DEFINITION,CLASSIFICATION

ETIOPATHOGENESIS AND CLINICAL FEATURES OF

HYPERTENSIVE DISORDERS IN PREGNANCY

INTRODUCTION Commonest medical disorders during

pregnancy. Being the major cause of maternal and

perinatal morbidity and mortality. INCIDENCE Hypertensive disorders complicate 5-10

% of all pregnancies. Incidence of eclampsia is reduced due to

adequate and better antenatal care. GHTN : 6-17% in nullipara Pre eclampsia – 3-10% in nullipara

MATERNAL ADAPTATIONS IN PREG CARDIOVASCULAR SYSTEM :

-Cardiac output -Blood pressure

BP = CO * SVR CO increases ; SVR decreases

BP overall Diastolic BP &

M.A.P

MEASUREMENT BP can be recorded either in sitting or lateral recumbent posture. Brachial artery and mercury manometer should be at the level of

heart. Appropriate sized cuff should be used. DISAPPEARANCE OF KOROTKOFF

PHASE V

Diastolic BP

CLASSIFICATION By NHBPEP (2000)

GESTATIONAL HYPERTENSIONPRE ECLAMPSIA & ECLAMPSIAPRE ECLAMPSIA SUPER IMPOSED ON

CHRONIC HYPERTENSIONCHRONIC HYPERTENSION

GESTATIONAL HYPERTENSION BP ≥ 140/ 90 mmHg for first time

during pregnancy after 20 weeks of gestation

No proteinuria Returns to normal before 12

weeks postpartum With / without other symptoms of

pre eclampsia

PRE ECLAMPSIAAbnormality Mild SevereDiastolic BP <110 mmHg ≥110 mmHgSystolic BP <160 mmHg ≥160 mm HgProteinuria ≤2+ ≥3+Headache - +Visual disturbances - +Epigastric pain - +Oliguria _ +Convulsion - +Serum creatinine normal Thrombocytopenia _ +Serum transaminase minimal markedGrowth restriction - obviousPulmonary edema - +

ECLAMPSIA :Seizures that cannot be attributed to other

causes in a women with pre eclampsia.

CHRONIC HYPERTENSION : BP ≥140/ 90 mmHg before pregnancy or

diagnosed first before 20 wks of gestation

or Hypertension diagnosed after 20 wks and

persists after 12 wks postpartum

SUPER IMPOSED PRE ECLAMPSIA ON CHRONIC HTN :

New onset proteinuria ≥ 300mg/24 hrs in a hypertensive women but no proteinuria before 20 wks of gestation

orSudden in proteinuria / BP / in platelet

count in hypertensive women with proteinuria before 20 wks.

TRANSIENT HYPERTENSION :GHTN reclassified if pre eclampsia doesnot develop and BP returns to normal by 12 wks postpartum.

ATYPICAL PRE ECLAMPSIA :Without hypertension/ proteinuria/ both

Clinical findings Chronic HTN GHTN Pre eclampsia

Time of onset of hypertension

<20 wks 3rd trimester ≥20 wks

Degree of hypertension

Mild / severe Mild Mild/ severe

Proteinuria --- --- +

S.Uric acid >5.5 --rare -- +

hemoconcentration

- - Severe

Thrombocytopenia

- - „

Hepatic dysfunction

- - „

GESTATIONAL HYPERTENSION

Incidence : 6-17% in nullipara

CRITERIA FOR MILD GHTN : BP <160/110mmHg Proteinuria <300mg/24 hrs Platelet count > 100000 Normal liver enzymes Absent maternal symptoms Absent IUGR & OLIGO by

USG

PRE ECLAMPSIA INCIDENCE – 3-10% IN NULLIPARAOccurs before 20 wks in trophoblastic diseases.Clinical findings of pre eclampsia can manifest

either as maternal or fetal syndrome.RISK FACTORS1.AGE AND PARITY : Young primigravida Elderly > 40yrs Long interval between pregnancies Nulliparity2.MATERNAL OBESITY BMI > 35kg/m2 – 13.3%

3.Genetic : Family h/o pre eclampsia Genetic predisposition Race and ethnicity By ovum donation4. OBSTERIC : Prev h/o pre eclampsia Multifetal gestation Hydrops Hydatiform mole Congenital & chromosomal fetal anomalies5.PARTNER RELATED FACTORS Change of partner Partner who fathered a pre eclamptic preg Limited sperm exposure By donor Insemination

6. UNDERLYING MEDICAL DISORDERSChronic hypertensionRenal diseasesType I diabetes mellitusThrombophiliaFactor V leiden deficiencySickle cell disease or traitCollagen vascular diseasesPCOSUncontrolled hyperthyroidismMigraineAutoimmune diseases

CHRONIC HYPERTENSION CAUSES :

ESSENTIAL ( IDIOPATHIC / PRIMARY ) SECONDARY :

RENAL DISEASE Renal artery stenosis Glomerulonephritis Pyelonephritis Interstitial nephritis Polycystic disease TB Neoplasm

ADRENAL DISEASE Phaeochromocytoma Cushing syndrome Conn’s syndrome

CONNECTIVE TISSUE DISORDER Polyarteritis nodosa SLE Scleroderma

COARCTATION OF AORTA

ETIOPATHOGENESISPOOR PLACENTATION

PLACENTAL OXIDATIVE STRESS

FETALGROWTH

RESTRICTION

RELEASE OF PLACENTAL FACTORS

SYSTEMIC INFLAMMATORY

RESPONSE

ENDOTHELIAL ACTIVATION

STAGE I

STAGE II

ETIOLOGY Placental implantation with

abnormal trophoblastic invasion

Immunological maladaptive tolerance between maternal,paternal and fetal tissues.

