3.2 Transport of O2 and CO2 1.pptx

Transport of Oxygen and Carbon Dioxide in the Blood Lecture Outline I. Transport of Oxygen by the Blood II. Oxyhemoglobin Dissociation Curve III. Transport of Carbon Dioxide by the Blood IV. Carbon Dioxide Dissociation Curve V. Bohr and Haldane Effects 1 Transport of Oxygen and Carbon Dioxide in the...

Transport of Oxygen and Carbon Dioxide in the Blood Lecture Outline I. Transport of Oxygen by the Blood II. Oxyhemoglobin Dissociation Curve III. Transport of Carbon Dioxide by the Blood IV. Carbon Dioxide Dissociation Curve V. Bohr and Haldane Effects 1 Transport of Oxygen and Carbon Dioxide in the Blood Objectives 1. Describe the relationship between the partial pressure of oxygen in the blood and the amount of oxygen physically dissolved in blood 2. Describe the chemical combination of oxygen with hemoglobin and the “oxyhemoglobin dissociation curve” 3. Define hemoglobin saturation, the oxygen-carrying capacity, and the oxygen content of blood 4. Describe the structure of hemoglobin, a heme molecule, and the protoporphyrin ring 5. Explain the physiologic consequences of the shape of the oxyhemoglobin dissociation curve 6. List the physiologic factors that influence the oxyhemoglobin dissociation curve and predict their effects on oxygen transport by the blood 7. State the relationship between the partial pressure of carbon dioxide in the blood and the amount of carbon dioxide physically dissolved in the blood 8. Describe the transport of carbon dioxide as carbamino compounds with blood proteins 9. Explain how most carbon dioxide is transported as bicarbonate 10.Describe the carbon dioxide dissociation curve for whole blood 11.Explain the Bohr and Haldane effects 2 References Assigned reading from your text: Levitzky Chapter 7 3 I. Transport of Oxygen by the Blood 4 Oxygen and Carbon Dioxide Transport CO2 O2 5 Transport Of Oxygen By The Blood  Volume of oxygen delivered to systemic vascular bed per min = CO x arterial O2 concentration Body has limited stores of oxygen so limiting cardiac output or pulmonary oxygenation is fatal within minutes Content or concentration of O2 (CaO2) is expressed in ml of O2/ 100 mL of blood Normally expressed as Volumes Percent = ml O2 per 100 mL of blood Oxygen content (concentration): 1. O2 dissolved in plasma (~3%) PO2 determines how much O2 combines with hemoglobin 2. O2 reversibly combined with hemoglobin (~97%) 6 Calculating Oxygen Content of the Blood  Oxygen content is composed of hemoglobin bound + dissolved  Equation for calculating oxygen content of the blood is: (CaO2) = (1.34 x Hb x SaO2) + (PaO2 x 0.003) 7  Volume of oxygen consumed by the tissue per min VO2 = cardiac output X the arteriovenous difference in oxygen content Cardiac output = SV X HR Arteriovenous difference in oxygen content = CaO2 – CvO2 Normal cardiac output = 5 L/min Normal arterial O2 content or CaO2 = 20 mL/dL Normal venous O2 content or CvO2 = 15 mL/dL Oxygen delivery to tissues: ~ 5 ml O2/100 ml blood at rest 5 ml O2/100 ml blood = 50 ml O2/1 L blood = 250 ml O2/ 5 L blood 8 Amount of O2 Dissolved In Plasma  Is measured by the PaO2 (partial pressure or oxygen tension)  Is insufficient to fulfill the body’s oxygen requirements at rest (normal FiO2 at sea level) Solubility coefficient of O2 = 0.003 ml O2/ 100 ml blood/mmHg (or per deciliter (dL)) Henry’s Law- At a temperature of 37°C, 1 mL of plasma contains 0.00003 mL O2/mm Hg PO2 Amount of O2 normally dissolved in arterial blood at PaO2 of 100 mmHg is: 100 mmHg (PaO2) x 0.003 ml O2/100 ml blood/mmHg = 0.3 ml O2/100 ml blood CaO2 from dissolved fraction of O2 = ___ ml O2/100 ml blood CvO2 from dissolved = 40 mmHg (pvo2) x 0.003 ml O2/dL blood/mmHg = O2 delivered to tissues from dissolved= ___ ml O2/dL – ___ ml O2/dL = ___ ml O2/dL blood During intense exercise- O2 demand rises to as high as 4 L/min Max cardiac output attainable is ~ 25 L/min The important point - Your patient will need hemoglobin to