Acid-base Balance – Part 1 – Metabolic acidosis, and Metabolic Alkalosis

November 24, 2020Chemical pathologyLab Tests

Sample

1. The better choice is the Radial artery.
   1. The sample may be taken from the femoral artery or brachial.
   2. Blood can be drawn from the indwelling arterial line.
2. The tests are done immediately because oxygen and carbon dioxide are unstable.
   1. Place the sample on ice and immediately transfer it to the lab.
3. Arterial blood is better than venous blood.
4. For venous blood syringe or tube is completely filled and apply a tourniquet for a few seconds.
5. Arterial blood is risky and it should be done by a trained person.
   1. Never apply a tourniquet.
   2. Don’t apply the pull to the plunger of the syringe.

Indications

It is advised in:

1. Diabetes mellitus.
2. Starvation.
3. Lactic acidosis.
4. Ingestion of NH4CL, ethylene glycol, methanol, salicylates, and paraldehyde.
5. In the case of diarrhea.
6. In the case of renal failure.
7. In the case of proximal tubular acidosis.

Precautions for the collection of blood

1. Avoid pain and anxiety to the patient which will lead to hyperventilation.
   1. Hyperventilation due to any cause leads to decreased CO2 and increased pH.
2. Keep blood cool during transit.
3. Don’t clench finger or fist. This will leads to lower CO₂ and increased acid metabolites.
4. pCO₂ values are lower in the sitting or standing position in comparison with the supine position.
5. Don’t delay the performance of the test.
6. Avoid air bubbles in the syringe.
7. Excess of heparin decreases the pCO₂  maybe 40% less.
8. Not proper mixing of the blood before running the test may give a false result.
9. A prolonged tourniquet or muscular activity decreases venous pO₂ and pH.
10. Best way to collect arterial or venous blood anaerobically.
11. Arterial blood precautions:
    1. Only syringe and needle, no tourniquet, no pull on the plunger.
12. Venous blood precautions:
    1. Needle and syringe of the heparinized evacuated tube completely filled, drawn a few seconds after the tourniquet.
    2. Liquid heparin is the only suitable anticoagulant with the proper amount.
       1. Less amount will lead to clot formation.
       2. The increased amount will lead to an increase in CO2 and a decrease in pH.
       3. This will leads to a dilutional error.
    3. Glass collection devices are better than plastic.

Pathophysiology

Definition of acid-base disturbance and control:

1. H⁺ ions and electrolytes disturbances may be:
   1. Acute.
   2. Chronic.
   3. Modest or severe.
   4. Simple or mixed.
2. When there is an accumulation of H+ ions is called acidosis.
   1. When blood pH is declining below 7.3, this process is called acidemia.
3. When there is a deficiency of H+ ions is called alkalosis.
   1. Blood pH rises above 7.45 is called alkalemia.
4. There are conditions related to the respiratory system that leads to respiratory acidosis or alkalosis.
5. There are metabolic conditions related to kidneys and abnormality of intake/output leads to metabolic acidosis/alkalosis.
6. The blood pH is normally maintained at 7.38 to 7.42. Any deviation from this range indicates a change in the H⁺ ions concentration.
   1. Blood pH is a negative logarithm of [H⁺] as shown in the following equation:
      1. pH = log₁₀ [H⁺]
      2. This equation shows that an increase in the H⁺ ions will lead to a fall in the blood pH is called acidemia.
      3. So a decrease in the H⁺ ions will lead to an increase in the pH of the blood called alkalemia.
      4. The conditions which cause the change in the pH are called acidosis and alkalosis.
7. The following diagram can give you the concept of how pH is maintained by the arterial carbon dioxide tension  (pCO2)  and plasma bicarbonate (HCO3^–).

Acid-base balance control mechanism

8. Plasma HCO3^– decrease in the plasma caused by gastrointestinal or renal losses will increase H⁺ ions and lowers the pH.
   

   Acid-base system control

Role of kidneys and lungs in acid-base control

Metabolic acidosis

1. Definition:
   1. Metabolic acidosis occurs whenever there is a primary decrease in the HCO3¯ in the blood.
   2. This may occur due to:
      1. Exogenous acid administration.
      2. Endogenous acid production.
      3. Impaired renal H+ secretion.
      4. HCO3^– losses from the kidney or in the gastrointestinal secretions.
2. Anion gap:
   1. The importance of the anion gap is to identify the etiology of metabolic acidosis.
   2. The anion gap is measured in meq/L.
   3. Definition of anion gap: This is the difference between the plasma concentration of major cation sodium (Na⁺) and other anions are HCO3^– and Cl^–.
      1. Anion gap = [Na⁺] – ([HCO3^–] + [Cl^–])
      2. The normal anion gap is 3 to 13 meq/L and the mean is 10 meq/L.
      3. This is dependant mainly on the plasma protein, primarily albumin.
      4. 2.5 meq/L falls for every 1 gram/dl of albumin concentration in the blood.
3. H⁺ ions changes in the blood lead to acid-base imbalance.
   1. A systemic increase in the H+ ions is called acidosis.
   2. In the case of acidemia pH of the arterial blood is <7.4.
4. While in alkalemia the pH of the arterial blood is >7.4.
   1. There is a systemic decrease in the H+ ions in the systemic blood is called alkalosis.

