DEVELOPMENT OF THE ADRENAL GLANDS

Historical Note

• First detailed anatomic description by Bartholomeo Eustacius in 1563.

Overview

• Each adrenal gland consists of:
  • Cortex: Derived from mesenchymal tissue.
  • Medulla: Derived from ectodermal neural crest tissue.
• Both parts are enveloped in a common capsule.

Cortical Development

1. Early Embryogenesis (5th–6th Week)
   • Proliferation of mesenchymal (coelomic) cells adjacent to the urogenital ridge → primitive cortex.
   • These cells penetrate retroperitoneal mesenchyme and form a fetal cortical mass.
2. Permanent Cortex Formation
   • Soon after the primitive cortex forms, a thin outer layer of cells (from the same mesodermal source) envelops it → permanent cortex.
   • By the 8th week, the forming cortex is in intimate contact with the cranial pole of the kidney and invests in a connective tissue capsule.
   • This early adrenal is very large compared to the kidney.
3. Fetal vs. Permanent Cortex
   • Fetal (Primitive) Cortex: Major bulk of the gland at birth; rapidly involutes after birth.
     • By 2 weeks postpartum, the glands lose ~1/3 of their weight.
     • The fetal cortex fully disappears by the end of the first year.
   • Permanent (Outer) Cortex: Thin at birth; differentiates further once fetal cortex involutes.
     • Full zonal differentiation (glomerulosa, fasciculata, reticularis) completes around the 3rd year of life.
4. Role of Transcription Factors
   • Differentiation dependent on temporal expression of genes (e.g., steroidogenic factor 1, zona glomerulosa–specific protein, inner zone antigen).

Medullary Development

1. Neural Crest Origin
   • Ectodermal cells from neural crest migrate to form sympathetic neurons (autonomic system).
   • Some neural crest cells differentiate into chromaffin cells instead of neurons.
2. Chromaffin Cells
   • Named for their brown staining with chromium salts (oxidation of catecholamines).
   • Migrate from primitive autonomic ganglia adjacent to the developing cortex into the adrenal to form the medulla (7th week onward).
3. Paraganglia and Organ of Zuckerkandl
   • Some chromaffin cells remain outside the adrenals → paraganglia along the aorta.
   • Organ of Zuckerkandl: A large paraganglion near the inferior mesenteric artery; prominent in fetuses, a key extra-adrenal catecholamine source in infancy.

Accessory and Absent Glands

• True Accessory Adrenal Glands (cortex + medulla) are rare; can be found in celiac plexus or kidney cortex.
• Adrenal “Rests” (usually cortical only) may occur near the main gland or in retroperitoneum, spleen, etc.
• Gonadal Proximity during embryonic life → ectopic adrenal tissue may appear in the spermatic cord, scrotum, ovary, or broad ligament.
• Absent Adrenal Gland on one side can occur but bilateral absence is extremely rare.

ANATOMY AND BLOOD SUPPLY OF THE ADRENAL GLANDS

Location and Gross Anatomy

1. Retroperitoneal
   • At the upper poles of the kidneys.
   • Level of ~T11 rib to L1 vertebra; each weighs ~3.5–6 g.
2. Capsule and Appearance
   • Surrounded by areolar (fatty) tissue; covered by a thin fibrous capsule.
   • Golden-yellow cortical tissue on section; reddish-brown medullary center.
3. Right Adrenal Gland
   • Triangular (“pyramidal”) shape.
   • Higher and more lateral; close to right diaphragmatic crus.
   • Surrounded by liver (anterosuperiorly), IVC (medially), upper pole of the right kidney (inferolaterally).
4. Left Adrenal Gland
   • Elongated or semilunar shape, slightly larger.
   • Often overlaps the lateral border of the aorta.
   • Posterior surface adjacent to diaphragm, splanchnic nerves.
   • Upper 2/3 behind lesser sac; lower 1/3 near pancreas body and splenic vessels.

Blood Supply

1. Arterial Supply: Extremely rich and variable, with 12 or more small arterial branches.
   • Superior Adrenal Artery (from inferior phrenic),
   • Middle Adrenal Artery (from aorta),
   • Inferior Adrenal Artery (from renal artery).
   • Arteries encircle the gland, forming a network to supply cortex and medulla.
2. Venous Drainage
   • Right Adrenal Vein → directly into IVC; ~4–5 mm long.
   • Left Adrenal Vein → left renal vein (often joined by left inferior phrenic vein).
   • Both adrenals have a single large central vein that collects blood from cortex & medulla.

