1. 学习要点 气体交换的原理 气体交换的原理 气体在血液中的运输 气体在血液中的运输 呼吸运动的神经调节与化学调节 呼吸运动的神经调节与化学调节 CO2 、 H+ 和 O2 对呼吸的影响 CO2 、 H+ 和 O2 对呼吸的影响

2. Gas exchange ( 气体交换 ) Tissue capillaries Tissue cells CO 2 O2O2 O2O2 Pulmonary capillary CO 2 O2O2 O2O2 Pulmonary gas exchangeTissue gas exchange

3. Physical principles of gas exchange （气体交换的原理） Diffusion （扩散） : continuous random motion of gas molecules. Diffusion （扩散） : continuous random motion of gas molecules. Partial pressure （分 压） : the individual pressure of each gas, eg. PO 2 Partial pressure （分 压） : the individual pressure of each gas, eg. PO 2

4.  D: Rate of gas diffusion   P: Difference of partial pressure  S: Solubility of the gas  T: Absolute temperature  A: Area of diffusion  d: Distance of diffusion  MW: Molecular weight Factors affecting gas exchange

5. Gas partial pressure (mmHg) Gas partial pressure (mmHg) AtmosphereAlveoli Arterial Venous Tissue AtmosphereAlveoli Arterial Venous Tissue Po 2 159104 10040 30 Pco 2 0.3 4040 46 50

6. Factors that affect the velocity of pulmonary gas exchange Thickness of respiratory membrane 呼吸膜 Surface area of respiratory membrane The diffusion coefficient 扩散系数 of the gas The pressure difference of the gas between the two sides of the membrane

7. Respiratory membrane 呼吸膜 surfactant epithelial cell interstitial space alveoluscapillary red blood cell endothelial cell O2O2O2O2 CO 2 Is the structure through which oxygen diffuse from the alveolus into the blood, and carbon dioxide in the opposite direction. Is the structure through which oxygen diffuse from the alveolus into the blood, and carbon dioxide in the opposite direction.

8. Ventilation-perfusion ratio 通气 / 血流比值 Alveolar ventilation (V) = 4.2 L Alveolar ventilation (V) = 4.2 L Pulmonary blood flow (Q) = 5 L Pulmonary blood flow (Q) = 5 L V/Q = 0.84 (optimal ratio of air supply and blood supply) V/Q = 0.84 (optimal ratio of air supply and blood supply)

9. Normal Po 2 Mismatching of the air supply and blood supply in individual alveoli. The main effect of ventilation-perfusion inequality is to decrease the Po 2 of systemic arterial blood.

10. Gas transport in the blood Respiratory gases are transported in the blood in two forms: Respiratory gases are transported in the blood in two forms: –Physical dissolution –Chemical combination AlveoliBloodTissue O 2 →dissolve→combine→dissolve→ O 2 O 2 →dissolve→combine→dissolve→ O 2 CO 2 ←dissolve←combine←dissolve← CO 2 CO 2 ←dissolve←combine←dissolve← CO 2

12. Transport of oxygen Forms of oxygen transported Forms of oxygen transported –Chemical combination: 98.5% –Physical dissolution: 1.5% Hemoglobin ( 血红蛋白， Hb) is essential for the transport of O 2 by blood Hemoglobin ( 血红蛋白， Hb) is essential for the transport of O 2 by blood

13. Normal adult hemoglobin is composed of four subunits linked together, with each subunit containing a single heme -- the ring-like structure with a central iron atom that binds to an oxygen atom. Normal adult hemoglobin is composed of four subunits linked together, with each subunit containing a single heme -- the ring-like structure with a central iron atom that binds to an oxygen atom.

14. Hemoglobin is the gas-transport molecule inside erythrocytes. Oxygen binds to the iron atom. Heme attaches to a polypeptide chain by a nitrogen atom to form one subunit of hemoglobin. Four of these subunits bind to each other to make a single hemoglobin molecule.

