教 案
首
页
授课时间 2008 年
课程名称
诊断学
年级
06 口本
专业、层次
临床医疗
授课方式
大班课
学时
1.5
教授
教员
孟红旗
专业技术职务
电话
授课题目（章、节）
发热
基本教材
1、 诊断学，第七版，北京：人民卫生出版社.
参考书目
3、 王鸿利主编，实验诊断学，第一版，北京：人民卫生出版社.
教学目的与要求
一、了解发热的概况。
二、掌握发热的机理、病因和分类。
三、掌握发热的临床表现及伴随症状。
四、掌握发热临床常见的几种热型和问诊要点。
大体内容与时间安排，教学方法
内容：1.体温的正常范围和发热的定义
2．发热的发生机制、病因分类
3．发热的分度和临床表现
4．常见热型：稽留热、弛张热、间歇热、波状热、回归热、不规则热的临床
意义
5.发热的伴随症状和问诊要点
教学时数：1.5 学时
教学方法：多媒体幻灯
教学重点、难点：
发热的机理、病因和分类
发热的临床表现及伴随症状
学员学习方法
大课授课
教
基
案
续
页
本 内 容
Fever
Definition
The core body temperature is kept constant (36.3-37.2o). Under
normal circumstances, it is tightly regulated, with circadian variations
over a range that usually does not exceed 1oC and a mean value of 37oC
(the normal “set point”). Fever is defined as an elevation of core body
temperature above the normal range. The rectal temperature is usually
辅助手段
时间分配
利用多媒体
幻灯授课
0.5oC greater than a simultaneous oral temperature, and more accurately
reflects the body’s core temperature. Axillary temperatures are repeatedly
0.50C below oral temperatures, but they have repeatedly been shown to
be unreliable. It is important to realize that fever is not equivalent to an
elevated core temperature but to an elevated set-point, for example, from
370C to 390C.
Hyperthermia is a term for fever due to a disturbance of thermal
regulatory control: excessive heat production(e.g., with vigorous exercise
or as a reaction to some anesthetics), decreased dissipation (e.g., with
dehydration), or loss of regulation (e.g., due to injury to the hypothalmic
regulatory center). It is characterized by an unchanged setting-point.
During episodes of fever, the thermoregulatory set-point is shifted
such that the same thermoregulatory mechanisms are used to maintain an
abnormally elevated temperature. Metabolic reactions proceed more
rapidly at an elevated temperature. Therefore, the passive warming effect
of a febrile state leads to accelerated energy production in the form of
heat: for each temperature increment of 0.6oC, the basal metabolic rate
increases by approximately 10%. This increase may at times be quite
significant from a nutritional point of view.
Pathophysiology
Core body temperature is determined by two opposing processes,
each of which is regulated by the central nervous system. On the one
hand, energy in the form of heat is generated by living tissues
(‘thermogenesis’). Energy may be passively absorbed from the
environment, chiefly through the emission of infrared radiation and
through transfer of energy to the surrounding medium. Regulation of
body temperature is under the control of the preoptic area of the anterior
hypothalamus. This area acts exactly like a thermostat, continuously
balancing heat production and heat loss. It is constantly receiving input
from both central receptors, which monitor the temperature of blood
perfusing the brain, and peripheral receptors, which monitor skin
temperature.
Heat production is controlled in several ways. The basal metabolic
rate is under the direct control of the hypothalamus, and can be varied
depending on demand for heat production. One way this is done is by
varying the level of circulating thyroxine, which increases cellular
metabolism. The fastest and most sensitive way to increase heat
production is by increasing muscle sensitivity (shivering when cold or
the shaking chill of a fever). The principle method of heat loss is by
varying the volume of blood flowing to the skin’s surface. Blood flow to
the fingertips can vary more than 100-fold over different environmental
temperatures. The exocrine sweating cools the body by vaporization
(conversion of a liquid to a vapor).
In febrile patient, because of an elevated set point, the processes of
heat conservation (vasoconstriction) and heat production (shivering and
increased metabolic activity) continue until the temperature of the blood
bathing the hypothalamic neurons matches the new thermostat setting.
Once that point is reached, the hypothalamus maintains the temperature
at the febrile level by the same mechanisms of heat balance that are
operative in the afebrile state. When the hypothalamic set point is again
reset downward (due to either a reduction in the concentration of
pyrogens or the use of antipyretic), the processes of heat loss through
vasodialtion and sweating are initiated. Loss of heat by sweating and
vasodilation continues until the blood temperature at the hypothalamic
level matches the lower setting.
Elevation of body temperature depends primarily on sympathetic
outflow and leads to shivering thermogenesis and dermal
vasoconstriction, whereas cooling mechanism (sweating and dermal
vasodilation) involve a mixture of sympathetic and parasympathetic
pathways.