transport sufficient O29 ml O2/dL blood Oxygen Chemically Combined With Hemoglobin  97% of oxygen delivered to tissues is combined with hemoglobin (Hb) Adult hemoglobin, HbA is a tetramer composed of: 4 heme molecules + 4 globin chains Cells must synthesize all parts except Fe2+ Four globin polypeptide chains 2 -globin subunits and 2  -globin subunits  A heme molecule is a protoporphyrin ring with a suspended iron molecule Fe in the Fe2+ state binds O2 - Not the Fe3+ state One molecule of Hb combines with 4 molecules/8 atoms of oxygen 10 Porphyrins The heme group is a prosthetic group consisting of a protoporphyrin ring and a central, suspended iron atom Acute intermittent porphyria (AIP) is caused by a gene mutation that interferes with cytoplasmic heme synthesis and causes the accumulation of toxic heme precursors- Any drug that induce ALA synthase can accelerate this process (barbiturates, etomidate, glucocorticoids, hydralazine)  From Covid article published 4/19 “surface glycoprotein could bind to the porphyrin… proteins could coordinate attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin. The attack will cause less and less hemoglobin that can carry oxygen and carbon dioxide. The lung cells have extremely intense poisoning and inflammatory due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images” A porphyrin is a heterocyclic compound containing four pyrrole rings arranged in a square with a metal atom in the central cavity (Hb+ Fe; a protoporphyrin lacks the central metal ion Porphyrin 11 Cooperative Binding Of Hemoglobin (Hb)  Hb forms a reversible bond with oxygen The reversibility of this reaction allows O2 to be released to the tissues  Hemoglobin occurs in two forms: T or “Tense” form = deoxyhemoglobin Hb not combined with O2 R or “Relaxed” form = oxyhemoglobin Hb combined with O2 Oxygen binding increases the affinity of hemoglobin for more oxygen The sequential loading/unloading of Hb produces the sigmoidal shape of the oxyhemoglobin dissociation curve 12 O2 Carrying Capacity of Hb  O2 carrying capacity of Hb is the maximal amount of O 2 that can bind with Hb O2 combines rapidly with Hb (halftime = 0.01 sec); Reversible binding is essential for unloading O2 in tissues One gram of Hb can combine with 1.34 ml O2 Each gram is capable of combining with 1.39 ml O 2 Some Hb may be combined with carbon monoxide (smoker) Some Hb exists in the form of methemoglobin and cannot combine with O 2 Iron in the Ferric state (+3) combined with Hb = methemoglobin (nitrites) Physiologic man with a Hb of 15g has an O2 carrying-capacity of ~20 ml O2/100 ml blood 13 Pulse Oximetry  SpO2 = Peripheral capillary oxygen saturation The oxygen saturation of Hb is the proportion of oxygenated hemoglobin compared to total hemoglobin Calculation to find % Hb saturation: O2 combined with Hb ÷ O2 carrying-capacity of Hb x 100% = % Hb saturation Reading is independent of Hb content 14 Sample problem  Evaluate oxygen content using measured Hb of blood An individual has: PaO2 = 70 mmHg % Hb Saturation = 94.1% Hb = 10 g/100 ml Blood 1. Find the amount of O2 dissolved in the plasma 0.003 x PaO2= 2. Determine the O2 carrying capacity g Hb x 1.34 ml O2= 3. Determine the amount of O2 combined to Hb carrying capacity x % saturation = 4. What is the oxygen content of this blood? (Hb bound O2) + (dissolved O2)= 15 II. Oxyhemoglobin Dissociation Curve 16 Oxyhemoglobin Dissociation Curve  Shows the relationship between PO2 and percent oxygen combined with Hb Standard conditions for a normal adult: Body temp.