Hypertention

Hypertensive disorders of pregnancy

Dr . Ishraq mohammed

Pathogenesis

Vasospasm
The concept of vasospasm based on direct observations of small blood vessels in the nail beds, ocular fundi, and bulbar conjunctivae.
Vascular constriction causes increased resistance and subsequent hypertension. At the same time, endothelial cell damage causes interstitial leakage through which blood constituents, including platelets and fibrinogen, are deposited subendothelially

With diminished blood flow because of maldistribution, ischemia of the surrounding tissues would lead to necrosis, hemorrhage, and other end-organ disturbances characteristic of the syndrome.
Intact endothelium has anticoagulant properties, and endothelial cells blunt the response of vascular smooth muscle to agonists by releasing nitric oxide. Damaged or activated endothelial cells may produce less nitric oxide and secrete substances that promote coagulation and increase sensitivity to vasopressors.
Endothelial Cell Activation

Increased Pressor Responses

Angiotensin II, and Plasma Volume, pregnant women normally develop refractoriness to infused vasopressors. Women with early preeclampsia, however, have increased vascular reactivity to infused norepinephrine and angiotensin II. Moreover, increased sensitivity to angiotensin II clearly precedes the onset of gestational hypertension.

Prostaglandins

A number of prostanoids are thought to be central to the pathophysiology of the preeclampsia syndrome. Specifically, the blunted pressor response seen in normal pregnancy is at least partially due to decreased vascular responsiveness mediated by endothelial prostaglandin synthesis. For example, compared with normal pregnancy, endothelial prostacyclin (PGI2) production is decreased in preeclampsia.

At the same time, thromboxane A2 secretion by platelets is increased, and the prostacyclin:thromboxane A2 ratio decreases. The net result favors increased sensitivity to infused angiotensin II, and ultimately, vasoconstriction .

Nitric Oxide

This potent vasodilator is synthesized from L-arginine by endothelial cells. Inhibition of nitric oxide synthesis increases mean arterial pressure, decreases heart rate, and reverses the pregnancy-induced refractoriness to vasopressors.
It appears that the pre-eclampsia syndrome is associated with decreased endothelial nitric oxide synthase expression, thus increasing nitric oxide inactivation.

Pathophysiology

Cardiovascular System

Severe disturbances of normal cardiovascular function are common with preeclampsia or eclampsia. These are related to: (1) increased cardiac afterload caused by hypertension; (2) cardiac preload, which is substantively affected by pathologically diminished hypervolemia of pregnancy or is iatrogenically increased by intravenous crystalloid or oncotic solutions; and (3) endothelial activation with extravasation of intravascular fluid into the extracellular space, and importantly, into the lungs.

Blood Volume

Women of average size should have a blood volume of nearly 5000 mL during the last several weeks of a normal pregnancy, compared with approximately 3500 mL when not pregnant. With eclampsia, however, much or all of the anticipated normal excess 1500 mL is lost. Such hemoconcentration results from generalized vasoconstriction that follows endothelial activation and leakage of plasma into the interstitial space because of increased permeability. In women with preeclampsia, and depending on its severity, hemoconcentration is usually not as marked. Women with gestational hypertension, but without preeclampsia, usually have a normal blood volume

Blood and Coagulation

Hematological abnormalities develop in some women with preeclampsia. Among those commonly identified is thrombocytopenia, which at times may become so severe as to be life threatening. In addition, the levels of some plasma clotting factors may be decreased, and erythrocytes may display bizarre shapes and undergo rapid hemolysis.


HELLP Syndrome

In addition to hemolysis and thrombocytopenia, it also became appreciated that elevated serum liver transaminase levels were commonly found with severe preeclampsia and were indicative of hepatocellular necrosis
Coagulation

Subtle changes consistent with intravascular coagulation, and less often erythrocyte destruction, commonly are found with preeclampsia and especially eclampsia. Some of these changes include increased factor VIII consumption, increased levels of fibrinopeptides A and B and of fibrin degradation products, and decreased levels of regulatory proteins—antithrombin III and protein C and S.

