OXIGEN & CARBON DIOXIDE TRANSPORT
Biochemistry Departement Medical Faculty Of Andalas University Padang
Total Body Oxygen Stores Oxygen in the Lung (~500 ml O2).
Oxygen in the Blood (~850 ml O2).
Oxygen in the Cells (very little except Mb-bound).
At the Lung Level
At the Tissue Level
Oxygen Is Carried in Blood in 2 FormsBound to hemoglobin in red blood cells.
Dissolved in plasma. Normally insignificant.
*HemoglobinEach heme molecule is capable of binding with 1 O2 molecule and each globin molecule is capable of binding with 1 CO2 molecule.So, each molecule of Hb can bind to either 4 molecules of O2 and 1 molecule of CO2100 ml of blood has about 15 gm of Hb, at Hct = 0.45
*Binding of O2 to 4 heme sites given by:
*Oxygen as Oxyhemoglobin
Each gram of Hb can store about 1.34 ml of O2:1 L of blood (150 gm of Hb) can store about 208 ml of O2 Oxygen Capacity of Hb.With normal cardiac output, about 1040 ml of O2 can be carried in blood per minute. (4 times of the metabolic demands).
O2 Saturation.Units: percent.
Fraction or percentage of all the hemoglobin binding sites that are currently occupied by oxygen.
*Oxygen Saturation of Hb
Four (5-6?) Things Change Oxyhemoglobin AffinityHydrogen Ion Concentration, [H+]2. Carbon Dioxide Partial Pressure, PCO23. Temperature4. [2,3-DPG] 5. Special Case: Carbon Monoxide6. Hemoglobin variants
*Factors Affecting Hb-O2 Affinity: SummaryHydrogen Ion: Increased H+ (decreased pH) increases H+ binding to Hb and reduces O2 affinity (HbO2+H+HbH++O2).
Carbon Dioxide (Bohr effect):Increased PCO2 increases CO2 binding to Hb and reduces O2 affinity (increased O2 delivery to tissue).Increased PCO2 increases H+ and reduces O2 affinity (fixed acid Bohr effect).
Temperature and 2,3-DPG (diphosphoglycerate): Increased temperature and 2,3-DPG reduces O2 affinity.
Effect of CO & Anemia on Hb-O2 AffinityNormal blood with Hb=15 gm/dl, anemia with Hb=7.5 gm/dl, and normal blood with 50% HbCO (carboxyhemoglobin).
Increased PCO2 and Decreased pH (acidosis)
2,3-DPG2,3-DPG is a glycolytic intermediateaccumulates to uniquely high levels in RBCs-Increased 2,3-DPG right shift-Decreased 2,3-DPG left shift
Increased 2,3-DPG associated with hypoxia.
Conditions with Increased 2,3-DPGacclimatization to high altitudes.chronic lung disease; emphysema.anemia.hyperthyroidism.right to left shunt.congenital heart disease.pulmonary vascular disease.
Blood Bank StorageCPD (citrate phosphate dextrose) Storage 2,3-DPG depletion
O.D.C. left-shifted oxygen
Oxygen unloading impaired
*Carbon Dioxide Transport
*At the Tissue Level
*At the Lung Level
*Carbon Dioxide TransportCO2 is transported in blood in dissolved form, as bicarbonate ions, and as protein-bound carbamino compound.
Protein-bound CO2 (carbamino compounds):
Amount of CO2 stored as carbamino compounds is about 21 ml/L (4% of the total art CO2).
*Carbon Dioxide TransportA majority amount of CO2 is transported in the form of bicarbonate ions (HCO3-):
Amount of CO2 in HCO3- form at PCO2=40 mmHg is about 420 ml/L (90% of the total arterial CO2).
*Carbon Dioxide Transport
Haldane Effect: Increasing O2-saturation reduces CO2 content and shifts the CO2 dissociation curve to right. This is because, increasing PO2 leads to :Decrease in the formation of carbamino compound.Release of H+ ions from the hemoglobin and resulting in dehydration of HCO3-.
