From the Guidelines
Acute iron toxicity results in high anion gap metabolic acidosis primarily due to the toxic effects of iron on cellular metabolism, leading to lactic acid production and tissue hypoperfusion. The mechanisms underlying this process involve the direct damage of mitochondria by free iron ions, disrupting cellular respiration and promoting anaerobic metabolism, as well as interference with electron transport in mitochondria, inhibiting ATP production and causing cellular dysfunction 1. When excessive iron is ingested, it causes direct damage to the gastrointestinal mucosa, liver, and kidneys, resulting in decreased perfusion to tissues and further lactic acid accumulation.
The development of high anion gap metabolic acidosis in acute iron toxicity is similar to other causes of high-anion gap metabolic acidosis, such as lactic acidosis, ingestion of drugs like salicylate, methanol, ethylene glycol, and paraldehyde, and chronic renal failure 1. However, the clinical history and measurement of specific laboratory tests, such as blood lactate and serum iron levels, can help distinguish iron toxicity from other causes.
Key factors contributing to the high anion gap metabolic acidosis in acute iron toxicity include:
- Direct mitochondrial damage leading to increased lactic acid production
- Tissue hypoperfusion due to gastrointestinal, liver, and kidney damage
- Interference with electron transport in mitochondria, inhibiting ATP production
- The presence of an osmolar gap in addition to the anion gap acidosis, similar to other low-molecular weight organic compound intoxications 1.
Given the potential for significant systemic toxicity and the need for aggressive management, including potential chelation therapy with deferoxamine if iron levels are significantly elevated, it is crucial to promptly recognize and treat acute iron toxicity to prevent long-term morbidity and mortality.
From the Research
Causes of High Anion Gap Metabolic Acidosis
- High anion gap metabolic acidosis can be caused by various factors, including lactate accumulation, ketoacid production, toxin/drug ingestion, and uremia 2.
- Toxins such as methanol, ethylene glycol, and salicylates can cause high anion gap metabolic acidosis, often with severe acidoses and elevated osmolar gaps 2.
- Lactic acidosis, which can be caused by decreased oxygen delivery or defective oxygen utilization, is associated with high mortality 2.
- Other causes of high anion gap metabolic acidosis include D-lactic acidosis, 5-oxoprolinuria, and acetaminophen use 3, 4.
Relationship Between Acute Iron Toxicity and High Anion Gap Metabolic Acidosis
- There is no direct evidence in the provided studies that links acute iron toxicity to high anion gap metabolic acidosis.
- However, it is known that high anion gap metabolic acidosis can be caused by various toxins and drugs, and it is possible that acute iron toxicity could lead to metabolic acidosis through similar mechanisms 2, 3, 5.
Diagnostic Approaches
- The anion gap calculation can provide vital clues for diagnosing high anion gap metabolic acidosis and guiding clinical decision making 5.
- Plasma osmolality and osmolal gap calculations can also be used to guide appropriate clinical decision making 5.
- It is essential to consider the time of blood collection when diagnosing D-lactic acidosis, as D-lactate has a fast clearance in the human body 4.