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Acid-base Balance:- Part 2 – Metabolic acidosis, Metabolic Alkalosis, and Anion Gap

March 14, 2025Chemical pathologyLab Tests

Table of Contents

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  • Metabolic Acidosis, Metabolic Alkalosis
        • What sample is needed for acid-base balance?
        • What are the indications for Acid-base Balance?
        • What are the precautions for the collection of blood?
        • How will you define acid-base balance?
        • Why H+ ions are needed?
        • What is the mechanism of body acid formation?
        • What are the various Buffer Systems?
        • What is the pH of different body fluids?
        • What is the significance of pH in our life?
        • What are the types of Acid-base balance?
        • What is the importance of blood pH?
    • What is the Anion gap?
        • How will you define the anion gap?
        • What causes a high anion gap (>12 meq/L)?
        • What causes a decreased anion gap (<6 meq/L)?
        • What causes the normal anion gap (6 to 12 meq/L)?
  • Metabolic acidosis
        • How will you define metabolic acidosis?
        • What are the causes of metabolic acidosis?
        • How is there compensation for metabolic acidosis?
        • What are the signs and symptoms of metabolic acidosis?
        • How will you diagnose metabolic acidosis?
        • How will you treat metabolic acidosis?
  • Metabolic Alkalosis
        • How will you define metabolic alkalosis?
        • What are the causes of metabolic alkalosis?
        • How will you summarize metabolic alkalosis?
        • What is the compensatory mechanism of metabolic alkalosis?
        • What are the signs and symptoms of metabolic alkalosis?
        • How will you diagnose metabolic alkalosis?
        • How will you treat metabolic alkalosis?
        • How will you summarize metabolic and respiratory acidosis/alkalosis?
      • Questions and answers:

Metabolic Acidosis, Metabolic Alkalosis

What sample is needed for acid-base balance?

  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 a venous blood syringe or tube, be 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.

What are the indications for Acid-base Balance?

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.

What are the precautions for the collection of blood?

  1. Avoid pain and anxiety in 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 your finger or fist. This will lead to lower CO2 and increased acid metabolites.
  4. pCO2 values are lower in the sitting or standing position than in 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 by maybe 40% less.
  8. Not mixing the blood properly before the test may give a false result.
  9. A prolonged tourniquet or muscular activity decreases venous pO2 and pH.
  10. The best way to collect arterial or venous blood is anaerobic.
  11. Arterial blood precautions:
    1. Only syringe and needle, no tourniquet, no pull on the plunger.
  12. Venous blood precautions:
    1. The needle and syringe of the heparinized evacuated tube were filled and 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 increased CO2 and a decrease in pH.
      3. This will lead to a dilutional error.
  13. Glass collection devices are better than plastic.

How will you define 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 concentration of H+ ions 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 slight change in the H+ ions can change the cell and tissue.

Why H+ ions are needed?

  1. To maintain the integrity of the membrane.
  2. Speed of the metabolic reactions.
  3. Any change in the pH will lead to more 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, the concentration changes 10-fold.

What is the mechanism of body acid formation?

  1. Metabolism of proteins.
  2. Metabolism of Carbohydrates.
  3. Metabolism of fats.
  4. 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 regulating acid-base balance.

What are the various Buffer Systems?

Buffer system (pairs) Buffer system Buffer reaction Mechanism
  • Hb-/HHb
  • Hemoglobin in the RBCs
  • HHb ↔H+ + Hb–
  1. Hb binds with H+ and CO2.
  • HCO3– / H2CO3

(Carbonic acid/bicarbonate buffer system)

  • Bicarbonate (HCO3–)
  • H++ HCO3–   =  H2O + CO2
  1. Lungs will regulate the retention or elimination of CO2 and H2CO3 concentration.
  2. Kidneys play a role in bicarbonate reabsorption regeneration and ammonia formation.
  3. Kidneys play a role in phosphate buffering.
  • Protein – (Pr–) / hydrogenated protein (HPr)
  • Plasma proteins
  • HPr ↔H–+ Pr

–

  1. The main role is Hb, which combines with H+ ions.
  2. Hb also combines with CO2.
  • HPO4 –/ H2PO4–
  • Phosphate in the blood
  • H2PO4 + H+ + HPO4–
  1. The bone will exchange calcium and phosphate
  2. Release carbonate.
  • Acid-base control by the various organs of the body.

What is the pH of different body fluids?

Body fluids pH range Explanation 
  • Arterial blood
  • 7.38 to 7.42
  • pH is higher due to less amount of carbonic acid
  • Venous blood
  • 7.37
  • pH is lower due to more carbonic acid
  • Gastric juice
  • 1.0 to 3.0
  • This is due to HCL acid
  • Pancreatic juice
  • 7.8 to 8.0
  • Exocrine glands produce bicarbonate (HCO3–)
  • Cerebrospinal fluid
  • 7.32
  • There is decreased HCO3- and increased CO2 contents.
  • Urine
  • 5.0 to 6.0
  • There are H+ ions excretion from waste products through the kidneys.

