CLINICAL CHEMISTRY PDF

‫اكاديمية المواهب الطبية‬ CLINICAL CHEMISTRY BLOOD GASSES LECTURE 6 DESIGNED BY : MJ-M6 Blood gasses Normal cell metabolism depends on the maintenance of blood pH within very narrow limits (7.35- 7.45). Even relatively mild excursions outside this normal pH range can have deleterious effects, includ...

‫اكاديمية المواهب الطبية‬ CLINICAL CHEMISTRY BLOOD GASSES LECTURE 6 DESIGNED BY : MJ-M6 Blood gasses Normal cell metabolism depends on the maintenance of blood pH within very narrow limits (7.35- 7.45). Even relatively mild excursions outside this normal pH range can have deleterious effects, including: reduced oxygen delivery to tissues electrolyte disturbances and changes in heart muscle contractility. survival is rare if blood pH falls below 6.8 or rises above 7.8. The problem for the body is that normal metabolism is associated with the continuous production of hydrogen ions (H+) and carbon dioxide (CO2), both of which tend to reduce pH. The mechanism which overcomes this problem and serves to maintain normal blood pH (i.e.,preserve acid-base homeostasis) is a complex synergy of action involving: chemical buffers in blood, the red cells (erythrocytes) which circulate in the blood, and the function of three organs: Lungs kidneys and brain. Before explaining how these five elements contribute to the overall maintenance of blood pH, it would be helpful to quickly review some basic concepts. What is an acid, what is a base, and what is pH? 1 An acid is a substance that releases hydrogen ions (H+) on dissociation in a solution. For example: Hydrochloric acid (HCl) dissociates into hydrogen ions and chloride ions Carbonic acid (H2CO3) dissociates into hydrogen ions and bicarbonate ions - A base is a substance that in solution accepts hydrogen ions. For example, bicarbonate (HCO ) accepts hydrogen ions to formcarbonic acid: HCO pH: is a measure of hydrogen ion concentration [H+]. pH is a scale of 0-14 of acidity and alkalinity. Pure water has a pH of 7 and is neutral (neither acidic nor alkaline). pH above 7 is alkaline below 7 is acidic 2 Thus, the pH of blood (7.35-7.45) is slightly alkaline although in clinical medicine: The term alkalosis is, reserved for blood pH greater than 7.45 The term acidosis is reserved for blood pH less than 7.35. The two are related according to the following equation H+] = 0.00000004 Eq/L] Log [H+] = log (0.00000004) Log[H+]=-(7.4) -log[H+]=7.4 pH 7.4 = H+ concentration of 40 nEq/L pH 7.0 = H+ concentration of 100 nEq/L pH 6.0 = H+ concentration of 1000 nEq/L What is a buffer? A buffer is a solution of a weak acid and its conjugate base. The bicarbonate (HCO3 ) buffer system Buffers are chemicals in solution which minimize the change in pH which occurs when acids are added by hydrogen ions. In blood, the principal buffer system is: the weak acid, carbonic acid (H2CO3), and its conjugate base, bicarbonate(HCO3 ). 3 To explain how this system minimizes changes in pH, suppose we add a strong acid, e.g., HCl, to the bicarbonate buffer: The acid will dissociate, releasing hydrogen ions The bicarbonate buffer in the process: HCO3 (carbonic acid). This relationship, known as the Henderson-Hasselbalch equation, shows that pH is governed by the ratio of base [HCO3 ] concentration to acid [H2CO3] concentration. pH = 6.1 + log ([HCO ] /[H2CO3]) physiology of acid-base balance: In fact, the lungs the kidneys ensure the removal of carbonic acid(as carbon dioxide) ensure continuous regeneration of bicarbonate. This role of the lungs is dependent on the characteristic of the bicarbonate buffering system and that is the ability of carbonic acid to be converted to carbon dioxide and water. the following equation outlines the relationship of all elements of the bicarbonate buffering system as it operates in the body H+ + HCO3 4 It is important to note that the reactions are reversible. Direction is dependent on the relative concentration of each element. So, for example, a rise in carbon dioxide concentration forces a reaction to the left with increased formation of carbonic acid and ultimately hydrogen ions. Lung function: transport of CO2, and acid-base balance. A constant amount of CO2 in blood, essential for normal acid-base balance, reflects a balance between that produced as a result of tissue cell metabolism and that excreted by the lungs in expired air. By varying the rate at which carbon dioxide is excreted, the lungs regulate the carbon dioxide content of the blood. Carbon dioxide diffuses out of tissue cells to surrounding capillary blood (Fig. 1a) a small proportion dissolves in blood plasma and is transported to the lungs unchanged but most diffuses into red cells where it combines with water to form carbonic acid. The acid dissociates with the production of hydrogen ions and bicarbonate. 5 Hydrogen ions combine with deoxygenated haemoglobin (haemoglobin is acting as a buffer here), preventing a dangerous fall in cellular pH, and bicarbonate diffuses along a concentration gradient from red cells to plasma. fig. 1a. CO2 produced in tissues converted to bicarbonate for transport to lungs. Thus, most of the carbon dioxide produced in the tissues is transported to lungs as bicarbonate in blood plasma. the alveoli in the lungs the process is reversed (Fig. 1b). Hydrogen ions are displaced from hemoglobin as it takes up oxygen from inspired air. Fig. 1b. At the lungs, bicarbonate is converted back to CO2 and eliminated by the lungs. 6 The hydrogen ions are now buffered by bicarbonate which diffuses from plasma back into the red cell, and carbonic acid is formed. As the concentration of this rises, it is converted to water and carbon dioxide. Finally, carbon dioxide diffuses down a concentration gradient from red cells to alveoli for excretion in expired air Respiratory chemoreceptors in the brain stem respond to changes in the concentration of carbon dioxide in the blood, causing increased ventilation (breathing) if carbon dioxide concentration rises and decreased ventilation if carbon dioxide falls. Kidneys and acid-base balance These two tasks, the elimination of hydrogen ions and regeneration of bicarbonate, are accomplished by the kidneys. Renal tubule cells are rich in the enzyme carbonic anhydrase, which facilitates the formation of carbonic acid from dioxide and water. carbon 7 Carbonic acid dissociates into bicarbonate and hydrogen ions. The bicarbonate is reabsorbed into the blood and the hydrogen ions pass into the lumen of the tubule and are eliminated from the body in urine. Disturbances of acid-base balance Most acid-base disturbances result from disease or damage to organs kidney lungs brain whose normal function is necessary for acid-base homeostasis disease which causes abnormally increased production of metabolic acids such that homeostatic mechanisms are overwhelmed medical intervention (e.g. mechanical ventilation, some drugs) Arterial blood gases (ABG) are the blood test used to identify and monitor acid-base disturbances. Three parameters measured during blood gas analysis: arterial blood pH partial pressure of carbon dioxide in arterial blood (pCO2) and concentration of bicarbonate (HCO3–) are of crucial importance. The results of these three allow the classification of acid-base disturbance into one of four etiological categories: 8