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Metabolic acidosis
Classification & external resources

Davenport diagram
ICD-10	E87.2
ICD-9	276.2
DiseasesDB	92
MedlinePlus	000335
eMedicine	emerg/312  med/1458 ped/15

In medicine, metabolic acidosis is a state in which the blood pH is low (under 7.35) due to increased production of H⁺ by the body or the inability of the body to form bicarbonate (HCO₃^-) in the kidney. Its causes are diverse, and its consequences can be serious, including coma and death. Together with respiratory acidosis, it is one of the two general types of acidosis.

Contents 1 Signs and symptoms 2 Diagnosis 3 Causes 3.1 Increased anion gap 3.2 Normal anion gap 4 Pathophysiology 4.1 Compensatory mechanisms 4.2 Buffer 5 Treatment 6 References

Symptoms are aspecific, and diagnosis can be difficult unless the patient presents with clear indications for arterial blood gas sampling. Symptoms may include chest pain, palpitations, headache, altered mental status, decreased visual acuity, nausea, vomiting, abdominal pain, altered appetite (either loss of or increased) and weight loss (longer term), muscle weakness and bone pains. Those in metabolic acidosis may exhibit deep, rapid breathing called Kussmaul respirations which is classically associated with diabetic ketoacidosis. Rapid deep breaths increase the amount of carbon dioxide exhaled, thus lowering the serum carbon dioxide levels, resulting in a compensatory respiratory alkalosis.

Extreme acidosis leads to neurological and cardiac complications:

• Neurological: lethargy, stupor, coma, seizures.
• Cardiac: arrhythmias (ventricular tachycardia), decreased response to epinephrine; both lead to hypotension (low blood pressure).

Physical examination occasionally reveals signs of disease, but is otherwise normal. Cranial nerve abnormalities are reported in ethylene glycol poisoning, and retinal edema can be a sign of methanol (methyl alcohol) intoxication. Longstanding chronic metabolic acidosis leads to osteoporosis and can cause fractures.

Arterial blood gas sampling is essential for the diagnosis. The pH is low (under 7.35) and the bicarbonate levels are decreased (<12 mmol/l). In respiratory acidosis (low blood pH due to decreased clearance of carbon dioxide by the lungs), the bicarbonate is elevated, due to increased conversion from H₂CO₃. An ECG can be useful to anticipate cardiac complications.

Other tests that are relevant in this context are electrolytes (including chloride), glucose, renal function and a full blood count. Urinalysis can reveal acidity (salicylate poisoning) or alkalinity (renal tubular acidosis type I). In addition, it can show ketones in ketoacidosis.

To distinguish between the main types of metabolic acidosis, a clinical tool called the anion gap is considered very useful. It is calculated by subtracting the chloride and bicarbonate levels from the sodium plus potassium levels.

Anion gap = ( [Na⁺]+[K⁺] ) - ( [Cl^-]+[HCO₃^-] )

As sodium is the main extracellular cation, and chloride and bicarbonate are the main anions, the result should reflect the remaining anions. Normally, this concentration is about 8-16 mmol/l. An elevated anion gap (i.e. > 16 mmol/l) can indicate particular types of metabolic acidosis, particularly certain poisons, lactate acidosis and ketoacidosis.

As the differential diagnosis is narrowed down, certain other tests may be necessary, including toxicological screening and imaging of the kidneys.

The causes are best grouped by their influence on the anion gap:

Causes include:

• lactic acidosis
• ketoacidosis
• chronic renal failure (accumulation of sulfates, phosphates, uric acid)
• intoxication:
  • organic acids (salicylates, ethanol, methanol, formaldehyde, ethylene glycol, paraldehyde, INH, toluene)
  • sulfates, metformin (Glucophage®)
• massive rhabdomyolysis

The mnemomic MUDPILES is commonly used to remember the causes of Increased anion gap metabolic acidosis.^[1][2]

• M-Methanol
• U-Uremia
• D-Diabetic Ketoacidosis
• P-Paraldehyde
• I-Infection, Iron, Isoniazid
• L-Lactic acidosis
• E-Ethylene Glycol, Ethanol
• S-Salicylates

Causes include:^[3]

• longstanding diarrhea (bicarbonate loss)
• pancreatic fistula
• uretero-sigmoidostomy
• RTA
• intoxication:
  • ammonium chloride
  • acetazolamide (Diamox®)
  • bile acid sequestrants
• renal failure (occasionally)

It bears noting that the anion gap can be spuriously normal in sampling errors of the sodium level, e.g. in extreme hypertriglyceridemia. The anion gap can be increased due to relatively low levels of cations other than sodium and potassium (e.g. calcium or magnesium).

