高血压英文ppt精品课件hypertensivedisease in

Hypertensive disease in pregnancy,Tom Archer, MD, MBA UCSD Anesthesia,Three causes of death in pregnancy:,#1 Thromboembolism #2 Hemorrhage #3 Hypertensive disorders / pre-E Stroke Seizures DIC,Traditional pre-eclampsia triad:,Hypertension Proteinuria Edema,Traditional pre-eclampsia triad:,Hypertension arteriolar constriction (endothelial dysfunction). Proteinuria leaky glomerulus (capillary) (endothelial dysfunction). Edema leaky capillaries in skin, muscle, liver, brain, airway, nose. (endothelial dysfunction).,Central thesis of pre-eclampsia: symptoms are due to arterial, arteriolar and capillary endothelial damage.,Damage how?,Pre-E: endothelial damage,Deranged (unbalanced) smooth muscle function, due to leaky, damaged endothelium overlying smooth muscle. Leaky capillary endothelium (no smooth muscle).,vasodilatory signals (NO, prostacyclin),vasoconstrictive signals (thromboxane, endothelin),Endothelial cells send molecular signals to surrounding smooth muscle,Vessel lumen,Insulin makes endothelium produce,Pre-eclampsia mediators (and glucose) make endothelium produce,Archer TL 2006 unpublished, Idea from Dandona P 2004,Endothelial factors in pre-E:,In health, there is a balance between vasodilatory factors: NO, PGI2 (Prostacyclin) and vasoconstrictive factors: thromboxane, endothelin. This normal balance is messed up in pre-E.,vasodilatory signals (NO, prostacyclin),vasoconstrictive signals (thromboxane, endothelin),Endothelial cells send molecular signals to surrounding smooth muscle,Vessel lumen,Insulin makes endothelium produce,Pre-eclampsia mediators (and glucose) make endothelium produce,Archer TL 2006 unpublished, Idea from Dandona P 2004,Obesity, hyperglycemia, sepsis and pre-eclampsia all “activate” (damage) endothelium, white cells and platelets, leading to white cell adhesion and infiltration, thrombosis and edema (inflammation).,Obesity, hyperglycemia, sepsis or pre-eclampsia,WBC,Platelet,Protein (edema),WBC,Platelets,Archer TL 2006 unpublished,Capillary endothelium (no underlying smooth muscle),Pre-E: disorder of endothelium,Genetic polymorphism of endothelial NO synthase predisposes certain Japanese women to pre-E. In other words, generation of vasodilatory signal from endothelium to underlying smooth muscle is messed up.,Endothelial damage causes problems in 3 sizes of blood vessels:,Muscular arteries increased wave reflection (heart work, augmentation index). Arterioles increased SVR Capillaries proteinuria and tissue edema (glomerulus, liver, skin, muscle, brain),Wave reflection comes from muscular arteries (larger than arterioles). Strong, early wave reflection increases hearts systolic workload (augmentation index).,MT, 22 yo, healthy, in labor, epidural in place and she is comfortable. AIx = -1%.,JM, 21 yo, in labor, recent onset lupus, on prednisone and plaquenil. Could see this in Pre-E. AIx = 6%,Figure 1. Pt HB, PreE for CS, superimposed on CHTN and CRF, 33 weeks. Hemodynamic parameters before and after treatment with antihypertensive medication A. Labetalol 25 mg and hydralazine 5 mg, B. Nicardipine 250 total in divided doses,Posterior reversible encephalopathy syndrome (PRES): Occipital-parietal cortical and white matter changes in pre-eclampsia. Is this due to capillary damage in the brain?,Port JD, Beauchamp RadioGraphics 1998; 18:353-36 ,Most SVR is provided by the arterioles (0.1-0.4 mm),/Characteristics+of.,Edema imagine same process in liver and brain!,Central thesis of pre-eclampsia: signs and symptoms are due to arterial, arteriolar and capillary endothelial damage.,Damage by what? Chemical mediators from placenta.,Pre-eclampsia:,Probably a disorder of placentation.,/dking2/erg/images/placenta.jpg,Say “OUCH!”,Pre-E mediators,Poor placentation,Pre-eclampsia: ischemic chorionic villi release pre-E mediators into maternal blood.,Proper placentation:,Syncytiotrophoblast invades and denervates maternal spiral arterioles to ensure a LOW RESISTANCE AV fistula in the intervillous spaces. This proper placentation