Fever发热

Fever,Fever,Normal body temperature:37oC (set point，体温调定点)Circadian variation oral T 0. 5oC axillary T（腋温）,Fever,Pyrogens 致热原,Maintaining an abnormally elevated Temperature,BMR(basal metabolic rate) increases,T = Elevated set-point,BMR 10% = T 0.6oC,Hyperthermia (过热）,fever due to a disturbance of thermal regulatory control excessive heat production (e.g. vigorous exercise, a reaction to some anesthetics) decreased dissipation (e.g. dehydration) loss of regulation (injury to the hypothalamic(下丘脑的) regulatory center),Hyperthermia,Pathophysiology,Body temperature is determined by two opposing processes heat production heat loss They are regulated by the central nervous system Energy in the form of heat is generated by living tissues (thermogenesis 生热作用) Energy may be passively absorbed from the environment and transfer the energy to the surrounding medium,Heat production,Increased BMR, by varying the level of circulating thyroxine （甲状腺素) ( controlled by hypothalamus 下丘脑) Increased muscle sensitivity (shivering),Heat loss,By varying the volume of blood flowing to skins surface (100 fold)By vaporization (exocrine sweating),Pathophysiology,The body temperature is under control of thepreoptic area of the anterior hypothalamus（视前区下丘脑前部）Thermostat （恒温器）It receives input from both central receptors and peripheral receptors,Pathophysiology,Elevation of body Temperature shivering thermogenesis and dermal vasoconstriction sympathetic (交感神经）outflow Cooling mechanismsweating and dermal vasodilationmixture of sympathetic and parasympathetic pathways,370C,390C,Heat Production,Heat Loss,Heat Production,Heat Loss,ShiveringMetabolic activity,vasoconstriction,SweatingVasodilation,Set -point,cooling,elevating,Pathophysiology,Hypothalamic thermostat Inherent Set Point: 37oC lowest: 4 a.m; peak: 610 p.mFever follow this patternFactors affect body Temperature exercise menstrual cycle environmental temperature,Pathogenesis of fever,Pyrogens (致热原） Substances that can cause fever Either exogenous or endogenous 外源性致热原 内源性致热原,Exogenous Pyrogens,From outside the host (some may be the endogenous products)Most of them are with high molecule weightCould not penetrate blood-brain barrierStimulating monocytes and macrophages to induce the formation of endogenous pyrogen,Exogenous Pyrogens,Majority are microorganism, their products or toxinsGram-: endotoxin 内毒素 (lipopolysaccaride 脂多糖, LPS)Gram+: lipoteichoic acid （脂磷壁酸） peptidoglycan（肽聚糖） exotoxins(外毒素)and enterotoxins(肠毒素）,Exogenous Pyrogens,Others complement products steroid hormone metabolites antigen-antibody complex with complement,Endogenous Pyrogen,In response to invasive stimuli: exogenous pyrogen chemical agents (amphotericin and other drug) 两性霉素BProduced by cells of immune system of the host (macrophages, lymphocytes)Proteins designated monokines and lymphokines cytokines （细胞因子）,Endogenous Pyrogen,CytokinesIL-1 IL-1 TNFTNF IFN IL-6Phagocytes and lymphocytes: major source of pyrogenic cytokinesIt may also released through autonomous production and secretion,Pathogenesis of fever,Bacteria provoke release of IL-1 Viral proteins stimulate IFNCombined production of several cytokines cause fever,Pathogenesis of fever,Pyrogenic cytokines bind receptors present on vascular endothelial cells that lie within the hypothalamusResetting the hypothalamic thermoregulatory center by increased prostaglandin (PGE, 前列腺素) and cAMP,Production of endogenous pyrogens,促肾上腺皮质激素,促皮质激素释放因子,Set point,hypothalamus,Heat loss,Heat production,ExP,Etiology and classification,Infective feverNon-infective fever,Infective fever,Metabolites from organism cause feverMost common causes of fever (50%60%) Bacteria pyrogens: common cause of infective fever (43%) Viral pyrogens: (6%),Non-infective fever,Absorption of necrotic substances: injury ischemic necrosis cell necrosis 缺血性坏死Allergy antibiotics (penicillin-based)Endocrine and metabolic disturbances: hyperthyroidism（甲亢） dehydration（脱水）Decreased elimination of heat from skin: heat failure,Non-infective fever,Dysfunction of central heat regulation physical: heat stroke 中暑 chemical: barbiturate poisoning 巴比妥酸盐中毒 mechanical: cerebral hemorrhage 脑出血Dysfunction of vegetative nervous system sympathetic overactivity 交感功能亢进,Clinical manifestation,The grade of fever Low grade fever: 37.338oC Moderate fever: 3839oC High fever: 39.141oC Hyperthermia fever: 41oC,Clinical manifestation,Clinical course of fever Onset: Sudden onset within few hours pneumonia 肺炎 Gradual onset gradually for few days typhoid 伤寒 Persistence: varies pattern Subsidence: by crisis or lysis,Character of fever,Continued （稽留热）T: kept at 39oC40oC constantlyCircadian variation: 39oC circadian variation 2oC rheumatic fever风湿热 tuberculosis 结核 septicaemia 败血症 septic inflammation脓毒血症,Character of fever,Intermittent （间歇热）T: sudden rising (few hours) and sudden decreasing malaria 疟疾 acute pyelonephritis 急性肾盂肾炎Recurrent （回归热）T: abruptly rising to the peak, lasting for several day, sudden decrease to the normal repeatedly Hodgkin disease 何杰金病,Character of fever,Undulant （波浪热）T: rising gradually to the peak (39oC) decreasing gradually to the normal repeatedly for several timesBrucellosis （布鲁氏杆菌病）Irregular （不规则热）tuberculosis rheumatic fever brochopneumonia,Fever pattern as diagnostic clues,Fever Pattern CauseAlternate-day fever Plasmodium vivax, P. Ovale fever every third day P. Malariae (间日疟原虫）Relapsing fever daily for 36 days Borrelia sp (包柔螺旋体菌), fever-free interval rat bite fever for about 1 weekContinuous “undulating” Brucellosis, typhoidPeriodic pyrexia Hodgkins disease (Pel-Ebstein Phenomenon) with variable cycles,Associated symptoms,Chills or rigor: septicemia acute infections 畏寒或寒战Congestion of conjunctiva: hemorrhage fever 结膜充血Herpes simplex: herpes virus (lobar pneumonia) 单纯疱疹Bleeding tendency: in severe infection (hepatitis) 出血倾向 blood dyscrasia (leukemia),Associated symptoms,Lymphadenopathy: lymphoma cancer metastasis 淋巴结病Enlargement of liver and spleen: hepatitis 肝脾肿大Rash: drug rash measles (麻疹） 皮疹Arthralgia: gout rheumatic disease 关节痛Coma: barbiturate posioning cerebral hemorrhage 昏迷,Diagnostic points,Other symptoms besides feverDuration and magnitude of feverClose contacts with similar illnessOccupational, travel, recreational exposureHistory of diseases associated with other organ(diabetes 糖尿病 chronic renal failure)Current medication (