Maternal maladaptation to CVS / inflammatory changes of normal pregnancy

Genetic factors – inherited predisposing genes & epigenetic influences

Coagulation abnormalities Dietary deficiency

ABNORMAL TROPHOBLAST INVASION

Incomplete trophoblast invasion

Shallow invasion upto decidual segments

Abnormally narrow spiral arteriolar lumen

Impairs blood flow

Diminished placental perfusion

Hypoxia Release of placental debris

Systemic inflammatory response

IMMUNOLOGICAL FACTORS uNK cells with HLA class I in extravillous

cytotrophoblasts control invasion.

Reduced expression of HLA-G by extravillous trophoblasts messenger RNA

Defective placental vascularisation

ENDOTHELIAL CELL ACTIVATIONDefective

placentation

Placental ischemia / hypoxia

Inflammatory mediators-

Il.TNF

Xanthine oxidase

activation

Oxidative stress

Free radical

PlacentaMaternal

endotheliumleucocytes

CEC

Platelet aggregation

fibrin ,thrombin

Lipid peroxides &Foam cells

NUTRITIONAL FACTORS : ascorbic acid < 85mg - incidenceGENETIC FATORS : - Multifactorial & Polygenic Disorder WARD AND LINDHEIMER (2009) 20-40 % for daughters of pre eclampsia

mothers 11-37 % for sisters of pre eclampsia women 22-47 % in twinsCANDIDATE GENES : Genome wide linkage studiesOUDEJANS Susceptibility loci on 10q22.1

2p122p259p13

GENETICS AND GENETIC IMPRINTINGGENETIC CONFLICT THEORY :

nutrients transfer limit the transfer

INCREASE BP REDUCE BP INADEQUATE UTEROPLACENTAL

BLOODFLOWFETAL RESCUE STRATEGY TO

INCREASE NON PLACENTAL RESISTANCE

ENDOTHELIAL DYSFUNCTION

FETAL GENES MATERNAL GENES

PATHOGENESISVASOSPASM : Vascular constriction increase in resistanceENDOTHELIAL CELL ACTIVATION : Placental factors activation & dysfunctionCEC of endothelial cells NO synthesisINCREASED PRESSOR RESPONSES - Sensitivity to AG

IINITRIC OXIDE – vasodilator

from L-arginine & fetal endothelium synthesisENDOTHELINS – vasoconstrictor human endothelium

PROSTAGLANDINS prostacyclin thrombaxene A2Vasodilatation & vasoconstrictionInhib plt aggregation plt aggregationIn pre eclampsia:PGI2 production TXA2 VasoconstrictionPGI2 : TXA2

endotheliumRenal cortex

PlateletTrophoblas

t

ANGIOGENIC AND ANTIANGIOGENIC PROTEINS

sFlt-1 reduced free VEGF & PLGF

endothelial dysfunction

sEng inhibits TGF- b

binding to endothelial receptors - NO dep vasodilatation

PATHOPHYSIOLOGYCVS : Preload affected Extravasation of fluid BLOOD VOLUME : HemoconcentrationBLOOD & COAGULATION :Endothelial activation plt activation &

aggreg plt exhaustion thrombocytopeniaHEMOLYSIS : LDH Schizocytosis,reticulocytosis,

spherocytosis

COAGULATION : INCREASED Factor VIII consumption fibrinopeptides & FDP DECREASED regulatory protein levelVOLUME HOMEOSTASIS :ENDOCRINE CHANGES

PLASMA NORMAL PRE ECLAMPSIA

ReninAngiotensin IIAldosterone

INCREASES DECREASES

Deoxycorticosterone

INCREASES NO CHANGE

Vasopressin Same SameANP -/ Increases Increases

FLUID AND ELECTROLYTE CHANGES :

Oncotic pressure Pathological fluid retention

LIVER :Periportal hemorrhage Subcapsular hemorrhage

stretching of glisson’s cap

Proteinuria Edema

SUBCAPSULAR LIVER HEMATOMA Can be unruptured or

ruptured. DD for unruptured :

Acute FLP, Ruptured uterus, abruption with DIC, TTP.

Presents with shoulder pain, shock, massive ascites, pleural effusion or respiratory difficulty.

BRAIN :

VISUAL CHANGES AND BLINDNESS : SCOTOMA, BLURRED VISION, DIPLOPIA BLINDNESS – Visual cortex of occipital lobe --AMAUROSIS Lateral geniculate nuclei Retina ---PURTSCHER RETINOPATHY RETINAL DETACHMENT

Acute and severe hypertension cerebrovascular over regulationVasospasm

Diminished cerebral flow – ischemia-cytotoxic edema-tissue infarction

Sudden in systemic BP exceed the normal cerebrovascular auto regulatory capacity

Posterior reversible encephalopathy syndrome

KIDNEY :- Renal Perfusion & GFR- Due to renal afferent arteriolar resistance- Glomerular capillery endotheliosis

blocking the filtration barrier.Pre renal

Urine osmolalityUrine :plasma

creatinineExcretion of

sodium

sr.creatinine- filtration

Uric acid - tubular

reabsorption

CLINICAL FEATURES–PRE ECLAMPSIA Onset : Insidious Symptoms :

MILD : Swelling over ankles, face, abdominal wall, vulva ALARMING : -Headache - Disturbed sleep

- Diminished urine output - Epigastric pain - Visual disturbances

Signs : -Abnormal weight gain -Rise of blood pressure -Oedema -Pulmonary edema -Abdominal examination

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