Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Respiratory Physiology (呼吸生理学) 赖蒽茵 浙江大学医学院生理系 求是特聘教授 浙江省“千人计划”人才,博导 [email protected] May 26 and 27, 8:00 – 9:35 am, 基础医学各论 I 紫金港校区西2-303, 2012级五年制临床, 共162人 Respiratory Exchange of oxygen (O2) and carbon dioxide (CO2) with environment Pulmonary ventilation 气体经呼吸道进出肺的过程 The process of moving air into and out of the lungs Pulmonary ventilation 呼吸过程中肺内压的变化 吸气时,肺内压为 尽力吸气时 -2 to -1mmHg (-100 to -30mmHg) 呼气时,肺内压为 1 to 2 mmHg 尽力呼气时 (60 to 140mmHg) Thorax The thorax is a closed compartment that is bounded at the neck by muscles and connective tissue and completely separated from the abdomen by the diaphragm. Mechanics of pulmonary ventilation Muscles that cause lung expansion and contraction 吸气肌:diaphragm (膈肌) external intercostals (肋间外肌) 呼气肌:abdominal muscles (腹肌) internal intercostals (肋间内肌) Structures of pulmonary ventilation Breathing is an active process To inhale • Contraction of external intercostal muscles →elevation of ribs & sternum →increased front-toback dimension of thoracic cavity →lowers air pressure in lungs →air moves into lungs • Contraction of diaphragm →diaphragm moves downward →increases vertical dimension of thoracic cavity →lowers air pressure in lungs →air moves into lungs •To exhale Relaxation of external intercostal muscles & diaphragm →return of diaphragm, ribs, & sternum (胸骨) to resting position →restores thoracic cavity to pre-inspiratory volume →increases pressure in lungs →air is exhaled Pattern of respiration •Abdominal breathing 腹式呼吸 •Thoracic breathing 胸式呼吸 •Eupnea平静呼吸 •Forced breathing 用力呼吸 Principles of pulmonary ventilation • Direct force of breathing – Pressure gradient between atmosphere and lung • Original force of breathing – Respiratory movement Respiration A processes involved in exchange of oxygen (O2) and carbon dioxide (CO2) between an organism and the environment •Consist of – Inspiration: the inhalation of air into the lung – Expiration: breathing out Respiratory system Upper airway Lower airway The relaxation/contraction of circular smooth muscle lining these “airways’” determines how easily airflow can occur. Most gas exchange occurs in the alveolar sacs. Four major steps of respiration • 1.Pulmonary ventilation • 2.Gas exchange – Lung – Tissue • 3.Gas transport in blood • 4.Cellular respiration Respiratory process }外呼吸External respiration 气体在血液中的运输 Gas transport in the blood }内呼吸Internal respiration Process of respiration: Fig. 13.06 Gas exchange Pulmonary gas exchange CO2 Tissue gas exchange Tissue cells CO O2 2 O2 CO2 O2 Pulmonary capillary O2 CO2 Tissue capillaries 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 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 Po2 Arterial Venous Tissue 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. In the interface of the blood and the active cells, these gradients are reversed due to the metabolic activities of cells. Pulmonary gas exchange factors • Thickness of respiratory membrane (呼吸膜) • Surface area of respiratory membrane • The diffusion coefficient of gas (扩散系数) • The pressure difference of gas between the two sides of membrane Alveoli Each of the clustered alveoli includes an abundance of pulmonary capillaries, thereby assuring that the ventilated air is brought into close proximity to the “pulmonary” blood, allowing efficient and thorough gas exchange between the air and the blood. Extensive branching of alveoli produces lots of surface area for exchange between air and blood. Alveolar and capillary walls are thin, permitting rapid diffusion of gases. 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 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. (porphyrin molecules,卟啉分子) • 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. High PO2 Hb + O2 HbO2 Low PO2 • 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 • is a physical sign causing bluish discoloration of the skin and mucous membranes. • is caused by a lack of oxygen in the blood. • is associated with cold temperatures, heart failure, lung diseases. It is seen in infants at birth as a result of heart defects, respiratory distress syndrome, or lung and breathing problems. Hb + O2 HbO2 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 (致命的). • A bright or cherry red coloration to the skin 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 tissues CO2 CO2 transport in tissue capillaries tissue capillaries CO2 CO2 + Hb HbCO2 CO2 + H2Ocarbonic anhydrase H2CO3 H+ HCO3- +HCO3Cl - plasma tissue capillaries CO2 transport in pulmonary capillaries alveoli CO2 pulmonary capillaries CO2 CO2 + Hb HbCO2 carbonic anhydrase H2CO3 CO2 + H2O HCO3H+ +HCO3plasma Clpulmonary capillaries Cl- Airflow (F) is a function of the pressure differences between the alveoli (Palv) and the atmosphere (Patm) divided by airflow resistance (R). Air