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Gas exchange Pulmonary gas exchange CO2 O2 CO2 O2 Pulmonary capillary Tissue gas exchange Tissue cells CO2 O2 CO2 O2 Tissue capillaries Physical principles of gas exchange Diffusion: continuous random motion of gas molecules. Partial pressure: the individual pressure of each gas, eg. PO2 Boyle’s law states that the pressure of a fixed number of gas molecules is inversely proportional to the volume of the container. Laws governing gas diffusion Henry’s law: The amount of dissolved gas is directly proportional to the partial pressure of the gas 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 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 Factors affecting gas exchange P S T A D d MW D: Rate of gas diffusion P: S: T: A: d: MW: Difference of partial pressure Solubility of the gas Absolute temperature Area of diffusion Distance of diffusion Molecular weight Gas partial pressure (mmHg) Atmosphere Alveoli Arterial Venous Tissue Po2 159 104 100 40 30 Pco2 0.3 40 40 46 50 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. 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 Respiratory membrane Is the structure through which oxygen diffuse from the alveolus into the blood, and carbon dioxide in the opposite direction. alveolus capillary endothelial cell surfactant CO2 epithelial cell O2 red blood cell interstitial space 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) Ventilation-perfusion ratio Effect of gravity on V/Q Physiologic dead space VA/QC Physiologic shunt 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. Gas transport in the blood Respiratory gases are transported in the blood in two forms: – Physical dissolution – Chemical combination Alveoli O2 Blood Tissue →dissolve→combine→dissolve→ O2 CO2 ←dissolve←combine←dissolve← CO2 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 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. 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. Two forms of Hb Deoxygenated state (deoxyhemoglobin) -when it has no oxygen Oxygenated form (oxyhemoglobin) -carrying a full load of four oxygen High PO2 Hb + O2 HbO2 Low PO2 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. 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% 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. Cyanosis Hb>50g/L 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 Oxygen-hemoglobin dissociation curve The relationship between O2 saturation of Hb and PO2 Cooperativity 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. Factors that shift oxygen dissociation curve PCO2 and [H+] Temperature 2,3-diphosphoglycerate (2,3-二磷酸甘油酸, DPG) 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. 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. High acidity and low acidity can be caused by high PCO2 and low PCO2, respectively. CO2+H2O H2CO3 H++HCO3- 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% Total blood carbon dioxide Sum of Dissolved carbon dioxide Bicarbonate carbon dioxide in carbamino hemoglobin CO2 transport in tissue capillaries tissues CO2 CO2 tissue capillaries CO2 + Hb HbCO2 CO2 + H2O carbonic anhydrase H2CO3 HCO3- H+ +HCO3Cl - plasma tissue capillaries CO2 transport in pulmonary capillaries alveoli CO2 pulmonary capillaries CO2 CO2 + Hb HbCO2 CO2 + H2O carbonic anhydrase H2CO3 HCO3H+ +HCO3plasma Clpulmonary capillaries Cl- 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. Cell Respiration • Oxidation • Glycolysis Regulation of respiration Breathing is controlled by the central neuronal network to meet the metabolic demands of the body – Neural regulation – Chemical regulation Respiratory center Definition: – A collection of functionally similar neurons that help to regulate the respiratory movement Respiratory center Medulla Pons Higher respiratory center: cerebral cortex, Basic respiratory center: produce and control the respiratory rhythm hypothalamus & limbic system Spinal cord: respiratory motor neurons Neural regulation of respiration Voluntary breathing center – Cerebral cortex Automatic (involuntary) breathing center – Medulla – Pons 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. Inspiratory neurons 吸气 神经元 Expiratory neurons 呼气 神经元 Respiratory center Dorsal respiratory group (medulla) – mainly causes inspiration Ventral respiratory group (medulla) – causes either expiration or inspiration Pneumotaxic center (upper pons) – inhibits apneustic center & inhibits inspiration,helps control the rate and pattern of breathing Apneustic center (lower pons) – to promote inspiration 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. Pulmonary inflation reflex Inflation of the lungs +pulmonary stretch receptor +vagus nerve - medually inspiratory neurons +eliciting expiration Summary: 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 Central chemoreceptors 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. 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 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- Effect of hydrogen ion on pulmonary ventilation [H+] respiratory activity Regardless of the source, increases in the acidity of the blood cause hyperventilation. Regardless of the source, increases in the acidity of the blood cause hyperventilation, even if carbon dioxide levels are driven to abnormally low levels. 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. 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. In summary: The levels of oxygen, carbon dioxide, and hydrogen ions in blood and CSF provide information that alters the rate of ventilation. Regulation of respiration Questions 1. Why is increased depth of breathing far more effective in evaluating alveolar ventilation than is an equivalent increase in breathing rate? 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. Questions 3. What is the major result of the ventilationperfusion 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?