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Introduction

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

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Normal Structure & Function of the Adrenal Medulla

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Anatomy

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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).

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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.)

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Histology

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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, where 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 paraganglions, 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.

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Physiology

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

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Formation, Secretion, & Metabolism of Catecholamines

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The adrenal medulla secretes three catecholamines: epinephrine, norepinephrine, and dopamine. Secretion occurs after release of acetylcholine from the preganglionic neurons that innervate the medullary cells. The major biosynthetic pathways and hormonal intermediates for the catecholamines are shown in Figure 12–2. In humans, most (80%) of the catecholamine output of the adrenal medulla is epinephrine. Norepinephrine is principally found in paraganglionic nerve endings of the sympathetic nervous system and in the CNS, where it functions as a major neurotransmitter.

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Figure 12–2

Biosynthesis and catabolism of catecholamines. The catecholamines are synthesized from tyrosine (TYR). The enzyme catechol-O-methyltransferase (COMT) generates metanephrine (MN) from epinephrine (E) and normetanephrine (NM) from norepinephrine. COMT ...

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