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 Table of Contents  
Year : 2020  |  Volume : 7  |  Issue : 4  |  Page : 214-218

Metabolic acidosis

1 Department of Paediatrics, Pt. B. D. Sharma, PGIMS, Rohtak, Haryana, India
2 Department of Medicine, Pt. B. D. Sharma, PGIMS, Rohtak, Haryana, India

Date of Submission08-Jun-2020
Date of Acceptance23-Jun-2020
Date of Web Publication13-Jul-2020

Correspondence Address:
Dr. Kundan Mittal
Department of Pediatrics, Pt. B. D. Sharma, PGIMS, Rohtak, Haryana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JPCC.JPCC_97_20

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Acid–base disturbances are common occurrence in acute care setting, their rapid assessment and analysis are important, and pH of 6.8–7.8 is compatible with life. The definition of acid and base is different for biochemist, physiologist, cook, and others. Acid–base analysis gives us information about oxygenation, ventilation, acid–base status, electrolytes, lactate level, and clue to etiology and probable diagnosis.

Keywords: Acid–base, bicarbonate, metabolic acidosis

How to cite this article:
Mittal K, Aggarwal H K. Metabolic acidosis. J Pediatr Crit Care 2020;7:214-8

How to cite this URL:
Mittal K, Aggarwal H K. Metabolic acidosis. J Pediatr Crit Care [serial online] 2020 [cited 2020 Aug 13];7:214-8. Available from: http://www.jpcc.org.in/text.asp?2020/7/4/214/289535

  Introduction Top

Acid–base physiology deals with the maintenance of hydrogen ion concentration (38–42 nmol/L), which is regulated by body buffers, liver, and kidney. For body cells to function normally, hydrogen ion concentration is maintained about 40 nmol/L (pH is negative logarithm of hydrogen ion). Two types of metabolic disturbances (metabolic acidosis and alkalosis) are seen which may occur in isolation or mixed or combined with one of the respiratory components of disorder. Acid–base disorders can be classified using three approaches (physiological, base excess [BE], and physiochemical)[1],[2],[3],[4],[5],[6],[7],[8] [Table 1].
Table 1: Classification of acid–base disorders using three approaches

Click here to view

  Metabolic Acidosis Top

Metabolic acidosis (MA) may develop due to:

  • Loss of bicarbonate (kidney or gastrointestinal tract [GIT])
  • Dilution or addition of exogenous/endogenous acids
  • Retention of H+ ion due to impaired renal function
  • Diminished NH4+ production.

Pathophysiology of MA differs according to the concept or approach used for its interpretation, i.e., in Henderson–Hasselbalch equation, decrease in pH is caused by the excess of plasma protons issued by organic acids or mineral acids or loss in plasma bicarbonate or alteration in BE, and Stewart concept, it involves multiple parameters and not only bicarbonate.

Clinical effects of metabolic acidosis

Clinical features primarily depend on underlying basic pathology and rapidity of the appearance of MA. Symptoms and signs may be acute or chronic depending on the duration. Intracellular buffer is better in restoring pH than extracellular buffer. MA is an ominous sign and needs immediate attention to define etiology and management.

  • Neurological features are headache, confusion, seizure, increased cerebral blood flow, decreased cerebral metabolism, increased sympathetic activity, altered mentation, and coma
  • Patient may have decreased intestinal mobility, nausea, vomiting, and diarrhea
  • Hyperkalemia, hypercalcemia
  • Hyperventilation, asynchronization if patient on ventilator, increased tidal volume, dyspnea, pulmonary vasoconstriction, and decreased diaphragm contractility
  • Increased heart rate (pH <7.2), decreased cardiac contractility (pH <7.1), poor response to catecholamines
  • Decreased hepatic blood flow
  • Acidosis can lead to hyperkalemia, and hyperkalemia may lead to acidosis
  • Reduced glomerular filtration rate (GFR), increased clotting time
  • Hyperchloremia decreases blood pressure and GFR
  • Prolonged MA may lead to insulin resistance, modified calcium metabolism, increased protein metabolism, and abnormal secretion of cortisol, aldosterone, thyroid and growth hormones, and osteodystrophy
  • Increased C-reactive protein and higher leukocyte count
  • Metabolic acidosis leads to shift of oxygen-haemoglobin dissociation curve to right, however decrease in 2,3-bisphosphoglycerate (2,3-DPG) in RBC's shifts the P50 to left may negate the effect of pH
  • Bone pain
  • In chronic case, there are increased bone reabsorption and demineralization, decreased sensitivity of parathyroid hormone to ionized calcium, short stature (impaired skeletal growth), nephrolithiasis, nephrocalcinosis, renal hypertrophy
  • Intracellular acidosis affects physiological functions of cardiac myocytes and energy usage. MA and hypoxia act synergistically to impair cardiac functions.

