A 52-year-old man with a 10-year history of essential hypertension presents for routine follow-up. His BP is 148/92 mmHg on current therapy with amlodipine 5 mg daily. Investigations show normal renal function, normal serum potassium, and normal plasma renin activity. Which of the following is NOT a recognized mechanism of essential hypertension?

Explanation

## Understanding Essential vs Secondary Hypertension **Key Point:** Essential (primary) hypertension is a multifactorial disorder with multiple pathophysiologic mechanisms, but by definition it excludes identifiable secondary causes such as primary hyperaldosteronism. ### Recognized Mechanisms in Essential Hypertension The following mechanisms are well-established in essential hypertension: | Mechanism | Pathophysiology | Evidence | |-----------|-----------------|----------| | Sympathetic overactivity | Increased norepinephrine release, enhanced α and β-adrenergic sensitivity | Elevated plasma catecholamines, ↑ heart rate variability | | Endothelial dysfunction | ↓ Nitric oxide (NO) production, ↑ endothelin-1, impaired vasodilation | Reduced flow-mediated dilation, ↑ vascular stiffness | | Sodium handling defect | ↑ Renal sodium reabsorption (proximal tubule, loop of Henle, collecting duct) | Positive sodium balance, volume expansion | | Renin-angiotensin-aldosterone dysregulation | Variable RAAS activity (not uniformly elevated) | Normal to low plasma renin in many patients | | Vascular smooth muscle dysfunction | ↑ Intracellular Ca²⁺, ↑ sensitivity to vasoconstrictors | Structural and functional changes | ### Why Primary Hyperaldosteronism Is NOT Part of Essential Hypertension **High-Yield:** Primary hyperaldosteronism (Conn's syndrome) is a **secondary cause** of hypertension, defined by: - Elevated plasma aldosterone concentration (PAC) ≥ 15 ng/dL - **Suppressed plasma renin activity (PRA) < 1 ng/mL/hr** — this is the hallmark - Positive aldosterone-to-renin ratio (ARR ≥ 20–30) - Hypokalemia (in ~50% of cases) - Metabolic alkalosis The patient in the stem has **normal plasma renin activity and normal serum potassium**, which rules out primary hyperaldosteronism. **Clinical Pearl:** In essential hypertension, the RAAS is typically suppressed or normal due to volume expansion and negative feedback. In secondary hyperaldosteronism (e.g., cirrhosis, nephrotic syndrome), both aldosterone AND renin are elevated. In primary hyperaldosteronism, aldosterone is high but renin is suppressed — this dissociation is diagnostic. **Mnemonic: SECONDARY causes of HTN (CHASED):** - **C**oarctation of aorta - **H**yperaldosteronism (primary) - **A**drenaline excess (pheochromocytoma) - **S**leep apnea, **S**tenosis (renal artery) - **E**ndocrine (thyroid, Cushing's) - **D**rugs (NSAIDs, oral contraceptives, decongestants) Primary hyperaldosteronism is a distinct entity excluded from the definition of essential hypertension.