Faisal I. Mohammed, MD, PhD Respiratory system L4 Faisal I. Mohammed, MD, PhD University of Jordan

Transport of Oxygen and Carbon Dioxide Oxygen transport Only about 1.5% dissolved in plasma 98.5% bound to hemoglobin in red blood cells Heme portion of hemoglobin contains 4 iron atoms – each can bind one O2 molecule Oxyhemoglobin Only dissolved portion can diffuse out of blood into cells Oxygen must be able to bind and dissociate from heme University of Jordan

OXYGEN IN THE BLOOD in Milliliters: 200 ml in 1litre arterial blood. Transport of O2 and CO2 Oxygen in blood: Blood of a normal person contains about 15 gm of Hb in each 100 ml of blood. Each gram of Hb can bind with a maximum of 1.34 ml of O2 - 6 OXYGEN IN THE BLOOD in Milliliters: 200 ml in 1litre arterial blood.

Relationship between Hemoglobin and Oxygen Partial Pressure Higher the PO2, More O2 combines with Hb Fully saturated – completely converted to oxyhemoglobin Percent saturation expresses average saturation of hemoglobin with oxygen Oxygen-hemoglobin dissociation curve In pulmonary capillaries, O2 loads onto Hb In tissues, O2 is not held and unloaded 75% may still remain in deoxygenated blood (reserve) University of Jordan

Hemoglobin and Oxygen Other factors affecting affinity of Hemoglobin for oxygen Each makes sense if you keep in mind that metabolically active tissues need O2, and produce acids, CO2, and heat as wastes Acidity (pH) PCO2 Temperature University of Jordan

Hemoglobin and 02 Transport 280 million hemoglobin/RBC. Each hemoglobin has 4 polypeptide chains and 4 hemes. In the center of each heme group is 1 atom of iron that can combine with 1 molecule 02. Insert fig. 16.32

Hemoglobin University of Jordan

How does Hemoglobin carry Oxygen? Hemoglobin exists in two forms: Oxyhemoglobin: HbO2 O2 + Hb HbO2 Iron in Hb binds to O2 4 O2 molecules per Hb molecule Deoxyhemoglobin The fraction of all the Hemoglobin in the form of Oxyhemoglobin is expressed as Hemoglobin saturation.

Hemoglobin (continued) Methemoglobin: Has iron in the oxidized form (Fe3+). Lacks electrons and cannot bind with 02. Blood normally contains a small amount. Carboxyhemoglobin: The reduced heme is combined with carbon monoxide. The bond with carbon monoxide is 210 times stronger than the bond with oxygen. Transport of 02 to tissues is impaired.

Hemoglobin (continued) Oxygen-carrying capacity of blood determined by its [hemoglobin]. Anemia: [Hemoglobin] below normal. Polycythemia: [Hemoglobin] above normal. Hemoglobin production controlled by erythropoietin. Production stimulated by PC02 delivery to kidneys. Loading/unloading depends: P02 of environment. Affinity between hemoglobin and 02.

Oxyhemoglobin Dissociation Curve Graphic illustration of the % oxyhemoglobin saturation at different values of P02. Loading and unloading of 02. Steep portion of the sigmoidal curve, small changes in P02 produce large differences in % saturation (unload more 02). Decreased pH, increased temperature, and increased 2,3 DPG: Affinity of hemoglobin for 02 decreases. Greater unloading of 02: Shift to the curve to the right.

Oxygen-hemoglobin Dissociation Curve University of Jordan

Oxyhemoglobin Dissociation Curve Insert fig.16.34

Effects of pH and Temperature The loading and unloading of O2 influenced by the affinity of hemoglobin for 02. Affinity is decreased when pH is decreased. Increased temperature and 2,3-DPG: Shift the curve to the right. Insert fig. 16.35

Effect of 2,3 DPG on 02 Transport Anemia: RBCs total blood [hemoglobin] falls, each RBC produces greater amount of 2,3 DPG. Since RBCs lack both nuclei and mitochondria, produce ATP through anaerobic metabolism. Fetal hemoglobin (hemoglobin f): Has 2 -chains in place of the -chains. Hemoglobin f cannot bind to 2,3 DPG. Has a higher affinity for 02.

Inherited Defects in Hemoglobin Structure and Function Sickle-cell anemia: Hemoglobin S differs in that valine is substituted for glutamic acid on position 6 of the b chains. Cross links form a “paracrystalline gel” within the RBCs. Makes the RBCs less flexible and more fragile. Thalassemia: Decreased synthesis of a or b chains, increased synthesis of g chains.

Muscle Myoglobin Red pigment found exclusively in striated muscle. Slow-twitch skeletal fibers and cardiac muscle cells are rich in myoglobin. Have a higher affinity for 02 than hemoglobin. May act as a “go-between” in the transfer of 02 from blood to the mitochondria within muscle cells. Insert fig. 13.37 May also have an 02 storage function in cardiac muscles.

Bohr Effect As acidity increases (pH decreases), affinity of Hb for O2 decreases Increasing acidity enhances unloading Shifts curve to right PCO2 Also shifts curve to right As PCO2 rises, Hb unloads oxygen more easily Low blood pH can result from high PCO2 University of Jordan

Temperature Changes Within limits, as temperature increases, more oxygen is released from Hb During hypothermia, more oxygen remains bound 2,3-bisphosphoglycerate BPG formed by red blood cells during glycolysis Helps unload oxygen by binding with Hb University of Jordan

Fetal and Maternal Hemoglobin Fetal hemoglobin has a higher affinity for oxygen than adult hemoglobin Hb-F can carry up to 30% more oxygen Maternal blood’s oxygen readily transferred to fetal blood University of Jordan

Carbon dioxide in blood CO2 produced by cells is carried by the blood in three forms In physical solution Plasma/Erythrocyte: 7% As Carbamino-Hemoglobin : 23% CO2 + Hb  HbCO2 As Bicarbonate ions: 70% Mostly in the Erythrocyte which has the enzyme, Carbonic anhydrase (Catalyses the formation of Carbonic acid 5000 times.) CO2 + H2O  H2 CO3 [H+] + [HCO3-]

Carbon dioxide in blood transported from the body cells back to the lungs (Tidal Co2) as:

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3- Chloride shift HCO3- accumulates inside RBCs as they pick up carbon dioxide Some diffuses out into plasma To balance the loss of negative ions, chloride (Cl-) moves into RBCs from plasma Reverse happens in lungs – Cl- moves out as moves back into RBCs University of Jordan

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