HYPERTENSIVE DISORDERS IN PREGNANCY

1. HYPERTENSIVE DISORDERS IN PREGNANCY ASSOCIATE PROFESSOR IOLANDA BLIDARU MD, PhD.

2. Introduction • Hypertensive disorders of pregnancy are leading causes of maternal mortality. • Worldwide: 50,000 women die each year.

3. Definitions • Hypertension in pregnancy • BP of 140/90 or more = abnormal. • If there is a rise of 30 mmHg or more in the systolic blood pressure or 15 mmHg or more in the diastolic blood pressure in 2 occasions 6 hours apart. • Mean arterial BP> 105 mmHg . Systolic + 2 Diastolic Mean arterial BP = ----------------------------- 3

4. Classification

5. Gestational hypertension (PIH). • Preeclampsia (mild, severe). • Eclampsia. • Superimposed preeclampsia upon chronic hypertension. • Chronic hypertension with pregnancy.

6. Definitions • Gestational hypertension: • Hypertension for first time after 20 w, without Proteinuria. BP returns to normal before 12 weeks postpartum (formerly PIH). • Chronic hypertension with pregnancy: • Hypertension antedates pregnancy and is detected before 20 w, & lasts more than 12 weeks postpartum.

7. Definitions • Preeclampsia: • The development of hypertension and Proteinuria after 20 w (earlier in vesicular mole or twins). • Eclampsia (in Greek= Flash of light): • The occurrence of tonic-clonic convulsions (without any neurological disease) in a woman with pre-eclampsia.

8. Definitions • Superimposed pre-eclampsia: • It is the new development of Proteinuria after 20 weeks gestation in a patient with chronic hypertension.

9. Definitions • Proteinuria: • ≥ 300mg/24 hours urine. • ≥ +1 dipstick. • Heavy Proteinuria : • = ≥ 2g/24 hours • ≥ +2 in dipstick.

10. Preeclampsia

11. Epidemiology of preeclampsia Incidence • Is a disease of humans only. • Is the most common medical disorder complicating pregnancy →5-15% • Is the most common hypertensive disorder in pregnancy. • More common in primigravidas and elderly multipara. • More common in winter. • More in black race.

12. Epidemiology Risk factors • Chronic hypertension. • Chronic nephritis. • Past history. • Family history. • Obesity. • Multiple pregnancy.

13. Epidemiology – Riskfactors • Polyhydramnios. • Vesicular mole. • Diabetes mellitus. • Nulliparity. • Teenage / over 35 years pregnancy. • Afro-American ethnicity. • Stress.

14. Etiology= theories 1. Abnormal trophoblastic invasion Incomplete invasion → atherosis

15. The development of uteroplacental vessels 1-st wave→ before 12 w. → invasion + modification of spiral arteries up to the border between decidua and myometrium. 2-nd wave→ 12 - 16 w. → invasion of the intramyometrial segments of spiral arteries. Remodelingof spiral arteries into dilated, low-resistance uteroplacental vessels. Significance -pathogenesis of preeclampsia, IUGR.

16. Triggers for PE Genetic Modulators Pre-existing Vascular Pathology Cytokines Ros Central players

17. Etiology= theories 2. Immunological Factors • abnormal trophoblast invasion • primigravidas • Multipara with 1st pregnancy from a new husband. • Abundant trophoblast (vesicular mole and multiple pregnancy).

18. Etiology= theories 3. Vasculopathy and inflammatory changes • Endothelin1(potent vasoconstrictor). • Nitric Oxide (vasodilator). • Vascular Endothelial Growth Factor (VEGF). • PE -an inflammatory disease =activated leukocytes in the maternal circulation.

