fever病理生理 发热课件

Chapter 6 Fever,赵赫男 PhD,,本章主要内容,Summarization,1,Etiology and Pathogenesis,2,Alterations of Metabolism and Function,3,Pathophysiological Basis of Prevention and Treatment,4,Normal body temperature (BT),Body Temperature is kept constant in a very small range. The average normal BT is 37 C, core BT is maintained within a range of 36.2-37.8 C. The temperature varies depending on individual differences, time of day.,BT,Normal range of BT Routine measurements: oral, axillary, rectal settings Lethal temperature: 43C,Thermoregulation,Thermoregulatory center: 视前区下丘脑前部(Preoptic anterior hypothalamus, POAH) Thermostat Set point hypothesis 调定点(Set point, SP)是指体温调节的参考信号 。 SP is constant, but sometimes shifts.,Thermoregulation,Thermoregulation is the balance between heat gain and loss mechanisms under the control of hypothalamus,,Section one Summarization,一、Concept of Fever,Normal oral temperature of human :37， Variations of approximately 1 ,The elevation of BT,Question ?,The elevation of BT 0.5 C,Physiological,Pathological,Fever BT = Set point,Hyperthermia BT Set point,Stress,When exercise,menstruation,病理性,生理性,,Concept of Fever,?,?,?,,Hyperthermia,癫痫大发作，甲亢 某些全麻药,中暑，汗腺缺乏症,下丘脑损伤 出血，炎症,Heat-production,Heat-loss,Thermoregulatory center,被动性体温升高,Body T SP,,Section 2 Etiology and Pathogensis,Pyrogenic activators,EP cells,EPs,SP,Heat-production heat-loss,Core body T ,,一、Pyrogenic activators,Fever can be caused by a number of microorganisms and non-microbial pyretic substances that are collectively called pyrogenic activators, including exogenous pyrogens and non-microbial pyretic substances.,,Exogenous pyrogen,Generally speaking, exogenous pyrogens involve various kinds of infectious microorganisms,细菌(bacterium)：G+、G- 病毒(virus) 真菌(fungus) 螺旋体(spirochete) 疟原虫(plasmodium),,Staphylococcus,Streptococcus,Diphtheria bacilli,Pyrogenic components：whole cell，exotoxin,exotoxin,（1）G+,Bacterium,,（2）G-,E. coli,Neisseria gonorrhoeae,Pyrogenic components：LPS or endotoxin (ET),O-specific polysaccharide core polysaccharide Lipid A: main substance,Bacterium,,Exotoxin & Endotoxin,Kinds,exotoxin,endotoxin,Source:,G+,G-,present site:,Secretion or dissolved from bacteria,Cell wall or dissolved from bacteria,Chemical composition:,proteins,LPS,Stability:,Unstable、6080 30 min,stable、160 24 h,Toxicity:,heavy-toxicity,weak,antigenicity :,strong,weak,,Virus,Pyrogenic components：whole virus body,Influenza virus,SARS,severe acute respiratory syndrome,Measles virus,,Fungi,Pyrogenic components：whole body, Capsular polysaccharide and proteins,Oral Candida albicans,Candida albicans,,Spirochete,Pyrogenic components：metabolic components and edotoxin,Leptospira,Treponema pallidum,,Plasmodium,Pyrogenic components: merozoite and malarial pigment,Plasmodium vivax,merozoite,,Non-microbial pyretic substances,1、Antigen-antibody complexes 2、Steroid,,二. Endogenous Pyrogens（EP）,产EP的细胞在PA诱导物的作用下，产生和释放的能引起体温升高的物质。,Pyrogenic activators(PA),IL-1 TNF INF IL-6,EPs,lipocyte？ 脂肪细胞能分泌包括IL-1, TNF-在内的众多cytokine 肥胖患者体温较正常人高,,三、Mechanisms,Positive (+),Negative (-),视前区-下丘脑前部 (POAH),Cold sensitive neurons + -heat-production Heat sensitive neurons + -heat-loss,medial amygdaloid nucleus，MAN、ventral septal area，VSA、arcuate nucleus，ARC,Thermoregulatory Center (Central mediators of fever),,致热信号传入中枢的途径,通过下丘脑终板血管器 (via organum vasculosum laminae terminalis, OVLT),通过刺激迷走神经 (via stimulation of vagal nerve),经血脑屏障直接进入 (direct entry through blood-brain barrier),三、 Mechanisms,三、发热时的体温调节机制,(二) 致热信号传入中枢 (thermal afferent pathway) 1. 