ACID-BASE METABOLISM

Saturday, April 09, 2005

Acid-Base Metabolism

This article has been published by the International Biopharmaceutical Association www.ibpassociation.org . Please note this article does not give any medical advice.

The project is sponsored by Kriger Research - CRO and Training Services ( www.kriger.com ) and ClinQua CRO (www.clinqua.com )

Start your Clinical Research Career Now


1. Buffer systems, the lungs and the kidneys maintain hydrogen ion levels in the body. Hydrogen ions are highly reactive and a slight change in their concentration can have serious consequences. Since hydrogen ion levels are low, they are usually expressed as pH, which is the negative log of the actual concentration. The pH of extracellular fluid needs to be kept at about 7.4.

a. Buffer systems - The Henderson-Hasselbalch equation shows the relationship between pH, carbon dioxide and bicarbonate. The equation is:

pH = pK + log [HCO3-]/S x PCO2;

where the constants pK = 6.1 (dissociation constant for carbonic acid) and S = 0.03 (solubility of carbon dioxide in plasma).

b. The kidney works on two fronts – reabsorption of bicarbonate ion and secretion of hydrogen ion. Over 4000 mEq of bicarbonate pass daily through the glomerulus; almost all is taken up again in the proximal tubules with the aid of carbonic anhydrase. The kidneys also secrete hydrogen ion that causes the formation of bicarbonate in the distal tubules.

c. Arterial pCO2 is maintained by differences in alveolar ventilation rates enabling the lungs to either hold in carbon dioxide or breathe it out.


RESPIRATORY ALKALOSIS

Definition:
Blood PCO2 less than 35 and pH greater than 7.45

Etiology:
1. low carbon dioxide due to increased losses via the lungs
2. Causes may be salicylate poisoning, hypoxia, gram-negative sepsis, liver failure, hyperventilation, mechanical ventilation, inflammation or tumor of the thorax, primary CNS disorder (tumor, infection, trauma or CVA), but also anxiety (hyperventilation) or pregnancy.

Manifestations:
1. CNS disorders may be expressed as anxiety or alterations in the state of consciousness.
2. Acute alkemia may cause symptoms of tetany and needs to be differentiated from hypocalcemia.

Principles of management:
1. Correct the underlying disorder.
2 If pH is greater than 7.6, controlled ventilation may be called for.


METABOLIC ALKALOSIS
Definition:
Blood pH greater than 7.45 and bicarbonate greater than 28

Etiology:
1. Increased production of bicarbonate is seen with vomiting (due to loss of acid) and with the rapid correction of hypercapnia from respiratory acidosis.
2 Excess bicarbonate from an exogenous source is also a problem.
3 Primary or secondary hyperaldosteronism stimulate hydrogen ion secretion in the distal tubule, raising bicarbonate levels. Diuretics have the same effect.

Manifestations:
of the underlying problem. May be symptoms of tetany

Diagnosis:
1. Blood analysis shows increased bicarbonate and decreased chloride, often with hypokalemia.
2 Urine chloride is increased in normovolemic states and very low with hypovolemia.
3 Arterial blood gases show increased bicarbonate and increased pCO2 and may also show hypoxia.

Principles of management:
1 Correct underlying disease state.
2 In cases where there is also hypokalemia, the best treatment is potassium chloride.
3 Metabolic alkalosis that occurs after hypercapnia correction may require acetazolamide as well.


RESPIRATORY ACIDOSIS

Definition:
Blood pCO2 greater than 40 mm Hg and pH less than 7.35

Etiology:
1. Diminished capacity of the lungs to clear CO2
2 May be due to primary lung disease, primary CNS dysfunction, neuromuscular disease or drugs causing hypoventilation.

Manifestations:
1. Respiratory acidosis stimulates blood flow to the brain that may cause cerebrospinal fluid pressure to increase above the normal limit. This may lead to CNS depression.
2 Acidemia decreases cardiac output and increases pulmonary hypertension, thereby decreasing blood flow to tissues.

Principles of management:
1. The underlying disorder needs to be corrected, if possible.
2 If blood pCO2 is more than 60 mm Hg, assisted respiration may be necessary.



METABOLIC ACIDOSIS

Definition:
pH less than 7.35 and bicarbonate less than 21

Etiology:
1. Is due to either loss of bicarbonate or accumulation of another acid (such as lactic acid)
2. Can be divided into metabolic acidosis with and without an anion gap. The anion gap refers to the anions actually present in the serum but usually not measured – mainly albumin, phosphates, sulfates and organic acids. It is calculated by the following formula (cations minus measured anions):

Anion gap = [Na+] – ([Cl-] + [HCO3-])

The normal value is 6-14 mEq/ml.

a. Metabolic acidosis with a normal anion gap (hyperchloremic metabolic acidosis) is due to loss of bicarbonate via the gastrointestinal tract (diarrhea, pancreatic fistula, ureterosigmoidostomy) or via the kidney. Renal loss may be due to proximal tubular acidosis (nephrotic syndrome, cystinosis, multiple myeloma, Wilson’s disease, heavy metal poisoning), distal tubular acidosis (SLE, Sjogren’s syndrome, obstructive uropathy, amphotericin B toxicity) or hyperkalemic renal tubular acidosis. Carbonic anhydrase inhibitors such as acetazolamide or mafenide inhibit bicarbonate reabsorption in the proximal tubule. Moderate renal failure, with GFR of 15-40 ml/min, shows a decline in ammonium excretion due to decreased renal mass.
b. Metabolic acidosis with positive anion gap is seen with ketoacidosis (diabetes, starvation, alcohol abuse), lactic acidosis (shock, sepsis), drug intoxications (salicylate, methanol, ethylene glycol) and renal failure.

Winter’s formula – With pure metabolic acidosis, pCO2 is 1.5 times the bicarbonate concentration plus 6-10 mm Hg. An actual pCO2 less than that predicted by this formula suggests primary respiratory alkalosis is also involved; if actual pCO2 is higher than predicted, the complication is a disorder of pulmonary function and CO2 retention.

Manifestations:
1. Decreased cardiac output may be seen if pH is less than 7.2.
2 Kussmaul breathing (deep and rhythmic) appears as the lungs increase ventilation rate to compensate.

Principles of management:
Bicarbonate treatment is necessary to raise pH to at least 7.2. The amount of bicarbonate to be administered is based on bicarbonate occupying half of the body weight, according to the formula:

(Desired bicarbonate level – actual bicarbonate level) x 0.5 x body weight


For more information on Clinical Research Career Training and Clinical Trials Services please contact Kriger Research Group ( www.kriger.com ) at info@kriger.com or call (866) 757-9791 (USA and Canada) or + 1(416) 630-0038 (Internationally)