RESPIRATORY SYSTEM LECTURE-6 (GAS TRANSPORT) Dr. Mohammed Sharique Ahmed Quadri Assistant Prof. physiology Al maarefa college 1 Gas Transport • O2 which is taken up by the blood at the lungs is transported to the tissues for use by the cells. • CO2 produced at the cell level is transported to the lungs for elimination. 2 Oxygen Transport • Most O2 in the blood is transported bound to hemoglobin. Method of O2 Transport • Chemically bound to Hemoglobin – 98.5% • Physically Dissolved in plasma – 1.5% 3 Oxygen Transport • • • • Hb is present inside red blood cells [RBC]. Hb is iron bearing protein molecule. It makes reversible combination with oxygen. When Hb combines with O2, we call Oxyhemoglobin [HbO2]. • Hb + O2 HbO2 • When O2 not combined with Hb, we call it reduced Hemoglobin or Deoxyhemoglobin. 4 Oxygen Transport • Cells consume 250ml of O2 /min at rest. • During exercise, it can increase 25 times. Why does Hb combine with O2 in the lungs and release O2 at the tissues? • Because of high partial pressure of O2 [PO ] in the lungs, O2 combines with the Hb. • When this blood with high po2 reaches the tissues, PO in the tissues is low, therefore, O is transferred from blood to tissues. 2 2 2 5 Oxygen Transport Important Points • O2 combination with Hb [Oxyhemoglobin] does not contribute to PO . • PO is only due to dissolved O2 in plasma which is 1.5 % ( 0.3ml/100ml) . PO is the primary factor determining the percent Hb saturation. 2 2 2 6 Oxygen Transport • In Hb, 4 atoms of iron are present in Heme portion of Hb. • Each atom can combine with O2 molecule, so Hb molecule can carry 4 molecules of O2. • Hb is considered fully saturated when all Hb present is carrying its maximum O2 load . • The percent Hb [% Hb] saturation can vary from 0 to 100%. 7 Oxygen Transport • The most important factor determining the % Hb saturation is PO of the blood [which refers to concentration of O2 physically dissolved in blood ]. 2 8 Oxygen-Hemoglobin (O2-Hb) dissociation (saturation) curve 9 Oxygen-Hemoglobin (O -Hb) dissociation (saturation) curve 2 • The relationship between blood PO and %Hb saturation is not linear. • The relationship is S – shaped for O2-Hb dissociation. • At pressures of PO 60 – 100mmHg curve flattens off or plateaus i.e. within this pressure range of 60-100mmHg change in PO produces only small change in extent to which Hb is binds to O2. 2 2 2 10 Oxygen-Hemoglobin (O -Hb) dissociation (saturation) curve 2 • If the PO range is 0 - 60mmHg, it shows small changes in PO results in large change in extent to which Hb combines with O2 i.e. lower part is steep. IMPORTANT • Upper part of curve – Plateau or Flat • Lower part of curve – Steep • Both parts have physiological significance. 2 2 11 Oxygen-Hemoglobin (O -Hb) dissociation (saturation) curve 2 Significance of Plateau Phase of O2-Hb curve • We can see if PO falls from 100mmHg to 60mmHg, there is little change in O percentage saturation. • Same way, if PO increases to 600mmHg [by breathing pure O ] there will be only little change in Hb saturation [instead of Hb 97.5% saturation, it can increase to 100% saturation]. 2 2 2 2 12 Oxygen-Hemoglobin (O -Hb) dissociation (saturation) curve 2 • Therefore PO range between 60 – 600mmHg, there is only little change in amount of O being carried by Hb. • It provides safety margin in O2 carrying capacity of blood. Clinical Application • In Pulmonary disease, PO may decrease due to poor ventilation or gas exchange. • Physiologically PO may decrease at high altitude. • In these circumstances, if PO falls up to 60mmHg, body will be little affected, but if PO falls below 60mmHg body will be affected. 