A 28-year-old male from Mumbai presents to the emergency department with acute-onset muscle weakness and paresthesias in both lower limbs. He reports consuming a large quantity of raw cashew nuts 2 hours prior. On examination, he has flaccid paralysis of bilateral lower limbs with preserved sensation. Serum potassium is 7.2 mEq/L (normal 3.5–5.0). ECG shows peaked T waves and prolonged PR interval. Which of the following best explains the neurophysiological basis of his muscle weakness?

Explanation

## Pathophysiology of Hyperkalemia-Induced Muscle Weakness ### Normal Resting Membrane Potential The resting membrane potential (RMP) in skeletal muscle is approximately **−90 mV**, maintained primarily by the Na+/K+ ATPase pump and differential ion permeability (K+ >> Na+ at rest). **Key Point:** The RMP is determined by the Nernst equation for potassium: $$E_K = 61 \log \frac{[K^+]_{out}}{[K^+]_{in}}$$ ### Effect of Hyperkalemia on RMP When extracellular K+ rises (from normal ~5 mEq/L to 7.2 mEq/L in this case): 1. The K+ concentration gradient decreases 2. The equilibrium potential for K+ becomes less negative (moves closer to 0 mV) 3. The resting membrane potential **depolarizes** (becomes less negative, e.g., from −90 mV to −70 mV) ### Critical Concept: Threshold vs. Excitability | Parameter | Normal State | Hyperkalemia | |-----------|--------------|---------------| | RMP | −90 mV | −70 mV (depolarized) | | Threshold | −55 mV | −55 mV (unchanged) | | Difference (RMP − Threshold) | 35 mV | 15 mV (reduced) | | Excitability | Normal | **Decreased** | **High-Yield:** The **threshold potential remains constant** (~−55 mV), but depolarization of the RMP reduces the voltage difference needed to reach threshold. This paradoxically *decreases* excitability because: - The membrane is already partially depolarized - Voltage-gated sodium channels (which open at threshold) become **inactivated** at depolarized potentials - Inactivation gates close, preventing sodium influx even if threshold is reached ### Clinical Correlation **Clinical Pearl:** Hyperkalemia causes a biphasic effect: 1. **Early phase:** Initial depolarization → brief increase in excitability (peaked T waves, palpitations) 2. **Late phase:** Sodium channel inactivation + further depolarization → **flaccid paralysis** (as seen in this patient) The peaked T waves on ECG reflect early depolarization of cardiac myocytes; the muscle weakness reflects sodium channel inactivation in skeletal muscle. ### Why This Patient Developed Paralysis Cashew nuts contain high levels of potassium. The massive K+ load caused: - Depolarization of the RMP from −90 mV toward −70 mV - Inactivation of voltage-gated Na+ channels - Loss of ability to generate action potentials in skeletal muscle - Flaccid paralysis despite preserved sensation (sensory neurons are less affected initially) [cite:Guyton & Hall Ch 5]