1. Hypertensive Disorders in Pregnancy
Professor Hassan
Chairman Department of Obstetrics and Gynecology
Faculty of Medicine
King Abdulaziz University

2. Definitions (Preeclampsia)
Pathogenesis
Diagnosis
Clinical Manifestations and Complications
Treatment
Eclampsia

3. Definitions Preeclampsia :
Systolic BP ≥ 140 Mm Hg Or Diastolic BP ≥ 90 Mm Hg
Occurring ≥ 20 Weeks' Gestation
Proteinuria ≥ 300 Mg In A 24 Hour Urine Collection.
Eclampsia: The Development Of Grand Mal Seizures In A Woman With Preeclampsia.
Chronic Hypertension:
Systolic Pressure > Or =140 mmHg, Diastolic Pressure > Or =90 mmHg, Or Both, That Is Present Before The 20th Week Of Pregnancy.
Gestational Hypertension (Transient Hypertension Of Pregnancy):
Systolic Pressure ≥ Or =140 mmHg, Diastolic Pressure ≥ Or =90 mmHg, Or Both, That Develop ≥ 20th Week Of Pregnancy In A Previously Normotensive Woman, But With Out Proteinuria.

4. Preeclampsia superimposed upon chronic hypertension:
New onset proteinuria or greatly increases proteinuria after 20 weeks of gestation.
Sudden exacerbation of BP to the severe range (systolic > or =160 mmHg or diastolic > or =110 mmHg) in the last half of pregnancy.
or other signs of multisystem involvement such as thrombocytopenia or transaminitis in a woman with prior hypertension.
Report of the National High Blood pressor Education program Working group on high blood pressure in pregnancy. Am J Obs gyn 2000;183:S1-22

5. (Special conditions)

6. Preeclampsia and other Hypertensive Disorders in Pregnancy
INCIDENCE:
Hypertensive disorders complicate 12 to 22 percent of pregnancies
Preeclampsia occurs in approximately 3 to 14 percent of all pregnancies worldwide
Incidence ranges between 3 and 7 percent in nulliparas and between 0.8 and 5.0 percent in multiparas

7. Pathogenesis

8. Pathogenesis of Preeclampsia
IMPAIRED TROPHOBLAST INVASION
ABNORMAL TROPHOBLAST DIFFERENTIATION
PLACENTAL ISCHEMIA
IMMUNOLOGIC FACTORS
GENETIC FACTORS
SYSTEMIC ENDOTHELIAL DYSFUNCTION

9. Representation of Myometrial arteries and endometrial arteries

10. In normal pregnancy
Invasive CTB invade maternal decidua and vasculature (zone v).

13. Placental Dysfunction May Initiate The Systemic Vasospasm, Ischemia, And Thrombosis That Eventually Damages Maternal Organs.
CNS
headache, local neurological deficits, and seizure
Renal necrosis leads to a decreased glomerular filtration rate and proteinuria
Liver injury from hepatocellular necrosis causes right upper quadrant pain and elevated liver function tests
Cardiovascular manifestations include a lower than normal intravascular volume, increased cardiac output, and an abnormally elevated peripheral vascular resistance
Microangiopathic hemolysis leads to anemia and thrombocytopenia.
Fetal: Placental infarction and abruptio placentae lead to intrauterine growth retardation and fetal death.

14. Impaired Trophoblast invasion
Medical conditions that predispose to vascular insufficiency
Obstetrical conditions that increase placental mass with a relative decrease in placental blood flow
Placental hyperfusion/ischemia
Fetal Growth retardation
Oligohydramnios
Imbalance of prostacyclin/Thromboxane
Systemic endothelial damage
Systemic Clinical Manifestations
CNS
Renal
Hematological
Hepatic

15. Prevention of PET

16. Methods Used to Prevent Preeclampsia
High-protein and low-salt diet Nutritional supplementation (protein) Calcium Magnesium Zinc Fish and evening primrose oil Antihypertensive drugs including diuretics Antithrombotic agents Low-dose aspirin Dipyridamole Heparin Vitamins E and C

17. Risk Factors for Preeclampsia
Primiparity
Prior personal or family history of preeclampsia
Obesity
Hypertension
Diabetes mellitus
Renal diseases
Collagen vascular diseases
Thrombophilia
Multiple gestation

18. Clinical Manifestations and Complications

19. Clinical Manifestation of Preeclampsia
Maternal:
Hypertension:
Renal:
Hepatic:
Hematologic:
Neurologic:
Fetal/Neonatal:
IUGR:

