Gas Transport and pH PDF

Chapter 35: Gas Transport and pH Intro ○ The concentrations for O2 and CO2 (measured As partial pressures, or po2 and pco2) change within each region of the lung, allowing for these gases to flow downhill or from higher partial pressures to lower partial pressures ○ for example, po2 is highest in th...

Chapter 35: Gas Transport and pH Intro ○ The concentrations for O2 and CO2 (measured As partial pressures, or po2 and pco2) change within each region of the lung, allowing for these gases to flow downhill or from higher partial pressures to lower partial pressures ○ for example, po2 is highest in the alveoli upon inspiration and lowest in the deoxygenated blood whereas pco2 is exactly the opposite ○ this allows for O2 to cross the alveoli and re-oxygenate the blood in the pulmonary vasculature, while CO2 leaves the bloodstream and enters the alveoli where it is expired ○ however the amount of both of these gases transported to and from the tissues would be grossly inadequate if it were not for the fact that about 99% of the oxygen that dissolves in the blood combines with the oxygen carrying protein hemoglobin and that about 94.5% of the CO2 that dissolves enters into a series of reversible chemical reactions that convert it into other compounds Oxygen transport: oxygen delivery to the tissues ○ oxygen delivery or by definition, the volume of oxygen delivered to the systemic vascular bed per minute, is the product of the cardiac output and the arterial oxygen concentration ○ the ability to deliver oxygen in the body depends on both the respiratory and the cardiovascular systems ○ O2 delivery to a particular tissue depends on the amount of oxygen entering the lungs, the adequacy of pulmonary gas exchange, the blood flow to the tissue, and the capacity of the blood to carry oxygen. ○ Blood flow to an individual tissue depends on cardiac output and the degree of constriction of the vascular bed in the tissue the amount of oxygen in the blood is determined by the amount of dissolved oxygen, the amount of hemoglobin in the blood, and the Affinity of the hemoglobin for oxygen reaction of hemoglobin and oxygen ○ the Dynamics of the reaction of hemoglobin with oxygen makes it a particularly suitable oxygen carrier ○ hemoglobin is a protein made up of four subunits Each of which contains a heme moiety attached to a polypeptide chain ○ in normal adults, most of the hemoglobin molecules contain two alpha and two beta chains ○ heme is a porphyrin ring complex that includes one atom of ferrous iron ○ each of the four iron atoms in hemoglobin can reversibly bind one oxygen molecule ○ the iron stays in the Ferrous state so that the reaction is oxygenation not oxidation ○ it has been customary to write the reaction of hemoglobin with O2 as HB + O2 hbo2 ○ because it contains four deoxyhemoglobin (Hb) units the hemoglobin molecule can be represented as Hb4 and it actually reacts with four molecules of O2 to form Hb4O8 Factors affecting the Affinity of hemoglobin for oxygen ○ three important conditions affect the oxygen hemoglobin dissociation curve: the ph, the temperature and the concentration of 2,3 diphosphoglycerate. ○ A rise in temperature or Fallen pH shifts the curve to the right ○ when the curve is shifted in this direction a higher po2 is required for hemoglobin to bind a given amount of o2 ○ conversely a fallen temperature or a rise in PH shifts the curve to the left and a lower po2 is required to bind a given amount of o2 ○ a convenient index for comparison of such shifts is the p50, the po2 at which hemoglobin is half saturated with O2 ○ the higher the p50 the lower the Affinity of hemoglobin 402 hemoglobin and O2 binding in Vivo: cyanosis ○ Reduce hemoglobin has a dark color, and a Dusky bluish discoloration of the tissues, called cyanosis, appears when the reduced hemoglobin concentration of the blood and the capillaries is more than 5 g/dL ○ Its occurrence depends on the total amount of hemoglobin in the blood, the degree of hemoglobin unsaturation, and the state of the capillary circulation. ○ Cyanosis is most easily seen in a nail beds and mucous membranes and in the earlobes, lips, and fingers, where the skin is thin and there are plenty of capillaries ○ Although visible observation is indicative of cyanosis, it is not fully reliable ○ Further tests of arterial oxygen tension and saturation, blood and hemoglobin counts can provide more reliable diagnosis Carbon dioxide transport molecular fate of carbon dioxide in blood ○ the solubility of CO2 and blood is about 20 times that of o2; therefore, considerably more CO2 than O2 is present in simple solution at equal partial pressures ○ the CO2 that diffuses into red blood cells is rapidly dehydrated to H2CO3 because of the presence of Carbonic anhydrase ○ The H2CO3 dissociates to H+ and HCO3- and the H+ is buffered, primarily by hemoglobin, while HCO3- enters the plasma ○ Some of the CO2 and the red cells react with the amino groups of hemoglobin and other proteins forming carbamino compounds chloride shift ○ Because the rise in the HCO3- content of red cells is much greater than that in plasma as the blood passes through the capillaries, about 70% of the HCO3formed in the red cells enters the plasma ○ The excess HCO3- leaves the red cells in exchange for Cl○ This process is mediated by anion exchanger 1 ( AE1; also called band 3) a major membrane protein in the red blood cell ○ Because of this chloride shift, the Cl- content of the red cells in venous blood is significantly greater than that in arterial blood ○ the chloride shift occurs rapidly and is essentially complete within one second ○ note that for each CO2 molecule added to a red cell, there is an increase of one osmotically active particle in the cell – either HCO3- or Cl○ consequently the red cells take up water and increase in size ○ For this reason plus the fact that a small amount of fluid in the arterial blood returns via the lymphatics rather than the veins, the hematocrit of venous blood is normally 3% greater than that of the arterial blood. in the lungs the Cl- moves back out of the cells and they shrink Henderson Hasselbalch ○ The third and major buffer system in the blood is the carbonic acid bicarbonate system ○ the Henderson hasselbalch Equation for the system is ○ The pK for the system in an ideal solution is low (about 3) and the amount of H2CO3 is small and hard to measure accurately. However in the body H2CO3is an equilibrium with CO2 ○ If the pK is changed to pK’ ( apparent ionization constant; distinguished from the true pK due to less than ideal conditions for the solution) and [CO2] is substituted for [H2CO3], pK’ is 6.1 Acidosis and alkalosis ○ The pH of the arterial plasma is normally 7.40 and that of venous plasma slightly lower. ○ a decrease in PH below the norm (acidosis) is technically present whenever the arterial pH is below 7.4 and an increase in pH ( alkalosis) is technically present whenever pH is above 7.4 ○ in practice variations of up to 05 pH unit occur without untoward effects ○ acid-base disorders are split into four categories respiratory acidosis, respiratory alkalosis, metabolic acidosis, and metabolic alkalosis ○ in addition, these disorders can occur in combination Hypoxia ○ hypoxia is O2 deficiency at the tissue level. it is more correct term than anoxia(lack of O2), since there is rarely no oxygen at all left in the tissues ○ numerous classifications for hypoxia have been used, but the more traditional four types systems still has considerable utility if the definitions of the terms are kept clearly in the mind ○ The four categories are Hypoxemia ( sometimes terms hypoxic hypoxia), in which the PO2 of the arterial blood is reduced anemic hypoxia, in which the arterial PO2 is normal but the amount of hemoglobin available to carry oxygen is reduced ischemic or stagnant hypoxia in which the blood flow to a tissue is so low that adequate oxygen is not delivered to it despite a normal po2 and hemoglobin concentration histotoxic hypoxia in which the amount of oxygen delivered to a tissue is adequate but because of the action of a toxic agent, the tissue cells cannot make use of the oxygen supply to them Erythropoietin ○ erythropoietin secretion increases promptly on ascent to high altitude and then falls somewhat over the following four days as the ventilatory response increases in the arterial PO2 rises. ○ the increase in circulating red blood cells triggered by the erythropoietin begins in two to three days and is sustained as long as the individual remains at high altitude ○ compensatory changes also occur in the tissues. ○ the mitochondria which are the site of oxidative reactions, increase in number, and myoglobin increases, which facilitates the movement of oxygen into the tissues ○ the tissue content of cytochrome oxidase also increases ○ the effectiveness of the acclimatization process is indicated by the fact that permanent human habitations exist in the Andes and Himalayas at elevations above 5,500 m ○ the natives who live in these Villages are barrel-chested and markedly polycythemic ○ they have low alveolar po2 values but in most other ways they are remarkably normal Carbon monoxide poisoning ○ small amounts of carbon monoxide are formed in the body, and this gas May function as a chemical messenger in the brain and elsewhere. ○ in larger amounts, it is poisonous. ○ outside the body it is formed by incomplete combustion of carbon. ○ It was used by the Greeks and Romans to execute criminals, and today it causes more deaths than any other gas. ○ CO poisoning has become less common in the United States since natural gas replace other Gases such as coal gas which contain large amounts of CO ○ is however so readily available as the exhaust of gasoline engines and 6% or more CO ○ Co is toxic because it reacts with hemoglobin to form carbon monoxyhemoglobin (Carboxyhemoglobin, COHb) and COHb does not take up O2 ○ CO Poisoning is often listed as a form of anemic hypoxia because the amount of hemoglobin that can carry O2 is reduced, but the total hemoglobin content of the blood is unaffected by CO ○ the Affinity of hemoglobin for Co is 210 times it's affinity for O2, and COHb liberates CO very slowly ○ An additional difficulty is that when COHb is present, the dissociation curve of the remaining HbO2 shifts the left decreasing the amount of O2 released ○ This is why anemic individuals who have 50% of the normal amount of HBO2 may be able to perform moderate work, whereas an individual with HBO2 reduced the same level because of the formation of COHb is seriously incapacitated Oxygen treatment of hypoxia ○ administration of oxygen rich gas mixtures is of very limited value in hypoperfusion, anemic, and histotoxic hypoxia because all that can be accomplished in this way is an increase in the amount of dissolved oxygen in the arterial blood ○ This is also true in hypoxemia When it is due to shunting of an oxygenated venous blood passed the lungs ○ In other forms of hypoxia, O2 is of great benefit. ○ treatment regimens that deliver less than 100% oxygen are of value both acutely and chronically, and administration of oxygen 24 hours a day for 2 years in this manner has been shown to significantly decrease the mortality of chronic obstructive pulmonary disease. Hypercapnia and hypocapnia ○ Hypercapnia retention of CO2 in the body (hypercapnia) initially stimulates respiration retention of larger amounts produces such symptoms as confusion, diminished sensory acuity and, eventually, with respiratory depression and death due to depression of the central nervous system In patients with these symptoms, the PCO2 is markedly elevated and severe respiratory acidosis is present. large amounts of HCO3 are excreted, but more HCO3 is reabsorbed, raising the plasma HCO3 and partially compensating for the acidosis CO2 is much more soluble than O2 that hypercapnia is rarely a problem in patients with pulmonary fibrosis however it does occur in ventilation– perfusion inequality and when for any reason alveolar ventilation is inadequate in the various forms of pump failure it is exacerbated when CO2 production is increased for example, in febrile patients there is a 13% increase in CO2 production for each 1*C rise in temperature and a high carbohydrate intake increases CO2 production because of the increase in the respiratory quotient normally alveolar ventilation increases and the extra CO2 is expired but it accumulates when ventilation is compromised