RCSI Carriage of Oxygen and Carbon Dioxide Respiratory Module PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Carriage of Oxygen and Carbon Dioxide Respiratory module Dr. Marc Sturrock – [email protected] Centre for Systems Medicine Department of Physiology and Medical Physics Presented by Dr Ebrahim Rajab [email protected] 5-Ma...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Carriage of Oxygen and Carbon Dioxide Respiratory module Dr. Marc Sturrock – [email protected] Centre for Systems Medicine Department of Physiology and Medical Physics Presented by Dr Ebrahim Rajab [email protected] 5-May-2023 LEARNING OUTCOMES CARRIAGE OF OXYGEN • Explain how oxygen is transported in blood • Describe the relationship between PO2 and haemoglobin saturation • Identify the factors which influence the oxygen-haemoglobin dissociation curve • Describe the different types of haemoglobin and their effects on O2 transport • Relate normal to abnormal transport of oxygen • Define cyanosis CARRIAGE OF CARBON DIOXIDE • Describe the various means of CO2 transport • Delineate the crucial role of CO2 transport in the form of bicarbonate • Identify the role of carbonic anhydrase and the chloride shift • Describe the Haldane effect • Describe the effects of hypo- and hyperventilation • Relate the effects of hypo- and hyperventilation to arterial blood PCO2 Gas exchange The transportation of gases throughout the body takes place in the bloodstream through the action of the cardiovascular system (heart and blood vessels). The sites of exchanges: 1. At the lungs between blood and air 2. At tissues between blood and tissues. LO: Explain how oxygen is transported in the blood Transfer of O2 and CO2 into and out of blood is controlled by Diffusion Diffusion is a passive process that pushes atoms and molecules from regions of high concentration to regions of low concentration until Equilibrium is established. Diffusion is “driven” by random, elastic collisions between gas molecules (no energy loss). Diffusion is “driven” by random, elastic collisions between gas molecules (no energy loss). Most gas molecules have velocities ~ near speed of sound (344 ms-1). Each molecule in air collides with another 1010 times per second: 10,000,000,000 At these high speeds, O2 and CO2 very quickly diffuse through the alveolar wall into capillaries. Equilibrium is established within 1 sec Transport of Oxygen in the Blood Oxygen (O2) is transported in two ways in the blood: Physically dissolved in plasma (~2 %) • Poor solubility of oxygen; • Compared to carbon dioxide (CO2), oxygen is relatively insoluble in plasma; • 100 ml arterial blood contains 0.3 ml of dissolved O2 at PO2 = 100 mmHg. Chemically bound to the haemoglobin molecule (Hb) in the red blood cells (RBC) (~98 %) • 100 ml arterial blood contains 19.5 ml of O2 bound to Hb LO: Explain how oxygen is transported in the blood Henry’s Law Henry's law states that the amount of dissolved gas in a liquid is proportional to its partial pressure in the gas form Haemoglobin • Cytoplasm of red blood cells is rich in haeomoglobin • Hb is a heterotetramer consisting of 4 subunits (2 α and 2 β chains) • Each haem iron atom molecule contains one • The haem molecules give haemoglobin its red colour • O2 binds loosely and reversibly with iron to form oxyhaemoglobin • The reversibility of this reaction allows O2 to be carried from the respiratory organs and released to the rest of the body (i.e. the tissues). LO: Describe how oxygen is transported in the blood • Each Hb can carry up to 4 O2 molecules. Hb + 4O2 deoxyhaemoglobin Hb4O2 oxyhaemoglobin a.k.a reduced Hb allosteric effect of oxygen: Hb conformation from a tense state (lower affinity for oxygen) to a relaxed state (higher affinity for O2). Oxygen binding is cooperative – binding of oxygen to one site increases the ability of the remaining sites to bind Oxygenated Hb, HbO2 Deoxygenated Hb, Hb Carboxyhaemoglobin, COHb Bright red (normal arterial blood) Dark red/Blue (venous blood) Cherry red (patients with CO poisoning) LO: Describe how oxygen is