20. Clinical Manifestation of Preeclampsia
Hypertension:
Systolic BP ≥ 40 mmHg or Diastolic ≥ BP 90 mmHg in a woman who was normotensive prior to 20 weeks of gestation.
Renal:
Proteinuria:
≥ 0.3 g protein in a 24-hour urine specimen (or 2+ on dipstick).
Proteinuria is due, in part, to impaired integrity of the glomerular barrier and altered tubular handling of filtered proteins (hypo filtration) leading to increased protein excretion.
Creatinine clearance: Decline
Uric acid: Reduced urinary excretion of uric acid (increase serum level of uric acid)

21. Edema and Intravascular volume:
edema is no longer part of the diagnostic criteria. However, sudden and rapid weight gain and facial edema often occur in women who develop preeclampsia.
Hematologic changes:
Thrombocytopenia:
Is the most common coagulation abnormality is due to formation of microthrombi.
The prothrombin time, partial thromboplastin time, and fibrinogen concentration:
are affected with complications such as abruptio placentae or with severe liver involvement.
Microangiopathic hemolysis:
Is detected by examination of a blood smear or elevation in the lactic dehydrogenase concentration.

22. Liver:
Affected due to periportal hemorrhage, ischemic lesions, and microvesicular fat deposition.
Clinically: right upper quadrant or epigastric pain, elevated liver enzymes and, in severe cases, subcapsular hemorrhage or hepatic rupture.
Neurologic:
Eclampsia is the most severe complications.
Early signs may include headache, blurred vision, photophobia or mental state.
Note: Only 50% of eclampsia cases have severe hypertension (> 160/110 mmHg)
No Reliable prediction for development of eclampsia in women with preeclampsia.

23. Pulmonary edema: The etiology is multifactorial.
Excessive elevations in pulmonary vascular hydrostatic pressure (PCWP).
Capillary leak, left heart failure, and iatrogenic volume overload

24. Fetus and placenta: IUGR:
The fetal consequences of chronic placental hypoperfusion are fetal growth restriction and oligohydramnios.
Severe or early onset preeclampsia results in the greatest decrements in birth weight compared to normotensive pregnancies.
Abruptio placenta:
Is infrequent (< 1 percent) in women with mild preeclampsia, but occurs in 3 percent of those with severe disease.

25. The HELLP Syndrome
HELLP syndrome is a group of symptoms that occur in pregnant women who have:
H – Hemolytic anemia H
EL -- elevated liver enzymes
LP -- low Platelet count

26. The HELLP Syndrome Incidence: ranged from 2 to 12 percent.
Classification:
Class I: platelet nadir below 50,000/mm
Class 2: platelet nadirs between 50,000 and 100,000/mm
Class 3: a platelet nadir between 100,000 and 150,000/mm
Severe hypertension is not a constant or even a frequent finding in HELLP syndrome.
Of 112 patients 66 percent had a diastolic BP of at least 110 mm Hg,
14.5 percent had a diastolic BP of less than 90 mm Hg.
The reported PNM has ranged from 7.7 to 60 percent.
maternal mortality from 0 to 24 percent. Maternal morbidity is common.

27. Criteria to Establish the Diagnosis of HELLP Syndrome
Hemolysis Abnormal peripheral blood smear Increased bilirubin <1.2 mg/dl Increased lactic dehydrogenase >600 IU/L Elevated liver enzymes Increased SGOT ≥72 IU/L Increased lactic dehydrogenase >600 IU/L Thrombocytopenia Platelet count <100,000/mm

28. It is important to emphasize that these patients may have a variety of unusual signs and symptoms, none of which are diagnostic of severe preeclampsia.
Pregnant women with probable preeclampsia presenting with atypical symptoms should have a complete blood count, a platelet count, and liver enzyme determinations irrespective of maternal blood pressure.

29. Medical and Surgical Disorders Confused with the HELLP Syndrome
Acute fatty liver of pregnancy Appendicitis Diabetes mellitus Gallbladder disease Gastroenteritis Glomerulonephritis Hemolytic uremic syndrome Hepatic encephalopathy Hyperemesis gravidarum Idiopathic thrombocytopenia Kidney stones Peptic ulcer Pyelonephritis Systemic lupus erythematosus Thrombotic thrombocytopenic purpura Viral hepatitis

30. Severe
(n+178)
Partial HELLP (n=71)
HELLP
(n=67)) 3
  4
25 *
Blood products transfusion (%)
  0
15 *
DIC (%)
2 §
11 §
14 ‡
Wound hematoma/infection (%) † 1
  6 ‡
Pleural effusion (%)  0
  3 ‡
Acute renal failure (%) 9
  7
  9
Eclampsia (%) 5
Abruptio placentae (%)
  8
Pulmonary edema (%)
  1.5
Subcapsular liver hematoma (%)
1.5
Intracerebral hemorrhage (%)
Death (%)
MATERNAL COMPLICATIONS IN 316 PREGNANCIES WITH HELLP SYNDROME, PARTIAL HELLP SYNDROME, OR SEVERE PREECLAMPSIA WITH NORMAL LABORATORY VALUES Am J Obstet Gynecol 175:460, 1996.

