Pregnancy Induced Hypertension- Pathophysiology

Just a presentation covering most of the known etiology and pathophysiology behind PIH

1. Pathophysiology of Pregnancy Induced Hypertension Dr. Anusha Rao P PGY-2 (OBG)

2. 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.

3. Normal pregnancy is characterised by: Increase in plasma volume(preload) starts from 6 th wk , plateaus at 30 th wk. (+50%) so fall in haematocrit . Increase in cardiac output, from 5 th wk , peaks at 30-34 wks , remains static till term, increases further in labour and 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.

4. 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.

5. EARLY GTN LATE GTN 6

6. ETIOLOGY O bservation 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.

7. 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.

8. IMMUNOLOGICAL MECHANISMS: Loss of maternal immune tolerance to paternally derived placental and fetal antigens is – dysregulation . R isk 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 trophoblasts early in pregnancy express reduced amounts of immunosuppressive non classic HLA G.

9. Incident risk for preeclampsia of 20 to 40 percent for daughters of preeclamptic mothers; 11 to 37 percent for sisters of preeclamptic women; and 22 to 47 percent for twins.

10. 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 )

11. Two stage disorder

12. 2 Stage process Preclinical ( ≤20 weeks): I nadequate invasion of maternal spiral arterioles by fetal cytotrophoblasts  Insufficient maternal vascular remodeling and angiogenesis Clinical (normally >20 weeks): Oxidatively stressed/hypoxic placenta  G eneralized systemic inflammatory response with release of anti- angiogenic factors, inflammatory cytokines, and trophoblast debris  M aternal syndrome

13. 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

14. Invasion defects in preeclampsia. (A) In a normal placenta, extravillous cytotrophoblast (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 preeclamptic patient, 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.

15. Cardiovascular system Cardiac preload affected by diminished hypervolemia of pregnancy. Increased cardiac afterload. Endothelial activation with extravasation of intravascular fluid into extravascular compartment. P ulmonary 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

16. Hemoconcentration is a hallmark of eclampsia from 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.

17. Hemolysis May be due to : M icroangiopathic hemolysis S erum 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.

18. KIDNEY glomerular capillary endotheliosis

19. 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.

20. 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. I nfarction 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.

21. 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 accompanying hypertension, elevated serum transaminase and creatinine levels , and thrombocytopenia

22. BRAIN Vasogenic edema due to loss of autoregulatory cerebral vasoconstriction leading to hyperperfusion . Supratentorial herniation is fatal. PRES.

23. Neurologic manifestations: Headache and scotomatas Convulsions Confusion- coma Visual 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

24. 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

25. 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

26. Hemolysis is due to a microangiopathic haemolytic 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 haptoglobin concentration is a more specific indicator.

27. Classifications TENNESSEE CLASSIFICATION Based on laboratory criteria Platelet count < 100,000/ µL AST ≥ 70 IU/L & LDH ≥ 600 IU/L Hemolysis on peripheral smear Partial HELLP Full HELLP Any 2 of 3 criteria All of 3 criteria

28. 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

29. 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%

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