What is the significance of pH in our life?

  • For normal body functions, the pH range is very narrow and needs to be maintained within these limits.
pH value  Effects on the body
  • <6.8
  • This is incompatible with life.
  • <7.2
  • The cell’s functions are seriously impaired.
  • <7.35
  • This is acidosis
  • 7.37 to 7.43
  • This is the normal range
  • >7.45
  • This is alkalosis
  • >7.55
  • The cell functions are seriously affected
  • >7.8
  • This is incompatible with life

What are the types of 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, it is called acidosis.
    1. When blood pH declines below 7.3, this process is called acidemia.
  3. Alkalemia. When there is a deficiency of H+ ions, it is called alkalosis.
    1. Blood pH rises above 7.45.
  4. Conditions related to the respiratory system lead to respiratory acidosis or alkalosis.
  5. There are metabolic conditions related to the kidneys, and abnormal intake/output leads to metabolic acidosis/alkalosis.

What is the importance of blood pH?

  1. It is normally maintained at 7.38 to 7.42. Any deviation from this range indicates a change in the concentration of H+ ions.
  2. 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 leads to a fall in the blood pH, which is called acidemia.
    3. So, a decrease in the H+ ions will lead to an increase in the blood’s pH, which is called alkalemia.
    4. The conditions that cause the pH change are called acidosis and alkalosis.
  3. H+ ion 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, the pH of the arterial blood is <7.4.
  4. In alkalemia, the pH of the arterial blood is >7.4.
    1. Alkalosis is a systemic decrease in the H+ ions in the systemic blood.
  5. The following diagram explains how pH is maintained by the arterial carbon dioxide tension  (pCO2)  and plasma bicarbonate (HCO3–).
Acid-base balance and diet

Acid-base balance and diet

  1. Plasma HCO3– decreases in the plasma caused by gastrointestinal or renal losses will increase H+ ions and lower the pH.
Acid-base buffer system

Acid-base buffer system

Acid-base mechanism

Acid-base mechanism

What is the Anion gap?

How will you define the anion gap?

  1. Anion gap refers to anions usually not measured in the laboratory, like sulfate, phosphate, and lactate.
  2. The anions usually measured are Chloride (Cl–) and bicarbonate (HCO3–).
  3. The sum of the anions is subtracted from the sum of cations (Na+ ); there is a gap of around 10 to 12 meq/L called an anion gap. An elevated anion gap gives clues for acidosis.
  4. The anion gap is measured in meq/L.
  5. This is the difference between the plasma concentration of the major cation sodium (Na+) and that of the other anions, HCO3—and Cl–.
    1. Anion gap = [Na+] – ([HCO3–] + [Cl–])
  6. The normal anion gap is 3 to 13 meq/L, and the mean is 10 meq/L.
  7. This is dependent mainly on the plasma protein, primarily albumin.
  8. 2.5 meq/L falls for every 1 gram/dl of albumin concentration in the blood.
  9. The anion gap is important in identifying the etiology of metabolic acidosis.

What causes 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.

What causes a decreased anion gap (<6 meq/L)?

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

What causes the normal anion gap (6 to 12 meq/L)?

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

Metabolic acidosis

How will you define metabolic acidosis?

  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.
Metabolic acidosis

Metabolic acidosis

What are the 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. 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, associated with a rise in the concentration of the inorganic anions, mostly CL¯ or a fall in Na+ concentration.

What are the 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.

How is there 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.
Acid-base metabolic acidosis compensatory

Acid-base metabolic acidosis compensatory

What are the signs and symptoms of metabolic acidosis?

  1. Kussmaul respiration suggests metabolic acidosis.
  2. The early symptoms are 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, which characterizes these ventilatory changes resulting from the low pH stimulating the brain stem respiratory center.
  7. 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.
  8. Ketoacidosis is associated with increased thirst and polyuria.
  9. There is secondary hypotension in severe acidotic patients.
  10. Severe acidosis produces life-threatening dysrhythmias, like ventricular fibrillation.
  11. Ultimately, the patient will go into a coma.

How will you diagnose metabolic acidosis?

  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.

How will you treat metabolic acidosis?

  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 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

How will you define metabolic alkalosis?

  1. There is excessive loss of metabolic acids.
  2. An increase in the plasma HCO3‾.
  3. An arterial pH >7.4 leads to metabolic alkalosis.

What are the causes of metabolic alkalosis?

