A 52-year-old man from rural Maharashtra presents with progressive muscle weakness and cramping for 3 weeks. He works as a farmer and was exposed to organophosphate pesticides during spraying without protective equipment. On examination, he has visible fasciculations in his limbs, muscle tenderness, and difficulty climbing stairs. Serum potassium is 6.8 mEq/L (normal 3.5–5.0). An ECG shows peaked T waves and prolonged PR interval. Which of the following best explains the cardiac conduction abnormality observed in this patient?

Explanation

## Pathophysiology of Hyperkalemia-Induced Conduction Abnormality ### Normal Resting Membrane Potential **Key Point:** The resting membrane potential in cardiac myocytes is approximately −85 to −90 mV, maintained primarily by the Na+/K+-ATPase and differential ion permeability. $$V_m = -61 \log \frac{[K^+]_{in}}{[K^+]_{out}} + \text{(Na+ contribution)}$$ Normally, [K+]out ≈ 5 mEq/L and [K+]in ≈ 140 mEq/L. ### Effect of Hyperkalemia (K+ = 6.8 mEq/L) 1. **Reduced K+ gradient:** As extracellular K+ rises, the ratio [K+]in / [K+]out decreases. 2. **Depolarization of resting potential:** The resting membrane potential becomes less negative (e.g., −75 mV instead of −85 mV). 3. **Reduced safety margin:** The difference between resting potential and threshold (approximately −55 mV) narrows. ### Consequence: Slowed Conduction Velocity **High-Yield:** In phase 0 (rapid depolarization), the rate of change of voltage (dV/dt) depends on the driving force for Na+ influx: $$\text{dV/dt} = g_{Na} \times (V_m - E_{Na})$$ When Vm is closer to threshold (less negative), the driving force (Vm − ENa) is smaller, so dV/dt decreases. This manifests as: - **Peaked T waves** (early repolarization due to shortened action potential duration) - **Prolonged PR interval** (slowed AV nodal conduction) - **Widened QRS** (slowed ventricular depolarization) **Clinical Pearl:** Hyperkalemia does NOT hyperpolarize cells; it depolarizes them. The membrane becomes "closer to firing" but depolarizes more slowly because the driving force is reduced. ### Why This Patient Has Hyperkalemia Organophosphate poisoning causes: - Sustained acetylcholine excess → muscle fasciculations and rhabdomyolysis - Rhabdomyolysis → myoglobinuria and acute kidney injury - Renal failure → potassium retention - Direct cellular damage → K+ leak from intracellular space [cite:Guyton and Hall Textbook of Medical Physiology Ch 5]