Acid-base Balance:- Part 2 – Introduction of Acid-Base Balance, Metabolic acidosis, and Metabolic Alkalosis

March 12, 2021Chemical pathologyLab Tests

Sample

1. The better choice is the Radial artery.
   1. May take the sample from the femoral artery or brachial.
   2. Can draw the blood 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 filled, and apply a tourniquet for a few seconds.
5. Arterial blood is risky, and a trained person should do it.
   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 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 balance:

1. This regulation of the extracellular fluid environment involves the ratio of acid to base, measured clinically as pH.
   1. Physiologically all positively charged ions are called acids, and all negatively charged ions are bases.
2. Physiological changes in the concentration of H⁺ ions in the blood lead to acid-base balance.
3. A systemic increase in the H⁺ ions concentration is called acidosis.
4. A systemic decrease in the H⁺ ions is called alkalosis.
5. The acid-base must be regulated within a narrow range for the body to function normally.
   1. A very slight change in the pH will affect the body.
   2. A very slight change in the H⁺ ions can bring changes in the cell and tissue.
   3. H⁺ ions are needed for:
      1. To maintain the integrity of the membrane.
      2. Speed of the metabolic reactions.
      3. Any change in the pH will lead to harmful effects than other diseases.
      4. The symbol pH represents the power of H⁺.
      5. When pH changes one unit like 7.0 to 6.0 = [H⁺] [H⁺] = H⁺ ions concentration changes 10 folds.
   4. Body acids are formed from end products of:
      1. Metabolism of proteins.
      2. Metabolism of Carbohydrates.
      3. Metabolism of fats.
   5. This must be balanced by the number of basic substances in the body to maintain the normal pH.
      1. Lungs, kidneys, and bones are the major organs involved in the regulation of acid-base balance.
   6. Body acids are of two types:
      1. Volatile acids:
         1. Carbonic acid (H2CO₃) is a week acid, and it does not easily release the H⁺ ions.
         2. In the presence of carbonic anhydrase enzyme can eliminate CO 2 gas and water H2O.
         3. CO 2 is eliminated through the lungs.
      2. Nonvolatile acids:
         1. These are sulfuric acid, phosphoric acid, and other organic acids that are eliminated through the kidneys.
         2. These are the strong acids and readily give up their H⁺ ions.
         3. Nonvolatile acids are secreted into the urine by the renal tubules.
         4. These acids are about 150 meq/L of H+ ions per day or about 1 meq/kg body weight.

Buffer systems of the acid-base balance:

The buffer systems become active in response to change in the pH of the body as acid-base balance.

1. Functions of the buffer system:
   1. Prevent the significant change in pH.
   2. Buffer can absorb the excess of the H⁺ ions (acid).
   3. Buffer system can absorb OH^– ions, Hydroxyl (base).
   4. The buffer system is present in the intracellular fluid (ICF) and extracellular fluid (ECF).
   5. The most buffer system is:
      1. Carbonic acid-bicarbonate system.
      2. Hemoglobin system.
      3. Phosphate and protein are the most important intracellular buffers (ICF).

Various Buffer systems and their role in the acid-base system:

Summary of the different buffer system in acid-base balance:

1. Renal buffering system:
   1. The distle tubule of the kidneys regulates acid-base balance by secreting the H⁺ ions in the urine and reabsorbs the HCO3^–.
   2. Dibasic phosphate (HPO4^—) and ammonia (NH3) are two important renal buffer.
   3. The renal buffering of H+ ions requires CO2 and water (H2O) to form the H₂CO3.
   4. The enzyme carbonic anhydrase catalyzes the reaction.
   5. H+ ions are secreted from the tubular cells and buffer in the lumen by PO4^— and NH3 = H2PO^–3 + NH4⁺.
   6. The rest of HCO3^– is reabsorbed.
      

      Kidneys role in the acid-base balance

2. Carbonic acid-bicarbonate buffering system:
   1. This buffer system operates both in the lungs and kidneys.
   2. This is the major extracellular buffer system.
   3. Lungs can decrease the carbonic acid by blowing out the CO2 and leaving water behind.
   4. Kidneys can reabsorb HCO3- or regenerate new HCO3- from CO 2 and water.
   5. Normal bicarbonate (24 meq/L) and normal carbonic acid (1.2 meq/L), producing a 20:1 relation and maintain the pH of 7.4
   6. Both the systems are very efficient because:
      1. HCO3^– is easily reabsorbed or regenerated by the kidneys.
      2. The lungs adjust acid concentration.
   7. Compensation of the pH is done as:
      1. The respiratory system compensates pH by decreasing or increasing CO2 by changing the rate of respiration.
      2. The renal system produces more acidic or more alkaline urine.
3. Protein buffering system:
   1. Hemoglobin (Hb) is the best intracellular buffer system, and it combines with H⁺ and forming HHb and CO2, forming the HHbCO2 complex.
   2. When Hb combines with H⁺ ions becomes weak acid.
   3. Venous blood Hb is a better to buffer system than arterial blood Hb.