Suspecting mixed disorders

  • No compensation or over compensation to primary disorder
  • pH and bicarbonate are normal, but AG is high (MA and metabolic alkalosis)
  • pH is normal, but bicarbonate is high (metabolic alkalosis with respiratory acidosis)
  • pH is normal, but bicarbonate is low (MA with respiratory alkalosis)
  • pH is low, but bicarbonate is normal (MA with respiratory acidosis)
  • pH is high, but bicarbonate is normal (respiratory alkalosis with metabolic alkalosis)
  • Normally, the relationship between sodium and chloride is 1.4:1, and in case of dehydration or overhydration, it will change proportionately. If the chloride does not change, it reflects acid–base abnormality. Disproportionate decrease in chloride indicates metabolic alkalosis or respiratory acidosis. Increase in chloride indicates respiratory alkalosis or hyperchloremic acidosis. Disproportionate decrease in both (more in chloride) in overhydration reflects metabolic alkalosis. Disproportionate increase in both (more in sodium) in dehydration also reflects metabolic alkalosis [Table 2].

Calculation of base deficit/excess

Standard BE (SBE) due to free water (SBEFW) = 0.3 × (Na − 140)
Table 2: Metabolic component assessment

Click here to view

SBE due to free chloride (SBECl) = 104 − (Cl × 140/Na)

SBE due to free albumin (SBEalb) = (0.148 × pH − 0.818) × (40 − serum albumin g/L)

SBE due to free unmeasured anions = SBE − SBEFW − SBECl − SBEalb

High value suggests anion gap (AG) acidosis

BE = ([HCO3] − 24.4+ [2.3 × Hb + 7.7] × [pH − 7.4] × 1 − 0.023 × Hb)

SBE = 0.9287 × [(HCO3) − 24 + 14.83 × (pH − 7.4)] OR

SBE (mmol/L) = (HCO3) − 24.8 + 16.2 × (pH − 7.4).

BE can be corrected by chronic respiratory changes: 0.4 mmol/L for every 1 mmHg change on PCO2.

Relationship of pH, PCO2, and BE: PCO212 mmHg, pH 0.1, and BE 6 mEq/L.

Relationship between actual and standard bicarbonate

  • Actual bicarbonate (ABC) > standard bicarbonate (SBC): respiratory alkalosis
  • ABC = SBC: respiratory balance
  • ABC is affected in both respiratory and metabolic disorders but SBC is unaffected in respiratory disorders
  • ABC and SBC are altered in same direction in metabolic disorders while in respiratory disorders in opposite direction
  • MA:
  • Metabolic alkalosis: >SBC
  • Calculated bicarbonate is 1–2 mEq less than measured value.

Anion gap

  1. AG represents the metabolic component in acid–base assessment. Number of cations must be equal to number of anions to maintain electroneutrality in the plasma. Normal serum sodium is excess of bicarbonate and chloride level and difference is known as AG. AG exists because not all electrolytes are routinely measured. Since potassium changes are minimal and hence not included in the AG calculation. AG is used to define high, normal, or low MA. There are two types of AG; plasma and urine AG (helpful in patients with hyperchloremic acidosis). Each gram per liter fall of albumin decreases AG by 2.5 [Table 3]
  2. Difference between patient AG and normal AG is known as delta AG
  3. AG can be further classified as:

    • Normal AG acidosis
    • High AG acidosis
    • High AG without acidosis
    • Low AG MA
    • In hyperglycemia, measured sodium is used to calculate AG.

  4. If measured chloride and bicarbonate are affected (chloride is added and bicarbonate is lost), this may result in normal AG MA. In high AG MA, unmeasured anions are added and bicarbonate is reduced
  5. AG also helps in detecting mixed disorder and used in association with osmol gap to detect exogenous poisoning
  6. Normally, △AG/△HCO3 (AG-10/24-HCO3) helps to detect mixed acid–base disorder and classify MA. The ratio of △ AG/△HCO3 is 1–1.6. Always take clinical details before reaching to conclusion, e.g., child weighing 50 kg with diabetic ketoacidosis (DKA), before episode has total body water (TBW) 10 L and bicarbonate 22 mEq/L(220 mEq) and after an attack of DKA TBW is 6 L and bicarbonate 12 mEq/L (72 mEq). Due to addition of ketoacid, AG will increase, but the concentration of bicarbonate decreases. This may not be same; hence, false reading (metabolic alkalosis) will be there
  7. One mmol of unmeasured acid titrates 1 mmol of bicarbonate
  8. Rise in AG may be due to fall in unmeasured cation or rise in unmeasured anions and vice versa
  9. High AG MA: Various causes of high AG MA are ketoacidosis, L and D lactic acidosis, uremic acidosis, acetaminophen, aspirin, menthol, ethylene and propylene glycol, acute kidney injury (AKI), small bowel resection, and paraldehyde.