transported in the blood • The oxygen content of the blood: the amount of O2 in the blood (sum of both forms, dissolved and bound to Hb) Typical ml O2 per 100 ml blood (or volume %) = 0.3 ml (plasma) + 19.5 ml (RBC) = 19.8 ml/100 ml blood. Arterial O2 blood content ~ 20 vol% Venous O2 blood content ~ 15 vol% ~ 5 vol% is taken up by the tissues • The oxygen carrying capacity of the blood: the maximum amount of O2 that can be carried by Hb. Each gram of Hb, when fully saturated, can combine with 1.34 ml of oxygen. Hb content = 15 g/100 ml blood, O2 carrying capacity = 1.34 x 15 = 20.1 ml O2 /100 ml blood. LO: Describe how oxygen is transported in the blood • % saturation = O2 bound to Hb O2 capacity • measured non-invasively using a pulse oximeter (SpO2) • Arterial blood gas pressures are measures using arterial blood samples and a blood gas analyser (SaO2) LO: Describe how oxygen is transported in the blood OXYGEN-HAEMOGLOBIN DISSOCIATION CURVE • • • • • LO: Describe how oxygen is transported in the blood the “s” or sigmoid shape means that at the plateau where the % saturation is almost 100%, the PO2 can fall without much of a fall in % saturation this is a protection against altitude and respiratory disease crucial PO2 = 8 kPa (60 mmHg) = 90% saturation however, the plateau reduces the usefulness of hyperventilation and O2 therapy the steep portion allows for O2 unloading in the tissues The position of the oxyhaemoglobin dissociation curve is not fixed and can vary depending on a few factors ”Right Releases” LO: Describe the factors which influence the oxygen-haemoglobin dissociation curve • • • in the tissues, the increase in PCO2 and H+ causes the haemoglobin to release more O2, the Bohr effect The Bohr effect states that haemoglobin’s oxygen binding affinity is inversely related to both acidity and PCO2 The Bohr effect facilitates O2 release from Hb at tissues (curve shifts right due to increased PCO2) LO: Define the relationship between PO2 and haemoglobin saturation • A similar effect is also caused by an increase in temperature and 2,3diphosphoglycerate • 2,3-DPG is formed in the RBC and binds to the beta chains of haemoglobin causing O2 release • 2,3-DPG is increased in exercise, altitude, anaemia and respiratory disease and is reduced in stored blood LO: Define the relationship between PO2 and haemoglobin saturation • haemoglobin F (fetal) binds O2 better than haemoglobin A (adult) because 2,3-DPG binds poorly to the gamma chains of haemoglobin F • this improves O2 transfer across the placenta • myoglobin is found in skeletal and cardiac muscle. It has a higher O2 affinity than Hb and acts as a tissue store of O2 LO: Describe the different types of haemoglobin and their effects on O2 transport • Abnormal transport of oxygen 1) Anemia • % Hb saturation is not affected, but the arterial content of blood is reduced because the decreased amount of Hb per 100 ml blood decreases the O2 carrying capacity of the blood LO: Describe abnormal transport of oxygen • haemoglobin binds carbon monoxide 240 times more avidly than O2 forming carboxyhaemoglobin which does not bind O2 (carboxyhaemoglobinaemia, carbon monoxide poisoning) 2) Carbon Monoxide (CO) • CO also shifts the oxyhaemoglobin dissociation curve to the left (interferes with the unloading of O2 at the tissues). • CO can lead to severe tissue hypoxia. Carbon monoxide is colourless, odourless, tasteless and does not elicit reflexes such as coughing or sneezing. It does not increase ventilation nor results in a sensation of shortness of breath (dyspnoea). LO: Describe abnormal transport of oxygen CYANOSIS • cyanosis is a blue colouration of the skin and mucous membranes, especially the tongue, mouth, lips and nail beds • it occurs when the arterial blood is 85% saturated (PO2=50 mmHg or 6.7 kPa) or when the capillary blood is 70% saturated (37.5 mmHg or 5 kPa) • central cyanosis is due to arterial blood desaturation • peripheral cyanosis is due to reduced tissue blood flow due to vasoconstriction (exposure to cold, Raynaud’s disease etc.), vascular