1. The alveolar-capillary unit is a complex structure that facilitates gas exchange through diffusion between alveoli and surrounding capillaries. It provides a thin barrier and large surface area for oxygen and carbon dioxide exchange. 2. Surfactant, produced by type II alveolar cells, reduces surface tension in alveoli to increase lung compliance and prevent collapse during expiration. It plays several roles including reducing work of breathing and stimulating the lung's immune system. 3. Gas exchange occurs through diffusion as blood passes through alveolar capillaries. Oxygen diffuses into the blood from alveoli while carbon dioxide diffuses out of the blood into alveoli based on partial pressure gradients

1. The Alveolar- Capillary Unit Dimitar Sajkov MD, DSc, PhD, FRACP

2. Alveolar - Capillary Unit

3. Alveolar - Capillary Unit Complex cardiovascular system with multiple functions: Gas exchange Oxygen sensing and redistribution of pulmonary blood flow Non-respiratory functions physical and chemical filter activating and endocrine functions fluid-balance regulator

4. Alveoli Small, thin-walled, inflatable sacs at end of bronchioles Surrounded by a jacket of pulmonary capillaries Provide thin barrier and enormous surface area for gas exchange by diffusion Type II cells secrete surfactant

5. Alveolar - Capillary Unit

6. Alveolar - Capillary Unit A scanning electron micrograph of the alveoli. Humans have a thin layer of about 700 million alveoli within their lungs. This layer is crucial in the process called respiration, exchanging O 2 and CO 2 with the surrounding blood capillaries.

8. Alveolar - Capillary Unit Structure

9. Alveolar - Capillary Unit 1 - Capillary 2 - Alveolus 3 - RBC 4 - Endothelium 5 - Basal Membrane 3 4 5

10. Gas Exchange

11. Gas Exchange - Diffusion

12. Gas Exchange Partial Pressures of O 2 and CO 2 in the body (normal, resting conditions): Alveoli PO 2 = 100 mm Hg PCO 2 = 40 mm Hg Alveolar capillaries Entering the alveolar capillaries PO 2 = 40 mm Hg (relatively low because this blood has just returned from the systemic circulation & has lost much of its O 2 ) PCO 2 = 45 mm Hg (relatively high because the blood returning from the systemic circulation has picked up CO 2 )

13. Gas Exchange While in the alveolar capillaries, the diffusion of gasses occurs: O 2 diffuses from the alveoli into the blood & CO 2 from the blood into the alveoli. Leaving the alveolar capillaries PO 2 = 100 mm Hg PCO 2 = 40 mm Hg

14. Gas Exchange Blood leaving the alveolar capillaries returns to the left atrium & is pumped by the left ventricle into the systemic circulation. This blood travels through arteries & arterioles and into the systemic, or body, capillaries. As blood travels through arteries & arterioles, no gas exchange occurs. Entering the systemic capillaries PO 2 = 100 mm Hg PCO 2 = 40 mm Hg Body cells (resting conditions) PO 2 = 40 mm Hg PCO 2 = 45 mm Hg

15. Because of the differences in partial pressures of O 2 & CO 2 in the systemic capillaries & the body cells, O 2 diffuses from the blood & into the cells, while CO 2 diffuses from the cells into the blood. Leaving the systemic capillaries PO 2 = 40 mm Hg PCO 2 = 45 mm Hg Blood leaving the systemic capillaries returns to the heart (right atrium) via venules & veins (and no gas exchange occurs while blood is in venules & veins). This blood is then pumped to the lungs (and the alveolar capillaries) by the right ventricle. Gas Exchange

16. Gas Exchange

17. Non-Respiratory Functions of the Lung Physical Filter Chemical Filter Activating Organ Endocrine Organ Fluid Balance regulator

18. Physical Filter All particles larger than red blood cells (e.g. bubbles, clots, fat cells, fibrin) Role in removing damaged white cells Rapidly cleared by phagocytosis and proteolytic enzymes

19. Chemical Filter (John Vane’s theory) Locally Acting (removed) serotonin (90%) noradrenaline (35%) acetylcholine (95%) bradykinin (90%) angiotensin I (30%) PGE 2 (95%) PGF 2a (95%) leukotrienes (95%) ATP, AMP (90+%) Circulating (not affected) dopamine adrenaline histamine vasopressin angiotensin II PGA 2 substance P oxytocin eledoisin

20. Compliance C =  V/  P Describes how much lung inflation can be achieved by a unit pressure increase Measures the elastic characteristics, or “stretchiness” of the lung Varies with the degree of lung inflation and is different on inspiration or expiration

21. Compliance

22. Surface Tension and Compliance Kurt von Neergard (1929) suggested that ST was less than that of water and that surface active substances were present

23. Surface Tension 75% of tendency of the lung to collapse is due to surface tension (ST) at the gas-liquid interface

24. Surface Tension in Lung Mechanics r = 1 cm r = 10  m = = 10 x 10 -4 cm Assume ST is constant at 72 dyne/cm Law of Laplace: P = 2T/r A ) P = 2T/r = 2 x 72/1 = = 144 dyne/cm 2 B ) P = 2T/r = 2 x 72/10 -3 = = 144,000 dyne/cm 2 = = 80 cmH 2 O 1000 X the pressure is required to maintain B than A A B

