Preeclampsia e rene: recenti acquisizioni e future ...· acquisizioni e future strategie Preeclampsia

Preeclampsia e rene: recenti

acquisizioni e future strategie

Preeclampsia e rene

Loreto Gesualdo

Universit di Bari

PREGNANCY AND RENAL DISEASES

Complications in the normal pregnancy

Urinary abnormalities 15 - 25 %

Hypertension in pregnancy 10 - 12 %

Urinary tract infections 2 - 10 %

Renal calculi 0.03 - 1 %

Acute Renal Failure 0.05 - 0.15 %

Incidence

Hypertension in

pregnancy

60

70

80

90

100

110

120

130

140

150

10 20 28 32 38 weeksPre-pregnancy6 12

NHLBI Working Group on Research on Hypertension during Pregnancy Roberts et al. Hypertension 2003; 41

Classification of hypertension in pregnancy

Delivery

Chronic Hypertension

160

Masked chronic hypertension

Pre-eclampsia super imposed

Pre-eclampsia/Eclampsia

Gestational Hypertension

When were talking about hypertension

during pregnancy ?

SBP > 140 mmHg

DBP > 90 mmHg

The woman should be rested

The blood pressure cuff should be of appropiate size and placed

on the right arm at the level of the heart

Recent studies have shown that the disappearance of the fifth

Korotkoff sound (K5) is greater than K4 to record diastolic

pressure in pregnancy.

Brown M.A.et al, Classification of hypertension in pregnancy, Clinical Obstetrics and Gynaecology;1999, 13

Walker J.J.,Pre-eclampsia, Lancet 2000; 356

Working group report on high blood pressure in pregnancy. NIH, Washington, DC 2000.

Hypertension in pregnancy: problems dimension

Hypertensive disorders complicate 10-

12% of pregnancies

Pre-eclampsia occurs in 3-4 % of

pregnancies (mild in 75% of cases and

severe in 25%)

Chronic Hypertension complicates 2-

3% of pregnancies

Gestational Hypertension occurs in 5-

6%

Hypertension in pregnancy: problems dimension

Risk factor for Preeclampsia

Maternal age < 17 years and > 35

Nulliparity

Multifetal gestation

Preeclampsia in previous pregnancy

Family history of pregnancy-induced hypertension

Chronic Hypertension

Chronic renal disease

Diabetes mellitus , insulin resistance

High BMI (obesity), dyslipidemia

Vascular or connective tissue diseases

Thrombophilia (AAS, fatt. V leiden, Antithrombin III, protein C orS deficiency)

Preeclampsia

Minime variazioni del volume plasmatico efficace

Aumento dellematocrito

Gittata cardiaca: normale o aumentata

Riduzione della Portata Renale Plasmatica (PRP)

e della VFG

Aumento delle resistenze vascolari periferiche

Gravidanza normale

Alto volume

Bassa pressione

Basse resistenze periferiche

Pre-eclampsia

Basso volume

Alta pressione

Alte resistenze periferiche

Pre-eclampsia

Eclampsia

Endotheliosis lesion and segmental

early thrombotic microangiopathy

Extensive severe thrombotic microangiopathy

Heptinstalls Pathology of the Kidney - 6th edition - 2007

Severe arteriolar lesion with fibrinoid necrosis

and intraluminal fibrin

Maternal mortality associated with pre-eclampsia and eclampsia (UK)

Walker J.J, Lancet, 2000, 356

600.000 donne/anno muoiono per cause connesse alla gravidanza

Almeno 50.000 di questi decessi sono attribuibili alla pre-eclampsia /eclampsia

Solo 1 su 2000 gravidanze

in alcune nazioni in via di sviluppo:

!! 1 caso ogni 100 gravidanze

99% di questi eventi sono nei paesi in via di sviluppo

Maternal Mortality

USA: 15/100,000 live births

Mali: 800/100,000 live births

Hemorrhage

Embolism

Preeclampsia

Infection

Greene M. N Engl J Med 2003;348:275-276

Autopsy Specimen from a 40-Year-Old Woman with Severe Preeclampsia and Subarachnoid Hemorrhage

Clinical Manifestation(after 20 wks gestation)

Mild(75%): DBP < 110 mmHg

Proteinuria < 3 gr/24h

Severe(25%): DBP > 110 mmHg

Proteinuria > 3 g/24h

Other manifestations:- Headache

- Blurred vision

- Renal impairment

- Seizures (eclampsia)

Sistolica >160 mmHg

o

Diastolica >110 mmHgalmeno 2 volte a distanza di 6 ore

Piastrine < 100.000 mm3

Transaminasi x 2

Proteinuria >5g/24h

o

+++ dipstick in 2

campioni separati

Complicanze pi gravi: Oliguria, edema polmonare, incidente CV, coagulopatia

Pre-eclampsia severaInsorgenza di ipertensione e proteinuria e almeno 1 delle seguenti condizioni

