病理學(xué)與病理生理學(xué)：9Stress

1、Walter Cannon (1871-1945 ) 生理學(xué)家，美國生理學(xué)家，美國“homeostasis” “fight or flight response” Claude Bernard (1813-1878) 生理學(xué)家，法國生理學(xué)家，法國“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)內(nèi)分泌學(xué)家，加拿大內(nèi)分泌學(xué)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劉士豪劉士豪(19001974)內(nèi)分泌學(xué)家，中國內(nèi)分泌學(xué)家，中國 中華人民共和國建立后，任北京同仁醫(yī)院院長，中國協(xié)和醫(yī)學(xué)院生物化學(xué)系教授。1961年在協(xié)和醫(yī)院建立第一個內(nèi)分泌科，任內(nèi)分泌科主任；1965年，首次在中國建立胰島素放射免疫及醛固酮的測定方法。 他最重要的貢獻是對鈣磷代謝的研究。19341942年與內(nèi)分泌專家朱憲彝合作研究“骨軟化癥的鈣磷代謝”，發(fā)表13篇論文；對腎性骨營養(yǎng)

5、不良、纖維性胃炎、敗血癥的鈣磷代謝研究，發(fā)表論著17篇；3040年代證明了骨軟化癥的主要原因是維生素D缺乏；在國際上首次證實維生素D可通過母乳治愈嬰兒佝僂?。皇状芜\用雙氫速變固醇治療腎性骨營養(yǎng)不良癥，首創(chuàng)腎性骨營養(yǎng)不良的病名。并將醫(yī)學(xué)界一直爭論不休的并將醫(yī)學(xué)界一直爭論不休的stress一詞定義為一詞定義為“應(yīng)激應(yīng)激”。發(fā)表論文60余篇，著有生物化學(xué)與臨床醫(yī)學(xué)的聯(lián)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防御意義防御意義不利影響不利影響循環(huán)系統(tǒng)循環(huán)系統(tǒng)心輸出量增加心輸出量增加,血壓升高血壓升高,血流血流重分布重分布,心、腦、骨骼肌血供充心、腦、骨骼肌血供充分分心肌負(fù)荷加重，心律失常心肌負(fù)荷加重，心律失常,誘發(fā)誘發(fā)原發(fā)性高血壓原發(fā)性高血壓,外周小器官缺血外周小器官缺血缺氧加重缺氧加重物質(zhì)與物質(zhì)與能量代謝能量代謝促進糖原分解促進糖原分解,脂肪動員，保證脂肪動員，保證能量供應(yīng)能量供應(yīng)能量

10、過渡消耗，機體消瘦能量過渡消耗，機體消瘦呼吸系統(tǒng)呼吸系統(tǒng)支氣管擴張，通氣量增加支氣管擴張，通氣量增加,機體機體攝取氧增多攝取氧增多其它其它ACTH、生長激素、生長激素、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,紅細(xì)胞增加，紅細(xì)胞增加，易引起血栓；脂質(zhì)過氧化物生成易引起血栓；脂質(zhì)過氧化物生成增加，生物膜受損增加，生物膜受損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警覺期警覺期alarm stage抵抗期抵抗期resistance stage衰竭期衰竭期exhausti

13、on stage特點特點意義意義Acute phase response，APR （急性期反應(yīng)（急性期反應(yīng) ） 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（急性期反應(yīng)蛋白）（急性期反應(yīng)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 稱反應(yīng)時間(h)分子量正常參考值(mg/ml)可能功能血漿銅

20、藍蛋白48-721320000.20-0.60減少自由基產(chǎn)生補體成分C348-721800000.75-1.65趨化作用，肥大細(xì)胞脫顆粒1-酸性糖蛋白24410000.6-1.2為淋巴細(xì)胞與單核細(xì)胞的膜蛋白，促進成纖維細(xì)胞生長1-抗胰蛋白酶10540001.1-2.0抑制絲氨酸蛋白酶(特別是彈性蛋白酶)活性1-抗糜蛋白酶10680000.3-0.6抑制組織蛋白酶G結(jié)合珠蛋白24860000.5-2.0抑制組織蛋白酶B、H、L纖維蛋白原243400002.0-4.0促血液凝固及組織修復(fù)時纖維蛋白基質(zhì)的形成C-反應(yīng)蛋白6-101100000.068-8.0激活補體，調(diào)理作用，結(jié)合磷脂酰膽堿血清淀粉

21、樣蛋白A6-1018000010清除膽固醇?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反應(yīng)蛋白（CRP）臨床意義： 急性時相反應(yīng)的一個極靈敏的指標(biāo)，血漿中CRP濃度在急性心肌梗死，創(chuàng)傷，感染，炎癥，外科手術(shù)，腫癌浸潤時迅速顯著地增高，可達正常水平的2000倍，特別在炎癥過程中，隨訪風(fēng)濕病，系統(tǒng)性紅斑狼瘡，白血病等。升高：1. 急性炎癥或組織壞死，如嚴(yán)重創(chuàng)傷，手術(shù)，急性感染等：CRP常在幾小時內(nèi)急劇顯著升高，且在血沉增快之前即升高，恢復(fù)期CRP亦先于血沉之前恢復(fù)正常；手術(shù)者術(shù)后7-10天CRP濃度下降，否則提示感染或并發(fā)血栓等；2. 急性心肌梗死：2448h