1、Hypertension https:/en.wikipedia.org/wiki/Hypertension,Tu Huiyin Ph.D tuhuiyin,研究生与本科生的区别,The importance of stupidity in scientific research. Martin A. Schwartz (Journal of Cell Science 2008) Research made me feel stupid Research is a whole different thing Research is that it allows us to bumble (犯错
2、误) along, getting it wrong time after time,Preview,Blood pressure Hypertension Supplemental Information,. Blood pressure (BP),Blood pressure (BP) is the pressure exerted by circulating blood upon the walls of blood vessels. When used without further specification, “blood pressure“ usually refers to
3、the arterial pressure in the systemic circulation. It is one of the vital signs along with respiratory rate, heart rate, oxygen saturation, and body temperature. Unit to express blood pressure kilopascal, kPa, Millimeters mercury, mmHg 1mmHg=0.133kPa,Measurement of blood pressure,Directly method Ind
4、irectly method Blood pressure is measured by a quick, painless test using a sphygmomanometer. sfgmmnmt: It is usually measured at a persons upper arm.,New type blood pressure meter,Automatic brachial sphygmomanometer (臂式血压计)showing grade 2 arterial hypertension (systolic blood pressure 158 mmHg, dia
5、stolic blood pressure 99 mmHg). Heart rate shown is 80 beats per minute.,Normal blood pressure values,Systolic arterial pressure (收缩压): the peak pressure value reached during systole. (100-120 mmHg) Diastolic arterial pressure(舒张压): the minimum pressure value reached during diastole. (60-80 mmHg) Pu
6、lse pressure(脉压): the difference between the systolic and the diastolic pressures. Mean arterial pressure(平均动脉压): the mean of the pressure values during the entire cardiac cycle(心动周期).,Normal blood pressure values,Ageing cause an increase in BP Exerciserestingsleeping Anger, emotional stress, anxiet
7、y increase BP,The formation of arterial pressure,Blood filling in circulation system is the premise of blood pressure Influenced by vascular capacitance and circulating blood volume. Circulating volume or vasconstriction: MFP Circulating volume or vasodilation: MFP Mean Circulatory Filling Pressure
8、(平均充盈压) is the pressure of the entire vasculature in the absence of cardiac activity (6-7 mmHg).,The formation of arterial pressure,Ventricular ejection (心室射血) builds up energy. Kinetic: push blood flow Potential energy: exert pressure on the wall of vessel Peripheral resistance (外周阻力) Convert part
9、of kinetic energy into potential energy Elasticity of Arteries (windkessel) (大动脉弹性) The elastic recoil of the large arteries during diastole permits these vessels to maintain the pressure.,Factors Affecting Blood Pressure,Stroke volume (搏出量) SV is a measure of Cardiac Output (心输出量) SV SP , DP , PP S
10、VSP , DP , PP ,Factors Affecting Blood Pressure,Heart rate HR increase from 60 to 120 beats/min, both SP and DP HR decrease from 60 to 40 beats/min, both SP and DP,Factors Affecting Blood Pressure,Peripheral resistance RPDP, sP Viscocity, R , DP .,Factors Affecting Blood Pressure,The ratio of circul
11、ating volume to capacitance of circulation Circulating volume ( bleeding) or capacitance (vessel relax) Mean Circulatory Filling Pressure,Factors Affecting Blood Pressure,Elasticity of the vessel walls Compliance of aorta and large arteries. Compliance, the ability of buffering dramatic changes in p
12、ressure decreases , BP. Atherosclerosis,Regulation of systemic arterial pressure,Neural regulation Baroreflex (depressor reflex) Chemoreceptor reflex Cardiopulmonary receptor reflex Humoral regulation Epinephrine /norepinephrine (E, NE). Renin angiotesion - aldosteron System Autoregulation Long term
