Anion gap

Renal Tub2ular Acidosis REF: Harrison’s Internal Medicine 17^th edition chapter 48 Table 48-4, http://en.wikipedia.org/ wiki/Anion_gap#High anion_gap

Repeat from December 2010

All evaluations of acid-base disorders should include a simple calculation of the AG; it represents those unmeasured anions in plasma (normally 10 to 12 mmol/L) and is calculated as follows: AG = Na’ – (C1- + HCO₃-). When acid anions such as acetoacetate and lactate accumulate in extracellular fluid, the AG increases causing a high AG acidosis. An increase in the AG is most often due to an increase in unmeasured anions and less commonly is due to a decrease in unmeasured cations (calcium, magnesium, potassium).

CAUSES OF HIGH-ANION-GAP METABOLIC ACIDOSIS

Lactic acidosis                              Toxins

Ketoacidosis                                  Ethylene glycol

Diabetic                                          Methanol

Alcoholic                                        Salicylates

Starvation                                       Propylene glycol Pyroglutamic acid Renal failure (acute and chronic)

Glue sniffing [Ref: Harrison I7^th/e p. 290 & 16^th/e p 265]

Causes of High anion gap acidosis I. Lactic acidosis

1. Toxins

– Ethylene glycol

– Methanol

– Salicylates

1. Renal failure
2. Ketoacidosis

a) Diabetes

b) Alcohol

c) Starvation

diarrhoea [Ref Harrison 17^th/e p 290 & 16′¹‘/e p 265 and 15^th/e p. 285] 

Causes of High anion gap acidosis

 Na⁺ -( HCO₃ ^–+ Cl^–)

Methanol

Urinary anion gap is calculated using the equation, urinary anion gap = ( Na+ + K+) – (Cl–). It reflects the ability of the kidney to excrete NH4Cl. During metabolic acidosis, kidneys normally eliminate NH4+Cl– to enhance the removal of excess H+ion. In response to acidosis, daily urinary excretion of NH4Cl can be increased from 30 mEq to 200 mEq.

Ref: Harrison’s Principle of Internal Medicine, 16th Edition, Page 368 ; Current Medical Diagnosis and Treatment 2012, Chapter 21

A normal anion gap metabolic acidosis is caused by the loss of bicarbonate with a reciprocal increase in chloride concentration.

It is also known as hyperchloremic acidosis. It most commonly results from abnormal gastrointestinal or renal losses of HCO3–.

Diarrhea is the most common cause of hyperchloremic metabolic acidosis.

Cholera is associated with massive diarrhea.

This diarrheal fluid consist of small bowel, biliary, and pancreatic fluids which contains 20–50 mEq/L of HCO 3 –. This loss of large volumes of fluids lead to hyperchloremic metabolic acidosis. 

Positive urinary anion gap is associated with distal RTA, as the kidney cannot excrete H+ as NH4Cl.

Both proximal and distal RTA causes normal anion gap metabolic acidosis.

Normal anion gap is 8 – 12 mEq/L.

Conditions associated with increased anion gap acidosis are lactic acidosis, ketoacidosis, ingestion of toxins ( alcohol, ethylene glycol, methanol, isopropyl alcohol), acute and chronic renal failure.

All evaluations of acid-base disorders should include a simple calculation of the AG; it represents those unmeasured anions in plasma (normally 10 to 12 mmol/L) and is calculated as follows: AG = Na+ – (CI– + HCOs ).

When acid anions such as acetoacetate and lactate accumulate in extracellular fluid, the AG increases causing a high AG acidosis.

An increase in the AG is most often due to an increase in unmeasured anions and less commonly is due to a decrease in unmeasured cations (calcium, magnesium, potassium).

CAUSES OF HIGH-ANION-GAP METABOLIC ACIDOSIS:

• Lactic acidosis
• Toxins
• Ketoacidosis
• Ethylene glycol
• Methanol
• Propylene glycol
• Diabeticketoacidosis
• Alcoholic
• Salicylates
• Starvation
• Renal failure (acute and chronic)

Alkali can be lost from the gastrointestinal tract in diarrhea or from the kidneys (renal tubular acidosis, RTA). In these disorders, reciprocal changes in [Cl–] and [HCO3–] result in a normal anion gap. In pure non–AG acidosis, therefore, the increase in [Cl–] above the normal value approximates the decrease in [HCO3–]. 

