Adrenal Histology
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Direct answer
Yellow outside, brown inside: the cut adrenal shows a lipid-rich cortex in three zones — glomerulosa, fasciculata, reticularis — wrapped around a chromaffin-cell medulla, and the colour difference is itself histology. The cortex, from mesoderm near the root of the dorsal mesentery, arranges its acidophilic cells in arches (glomerulosa, secreting aldosterone under renin-angiotensin), long radial columns of pale, foamy spongiocytes (fasciculata, the thickest zone, secreting cortisol under ACTH), and dark, compact cords (reticularis, secreting androgens). The medulla, a neurocrest derivative, is essentially a sympathetic ganglion whose neurons never grew axons: large granule-filled chromaffin cells that release adrenaline and noradrenaline on direct splanchnic stimulation, stained brown by chromium salts — the chromaffin reaction — and capped by the cortex on all sides save the hilum.
What you must remember
- Zone mnemonic GFR: glomerulosa — aldosterone; fasciculata — cortisol; reticularis — androgens (DHEA); "salt, sugar, sex" from surface inward.
- Zona glomerulosa: discontinuous layer of small cells in rounded clusters just under the capsule; the renin-angiotensin system, not ACTH, is its main driver.
- Zona fasciculata: the widest zone; pale, lipid-laden spongiocytes in straight cords with sinusoids between them — lipid droplets dissolve in processing, leaving vacuolated cytoplasm.
- Zona reticularis: dark, lipofuscin-laden compact cells in anastomosing networks adjacent to the medulla; major androgen source at adrenarche.
- Medulla: polyhedral chromaffin cells in clusters around large, muscular medullary veins; granules stain brown-black with potassium dichromate (chromaffin reaction) or with osmium.
- Embryological divide: cortex from intermediate mesoderm; medulla from neural crest — the reason medullary tumours (phaeochromocytoma) can be part of neurocristopathy syndromes.
- Clinical anchors: phaeochromocytoma follows the rough rule of tens (10 per cent familial, bilateral, extra-adrenal, malignant); cortical atrophy follows chronic exogenous steroid use via ACTH suppression; congenital adrenal hyperplasia shows a hyperplastic cortex with lipid-depleted cells.
- Blood supply logic: short cortical arteries feed the subcapsular plexus, and venous blood washes catecholamine-rich blood from medulla to cortex — cortisol induces phenylethanolamine-N-methyltransferase to methylate noradrenaline to adrenaline.
Working through a section capsule to hilum
Begin at the capsule and walk inward. Immediately beneath it, small round clusters of cells with round nuclei — the glomerulosa — may be patchy, and examiners accept that it is sometimes inapparent in adults. Next comes the desert of the fasciculata: long, pale, two-cell-wide cords of spongiocytes whose dissolved lipid leaves a moth-eaten, vacuolated look, with intervening capillaries running straight as irrigation channels toward the medulla. The reticularis darkens the field, its compact, eosinophilic cells often carrying lipofuscin pigment, before everything changes at the medulla: clumps of large, granular, basophilic-to-amphophilic chromaffin cells grouped around conspicuously thick-walled veins.
That layout is functional, not decorative. Cortical sinusoidal blood drains centripetally and bathes the medulla in high-dose cortisol, which is exactly what the medulla needs to methylate noradrenaline to adrenaline — one of the few facts that links two embryologically unrelated tissues into one endocrine organ. Clinically, take a hypertensive crisis patient whose urine shows raised metanephrines: the tumour is a phaeochromocytoma of the chromaffin cells, and histology after adrenalectomy shows an alveolar or trabecular pattern of cells with basophilic granular cytoplasm, best demonstrated by chromogranin immunostain. Conversely, a patient on long-term prednisolone has a thinned, suppressed fasciculata — ACTH suppression literally shrinks the zone it drives.
Where students slip
Two pairs get swapped in every batch. First, glomerulosa and reticularis positions: the salt hormone sits just under the capsule and the sex hormones at the deepest cortical level, so candidates who reverse them place aldosterone beside the medulla where no angiotensin signal reaches. Second, the adrenal medulla is called a ganglion or a paraganglion loosely — the precise statement is modified postganglionic sympathetic neurons without axons, innervated directly by preganglionic sympathetic fibres (T5-T9 greater splanchnic), which is why secretion is neural, fast and independent of pituitary control. The viva favourite is why adrenaline is essentially adrenal-only: the methylating enzyme PNMT needs the high cortisol delivered by cortical veins, so extra-adrenal chromaffin tissue mostly makes noradrenaline.
Frequently asked questions
Which cortical zone secretes aldosterone and what controls it?
The zona glomerulosa under the capsule; the renin-angiotensin-aldosterone axis mainly drives it, with hyperkalaemia as an additional stimulus.
Why do fasciculata cells look pale and vacuolated?
They are loaded with cholesterol ester droplets for steroidogenesis; routine processing dissolves the lipid, leaving empty vacuoles — hence spongiocytes.
What is the chromaffin reaction?
Chromaffin-cell catecholamine granules oxidise to a brown colour with potassium dichromate, identifying the medulla and extra-adrenal paraganglia.
From which germ layer do the cortex and medulla arise?
Cortex from mesoderm (celomic epithelium near the root of the mesentery); medulla from neural crest — they are two organs in one capsule.
Why does chronic steroid therapy shrink the adrenal cortex?
Exogenous glucocorticoids suppress ACTH, and the zona fasciculata and reticularis, which depend on trophic ACTH drive, undergo atrophy — a reason for tapering steroids.