Lecture 21: Gas Transport PDF (BChD I HUB 105 2023)

Lecture 21 Gas Transport BChD I HUB 105 2023 Dept. Medical Biosciences University of the Western Cape Introduction Blood transports oxygen (O2) and carbon dioxide (CO2) between lungs and the tissues of the body These gases are transported in different states either:...

Lecture 21 Gas Transport BChD I HUB 105 2023 Dept. Medical Biosciences University of the Western Cape Introduction Blood transports oxygen (O2) and carbon dioxide (CO2) between lungs and the tissues of the body These gases are transported in different states either: 1. Dissolved in plasma 2. Chemically combined with hemoglobin 3. Converted to a different molecule Both gases have limited solubility in plasma. This could be a major problem, because tissues need more O2 and generate more CO2 than blood plasma can absorb and transport Problem solved by red blood cells (RBC) which remove the O2 and CO2 from the plasma and bind them or transform them into another molecule, Since the gases are removed from the plasma, more O2 and CO2 can diffuse into the blood and be transported Reactions btwn gases and RBC are only temporary and reversible. When the plasma concentrations of O2 and CO2 decline, the RBC release bound O2 and CO2 Introduction Exchange of gases between lungs, RBC and gas movement at the tissue level progress passively by diffusion, caused by pressure gradients. PO2 in alveoli ~ 100 mm Hg PO2 in pulmonary capillaries ~ 40 mm Hg (tissues) Result: O2 moves into pulmonary capillaries PCO2 in pulmonary capillaries ~ 46 mm Hg (tissues) Average arterial blood gases: PO2 100 mm Hg and PCO2 40 mm Hg Pressure differences causes gas to diffuse Gas diffuses from a high pressure to a low pressure Alveolus Capillaries Tissues (fluid) Tissues (cells) pO2 104 mmHg 95 mmHg 40 mmHg 5-40 (ave 23) mmHg pCO2 40 mmHg 45 mmHg 45 mmHg 46 mmHg Transport of O2 Blood plasma cannot transport enough O2 or CO2 to meet physiological needs. Due to its low solubility, only 1.5 % of oxygen is dissolved in plasma. 98.5 % of oxygen combines with hemoglobin (Hb) in RBC. O2 combines loosely and reversibly with hemoglobin - Inc PO2 = O2 combines with Hb (pulmonary capillary) - Dec PO2 = O2 is released from Hb (tissue capillaries) Oxygen once in blood will either - remain as dissolved oxygen in plasma - Bind to Hb to make oxhemoglobin /HbO2  Hb + O2 HbO2 Oxygen Gas Transport Mechanisms within alveoli O2 pickup Pulmonary capillary Plasma Red blood cell Alveolar air space Oxygen delivery at the tissue level O2 delivery Systemic capillary Red blood cell Cells in peripheral tissues Transport of O2 Oxygen-Hemoglobin Dissociation Curve/Saturation Curve Hb saturation is determined by the partial pressure of Oxygen value. @ High PO2 – lungs – Hb is 98% saturated @ Low PO2 – tissues – Hb is only 75% saturated Cooperative binding  Hb’s affinity for O2 increases as its saturation increases (similarly its affinity decreases when saturation decreases) Graph indicates the % of Hb sites that have bound O2 at different PO2 – It reflects the loading and unloading of O2 Differences in % saturation in lungs and tissues are shown in graph abv. At the lower part ,steep part of curve, small changes in PO2 causes big changes in % saturation ie. Hb releases more O2 to tissues as they use more O2 Transport of O2 Oxygen-Hemoglobin Dissociation Curve/Saturation Curve this curve describes the percentage saturation of Hb in the blood at different blood PO2 values it is based on the reversible reaction of binding and dissociation of oxygen to hemoglobin: Hb + O2 ↔ HbO2 Hb will be 100% saturated with O2 when four molecules of O2 bind to the four heme groups in a Hb molecule - at a PO2 of 100 mm Hg (blood leaving pulmonary capillaries), Hb is 98% saturated - at a PO2 of 40 mm Hg (blood leaving tissue This graph is not a straight line but capillaries), Hb is 75% saturated rather sigmoid or S-shaped, because - i.e. only 23% of the oxygen picked up Hb each time a O2 molecule binds, it enhances hemoglobin’s ability to bind in the lungs is released at the tissues (the another O2 molecule until reaching a remaining 75% of oxygen still bound to Hb plateau near 100% saturation. acts as an oxygen reserve that can be released if blood ↓ PO2 further) Transport of O2 Oxygen-Hemoglobin Dissociation Curve/Saturation Curve Factors altering Hb saturation 1. Blood pH (Carbonic Acid, Lactic Acid) 2. Temperature 3. 2,3 Bisphosphoglycerate concentration (2,3 BPG) (a by-product of glucose metabolism in RBC which is produced when blood O2 levels are low) 4. Partial pressure of Carbon Dioxide (PCO2) All of the above either directly/indirectly change the structure of Hb, causing a decrease in its ability to bind oxygen, and therefore results in the release of oxygen. These factors as well as the PO2 gradient within the body will determine the appropriate extraction of O2 from Hb and determine the oxygen utilization coefficient (the fraction of O2 removed from bld as it travels thru tissues) in any particular tissue. Eg normal activity, ~25% O2 extracted from Hb but under exercise up to 75% - 85% O2 removed from Hb. Transport of CO2 Produced by cells thru-out the body, generated as a by-product of cell metabolism. CO2 diffuses from tissue cells into the capillary blood CO2 in the bloodstream can be carried three ways 1. 7% dissolves in plasma 2. 93% diffuses into the RBC: some combine with Hb to form carbaminohemoglobin (HbCO2) or 3. is converted to Carbonic acid, that easily dissociates into H ions and Bicarbonate ions. Binding to Hb 23% CO2 carried and stored in blood by Hb molecule. Attached to an exposed amino grp (-NH) of the Hb molecule to form carbaminohemoglobin = HbCO2 CO2 + Hb HbCO2 (HbNHCOOH) Transport of CO2 Carbonic Acid Formation 70% is transported as carbonic acid (H2CO3) Within the RBC, CO2 combines with water and thru the activity of the enzyme carbonic anhydrase , it transforms into Carbonic acid (H2CO3) H2CO3 dissociates into H+ and bicarbonate (HCO3−) CO2 travels in bloodstream primarily as HCO3− - H+ removed by binding to Hb (buffer), prevents the H+ from inc. pH. - HCO3− move into the plasma with the aid of a counter- transport mechanism. HCO3− moves out RBC in exchange for Chloride (Cl− moves in), know as the chloride shift (Hamburger phenomenon) RBC takes in Cl− ions without using ATP. Result in mass movement of Cl− into the RBC. Helps maintain the neutral charge within the RBC membrane. Transport of CO2 CO2 diffuses 7% remains into the dissolved in bloodstream plasma (as CO2) 93% diffuses into RBCs 23% binds to Hb, 70% converted to forming H2CO3 by carbonic carbaminohemoglobin, anhydrase Hb CO2 RBC H2CO3 dissociates into H+ and HCO3− H+ removed by buffers, especially Hb HCO3− moves out of RBC in PLASMA exchange for Cl− (chloride shift) CO2 Gas Transport from tissues Chloride shift Cells in Systemic peripheral capillary tissues CO2 pickup CO2 delivery to alveoli for release during exhalation Alveolar air space Pulmonary capillary CO2 delivery Revision Questions: 1. Define following: carbaminohemoglobin, oxyhemoglobin, oxygentated, deoxygenated, hemoglobin saturation 2. Explain the pressure difference for partial pressure of oxygen and carbon dioxide between the alveoli and pulmonary capillaries and why is it significant. 3. Name two ways oxygen is transported. 4. Explain the oxygen-Hb dissociating curve. 5. Using a diagram, explain how oxygen is transported to the tissues. 6. Name the factors that affects the Hb affinity for oxygen. 7. Name 3 ways carbon dioxide is transported. 8. What is the chemical reaction for the production of carbonic acid. 9. Using a diagram, explain the off loading of carbon dioxide at the alveoli.