1. Ventilation

2. Intro: why do we breathe?

3. Key Terms Ventilation: Movement of air into and out of the lungs Gas exchange: Movement of gases across membranes according to pressure gradients Pressure gradients: Determined by the partial pressure of the gas Gases: Oxygen necessary for cellular respiration; Carbon dioxide is a volatile acid

4. Breathing, ventilation and respiration Used synonymously –Used to think respiration occurred in the lung Ventilation: movement of air Respiration: cellular utilization of O 2

5. Pulmonary minute ventilation (V E ) –The rate of expired ventilation –Usually expressed in L/min –V E = V T x f –Expired ventilation and inspired essentially the same, may differ in transition from rest to exercise Ventilation.

6. Temperature, pressure, water vapor all impact gas volumes Gas laws –Boyle’s law: Pressure and volume inversely related; P 1 V 1 =P 2 V 2 So, as pressure goes up, volume goes down and vice versa –Charles’ law: Temp and volume directly related; V 1 /T 1 = V 2 /T 2 So, as temperature goes up, volume goes up and vice versa –Dalton’s law: The total P of a gas is determined by the partial pressures of all the constituent gases –STPD Standard temperature, pressure, dry ST=0°C, P=760 mmHg, 0 mmHg H 2 O vapor pressure (P H2O ) –BTPS Body temperature, pressure, saturated Body temperature, P= ambient pressure, P H20 =47 mmHg at 37°C –ATPS Ambient temperature, pressure, saturated T=ambient, P=ambient, P H20 =47 mmHg at 37°C –Typically you collect at ATPS and convert to BTPS (ventilation) or STPD (Vo 2, Vco 2 ); allows comparison across studies Environmental influences

7. Entry of O 2 into the blood

8. Determined Entirely by pressure gradients Partial pressure –Pressure exerted by each gas in a composition –Atmospheric pressure (P Atm ): 760 mmHg –Partial pressure of O 2 (Po 2 ): 159 mmHg (.2094 x 760) –Rest is nitrogen, some argon and very little CO 2 –When air reaches alveoli, Po 2 falls, why? Think of gas laws

9. Entry of O 2 into the blood 1) Water vapor Gas is fully humidified, so at normal body temp, water vapor pressure is 47 mmHg 2) Co 2 is also higher in the alveoli Thus, Po 2 of alveoli about 100-105 mmHg 760 – 47 = 713 or the pressure of the air in the lung –Dalton’s Law 713 x.2094 = 149 (inspired pressure of O 2 ; PiO 2 ) P A O 2 = PiO 2 – (P A CO 2 /RER) –Alveolar gas equation P A O 2 = 149 – (40/.85) or 149-47 = 102 RER = respiratory exchange ratio or Vco 2 /Vo 2 –Usually about 0.85 at rest with mixed diet

10. Entry of O 2 into the blood Once O 2 gets into alveoli it diffuses into the blood –Due to favorable oxygen gradient (~100 to 40 mmHg) –Most binds with Hb (~97%) –Some dissolved in plasma (3%) Oxygen content of blood (CaO 2 ) CaO 2 =1.34*[Hb]*(%sat of Hb) + 0.003 * PaO 2 CaO 2 = 1.34 * (15mg/dl)*(.98) + 0.003* (100mmHg) CaO 2 = ~20 ml/dl [Hb]= hemoglobin concentration PaO 2 = partial pressure of oxygen

11. Diffusion of gases: Lung

12. Pulmonary diffusion Diffusion of gases through tissues (gel) Major determinants –Partial pressure difference (major) –Solubility of the gas (minor) Gases of lower solubility typically have greater partial pressure gradients

13. Rate of diffusion Determined by –Area available –Thickness –Partial pressure gradient (P 1 -P 2 ) –Diffusion coefficient Determined by solubility and molecular weight

