THE AUSTRALIAN NATIONAL UNIVERSITY

1. THE AUSTRALIAN NATIONAL UNIVERSITY Alveolar Ventilation and Factors Influencing ItChristian StrickerAssociate Professor for Systems PhysiologyANUMS/JCSMR - ANUChristian.Stricker@anu.edu.auhttp://stricker.jcsmr.anu.edu.au/Ventilation.pptx

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 CO2; • recognise that RAW and compliance determine the speed of gas exchange in alveoli; and • illustrate how uneven ventilation of lung tissue can arise.

4. Contents • Review of • Global ventilation • Physiological dead space and its elements • Total ventilation, dead space ventilation • Alveolar ventilation and alveolar CO2 • Speed of gas exchange • Local ventilation • Larger compliance at base than apex • Local RAWand CL • Factors determining uneven pulmonary ventilation

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

6. 1. Global Ventilation (over whole lung) Total Pulmonary Ventilation = Physiological Dead Space Ventilation+ Alveolar Ventilation

7. 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. Physiological Dead Space Ventilation

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

10. 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: CO2 retention.

11. Physiological Dead Space (VD) • 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 , VD sets limits how much CO2 can be breathed off: sets alveolar gas concentrations (FRC). • Modulation of RAW(modulated by CO2).

12. 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. [CO2] during Breathing Cycle • [CO2] can be measured on-line. • At beginning of E, [CO2] = 0: absolute dead-space. • [CO2]↑ after delay. • Steep rise in [CO2]. • [CO2]↑ linearly towards end of E (CO2 delivery rate to alveoli). • At end of E, [CO2] = . • During early I, rapid drop of [CO2] to 0.

14. Alveolar Ventilation

15. 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, VD and, therefore, VA are proportional to body height, age, sex and ethnicity.

16. 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,τis ~23 s. • if is halved, thenτ is doubled and vice versa. • Slow replacement of alveolar air • prevents sudden changes in and ; and • stabilises feed-back mechanisms for respiratory control ( ). Modified from Guyton & Hall, 2001

17. and Modified after Berne et al., 2004 • ↑ causes ↓ and vice versa. • Relevance: Mountain climbing, diving, many clinical conditions. • Consequence of ↑: → ↓ → ↑ → ↑

18. Alveolar Ventilation in Exercise Guyton & Hall,12. ed., 2011 • 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 (τbecomes shorter). • increases more than : improvement with exercise.

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

20. Local Ventilation Differences Modified after West, 6. ed., 2003 • 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.

21. Distribution of Ventilation • If upright, PL (= PA - Ppl) biggest at top and smallest at base (“hanging from the top” - due to gravity): apex is more inflated than base as PLtracks volume. • Lung at apex is more inflated than at base (PL). Berne et al., 2004 • For same ΔPL, ΔV at base bigger than at apex (CLlarger). • Ventilation is smallest at apex, biggest at base (CL). • Difference largely disappears when laying down or in zero gravity (space): Lay down when lung function is poor… • Emphysema starts at apex of lung…

22. 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 CL) and resistance (local RAW) determine time constant of filling (local ventilation). • RAW↑and CL↑→slower filling. • RAW↓and CL↓→faster filling. Berne et al., 2004

23. Ventilation between Lobuli • Ideally, time constant of filling isi.e. product of RAWand CL. • Consequence: uneven alveolar ventilation if local RAWand CLvary 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. 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. • RAWand CLdetermine extent of ventilation: if increased, exchange is longer and vice versa. • Ventilation is not uniform across lung: worse at top; better at bottom.

25. MCQ During strenuous exercise, O2 consumption and CO2 formation can increase up to 20-fold. Ventilation increases almost exactly in step with this increase in O2 consumption. Which of the following statements best describes the changes of , and arterial pH in a healthy athlete during such exercise?

26. That’s it folks…

27. MCQ During strenuous exercise, O2 consumption and CO2 formation can increase up to 20-fold. Ventilation increases almost exactly in step with this increase in O2 consumption. Which of the following statements best describes the changes of , and arterial pH in a healthy athlete during such exercise?