Gas Transport & pH PDF

GAS TRANSPORT & pH Mehmet OZANSOY, Ph.D. Dept. of Physiology OXYGEN DELIVERY TO THE TISSUES ⚫ The O2 delivery system in the body consists of the lungs and the cardiovascular system. ⚫ O2 delivery to a particular tissue depends on ⚫ the amount of O2 entering the lungs, ⚫ the adequacy of pulm...

GAS TRANSPORT & pH Mehmet OZANSOY, Ph.D. Dept. of Physiology OXYGEN DELIVERY TO THE TISSUES ⚫ The O2 delivery system in the body consists of the lungs and the cardiovascular system. ⚫ O2 delivery to a particular tissue depends on ⚫ the amount of O2 entering the lungs, ⚫ the adequacy of pulmonary gas exchange, ⚫ the blood flow to the tissue, and the capacity of the blood to carry O2. ⚫ The blood flow depends on ⚫ the degree of constriction of the vascular bed in the tissue and ⚫ the cardiac output. ⚫ The amount of O2 in the blood is determined by the amount of dissolved O2, the amount of hemoglobin in the blood, and the affinity of the hemoglobin for O2 ⚫ The oxygen–hemoglobin dissociation curve relates percentage saturation of the O2 carrying power of hemoglobin to the PO2. ⚫ Combination of the first heme in the Hb molecule with O2 increases the affinity of the second heme for O2, and oxygenation of the second increases the affinity of the third, and so on, so that the affinity of Hb for the fourth O2 molecule is many times that for the first 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-biphosphoglycerate (BPG; 2,3-BPG) MYOGLOBIN ⚫ Myoglobin is an iron-containing pigment found in skeletal muscle. ⚫ It resembles hemoglobin but binds 1 rather than 4 mol of O2 per mole. ⚫ Its dissociation curve is a rectangular hyperbola rather than a sigmoid curve ACID–BASE BALANCE & GAS TRANSPORT ⚫ Acid and base shifts in the blood are largely controlled by three main buffers in blood: ⚫ proteins, ⚫ hemoglobin, ⚫ the carbonic acid–bicarbonate system. ACIDOSIS & 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 7.40 and ⚫ An increase in pH (alkalosis) is technically present whenever pH is above 7.40 ⚫ Acid–base disorders are split into four categories: ⚫ ⚫ ⚫ ⚫ respiratory acidosis, respiratory alkalosis, metabolic acidosis, and metabolic alkalosis RESPIRATORY ACIDOSIS Any short-term rise in arterial PCO2 (ie, above 40 mm Hg) due to decreased ventilation results in respiratory acidosis. RESPIRATORY ALKALOSIS Any short-term increase in ventilation that lowers PCO2 below what is needed for proper CO2 exchange (ie, below 35 mm Hg) results in respiratory alkalosis. METABOLIC ACIDOSIS & ALKALOSIS ⚫ Blood pH changes can also arise by nonrespiratory mechanism. ⚫ Metabolic acidosis (or nonrespiratory acidosis) occurs when strong acids are added to blood. ⚫ If, for example, a large amount of acid is ingested (eg, aspirin overdose), acids in the blood are quickly increased, lowering the available Hb–, Prot–, and HCO3– buffers. ⚫ When the free [H+] level falls as a result of addition of alkali, or more commonly, the removal of large amounts of acid (eg, following vomiting), ⚫ Metabolic alkalosis results. RESPIRATORY & RENAL COMPENSATION ⚫ The respiratory system compensates for metabolic acidosis or alkalosis by altering ventilation, and consequently, the PCO2, which can directly change blood pH. ⚫ Respiratory mechanisms tend to be fast ⚫ In response to metabolic acidosis, ventilation is increased, resulting in a decrease of PCO2 (eg, from 40 mm Hg to 20 mm Hg) and a subsequent increase in pH toward normal. ⚫ In response to metabolic alkalosis, ventilation is decreased, PCO2 is increased, and a subsequent decrease in pH occurs. HYPOXIA ⚫ Hypoxia is O2 deficiency at the tissue level. ⚫ Traditionally, hypoxia has been divided into four types: ⚫ hypoxic hypoxia ⚫ anemic hypoxia ⚫ stagnant or ischemic hypoxia ⚫ histotoxic hypoxia ⚫ 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 O2 is reduced; ⚫ Stagnant or ischemic hypoxia, in which the blood flow to a tissue is so low that adequate O2 is not delivered to it despite a normal PO2 and hemoglobin concentration ⚫ Histotoxic (Cytotoxic) hypoxia, in which the amount of O2 delivered to a tissue is adequate but, because of the action of a toxic agent, the tissue cells cannot make use of the O2 supplied to them HYPOXIC HYPOXIA ⚫ Hypoxic hypoxia is a condition of reduced arterial PO2. ⚫ Hypoxic hypoxia is a problem in normal individuals at high altitudes and is a complication