Transport of Gases in Blood Oxygen Transport Carbon Dioxide Transport 22-Nov-18 Transport of Gases

Dissolved O2 in Plasma At 37 0C and PO2 of 95 mmHg Only 0.30 ml O2/ 100 ml of blood Thus total quantity of O2 transported Would be equal to 5000 * (0.3/100) = 15.0 ml O2/min This amount is not sufficient for the metabolic processes 22-Nov-18 Transport of Gases

Transport of O2 Bound to Hb Haemoglobin Found in RBCs Composed of 4 polypetide chains Each containing a pigment (heme) Of the total amount of O2 transported in blood, about 98.5% is bound to Hb 1.5% is dissolved in plasma 22-Nov-18 Transport of Gases

Binding of O2 to Hb After diffusing across the RM O2 dissolves in plasma Then into RBC Where it combine reversibly with Hb Converts deoxy-Hb into Oxy-Hb Alveoli PACO2 = 40 PAO2 = 100 CO2 O2 O2 CO2 O2 Hb PvCO2 = 46 mm Hg PaCO2 = 40 mm Hg PvO2 = 40 mm Hg PaO2 = 97 mm Hg 22-Nov-18 Transport of Gases

Binding of O2 to Hb HB + 4(O2) ⇆ Hb(O2)4 Reactive sites are the 4 Fe++ atoms One mole of Hb is capable of combining with 4 moles of O2 Alveoli PACO2 = 40 PAO2 = 100 CO2 O2 O2 CO2 O2 Hb PvCO2 = 46 mm Hg PaCO2 = 40 mm Hg PvO2 = 40 mm Hg PaO2 = 97 mm Hg 22-Nov-18 Transport of Gases

Binding of O2 to Hb Under ideal conditions In the normal human body 1 gm of Hb Combine with 1.39 ml O2 In the normal human body 1 gm of Hb combine with 1.34 to 1.36 ml of O2 (Huffner’s number) Small fraction of Hb is in an inactive form 22-Nov-18 Transport of Gases

Binding of O2 to Hb When the Fe++ is oxidized to Fe+++ Carbon monoxide The haemoglobin is known as Methaemoglobin Its ability to combine with O2 is lost Carbon monoxide Combine with Fe++ Displaces the O2 from it 22-Nov-18 Transport of Gases

Binding of O2 to Hb Cyanide combine and inactivate Hb It combines with Fe+++ of the methaemoglobin Hb (Fe++) ⇆ Hb (Fe+++) + CN  Cyano –methaemoglobin Normally methaemoglobin is <1% Cyano-methaemoglobin Is stable Reaction is one way 22-Nov-18 Transport of Gases

Binding of O2 to Hb Other respiratory pigments include Myoglobin Has one Fe++ atom Functions as for 1 atom of Fe++ in Hb Cytochrome Change from O2 poor to O2 rich Associated with oxidation of Fe++ to Fe+++ 22-Nov-18 Transport of Gases

Oxygen Capacity of Blood Maximum amount of O2 that can be bound by the Hb 1 gm of Hb combine with 1.34 ml O2 Amount of Hb available = 15 gm Hb/100 ml of blood 15*1.34 = 20.1 ml O2 / 100 ml blood This is the O2 carrying capacity of blood 22-Nov-18 Transport of Gases

Oxygen Flux Total amount of O2 transported by blood per minute O2 flux = C.O*(arterial O2 content) = 5000*(20/100) = 1000 ml O2 /min Under normal condition 250 ml of O2 is utilized (25% of O2 flux) Thus circulating blood loses 25% of its Oxygen Venous blood is approx 75% saturated with O2 The 75% of the un-extracted O2 forms “reserve” 22-Nov-18 Transport of Gases

Oxygen Flux Determined by Cardiac output Hb concentration Saturation with O2 22-Nov-18 Transport of Gases

O2-Hb Dissociation (Association) Curve The property of Hb Ability to change from deoxy-Hb to Oxy-Hb at extremely rapid rate at PO2 in lungs Hb + O2 ⇌ Hb(O2) The ability to give up O2 in tissue Hb(O2) ⇌ Hb + O2 This ability varies & depends on Metabolic activities & requirements 22-Nov-18 Transport of Gases