32. DIAGNOSIS AND INITIAL EVALUATION

34. Confirm the Diagnosis:
The initial goal is to distinguish women with PET from those with other hypertensive disorders
Assess the severity of disease (whether mild or severe).

35. DIFFERENTIAL DIAGNOSIS Of Preeclampsia
Other causes of High Blood Pressure (renal, Vascular, Endocrinological)
Preeclampsia versus essential hypertension:
Onset – Hypertension occurring before the 20th week is usually due to an underlying tendency to hypertension rather than to preeclampsia.
Parity – Preeclampsia is far more common in primiparas than in multiparas.
Age – Preeclampsia is somewhat more common in both young (<20 years) and older (>35 years) primigravidas.
Proteinuria: – Proteinuria is present and increases with time in preeclampsia, occasionally reaching the nephrotic range; by comparison, protein excretion is usually less than 1 g/day in hypertensive nephrosclerosis.
Plasma uric acid concentration: – Preeclampsia is typically associated with a rise in the plasma urate level to above 5.5 to 6 mg/dL (327 µmol/L).

36. Criteria for Severe PET
Symptoms of CNS dysfunction:
e.g. Blurred vision, scotomata, altered mental status, severe headache
Symptoms of liver capsule distension:
Right upper quadrant or epigastric pain.
Nausea, vomiting.
Hepatocellular injury:
Serum transaminase concentration at least twice normal
Severe blood pressor elevation:
Systolic ≥ 160 mmhg or diastolic ≥ 110 mmHg on two occasions 6 hours apart
Proteinuria:
Over 5 gram in 24 hours or 3+ on two random sample four hours apart
IUGR:
Pulmonary edema or cyanosis:
Cerebrovascular accident:

37. Renal Function Evaluation: Quantification of protein excretion.
Laboratory evaluation to determine disease severity and characterize end organ involvement:
Renal Function Evaluation:
Quantification of protein excretion.
Serum creatinine concentration
Serum uric acid concentration
Hematological tests:
Hematocrit
Platelet count
Lactic acid dehydrogenase concentration (LDH): and review of the red blood cell smear may indicate the presence of microangiopathic hemolysis.
Hepatic function:
Serum alanine and aspartate aminotransferase concentrations (ALT,AST)
Fetal well-being:
Ultrasound to evaluate growth and amniotic fluid volume
Non stress test and Biophysical profile

38. Treatment of PET

39. The Definitive Treatment Of Preeclampsia Is Delivery To Prevent Potential Maternal Complications. However, Preterm Delivery Is Not Always In The Best Interests Of The Fetus; Therefore, Exceptions To This Recommendation May Be Made For Selected Women Remote From Term. In General, Intervention Is Based Upon: - The Severity Of Preeclampsia. - Maternal And Fetal Condition Gestational Age.

40. Treatment of Mild PET
Women with mild disease at ≥ 37 weeks of gestation are induced if there are no contraindications to vaginal birth.
Expectant management for mild disease remote from term :
Inpatient versus outpatient care: Indication for Hospitalization signs or symptoms of disease progression
Rest Vs. Restricted activity:
Laboratory follow-up:
platelet count, creatinine, Quantification of urine protein, and liver enzymes should be repeated once or twice weekly.
lactic acid dehydrogenase (LDH) concentration is a better sign of hemolysis. Hemolysis can be confirmed by observation of schistocytes on a blood smear.

41. Antihypertensive agents:
- Does not alter the course of the disease nor diminish perinatal morbidity or mortality.
- Are administered to prevent a maternal cerebrovascular accident from severe hypertension (if systolic BP ≥160 mmHg or diastolic BP ≥ 105 to 110 mmHg.
- The goal of therapy is a systolic pressure of 140 to 155 mmHg and diastolic pressure of 90 to 105 mmHg
Assessment of fetal well-being:
daily fetal movement counts and nonstress testing and/or BBP at periodic intervals
Assessment of fetal growth:
Administration of antenatal corticosteroids:
Timing and indications for delivery:

43. Treatment of Severe PET
Severe preeclampsia is generally regarded as an indication for delivery, regardless of gestational age, to minimize maternal as well as fetal complications.
Delivery is usually by the vaginal route, with cesarean delivery reserved for the usual obstetrical indications.

