Fisiología Respiratoria I. Mecánica de la respiración A. Anatomía B. Ventilación

1. Fisiología Respiratoria I. Mecánica de la respiración A. Anatomía B. Ventilación 1. Músculos respiratorios 2. Flujo del aire 3. Presión Intrapleural 4. Volúmenes pulmonares 5. Trabajo respiratorio 6. Compliance pulmonar 7. Tensión superficial alveolar 8. Resistencia de vías aéreas 9. Compresión dinámica de vías aéreas 10. Espacio muerto 11. Factores determinantes de pCO2 y pO2

2. A. Anatomy

4. (Thoracic Cavity) Intrapleural space

5. Surface area 2.5 cm2 300 millones de alvéolos 0,3 mm dam. 85 m2! (en 5-6 litros) > 1 x 106 cm2

6. Problemas: -humo de cigarrillo -fibrosis quística

7. Structure of lung lobule Each cluster of alveoli is surrounded by elastic fibers and a network of capillaries.

10. B. Ventilation (how we breathe)

12. V2 V1 descent of diaphragm V1 < V2 Vb elevation of rib cage Va Va < Vb

14. Normal Lung at rest Pneumothorax lung collapses to unstretched size Pleural membranes

15. F P1 P2 Respirometer Flow (F) of air F = k(P1 - P2) = (P1 - P2)/R P = pressure; k = conductance = 1/R; R = resistance

16. Lung Volumes VT = Tidal volume ERV = expiratory reserve vol IRV = inspiratory reserve vol RV = residual vol FRC = functional residual capacity Vital capacity Total lung capacity Minute Volume = V = VT x resp. rate e.g., 0.5 L/breath x 12 breaths/min = 6 L/min

17. Functional residual capacity Vital capacity (sum total of all except RV)

18. Work of Breathing Compliance Work: force to expand lung against its elastic properties Force to overcome viscosity of lung & chest wall Airway Resistance Work: force to move air through airways

19. expiration 3 TLC lung volume (% TLC) inspiration 2 Volume, liters ∆V = 1.8 L Translung pressure (cm H2O) FRC 1 ∆P = 6.5 cm H2O RV MV 0 Compliance Work: Compliance of lung & chest wall The ability of the lung to stretch is measured as the COMPLIANCE, C C = ∆V/∆P where V is lung volume and P is pressure 1. Curves are not linear 2. Difference between inspiratory & expiratory curves called hysteresis ∆V/∆P = 1.8 L/6.5 cm H2O = 0.28 L/cm H2O For comparison: vein = 0.04 and artery = 0.002 L/cm H2O

20. What is surface tension? air air air

21. x x T P

22. x x

23. A major component of lung surfactant is dipalmitoylphosphatidylcholine (DPPC). DPPC has typical phospholipid structure: two fatty acid residues are water insoluble, hydrophobic; phosphocholine at other end is charged and water soluble, hydrophilic.

24. x x

25. What is the origin and composition of Lung Surfactant? Approximate composition of surfactant Component percent composition Dipalmitoylphosphatidylcholine 62 Other phospholipids 15 Neutral lipids 13 Proteins 8 Carbohydrates 2

26. Importance of Surfactant: 1. Reduces surface tension, therefore increases compliance 2. Stability of alveoli; LaPlace 3. Helps keep alveoli dry; helps prevent pulmonary edema 4. Expansion of lungs at birth

27. Resistance Work: Conductive Airway Resistance. Remember: ∆P = Raw x Flow Raw = (Palv - Patm)/ Flow Like Poiseuille flow in blood vessels, i.e., inversely µ to r4 8hl R = pr4 Agents that constrict vessels (bronchioles) or accumulate debris (e.g., mucus) increase resistance (makes airflow difficult). One might think that because the terminal bronchioles are very narrow they would represent very high resistance. However, because there are so many (>106) and because they are in parallel they represent a relatively small portion of the total Raw. Bronchiolar smooth muscle is under neurohumoral control Sympathetic stimulation (adrenaline): bronchiole dilation Parasympathetic stimulation (Ach): bronchiole constriction Histamine release from mast cells -- allergic/asthmatic response bronchiole constriction

28. Dead Space

29. Volumen corriente = 500 ml Espacio muerto = 150 ml Llegan al alvéolo = 350 ml Ventilación pulmonar = volumen corriente x frec.ventilatoria Ventilación alveolar = (volumen corriente-espacio muerto) x frec.ventilatoria ¿Conviene modificar volumen corriente o frecuencia ventilatoria?

30. Does Dead Space Matter? How? VT = VA + VT It is necessary to correct for dead space to effectively measure ventilation rate We have already been introduced to the respiratory minute volume, V V = freq x VT A more important “minute volume” is the alveolar ventilation rate Alveolar vent. rate = total volume of "new air" entering alveoli each minute,VA VA = freq x (VT - VD) Think about and Do homework questions from reader Calculate some VD’s Is it more efficient to change VAby frequency or by VT? What are the consequences of breathing through a long tube? What is an absolute upper limit for the length of the tube?

