ACID-BASE BALANCE

Pharmacy II-nd Year, Practical Classes, 2010. I. Petkova, M.D., Ph.D.

Regulation of Acid-Base Balance

H+ concentration is expressed as pH. The pH of blood depends on the ratio of HCO3- to CO2 concentration: pH = pK + log [HCO3-] / [CO2]. pK contains the dissociation constant of H2CO3 and the reaction constant of CO2. H+ concentration is precisely regulated. pH is maintained between 7.35 - 7.45 in the plasma. Defenses against changes in [H+] The body has three primary lines of defense against changes in hydrogen ion concentration in the body fluids: Chemical buffer systems immediately combine with acid or base to prevent excessive changes in hydrogen ion concentration. Respiratory system regulates removal of CO2, and therefore H2CO3 from the extracellular fluid. This mechanism operates within seconds to minutes and acts as a second line of defense. The kidneys, which excrete either alkaline or acidic urine, thereby adjusting the extracellular fluid hydrogen concentration toward normal during alkalosis and acidosis. This mechanism operates slowly but powerfully over a period of hours or several days to regulate acid-base balance. Laboratory Assessment We assess acid-base state mainly by 3 laboratory tests: On the basis of plasma pH we distinguish between compensated, subcompensated, and noncompensated disorders. pCO2 refers to respiratory disorders of acid-base balance. Respiratory disorders are caused by increased or decreased pCO2. HCO3- refers to metabolic disorders of acid-base balance. Metabolic disorders result from decrease or increase in bicarbonate in body fluids. pCO2 decreases to compensate metabolic acidosis, and increases to compensate metabolic alkalosis. HCO3- increases to compensate respiratory acidosis and decreases to compensate respiratory alkalosis. Additionally decreased pO2 and/or saturation of hemoglobin (HbO2) can point towards respiratory disorder, when both pCO2 and bicarbonate are altered.

Disorders
Alkalosis develops when [H+] is decreased (increased pH). Acidosis develops when [H+] is increased (decreased pH). Breathing disorders, which decrease or increase pCO2 cause respiratory alkalosis or acidosis, respectively. Nonrespiratory disorders, which cause a decrease or an increase of [HCO3-] are called metabolic acidosis and alkalosis, respectively. Compensations: Respiratory disorders are compensated by ion exchange between extracellular and intracellular fluid, and by the kidneys. Metabolic disorders are compensated by the respiratory mechanisms and by the kidneys, when they are not involved in the disease.

Alkalosis
Respiratory alkalosis is caused by increased ventilation, which decreases pCO2 in the blood (hypocapnia).

 Metabolic alkalosis results from increased HCO3- in the extracellular fluid. Respiratory alkalosis occurs in hyperventilation. Causes include emotional excitement, salicylate poisoning, and damage to the respiratory neurons (inflammation). Lack of oxygen supply (e.g. at high altitude) in inspiratory air causes also hyperventilation, resulting in hypocapnia. Numerous disorders can lead to metabolic (i.e. non-respiratory) alkalosis. Hypokalemia causes hyperpolarization of renal tubule cells, and thus HCO3- efflux of the cell. Resulting intracellular acidosis promotes H+ secretion into the tubule lumen and loss of H+ with urine. Production of HCO3- in the tubule cells is also activated. Both events lead to alkalosis. In vomiting of stomach contents the body loses H+. When blood volume is reduced (vomiting, renal loss of fluid etc.) Na+/H+ exchange in the proximal tubule of the kidney is activated to compensate for the reduced volume. Thus, Na+ and HCO3- are reabsorbed and H+ is lost in urine, resulting in alkalosis. Effects of Alkalosis Respiratory alkalosis is compensated by the decreased reabsorption of HCO3- in the kidneys. Metabolic alkalosis can theoretically be compensated by hypoventilation. But the need to take up sufficient O2 sets narrow limits to this compensation. Hypokalemia is result of alkalosis, because all cells of the body (especially Erys) release less HCO3-, depolarize less, and thus lose less K+, and K+ in plasma is decreased. In alkalosis, more Ca2+ is bound to plasma proteins, thus ionized Ca falls, which can cause raised neuromuscular excitability.

Acidosis
A decrease in pH caused by the increase in pCO2 is referred to as respiratory acidosis. If the decrease in pH is caused by a decrease in HCO3-, the condition is referred to as metabolic acidosis. Causes of Respiratory Acidosis Pulmonary hypoventilation results in increased pCO2 and thus acidosis. Causes include: Obstructive or restrictive hypoventilation disorders in lung diseases. Restrictive hypoventilation disorders in pleural diseases or chest conditions. Abnormal regulation of breathing. Causes of Metabolic Acidosis There are several causes of metabolic (i.e. non-respiratory) acidosis. In Hyperkalemia the chemical gradient across the cell membrane is reduced. The resulting depolarization of renal tubule cells diminishes the electrical driving force for HCO3- transport (Na+ / [HCO3-]3 cotransport) and slows down the efflux of HCO3- out of the cell. The resulting intracellular alkalosis inhibits Na+ / H+ exchange and thus secretion of H+ into the tubule lumen decreases. Renal failure, transport defects, and hypaldosteronism cause reduced renal excretion of H+ and production of HCO3-. Vomiting of intestinal content, diarrhea or fistules result in loss of bicarbonate from the gut. Infusion of large amounts of NaCl, resulting in expansion of the extracellular volume inhibits Na+/H+ exchange in proximal tubule, and thus excretion of H+ decreases. Production of organic acids as lactate, resulting from hypoxia, aceto-acetic acid in starvation and diabetes mellitus also causes acidosis.

Ca2+ in the form of alkaline salts is deposited in the bone during mineralization. In this way bicarbonate from the extracellular space is lost. Effects of Acidosis Respiratory acidosis is compensated by the increased renal excretion of acids, reabsorption of HCO3-, or formation of new HCO3-. Metabolic acidosis can be compensated by respiratory reduction in plasma pCO2 via hyperventilation. In extracellular acidosis the cells lose HCO3-. Acidosis inhibits Na+/K+ ATP-ase and the cells lose their K+. Result is increased K+ in plasma - hyperkalemia. Intracellular acidosis inhibits K+ channels and has a negative inotropic and dromotropic effect. Hypercapnia induces vasodilation (fall of blood pressure, rise in intracerebral pressure). Prolonged acidosis promotes demineralization of bone because alkaline salts of the bone are dissolved by acids.