**Question:** Causes of high anion-gap metabolic acidosis include the following EXCEPT

A. Diabetic ketoacidosis
B. Acidosis due to excessive hydrogen ion production
C. Acidosis due to loss of bicarbonate
D. Acidosis due to loss of chloride ions

**Correct Answer:** D. Acidosis due to loss of chloride ions

**Core Concept:**
Metabolic acidosis is a condition characterized by an accumulation of hydrogen ions in the blood, leading to a decrease in blood pH. An anion-gap is calculated as the difference between the sum of measured anions and measured cations in the blood. An anion gap is typically between 10-16 mmol/L in adults and 5-10 mmol/L in neonates. High anion-gap acidosis is a condition characterized by an anion gap above the normal range.

**Why the Correct Answer is Right:**
High anion-gap acidosis is divided into two types:
1. Diabetic ketoacidosis: This is caused by the accumulation of ketone bodies (acetoacetic acid and beta-hydroxybutyric acid) during the process of carbohydrate deprivation due to diabetes mellitus. This condition is characterized by high anion gap due to the presence of ketone bodies which are anions.
2. Acidosis due to loss of bicarbonate: This type is caused by a decrease in blood bicarbonate levels, leading to an increase in the anion gap. Loss of bicarbonate can result from conditions like severe respiratory alkalosis, severe liver dysfunction, or severe burns.
3. Acidosis due to loss of chloride ions: This type is caused by a decrease in blood chloride levels. It is typically seen in conditions like severe gastrointestinal losses (e.g., severe diarrhea) or renal losses (e.g., severe diuretic use). In this case, the loss of chloride ions leads to an increase in the anion gap.
4. Acidosis due to increased anions: This type is caused by an increase in blood anions (e.g., lactic acidosis, non-ketonic diabetic acidosis, or hypokalemic alkalosis).

**Why Each Wrong Option is Incorrect:**
A. Acidosis due to increased cations (e.g., hypokalemic acidosis) - This type is caused by a decrease in blood potassium levels, leading to a decrease in the cation-anion ratio and an increase in the anion gap.
B. Acidosis due to increased bicarbonate (e.g., respiratory alkalosis) - This type is caused by a decrease in blood bicarbonate levels, leading to an increase in the cation-anion ratio and anion gap.
C. Acidosis due to increased chloride (e.g., severe diuretic use) - This type is caused by a decrease in blood chloride levels, leading to an increase in the cation-anion ratio and anion gap.

**Clinical Pearls:**
1. High anion gap acidosis is a