Pathophysiology
Chapter 1.
Introduction to Pathophysiology
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1.What is Pathophysiology
2.Why do we need Pathophysiology?
3.What will we learn in the classroom?
4.The position of Pathophysiology in
medical education
5.The research methods
6.Learn the ability of clinical thinking
1.What is Pathophysiology
Patho—physiology ?
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(1) Etiology病因学
(2)Pathogenesis发病学
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Functional change(dysfunction)
Metabolic change
Reasons of symptoms and signs
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(3)Basic principle of management
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2.Why do we need
Pathophysiology?
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Two cases
(1) A case of infantile diarrhea
(2) A case of breathing with difficulty
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学习园地的 humour
3.What will we learn in the
course of Pathophysiology
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(1)A general outline of disease(Chapter 2)
(2)Cellular and molecular pathophysiology
(Chapter 3-5)
(3)Basic pathological process (Chapter 6-14)
(4)Systemic pathological process (15-20)
4.The position of Pathophysiology
in medical education?
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As a bridge-science
(1) Explain the functional (effect of decreased myocardial
contraction on the body) and metabolic changes
(increased ATP consumption) in diseases with the
knowledge of Physiology, Biochemistry ....
( 2 ) Pathology (Pathological Anatomy) pays
attention to morphological changes in diseases.
with microscope. (myocarditis)
(3) Base of clinical courses
5.Research methods
(1)Duplicate the disease model in animals
(特色)
(2)Clinical survey
(3)Epidemiological Study (Framinghan Study)
(4) Cell culture, organ culture,
molecular biiology..….
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6. Learn the ability of clinical thinking
(finding, analyzing and resolving
abnormal manifestations)
Case discussion
Ask question
Climb a tree (a story)
Chapter 2.
Etiology and Pathogenesis
1.Some concepts
2.Etiology
3.Pathogenesis
4.Ending of disease
1.Some concepts
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(1) Health
(2)Sub-health
(3) Disease
(4)Pathological process
(5)Senescence 衰老
(1)Health≠no disease
According to the definition forwarded
by WHO, the health means the state of
complete well-being in body, mind and
society.
utopia
The health at least means no illness and
no mental problems.
(2) Sub-health
Chronic fatigue syndrome
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Intermediate state between disease
and health.
The sub-healthy state, referred to
a functional change without organic
pathological process, and also called a
third state or a gray state, without
positive finding in physical and
laboratory investigation.
(3)Disease
Disease is not dis(no) - ease.
The definition of disease:
① Disease is an abnormal life process caused
by certain reasons and conditions. There is no
disease without cause.
②There must be some functional , metabolic
and structural changes in the body with disease.
③The patients should have some symptoms
and signs.
④ Conforming the laws of the happening,
developmentand ending of the diseases.
Symptom is the subjective complaint which is
noted by patients, such as pain, (headache),
nausea, dizziness, and itching.
Sign is the objective manifestation that is
noted by doctors, nurses or other observers such
as high temperature (measured by thermometer),
cyanosis (purple skin), jaundice(yellow skin and
cornea).
Patients might tell lies.
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Fatigue
Loss of appetite
Someone may make a
show to deceive.
Syndrome
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Syndrome is a group of symptoms and
signs that occur together, which have close
internal relations.In many cases, syndrome is a
new disease in which the exact reason is
unknown at the beginning, for example:
SARS (severe acute respiratory syndrome).
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The SARS consists of
(1)low artery oxygen pressure (PaO2),
(2)dyspnea (shortness of respiration),
(3)symptoms and signs of hypoxia,
(4) cyanosis.
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The internal relation may be the
special kind of virus infection from
animals, but at first ,it is not clear.
WHO report:
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Health 5%
Sub-health 75%
Disease 20%
Dynamic transforming
(4) Pathological Process
The pathological process indicates a set of
functional, metabolic and structural disturbances ,
which occur in the diseases.
These functional, metabolic and structural
changes have close internal relations.
There is a set of functional (increased heart
rate), metabolic (cyanosis) and structural
changes (cellular edema) in hypoxia. Hypoxia is
a pathological process.
Hypoxia is not a disease.
Hypoxia can occur in pneumonia, bronchitis,
heart failure, anemia and some other diseases.
