Exam 3 Review:  Chapter 22:  Hemoglobin

oxyhemoglobin - The bright-red chemical complex of hemoglobin and oxygen which transports oxygen to the tissues; it predominates in the blood returning to the heart from the lungs via the pulmonary veins and in systemic arterial blood.

reduced hemoglobin = deoxyhemoglobin - The dark, brick-red form of hemoglobin when it is complexed with less oxygen; it predominates in the blood returning to the heart from the body tissues in the systemic veins and in the pulmonary arterial blood.

oxygen-hemoglobin dissociation curve - A mathematical relationship or function for understanding how erythrocytes in the blood bind, carry and release oxygen; specifically, the oxyhemoglobin dissociation curve relates oxygen saturation* (SO₂) and partial pressure of oxygen in the blood (PO₂), and is determined by what is called "hemoglobin's affinity for oxygen," that is, how readily hemoglobin acquires and releases oxygen molecules from its surrounding tissues.  [Note:  *The oxygen saturation, expressed as a percentage,  is the ratio of the amount of oxygen bound to the hemoglobin, to the oxygen carrying capacity of the hemoglobin. The oxygen carrying capacity is determined by the amount of hemoglobin present in the blood.]

affinity - An attraction or force (generally a result of the formation on one or more non-covalent bonds) between particles, chemicals, molecules which causes them to combine; its strength is measured by the dissociation constant of the complex under various environmental conditions, e.g., temperature, pH, ionic strength of solution, etc.

Bohr effect - A reaction by which an increase of carbon dioxide in the blood and a decrease in pH results in a reduction of the affinity of hemoglobin for oxygen; it results in a "right shift" to the oxygen-hemoglobin dissociation curve reflecting the release of oxygen from hemoglobin.

carbonic anhydrase - An enzyme found in erythrocytes and renal tubular epithelial cells which catalyzes the reversible reaction in which carbon dioxide and water combine to form carbonic acid; it is an enzyme with great catalytic efficiency so it can be present in very low concentration and still be effective.  [Note:  Carbonic acid spontaneously dissociates into hydrogen ion and bicarbonate ion at normal body fluid pH.]

                                        (carbonic anhydrase)

    CO₂             +     H₂O <============> H₂CO₃ <============> H⁺         +     HCO₃^-  

carbon dioxide +     water                            carbonic acid                       hydrogen ion + bicarbonate ion 

bicarbonate ion - The anion, HCO₃^-, formed from the dissociation of carbonic acid, H₂CO₃, which is an important body fluid buffer; the concentration of bicarbonate ions is regulated by both the respiratory system and the kidneys; the concentration of bicarbonate ions in the blood is the major indicator of the buffering capacity of the blood at any given moment.

BPG = biphosphoglycerate - A three-carbon carbohydrate compound which is an intermediary product in the glycolytic pathway for the oxidation of glucose; its release in metabolically active tissues permits it to diffuse into the cytoplasm of red blood cells where it lessens hemoglobin's affinity for oxygen; therefore, metabolically active tissues encourage the delivery of oxygen from hemoglobin by this means of local regulation.

carbonic acid-bicarbonate buffer* - Bicarbonate ions can absorb H+ ions to form carbonic acid which can be transported to the lungs where the reaction is reversed, the H+ ions are converted to water molecules and CO₂ is excreted.  [See the chemical equation under carbonic anhydrase above.]  It is an extracellular buffer. The main role of this system is to buffer against the acids produced by fat & protein metabolism or ones produced in oxygen deficiency or starvation; it cannot buffer against the acidity of excess CO₂, which occurs with hypoventilation;  this buffer system is dependent on a functioning respiratory system to excrete the carbon dioxide.  [Note*:   A buffer is a substance which minimizes change in the pH (acidity) of a solution when an acid or base is added to that solution.]

fetal hemoglobin (HbF) - The predominant form of hemoglobin in a fetus and a newborn; it differs from adult hemoglobin in having two gamma globin chains instead of beta globin chains; it exhibits a higher average affinity for O₂ than adult hemoglobin, and as a result, its oxygen dissociation curve is shifted to the left of the adult hemoglobin oxygen dissociation curve; this left shift insures that O₂ will move from the maternal circulation to the fetal circulation. [Note:  HbF is normally present in small amounts in an adult, it may be abnormally elevated in certain forms of anemia.]

