Chapter 1(2)
Conspectus of Disease
1.Concepts of health and disease
2.Etiology
3.Pathogenesis
1. Concepts of health and disease
(1)The definition of health from WHO: health indicates not
only without any evidence of disease, but also a state of
complete well-being physically, mentally and socially.
Biomedical model→Bio-psycho-social medical model
(2)Senescence:
(3)Sub-health/chronic fatigue syndrome (CFS): a situation, in
which the person does not show specific symptoms and signs of
disease, but lives a low-quality of life both physically and
mentally.
(4)Disease:
An abnormal life process which is induced
by disorders of homeostasis under the action
of certain causes and conditions.
A pathologic process with disturbances of
function, metabolism, and structure in the body,
which are manifested by a characteristic set
of signs and symptoms.
2. Etiology
Etiology studies the contributing factors that
cause diseases including causative,
predisposing, and precipitating factors.
(1)Etiological factors / Causes of diseases
(2)Conditions for / Precipitating factors of disease
(3) Predisposing factors of disease
(1)Etiological factors /Causes of diseases
①A etiological factor causes a disease and determines
its characteristics.
② Classification of etiological factors
•Biological factors
•Physical factors
•Chemical factors
•Nutritional factors
•Immunological factors
•Hereditary factors
•Congenital factors
•Social and psychological factors
Biological factors
Biological agents: microorganisms (such as bacteria,
virus, fungi, rickettsia, spirochete, etc.), parasites,
and their toxins and metabolic products.
Physical factors
Physical agents include mechanical injuries,
extremes of temperature, electricity and
radiation.
Chemical factors
Chemical agents: can damage cells by varies
pathways.
For instance, corrosive chemicals, such as strong
acids and alkalis, can destroy cells at the site of
contact.
Other chemicals are selective in their sites of
action, such as binding of carbon monoxide to
hemoglobin.
Nutritional imbalance
Either excesses or deficiencies of nutrients
predispose cells to injury.
For example, high lipids and carbohydrates diet
predispose a person to obese disease,
atherosclerosis and diabetes.
The most common nutritional deficiency is the lack
in certain constituents, such as vitamins, calcium,
and trace elements.
Immunological factors
Although the immune response is a normal
protective mechanism, it may cause diseases when
the response is
•inappropriately strong (allergy or
hypersensitivity)
misdirected (autoimmune disease)
deficient (immunodeficiency disease)
Genetic factors
Genetic aberrancies may be caused by single or
polygenic mutations. they are transmitted by
defective genes, such as sickle cell anemia, and
colorblindness.
•Gene mutation
•Chromosomal aberration
Congenital factors
The disorders result from abnormal embryonic
development, and most of them are nongenetic.
For example, congenital birth defects, mental or
physical, may be due to a developmental error
during pregnancy. The fetus is usually susceptible
to not only infectious diseases but also diet and
drug-taking of the mother during intrauterine life;
Social and psychological factors
Strong or persistent psychological stimulation or
stress may lead to mental illness and may be related to
some diseases, such as hypertension, peptic ulcer,
coronary heart disease, and depression.
(2) Conditions for disease
Precipitating factor: intensify the effects of
causative factors and promote the onset and development of
diseases, including natural, physical, and social conditions.
Risk factor
(3) Predisposing factors of disease
•A predisposing factor refers to the factor that
influences the susceptibility or resistance to
certain disease. It includes the genetic
constitution, physiological make up, as well as
various psychological characteristics.
•Genetic predisposition
Summary
•Specific causes and predisposing factors together
determines the disease occurrence; precipitating
factors influence the onset and development of illness.
•Some diseases only have one cause. However, many
diseases are multifactorial in origin, such as
hypertension, atherosclerosis and diabetes, etc
Environmental and genetic factors
3. Pathogenesis
The general rules and common mechanisms
underlying the development of diseases
(1) The basic mechanisms of disease
(2) General rules of disease development
(3)Outcome of disease
(1) The basic mechanisms of disease
Although various specific mechanisms may underlie different
disorders,they all generally involve the following four levels
of deregulations: neural, humoral, cellular and molecular
mechanisms.
Neural mechanism
•Neural system plays a central role in regulating
entire life activities; the disturbance occurred in
neural system and in periphery organs are mutually
affected.
•Encephalitis B virus can damage neural system
directly; some poisons may interrupt the metabolism
of neural cells and the production and release of
neurotransmitters.
