Metabolic acidosis

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Metabolic acidosis
ICD-10	E87.2
ICD-9	276.2
DiseasesDB	92

Template:Search infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.D. [2]

Overview

In medicine, metabolic acidosis is a state in which the blood pH is low (less than 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 diarrhea, coma and death. Together with respiratory acidosis, it is one of the two general types of acidosis, the other being respiratory acidosis.

Pathophysiology

Compensatory mechanisms

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

Respiratory compensation of metabolic acidosis

• For 1 meq/L fall of serum HCO3 levels there is a 1.2 mmHg fall in arterial pCO2.
• The respiratory compensation of metabolic acidosis is fast and begins within half an hour of metabolic acidosis.
• In cases where the metabolic acidosis develops slowly, the respiratory compensation occurs simultaneously with the metabolic acidosis.
• The respiratory compensation usually completes within 12 to 24 hours
• A failure to develop adequate respiratory response indicates an acute underlying respiratory diseases, neurologic disease or a very acute development of metabolic acidosis.
• Formula for checking appropriate respiratory compensation to metabolic acidosis include:
  • Arterial pCO2 = 1.5 x serum HCO3 + 8 ± 2 (Winters’ equation)
  • Arterial pCO2 = Serum HCO3 + 15

Role of the urine anion gap in the patient with a normal anion gap metabolic acidosis

• Urine anion gap helps to differentiate renal tubular acidosis (specifically a Type 1 or Type 4 RTA) from other causes of normal anion gap acidosis.
• The urine anion gap is calculated as the urine sodium plus urine potassium, minus the urine chloride
• Urine anion gap = (Urine Na + Urine K) - Urine Cl
• The pathophysiology behind this is:
  • When kidney is exposed to acidosis, the normal response of the kidney is to excrete acid.
  • Kidney excretes the excess acid in the form of ammonium, NH4+.
  • To maintain neutrality, Cl- is excreted along with ammonium, NH4+.
  • Thus, urine chloride act as a surrogate marker for urine ammonium (acidosis)
  • In Types 1 and 4 renal tubular acidosis, the kidney's function of acid excretion is compromised (decreased excretion of NH4+ and Cl).
  • Thus, in renal tubular acidosis (specifically a Type 1 or Type 4 RTA) urine anion gap will be high (> than zero).
  • A urine anion gap less than zero in the normal anion gap metabolic acidosis suggests the kidney is excreting acid, making renal tubular acidosis less likely.

Role of osmolar gap in differential diagnosis of elevated anion gap

• Methanol, ethylene glycol, isopropyl alcohol, toluene are osmotically active substance
• Ingestion of these substances may lead to disturbances that have significant overlap. They can be differentiated because of these following characteristics:
  • Methanol
    • Also called wood alcohol
    • Used in antifreeze and solvents
    • Presentation: Delirium, papilledema, and retinal hemorrhages
    • Elevated anion gap metabolic acidosis
  • Ethylene glycol
    • Used in antifreeze and solvents
    • Presentation: Delirium
    • Elevated anion gap metabolic acidosis
    • Presence of oxalate crystals in urine
  • Isopropyl alcohol
    • Also called rubbing alcohol
    • No acid-base disorder
    • Metabolism causes increase acetone in the blood
    • Other conditions with elevated acetones in blood are: diabetes, starvation, and isopropyl alcohol.
  • Toluene
    • Initial elevated anion gap followed with normal anion gap
• Estimated serum osmolality = (2 * serum sodium + BUN/2.8 + Glucose/18)

Buffer

• 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

Causes

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

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

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

Diagnosis

Symptoms

Symptoms are non-specific, 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)
• Weight loss (longer term)
• Muscle weakness and bone pains
• Kussmaul respirations (deep rapid breathing, classically associated with diabetic ketoacidosis). Rapid deep breaths increase the amount of carbon dioxide exhaled, thus lowering the serum carbon dioxide levels, resulting in some degree of compensation. Over compensation to form a respiratory alkalosis does not occur.
• Lethargy, stupor, coma, seizures.
• 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

Eyes

• retinal edema can be a sign of methanol (methyl alcohol) intoxication

Neurologic

• Cranial nerve abnormalities can be observed in ethylene glycol poisoning

Extremities

• Longstanding chronic metabolic acidosis leads to osteoporosis and can cause fractures.

Laboratory Studies

The following laboratory studies should be considered:

• Arterial blood gas sampling
• Anion gap
• Serum lactate, ketone
• Toxicological screening, salicylate level (methanol or ethylene glycol)
• ECG (to assess for arrhythmias)
• Electrolytes basic metabolic panel), complete blood count.
• Urinalysis can reveal acidity, (salicylate poisoning) or alkalinity (renal tubular acidosis type I), and ketones in ketoacidosis.
• Imaging of the kidneys

Treatment

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.

References

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