Causes of metabolic acidosis:

1. In metabolic acidosis, noncarbonic acid increases, or HCO3¯ is lost from the extracellular space.
   1. The buffering system becomes active and maintains the pH.
   2. In case of failure of the buffering system then the anion gap  HCO3¯: H2CO3 = 20:1 changes.
2. Increased noncarbonic acid with an elevated anion gap, and Increased H+ load:
   1. Diabetes mellitus with ketoacidosis. There is a production of acetoacetic acid and β-hydroxybutyric acid in diabetic acidosis.
   2. In the case of starvation.
   3. Lactic acidosis in shock and hypoxemia. There is the production of lactic acid.
   4. Ingestion of drugs like NH4CL, salicylates, methanol, ethylene glycol, and paraldehyde.
3. Decreased H+ ions excretion was seen in:
   1. Uremia.
   2. Distal renal tubular acidosis (decreased renal H+ secretion).
      1. 1. There is an accumulation of the acid that consumes the bicarbonate (HCO3¯).
4. Bicarbonate (HCO3¯) loss from the extracellular space and normal anion gap:
   1. Renal failure.
   2. Diarrhea.
   3. Proximal tubular acidosis (there is renal HCO3¯ loss).
      1. Plasma HCO3¯ falls, and the fall is associated with a rise in the concentration of the inorganic anions mostly CL¯ or maybe a fall in Na⁺ concentration.
5. Biochemical changes in metabolic acidosis:
   

   Biochemical parameters	Value
   Anion gap HCO3¯: H2CO3   20:1	Changes to 10:1
   pH	Decreased
   pCO2	No change
   HCO3¯	Decreased because of the excess of ketones, CL¯, or organic acid ions.

Metabolic acidosis changes

Causes of a high anion gap (>12 meq/L):

1. Methanol toxicity.
2. Uremia due to renal failure.
3. Starvation.
4. Diabetes mellitus (ketoacidosis).
5. lactic acidosis.
6. Salicylates toxicity.
7. Ethyl alcohol toxicity.
8. Isoniazid toxicity.
9. Iron toxicity.

Causes of decreased anion gap (<6 meq/L):

1. Hypoalbuminemia.
2. Plasma cell disorders.
3. Bromide intoxication.

Causes of normal anion gap (6 to 12 meq/L):

1. Intestinal fistula.
2. Pancreatitis.
3. Renal tubular acidossis.
4. Acid and chloride administration:
   1. NH4Cl, HCL for the treatment of severe metabolic acidosis.
   2. Hyperalimentataion.
5. Bicarbonate or other alkali losses:
   1. Diarrhea.
   2. Recovery from ketoacidosis.

Compensation for metabolic acidosis:

1. Hyperventilation by rapid breathing from the lungs will blow off CO2.
2. Kidneys will conserve HCO3¯ and eliminate H⁺ ions in the urine where urine will be acidic.
   

   Metabolic acidosis causes

Signs and symptoms:

1. Kussmaul respiration suggests metabolic acidosis.
2. The early symptom is a headache and lethargy.
3. There is anorexia, nausea, vomiting, diarrhea, and abdominal discomfort.
4. If acidosis progresses then ultimately the end is death.
5. The patient can have neurological, respiratory, gastrointestinal, and cardiovascular signs and symptoms.
6. Deep rapid respiration indicates respiratory compensation.
   1. There is increased tidal volume, rather than respiratory rate, this characterizes these ventilatory changes results from stimulation of the brain stem respiratory center by the low pH.
   2. Decreased blood pH leads to:
      1. Decreased myocardial contraction, causing decreased blood pressure.
      2. Arterial vasodilatation.
      3. pH below 7.15 to 7.20 the effect of acidemia is prominent.
7. Ketoacidosis is associated with increased thirst and polyuria.
8. There is secondary hypotension in severe acidotic patients.
9. Severe acidosis produces life-threatening dysrhythmias, like ventricular fibrillation.
10. ultimately the patient will go into a coma.