enters the lungs when Palv < Patm Air exits the lungs when Palv > Patm Intrapleural pressure (胸内压) Intrapleural pressure is the pressure within pleural cavity (胸膜腔) Intrapleural pressure • Pleural cavity – Pleural cavity is the closed space between parietal pleura & lungs covered with visceral pleura Intrapleural pressure the pressure within pleural cavity Direct measurement of intrapleural pressure Indirect measurement of intrapleural pressure Measurement of the pressure inside the esophagus Formation of intrapleural pressure •Fetus lung Air in lungs after delivery Formation of intrapleural pressure • Air in lungs after delivery • Because the elastic recoil (弹性回缩) causes the lungs to try to collapse, a negative force is always needed to the outside of the lungs to keep the lungs expanded. This force is provided by negative pressure in the normal pleural space. Intrapleural pressure • Intrapleural pressure = Intrapulmonary pressure – the recoil pressure of the lung • Intrapleural pressure = – the recoil pressure of the lung Pressures involved - intrapulmonary pressure = atmospheric pressure (760 mmHg) - collapsing force of lung (肺回缩力) - intrapleural pressure Physiological significance of intrapleural negative pressure (胸膜腔负压) •Allow expansion of the lungs (利于肺的扩张) • Facilitate the venous & lymphatic return (促进静脉血和淋巴液的回流) Pneumothorax (气胸) Air escapes from the lungs or leaks through the chest wall and enters the pleural cavity Lateral 单侧 Bilateral双侧 Compliance of the lungs (肺的顺应性) •The extent to which the lungs expand for each unit increase in pressure C=ΔV/ΔP (L/cmH2O) •Determined by the elastic forces of the lungs (R, 肺弹 性阻力) C=1/R Compliance of the lungs • Compliance (顺应性): the expand ability of elastic tissues when acted on by foreign forces or the extent to which the lungs expand for each unit increase in pressure. • C=ΔV/ΔP (L/cmH2O) • Elastic Resistance (R) C=1/R Compliance (顺应性)varies within the lung according to the degree of inflation. Poor compliance is seen at low volumes (because of difficulty with initial lung inflation) and at high volumes (because of the limit of chest wall expansion), with best compliance in the mid-expansion range. Resistances to Ventilation • Elastic resistance: The ability of an elastic structure to resist stretching or distortion. 70% • Non-elastic resistance: 30% 气道阻力 咽喉 + 直径 > 2mm气道 的气道阻力 = 80% 直径 < 2mm气道 的气道阻力 = 20% Lung compliance is a measure of the lung’s “stretchability.” When compliance is abnormally high, the lungs might fail to hold themselves open, and are prone to collapse. When compliance is abnormally low, the work of breathing is increased. 肺气肿 肺纤维化 Elastic forces of the lungs • 1/3 Elastic forces of the lung tissue itself (肺组织本身 的弹性回缩力) • 2/3 Elastic forces caused by surface tension (表面张力) of the fluid that lines the inside walls of the alveoli Surface tension • Elastic-like force existing in the surface of a liquid, tending to minimize the area of surface • Caused by asymmetries (不对称) in the intermolecular forces between surface molecules Surface tension • The surface tension at the air-water interfaces within the alveoli. • At an air-water interface, the attractive forces between the water molecules (surface tension) make the alveoli like stretched balloons that constantly try to shrink and resist further stretching. Pierre Simon Laplace (1749 -1827) Laplace’s law: P=2T/r P=肺泡內压力, T=表面张力, r=肺泡半径 Laplace’s law: P=2T/r In the absence of surfactant, the attraction between water molecules can cause alveolar collapse. Alveolar surfactant (表面活性物质) • Secreted by type II alveolar epithelial cells • Surfactant is a complex mixture of – Several phospholipids (二软脂酰卵磷脂 dipalmitoyl phosphatidyl choline, DPPC) – Surfactant-associated proteins – Ions (calcium) Type II alveolar epithelial cells Physiological effect of Alveolar surfactant • Reduces surface tension, eases expansion of lung • Maintains the stability of alveoli in different size • Keeps the dryness of alveoli Neonatal respiratory distress syndrome (NRDS) (新生儿呼吸窘迫综合征) lack of surfactant retraction of soft tissue on inspiration By reducing the surface tension of water, surfactant helps prevent alveolar collapse. Laplace’s law: P=2T/r Ta=Tb Ta>Tb ra>rb ra>rb Pa<Pb Pa=Pb Pulmonary surfactant • Pulmonary surfactant is a mixture of phospholipids and protein. • It is secreted by type II alveolar cells. • It lowers the surface tension of the water layer at the alveolar surface, which increases lung compliance, makes the lungs easier to expand. • Its surface tension is lower in smaller alveoli thus stabilizing alveoli. • A deep breath increases its secretion by stretching the type II cells. Its concentration decreases when breaths are small. • Production in the fetal lung occurs in late gestation (妊娠). Non-elastic resistance (非弹性阻力) • Airway resistance气道阻力: 