Adrenal gland anatomy and physiology

Morphology & Location

• Shape: Left = crescent-shaped; Right = pyramidal
• Size: ~5 cm height, 1-2 cm width
• Weight: 4-6 grams each in adults
• Location: Retroperitoneal, superior to kidney upper poles
• Enclosure: Renal fascia and adipose capsule

Vascular Supply

Adrenal Cortex Structure

• G: Glomerulosa (outermost) → Aldosterone
• F: Fasciculata (middle) → Cortisol
• R: Reticularis (innermost) → Androgens

Adrenal Medulla Structure

• Composition: Chromaffin cells (modified sympathetic neurons)
• Organization: Clusters and cords around blood vessels
• Innervation: Preganglionic sympathetic fibers (splanchnic nerves)
• Special Features:
  • Chromaffin reaction: cells stain brown with chromium salts
  • Contain neurosecretory granules
  • No axons (hormones released directly into blood)

• Mineralocorticoids (Zona Glomerulosa)
  • Aldosterone → The Salt Saver
    • Primary Action: ↑ Na+ reabsorption, ↑ K+ excretion
    • Target: Principal cells of collecting duct
    • Mechanism: Genomic (slow) via mineralocorticoid receptors
    • Clinical Correlation: Hyperaldosteronism → Hypertension + Hypokalemia
      

      Aldosterone – Functional Effects
      Function	Mechanism	Clinical Effect
      Sodium Retention	↑ ENaC channels ↑ Na-K-ATPase	↑ Blood volume ↑ Blood pressure
      Potassium Excretion	↑ K⁺ secretion in DCT/CD	Risk of hypokalemia
      Hydrogen Excretion	↑ H⁺ secretion	Metabolic alkalosis

• Glucocorticoids (Zona Fasciculata)
  • Cortisol→ The Stress Master
    • Peak Time: 8 AM (circadian rhythm)
    • Binding: 90% protein-bound (cortisol-binding globulin)
    • Half-life: 90 minutes
    • Most Common Cause of Excess: Exogenous administration
      

      Cortisol - Systemic Effects
      System	Physiologic Effects	Pathologic Effects (Excess)
      Metabolism	• ↑ Gluconeogenesis • ↑ Lipolysis • ↑ Protein catabolism	• Diabetes mellitus • Central obesity • Muscle wasting
      Immune	• Anti-inflammatory • Immunosuppression	• ↑ Infection risk • Poor wound healing
      Cardiovascular	• ↑ Cardiac output • ↑ Vascular tone	• Hypertension • Atherosclerosis
      Bone	• ↓ Bone formation • ↑ Bone resorption	• Osteoporosis • Fractures

• Adrenal Androgens (Zona Reticularis)
  • Primary Hormones:
    • DHEA (Dehydroepiandrosterone)
    • DHEAS (DHEA-Sulfate) - most abundant
    • Androstenedione
  • Clinical Significance:
    • Women: Major source of androgens
    • Men: Minimal contribution (testicular androgens dominate)
    • Children: Responsible for pubarche

• Catecholamines (Adrenal Medulla)
  • Epinephrine (Adrenaline) – 80% of medullary output
    • Primary Effects: ↑ Heart rate, ↑ BP, ↑ Glucose, Bronchodilation
    • Receptors: β₁, β₂ > α₁
    • Unique Feature: Only made in adrenal medulla
    • Clinical Correlation: Pheochromocytoma → Episodic hypertension

    Catecholamine Output & Effects
    Catecholamine	% of Output	Primary Receptors	Key Actions
    Epinephrine	80%	β₁, β₂ > α₁	• Cardiac stimulation • Bronchodilation • Glycogenolysis • Lipolysis
    Norepinephrine	20%	α₁, β₁ > β₂	• Vasoconstriction • ↑ Blood pressure • Modest cardiac effects
    Dopamine	<5%	D₁, D₂	• Renal vasodilation • Neurotransmitter

     

  • Catecholamine Synthesis Pathway
    • Tyrosine → L-DOPA → Dopamine → Norepinephrine → Epinephrine
    • Tyrosine hydroxylase: Tyrosine → L-DOPA (rate-limiting)
    • Aromatic L-amino acid decarboxylase: L-DOPA → Dopamine
    • Dopamine β-hydroxylase: Dopamine → Norepinephrine
    • PNMT: Norepinephrine → Epinephrine (requires cortisol)
  • Metabolic Effects of Catecholamines
    