Metabolic acidosis is either due to increased generation of acid or an inability to generate sufficient bicarbonate. The body regulates the acidity of the blood by four buffering mechanisms.

• bicarbonate buffering system
• Intracellular buffering by absorption of hydrogen atoms by various molecules, including proteins, phosphates and carbonate in bone.
• Respiratory compensation
• Renal compensation

The decreased bicarbonate that distinguishes metabolic acidosis is therefore due to two separate processes: the buffer (from water and carbon dioxide) and additional renal generation. The buffer reactions are:

H⁺ + HCO₃^- <--> H₂CO₃ <--> CO₂ + H₂O

The Henderson-Hasselbalch equation mathematically describes the relationship between blood pH and the components of the bicarbonate buffering system:

pH=pKa + log [HCO₃^-]/[CO₂]

Using Henry's Law, we can say that [CO₂]=0.03xPaCO₂

(PaCO₂ is the pressure of CO₂ in arterial blood)

Adding the other normal values, we get

pH = 6.1 + log (24/0.03x40)

= 6.1 + 1.3

= 7.4

A pH under 7.1 is an emergency, due to the risk of cardiac arrhythmias, and may warrant treatment with intravenous bicarbonate. Bicarbonate is given at 50-100 mmol at a time under scrupulous monitoring of the arterial blood gas readings. This intervention however, is not effective in case of lactic acidosis.

If the acidosis is particularly severe and/or there may be intoxication, consultation with the nephrology team is considered useful, as dialysis may clear both the intoxication and the acidosis.

1. ^ Mnemonic at medicalmnemonics.com 1203 3255
2. ^ http://fitsweb.uchc.edu/student/selectives/TimurGraham/Anion_Gap.html
3. ^ Mnemonic at medicalmnemonics.com 2001

v • d • e Metabolic pathology (E70-90)
Amino acid	Phenylketonuria - Alkaptonuria - Ochronosis - Tyrosinemia - Maple syrup urine disease - Propionic acidemia - Methylmalonic acidemia - Isovaleric acidemia - Primary carnitine deficiency - Cystinuria - Cystinosis - Hartnup disease - Homocystinuria - Citrullinemia - Hyperammonemia - Glutaric acidemia type 1
Carbohydrate	Lactose intolerance - Glycogen storage disease (type I, type II, type III, type IV, type V, type VI), Fructose intolerance, Galactosemia
Lipid	Lipid storage disorders Sphingolipidoses: Gangliosidosis - GM2 gangliosidoses (Sandhoff disease, Tay-Sachs disease) - GM1 gangliosidoses - Mucolipidosis type IV - Gaucher's disease - Niemann-Pick disease - Farber disease - Fabry's disease - Metachromatic leukodystrophy - Krabbe disease Neuronal ceroid lipofuscinosis (Batten disease) - Cerebrotendineous xanthomatosis - Cholesteryl ester storage disease (Wolman disease) Hyperlipidemia - Hypercholesterolemia - Familial hypercholesterolemia - Xanthoma - Combined hyperlipidemia - Lecithin cholesterol acyltransferase deficiency - Tangier disease - Abetalipoproteinemia
Mineral	Cu Wilson's disease/Menkes disease - Fe Haemochromatosis - Zn Acrodermatitis enteropathica - PO43− Hypophosphatemia/Hypophosphatasia - Mg2+ Hypermagnesemia/Hypomagnesemia - Ca2+ Hypercalcaemia/Hypocalcaemia/Disorders of calcium metabolism
Fluid, electrolyte and acid-base balance	Electrolyte disturbance - Na+ Hypernatremia/Hyponatremia - Acidosis (Metabolic, Respiratory, Lactic) - Alkalosis (Metabolic, Respiratory) - Mixed disorder of acid-base balance - H2O Dehydration/Hypervolemia - K+ Hypokalemia/Hyperkalemia - Cl− Hyperchloremia/Hypochloremia
Porphyrin and bilirubin	Acatalasia - Gilbert's syndrome - Crigler-Najjar syndrome - Dubin-Johnson syndrome - Rotor syndrome - Porphyria (Acute intermittent porphyria, Gunther's disease, Porphyria cutanea tarda, Erythropoietic protoporphyria, Hepatoerythropoietic porphyria, Hereditary coproporphyria, Variegate porphyria)
Glycosaminoglycan	Mucopolysaccharidosis - Hurler syndrome - Hunter syndrome - Sanfilippo syndrome - Morquio syndrome
Glycoprotein	I-cell disease - Pseudo-Hurler polydystrophy - Aspartylglucosaminuria - Fucosidosis - Alpha-mannosidosis - Sialidosis
Other	Alpha 1-antitrypsin deficiency - Cystic fibrosis - Familial Mediterranean fever - Lesch-Nyhan syndrome