Lecture 21: Gas Transport in the Blood - PDF

Lecture 21: Gas transport in the blood Dr. Ann Revill [email protected] Office: Dr. Arthur G. Dobbelaere Science Hall 380E 1 Review: Top Hat Question Join code: 43...

Lecture 21: Gas transport in the blood Dr. Ann Revill [email protected] Office: Dr. Arthur G. Dobbelaere Science Hall 380E 1 Review: Top Hat Question Join code: 437994 2  Lecture objectives By the end of this lecture, you will be able to: 1. List how oxygen is transported in blood 2. Describe the relationship between partial pressure of oxygen and hemoglobin oxygen saturation 3. Describe the shape of the oxygen-hemoglobin dissociation curve 4. Summarize factors that affect hemoglobin affinity for oxygen 5. Discuss clinical scenarios that affect the oxygen carrying capacity of blood: hemoglobin variants, blood doping, carbon monoxide poisoning 6. Summarize how carbon dioxide is transported in blood 7. Describe the contribution of the lungs to short-term pH regulation 3  Review of gas exchange By what process does air get to respiratory zone? Primarily bulk flow In lung: Which direction does O2 diffuse? CO2? O2 into blood from alveoli CO2 into alveoli from blood In systemic circulation: What is the main form of O2 for transport? CO2 for transport? O2 = bound to Hb CO2 = chemically modified as HCO3- At tissue: Which direction does O2 diffuse? CO2? O2 into tissue from blood 4 CO2 into blood from tissue  How do we transport enough oxygen in the blood? Dissolved O 2 O2 bound to O2 transport hemoglobin 1. Dissolved O2 2. Bound to hemoglobin O2 solubility - low (Hb) in RBCs ~2% of O2 transported as Most O2 (~98%) carried dissolved O2 attached to hemoglobin in red blood cells 5  Hemoglobin (Hb) Protein composed 4 polypeptide chains called globins, each with a heme group Adult Hb has 2 α and 2 β globins (α2β2) Each Hb molecule can reversibly bind up to four O2 molecules Each heme group is a porphyrin ring structure that contains an iron atom in the ferrous (Fe2+) form, to which O2 binds Hb + O2 HbO2 6  Hemoglobin saturation Hb + O2 HbO2 When not combined with O2 – Hb referred to as reduced Hb or deoxyhemoglobin When combined with O2 – Hb referred to as oxyhemoglobin CO2 can also bind Hb at amino terminals, called carbaminohemoglobin When all heme portions combine with O2, Hb is fully saturated % saturation varies from 0-100% 7 PO2 is primary factor determining % Hb saturation PO2 is related to the concentration of O2 dissolved in the plasma When blood PO2 ↑ – ↑ formation of HbO2 – what happens to % saturation of Hb? increases Hb + O2 HbO2 8 PO2 is primary factor determining % Hb saturation When blood PO2 ↓ – O2 released from Hb as HbO2 dissociates – decrease % saturation Hb + O2 HbO2 Because of differences in PO2 at lungs and in tissue: – Hb loads up on O2 at the lungs – Hb unloads O2 at the tissues 9  Hb facilitates large transfer of O2 10 Sherwood 13-29 Comparison of dissolved to Hb-bound O2 Hemoglobin increases O2 blood transport by approximately 50X Positive cooperative binding action produces the characteristic sigmoidal oxygen binding curve of Hb 11 O2-Hb dissociation curve Sigmoidal shape % saturation ↑ sharply as O2 ↑ from 0-40 mm Hg % saturation levels off from 60-100 mm Hg P50 = PO2 at which Hb is 50% saturated 12 Costanzo 5-20 Using the O2-Hb dissociation curve Example 1: what is the % saturation of Hb in blood that has a PO2 of 25 mmHg? use dissociation curve % sat. = 50 % Example 2: what is the PO2 of blood that is 95 % saturated? ~75 mm Hg 13 Significance of sigmoidal dissociation curve Why? Many conditions 100 result in reduced Percent O2 Saturation of Hb 80 PAO2 and therefore PaO2. 60 Plateau: saturation stays high over wide 40 range of PAO2. E.g. with drop in PO2 to 20 Venous PO2 Arterial PO2 60, saturation drops only 10%. 