《病理生理学》课件：08发热fever

1、发热Fever,周文华 Wenhua Zhou Ph.D School of Medicine,Ningbo University Contact: ,病案 Case,A 36-year-old man, One day prior to admission he was made worse by headache ,dizzy(头昏）,aching pain of muscle and joint(肌肉和关节酸痛） and fever. Check: T 39,100/min,R 20/min,Bp 100/70mmHg, congestion of throat（咽喉充血）, swell

2、ing of tonsil（扁桃体肿大）, respiratory rudeness, no bubbling sound,Lab findings:,WBC：13.3109/L,lymphocyte 16%, neutrophil 83%。 Treatment: He was given antibiotic（抗生素）. During transfusion, the patient suffer from chilly, shake, dysphoria and tempetature rose to 41.3, 120/min, R 24/min, Dexamethasone intra

3、venous injection,Questions,1.What pathogenic mechanism account for this patients fever? 2.Why the patient shown chilly , shake, dysphoria and tempreture rose more? 3.How to treat and give medical order of nursing?,正常体温Normal,Axillary temperature （腋温）3637 .0 C Sublingual temperature（舌下温度） 36.737.7 C

4、rectal temperature（肛温） 36.937.9 C,37,37,37,Set point,BT,normal,Pyrogen affected body,Fever happened,Fever：调定点set point,Definition,Fever is defined as a regulatory body temperature elevation response to the pyrogen, it is induced by an upward shift of the set-point in thermoregulatory center.,An elev

5、ation of body temperature is fever?,Physiologic elevation of body temperature,A pathologic elevation of body temperature is fever?,Heatstroke,Hyperthyroidism 甲状腺机能亢进,Central nervous system damage,hyperthermia 非调节性体温升高，过热,Temperature homeostasis,Central thermo- receptors,Peripheral thermo- receptors,

6、POAH,Effect organs,Heat production,Heat dissipation,36 ,40 ,下丘脑视前区,Physiologic temperature elevation,Pathologic temperature elevation,Temperature elevation,Fever,Hyperthermia,Classification,Hyperthermia is an unregulatory temperature rising,It is a passive process,There is no change of the set point

7、,Fever is a regulatory temperature rising,It is an active process,It is the bodys active reaction to pyrogen,Pathogenesis,Pyrogenic Activator发热激活物,Activator : the substance can activate the cells that can produce the pyrogen. pyrogen: the substance can cause fever Microbial agents: G+, G-, exotoxins

8、，TB, etc 病毒，真菌，螺旋体，疟原虫 Non-microbial agents: steroid, antigen-antibody complex, urate crystal，体内组织破坏， ect,Endogenous Pyrogens,白介素1（IL-1）: MC, fibroblast，etc， IL-1，IL-1 白介素6（IL-6）: T,B lymphocyte,tumor cell 肿瘤坏死因子（TNF）: TNF M TNF (lymphotoxin) active T 干扰素（INF）: T lymphocyte IL-8，MIP-1（巨噬细胞炎症蛋白）,Prod

9、ucing and releasing of EP,trigger NF-B,sCD14,LPS sCD14 complexes,T,T 细胞受体介导激活,IV of IL-1,TNF or IFN on fever,Thermoregulatory Center,Warm-sensitive neurons,Cold-sensitive neurons,Pathway of Pyrogenic Signal to The Thermoregulatory Center致热源如何进入体温调节中枢？,The blood-brain barrier（血脑屏障） Organum vasculosum

10、 laminae terminalis （终板血管器） Vagal afferent nerve fibers（迷走神经）,Hypertension: high blood pressure opens the BBB Development: the BBB is not fully formed at birth. Radiation: exposure to radiation can open the BBB. Infection: exposure to infectious agents can open the BBB. Trauma, Ischemia, Inflammatio

11、n, Pressure: injury to the brain can open the BBB.,The BBB can be broken down by:,Pathways of EP to the thermoregulation center,a. blood brain barrier,Activator,Activator,Activator,Activator,Cell of Producing EP,EP,blood brain barrier,SP,T,OVLT(organum vasculosum laminace terminalis） 终板血管器 MC capill

12、ary POAH EP neuron third ventricles of brain optic chiasma,Vagal afferent nerve fibers,The mechanism: increase of set point,a. Warm sensitive neuron: thermolysis b. Cold sensitive neuron: thermogenesis,Thermoregulation mechanism of fever,Thermoregulation center 1. The positive regulation preoptic an

13、terior hypothalamus, POAH 2. The negative regulation medial amygdaloid nucleus（杏仁核）,MAN ventral septal area（内侧隔核）,VSA,Regulatory Mediators,42,thermometer,Regulatory mediators调节介质,Positive regulatory mediators PGE,CRH,NO,CAMP,Na+/Ca2+ ect Negative regulatory mediators AVP,-MSH, lipocortin-I， IL-10 ec

