Metabolic acidosis causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Causes

Low Anion Gap

A low anion gap is relatively rare but may occur from the presence of abnormal positively charged proteins, as in multiple myeloma, or in the setting of a low albumin level. The mnemonic for low anion gap is BAM

• B - Bromism
• A - (Low) Albumin (hypoalbuminism)
• M - Multiple myeloma

Normal Anion Gap (hyperchloremic acidosis)

Usually the HCO₃^- lost is replaced by a chloride anion, and thus there is a normal anion gap. In normal anion gap acidosis, the increased anion is chloride, which is measured, so the anion gap does not increase. Thus, normal anion gap acidosis is also known as hyperchloremic acidosis. Urine anion gap is useful in evaluating a patient with a normal anion gap (see above).

The mnemonic for the most common causes of a normal-anion gap metabolic acidosis is "DURHAM."

• D- Diarrhea

• U- Ureteral diversion

• R- Renal tubular acidosis

• H- Hyperailmentation

• A- Addison's disease, acetazolamide, ammonium chloride

• M- Miscellaneous (chloridorrhea, amphotericin B, toluene - toluene causes high anion gap metabolic acidosis followed by normal anion gap metabolic acidosis.

High Anion Gap

The bicarbonate lost is replaced by an unmeasured anion and thus you will see a high anion gap. Low serum albumin will decrease the apparent anion gap. To correct the anion gap for low serum albumin, we have to add 2.5 to the anion gap for every 1g/dl that serum albumin is decreased from the normal value of 4g/dl. The mnemonic "MUDPILES" is used to remember the causes of a high anion gap.

M - Methanol/Metformin
U - Uremia
D - Diabetic ketoacidosis
P - Paraldehyde/Propylene glycol
I - Infection/Ischemia/Isoniazid
L - Lactate
E - Ethylene glycol/Ethanol
S - Salicylates/Starvation

Some people, especially those not in the emergency room, find the mnemonic KIL-U easier to remember and also more useful clinically:

K - Ketones
I - Ingestion
L - Lactic acid
U - Uremia

All of the components of "mudpiles" are also covered with the "KIL-U" device, with the bonus that these are things that can kill you.

Ketones: more straightforward than remembering diabetic ketosis and starvation ketosis, etc.

Ingestion: methanol, metformin, paraldehyde, propylene glycol, isoniazid, ethylene glycol, ethanol, and salicylates are covered by ingestion. These can be thought of as a single group: "ingestions" during the initial consideration, especially when not triaging a patient in the emergency room.

Lactate: including that caused by infection and shock

Coexistent Elevated Anion Gap and Normal Anion Gap Metabolic Acidosis

• An elevated anion gap can coexist with a normal anion gap metabolic acidosis.
• In a single acid-base disorder of elevated anion gap metabolic acidosis, serum bicarbonate (HCO3) will decrease by the same amount that the anion gap increases.
• However, a situation in which the anion gap increases less and serum bicarbonate decreases significantly indicates that there is another metabolic acidosis present, which is decreasing the the serum bicarbonate, but not affecting the anion gap i.e. normal anion gap metabolic acidosis is also present.
• Thus, it is advised to compare the changes in the anion gap with the changes in the serum bicarbonate.
• This is often referred as the delta-delta equation, or the corrected bicarbonate equation.
• Delta-Delta equation: Change in anion gap = Change in bicarbonate

