Pathophysiology of Pregnancy Induced Hypertension

Dr. Anusha Rao P

PGY-2 (OBG)

• Hypertension is one of the commonest medical disorders in pregnancy, and a leading cause of maternal and perinatal mortality.

• Incidence lies between 5-10% and is gradually increasing.

• Normal pregnancy is characterised by:

• Increase in plasma volume(preload) starts from 6th wk, plateaus at 30th wk. (+50%) so fall in haematocrit.

• Increase in cardiac output, from 5th wk, peaks at 30-34 wks, remains static till term, increases further in labourand immediately following delivery.

• Decrease in PVR.

• So results in physiological decrease in mean BP during second trimester but it raises to normal value as pregnancy advances.

• Hypercoagulable state

• 50% Increase in fibrinogen

• 15% fall in platelets

• ESR raised by 4times

• Decreased fibrinolytic activity

• Increase in clotting factors I, VII, IX, X but others decrease

• All these help to effectively achieve hemostasis during delivery.

EARLY GTN

AETIOLOGY

• BEFORE 30WKS

• SEVERE ADVANCES TO PREECLAMPSIA

PATHOPHYSIOLOGY

• HIGH INCIDENCE OF POOR PLACENTATION

• HEMODYNAMIC CHANGES-VASOCONSTRICTION, DECREASE CO

PROGNOSIS

POOR PERINATAL PROGNOSIS

LATE GTN

AETIOLOGY

AFTER 34WKS

BENIGN N RARELY ADV TO PREECLAMPSIA

PATHOPHYSIOLOGY

NO E/O PLACENTAL ISCHAEMIA

HEMODY-INC PLASMA VOL,CO,NORMAL PVR

PROGNOSIS

GOOD PERINATAL OUTCOME

6

ETIOLOGY

Observation that gestational hypertensive disorders are more likely to develop in women with the following characteristics: • Are exposed to chorionic villi for the first time • Are exposed to a superabundance of chorionic villi, as with twins or hydatidiform mole • Have preexisting conditions of endothelial cell activation or

inflammation such as diabetes or renal or cardiovascular disease • Are genetically predisposed to hypertension developing during pregnancy.

ETIOLOGY-MECHANISMS

• Placental implantation with abnormal trophoblastic invasion of uterine vessels

• Immunological maladaptive tolerance between maternal, paternal (placental), and fetal tissues

• Maternal maladaptation to cardiovascular or inflammatory changes of normal pregnancy

• Genetic factors including inherited predisposing genes and epigenetic influences.

• IMMUNOLOGICAL MECHANISMS:

• Loss of maternal immune tolerance to paternally derived placental and fetal antigens is –dysregulation.

• Risk of pre- eclampsia is appreciably enhanced in circumstances in which formation of blocking antibodies to placental antigenic sites might be impaired.

• Immune maladaptation in preeclampsia in women destined to be preeclamptic, extravillous trophoblastsearly in pregnancy express reduced amounts of immunosuppressive non classic HLA G.

Incident risk for preeclampsia of

• 20 to 40 percent for daughters of preeclamptic mothers;

• 11 to 37 percent for sisters of preeclampticwomen;

• and 22 to 47 percent for twins.

PATHOGENESIS

• Vasospasm

• Endothelial cell activation

• Increased pressor response

• Prostaglandins

• Nitric oxide

• Endothelins

• Angiogenic and antiangiogenic proteins

(soluble Fms-like Tyrosine kinase 1 and soluble endoglin)

Two stage disorder

• 2 Stage process1. Preclinical (≤20 weeks):

– Inadequate invasion of maternal spiral arterioles by fetal cytotrophoblasts Insufficient maternal vascular remodeling and angiogenesis

2. Clinical (normally >20 weeks): – Oxidatively stressed/hypoxic placenta

Generalized systemic inflammatory response with release of anti-angiogenic factors, inflammatory cytokines, and trophoblast debris

Maternal syndrome

NORMAL PREGNANCY:• Fetal trophoblast invade walls of spiral arteries• This disrupts their smooth muscle layer and

converts them into venous-like channels• Remodelling begins about 10-12 weeks and

continues until around 16-18 weeks• This allows blood supply to uterus to increase

from 10-15 ml (pre-pregnancy) to 600-800 ml per minute to meet placental blood flow requirements at term

• Invasion defects in preeclampsia.

• (A) In a normal placenta, extravillouscytotrophoblast (ECTB) cells (green) move into the decidua (endometrium) and myometrium via interstitial invasion. Some ECTB cells enter maternal spiral arteries and replace the endothelial cells of the vessel walls, becoming endovascular ECTB (eECTB) cells, increasing vessel compliance and maximizing blood flow into placental blood spaces.

• (B) In the placenta of a preeclampticpatient, interstitial invasion is shallow and limited, with many ECTB cells in the basal plate remaining attached to anchoring villi (AV). Endovascular invasion is nearly absent, and spiral arterioles remain ‘stiff’. FV, floating villi.

