Histology of the Adrenal Glands

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-The adrenal gland is a paired gland
-Location: Lie on the superior pole of each kidney, hence they are called the suprarenal glands, supra-above
-Suprarenal gland is located in the retroperitoneal space of abdominal cavity
-Right gland: flattened and triangular; left gland: semilunar in shape

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-Adrenal gland is covered: thick connective tissue: CAPSULE-invaginate inwards towards the adrenal
parenchyma making a trabeculae(carries blood vessels and nerves towards the parenchyma of the parenchyma
of the AG).

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-Each gland is an organ composed of 2 distinct parts
-Histologically: the secretory parenchymal tissue is organized into two distinct regions: adrenal cortex, medulla

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ADRENAL CORTEX
-Steroid secreting region of the gland, it lies immediately below the capsule
-constitutes nearly 90% of the gland by weight.

ADRENAL MEDULLA
-catecholamine secreting portion
-lies deep to the adrenal cortex, and forms the central portion of the gland

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OVERVIEW
-The adrenal gland is supplied with blood by the suprarenal arteries: these bv branch before entering the
capsule, this created many small arteries that will eventually penetrate the capsule
-The adrenal cortex receives blood from many arterioles in the capsule that enter the gland and break-up into
sinusoidal capillaries. This passes downward in close association with the parenchymal cells in the cortex.
-The capillaries within endothelium and fenestrations are able to pass through all these layers of the cortex
-At the corticomedullary junction they eventually drain into veins which eventually enters the medulla.
-Some arterioles from the capsule do not supply the cortex instead it goes directly into the medulla not flowing
through the adrenal cortex layers.
-The adrenal medulla has dual blood supplies, one is the veins from the adrenal cortex, other one is the arteriole
that directly supplies the medulla
*all the blood from the cor and med is drained PIC by a large central vein which exits at the hilum of the gland.

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Development of the Adrenal Glands
-AG arises from 2 distinct embryonic tissues:
1. Mesoderm-eventually develops into the adrenal cortex
2. Neural crest ectoderm-which develops into the adrenal medulla

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-Rarely in gestation the provisional cortex reaches the fetal adrenal cortex arises from the mesodermal cells of
the peritoneal lining and the location is closely associated to the Mesonephros: which is the primitive kidney.
This close anatomic location between the primitive kidney ad the primitive cortex remains throughout life and
is very evident to the anatomic location shared by the kidney and the adrenal gland

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-The fetal cortex is very active during fetal life. It produces corticosteroids, and at birth it constitutes 80% of
the gland.
-It then undergoes rapid involution and within the 1st months after birth the permanent cortex replaces it.
-It then eventually differentiates into 3 layers for the 1st 3 yrs. of life

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-The medulla derives from the neural crest cells, these migrates towards the adrenal cortex and invade to form
the inner medulla
-Their content epinephrine causes the cells of the AM to stain yellow brown when exposed to chrome salts
hence the name: Chromaffin Cells
-Chromaffin Cells, forms synapses with preganglionic synaptic nerve fibers but rather than becoming ganglionic
cells they form secretory epithelial cells that are able to synthesize and secrete hormones.

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HISTOLOGY OF THE ADRENAL MEDULLA
-The parenchyma of the adrenal medulla: composed of large, pale staining epithelial cells called
chromatin/chromaffin cells
-The stroma: the supportive structure of the gland is composed of connective tissues primarily with reticular
fibers numerous sinusoidal blood capillaries and nerves.
-The chromaffin cells are modified neurons that it is innervated by pre-synaptic sympathetic nerve fibers.
When impulses carried by the sympathetic fibers reach chromaffin cells they release their secretory products,
therefore chromaffin cells are considered equivalent of post-synaptic sympathetic neurons, however they lack
axonal processes.
-The lack of axonal growth among chromaffin cells is because of the inhibition imposed by the glucocorticoid
produced in the adrenal cortex, hence we include that the hormones of the adrenal cortex exert control over
the morphology of the chromaffin cells therefore they closely resemble typical endocrine cell.
*When impulses carry by sympathetic fiber reach the chromaffin cells, they release secretory products hence
they are considered as equivalent of post-synaptic neurons.

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-Chromaffin cells are organized in ovoid clusters and short interconnecting chords. The blood capillaries are
arranged in intimate relation into the parenchyma.

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-Ultra structurally the CC are *** by numerous secretory vesicles, RER, and a well-developed Golgi apparatus
-There are 2 populations of the CC in the adrenal medulla
-One population of cell contain only large, dense, or** vesicles these cells are known to secrete norepinephrine
-The other population contain vesicles that are smaller more homogenous and less dense, these cells secrete
epinephrine.
-Glucocorticoids does not only exert an effect to the morphology of the CC, glucocorticoids also induce the
enzyme that catalyzes the methylation of norepinephrine to produce epinephrine
-The nature of the bloodflow correlates with regional differences in the distribution of epinephrine and
norepinephrine containing CC
-The epinephrine containing cells with small, faint staining granules are numerous in areas of the medulla
supplied with blood, that has pass through from the cortical sinusoids and thus contains secreted glucocorticoids
-sudden release of catecholamines in established conditions for maximum use of energy and does maximum
physical effort: FIGHT OR FLIGHT RESPONSE.
-epinephrine and norepinephrine stimulate glycogenolysis which is the process of glucose release from glycogen
primarily in the liver.