14. Rate of diffusion CO 2 is slightly larger than O 2 (MW; 44 vs 32 g/mol) CO 2 has a much higher solubility coefficient (0.57 vs 0.024) Thus, CO 2 has a greater relative diffusion coefficient (~20 x higher) Thus, O 2 needs a larger pressure gradient to “force” itself across biological membranes

15. Arterial blood gas homeostasis Maintenance of blood gases (PaO 2 and PaCO 2 ) very important –Keep driving pressure for CO 2 and O 2 high –Driving pressure is the difference between arterial and venous pressure (PaO 2 -PvO 2 ) –Note that gradients increase with exercise

16. Oxygen transport Oxygen content CaO 2 = 1.34[Hb]*(%sat) + 0.003 * PaO 2 Cardiac output (Qc) = HR * stroke volume –Thus, total oxygen transport capacity (or delivery) is Qc*CaO 2 or Qo 2 Qo 2 is a measure of how much oxygen is circulated around by the heart in one minute –So, if CaO 2 = 20 ml/dl and Qc equals 30 L/min –Qo 2 = 30 * 0.2 or –Qo 2 = 6L/min

17. Shifting of O 2 dissociation curve Remember: we noted that exercise increases the pressure gradients How?: O 2 dissociation curve shifts –Curve shows the relationship between Po 2, CaO 2 and % Hb saturation Right shifting increases O 2 unloading –Right shift called Bohr effect What shifts the curve?

18. Effects of Co 2 and pH on O 2 transport The shape of the O 2 dissociation curve is altered by 4 variables –pH < 7.4 = right shift >7.4 = left shift –Temperature >38C = right shift <38C = left shift –Co 2 >40 mmHg = right shift <40 mmHg = left shift –2,3 DPG (diphosphoglycerate) Altitude increases this

19. Co 2 transport Co 2 must be transported from tissues to blood and lungs for removal Carried in 3 ways –Bound to Hb (carbamino compounds) (15-20%) –Dissolved in plasma (5- 10%) –As bicarbonate (HCO 3 - ), ~70%

20. Co 2 transport More Co 2 dissolves (than O 2 ) in plasma due to greater solubility Binding of Co 2 to Hb occurs at different site than O 2 Co 2 combines with H 2 O to form bicarbonate

21. Co 2 content Amount of Co 2 carried in the blood depends upon Pco 2 Unlike oxygen, the Co 2 curve is linear over a much greater range Thus, as Co 2 production increases –greater driving pressure (from tissue to blood) –As Co 2 is extremely soluble, this increases Co 2 transport (No upper limit)

22. When Co 2 increases in blood –Shifts O 2 curve to right –Facilitates unloading of O 2 at the tissues –Called Bohr effect When O 2 falls –Shifts Co 2 curve up and right –Facilitates greater Co 2 loading –Called Haldane effect Thus, at the level of the tissue, high CO 2 facilitates unloading of O 2 which allows greater amount of CO 2 to be carried in blood At the lung, high O 2 forces CO 2 from Hb (and plasma) and it is then exhaled Effect of O 2 on Co 2 transport (and vice versa)

23. Arterial blood gases Note how ventilation and PaCo 2 inversely mirror each other Note also the effect on pH Major function of the ventilatory system is to rid the body of Co 2 and control pH V A = VCo 2 /PaCo 2

24. Buffering of metabolic acids pH is a measure if the acidity of the blood Several sources of acid are during exercise –Lactic acid (HLa) –Carbon dioxide These cause a fall in pH –Bicarbonate is a very effective buffer A buffer helps to prevent a change in pH pK: Dissociation constant. pH at which acid (or base) is 50% dissociated (50% acid and 50% base)

25. Buffering of metabolic acids Lactic acid produced –HLa → La - + H + –H + + HCO 3 - → H 2 CO 3 → H 2 O + CO 2 (exhaled) Co 2 produced –CO 2 + H 2 O → H 2 CO 3 → HCO 3 - + H + (reverses at lung) pH –Negative logarithm of the hydrogen concentration –pH = pk for HCO 3 - + log [base/acid) –pH = 6.1 + log [HCO 3 - /(pCO 2 *0.03)] (Henderson-Hasselbalch eq.) –pH = 6.1 + log [24 /1.2) –pH = 6.1 + 1.3 –pH = 7.4