*Carbon Dioxide Dissociation CurveOver the normal physiological range (PCO2 = 30 to 55 mmHg and PO2 = 40 to 100 mmHg), the CO2 equilibrium curve is nearly linear. But, O2 equilibrium curve is highly nonlinear.
Bicarbonate in RBCs.Carbonic anhydrase is present in RBCsCO2 forms carbonic acid which dissociates to H+ and HCO3- Released H+ is buffered by histidine residues (imidazole group) Percent of the total PaCO2: 70%
Carbamino Compounds in RBCs.Approximately 30% of RBC contents is Hb
CO2 forms carbamino hemoglobin
Released H+ is buffered by histidine residues (imidazole group) Percent of the total PaCO2: 23 %
CO2 Formation in PlasmaCarbamino compounds CO2 binds the amine groups of plasma proteins to form carbamino compounds.
Chloride Shift (Hamburger Shift)Newly formed HCO3- passes out of RBC
Cl- diffuses into RBC to maintain electroneutralityChloride shift is rapidComplete before the RBCs exit capillary
*Tissue-Gas Exchange: SummaryGas exchange processes in the peripheral organs are essentially opposite those in the lungs.O2 is released from the capillary blood to the tissues and diffuses to the mitochondria energy (ATP) through cellular metabolism.CO2 diffuses from the tissues to the blood stream and is transported to the lungs for elimination.The exchange of O2 and CO2 in the blood-tissue exchange unit depends on PO2, PCO2, and also on O2 and CO2 saturation curves.
*ResourcesBIOEN 589: Integrative Physiology. Download 24 jan 05.Kennelly, PJ., Rodwell, V W. Proteins: Myoglobin & Hemoglobin. In: Harpers Illustrated Biochemistry. 27th Ed. 41- 8.Miliefsky, M. Respiratory System Ch.23. Download 24 Nov 10.Sheardown, H. Blood Biochemistry. McMaster University. Download 20 Mei 07. Irvin, CG. Respiratory Physiology. Lecture 4A CO2 Transport. In: MEDICAL PHYSIOLOGY 30. Download 22 Jun 09.Marks, DB., Marks, AD., Smith CM. Basic medical biochemistry: a clinical approach. 1996. Dalam: B.U. Pendit, penerjemah. Biokimia Kedokteran Dasar: Sebuah Pendekatan Klinis. Eds. J. Suyono., V. Sadikin., L.I. Mandera. Jakarta: EGC, 2000R.K. Murray, D.K. Granner, P.A. Mayes, V.W. Rodwell Harpers Biochemistry. 27th ed. McGraw-Hill Companies, New York. 2006.
*5*10*10*13****17*Saturation at the arterial end (PO2 = 100 mmHg) is about 97% and oxygen content of blood is about 20 ml of O2 per 100 ml of blood. Saturation at the venous end (pO2 = 40 mmHg) is about 75% and oxygen content of blood is about 15 ml of O2 per 100 ml of blood. P50 is about 26 mmHg. Concentration of bound oxygen is considerably high compared to that of the dissolved oxygen. The saturation profile is mostly flat in the physiological range of PO2 (40 mmHg 100 mmHg).*31*Normal CO2 Bohrs effect and fixed acid Bohrs effect. CO2 hydration reaction in RBCs is catalyzed by the Carbonic Anhydrase (CA).*Carbon monoxide (CO) and O2 bind reversibly to the same site on the hemoglobin molecule. Binding of CO prevent O2 binding. Because hemoglobin has an affinity for CO that is about 250 times greater than that for O2, it takes a small amount of CO to displace O2 from the heme binding site. CO binding not only decreases the O2 content but also increases the hemoglobin-oxygen affinity of the remaining heme sites. The resulting O2 equilibrium curve is reduced in magnitude as well as shifted to the left. The venous PO2 is reduced, due both to a lower O2 content and a higher O2 affinity.*37*38*39*40***61*54*53*51*56