80~90% – caused by gas molecules and the inner wall of airway – R1/r4 • Inertial resistance惯性阻力 • Viscous resistance粘滞阻力: The effect of surface friction between a particle and a liquid. • Regulation of the respiratory smooth muscle by autonomic nervous system: – Vagus nerve: Ach M receptor Contraction – Sympathetic nerve: NE 2-receptor Relaxation • Regulation of the respiratory smooth muscle by endocrine or paracrine factors: – Histamine, Bradykinin Contraction – NE, E, Isoproterenol Relaxation Timed vital capacity (时间肺活量) Pulmonary volumes and capacities • Spirometer (肺活量计) a spirometer---a device used to measure lung health. Blowing forcefully into the tube provides a quick, easy measure of FEV (Forced expiratory volume, 用力呼气量 = timed vital capacity, TVC 时间肺活量). To learn your FEV, you will be asked to hold the tube of a spirometer in your mouth, inhale as much air as possible, then exhale forcefully into the spirometer. Pulmonary volumes • Tidal volume (潮气量TV) Volume of air inspired or expired with each normal breath Normal value: 400~500 ml • Inspiratory reserve volume (补吸气量IRV) Amount of air that can be inspired above and beyond TV Normal value: 1500~2000 ml • Expiratory reserve volume (补呼气量ERV) Amount of air that can be expired after a tidal expiration Normal value: 900~1200 ml • Residual volume (残气量RV) The volume of air remaining in the lungs at the end of a maximal exhalation Normal value: M 1500 ml, F 1000 ml The tidal volume is the amount of air moved in/out of the airways in a single breathing cycle. Inspiratory and expiratory reserve volumes are the additional volume that can inspired or expired; all three quantities sum to the lung’s vital capacity. The residual volume is the amount of air that must remain in the lungs to prevent alveolar collapse. Pulmonary capacities • Inspiratory capacity 深吸气 = IRV+TV • Functional residual capacity 功能残气量 The volume of air that still remains in the lungs after expiration of a resting tidal volume. FRC = ERV+RV • Vital volume (肺活量 Vital capacity, VC) The maximal of air that a person can expire after a maximal inspiration VC = TV+IRV+ERV Normal value: M 3500 ml, F 2500 ml Pulmonary capacities • Total lung capacity 肺总量 = VC+RV The maximal volume of air the lungs can accommodate Pulmonary capacities • Forced expiratory volume (用力肺活量,timed vital volume时间 肺活量) The maximal volume of air that can be exhaled as fast as possible from the lungs following a maximal inspiration Normal value: 1st sec. (FEV1) -- 83% 2nd sec. (FEV2) -- 96% 3rd sec. (FEV3) -- 99% Pulmonary ventilation • Pulmonary ventilation (每分通气量VE) The total amount of air inspired/expired during one minute VE = TV x breaths/min = 500 X12 = 6000 ml Pulmonary ventilation • Alveolar ventilation (肺泡通气量VA) The amount of inspired air that is available for gas exchange each minute VA = (TV - dead space无效腔) x breaths/min = (500-150) X12 = 4200 ml Dead space Dead space • Anatomical dead space Volume in respiratory passageways which can not be exchanged ~ 150ml • Alveolar dead space Alveoli which have little or no blood supply and cease to function in gas exchange Normally ~ 0 Because of the anatomic dead space, “Fresh” inspired air is diluted by the left over air remaining in the lungs from the previous breathing cycle. 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 低位脑干--脑桥和延髓 • Medulla • Pontine (脑桥) Basic respiratory center: produce and control the respiratory rhythm • Higher respiratory center: cerebral cortex, hypothalamus & limbic system (下丘脑和边缘系统) • Spinal cord: respiratory motor neurons 低位脑干--脑桥和延髓 Basic respiratory center: produce and control the respiratory rhythm Respiratory center • Dorsal respiratory group (medulla) – mainly causes inspiration • Ventral respiratory group (medulla) – causes either expiration or inspiration • Pneumotaxic center (upper pons 脑桥上部) – inhibits apneustic center & inhibits inspiration,helps control the rate and pattern of breathing • Apneustic center (lower pons) – to promote inspiration Neural regulation of respiration • Voluntary breathing center – Cerebral cortex • Automatic (involuntary) breathing center – Medulla 髓 – Pontine 脑桥 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. 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. 舌咽神经 迷走神经 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 (迷走神经): – 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 - medualar inspiratory neurons +eliciting expiration 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. Summary Questions 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 • What is the major result of the ventilationperfusion inequalities throughout the lungs? • Describe the factors that influence gas exchange in the lungs. • If an experimental rabbit’s vagi were obstructed to prevent them from sending action potential, what will happen to respiration?