Gas_Transport.pdf

Gas Transport Dr John P Winpenny Senior Lecturer in Physiology School of Medicine University of St Andrews ([email protected]) Footer: Gas Transport 1 Learning Outcomes • • • • • • • • • • List the ways by which oxygen is carried in the blood Recognise what proportion of oxygen is carried...

Gas Transport Dr John P Winpenny Senior Lecturer in Physiology School of Medicine University of St Andrews ([email protected]) Footer: Gas Transport 1 Learning Outcomes • • • • • • • • • • List the ways by which oxygen is carried in the blood Recognise what proportion of oxygen is carried in each form Describe the oxygen-haemoglobin dissociation curve Explain the physiological significance of the shape of the curve Describe the factors that cause the curve to shift to the right or to the left Calculate how much oxygen is carried in the blood List the ways by which carbon dioxide is carried in the blood Recognise what proportion of carbon dioxide is carried in each form Describe the role of the red blood cells in carbon dioxide carriage Describe how carbon dioxide is converted to bicarbonate Primary Functions Of The Respiratory and Cardiovascular Systems • One of the primary functions of the cardiovascular systems is to transport O2 from the lungs to all tissues in the body • And CO2 from the tissues to the lungs • The lungs expire this CO2 to the atmosphere • Both gases move by diffusion down their concentration gradients Figure from Review of Medical Physiology by Ganong Oxygen Transport • Oxygen is transported in blood in two ways: – Physically dissolved in plasma – Combined with haemoglobin ~2% ~98% Physically Dissolved in Plasma • Amount of O2 dissolved in plasma depends on its solubility and partial pressure in blood (Recall Henry’s Law) • Henry’s law states that at equilibrium for a given temperature [O2]Dis = solubility O2 x PO2 • • • At 37oC the solubility of O2 in plasma is poor - only 0.03ml/L/mmHg Partial pressure of O2 in arterial blood is ~100 mmHg Therefore only 3ml O2/L of blood can be transported in solution • Equates to 15ml O2/min delivery to tissues • BUT our bodies consume 250ml O2/min • So this mechanism of O2 transport is completely inadequate The Structure of Haemoglobin • • Normal Hb (HbA) is a tetramer Four O2-binding heme groups each attached to a polypeptide (globin) chain • HbA consists of 2α and 2β chains • In Fetal haemoglobin (HbF) the β- chains are replaced by γ-chains • HbS causes sickle cell anaemia – glutamate at position 6 in the β- globin is replaced with a valine. • Each haem group consists of a porphyrin ring surrounding an Fe2+ molecule • • O2 can only be bound in Fe2+ (ferrous state) If iron oxidised to ferric (3+) state leads to methaemoglobin (~1.5% Hb is in this state) – methaemoglobin reductase uses the NADPH chain to reduce metHb back to Hb Haemoglobin Structure Changes With Oxygenation • • Deoxygenated Hb exists in a tensed state (T) compared with oxygenated Hb in a relaxed state (R) In the tensed state strong ionic bounds form between the 4 polypeptide chains – immobile and apart • β-globins also bind 2,3 DPG • The consequence of this is that the Fe lies deeper in the pocket and cannot bind O2 As O2 binds the bonds break and the Fe moves to the plane of the porphyrin rings – relaxed state The colour of blood changes from dark blue to bright red • • Haemoglobin Oxygen Dissociation Curve • Binding of one O2 molecule makes it easier for the subsequent ones to attach • Haem-haem interaction – cooperatively. This accounts for the shape of O2-Hb dissociation curve • The colour change is utilised clinically to measure the O2 saturation of blood using the pulse oximeter 100mmHg  13.3 kPa 40mmHg  5.33 kPa 7.5mmHg = 1kPa Combined With Haemoglobin (Hb) • Amount of O2/L of blood attached to Hb, at full saturation, is called O2 capacity and depends on the Hb concentration in blood • Each g of Hb, when fully saturated carries 1.35ml of O2 • Maximal O2 bound to Hb can be calculated as: max 𝑂2 𝑏𝑜𝑢𝑛𝑑 𝐻𝑏 = 𝑂2 𝑐𝑎𝑝𝑎𝑐𝑖𝑡𝑦 ∗ [𝐻𝑏] max 𝑂2 𝑏𝑜𝑢𝑛𝑑 𝐻𝑏 = 1.35𝑚𝑙/𝑔 ∗ 150𝑔/𝐿 =203ml O2/L blood • Equates to 235ml O2/min delivery to tissues • % 𝑠𝑎𝑡𝑟𝑛 𝐻𝑏 = 𝑂2 𝑎𝑐𝑡𝑢𝑎𝑙𝑙𝑦 𝑏𝑜𝑢𝑛𝑑 𝑡𝑜 𝐻𝑏 𝑂2 𝑐𝑎𝑝𝑎𝑐𝑖𝑡𝑦 𝑜𝑓 𝐻𝑏 ∗ 100 Myoglobin & Foetal Haemoglobin • MyHb and HbF shift the curve to the left • HbF Consists of 2 