15. Two forms of Hb Deoxygenated state (deoxyhemoglobin) -- when it has no oxygen Deoxygenated state (deoxyhemoglobin) -- when it has no oxygen Oxygenated form (oxyhemoglobin) -- carrying a full load of four oxygen Oxygenated form (oxyhemoglobin) -- carrying a full load of four oxygen

16. Hb + O 2 HbO 2 High PO 2 Low PO 2

17. Oxygen capacity 氧容量 Oxygen capacity 氧容量 –The maximal capacity of Hb to bind O 2 in a blood sample Oxygen content 氧含量 Oxygen content 氧含量 –The actual binding amount of O 2 with Hb Oxygen saturation 氧饱和度 Oxygen saturation 氧饱和度 –Is expressed as O 2 bound to Hb devided by the maximal capacity of Hb to bind O 2 –(O 2 content / O 2 capacity) x 100%

18. Hb>50g/L ---  Cyanosis 紫绀 Cyanosis is a physical sign causing bluish discoloration of the skin and mucous membranes. Cyanosis is a physical sign causing bluish discoloration of the skin and mucous membranes. Cyanosis is caused by a lack of oxygen in the blood. Cyanosis is caused by a lack of oxygen in the blood. Cyanosis is associated with cold temperatures, heart failure, lung diseases, and smothering. It is seen in infants at birth as a result of heart defects, respiratory distress syndrome, or lung and breathing problems. Cyanosis is associated with cold temperatures, heart failure, lung diseases, and smothering. It is seen in infants at birth as a result of heart defects, respiratory distress syndrome, or lung and breathing problems.

19. Cyanosis Hb>50g/L Hb>50g/L

20. Carbon monoxide poisoning CO competes for the O 2 sides in Hb CO competes for the O 2 sides in Hb CO has extremely high affinity for Hb CO has extremely high affinity for Hb Carboxyhemoglobin---20%-40%, lethal. Carboxyhemoglobin---20%-40%, lethal. A bright or cherry red coloration to the skin A bright or cherry red coloration to the skin

21. Cooperativity （协同性） of Hb Deoxy-hemoglobin is relatively uninterested in oxygen, but when one oxygen attaches, the second binds more easily, and the third and fourth easier yet. Deoxy-hemoglobin is relatively uninterested in oxygen, but when one oxygen attaches, the second binds more easily, and the third and fourth easier yet. The same process works in reverse: once fully loaded hemoglobin lets go of one oxygen, it lets go of the next more easily, and so forth. The same process works in reverse: once fully loaded hemoglobin lets go of one oxygen, it lets go of the next more easily, and so forth.

22. Oxygen-hemoglobin dissociation curve The relationship between O 2 saturation of Hb and PO 2 The relationship between O 2 saturation of Hb and PO 2 Cooperativity Cooperativity

23. As the concentration of oxygen increases, the percentage of hemoglobin saturated with bound oxygen increases until all of the oxygen-binding sites are occupied (100% saturation). Note that venous blood is typically 75% saturated with oxygen.

25. Factors that shift oxygen dissociation curve PCO 2 and [H + ] PCO 2 and [H + ] Temperature Temperature 2,3-diphosphoglycerate ( DPG) 2,3-diphosphoglycerate (2,3- 二磷酸甘油酸， DPG)

26. Chemical and thermal factors that alter hemoglobin’s affinity to bind oxygen alter the ease of “loading” and “unloading” this gas in the lungs and near the active cells.

27. Chemical and thermal factors that alter hemoglobin’s affinity to bind oxygen alter the ease of “loading” and “unloading” this gas in the lungs and near the active cells.

28. PCO 2 and low PCO 2, respectively. High acidity and low acidity can be caused by high PCO 2 and low PCO 2, respectively. CO 2 +H 2 OH 2 CO 3 H + +HCO 3 - CO 2 +H 2 O  H 2 CO 3  H + +HCO 3 -

30. Transport of carbon dioxide Forms of carbon dioxide transported Forms of carbon dioxide transported –Chemical combination: 93%  Bicarbonate ion ( HCO 3 - ) : 70%  Carbamino hemoglobin( 氨基甲酸血红蛋白 ): 23% –Physical dissolve: 7%

31. tissue capillaries tissues CO 2 transport in tissue capillaries CO 2 + HbHbCO 2 CO 2 plasma tissue capillaries CO 2 + H 2 O H 2 CO 3 H + +HCO 3 - HCO 3 - carbonic anhydrase CO 2 Cl -

32. pulmonary capillaries CO 2 + HbHbCO 2 H + +HCO 3 - HCO 3 - H 2 CO 3 carbonic anhydrase CO 2 + H 2 O plasma alveoli Cl- pulmonary capillaries CO 2 transport in pulmonary capillaries CO 2 Cl-

33. Cell Respiration Cellular respiration is the process by which the chemical energy of "food" molecules is released and partially captured in the form of ATP. Carbohydrates, fats, and proteins can all be used as fuels in cellular respiration, but glucose is most commonly used as an example to examine the reactions and pathways involved.

