Acid-base disorders and what we should know

The physiology of acid-base balance

Acids are substances that dissociate to release hydrogen ion in aqueous solutions. Conjugate bases are substances that receive hydrogen ions in aqueous medium. In normal human metabolism, our body produces CO₂, H₂0 & energy from the breakdown of carbohydrates, fatty acids, and amino acids in the Krebs cycle pathway.

CO₂ dissolves in blood to form carbonic acid (H₂CO₃) by the action of carbonic anhydrase. The carbonic acid then dissociates into hydrogen ion (H⁺) & carbonate (HCO₃^–). H⁺ binds with hemoglobin in plasma, and at the alveoli it is released during oxygenation at the pulmonary capillary. Carbonic anhydrase converts carbonic acid into H₂O & CO₂. H₂O is secreted by the kidney, while CO₂ exhaled by the lungs.  The release of C02 reduces H production and furthermore, acidity.

          H⁺ + HCO₃^– <—>H₂C0₃ <——>H₂O + CO₂

Acid-base disorders produce protonated hydrogen ion that may be more or less contrary to their standard amount of 37-43nmol/l.

Sources of organic acids include: lactic acid; ketoacids; sulfuric acid from cysteine and methionine metabolism; hydrolysis of dietary phosphates; arginine; lysine.

Sources of organic bases include: Citrate, lactate, glutamate, and aspartate.  

The definition of a buffer system

A buffer is a substance that is able to resist changes in body pH. They work best at pH nearer to their equilibrium constant, at which point they can dissociate and neutralize either an acid or base.

An important chemical buffer for humans is the carbonic acid (H₂CO₃) whose action is immediate. H₂CO₃ is converted to water and carbon dioxide in a case of low blood pH. Its conjugate base (HCO₃^–) also neutralizes acid in the blood.   

To derive the pH of the buffer, the Henderson-Hasselbalch equation is used:

          PH= pKa + log (anion)/(weak acid)

In simpler terms, the partial pressure of CO₂ with plasma or serum HCO₃^– are regulators of acid-base balance.

The lung regulates pH by exhaling excess CO₂ out of the body to increase pH. Respiratory rate increases when arterial chemoreceptors detect low blood PH.

The kidney regulates pH by filtering out HCO₃^–, reabsorbing HCO₃^–, & secreting H⁺ out of the body. The proximal tubule is the main site for bicarbonate reabsorption. A high PCO₂, low sodium level in the blood would cause bicarbonate reabsorption.

Excretion of potassium, K⁺ would also result in hydrogen ion loss. H⁺ combines with creatinine, uric acid, phosphate and ammonia in renal tubule to be excreted out.

Types of acid-base disorders

Acid base disorders are pathological disbalances between PCO2 and serum HCO3- that produce abnormal pH levels. Normal pH level is 7.35-7.45

Metabolic acidosis is the primary reduction in bicarbonate level <22mmol/l, with a compensatory reduction in PCO₂ (respiratory alkalosis). Here PH may be severely or slightly low.

The followings are the causes of metabolic acidosis:

1. Lactic acidosis from shock
2. Ketoacidosis from type 1 diabetes
3. Rhabdomyolysis
4. Renal failure which decreases acid excretion and HCO₃^– reabsorption.
5. Diarrhea, drainage which cause G.I loss of bicarbonate
6. Salicylate, methanol, and ethylene glycol poisoning.

Metabolic alkalosis is the primary increase in bicarbonate level >26mmol/l, with/without compensatory increase in PCO₂ level (respiratory acidosis). Here PH may be nearly normal or high.

The followings are the causes of metabolic alkalosis:

1. Loss of acid from vomiting
2. Conns syndrome/primary hyperaldosteronism
3. Diuretics
4. Hypokalemia

Respiratory acidosis is the primary increase in the partial pressure of CO₂ >42mmHg, with/without compensatory increase in HCO₃^– (metabolic alkalosis). Here, PH may be low or nearly normal. The causes include: pulmonary disorders, chest trauma, brainstem stroke, hypoventilation & coma.

Respiratory alkalosis is the primary decrease in the partial pressure of CO₂ <38mmHg, with/without compensatory decrease in HCO₃^– (metabolic acidosis). Here, Ph may be high or nearly normal.

A physiological response to hypoxia and metabolic demands results in respiratory alkalosis. This response triggers increased respiratory rate. The causes of respiratory alkalosis include: panic attack, anxiety, fever, high altitude, metabolic acidosis.

Symptoms may include light headedness, confusion, paresthesia, & cramps.  

Diagnosis of acid-base disorders

Acid-base disorders can be diagnosed by: ordering arterial blood and electrolyte, calculating the anionic gap.

The anion gap is the serum Na⁺ concentration minus the sum of serum Cl^– & HCO₃^– concentration. Below is the equation:

anion gap= Na – (CL^– + HCO₃^–)

Normal anion gap is 6-12mmol/l. A value >12mmol/l indicates metabolic acidosis. In some cases, a normal anion gap may arise may indicate hyperchloremic metabolic acidosis. In hyperchloremic acidosis there is high serum Cl^– & low serum HCO₃^– in response to chloride loss from vomiting.

Lab references:

PH=7.35 -7.45

HCO₃^– = 22-26mmol/l (also as mEq/l)

Pco₂₌ 38-42mmHg

pO₂= 75-100mmHg

It is important to know that acid-base disorders can be single or mixed. Single acid-base disorders consist of one one primary disorder with accompanying compensatory response. Mixed acid-base disorders consist of morethan 1 primary disorder.

How to calculate Expected Compensatory Response (ECR) for each disorder:

Expected fall in partial pressure of CO₂ during metabolic acidosis: = (1.5 x HCO₃^–) + 8

Expected rise in partial pressure of CO₂ during metabolic alkalosis= 0.75 x rise in HCO₃^–

Forecasted fall in bicarbonate level in respiratory alkalosis= 0.2 x fall in PCO₂

Predicted rise in bicarbonate level during respiratory acidosis= 0.1 x rise in PCO₂

Average level of PCO₂ should be 40mmHg, and HCO3- should be 24mEq/l.

Calculating Delta gap and corrected bicarbonate level

Delta gap is the difference between patients’ anion gap and the standard anion gap range(12mm/l). Used when anion gap is ≥20mmol/l to check for metabolic alkalosis. After getting Delta gap value, then check for corrected bicarbonate level.

Delta gap = patients’ anion gap – normal anion gap(12mmol/l)

Corrected bicarbonate level= Delta gap value + given lab value. A corrected bicarbonate value>26 confirms metabolic alkalosis.