病理生理學(xué)(pathophysiology)病理生理學(xué)是一門研究患病

1、Chapter 1(2) Conspectus of Disease 1.Concepts of health and disease 2.Etiology 3.Pathogenesis,,(1)The definition of health from WHO: health indicates not only without any evidence of disease, but also a stat

2、e 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

3、specific symptoms and signs of disease, but lives a low-quality of life both physically and mentally.,1. Concepts of health and disease,(4)Disease: An abnormal life process which is induced by disorders of homeost

4、asis 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 sympt

5、oms.,2. EtiologyEtiology studies the contributing factors that cause diseases including causative, predisposing, and precipitating factors.(1)Etiological factors / Causes of diseases (2)Conditions for / Precipita

6、ting 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 facto

7、rsBiological factorsPhysical factorsChemical factorsNutritional factorsImmunological factorsHereditary factorsCongenital factorsSocial and psychological factors,Biological factorsBiological agents: microorganis

8、ms (such as bacteria, virus, fungi, rickettsia, spirochete, etc.), parasites, and their toxins and metabolic products.,Physical factorsPhysical agents include mechanical injuries, extremes of temperature, electricity a

9、nd radiation.,Chemical factorsChemical 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 s

10、elective in their sites of action, such as binding of carbon monoxide to hemoglobin.,Nutritional imbalanceEither excesses or deficiencies of nutrients predispose cells to injury. For example, high lipids and carbohydr

11、ates 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 fact

12、orsAlthough 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 (immunodefici

13、ency disease),Genetic factorsGenetic 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 ab

14、erration,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 du

15、ring 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 persis

16、tent 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,,Precipitat

17、ing 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 diseaseA predisposi

18、ng 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

19、 predisposition,SummarySpecific causes and predisposing factors together determines the disease occurrence; precipitating factors influence the onset and development of illness. Some diseases only have one cause. Howe

20、ver, 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 develop

21、ment of diseases (1) The basic mechanisms of disease (2) General rules of disease development (3)Outcome of disease,(1) The basic mechanisms of diseaseAlthough various specific mechanisms may underlie dif

22、ferent 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 enti

23、re 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 ce

24、lls 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

25、 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

26、 .,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 sys

27、tem (cerebral cortex and hypothalamus)--- sympathetic-adrenal medulla system----increased secretion of norepinephrine and epinephrine--- constriction of arteries/ constriction of renal afferent arterioles will activate r

28、ennin-angiotensin-aldosterone 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

29、 alkali destroy the cells with no selection; hepatitis virus damages specifically the hepatocytes. Disease genomics: Disease proteomics,整體水平,細(xì)胞水平,分子水平,,研究疾病時(shí)功能代謝結(jié)構(gòu)的變化及其發(fā)生機(jī)制,器官水平,Integrated medicine,Systems biology,(

30、2) General rules of disease development The general rules for a disease to take place and developDisruption of homeostasis by pathological insultsBody’s responses to damages and anti-damage activitiesReversal role o

31、f cause-consequence in the disease processRelationship between systemic and local alterations,Regulation and disruption of homeostasis Homeostasis: the process whereby the internal environment of an organism tends to

32、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 o

33、f damages and anti-damages Damages induce anti-damage responses, and the interactions go through the whole process of diseases and determines the development of diseasesOverdo of anti-damages cause new injurese.g. Bu

34、rning injury (damage)-- constriction of small blood vessels: maintaining proper blood pressure (anti-damage). However, sustained vasoconstriction--hypoxia, cellular necrosis, and dysfunction.,Alternation of cause

35、 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.,Correlation be

36、tween 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 sys

37、temic 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 recove

38、ry, 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 recoveryThe best outcome of a disease:th

39、e etiological factors disappearthe pathologically altered metabolism, structure and function are perfectly restoredthe symptoms and signs of the disease disappear entirely homeostasis is recovered,Incomplete recovery

40、 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.

41、 For example, the permanent damage to the heart valve after rheumatic fever.,Deathagonal stagestage of clinical deathstage of biological death,,Brain deathBrain death is a state of prolonged irreversible cessation o

42、f 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 un

43、responsibilityCessation of spontaneous respirationAbsence of cephalic reflexes and dilated pupils Absence of electrical activity of brainCessation of cerebral circulation Precise diagnosis of brain death is importa

44、nt for having proper donors in organic transplantation.,SummaryResearch (Molecular, genetic, comprehensive, multi-discipline) Purpose: mechanisms, prevention, diagnosis, and treatment Disease spectrum changes