1625915643-5d53d156c9525bd62bd0d3434ecdc231 (843955), страница 50
Текст из файла (страница 50)
15.3):■Approximately 7% of CO2 in blood is dissolved CO2.Because solubility of CO2 in plasma is relatively high(20 times the solubility of O2), the dissolved form of CO2has a significant role in its transport.182Respiratory PhysiologyOxyhemoglobin Dissociation Curve(at pH 7.4, PCO2 40 mm Hg, 37° C)1008012O2 combinedwith Hb60SO2 (%)10408204O2 in solutionin plasma804060PO2 (mm Hg)20100100PCO2 20PCO2 40SO2 (%)Effects of PCO2, pH,and Temperature onO2 Dissociation Curve2100100pH 7.66040pH 7.46040PCO2 80602040 60 80PO2 (mm Hg)10037° C40pH 7.243° C20202020° C808080O2 content (mL/100 mL blood)202040 60 80PO2 (mm Hg)1002040 60 80PO2 (mm Hg)100Figure 15.2 Oxyhemoglobin Dissociation Curves The oxyhemoglobin binding curve describes the association between partial pressureof oxygen and the degree of oxygen saturation of hemoglobin. Saturation of hemoglobin is nearly 100% (97.5%) when PO2 is 100 mm Hg.
The sigmoidal shape of this curve results in a high degree of oxygen saturation of blood after passing through alveolar capillaries and significant dissociationof oxygen from hemoglobin at the PO2 levels to which blood is exposed as it perfuses systemic capillaries. The values given for oxygen content onthe graph are those expected at the normal blood hemoglobin concentration of 15 g/100 mL blood. Note that the amount of dissolved hemoglobinin blood is very low over a wide range of PO2. High PCO2, low pH, and high temperature shift the oxyhemoglobin dissociation curve to the right,which promotes oxygen dissociation from hemoglobin in capillaries supplying actively metabolizing tissues.B.
Carbon dioxide transportA. CO2 equilibrium curves(for normal arterial and venous blood)CO2 content (mL/dL blood)55Mixed venous50Red bloodcellHb•NH2Hb•NH2Hb•NHCOO–Hb•NHCOO–Carbonicanhydrase+H2OCO2CO2Arterial45Hb•NHCOO–(carbaminoHb)Alveoliof lung40Bicarbonate3040PCO2 (mm Hg)50Cl–HCO3– + H+CO2 in physical solution+ H2OBodytissuesFigure 15.3 Carbon Dioxide Transport Carbon dioxide is transported in blood as bicarbonate anion (approximately 70%), carbaminohemoglobin (approximately 23%), and dissolved CO2 (approximately 7%).
The CO2 equilibrium (dissociation) curve (A) is steep and linear, unlike the oxyhemoglobin dissociation curve, accounting for the relatively small difference in PCO2 between arterial and venous blood (40 mm Hg vs. 45 mm Hg). Notealso that the dissociation curve is shifted to the left when hemoglobin is in the form of deoxyhemoglobin, as in venous blood (the Haldane effect).Oxygen and Carbon Dioxide Transport and Control of RespirationCLINICAL CORRELATESickle Cell DiseasePatients suffering from sickle cell disease have a variant form ofhemoglobin known as hemoglobin S. The allele causing thisdisease is recessive and is most common in people of subSaharan African origin.
Hemoglobin S has the tendency topolymerize when it is deoxygenated, causing red blood cells toassume a sickle-like shape. In a “sickle cell crisis,” red blood cellslodge in the microcirculation, causing painful ischemia andinfarction of tissue. Sickle cell disease confers resistance tomalaria, a parasite attacking red blood cells, and is believed tohave evolved and persisted in sub-Saharan Africa due to evolutionary advantage associated with malaria resistance.183In normal venous blood, the partial pressures of carbondioxide and oxygen are similar (approximately 45 mm Hgand 40 mm Hg, respectively).
According to Henry’s law, theconcentration of dissolved gas in a solution is directly proportional to its partial pressure. Although this law applies to bothoxygen and carbon dioxide, because the solubility of carbondioxide is 20 times that of oxygen, at similar partial pressures,much more carbon dioxide is present in blood in the form ofdissolved gas than is the case for oxygen.Although the approximate values given earlier for CO2 transport as dissolved gas, carbaminohemoglobin, and bicarbonateanion are prevalent in the literature and textbooks, the value forcarbaminohemoglobin may be significantly overstated, becausethe original studies of CO2 carriage in blood were performed inthe absence of 2,3-DPG, which binds with higher affinity tohemoglobin than CO2.formed, it diffuses out of the red blood cell while Cl− diffusesinto the cell to maintain electrochemical equilibrium.
Thisprocess is known as the chloride shift. Most of the H+ formedis buffered within the red blood cell by binding to hemoglobin. The reaction forming H2CO3 is driven forward in capillary blood, as CO2 diffuses from tissues into the blood. At thelungs, the reverse reaction occurs, as CO2 is breathed off.The Haldane EffectSickled Red Blood Cells■■Up to 23% of CO2 may be combined with protein,including hemoglobin (as carbaminohemoglobin, whichgives venous blood its bluish tinge). CO2 binds to terminal amino groups of blood proteins.About 70% of CO2 in blood is carried in the form ofbicarbonate anion (HCO3-).Carbon Dioxide Transport in the Form ofBicarbonate IonThe bulk of CO2 is transported in the form of HCO3− withinred blood cells (see Fig.