    Catecholamine Effects by System
    System	Epinephrine Effects	Norepinephrine Effects
    Cardiovascular	• ↑ Heart rate • ↑ Contractility • ↓ Peripheral resistance	• ↑ Blood pressure • ↑ Peripheral resistance • Minimal heart rate change
    Metabolic	• ↑ Glucose (major) • ↑ Lipolysis • ↑ Metabolic rate	• ↑ Glucose (minor) • ↑ Lipolysis • ↑ Metabolic rate
    Respiratory	• Bronchodilation • ↑ Respiratory rate	• Minimal effects

• Hypothalamic-Pituitary-Adrenal (HPA) Axis
  • Cortisol Regulation – "The Stress Response"
    • Pathway: Stress → CRH → ACTH → Cortisol → Negative Feedback
    • Circadian Pattern: Peak at 8 AM, trough at midnight
    • Stress Response: Overrides negative feedback
    • Clinical Pearl: Dexamethasone suppresses normal axis
  • HPA Axis Components
    1. Hypothalamus:
       • Releases CRH (Corticotropin-Releasing Hormone)
       • Responds to stress, circadian rhythm
    2. Anterior Pituitary:
       • Releases ACTH (Adrenocorticotropic Hormone)
       • Responds to CRH
    3. Adrenal Cortex:
       • Releases Cortisol
       • Responds to ACTH
    4. Negative Feedback:
       • Cortisol inhibits CRH and ACTH
       • Maintains homeostasis
• Renin-Angiotensin-Aldosterone System (RAAS)
  • Aldosterone Regulation – "The Volume Controller"
    • Triggers: ↓ Blood volume, ↓ BP, ↓ Na⁺, ↑ K⁺
    • Primary Stimulus: Angiotensin II
    • Secondary Stimulus: Hyperkalemia
    • Clinical Pearl: ACE inhibitors block aldosterone production
      

      Step	Stimulus	Response	Clinical Significance
      1. Renin Release	↓ BP, ↓ Volume, ↑ Sympathetic	Kidney releases renin	JGA cells sense pressure
      2. Angiotensin I	Renin + Angiotensinogen	Forms Angiotensin I	Liver produces substrate
      3. Angiotensin II	ACE converts Ang I	Forms Angiotensin II	Lungs have highest ACE
      4. Aldosterone	Ang II stimulates zona glomerulosa	Aldosterone secretion	Independent of ACTH

• Sympathetic Nervous System Control
  • Preganglionic Innervation:
    • Splanchnic nerves (T5–T12)
    • Acetylcholine → Nicotinic receptors
  • Stimulus-Secretion Coupling:
    • Calcium-dependent exocytosis
    • Rapid response (seconds)
  • Clinical Correlations:
    • Spinal cord injury: Loss of sympathetic control
    • Pheochromocytoma: Autonomous catecholamine release

• Major Adrenal Disorders
  • Most Common Adrenal Pathologies
    • Benign: Adrenal adenoma (hyperaldosteronism)
    • Malignant: Metastatic disease (lung, breast, kidney)
    • Functional: Cushing syndrome (excess cortisol)
    • Pediatric: Congenital adrenal hyperplasia
      

      Major Adrenal Disorders
      Condition	Hormone Involved	Key Features	Diagnostic Test
      Cushing Syndrome	↑ Cortisol	• Central obesity • Striae • Hypertension • Diabetes	• 24h urine cortisol • Dexamethasone suppression • Midnight salivary cortisol
      Addison Disease	↓ Cortisol + Aldosterone	• Fatigue • Hyperpigmentation • Hypotension • Hyperkalemia	• AM cortisol • ACTH stimulation test • Renin/aldosterone
      Hyperaldosteronism	↑ Aldosterone	• Hypertension • Hypokalemia • Metabolic alkalosis	• Aldosterone/renin ratio • Salt loading test • Aldosterone suppression
      Pheochromocytoma	↑ Catecholamines	• Episodic hypertension • Headache • Palpitations • Sweating	• 24h urine catecholamines • Plasma metanephrines • Clonidine suppression

  • Adrenal Crisis
    • Triggers: Stress, infection, surgery, abrupt steroid withdrawal
    • Symptoms: Shock, hypotension, nausea, vomiting, abdominal pain
    • Laboratory: Hypoglycemia, hyponatremia, hyperkalemia
    • Treatment: IV hydrocortisone 100mg q8h + IV fluids
• Clinical Pearls
  • Bilateral adrenal enlargement: Think metastases, lymphoma, or hemorrhage
  • Incidental adrenal mass: "Incidentaloma" – most are benign
  • Waterhouse-Friderichsen: Adrenal hemorrhage in meningococcemia
  • Adrenal insufficiency: May be first sign of autoimmune polyglandular syndrome