Conspectus of Disease

1. Conspectus of Disease 疾病概论 --疾病的概念（Concept of Disease） --病因学（Etiology） --发病学（Pathogenesis）

2. Concept of Health • Traditional definition: The state of the organism when it functions optimally without any evidence of disease. • The definition of health from WHO: Without any evidence of disease, and a state of complete well-beingphysically, socially and psychologically.

3. Concept of Disease • Homeostasis（稳态）: The body maintains a steady state of the internal environment in the face of continual environmental variation, which is required for optimum functioning. • Disease: An abnormal life process or a pathologic process which is induced by disorders of homeostasis under the action of certain causes and conditions, with a characteristic set of signs and symptoms. • Symptom: Subjective feeling of discomfort that can be reported by the affected individual. • Sign: Objectively identifiable aberration of the disease. • Syndrome: A collection of different signs and symptoms that occur together in specific disease.

4. Concept of Sub-health 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，with possible latent alterations, or functional alterations. e.g. chronic fatigue syndrome (CFS)

5. Etiology of Disease Etiology studies the contributing factors that cause diseases, including: (1) Etiological factors / Direct causes of diseases (2) Conditions for / Precipitating factors of disease (3) Predisposing factors of disease

6. 1. Etiological Factors （Direct causes of diseases） An etiological factor causes a disease and determines its characteristics. • Extrinsic Causes • Intrinsic Causes

7. (1) Extrinsic Factors • Biological agents: microorganisms, parasites, and products（toxins, LPS, etc） • Chemical agents: non-specific and specific • Physical agents: mechanical injuries, extremes of temperature, electricity, radiation, etc • Nutritional imbalance: excesses or deficiencies

8. (2) Intrinsic Factors • Genetic factors: gene mutation, chromosome aberration（e.g. sickle cell anemia, colorblindness）. • Epigenetic factors: DNA methylation, histone code, ncRNA, chromosome remodeling. • Congenital factors: abnormal embryonic development (resulting from maternal infections, diet and drug-taking during pregnancy). • Immunological factors: immune response is deficient, inappropriately strong, or misdirected (immunodeficiency, allergy, autoimmune diseases). • Psychological factors: anxiety, strong or persistent psychological stress (e.g. hypertension, peptic ulcer, coronary heart disease, and depression）.

9. 2.Conditions for disease Precipitating factorsenhancethe effects of causative factors and promote the onset and development of diseases, through influence upon the role of etiological factors or body condition: • Natural condition: exposed to cold environment ---develop a cold • Physical condition: hypertension --- vulnerable to myocardial infarction • Social condition: poor labor and hygiene conditions

10. 3.Predisposing factors A predisposing factor refers to the factor that influences the susceptibility or resistance tocertain disease: • Genetic constitution (Genetic predisposition) • Physiological diathesis • Psychological characteristics

11. Pathogenesis Pathogenesis studies the general rules and common mechanisms underlying the development of diseases, including how the primary pathological agents cause disease and how the disease develops.(1) Basic mechanisms of disease(2) General rules of disease development (3) Outcome of disease

12. 1. Fundamental mechanism of disease Mechanism of disease: to explain alteration during disease, including how and why the symptoms and signs of the disease may occur and develop, how the body attempts to overcome the disease. Although various specific mechanisms may underlie different disorders, they all generally involve the following four levels of deregulations: • Neural dysregulations • Hormonal dysregulations • Organic dysregulations • Cellular and Molecular dysregulations

13. 2. General rules for the onset and development of diseases • Disruption of homeostasis • Process of damage and anti-damage • Reversal role of cause and result • Correlation between systemic and local alterations

14. (1) Regulation and disruption of homeostasis • Homeostasis: to keep the internal environment of an organism to remain balanced and stable. e.g. maintenance of body temperature homeostasis. • Disruption of homeostasis by harmful agents may cause diseases. e.g. fever.