of pneumonia and a variety of other diseases of the respiratory system. DISEASES CAUSING HYPOXIC HYPOXIA ⚫ Hypoxic hypoxia is the most common form of hypoxia seen clinically. ⚫ The diseases that cause it can be roughly divided into those in which the gas exchange apparatus fails, those such as congenital heart disease in which large amounts of blood are shunted from the venous to the arterial side of the circulation, and those in which the respiratory pump fails. ⚫ Lung failure occurs when conditions such as ⚫ pulmonary fibrosis produce alveolar–capillary block, ⚫ or there is ventilation–perfusion imbalance ANEMIC HYPOXIA ⚫ Hypoxia due to anemia is not severe at rest unless the hemoglobin deficiency is marked, because red blood cell 2,3-BPG increases. ⚫ However, anemic patients may have considerable difficulty during exercise because of limited ability to increase O2 delivery to the active tissues CARBON MONOXIDE POISONING ⚫ CO is toxic because it reacts with hemoglobin to form carbon monoxyhemoglobin (carboxyhemoglobin, COHb), and COHb cannot take up O2 ⚫ Carbon monoxide 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 its affinity for O2, and COHb liberates CO very slowly. ⚫ CO is also toxic to the cytochromes in the tissues, but the amount of CO required to poison the cytochromes is 1000 times the lethal dose; tissue toxicity thus plays no role in clinical CO poisoning. HYPOPERFUSION HYPOXIA ⚫ Hypoperfusion hypoxia, or stagnant hypoxia, is due to slow circulation and is a problem in organs such as the kidneys and heart during shock. ⚫ The liver and possibly the brain are damaged by hypoperfusion hypoxia in congestive heart failure. HISTOTOXIC HYPOXIA ⚫ Hypoxia due to inhibition of tissue oxidative processes is most commonly the result of cyanide poisoning. ⚫ Cyanide inhibits cytochrome oxidase and possibly other enzymes. HYPERCAPNIA ⚫ Retention of CO2 in the body (hypercapnia) initially stimulates respiration. ⚫ Retention of larger amounts produces symptoms due to depression of the central nervous system: confusion, diminished sensory acuity, and, eventually, coma with respiratory depression and death. ⚫ In patients with these symptoms, the PCO2 is markedly elevated, severe respiratory acidosis is present, and the plasma HCO3– may exceed 40 mEq/L ⚫ CO2 is so much more soluble than O2 that hypercapnia is rarely a problem in patients with pulmonary fibrosis. ⚫ In febrile patients there is a 13% increase in CO2 production for each 1°C rise in temperature HYPOCAPNIA ⚫ Hypocapnia is the result of hyperventilation. ⚫ During voluntary hyperventilation, the arterial PCO2 falls from 40 to as low as 15 mm Hg while the alveolar PO2 rises to 120 to 140 mm Hg. ⚫ The more chronic effects of hypocapnia are seen in neurotic patients who chronically hyperventilate ⚫ Cerebral blood flow may be reduced 30% or more because of the direct constrictor effect of hypocapnia on the cerebral vessels. ⚫ The cerebral ischemia causes light-headedness, dizziness, and paresthesias. ⚫ Hypocapnia also increases cardiac output. ⚫ It has a direct constrictor effect on many peripheral vessels, but it depresses the vasomotor center Pneumonia ⚫ The term pneumonia includes any inflammatory condition of the lung in which some or all of the alveoli are filled with fluid and blood cells ⚫ This disease begins with infection in the alveoli ⚫ The pulmonary membrane becomes inflamed and highly porous so that fluid and even red and white blood cells leak out of the blood into the alveoli. ⚫ Thus, the infected alveoli become progressively filled with fluid and cells, and the infection spreads by extension of bacteria or virus from alveolus to alveolus. ⚫ Eventually, large areas of the lungs, sometimes whole lobes or even a whole lung, become “consolidated,” which means that they are filled with fluid and cellular debris ⚫ In pneumonia, the gas exchange functions of the lungs change in different stages of the disease. ⚫ In early stages, the pneumonia process might well be localized to only one lung, with alveolar ventilation reduced while blood flow through the lung continues normally. ⚫ This results in two major pulmonary abnormalities: ⚫ reduction in the total available surface area of the respiratory membrane and ⚫ decreased ventilation perfusion ratio. ⚫ Both these effects cause hypoxemia (low blood oxygen) and hypercapnia (high blood carbon dioxide).