Humoral mechanism (humoral factors, cytokines)
Humoral regulation is crucial in maintaining internal
homeostasis. Humoral dysfunction generally indicates the
alterations in number and in activities of some humoral
factors( hormones, chemical mediators, cytokines). They
function through endocrine, paracrine, and autocrine to
regulate the metabolism and activities of the cells .
During the development of diseases, the regulations
in humoral and neural system are usually simultaneous
e.g. disturbance of neural-humoral regulation in hypertension:
constant stress--- dysfunction of neural system (cerebral
cortex and hypothalamus)--- sympathetic-adrenal medulla
system----increased secretion of norepinephrine and
epinephrine--- constriction of arteries/ constriction of renal
afferent arterioles will activate rennin-angiotensinaldosterone system, and finally causes hypertension.
Cellular and molecular mechanism
Cellular and molecular damages or alterations are fundamental
in the development of disease.
Strong acid and alkali destroy the cells with no selection;
hepatitis virus damages specifically the hepatocytes.
•Disease genomics:
Disease proteomics
Integrated medicine,
Systems biology
整体水平
器官水平
细胞水平
分子水平
研究疾病
时功能代谢结
构的变化及其
发生机制
(2) General rules of disease
development
The general rules for a disease to take place and
develop
•Disruption of homeostasis by pathological
insults
•Body’s responses to damages and anti-damage
activities
•Reversal role of cause-consequence in the
disease process
•Relationship between systemic and local
alterations
Regulation and disruption of homeostasis
•Homeostasis: the process whereby the internal environment of
an organism tends to remain balanced and stable, which is
required for optimum functioning. e.g., maintenance of
temperature homeostasis.
•Disruption of homeostasis by harmful agents may cause
diseases. e.g., hyperthermia
Responses of damages and anti-damages
•Damages induce anti-damage responses, and the interactions
go through the whole process of diseases and determines the
development of diseases
•Overdo of anti-damages cause new injures
e.g. Burning injury (damage)-- constriction of small blood
vessels: maintaining proper blood pressure (anti-damage).
However, sustained vasoconstriction--hypoxia,
cellular necrosis, and dysfunction.
Alternation of cause and result in disease
process
•A cause of a disease leads to a result, which can be a
new cause for another results in the development of
the disease, even forming vicious cycle, e.g.
hemorrhagic shock.
机械力
创伤大失血
心输出量↓
交感-肾上腺系统兴奋
心率↑
血管收缩
细胞缺氧
心收缩力↑
良
性
循
环
微循环障碍
维持动脉血压
休克
恢复
死亡
大失血时的因果交替示意图
恶
性
循
环
Correlation between systemic and local
regulations
Local alterations and the systemic statues can affect each other
and disease development.
e.g., a severe furuncle will not only cause local
inflammation, but also lead to systemic reactions of fever and
elevated leukocytes.
On the other hand, a furuncle may be caused by diabetes
and could only be cured by proper control of diabetes.
(3) Outcome of disease
----complete recovery, incomplete recovery,
death
The outcome of a disease is determined by the fight
between the evil forces and the defending forces,
correct diagnosis and treatment.
Complete recovery
The best outcome of a disease:
•the etiological factors disappear
•the pathologically altered metabolism, structure and function
are perfectly restored
•the symptoms and signs of the disease disappear entirely
• homeostasis is recovered
Incomplete recovery
The main symptoms and signs disappear but some
pathological changes are left behind, namely sequela.
Sequela is generally brought about by the
compensatory response to maintain a relatively
normal activity.
For example, the permanent damage to the heart
valve after rheumatic fever.
Death
agonal stage
stage of clinical death
stage of biological death
Brain death
Brain death is a state of prolonged irreversible cessation
of all brain activity with the complete absence of
conscious and voluntary movements, responses to stimuli,
brain stem reflexes, and spontaneous respirations.
Criteria for brain death (WHO)
•Irreversible coma
cerebral unresponsibility
•Cessation of spontaneous respiration
•Absence of cephalic reflexes and dilated pupils
•Absence of electrical activity of brain
•Cessation of cerebral circulation
Precise diagnosis of brain death is important for having
proper donors in organic transplantation.
Brain death (脑死亡)
定义
自主呼吸
意识
脑干反射
恢复的可能性
全脑功能丧失
无
丧失
无
无
Vegetative state（植物状态）
脑的认知功能丧失
有
有睡眠—醒觉周期，但无意识
有
有
Summary
•Research (Molecular, genetic, comprehensive, multidiscipline)
•Purpose: mechanisms, prevention, diagnosis, and
treatment
•Disease spectrum changes