Pathophysiology
I-22. Primary and secondary hyperaldosteronism
原発性・続発性アルドステロン症
Mineralocorticoid (Aldosterone) Physiology
- Essential for water/salt and acid-base balance: ↑Na⁺ + water reabsorption, ↑K⁺ and H⁺ secretion.
- Regulated by renin (released for low BP or SYM activation). Negative feedback: hyperkalemia → ↑aldosterone → ↑K⁺ excretion.
Hyperaldosteronism (Conn’s Syndrome)
Primary
- High aldosterone → inhibits renin → low plasma renin activity (PRA).
- Causes: aldosterone-producing adenoma (~80%), idiopathic hyperaldosteronism (~20%).
Secondary
- High PRA drives aldosterone secretion (aldosterone high).
- Hypertonia (↑renin): renal artery stenosis, renin-producing tumor.
- Normotension (↑renin from reduced effective circulating volume/edema, sensed by low-pressure baroreceptors): heart failure, liver cirrhosis, kidney disease.
Leading Symptoms (Primary)
- Hypertension — excess Na⁺ retention/hypervolemia (principal cells).
- Hypokalemia (<3.5 mM) — enhanced K⁺ secretion (principal cells).
- Metabolic alkalosis — ↑H⁺ secretion (intercalated cells).
Organ Pathomechanisms
Circulatory
- Heart: remodeling → LV hypertrophy + fibrosis (local ANGII).
- Vessels: remodeling → ↑stiffness; vasoconstriction/↑TPR (VSMC Ca²⁺), ↓vasodilation (↓NO via ROS), atherosclerosis → stroke + AMI risk.
Hypokalemia-induced disturbances
- Heart: arrhythmias, flat T-wave, prolonged QT.
- Muscle: weakness, paralysis.
- GI: constipation (resting-membrane hyperpolarization).
- Kidney: polyuria, renal diabetes insipidus (loss of urine concentration, ↓ADH sensitivity).
- Metabolism: ↓glucose tolerance + insulin secretion.
Treatment
- Surgery; ACE inhibitors; ANGII receptor antagonists; aldosterone receptor antagonists.
一問一答
▶How is aldosterone secretion normally regulated?
Stimulated by the RAAS (renin → ANGII), by hyperkalemia, and to a minor degree by ACTH.
▶What is the classic clinical triad of primary hyperaldosteronism?
Hypertension, hypokalemia, and metabolic alkalosis (with low renin).
▶What is the physiological action of aldosterone?
Acting on distal tubule/collecting duct mineralocorticoid receptors, it increases Na+/water reabsorption and K+/H+ secretion, raising blood volume and pressure.
▶What are the causes of primary hyperaldosteronism (Conn's syndrome)?
Aldosterone-producing adrenal adenoma (~80%) and bilateral idiopathic adrenal hyperplasia (~20%).
▶How is primary hyperaldosteronism distinguished from secondary by renin?
Primary: aldosterone excess with LOW renin/plasma renin activity (autonomous). Secondary: aldosterone excess driven by HIGH renin/PRA.
▶Why does primary hyperaldosteronism cause hypertension?
Increased Na+/water reabsorption expands blood volume; aldosterone also enhances vascular tone and remodeling → sustained hypertension.
▶Why does hyperaldosteronism cause hypokalemia and metabolic alkalosis?
Aldosterone drives renal K+ and H+ secretion → hypokalemia and metabolic alkalosis.
▶What symptoms result from hypokalemia in hyperaldosteronism?
Muscle weakness/cramps, arrhythmias, constipation, polyuria/polydipsia (nephrogenic DI), and decreased glucose tolerance (impaired insulin release).
▶Why is edema typically ABSENT in primary hyperaldosteronism?
Aldosterone escape — pressure natriuresis and natriuretic peptides limit Na+/water retention, so overt edema usually does not develop.
▶What are the cardiovascular organ effects of chronic aldosterone excess?
Left ventricular hypertrophy and myocardial fibrosis, plus vascular stiffness and remodeling — independent of the blood pressure effect.
▶What distinguishes hypertensive secondary hyperaldosteronism?
High renin/PRA with hypertension — e.g., renal artery stenosis (renovascular) or a renin-secreting tumor.
▶What characterizes normotensive secondary hyperaldosteronism?
High renin from reduced effective circulating volume — heart failure, liver cirrhosis, or nephrotic syndrome/kidney disease — with edema and normal/low BP.
▶Why does heart failure cause secondary hyperaldosteronism?
Low cardiac output reduces renal perfusion → RAAS activation → high renin and aldosterone → Na+/water retention and edema.
▶How does renal artery stenosis produce secondary hyperaldosteronism?
Reduced renal perfusion pressure stimulates renin release → ANGII → aldosterone, producing renovascular hypertension with high renin.
▶What is the treatment of primary hyperaldosteronism?
Surgical removal of an adenoma; for bilateral hyperplasia or non-surgical cases, mineralocorticoid receptor antagonists (e.g., spironolactone) and ACEi/ARB.
▶How does hypokalemia from hyperaldosteronism cause polyuria?
Hypokalemia impairs the renal concentrating mechanism (nephrogenic diabetes insipidus) → polyuria and polydipsia.
▶Why may primary hyperaldosteronism cause mild hypernatremia but not severe hypervolemia?
Na+ retention slightly raises serum Na+, but aldosterone escape limits net volume expansion, so severe volume overload is uncommon.
▶Why does hypokalemia in hyperaldosteronism impair glucose tolerance?
Low potassium reduces insulin secretion from pancreatic β-cells, decreasing glucose tolerance.
▶What is the typical renin/aldosterone profile in primary vs secondary hyperaldosteronism?
Primary: ↑aldosterone, ↓renin (high aldosterone:renin ratio). Secondary: ↑aldosterone, ↑renin.
▶Why is aldosterone excess harmful beyond raising blood pressure?
It directly promotes cardiac and vascular fibrosis, inflammation, and remodeling, increasing cardiovascular risk independent of BP.