Kidney

With development of preeclampsia, there may be a number of reversible anatomical and pathophysiological changes. Of clinical importance, renal perfusion and glomerular filtration are reduced. Levels that are much less than normal nonpregnant values are infrequent and are the consequence of severe disease.

Proteinuria

Dipstick qualitative determinations depend on urinary concentration and are notorious for false-positive and negative results. For a 24-hour quantitative specimen, the standard "consensus" threshold value used is > 300 mg/24.
Liver

liver involvement with preeclampsia may be clinically significant in the following circumstances:
• Symptomatic involvement, typically manifest by moderate to severe right-upper or midepigastric pain and tenderness, is usually only seen with severe disease.

2.Asymptomatic elevations of serum hepatic transaminase levels—AST and ALT—are considered markers for severe preeclampsia. Values seldom exceed 500 U/L, but have been reported to exceed 2000 U/L in some women.
3.Hepatic hemorrhage from areas of infarction may extend to form a hepatic hematoma. These in turn may extend to form a subcapsular hematoma that may rupture. They can be identified using computed tomography (CT) scanning or magnetic resonance (MR) imaging. Unruptured hematomas are probably more common than clinically suspected, and are more likely with HELLP syndrome
4.Acute fatty liver of pregnancy is sometimes confused with preeclampsia .It too has an onset in late pregnancy, and often there is accompanying hypertension, elevated serum transaminase and creatinine levels, and thrombocytopenia.


Brain

Headaches and visual symptoms are common with severe preeclampsia, and associated convulsions define eclampsia.
• gross intracerebral hemorrhage.
• cortical and subcortical petechial hemorrhages.
• subcortical edema, multiple nonhemorrhagic areas of "softening" throughout the brain, hemorrhagic areas in the white matter, and hemorrhage in the basal ganglia or pons.
• The classical microscopic vascular lesions consist of fibrinoid necrosis of the arterial wall and perivascular microinfarcts and hemorrhages.

Prevention

1-Dietary Manipulation
• Low-Salt Diet
• Calcium Supplementation
• Fish Oil Supplementation
2-Antihypertensive Drugs
3-Antioxidants
4-Antithrombotic Agents:low dose Aspirin:50-150mg daily;low dose Aspirin+Hep.

Management

Pregnancy complicated by gestational hypertension is managed according to severity, gestational age, and presence of preeclampsia.
The basic management objectives for any pregnancy complicated by preeclampsia are:


1-Termination of pregnancy with the least possible trauma to mother and fetus

2-Birth of an infant who subsequently thrives

3-Complete restoration of health to the mother.

Evaluation

Hospitalization is considered at least initially for women with new-onset hypertension, especially if there is persistent or worsening hypertension or development of proteinuria. A systematic evaluation is instituted to include the following:

1.Detailed examination followed by daily scrutiny for clinical findings such as headache, visual disturbances, epigastric pain, and rapid weight gain
2. Weight determined daily
3.Analysis for proteinuria on admittance and at least every 2 days thereafter
4.Blood pressure readings in the sitting position with an appropriate-size cuff every 4 hours.

5.Measurements of plasma or serum creatinine and liver transaminase levels, and hemogram to include platelet quantification. The frequency of testing is determined by the severity of hypertension.
6.Evaluation of fetal size and well-being and amnionic fluid volume either clinically or using sonography.
Consideration for Delivery

Termination of pregnancy is the only cure for preeclampsia. Headache, visual disturbances, or epigastric pain is indicative that convulsions may be imminent, and oliguria is another ominous sign. Severe preeclampsia demands anticonvulsant and usually antihypertensive therapy followed by delivery. Treatment is identical to that described subsequently for eclampsia. The prime objectives are to forestall convulsions, to prevent intracranial hemorrhage and serious damage to other vital organs, and to deliver a healthy infant.


