Gas exchange

1. Tissue cells O2 CO2 O2 CO2 Tissue capillaries Gas exchange Pulmonary gas exchange Tissue gas exchange O2 CO2 CO2 O2 Pulmonary capillary

2. Diffusion: continuous random motion of gas molecules. Partial pressure: the individual pressure of each gas, eg. PO2 Physical principles of gas exchange

3. Boyle’s law states that the pressure of a fixed number of gas molecules is inversely proportional to the volume of the container.

4. Laws governing gas diffusion • Henry’s law: The amount of dissolved gas is directly proportional to the partial pressure of the gas

5. Laws governing gas diffusion • Graham's Law When gases are dissolved in liquids, the relative rate of diffusion of a given gas is proportional to its solubility in the liquid and inversely proportional to the square root of its molecular mass

6. Laws governing gas diffusion • Fick’s law The net diffusion rate of a gas across a fluid membrane is proportional to the difference in partial pressure, proportional to the area of the membrane and inversely proportional to the thickness of the membrane

7. Factors affecting gas exchange • 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

8. Gas partial pressure (mmHg) Atmosphere Alveoli Arterial Venous Tissue Po2 159 104 100 40 30 Pco2 0.3 40 40 46 50

9. In the lungs, the concentration gradients favor the diffusion of oxygen toward the blood and the diffusion of carbon dioxide toward the alveolar air; owing to the metabolic activities of cells, these gradients are reversed at the interface of the blood and the active cells.

10. 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

11. Respiratory membrane alveolus capillary endothelial cell surfactant CO2 epithelial cell O2 red blood cell interstitial space • Is the structure through which oxygen diffuse from the alveolus into the blood, and carbon dioxide in the opposite direction.

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

13. VA/QC Ventilation-perfusion ratio Effect of gravity on V/Q Physiologic dead space Physiologic shunt

14. Normal Mismatching of the air supply and blood supply in individual alveoli. The main effect of ventilation-perfusion inequality is to decrease the Po2of systemic arterial blood.

15. Gas transport in the blood • Respiratory gases are transported in the blood in two forms: • Physical dissolution • Chemical combination Alveoli Blood Tissue O2 →dissolve→combine→dissolve→ O2 CO2 ←dissolve←combine←dissolve← CO2

17. Transport of oxygen • Forms of oxygen transported • Chemical combination: 98.5% • Physical dissolution: 1.5% • Hemoglobin (血红蛋白，Hb) is essential for the transport of O2 by blood

18. 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.

19. 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.

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

21. High PO2 Hb + O2 HbO2 Low PO2

22. Cooperativity 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. • 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.

23. Oxygen capacity 氧容量 • The maximal capacity of Hb to bind O2 in a blood sample • Oxygen content 氧含量 • The actual binding amount of O2 with Hb • Oxygen saturation 氧饱和度 • Is expressed as O2 bound to Hb devided by the maximal capacity of Hb to bindO2 • (O2 content / O2 capacity) x 100%

24. Hb>50g/L ---Cyanosis紫绀 • 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 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.

25. Cyanosis • Hb>50g/L

26. Carbon monoxide poisoning • CO competes for the O2 sides in Hb • CO has extremely high affinity for Hb • Carboxyhemoglobin---20%-40%, lethal. • A bright or cherry red coloration to the skin

27. Oxygen-hemoglobin dissociation curve • The relationship between O2 saturation of Hb and PO2 • Cooperativity

28. Note that venous blood is typically 75% saturated with oxygen. 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).

30. Factors that shift oxygen dissociation curve • PCO2 and [H+] • Temperature • 2,3-diphosphoglycerate (2,3-二磷酸甘油酸，DPG)

31. 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.

32. 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.

33. High acidity and low acidity can be caused by high PCO2 and low PCO2, respectively. CO2+H2O H2CO3  H++HCO3-

35. Transport of carbon dioxide • Forms of carbon dioxide transported • Chemical combination: 93% • Bicarbonate ion (HCO3-) : 70% • Carbamino hemoglobin(氨基甲酸血红蛋白 ): 23% • Physical dissolve: 7%

36. Total blood carbon dioxide Sum of • Dissolved carbon dioxide • Bicarbonate • carbon dioxide in carbamino hemoglobin

37. CO2 transport in tissue capillaries tissues CO2 CO2 tissue capillaries CO2 + Hb HbCO2 carbonic anhydrase CO2 + H2O H2CO3 HCO3- H+ +HCO3- Cl- plasma tissue capillaries

38. CO2 transport in pulmonary capillaries CO2 + Hb HbCO2 alveoli CO2 pulmonary capillaries CO2 carbonicanhydrase CO2 + H2O H2CO3 HCO3- H+ +HCO3- plasma Cl- Cl- pulmonary capillaries

39. 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.

40. Cell Respiration • Oxidation • Glycolysis

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

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

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

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

46. 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.

47. Inspiratory neurons 吸气神经元 Expiratory neurons 呼气神经元

48. Respiratory center • Dorsal respiratory group (medulla) – mainly causes inspiration • Ventral respiratory group (medulla) – causes either expiration or inspiration • Pneumotaxic center(upper pons) 脑桥呼吸调整中枢– inhibits apneustic center & inhibits inspiration,helps control the rate and pattern of breathing • Apneustic center (lower pons) 长吸中枢– to promote inspiration

50. 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.