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

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

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 Po
Pco

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

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. Ventilation-perfusion ratio
Effect of gravity on V/Q
VA/QC
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 Po2 of 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.
HB分子由一个珠蛋白和4个含铁血红素组成。
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 + O 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 saturation 氧饱和度
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 bind O2
(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 transport in tissue capillaries
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
alveoli
CO2
pulmonary capillaries
CO2
CO2 + Hb
HbCO2
carbonic anhydrase
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.

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

53. Summary:

54. Chemical control of respiration
Chemoreceptors
Central chemoreceptors中枢化学感受器: medulla
Stimulated by [H+] in the CSF
Peripheral chemoreceptors外周化学感受器:
Carotid body
Stimulated by arterial PO2 or [H+]
Aortic body

55. Central chemoreceptors

56. Peripheral chemoreceptors
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.

59. Effect of carbon dioxide on pulmonary ventilation
Small changes in the
carbon dioxide content
of the blood quickly
trigger changes in
ventilation rate.
CO2    respiratory activity

60. Central and peripheral
chemosensory neurons that respond to increased carbon dioxide levels in the blood are also stimulated by the acidity from carbonic acid, so they “inform” the ventilation control center in the medulla to increase the rate of ventilation.
CO2+H2O  H2CO3  H++HCO3-

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

62. Regardless of the source, increases in the acidity of the blood cause hyperventilation, even if carbon dioxide levels are driven to abnormally low levels.

63. Effect of low arterial PO2 on pulmonary ventilation
PO2    respiratory activity
A severe reduction in the arterial concentration of
oxygen in the blood can stimulate hyperventilation.

64. Chemosensory neurons
that respond to decreased
oxygen levels in the blood
“inform” the ventilation
control center in the
medulla to increase the rate of ventilation.

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

66. Regulation of respiration

67. Questions
1. Why is increased depth of breathing far more effective in evaluating alveolar ventilation than is an equivalent increase in breathing rate?

68. Questions
2. Describes the effects of PCO2, [H+] and PO2 on alveolar ventilation and their mechanisms.
CO2 ­-­  respiratory activity; Peripheral mechanism and central mechanism, the latter is the main one.
[H+]  ­-­  respiratory activity; Peripheral mechanism and central mechanism, the former is the main one.
PO2  ­-­  respiratory activity; Peripheral mechanism is excitatory.

69. Questions
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.
5. If an experimental rabbit’s vagi were onstructed to prevent them from sending action potential, what will happen to respiration?