O2-Hb Dissociation (Association) Curve The effective release of O2 at tissue capillaries occurs because Amount of O2 combined to Hb varies with Po2 Acidity Temperature 22-Nov-18 Transport of Gases

O2-Hb Dissociation (Association) Curve The relationship between the PO2 & Degree of Hb oxygenation Is known as O2 – Hb dissociation (association) curve The proportion of HbO2 to the total Hb of blood Give % saturation of Hb 100 Loading zone 80 Hb saturation (%) 60 50 Unloading zone 40 20 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

O2-Hb Dissociation (Association) Curve % Saturation of Hb is given by (HbO2/Hb)*100 (O2 content /capacity) * 100 Curve is sigmoid shaped Steep slope between PO2 10 to 60 mm Hg Flat portion between PO2 70 to 100 mm Hg 100 Loading zone 80 Hb saturation (%) 60 50 Unloading zone 40 20 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

O2-Hb Dissociation (Association) Curve The extent to which Hb combine with O2 Increase very rapidly from 10 to 60 mm Hg At PO2 60 mm Hg 90% of Hb is combined with O2 Above PO2 60 mm Hg Further increase in PO2 Produces only a small increase in HbO2 100 Loading zone 80 Hb saturation (%) 60 50 Unloading zone 40 20 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

PO2 Vs Quantity of O2 Bound to Hb 97% sat ; 19.4 ml O2 Normal arterial blood 97% saturated Hb Has 19.4 ml O2 / 100 ml blood At the tissue level PO2 is 40 mm Hg Hb sat is 75% Blood has 14.4 ml O2 /100 ml blood 20 5 mls Loading zone 16 75% sat, 14.4 ml O2 12 O2 content ( ml O2/100 ml blood) [V%] Unloading zone 8 4 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

PO2 Vs Quantity of O2 Bound to Hb 97% sat ; 19.4 ml O2 Thus under normal conditions About 5 ml O2/100 ml blood are transported from lungs to tissue 20 5 mls Loading zone 16 75% sat, 14.4 ml O2 12 O2 content ( ml O2/100 ml blood) [V%] Unloading zone 8 4 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

PO2 Vs Quantity of O2 Bound to Hb 97% sat ; 19.4 ml O2 During exercise Tissue PO2 can fall to 15 mm Hg At this pressure only about 4.4 ml O2 remain bound to Hb/ 100 ml blood Thus 15 ml O2 / 100 ml blood Delivered to tissues (3 times normal) 20 5 mls Loading zone 16 75% sat, 14.4 ml O2 12 O2 content ( ml O2/100 ml blood) [V%] Unloading zone 8 4 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

Factors Affecting O2-Hb Dissociation curve Influence of acidity & CO2 Bohr effect Changes in pH Alters the affinity of Hb for O2 An increase in H+ conc shift the curve to the right Decrease in affinity of Hb for O2 100 pH 7.6 80 pH 7.4 pH 7.2 Hb saturation (%) 60 50 40 20 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

Factors Affecting O2-Hb Dissociation curve Influence of acidity & CO2 Bohr effect Co2 combines with The  - amino gps of Hb This lowers the affinity of Hb for O2 100 pH 7.6 80 pH 7.4 pH 7.2 Hb saturation (%) 60 50 40 20 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

Factors Affecting O2-Hb Dissociation curve Changes in pH Alters the affinity of Hb for O2 An increase in H+ conc shift the curve to the right There is an increase in P50 Lowers the affinity of Hb for O2 100 pH 7.6 80 pH 7.4 pH 7.2 Hb saturation (%) 60 50 40 20 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

Factors Affecting O2-Hb Dissociation curve 5 ml O2 /100 ml blood When the curve is shifted to the right Decreased affinity of Hb for O2 Any fall in PO2 releases more O2 to the tissues 100 pH 7.6 80 pH 7.4 > 5 ml O2 released pH 7.2 Hb saturation (%) 60 50 40 20 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