  10. Mnemonics: Increased anion gap metabolic acidosis

    • KUSMALE: Ketoacidosis, Uremia, Salicylate, Methanol, Aldehyde, Lactate, Ethylene glycol
    • MUDPILES: Methanol, Uremia, Diabetes, Paraldehyde, Iron and Isoniazid, Lactate, Ethylene glycol, Salicylate
    • GOLDMARK: Glycol, Oxoproline, Lactate, Methanol, Aspirin, Renal failure, Ketoacidosis.

  11. Normal AG MA results either due to loss of bicarbonate from GIT or kidney, inadequate excretion of acids by kidney, or ingestion of toxins. To assess the etiology of normal AG MA, it is essential to measure the serum potassium, urinary pH, and urinary AG. Various causes of normal AG MA are diarrhea, chronic kidney disease (CKD) stage 4–5, proximal Renal Tubular Acidosis (RTA) type II, distal RTA type I, II, IV, dilutional acidosis, dilutional acidosis, recovery phase of ketoacidosis, ureterosigmoidostomy, ammonium chloride ingestion, hypoaldosteronism
  12. Low AG: Hypoalbuminemia (1 g decrease in albumin decreases AG 2.5, decreased number of anions), hypertriglyceridemia (different laboratory analysis), IgG myeloma (decreased cations), hypotonic hyponatremia, overestimation of chloride, bromide intoxication (bromide measured as chloride), lithium toxicity (increased cations), salicylates overdose (measured as chloride), hypercalcemia, hypermagnesemia (increased cations), increased nonsodium cation. Increase in unmeasured cation or decrease in unmeasured anion also decreases the AG
  13. Bicarbonate and chloride move in opposite direction
  14. Osmol gap: Measured osmolality – Calculated osmolality

  15. Plasma osmolality = 2 × sodium + glucose/18 + blood urea nitrogen (BUN)/1.8 OR

    [1.86 × sodium) + Glucose/18 + BUN/2.8 + 9

    Difference of more than 10 is abnormal.

  16. Urine AG (normal + 30 to + 50 mmol/L): Urinary sodium + urinary potassium − urinary chloride.

Corrected anion gap

Normal AG also depends on phosphate and albumin level.
Table 3: Anion Gap

Click here to view

  • AG = 0.2 × albumin (g/L) + 1.5 (phosphate)
  • Albumin gap = 40 − albumin level/4
  • AG + albumin gap = actual AG
  • ([4.4 – (observed serum albumin (g/dL]) × 0.25] + AG) – (serum lactate [mmol/L]).
  • ([Na] + [K] − [Cl] − [HCO3]) − (2 × albumin g/dL + 0.5 × phosphate mg/dL) – (lactate [mmol/L])
  • AG may be spuriously normal in lactic acidosis and low in hypoalbuminemia.

Based on the Stewart concept, metabolic acidosis can be classified as:

  • Increase in strong anions, e.g., lactate, ketone bodies
  • Decrease in difference between major strong nonorganic extracellular cations and anions
  • Presence of exogenous strong anions.

Classification of metabolic acidosis using strong ion gap and urinary strong ion difference

High strong ion gap metabolic acidosis

  • DKA, fast ketoacidosis, hyperlactatemia
  • Salicylate, methanol, ethylene glycol, and paraldehyde toxicity
  • Intermediate substrates of Krebs cycle.

Normal strong ion difference with urinary strong ion difference > 0

  • Renal pathology.

Normal strong ion difference with urinary strong ion difference < 0

  • Extrarenal pathology.

Urinary strong ion difference (SID) = (urinary sodium + potassium) − urinary chloride.

Calculation of base excess using Stewart approach

  • Na-Cl BE effect (mEq/L) = measured Na – measured Cl − 35
  • Lactate BE effect (mEq/L) = 1 – measured lactate
  • Albumin BE effect (mEq/L) = 0.25 × (40 – measured albumin g/L)
  • BE = Na-Cl effect + lactate effect + albumin effect + OI (other ions)
  • OI = BE – (Na-Cl – 35) + (1 – lactate) − (0.25 × [25 – measured albumin]).


Primary treatment is identifying the primary pathology and correcting the underlying cause. However, in some conditions, one may require bicarbonate therapy.