Certain neutotropic drugs can disrupt the hypothalamic
thermosensory mechanism--- or blunt the hypothalamic response--- and
thus may interfere with the development of fever.
The hypothalamic thermostat has an inherent set-point of about
37oC. Temperatures are lowest around 4 a.m. and then gradually increase
until they peak between 6 and 10 p.m. The reason for this circadian
rhythm is unclear, but, unlike other circadian rhythms, such as cortisol
secretion, it is not reversed in shift workers who are up at night and sleep
during the day. Most fevers follow this pattern, being higher in the
evening and lower in the morning. Other physiologic parameters that
affect body temperature are exercise, the menstrual cycle, and the
environmental temperature. Strenuous exercise can significantly elevate
temperature. There is a rapid fall to normal, usually over 30 minutes after
cessation of activity. At ovulation there is a 0.5oC increase in temperature
that persists until just before the next menses.
Exogenous pyrogen
Hypothalamic dysregulation and fever are triggered by proteins
released from cells of the immune system and the nervous system. This
communication between the immune system and the nervous system is
perhaps is the most thoroughly studied ‘neuroimmunoendocrine’ link.
Any substances that cause fever are called pyrogens and may be either
exogenous or endogenous.
Exogenous pyrogens are from outside the host, whereas endogenous
pyrogens are produced by the host, generally in response to stimuli
usually triggered by infection or inflammation. The majority of
exogenous pyrogens are microorganisms, their products, or toxins. The
best characterized exogenous pyrogen is the heterogeneous group of
molecules common to all gram-negative bacteria referred to as endotoxin
(lipopolysaccaride. LPS). Gram-positive organisms also produce potent
exogenous pyrogens. These include lipoteichoic acid, peptidoglycan and
various exotoxins and enterotoxins.
Other exogenous pyrogens include complement products, steroid
horme metablites, antigen – antibody complex with complement. Most of
them are of high molecule weight, could not penetrate blood-brain
barrier, act directly at the central nerve system. In general, exogenous
pyrogens act primarily by inducing the formation of endogenous
pyrogens by stimulation of host’s cells, generally monocytes and
macrophages.
Endogenous pyrogen
In response to invasive stimuli, including components of various
microorganisms (e.g., lipoteichoic acid, lipopolysaccharids, and other
constituents collectively termed ‘exogenous pyrogen’) or certain
chemical agents (e.g.; amphotericin and perhaps other drugs), cells of
immune system (principally macrophages and, to a lesser extent,
lymphocytes) produce proteins that behave as “endogenous pyrogens’.
These proteins are designated ‘monokines’ and lymphokines’,
respectively, and are often denoted under the more general heading of
‘cytokines’.
The major pyrogenic cytokines appear to be IL-1β, IL-1α, tumor
necrosis factor α (TNF α ), tumor necrosis factor β (TNF β ,
lymphotoxin), interon α, and interleukin 6 (IL-6). During the past
decade, several of cytokines active in the pathogenesis of fever have
been isolated, and their structures have been determined by molecular
cloning. Although mononuclear phagocytes are the principal source of
pyrogentic cytokines, the same proteins may through autonomous
production and secretion.
Pyrogenic cytokines are presumed to bind receptors present on
vascular endothelial cells that lie within the hypothalamus. They act to
reset the hypothalamic thermoregulatory center by resenting increased
prostaglandin causes an elevated cyclic adenosine monophosphate level,
resulting an elevation in core body temperature.
Different antigenic stimuli result in the production of different
endogenous pyrogens. Bacteria and their products of metabolism
typically provoke release of IL-1; viral proteins stim t to that elicited by
endotoxin, it is probable that combined production of several cytokines is
sufficient to explain most fevers. ulate IFN. Although no single cytokine
is capable of provoking fever of a magnitude equivalen
Two types of pyrogen: exogenous pyrogen and endogenous pyrogen
1. Exogenous pyrogen: various microorganisms (such as endotoxin),
mostly are polysaccharides, can cause muscle contraction and rigor.
2. Endogenous:
polymorphonuclear myelocytes and monocytes,
activated by exogenous pyrogen, synthesize cytokines, which cause
liberation of PGE from hypothalamus. The PGE is believed to
reset the hypothalamic thermoregulatory center by prompting an
elevation in core body temperature.
Etiology and classification
1. Infective fever: After infection, metabolites from organism or
pyrogen from WBC cause fever. It is the most common cause of
fever. Bacteria pyrogen are the common causes of infective fever.
2. Non-infective fever:
1). Absorption of necrotic substances: injury; ischemic necrosis;
cell necrosis
2). Allergy
The penicillin-based antibiotics are the most
common cause.
