Mechanism of Action of Aluminum Phosphide Poisoning
Aluminum phosphide poisoning causes death primarily through liberation of phosphine gas, which induces cellular hypoxia by inhibiting cytochrome C oxidase in mitochondria and generating highly reactive hydroxyl radicals that lead to cardiovascular collapse and multi-organ failure. 1
Primary Toxic Mechanism
The fundamental toxicity occurs when aluminum phosphide (AlP) contacts moisture—either atmospheric humidity or gastric hydrochloric acid—releasing lethal phosphine gas 1, 2. This phosphine gas is then rapidly absorbed through both respiratory and gastrointestinal tracts 3.
Cellular Level Toxicity
The phosphine gas exerts its lethal effects through multiple interconnected mechanisms:
- Mitochondrial dysfunction: Phosphine directly inhibits cytochrome C oxidase, the terminal enzyme in the electron transport chain, blocking oxidative phosphorylation and ATP production 1, 3, 4
- Free radical formation: The compound generates highly reactive hydroxyl radicals that cause widespread cellular damage 1, 3
- Cellular hypoxia: The combined effect of these mechanisms produces profound cellular oxygen deprivation despite adequate oxygen delivery 1, 5
Organ System Effects
Cardiovascular Toxicity (Primary Cause of Death)
The cardiac and vascular tissues are particularly vulnerable to phosphine toxicity 1. This manifests as:
- Profound refractory hypotension and circulatory failure due to direct myocardial depression 1, 2, 5
- Congestive heart failure from myocardial dysfunction 1, 5
- Electrocardiographic abnormalities and life-threatening arrhythmias 1
The cardiovascular collapse occurs rapidly and is the most common cause of mortality in aluminum phosphide poisoning 5.
Metabolic Derangements
- Severe metabolic acidosis develops as a consequence of impaired cellular respiration and lactate accumulation 2, 3, 4
- The presence of acidosis is a poor prognostic factor and correlates with mortality 1
Clinical Implications
The lethality of aluminum phosphide is extreme—ingestion of as little as 150-500 mg can be fatal 6. The toxicity is instantaneous with nonspecific signs and symptoms 1. Importantly, phosphine gas poses a secondary hazard to healthcare providers, requiring proper ventilation of treatment areas 6.
Key Pathophysiologic Points
The mechanism differs fundamentally from simple hypoxia because:
- Tissue oxygen delivery may be adequate, but cells cannot utilize oxygen due to cytochrome oxidase inhibition 5
- This explains why supplemental oxygen alone is insufficient treatment 1
- The rapid onset and severity reflect phosphine's direct cellular toxicity rather than gradual accumulation 1
There is no specific antidote available because the mechanism involves irreversible enzyme inhibition and free radical damage 1, 2, 3. Treatment remains entirely supportive, focusing on maintaining cardiovascular function until tissue poison levels decrease and spontaneous circulation can be restored 1.
Prognostic Factors
The two most critical determinants of outcome are:
Both reflect the degree of cellular dysfunction from phosphine's inhibition of oxidative metabolism.