Causes by Organ System

Cardiovascular	Aortic arch interruption, Hypoplastic left heart syndrome, Shock, Fanconi-Albertini-Zellweger syndrome
Chemical / poisoning	1,2-Dibromoethane, 4-Aminopyridine, Aldicarb, Ammonium bifluoride, Ammonium chloride, Aristolochic acid , Borates, Bromophos, Carbaryl, Chloralose, Chlorfenvinphos, Chlorpyrifos, Cleistanthus Collinus, Coumaphos, Cyanides, Demeton-S-methyl, Diazinon, Dichlorvos, Dicrotophos, Dinitrophenol, Dioxathion, Disulfoton, Ethanol, Ethion, Ethylene glycol, Fensulfothion, Fenthion, Glycol Ether, Glyphosate, Imazapyr, Iron compounds, Malathion, Margosa oil, Metaldehyde, Methanol, Methidathion, Methiocarb, Methomyl, Monochloroacetate, Parathion, Phenol, Phosdrin, Polyethylene glycol , Profenofos, Propoxur, Propylene glycol, Pyrimidifen, Strychnine, Terbufos, Tetraethyl Pyrophosphate, Toluene, Toxic mushrooms , Triethylene Glycol, Tungsten, Salicylate poisoning, Clove
Dermatologic	No underlying causes
Drug Side Effect	Abacavir, Acetazolamide, Amitriptyline, Amlodipine, Amoxapine, Amphotericin B, Aspirin, Cholestyramine, Clomipramine, Clove, Cocaine, Desipramine, Didanosine, Doxepin, Emtricitabine, Felodipine , Imipramine, Isoniazid, Isradipine, Metformin, Neuroleptic malignant syndrome, Nifedipine, Nimodipine, Nitroprusside, Nortriptyline, Paracetamol, Phenformin, Protriptyline, Salicylate poisoning, Stavudine, Trimipramine, Malignant hyperpyrexia, Malignant hyperthermia, Reye's Syndrome
Ear Nose Throat	No underlying causes
Endocrine	Adrenal cortex insufficiency, Diabetes, Diabetic ketoacidosis, Glucocorticoid resistance, Hyperosmolar non-ketotic diabetic coma, Hypoaldosteronism, VIPoma, Lipoid congenital adrenal hyperplasia, Pseudohypoaldosteronism, 17- beta-hydroxysteroid dehydrogenase deficiency
Environmental	No underlying causes
Gastroenterologic	Acute liver failure, Bacterial overgrowth of small intestine, Biliary fistula, Congenital chloride diarrhea, Diarrhea, Duodenal atresia, GI HCO3- loss, Hepatic failure, Intestinal fistulas, Intestinal ischaemia, Lactose intolerance, Necrotizing enterocolitis, Pancreatic fistula, VIPoma, Boichis syndrome
Genetic	17- beta-hydroxysteroid dehydrogenase deficiency, 3-Hydroxyacyl-CoA dehydrogenase deficiency, 3-Hydroxyisobutyric aciduria, 3-Methylcrotonyl-CoA carboxylase deficiency, 3-methylglutaconic aciduria, Alsing syndrome, Biotinidase deficiency, Coenzyme Q10 deficiency, Cystinosis, Dihydrolipoamide dehydrogenase deficiency, Ethylmalonic encephalopathy, Fanconi-Albertini-Zellweger syndrome, Fructose-1, 6-diphosphatase deficiency, Fructose-1-phosphate aldolase deficiency, Galactosemia, Glucose transporter type 1 deficiency, Glutaric aciduria, Glutathione synthase deficiency, Glycerol kinase deficiency, Glycogenosis, GRACILE syndrome, Hawkinsinuria, Hepatocerebral form of mitochondrial DNA depletion syndrome, HMG-CoA lyase deficiency, Holocarboxylase synthase deficiency, Isovaleric acidaemia, Lipoid congenital adrenal hyperplasia, Long chain hydroxyacyl-CoA dehydrogenase deficiency, Lowe Syndrome, Lutz-Richner-Landolt syndrome, Malignant hyperpyrexia, Malignant hyperthermia, Malonyl-CoA decarboxylase deficiency, Maple syrup urine disease, Medium chain acyl-CoA dehydrogenase deficiency, Medullary cystic kidney disease, MELAS, MERRF, Methylmalonic acidemia, Microcephaly, Amish type, Mitochondrial acetoacetyl-CoA thiolase deficiency, Mitochondrial aspartyl-tRNA synthetase deficiency, Molybdenum cofactor deficiency, Myopathy with deficiency of succinate dehydrogenase and aconitase, Nephronophthisis, Phosphoglucomutase deficiency, Propionic Acidemia, Propionyl-CoA carboxylase deficiency, Pseudohypoaldosteronism, Pyruvate carboxylase deficiency, Pyruvate dehydrogenase deficiency, Senior-Loken Syndrome, Short chain acyl-CoA dehydrogenase deficiency, Succinyl-CoA acetoacetate transferase deficiency, Succinyl-CoA synthetase deficiency, Vitamin B12-responsive methylmalonic acidemia, Congenital chloride diarrhea, Osteopetrosis with renal tubular acidosis
