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In medicine
Medicine

Medicine is the art and science of healing. It encompasses a range of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
, metabolic acidosis is a process which if unchecked leads to acidemia, i.e. blood pH
PH

pH is a measure of the Acid or Base of a solution. It is defined as the cologarithm of the Activity of dissolved hydrogen ions . Hydrogen ion activity coefficients cannot be measured experimentally, so they are based on theoretical calculations....
 is low (less than 7.35) due to increased production of H+
Hydrogen

Hydrogen is the chemical element with atomic number 1. It is represented by the chemical symbol H. At standard temperature and pressure, hydrogen is a colorless, odorless, nonmetallic, tasteless, highly combustion and explosive Diatomic molecule gas with the molecular formula H2....
 by the body or the inability of the body to form bicarbonate
Bicarbonate

In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid. Its chemical formula is HCO3−....
 (HCO3-) in the kidney
Kidney

The kidneys are Organ that have numerous biological roles. Their primary role is to maintain the homeostasis balance of bodily fluids by filtering and secreting Metabolomics#Metabolitess and minerals from the blood and excreting them, along with water , as urine....
. Its causes are diverse, and its consequences can be serious, including coma
Coma

In medicine, a coma is a profound state of unconsciousness. A comatose person cannot be awakened, fails to respond normally to pain or light, does not have sleep-wake cycles, and does not take voluntary actions....
 and death
Death

Death is the permanent termination of the biological functions that define a life organism. It refers to both a particular event and to the condition that results thereby....
. Together with respiratory acidosis
Respiratory acidosis

Respiratory acidosis is acidosis due to decreased Ventilation of the lung alveoli, leading to elevated artery carbon dioxide concentration ....
, it is one of the two general causes of acidemia.

toms are aspecific, and diagnosis can be difficult unless the patient presents with clear indications for arterial blood gas
Arterial blood gas

An arterial blood gas is a blood test that is primarily performed using blood from an artery. It involves puncturing an artery with a thin needle and syringe and drawing a small volume of blood....
 sampling.






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In medicine
Medicine

Medicine is the art and science of healing. It encompasses a range of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
, metabolic acidosis is a process which if unchecked leads to acidemia, i.e. blood pH
PH

pH is a measure of the Acid or Base of a solution. It is defined as the cologarithm of the Activity of dissolved hydrogen ions . Hydrogen ion activity coefficients cannot be measured experimentally, so they are based on theoretical calculations....
 is low (less than 7.35) due to increased production of H+
Hydrogen

Hydrogen is the chemical element with atomic number 1. It is represented by the chemical symbol H. At standard temperature and pressure, hydrogen is a colorless, odorless, nonmetallic, tasteless, highly combustion and explosive Diatomic molecule gas with the molecular formula H2....
 by the body or the inability of the body to form bicarbonate
Bicarbonate

In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid. Its chemical formula is HCO3−....
 (HCO3-) in the kidney
Kidney

The kidneys are Organ that have numerous biological roles. Their primary role is to maintain the homeostasis balance of bodily fluids by filtering and secreting Metabolomics#Metabolitess and minerals from the blood and excreting them, along with water , as urine....
. Its causes are diverse, and its consequences can be serious, including coma
Coma

In medicine, a coma is a profound state of unconsciousness. A comatose person cannot be awakened, fails to respond normally to pain or light, does not have sleep-wake cycles, and does not take voluntary actions....
 and death
Death

Death is the permanent termination of the biological functions that define a life organism. It refers to both a particular event and to the condition that results thereby....
. Together with respiratory acidosis
Respiratory acidosis

Respiratory acidosis is acidosis due to decreased Ventilation of the lung alveoli, leading to elevated artery carbon dioxide concentration ....
, it is one of the two general causes of acidemia.

Signs and symptoms

Symptoms are aspecific, and diagnosis can be difficult unless the patient presents with clear indications for arterial blood gas
Arterial blood gas

An arterial blood gas is a blood test that is primarily performed using blood from an artery. It involves puncturing an artery with a thin needle and syringe and drawing a small volume of blood....
 sampling. Symptoms may include chest pain
Chest pain

In medicine, chest pain is a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the chest pain is non-cardiac in origin this is often a diagnosis of exclusion made after ruling out more serious causes of pain....
, palpitations, headache
Headache

In medicine a headache or wiktionary:cephalalgia is a symptom of a number of different conditions of the head and sometimes neck. Some of the causes are benign while others are medical emergencies....
, altered mental status, decreased visual acuity, nausea
Nausea