Proximal and distal renal tubular acidosis is associated with non anion gap metabolic acidosis. In this, the reciprocal changes in chloride and bicarbonate result in a normal anion gap.

• Lactic acidosis
• Ketoacidosis: Diabetic, alcoholic, starvation
• Toxins: Ethylene glycol, methanol, salicylates, propylene glycol and pyroglutamic acid
• Acute and chronic renal failure

Ref: Harrison’s Principles of Internal Medicine, 18th edn, chapter 47

A i.e. Proteins

Anion gap (AG) -Represents unmeasured anions in plasmaQ

–      AG is mostly due to proteinsQ

–       Normal AG is 10 -12 mmol/LQ.

–      Decrease in serum albumin by 1g/di decreases AG by 2.5meq/LQ

– 0 O_ ” align=”left” height=”183″ width=”53″>The concentration of anions and cations in plasma must be equal to maintain electrical neutrality. However, only certain cations (Na^t) and anions (C1-, HCO₃– ) are routinely measured in clinical laboratory.

Anion gap (AG) represents the unmeasured anions in the plasma. (difference between ‘unmeasured cations & unmeasured anions’)

• It is calculatedQ as follows:

AG = [Nal – [HCO₃ + C1-]

• The most important unmeasured cations: Ca²⁺, Mg²⁺, K+ The most important unmeasured anions: Proteins (Albumin), sulphate, phosphates

• Proteins are present in our body in much more quantities as compared to other unmeasured anions.

C i.e. Lactic acidosis

Answer is C (Renal Tubular Acidosis):

Positive Urinary Anion gap helps in establishing a diagnosis of Renal Tubular Acidosis

Urinary Anion Gap (UAG) can be used to estimate renal ammonium production and distinguish Renal Tubular Acidosis (Positive UAG) from GI bicarbonate loss (Negative UAG)- Harrisons

Urinary Anion Gap (UAG)

• Urinary Anion Gap (UAG) calculation is useful in cases of Normal Anion Gap (Hyperchloremic) Metabolic Acidosis
• Normal Anion Gap Acidosis may result from excessive bicarbonate losses from either the gastrointestinal tract (eg diarrhea) or renal sources (eg Renal Tubular Acidosis)
• Urinary Anion Gap Estimation helps to distinguish Renal bicarbonate loss from Gastrointestinal bicarbonate loss thereby helping in establishing the cause of normal anion gap metabolic acidosis

Positive Urinary Anion Gap:

– Implies Renal loss of Bicarbonate and the diagnosis is usually distal RTA

Negative Urinary Anion Gap:

–  Implies Gastrointestinal loss of Bicarbonate

Note

In type II (Proximal RTA) the kidney has defective HCO3- reabsorption leading to increased HCO3- excretion rather than decreased NH4C1 excretion.

Thus the urinary anion gap is often negative

Answer is B (NH₄⁺ ion):

Ans. D i.e. Ureterosigmoidostomy

Anion gap

Increased anion gap is seen in:

–        Starvation,

–        Salicylate poisoning,

–        Renal failure etc.

Ans. B: Cholera

USEDCARP:

• Ureterostomy
• Small bowel fistula
• Extra chloride
• Diarrhea
• Carbonic anhydrase inhibitors (e.g., acetazolamide)
• Adrenal insufficiency
• Pancreatic fistula

An elevated anion gap is created by inorganic (e.g., phosphate or sulfate), organic (e.g., ketoacids or lactate), or exogenous (e.g., salicylate) acids incompletely neutralized by bicarbonate. Frequent causes of an elevated anion gap metabolic acidosis is represented by the mnemonic MUDPILES:

• Methanol
• Uremia
• Diabetic ketoacidosis
• Paraldehyde
• Iron, isoniazid (INH)
• Lactic acid
• Ethanol, ethylene glycol
• Salicylates

Ans. is `b’ i.e., 10-12