Metabolic acidosis pathophysiology

Jump to navigation Jump to search


Metabolic acidosis Microchapters


Patient Information





Differentiating Metabolic Acidosis from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis


History and Symptoms

Physical Examination

Laboratory Findings


Other Imaging Findings

Other Diagnostic Studies


Medical Therapy

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Metabolic acidosis pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides


American Roentgen Ray Society Images of Metabolic acidosis pathophysiology

All Images
Echo & Ultrasound
CT Images

Ongoing Trials at Clinical

US National Guidelines Clearinghouse

NICE Guidance

FDA on Metabolic acidosis pathophysiology

CDC on Metabolic acidosis pathophysiology

Metabolic acidosis pathophysiology in the news

Blogs on Metabolic acidosis pathophysiology

Directions to Hospitals Treating Metabolic acidosis

Risk calculators and risk factors for Metabolic acidosis pathophysiology

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



Metabolic acidosis is the state of low blood pH that can result from:

  • Failure of the kidneys to excrete H+
  • Increased H+ load
  • Loss of bicarbonate

Shown below is a table summarizing the mechanisms of metabolic acidosis.

Mechanism Conditions
Failure to excrete H+

Decreased production of NH4+:

  • Renal failure
  • Renal tubular acidosis type 4 (hypoaldosteronism)

Decreased secretion of H+

  • Renal tubular acidosis type 1
Increased H+ load
  • Lactic acidosis
  • Ketoacidosis
  • Ingestions
  • Massive rhabdomyolysis
Loss of bicarbonate

Gastrointestinal loss of bicarbonates:

  • Diarrhea
  • Cholestyramine

Renal loss of bicarbonate:

  • Renal tubular acidosis type 2
  • Diuretics such as carbonic anhydrase inhibitors)

High Anion Gap Metabolic Acidosis

High anion gap metabolic acidosis can be caused by one of the following:

  • Lactic acidodis
  • Ketoacidosis
  • Renal failure
  • Ingestions

Lactic Acidosis


Renal Failure


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.

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 disease, 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' formula)
    • Arterial pCO2 = Serum HCO3 + 15

Role of the Urine Anion Gap in the Patient with a Normal Anion Gap Metabolic Acidosis

  • A 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 the 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 acts 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 substances.
  • The estimated serum osmolality should be close to the actual, measured serum osmolality (within 10 points).
  • If the measured serum osmolality is much higher (i.e. >10 points) than the estimated serum osmolality then presence of osmotically active substances should be suspected.
  • They can be differentiated because of these following characteristics:
    • Methanol
    • 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)


  • 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


Template:WH Template:WS