34. Oxidation Glycolysis Cell Respiration

35. Regulation of respiration Breathing is controlled by the central neuronal network to meet the metabolic demands of the body Breathing is controlled by the central neuronal network to meet the metabolic demands of the body –Neural regulation –Chemical regulation

36. Respiratory center Definition: Definition: –A collection of functionally similar neurons that help to regulate the respiratory movement

37. Respiratory center Medulla Medulla Pons Pons Higher respiratory center: cerebral cortex, hypothalamus & limbic system Higher respiratory center: cerebral cortex, hypothalamus & limbic system Spinal cord: respiratory motor neurons Spinal cord: respiratory motor neurons Basic respiratory center: produce and control the respiratory rhythm

38. Voluntary breathing center Voluntary breathing center –Cerebral cortex Automatic (involuntary) breathing center Automatic (involuntary) breathing center –Medulla –Pons Neural regulation of respiration

40. Neural generation of rhythmical breathing The discharge of medullary inspiratory neurons provides rhythmic input to the motor neurons innervating the inspiratory muscles. Then the action potential cease, the inspiratory muscles relax, and expiration occurs as the elastic lungs recoil.

41. Inspiratory neurons Inspiratory neurons 吸气 神经元 Expiratory neurons Expiratory neurons 呼气 神经元

42. Hering-Breuer inflation reflex (Pulmonary stretch reflex 肺牵张反射 ) The reflex is originated in the lungs and mediated by the fibers of the vagus nerve: – –Pulmonary inflation reflex 肺扩张反射 :   inflation of the lungs, eliciting expiration. – –Pulmonary deflation reflex 肺缩小反射 :   deflation, stimulating inspiration.

43. Pulmonary inflation reflex Inflation of the lungs  +pulmonary stretch receptor  +vagus nerve  - medually inspiratory neurons  +eliciting expiration

45. Summary:

46. Chemical control of respiration Chemoreceptors Chemoreceptors –Central chemoreceptors: medulla –Central chemoreceptors 中枢化学感受器 : medulla  Stimulated by [H + ]  in the CSF –Peripheral chemoreceptors –Peripheral chemoreceptors 外周化学感受器 :  Carotid body –Stimulated by arterial PO 2  or [H + ]   Aortic body

47. Central chemoreceptors

48. Chemosensory neurons that respond to changes in blood pH and gas content are located in the aorta and in the carotid sinuses; these sensory afferent neurons alter CNS regulation of the rate of ventilation. Peripheral chemoreceptors

49. Small changes in the carbon dioxide content of the blood quickly trigger changes in ventilation rate. Effect of carbon dioxide on pulmonary ventilation CO 2    respiratory activity CO 2 +H 2 OH 2 CO 3 H + +HCO 3- CO 2 +H 2 O  H 2 CO 3  H + +HCO 3-

50. Regardless of the source, increases in the acidity of the blood cause hyperventilation. Effect of hydrogen ion on pulmonary ventilation [H + ]    respiratory activity

51. A severe reduction in the arterial concentration of oxygen in the blood can stimulate hyperventilation. Effect of low arterial PO 2 on pulmonary ventilation PO 2    respiratory activity

52. The levels of oxygen, carbon dioxide, and hydrogen ions in blood and CSF provide information that alters the rate of ventilation. In summary:

53. 1.Why is increased depth of breathing far more effective in evaluating alveolar ventilation than is an equivalent increase in breathing rate? 2.Describes the effects of PCO2, [H+] and PO2 on alveolar ventilation and their mechanisms. Questions

54. Questions 3. What is the major result of the ventilation- perfusion inequalities throughout the lungs? 3. What is the major result of the ventilation- perfusion inequalities throughout the lungs? 4. Describe the factors that influence gas exchange in the lungs. 4. Describe the factors that influence gas exchange in the lungs. 5. If an experimental rabbit’s vagi were onstructed to prevent them from sending action potential, what will happen to respiration? 5. If an experimental rabbit’s vagi were onstructed to prevent them from sending action potential, what will happen to respiration?