Pneumonia is a disease with hypoxia.
Bronchitis is a disease with hypoxia.
Almost all the names of chapters and sections
(hypoxia, fever, acidosis, alkalosis, etc.) are
pathological processes.
(5) Senescence 衰老
Aging老化
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是机体的正常生理功能随着年龄
的增长而缓慢减退的一个不可逆的过程.
是机体在退化时期功能下降和生理紊乱
的综合表现.
原因:自由基水平
染色体端粒长度
衰老相关基因
2.Etiology of Disease
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Etiology is the science to study
the causes of the diseases.
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(1) Etiological factors (causes of diseases)
(2) Conditions of disease development
(1) Etiological factors
Etiological factor is the cause which
determines the characters or nature of the
disease.
There are two kinds of etiological
factors:
1)extrinsic etiological factors,
2)intrinsic etiological factors.
1)Extrinsic etiological
factors:
Extrinsic etiological factors come from
outside of the body, such as:
(1)Infection of hepatitis virus leads to the
hepatitis. The hepatitis virus determines the nature
of disease (hepatitis). The hepatitis virus never leads
to pneumonia directly .
The hepatitis virus is the extrinsic etiological
factor of hepatitis.
(2)Infection of pneumococcus leads to
pneumonia.
2)Intrinsic etiological
factors
Intrinsic etiological factors
come from the inside of the
body,
for
example:
Mutation of LDLR gene
causes
familial
hypercholesterolemia.
Gene
mutations
determine the nature of
diseases, gene is within the
body, so gene mutation is the
intrinsic etiological factor.
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Atherosclerosis
of coronary artery is
the cause
(etiological factor) of
myocardial infarction.
(2) Conditions of disease
development
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有病因作用的前提下,影响发生发
展的因素, 条件本身不直接引起疾病.
1) Precipitating factors(诱因)
2) Predisposing factor(易感性）
3) Risk factors
1)Precipitating factors(诱因)
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A precipitating factor is
the condition which promotes
the development of disease in
short time through enhancing
the effect of etiological factors.
The sudden increase of vasoconstriction is the
precipitating factor to myocardial infarction.
Lean meat for patients with cirrhosis???
2) Predisposing factor(易感性）
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Predisposing factors are the conditions
which influence the susceptibility or
resistance of the body to certain disease.
The etiological factor of common cold is
influenza virus.
The cold weather reduces the person’s
resistance to influenza virus.
The cold weather is the predisposing
factor of common cold.
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Malnutrition:
for tuberculosis, ?
for edema ?
3) Risk factors
prospective study
The Framingham Heart Study (FHS)
was started in 1948 as a prospective
investigation of cardiovascular disease in a
cohort of adult men and women.
Continuous surveillance of this sample of
5209 subjects (1800 families) has been
maintained through biennial physical
examinations.
In 1971 examinations were begun on
the children of the FHS cohort(5124 offspring
and their spouses). This study, called the
Framingham Offspring Study (FOS), was
undertaken to expand upon knowledge of
cardiovascular disease, particularly in the area
of familial clustering of the disease and its risk
factors.
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Till 1960s, they found that persons
with
fat,
smoking,
hypoactivate,
hypercholesterolemia, diabetes, stress
are susceptible to CHD.
3. Pathogenesis 发病学
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（1） Fundamental mechanisms for
diseases
（2）General rules for the development
and ending of the diseases
(3) Stages of disease
（1）Fundamental
mechanisms for diseases
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1)
2)
3)
4)
Neural mechanism
Humoral mechanism
Cellular mechanism
Molecular mechanism
1)Neural
mechanism
increase of ECF
osmolality (1~2%)
hypovolemia
osmoreceptor
(anterior
volume receptor
in venae cavae
and atrium
hypothalamus)
elevated
angiotensin II
dryness of
mouth
thirst center (anterior hypothalamus)
sense of thirst and drink of water
decrease of ECF
osmolality
increase of
ECF volume
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decrease of
angiotensin
concentration II
no thirst
disappear of dryness
renal
blood flow
2) Humoral
mechanism
[Na+] in
macula densa
excitement of
sympathetic nerve
renin release from the
juxtaglomerular cells
increase of angiotensin II
releases
aldosterone secretion from
adrenal cortex
Na+ reaborption in
renal tubules
[K+], [Na+]
blood flow in plasma
K+ and H+ excretion
from kidneys
Neurohormoral regulation
(systemic level)
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The data showed the bus
drivers in London were susceptible to
hypertension.
