SPECIFIC ACID-BASE DISORDERS

Salient features of major acid-base abnormalities are as follows:

Metabolic acidosis: Primary abnormality in metabolic acidosis is decreased in HCO₃^- levels, either due to external losses or excess utilization to titrate H⁺ ions during buffering process.

TABLE 7.13: Causes of metabolic acidosis

With normal anion gap (Hyperchloremic acidosis):

• Renal loss of HCO₃^-: Proximal RTA, renal failure

• GIT loss of HCO₃^-: Diarrhea

• 4 H⁺ excretion: RTA type I/IV, potassium sparing diuretics

• #8593; H⁺ production: TPN, ammonium chloride poisoning

With high anion gap (Normochloremic acidosis)

• #8593; acid production/accumulation

- Lactic acidosis: Sepsis, shock, hypoxia

- Ketoacidosis: Diabetes ketoacidosis, starvation

- Others: IEM, organic acidemia, salicylate poisoning

• Failure of acid excretion, e.g. renal failure

• Dilutional hypobicarbonatemia (HCO₃^- free fluid therapy) RTA: Renal tubular acidosis; TPN: Total parenteral nutrition; IEM: Inborn errors of metabolism.

compensated by relative increase in chloride levels (hyperchloremia).

Etiology: Metabolic acidosis may be with: (a) normal anion gap due to loss of bicarbonates or accumulation of H ions or with, (b) increased anion gap due to accumulation of other acids, e.g. lactic acid or ketoacids, etc. Relative HCO₃^- deficiency due to bicarbonate-free fluid therapy (dilutional hypobicarbonatemia) may also lead to metabolic acidosis with normal anion gap (Table 7.13).

Clinically, acute metabolic acidosis presents with signs of:

• Compensatory respiratory effort, e.g.

• Acidosis per se leading to peripheral vasodilatation and consequently hypotension, pulmonary edema and tissue hypoxia.

Chronic metabolic acidosis may be asymptomatic or present with anorexia, weight loss, vomiting and muscle weakness.

Diagnosis of acute metabolic acidosis is indicated by lower pH lt; 7.35, and low HCO₃^- levels, while compensated state is also associated with low pCO₂ levels. For full compensation, 1 mEq/L drop in HCO₃^- is compensated by 1.2 mm Hg drop in pCO₂.

Anion gap: Next step in etiological evaluation of metabolic acidosis is calculation of anion gap, i.e. the difference between total measurable cations and anions, i.e. serum Na⁺ and K⁺ on one side and serum HCO₃^- and Cl^- on other side. Normally, cationic side exceeds anionic side by ~12 mEq/L, due to a pool of non-titrable acids (*), as shown in following equation:

(Serum) Na⁺ + K⁺ = HCO₃^- + Cl^- + (*)

Anion gap is increased (gt;16 mEq/L) in metabolic acidosis due to accumulation of non-titratable acid (with corresponding fall in measurable anions), e.g. in renal failure, lactic acidosis, diabetic ketoacidosis, salicylate poisoning, inborn errors of metabolism, etc.

Anion gap remains normal in metabolic acidosis due to bicarbonate losses with: (a) corresponding increase in Cl^- levels (hyperchloremic acidosis), e.g. renal tubular acidosis, hypoadrenal states, etc. or (b) corresponding drop in K⁺ levels, e.g. diarrhea.

Management of metabolic acidosis mainly includes correction of underlying cause, though alkali therapy may be necessary in severe acidosis (pH lt;7 or HCO₃^- lt;5 mEq/L or salicylate poisoning) as follows:

• Calculate precise HCO₃ requirement by following formula:

= (desired HCO₃ - actual HCO3) ? weight ? 0.6* (*distribution coefficient for bicarbonates in body).

• Infusion only half of this amount as 7.5% NaHCO₃ over 3-4 hours (1 ml = 0.9 mEq/L) along with fluid correction for hypotension/shock.

IV bicarbonate correction should be done slowly, as rapid correction of acidosis may precipitate tetany due to intracellular movement of calcium. In addition, these cases should be treated for primary cause, along with IV fluids to manage hypotension and shock.

Metabolic alkalosis: Primary event in acute metabolic alkalosis is actual or relative (due to H⁺ ion depletion) increase in HCO₃^- levels, which is partly compensated by respiratory depression to retain CO2. However, this compensatory response is always inadequate, limited by increasing hypoxia.

Etiology: Metabolic alkalosis is mainly caused by: (a) excessive GIT losses of H⁺ ions with chlorides, e.g. loss of gastric acids in vomiting, or (b) bicarbonate excess, due to exogenous administration or increased renal reabsorption (Table 7.14). Infantile hypertrophic pyloric stenosis (IHPS) is an important cause of hypochloremic metabolic alkalosis.