19. Etiology= theories 4. Nutritional factors • Dietary deficiencies • Zn, Ca, Mg • obesity

20. Etiology= theories 5. Genetic Predisposition Genetic factors including inherited predisposing genes

21. PATHOGENESIS I. Arteriolar vasospasm II. Endothelial cell activation Increased pressor responses (AII) Prostaglandins (decreased prostacyclin / thromboxane A2 ratio) Nitric oxide Endothelins (endothelin-1) Angiogenic factors (VEGF, PIGF)

22. Pathology PE is the clinical ice-berg tip manifestation of the disturbances in the maternal homeostasis, involving many systems and organs.

23. Pathophysiological Changes Cardiovascular system (hemodynamic changes, blood volume, platelets, coagulation, hemolysis) Kidney (proteinuria, anatomical changes) Liver Brain (cerebral blood flow, blindness, cerebral edema) Uteroplacental perfusion

24. Proteinuria Hypertension Systemic blood vessels Kidneys Multi-organ disease Cerebral vessels Liver Eclampsia HELLP syndrome Fetus Intra-uterine growth restriction Multisystem Features Of Preeclampsia

25. Diagnosis 1) Prediction 2)Clinical presentation & Severity 3)Eclampsia

26. Diagnosis • I. Prediction: • High risk factors. • Rapid weight gain during the 2nd half of pregnancy (due to occult edema). • Any increase above 3/4 kg/week in late pregnancy is abnormal.

27. Tests for Prediction • Roll over test is positive (rise of diastolic blood pressure 20 mmHg or more after turning from left lateral to dorsal position). • Increased pressor response to AII. • Uric acid: is elevated (> 5.9mg/dL). • Hypercalciuria. • Doppler velocimetry to detect Uteroplacental hypo perfusion.

28. Tests for Prediction Coagulation activation (increased PAI-1/PAI-2 ratio; PAI = plasminogen activator inhibitors). Oxidative stress. Cytokines. Placental peptides (HCG, CRH, VEGF, PIGF, inhibin A, activin A). Fetal DNA in the maternal serum.

29. Diagnosis of PE Hypertension + Proteinuria = Two facets of a complex pathophysiological process

30. A): Signs: : it is a disease of signs: 2 cardinal signs • Hypertension • usually precedes Proteinuria, • Proteinuria • + / - Edema

31. + / - Edema • occult or manifest: • The lower extremities. • Abdominal wall, vulva or may be generalized. • usually after hypertension.

32. B) Symptoms (non specific) • Headache. • Blurring of vision. • Nausea and vomiting. • Epigastric pain (distension of the liver capsule) • Oliguria or anuria

33. Severity of Pre-eclampsia • The severity of pre-eclampsia(assessed bythe frequency and intensity of the signs and symptoms) • Mild PE • Severe PE The more the severity of PE, the more likely is the need to terminate pregnancy.

34. Differential Dg., mild & severe PE

35. DEFINITION OF ECLAMPSIA: Eclampsia is the occurrence of seizures(generalized tonic-clonic convulsionsthat cannot be attributed to other causes) in a woman with preeclampsia. The seizures are grand mal and may appear antepartum, intrapartum, or postpartum (48 hours postpartum up to 10 days postpartum) .

36. ECLAMPSIA ☼Almost without exception, preeclampsia precedes the onset of eclamptic convulsions. ☼The incidence: about 1 in 3250 up to1 in 2000 deliveries.

37. DIAGNOSIS OF ECLAMPSIA • Eclamptic seizure stages (4 stages): • Premonitory stage (1/2 minute): • Eye rolled up. • Twitches of the face and hands. • Tonic stage (1/2 minute): • Generalized tonic spasm with opisthotonus. • Cyanosis. • Tongue may be bitten between the clenched teeth.

38. DIAGNOSIS OF ECLAMPSIA: • Clonic stage (1-2 minutes): • Convulsions. • Tongue may be bitten. • Face is congested and cyanosed. • Conjunctival congestion. • Blood stained froth from the mouth. • Stertorous breathing, • Temperature may rise. • Involuntary passage of urine or stool. • Gradually convulsions stop.