20 40 60 80 100 PO2 (mm Hg) 14  Significance of sigmoidal dissociation curve 100 Percent O2 Saturation of Hb 80 60 40 20 Venous PO2 Arterial PO2 20 40 60 80 100 PO2 (mm Hg) Shoulder portion: Unload large amounts of O2 with only small decrease in PO2 High capillary PO2 maintains pressure necessary to drive diffusion of O2 from RBC, to blood to cells and mitochondria At rest, most Hb leaving tissues still 75% saturated 15 Significance of sigmoidal dissociation curve 100 Percent O2 Saturation of Hb 80 60 40 20 Venous PO2 Arterial PO2 20 40 60 80 100 PO2 (mm Hg) Steep portion: Increases in metabolic rate cause further decrease in tissue PO2, which facilitates diffusion from plasma which leads to a drop in plasma PO2, diffusion of O2 from RBC, drop in PO2 in RBC, additional dissociation of O2 from Hb 16  Factors to decrease Hb affinity for O2 i.e. facilitate release of O2 Release Right Shift ↓ pH/ ↑ CO2 – Due to increased metabolic activity Percent O2 Saturation of Hb (at tissue) 100 – Bohr shift ↑ Temperature – Due to increased metabolic activity 50 ↑ 2,3-DPG – 2,3-diphosphoglycerate – RBC glycolysis byproduct 0 – Seen in chronic hypoxia (i.e. 0 50 100 altitude) PO2 (mm Hg) Note: 2,3-DPG is equivalent to 2,3-BPG (term used in BIOCG 1551) 17  Factors to increase Hb affinity for O2 Load up i.e. inhibit release of O2 Left Shift ↑ pH/ ↓ CO2 Percent O2 Saturation of Hb 100 – Decreased metabolic activity – Bohr shift ↓ Temperature 50 – Decreased metabolism ↓ 2,3-DPG – RBC glycolysis byproduct 0 Note: 2,3-DPG is equivalent to 2,3-BPG 0 50 100 (term used in BIOCG 1551) PO2 (mm Hg) 18 Clinical connection: Hb variants Methemoglobin Ferric/oxidized vs normal ferrous form – Iron part of the heme in Fe3+ state – Does NOT bind O2 – Caused by chemicals: nitrites or sulfonamides Genetics: methemoglobin reductase deficiency Fetal Hb (HbF) – Greater affinity for O 2 – Facilitates movement of O2 from mother to fetus – 2 γ subunits that are replaced with 2 β subunits over first year of life Sickle cell hemoglobin (HbS) – O2 affinity for HbS < Hb – Causes sickle cell disease 19  Clinical Connection: Blood Doping Temporarily increase O2 carrying capacity of the blood, to gain competitive advantage How might people blood dope? 1. Withdraw blood, freeze RBCs then reintroduce before performance event 2. Inject synthetic EPO to stimulate RBC production Problems? – (other that it’s highly illegal!) – Increase blood viscosity (can lead to death due to cardiovascular complications) When might EPO levels increase naturally? Acclimatization to living at high altitude 20 Clinical connection: carbon monoxide poisoning Carbon monoxide is a lethal gas because it is a competitive inhibitor for the oxygen binding sites on hemoglobin. Based on what you know about hemoglobin activity, what impact would Carbon Monoxide have on hemoglobin activity? Decreased oxygen binding capacity and left shift of dissociation curve 21  Dissolved CO2 CarbaminoHb Bicarbonate CO2 transport 1. Dissolved CO2 2. CarbaminoHb 3. Bicarbonate ~5% of total CO2 binds terminal CO2 + H2O react to transported CO2 amino groups on Hb form HCO3- + H+ ~3% of CO2 90+% of CO2 transported transport 22 Bicarbonate production at tissue Cl- HCO3- exchange CO2 Diffusion H2CO3 dissociates into HCO3- and H+ H+ buffering Carbonic anhydrase catalyzes carbonic acid production 23  CO2 is exhaled at the lungs Chloride shift is reversed Equilibrium reaction favors CO 2 production Dissolved CO2 is driving force for CO2 diffusion into alveoli 24 Non-respiratory functions of the lungs: acid-base Blood acid/base status controlled by relative levels of CO2 and bicarbonate: pH = pK + log [HCO3-]/.03 PCO2 (H-H eq) Blood bicarbonate ions are regulated by the kidney Blood CO2 levels are regulated by the lungs – hyperventilate (↑ VA): lower PaCO2 (less acid) – hypoventilate (↓ VA): raise PaCO2 (more acid) – short-term control 25  Summary: O2 movement in lungs and tissues In lung, between alveoli, plasma and RBC Alveolar membrane RBC membrane & capillary wall alveoli plasma RBC (~2% of O2 dissolved in plasma) Dissolved O2 Inspired O2 PAO2 Dissolved O2 + HbO2 (determines PaO2) (only dissolved O 2 Hb (>98% of contributes to Pa O2) total O2) In tissue capillaries Cells Intersitial plasma RBC fluid (~2% of O2 dissolved in plasma) Dissolved O2 O2 Dissolved Dissolved O2 + HbO2 Used in mitochondria O2 (only dissolved O 2 Hb (>98% of contributes to PaO2) total O2) 26  Summary: CO2 movement in tissues and lungs In tissue capillaries Cells Intersitial plasma RBC (4% remains dissolved) (3% remains dissolved) fluid CO2 Dissolved Dissolved CO2 Diss CO2 + Hb HbCO2 Produced in CO2 (only dissolved CO2 + (23%) mitochondria contributes to PaCO2) H2O Carbonic anhydrase H2CO3 HCO3- HCO3- + H+ Cl- Cl- 27  Summary: CO2 movement in tissues and lungs In lung/alveoli alveoli plasma RBC Expired CO2 Dissolved CO2 Diss CO2 + Hb HbCO2 CO2 (only dissolved CO2 + (23%) contributes to PaCO2) H2O Carbonic anhydrase H2CO3 HCO3- HCO3- + H+ Cl- Cl- 28