高血压英文ppt精品课件genderdifferences in physiology

APS 2006 Refresher Course Gender Differences in Physiology: Cardiovascular Virginia H. Huxley, Ph.D. Director, National Center for Gender Physiology University of Missouri School of Medicine Columbia, MO USA Research Support from the National Institutes of Health (NIH), Heart, Lung correct Scientific term. “Gender” = psychological term describing the self-designation of male or female vs. Societal: “Sex” is reproduction and has negative connotation “Gender” is softer and less likely to be misinterpreted. APS 2006 Refresher Course Physiology: Cardiovascular Women less tolerant to upright posture or gravitational stress than men - primarily due to reduced ability to maintain venous return and cardiac output. Mechanisms behind sex difference in BP control unknown. Heart Rate: Women Men; sleep, rest, exercise In response to cardiovascular stress: HR*SV = CO = P/TPR Women increase heart rate Men increase vascular resistance APS 2006 Refresher Course QT interval longer in Women than Men Atrial Fibrillation in Men who are heavy drinkers Contractility Women Men Cardiac myocyte expression of glycolytic after 75 reverses Women with CHF more likely to have co-morbid diabetes and hypertension than Men. APS 2006 Refresher Course Pathophysiology: Type II Diabetes & CVD Type II Diabetic Women 3-4X more likely to develop CHD 2X risk of a 2nd heart attack have lower E2 & loose “estrogens protective effect” experience reproductive problems 2-4X more likely to be African American, Hispanic, American Indian, or Asian Pacific Islander than Caucasian Diabetes associated with low total testosterone in Men high levels of bioavailable testosterone in Women Lower estrogen levels may account for the same rate of kidney and CV disease-related conditions. APS 2006 Refresher Course 70 kg Male Caucasian: 18-22 yr, military/athlete or European Medical Student Frequency Measured variable How could it be that we did not recognize the differences until now? APS 2006 Refresher Course ? What is the physiological basis for these cardiovascular “Sex“ differences? APS 2006 Refresher Course More than the Sex Hormones: XX vs. XY Obvious: why only males develop prostate cancer and only females get ovarian cancer Not Obvious: why Females are more likely than Males to recover language ability after suffering a left-hemisphere stroke, or why Females have a far greater risk than Males of developing life-threatening ventricular arrhythmias in response to a variety of K+ channel-blocking drugs APS 2006 Refresher Course Basic truths Every Cell Has a Sex Sex Begins in the Womb Pre-natal environment Testosterone produced first Prepubertal sex hormone differences E2 higher in girls than boys Sex Affects Health Susceptibility/prevalence Natural history Mobility/mortality APS 2006 Refresher Course Estrogen: The (?) Mediator of Sex Differences Estrogen, E2 & Estrogen Receptors ER & ER Nongenomic, cytoplasmic actions Genomic actions Male/Female differences in receptor distribution E2 Required by Males and Females APS 2006 Refresher Course Estrogen: The (?) Mediator of Sex Differences ERactivation “protective“ Re-endothelialization post injury Smooth muscle proliferation & matrix deposition inhibited Lipid profile via prostacyclin production & hepatic actions Reduced function in Males results in impaired vascular tone & coronary arterial calcification Associated with eNOS activation in endothelial cells Polymorphisms in ER identified with advanced cardiovascular disease in both men and women ER BP regulation Vasodilitation via NO production & NOS gene induction APS 2006 Refresher Course Remember the others. Thus far we have left out: Progesterone, Testosterone, their receptors 2 PR 1 AR, the aromatases, and dC/dt vs. C Figure from Mendelsohn and Karas (Science) APS 2006 