Physiology of gas exchange

gas exchange in lungs

1. PHYSIOLOGY OF GAS EXCHANGE, OXYGEN TRANSPORT Dr. HIMANSHU JANGID

2. In order to survive humans have to be able to extract oxygen from the atmosphere and transport it to their cells where it is utilised for essential metabolic processes anaerobic metabolism is inefficient

3. Alveolar gas transfer Gas flow is convective in larger and medium-sized airways, down to 14th generation Total cross-sectional area of the airway tree 2.5 cm 2 in trachea 70 cm2 in 14th generation 0.8 m2 in 23rd generation Total alveolar surface is 140 m2 Transport of O2 and CO2 accomplished by diffusion in peripheral airways and in the alveoli

4. Gases diffuse according to their partial pressures External respiration : gases exchanged between air and blood Internal respiration : gases exchanged with tissue fluids Oxygen transport : bound to hemoglobin in red blood cells or dissolved in blood plasma Carbon dioxide transport : dissolved in blood plasma, bound to hemoglobin, or in the form of plasma bicarbonate Gas Exchange & Transport: A Passive Process

5. Gaseous Diffusion at Alveolar level Alveoli are the basic units of gas exchange There are 300 million Alveoli. Their size is variable – largest in upper lung & smallest in lower lungs Blood gas barrier is formed by alveolar epithelium, capillary endothelium, basement membrane of each and the interstitial space in between Alveolar epithelium is composed of – mainly type I squamous epithelial cells and some type II alveolar cells that produce surfactant

6. KEY STEPS IN OXYGEN CASCADE Uptake in the lungs Carrying capacity of blood Delivery from lungs to tissue capillaries Delivery from capillary blood to interstitium Delivery from interstitium to individual cells Cellular use of oxygen

7. Physical Principles of Gas Exchange Diffusion of gases through the respiratory membrane Depends on membrane’s thickness, the diffusion coefficient of gas, surface areas of membrane, partial pressure of gases in alveoli and blood Relationship between ventilation and pulmonary capillary flow Increased ventilation or increased pulmonary capillary blood flow increases gas exchange Physiologic shunt is deoxygenated blood returning from lungs

8. Gaseous Diffusion at Alveolar capillary level O2 & CO2 cross the blood gas barrier by passive diffusion along a concentration gradient According to Fick’s law – The rate of transfer of gas through a tissue is proportional to its area and to the partial pressure gradient of the gas and is inversely proportional to the tissue thickness. The diffusion constant depends on the solubility of the gas and is inversely proportional to the square root of its molecular weight. CO 2 diffuses 20 times faster than O 2 due to its higher solubility.

9. Partial pressure Dry air is composed of a mixture of gases. Each gas exerts a partial pressure which is the pressure it would exert if it alone occupied a given volume. Barometric pressure [PB] is the total pressure exerted by this mixture of gases = 760 mmHg at sea level

10. Partial pressure In dry air at sea level PO2 = 760 mmHg X 0.21= 160 mmHg Inspired air is heated to 37ºC, humidified & saturated with water vapour PH2O = 47 mmHg During inspiration in the conducting airways PO2 = [760 – 47 mmHg) X 0.21 = 150 mmHg At alveoli the PO2 has fallen to about 100 mmHg -removal of oxygen by the pulmonary capillaries and by alveolar ventilation

11. DIFFUSION FROM ALVEOLI TO PULMONARY CAPILLARIES PAO2 – Driving Pressure for O2 Diffusion Into Pul Capillary Bed and Main Determinant of PaO2 normally PAO2-PaO2 reflects overall efficiency of O2 uptake from alveoli to arterial blood Capillary blood fully oxygenated before traversing 1/3 distance of alveolo -capillary interface Inadequate oxygenation due to reduced pul capillary time occurs only with very high C.O. or severe desaturation of mixed pul arterial blood

12. GAS EXCHANGE ACROSS THE PULMONARY CAPILLARY Transit time for red cells through pulmonary capillaries is 0.75 seconds. Haemoglobin is fully saturated with O2 in 0.25 seconds

13. External respiration (in lungs) pO 2 = 104 mm Hg pCO 2 = 40 mm Hg Alveoli Capillaries pO 2 = 40 mm Hg pCO 2 = 45 mm Hg pO 2 = 104 mm Hg pCO 2 = 40 mm Hg pO 2 = 104 mm Hg pCO 2 = 40 mm Hg

14. Internal respiration (in tissue) pO 2 = 100 mm Hg pCO 2 = 40 mm Hg Capillaries Tissue pO 2 < 40 mm Hg pCO 2 > 45 mm Hg pO 2 = 40 mm Hg pCO 2 = 45 mm Hg pO 2 = 40 mm Hg pCO 2 = 45 mm Hg