2 2 2 2 2 2 13 Oxygen-Hemoglobin (O -Hb) dissociation (saturation) curve 2 Significance of Steep Portion of O – Hb curve • Steep portion of O – Hb dissociation curve is from 0 – 60mmHg i.e. present at systemic capillaries when O2 is unloaded from the Hb. • At tissue level, PO falls from 100mmHg to 40mmHg but % of Hb saturation is still 75% [i.e. 25% of O2 is given to tissues]. • Hb in venous blood is 75% saturated at 40mmHg. 2 2 2 14 Oxygen-Hemoglobin (O -Hb) dissociation (saturation) curve 2 • If tissue cells are metabolizing more actively and need more O2, PO can drop from 40mmHg to 20mmHg in tissues, more O2 can be given by blood and O percent can drop from 75% to 30%. • Therefore small drop of PO can give more O2 to tissues. • This is important in providing more oxygen when tissue metabolism increases as in exercising muscles . 2 2 2 15 Factors At The Tissue Level Promote The Unloading Of O2 From Hb • Shifting of O dissociation curve to right or more dissociation [giving] of O2 to tissues or less affinity of O2 for Hb. • The factors are 1- Increase CO2 2- Increase Acidity [increase H+ ion] 3- Increase Temperature 4- Increase 2,3-BPG [bisphosphoglycerate] 2 16 17 BOHR EFFECT • Increase CO2 and increase H+ ion causes more release of O2 from Hb [i.e. less affinity of O2 with Hb]. It is known as ‘Bohr Effect’. • Both CO and H+ combine with Hb reversibly at sites other than O2 binding sides and cause release of O2. 2 18 Effect of 2,3 – BPG on O -Hb Dissociation Curve 2 • 2,3 – BPG is factor inside the RBC, which affect O2-Hb binding. It is produced during RBC metabolism. • 2,3 – BPG can bind reversibly with Hb and decreases its affinity for O2 therefore shifts Hb-O dissociation curve to right. • BPG increases in RBC whenever Hb in arterial blood is under saturated Examples - People living at high altitude - People suffering from respiratory disease - Anemia • 2,3 – BPG, by increasing O2 unloading helps to maintain O2 availability to tissues. 2 19 Applied: Hb Has Higher Affinity For Carbon monoxide [CO] Than O2 • CO and O2 compete for same binding sites on Hb, but this affinity is 240 times more for CO. • Combination of CO with Hb is know as ‘Carboxyhemoglobin’ [HbCO]. • Even when Hb and O2 are normal. If CO is there Hb will not be available for O2 combination. • CO poisoning occurs in coal burning. • CO is odorless, colorless, tasteless and nonirritating. 20 CO2 Transport • CO2 is transported in the blood by three ways: 1. Physically dissolved in Plasma – 10% 2. Bound to Hb – 30% 3. As Bicarbonate – 60% 21 22 CO2 Transport • CO2 combines with Hb to form Carbamino hemoglobin (HbCO2). • CO2 combines with globin portion of Hemoglobin [in contrast to O2 which combines with Heme portion]. • REDUCED Hb has more affinity for CO2 HALDANE EFFECT • Removing O2 from Hb, increases the ability of reduced Hb to pick up CO2 and H+ ion [CO2 generated H+ ion]. This effect is known as ‘Haldane Effect’. 23 CO2 Transport • CO2 combines with Hb to form Carbamino hemoglobin (HbCO2). • CO2 combines with globin portion of Hemoglobin [in contrast to O2 which combines with Heme portion]. • As bicarbonate – it is most important means of CO2 as 60% of CO is converted into bicarbonate by the chemical reaction. • CO2 + H2O H2CO3 H+ + HCO3• This reaction takes place slowly in plasma but quickly within RBC due to presence of enzyme carbonic anhydrase. 2 24 25 CO2 Transport Chloride Shift • As CO2 combines with H2O and HCO3 is formed in RBC. • RBC membrane has HCO3 – Cl carrier that passively facilitates the diffusion of these ions in opposite direction across the membrane. • HCO3 is moved out of the cell and in its place Cl is moved into RBC from plasma to restore electric neutrality. • This inward shift of Cl in exchange for HCO3 [generated by CO2] is known as chloride shift. 26 ‘IMPORTANT’ Remember • Bohr Effect - Increase CO2 and increase H+ ion causes more release of O2 from Hb [i.e. less affinity of O2 with Hb]. It is known as ‘Bohr Effect’. • Haldane Effect - Removing O2 from Hb, increases the ability of reduced Hb to pick up CO2 and H+ ion [CO2 generated H+ ion]. This effect is known as ‘Haldane Effect’. 27 References • Human physiology by Lauralee Sherwood, seventh edition • Text book physiology by Guyton &Hall,11th edition • Text book of physiology by Linda .s contanzo,third edition Thank you 29