Respiratory System ssrisuma@rics.bwh.harvard.edu Lung Volumes and Ventilation Minute ventilation Volume of an inspired or expired air per minute = tidal volume (V T ) x respiratory rate Dead space ventilation The portion of minute ventilation that fails to reach the area of the lungs involved in gas exchange Anatomic dead space(v D ) is the volume of gas that occupies the conducting zone of respiratory system (plus the accessory tubings), which does not participate in gas exchange Alveolar dead space :- some alveoli do not receive any blood flow Alveolar ventilation Volume of gas that reaches the alveolar portion for the exchange of O 2 and CO 2 = (V T V D ) x respiratory rate Adequate alveolar ventilation is critical because it determines the PAO 2 and PACO 2 PACO 2 and PaCO 2 RESP -1-
Are essentially equal because of the high diffusibility of CO 2 Are determined by the ratio of the rate of CO 2 production to alveolar ventilation Normal values = 40 + 4 mmhg (36 44 mmhg) Hyperventilation (constant VCO 2 ) hypocapnia respiratory alkalosis Hypoventilation (constant VCO 2 ) hypercapnia respiratory acidosis Static Mechanics of Breathing Generation of a pressure gradient between atmosphere and alveoli Air moves from a region of higher pressure to one of lower pressure Intra-alveolar pressure (Palv) Inspiration: Palv < Patm Passive expansion of alveoli response to an increased distending pressure across the alveolar wall generated by contraction of muscles of inspiration Expiration: Palv > Patm Intrapleural pressure or intrathoracic pressue (Pel) Pressure in the space between the visceral and parietal pleura is normally subatmospheric Caused by the mechanical interaction between the lung and the chest wall There is normally no gas in the intrapleural space Lung is held against the chest wall by the thin layer of serous intrapleural liquid (~8mL) Transmural pressure (PTM) The pressure across the wall; PTM = Pin Pout Positive transmural pressure (Pin > Pout) force expanding a structure Negative transmural pressure (Pin < Pout) force deflating a structure Transpulmonary pressure = alveolar-distending pressure = Palv Ppl Transpulmonary pressure is same as alveolar elastic recoil pressure (Pel), but different direction Alveolar pressure (Palv) = intrapleural pressure (Ppl) + alveolar elastic recoil pressure (Pel) RESP -2-
Elastic Resistance Elasticity = ability to return to its original configuration Compliance = change in volume divided by change in pressure (ΔV/ΔP) Elastic recoil of the lung inward to smaller volume Collagen, elastin, fibrous tissue in pulmonary parenchyma Surface tension at the air-liquid interface in the alveoli Elastic recoil of the chest wall spring outward to larger volume Surface tension Generated by cohesive forces between the molecules of the liquid that balance within the liquid phase cause a liquid to shrink to form the smallest possible surface area Laplace Law Small bubble generates a larger pressure, it blows up the large bubble Pulmonary surfactant produced by type II alveolar epithelial cells helps equalize alveolar pressure through out the lung and to stabilize alveoli by decreasing surface tension Decreased lung compliance Fibrosis :- sequelae from lung injury (ARDS), autoimmune disease Atelectasis or collapsed alveoli from IRDS/ARDS air, excess fluid, blood in the pleural space Increased lung compliance pulmonary emphysema (destroying alveolar septal tissue) aging Decreased chest wall compliance obesity kyphoscoliosis non-functioning diaphragm RESP -3-
Dynamic Mechanics of Breathing Airway Resistance :- Frictional Resistance of the airways to the flow of air Pressure = Flow x Resistance Poiseuille Law R = resistance, η = viscosity of fluid, l = length of tube, r = radius of tube Determinants of cross-sectional area of the airway Airway structure Bronchial smooth muscle tone Lung volume Elastic recoil of the lung Dynamic compression of airways Forced expiratory effort generates positive intrapleural pressure Palv is higher than Ppl because Palv = Ppl + Pel During forced expiration, there is a point along the airways where pressure inside the airways is just equal to the pressure outside the airway transmural pressure = 0, but above this point is negative, so airway will collapse if cartilaginous support or alveolar septal traction is insufficient to keep it open In healthy subject, airway closure can be demonstrated at low lung volume, but the closing volume may occur at higher lung volume in patients with emphysema RESP -4-