Nausea is the sensation of unease and discomfort in the stomach with an urge to vomit....
, vomiting
Vomiting

Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Undesired vomiting may result from many causes, ranging from gastritis or poisoning to brain tumors, or elevated intracranial pressure....
, abdominal pain
Abdominal pain

Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom....
, altered appetite (either loss of or increased) and weight loss
Weight loss

Weight loss, in the context of medicine or health or physical fitness, is a reduction of the total body weight, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue....
 (longer term), muscle weakness
Muscle weakness

Muscle weakness is a direct term for the inability to exert force with one's muscles to the degree that would be expected given the individual's general physical fitness....
 and bone pain
Bone pain

The term 'Bone pain' generally is used to refer to pain felt within a bone.The cause of the bone pain may not be immediately apparent, and further testing is usually warranted ....
s. Those in metabolic acidosis may exhibit deep, rapid breathing called Kussmaul respirations which is classically associated with diabetic ketoacidosis
Ketoacidosis

Ketoacidosis is a type of metabolic acidosis which is caused by high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids....
. 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 via respiratory alkalosis to form an alkalemia does not occur.

Extreme acidemia leads to neurological and cardiac complications:
  • Neurological: lethargy, stupor, coma
    Coma

    In medicine, a coma is a profound state of unconsciousness. A comatose person cannot be awakened, fails to respond normally to pain or light, does not have sleep-wake cycles, and does not take voluntary actions....
    , seizure
    Seizure

    An epileptic seizure is a transient symptom of abnormal, excessive or synchronous neuronal activity in the brain. It can manifest as an alteration in mental state, tonic or clonic movements, convulsions, and various other psychic symptoms ....
    s.
  • Cardiac: arrhythmias (ventricular tachycardia
    Ventricular tachycardia

    Ventricular tachycardia is a tachycardia, or fast heart rhythm that originates in one of the left ventricle of the heart. This is a potentially life-threatening Cardiac arrhythmia because it may lead to ventricular fibrillation and sudden cardiac death....
    ), decreased response to epinephrine
    Epinephrine

    Epinephrine is a hormone and neurotransmitter.Epinephrine increases the "fight or flight" response of the Sympathetic nervous system of the autonomic nervous system....
    ; both lead to hypotension
    Hypotension

    In physiology and medicine, hypotension refers to an abnormally low blood pressure. This is best understood as a physiologic state, rather than a disease....
     (low blood pressure).


Physical examination
Physical examination

File:Reeve 978.jpgPhysical examination or clinical examination is the process by which a health care provider investigates the body of a patient for sign of disease....
 occasionally reveals signs of disease, but is otherwise normal. Cranial nerve abnormalities are reported in ethylene glycol
Ethylene glycol

Ethylene glycol is an alcohol with two -OH groups , a chemical compound widely used as an automobile antifreeze. In its pure form, it is an odorless, colorless, syrupy, sweet tasting, toxic liquid....
 poisoning, and retina
Retina

The vertebrate retina is a light sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera....
l edema
Edema

File:Oedema.jpgEdema or Oedema , formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body....
 can be a sign of methanol
Methanol

Methanol, also known as methyl alcohol, carbinol, wood alcohol, wood naphtha or wood spirits, is a chemical compound with chemical formula carbonhydrogen3oxygenhydrogen ....
 (methyl alcohol) intoxication. Longstanding chronic metabolic acidosis leads to osteoporosis
Osteoporosis

Osteoporosis is a disease of bone that leads to an increased risk of bone fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is disrupted, and the amount and variety of collagen proteins in bone is altered....
 and can cause fracture
Fracture

A fracture is the separation of an object or material into two, or more, pieces under the action of stress .The word fracture is often applied to bones of living creatures, or to crystals or crystalline materials, such as gemstones or metal....
s.

Diagnosis

Arterial blood gas
Arterial blood gas

An arterial blood gas is a blood test that is primarily performed using blood from an artery. It involves puncturing an artery with a thin needle and syringe and drawing a small volume of blood....
 sampling is essential for the diagnosis. The pH is low (under 7.35) and the bicarbonate levels are decreased (<24 mmol/l). Due to respiratory compensation (hyperventilation), carbon dioxide is decreased and conversely oxygen is increased. An ECG can be useful to anticipate cardiac complications.