Once severe preeclampsia is diagnosed, labor induction and vaginal delivery have been considered ideal. Temporization with an immature fetus is considered subsequently. Several concerns, including an unfavorable cervix, a perceived sense of urgency because of the severity of preeclampsia, and the need to coordinate neonatal intensive care, have led some to advocate cesarean delivery.
Antihypertensive Therapy for Mild to Moderate Hypertension

The use of antihypertensive drugs in attempts to prolong pregnancy or modify perinatal outcomes in pregnancies complicated by various types and severities of hypertensive disorders .

Adrenergic-Blocking Agents

Some of these drugs act centrally by reducing sympathetic outflow to effect a generalized decreased vascular tone. Central-acting agents include alfa -methyldopa. Peripherally acting Beta -adrenergic receptor blockers also cause a generalized decrease in sympathetic tone. Examples are propranolol, metoprolol, and atenolol. Labetalol is a commonly used alfa /Beta-adrenergic blocker. Peripheral blockers are thought to have more potential for postural hypotension than centrally acting agents. The most commonly used drugs in pregnancy to treat hypertension are methyldopa or a Beta – or alfa /Beta-receptor blocker.

Vasodilators

Hydralazine relaxes arterial smooth muscle and has been used parenterally to safely treat severe peripartum hypertension. Oral hydralazine monotherapy for chronic hypertension is not recommended because of its weak antihypertensive effects and resultant tachycardia. It may be an effective adjunct for long-term use with other antihypertensives, especially if there is chronic renal insufficiency.

Calcium-Channel Blockers

Common agents include nifedipine

Management of Eclampsia

• Control of convulsions using an intravenously administered loading dose of magnesium sulfate. This is followed by a continuous infusion of magnesium sulfate
• Intermittent administration of an antihypertensive medication to lower blood pressure whenever it is considered dangerously high
• Avoidance of diuretics unless there is obvious pulmonary edema, limitation of intravenous fluid administration unless fluid loss is excessive, and avoidance of hyperosmotic agents
• Delivery of the fetus to achieve a "cure."


Magnesium Sulfate to Control Convulsions
• Give 4- to 6-g loading dose of magnesium sulfate diluted in 100 mL of IV fluid administered over 15–20 min
• Begin 2 g/hr in 100 mL of IV maintenance infusion. Some recommend 1 g/hr
• Monitor for magnesium toxicity: Assess deep tendon reflexes periodically Some measure serum magnesium level at 4–6 hr and adjust infusion to maintain levels between 4 and 7 meq/L (4.8 to 8.4 mg/dL) Measure serum magnesium levels if serum creatinine 1.0 mg/dL
• Magnesium sulfate is discontinued 24 hr after delivery

Management of Severe Hypertension

Dangerous hypertension can cause cerebrovascular hemorrhage, hypertensive encephalopathy and can trigger eclamptic convulsions in women with preeclampsia. Other complications include hypertensive afterload congestive heart failure and placental abruption.

Antihypertensive Agents

Hydralazine is administered intravenously with a 5-mg initial dose, and this is followed by 5- to 10-mg doses at 15- to 20-minute intervals until a satisfactory response is achieved
Labetalol

Another effective antihypertensive agent is intravenous labetalol—an alfa1- and nonselective Beta-blocker. Some prefer its use over hydralazine because of fewer side effects.

10 mg intravenously initially. If the blood pressure has not decreased to the desirable level in 10 minutes, then 20 mg is given. The next 10-minute incremental dose is 40 mg and is followed by another 40 mg if needed. If a salutary response is not achieved, then an 80-mg dose is given.
Nifedipine

This calcium-channel blocking agent has become popular because of its efficacy for control of acute pregnancy-related hypertension.
10-mg initial oral dose to be repeated in 30 minutes if necessary.


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