病理学与病理生理学：9Stress

1、Walter Cannon (1871-1945 ) 生理学家，美国生理学家，美国“homeostasis” “fight or flight response” Claude Bernard (1813-1878) 生理学家，法国生理学家，法国“milieu intrieur” Walter Cannon- Harvard Medical SchooluFirst to describe the effects of acute stressuTermed this stress reaction as the fight-or-flight response.uA primitive re

2、sponse that quickly increases heart rate, respiration, blood pressure, and serum cholesterol.Hans Selye(19071982)内分泌学家，加拿大内分泌学家，加拿大“general adaptation syndrome”“stress”Publications1. A Syndrome Produced by Diverse Nocuous Agents - 1936 article by Hans Selye from The journal of neuropsychiatry and cl

3、inical neurosciences2. He was a nominee to the Nobel prize for the first time in 19493. The stress of life. New York: McGraw-Hill, 19564. Selye, H. Stress and disease. Science 1955, 122: 625631. 5. From dream to discovery: On being a scientist. New York: McGraw-Hill 19646. Hormones and resistance. B

4、erlin; New York: Springer-Verlag, 19717. Stress without distress. Philadelphia: J. B. Lippincott Co., c1974刘士豪刘士豪(19001974)内分泌学家，中国内分泌学家，中国 中华人民共和国建立后，任北京同仁医院院长，中国协和医学院生物化学系教授。1961年在协和医院建立第一个内分泌科，任内分泌科主任；1965年，首次在中国建立胰岛素放射免疫及醛固酮的测定方法。 他最重要的贡献是对钙磷代谢的研究。19341942年与内分泌专家朱宪彝合作研究“骨软化症的钙磷代谢”，发表13篇论文；对肾性骨营养

5、不良、纤维性胃炎、败血症的钙磷代谢研究，发表论著17篇；3040年代证明了骨软化症的主要原因是维生素D缺乏；在国际上首次证实维生素D可通过母乳治愈婴儿佝偻病；首次运用双氢速变固醇治疗肾性骨营养不良症，首创肾性骨营养不良的病名。并将医学界一直争论不休的并将医学界一直争论不休的stress一词定义为一词定义为“应激应激”。发表论文60余篇，著有生物化学与临床医学的联系。greatly enlarged adrenal glandsovarian extract peptic ulcerssaline solution n The body has a set of similar response

6、s to a broad array of stressors. n Under certain conditions, the stressors will make you sick shrunken immune tissues on the roof of the research buildingin the boiler roomwere forced to exerciseunderwent surgical proceduresLoss of bloodinfectious diseaseadvanced cancerfacial expression betrays that

7、 he is ill It is generally agreed by the scientific community that ：n Stress is not what happens to someone. n Stress is how a person reacts to stressors. the conditioning of the person being stressedthe properties of the stressorMild, brief, and controllable periods of stress could be perceived as

8、positive stimuli to emotional and intellectual growth and development.Severe, protracted, and uncontrolled situations of psychological and physical distress are disruptive of health. + Gluconeogenesis+ Lipolysis+ Proteolysis+ Insulin Resistance- Inflammation+ Blood Pressure+ Heart Rate+ Blood Sugar-

9、 GI Blood Flow + Anxiety+/- Psychomotor symptoms - Slow wave sleep - Appetite - Libido + LC + Pyramidal cell防御意义防御意义不利影响不利影响循环系统循环系统心输出量增加心输出量增加,血压升高血压升高,血流血流重分布重分布,心、脑、骨骼肌血供充心、脑、骨骼肌血供充分分心肌负荷加重，心律失常心肌负荷加重，心律失常,诱发诱发原发性高血压原发性高血压,外周小器官缺血外周小器官缺血缺氧加重缺氧加重物质与物质与能量代谢能量代谢促进糖原分解促进糖原分解,脂肪动员，保证脂肪动员，保证能量供应能量供应能量

10、过渡消耗，机体消瘦能量过渡消耗，机体消瘦呼吸系统呼吸系统支气管扩张，通气量增加支气管扩张，通气量增加,机体机体摄取氧增多摄取氧增多其它其它ACTH、生长激素、生长激素、EPO、胰、胰高血糖素等分泌增加高血糖素等分泌增加促使血小板增多促使血小板增多,红细胞增加，红细胞增加，易引起血栓；脂质过氧化物生成易引起血栓；脂质过氧化物生成增加，生物膜受损增加，生物膜受损because the effect is a generalsystemic reaction. because the response is in reaction to a stressor. because the physica

11、l manifestations are coordinated and dependent on each other.Alarm Reaction Person perceives stressor, defense mechanisms activated Fight-or-flight response Hormone levels rise, body prepares to react Shock and counter-shock phases (1 min - 24 hrs)Resistance Body attempts to adapt to stressor. Vital