Other tests that are relevant in this context are electrolyte
Electrolyte

An electrolyte is any substance containing free ions that behaves as an electrical conductor medium. Because they generally consist of ions in solution, electrolytes are also known as ionic solutions, but molten electrolytes and solid electrolytes are also possible....
s (including chloride
Chloride

The chloride ion is formed when the chemical element chlorine picks up one electron to form an anion Cl−....
), glucose
Glucose

Glucose , a monosaccharide also known as grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology....
, renal function
Renal function

Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney....
 and a full blood count. Urinalysis
Urinalysis

File:Pyuria2.JPGA urinalysis is an array of tests performed on urine and one of the most common methods of medical diagnosis. A part of a urinalysis can be performed by using urine dipsticks, in which the test results can be read as color changes....
 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
Anion gap

The anion gap is used to aid in the differential diagnosis of metabolic acidosis.Although the term "anion gap" usually implies "serum anion gap", the Urine anion gap is also a clinically useful measure....
 is considered very useful. It is calculated by subtracting the chloride and bicarbonate levels from the sodium.

Anion gap = ( [Na+] ) - ( [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 (12±4). 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
Differential diagnosis

A differential diagnosis is a systematic method used to identify unknowns. This method, essentially a process of elimination, is used by taxonomy to identify living organisms, and by physicians and other qualified healthcare professionals to diagnosis the specific disease in a patient....
 is made, certain other tests may be necessary, including toxicological screening and imaging of the kidneys.

Causes

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

The anion gap is used to aid in the differential diagnosis of metabolic acidosis.Although the term "anion gap" usually implies "serum anion gap", the Urine anion gap is also a clinically useful measure....
:

Increased anion gap

Causes include:
  • lactic acidosis
    Lactic acidosis

    Lactic acidosis is a condition caused by the buildup of lactic acid in the body. It leads to acidification of the blood , and is considered a distinct form of metabolic acidosis....
  • ketoacidosis
    Ketoacidosis

    Ketoacidosis is a type of metabolic acidosis which is caused by high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids....
  • chronic renal failure
    Chronic renal failure

    Chronic kidney disease , also known as chronic renal disease, is a progressive loss of kidney over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling malaise and experiencing a anorexia....
     (accumulation of sulfate
    Sulfate

    In inorganic chemistry, a sulfate is a salt of sulfuric acid....
    s, phosphate
    Phosphate

    A phosphate, an inorganic chemical, is a Salt of phosphoric acid. Inorganic phosphates are mining to obtain phosphorus for use in agriculture and industry....
    s, uric acid
    Uric acid

    Uric acid is an organic compound of carbon, nitrogen, oxygen and hydrogen with the formula C5H4N4O3....
    )
  • intoxication:
    • organic acid
      Organic acid

      An organic acid is an organic compound with acidic properties. The most common organic acids are the carboxylic acids whose acidity is associated with their carboxyl group -COOH....
      s (salicylates, ethanol
      Ethanol

      Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatility , flammable, colorless liquid....
      , methanol
      Methanol

      Methanol, also known as methyl alcohol, carbinol, wood alcohol, wood naphtha or wood spirits, is a chemical compound with chemical formula carbonhydrogen3oxygenhydrogen ....
      , formaldehyde
      Formaldehyde

      Formaldehyde is a chemical compound with the chemical formula H2CO. It is the simplest aldehyde. Formaldehyde exists in several forms aside from H2CO: the cyclic trimer trioxane and the polymer Polyoxymethylene....
      , ethylene glycol
      Ethylene glycol

      Ethylene glycol is an alcohol with two -OH groups , a chemical compound widely used as an automobile antifreeze. In its pure form, it is an odorless, colorless, syrupy, sweet tasting, toxic liquid....
      , paraldehyde
      Paraldehyde

      Paraldehyde is the cyclic form of three acetaldehyde molecules . A colourless to pale yellow pungent liquid, it is sparingly soluble in water and highly soluble in alcohol....
      , INH, toluene
      Toluene

      Toluene, also known as methylbenzene or phenylmethane, is a clear, Water -insoluble liquid with the typical smell of paint thinners, redolent of the sweet smell of the related compound benzene....
      )
    • sulfates, metformin
      Metformin

      Metformin is an oral anti-diabetic drug from the biguanide class. It is the first-line treatment drug for the treatment of diabetes mellitus type 2, particularly in overweight and obesity people and those with normal kidney function, and evidence suggests it may be the best choice for people with heart failure....
       (Glucophage)
  • massive rhabdomyolysis
    Rhabdomyolysis

    Rhabdomyolysis is the rapid breakdown of skeletal muscle tissue due to injury to muscle tissue. The muscle damage may be caused by physical , chemical, or biological factors....