13、 and short term regulation of BP,Baroreflex (压力感受反射),Reflex arc,Baroreflex,Innervation of the heart Cardiac sympathetic nerve Cardiac vagus nerve,Autonomic nerve,Autonomic nerve,cAMP Chronotropic actionheart rate Inotropic action contractilty Dromotropic action-conduction,NE + 1-receptor,Ach + Musca
14、rinic cholinergic receptors,Innervation of blood vessel,Vasoconstrict fiber Sympathetic vasoconstrict fiber Vasodilator fibers Sympathetic vasodilator fibers Parasympathetic vasodilator fibers Vasodilator fibers in spinal dorsal root,Sympathetic vasoconstritor fibers,Preganglionic fiber,ACh,NE,NE,-r
15、eceptor,-receptor,Vasodilatation,Vasoconstriction,Affinity to to ,Postganglionic fiber,Parasympathetic vasodilator fibers,Preganglionic fibers,ACh,ACh,ACh+M receptor,Vasodilatation,Cadiovascular centers at different level,Spinal cord - final path, operational center Medulla - basic center, a source
16、of tonic activity for cardiovascular system. Higher center - sites of integration upon different kind of stimuli (internal to external environment changes) Hypothalamus Limbic system Cortex,Vasomotor center in medulla,Sensory area receives sensory inputs and then controls vasoconstrictor and vasodil
17、ator areas. Vasoconstrictor area (RVLM) neurons here secrete norepinephrine and excite vasoconstrictor neurons. Vasodilator area (CVLM) inhibits vasoconstrictor area. Cardiac inhibitor area are the central part of vagus nerve.,NTS: Nucleus Tractus Solitarius(孤束核); NA: Nucleus Ambiguus (迷走神经背核); RVLM
18、: Rostral Ventrolateral Medulla (延髓头端腹外侧); PA: Arterial Pressure，IML: intermediolateral cell column (中间外侧细胞柱).,Vasomotor center in medulla,Hypothalamus (下丘脑),Receives information from cerebrum above. Receives information from brain stem and spinal cord below Detects (monitors) composition of blood C
19、ontrols autonomic nervous system, controls HR, BP.,Input to the cardiovascular center,Sensors,The carotid sinus (颈动脉窦) Swellings in internal carotid artery wall. Glossopharyngeal nerve to cardiovascular center in medulla Maintains normal BP in the brain The aortic arch (主动脉弓) Receptors in wall of as
20、cending aorta. Vagus nerve to cardiovascular center. Maintains general systemic BP,Baroreflexes,Negative feedback to control BP,Bursts of activity with each pressure pulse,Barreflexes,Following an increase in BP, 4 events occur leading to a decrease in BP and return to control levels: 1. Bradycardia
21、 2. Reduced cardiac vigor 3. Vasodilatation 4. Venodilation,Set Point for Control of BP,Resetting of baroreflex,The set point of the baroreflex can be reset (重调定) by central or peripheral process: Central resetting: In exercise, the rise in BP that occurs does not cause a reduced CO or TPR because t
22、here has been a central influence to operate the baroreflex at a new higher level. Peripheral resetting: If the pressure has been increased or decreased for a long time, the set point is reset to this new pressure level. This allows the baroreflex to operate in its optimal range. For example: hypers
23、tension (高血压),Epinephrine /norepinephrine (E, NE). Renin-angiotesion-aldosteron System (RAAS). Vasopressin (AVP or ADH).,Endothelium derived vasodialator substance, NO. Endothelium derived vasoconstrict substance, ET. Atrial natriuretic peptide (ANP, 心房尿钠肽) or cardionatrin (心钠素).,Humoral regulation,
24、Epinephrine & Norepinephrine,Source: Adrenal gland Sympathetic terminals. Chemical structure: Catecholamine (儿茶酚胺类) Binding receptors: 1 , 2 1 , 2,Epinephrine,Increased heart rate and inotropy (1 ). Vasoconstriction in most systemic arteries and veins (1). Vasodilatation in muscle and liver vasculat
25、ures at low concentrations (2). The overall cardiovascular response to low-to-moderate circulating concentrations of epinephrine is increased cardiac output and a redistribution of the cardiac output to muscular and hepatic circulations with only a small change in mean arterial pressure . Vasoconstr