Diagnosis:

1. Take the history of the patient.
2. There are clinical signs and symptoms.
3. Lab. findings are:
   1. pH = <7.35. (low pH).
   2. HCO3¯ = <24 meq/L (low plasma bicarbonate).
   3. Anion gap can help you make the diagnosis of the cause.
4. There may be concomitant hypokalemia or hyperkalemia which helps in the diagnosis.

Treatment:

1. Until arterial pH falls below 7.15 to 7.20, the adverse effect of acidemia is usually compensated for by elevated plasma catecholamines.
2. In case of severe acidosis, give NaHCO3 to elevate the pH.
3. Correct the sodium and water deficiency.

Metabolic Alkalosis

There is excessive loss of metabolic acids and an increase in the plasma HCO3‾ and an arterial pH >7.4 leads to metabolic alkalosis.

Causes:

1. This is a common condition which most often is induced by diuretic therapy or loss of gastric secretions (in vomiting or nasogastric suction).
   1. This condition is caused by:
      1. There must be an initial increase in the HCO3^– level caused by the H⁺ ions loss in the gastrointestinal secretions or in the urine.
      2. H⁺ ions movement into the cell.
      3. Akali administration.
         1. Volume contraction around a relatively constant amount of extracellular HCO3^-.
      4. One of the following factors in case of absence of renal failure to maintain high HCO3^–:
         1. Chloride (Cl^–) depletion.
         2. Hypochloremia or hypokalemia.
         3. Effective circulating volume depletion.
2. This occurs in the acid loss by vomiting or nasogastric suction.
3. Pyloric or upper duodenal obstruction.
4. In the case of villous adenoma.
5. Prolonged diuretic therapy.
6. Cystic fibrosis.
7. Primary Hyperaldosteronism leads to retention of the NaHCO3 and loss of H+ and K+.
8. Secondary hyperaldosteronism.
9. Bilateral adrenal hyperplasia.
10. Congenital adrenal hyperplasia.
11. Cushing’s syndrome.
12. Pituitary adenoma secreting ACTH (Cushing’s syndrome).
13. Exogenous cortical therapy.
14. Excessive licorice ingestion.
15. Diuretics also produce mild alkalosis because they produce excretion of Na⁺, K+, and CL¯ than of HCO3¯.
16. Milk-alkali syndrome.
17. Massive blood transfusion.
18. High doses of carbenicillin or penicillin.

Summary of metabolic alkalosis:

1. Before alkalosis HCO3: H2CO3 ratio is 20:1.
2. Then pH increases, PCO2 no change, and HCO3¯ also increases.
   1. HCO3: H2CO3 = 40 :1
3. HCO3¯ increases because of the loss of CL¯ ions or excess ingestion of NaHCO3.

Compensatory mechanism:

1. Breathing will be suppressed to hold the CO2.
   1. The increase in the pH depresses the respiratory center causing retention of CO2 which will increase in H2CO3 and CO2.
2. The kidney will conserve H⁺ ions and excrete more HCO3¯ in the urine and urine will be alkaline.
   

   Changes in the metabolic alkalosis

Signs and symptoms:

1. In some of the patients may have severe cramping, paresthesia, or even tetany, but in others with similar electrolytes data have no such S/S, the reason is unknown.
2. Ask the history of vomiting or diuretic therapy.
3. There is a weakness.
4. There are muscle cramps.
5. There are hyperactive reflexes.
6. There is shallow and slow respiration.
7. There will be tetany.
8. The patient will have confusion and convulsions.
9. Ultimately patient will have atrial tachycardia.

Lab diagnosis:

1. Ther arterial blood shows increased pH and HCO3¯.
2. Serum K⁺ and CL¯ are decreased.
3. There may be an increased anion gap.
4. Measurement of the Na⁺ in a random urine sample differentiate urinary volume depletion Na⁺ <20 meq/L and euvolemic Na⁺ >40 meq/L.
   1. Metabolic alkalosis is the condition is which volume depletion may not lead to a low urinary Na⁺.
   2. The capacity to retain the Na⁺ in this situation is maybe antagonized by the need to excrete HCO3^– (as Na+ salt) in an attempt to correct the alkalosis.
   3. in such cases, a random urinary Cl^– determination is more useful.
5. Summary:
   1. pH = >7.4,        pCO2 = 45 to 55 mmHg,       HCO3- = >27 meq/L

Treatment:

1. In the case of mild alkalosis, the patient can tolerate it.
2. In the case of severe cases of pH >7.6, urgent treatment is needed.

Table showing characteristic features of acidosis and alkalosis: