Gas Exchange and Gas Transport

1. Gas Exchange and Gas Transport

2. Gas Transport The amount of gas that is transported across a surface can be calculated using Fick’s Law. Vgas = (AD/T)*(P1-P2) D = “DIFFUSIVITY” or “DIFFUSION COEFFICIENT” a SOLUBILITY/ Ö MW

3. 3 Important Factors For Diffusion • Area – larger area, more gas transfer • Thickness – thicker barrier, less gas transfer • Pressure gradient – higher gradient, more gas transfer • Diffusion coefficient - high solubility with low mass = large D large D – more gas transfer

4. 4 Lung Structure has maximized these variables • Area – large 75 m2 in adult • Thickness – very thin, as low as 0.3 mm ! • Pressure gradient – around 60 mm Hg O2 • O2 and CO2 – not great solubility but very small molecules

5. EFFECT OF SURFACE AREA ON GAS EXCHANGE Increase in Surface Area EXERCISE ↑ CARDIAC OUTPUT ↑PULMONARY VASCULAR PRESSURE ↑ TIDAL VOLUME ↑ RECRUITMENT & DISTENSION OF PULMONARY CAPILLARIES ↑ SURFACE AREA FOR GAS EXCHANGE → IMPROVE GAS EXCHANGE ↑ SURFACE AREA ↓ ALVEOLAR THICKNESS

6. EFFECT OF SURFACE AREA ON GAS EXCHANGE Loss of Surface Area EMPHYSEMA DESTRUCTION OF ALVEOLAR WALLS ↑LUNG COMPLIANCE MECHANICAL COMPLICATION ↓ AREA FOR GAS EXCHANGE GAS EXCHANGE Other •Athelectasis (Collapse Of Lung Parenchyma) •Surgical Removal Of Lung Tissue E.M. Healthy Lung Tissue E.M. Emphysematous Lungs

7. EFFECT OF THICKNESS ON GAS EXCHANGE Increased Thickness PULMONARY FIBROSIS (scar formation) results in response to exposure to-- • industrial dust [asbestosis, silicosis] • spores from moldy hay [Farmers lungs] • antigens in avian feather/excreta [Bird breeders lung] • therapeutic drugs, radiation, poisons [weed killer, paraquat]

8. Pneumonia- inflammatory fluid accumulation in & around the alveoli from viral/bacterial (common: Streptococcal pneumonia- deadly: Severe Acute Respiratory Syndrome (SARS)-the alveolar infection can reach blood—sepsis or the pleural space--empyema) /fungal infections or accidental aspiration of food, vomitus, chemicals or indirectly as result of other illness. Pneumonia is the leading cause of death amongst chronically ill elderly • Pulmonary Edema abnormal build up of fluid in the interstitial or alveolar space as a result of direct damage to lung tissue or inability of heart to pump blood --as in left heart failure

9. TRANSPORT OF OXYGEN BY BLOOD Oxygen Is Transported In Two Forms In The Blood— 1. physically dissolved [2 %] 2. chemically bound to the Hemoglobin, Hb, molecule [98 %] OXYGEN PHYSICALLY DISSOLVED IN BLOOD Compared to carbon dioxide, oxygen is relatively insoluble in the blood-- at PO2 = 100 mmHg, 100 ml blood contains 0.3 ml of O2

10. Oxygen Content of Plasmai.e. solubility of oxygen • Solubility of oxygen – 0.003 ml O2 per 100 ml of plasma • PO2 and oxygen content are proportionate [O2]dissolved = PO2 x s • Therefore [O2]dissolved = 100 x 0.003 =0.3 ml O2 100 ml-1 • Since O2 consumption >250 ml min, would need to pump 83 L blood min-1 to suppy needs! • Dissolved oxygen is not the answer. Blood oxygen content is increased by oxygen carrier molecule – hemoglobin

11. TRANSPORT OF OXYGEN BY BLOOD Chemically Bound to the Hemoglobin Molecule Hb can combine rapidly & reversibly with O2. • The reversibility of this chemical reaction allows O2 to be released to the tissues. Hb + O2 <---------> O2Hb Deoxyhemoglobin oxygen oxyhemoglobin a.k.a reduced hemoglobin

12. Hemoglobin • Tetramer (4 units) • Each monomer contains a heme group (porphyrin ring with Fe held in the center) and a polypeptide (globin) which is either a or b in form • Tatramer is aHeme2, bHeme2 – and each heme group can bind 1 O2 molecule