3). Endocrine and metabolic disturbances: hyperthyroidism and
dehydration
4). Decreased elimination of heat from skin: heat failure
5). Dysfunction of central heat regulation:
a: Physical, as heat stroke;
b: chemical , as barbiturate poisoning;
c: Mechanical, as cerebral hemorrhage.
6). Dysfunction of vegetative nervous system; as the cases of
sympathetic overactivity.
Clinical manifestations:
1. The grade of fever
Low grade fever:
Moderate fever:
High fever:
Hyperthermia fever:
2.
37.3~38oC
38~39oC
39.1~41oC
over 41oC
The clinical course and character of fever
The clinical courses of fever are consisted of the following three
steps
1). Onset of fever
a:
Sudden onset:
fever rises within few hours, as
pneumonia, up to 39~40oC
b: Gradual onset: fever rises gradually for few days, as
typhoid
2). Persistence of fever: may be
a: continued:
The body temperature is constantly kept at
39oC~40oC for several days or several weeks. The circadian variation is
less 1oC. Such as pneumonia, typhoid fever
b: remittent
The body temperature is usually above 39oC,
with circadian variation great than 2oC. Such as rheumatic fever,
tuberculosis, septicaemia, septic inflammation
c: intermittent:
The temperature reaches the peak with sudden
arising, which lasts only about few hours, it subsides to the normal range
with lysis lasts for several days. As seen in malaria, acute pyelonephritis.
d: recurrent: The body temperature rises to peak (over 39oC)
abrubtly, lasting for several days, and than decreases to the normal with
suddenness. High fever and fever free interval interchangeable for
several times. Seen in Hodgkin’s disease.
e: undulant: The body temperature arise gradually over 39oC, it
goes down to the normal range gradually few days later, and this pattern
are repeated for several times. Seen in Brucellosis.
f: irregular type:
as seen in tuberculosis, rheumatic fever,
bronchopneumonia
Intermittent fevers are seen in many conditions and are therefore of
little help in discriminating between various disorders. Intermittent fever
may also occur when a continuous fever is interrupted with antipyretics
or cooling measures; such inventions must be taken into account in
analysis of a temperature curve.
3). Subsidence of fever: may be subside by crisis or lysis
Although fever patterns tend to be non-specific, they may
sometimes provide diagnostic clues. Such as the alternate-day fever in
established Plasmodium vivax infections, the sustained fever in
untreated Salmonella typhi infections and other continuous bacteremias,
and the relapsing (Pel-Ebstein) fever in Hodgkin’s disease and other
lymphomas.
Associated symptoms
1. Chills or rigor: as in septicemia and any acute infections
2. Congestion of conjunctiva: as in hemorrhagic fever
3. Herpes simplex: caused by herpes virus, frequently seen in cases of
lobar pneumonia
4. Bleeding tendency: in severe infection as hepatitis and blood
dyscrasia as leukemia
5. Lymphadenopathy: in cases of lymphoma, of metastasis of cancer
6. Enlargement of liver and spleen: in cases of hepatitis, leukemia
7. Arthralgia: in gout, rheumtic disease
8. Rash: drug rash, measles
9． Coma: in barbiturate poisoning, cerebral hemorrhage
Diagnostic points
Important points in the history include:
1. Other symptoms besides fever (eg, vomiting, dysuria, cough,
joing pain)
2. Duration and magnitude of fever
3. Close contacts with similar illness
4. Occupational, travel, or recreational exposure
5. History of diseases associated with immunocompromise,
diabetes, chronic renal failure, blood dyscrasia, alcohol or drug
abuse, chronic lung disease, and cardiac valve disease
6. Current medication, particularly antibiotics and antipyretics
7. Alleties.
Acute fever of less than two weeks are most of infectious origin,
with an inflammatory focus. Thus, either history or physical examination
would show some suggestive points about the cause of fever.
Fever of unexplained origin
It is defined in adults as an illness lasting more than 3 weeks with
temperatures greater than 38.30C in which a diagnosis ahs not been made
despite a good hospital or office evaluation. With careful further
evaluation a diagnosis can be made in 70% to 90% of the cases.
教
案
末 页
Summary
Fever: elevation of set point
小
Heat production/conservation: shivering dermal vasoconstriction
Heat loss:
Pyrogen:
sweating
exogenous or endogenous
endotoxin (LPS)
结
dermal vasodilation
pyrogenic cytokines
PGEs
Etiology:
cAMP
Set-point
infective or noninfective
Fever types: remittent fever, intermittent fever, undulant fever, recurrent
fever, irregular fever
复
习
思
考
题
及
作
业
题
1． 发热常见的病因有那些？
2． 什么是弛张热? 常见于哪些疾病?
3． 叙述发热的伴随症状对疾病诊断的意义。