Hypertensive

• Hypertensive disorders of pregnancy

  Complications that affect about 10% of pregnancies and are a leading cause of maternal and perinatal morbidity and mortality
• Worldwide: 50,000 women die each year from hypertensive disorders of pregnancy
• In the US, hypertensive disorders of pregnancy are the second leading cause of maternal mortality (12-18% of deaths)
• Infant outcomes include still birth and IUFGR
• Classification of hypertensive disorders of pregnancy

  • Pre-existing (chronic) hypertension
  • Preeclampsia with or without severe features or eclampsia
  • Preeclampsia superimposed on chronic hypertension
  • Gestational hypertension (previously called pregnancy induced hypertension)
• Risk factors for gestational hypertension and preeclampsia

  • Advanced maternal age
  • Diabetes mellitus
  • Primiparity
  • Chronic hypertension
  • Multiple gestation
  • Obesity
  • Autoimmune diseases (e.g. SLE)
  • Antiphospholipid syndrome
  • Previous history of preeclampsia
  • In vitro fertilization
  • Thrombocytopenia
• Preeclampsia


  Hypertension (SBP ≥140 mmHg and/or DBP ≥90 mmHg) and proteinuria (≥0.3g in 24-hour urine, or protein/creatinine ratio ≥0.3 mg/mg, or urine dipstick ≥1+) in a previously normotensive patient
• Preeclampsia with severe features

  Preeclampsia plus one of the following: SBP ≥160 mmHg and/or DBP ≥110 mmHg, impaired liver function, right upper quadrant or epigastric pain, renal insufficiency, new onset cerebral or visual disturbances, pulmonary edema, thrombocytopenia
• A urinary dipstick for protein is not usually sufficient for the diagnosis of preeclampsia with severe features
• Eclampsia


  New-onset seizures in a patient with preeclampsia
• Gestational hypertension


  SBP ≥140 or DBP ≥90 mmHg after 20 weeks gestation on two occasions separated by 4 hours, without proteinuria or end-organ dysfunction
• Chronic hypertension


  BP ≥140/90 mmHg on two occasions 4 hours apart at 20 weeks' gestation or earlier
• Treating mild to moderately elevated BP in chronic hypertension does not benefit the fetus or prevent preeclampsia
• Overtreatment of chronic hypertension may cause adverse perinatal outcomes due to placental hypoperfusion, so medication is reserved for BP persistently >150/100 mmHg
• Clinical features of preeclampsia with severe features

  • Headache
  • Blindness, blurred vision, scotomata
  • Altered mental status
  • Dyspnea
  • Sudden increase in or facial edema
  • Epigastric or right upper quadrant abdominal pain
  • Weakness or malaise (possible evidence of hemolytic anemia)
  • Clonus (increased risk of convulsions)
• Medications for hypertension in pregnancy

  • Methyldopa
  • Nifedipine
  • Labetalol
• Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are never used as they are associated with IUFGR, neonatal renal failure, oligohydramnios, and death
• Atenolol should also be avoided as it may cause IUFGR
• Superimposed preeclampsia on chronic hypertension

  Increase in blood pressure alone is not sufficient to diagnose, requires development of maternal end-organ dysfunction consistent with preeclampsia
• In women with proteinuric renal disease, an increase in proteinuria during pregnancy is not sufficient to diagnose superimposed preeclampsia
• Gestational hypertension


  Onset of hypertension after 20 weeks' gestation without proteinuria or other criteria for preeclampsia
• Approximately 50% of women diagnosed with gestational hypertension between 24 and 35 weeks' gestation ultimately develop preeclampsia
• Globally, 76,000 women and 500,000 babies die each year from preeclampsia
• Women in low-resource countries are at higher risk of developing preeclampsia compared to those in high-resource countries
• Preeclampsia


  Gestational hypertension accompanied by one or more of the following new-onset conditions at or after 20 weeks of gestation: proteinuria, acute kidney injury, liver involvement, neurological complications, hematological complications, or uteroplacental dysfunction
• Subclassifications of preeclampsia

  • Early-onset preeclampsia (delivery <34 weeks)
  • Preterm preeclampsia (delivery <37 weeks)
  • Late-onset preeclampsia (delivery ≥34 weeks)
  • Term preeclampsia (delivery ≥37 weeks)
• Early-onset preeclampsia is associated with a substantial risk of both short- and long-term maternal and perinatal morbidity and mortality
• Pathophysiology of preeclampsia

  1. Stage 1: Shallow invasion of trophoblasts resulting in inadequate remodeling of spiral arteries

  2. Stage 2: Maternal response to endothelial dysfunction and imbalance between angiogenic and antiangiogenic factors, resulting in clinical features
• In late-onset preeclampsia, placentation is usually normal but feto-placental demands exceed supply, triggering the clinical phenotype
• The maternal cardiovascular system may have a significant contribution to the development of preeclampsia, in addition to the placenta
• Risk factors for preeclampsia

  • Advanced maternal age (≥35 years)
  • Nulliparity
  • Previous history of preeclampsia
  • Short or long interpregnancy interval
  • Assisted reproductive technology
  • Family history of preeclampsia
  • Obesity
  • Race and ethnicity (higher risk in Afro-Caribbean and South Asian women)
  • Comorbidities (diabetes, chronic hypertension, chronic renal disease, autoimmune disorders)
• Pathogenesis of preeclampsia

  1. Relative or absolute deficiency of vasodilator prostaglandin (PGI2) and increased synthesis of vasoconstrictor thromboxane (TXA2)

  2. Increased vascular sensitivity to angiotensin-II

  3. Depressed angiotensinase activity following proteinuria

  4. Nitric oxide deficiency

  5. Increased endothelin-1 synthesis

  6. Endothelial injury from inflammatory mediators and abnormal lipid metabolism
• Endothelial dysfunction and vasospasm

  Result from the imbalance of vasodilators and vasoconstrictors, oxidative stress, and inflammatory mediators
• Edema


  Excessive accumulation of fluids in the extracellular tissue spaces, likely due to increased oxidative stress, endothelial injury, and increased capillary permeability
• Pathogenesis of proteinuria

  Spasm of afferent glomerular arterioles leading to glomerular endotheliosis and increased capillary permeability, with simultaneous decreased tubular reabsorption
• The net physiological changes in preeclampsia include decreased renal blood flow, decreased glomerular filtration rate, and impaired tubular function, which are likely to recover completely
• Vasospasm results from the imbalance of vasodilators and vasoconstrictors, both of which are in a vicious cycle
• Edema


  Excessive accumulation of fluids in the extracellular tissue spaces whose cause is not clear, probably due to increased oxidative stress, endothelial injury, and increased capillary permeability. The leaky capillaries and decreased blood osmotic pressure are the probable explanations.
• Proteinuria


  Spasm of the afferent glomerular arterioles -> glomerular endotheliosis -> increased capillary permeability -> increased leakage of proteins. There is also simultaneously depressed tubular reabsorption. Total proteins excreted constitute 50-60% albumin and 10-15% globulin.
• Physiological changes

  Decreased blood flow of about 1/3 -> changes in maternal blood vessels -> anatomical and functional placental changes -> fetal jeopardy