obstruction or decreased cardiac output (heart failure, shock etc.) LO: Define cyanosis Transport Of Carbon Dioxide in the Blood Carbon dioxide (CO2) is transported in three different ways in the blood: Arterial CO2 blood content ~ 48 vol% Venous CO2 blood content ~ 52 vol% ~ 4 vol% produced by the tissues physically dissolved (5%) combined with Hb as carbaminohaemoglobin (HbCO2) (3%) chemically combined as bicarbonate ion (HCO3–) (92%) LO: Describe the various means of CO2 transport • In plasma, carbon dioxide slowly combines with water to form carbonic acid CO2 + H2O --> H2CO3 (carbonic acid) • This reaction proceeds much more rapidly inside RBCs as a result of the action of the enzyme carbonic anhydrase • Carbonic acid is an unstable intermediate molecule and quickly dissociates into hydrogen ions and bicarbonate ions H2CO3 --> H+ + HCO3- (bicarbonate ion) Ca = carbonic anhydrase - an enzyme present in red blood cells but not in plasma that accelerates the formation of carbonic acid from water and CO2 over 1000 times. LO: Describe the various means of CO2 transport Since carbon dioxide is quickly converted into bicarbonate ions, this carbonic anhydrase reaction allows for continued uptake of carbon dioxide into the blood, allowing for a large amount of carbon dioxide to be transported as bicarbonate It also results in the production of H+ ions. If too much H + is produced, it can alter blood pH. Most hydrogen ions released from the carbonic acid combine with haemoglobin, which is a very effective buffer, thus limiting shifts in pH LO: Describe the various means of CO2 transport Chloride shift at tissues • CO2 diffuses into the red blood cells (while oxygen diffuses out) • CO2 is converted into bicarbonate and hydrogen ions in the red blood cell • Cell membranes are generally impermeable to charged ions (i.e. H+) but RBCs can exchange bicarbonate for chloride using the anion exchanger protein Band 3 • Without the inward movement of negative chloride ions (in exchange for the outward movement of the bicarbonate) , the red blood cell would develop a net positive charge (because of its retention of positive ions) • This process ensures ionic and electrical stability of the RBC during the transport of carbon dioxide LO: Identify the role of carbonic anhydrase and the chloride shift Reverse chloride shift at lungs • O2 diffuses into the red blood cells (while CO2 diffuses out) • O2 binds to haemoglobin and causes it to release hydrogen ions • The fall in RBC pH results in the reverse conversion of bicarbonate into CO2 and water • As the concentration of bicarbonate in the cell falls, more bicarbonate is exchanged with chloride (by the Band 3 protein) • This movement of ions is driven by the concentration gradient of HCO3- that is created as HCO3- levels inside the RBCs decrease. HALDANE EFFECT • the deoxygenation of blood increases its ability to carry CO2 • the loss of O2 allows Hb to bind more CO2 and H+ so more CO2 is carried as carbamino compounds and as HCO3• the pH falls from 7.4 in the arterial blood to 7.35 in the venous blood LO: Define the Haldane effect CO2 DISSOCIATION CURVE • is linear; deoxygenated blood • the transport of CO2 is dependent on O2 release; 52 CO2 content ( ml%) oxygenated blood 48 40 46 PCO2 (mmHg) LO: Define the Haldane effect • the CO2 dissociation curve is influenced by the state of oxygenation of the Hb (Haldane effect). • hyperventilation means “overbreathing” i.e. the PaCO2 is less than 40 mmHg • hypoventilation means that the PaCO2 is greater than 40 mmHg • hyperventilation (altitude, hysteria) causes respiratory alkalosis, and hypoventilation (respiratory disease) causes respiratory acidosis LO: Describe the effects of hypo- and hyperventilation Carriage of oxygen and carbon dioxide Reading Sherwood – Human Physiology, 7th ed. – Chapter 13 Berne & Levy 7th Ed ‘Physiology’ – Chapter 22 PANOPTO LINKS Please view the below videos before the class (I split it into 4 parts): https://rcsi.cloud.panopto.eu/Panopto/Pages/Sessions/Li st.aspx?folderID=f452dcd9-d762-4318-bb6caff3011323da