39. DIAGNOSIS OF ECLAMPSIA: • Coma • Variable duration due to respiratory and metabolic acidosis. • Deep coma → cerebral hemorrhage. • Labor starts shortly after the seizure. • Sometimes labor does not start and convulsions recur again the so called ‘intercurrenteclampsia’ and carries a bad prognosis.

40. CLASSIFICATIONS OF ECLAMPSIA • IntercurrentEclampsia: eclamptic seizures recur in the same pregnancy. • Recurrent Eclampsia: eclampsia recurs in subsequent pregnancy.

41. CLASSIFICATIONS OF ECLAMPSIA • Ante partum (65%) with the best prognosis. • Intrapartum (20%). • Postpartum (15%) with the worst prognosis as it indicates extensive pathology and multisystem damage.

42. CLASSIFICATIONS OF ECLAMPSIA 1)Mild • Coma > 6 hours. 2) Severe (Eden's criteria): • Temperature > 39˚C(pneumonia or pontine hemorrhage) • Systolic Bp > 200 (cerebral hemorrhage risk) • Pulse > 120/min (acute heart failure). • Anuria or Oliguria(renal failure). • Respiratory rate > 40/min (pneumonia) • More than 10 fits (status eclampticus).

43. PATHOLOGYOF ECLAMPSIA ►Pathological deterioration of function in several organs and systems, as a consequence of vasospasm and ischemia. ►Maternal and fetal consequences often occur simultaneously. ►The major cause of fetal compromise occurs as a consequence of reduced uteroplacental perfusion.

44. PATHOLOGYOF ECLAMPSIA CARDIOVASCULAR CHANGES ►increased cardiac afterload caused by hypertension, ►cardiac preload, affected by pathologically diminished hypervolemia of pregnancy or iatrogenically increased by intravenous crystalloid or oncotic solutions ►endothelial activation with extravasation into the extracellular space, especially the lung.

45. PATHOLOGYOF ECLAMPSIA BLOOD VOLUME ►hemoconcentration → hallmark of eclampsia. ► the woman with eclampsia → unduly sensitive to vigorous fluid therapy (an attempt to expand the contracted blood volume to normal pregnancy levels). She is sensitive as well to even normal blood loss at delivery.

46. PATHOLOGYOF ECLAMPSIA HEMATOLOGICAL CHANGES.COAGULATION ►the level of plasma clotting factors →decreased; ►erythrocytes may be traumatized → display bizarre shapes and undergo rapid hemolysis ►intravascular coagulation ►maternal thrombocytopenia can be induced acutely; the lower the platelet count, the greater are maternal and fetal morbidity and mortality.

47. PATHOLOGYOF ECLAMPSIA KIDNEY ►proteinuria ►renal perfusion and glomerular filtrationreduced ►plasma uric acid concentrationis typically elevated ►glomerular capillary endotheliosis= glomerular capillary endothelial swelling + subendothelial deposits of protein material (electron microscopy) ►renal tubular lesions→acute renal failure from tubular necrosis (oliguria / anuria and azotemia);rarely, renal cortical necrosis develops.

48. PATHOLOGYOF ECLAMPSIA LIVER ►elevation of serum aspartate aminotransferase levels ► periportal hemorrhagic necrosis → bleeding from these lesions may cause hepatic rupture, or a subcapsular hematoma.

49. PATHOLOGYOF ECLAMPSIA BRAIN ► central nervous system → convulsions of eclampsia ►visual symptoms, blindness, retinal artery vasospasm, retinal detachment ►symptomatic cerebral edema: lethargy, confusion, and blurred vision to obnubilation and coma. ► nonspecific electroencephalographic abnormalities. The principal postmortem cerebral lesions are edema, hyperemia, focal anemia, thrombosis, and hemorrhage.

50. Investigations • A. Laboratory • Urine: 24 hour urine, Proteinuria. • Kidney functions: serum creatinine, urea, creatinine clearance and uric acid. • Liver functions: bilirubin, enzymes (SGPT and SGOT). • Blood: CBC, HCt, Hemolysis indices, Platelet count. • Coagulation Profile: Bleeding + clotting time