Medical brain notes 30

  DISORDERS OF ACID–BASE BALANCE INTRODUCTION Th e concentration of hydrogen ions, H + , in the blood is kept within a narrow reference range to give the blood a pH of approximately 7.4. The body possesses physiological and biochemical mechanisms that maintain this pH by removing excess H +  and carbon dioxide produced during metabolism ( Figure9.1 ). These activities are vital for normal bodily functions and are performedby the renal and respiratory systems respectively. Failure to maintain the acid–base balance at an appropriate value will give rise either to an acidosis, with a blood pH below the reference range, or an alkalosis with the pH above it. Different types of acidoses and alkaloses produce specific characteristic clinical features. Once a specific acid–base disorder has been identified, a clinical strategy must be adopted to manage the symptoms and to treat the underlying cause(s).

  THE PRODUCTION AND TRANSPORT OF CARBON DIOXIDE Body tissues produce about 20 moles of CO 2  per day during oxidative metabolism. The CO 2  diffuses from the cells into the extracellular fluid (ECF), that is the blood and tissue fluid, and eventually enters the plasma in quantities with the potential to form enough carbonic acid to disturb its pH. However, in normal circumstances this does not occur because the CO 2  is transported to the lungs and excreted. During transport, a substantial proportion of the CO 2  enters the erythrocytes by diffusion. Within the erythrocytes, a small proportion of the CO 2  remains dissolved or combines with proteins, mainly hemoglobin, to form carbamino compounds: The major portion, however, combines with water to produce carbonic acid in a reaction catalyzed by carbonic anhydrase ( Figure 9.2 ): Carbonic acid dissociates to H +  and hydrogen carbonate (HCO 3 – , ‘bicarbonate’) Figure 9.3  shows how H + are remov...

  BUFFERING AND THE EXCRETION OF H + About 60 mmol of H +  are produced each day from the oxidation of sulfur-containing amino acid residues or from incomplete metabolic activities, such as anerobic glucose metabolism or ketone body formation . If all the H +  were released into the approximately 14 dm 3  of ECF, the concentration of H +  would be 4 mmol dm –3  or about 100 000 times more acidic than normal. In reality, the concentration of H +  is kept within the narrow limits of 40  p 5 nmol dm –3  to maintain the appropriate body physiological pH of 7.4 ± 0.05. This pH is necessary for normal physiological functions and is maintained by temporary buffering systems that resist changes to the pH of the plasma until the excessive H +  are excreted by the kidneys .   When H + are released by cells, the ECF is buffered by the hydrogen carbonate– carbonic acid buffer system: Other buffering systems, such as hemoglobin in the erythrocyt...

  TYPES OF ACID–BASE DISORDERS Disorders of acid–base balance are either acidoses or alkaloses. In an acidosis, there is accumulation of H +  in the blood and its pH falls below the reference range. In an alkalosis there is a depletion of H +  and therefore the blood has a pH above its reference range. Acid–base disorders can be further divided into two groups depending on their causes. If the abnormal pH occurs because of a metabolic or renal dysfunction, it is referred to as a  metabolic  acid–base disorder. When the abnormal pH is due to lung dysfunction, then it is a  respiratory  acid–base disorder. Physiological mechanisms that attempt to return the pH back to values within the reference range are referred to as  compensation . Metabolic disorders cause a change in the concentration of HCO 3 –  in the blood but respiratory disorders cause a change in its  P CO 2  ( Table 9.1 ). In any acid–base disorder, the pH of the blood de...

  METABOLIC ACID–BASE DISORDERS Metabolic acid–base disorders lead to an accumulation or a loss of H +  resulting in changes in the concentration of HCO 3 –  in the blood. The direct loss or gain of HCO 3 –  will also cause a metabolic acid–base disorder. Thus metabolic disorders are recognized by investigating the concentration of HCO 3 –  in the blood. Respiratory compensation occurs quickly, often within hours, and patients will show some change in blood  P CO 2  because of hypo-or hyperventilation. Metabolic acidosis may arise from an increase in the amount of H +  formed or a decrease in the concentration of HCO 3 – . Diabetic ketoacidosis ,  lactic acidosis, poisoning with, for example, salicylate, methanol, ethylene glycol or the condition known as inherited organic acidosis all increase the production of H + . In contrast, a decreased excretion of H +  as in renal tubular acidosis, acute and chronic renal failure , the use of inh...

  RESPIRATORY ACID–BASE DISORDERS In respiratory acid–base disorders, the primary disturbance is caused by a change in the partial pressure of arterial CO 2 . Respiratory disorders are related to a defect in the rate of ventilation of lungs or the exchange of gases across the alveolar membrane. The changes in  P CO 2   alter the concentrations of carbonic acid in the blood, which, in turn, dissociates to HCO 3 –  and H + . Some causes of respiratory acidosis are shown in  Table 9.2 . In general, obstruction of the airways by disease, or inhibition of the respiratory center in the brain by disease, trauma or drugs can cause respiratory acidosis. Respiratory acidosis may be acute or chronic. Acute conditions occur within minutes or hours. It is usually the low  P O 2  ( hypoxemia)  that is more dangerous than the high  P CO 2  ( hypercapnia ). Further, renal compensation is slow, taking two or three days to become effective, so respir...

  MIXED ACID–BASE DISORDERS Sometimes patients may present with more than one acid–base disorder and this is known as a  mixed acid–base disorder . These may present as (i) severe acidemia, that is a low blood pH, (ii) with a normal or near normal pH or (iii) with alkalemia, that is, a high blood pH. Whatever the underlying cause, all mixed acid–base disorders are associated with abnormal levels of blood  P CO 2  and HCO 3 – .   For example, a patient with chronic bronchitis may also have renal failure. Both these disorders increase the concentration of H +  in the blood. Chronic bronchitis leads to respiratory acidosis while the renal failure causes metabolic acidosis. This patient will therefore present with a mixed acid–base disorder with a high blood  P CO 2  and H +  concentration but a low concentration of HCO 3 – . In some cases, however, the two disorders in a mixed acid–base disorder can be antagonistic, that is, have opposing effect...