Hematologic	Myeloma
Iatrogenic	Hyperailmentation, Reye's Syndrome, Short bowel syndrome, Ureterosigmoidostomy, Uretral diversion, Malignant hyperpyrexia, Malignant hyperthermia
Infectious Disease	No underlying causes
Musculoskeletal / Ortho	Osteopetrosis with renal tubular acidosis, Myopathy with deficiency of succinate dehydrogenase and aconitase
Neurologic	Leigh syndrome, Lowe Syndrome, Microcephaly, Amish type
Nutritional / Metabolic	Bicarbonate deficit, Hyperkalaemia, Hypoalbuminism, Ketoacidosis, Lactic acidosis, Organic acidemia, Diabetic ketoacidosis, Hyperosmolar non-ketotic diabetic coma, 3-Hydroxyacyl-CoA dehydrogenase deficiency, 3-Hydroxyisobutyric aciduria, 3-Methylcrotonyl-CoA carboxylase deficiency, 3-methylglutaconic aciduria, Biotinidase deficiency, Coenzyme Q10 deficiency, Cystinosis, Dihydrolipoamide dehydrogenase deficiency, Ethylmalonic encephalopathy, Fructose-1, 6-diphosphatase deficiency, Fructose-1-phosphate aldolase deficiency, Galactosemia, Glutaric aciduria, Glutathione synthase deficiency, Glycerol kinase deficiency, Glycogenosis, Hawkinsinuria, HMG-CoA lyase deficiency, Holocarboxylase synthase deficiency, Isovaleric acidaemia, Long chain hydroxyacyl-CoA dehydrogenase deficiency, Malonyl-CoA decarboxylase deficiency, Maple syrup urine disease, Medium chain acyl-CoA dehydrogenase deficiency, Methylmalonic acidemia, Mitochondrial acetoacetyl-CoA thiolase deficiency, Molybdenum cofactor deficiency, [, Myopathy with deficiency of succinate dehydrogenase and aconitase]],Phosphoglucomutase deficiency, Propionic Acidemia, Propionyl-CoA carboxylase deficiency, Pyruvate carboxylase deficiency, Pyruvate dehydrogenase deficiency, Short chain acyl-CoA dehydrogenase deficiency, Succinyl-CoA acetoacetate transferase deficiency, Succinyl-CoA synthetase deficiency, Vitamin B12-responsive methylmalonic acidemia, Leigh syndrome, Fanconi-Albertini-Zellweger syndrome, 17- beta-hydroxysteroid dehydrogenase deficiency
Obstetric/Gynecologic	No underlying causes
Oncologic	Myeloma
Opthalmologic	Lowe Syndrome, Senior-Loken Syndrome
Overdose / Toxicity	Abacavir, Acetazolamide, Amitriptyline, Amlodipine, Amoxapine, Amphotericin B, Aspirin, Cholestyramine, Clomipramine, Clove, Cocaine, Desipramine, Didanosine, Doxepin, Emtricitabine, Felodipine , Imipramine, Isoniazid, Isradipine, Metformin, Neuroleptic malignant syndrome, Nifedipine, Nimodipine, Nitroprusside, Nortriptyline, Paracetamol, Phenformin, Protriptyline, Salicylate poisoning, Stavudine, Trimipramine, Malignant hyperpyrexia, Malignant hyperthermia, Reye's Syndrome
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal / Electrolyte	Acute renal failure, Analgesic nephropathy syndrome, Boichis syndrome, Chronic interstitial nephritis, Chronic renal failure, Compensatory in primary respiratory alkalosis, Lightwood-Albright syndrome, Renal HCO3- loss, Renal tubular acidosis, Lowe Syndrome, Senior-Loken Syndrome, Hypoaldosteronism, Medullary cystic kidney disease, Nephronophthisis, Uretral diversion, Osteopetrosis with renal tubular acidosis
Rheum / Immune / Allergy	No underlying causes
Sexual	17- beta-hydroxysteroid dehydrogenase deficiency
Trauma	No underlying causes
Urologic	Uretral diversion
Dental	No underlying causes
Miscellaneous	Cuffed blood sample, Near-drowning, Starvation

