Adrenal Cortex and Medulla

Adrenal Gland Anatomy & Zones - Gland Central

• Location: Suprarenal (on superior kidney poles), retroperitoneal.
• Parts: Outer Cortex (~90%), Inner Medulla (~10%).
• Cortex Zones (Outer→Inner): 📌 GFR (Salt, Sugar, Sex)
  • Zona Glomerulosa (ZG): Aldosterone (Mineralocorticoids)
  • Zona Fasciculata (ZF): Cortisol (Glucocorticoids)
  • Zona Reticularis (ZR): Androgens (e.g., DHEA)
• Blood Supply: Rich; 3 suprarenal arteries. 1 central medullary vein.
• Innervation: Medulla: direct preganglionic sympathetic fibers (splanchnic nerves). Cortex: minimal.

⭐ R. adrenal vein → IVC; L. adrenal vein → L. renal vein.

Cortisol & Glucocorticoids - Stress Steroid Saga

• Synthesis: Zona fasciculata (adrenal cortex) from cholesterol.
  • Key enzyme: 17α-hydroxylase.
• Regulation (HPA Axis): CRH (hypothalamus) → ACTH (anterior pituitary) → Cortisol.
  • Negative feedback by cortisol on CRH & ACTH. Diurnal rhythm.
• Transport: ~90% bound to Corticosteroid-Binding Globulin (CBG), ~5-10% free (active).
• Key Actions (Stress Adaptation & Permissive Effects):
  • Metabolic: ↑Gluconeogenesis, ↑Proteolysis, ↑Lipolysis. Insulin resistance (diabetogenic).
  • Anti-inflammatory & Immunosuppressive: Inhibits Phospholipase A2, ↓cytokines (e.g., IL-2).
  • Cardiovascular: ↑BP (maintains vascular tone, permissive for catecholamines).
  • Musculoskeletal: ↓Bone formation, ↑muscle catabolism.
  • CNS: Influences mood, memory, sleep.

⭐ Cortisol exhibits a diurnal rhythm: peak in early morning, nadir at night.

Aldosterone & Mineralocorticoids - Salt Saver Star

• Source: Zona Glomerulosa (Adrenal Cortex). 📌 GFR: Salt (Glomerulosa), Sugar (Fasciculata), Sex (Reticularis).
• Primary Mineralocorticoid: Aldosterone.
• Synthesis: From cholesterol; key enzyme Aldosterone Synthase (stimulated by Angiotensin II & ↑K+).
• Regulation: Renin-Angiotensin-Aldosterone System (RAAS) is primary.

• Actions: Acts on principal & intercalated cells (late Distal Convoluted Tubule & Collecting Ducts).
  • ↑ Na+ reabsorption (via ENaC channels)
  • ↑ K+ secretion (via ROMK channels)
  • ↑ H+ secretion (via H+-ATPase)
  • Water follows Na+ → ↑ ECF volume, ↑ Blood Pressure.

⭐ Aldosterone escape: In primary hyperaldosteronism, chronic aldosterone excess leads to volume expansion, but edema is limited due to pressure natriuresis and ANP action.

Adrenal Androgens & Cortex Pathologies - Cortex Chaos

• Adrenal Androgens: DHEA, Androstenedione (Zona Reticularis). Peripheral conversion to sex steroids.
• Cushing's Syndrome: ↑ Cortisol. Features: central obesity, striae, HTN. Screen: Low-dose DST, 24hr UFC.
• Addison's Disease: ↓ Cortisol, ↓ Aldosterone. Features: weakness, pigmentation, hypotension, ↑K+, ↓Na+. ACTH stim test.
• Conn's Syndrome: ↑ Aldosterone. Features: HTN, ↓K+, alkalosis. Aldosterone:Renin ratio > 20.
• CAH: Enzyme defects (e.g., 21-hydroxylase def.). ↓ Cortisol, ↓/normal Aldo, ↑ Androgens (virilization). 📌 Salt wasting, virilization.

⭐ Nelson's syndrome: Rapid enlargement of pituitary ACTH-secreting adenoma after bilateral adrenalectomy for Cushing's disease. Presents with hyperpigmentation & visual field defects.

Adrenal Medulla & Pheochromocytoma - Catecholamine Rush

• Adrenal Medulla: Chromaffin cells (neural crest) secrete catecholamines: Epinephrine (E), Norepinephrine (NE).
  • PNMT (cortisol-induced) converts $NE \rightarrow E$.
  • Actions: "Fight-or-flight" (↑HR, ↑BP, ↑glucose).
• Pheochromocytoma: Chromaffin cell tumor.
  • 📌 Rule of 10s (approximate values for malignant, bilateral, extra-adrenal, pediatric, familial).
  • Symptoms (episodic): 5 P's - Pressure (HTN), Pain (headache), Perspiration, Palpitations, Pallor.
  • Diagnosis: ↑ 24hr urinary/plasma metanephrines & VMA.
  • Treatment: Pre-op α-blockade (e.g., phenoxybenzamine) THEN β-blockade, then surgery.

  ⭐ Plasma free metanephrines are the most sensitive screening test for pheochromocytoma. oka

High‑Yield Points - ⚡ Biggest Takeaways

• Adrenal cortex: Glomerulosa (Aldosterone), Fasciculata (Cortisol), Reticularis (Androgens).
• Aldosterone: Regulated by RAAS & K+; acts on DCT/CD for Na+ reabsorption.
• Cushing's syndrome: Excess cortisol; features central obesity, striae, hypertension.
• Addison's disease: ↓Cortisol & ↓Aldosterone; causes hypotension, hyperpigmentation, hyperkalemia.
• Pheochromocytoma: Medullary tumor of catecholamines; causes paroxysmal hypertension, palpitations, headache.
• 21-hydroxylase deficiency: Most common CAH; ↓Cortisol, ↓Aldosterone, ↑Androgens, causing virilization.