Pathophysiology

1. Pathophysiology

2. Chapter 1. Introduction to Pathophysiology • 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

3. 1.What is Pathophysiology Patho—physiology ? • (1) Etiology病因学 • (2)Pathogenesis发病学 • Functional change(dysfunction) • Metabolic change • Reasons of symptoms and signs • (3)Basic principle of management

4. 2.Why do we need Pathophysiology? • Two cases • (1) A case of infantile diarrhea • 　(2) A case of breathing with difficulty • 学习园地的 humour 　

5. 3.What will we learn in the course of Pathophysiology • (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)

6. 4.The position of Pathophysiology in medical education? • 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

7. 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..….

10. 6. Learn the ability of clinical thinking (finding, analyzing and resolving abnormal manifestations) • Case discussion • Ask question • Climb a tree (a story)

11. Chapter 2. Etiology and Pathogenesis 1.Some concepts 2.Etiology 3.Pathogenesis 4.Ending of disease

12. 1.Some concepts • (1) Health • (2)Sub-health • (3) Disease • (4)Pathological process • (5)Senescence 衰老

13. (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.

14. (2) Sub-healthChronic fatigue syndrome • 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.

15. (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.

17. 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.

18. Fatigue • Loss of appetite Someone may make a show to deceive.

19. Syndrome • 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).

20. The SARS consists of (1)low artery oxygen pressure (PaO2), (2)dyspnea (shortness of respiration), (3)symptoms and signs of hypoxia, (4) cyanosis. • The internal relation may be the special kind of virus infection from animals, but at first ,it is not clear.

21. WHO report: • Health 5% • Sub-health 75% • Disease 20% • Dynamic transforming

22. (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.

23. 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.

24. (5) Senescence 衰老Aging老化 • 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

25. 2.Etiology of Disease • Etiology is the science to study the causes of the diseases. (1) Etiological factors (causes of diseases) (2) Conditions of disease development

26. (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.

27. 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.

28. 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.

29. Atherosclerosis of coronary artery is the cause (etiological factor) of myocardial infarction.

30. (2) Conditions of disease development • 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

31. 1)Precipitating factors(诱因) • 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???

32. 2) Predisposing factor(易感性） • 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.

33. Malnutrition: • for tuberculosis, ? • for edema ?

34. 3) Risk factorsprospective 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.

35. 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.

36. Till 1960s, they found that persons with fat, smoking, hypoactivate, hypercholesterolemia, diabetes, stress are susceptible to CHD.

39. 3. Pathogenesis 发病学 • （1） Fundamental mechanisms for diseases • （2）General rules for the development and ending of the diseases • (3) Stages of disease

40. （1）Fundamental mechanisms for diseases • 1) Neural mechanism • 2) Humoral mechanism • 3) Cellular mechanism • 4) Molecular mechanism

41. increase of ECF osmolality (1~2%) elevated angiotensin II dryness of mouth hypovolemia 1)Neural mechanism osmoreceptor (anterior hypothalamus) volume receptor in venae cavae and atrium • no thirst thirst center (anterior hypothalamus) sense of thirst and drink of water decrease of ECF osmolality increase of ECF volume decrease of angiotensin concentration II disappear of dryness

42. renal blood flow [Na+] in macula densa excitement of sympathetic nerve 2) Humoral mechanism renin release from the juxtaglomerular cells increase of angiotensin II releases [K+], [Na+] blood flow in plasma aldosterone secretion from adrenal cortex Na+ reaborption in renal tubules K+ and H+ excretion from kidneys

44. Neurohormoral regulation(systemic level) • The data showed the bus drivers in London were susceptible to hypertension.

45. 3) Cellular mechanism In hypoxia

46. 4) Molecular mechanism Familial lipoprotein lipase(LPL) deficiency is caused by LPL gene mutation. Disease proteomics (蛋白质组学)

47. （2）General rules for the development and ending of the diseases • 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)

48. 1)Disturbance of homeostasis • 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.

49. 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。”

50. 2) 因果转化（causality） • 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.