Refresher Course Progesterone Declines in Women at menopause May partake in variability of vascular tone with menstrual cycle Lowers BP whereas synthetic progesterone elevates BP ? APS 2006 Refresher Course Testosterone Declines with age in Men & Women but more slowly than E2 Increases in E2-deficient Males Androgen replacement therapy (ART) Controversial Improves cardiac ischemic indices in Men W/o effect on peripheral vascular ischemia Lower HDL-C & Lipoprotein (a) Activates AR & ER (via aromatase conversion to E2) Aromatase AR inhibition disrupts regulation of VSM tone in Males Vasodilitation APS 2006 Refresher Course Solution Teach Physiology of what is known Desire to learn the basis for the differences Encourage use of differences to learn mechanisms Hallmarks of disease as means for sussing out pathways Question assumptions Think APS 2006 Refresher Course waterTissue Blood Basic Physiology: Starlings Law of Filtration in Males & Females APS 2006 Refresher Course Volume flow is determined by the balance of hydrostatic and osmotic pressures across a semipermeable membrane. Starlings Law of Filtration Text Book for Water: Tissue BloodPcap p Pint int P = Pcap - Pint = p - int Gradient Men & Women are in volume balance, except APS 2006 Refresher Course Geigy Scientific Tables Vol. 3, 1984 p. 140-141 “adults” Plasma Protein APS 2006 Refresher Course “Oncotic Pressure, ” Onsagers Law: = FnC male female Text Book for Water: APS 2006 Refresher Course Right Heart (Right Atrium) Left Heart (Left Ventricle) BP lower in women than men Pcap APS 2006 Refresher Course Males = Females? Pcap: FemalesMales : FemalesMales P P APS 2006 Refresher Course Pcap: FemalesMales Oncotic pressure: FemalesMales Pathophysiology: Hypertension P P APS 2006 Refresher Course Assume: Lp and S are the same in M & F in health and disease In fact: Capillary density (S) Hypertensive Males Females Pathophysiology: Hypertension P P P APS 2006 Refresher Course Males = Females? From the perspective of Basal Coronary Exchange Properties, Sure, the statistics say males = females. Albumin Female n=55 Male n=21 Female n=36 Male n=25 * 0 5 10 15 20 Ps x 10-7 cm s-1 -lactalbumin APS 2006 Refresher Course With respect to response, NO! APS 2006 Refresher Course APS 2006 Refresher Course Venules SED EX * * N=35 N=251.0 2.5 1.5 0.5 2.0 PSControl PSADO SED EX * * N=35 N=36 SED EX* N=7N=6 SED EX 1.0 2.5 1.5 0.5 2.0 * * N=7N=9 Arterioles * Response to Exercise Influenced by Sex APS 2006 Refresher Course How can “sex” influence one parameter, permeability response to a stimulus, and not another, basal permeability? APS 2006 Refresher Course -20 2000 6000 10000 14000 miles 2000 0 Rainfall, mm 2000 6000 10000 14000 miles Temp, C 0 20 40 2 Investigators traveling from A to B ND * APS 2006 Refresher Course London, UK Christchurch, NZ Tahiti, French Polynesia Monterrey, Mexico Memphis, USA Ottawa, Canada 2000 1000 0 2000 6000 10000 14000 Rainfall, mmTemp, C 2000 1000 2000 6000 10000 14000 0 Rainfall, mmTemp, C Moscow, Russia Bangkok Brisbane, Australia Christchurch, NZ APS 2006 Refresher Course Just as the direction of travel between London and Christchurch can matter, so too can males and females of the same species be in balance with respect to volume and solute exchange, but not by the same means. Consequences APS 2006 Refresher Course Why should Teachers of Physiology care? APS 2006 Refresher Course Signs of Heart Attack: 1. Chest discomfort or uncomfortable pressure, fullness, squeezing or pain in the center of the chest that lasts longer than a few minutes, or comes and goes. 2. Spreading pain to one or both arms, back, jaw, or stomach. 3. Cold sweats and nausea. APS 2006 Refresher Course But, Women often dont experience the “hallmarks” (only 30%), instead: shortness of breath, nausea, vomiting sleeplessness back pain