Normal anion gap

Causes include:
  • longstanding diarrhea
    Diarrhea

    In medicine, diarrhea, also spelled diarrhoea , is characterized by frequent loose or liquid bowel movements. The spelling of "diarrhea" is an appropriation of the Greek "diarrhoia" meaning "a flowing through." ....
     (bicarbonate loss)
  • pancreatic fistula
    Pancreatic fistula

    A pancreatic fistula is an abnormal communication between the pancreas and other organs due to leakage of pancreatic secretions from damaged pancreatic ducts....
  • uretero-sigmoidostomy
  • Renal tubular acidosis
    Renal tubular acidosis

    Renal tubular acidosis is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately wiktionary:acidify the urine....
     (RTA)
  • intoxication:
    • ammonium chloride
      Ammonium chloride

      Ammonium chloride is, in its pure form, a clear white water-soluble crystalline salt of ammonia. The aqueous ammonium chloride solution is mildly acidic....
    • acetazolamide
      Acetazolamide

      Acetazolamide, sold under the trade name Diamox, is a carbonic anhydrase inhibitor that is used to treat glaucoma, epileptic seizures, benign intracranial hypertension , altitude sickness, cystinuria, and dural ectasia....
       (Diamox)
    • bile acid sequestrant
      Bile acid sequestrant

      The bile acid sequestrants are a group of medications used for binding certain components of bile in the gut. They disrupt the enterohepatic circulation of bile acids by sequestering them and preventing their reabsorption from the gut....
      s
    • isopropyl alcohol
      Isopropyl alcohol

      Isopropyl alcohol is a common name for isopropanol, a colorless, flammable chemical compound with a strong odor. It has the molecular formula C3H7OH and is the simplest example of a Alcohol#Primary.2C secondary.2C and tertiary alcohols, where the alcohol carbon is attached to two other carbons....
  • renal failure
    Renal failure

    Renal failure or kidney failure is a situation in which the kidneys fail to function adequately. It is divided in acute and chronic forms; either form may be due to a large number of other medical problems....
     (occasionally)


It bears noting that the anion gap can be spuriously normal in sampling errors of the sodium level, e.g. in extreme hypertriglyceridemia
Hypertriglyceridemia

In medicine, hypertriglyceridemia denotes high blood levels of triglycerides, the most abundant fatty molecule in most organisms. It has been associated with atherosclerosis, even in the absence of hypercholesterolemia ....
. The anion gap can be increased due to relatively low levels of cations other than sodium and potassium (e.g. calcium or magnesium).

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
    Bicarbonate buffering system

    The Bicarbonate buffering system is the most important buffer solution for maintaining a relatively constant pH in the plasma.It functions via blood buffering with bicarbonate....
  • Intracellular
    Intracellular

    Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell "....
     buffering by absorption of hydrogen atoms by various molecules, including proteins, phosphates and carbonate in bone.
  • Respiratory compensation
    Respiratory compensation

    Respiratory compensation is a mechanism by which plasma pH can be altered by varying the respiratory rate. It is faster than renal compensation, but has less ability to restore normal values....
  • Renal compensation
    Renal compensation

    Renal compensation is a mechanism by which the kidneys can regulate the Blood plasma pH. It is slower than respiratory compensation, but has a greater ability to restore normal values....


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:

The Henderson-Hasselbalch equation
Henderson-Hasselbalch equation

In chemistry, the Henderson?Hasselbalch equation describes the derivation of pH as a measure of acidity in biological and chemical systems....
 mathematically describes the relationship between blood pH and the components of the bicarbonate buffering system:

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

Treatment

A pH under 7.1 is an emergency, due to the risk of cardiac arrhythmia
Cardiac arrhythmia

Cardiac arrhythmia is a term for any of a large and heterogeneous group of conditions in which there is abnormal Electrical conduction system of the heart in the heart....
s, 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
Lactic acidosis

Lactic acidosis is a condition caused by the buildup of lactic acid in the body. It leads to acidification of the blood , and is considered a distinct form of metabolic acidosis....
.

If the acidosis is particularly severe and/or there may be intoxication, consultation with the nephrology
Nephrology

Nephrology is a branch of internal medicine and pediatrics dealing with the study of the function and diseases of the kidney....
 team is considered useful, as dialysis
Dialysis

In medicine, dialysis is primarily used to provide an artificial replacement for lost kidney function due to renal failure. Dialysis may be used for very sick patients who have suddenly but temporarily, lost their kidney function or for quite stable patients who have permanently lost their kidney function ....
 may clear both the intoxication and the acidosis.

Additional Information

The ability to differentiate hyperventilation due to metabolic acidosis from asthma. This has led to inappropriate bronchodilation.