Acid-base imbalance

# Overview
Acid-base imbalance has several possible causes. An excess of acid is called acidosis and an excess in bases is called alkalosis. Acidosis is much more common than alkalosis. The imbalance is compensated by negative feedback to restore normal values. Acid-base balance is maintained by normal respiratory and renal excretions of carbon dioxide and acids respectively.

# Definition

## Acidosis
Acidosis occurs when the pH is less or equal to 7.35 due to excess of hydrogen ions or loss of bicarbonate ions (HCO3-).

## Alkalosis
Alkalosis refers to a condition reducing hydrogen ion concentration of arterial blood plasma (alkalemia) through the loss of acids or retention of bicarbonate. Generally alkalosis is said to occur when pH of the blood exceeds 7.45.

# Approach to acidbase imbalance

## The following steps can help to generate a differential diagnosis on a patient with a suspected acid/base disorder:
- Evaluate the complete clinical picture and laboratory data in patients with suspected acid-base disorder.
- Single acid-base disorders are common compared to double (mixed) acid-base disorders, which are more common compared to triple acid-base disorders.
- A normal pH doesn't exclude an acid-base disorder as a co-existing acidosis and alkalosis may result in a normal pH.
- When the clinical picture raises a suspicion of an acid-base imbalance and the pH is normal, always check for the anion gap. For e.g., patient with diabetic ketoacidosis (metabolic acidosis) and vomiting (metabolic alkalosis) will present as a normal pH but with elevated anion gap.
- When the primary disorder is acidosis, the body will compensate by developing an alkalosis (and vice-verse if the primary disorder is an alkalosis). When the primary disorder is respiratory, the body compensate with a metabolic (renal) process.

## Steps in determining the presence of an acid-base disorder are:
- Check serum pH
Normal is 7.40 (7.35-7.45). Values lower than normal represent an acidosis; values higher than normal represent an alkalosis.
Serum HCO3- drops of 4 to 5 mEq/L (4-5 mmol/L) for each 10 mm Hg (1.3 kPa) decrease in the pCO2.
- Normal is 7.40 (7.35-7.45). Values lower than normal represent an acidosis; values higher than normal represent an alkalosis.
- Serum HCO3- drops of 4 to 5 mEq/L (4-5 mmol/L) for each 10 mm Hg (1.3 kPa) decrease in the pCO2.
- Check the pCO2 and the HCO3- to decide whether the process is respiratory vs metabolic.
Normal serum bicarbonate is 24mEq/dl; normal serum pCO2 is 40.
- Normal serum bicarbonate is 24mEq/dl; normal serum pCO2 is 40.
- Check the anion gap: serum sodium - (serum chloride plus serum HCO3-).
Normal is 10 mEq/L )
- Normal is 10 mEq/L )
- Check for respiratory compensation 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
Arterial pCO2 = (pH  7)  100. This is the coincidence rule.
For each increase in the PaCO2 of 10 mmHg, the pH decreases by 0.08.
- Arterial pCO2 = 1.5 x serum HCO3- + 8  2 (Winters' formula)
- Arterial pCO2 = Serum HCO3- + 15
- Arterial pCO2 = (pH  7)  100. This is the coincidence rule.
- For each increase in the PaCO2 of 10 mmHg, the pH decreases by 0.08.
- Calculate the corrected bicarbonate to check for any coexistent metabolic acidosis (see below delta-delta formula).
- Measure the osmolar gap (online calculator). A high osmolar gap (online calculator) suggestions intoxication with osmotically active agents such as methanol, ethylene glycol, isopropyl alcohol, and toluene.

## Coexistent elevated anion gap and normal anion gap metabolic acidosis
- An elevated anion gap can coexist with a normal anion gap metabolic acidosis.
- Delta-Delta equation: Change in anion gap = Change in bicarbonate.
Change in gap (current gap - 12 mEq/L )
Change in bicarb (current bicarb -  24 mEq/L )
If the anion gap increases less and than the serum bicarbonate decreases suggests 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.
- Change in gap (current gap - 12 mEq/L )
- Change in bicarb (current bicarb -  24 mEq/L )
- If the anion gap increases less and than the serum bicarbonate decreases suggests 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.

## 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' formula)
Arterial pCO2 = serum HCO3- + 15
If the measured pCO2 is not close to predicted, a second disorder coexists.
If the pCO2 is less than predicted, respiratory alkalosis is present; if the pCO2 is higher than predicted, respiratory acidosis is present.
The maximum limit of respiratory compensation for a metabolic acidosis is pCO2 of 20.
- Arterial pCO2 = 1.5 x serum HCO3- + 8  2 (Winters' formula)
- Arterial pCO2 = serum HCO3- + 15
- If the measured pCO2 is not close to predicted, a second disorder coexists.
- If the pCO2 is less than predicted, respiratory alkalosis is present; if the pCO2 is higher than predicted, respiratory acidosis is present.
- The maximum limit of respiratory compensation for a metabolic acidosis is pCO2 of 20.

## 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.
- 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 substances.
- 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 and starvation
Toluene
Initial elevated anion gap followed with normal anion gap
- Methanol
Also called wood alcohol
Used in antifreeze and solvents
Presentation: Delirium, papilledema, and retinal hemorrhages
Elevated anion gap metabolic acidosis
- 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
- 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 and starvation
- Also called rubbing alcohol
- No acid-base disorder
- Metabolism causes increase acetone in the blood
- Other conditions with elevated acetones in blood are: diabetes and starvation
- Toluene
Initial elevated anion gap followed with normal anion gap
- Initial elevated anion gap followed with normal anion gap
- Estimated serum osmolality = (2 - serum sodium + BUN/2.8 + Glucose/18)

# Blood Gas Analysis
Venous blood gas sampling should not replace arterial blood gas sampling, but may supplement arterial blood gas monitoring as a mechanism of trending results and minimizing arterial sampling. Central venous blood is preferable to peripheral venous blood, as it more accurately represents the arterial blood gas results. Venous blood is more acidic than arterial blood, so venous pH is lower than arterial pH.

# Compensation
- There are compensation mechanisms in the body in order to normalizing the pH inside the blood.
- The amount of compensation depends on proper functioning of renal and respiratory systems. However, it is uncommon to compensate completely. Compensatory mechanisms might correct only 5075% of pH to normal.
- Acute respiratory compensation usually occurs within first day. However, chronic respiratory compensation takes 1 to 4 days to occur.
- Renal compensation might occur slower than respiratory compensation.

# Mixed AcidBase Disorders

# Related Chapters
- Acidbase homeostasis
- Acidbase imbalance
- Acidosis
- Alkalosis
- Arterial blood gas
- Metabolic acidosis
- Metabolic alkalosis
- Respiratory acidosis
- Respiratory alkalosis
- Anion gap