12、 signs, hormone levels, and energy production return to normal. Body regains homeostasis or adaptive mechanisms fail.Exhaustion Results when adaptive mechanisms are exhausted Body either rests and mobilizes its defenses to return to normal or dies警觉期警觉期alarm stage抵抗期抵抗期resistance stage衰竭期衰竭期exhausti

13、on stage特点特点意义意义Acute phase response，APR （急性期反应（急性期反应 ） The acute phase response is a quickly mobilized, non-specific defensive response elicited in response of the host to infection, tissue injury or inflammation, etc. APP have been defined as one whose plasma concentration increases (positive acut

14、e phase proteins) or decreases (negative acute phase proteins) during the acute phase responses. Acute phase proteins, APP（急性期反应蛋白）（急性期反应蛋白） uThe discovery of large amounts of C-reactive protein (CRP) in the serum of patients during the acute phase of pneumococcal pneumonia in 1930 focused interest

15、on the plasma protein changes that accompany inflammatory states. uCRP and other plasma proteins whose concentrations rose significantly under such circumstances were accordingly referred to as acute-phase proteins (APP). uThe subsequent realization that concentrations of some other plasma proteins

16、decrease led to their designation as negative APPs, while the earlier recognized APPs are often referred to as positive APPsuA change of approximately 25% in plasma concentration has been suggested as the definition of an APP (Morley and Kushner, 1982).uChanges in plasma protein concentrations large

17、ly result from alterations in synthesis by hepatocytes in response to circulating inflammation-associated cytokines. uWhile other cells, including macrophages, fibroblasts, epithelial cells and adipocytes can also produce APPs, it is unlikely that synthesis at these sites contributes significantly t

18、o plasma concentrations.uIn humans, many different stimuli can induce the acute phase response, including bacterial (and to a lesser extent viral) infection, trauma, surgical procedures, burn injury, tissue infarction, various immunologically and crystal-mediated inflammatory disorders, advanced mal

19、ignancies, strenuous exercises, childbirth and heatstroke.ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / l Inhibition of protease activationreduce tissue injury l Remove foreign bodies and necrotic tissue l Inhibit free radical productionl Others名 称反应时间(h)分子量正常参考值(mg/ml)可能功能血浆铜

20、蓝蛋白48-721320000.20-0.60减少自由基产生补体成分C348-721800000.75-1.65趋化作用，肥大细胞脱颗粒1-酸性糖蛋白24410000.6-1.2为淋巴细胞与单核细胞的膜蛋白，促进成纤维细胞生长1-抗胰蛋白酶10540001.1-2.0抑制丝氨酸蛋白酶(特别是弹性蛋白酶)活性1-抗糜蛋白酶10680000.3-0.6抑制组织蛋白酶G结合珠蛋白24860000.5-2.0抑制组织蛋白酶B、H、L纤维蛋白原243400002.0-4.0促血液凝固及组织修复时纤维蛋白基质的形成C-反应蛋白6-101100000.068-8.0激活补体，调理作用，结合磷脂酰胆碱血清淀粉

21、样蛋白A6-1018000010清除胆固醇?C-reactive protein (CRP) u CRP was so named because it was first identified as a substance in the serum of patients with acute inflammation that reacted with the C-polysaccharide of Pneumococcus.u Discovered by Tillett and Francis in 1930, it was initially thought that CRP migh

22、t be a pathogenic secretion as it was elevated in people with a variety of illnesses including cancer. The later discovery of hepatic synthesis demonstrated that it is a native protein.u The physiological role of CRP is to bind to phosphocholine expressed on the surface of dead or dying cells (and s

23、ome types of bacteria) in order to activate the complement system. CRP binds to phosphocholine on microbes and damaged cells and enhances phagocytosis by macrophages. Thus, CRP participates in the clearance of necrotic and apoptotic cells.u An elevated CRP level does not diagnose a specific disease.

24、 An elevated CRP level can provide support for the presence of an inflammatory diseaseThe CRP gene is located on the first chromosome (1q21-q23). CRP is a 224-residue protein with a monomer molecular mass of 25106 Da. The protein is an annular pentameric disc in shape and a member of the small pentraxins family.C反应蛋白（CRP）临床意义： 急性时相反应的一个极灵敏的指标，血浆中CRP浓度在急性心肌梗死，创伤，感染，炎症，外科手术，肿癌浸润时迅速显著地增高，可达正常水平的2000倍，特别在炎症过程中，随访风湿病，系统性红斑狼疮，白血病等。升高：1. 急性炎症或组织坏死，如严重创伤，手术，急性感染等：CRP常在几小时内急剧显著升高，且在血沉增快之前即升高，恢复期CRP亦先于血沉之前恢复正常；手术者术后7-10天CRP浓度下降，否则提示感染或并发血栓等；2. 急性心肌梗死：2448h