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Histology - Lecture 2 - Adrenal Glands

Note, make sure you know the learning objectives.
Basic structure and subdivisions of the adrenal gland, and how to recognize them in histological sections.

Difference in embryological origin of the major subdivisions of the adrenal gland, and how this relates to their functions.

Basic function and structure of the major cell types and different zones of the adrenal cortex.

Basic function and structure of the major cell types of the adrenal medulla.

How the vasculature of the adrenal gland is organized to allow communication within the gland and to the rest of the body.

Fundamentals of feedback loops and adrenal gland hormones.

Introduction to disorders that arise due to disruptions of adrenal gland function.
Where are the adrenal cortex cells derived from embryologically?
Where are the adrenal medulla cells derived from embryologically?
Neural crest cells.

Most are chromaffin cells. have some scattered sympathetic ganglion neurons.
What are the three gross layers of the adrenal gland?
1. The connective tissue capsule.

2. The cortex, which constitutes 90% of the weight of the gland.

3. The medulla.

Note that if you cut the adrenal gland in half, the cortex completely wraps around the medulla. So above and below the medulla is the cortex.
What are the three zones of the adrenal cortex? What do the cells look like in each zone?
1. Zona glomerulosa. - Looks like spheres.

2. Zona fasciculata. - Looks like rods.

3. Zona reticularis. - Looks like nets.
What type of secreting cells are the cells of the adrenal cortex?

Histologically what would you expect to see in the cells?
All are steroid secreting cells. So these cells are specialized for lipid metabolism.

1. They have abundant SER. This will look like grey filler background on TEM.

2. They have lipofuscin pigment granules that are common in the spongiocytes of the zona fasciculata.

3. They have lipid droplets for cholesterol storage.

4. Numerous mitochondria with tubulovesicular cristae for steroid biosynthesis.
Describe the histological appearance of the zona glomerulosa.
The cells are arranged in ovoid clusters which are continuous with the cords of the cells of the zona fasciculata. (So will not see clear distinction between the glomerulosa and the fasciculata!)

A network of FENESTRATED capillaries surround each cluster.

Cells of the zona glomerulosa secrete mineralocorticoids, mainly aldosterone.
Describe the histological appearance of the zona fasciculata.
The cells are called "spongiocytes" because of their full of holes appearance due to abundant lipid droplets. (You can see these on TEM. So will have grey mass for cells with lots of white dots, which are the lipid droplets).

Arranged in long cords, or fascicles, and are separated by SINUSOIDAL capillaries.

The cells secrete glucocorticoids such as cortisol and corticosterone. This regulates carbohydrate metabolism by promoting gluconeogenesis and the breakdown of proteins and fats.
Describe the histological appearance of the zona reticularis.
Cells are smaller than in the fasciculata. These are arranged in an irregular network.

The zona reticularis secretes weak androgens, like DHEA and androstenedione. These exert their actions after conversion into testosterone. Also have some secretion of glucocorticoids.

Note: the best way to differentiate the zona reticularis is to identify the medulla next to it.

Also note: can sometimes have spongiocytes in the reticularis in addition to the fasciculata.
How do you identify the medulla on a histological slide?
The central medullary vein is often a clue.

But just need to find the lowest region away from the capsule in which have large cells. So are looking for the chromaffin cells.
Describe the histological appearance of the chromaffin cells in the adrenal medulla.
These are large epitheloid cells.

They are the primary parenchymal cells of the adrenal medulla.

*Resemble typical peptide secreting endocrine cells: scattered organelles, secretory vesicles, and moderate RER.

Have different cells that secrete NE and Epi.
Why are the hormone-secreting cells of the adrenal medulla called chromaffin cells?
The adrenal medulla cells make proteins called chromagranins.

These are catecholamine-binding proteins and are found in secretory granules along with the catecholamines.

The staining properties of these secretory granules is what gives adrenal chromaffin cells their name -- secretory granules stain brown when exposed to chromium salts (chromaffin reaction)

Those cells containing norepinephrine stain much more intensely than cells containing epinephrine.
Where are chromaffin cells derived from embryologically?
Neural crest cells. This is why chromaffin cells are similar to paravertebral sympathetic neurons.