FAILS in pre-eclampsia, leading to release of endothelium-damaging mediators from ischemic placenta Result is hypertension, proteinuria and edema, plus IUGR (poor O2 and nutrient transfer to fetus).,/images/preeclampsia_model.jpg,Poor-placentation theory of pre-E: Synciotrophoblast invades myometrium but does not denervate spiral arteries of mother properly. Hence, intervillous flow is sub-optimal. Chorionic villi are ischemic and release mediators (VEGF, etc) which damage maternal endothelium.,Gestational trophoblastic disease (hydatidiform mole et al) often causes first trimester pre-eclampsia, presumably due to pre-E mediators coming from edematous chorionic villi.,/dking2/erg/images/placenta.jpg,Say “OUCH!”,Pre-E mediators,Poor placentation,Pre-eclampsia: ischemic chorionic villi release pre-E mediators into maternal blood.,/invest/annual99/prod_vegf2.htm,/wayneheim/vegf.jpg,VEGF vascular endothelial growth factor. Is it good, or bad? Both, of course. Helps to build new blood vessels and breaks down basement membrane in the process.,/invest/annual99/prod_vegf2.htm,What do we observe in pre-E?,Evidence of vasoconstriction Increased wave reflection from muscular arteries (augmentation index). Increased SVR of arterioles, reflex decreased CO Increased cardiac natriuretic peptides (heart tries to compensate for increased wall stretch (afterload).,Wave reflection comes from muscular arteries (larger than arterioles),Ayten Elvan-Tas pinar, Arie Franx, Michiel L. Bots, Hein W. Bruinse, and Hein A. KoomansAm J Hypertens 2004;17:941946,Visual example of increased augmentation index in pre-eclampsia.,Normotensive 29 yo pregnant woman,Pre-eclamptic patient, 29 yo.,Mats Ro nnback, M.D.,1, 2,* Katja Lampinen,2,3 Per-Henrik Groop,1,2 and Risto Kaaja3 Hypertension in Pregnancy, 24:171180, 2005,Pre-eclampsia is associated with an increase in augmentation index.,Most SVR is provided by the arterioles (0.1-0.4 mm),/Characteristics+of.,Cite this article as: Tihtonen KM, Kbi T, Vuolteenaho O, et al. Natriuretic peptides and hemodynamics in preeclampsia. Am J Obstet Gynecol 2007;196:328.e1-328.e7.,In pre-eclampsia, we see increased SVR (arteriolar constriction), MAP and decreased CO. Atria and ventricles respond by increasing natriuretic peptide secretion.,10 0,3000 2000 1000 0,Nominal cardiac output L/min,Nominal systemic vascular resistance dyn.sec.cm-5,Blood pressure mm Hg,Heart rate beats/min and nominal stroke volume mL,300 200 100 0,150 100 50 0,FIGURE 3 etomidate induction in preE and lupus,0 A B 5 10 15 C D 20 SV minutes,Nicardipine lowers SVR and increases CO in patient with pre-E.,Nicardipine lowers SVR and increases CO in patient with pre-E.,Clark SL, Cotton DB, Lee W, et al: Central hemodynamic assessment of normal term pregnancy. Am J Obstet Gynecol 1989; 161: 14391442 reproduced in Fujitani Crit Care Med 2005 Vol. 33, No. 10 (Suppl.),Hemodynamics of normal pregnancy: increased CO, normal BP, decreased SVR.,Modern concepts of vascular disease,Stiff large arteries (e.g. atherosclerosis) Systolic hypertension Increased pulse wave velocity (reflected wave returns faster) “Endothelial dysfunction” Say what? Endothelium send signals to underlying smooth muscle. Obesity, hyperglycemia, hypertension, pre-eclampsia, sepsis all make for unhealthy signals vasoconstrictive bias. Exercise, weight loss, red wine make for healthy signals,How can we measure endothelial function?,Flow-mediated vasodilation- difficult Decrease in augmentation index in response to salbutamol (beta-agonist smooth muscle dilator) easier.,http:/www.iua.upf.es/activitats/semirec/medicalImageAnalysis/vessel.png,Flow-mediated vasodilation (FMD) measures dilation of brachial artery proximal to a BP cuff inflated for 5 minutes on the forearm. Normal is 10.4% dilation. It is a measure of endothelial function. Normal endothelium responds to increased distal flow by dilating. In studies from Colombia and Bangladesh, Ca+ and linoleic acid supplementation enhances FMD and decreases clinical pre-E.,Weight reduction