Hemoglobin_and_Gas_Transport_in_Blood_2023.pptx

Human Physiology Time for some heavy lifting O2 and CO2 Hemoglo bin avid L. Osborne, PhD. Physiology Hemoglobin and Gas transport Class 2023 Academic year Objectives Describe how CO2 is added to blood in the tissue capillary and the importance of the RBC in CO2 transport and the buffering of h...

Human Physiology Time for some heavy lifting O2 and CO2 Hemoglo bin avid L. Osborne, PhD. Physiology Hemoglobin and Gas transport Class 2023 Academic year Objectives Describe how CO2 is added to blood in the tissue capillary and the importance of the RBC in CO2 transport and the buffering of hydrogen ions. Distinguish between hemoglobin saturation, oxygen-carrying capacity, and oxygen content of blood. Draw and describe the CO2 dissociation curve. Draw the oxyhemoglobin dissociation curve and state the physiological significance of the sigmoidal shape. Explain the relationship between the partial pressure of oxygen in blood and the concentration or content of O2 in plasma and whole blood. List reasons why the red blood cell is important in the transport of O2 and CO2. List the factors that cause a shift in the oxyhemoglobin dissociation curve and their effect upon affinity of O2 for Hb and David O2 deliveries L. Osborne, to What gases are we talking about? Oxyg Carried en as: Dissolved 02 Bound to Hemoglobin “oxyhemogl obin” Hemoglob in Carbon Carried dioxide as: Dissolved C02 Bound to “carbaminohemogl Hemoglobin obin” Bicarbonate ion David L. Osborne, Oxygen Transport David L. Osborne, Hemoglobin A Molecular weight: 64,458 Daltons Heme + Alpha and Beta chains Each Heme Reversibly binds: 4 oxygens molecules Each binding makes it easier for the next oxygen to load or David L. Osborne, Without getting into great detail here! What is the barometric pressure of air at sea level ? How much of that is oxygen? How much of that is carbon dioxide? How much of that is nitrogen? 760 mm Hg or 1 atm How does this vary with elevation? 21 % .04% or essentially 0 78 % What is the partial pressure of oxygen at sea level ? Atmospheric pressure X Percent composition of oxygen 760 mmHg X 0.21 = 160 mmHg David L. Osborne, Partial Pressures of Oxygen and Carbon dioxide in the blood • 21% oxygen  760 mmHg x 0.21 = 160 mmHg (partial pressure of O2 at sea level, in air) • 0.04% carbon dioxide  760 mmHg x 0.0004 = 0.3 mmHg (partial pressure of CO2 at sea level) • PiO2 (inspired oxygen) = 0.21 x (760 – 47) = 150 mmHg • • • • • Alveolar PO2 = 104 mmHg [PAO2] Arterial PO2 = 100 mmHg [PaO2] Interstitial PO2 = 40 mmHg Intracellular PO2 = 23 mmHg Venous PO2 = 40 mmHg • • • • • Alveolar PCO2 = 40 mmHg Arterial PCO2 = 40 mmHg Interstitial PCO2 = 46 mmHg Intracellular PCO2 = >46 mmHg Venous PCO2 = 46 mmHg Atm  Alveoli  Artery  tissue O2: 160  104  100  40 tissue  CO2: 46  Vein  Alveoli  Atm 46  40  0.3 David L. Osborne, Clinical Application of this info Alveolar – Arterial PO2 Difference (A-a gradient) • Alveolar vs. arterial oxygen concentration; normally a small difference (100 vs. 95 mmHg) in a healthy patient – can be affected by supplemental oxygen delivery. • can be approximated: Should be LESS THAN (age + 4) / 4 For a 27yo: 27 + 4 = 31 Less than this value 31 / 4 = 7.75 is: normal If the value is greater than this… this indicates a clinical problem associated with hypoxiaDavid or hypoxemia L. Osborne, How much oxygen can blood carry? (based on O2 solubility) • Without Hb: – Carrying capacity for dissolved oxygen is ~0.3 mL per 100 mL of blood at a PaO2 of 100 mmHg 0.3 ml O2 /100 ml blood • With Hb: – Each gram of Hb can bind with 1.39 mL of oxygen ( normally seen as 1.34 mL due to small amt of Hb Oxygen) – Normal ranges for hemoglobin content: MEN - 13.5 to 17.5 