高血压英文ppt精品课件hypertensive disorders in _1

1,Hypertensive Disorders in Pregnancy (I),Williams Obstetrics 22nd Edition Chapter 34 ,2,Index,Diagnosis Etiology Pathogenesis Pathophysiology Prediction and Prevention Management Long-term consequences,3,Gestational Hypertension 3.7% in 150,000 (National Center for Health Statics, 2001) Pregnancy-related hypertension : Pregnancy-related deaths(3201 in US, 1991-1997) 16% Black women are 3.1 times to die as white women Hypertensive disorders remain among the most significant and intriguing unsolved problems in obstetrics,4,Diagnosis,Gestational hypertension Preeclamsia Eclamsia Superimposed preeclamsia (on chronic hypertension) Chronic hypertension,5,Gestational hypertension,BP 140/90mmHg for first time during pregnancy No proteinuria BP returns to normal 12 weeks postpartum Final diagnosis made only postpartum May have other signs or symptoms of preeclampsia, for example, epigastric discomfort or thrombocytopenia,6,Preeclampsia, Minimum Criteria - BP140/90mmHg after 20weeks gestation - Proteinuria 300mg/24hrs or 1+dipstick Increased certainty of preeclampsia - BP160/110mmHg - Proteinuria 2.0g/24hrs or 2+dipstick - Serum creatinine 1.2mg/dl unless known to be previously elevated - Platelets 100000/mm3 - Microangiopathic hemolysis (Increased LDH) - Elevated ALT or AST - Persistent headache or other cerebral or visual disturbance - Persistent epigastric pain,7,Preeclampsia,Diastolic hypertension 95mmHg Fetal death rate : 3 Worsening proteinuria preterm labor Neonatal survival Epigastric or RUQ pain Hepatocellur necrosis, ischemia, edema that stretches the Glisson capsure AST/ALT : sign Hepatic rupture : rare Thrombocytopenia severe vasospasm - microangiopathic hemolysis - Platelet activation, aggregation,8,Severity of Preeclampsia,Rapid increase in BP followed by convulsions is usually preceded by unrelenting severe headache or visual disturbances.,Differentiation between mild & severe preeclampsia can be misleading -because apparently mild disease may progress rapidly to severe disease,9,10,Eclampsia,preeclampsia+convulsion Seizures that cannot be attributed to other causes in woman with preeclampsia Seizures are generalized and may appear before, during, of after labor,11,Chronic hypertension,BP 140/90 mmHg before pregnancy or diagnosed before 20weeks gestation (not attributable to gestational trophoblastic disease) or Hypertension first diagnosed after 20weeks gestation and persistent after 12weeks postpartum,12,Chronic Hypertension,Chronic hypertension . : BP decreases during the second and early third trimesters in both normotensive and chronically hypertensive women Underlying hypertension Essential familial hypertension (90%),13,Underlying Causes of Chronic hypertensive Disorder Essential familial hypertension (hypertensive vascular disease) Obesity Atrterial abnormalities Renovascular hypertension Coarctation of the aorta Endocrine diorders Diabetes mellitus Cushing syndrome Primary aldosteronism Pheochromocytoma Thyrotoxicosis Glomerulonephritis (acute and chronic) Renoprival hypertension Chronic glomerulonephritis Chronic renal insufficiency Diabetic nephropathy Connetive tissue disease Lupus erythematosus Systemic sclorosis Periarteritis nodosa Polycystic kidney disease Acute renal failure,14,Chronic Hypertension,Chronic HT ventricular hypertrophy, cardiac decompensation, cerebrovascular accidents, renal damage superimposed preeclampsia ( 25% , 1998, Sibai) .,15,Preeclampsia superimposed on Chronic Hypertension,New-onset proteinuria 300mg/24hours in hypertensive women but no proteinuria before 20 weeks gestation A sudden increase in proteinuria or blood pressure or platelet count 100,000/mm3 in women with hypertension and proteinuria before 20weeks gestation,16,Superimposed preeclampsia,Placental abruption, growth restriction, preterm delivery, death “Pure” preeclampsia severe fetal growth restriction .,17,Incidence and Risk Factor,Nulliparous women . Incidence : 5% (wide variation) Influence by Parity, race, ethnicity, genetic predisposition Nulliparous Total :7.6% / severe : 3.3% (Hauth, 2000) Risk factor Chronic hypertension, multifetal gestation, maternal old age(35 yrs), obesity, African-American ethnicity,18,Incidence and Risk Factor,Maternal