26. Control of pH Co 2 and pH (actually the H + ) stimulate ventilation –Chemoreceptors Carotid sinus Centrally (medulla) –Sensitive to changes in Pco 2 and H + Stimulate breathing to expel CO 2 and partially compensate for the metabolic acidosis

27. Ventilation Gross Anatomy –Pharynx –Trachea –Bronchus –Alveolus

28. Ventilation –Moves air into and out of lung Two separate areas of lung –Conducting zone –Respiratory zone –Conducting zone Network of tubes whose function is movement of air –Trachea and Bronchi –Respiratory zone Large, thin area where gas exchange occurs –Respiratory bronchioles and alveolar ducts

29. Ventilatory mechanics Diaphragm –Main muscle of ventilation –Only skeletal muscle necessary for life Accessory muscles –Intercostals External –Inspiration Internal –Expiration –Sternocleidomastoid, Scalenes Inspiration –Abdominal muscles Expiration

30. Note how much ventilation can increase –Due to large increases in tidal volume and frequency –Increases in tidal volume (V T ) largely due to accessory muscles –Increases in frequency (f) due to diaphragm Ventilatory volumes

31. Dead space and alveolar ventilation Ventilation (V E ) is the total amount of air moved in and out of the lungs –V E = V DS + V A –Dead space (V DS ) Anatomic dead space –Conducting zone Physiologic dead space –Diseased areas Dead space/tidal volume ratio –At rest ratio of V D /V T ~25- 40% –With exercise V D /V T falls, why? –Alveolar ventilation Ventilation of the gas exchange units

32. Static lung volumes Volumes and capacities –Volume: single measure Residual volume (RV) –The amount of air in the lung after a maximal expiration Expiratory reserve volume (ERV) –The amount by which you can increase expiration after a normal exhalation Inspiratory reserve volume (IRV) –The amount by which you can increase inspiration after a normal inspiration Tidal volume (V T ) –The volume of a normal breath Total lung capacity (TLC) –RV, ERV, V T and IRV Vital capacity –ERV, V T and IRV Functional residual capacity –RV, ERV Where humans breath from Inspiratory capacity –V T, IRV

34. Composition of Alveolar gases 100% oxygen Air breathing; no water or CO 2

35. Movement of gas: diffusion

36. Diffusion Oxygen –Breathed into lungs –Diffuses across blood gas barrier –Binds with hemoglobin (97%) –Dissolved in plasma (3%) –Circulated to tissues –Diffuses into tissues –Binds with myoglobin Keeps oxygen pressure homogeneous within tissues –Utilized in mitochondria Mb

37. Transit time Capillary blood volume (Vc) –The blood that is in the capillaries at one instant in time Transit time –the ratio of V C /blood flow V C =~70 ml Qc = 100 ml/s TT = 0.7 sec More than adequate for equilibration of blood gases Note that CO 2 equillibrates MUCH faster than O 2 ; why?

38. Control of ventilation Respiratory control center –Brainstem Medulla Pons Feed forward –Central command Feedback –Peripheral and central chemoreceptors

39. Central and peripheral control Feed forward –Sometimes called “central command” –Co-activation of cardiovascular, ventilatory and musculoskeletal systems Central chemoreceptors –Sensitive to changes in pH –Caused by Co 2 as H + cannot cross Blood brain barrier CO 2 + H 2 O H 2 CO 3 HCO 3 - + H + Peripheral chemoreceptors –Carotid sinus –Muscle metaboreceptors Both sensitive to changes in pH, PCO 2 and PO 2 (particularly at high atltitude) Peripheral mechanoreceptors –Sensitive to limb movement

40. Feed forward 1 1 Peripheral 3 2 3 & 4 Central Peripheral chemoreceptors and mechanoreceptors