31. II. PHYSICAL PRINCIPLES OF GAS EXCHANGE A. Properties of GASES General Gas Law: PV = nRT

32. STPD BTPS ATPS Partial Pressure = pressure exerted by any one gas in a mixture Partial Pressure = total pressure x fraction of total represented by the gas (Dalton’s law), i. e., Pgas = Ptotal x fgas What is the composition of the room air that we breathe? (in percent & in partial pressure) • Accounting for water • Dry atm. air Partial pressure vapor pressure = 47mmHg • % mm Hgmm Hg • O2 20.9 160 149 • CO2 0.04 0.3 0.3 • N2 & other 79 600 564 • total 100 760 713 (0.21x760) (0.0004x760) (0.79x760)

33. How do we deal with gases in solution?

34. Henry’s Law: Conc. of gas in solution = partial pressure of gas X solubility coefficient e.g., [O2] in moles/L: [O2] = PO2 x SO2

35. SCO2 is 20x higher than SO2 Therefore [Gas] depends on bothPgas and Sgas SCO2 = 0.03 mmol/L / mm Hg SO2 = 1.37 µmol/L / mm Hg

36. What is DIFFUSION? start intermediate equilibrium How fast is DIFFUSION? Diffusion distance (µm) Time required for diffusion 1 10 100 1,000 (1 mm) 10,000 (1 cm) 0.5 msec 50 msec 5 seconds 8.3 minutes 14 hours CONCLUSION?

37. Rate of diffusion = dm/dt = D·A· A = area available for diffusion C = concentration of the substance x = the distance for the diffusion D = the diffusion coefficient Rate of Diffusion µ Area x Concentration O2 Distance CO2 Area P2 P1 thickness Fick's 1st Law of Diffusion dC dx What is the strategy in the evolution of the respiratory apparatus? available surface area distance required for diffusion (i.e., thickness)

38. FACTORES QUE INFLUYEN SOBRE EL TRANSPORTE DE GASES • Gradientes de presión parcial • Oxígeno: • 105 100 40 40 15 5-2 • alvéolos arterias capilares intersticio citosol mitocondrias 2. Superficie de intercambio 3. Distancia de difusión

39. Total AREA available for diffusion of gases is large in human ~50-100 m2 Enfisema! Diffusion PATH LENGTH is very small, <1 µm Edema!

40. Characteristics of the Pulmonary Circulation

41. “Special” Characteristics of the Pulmonary Circulation Systemic Circ.Pulmonary Circ. C.O. (L/min) 6.0 ≈ 5.9 Arterial B.P. (mm Hg) 100 >> 15 Venous B.P. (mm Hg) 2 “≈” 5 Vascular resistance (∆P/flow) 100-2/6=16.3 > 15-5/5.9=1.7 Vascular compliance (∆V/∆P) Csystemic << Cpulm

42. Special Characteristics of the Pulmonary Circulation: high compliance Ability to promote a decrease in resistance as blood pressure rises viscosity length 8hl R = Remember that resistance to Flow = pr4 radius

43. Pulmonary blood vessels are much more compliant than systemic blood vessels. Also the system has a remarkable ability to promote a decrease in resistance as the blood pressure rises. Two reasons are responsible: Recruitment: opening up of previously closed vessels Distension: increase in caliber of vessels

44. Special characteristic of blood vessels surrounding alveoli: hypoxic vasoconstriction When PO2 within the alveoli decreases there is a decrease in blood flow to that alveolus This is called hypoxic vasoconstriction Thought to be the result of O2-sensitive K+ channels in the smooth muscle membrane. At low O2 the K+ channels close, the Em rises, and the cell reaches threshold and depolarizes and contracts. smooth muscle cell This phenomenon is just the opposite the response to hypoxia you get with arteriole smooth muscle in the systemic circulation, but it is an important feature of the pulmonary circulation that helps to match perfusion with ventilation

45. Pathological Examples of Altered Respiratory Mechanics Pulm. Circ. Normal Emphysema Asthma Longer paths for diffusion Capillary enlargement (e.g., Mitral Stenosis) Exercise

46. Carriage of blood gases How are gases carried by the blood?? all values are in ml of gas/100 ml solution H2O or plasma (pH = 7.4)Whole blood (Hct = 0.45) dissolved combined dissolved combined O2(at a PO2 = 100 mm Hg) 0.3 0 0.3 19.5 CO2(at a PCO2 = 40 mm Hg) 2.6 43.8 2.6 46.4 SCO2 = 0.03 mmol/L / mm Hg SO2 = 1.37 µmol/L / mm Hg note the difference in units

47. Carriage of blood gases How are gases carried by the blood?? all values are in ml of gas/100 ml solution H2O or plasma (pH = 7.4)Whole blood (Hct = 0.45) dissolved combined dissolved combined O2(at a PO2 = 100 mm Hg) 0.3 0 0.3 19.5 CO2(at a PCO2 = 40 mm Hg) 2.6 43.8 2.6 46.4 SCO2 = 30.0 µmol/L / mm Hg = 0.65 ml/L / mm Hg SO2 = 1.37 µmol/L / mm Hg = 0.03 ml/L / mm Hg O2: 99% como oxihemoglobina, 1% disuelto CO2: 67% como bicarbonato, 24% como carboxihemoglobina, 9 % disuelto

48. The oxygen-binding site of oxyhemoglobin, space filling model (a) and stick model (b). The Fe2+ ion is bound to oxygen. The Fe2+ ion lies almost in the heme plane. Valine E11 and phenylalanine CD1 provide a hydrophobic environment at the oxygen-binding site.

49. a a b b Myoglobin molecule heme + globin monomer Hemoglobin molecule tetramer, 2a2b

50. Spectral characteristics of Hemoglobin: color changes with reaction of iron heme Oxygenation: Hb(deep red to bluish) + O2HbO2(oxyhemoglobin; red) readily reversible in fact, since Hb is a tetramer the reaction is really Hb + 4O2Hb(O2)4 Oxidation:Hb(Fe2+)Hb(Fe3+)(methemoglobin; brownish) difficult to reduce CO reaction: Hb + CO HbCO(carboxyhemoglobin; bright red, pink)very high affinity (230X greater than for O2) (deoxyhemoglobin)