increases endothelial response (dilation of muscular arteries) to salbutamol, but not to NTG. NTG works independently of endothelium does not need good endothelium to dilate smooth muscle.,Endothelial vs. non-endothelial mediated vasodilation,Salbutamol (beta agonist) works by making endothelium produce more NO NTG works independently of endothelium to dilate arteries,Augmentation index increases along with other inflammatory markers in antineutrophil cytoplasmic antibodyassociated systemic vasculitis (AASV),A. D. Booth,1 S. Wallace,2 C. M. McEniery,1 Yasmin,1 J. Brown,2 D. R. W. Jayne,3and I. B. Wilkinson1 ARTHRITIS & RHEUMATISMVol. 50, No. 2, February 2004, pp 581588,Pre-E and CHTN show increased atrial and BNP peptides produced by heart when it is under strain due to volume overload. These peptides eliminate sodium and increase vascular permeability. VEGF also contributes to vascular permeability.,Tihtonen KM, Kbi T, Vuolteenaho O, et al. Natriuretic peptides and hemodynamics in preeclampsia. Am J Obstet Gynecol 2007;196: 328.e1-328.e7.,Causes of Preeclampsia:,Third World: calcium and vitamin deficiency may play a big role. Developed world: With better diet, genetic and immunologic factors play bigger role. There probably are many causes of pre-E syndrome. Many stages of pre-E syndrome.,Lopez-Jaramillo P. Garcia RG. Lopez M. Preventing pregnancy-induced hypertension: are there regional differences for this global problem?see comment. Review 81 refs Journal Article. Research Support, Non-U.S. Govt. Review Journal of Hypertension. 23(6):1121-9, 2005 Jun.,Double blind RCT: Ca+ supplementation reduces pregnancy induced hypertension in Ecuadorean women.,Herrera JA International Journal of Gynecology and Obstetrics (2005) 91, 221227,Renin-Angiotensin-Aldosterone System (RAAS) in pre-E:,Increased in activity with normal pregnancy. Paradoxically, is diminished in pre-E. Remember that RAAS system increase leads to fluid retention, increased erythropoiesis and cardiac hypertrophy in normal pregnancy.,BP control in pre-E:,BP control is distinct from seizure prophylaxis. We use hydralazine or labetalol for HBP in pre-E. Mg will tend to lower BP, but that is not why it is used.,Hemodynamics in pre-E:,Progression from high CO, normal SVR to low CO, increased SVR? CVP not reliable as index of volume status! Colloid osmotic pressure is down in pre-E (leaky capillaries?). Keep down the fluids! Use colloid if you want to volume expand. Pre-E patients probably do NOT drop their pressure with SAB/ epidural more than normal pregnant women. OBs worry about post-op / delivery pulmonary edema.,Mean BP in 30 normals and 30 preeclamptic (preterm) women for C/S under SAB,SAB in C/S patients with preeclampsia: Does SAB cause worse hypotension in pre-E (preterm) C/S patients than in non-preE (term) C/S patients?,SAB in C/S patients with preeclampsia: Does SAB cause worse hypotension in pre-E (preterm) C/S patients than in non-preE (term) C/S patients?,Aya AGM 2003,Questions about Aya study:,Pre-E patients were on average also preterm pregnancies. Was greater hemodynamic stability in pre-E patients due to smaller uterus and fetus and less aortocaval compression? Both pre-E and normal patients had considerable crystalloid preload (1500 ml) before SAB.,Practical management of pre-E:,Mg is anticonvulsant. Mg use in mild pre-E is controversial! Mg use in severe pre-E is well established (MAGPIE Trial and others). Mg in severe pre-E reduces seizures by about 60% (1.9% 0.8%, NNT 91), so the effect is NOT overwhelming and NNT is high.,Mg+ toxicity,Ca+ influx into nerve terminal releases Ach for N-M transmission. Mg+ will counteract this, so Mg+ toxicity can be N-M blockade. Mg+ potentiates non-depolarizing NMBs. Respiratory depression (sedation + weakness) Rx symptomatic hypermagnesemia with IV Ca+. Poor mans Mg+ levels: patellar reflexes. Hold Mg+ if reflexes disappear. If epidural in place, check DTRs in arms!,Mg+ toxicity to neonate?,50 gm MgSO4 total dose to mother associated with neonatal brain da