1. CS 2015 Alveolar Ventilation and Factors Influencing It Christian Stricker Associate Professor for Systems Physiology ANUMS/JCSMR - ANU Christian.Stricker@anu.edu.au http://stricker.jcsmr.anu.edu.au/Ventilation.pptx Christian.Stricker@anu.edu.au http://stricker.jcsmr.anu.edu.au/Ventilation.pptx THE AUSTRALIAN NATIONAL UNIVERSITY

2. CS 2015

3. Aims At the end of this lecture students should be able to outline different components of ventilation; discuss the components of physiological dead space; explain how ventilation determines partial pressure of CO 2 ; recognise that R AW and compliance determine the speed of gas exchange in alveoli; and illustrate how uneven ventilation of lung tissue can arise.

4. CS 2015 Contents Review of Global ventilation –Physiological dead space and its elements –Total ventilation, dead space ventilation –Alveolar ventilation and alveolar CO 2 –Speed of gas exchange Local ventilation –Larger compliance at base than apex –Local R AW and C L –Factors determining uneven pulmonary ventilation

5. CS 2015 Review of Changes in Axis along bottom indicates distance from nose. At each step, ↓. Note notation.

6. CS 2015 1. Global Ventilation (over whole lung as an entity) Total Pulmonary Ventilation = Physiological Dead Space Ventilation + Alveolar Ventilation

7. CS 2015 Total Ventilation Total ventilation: (Volume per minute) –Example: Breathing frequency (12 bpm) and tidal volume (TV; 0.5 L) Two components of air volume: –“dead space” (NO gas exchange) and –alveoli (ONLY gas exchange). In a healthy person, “dead space” is called physiological dead space. How big is ventilation of physiological dead space at TV (“inefficiency”)? ¼ - ⅓. How can physiological dead space be determined?

8. CS 2015 Physiological Dead Space Ventilation

9. CS 2015 Measuring Dead Space Single breath method (Christian Bohr, ~1900). Clinical relevance: Bronchiectasis, ventilation-perfusion disturbances (obstruction by tumour, emboli, etc.). Despopoulos & Silbernagl 2003

10. CS 2015 Dead Space Ventilation ( ) If TV increased from 0.5 to 0.7 L, as part of will be smaller and vice versa. Consideration for snorkel: –Snorkel volume increases physiological dead space. –Volume must be limited (in relation to TV): standards! –Consequences for alveolar gas pressures and/or breathing work: CO 2 retention.

11. CS 2015 Physiological Dead Space (V D ) Two components –Anatomical dead space: airways (nose → bronchioli) –Functional dead space: ventilated lung parts, which are not perfused (~0 for healthy person; next lecture). Roles of anatomical dead space: –Preparation for gas exchange (within first few cm): Cleaning of air (respiratory epithelia) Water saturation (100%) Temperature control (warming up) –For particular, V D sets limits how much CO 2 can be breathed off: sets alveolar gas concentrations (FRC). –Modulation of R AW (modulated by CO 2 ).

12. CS 2015 Functional Dead Space Functional dead space: ventilated parts of lung, which are not perfused (see next lecture). –In a healthy human, physiological dead space is equivalent to anatomical dead space; i.e. functional dead space is very small (~ 0 L). –Rises in pathology: atelectasis (“air free” areas). Problem with functional dead space: –Hypoxaemia ( ↓, ↑): no gas exchange – shunt. –See next lecture (control of gas exchange under patho- logical conditions: mixing of venous and arterial blood).

13. CS 2015 [CO 2 ] during Breathing Cycle [CO 2 ] can be measured on- line. At beginning of E, [CO 2 ] = 0: absolute dead-space. [CO 2 ]↑ after delay. Steep rise in [CO 2 ]. [CO 2 ]↑ linearly towards end of E (CO 2 delivery rate to alveoli). At end of E, [CO 2 ] =. During early I, rapid drop of [CO 2 ] to 0.

14. CS 2015 Alveolar Ventilation

15. CS 2015 Alveolar Ventilation (Physiologically relevant part of ventilation) Alveolar ventilation ( ) = total ventilation - dead space ventilation (≈ const): Properties of –Under resting conditions, is ~ 70 - 75 % of. –TV, V D and, therefore, V A are proportional to body height, age, sex and ethnicity.