Sintomi neurologiciRitardo crescita

http://images.google.com/imgres?imgurl=klahaniechiropractic.com/_borders/headache.jpg&imgrefurl=http://klahaniechiropractic.com/headaches.htm&h=1396&w=729&prev=/images%3Fq%3Dheadache%26svnum%3D10%26hl%3Den%26lr%3D%26ie%3DUTF-8%26oe%3DUTF-8http://images.google.com/imgres?imgurl=www.globalrph.com/antibiotic/liver.jpg&imgrefurl=http://www.globalrph.com/antibiotic/hepatic.htm&h=188&w=270&prev=/images%3Fq%3Dliver%26svnum%3D10%26hl%3Den%26lr%3D%26ie%3DUTF-8%26oe%3DUTF-8

HELLP Syndrome

Microangiopathic hemolysis

Platelet count

Development and validation of the fullPIERS model

Gestational age

Chest pain or dyspnoea

Oxygen saturation

Platelet count

Creatinine and aspartate transaminase concentration

von Dadelszen P et al Lancet 377, 219-227, 2011

Prediction of adverse maternal

outcome in pre-eclampsia

Identificata la causa della pre-eclampsia?

Preeclampsia

Eziologia:

Sconosciuta, patologia inesistente negli animali

Patogenesi:

Non chiarita

Obiettivo principale:

Individuazione della pre-eclampsia e trattamento perprevenire severe complicanze.

Non disponiamo al momento di terapia specifica preventiva per la malattia!

DISFUNZIONE ENDOTELIALE SISTEMICA

Tutte le manifestazioni cliniche della PREECLAMPSIApossono essere spiegate come una risposta materna ad unadisfunzione endoteliale generalizzata.

Lalterato controllo endoteliale del tono vascolare determinaipertensione arteriosa, incremento della permeabilitvascolare con conseguente edema e proteinuria ed anomalaespressione endoteliale di fattori procoagulanti in grado diattivare la cascata coagulativa.

Queste modificazioni causano inoltre ischemia di organibersaglio, quali il cervello, il fegato e la placenta.

The capillary lumen is decreased secondary to swelling of the endothelial cell (END.) The intercapillary

cell mass, including mesangium (MES), appears increased, and there is an increase in amorphous

material along the inner surface of basement membrane, especially in the region of the intercapillary cell

mass. Epithelial cell (EPITH) changes are mild, except for occasional large blebs showing almost no

filamentous matrix or cytoplasmic particulates.

Heptinstalls Pathology of the Kidney - 6th edition - 2007

Etiology

Multiple theories: toxins, nephritis, parasites,

malnutrition, vitamin deficiency, genetic,

immunologic, inflammation, oxidation,

prostaglandin imbalance, angiogenic

factors,..

Pathophysiology

Endothelial cell injury

Generalized vasoconstriction

Pathophysiology

Maternal immunologic intolerance

Abnormal placental implantation

Genetic, nutritional, and environmental

factors

Cardiovascular and inflammatory

changes

Atherosis in placental bed

Rogers et al: Obst Gynecol Survey 54:189,1999

Roberts, J. M. et al. Hypertension 2005; 46:1243-1249

Two-stage model of the pathophysiology of preeclampsia

Stage 2 develops in

some, but not all

women with stage 1

C. W. Redman et al., Science 308, 1592 -1594 (2005)

Poor placentation and preeclampsia

Uterine spiral artery

unwinds and becomes

a wider, flaccid tube to

accommodate increased

blood flow.

Uterine spiral artery

remains tightly coiled,

diminishing placental

blood flow

The Journal of Clinical Investigation http://www.jci.org Volume 120 Number 11 November 2010

March 2011 | Volume 8 | Issue 3 |

Defective invasion of

endovascular trophoblast into the

myometrial segments of spiral

arteries?

Villi Coriali

Placenta Normale

Villi Coriali

Placenta Gestosica

L. Resta & L. Gesualdo Placenta 27:735-739, 2006.

Ipotesi Patogenetica

Predisposizione Genetica

Mancato o incompleto impianto del trofoblasto nelle arterie spiraliformi materne

Ridotta perfusione del citotrofoblasto

Attivazione del sistema immune

Aumentata produzione di radicali liberi dellossigeno

Danno Endoteliale

Alterazione di

Bilancia vasocostrittiva/ vasodilatativa

Coagulazione

PREECLAMPSIA

Sistema delle Integrine ed Angiogenesi

Gravidanza Normale

Pre-eclampsia

Ute

ro

Rimodellamento

Vasale adeguato Flusso Ematico

Rimodellamento