终板血管器的作用 2. 通过血脑屏障 3. 通过迷走神经,三、发热时的体温调节机制,(二) 致热信号传入中枢 (thermal afferent pathway) 1. 终板血管器的作用 2. 通过血脑屏障 3. 通过迷走神经,三、发热时的体温调节机制,(二) 致热信号传入中枢 (thermal afferent pathway) 1. 终板血管器的作用 2. 通过血脑屏障 3. 通过迷走神经,Vagus nerve,,The positive regulatory mediators,无论EP能否通过血脑屏障到达下丘脑，它们引起发热都有一个潜伏期，提示EP需要通过一定作用方式才能引起发热。,EP,SP ,？,三、Mechanisms,,PGE2 PGE2注入动物脑室引起发热，潜伏期比EP短 EP诱导发热期间，动物CSF中PGE水平升高 PGE合成抑制剂解热的同时也降低了CSF中PGE水平 Na/Ca2ratio 脑室内灌注Na升高体温， Ca2降低体温 EP先引起体温中枢内Na/Ca2比值升高，促使体温调定点上移 cAMP CRH NO,三、 Mechanisms,,热限的存在(upper limit),Fever时体温很少会超过41 C-42C，为什么？ 机体存在一个负反馈调节机制（Negative Feed-Back Mechanism), 阻止体温无限上升。,发热时，负调节中枢会释放出某些内源性降温物质，阻止体温调定点无限上升，这类物质被称为内生致冷原。（endogenous cryogen),三、 Mechanisms,,Endogenous cryogen,精氨酸加压素(Arginine Vasopressin, AVP)：视上核与室旁核合成，投射至下丘脑腹隔区的神经末梢释放。 -黑素细胞刺激素(-Melanocyte-Stimulating Hormone, -MSH)：室旁核分泌CRH a-MSH,,发热激活物,单核细胞,EP,下丘脑,Set points be elevated,Na+/Ca2+ ,cAMP ,PGE2 ,皮肤血管收缩,骨骼肌紧张、寒战,散热,产热,体温上升,AVP -MSH,三、Mechanisms,,Stages of Fever (发热的时相),三、Mechanisms,,体温上升期,症状：发冷恶寒、鸡皮、寒战和皮肤苍白 关系：体温调定点上移，中心温度散热，体温上升 (Cold response ),The fervescence stage (体温上升期),Blue：调节点动态曲线；Red：体温曲线,,高峰期,症状：皮肤发红、干燥，自觉酷热 关系：中心体温与上升的调定点水平相适应 特点：heat production balances the heat loss to maintain the temperature at the elevated level.,The persistence febrile stage (高峰期),Blue：调节点动态曲线；Red：体温曲线,,退热期,症状：Skin is warm and flushed, steating occurs. 关系：体温调定点回降，中心温度调定点 特点：散热产热，体温下降 (Heat-response ),The defervescence stage (退热期),Blue：调节点动态曲线；Red：体温曲线,,Section 3 Alterations of metabolism and function,一、Metabolism,The basal metabolic rate increase 13% while 1 elevation in body temperature. Glucose and glycogen are catabolized to produce energy Adipose tissue utilization increases Endogenous protein is catabolized Vitamins Metabolism , VitB and C Dehydration and electrolyte disturbance 高热持续期: 皮肤、呼吸道水分蒸发。 体温下降期: 尿量恢复、大量出汗。,,二、Alterations of Physical Functions,（一）Central nervous system Fever can increase the excitability of the central nervous system. Irritability, delirium, headache, hallucinatious may occur when the temperature reaches 40-41. Febrile convulsions can occur in some children.,,（二）Cardiovascular system,During fever, every 1 rise in temperature leads to a 18 b/min. HB150 b/min，CO Heart rate，contractily ， cardiac load During the fervescence stage, the blood pressure may slightly increase because of peripheral vasoconstriction and high CO. During the febrile persistent stage and the defervescence stage, the BP may slightly decrease because of water loss and peripheral vasodilation,,（三）Respiratory system The elevation of blood temperature leads to hyperventilation, which is beneficial to increase the oxyge supply for the body tissue. Meanwhile, an increase in respiratory rates can increase the heat loss through the respiratory airways. （四）Digestive system The function of the digestive system is often suppressed. Anorexia, abdominal distension, constipation.,,三、Self-defense,Elevation of body temperature kill many microorganisms Heat increases lymphocyte transformation and motility of polymorphocyte neutrophils Higher body temperature decrease serum levels of ions, zinc and cooper, all which are needed for bacterial replication.,（一）Anti-infection capacity,,（二）Anti-turmor activity,Tumor