1. Charles University in Prague, 1 st Medical Faculty, Lab. of biocybernetics & Computer-Aided Learning Assessment of respiratory system function Stanislav Matoušek

2. What is the function of lungs? Alveolus Ventilation – mechanical function of the lung – get air in and out Perfusion with blood – get blood in and out Diffusion – get gas molecules from air to blood and back Matching of ventilation and perfusion

3. Possible respiratory system disturbances // ventilation // perfusion // distribution of ventilation and per- fusion = ventilation perfusion mismatch // diffusion Important: Ventilation, perfusion and their distribution are feedback regulated processes. Disturbance: – 1. In the effector part (lungs, resp. muscles for ventilation, heart for perfusion) – 2. In the regulator part (sensors, CNS eg. in uremia, liver in hepatopulmonary syndrome)

4. The overall measure of respiratory system function pO2 & pCO2 in arterial blood - („Astrup“) O2 solubility in water is low => need of Hemoglobin pO2 = 13,3 kPa = 100 Torr pCO2 = 5,3 kPa = 40 Torr (1 kPa = 10 cm H2O = 7,6 mmHg or Torr)

5. Solubility of gases in liquids

6. Oxygen-hemoglobin dissociation curve

7. Ventilation Is carried out by respiratory muscles, that change volume of thorax. Volume changes cause changes of pressures Changes of pressure in alveoli cause air flow ( ↑ transthoracic pressure – expiration; ↓ transthoracic ressure – inspiration) Flow behaves according to Ohm’s law

8. Spirometry - Measure of ventilation volumes (and air flow)

9. Spirometry

10. Spirometry – Volume-flow loop

11. Pressures in the lungs Transthoracic pressure Transpulmo- nary pressure -12 mmHg +1 mmHg

12. Normal lung

13. Lung compliance Is a measure of the pressures developed by the effect of the lung elasticity while the lung is at rest. C = V breath / (p endin. - p endexp. ) = ΔV /Δ p The pressures are not pressures needed to make the air flow (it is measured at rest/0 flow points They are pressures needed to keep the lung inflated !! The more you want to have the lung inflated, the more pressure you need Decreased compliance = stiff lung = restrictive disease Increased compliance - loose lung – emphysema – (increased compliance does not cause problems by itself. However, it causes increased resistance during expiration)

14. Restrictive disease

15. Lung resistence Depends on pressures needed to make the air flow (transthoracic in normal breathing) R = (p environ. - p alv. )/ F = Δ p / F Increased resistance – obstruction in the lungs – obstructive desease

16. Obstructive disease

17. Measuring of the Compliance of the lungs C = V breath / (p endin. - p endexp. ) Direct – difficult, because you need to measure the transpulmonary pressure difference Easy in artificial ventilation Indirect - decreased lung compliance = stiff lung - will cause ↓ decreased static lung volumes, especially ↓ in VC a FVC.

18. Measuring of the resistance of the airways R = (p environ. - p alv. )/ F Direct: Temporary occlusion method (spirometry, whole body pletysmography) Indirect: Increased airway resistance = blonchoconstriction will cause decrease of flow and „dynamic lung volumes“ FEV1, FEF25- 75% and MEFs. -12 mmHg +1 mmHg

19. What type of lung disease? a) b) c)

20. Normal spirogram

21. Obstruction- medium degree

22. Obstruction parameters

23. Restrictive disease

25. Real world situation

26. Whole body plethysmography

27. Other methods of measuring Residual volume and TLC Nitrogen washout method -person breathes in pure oxygen - concentration of N2 in the expired air is measured Helium dilution method – Given amount of Helium

28. Ventilation disorders Lung impairment (mechanical properties change) – Obstructive disease - ↑ increased resistance R of airways (R = “dynamic lung resistance”) – Restrictive disease – ↓ decreased lung compliance C (‘ ↑ static resistance” `; C = 1/ static lung resistance) Chest wall impairment –↓ decreased C of chest wall – severe scoliosis, extensive fibrosis, serial fractures Insufficient activity of respiratory muscles (// innervation or // muscle strength, // of CNS ) – E.g.. Respiratory centre suppression in barbiturate poisoning, myasthenia gravis

29. Perfusion All the blood volume flows through lungs Also behaves according to Ohm’s law

30. Disorders of perfusion Causes – Embolization to the pulmonary artery (increased resistante to the blood flow) – Pulmonary hypotension (right heart failure) – Pulmonary hypertension Manifestation – Pulmonary hypertension causing ever right heart failure in massive embolism – Decrease in pO2 (increase in pCO2), Increase of shunting Blood flows fast through a small part of the lungs only – the rest functions as dead space