Adrenal Vasculature Integration

• Cortical->Medullary Flow
  • Cortisol-rich blood from cortical sinusoids flows into medullary sinusoids.
  • Enhances phenylethanolamine-N-methyltransferase (PNMT) activity, converting norepinephrine to epinephrine in medulla.
  • Extra-adrenal chromaffin sites lack this high cortisol → produce mostly norepinephrine.

Surgical Approaches to the Adrenal Glands

1. Open Transabdominal
   • Incision: Extended subcostal or midline (for bilateral disease).
   • Left adrenal: via gastrocolic ligament into lesser sac → mobilize pancreas, open Gerota fascia, retract kidney.
   • Right adrenal: mobilize hepatic flexure, retract right liver lobe upward.
2. Open Posterior
   • Patient prone; less postoperative pain, reduced ileus.
   • Curvilinear incision (10th rib to iliac crest) or resection of 12th rib. Access behind kidney.
3. Laparoscopic Transabdominal
   • Standard approach for unilateral masses <8 cm with no suspicion of invasive malignancy.
   • Patient lateral decubitus; typically 4 trocars below costal margin.
   • Right side: Retract liver; left side: mobilize colonic flexure.
   • Lower morbidity, faster recovery.
4. Posterior Retroperitoneoscopic
   • Patient prone, 3 trocars in flank.
   • Insufflation of retroperitoneal space (20–25 mm Hg).
   • Good for patients with prior abdominal surgeries (no adhesions).
5. Keys to Success
   • Careful patient selection, knowledge of anatomy, gentle tissue handling, meticulous hemostasis, awareness of vascular anomalies.
   • Adrenal parenchyma is fragile.

INNERVATION OF THE ADRENAL GLANDS

Sympathetic Innervation

1. Preganglionic Fibers
   • Arise from T11–L2 spinal cord segments (lateral horns).
   • Travel via white rami → splanchnic nerves (greater, lesser, least) → celiac, aorticorenal, renal ganglia.
   • Many fibers pass through these ganglia without synapsing → form adrenal plexus on the gland’s medial border.
2. Medullary Innervation
   • Preganglionic fibers terminate directly on chromaffin cells (equivalent to postganglionic sympathetic neurons).
   • Some small ganglia exist within medulla or near vessels.
   • Parasympathetic supply from the celiac branch of posterior vagal trunk may also reach the adrenal plexus.

Functional Significance

• Chromaffin Cells (in medulla) release epinephrine, norepinephrine, and dopamine.
• Fight-or-Flight Response triggered by hypothalamus, pons, medulla → sympathetic outflow to T/L spine → adrenal medulla.

HISTOLOGY OF THE ADRENAL GLANDS

Cortex and Medulla

• Cortex (~90% of adult adrenal)
  • Embryological origin: Mesoderm.
  • 3 Zones: Zona glomerulosa, fasciculata, reticularis.
• Medulla (~10% of adult adrenal)
  • Embryological origin: Neural crest.
  • Contains chromaffin cells producing catecholamines (epinephrine > norepinephrine).

Adrenal Cortex Details

1. Zona Glomerulosa
   • Outer thin layer: cells arranged in loops or “glomeruli.”
   • Secretes aldosterone (mineralocorticoid), regulates Na⁺/K⁺ balance.
   • Largely independent of ACTH; controlled by renin–angiotensin system.
2. Zona Fasciculata
   • Middle broad layer: cells in long straight cords (“fascicles”), rich in lipid vacuoles.
   • Produces cortisol (glucocorticoid).
   • Dependent on pituitary ACTH.
3. Zona Reticularis
   • Inner layer next to medulla, cords form reticular network.
   • Secretes cortisol and some adrenal androgens (e.g., DHEA).
   • Also dependent on ACTH.
4. Blood Supply
   • 30–50 small arteries → capsular plexus → radial capillaries in cortex → drains into medullary sinusoids → single central adrenal vein.

Adrenal Medulla Details

• Columnar Chromaffin Cells
  • Produce epinephrine (∼80%) and norepinephrine (∼20%), small amounts of dopamine.
  • Stain brown with chromium salts (oxidation of catecholamines).
• Direct Sympathetic Innervation
  • Preganglionic fibers release ACh onto chromaffin cells → catecholamine secretion.
• Vessels
  • Arterial supply from short cortical arteries passing straight into medulla + venous outflow from cortical sinusoids.