Acid-base control by the various organs of the body

The pH of different body fluids:

pH significance in our life:

For normal body functions, the pH range is very narrow and needs to be maintained within these limits.

Acid-base balance:

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 explain how pH is maintained by the arterial carbon dioxide tension  (pCO2)  and plasma bicarbonate (HCO3^–).
   

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

   Acid-base buffer system

Acid-base balance, the role of lungs and kidneys

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. Definition of the anion gap:
      1. Anion gap referred to anions usually not measured in the laboratory like sulfate, phosphate, and lactate. The anions usually measured are Chloride (Cl-) and bicarbonate (HCO3-). The sum of the anions is subtracted from the sum of cations (Na⁺ and ⁺); there is a gap around 10 to 12 meq/L, which is called an anion gap. An elevated anion gap gives clues for acidosis.
   2. The importance of the anion gap is to identify the etiology of metabolic acidosis.
   3. The anion gap is measured in meq/L.
   4. 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.
      

      Metabolic acidosis changes and findings

Acid-base balance: Metabolic acidosis and compensatory mechanism

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 the buffering system’s failure, 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 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 (normal)
   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.

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 result 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 = >14 meq/L  seen in:
      1. High-anion metabolic acidosis.
      2. Lactic acidosis.
      3. Ketoacidosis.
      4. Asprin over-dose.
      5. Renal failure.
      6. Overuse of alcohol.
   4. Anion gap = 12 meq/L or less is seen in:
      1. Increased acid load.
      2. Rapid I/V saline administration.
      3. Other diseases are characterized by HCO3^– loss.
4. Urine pH = <4.5 in the absence of renal disease.
5. Lactic acid = Increased (in lactic acidosis).
6. There may be concomitant hypokalemia or hyperkalemia, which helps in the diagnosis.

Treatment:

1. Until arterial pH falls below 7.15 to 7.20, acidemia’s adverse effect 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.
4. Give lactate ringer’s solution.
5. Correct the electrolyte imbalance.
6. Try to treat the underlying cause of the acidosis.
7. In case mechanical ventilation may be needed.
8. May need dialysis for patients with renal failure.
9. Needs antibiotics to treat the infection.

Metabolic Alkalosis

Definition of 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.

Changes in metabolic alkalosis:

Summary of metabolic alkalosis:

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

Compensatory mechanism of metabolic alkalosis:

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 H2CO3 and CO2.
2. The kidney will conserve H⁺ ions and excrete more HCO3¯ in the urine, and urine will be alkaline.
   

   Changes in Metabolic alkalosis

Acid-base balance: Metabolic alkalosis and compensatory mechanism

Signs and symptoms of metabolic alkalosis:

1. The patients are irritated, twitching, and confused.
2. There are nausea, vomiting, and diarrhea.
3. Some 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.
4. Ask the history of vomiting or diuretic therapy.
5. There is a weakness.
6. There are muscle cramps.
7. There are hyperactive reflexes.
8. There is shallow and slow respiration. There are cyanosis and apnoea.
9. There will be tetany.
10. The patient will have confusion and convulsions.
11. There are cardiovascular abnormalities due to hypokalemia.
    1. Ultimately patient will have atrial tachycardia.

Lab diagnosis of metabolic alkalosis:

1. The arterial blood shows increased pH and HCO3¯.
2. pH = >7.45.
3. HCO3^– = >29 meq/L.
4. K⁺ = <3.5 meq/L (low).
5. Calcium  (Ca⁺⁺)= <8.9 mg/dl.
6. Chloride (Cl^–) = <98 meq/L..
7. There may be an increased anion gap.
8. 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 in 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) to correct the alkalosis.
   3. In such cases, a random urinary Cl^– determination is more useful.
9. Summary of metabolic alkalosis:
   

   Lab parameter	Value
   pH	>7.45
   HCO3–	>29 meq/L
   K+	<3.5 meq/L
   Ca++	<8.9 mg/dL
   Cl–	<98 meq/L
   pCO2	45 to 55 mm Hg

Treatment of metabolic alkalosis:

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.
3. Can give KCl and normal saline.
4. Discontinue diuretics and supplementary KCl.

Causes of metabolic alkalosis:

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 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 HCO3¯.
16. Milk-alkali syndrome.
17. Massive blood transfusion.
18. High doses of carbenicillin or penicillin.

Table showing characteristic features of acidosis and alkalosis:

Panic values:

Summary of the parameters needed for the acid-base balance: