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{{Infobox medical condition (new)
| name
| synonyms
| image = Bicarbonate Levels in Metabolic
| caption = The calculated level of bicarbonate in the blood (HCO<sub>3</sub><sup>−</sup>) reflects the severity of acidosis.
| pronounce
| field
| types =
Chronic Metabolic Acidosis
| symptoms
| complications =
'''Chronic:''' adverse outcomes on kidney function, musculoskeletal system, possible cardiovascular effects
| onset
| duration
| causes =
'''Chronic:''' Impaired kidney function
| risks
| diagnosis =
| differential
| prevention
| treatment = '''Acute:''' Mitigation of the underlying cause for the metabolic problem, such as administration of insulin in cases of diabetic ketoacidosis or restoration of effective circulating intravascular volume in cases of lactic acidosis. The administration of IV bicarbonate, although intellectually appealing, is rarely indicated or administered
'''Chronic:''' Diet rich in fruits and vegetables, oral alkali therapy<ref>{{cite journal |last1=Navaneethan |first1=Sankar D. |last2=Shao |first2=Jun |last3=Buysse |first3=Jerry |last4=Bushinsky |first4=David A. |title=Effects of Treatment of Metabolic Acidosis in CKD: A Systematic Review and Meta-Analysis |journal=Clinical Journal of the American Society of Nephrology |volume=14 |issue=7 |pages=1011–1020 |language=en |doi=10.2215/CJN.13091118 |pmid=31196951 |pmc=6625635 |date=5 July 2019}}</ref>
| medication
| prognosis
| frequency
'''Chronic:''' Highly prevalent in people with Chronic Kidney Disease: 9.4% CKD Stage 3a; 18.1% CKD Stage 3b; 31.5% CKD Stage 4 and 5 <ref>{{cite journal |last1=Inker |first1=Lesley A. |last2=Coresh |first2=Josef |last3=Levey |first3=Andrew S. |last4=Tonelli |first4=Marcello |last5=Muntner |first5=Paul |title=Estimated GFR, Albuminuria, and Complications of Chronic Kidney Disease |journal=Journal of the American Society of Nephrology |volume=22 |issue=12 |pages=2322–2331 |language=en |doi=10.1681/ASN.2010111181 |pmid=21965377 |pmc=3279937 |date=1 December 2011}}</ref>
| deaths =
| '''Metabolic acidosis''' is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of [[bicarbonate]], and a reduced ability of the [[
Acute metabolic acidosis, lasting from minutes to several days, often occurs during serious illnesses or hospitalizations, and is generally caused when the body produces an excess amount of organic acids ([[
==Signs and symptoms==
=== Acute metabolic acidosis ===
Symptoms are not specific, and diagnosis can be difficult unless patients present with clear indications for
Extreme acidemia can also lead to neurological and cardiac complications:
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=== Chronic metabolic acidosis ===
Chronic metabolic acidosis has non-specific clinical symptoms but can be readily diagnosed by testing serum bicarbonate levels in patients with
==Diagnostic approach and causes==
Metabolic acidosis results in a reduced serum pH that is due to metabolic and not respiratory dysfunction. Typically the serum bicarbonate concentration will be <22 mEq/L, below the normal range of 22 to 29 mEq/L, the standard base will be more negative than -2 (base deficit) and the pCO<sub>2</sub> will be reduced as a result of hyperventilation in an attempt to restore the pH closer to normal. Occasionally in a mixed acid-base disorder where metabolic acidosis is not the primary disorder present, the pH may be normal or high.<ref name=":2" /> In the absence of chronic respiratory alkalosis, metabolic acidosis can be clinically diagnosed by analysis of the calculated serum bicarbonate level.
=== Causes ===
Generally, metabolic acidosis occurs when the body produces too much acid (e.g., lactic acidosis, see below section), there is a loss of bicarbonate from the blood, or when the kidneys are not removing enough acid from the body.
Chronic metabolic acidosis is most often caused by a decreased capacity of the kidneys to excrete excess acids through renal ammoniagenesis. The typical Western diet generates
There are many causes of acute metabolic acidosis, and thus it is helpful to group them by the presence or absence of a normal anion gap.<ref>{{Cite book|title=Symptom to diagnosis: an evidence-based guide|url=https://accessmedicine.mhmedical.com/book.aspx?bookID=1088|url-access=subscription|last1=Stern|first1=Scott D. C.|last2=Cifu|first2=Adam S.|last3=Altkorn|first3=Diane|isbn=9780071803441|edition= 3rd|location=New York|publisher=[[McGraw-Hill Education]]|date=2015|oclc=896866189}}</ref>
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Causes of increased anion gap include:
* [[Lactic acidosis]]<ref>{{Cite book|title=Current medical diagnosis & treatment study guide|editor-last1=Quinn|editor-first1=Gene R.|editor-last2=Gleason|editor-first2=Nathaniel W.|editor-last3=Papadakis|editor-first3=Maxine A.|editor-last4=McPhee|editor-first4=Stephen J.|isbn=9780071848053|edition= 2nd|location=New York|publisher=[[McGraw-Hill]]|date=2016|oclc=910475681}}</ref>
* [[Ketoacidosis]] (e.g.,
* [[Chronic kidney failure]]<ref>{{Cite book|title=Morgan & Mikhail's clinical anesthesiology|others=Butterworth, John F., IV,, Mackey, David C.,, Wasnick, John D.,, Morgan, G. Edward,, Mikhail, Maged S.,, Morgan, G. Edward.|isbn=9781259834424|edition= Sixth|location=New York|oclc=1039081701|date = 2018-08-21}}</ref>
*
* Intoxication:
**Salicylates, [[methanol]], [[ethylene glycol]]<ref name="DeGowin's diagnostic examination"/>
**Organic acids, [[paraldehyde]], [[ethanol]], [[formaldehyde]]<ref>{{Cite book|title=Critical care|others=Oropello, John M.,, Pastores, Stephen M.,, Kvetan, Vladimir|isbn=9780071817264|location=[New York]|oclc=961480454|date = 2016-11-22}}</ref>
**[[Carbon monoxide]], [[cyanide]], [[ibuprofen]], [[metformin]]<ref>{{Cite book|title=Current medical diagnosis & treatment 2020|others=Papadakis, Maxine A.,, McPhee, Stephen J.,, Rabow, Michael W.|isbn=9781260455281|edition= Fifty-eighth |location=New York|oclc=1109935506|date = 2019-09-02}}</ref>
* [[Propylene glycol]] (metabolized to L and D-lactate and is often found in infusions for certain intravenous medications used in the [[intensive care unit]])<ref>{{Cite book|title=Harrison's principles of internal medicine.|others=Jameson, J. Larry,, Kasper, Dennis L.,, Longo, Dan L. (Dan Louis), 1949-, Fauci, Anthony S., 1940-, Hauser, Stephen L.,, Loscalzo, Joseph|isbn=9781259644030|edition= 20th |location=New York|oclc=1029074059|date = 2018-08-13}}</ref>
* Massive [[rhabdomyolysis]]<ref>{{Cite book|title=Morgan & Mikhail's clinical anesthesiology|others=Butterworth, John F., IV,, Mackey, David C.,, Wasnick, John D.,, Morgan, G. Edward,, Mikhail, Maged S.,, Morgan, G. Edward.|isbn=978-1259834424|edition= Sixth|location=New York|oclc=1039081701|date = 2018-08-21}}</ref>
*[[Isoniazid]], iron, [[phenelzine]], [[tranylcypromine]], [[Valproate|valproic acid]], [[verapamil]]<ref>{{Cite book|title=Katzung & Trevor's pharmacology : examination & board review|last=Katzung, Bertram G.|others=Kruidering-Hall, Marieke,, Trevor, Anthony J.|isbn=978-1259641022|edition= Twelfth |location=New York|oclc=1052466341|date = 2018-09-05}}</ref>
*[[Topiramate]]
*Sulfates<ref>{{Cite book|title=Pulmonary physiology|last=Levitzky, Michael G.|date=2007|publisher=McGraw-Hill Medical|isbn=9780071437752|edition= 7th|location=New York|oclc=75713147}}</ref>
'''Normal anion gap'''{{Main|Normal anion gap acidosis}}
Causes of normal anion gap include:<ref>{{Cite book|title=The renal system: basic science and clinical conditions|date=2010|publisher=Churchill Livingstone/Elsevier|last1=Field|first1=Michael J.|last2=Pollock|first2=Carol A.|last3=Harris|first3=David C.|isbn=9780702033711|edition=2nd|location=Edinburgh|oclc=319855752|url-access=registration|url=https://archive.org/details/renalsystembasic0000fiel}}</ref>
* Inorganic acid addition
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** [[Proximal renal tubular acidosis]]
** [[Distal renal tubular acidosis]]
*[[Hyperalimentation]]
*[[Addison's disease|Addison disease]]
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* Saline infusion
To distinguish between the main types of metabolic acidosis, a clinical tool called the [[anion gap]] is
<!--
Anion gap = ( [Na<sup>+</sup>] + [K<sup>+</sup>] ) − ( [Cl<sup>−</sup>] + [HCO<sub>3</sub><sup>−</sup>] )
-->
Because the concentration of serum sodium is greater than the combined concentrations of chloride and bicarbonate an 'anion gap' is noted. In reality serum is electoneutral because of the presence of other minor cations (potassium, calcium and magnesium) and anions (albumin, sulphate and phosphate) that are not measured in the equation that calculates the anion gap.
The normal value for the anion gap is 8–16 mmol/L (12±4). An elevated anion gap (i.e. > 16 mmol/L) indicates the presence of excess 'unmeasured' anions, such as lactic acid in anaerobic metabolism resulting from tissue hypoxia, glycolic and formic acid produced by the metabolism of toxic alcohols, ketoacids produced when acetyl-CoA undergoes ketogenesis rather than entering the tricarboxylic (Krebs) cycle, and failure of renal excretion of products of metabolism such as sulphates and phosphates.