3) Cellular mechanism
In hypoxia
4) Molecular mechanism
Familial lipoprotein lipase(LPL) deficiency is
caused by LPL gene mutation.
Disease proteomics (蛋白质组学)
（2）General rules for the
development and ending of the
diseases
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1 ) 自 稳 态 紊 乱 ( disturbance of
homeostasis)
2)因果转化（causality）
3)损伤和抗损伤反应(conflict of injury
and anti-injury )
4)局部和整体的关系(relation between
parts and entirety)
1)Disturbance of homeostasis
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各器官机能代谢活动在不断变化的内外环
境中保护动态平衡，表现为各种生理性指标控
制在一个狭隘的范围内波动为homeostasis.
如：T：36±0.5℃;
pH=7.35~7.45,
heart rate 60~100/min。
Disturbance：
Increased body fluid causes edema.
No sweat may lead to fever.
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1859年实验医学的鼻祖founder,法
国 Claude Bernard名言：“生命只所以
能生存，是因为不管外界如何变化，自
身总有一个稳定的内环境。”
2) 因果转化（causality）
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The primary cause leads to injury
(result), which as a cause leads to another
injury (result), then interchange of causes
and results continuously. That is the way
for both exacerbation and improement of
diseases.
Sometime it is vicious circle, or benign
circle.
To recognize the leading (key) link is very
important.
trauma
rupture of
blood vessel
hypovolemia
decreased
venous
return
tissue
hypoxia
acidosis
vasodilation
leading (key) link ????
3) Conflict of injury and
anti-injury
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Manifestations can be divided into:
（1）changes of injury
（2）changes of anti-injury.
相互依存，贯穿始终.
相互斗争，主要矛盾方面决定疾病发展方向.
有阶段性，如:
烧伤, 疼痛、失液、感染三阶段。
腹泻，开始为抗损伤，严重时为损伤。
4) Relation between parts and
entirety
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Any local manifestation should be
regarded as a part of systemic disease. A
focus of infection can cause the increased
WBC in blood and fever.
Patients with diabetes susceptible to
local infection.
(3)Stages of disease
For most of the diseases the
course of disease can be divided into
four stages.
1) Latent period
2) Prodromal stage
3) Period of manifest illness
4) Ending of disease
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1) Latent period
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This stage indicates the time after
exposure to the injurious agent (such as a child
has exposed to the measles virus) and before the
first appearance of signs and symptoms.
The latent period lasts several hours to
several days in cholera.
In AIDS the latent period is several months
to several years.
There is no latent period in some diseases.
Such as electric shock.
2) Prodromal stage
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There are some nonspecific signs
and symptoms during this stage, such
as :
38℃ of body temperature,
mild cough
mild headache.
3) Period of manifest illness
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In this stage the patients appear
all the specific and obvious signs and
symptoms, such as in children with
measles:
high temperature,
severe cough and
skin rash.
Measles can be diagnosed by
these signs and symptoms.
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Etiological factor
Sign and symptom
--------------------------------------------------------------------------Latent period
exposed
no
--------------------------------------------------------------------------Prodromal stage
nonspecific
--------------------------------------------------------------------------Period of manifest
specific
illness
obvious
---------------------------------------------------------------------------
4) Ending of disease
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There are three kinds of possibility
in the ending of diseases:
(a)complete recovery;
(b)incomplete recovery;
(c)death.
(a) Complete recovery
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The alterations of the function,
metabolism and structure of the body which
appeared in disease are perfectly restored.
All the signs and symptoms
disappear
entirely.
Common cold may have the outcome
of complete recovery. (most cannot)
(b)Incomplete recovery
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The main signs and symptoms are
disappeared after treatment, but some
pathological changes are still present in
the body.
A relatively normal life activity can be
maintained by mainly compensatory response.
Many patients have this kind of outcome.
Atherosclerotic lesions
in coronary artery reduce
the blood supply to the
heart of the patient with
CHD , the patient will
have chest pain.