  • Maintain airway, breathing, and circulation
  • Identify underlying disorder
  • No data to support use of bicarbonate, but it is life-saving in certain conditions
  • If pH is < 7.0 or HCO3<5 and adequate ventilation, give intravenous sodium bicarbonate (weight in kg × base deficit × 0.3)
  • AKI: If bicarbonate level is <10 mEq/L, give sodium bicarbonate or renal replacement therapy (RRT)
  • CKD: Sodium bicarbonate and protein restriction
  • Lactic acidosis: Type I results due to tissue hypoxia and Type II results from biochemical abnormalities due to toxins or systemic diseases. ΔAG/ΔHCO3 of 1.6 is suggestive of lactic acidosis. Other laboratory abnormalities are hyperphosphatemia, leukocytosis, normokalemia, and hyperuricemia. Correct underlying etiology, fluid resuscitation, antibiotics, sodium bicarbonate (role questionable). Calculate bicarbonate requirement as ΔHCO3 × weight × 0.5, and administer 0.1 mEq/kg/min. Give calcium to prevent fall due to alkali administration and to improve cardiac function
  • DKA: Correct fluid and electrolytes abnormality and insulin therapy
  • Starvation ketoacidosis: Food intake
  • Salicylate toxicity: Supportive management, oral activated charcoal 1 g/kg, urinary alkalinization, and hemodialysis.
  • No role of buffer solution in the treatment of strong ion gap (SIG) acidosis
  • No role of buffer solution in the treatment of low SID and non-SIG acidosis
  • Some role of RRT in child with severe metabolic acidosis.

Example: A 12-year-old child, with sepsis with multiple organ dysfunction in shock, received normal saline as bolus and vasoactive infusions, tachycardic, on oxygen therapy with nasal cannula, having decreased urine output. Laboratory values are as follows:

  • Measured values

  • Na+ = 131 mEq/L

    Cl = 112 mEq/L

    K+ = 3.0 mEq/L

    pH = 7.10

    PCO2= 30 mmHg

    HCO3 = 9.0 mEq/L

    PaO2= 62 mmHg

    BE = −15 mEq/L

    Albumin = 10 g/L

    Phosphate = 2.0 mg/dL

  • Calculated values (mEq/L): See formula for calculation above

  • AG (AG; uncorrected) = 10

    AG (corrected) = 17.5

    ⧍AG = 17.5–10 = 7.5

    ⧍HCO3 = 24–9.0 = 15

    SIDa = 22 (normal 40)

    SIDe = 14 (normal 40).

  • Assessment of validity of pH using Henderson-Hasselbalch equation is correct
  • Acidosis or alkalosis: Acidosis
  • Primary disorder: pH, bicarbonate, and PCO2 moving in the same direction and decreasing indicates MA
  • Calculation of AG = 131 − (112 +9 ) = 10 Corrected AG = (10+7.5)= 17.5 as in the present case, albumin is decreased by 30 g/L from baseline, indicating high AG MA. Lactate (hypoperfusion and hypotension) and ketone bodies (starvation) may be contributing to high AG MA
  • Compensation of PCO2: PCO2= HCO3× 1.5 + 8 ± 2 or for each mEq/L decrease in HCO3.

  • PCO2 decreases by 1.2 mmHg.

    In the present case, expected fall was 18 and it is 10 indicating respiratory acidosis.

  • △AG/△HCO3: 10/15 = 0.6 (Due to saline infusion)
  • Hyperchloremic MA due to saline infusion
  • Difference in expected and measure bicarbonate difference is due to increased chloride concentration
  • Low SID due to hyperchloremia
  • High SIG due to lactate accumulation
  • Respiratory acidosis
  • Hypolabuminemic alkalosis (hypoalbuminemia contributes to metabolic alkalosis).

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Conflicts of interest

There are no conflicts of interest.

  References Top

Ingelfinger JR. Diagnostic use of base excess in acid-base disorders. N Engl J Med 2018;378:1419-28.  Back to cited text no. 1
Reddi AS. Acid-Base Disorders: Clinical Evaluation and Management. Newark: Springer; 2020.  Back to cited text no. 2
Agro FE. Body Fluid Management: From Physiology to Therapy. Rome: Springer; 2013.  Back to cited text no. 3
Marik PE. Evidence Based Critical Care. 3rd ed. USA: Springer; 2015.  Back to cited text no. 4
Hasan A. Handbook of Blood Gas/Acid-Base interpretation. 2nd ed. Hyderabad: Springer; 2013.  Back to cited text no. 5
Ronco C, Kellum JA, Bellomo R, Ricci Z. Critical Care Nephrology. 3rd ed. Philadelphia: Elsevier; 2019.  Back to cited text no. 6
Wesson DE. Metabolic Acidosis: A Guide to Clinical Assessment and Management. New York: Springer; 2016.  Back to cited text no. 7
Rayner HC, Thomas ME, Milford DV. Understanding Kidney Diseases. 2nd ed. Switzerland: Springer; 2020.  Back to cited text no. 8


  [Table 1], [Table 2], [Table 3]


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