13. O2 O2 O2 O2 Hemoglobin

14. O2 O2 O2 O2 • O2Saturation-fraction of O2 binding sites that are actually occupied by oxygen the total amount of binding sites is therefore simply the amount of Hb molecules x 4 (a lot!). 25% Sat 50% Sat 75% Sat 100% Sat

15. Saturation and Content • fraction of hemoglobin binding sites that are currently occupied by O2 • Commonly expressed as a percentage • 1 g of hemoglobin can bind 1.36 ml O2 • Blood contains 15 g 100 ml-1 – so what is O2content? • Therefore – 1.36*15 = 20.4 ml O2 100 ml-1 blood is full capacity of HbO2 • Blood also carries 0.3 ml 100 ml-1 dissolved O2 (100 mm Hg PO2) • Total = 20.4+0.3 = 20.7 ml O2 100 ml-1 blood • If breathing 100% O2 with PO2 of (e.g. 600 mm Hg) then [O2]dissolved = 1.8 ml + 20.4 = 22.2 ml 100 ml-1

16. Saturation and Oxygen Content Oxygen content = (1.36*Hb content)x(measured saturation/maximum saturation) saturation Max possible saturation ml O2 g-1 g Hb 100ml-1

17. Saturation Curve 24 100 22 20 80 18 16 14 60 O2 content ml 100 ml-1 12 % Hb saturation 10 40 [O2]dissolved 8 6 20 4 2 0 0 0 20 40 60 80 100 600 PO2 (mm Hg) pH 7.4, PCO2 40 mm Hg 37°C

18. PULSE OXIMETER A Non-invasive Device Measuring Percentage of Oxyghemoglobin in the arterial blood [Hb Saturation/SaO2/SpO2] These monitors can be clipped on to the finger and continuously record saturation. These monitors rely on the fact that blood changes color with oxygen content. Deoxygenated blood is dark red, whilst oxygenated blood becomes vibrant cherry red – the pulse oximeter simply measures blood color and calculates saturation based on this parameter! This type of monitor is useless when the patient has CO poisoning – since Hb bound to CO is the same color as oxygenated blood – vibrant red!

19. 19 Saturation Curve 24 oxygenated 100 22 20 deoxygenated 80 18 16 14 60 O2 content ml 100 ml-1 12 % Hb saturation 10 40 8 6 20 4 2 0 0 0 20 40 60 80 100 600 PO2 (mm Hg)

20. Co-operativity The binding of O2 to hemoglobin can be considered in terms of affinity – i.e. how easy it is for O2 to bind to Hb • If it is difficult for O2 to bind, then Hb has a low affinity for O2 – and a lot of O2 is needed to get. • If it is easy for O2 to bind, then Hb has a high affinity for O2 – and very little O2 is needed to get, e.g. 50% of Hb molecules bound to O2. • Hemoglobin has a low affinity for O2 when no oxygen is bound, however, when the first oxygen binds to hemoglobin, the protein changes shape slightly and enters a higher affinity state, thus the next O2 molecule can bind more easily than the first. • This property is called co-operative binding. • The affinity of Hb for O2 can be measured by considering how much PO2 is needed to get 50% of Hb bound to O2. • e.g. if PO2 of 600 mm Hg is needed to have half of the Hb molecules bound to O2 then those Hbmolecules must have a very low affinity for O2. • e.g. if a PO2 of only 10 mm Hg is needed to have half of the Hb molecules bound to O2 then Hb must have a high affinity.

21. P50 The partial pressure of oxygen required to get 50% Hb bound to O2, and is thus an index of the affinity of Hb for O2 – and is termed the P50. ↑ P50 means a lot of PO2 is needed for 50% binding – thus ↓ affinity ↓ P50 means little PO2 is needed for 50% binding – thus ↑ affinity

22. 22 Saturation Curve 24 100 22 20 80 18 16 14 60 O2 content ml 100 ml-1 12 % Hb saturation Decreased P50 = left shift in curve 10 40 8 6 20 4 2 0 0 0 20 40 60 80 100 600 PO2 (mm Hg)

23. 23 Saturation Curve 24 100 22 20 80 18 16 14 60 O2 content ml 100 ml-1 12 % Hb saturation Increased P50 = right shift in curve 10 40 8 6 20 4 2 0 0 0 20 40 60 80 100 600 PO2 (mm Hg)