grams per 100 mL of blood WOMEN - 12.0 to 15.5 grams per 100 mL blood Bound O2 = (1.34 mL O2 / g Hb x 15 g Hb / 100 mL blood ) X .98 (% saturation) 19.7 ml O2 /100 ml blood Concentration/Carrying Capacity: that cannot bind Also, can be shown in units of g% or g/dL given as vol% or mL O2 per 100 mL of blood O2 bound to Hb + O2 dissolved = Total 0.3 19.capacity 20.0 ml/100 ml carrying 7 98.5 1.5 blood 100 David L. Osborne, Let’s get back to Hemoglobin and gas transport • Oxygen – bound to hemoglobin (Hb), or as a dissolved gas in solution • Oxyhemoglobin – site 4 – binds at PO2 100 mmHg (97% saturated) site 3 – binds at PO2 40 mmHg (75% saturated) site 2 – binds at PO2 26 mmHg (50% saturated) site 1 – usually remains attached under physiological conditions “Deoxyhemoglobin” is without oxygen bound Related “Carbaminohemoglobin” terms is Hb bound to CO2 “Carboxyhemoglobin” has CO bound; CO binds with HIGH AFFINITY to Hb and can displace oxygen (same binding site) David L. Osborne, Same graph 2 different y axes Tiss ue Lun g Sigmoidal shape due to facilitated binding of O2 after some O2 is already bound How much are we delivering off each hemoglobin molecule? Does this make sense? No Not very efficient… how do we make this more effective? David L. Osborne, Factors that alter oxygen binding to Hemoglobin How does this relate to the concept of efficiency of work done by the CV system? Same graph as previous slide Binding affected by conditions in Lung and Tissue Haldane Effect Bohr Effect How does exercise affect this? David L. Osborne, p H Effect of blood flow and metabolic rate on tissue PO2 • Balance between oxygen delivery and oxygen utilization • Increasing blood flow to a tissue increases oxygen delivery, and the PO2 in that tissue see point B increases (solid line) • Tissue PO2 can’t rise above arterial PO2 (95 mmHg) • If you USE more oxygen (increased metabolism), the tissue oxygen levels will be reduced, even with an increase in blood flow to that tissue Carbon Monoxide Dissociation Curve 200 X greater binding to hemoglobin than oxygen Once bound it does not let go : analogous to removing HB from the blood Per cent Saturation 120 100 80 This entire curve fits here!!!!!!!!! !!! 60 40 20 0 0.0 PCO 0.4 Carbon Dioxide Transport David L. Osborne, Carbon Dioxide Transport in Blood • Carbon Dioxide – as bicarbonate (70-90%), bound to Hb, or as a dissolved gas H2O + CO2  H2CO3 carbonic carbonic + H + HCO acid 3 anhydras  e bicarbon ate CHLORI DE SHIFT • Carbaminohemoglobin – CO2 binds to Hb at amine groups (not the same binding sites as O 2) • CO2 is 24x more soluble in blood than O 2 is, so even at lower partial pressures like those seen at the level of the tissues, relatively more CO 2 than O2 is carried as a dissolved gas in plasma 7% CO2 transport, Bicarbonate buffering system, and Chloride shift The body is really sensitive to CO2 levels Accumulation of CO2 is toxic You have to transport CO2 to get rid of it Why not use it for something along the way? CO2 + H2O  H2CO3  H+ + HCO3- * Hb is major buffer agent Chloride shift - Exchange of Cl- for HCO3- gets HCO3- into the plasma * Carbon dioxide transport rbon dioxide dissociation curve: At the lung, binding more O2 to Hb displaces CO2 from the blood: 1) With O2 bound, Hb becomes more acidic and fewer carbamino-Hb compounds form 2) Acidic Hb releases excess H+ ions which combine + CO + H O  H CO  H + HCO 2 2 2 3 3 with HCO3 to form carbonic acid and CO2 which can then be exhaled mal operating range in the body is VERY narrow 40-46 mmHg ~50 vol% (±2) concentration • Haldane effect promotes CO2 transport • This is quantitatively more important than the Bohr effect that promotes O2 transport HALDANE EFFECT The End David L. Osborne,