16. CS 2015 Rate of Gas Renewal in Alveoli TV = 350 mL FRC = 2300 mL (average ♂) With every TV, only 15% of gas volume in FRC refreshed. Exponential decay of concentration: time constant ( τ ). For normal ventilation, τ is ~23 s. –if is halved, then τ is doubled and vice versa. Slow replacement of alveolar air –prevents sudden changes in and. –stabilises feed-back mechanisms for respiratory control ( ). Modified from Guyton & Hall, 2001

17. CS 2015 and ↑ causes ↓ and vice versa (40 mmHg = 5.3 kPa). Relevance: Mountain climbing, diving, many clinical conditions. Consequence of ↑: → ↓ → ↑ → ↑ Modified after Berne et al., 2004

18. CS 2015 Alveolar Ventilation in Exercise Linear increase in with increasing exercise. Alveolar gasses remain largely identical with increasing exercise: central control of respiration (see that lecture). Gas exchange rate ↑ with exercise ( τ becomes shorter). increases more than : improvement with exercise. Guyton & Hall,12. ed., 2011

19. CS 2015 2. Local Ventilation (between different alveoli and lung segments)

20. CS 2015 Local Ventilation Differences Radioactive gas inhaled to track rate of local ventilation via radiation counting (scintigraphy). Finding to explain: upper lung areas are less ventilated than the lower ones. Modified after West, 6. ed., 2003

21. CS 2015 Distribution of Ventilation For same ΔP L, ΔV at base bigger than at apex (C L larger). Ventilation is smallest at apex, biggest at base (C L ). Difference largely disappears when laying down or in zero gravity (space): Lay down when lung function is poor… Emphysema starts at apex of lung… Berne et al., 2004 If upright, P L (= P A - P pl ) biggest at top and smallest at base (“hanging from the top” - due to gravity): apex is more inflated than base as P L tracks volume. Lung at apex is more inflated than at base (P L ).

22. CS 2015 Ventilation between Lobuli How fast can an alveolus equilibrate after a volume change? Alveolar filling takes time due to small flow in terminal bronchioli. BOTH, compliance (local C L ) and resistance (local R AW ) determine time constant of filling (local ventilation). R AW ↑ and C L ↑ → slower filling. R AW ↓ and C L ↓ → faster filling. Berne et al., 2004

23. CS 2015 Ventilation between Lobuli Ideally, time constant of filling is i.e. product of R AW and C L. Consequence: uneven alveolar ventilation if local R AW and C L vary within lung areas. Consequence for –ventilation: uneven and in different lung areas; and –perfusion (see next lecture…). Application: in COPD, asthma, emphysema, tumours, foreign body aspiration (peanut), etc. Berne et al., 2004

24. CS 2015 Take-Home Messages Two parts of physiological dead space: anatomical and functional; latter normally small. Alveolar ventilation ≈ 0.7 of total ventilation. Gas exchange is slow (TV vs FRC ≈ 15%): stabilises and. is inversely proportional to ventilation. R AW and C L determine extent of ventilation: if increased, exchange is longer and vice versa. Ventilation is not uniform across lung: worse at top; better at bottom.

25. CS 2015 pH A↓↓↓ B↓↑↑ C↓↑↓ D↑↑↓ E↑↓↑ MCQ During strenuous exercise, O 2 consumption and CO 2 formation can increase up to 20-fold. Ventilation increases almost exactly in step with this increase in O 2 consumption. Which of the following statements best describes the changes of, and arterial pH in a healthy athlete during such exercise?

26. CS 2015 That’s it folks…

27. CS 2015 pH A↓↓↓ B↓↑↑ C↓↑↓ D↑↑↓ E↑↓↑ MCQ During strenuous exercise, O 2 consumption and CO 2 formation can increase up to 20-fold. Ventilation increases almost exactly in step with this increase in O 2 consumption. Which of the following statements best describes the changes of, and arterial pH in a healthy athlete during such exercise?