Adjunctive tests are useful in determining the aetiology of a raised anion gap metabolic acidosis including detection of an osmolar gap indicative of the presence of a toxic alcohol, measurement of serum ketones indicative of ketoacidosis and renal function tests and urinanalysis to detect renal dysfunction.
Elevated protein (albumin, globulins) may theoretically increase the anion gap but high levels are not usually encountered clinically. Hypoalbuminaemia, which is frequently encountered clinically, will ''mask'' an anion gap. As a rule of thumb, a decrease in serum albumin by 1 G/L will decrease the anion gap by 0.25 mmol/L
==Pathophysiology==
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* [[Bicarbonate buffering system]]
* [[Intracellular]] buffering by absorption of hydrogen atoms by various molecules, including proteins, phosphates and carbonate in bone.
* [[Respiratory compensation]]. Hyperventilation will cause more carbon dioxide to be removed from the body and thereby
* [[Renal compensation|Kidney compensation]]
===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: <chem display=block>H+ + HCO3- <=> H2CO3 <=> CO2 + H2O</chem>
The [[Henderson–Hasselbalch equation]] mathematically describes the relationship between blood pH and the components of the bicarbonate buffering system: <math chem display=block>p\ce{H}=pK_\text{a}+\operatorname{\mathrm{Log}}\frac{\left[\ce{HCO3^-}\right]}{\left[\ce{CO2}\right]}\text{,}</math> where {{math|''pK''<sub>a</sub> ≈ 6.1}}. In clinical practice, the {{CO2}} concentration is usually determined via [[Henry's law]] from {{math|''P''<sub>a{{CO2}}</sub>}}, the {{CO2}} partial pressure in arterial blood: <math chem display=block>[\ce{CO2}] = (0.03\text{ L}^{-1}/\text{mmHg})\times P_{\text{a}\ce{CO2}}\text{.}</math>
For example, blood gas machines usually determine bicarbonate concentrations from measured ''p''H and {{math|''P''<sub>a{{CO2}}</sub>}} values. Mathematically, the algorithm [[substitution (algebra)|substitutes]] the Henry's law formula into the Henderson-Hasselbach equation and then rearranges: <math chem display=block>\left[\ce{HCO3^-}\right]=(0.03\text{ L}^{-1}/\text{mmHg})P_{\text{a}\ce{CO2}}\cdot 10^{p\ce{H}-pK_\text{a}}</math> At [[sea level]], normal numbers might be {{math|''p''H ≈ 7.4}} and {{math|''P''<sub>a{{CO2}}</sub> ≈ 40 mmHg}}; these then imply <math chem display=block>\begin{align}
\left[\ce{HCO3^-}\right]&=(0.03\text{ L}^{-1}/\text{mmHg})(40\text{ mmHg})\cdot10^{7.4-6.1} \\
&=24\text{ L}^{-1}
\end{align}</math>
== Consequences ==
=== Acute
Acute
=== Chronic
Chronic metabolic acidosis commonly occurs in people with
The most adverse consequences of chronic metabolic acidosis in people with
==Treatment==
Treatment of metabolic acidosis depends on the underlying cause, and should target reversing the main process. When considering course of treatment, it is important to distinguish between acute versus chronic forms.
=== Acute
Bicarbonate therapy is generally administered In patients with severe acute acidemia (pH < 7.11), or with less severe acidemia (pH 7.
=== Chronic
For people with
Currently, the most commonly used treatment for chronic metabolic acidosis is oral bicarbonate. The NKF/KDOQI guidelines recommend starting treatment when serum bicarbonate levels are <22 mEq/L, in order to maintain levels ≥ 22 mEq/L.<ref name=":4">{{Cite journal
Veverimer (TRC 101) is a promising investigational drug designed to treat metabolic acidosis by binding with the acid in the gastrointestinal tract and removing it from the body through excretion in the feces, in turn decreasing the amount of acid in the body, and increasing the level of bicarbonate in the blood. Results from a Phase 3, double-blind placebo-controlled 12-week clinical trial in people with CKD and metabolic acidosis demonstrated that Veverimer effectively and safely corrected metabolic acidosis in the short-term,<ref>{{Cite journal|last1=Wesson|first1=Donald E.|last2=Mathur|first2=Vandana|last3=Tangri|first3=Navdeep|last4=Stasiv|first4=Yuri|last5=Parsell|first5=Dawn|last6=Li|first6=Elizabeth|last7=Klaerner|first7=Gerrit|last8=Bushinsky|first8=David A.|date=2019-04-06|title=Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: a multicentre, randomised, double-blind, controlled, phase 3 trial|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32562-5/abstract|journal=The Lancet|language=
==See also==
* [[Delta ratio]]
* [[Metabolic alkalosis]]
* [[Pseudohypoxia]]
* [[Respiratory acidosis]]
* [[Respiratory alkalosis]]
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