26、iction at high concentrations ( 1).,Epinephrine,Norepinephrine,Increased heart rate (although only transiently) and increased inotropy (1) are the direct effects of norepinephrine on the heart. Vasoconstriction occurs in most systemic arteries and veins (1) The overall cardiovascular response is inc
27、reased cardiac output and systemic vascular resistance, which results in an elevation in arterial blood pressure. Heart rate, although initially stimulated by norepinephrine, decreases due to activation of baroreceptor and vagal-mediated slowing of the heart rate.,Norepinephrine,Renin-angiotensin-al
28、dosterone System,Renin (肾素) Angiotensin (血管紧张素) Aldosterone (醛固酮),Functions of Angiotensin,Constricts resistance vessels, increase TPR. Constricts resistance vessels (via AngII receptors, AT1) thereby increasing systemic vascular resistance and arterial pressure. Facilitates norepinephrine release f
29、rom sympathetic nerve endings and inhibits norepinephrine re-uptake by nerve endings, thereby enhancing sympathetic adrenergic function. Binding to AT1 in RVLM (Vasoconstrictor area )-sympathetic vasoconstrict fiber,Functions of Angiotensin,Effective circulating volume (ECV) Acts upon the adrenal co
30、rtex to release aldosterone (醛固酮), which in turn acts upon the kidneys to increase H2O & Na+ reabsorption. Stimulates the release of vasopressin (antidiuretic hormone, ADH 抗利尿激素) from the posterior pituitary (垂体后叶) which acts upon the kidneys to increase fluid retention. Stimulates thirst centers wi
31、thin the brain.,Angiotensin II Actions at the Cellular Level,Ang II promotes cell proliferation in heart and blood vessels, stimulates cardiac hypertrophy (increase stroke volume) and vascular hypertrophy (increase TPR). These actions are associated with activation of p42 and p44 MAP kinases, Raf-1
32、kinase and c-fos. They are independent of Ca+ influx.,The action sites of Angiotensin II,In clinical practice, ACE inhibitors and AnglI receptor blockers are very important in treating hypertension and heart failure,Regulation of renin releasing,Nitric Oxide-NO,NO is produced from the amino acid L-a
33、rginine by endothelial nitric oxide synthase (eNOS). NO is a gas and diffuses into adjacent VSM where it activates soluble guanylate cyclase, (鸟苷酸环化酶)produces cGMP and causes vasodilatation.,Shear stress：搏动性血流对内皮产生的切应力刺激,Nitric oxide-NO,Vasodilation (ligand mediated and flow dependent). Inhibition o
34、f vasoconstrictor influences (e.g., inhibits angiotensin II and sympathetic vasoconstriction). Inhibition of platelet adhesion to the vascular endothelium (anti-thrombotic). Inhibition of leukocyte adhesion to vascular endothelium (anti-inflammatory). Antiproliferative (e.g., inhibits smooth muscle
35、hyperplasia following vascular injury). Scavenging superoxide anion (anti-inflammatory).,Autoregulation,Metabolic mechanism Decreased tissue pO2 Tissue Metabolites and Ions Adenosine CO2 , H+, K+ Lactic acid Inorganic phosphate Myogenic activity,Summary,Baroreflex buffers arterial blood pressure. Ep
36、inephrine cardiac output. Norepinephrine blood pressure Renin-angiontensin system Nitric oxide (NO),. Hypertension,Hypertension (HTN or HT), also known as high blood pressure or arterial hypertension, is a chronic medical condition in which the blood pressure in the arteries is persistently elevated
37、. Hypertension usually does not cause symptoms initially. Sustained hypertension is a major risk factor for heart disease, coronary artery disease, stroke, aortic aneurysm (主动脉瘤), peripheral artery disease, and chronic kidney disease.,Hypertension,Hypertension is classified as: Primary (essential) h
