A 32-year-old woman from rural Maharashtra presents to the emergency department with a 3-day history of severe watery diarrhea, vomiting, and abdominal cramps. She reports that her symptoms began 6 hours after consuming well water from her village. On examination, she is dehydrated (BP 88/54, HR 118), with garlic-smelling breath. Her skin shows hyperpigmentation and hyperkeratosis on the palms and soles. Laboratory investigations reveal serum creatinine 2.8 mg/dL, elevated transaminases, and 24-hour urine arsenic level of 85 µg/L (normal <50 µg/L). What is the most likely diagnosis and the primary mechanism of toxicity in this acute presentation?

Explanation

## Acute Arsenic Poisoning: Clinical Presentation and Mechanism ### Clinical Features in This Case **Key Point:** The triad of acute gastrointestinal symptoms (watery diarrhea, vomiting, cramping), garlic odor on breath, and acute renal/hepatic dysfunction within 6 hours of well water consumption is pathognomonic for acute arsenic poisoning. **High-Yield:** Garlic odor (dimethyl arsine) on the breath is a characteristic sign of acute arsenic toxicity and indicates systemic absorption. ### Mechanism of Acute Arsenic Toxicity **Key Point:** Arsenic (As³⁺) binds to sulfhydryl (-SH) groups on proteins, particularly: 1. **Pyruvate dehydrogenase** — inhibition blocks the TCA cycle, causing cellular energy depletion 2. **Lipoic acid-dependent enzymes** — disrupts oxidative metabolism 3. **Mitochondrial proteins** — triggers apoptosis and multi-organ failure **Clinical Pearl:** The acute phase (hours to days) manifests as hemorrhagic gastroenteritis due to direct epithelial necrosis and increased vascular permeability, leading to severe dehydration and shock. ### Skin Findings: Clue to Chronic Exposure The hyperpigmentation and hyperkeratosis (Mees' lines, raindrop hyperpigmentation) indicate **chronic exposure** superimposed on acute poisoning — common in endemic areas with contaminated groundwater. ### Laboratory Confirmation | Parameter | Finding | Significance | |-----------|---------|---------------| | 24-hr urine arsenic | 85 µg/L (normal <50) | Confirms systemic absorption | | Serum creatinine | 2.8 mg/dL | Acute kidney injury from direct tubular toxicity | | Transaminases | Elevated | Hepatocellular injury | | Garlic odor | Present | Volatile dimethyl arsine metabolite | **Mnemonic: ARSENIC ACUTE** — **A**cute gastroenteritis, **R**enal dysfunction, **S**hock, **E**levated transaminases, **N**ausea/vomiting, **I**ncreased urine arsenic, **C**ardiovascular collapse (in severe cases) ### Management Principles 1. **Aggressive fluid resuscitation** — correct hypovolemia and maintain urine output >200 mL/hr 2. **Activated charcoal** — if within 1–2 hours of ingestion (limited efficacy in acute cases) 3. **Chelation therapy** — BAL (dimercaprol) 3–5 mg/kg IM every 4–6 hours for severe poisoning; DMSA (succimer) as oral alternative 4. **Supportive care** — electrolyte correction, renal support if needed **Warning:** Do NOT use penicillamine — it increases arsenic toxicity by mobilizing tissue stores. [cite:Forensic Medicine & Toxicology, Reddy 34e, Ch. Poisoning]