15.3). CO2 dissolved in blood reactswith H2O to form carbonic acid (H2CO3), which dissociatesto form H+ and HCO3−:CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3−This reaction, which is normally slow, is catalyzed by theenzyme carbonic anhydrase in red blood cells. As HCO3− isUnlike the sigmoidal oxyhemoglobin dissociation curve, thedissociation curve for CO2 in blood is linear (see Fig. 15.3).However, it is shifted to the left when hemoglobin is in theform of deoxyhemoglobin, as in venous blood. This is knownas the Haldane effect. As a result of the Haldane effect, ashemoglobin is deoxygenated in systemic capillaries, its affinityfor CO2 is increased, facilitating CO2 transport.
Binding affinity for H+ (generated in red blood cells along with HCO3−) isalso increased. In the pulmonary circulation, as hemoglobinis oxygenated, its affinity for CO2 is reduced, and as a result,transfer of CO2 from blood to alveolar air is facilitated.CARBON DIOXIDE TRANSPORT ANDACID–BASE BALANCENormal blood pH is approximately 7.4 and is regulatedwithin a tight range (7.35 to 7.45) by renal and respiratorymechanisms and by various other buffering systems (Fig. 15.4and see Chapter 20). Significant deviation of pH from thenormal range is incompatible with life, as protein structure isaffected and enzymatic function is disturbed. CO2 transportplays an important role in maintaining acid–base equilibrium.
The “acid load” of the body consists of volatile acid,which is CO2 in its various forms, and nonvolatile acids suchas lactic acid and amino acids. Nonvolatile acids are bufferedby intracellular and extracellular mechanisms; the bicarbonate buffering system of extracellular fluids including blood are184Respiratory PhysiologyCLINICAL CORRELATECarbon Monoxide PoisoningCarbon monoxide (CO) is a toxic compound produced duringcombustion of gasoline, propane, charcoal, natural gas, and otherfuels.
Prolonged exposure to air containing CO concentrations aslow as 0.04% can be lethal. CO binds to hemoglobin, myoglobin,and cytochrome oxidase, producing its toxic effects. Its affinity forhemoglobin is 240 times higher than that of oxygen, and as aresult, CO displaces oxygen bound to hemoglobin, forming carboxyhemoglobin and reducing oxygen-carrying capacity of hemoglobin (note the effects of a small concentration of CO on theoxyhemoglobin dissociation curve, compared with the effects ofsevere anemia). In addition, because binding at oxygen-bindingsites of hemoglobin is cooperative, the presence of bound CO onhemoglobin increases hemoglobin affinity for oxygen (the oxyhe-moglobin dissociation curve is shifted to the left), compromisingdissociation of oxygen from hemoglobin and thus its delivery atnormal tissue pH.
Carbon monoxide poisoning is treated by respiration with 100% oxygen. Hyperbaric oxygen is also used as atreatment (patients are placed in high-pressure chambers andbreathe pure oxygen), although the degree of benefit derived fromthis therapy is somewhat controversial. The pulse oximeter typically used in clinical settings to monitor arterial SO2 relies on colorimetric measurements, but because carboxyhemoglobin, likeoxyhemoglobin, is red in color, false, high SO2 readings areobtained when this instrument is used in patients suffering fromCO poisoning. Stated another way, the finger-probe and earlobeprobe pulse oximeters cannot differentiate between carboxyhemoglobin and oxyhemoglobin. CO poisoning results in symptomsof hypoxia, but without the typical blue appearance.20O2 content (mL O2/100 mL blood)Normal Hb (15 g/100 mL)15Normal Hb; 50% as carboxyhemoglobin10Anemia (7.5 g /100 mL)50020406080100PO2 (mm Hg)Oxygen Content of Blood: Effects of Carbon Monoxide and Anemia The arterial oxygencontent of normal blood containing 15 g Hb/100 mL blood is approximately 20 mL/100 mL.
In severeanemia, if hemoglobin is reduced by half, oxygen content at 100% saturation is also reduced by half. Incarbon monoxide poisoning, CO binds tightly to hemoglobin, reducing the number of sites available foroxygen binding, and also shifting the oxyhemoglobin curve to the left.
In the example shown above, half ofthe oxygen binding sites have been occupied by CO, forming carboxyhemoglobin. Thus, despite normalhemoglobin concentration, oxygen content is reduced by half in arterial blood at PaO2 of 100 mm Hg. Dueto the left-shift of the dissociation curve, delivery of O2 to tissues at normal tissue pH and PO2 is greatlycompromised, and thus venous PO2 is profoundly reduced.Oxygen and Carbon Dioxide Transport and Control of Respiration185CO2Volatile Acid(CO2)“Acid Load”H+ + HCO3–H2O + CO2CO2H+H+H+H+H+H+H+H+Nonvolatile Acid(HA)H+H+H+ + A–HACO2+H2O+NaANH4+BodytissuesNaHCO3NaHCO3ReplenishNH4AFigure 15.4 Role of Lungs and Kidneys in Acid–Base Balance The lungs and kidneys have a critical role in maintaining proper acid–basebalance in the face of the acid load created by cellular metabolism of nutrients. Carbon dioxide (“volatile acid”) produced by oxidative metabolismof carbohydrates and fats is efficiently eliminated by respiration in the lungs to maintain pH balance, whereas nonvolatile acids are primarily bufferedby bicarbonate anion in extracellular fluid and intracellular proteins, with the kidneys replenishing the bicarbonate anion and excreting acid.
H+ isalso eliminated in the urine as bicarbonate is regenerated. When a metabolic acid–base disturbance occurs, intracellular and extracellular bufferingsystems (involving primarily proteins and bicarbonate, respectively) are the first line of defense, along with rapid compensation by the lungs, whichadjust the rate of CO2 (volatile acid) elimination.
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
