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1. Homeostasis in Pre Eclampsia Mohammad A Emam
Prof. of Obstetrics and Gynecology
Mansoura Faculty of Medicine
Member of Mansoura integrated fertility center (MIFC)
Faculty of Medicine,
Mansoura University - Egypt
2003
2. Toxaemia Of Pregnancy Ancient Egyptian & Hippocrates
(Bernhart 1930& Lindheimer et al.,1999)
Zweifel (1916)
Termed toxaemia the disease of theories
Many Classifications (change of toxaemia)
3. Traditional Diagnosis Of pre eclampsia (PET) Hypertension + Proteinuria
=
Two facets of a complex pathophysiological process
4. The Constant Pathological Feature Is
Vascular endothelial damage, dysfunction and spasm
(wolf et al, 2001)
5. Homeostasis Homeo= same & stasis= standing (Fox 1999)
Steady internal environment (ECF)
Regulations:
-Intrinsic
-Extrinsic
(Guyton 2000)
6. Homeostatic Control Systems Negative Feed back (Stablity)
Positive Feed back (Amplification)
(Vender et al, 1998)
7. Central Players in PET(Homeostats) 1. The Endothelium
2. Neutrophils
3. Platelets
4. Coagulation system
Once one is triggered
Others are activated.
Many co- workers are initiated (NO, PGs, ROS, Homocystein, Endothelins, VEGF, etc)
8. Endothelial Paradox 1. Thrombogenic
2. Thrombolytic
3. VC
4. VD
(Hayman et al, 2000)
9. Neutrophil Activation
12. Homeostasis In Normal Pregnancy And Pre eclampsia Rationale:
During pregnancy, the mother must alter her entire physiological and biochemical environment in order to provide conditions which are best suited to her fetus.
13. Volume Homeostasis
14. Sodium Homeostasis
15. Other Electrolytes Homeostasis
16. Homeostasis in Eclampsia The convulsive phase of PET (cerebral edema + neuronal irritation)? +ve feedback loop still acting?lactic acidosis??bicarbonate concentration ?compensatory loss of Co2.
17. Manifestations of The Positive Feedback Mechanisms of Homeostasis in Preeclampsia Concept:
PET disrupts the normal maternal homeostatic mechanisms occuring during normal pregnancy. In other words, homeostasis in PET occurs mainly via the +ve feedback loop, so the changes present are amplified.
This disruption results in different pathophsiological manifestations.
19. 1) Hypertension & proteinuria represent the ice-berg tip of the disturbances in the maternal homeostasis, involving many systems and organs in PET. CONCLUSIONS
20. 2) Homeostasis in PET is a dilemma, because the pathophysiology, presentation and the progression are so varied !!
This may be due to genetic factors that modify the maternal immunological response.
Also a pre-existing vascular pathology could be a modulating factor.
21. 3) Homeostasis in PET is achieved mainly through the positive feedback system where amplification of the disturbances occurs.
On the other hand, homeostasis of the fetoplacental circulation depends mainly upon the local vasoactive substances.
22. In PET, many complex homeostatic alterations occur, some are potentially harmful to the mother and fetus, while others are beneficial.
23. Clinical Implications 1) Peripehral edema is not a useful diagnostic criterion for PET, as it is so common in normal pregnancy.
Also, PET can occur without edema (dry type), so its presence does not ensure a poor prognosis and its absence not ensure a favorable outcome.
24. 2) Active volume expansion using the crystalloids should be prohibited.
But the use of colloids does improve maldistribution of fluid between the intra and extravascular space, and still carry the risk of volume overload and pulmonary edema.
25. 3) Large scale controlled studies (Cochrane 2002) have concluded that:
a) Low-dose aspirin have small to moderate benefits in preventing preeclampsia, and further information is required regarding the proper dose and the time of starting treatment.
b) Calcium supplementation during pregnancy is beneficial for women at high risk of preeclampsia, and in communities with low dietary calcium intake.
26. c) Salt consumption during pregnancy should remain a matter of personal preference, should not absolutely prohibited.
d) Maternal thrombocytopenia developed in preeclampsia usually not affect fetus or neonate, and hence, it is not a fetal indication for cesarean delivery.
27. e) No evidence that dietary magnesium supplementation during pregnancy is beneficial for prevention of preeclampsia.
f) Diuretics should be avoided in PET (due to reduction of PL V and decrements in placental perfusion).
28. 4) Nitric oxide donors may improve pregnancy outcome in PET; by decreasing:
the associated endothelial cell injury, improving the fetal blood supply and can lower MAP.
29. Recommendations for Future Researches 1. The genetic defects responsible for PET, to allow the prediction of women at risk.
2. The role of Antioxidants in prevention of the development of preeclampsia.
30. , multicenter studies are needed to identify latent hemodynamic abnormalities in symptom- free women with history of PET , to identify those with persistant endothelial dysfunction who are liable to develop hypertention in the future.
31. T HANK YOU