These cells secrete catecholamines.

Receive direct innervation from cholinergic preganglionic nerve fibers of sympathetic NS.
Are chromaffin cells neurons?

They lack axonal processes.

They secrete catecholamines into the bloodstream via fenestrated capillaries.
Describe the blood supply of the adrenal gland.
Arterial blood is supplied to the adrenal gland in two ways: 1) to the cortex through the SHORT CORTICAL ARTERIES. 2) to the medulla through the LONG CORTICAL ARTERIES.

Blood output converges to the central medullary veins. Also called the suprarenal vein.
Describe blood supply to the cortex of the adrenal gland.
The short cortical arteries enter the cortex and form fenestrated capillary network that bathes the zona glomerulosa.

Extending from these are STRAIGHT SINUSOIDAL CAPILLARIES which supply the zona fasciculata and the zona reticularis.

These cortical sinusoids drain blood, which is now rich in hormones, into a FENESTRATED capillary plexus in the zona reticularis and the medulla.

Venules from the plexus drain into the central medullary artery.
Describe blood supply to the medulla of the adrenal gland.
The long cortical arteries branch from the capsular arteries.

They transverse the adrenal cortex brining blood directly to the CAPILLARY SINUSOIDS OF THE MEDULLA.

These capillaries train into the central medullary vein.
How does the adrenal medulla have a dual blood supply?
It gets arterial blood directly from the long cortical arteries and "venous" blood from the cortical sinusoidal capillaries from the adrenal cortex.

The VENOUS BLOOD SUPPLY is analogous to the HYPOPHYSEAL PORTAL SYSTEM that communicates between the hypothalamus and anterior pituitary.
What is the physiological significance of the adrenal medulla have two blood supplies?
GLUCOCORTICOIDS, produced in the adrenal cortex, reach the adrenal medulla via the cortical sinusoids.

These glucocorticoids induce expression of PNMT (phenylethanolamine-N methyltransferase) by chromaffin cells.

PNMT catalyzes conversion of norepinephrine to epinephrine.

What is Conn's syndrome?
PRIMARY HYPERALDOSTERONISM caused by an ALDOSTERONE-producing adrenocortical adenoma. This lesion accounts for about two-thirds of cases of primary hyperaldosteronism (PHA), while bilateral adrenal hyperplasia accounts for about 30% of PHA.

Symptoms include: hypertension (due to Na+ retention, K+ secretion - think marrying equation), polyuria, muscular weakness. Will have low renin.
What is Cushing's syndrome?

This can be the result of several things:
1. Prolonged treatment with glucocorticoid drugs.
2. Cortisol-producing tumor of the adrenal cortex.
3. Ectopic production of ACTH by a non-pituitary tumor.
4. Excess stimulation by pituitary ACTH from a pituitary tumor. THIS BYPASSES THE NEGATIVE FEEDBACK LOOP

Symptoms include: obesity of face and trunk with thin legs, osteoporosis, disruption of sexual function, facial hirsutism.
What is Addison's disease?

Caused by destruction of adrenal cortex, due to tuberculosis or autoimmune disorders.

Symptoms: asthenia, pigmentation of skin and mucous membranes (lots of ACTH being made), anorexia, nervous symptoms.
What is a neuroblastoma?
Highly malignant pediatric tumor with neural characteristics.

This is considered a disorder of the adrenal medulla since it cancer of nerve tissue.
What is pheochromocytoma?
Rare tumor arising in catecholamine-secreting chromaffin cells of the adrenl medulla.

Often benign; symptoms include those associated with increased secretion of catecholamines (hypertension, nervousness, tachycardia, sweating, trembling).

If left uncorrected (e.g. by surgical removal of the tumor), hypertension due to sustained production of catecholamines can prove fatal.

Remember 10% when you think of a pheochromacytoma: 10% are bilateral, 10% are in children, 10% are malignant.