Metabolic alkalosis is also classified as Chloride­responsive when caused by gastrointestinal losses of H⁺

TABLE 7.14: Causes of metabolic alkalosis

Increased loss of H⁺ ions (hypochloremic/Chloride-responsive)

• Persistent vomiting

• Prolonged nasogastric aspiration

• Infantile hypertrophic pyloric stenosis

• Others: Cystic fibrosis, chloride losing diarrhea

• Severe dehydration: Diuretics

Increased reabsorption of HCO₃ (chloride-resistant)

• Congenital adrenal hyperplasia*

• Cushing syndrome*

• Hyperaldosteronism*

• Renovascular diseases*

• Others: Bartter syndrome, Gitelman syndrome

Exogenous intake of bicarbonates

• IV/oral bicarbonate therapy

• Milk-alkali syndrome

• Large blood transfusions (citrate blood)

*With hypertension and Cl ions, and chloride-resistant when due to renal causes.

Clinically, metabolic alkalosis presents with:

• Shallow respiration due to compensatory respiratory depression, and

• Signs of hypocalcemia, e.g.

Diagnosis of acute metabolic alkalosis is indicated by: (a) higher pH gt;7.45 and (b) elevated HCO₃^- levels, while partially compensated state is associated with some rise in pCO2 levels. For full compensation, 0.7 mm Hg rise in pCO₂ is expected for each mEq/L rise in HCO₃ levels, though it is rarely achieved.

Urinary chloride levels may be used to differentiate between chloride-responsive (lt;10 mEq/L) and chloride- resistant (gt; 20 mEq/L).

Management depends on the primary cause. Chloride­responsive metabolic alkalosis may be corrected with replenishment of contracted ECF with normal saline and added potassium chloride to bring pH lt;7.55 and biocarbonate levels lt; 40 mEq/L.

Chloride-resistant metabolic alkalosis is difficult to treat and treatment includes: (a) acetazolamide therapy to promote urinary bicarbonate excretion, (b) cautious administration of IV hydrochloric acid (0.5 x weight x desired fall in plasma bicarbonates) or oral ammonium chloride supplementation, and (c) dialysis in severe cases. Respiratory acidosis: Primary event in respiratory acidosis is CO₂ retention during acute phase (PaCO₂ gt;45 mm Hg), subsequently compensated by increased tubular reabsorption of bicarbonates as well as increased excretion of H⁺ ions (as ammonium and titratable acids). Some cases may have coexistent metabolic acidosis, due to secondary effects of hypoxia and consequent lactic acidosis.

Etiology: Respiratory acidosis is usually caused by inadequate CO₂ excretion due to poor alveolar ventilation or rarely due to increased CO₂ production, e.g. high fever or extensive burns (Table 7.15).

Clinically, these cases present with:

• Signs of respiratory distress due to primary cause, and

• Signs of hypercapnia (CO₂ narcosis), e.g.

Diagnosis of acute respiratory acidosis is indicated by lower pH lt;7.35, and elevated pCO₂, while compensated state is associated with rise in plasma HCO₃^- levels. While compensation begins in 6-12 hours, full compensation may take 3-5 days and needs HCO₃^- levels to rise by 3.5 mEq/L for each 10 mm Hg rise in pCO₂

TABLE 7.15: Cause of respiratory acidosis

Loss of central respiratory drive

• CNS infections, tumors, etc.

• Drugs, e.g. narcotics, alcohol

Weakness of respiratory musculature

• Chronic neuromuscular disorders

• Acute respiratory muscle paralysis

Pulmonary diseases

• Restrictive lung diseases, e.g. severe scoliosis

• Extensive lung/airway disease

Miscellaneous (Increased CO₂ production)

• High fever or extensive burns

Management includes adequate ventilation/perfusion for treatment of primary cause and ventilator assistance, if necessary. Alkali therapy should never be used till adequate ventilation is established as it will worsen CO₂ retention (HCO₃^- + H⁺ gt; H₂CO₃ gt; H₂O + CO₂) and may produce hyperosmolality and cardiac failure.

Respiratory alkalosis: Primary change in the respiratory alkalosis is decreased pCO₂, subsequently compensated by decreased tubular absorption of bicarbonates.

Etiology: Respiratory alkalosis is caused by excessive CO₂ wash-out, due to hyperventilation, e.g. psychogenic causes, high fever, mechanical overventilation or early salicylate poisoning.

Clinically, these cases present with:

• Hyperventilation due to primary cause, and

• Signs of hypocalcemia, e.g. neuromuscular irritability, peri-oral paresthesia and alkalotic tetany, as alkalosis promotes calcium-binding with albumin, leading to ionic hypocalcemia.

Diagnosis of acute respiratory alkalosis is indicated by higher pH gt;7.45, and reduced pCO₂, while compensated state is associated with drop in HCO₃^- levels. Full renal compensation is rarely achieved and requires ~5 mEq/L drop in HCO₃^- for each 10 mm Hg drop in pCO₂.

Management depends on primary cause and correction of ventilatory settings. Acidifying agents, e.g. ammonium chloride are not indicated.

7.7