Nitroglycerin can dilate the blood vessel (coronary
artery) and increase the blood supply, but the lesions
cannot disappear.
The outcome of patients with CHD can only have
incomplete recovery, and may have chest pain again
some time later.
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4. Death
(1) Traditional concept of death
(2) Modern concept of death (brain death)
(3) Difference between brain death and
persistent vegetative state
(1)Traditional concept of death
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Death is a process consisting of
①agonal stage;
②stage of clinical death;
③stage of biological death.
① Agonal stage
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Severe functional, metabolic and
structural disturbances:
lower temperature
weak heart beat
weak respiration
retardatory (delayed) nerve reflex.
Not all the death has the agonal stage,
death from electricity has no this stage.
②Stage of clinical death
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The standards of this stage are:
cessation of heart-beat ,
cessation of respiration,
disappear of nerve reflex.
If the patient gets effective treatment, the
heart-beat, respiration and nerve reflex can be
restored.
The stage of clinical death lasts 5~6 minutes,
that means the doctor has only 5-6 minutes of
time to save the life of patients.
③Stage of biological death
The death is irreversible 5~6 minutes
later after the stop of heart beat and
respiration. (something useful)
agonal stage
clinical death biological death
--------------------------------------------------------------------------heart-beat
weak
no, reversible
no
irreversible
respiration slow, shallow no, reversible
no
irreversible
nerve reflex retardation
no, reversible
no
irreversible
time
2~3 days
5~6 minutes
------------------------------------------------------------------------
New challenge
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(1)1983年4月10日参考消息：1983年1
月24日美国一25岁孕妇脑出血，第二天宣布
死亡。但用支持生命系统让她继续生理活动，
让胎儿继续活，至3月29日剖腹产取出1360
克婴儿，然后停机器，母亲便死了。
(2)1984年2月22日参考消息：在芝加哥
州一20岁青年阿伦。因车祸受伤，被宣布死
亡。待取肾脏移植时，他咳嗽了一声。
Modern view
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(1)认识的提高：生命意义在于机
体在神经体液调节下成为一个整体
（integrity）。机体内部各器官系统相互
协 调 ( coordination)； 与 外 界 环 境 适 应
（adaptation）。
仅有呼吸，只能说是肺在扩张和回缩
仅有心跳，只能说心脏在跳。
完整性主要靠脑（中枢神经系统）协调。
(2)Modern concept of death
Te most important for human life is the
integity of the brain function. If the cessation
of brain function is irreversible, the heart-beat
only does not make sense for the life.
The
electroencephalogram
(EEG) is useful to confirm
the cessation of the activity
of central nervous system.
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1)Concept of brain death
Brain death indicates that all the activity
(function) of whole brain (including the brain
stem) has irreversibly stopped.
2)Criteria of brain death
from WHO
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(A)Irreversible coma and cerebral
irresponsibility.
That means the complete lack of
cerebral response to any form of external
excitations.
(B) Cessation of spontaneous
respiration.
No spontaneous respiration after 15 minutes
of artificial respiration.
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(C)Absence of cephalic(brain stem)
reflexes:
(a) The pupillary reflex (The
pupils will shrink, if a strong light
shine.)
is absent. the both pupils are dilated
and fixed.
(b) The corneal reflex (There
will be a blink if touch the corneal with
cotton) is absent.
( D) Absence of
any electrical activity of
the
brain
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Linear EEG may
appear
even
when
stimulating the patient
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(E) Stopping of cerebral blood circulation.
(3) Difference between brain death
and persistent vegetative state
A person who is in persistent vegetative state is called
plant person. A plant person cannot speak and think by
himself or herself.( cerebral function is lost irreversibly)
A plant person has:
(a) autonomic respiration and heartbeat,
(b) normal body temperature( if the room temperature is
normal),
(c) normal digestion and absorption( if food is given by nasal
feeding).
So the plant person is not brain death, because the
function of brain stem is normal.
意义
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器官移植，有法可依，法律保护。
不进行无效抢救（2002年10月28日
济南时报文章：中国缺少脑死亡法，每年
安慰性、仪式性抢救花费数百亿元，
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Euthanasia 安乐死