Baseline Addison's Disease
No aldosterone means kidneys waste sodium and retain potassium.
- 122: Serum Sodium (mEq/L, low)
- 6.4: Serum Potassium (mEq/L, high)
- 82/54: Blood Pressure (mmHg, hypotensive)
- ~0: Aldosterone (adrenal cortex destroyed)
Adrenal cortex failure
Autoimmune or other destruction eliminates zona glomerulosa aldosterone output.
Sodium wasting
Without aldosterone, distal nephron sodium reabsorption collapses, causing volume loss.
Hyperkalemia risk
Potassium excretion falls, raising serum potassium toward dangerous levels.
Fludrocortisone Initiated
Synthetic mineralocorticoid drug starts binding renal receptors.
- 50–200: Starting Dose (mcg/day typical)
- MR: Receptor Target (mineralocorticoid receptor)
- DCT/CD: Site of Action (distal tubule / collecting duct)
- Hours–days: Onset (to initial effect)
Drug structure
Fludrocortisone is a synthetic steroid with strong mineralocorticoid activity.
Receptor binding
Molecule diffuses into tubule cells and binds cytoplasmic mineralocorticoid receptors.
Gene transcription
Receptor complex enters nucleus, upregulating sodium/potassium transport proteins.
Sodium Reabsorption & Potassium Excretion
New channels drive sodium back into blood, potassium out to urine.
- ↑: ENaC Channels (sodium reabsorption)
- ↑: ROMK Channels (potassium secretion)
- ↑: Na/K-ATPase (basolateral pump activity)
- 1–2: Response Time (weeks to steady state)
ENaC upregulation
Epithelial sodium channels increase, pulling sodium from urine back into blood.
Potassium secretion
ROMK channels open, moving potassium from blood into urine for excretion.
Electrochemical gradient
Sodium reabsorption creates a lumen-negative charge favoring potassium loss.
Dose Titrated to Response
Clinicians adjust dose using BP, sodium, and potassium trends.
- 135–145: Target Sodium (mEq/L)
- 3.5–5.0: Target Potassium (mEq/L)
- 110–130: Target BP (systolic mmHg)
- Q1–3mo: Monitoring (labs + BP checks)
Titration logic
Dose raised if hypotensive/hyponatremic, lowered if hypertensive/hypokalemic.
Postural BP
Orthostatic blood pressure drop signals under-replacement of mineralocorticoid.
Renin feedback
Plasma renin activity helps guide dose adequacy alongside electrolytes.
Balance, Overshoot, or Persistent Deficit
Correct dosing normalizes labs; wrong dosing causes new problems.
- ~125: Optimal Dose (mcg/day (individualized))
- HTN + ↓K: Over-Replacement (hypertension, hypokalemia)
- ↓Na + ↑K: Under-Replacement (hyponatremia, hyperkalemia)
- 118/76: Well-Titrated BP (mmHg, normal)
Properly titrated
Sodium, potassium, and BP settle into normal ranges with stable dosing.
Over-replacement
Excess dose drives hypertension and hypokalemia from too much sodium retention.
Under-replacement
Insufficient dose leaves hyponatremia, hyperkalemia, and hypotension unresolved.