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Measurement Obstructive Restrictive FVC (L) FEV 1 (L) FEV 1 /FVC (%) Normal (N) to N to FEF 25-75 (L/sec) N to Peak expiratory flow (L/sec) N to FEF 50 (L/sec) N to Slope of Flow-volume curve Maximal voluntary ventilation (L/min) N to TLC (L) N to RV (L) RV/TLC (%) N Work of breathing Work required to move the lung and chest wall to let the air in o The pressure expanding the respiratory system is stored temporarily in elastic tissues and then dissipated in driving expiratory flow Patients with restrictive diseases tend to breath with a rapid, shallow pattern Patients with obstructive diseases tend to adopt a slower breathing pattern with large tidal volume RESP -6-
Mechanisms of airway narrowing in asthma Airway smooth muscle contraction and mucus hypersecretion narrows airway lumen and increases airway resistance Airway wall cellular infiltration and edma AND smooth muscle hyperplasia/hypertrophy increased airway wall thickness COPD = chronic bronchitis + emphysema Chronic bronchitis Goblet cell metaplasia (a change from ciliated airway epithelium into mucus-secreting cell) Airway smooth muscle hypertrophy/hyperplasia Excess mucus, edema, inflammatory cell infiltration at airway wall Emphysema Chronic inflammation and destruction of alveolar space with coalescence into larger alveolar space Loss of alveolar attachments with airway distortion and narrowing in COPD Elastolysis loss of elastin decreased elastic lung recoil decreased driving pressure for expiratory airflow from alveoli to mouth Air trapping increased lung volume increased antero-posterior diameter of chest wall limited respiratory excursion of the diaphragm Reduced alveolar-capillary surface area Ventilation/perfusion inequality o Perfusion of poorly-ventilated areas reduction in arterial oxygenation o Overventilation of poorly perfused areas increased dead space ventilation impaired CO 2 excretion Gas Exchange Partial Pressure = total pressure X fractional concentration = (PB PH 2 O) X Fx PB = 760 mmhg at sea level, PH 2 O = 47 mmhg, FIO 2 = 0.21 In dry inspired air at sea level, PIO 2 = 760 X 0.21 = 160 mmhg In humidified tracheal air at 37C, PIO 2 = (760-47) X 0.21 = 713 X 0.21 = 150 mmhg Alveolar oxygen tension is calculated by means of the alveolar gas equation RESP -7-
PAO 2 = (PB 47) X FIO 2 PACO 2 /R R = respiratory quotient = ratio of CO 2 production to oxygen consumption = 0.8 At sea level, PAO 2 = (760 47) X 0.21 (40/0.8) = 100 mmhg A-aDO 2 PaCO 2 Significant Present at rest response to supplemental O 2 Decreased PIO 2 Normal Decreased Yes Yes Alveolar hypoventilation Normal Increased Yes Yes Ventilation-perfusion Increased Increased Yes Yes mismatch Shunt Increased Decreased to normal No Yes Diffusion abnormality Increased Decreased to normal Yes Not usually, unless severe Gas Transport Oxygen dissolves in the plasma of the pulmonary capillaries after diffusing across the alveolar capillary membrane From the plasma, oxygen diffuses into the red blood cell, where it combines reversibly with the iron atoms of hemoglobin and converts deoxyhemoglobin into oxyhemoglobin 1 gram of hemoglobin can combine with 1.35 ml of O 2 Solubility coefficient of O 2 :- 1 mmhg PO 2 can dissolved and generate 0.003 ml of O 2 / 100 ml blood Oxygen content = O 2 bound to Hb + dissolved O 2 in blood = 1.35 X [Hb] X SO 2 + 0.003 X PO 2 Oxygen hemoglobin dissociation curve Arterial oxygen tension 100 mmhg, arterial oxygen saturation 97 % Mixed venous oxygen tension 40 mmhg, mixed venous oxygen saturation 75% Loading (association) zone Unloading (dissociation) zone Plateau portion of the curve Steep portion of the curve Occurs above 60 mmhg of PO 2 Occurs below 60 mmhg of PO 2 RESP -8-
Hemoglobin affinity for oxygen Is inversely related to P 50 Increased Hb affinity P 50 H +, 2,3-diphosphoglycerate, PCO 2, temperature increased Hb affinity Decreased Hb affinity P 50 H +, 2,3-DPG, PCO 2, temperature decreased Hb affinity Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) Injury to alveolar-capillary membrane permeability pulmonary edema Injury to alveolar epithelial type 2 reduction of pulmonary surfactant atelectasis right-to-left shunt hypoxemia with unresponsiveness to oxygen therapy RESP -9-
Solutions 1. 2 2. 4 3. 4 4. 4 5. 1 6. 5 7. C 8. B 9. 4 10. 3 11. 5 12. 5 13. 1 14. 5 15. 2 16. 4 17. 2 18. 6 19. 3 20. 5 21. 4 22. 1 23. 3 24. C 25. B 26. A RESP -10-