ZONATION OF THE ADRENAL CORTEX

3 Zones on the basis on the arrangement of its cells
1. Zona glomerulosa- the outer, narrow zone that constitutes up to 15% of the cortical volume
2. Zona Fasciculata- the thick middle zone: 80% of the cv
3. Zona Reticularis- inner zone: 5-7% CV, but relatively thicker than the ZG bcz of its more central location
Parenchyma of the Adrenal Cortex
ZONA GLOMERULOSA
-the cells of the zona glomerulosa are arranged in a closely packed, ovoid clusters and sometime curved
columns, apparently the cells of the ZG appears to be continuous with the cellular chords of the Zona
Fasciculata.
-Cells of the Zona Glomerulosa are relatively small and characteristically columnar or pyramidal in shape
-Their spherical nuclei appear closely pack and stain densely a rich network of fenestrated network of capillaries
surrounds each cell cluster.
-Ultra structurally the cells have an abundant SER, multiple golgi complexes, and the large mitochondria with a
shelf-like cristae
-Cytoplasmic lipid droplets are sparsed
-The cells of the ZG SECRETES Mineralocorticoids primarily Aldosterone: a hormone that regulates plasma
sodium and with this K levels. Aldosterone acts on the principal cells of the DCT, the sweat glands, salivary
glands, and even the intestines to conserve sodium. This is always in exchange of K.
-Aldosterone tend to increase the sodium level in the blood=enhances excretion of K=Na conservation effect
of the hormone secondary effect is seen on water conservation.
-Rule of thumb: Whenever Na is water always follows hence effectively enhancing the plasma volume of the
blood
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-The ZG cells, lack the enzymes 17 alpha(α)-hydroxylase and 17,20-lyase, and therefore cannot produce other
adrenal steroid hormones such as: GLUCOCORTICOIDS and the ADRENAL ANDROGEN
-Only ZG cells contain the enzyme aldosterone synthase making it the only cell able to produce aldosterone.

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ZONA FASCICULATA
-the cells of the zona fasciculata are large and assumes polyhedral shape
-Cells are arranged in long straight chords, one or two cells thick
-the chords are separated from each other by sinusoidal capillaries
-The cells of the Zona Fasciculata have a lighter staining nucleus compared to the cells of the ZG, some cells even
exhibit binucleate characteristics
-Ultra structurally the ZF cells characteristic: consistent with a steroid secreting endocrine cell
-The cell exhibit a highly developed SER and they appear more numerous compared to the ZG cells
-Mitochondria is with a tubular cristae rather than shelf-like seen in ZG
-Cytoplasmic vacuoles contain neutral fats, cholesterol, and fatty acids.
-The cytoplasm is acidophilic although it usually appears vacuolated in routine histologic sections, because of
the extraction of lipid during the dehydration process while on tissue processing
-The principle secretion of the ZF is the glucocorticoids they cannot produce aldosterone because they lack the
enzyme aldosterone synthase.
-They do possess 17 alpha(α)-hydroxylase and 17,20-lyase, thus being able to synthesize and secrete
glucocorticoids, they are able to produce amounts of androgens but very minimal compared to the ZR
-Major glucocorticoids secreted by ZF: CORTISOL
-Other glucocorticoids produced: Corticosterone- circulates in the blood at a 10-20 folds lower that the cortisol
level
-Glucocorticoids have different effects on diff. tissues of the human body
• Liver-glucocorticoids stimulate the formation o glycogen from glucose. Also promotes the uptake of
amino acids and fatty acids.
• Other tissues-they reduce the rate of glucose and promote utilization of fatty acids by oxidation reaction
• In cells such as fibroblast they inhibit protein synthesis and even promote protein catabolism to provide
amino acids for conversion to glucose in the liver
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ZONA RETICULARIS
-deepest zone of the adrenal cortex
-cells: smaller than ZF
-Nuclei: more deeply stained and the arrangement of the cells are described as ANASTOMOSING CHORDS,
chord with branches.
-The anastomosing chords are separated with each other by capillary sinusoids
-The cells have relatively few lipid droplets and the presence of abundant lipofuscin pigment granules. This
lipofuscin pigment granules are due to the tertiary lysosomes seen in cytoplasm of these cells.
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-General appearance of all steroid secreting endocrine hormones
-ZR cell have well developed SER but the mitochondria appears elongated and cristae appears tubular
-Principle secretion of the ZR cell: adrenal androgens called: GONADOCORTICOIDS
-GONADOCORTICOIDS: Dehydroepiandrosterone (DHEA); Dehydroepiandrosterone-sulfate (DHEAS);
androstenedione
-The cell also secrete some glucocorticoid but in much smaller amount due to the presence of the same enzyme
as the ZF cells
-Adrenal androgens are less potent than the androgens produced by the Gonads but they do have an effect on
the development of secondary sex characteristics.
-MALES: have negligible importance because of the testosterone produced by the testis
-FEMALES: adrenal androgens stimulate the growth of axillary and pubic hair during puberty and adolescence
-DHEA can be converted into Androstenedione and more potent androgen such as : Testosterone and
estrogens in the peripheral tissues. Key enzyme that facilitates this conversion of androstenedione to estrogen
and testosterone is 17-ketosteroid reductase. And this is the pathway for the testosterone production among
women.

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