= 37o C PaCO2 = 40 mmHg Ph = 7.4 PaO2 = 100 mmHg Saturation follows a sigmoid curve – four Hb chains load with O2 sequentially The saturation curve is independent of blood Hb content. An anemic person will still have existing Hb saturated with O2 at the usual PaO2. The difference between anemia and normal the oxygen carrying capacity of blood 17 Oxyhemoglobin Dissociation Curve And Pao2  As PaO2 increases so does the % Hb saturation Normal PaO2 of 100 mmHg = 97.5% It takes a PaO2 of ~ 250 mmHg blood to achieve a 100% Hb saturation Increase the Hb saturation by 2.5% (97.5%  100%) requires an additional 150 mmHg Maximum O2 loading occurs at PaO2 of ~ 100mHg; a PaO2 above this doesn’t improve loading- it increases dissolved O2 Hyperventilating can only raise PaO2 to 130 mmHg no significant effect P50 50% Hb saturation occurs at a very low PaO2 A lower P50 reflects a left shift A higher P50 reflects a right shift 18 Volumes Percent Curve  Compares: % Hb Saturation (SpO2) O2 bound to Hb And dissolved PO2  Assumes 15 g Hb/dL blood Red indicates O2 bound to Hb Total o2 curve is dissolved + bound Green is only dissolved 19 Venous PaO2  Normal venous blood has a normal paO2 of 40 mmHg and the Hb Is 75% saturated Blood has given up 25% of its O2 as it passed through systemic capillaries This corresponds to 15 volumes percent; Arterial blood (Hb 97.5% saturated, PaO2 of 100 mmHg) =20 volumes percent 5 volumes percent or 5 ml O2/100 ml blood was given up to tissues Utilization coefficient is the percentage of oxyhemoglobin that gave up O 2 to tissues passing through systemic capillaries 25% in the normal individual at rest  Physiologic man has: 15 g Hb/100 ml blood and PaO2 = 100 mmHg 1.34 ml O2 x 15 g Hb = 20 = 20 ml o2/100 ml blood What is the volumes percent with a PaO2= 60 mmHg and a saturation of 90%?_______ 20 21 Comparison of Volumes Percent  When Hb is 100% saturated Hb is carrying 20 volumes percent Blood oxygen content is expressed in ml of oxygen per 100 ml volumes percent Hb is 100% saturated at 20 volumes percent Volumes percent varies with concentration of Hb: Percent saturation does not change with Hb  Comparison of 2 individuals with SpO2 100% A person with 15 g Hb/dL blood has a volumes percent of ~20 A person with 7.5 g Hb/100 ml blood has a volumes percent of ~10 Half the normal Hb content half the volumes percent of normal (10 vs 20) 22 Characteristics Of The Oxyhemoglobin Dissociation Curve  Steep portion of the oxyhemoglobin-dissociation curve: Corresponds to the tissue oxygen tension: PaO2 = 40 to 10 mmHg Significance: a relatively small drop in PaO2 yields a large amount of O2 being unloaded A steeper curve indicates more O2 released for the same amount of O2 tension  Upper flattened portion of the oxyhemoglobin dissociation curve: Significance: even though PaO2 may decrease, O2 saturation remains relatively high Normally arterial blood has a PaO2 = 100 mmHg and Hb saturation = 97.5% A decrease in PaO2 to 60 mmHg shows a Hb saturation of 90% Safety decrease in PO2 of 40mmHg decreases saturation only by 7.5% Reducing the initial pressure gradient reduces the rate of diffusion at the respiratory membrane and tissue 23 Shifting Of The Oxyhemoglobin Dissociation Curve And Its Significance  When shifting the curve to the right or left: The greatest movement occurs in the steep portion of the curve: Corresponds to tissue oxygen tensions Reflects a change over the PaO2 range of 10-40 mmHg Oxygen unloading in tissues will be significantly affected There is less movement in the upper flat portion of the curve  The P50 is a convenient way to discuss shifting of the curve Venous curve is shifted right Lower pH Higher PCO2 24 Shifting Of The Curve To The Right  Hb has a decreased affinity for oxygen (right = release) Hb gives up oxygen more easily than normal Occurs near metabolically active tissue  Factors that shift the curve to the right: 1. 2. 3. 