38、ypertension (9095%), defined as high blood pressure with no obvious underlying cause. Secondary hypertension (510%), defined as hypertension due to an identifiable cause. Chronic kidney disease, narrowing of the aorta or kidney arteries; Endocrine disorder such as excess aldosterone, cortisol, or ca
39、techolamines.,Hypertension,The treatment of moderately high arterial blood pressure (defined as 160/100 mmHg) with medications is associated with an improved life expectancy. Dietary and lifestyle changes can improve blood pressure control and decrease the risk of health complications. Treatment wit
40、h medication is still often necessary in people for whom lifestyle changes are not enough or not effective. The benefits of treatment of blood pressure that is between 140/90 mmHg and 160/100 mmHg are less clear.,Hypertension Contents,1 Signs and symptoms 1.1 Secondary hypertension 1.2 Hypertensive
41、crisis 1.3 Pregnancy 1.4 Children 2 Causes 2.1 Primary hypertension 2.2 Secondary hypertension 3 Pathophysiology 4 Diagnosis 4.1 Adults 4.2 Children 5 Prevention 6 Management 6.1 Target blood pressure 6.2 Lifestyle modifications 6.3 Medications 6.4 Resistant hypertension,7 Epidemiology 7.1 Adults 7.
42、2 Children 8 Outcomes 9 History 9.1 Measurement 9.2 Identification 9.3 Treatment 10 Society and culture 10.1 Awareness 10.2 Economics,1. Signs and symptoms,Hypertension is rarely accompanied by any symptoms, and its identification is usually through screening, or when seeking healthcare for an unrel
43、ated problem. Some with hypertension report headaches (头疼) (particularly at the back of the head and in the morning), lightheadedness(头晕), vertigo (眩晕), tinnitus (buzzing or hissing in the ears), altered vision or fainting episodes(晕厥). These symptoms, however, might be related to associated anxiety
44、 rather than the high blood pressure itself.,1. Signs and symptoms,On physical examination, hypertension may be associated with the presence of changes in the optic fundus (眼底) seen by ophthalmoscopy(检眼镜). The severity of the retinopathy (视网膜病变) correlates roughly with the duration and/or the severi
45、ty of the hypertension.,1.1. Secondary hypertension,Hypertension with certain specific additional signs and symptoms may suggest secondary hypertension, i.e. hypertension due to an identifiable cause. For example, Cushings syndrome frequently causes truncal obesity, glucose intolerance, moon face, a
46、 hump of fat behind the neck/shoulder, and purple abdominal stretch marks (妊娠纹). Hyperthyroidism (甲亢) frequently causes weight loss with increased appetite, fast heart rate, bulging eyes (眼睛凸出), and tremor.,Signs and symptoms,1.1. Secondary hypertension,Renal artery stenosis (RAS) may be associated
47、with a localized abdominal bruit to the left or right of the midline (unilateral RAS), or in both locations (bilateral RAS). Coarctation of the aorta(主动脉缩窄) frequently causes a decreased blood pressure in the lower extremities relative to the arms, and/or delayed or absent femoral arterial pulses. .
48、 Pheochromocytoma (嗜铬细胞瘤) may cause abrupt (“paroxysmal“) episodes of hypertension accompanied by headache, palpitations (心悸), pale appearance, and excessive sweating.,Signs and symptoms,1.2 Hypertensive crisis,Severely elevated blood pressure (equal to or greater than a systolic 180 or diastolic 11
49、0) is referred to as a hypertensive crisis(高血压危象). Hypertensive crisis is categorized as either hypertensive urgency (高血压急症) or hypertensive emergency, according to the presence or absence of end organ damage.,Signs and symptoms,1.2 Hypertensive crisis,In hypertensive urgency, there is no evidence of end organ damage resulting from the elevated blood pressure. In these cases, oral medications are used to lower the BP gradually over 24 to 48 hours.,In hypertensive emergency, t