Factors Affecting O2-Hb Dissociation curve < 5 ml O2 A decrease in H+ conc shift the curve to the left There is a decrease in P50 Increase affinity of Hb for O2 Normally About 5 ml O2 released at the tissue When curve is shifted to left Less the 5 ml O2 / 100 ml blood is released 100 pH 7.6 5 ml O2 80 pH 7.4 pH 7.2 Hb saturation (%) 60 50 40 20 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

Factors Affecting O2-Hb Dissociation Curve 5 ml O2 /100 ml blood At tissue level a fall in pH Facilitates O2 dissociation from Hb At the lung level The increase in ph facilitates Combination of O2 with deoxy - Hb 100 pH 7.6 80 pH 7.4 > 5 ml O2 released pH 7.2 Hb saturation (%) 60 50 40 20 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

Influence of temperature A rise in temperature Shift the curve to the right Decrease affinity of Hb for O2 Favours off loading of O2 to the tissues The opposite is true when temperature decreases 100 10OC 20OC 80 37OC 43OC Hb saturation (%) 60 50 40 20 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

Influence of 2:3 Diphospoglycerate Affinity of Hb for O2 is affected by organic phosphates 2:3 DPG is plentiful in RBC End product of glycolysis via E-M pathways Binds to  chain of deoxy-Hb 100 2:3 DPG 80 2:3 DPG 2:3 DPG Hb saturation (%) 60 50 40 20 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

Influence of 2:3 Diphospoglycerate 1 mol of deoxy-Hb binds to 1 mol of 2:3 DPG HbO2 + 2:3 DPG ⇌ Hb – 2:3 DPG + O2 An increase in 2,3DPG shift the reaction to right Causing more O2 to be liberated 100 2:3 DPG 80 2:3 DPG 2:3 DPG Hb saturation (%) 60 50 40 20 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

Influence of 2:3 Diphospoglycerate Factors affecting 2,3 DPG conc in RBC Acidosis inhibit glycolysis 2,3 DPG levels falls Hormones Thyroid, GH, androgens Increase 2,3 DPG 100 2:3 DPG 80 2:3 DPG 2:3 DPG Hb saturation (%) 60 50 40 20 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

Influence of 2:3 diphospoglycerate Ascent to high altitudes Increase 2,3 DPG Anaemia 100 2:3 DPG 80 2:3 DPG 2:3 DPG Hb saturation (%) 60 50 40 20 20 40 60 80 100 27 PO2 (mm Hg) P50 22-Nov-18 Transport of Gases

Transport of CO2 22-Nov-18 Transport of Gases

CO2 Transport CO2 is produce in the cells as end product of oxidative metabolism Diffuses from the cells into Interstitial fluid Plasma where it Raises the PCO2 of capillary and venous blood 22-Nov-18 Transport of Gases

CO2 Transport CO2 is transported in three forms Physically dissolved in plasma (10%) As bicarbonate ions in plasma (60%) As carbamino compounds (30%) 22-Nov-18 Transport of Gases

CO2 Transport in Plasma Physically dissolved depend on the Partial pressure Solubility coefficient Hydration of CO2 CO2+ H2O ⇌ H2CO3 ⇌ H+ + HCO3- In plasma there is no carbonic anhydrase Equilibrium is far to the left Accumulation of H2CO3 stops the reaction H+ are buffered by plasma buffers 22-Nov-18 Transport of Gases

CO2 Transport in Plasma Formation of carbamino compounds Amino groups have ability to combine with CO2 To form carbamino compounds R-N(H2) + CO2 ⇌ R-NH-COO- + H+ This reaction restricted to terminal AA or Side chains AA (lysine, arginine) 22-Nov-18 Transport of Gases

CO2 Transport by RBC Small amount of CO2 dissolved in fluid in RBC Hydration of CO2 CO2+ H2O ⇌ H2CO3 ⇌ H+ + HCO3- In RBC reaction proceed to right because Presence of carbonic anhydrase H+ and HCO3- do not accumulate 22-Nov-18 Transport of Gases

CO2 Transport by RBC H+ cannot readily move out of RBC It is buffered by Hb buffer H+ + HbO2 ⇌ H+.Hb + O2 As H+ binds to Hb Reduces Hb affinity for O2 Cause unloading of O2 to tissues Cl- HCO3- CO2 Cl- CA CO2 + H2O2⇌ H2CO3⇌ H+ + HCO3- H++ HbO2 HHb + CO2 HHb + O2 Carbamino-Hb O2 22-Nov-18 Transport of Gases