4. Increased CO2 (shown) Decreased pH (Increase in [H+]) (shown) Increased Temperature Increased 2,3 DPG  Right shift = Bohr effect: CO2 and H+ cause Hb to release oxygen CO2 enters erythrocytes where H+ is generated CO2 and hydrogen ions cause a conformational change in the Hb molecule Facilitates release of O2 Factors that cause a right shift are r/t metabolism or acidosis (ketoacidosis, lactic acidosis, etc) 25 Right Shift- Bohr Effect (CO2 and H+)  Right shift = Bohr effect: CO2 and H+ cause Hb to release oxygen CO2 enters erythrocytes where H+ is generated CO2 and hydrogen ions cause a conformational change in the Hb molecule Facilitates release of O2 Factors that cause a right shift are r/t: 1. Increased PCO2 from metabolism 2. Decreased pH - acidosis (ketoacidosis, lactic acidosis, etc) 26 Right Shift- Temperature and 2,3 DPG 3. Increase in temperature 4. Increase in 2,3 diphosphoglycerate (2,3 DPG)  2,3 DPG: Is produced during RBC glycolysis Maintains the curve slightly right at all times Is increased by hypoxia- facilitates offloading Is an important compensation during chronic anemia 27 Left Shift (Reverse Bohr Effect) (CO2 and H+)  Left shift is due to less [H+] interacting with Hb inside erythrocytes Hb has an increased affinity for oxygen (”L”eft is for Love) Occurs in the lungs  Factors that shift the curve to the left: 1. Decreased CO2 (shown) 2. Increased pH (Decrease in [H+]) (shown) 3. Decreased Temperature 4. Decreased 2,3 DPG 5. Most hemoglobinopathies Methemoglobin (Fe3+) Carboxyhemoglobin Fetal hemoglobin (HbF) 28 Left Shift- Temperature and 2,3 DPG 3. Decreased temperature 4. Decreased 2,3 diphosphoglycerate (2,3 DPG) In packed cells/banked blood, 2,3-DPG is lower Shifts the curve left and reduces available O2 29 Left Shift- Hemoglobinopathies 5. Most hemoglobinopathies shift the curve left 30 Myoglobin  Myoglobin is a single-polypeptide heme protein that stores O2 in muscle cells Combines with a single molecule O2 Structurally similar to a single Hb subunit Hyperbolic dissociation curve P50 far left of HbA O2 remains bound for conditions with lower PO2 31 Carbon Monoxide  Shifts the O2-dissociation curve to the left in the steep portion of the curve Decreases the upper flat portion of the curve CO has an affinity for Hb 210x that of O2 – takes 210x less CO than O2 to bind with Hb Bound to Hb at low PO2 alters the configuration of Hb and increases Hb’s affinity for O2 CO-Hb combination is called carboxyhemoglobin Partial pressure of each gas in a mixture exerts a partial pressure independent of the others CO gas dissolved in plasma does not affect the PO2 in the plasma Individual exposed to CO can have normal PaO 2 and Hb decreased total oxygen content  Binds at same ferrous site on Hb as does O2 Inhibits O2 binding in the lungs & Prevents unloading at the tissues 32 III. Transport of Carbon Dioxide by the Blood 33 Transport of CO2 By the Blood  CO2 production at rest = ~200-250 ml/min Under resting conditions, 4-5 ml of CO2/100 ml blood are unloaded in the lungs at CO 5L/min  Forms of CO2 transport Physically dissolved 5-10% Bicarbonate ion (HCO3-) Most Combined with Hb (Carbamino) 34 Distribution Of CO2 In The Plasma And RBC Dissolved Plasma (~11%) RBC (~89%) Carbamino Compounds Bicarbonate 6% Insignificant With plasma proteins 5% Forms and remains in plasma 4% 21% 64% 35 IV. Carbon Dioxide Dissociation Curve 36 CO2 dissociation curve for total CO2 content in venous and arterial blood  Venous blood CO2 content: ~ 52.5 ml CO2/100 ml blood PvCO2 = 45 mmHg pH of ~ 7.36 PvCO2 5 mmHg than PaCO2 Venous blood is more acidic than arterial  Arterial blood CO2 content: ~ 48 ml CO2/100 ml blood PaCO2 = 40 mmHg pH of ~ 7.4  ~5% CO2 in blood is in physical solution At a temperature of 37°C, 1 mL of plasma contains 0.00067 mL CO2/mm Hg PO2 Solubility coefficient of CO2 is 20 x that of O2 - Diffuses ~ 20 x faster than O2 Venous 0.06 x 45 mmHg = 2.7 ml CO2 / 100 ml blood Arterial 0.06 x 40 mmHg = 2.4 ml CO2 /100 ml blood 2.7 – 2.4 ml CO2 = 0.3 ml CO2/100 ml blood transported in plasma 37 Transport Of CO2 By The Red Blood Cells  PCO2 high in the tissues CO2 diffuses from cells into systemic capillaries into erythrocytes  Carbamino compounds In the RBC, CO2 combines with the terminal amino acids of Hb to form carbaminohemoglobin A hydrogen ion is released when a carbamino compound is formed Deoxyhemoglobin binds more CO2 than oxyhemoglobin Presence of one interferes with