15. Changes in Partial Pressures

16. Transport of gases Oxygen Carried from pulmonary vessels into dissolved form and bound with Hemoglobin Dissolved O2 Very small portion (~2% of total O 2 content) Alone reflects tension of 02 in blood Taken up by tissue and replaced by liberated O2 from haemoglobin

17. Dissolved oxygen HENRYS LAW “ Concentration of any gas in solution is proportional to its partial pressure “ Mathematical Expression Gas concentration = a X partial pressure a – gas solubility coefficient for given solution at given temperature For oxygen =0.003 ml/dl/mmHg normal arterial blood at 100 mm PO2 of Hg contains 3 ml per ltr

18. Hb bound oxygen Hb Protein ‘ globin ’ having 4 amino acid chains ( 2 α , 2 β ) iron-containing porphyrin “ haem ” with 4 pyrrol rings, having one fe ++ ion each Increases oxygen transport capacity by 30-100 fold Increases CO2 transport capacity 15-20 fold

19. O2 Dissociation Curve

20. O2 Dissociation Curve Flat upper portion - loading of O2 will be little affected even if the PO2 in alveolar gas falls somewhat large partial pressure difference between alveolar gas and blood continues to exist when most of the O2 has been transferred steep lower part of the dissociation curve means that the peripheral tissues can withdraw large amounts of O2 for only a small drop in capillary PO2

21. Shifts in the Curve To left (lower P50) Alkalosis Hypothermia abnl fetal Hgb Methemoglobin Carboxyhemoglobin ↓2,3-DPG, can be seen with transfusion of old blood

22. To right (higher P50) Acidosis Hyperthermia abnl hemoglobin ↑2,3-DPG Inhaled anesthetics Isoflurane shifts the P50 to the right be 2.6±0.07mmHg at 1 MAC Shifts in the Curve

23. Temperature effects:

24. EFFECT OF PCO2 Shift of O2-Hb dissociation curve to right by  PCO2 ( BOHR EFFECT ) - Important to enhance oxygenation of blood in lungs and to enhance release of O2 in the tissues In the lungs, CO2 diffuses out of the blood (H+ conc also  due to  in H2CO3 conc )  S hift of O2-Hb curve to left & more avid binding of O2 to Hb   in quantity of O2 bound to Hb   O2 transport to tissues

25. Bohr effect:

26. 2,3-diphosphoglycerate (DPG) end product of red cell metabolism shifts the curve to the right Chronic hypoxia - high altitude , CLD unloading of O2 to peripheral tissues is assisted depleted in stored blood in a blood bank  delivery to tissues

27. Carbon monoxide combining with Hb form carboxyhemoglobin ( COHb ) 240 times the affinity of O2 for Hb making Hb unavailable for O2 carriage Hb concentration & PO2 of blood may be normal But O2 concentration is grossly reduced shifts the O2 dissociation curve to the left

28. O2 capacity Maximum amount of O2 that can be combined with Hb 1gm Hb Binds 1.31 Though Expected 1.39 Due to Presence of Iron in non- heme form A person with 15 gm Hb /deciliter can carry: Max O2 carriage = 1.31 mL O2/gm X 15 gm/deciliter = 20 mL O2/deciliter

29. OXYGEN CARRYING CAPACITY OF BLOOD 97-98 % Carried in Combination With Hb (2-3% Dissolved in Plasma) O2 CONTENT = 1.31 x Hb x Sat + 0.0031 x PO2 O2 content in 100 ml blood (in normal adult with Hb 15 gm/dl) ~ 20 ml (19.4 ml as OxyHb + 0.3 ml in plasma)

30. O2 saturation of Hb percentage of the available binding sites that have O2 attached In arterial blood with PO2 of 100 mm Hg is about 97.5% In mixed venous blood with a PO2 of 40 mm Hg is about 75%

31. Oxygen flux Amount of oxygen delivered to the peripheral tissues per minute O2 flux = O2 bound to Hb  + Dissolved O2 Oxygen bound to Hb = Cardiac output x [ Hb ] x SO2 x k k is Hufner's number - Amount of O2 that can bind with 1g of Hb when fully saturated ( 1.34) Dissolved O2 = CO x pO2 x 0.03

32. Arterial O2 flux is = 5 x 150 x 0.98 x 1.34 + 5 x 100 x 0.03 = 984.9 + 15 = appr . 1000mL O2 per min Mixed venous O2 delivery rate is = 5 x 150 x 0.75 x 1.34 + 5 x 40 x 0.03 = 753.75 + 6 =759.75 = appro . 750mL O2 per min

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