  1. This common condition is often induced by diuretic therapy or loss of gastric secretions (in vomiting or nasogastric suction).
  2. This condition is caused by:
    1. There must be an initial increase in the HCO3— level caused by the loss of H+ ions in the gastrointestinal secretions or the urine.
    2. H+ ions move into the cell.
    3. Akali administration.
      1. Volume contraction around a relatively constant amount of extracellular HCO3-.
  3. 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.
  4. This occurs in the acid loss by vomiting or nasogastric suction.
    1. Pyloric or upper duodenal obstruction.
    2. 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 more Na+, K+, and CL¯ excretion than HCO3¯.
  16. Milk-alkali syndrome.
  17. Massive blood transfusion.
  18. High doses of carbenicillin or penicillin.

What are the changes in metabolic alkalosis?

Biochemical parameters Value
  • pH
  • Increased
  • pCO2
  • Normal
  • HCO3-
  • Increased

How will you summarize metabolic alkalosis?

  1. Before alkalosis, the HCO3: H2CO3 ratio was 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.

What is the 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 CO2 to be retained, which will increase H2CO3 and CO2.
  2. The kidney will conserve H+ ions and excrete more HCO3¯ in the urine, which will be alkaline.
Acid-base metabolic alkalosis compensatory mechanism

Acid-base metabolic alkalosis compensatory mechanism

What are the 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 about 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, the patient will have atrial tachycardia.

How will you diagnose 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 differentiates 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 may be 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.

How will you summarize 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

How will you treat 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.

How will you summarize the characteristic features of acidosis and alkalosis?

Clinical condition Etiology of the condition pH (7.37 to 7.43) HCO3– (19 to 25 meq/L) pCO2 (38 to 42 mmHg)
  • Acute respiratory acidosis
  1. Muscle weakness (paralysis)
  2. Guillain-Barre syndrome
  3. Botulism
  4. Severe hypokalemia
  • <7.35
  • >27 meq/L
  • 50 to 100 mm Hg
  • Chronic respiratory acidosis
  1. Muscle weakness like poliomyelitis
  2. Amyotrophic lateral sclerosis
  3. Myxedema
  • <7.35
  • >35
  • 50 to 100
  • Respiratory alkalosis
  1. Pneumonia
  2. Emboli
  3. Interstitial fibrosis
  4. Congestive heart failure
  5. Hyperventilation syndrome
  6. Hepatic encephalopathy
  7. Sepsis or fever
  • >7.45
  • 14  to 20
  • <30
  • Metabolic acidosis
  1. Renal failure
  2. Lactic acidosis
  3. Ketoacidosis
  4. Salicylates poisoning
  5. Methanol
  • <7.35
  • <15
  • May become zero
  • <30
  • Metabolic alkalosis
  1. Vomiting or nasogastric suction
  2. laxative abuse
  3. Hypokalemia
  4. Diuretics
  5. Administration of alkali
  • >7.45
  • >27
  • 45 to 55

What are the Panic values?

Clinical parameter Panic value
  • pH
  • <7.25   or  >7.55
  • pO2
  • <50 mm Hg
  • pCO2
  • >60 mm Hg

What are the parameters needed for the acid-base balance?

Lab test Importance
  • pH
  • This will tell:
    1. Increased pH value indicates alkalosis
    2. A decreased value of pH indicates acidosis
  • pCO2
  • This is the partial pressure of CO2, and it will tell:
    1. The respiration modulates this pCO2
    2. This is the index of ventilation
  • pO2
  • This is the partial pressure of the O2 in the arterial blood and tells:
    1. Low values indicate hypoxia
    2. pO2 is the indirect measure of O2 contents of arterial blood.

How will you summarize metabolic and respiratory acidosis/alkalosis?

Clinical condition pH HCO3– pCO2
  • Acidosis
     
Acute metabolic acidosis Decreased Decreased Normal
Compensated metabolic acidosis Normal Decreased Decreased
Acute respiratory acidosiss Decreased Normal Increased
Acute compensated respiratory acidosis Normal Increased Increased
  • Alkalosis
Acute metabolic alkalosis Increased Increased Normal
Chronic metabolic alkalosis Increased Increased Increased
Acute respiratory alkalosis Increased Normal Decreased
Compensated respiratory alkalosis Normal Decreased Decreased
Acid-base summary

Acid-base summary

Questions and answers:

Question 1: What is the panic value in acid-base balance?
Show answer
The common panic values are: 1. pH <7.25 or >7.55 2. pCO2 >60 mm Hg and pO2 <50 mm Hg
Question 2: What are decreased anion gap causes.
Show answer
It is hypoalbuminemia, Bromide intoxication, and plasma cell disorders.
Possible References Used
Go Back to Chemical pathology

Comments

Jouweda Reply
October 12, 2020

Thank you

Dr. Riaz Reply
October 12, 2020

Thanks.

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