α-chains and 2 γ-chains • HbF has higher O2 affinity than HbA due to special properties of γ-chains • May take up to 2 years to convert all HbF to HbA Factors that Affect Haemoglobin Affinity for O2 • • • CO2, H+ and 2,3 DPG affects the affinity of Hb for O2 Left shift – high affinity Right shift – low affinity • CO2, H+ and 2,3 DPG affect the globins • In systemic capillaries increases in CO2, temperature and decrease in pH, move Hb to low affinity tensed state, so more O2 released (right shift) • In pulmonary capillaries temperature is lower, Pco2 is lower and pH is higher, moves Hb to higher affinity relaxed state , so more O2 taken up by Hb (left shift) Bohr Effect (Shift) • Bohr observed that respiratory acidosis shifted the Hb-O2 dissociation curve to right • This respiratory acidosis has two components – Decrease in pH (more acidic) – Increase in Pco2 Effects of Temperature and pH on the O2-Hb Dissociation Curve • Temperature affects the O2 capacity of Hb, by affecting Hb structure • Changes in pH account for most of Bohr effect • Metabolic acidosis • Hb good buffer for H+, as [H+] increases conformational change in Hb structure and O2 affinity reduces Effects of Hypercapnia on the O2-Hb Dissociation Curve • Small portion of the Bohr effect • Pco2 increase – CO2 combines with unprotonated amino group on Hb – carbamino groups • Carbamino haemoglobin Effects of 2,3-diphosphoglycerate (DPG) on the O2-Hb Dissociation Curve • RBC do not have mitochondria – by-product of glycolysis – ing PO2 of rbc’s stimulates glycolysis resulting in ed levels of 2,3-DPG • 2,3-DPG interacts with β chains destabilising interaction of O2 with Hb Affect of Carbon Monoxide (CO) on Hb Affinity for O2 • CO, NO and H2S can also bind to Hb and snap it into relaxed state • CO has a 200 fold greater affinity for Hb than O2 • maximal O2 capacity falls to extent that CO binds • However, CO also increases O2 affinity of Hb and shifts dissociation curve to left • Hb does not release O2 when it gets to tissue CO2 Blood Transport • Metabolism generates 200 ml CO2/min at rest • Solubility of CO2 in plasma is 20 times that of O2 • CO2 is transported in blood in two main ways: • In plasma – physically dissolved, combined with plasma proteins and as bicarbonate ions • In red blood cells – in physical solution, combined with Hb and as bicarbonate ions CO2 Transport in Blood from Tissues • HCO3- (majority – 70%) • CO2 dissolved in plasma (10%) • Carbaminohaemoglobin (20%) CO2 Release from Blood in Lungs • Partial Pressure gradients for O2 and CO2 reverse • High PO2 causes H+ to dissociate from Hb • H+ and HCO3- combine to form CO2 and H2O • HCO3- reenters RBCs and combines with H+ to form H2CO3 which dissociates to release CO2 and H2O CO2 Dissociation Curves • • CO2 dissociation curves demonstrate how changes in PCO2 affect total CO2 blood content Carriage of CO2 in blood depends on: – – – PCO2 plasma pH PO2 • Near linear relationship between PCO2 and PO2 in physiological range • Upshift of curve with decreasing PO2 – Haldane effect As blood enters systemic capillaries and release O2 , CO2 carrying capacity rises • • As blood enters pulmonary capillaries and binds O2, CO2 carrying capacity falls and blood dumps CO2 Summary • O2 consumption in adults 250 ml/min, rising to 4L/min in heavy exercise • High PO2 in lungs facilitates O2 binding to Hb (left shift in dissociation curve due to ↓PCO2, ↓ Temp, ↑ pH) • Low PO2 in the tissues encourages O2 release (right shift in dissociation curve - Bohr shift - due to ↑PCO2, ↑ Temp, ↓ pH) • CO2 carried predominantly as HCO3- in red blood cells References • Boron, WF & Boulpaep, EL (2017) Medical Physiology (3rd Edition) – Chapter 29 Transport of oxygen and carbon dioxide in the blood p647-659 • Guyton & Hall (2016) Textbook of Medical Physiology (13th Edition) – Chapter 41 Transport of Oxygen and Carbon Dioxide in Blood and Tissue Fluids p527-537 • Preston RR & Wilson TE (2013) Lippincott’s Illustrated Reviews: Physiology (1st Edition) – Chapter 23 Gas Exchange p280-297 • Naish, J & Syndercombe Court, D. (2019). 3rd Edition. Medical Sciences – Chapter 13 The Respiratory System p603-642 • Ward, J, Clarke, R & Linden, R (2005). Physiology at a Glance – Chapter 24 Carriage of oxygen and carbon dioxide by the blood p56-57