CO2 Transport by RBC Presence of deoxy-Hb in blood Increase ability to carry CO2 from the tissues Oxygenation in pulmonary capillaries Increase Hb ability to unload CO2 This is the Haldane effect Cl- HCO3- CO2 Cl- CA CO2 + H2O2⇌ H2CO3⇌ H+ + HCO3- H++ HbO2 HHb + CO2 HHb + O2 Carbamino-Hb O2 22-Nov-18 Transport of Gases

CO2 Transport by RBC HCO3- leaves the RBC Concentration gradient Chloride shift Chloride/bicarbonate carrier protein Cl- move into RBC HCO3- move into plasma Cl- HCO3- CO2 Cl- CA CO2 + H2O2⇌ H2CO3⇌ H+ + HCO3- H++ HbO2 HHb + CO2 HHb + O2 Carbamino-Hb O2 22-Nov-18 Transport of Gases

CO2 Transport by RBC In the pulmonary capillaries Opposite movement of Cl- shift occurs Cl- move into plasma HCO3- move into RBC Cl- HCO3- CO2 Cl- CA CO2 + H2O2⇌ H2CO3⇌ H+ + HCO3- H++ HbO2 HHb + CO2 HHb + O2 Carbamino-Hb O2 22-Nov-18 Transport of Gases

CO2 Transport by RBC CO2 can also combine with amino-terminals of Hb CO2 + HbNH2 ⇌ HbCOOH Carbamino-haemoglobin Cl- HCO3- CO2 Cl- CA CO2 + H2O2⇌ H2CO3⇌ H+ + HCO3- H++ HbO2 HHb + CO2 HHb + O2 Carbamino-Hb O2 22-Nov-18 Transport of Gases

CO2 Transport Although the major reactions regarding transport of CO2 Occur in the RBCs The bulk of CO2 is transported in plasma In the form of HCO3- 22-Nov-18 Transport of Gases

CO2 Dissociation Curve CO2 can exist in blood in many forms Normal operating range CO2 can exist in blood in many forms As free CO2 In chemical combination with H2O Hb Plasma proteins Total quantity of CO2in all these forms in blood depend on PCO2 60 40 CO2 in blood (vol%) 20 10 20 30 40 50 60 PCO2 mm Hg 22-Nov-18 Transport of Gases

CO2 Dissociation Curve Normal operating range The relationship of the total CO2 in all these forms vs PCO2 is known as The CO2 dissociation curve The curve is nearly straight line with no plateau or steep region 60 40 CO2 in blood (vol%) 20 10 20 30 40 50 60 PCO2 mm Hg 22-Nov-18 Transport of Gases

CO2 Dissociation Curve The normal PCO2 range is Normal operating range The normal PCO2 range is 40 mm Hg in arterial blood 45 mm Hg in venous blood Normal concentration of CO2 in all its forms is 50 volumes% 60 40 CO2 in blood (vol%) 20 10 20 30 40 50 60 PCO2 mm Hg 22-Nov-18 Transport of Gases

The Haldane Effect Presence of O2 As blood passes through the tissues Normal operating range Presence of O2 Shift the curve to the right As blood passes through the tissues Point A PO2 = 40 mm Hg Normal PCO2 = 45 mm Hg Concentration rises to 52 volumes% 55 PO2 = 40 A 50 CO2 in blood (vol%) PO2 = 100 B 45 35 40 45 50 PCO2 mm Hg 22-Nov-18 Transport of Gases

The Haldane Effect In the lungs (Point B) Normal operating range In the lungs (Point B) PO2 = 100 mm Hg PCO2 = 40 mm Hg Conc falls to 48 vol% During transport of CO2 from tissue to lungs Only 4 volume% of CO2 is exchanged 55 PO2 = 40 A 52 50 CO2 in blood (vol%) PO2 = 100 48 B 45 35 40 45 50 PCO2 mm Hg 22-Nov-18 Transport of Gases