25. Alveolar Surface Tension Forces Attraction of liquid molecules produces surface tension (ST), which draws liquids closer together resists force that would increase the area of the surface ST is reduced by surfactant

26. Surfactant Phospholipid produced by type II alveolar cells  surface tension in alveoli  total lung compliance  lung “stability”

27. Reduces “stiffness” of the lungs Protects patency of small airways Prevents total collapse of the alveoli (i.e. stabilises alveoli) Reduces work of breathing Prevents small alveoli emptying into larger ones Roles of Surfactant

28. Roles of Surfactant Prevents movement of fluid into the alveolus and keeps lungs dry (osmotic > hydrostatic pressure) Acts as an anti-glue Stimulates Lung host defence system: Immunosuppresses Acts as a chemotactic agent Opsonises bacteria Enhances mucous clearance

29. Surfactant Composition Phospholipids 80% dipalmitoyphosphatidylcholine (DPCC) 60% Phosphatidylglycerol/ethanolamine/inositol 20% Neutral Lipids 10% Mostly Cholesterol Surfactant Proteins 10% SP-A; SP-D: hydrophilic SP-B; SP-C: hydrophobic L/S ratio: predictor of foetal lung maturity L – lecithin S – Sphyngomyelin

30. Surfactant Proteins SP-A: Hydrophilic formation of tubular lattice regulatory function defence function SP-B: Hydrophobic re-formation of layer after compression SP-C: Hydrophobic spreading function SP-D: Hydrophilic regulatory function defence function

31. Surfactant Metabolism Produced, stored and secreted by type II alveolar cells and Clara cells Half-time for turnover 5 - 10 hours 90% recycled by type II pneumocytes 10% cleared by alveolar macrophages SP-A is primary regulator of metabolism and lung defence mechanisms

32. Type II Alveolar Cell

33. Surfactant

34. Loss of Surfactant Function Inhibition by serum proteins (albumin), fibrinogen, meconium, bilirubin and degradation products Inactivation by O 2 radicals and enzymes (phospholipases) Decreased pool size due to lung injury Mechanical factors (eg. Alveolar collapse) Enhanced conversion to small aggregate forms of lipids

35. Interdependence

36. Interdependence

37. The Foetal Lung Airways formed by week 16 Alveoli start to form ~ at week 20; ~20 million alveoli present at birth Alveolar type II cells appear ~ at week 24 Foetal lung fluid (5 ml/kg/hr) maintains lung at FRC [high Cl - , low HCO 3 and protein c.f. plasma] Foetal breathing: development of neural control

38. Amniocentesis: phosphatidylcholine increases rapidly after ~ 33 wk Lecithin/Sphingomyelin ratio + 2.0 at ~ 35 wk 80% of infants < 30 wk have RDS 45% of infants < 32 wk have RDS At birth: adrenaline activates Na channels in type II cell (vasopressin, cortisol and T 3 are also involved); aquaporins: water channel-forming proteins The Foetal Lung

39. Not conducive to gas exchange Thick blood gas barrier Low compliance Immature epithelial cells Low surfactant levels Small area for gas exchange Poorly vascularized High resistance to blood flow Conducive to gas exchange Thin blood gas barrier Highly compliant Mature epithelial cells Adequate surfactant Large area for gas exchange Highly vascular Low resistance to blood flow Immature lung Mature lung

40. Surfactant - Acute Effects Oxygenation improvement Improved lung compliance More uniform lung inflation  inflammation and implementation of lung defence mechanisms

41. Acute Lung Injury: A Condition Involving Impaired Oxygenation Defined as: A ratio of the partial pressure of arterial oxygenation (PaO 2 ) to the fraction of inspired oxygen (FiO 2 ) that is < 300 regardless of whether or how much positive end-expiratory pressure is used to provide respiratory support Bilateral pulmonary infiltrates on chest radiograph Pulmonary Artery Occlusion Pressure of < 18 mmHg or no clinical evidence of elevated left atrial pressure When the injury is “severe”, we have recognizable clinical features of ARDS.

42. ARDS – Predisposing Factors Direct Injury Inhalation Injury (i.e. Burns) Aspiration (i.e. chemical pneumonitis) Indirect Injury Bacterial Sepsis (i.e. endotoxemia) Pancreatitis With some of these “predisposing conditions”, the risk of A.R.D.S. is substantial Gastric Aspiration & Sepsis: Overall Mortality of 30 - 40 %

43. ARDS - Management Measures to correct the abnormality in vascular permeability or to limit the degree of inflammatory reaction present in ARDS, do not exist. Clinical management involves primarily supportive measures aimed at maintaining cellular and physiologic function, while the acute lung injury resolves. What cellular functions are you trying to maintain ? Alveolar Gas Exchange Organ Perfusion Aerobic Metabolism

44. Alveolar – Capillary Unit