weight and the risk of preeclampsia is progressive. Smoking during pregnancy reduced risk of hypertension during pregnancy (Bainbridge,2005 ; Zhang, 1999) Placenta previa also reduced the risk of hypertension,(Sibai, 2000),19,Incidence and Risk Factor (Eclampsia),Eclampsia Somewhat preventable Receive adquate prenatal care 1976 (williams Obstetrics 15th edition) 1/700 deliveries (Parkland Hospitial) 1983-1986 1/1150 deliveries 1999 1/1750 deliveries 2000, National Vital Statistics Report, in US 1/3250 1994, Douglas and Redman in UK 1/2000,20,Etiology,Basic concepts Exposed to chorionic villi for the first time Exposed to a superabundance of chorionic villi, as with twins or hydatidiform mole Have preexisting vascular disease Genetically predisposed to hypertension developing during pregnancy,21,Vascular endothelial damage with vasospasm, transudation of plasma, and ischemic and thrombotic sequelae. Currently plausible potential cause (2003, Sibai) Abnormal trophoblastic invasion of Uterine vessels Immunological intolerance between maternal and fetoplacental tissues Maternal maladaptation to cardiovascular or inflammatory changes of normal pregnancy Diatary deficiencies Genetic influences,22,Abnormal Trophoblastic Invasion,In normal implantation, endovascular trophoblasts invade the uterine spiral arteries,23,24,In preeclampsia Incomplete trophoblastic invasion The magnitude of defective trophoblastic invasion of the spiral arteries correlated with the severity of the hypertensive disorder (2000, Madazli) Using electron micorscopy Endothelial damage Insudation of plasma constituents into vessel walls Proliferation of myointimal cells Medial necrosis Lipid and macrophage accumulates in myointimal cells,Abnormal Trophoblastic Invasion,25,Lipid-laden cells - atherosis (Hertig, 1945) Obstruction of the spiral arteriolar lumen by atherosis may impair placental blood flow Placental perfusion - diminished,26,Immunological Factors,Theory Formation of blocking antibodies of placental antigenic sites might be impaired. Number of antigenic sites provided by the placenta is unusually great compared with the amount of antibody, as with multiple fetuses. (Beer, 1978) Effective immunization by a previous pregnancy is lacking, as in first pregnancies. The immunization concept was supported by their observations that preeclampsia developed less often in multiparas who had a prior term pregnancy (Mostello, 2002; Trupin, 1996),27,Early second timester - Develop preeclampsia women Lower proportion of helper T cells (Th1) Th2 dominance, mediated by adenosine, which is found in higher serum level in preeclamptic compared with normotensive women (Yoneyama, 2002) These helper T lymphocytes secrete specific cytokines that promote implantation, and their dysfunction may favor preeclampsia (Hayashi, 2004; Whitecar, 2001),Immunological Factors,28,The Vasculopathy and the Inflammatory Changes,The decidua contains an abundance of cells that, when activated, can release noxious agents. (Staff, 1999) - mediators to provoke endothelial cell injury Preeclamsia due to an extreme state of activated leukocytes in the maternal circulation (Faas, 2000) Cytokines : TNF-a, interleukin oxidative stress (highly toxic radicals) Potential benefit of antioxidants to prevent preeclampsia (Chappell, 1999; Zhang, 2002),29,Nutritional Factors,Dietary deficiencies and Excesses over the centuries have been blamed as the cause of eclampsia. Supplementation with various elements such as zinc, calcium, and magnesium to prevent preeclampsia (John, 2002) Obesity, is a potent risk factor for preeclampsia C-reactive protein, an inflammatory marker, was shown to be increase in obesity, which in turn was associated with preeclampsia (Wolf, 2001),30,Genetic Factors,Hereditary hypertension is linked to preeclampsia (Ness, 2003) Preeclampsia- eclampsia is highly heritable in sisters, daughters, granddaughters, and daughters-in-law. (Chesley and Cooper, 1986) 60% concordance in monozygotic female twin pairs (Nilsson, 2004) HLA-DR4 preeclampsia (kilpatrick,1989),31,Pathogenesis Vasospasm,Vascular constriction resistance and subsequent hypertension Maldistribution, ischemia of the surrounding tissues blood flow necrosis, hemorrhage, and other end-organ disturbances,32,Pathogenesis Endothelial cell activation,Unknown factors (from placenta) are secreted into the maternal circulation activation and dysfunction of the vascular endothelium. Damaged or activated endothelial cells secrete substances promote coagulation and increase the sensitivity to vasopressors changes in glomerular capillary endothelial morphology increasd capillary permeability elevated blood concentrations,33,34,Increased Pressor Responses,Normally, pregnant women develop refractoriness to infused vasopressors (Abdul-Karim an Assali, 1961) But, early preeclampsia women have increased vascular reactivity to infused norepinephrine and angiotensin II (Raab, 1956),35,36,Increased Pressor Responses Prostaglandins,In preeclampsia Endothelial prostacyclin (PGI2) production is decreased Thromboxane A2 (TXA2) secretion by platelets is increased Increased sensitivity to infused angiotensin II vasoconstriction,Membrane phospholipid,Arachidonic acid,COX1,2,TXA2,PGI2, PGE2,Phospholipase A2,Platelet,37,Synthesized from L-arginine by endothelial cells. (potent vasodilator) Nitric oxide maintains the normal low-pressure vasodilated state characteristic of fetoplacental perfusion (Myatt, 1992) Preeclampsia is associated with decreased endothelial nitric oxide synthase expression, which increases cell permeability (Wang, 2004),Increased Pressor Responses Nitric oxide,38,Endothelin-1 (ET-1) : potent vasoconstrictors Produced by human endothelium Plasma ET-1 is increased in normotensive pregnant women, but women with preeclampsia have even higher levels (Ajne, 2003 ; Clark, 1992),Increased Pressor Responses Endothelins,39,Vascular endothelial growth factor (VEGF), Placental growth factor (PIGF), which secretion increases in normal pregnancy Promote angiogenesis Induce nitric oxide Vasodilatory prostaglandins Paradoxically, VEGF is increased in serum from women with preeclampsia, but its bioavailability is decreased (Baker, 1995 ; Simmons, 2000),Increased Pressor Responses Angiogenic factors,40,Pathophysiology Cardiovascular System,Increased cardiac afterload caused by hypertension Cardiac preload in preeclampsia Pathologically diminished hypervolemia of pregnancy Iatrogenically increased by iv crystalloid or oncotic solution Extravasion into the extracellular space, especially the lung,41,Cardiovascular System Hemodynamic Changes,Preeclampsia Cardiac output elevated before hypertension developed than normal pregnancy. With clinical onset of preeclampsia Marked reduction in cardiac output. Increased peripheral resistance. By contrast, Gestational hypertension Elevated cardiac outputs with development of hypertension.,42,43,(Hankin, 1984),44,Blood volume in term Normal pregnancy : 5000ml Not pregnancy : 3500ml Eclampsia : 3500ml Hemoconcentration in preeclampsia Vasoconstriction and Endothelial dysfunction with vascular permeability. Sevirity . Whereas, gestational hypertension have a normal blood volume (Silver, 1998),Cardiovascular System Blood volume,45,46,With severe hemoconcentration, an acute fall in hematocrit suggested resolution of preeclampsia Intravascular compartment in eclamptic women is usually not underfilled. vasospasm and endothelial leakage of plasma has contracted the space to be filled. It persist some time after delivery when the vascular endothelium repairs. Sensitive to vigorous fluid therapy to expand the contracted blood volume to normal pregnancy levels. Sensitive to even normal blood loss at delivery.,Cardiovascular System Blood volume,47,Blood and Coagulation Platelet,Thrombocytopenia life threatening Severe disease : indication of delivery - 3-5 days, Platelet activation, aggregation, consumption - “exhausion” - thrombocytopenia (Harlow, 2002) HELLP syndrome : hemolysis (H) , elevated liver enzymes (EL), and low platelets (LP) (Weinstein, 982) Neonatal thrombocytopenia Maternal thrombocytopenia . (Prichard, 1987),48,PT, aPTT, fibrinogen level (routine lab assessment of coagulation) - preeclampsia management . FDP : unknown (but, hepatic derangements (Leduc, 1992) ) Thrombophilias : clotting factor deficiencies - early onset preeclampsia Antithrombin preeclampsia (Chang, 1992) Fibronectin Glycoprotein-vascular endothelial cell basement membrane Preeclampsia ,Blood and Coagulation