Cardiovascular system

• Cardiac preload affected by diminished hypervolemia of pregnancy.

• Increased cardiac afterload.• Endothelial activation with extravasation of

intravascular fluid into extravascular compartment.

Pulmonary edema may develop despite normal ventricular function because of an alveolar endothelial-epithelial leak, compounded by decreased oncotic pressure from a low serum albumin concentration

• Hemoconcentration is a hallmark of eclampsiafrom generalized vasoconstriction that follows endothelial activation and leakage of plasma into the interstitial space because of increased permeability.

• It’s however not as marked in preeclampsia and gest. HTN.

• Hemolysis

May be due to : Microangiopathic hemolysis

Serum lipid alterations

Erythrocyte membrane changes

Manifested by elevated serum lactate dehydrogenase levels and decreased haptoglobin levels.

Other evidence comes from schizocytosis, spherocytosis, and reticulocytosis in peripheral blood.

KIDNEYglomerular capillary endotheliosis

• GFR and Renal blood flow- decreased

- Inc. S. Uric Acid.

• Decreased excretion of Ca. due to tubular reabsorption.

• Acute renal failure induced by hypotension and hypovolemia and associated with obst. Hemorrhage.

LIVER

• First, symptomatic involvement is considered a sign of severe disease. It typically manifests by moderate to severe right-upper quadrant or mid epigastric pain and tenderness.

Infarction may be worsened by hypotension from obstetrical hemorrhage, and it occasionally causes hepatic failure.

• Second, asymptomatic elevations of serum hepatic transaminase levels—AST and ALT—are also considered markers for severe preeclampsia.

• In a third example of liver involvement, hemorrhagic infarction may extend to form a hepatic hematoma. These in turn may extend to form a subcapsular hematoma that may rupture.

More than 90 percent had HELLP syndrome, and in 90 percent, the capsule had ruptured. The maternal mortality rate was 22 percent, and the perinatal mortality rate was 31 percent.

• Last, acute fatty liver of pregnancy is sometimes confused with preeclampsia

With its onset in late pregnancy, and often accompanyinghypertension, elevated serum transaminase and creatinine levels, and thrombocytopenia

BRAIN

• Vasogenic edema due to loss of autoregulatory cerebral vasoconstriction leading to hyperperfusion.

• Supratentorial herniation is fatal.

• PRES.

Neurologic manifestations:• Headache and scotomatas• Convulsions• Confusion- comaVisual changes:• Scotomata/ blurred vision/ diplopia • Occipital blindness - amaurosis• Blindness from retinal lesions is caused either by

serous retinal detachment or rarely by retinal infarction, which is termed Purtscher retinopathy

HELLP

• It is a syndrome that is characterized by hepatic endothelial disruption followed by platelet activation, aggregation and consumption, ultimately resulting in ischemia and hepatocyte death.

• Occurs in up to 40% of pregnancies complicated by severe preeclampsia.

• Variable clinical presentation; 12 to 18% are normotensive and 13% do not have proteinuria.

• At diagnosis, 30% of women are postpartum, 14% are term, and 56% are preterm ,among them 49% are <37wks,7% are <27wks

• Periportal or focal parenchymal necrosis in which hyaline deposits of fibrin like material

↓

Obstruction of hepatic blood flow

↓

Periportal necrosis

Intra hepatic hemorrhage

Subcapsular hematoma

Eventual rupture of Glisson’s capsule

• Hemolysis is due to a microangiopathichaemolytic anaemia (MAHA).

• Presence of fragmented (schizocytes) or contracted red cells with spicula (Burr cells) in the peripheral blood smear.

• The diagnosis of haemolysis is supported by high LDH concentration and the presence of unconjugated bilirubin, but the demonstration of low or undetectable haptoglobinconcentration is a more specific indicator.

Classifications

TENNESSEE CLASSIFICATIONBased on laboratory criteria

1. Platelet count < 100,000/µL

2. AST ≥ 70 IU/L & LDH ≥ 600 IU/L

3. Hemolysis on peripheral smear

Partial HELLP Full HELLP

Any 2 of 3 criteria All of 3 criteria

• MISSISSIPI CLASIFICATION (2006)CLASS I – Platelet ≤ 50,000/µL(severe thrombocytopenia)

– AST ≥ 70 IU/L

– LDH ≥ 600 IU/L

– Hemolysis on smear

CLASS II– Platelet 50,000/µL to100,000/µL (moderate thrombocytopenia)

– AST ≥ 70 IU/L

– LDH ≥ 600 IU/L

– Hemolysis on smear

CLASS III– Platelet 100,000/µL to150,000/µL (mild thrombocytopenia)

– AST ≥ 40 IU/L

– LDH ≥ 600 IU/L

– Hemolysis on smear

• Maternal morbidity assoc. with HELLP syndrome:

Abruptio placenta 10-15%

DIC 10-15%

Pulmonary edema 6-8%

Acute renal failure 5-6%

ARDS 1-2%

Death 1%

THANK YOU