44. Anticonvulsant therapy: Control of Blood Pressure:
Treatment of Severe PET
Anticonvulsant therapy:
Control of Blood Pressure:
Preparation for Delivery:
Prevention of Complications:

45. Anticonvulsant therapy: Magnesium Sulphate:
Initiated at onset of labor or induction or prior to CS delivery and continued for 24 hours postpartum
The most common regimen:
A loading dose of 4 to 6 g intravenously in 150 ml of 5% Dextrose Injection, at a rate not exceeding 3 ml per minute
followed by 1 to 2 g per hour as a continuous infusion.
Maintenance Dose: is given only if;
- A patellar reflex is present (loss of reflexes being the first manifestation of symptomatic hypermagnesemia)
- Respirations exceed 12 per minute.
- The urine output exceeds 100 mL per four hours.

46. Magnesium sulfate –Mechanism of action
It prevent eclampsia in part by selectively dilating the cerebral vasculature and relieving the cerebral vasospasm associated with preeclampsia It exerts this vasodilatory effect by:
Decreasing the release of acetylcholine at motor end plates within the neuromuscular junction, thereby suppressing nerve transmission to vascular smooth muscle.
Acting as a physiologic calcium antagonist to lower the intracellular calcium concentration within vascular smooth-muscle cells, which is necessary for activation of the myosin-actin contractile unit.
Blocking excitatory amino acid receptors, including N-methyl-D-aspartate receptors, which have been implicated in the initiation and propagation of seizures .

47. Complication of magnesium: sulfate:
Rapid infusion:
Flushing, and warmth, probably related to peripheral vasodilation and a drop in blood pressure. Nausea, vomiting, headache, muscle weakness, visual disturbances, and palpitations can also occur.
Dyspnea or chest pain may be symptoms of pulmonary edema, a rare side effect of magnesium sulfate administration.
Magnesium toxicity is related to serum concentration:
- loss of deep tendon reflexes occurs at 8 to 10 mEq/L
- respiratory paralysis at 10 to 15 mEq/L,
- cardiac arrest at 20 to 25 mEq/L.
Antidote:
Calcium gluconate (1 g intravenously over at 5 to 10 minutes) may be administered to counteract magnesium toxicity.

48. Antihypertensives
Hydralazine (Apresoline):
Decreases systemic resistance by means of direct vasodilation of arterioles Adult Dose Initial: 5 mg IV Maintenance: 5-10 mg IV q20-30min
Labetalol (Normodyne):
Used as an alternative to hydralazine in eclampsia. It blocks beta1-adrenergic, alpha-adrenergic, and beta2-adrenergic receptor sites,
Adult Dose20-30 mg IV initially; mg IV q10-20 min; not to exceed 300 mg

49. INTRAPARTUM CARE:
Close, continuous maternal-fetal monitoring:
- worsening hypertension:
- deteriorating maternal hepatic:
- renal.
- cardiopulmonary
- hematologic function:
- uteroplacental insufficiency or abruption (often manifested by nonreassuring fetal heart rate tracings, vaginal bleeding).

51. Eclampsia

52. Eclampsia
Eclampsia refers to the occurrence of one or more generalized convulsions and/or coma in the setting of preeclampsia and in the absence of other neurologic conditions.
The clinical manifestations appear anytime from the second trimester to the puerperium.
INCIDENCE AND EPIDEMIOLOGY:
An eclamptic seizure occurs in 0.5 percent of mildly preeclamptic pregnancies and 2 percent of severe preeclamptics.
Antepartum (38 to 53 percent)
Intrapartum (18 to 36 percent),
< or =48 hours postpartum (5 to 39 percent),
>48 hours postpartum (5 to 17 percent).

53. CLINICAL MANIFESTATIONS AND DIAGNOSIS:
Maternal:
Eclamptic seizures are almost always self-limiting and seldom last longer than 3 to 4 minutes.
The diagnosis of preeclampsia/eclampsia sometimes may not be suspected prior to the development of seizures in women with relative hypertension (ie, blood pressure elevated compared to patient's baseline, but less than 140/90 mmHg) and no proteinuria.
Fifteen to 22 percent of eclamptic women have no evidence of proteinuria prior to their seizure.

54. DIFFERENTIAL DIAGNOSIS Of Eclampsia:
Cerebrovascular accident (hemorrhage, arterial or venous thrombosis).
Hypertensive disease (hypertensive encephalopathy, pheochromocytoma). (
Space-occupying lesions of the central nervous system (brain tumor, abscess).
Metabolic disorders (hypoglycemia, uremia, inappropriate antidiuretic hormone secretion resulting in water intoxication).
Infection (meningitis, encephalitis).
Thrombotic thrombocytopenic purpura or thrombophilia
Idiopathic epilepsy.
Use of illicit drugs (eg, methamphetamine, cocaine)
Cerebral vasculitis.