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INTRODUCTION

The adrenal medulla secretes catecholamines (epinephrine, norepinephrine, dopamine). The catecholamines help prepare the body to deal with emergency situations. The major disorder of the adrenal medulla is pheochromocytoma, a neoplasm characterized by excessive catecholamine secretion.

NORMAL STRUCTURE & FUNCTION OF THE ADRENAL MEDULLA

ANATOMY

The adrenal medulla is the reddish-brown central portion of the adrenal gland. Accessory medullary tissue is sometimes located in the retroperitoneum near the sympathetic ganglia or along the abdominal aorta (paraganglia) (Figure 12–1).

FIGURE 12–1

Anatomic distribution of extra-adrenal chromaffin tissue in the newborn. (Redrawn, with permission, from Coupland R. The Natural History of the Chromaffin Cell. Longman, Green, 1965.)

HISTOLOGY

The adrenal medulla is made up of polyhedral cells arranged in cords or clumps. Embryologically, the adrenal medullary cells derive from neural crest cells. Medullary cells are innervated by cholinergic preganglionic nerve fibers that reach the gland via the splanchnic nerves. The adrenal medulla can be regarded as a specialized sympathetic ganglion, in which preganglionic sympathetic nerve fibers (using acetylcholine as a neurotransmitter) directly make contact with postganglionic cells, which secrete catecholamines (mainly epinephrine) directly into the circulation. This relationship is analogous to the other sympathetic ganglia, which connect preganglionic cholinergic sympathetic nerve fibers with postganglionic fibers using catecholamines (mainly norepinephrine) as neurotransmitters. Medullary parenchymal cells accumulate and store their hormone products in prominent, dense secretory granules, 150–350 nm in diameter. Histologically, these cells and granules have a high affinity for chromium salts (chromaffin reaction) and thus are called chromaffin cells and contain chromaffin granules. The granules contain the catecholamines epinephrine and norepinephrine. Morphologically, two types of medullary cells can be distinguished: epinephrine-secreting cells, which have larger, less dense granules, and norepinephrine-secreting cells, which have smaller, very dense granules. Separate dopamine-secreting cells have not been identified. Ninety percent of medullary cells are the epinephrine-secreting type, and 10% are the norepinephrine-secreting type.

PHYSIOLOGY

The catecholamines help to regulate metabolism, the contractility of cardiac and smooth muscle, and neurotransmission.

Formation, Secretion & Metabolism of Catecholamines

The adrenal medulla secretes three catecholamines: epinephrine, norepinephrine, and dopamine. Secretion occurs after the release of acetylcholine from the preganglionic neurons that innervate the medullary cells. Figure 12–2 illustrates the major biosynthetic pathways and hormonal intermediates for the catecholamines. In humans, most (80%) of the catecholamine output of the adrenal medulla is epinephrine. This epinephrine predominance occurs because the enzyme phenylethanolamine N-methyltransferase (PMNT), which converts norepinephrine to epinephrine, is upregulated by cortisol, which is found in high concentration locally from the surrounding adrenal cortex. Norepinephrine is principally found in paraganglial cells associated with the sympathetic nervous system and in the central nervous system, where it functions as a major neurotransmitter.

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