carbaminohemoglobin - The form of hemoglobin when it is complexed with carbon dioxide which binds reversibly with a reactive amino group on one of the globin chains; ~23% of the carbon dioxide in blood is transported in this manner; it is present in modest amounts in the blood, with a somewhat higher concentration  in the blood returning to the heart from the body tissues in the systemic veins and in the pulmonary arterial blood.

chloride shift - Bicarbonate and chloride ions are transported across the red blood cell membrane in opposite directions by the bicarbonate-chloride carrier protein; the chloride shift is extremely rapid, occurring within 1 second; the chloride shift results in the plasma chloride content of venous blood being greater than that of arterial blood; it is of little clinical significance.

Haldane effect - A reaction by which an increase of H+ ions in the blood within systemic capillaries results in a reduction of the affinity of hemoglobin for oxygen; it results in a "right shift" to the oxygen-hemoglobin dissociation curve reflecting the release of oxygen from hemoglobin; while at the same time, the removal of oxygen from oxyhemoglobin increases the affinity of hemoglobin for H+ ions which then reversibly bond with hemoglobin; as a result some of the increase of H+ ions in the blood is temporarily reversed and the blood is buffered by hemoglobin; in the lungs the situation is reversed, hemoglobin gives up H+ ions and then has a greater affinity for oxygen where there is a slight increase in pH.

Describe:

2. The affects of acidity, carbon dioxide, temperature, and BPG, on the affinity of hemoglobin for oxygen by use of oxygen-hemoglobin dissociation curves.

Factor Effect on Affinity Of Hemoglobin For Oxygen acidity = pH = [H+] increased acidity = decreased pH = increased [H+] (acidosis) decreased hemoglobin oxygen affinity decreased acidity = increased pH = decreased [H+] (alkalosis) increased hemoglobin oxygen affinity carbon dioxide = pCO2 increased carbon dioxide = increased pCO2 decreased hemoglobin oxygen affinity decreased carbon dioxide = decreased pCO2 increased hemoglobin oxygen affinity temperature increased temperature decreased hemoglobin oxygen affinity decreased temperature increased hemoglobin oxygen affinity BPG = biphosphoglycerate increased BPG = increased biphosphoglycerate decreased hemoglobin oxygen affinity decreased BPG = decreased biphosphoglycerate increased hemoglobin oxygen affinity

Remember the following relationships: In the air-cooled alveolar capillary beds where CO2 is being eliminated and the metabolism of lung tissues is relatively low, acidity, blood pCO2, temperature and BPG levels will be all be reduced and that set of conditions increases hemoglobin oxygen affinity so that oxygen will load onto hemoglobin for transport to the systemic tissues. In contrast, in the warm systemic capillary beds and tissues where CO2 is being generated and the metabolism of these tissues is relatively high, acidity, blood pCO2, temperature and BPG levels will be all be increased and that set of conditions decreases hemoglobin oxygen affinity so that oxygen will unload from hemoglobin for diffusion to the cells of the systemic tissues.

5. The chemical equations for the transport of carbon dioxide in the blood by hemoglobin and as bicarbonate ion.

See also the figures below:

Sketch and label:

4. A diagram of the partial pressure changes of carbon dioxide and oxygen in the blood as it travels through the pulmonary and systemic circulations.

In brief:  pCO2 is ~ 40 mm Hg in the pulmonary venous circulation, within the left chambers of the heart, and in the systemic arterial circulation and pCO2 rises to ~ 45 mm Hg in the systemic venous circulation, within the right chambers of the heart, and in the pulmonary arterial circulation.  (pCO2 rises because the cells of systemic tissues are giving off CO2 as a waste product from the oxidation of nutrients to generate ATP energy.) pO2 is ~ 104 mm Hg in the pulmonary venous circulation, within the left chambers of the heart, and in the systemic arterial circulation and pO2 drops to ~40 mm Hg in the systemic venous circulation, within the right chambers of the heart, and in the pulmonary arterial circulation.  (pO2 drops because the cells of systemic tissues are taking up O2 to use in the oxidation of nutrients to generate ATP energy.)