the other  Bicarbonate Remainder of the intracellular CO2 reacts very rapidly with water via carbonic anhydrase present in the RBC (13,000x faster than plasma) CA CO2 + H2O  H2CO3  H+ + HCO3- 38 Hb A Better Buffer Than Plasma Proteins  Deoxyhemoglobin favors the formation of carbamino compounds, and it promotes the transport of CO2 as bicarbonate ions by buffering hydrogen ions formed by the dissociation of carbonic acid. Carbonic anhydrase reaction generates H+ and HCO3- At low PO2s, deoxyhemoglobin in RBCs accept H+ ions liberated by dissociation of carbonic acid and formation of carbamino compounds These H+ ions bind to amino acid residues on the globin chains and facilitate release of O2 from Hb (Bohr effect) The Bohr Effect – the oxygen dissociation curve shifts to the right facilitates and facilitates the unloading of O2 for release to tissues 39 Chloride Shift (Hamburger Shift)  The uptake of chloride in exchange for HCO3 When carbonic acid dissociated rapidly into H+ andHCO 3 Hydrogen is buffered by Hb HCO3- is transported to the plasma to function as a buffer There is a 1:1 exchange HCO3- enters plasma, Cl- enters Erythrocytes; chloride shift This preserves electrical neutrality across the erythrocyte cell membrane Chloride shift adds osmotically active ions (Cl-) to RBC in venous circulation Water follows isosmotically causing the erythrocyte to swell This increased RBC volume relative to plasma volume explains Explains why the venous hematocrit is ~ 3% higher than arterial hematocrit 40 Comparison of Reactions In Lungs Versus Tissues  In the lung, reactions are the reverse of what occurs in the tissues: PvCO2 = 45 mmHg; PaCO2 = 40 mmHg CO2 diffuses from pulmonary capillaries into alveoli following Its pressure gradient and O2 enters pulmonary capillaries from alveoli following its pressure gradient; There is a displacement (unloading) of CO2 from HHb and O2 combines with HHb yielding Hbo2 and H+ 41 Carbonic Anhydrase Reaction  Carbonic anhydrase reaction reverses by the law of mass action CA H2CO3  H+ + HCO3- CO2 + H2O  The RBC intracellular [H+] decreases/ pH increases The oxyhemoglobin dissociation curve shifts to the left Reverse Bohr effect occurs  Increased Hb affinity for O2 HCO3- and Cl- exchange in reverse from tissues Cl- moves into plasma and HCO3- moves into erythrocytes to maintain the CA reaction CA CO2 + H2O  H2CO3  H+ + HCO3-  HCO3- from plasma 42 V. Haldane and Bohr Effects 43 The Haldane And Bohr Effects Work In Synchrony For Uptake And Release Of O2 And C  Bohr Effect- At the tissues: Bohr effect = a change in oxygen affinity of Hgb occurs with a change in pH Beneficial at the tissue level where the lower pH decreases O2 affinity and promotes O2 release. Increased CO2/ lower pH of blood causes: O2 to dissociate from Hb CO2 to combine with Hb, form HCO3-  Haldane Effect- At the lungs & tissues: Haldane Effect = the amount of CO2 transported is markedly affected by the PO2 This situation is reversed in the pulmonary circulation 44 45 Haldane Effect Position of the CO2 curve is affected by the oxygen tension (PO2) due to the Haldane effect Haldane effect relates to CO2 transport; Bohr effect relates to O2 transport An increase in O2 will shift the CO2 dissociation curve right decreasing the affinity for CO2 A decrease in O2 will shift the curve left increasing the affinity for CO2 46 1. Oxygen is normally transported in the blood directly combined with: A. A globin chain B. A ferrous atom C. A ferric atom D. Plasma proteins 2. Which of the following shifts the oxyhemoglobin dissociation curve to the left? A. Hypoventilation B. Anemia C. Carbon monoxide D. Ketoacidosis 3. The decrease in O2 affinity of hemoglobin when the pH of blood falls is the ________. A. Bohr effect B. Haldane effect C. Chloride shift 4. Due to the Haldane effect, the high PO2 in the lungs causes ________ of the carbon dioxide hemoglobin dissociation curve. A. A left shift B. A right shift C. A sigmoid shape 47