Coagulation,49,Severe preeclampsia LDH hemolysis Peripheral blood change : Schizocytosis, spherocytosis, reticulocytosis,Blood and Coagulation Fragmentation Hemolysis,50,Volume Homeostasis Endocrine changes,Renin, angiotensin, aldosterone But, preeclampsia level : Na + retension, hypertension Juxtaglomerular apparatus renin Angiotensinogen angiotensin I conversion (renin ) Angiotensin II - aldosterone preeclampsia Na retension . (Brown, 1988),51,Deoxycorticosterone (DOC) Another potent mineralocorticoid 3rd trimester Maternal adrenal gland plasma progesterone . Na retension hypertension - preeclampsia .,Volume Homeostasis Endocrine changes,52,Atrial Natriuretic peptide (ANP) Blood vol. expansion atrial wall streching Vasoactive , aldosterone, renin activity, angiotension II, vasopressin action sodium water excretion . preeclampsia ,Volume Homeostasis Endocrine changes,53,Volume Homeostasis Fluid and Electrolyte Changes,Preclampsia ECF vol. . Pathologic retension : endothelial injury Electrolyte concentration do not differ. Electrolyte unbalance Vigorous diuretic therapy Sodium restriction Administration of water with sufficient oxytocin to produce antidiuretisis. Following eclamptic convertion - lower HCO3,54,Kidney,Renal perfusion and glomerular filtration (in preeclampsia) Due to vasospasm But, Cr. Level - severe 2-3 . (Pritchard, 1984) Oligouria preeclampsia intensive iv fluid therapy indication .,55,Kidney,Proteinuria Preeclampsia-eclampsia Late . 24hr UA Anatomical changes Glomeruli : 20% Glomerular capillary endotheliosis Capillary endothelial swelling with subendothelial deposits of protein materials Acute renal failure Tubular necrosis, cortical necrosis - oligouria, anuria, rapidly develped azotemia : HELLP synd. , placental abruption, postpartum hemorrhage,56,Liver,Periportal hemorrhagic necrosis in the periphery of the liver lobule Serum liver enzyme Nonfatal case Autopsy Hepatic rupture(more rare), subcapsular hematoma(more common) . Treatment Surgical intervention , life saving Blood T/F . Liver transplantation Spontaneous hepatic rupture mortality :30%,57,58,Liver,HELLP syndrome Hemolysis, Elevated Liver enzyme and Low Platelet 20% of severe preeclampsia and eclampsia Adverse outcome : 40% Other complication Eclampsia (6%), Placental abruption (10%), ARF (5%), pulmonary edema (10%), subcapsular liver hematoma (1.6%) Steroid Tx. - controversial,59,Brain,Common Sx. Headache, visual disturbance associated convulsion (eclampsia) Anatomical pathology Gross hemorrhage severe hypertension Chronic hypertension Postmortem cerebral lesion Edema, hyperemia, focal anemia, thrombosis, hemorrhage,60,Brain,Neuroimaging study CT 50% abnormal finding Hypodense cotical area petechial hemorrhage and infarction site (at autopsy) MRI post. Cerebral artery area remarkable change . Convulsion Convulsion 25% cerebral infarction area .,61,62,Brain,Cerebral Blood Flow Eclampsia : loss of autoregulation of cerebral blood flow (Apollon, 2000) Hyperperfusion similar in hypertensive encephalopathy. Increased cerebral perfusion headache Cerebral vasospasm .,63,Brain,Blindness Rare 4hr to 8days . Visual disturbance More common Retinal detachement Total loss one side involve . prognosis good, 1 ,64,Brain,Cerebral Edema Sx Letharge, confusion, blurred vision, coma Mental change brain involvement . (CT, MRI ) Sudden severe blood pressure elevatoin vasogenic edema Blood pressure control . Electroencephalopgraphy Eclampsia 75% abnormal finding . (48hr ) 50% 1 , 3 .,65,Uteroplacental perfusion,Vasospasm - placental perfusion - perinatal mortality and morbidity Measurement Spiral a. : 500m (), 200 m (preeclampsia) Placental blood flow Inaccesibility, complexity, unsuitablity DHAS sulfate- estradiol-17B (in placenta) clearance rate (Everett, 1980),66,Uteroplacental perfusion,Doppler Doppler measurement of blood velocity through uterine artery. - estimate uteroplacental blood flow S/D ratio in preeclampsia : Abnormal wave form - fetal indication c/sec. HELLP synd. 18-36% : abnormal wave form . Preeclampsia mean resistance .,67,Prediction and Prevention,Prediction Lots of attemption to predict preeclampsia in early pregnancy - poor sensitivity, poor positive predictive value,68,Roll over test 28-32wks Lt. lat. Recumb