15. (2) Damages and anti-damage responses • Damages induce anti-damage responses, and their interactions go through the whole process of diseases, which determine the development and outcome of diseases. e.g. Microbe—anti-infection (Physic barrier, Monocyte, Inflammation, Immunoreaction) • Overdo of anti-damages cause new injuries, becoming a damaging factor. e.g. allergy, or autoimmune diseases

16. Primary causes Further alterations Responses Secondary alterations (causes) (3) Reversal rule of cause and result A cause of a disease leads to a result, which can be a new cause for another result in the development of the disease, even forming vicious cycle. e.g. hemorrhagic shock.

17. (4) Systemic and local regulations Local alterations and the systemic states 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, even sepsis. on the other hand, a furuncle may be a complication of diabetes and could only be cured by proper control of diabetes.

18. 高潮 前奏 尾声 潜伏 Clinic symptoms Prodrome Recovery Latency 3. Outcome of Disease Phases of A Disease

19. Complete recovery Recovery Incomplete recovery Outcome of a disease Death Prognosis: Probable course and outcome of a disease.

20. (1) Complete recovery The alterations of the function, metabolism, and structure of the body during the disease are perfectly restored, and the symptoms and signs of the disease are disappeared entirely. • 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

21. (2) Incomplete recovery the main symptoms and signs are absent, but some pathological changes are still present in the body. • Transition to chronicity • Sequela is generally brought about by the compensatory response to maintain a relatively normal activity. e.g. the permanent damage to the heart valve after rheumatic fever.

22. (3) Death The body as a whole stop working forever. Brain dearth is the marker for the diagnosis. 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. Brain Death (WHO criteria) • Cessation of spontaneous respiration • Irreversible coma • Absence of cephalic reflexes • Dilated or fixed pupils • Absence of any electrical activity of the brain • Absence of brain blood flow

23. Significance for diagnosis of brain death • In favor of recording the time of death • Define the time to terminate for the rescue • In favor of organ transplantation

24. Case study A 34-year-old man was well until 3 days prior to admission, when he noted the onset of fever, weakness, fatigue, headache, sore throat, and a cough productive of white sputum. One day prior to admission he awakened with burning chest discomfort that was made worse by coughing and by deep breathing. He developed shortness of breath and was seen at a university infirmary, where he appeared acutely ill with a fever. A chest radiograph demonstrated bilateral infiltrates consistent with pneumonia. An arterial blood gas analysis, done while the patient was breathing room air, was notable for significant hypoxemia (PaO2, 48mmHg; normal, 85-100mmHg). The patient’s shortness of breath increased markedly, and he was transferred to the hospital, where he was found to be cyanotic and febrile to 39.8℃ and to have a respiratory rate of 44/min with labored respirations. Examination of the sputum revealed a grossly bloody background, numerous neutrophils, and sheets of gram-positive cocci in clusters. Questions 1.What disease did the patient suffer from: bacterial infection or viral disease? 2. What pathogenic mechanism accounts for this patient’s fever? 3. What alterations of metabolism and function may occur in a patient suffering from fever?

25. 专业英文词汇 • Pathophysiology 病理生理学 • Disease 疾病 • Bio-psycho-social medical model 生物－心理－社会医学模式 • Etiology 病因学 • Pathogenesis 发病学 • genetic predisposition 遗传易感性 • Prognosis 预后 • brain death脑死亡 • Vegetative state植物状态

26. Learning Objectives • 了解病理生理学的知识结构、基本内容及其与其它医学学科的关系。 • 熟悉病理生理学/疾病机制的研究方法。 • 熟悉健康的定义、疾病的概念。 • 掌握疾病发生的病因学。 • 掌握疾病发生发展的一般规律和基本机制。 • 掌握疾病转归概念。 • 熟悉脑死亡概念和判断标准。了解植物状态与脑死亡的区别。

27. Exercises • 简述生物、物理以及化学致病因素作用于机体时具有哪些特点。 • 简述环境因素、遗传因素、以及社会和心理因素在疾病发生中的作用。 • 试述内源性病因的种类和基本概念 • 举例说明遗传易感性在疾病发生中的作用。 • 简述疾病发生发展的一般规律。 • 举例说明疾病过程中损伤和抗损伤相应的表现和在疾病发展中的意义。 • 举例说明疾病过程中因果转化在疾病发展中的意义。 • 简述脑死亡的概念和判断标准。 • 研究一个疾病的发病机制的基本策略和方法途径有哪些？