14、t,Positive regulation mediators,1.PGE2: warm sensitive neuron cold sensitive neuron Effective medicine: Asprin,buprofen (Fenbid) 2.CRH(corticotrophin releasing hormone) EP (IL-1, IL-6 ) CRH media fever TNF, IL-1 PGE2 media fever,SP,3. cAMP : SP EP hypothalamus: Na+ /Ca2+ cAMP SP 4. Na+ /Ca2+ : 5. NO

15、: a. Activate metabolism Brown fat b. Inhibit Negative regulation mediators c. OVLT POAH T,PGE2的合成,花生四烯酸在环氧酶（COX）作用下合成前列腺素 在脂氧酶（LPO）作用下合成白三烯。,Observation relate to the appearance of number of PGE more or less simultaneously to the development of fever(量变同步） Injections of PGE evoke fever in various s

16、pecies of experimental animals（具有发热作用） Injections of inhibitor suppress fever（抑制剂抑制）,Negative regulation mediators,Negative feedback: Febrile ceiling: 42 endogenous cryogens AVP -MSH,T center,T,Heat production Heat conservation Heat loss,Set point,Pyrogen affected body,Heat production Heat conservat

17、ion Heat loss, Chemical reactions of metabolism Sketal muscle tone and contraction Chemical thermogenesis,Chills and shivering,Mechanism of fever,Period and metabolism of fever,The period of febrile: 1.the fervescence period 产热期 characteristic: thermogenesisthermolysis chill brown adipose tissue sca

18、pula ,large vessle of thoracic and cervical metabolic rate,Thermogenesis,Manifestation:,pale , gooseflesh, chill warm sensitive neuron (POAH) Chill center Chill cold sensitive neuron (POAH) cold stimuli Chill center Chill skin T,运动神经,Chill Rubro nucleus Lateral spinothalamic tract Rubrospinal tract

19、Reticulospinal tract anterior motor cells,Up,Down,2.the persistent febrile period高温持续期,The temperature reaches the new set point Thermogenesis = thermolysis : SP on higher level Manifestation: febrile , headache metabolic rate and pulse rate anorexia(厌食) 皮肤和口唇干燥,3.The defervescence period退热期, charac

20、teristic: Thermogenesis thermolysis SP is reset to the normal level Manifestation: the skin is warm and flush, sweat,fervescence persistent defervescence set point period period period 39 38 T 37 time,Alteration in Metabolism and Function,Carbohydrates Lipids proteins,Metabolism change of fever,1. G

21、lycometabolism Glycogenolysis Glycogen storage 2. Fat metabolism lipodieresis Fat storage Ketosis酮症 magersucht消瘦症 3. proteometabolism Protein catatabolism, negative nitrogen 4. watereletrolyte metabolismvitamin,Metabolism change of fever,metabolism T 1 metabolism rate 13% acute phase response WBC,Ph

22、ysiological changes:,1.CNS: headache , dizzy,drowsiness, febrile convulsion: 24h inheritance hypoxia discharge,convulsion,Physiological changes:,2.immunity system IL-1: activator of lymphocyte IL-6：differentiation factor IFN: humoral factor TNF: anti-tumor,Physiological changes:,3.Digestion system S

23、ympathetic digestive juice EP hypothalamus nauseated,vomit abdorminal distention constipation,Physiological changes:,4. circulation system HR 1 HR 18/min CO induce heart failure 5. Respiratory system,Benefits of Fever,Simply raising of body temperature kills many microorganisms and adversely affects

24、 their growth and replication Higher body temperatures decrease serum levels of iron, zinc, and copperminerals needed for bacterial replication Increased temperature causes lysosomal breakdown and autodestruction of cells, preventing viral replication in infected cells Heat increases lymphocytic tra

25、nsformation and motility of polymorphonuclear neutrophils, facilitating the immune response.,Principles of Treatment,Treatment of primary affections (原发病 ） General treatment to fever（一般处理） Antifebrile treatment（解热治疗，小儿，孕妇，心脏病患者） alcohol sponging, aspirin, corticosteroids,Case,A 36-year-old man, One

26、day prior to admission he was made worse by headach ,dizzy,aching pain and fever. Check: T 39,100/min,R 20/min,Bp 100/70mmHg, congestion of throat, swelling of tonsil, respitatory rudeness, no bubbling sound,Lab findings:,WBC：13.3109/L,lymphocyte 16%, neutrophil 83%。 Treatment: He was given antibiot

27、ic. During transfusion, the patient suffer from chilly, shake, dysphoria and tempreture rose to 41.3, 120/min, R 24/min, Dexamethasone intravenous injection,Questions,1.What pathogenic mechanism account for this patients fever? 2.Why the patient shown chilly , shake, dysphoria and tempreture rose more? 3.How to treat and give medical order of nursing?,Heat Production,Chemical reactions of metabolism Sketal muscle tone and contraction Chemical thermogenesis,Chills and shivering,Time course of typical fever,The BBB can be bro