Causes in Alphabetical Order

1,2-Dibromoethane 17- beta-hydroxysteroid dehydrogenase deficiency 3-Hydroxyacyl-CoA dehydrogenase deficiency 3-Hydroxyisobutyric aciduria 3-Methylcrotonyl-CoA carboxylase deficiency 3-methylglutaconic aciduria 4-Aminopyridine Abacavir Acetazolamide Acute liver failure Acute renal failure Adrenal cortex insufficiency Aldicarb Alsing syndrome Amitriptyline Amlodipine Ammonium bifluoride Ammonium chloride Amoxapine Amphotericin B Analgesic nephropathy syndrome Aortic arch interruption Aristolochic acid Aspirin Bacterial overgrowth of small intestine Bicarbonate deficit Biliary fistula Biotinidase deficiency Boichis syndrome Borates Bromophos Carbaryl Chloralose Chlorfenvinphos Chlorpyrifos Cholestyramine Chronic interstitial nephritis Chronic renal failure Cleistanthus Collinus Clomipramine Clove Cocaine Coenzyme Q10 deficiency Compensatory in primary respiratory alkalosis Congenital chloride diarrhea Coumaphos Cuffed blood sample Cyanides Cystinosis Demeton-S-methyl Desipramine Diabetes Diabetic ketoacidosis Diarrhea Diazinon Dichlorvos Dicrotophos Didanosine Dihydrolipoamide dehydrogenase deficiency Dinitrophenol Dioxathion Disulfoton Doxepin Duodenal atresia Emtricitabine Ethanol Ethion Ethylene glycol Ethylmalonic encephalopathy Fanconi-Albertini-Zellweger syndrome Felodipine Fensulfothion Fenthion Fructose-1, 6-diphosphatase deficiency Fructose-1-phosphate aldolase deficiency Galactosemia GI HCO3- loss Glucocorticoid resistance Glucose transporter type 1 deficiency Glutaric aciduria Glutathione synthase deficiency Glycerol kinase deficiency Glycogenosis Glycol Ether Glyphosate GRACILE syndrome Hawkinsinuria Hepatic failure Hepatocerebral form of mitochondrial DNA depletion syndrome HMG-CoA lyase deficiency Holocarboxylase synthase deficiency Hyperailmentation Hyperkalaemia Hyperosmolar non-ketotic diabetic coma Hypoalbuminism

Hypoaldosteronism Hypoplastic left heart syndrome Imazapyr Imipramine Intestinal fistulas Intestinal ischaemia Iron compounds Isoniazid Isovaleric acidaemia Isradipine Ketoacidosis Lactic acidosis Lactose intolerance Leigh syndrome Lightwood-Albright syndrome Lipoid congenital adrenal hyperplasia Long chain hydroxyacyl-CoA dehydrogenase deficiency Lowe Syndrome Lutz-Richner-Landolt syndrome Malathion Malignant hyperpyrexia Malignant hyperthermia Malonyl-CoA decarboxylase deficiency Maple syrup urine disease Margosa oil Medium chain acyl-CoA dehydrogenase deficiency Medullary cystic kidney disease MELAS MERRF Metaldehyde Metformin Methanol Methidathion Methiocarb Methomyl Methylmalonic acidemia Microcephaly, Amish type Mitochondrial acetoacetyl-CoA thiolase deficiency Mitochondrial aspartyl-tRNA synthetase deficiency Molybdenum cofactor deficiency Monochloroacetate Myeloma Myopathy with deficiency of succinate dehydrogenase and aconitase Near-drowning Necrotizing enterocolitis Nephronophthisis Neuroleptic malignant syndrome Nifedipine Nimodipine Nitroprusside Nortriptyline Organic acidemia Osteopetrosis with renal tubular acidosis Pancreatic fistula Paracetamol Parathion Phenformin Phenol Phosdrin Phosphoglucomutase deficiency Polyethylene glycol Profenofos Propionic Acidemia Propionyl-CoA carboxylase deficiency Propoxur Propylene glycol Protriptyline Pseudohypoaldosteronism Pyrimidifen Pyruvate carboxylase deficiency Pyruvate dehydrogenase deficiency Renal HCO3- loss Renal tubular acidosis Reye's Syndrome Salicylate poisoning Senior-Loken Syndrome Shock Short bowel syndrome Short chain acyl-CoA dehydrogenase deficiency Starvation Stavudine Strychnine Succinyl-CoA acetoacetate transferase deficiency Succinyl-CoA synthetase deficiency Terbufos Tetraethyl Pyrophosphate Toluene Toxic mushrooms Triethylene Glycol Trimipramine Tungsten Ureterosigmoidostomy Uretral diversion VIPoma Vitamin B12-responsive methylmalonic acidemia