External environmental changes can create scenarios that the human brain interprets as dangerous or stressful. The body can be equipped to face these changes under the influence of the adrenal glands. These yellow, asymmetrical organs, located suprarenally and bilaterally in the retroabdominal cavity, are responsible for secreting stress hormones that stimulates the physiological adaptations necessary to mitigate the change in the external environment. This article will evaluate the development of the adrenal glands, the relationship between its structure and function, neurovascular and lymphatic components and some pathological conditions that they are associated with.
The adrenal glands have two embryonic origins, and consequently produce two different types of signalling chemicals. The outer cortex is of mesodermal origin and releases steroidal hormones, while the inner medulla is derived from ectoderm and secretes adrenergic neurotransmitters (also known as catecholamines). In the 5th developmental week, mesothelial cells enter the mesenchymal layer. Subsequently, large acidophilic cells differentiate, forming a primitive cortex. Smaller cells then migrate and engulf the acidophilic cells; these will go on to form the definitive cortex.
In the 7th developmental week, neural crest cells that are formed at the apex of the neural folds migrate (after the neural tube is completely closed) via a ventral pathway. These cells enter the gland from the medial face and subsequently differentiate into chromaffin cells that are organized centrally, in cords and masses. The chromaffin cells are so named because of the yellow-brown stain they produce after reacting with chromium based salts.
Structure – Function Relationship
The left and right suprarenal glands differ slightly in their shape and location on top of their respective kidneys. The right gland is more pyramidal and sits on top of the upper pole of the kidney, while the left gland is more crescenteric and hangs more over the medial side of the left kidney, superior to the hilum. The right adrenal gland rests on the diaphragm and the medial anterior portion is crossed by the inferior vena cava. While on the left side, the adrenal gland rests on the left crus of the diaphragm and the upper anterior surface is covered by the peritoneum. On both sides, the adrenal glands are enclosed in the renal fascia of Gerota, with a sheath of fascia separating it from its kidney.
Essentially the gland is divided into three layers. However, only two of these layers are of homeostatic significance. There is an outer fatty capsule just deep to the renal fascia that functions as an added protective layer.
Deep to the capsule, is the adrenal cortex. The cortex can be subdivided into the zona glomerulosa, the zona fasciculata and the zona reticularis. The zona glomerulosa is comprised of small rounded cells that are responsible for secreting mineralocorticoids such as aldosterone. Aldosterone regulates the uptake of water in the distal convoluted tubules, which consequently alters the body’s blood pressure. Zona fasciculata is significantly thicker than the other two cortical layers. It is made up of pale staining vacuolated cells arranged in parallel rows. This layer is responsible for secreting glucocorticoids to increase the overall blood glucose level in an effort to provide more energy for a system under stress. Finally, the zona reticularis consists of smaller cells that stain darker relative to cells of the aforementioned layers. Here, adrenal androgens are produced, which serve as precursors for testosterone.
At the center of the organ is a thin, grey medulla. Residing here are chromaffin cells, splanchnic nerves and dilated capillaries. The chromaffin cells are responsible for the production of catecholamines, namely epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine. Epinephrine is released directly into the medullary capillaries and carried to their site of action via systemic circulation. The physiological effect it has is dependent on the neuroreceptors present at the site at which the chemical acts.
The action of the adrenal gland is regulated both by neuronal and hormonal stimulation. The cortex is activated by adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. ACTH subsequently stimulates the respective cortical zones to produce corticosteroids. On the other hand, the adrenal medulla is innervated by type B (medium diameter, myelinated) preganglionic nerve fibers. These nerve fibers leave the intermediolateral cell column of the lateral horn of the spinal cord from the T5 – T8 segments of the spinal cord and bypass the paravertebral sympathetic ganglion chain. The fibers converge after bypassing the sympathetic trunk, forming the greater splanchnic nerve. Some of these fibers will synapse at the celiac ganglion and post-synaptic fibers of the celiac ganglion will innervate the blood vessels supplying the suprarenal gland. Other fibers of the greater splanchnic nerve will bypass the celiac ganglion and enter the adrenal gland to synapse on the membranes of chromaffin cells.
For this reason, the adrenal medulla is sometimes considered as a neuroendocrine bridge between the two physiological segments. The chromaffin cells act as enlarged post-ganglionic fibers that release their neurochemicals directly into the blood stream instead of at a neuroeffector junction.
Vascular and Lymphatic System
The adrenal glands receive arterial supply directly from the abdominal aorta as well as from the inferior phrenic arteries and the renal arteries. The inferior phrenic arteries leave the anterior surface of abdominal aorta just superior to the celiac trunk. Each inferior phrenic artery travels superolaterally and at the upper medial borders of the adrenal glands, they branch into several superior suprarenal arteries that enter the gland. The middle suprarenal arteries branch directly from the anterolateral surface of the abdominal aorta, adjacent to the celiac trunk. These vessels travel horizontally and pierce the lower medial border of the adrenal glands by way of their branches. Also, each renal artery provides an inferior suprarenal artery that enters the inferior aspect of the gland. The left inferior suprarenal artery travels vertically and cranially towards the gland, while the right vessel travels more horizontally and obliquely towards its destination. Both glands return deoxygenated blood to systemic circulation by way of a right and a left suprarenal vein. The right suprarenal vein takes a short horizontal course to drain directly into the inferior vena cava. However, the left suprarenal vein travels vertically to the renal vein, which then drains to the inferior vena cava. Lymphatic drainage is achieved by para-aortic lymph nodes.
Pathologies of the suprarenal gland can arise from either the cortex or the medulla. Pituitary adenomas can result in a hypersecretion of ACTH. The excess ACTH will overstimulate the adrenal cortex, resulting in hypercortisolism, or Cushing syndrome. The disease is more predominant in women in the young adult age group. Immunosuppression, muscular atrophy, weight gain and hyperglycaemia are some of the clinical manifestations of the disease. Both medical and surgical options can be implemented to correct this disorder.
Pheochromocytoma (PCC) is the primary neoplasm of the adrenal medulla. These tumors are rare and may precipitate life threatening hypertension. The neoplasms can also affect extra-adrenal chromaffin tissue. The lesion results in a hyper production of catecholamines, which consequently results in an overactive sympathetic response. Diaphoresis (excessive sweating), flank pain, anxiety, tremors, tachyarrhythmia (fast, irregular heartbeats), cardiomyopathy (weakness of the cardiac muscles) and postural hypertension (increase in blood pressure when moving from a sitting to standing position) are all clinical presentations associated with the disease. PCC can be managed surgically in conjunction with medical treatment.