels↑) -Nitric oxide synthesis ↑ Renin-angiotensin-aldosterone system(RAAS) is stimulated, aldosterone is critical in maintaining sodium balance

Volume Regulation Circulating blood volume ↑ 50% Red blood cell mass ↑20-30% Cumulative sodium retention (500-900mEq) → extrasellular fluid volume ↑ → weight gain → ‘’benign ‘’ edema of lower extremities

Renal Hemodynamics GFR: second trimester ↑ 50% last trimester ↑20% return to prepartum levels within 3 monts Normal plasma creatinine fall to 0.5 mg/dl >0.8 mg/dl shoud be considered abnormal Renal blood flow ↑85% ↑ cardiac output (30-40%max) ↑ renal vasodilatation (afferent and efferent)

Hypertensive disorders Systolic BP >140 mm Hg /125mmHg Diastolic BP >90 mm Hg /75mmHg Most common (10% of pregnancies) ↑maternal and fetal mortality and morbidity Leading to premature birth

Causes of Hypertansion in pregnancy

Chronic Hypertention HT present before pregnancy or diagnosed before twentieth week of gestation May include HT diagnosed during pregnancy that does not resolve after delivery May be associated with nephrosclerosis with minimal proteinuria İncreased risk of preeclampsia, abruptio placentae, intrauterin growth retardation and second trimester fetal death

Treatment

Treatment İn stage 1 and 2 HT, may require less or even antihypertansives if BP is controlled Methyldopa is preferred agent for treatment İn women who enter pregnancy with well- controlled BP, same regimen can be continued ACE and ARBs are contraindicated

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

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

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

Pathogenesis of preeclampsia

Risk factors

Risk factors

Renal abnormalities in preeclampsia

Renal Abnormalities Renal blood flow and GFR fall Decreased urate clearence and increased calcium reabsorption→hyperuricemia and hypocalciuria GFR can decrease by 30-40%→creatinine levels increased (1.0-1.5mg/dL) Hyperuricemia may correlate with clinical severity of preeclampsia (>4.5mg/dL)

Clinical features Usually begins after the thirty-second week and may seen postpartum within 24-48 h after delivery Usually resolves within 10 days after delivery Diastolic HT is prominent, with SP<160mmHg SBP>200mmHg suggest preeclampsia superimposed on chronic HT When HT and proteinuria occur before 20 w, etiologies other than preeclampsia should be sought

Clinical features Pulmonary edema can occur due to changes in pulmonary capillary permeability Hyperreflexia secondary to central nervous system excitability reflects of neurologic involvement

Classification of Preeclampsia

Severe preeclampsia 2013 criteria do not include -proteinuria >5 grams/24 hours and -fetal growth restriction as features of severe disease Hypertension in pregnancy: Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013; 122:1122

HEELP Syndrome HEmolysis Elevated Liver Function Tests Low Platelets

HEELP Syndrome Commonly associated with severe HT and variable degrees of renal failure May be associated with -pulmonary edema -ascites -acute renal failure -disseminated intravascular coagulation

Treatment of Preeclampsia Prophylactic low-doze aspirin or calcium→ no evidence of significant reduction or improved outcomes Bed rest→ therapy of choice for mild disease (BP<140/90 mmHg, proteinuria<500mg/24h, normal renal fonction,urate levels<4.5mg, normal PLT, and no evidence of hemolysis or hepatic dysfunction) Optimal levels has not be defined

Treatment of Preeclampsia 2

Preeclampsia superimposed upon chronic hypertension Difficult to distinguish from worsening hypertansion Suspect in women with HT before 20 week of gestation who developt proteinuria or sudden increase in BP More likely to occur in older patients Hyperuricemia, proteiuria, or rise in serum creatinine suggests preeclampsia Risk in women with some form of renal disease is between 20-40%

Acute Renal Failure in Pregnancy Early pregnancy 1.Prerenal azotemia→ hyperemesis, hemorrage of spontaneus abortion 2. Acute tubular necrosis→ volume depletion secondary to hyperemesis, hemorrage of spontaneus abortion, septic abortus, Gram- negative sepsis, myoglobulinuria secondary to Clostridium induced myonecrosis of uterus 3.Renal cortical necrosis

Renal Cortical Necrosis Frequently seen in older women, multigravidas, multipl gestations Causes: abruptio placentae, septic abortion, severe preeclampsia, amniotic fluid embolism, retained fetus Presents with gross hematuria, flank pain, severe oliguria or anuria Renal functional recovery requires monts and is incomplete, may lead to ESRD

Acute Renal Failure in Pregnancy Late pregnancy 1. Acute tubular necrosis→ preeclampsia, HEELP syndrome, bleeding in abruptio placentae 2. Acute fatty liver of pregnancy→ present after 34 week with jaundice and abdminal pain; associated with ARF

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

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 HEELP syndrome -Treatment: plasma exchange or plasmapheresis

What Did We Learn? - Cardiovascular and renal hemodynamic changes in normal pregnancy Preaclampsia-eclampsia Chronic hypertension Preeclampsia-eclampsia superimposed chronic hypertension Gestational hypertension Maternal evaluation Indication for treatment of hypertensive disorders Acute therapy Long-term oral therapy