Pathophysiology Department of Pathophysiology Shanghai Jiao-Tong University School of Medicine

General Introduction of Pathophysiology CHAPTER 1 General Introduction of Pathophysiology •Main teaching content and Syllabus •Why do we study pathophysiology ？ •What is pathophysiology?

What is pathophysiology? Pathophysiology may be defined as the physiology of disease, of disordered function, or derangement of function seen in disease that is produced by the action of an etiologic agents on susceptible tissues or organs. Pathophysiology includes also the study of the mechanisms underlying disease. ■ Concept of Pathophysiology

Why do we study pathophysiology？ Pathophysiology is an important subject bridging Basic sciences and clinical medicine. ■Position bridge subject basic sciences clinical medicine pathophysiology

Main teaching content and Syllabus ●Conspectus of disease The general concept of diseases and general etiology and pathogenesis of diseases. ●Fundamental pathological process Common changes of function, metabolism and structure occurred in the different diseases, e.g. ● Systemic pathophysiology Heart failure, respiratory failure, hepatic failure, renal failure, e.g.

Format Time Teaching content ■Syllabus Format Time Teaching content Lecture 42h Introduction; Conspectus of disease; Apoptosis and related disease; Water and electrolytes imbalance; Acid-base imbalance; Fever; Stress; Hypoxia; DIC; Shock; Ischemia-reperfusion injury; Respiratory failure; Heart failure; Hepatic failure; Renal failure. Self-study Signal transduction and related disease. CBL 4h Four case; Group learning.

李稻 赵倩、蒋益、黄莺 吴英里、韩玉慧

CHAPTER 2 Conspectus of Disease •Concepts of Health and Disease •Etiology of Disease •Pathogenesis of Disease •Outcome of Disease

Concepts of Health and Disease The World Health Organization affirms that health is “more than the absence of disease,” but rather a state of “complete physical, mental, and social well-being,” This definition sets a lofty goal for patients seeking health as well as for health care professionals. ●Factor in health ▲ physical well-being ▲ mental well-being ▲ social well-being

■Sub-Health There is a situation, in which the person dose not show specific symptoms and signs of disease, but lives a low-quality of life both physically and mentally. ●Manifestation of sub-health ▲physical sub-health: fatigue & disability; hyponoia; gastralgia; heart-throb, etc. ▲mental sub-health: angst; fidget; irascibility; insomnia, etc. ▲social sub-health: not concerned with our roles within society as a whole. irascibility angst

Signal regulated in cell ■Disease Disease is referred as aberrant manifestation of deregulated homeostasis caused by harmful agents. Disease is defined as an abnormal life process which is induced by disorders of homeostasis under the action of certain cause(s). Homeostasis Neural regulated Humoral regulated Signal regulated in cell ▲disease is caused by the etiological factors. ▲base of disease is deregulated homeostasis. ●Factor in disease deregulated

■Senescence Senescence is a biological process of dyfunctional change by which organisms become less capable of maintaining physiological function and homeostasis with increasing survival. This leads to a reduced probability of reproduction and an increased susceptibility to death from both exogenous and endogenous causes.

Etiology of Disease ■Concept of Etiological Factors & Predisposing Etiologic factors involved in diseases include causative, predisposing and precipitating factors, which contributes to the onset of diseases. ●Etiological factors ▲The factor that causes the disease and determine the clinical features of the disease ▲Among the etiological factors, a wide range of extrinsic factors in the environment and intrinsic factors in the body must be considered.

●Predisposing factors The function of these factors is to intensify the effects of causative factors and promote the onset and development of diseases. ▲precipitating factor The factors promotes the development of disease and influences the timing of illness onset. ▲risk factors The risk factor concept is epistemological in nature: it is often not clear exactly what a risk factor contributes to understanding and explanation.

Genetic aberrancies may be caused by single or polygenic mutations. ■Classification of etiological factors ▲chromosomal aberration 21三体综合症患儿（先天愚型） ●Factors of environment ▲biological agents ▲physical agents ▲chemical agents Genetic aberrancies may be caused by single or polygenic mutations. ●Inherited factors ▲gene mutation 【genetic predisposition】 The genetic mutations cause problems only when a person is eposed to certain environmental agents.

●Congenital factors The disorders are of a developmental nature and most of them are nongenetic. “反应停”儿童 ●Nutritional imbalance Either excesses or deficiencies of nutrients predispose cells to injury.

●Immunological factors ▲immunodeficiency disease ▲autoimmune disease ▲anaphylactic reaction ●Psychological and social factors Anxiety, 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.

Pathogenesis •Molecular mechanism Pathogenesis of disease refers to the rules and mechanisms underlying the development or evolutin of diseases. It studies how the primary pathological agents cause disease in organism and how the disease develops. ■Basic Mechanism of Disease •Neural mechanism •Humoral mechanism •Cellular mechanism •Molecular mechanism

●Neural mechanism ●Humoral mechanism ●Cellular mechanism Neural system plays a central role in regulating entire life activities; therefore, the disorders in central nerve system will definitely affect the corresponding periphery system. ●Humoral mechanism humoral factor ▲hormones ▲chemical mediators ▲cytokines ●Cellular mechanism ●Molecular mechanism

●Neural mechanism ●Humoral mechanism ●Cellular mechanism Neural system plays a central role in regulating entire life activities; therefore, the disorders in central nerve system will definitely affect the corresponding periphery system. ●Humoral mechanism humoral factor ▲hormones ▲chemical mediators ▲cytokines ●Cellular mechanism ●Molecular mechanism

Damage Anti-damage ●Damage and anti-damage responses ■General Rules for Pathogenesis of Diseases ●Damage and anti-damage responses Damages are usually made when a variety of harmful insults attack the body. During this process, anti-damage responses are also induced in the body to restore the normal situation. pain Infection (fever) plasma loss shock ischemia & injury of Cells Bp↓, blood volume↓ Severe burn Damage Stress WBC↑, Blood coagulation↑ SAMS excitation(+) C.O↑, Blood redistribution Rehabilitation blood flow heart & brain↑ Anti-infection↑, plasma loss↓ Anti-damage SAMS: Sympathetico-adrenal-medullay system; c.o: cardiac output

●Alternation of cause and result In the evolution of a disease, the cause of the disease can produce a result, and this result can also become another cause in the evolution proess of disease. ▲ benign circle ▲ vicious circle ●Local-systemic relationship Diseases are generally systemic whereas the local pathological alterations caused by insults are recognized to be representative of systemic diseases.

Outcome of Disease Outcome of Disease The course of a disease varies. An acute disease has relatively sudden onset and lasts for a short term, whereas a chronic disease, sometimes begins with an acute phase, usually lasts for a long period of time. There are generally three types of outcomes for a disease. •Complete recovery •Incomplete recovery •Death Outcome of Disease

■Complete recovery This is best outcome of a disease. In this case, the pathologically altered metabolism, structure and function are perfectly restored, and the symptoms and signs of the disease disappear entirely. ■Incomplete recovery The main symptoms 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.

■Death The cessation of heart-beats and breath is used as the criterion of death of a body. ●Traditionally death ▲agonal stage ▲stage of clinical death ▲stage of biological death ●Brain death The functions of cerebrum and brain stem stop forever.

●Criteria for brain death ▲irreversible coma. ▲cessation of spontaneous respiration. ▲norpurposeful movement. ▲absence of cephalic reflexes. ▲absence of any electric activity of the brain. ▲absence of cerebral circulation. ●Criteria for brain death

When cerebral function is lost, the reticular activating system and brain stem can maintain a crude waking state known as a vegetative state. Human Vegetable Human vegetable: Terri Schiavo