The O2 content curves demonstrate the significant reduction in the O2 transport system caused by carboxyhemoglobin (HgbCO). When 50% of Hgb binds with carbon monoxide (CO), it results in the formation of HgbCO. Both the 50% hemoglobin and 50% HgbCO curves display a decreased O2 content in arterial blood. However, CO has a profound effect on lowering the venous partial pressure of oxygen. The arterial (a) and mixed venous (v) points of constant cardiac output are indicated.

Tissue hypoxia occurs when cells do not have sufficient O2 for adequate aerobic metabolism, leading to the stimulation of anaerobic metabolism. This results in increased levels of lactate and H+ ions, leading to the formation of lactic acid. Consequently, blood pH can significantly decrease. Severe hypoxia can cause the extremities, toes, and fingertips to appear blue-gray (cyanotic) due to the lack of O2 and increased levels of deoxyhemoglobin. Detailed information about the four major types of tissue hypoxia (hypoxic hypoxia, circulatory hypoxia, anemic hypoxia, histotoxic hypoxia) can be found in Chapter 23.

The concentration of Hgb, which depends on the number of red blood cells in circulation, is crucial for tissue oxygenation. Erythropoiesis, the production of red blood cells, is regulated by the hormone erythropoietin, synthesized by cortical interstitial cells in the kidneys. Although Hgb levels are usually stable, decreased O2 delivery, low Hgb concentration, and low PaO2 stimulate the secretion of erythropoietin, leading to increased red blood cell production. In chronic renal disease, damage to the cortical interstitial cells suppresses their ability to synthesize erythropoietin, resulting in anemia and decreased Hgb levels. Red blood cell production can be effectively increased through erythropoietin replacement therapy using epoetin alfa (Epogen, Procrit) or darbepoetin alfa (Aranesp).

Under healthy conditions, CO2 is produced at a rate of approximately 200 mL/minute. Typically, for every 100 molecules of O2 entering the capillary bed, the lung expels 80 molecules of CO2. This ratio of expired CO2 to O2 uptake is known as the respiratory exchange ratio and is 0.8 (80 molecules of CO2 to 100 molecules of O2) under normal conditions. A similar ratio, referred to as the respiratory quotient, exists between the tissue and blood compartments.

Compared to O2, the body has greater storage capabilities for CO2. Therefore, PaO2 is more sensitive to changes in ventilation than PaCO2. While several factors influence PaO2, arterial PaCO2 is solely dependent on alveolar ventilation and CO2 production. Alveolar ventilation and PaCO2 have an inverse relationship.

In the blood, CO2 is primarily transported in red blood cells as bicarbonate (HCO3 −). However, it can also be transported as dissolved CO2 and in the form of carbamino protein complexes, where CO2 binds to plasma proteins and hemoglobin (Hgb).
•Fig. 24.7 AcomparisonofO2contentcurvesunderthreeconditionsshowswhycarboxyhemoglobin(HgbCO)dramaticallyreducestheO2transportsystem.FiftypercentHgbCOrepresentsthebindingofhalfthecirculatingHgbwithcarbonmonoxide(CO).The50%hemoglobinand50%HgbCOcurvesshowthesamedecreasedO2contentinarterialblood.However,COhasaprofoundeffectinloweringvenouspartialpressureofoxygen.Thearterial(a)andmixedvenous(v)pointsofconstantcardiacoutputareindicated.
Tissue hypoxia is a condition in which O2 available to cells is insufficient for maintaining adequate aerobic metabolism. Thus anaerobic metabolism is stimulated and results in the increases in levels of lactate and H+ and the subsequent formation of lactic acid. The net result can lead to a significant decrease in blood pH. In cases of severe hypoxia, the extremities, toes, and fingertips may appear blue-gray (cyanotic) because of lack of O2 and increased deoxyhemoglobin levels. There are four major types of tissue hypoxia (hypoxic hypoxia, circulatory hypoxia, anemic hypoxia, histotoxic hypoxia), discussed in detail in
Chapter 23.
Tissue oxygenation depends on the concentration of Hgb and thus on the number of red blood cells available in the circulation. Red blood cell production (erythropoiesis) in the bone marrow is controlled by the hormone erythropoietin, which is synthesized in the kidneys by cortical interstitial cells. Although Hgb levels are normally very stable, decreased O2 delivery, low Hgb concentration, and low PaO2 stimulate the secretion of erythropoietin. This increases the production of red blood cells. Chronic renal disease damages the cortical interstitial cells and thereby suppresses their ability to synthesize erythropoietin. This causes anemia, along with decreased Hgb because of the lack of erythropoietin. Erythropoietin replacement therapy using epoetin alfa (Epogen, Procrit) or darbepoetin alfa (Aranesp) effectively increases red blood cell production.
CO2 is produced at a rate of approximately 200 mL/minute under healthy conditions, and typically, 80 molecules of CO2 are expired by the lung for every 100 molecules of O2 that enter the capillary bed. The ratio of expired CO2 to O2 uptake is referred to as the respiratory exchange ratio and, under normal conditions, is 0.8 (80 molecules of CO2 to 100 molecules of O2). This ratio is similar at the tissue to blood compartment, where it is referred to as the respiratory quotient.
The body has enhanced storage capabilities for CO2, in comparison with O2, and hence PaO2 is much more sensitive to changes in ventilation than is PaCO2. Whereas PaO2 is dependent on several factors, in addition to alveolar ventilation, arterial PaCO2 is solely dependent on alveolar ventilation and CO2 production. There is an inverse relationship between alveolar ventilation and PaCO2.
In blood, CO2 is transported in red blood cells primarily as bicarbonate (HCO3 −) but also as dissolved CO2 and as
H2CO3 = PCO2 ˜ 0.0301 •Fig. 24.8 Mechanisms of CO2Transport in Blood. v. ThepredominantmechanismbywhichCO2istransportedfromtissuecellstothelungisintheformofbicarbonateanion(HCO3−).H2CO3,carbonicacid;HgbO,oxyhemoglobin;NaHCO3,sodiumbicarbonate;RBC,redbloodcell.
carbamino protein complexes (i.e., CO2 binds to plasma proteins and to Hgb;