31. Measuring perfusion a) Ventilation - perfusion scan - diagnosis of pulmonary embolism and parenchymal lung disease should be performed in all clinically stable patients with the suspicion of pulmonary embolism should be performed in all clinically stable patients with the suspicion of pulmonary embolism - Ventilation scan - 133Xe gas - Perfusion scan – microspheres of albumin (50-100 mm labeled with gamma emitting isotope 99mTc - “Mismatch” in ventilation and perfusion is characteristic for PTE

32. Lung scintigraphy -perfusion

33. Lung scintigraphy - ventilation

34. West’s weir

35. Physiological ventilation distribution

36. Distribution of ventilation and perfusion In healthy lung, the most perfused part is at the base… this part is at the same time the most ventilated one (No mismatch ) Various pathologies can cause ventilation perfusion mismatch Every lung region (size is on us to decide) has its ventilation perfusion ratio V A /Q - number from O to ∞ … norm 0,8 - 1

37. Pulmonary shunt Extreme case of ventilation perfusion mismatch Zero local ventilation V A /Q = O Causes: – Atelectasis – Lung edema (alveolar) – Lung inflammation (inflammatory exsudate) – Collapsed lung (pneumothorax) Blood leaving the defect area has low ↓ pO2 and high ↑ pCO2 (no gas exchange) After mixing with blood from healthy regions, ↓ pO2 stays low, but pCO2 normalizes. Why?

38. Dead space Opposite extreme case of ventilation-perfusion mismatch. No perfusion. V A /Q = ∞ Increases of dead space: – Embolism – Emphysema – Bronchiectasia Ventilation of dead space has by itself no influence on blood gases, but it is wasted respiratory work! => Excessive ventilation of dead space can lead to insufficient ventilation of healthy alveoli.

39. Physiological dead space

40. Ventilation perfusion mismatch

41. Is a very common cause of hypoxemia - ↓ pO 2 (low ↑ pCO2 might probably not occur) Etiological factor of dyspnea onset in: – ARDS – COPD, especially chronic bronchitis (smoker) – Asthma

42. Diffusion

43. Diffusion in lungs

44. Rate of diffusion

45. Diffusion impairments Decrease ↓ of diffusion surface S: Emphysema Pneumothorax Increase ↑ in diffusion distance d: Lung fibrosis Lung edema Interstitial pneumonia

46. Measuring „diffusion“ Transfer factor / Lung diffusion capacity

47. Respiratory insufficiency!! Respiratory insufficiency type I (partial, hypoxemic) – pO2 is ↓ low, but pCO2 is normal or even also ↓ lower Respiratory insufficiency type II (global, hypoventilation) – pO2 is ↓ low and pCO2 is ↑ high (respiratory a….)

48. Partial respiratory insufficiency (Type I) Impaired // distribution – Ventilation perfusion mismatch - uneven V A /Q in different lung regions – True shunting (right-left) Impaired // diffusion Through water O2 diffuses about 20x slower than CO2

49. Global respiratory insufficiency (type II) Impaired // ventilation - overall alveolar hypoventilation

50. ARDS Adult/acute respiratory distress syndrom Cause: Sudden damage to alveolo-capillary membrane – interstice and alveoli get infiltrated by plasma and proteins Ventilation-perfusion mismatch appears, in some parts of lungs to the degree of shunting Consequence: Partial respiratory insufficiency in serious cases evolving into global respiratory insufficiency With edema, lung compliance decreases ↓ C, where only interstitial edema => // diffusion

52. ARDS

53. Signs of ARDS Dyspnea – decrease ↓ pO2 Low ↓ lung compliance – breathing faster and more shallow, increased breathing effort Dry irritating cough (sometimes pink sputum) CO2 often decreased ↓ !! = hypocapnia – respiratory acidosis

54. < Osmotic pressure C1C1 C2C2 > = P2P2 P1P1 > = Membrane permeable to water, but NOT to solutes H2OH2O H2OH2O H2OH2O H2OH2O [H 2 O] 1 [H 2 O] 2 =

55. Cell Isotonic environment 290 ± 10 mmol/l Vessel Interstice H20H20 Gradient of hydraulic pressures Gradient of oncotic pressures H20H20

56. arteriole venule capillary Oncotic pressure gradient Hydraulic pressure gradient filtrate movement Lymphatic drainage proteins Interstitial liquid Movement of H 2 O across the lung capillary

57. arteriole venule capillary Oncotic pressure gradient Hydraulic pressure gradient Filtrate movement Lymphatic drainage proteins Interstitial fluid ARDS

58. Causes of ARDS Shock and inflammation – Circulatory shock and severe hypotension – Pulmonary embolism – DIC – Extensive burns – Extensive pneumonia – Sepsis and septic shock – Post-transfusion TRALI Damage from alveolar side – Inhalation of toxic gases and fumes – Long-time O2 toxicity – Aspiration of gastric content – Water aspiration in drowning Other – Lung contusion and chest trauma – Head trauma – Pancreatitis – Heroin overdose

60. Summary