adrenal glands anatomy and physiology and function

1. ADRENAL GLANDS
RIMSHA RIZWAN
ROLL NO: 206-BH-
CHEM-20
SEMESTER: VII (M)
SUBMITTED TO:
DR SAMINA
DEPARTMENT OF
CHEMISTRY
GOVERNMENT
UNIVERSITY,
LAHORE

2. Contents
Abstract........................................................................................................................................... 2
Adrenal glands ................................................................................................................................ 3
1.1 Anatomy of the Adrenal Glands ............................................................................................... 3
1.1.1 Cortex............................................................................................................................. 4
1.1.2 Medulla .......................................................................................................................... 5
1.2 Vasculature ........................................................................................................................... 5
2. Embryology................................................................................................................................. 8
3. Hormones of the Adrenal Glands ............................................................................................... 9
3.1 Cortisol.............................................................................................................................. 9
3.1.1 How Adrenal Glands Work to Produce Cortisol ......................................................... 10
3.2 Aldosterone..................................................................................................................... 11
3.3 DHEA and Androgenic Steroids..................................................................................... 11
3.4 Epinephrine (Adrenaline) and Norepinephrine (Noradrenaline) .................................... 12
4. Adrenal Gland Disorders .......................................................................................................... 13
4.1 Adrenal Insufficiency.......................................................................................................... 13
4.1.2 Congenital Adrenal Hyperplasia.................................................................................. 14
4.1.3 Addison's disease ......................................................................................................... 15
4.2 Overactive Adrenal Glands................................................................................................. 15
4.2.1 Excess of Cortisol: Cushing Syndrome ....................................................................... 16
4.2.2 Excess of Aldosterone: Hyperaldosteronism............................................................... 16
4.2.3 Pheochromocytoma...................................................................................................... 17
4.3 Adrenal Cancer ............................................................................................................... 17
5. Conclusion ................................................................................................................................ 17

3. Abstract
The adrenal glands are essential endocrine organs located above the kidneys. This assignment
provides a brief overview of their structure, function, and significance. The adrenal glands consist
of two parts: the outer adrenal cortex and the inner adrenal medulla. The cortex produces hormones
like cortisol, which regulate metabolism and immune response, and aldosterone, which controls
electrolyte balance. Meanwhile, the medulla produces adrenaline and noradrenaline, crucial for
the body's "fight or flight" response. Understanding the adrenal glands is crucial for
comprehending stress, blood pressure regulation, and various medical conditions like Cushing's
syndrome and Addison's disease. This assignment aims to shed light on the pivotal role these
glands play in maintaining physiological balance.

4. Adrenal glands
Adrenal glands may develop nodules that can be benign or malignant, which can potentially
produce excessive amounts of certain
hormones leading to various health.
The adrenal glands are located in the
posterior abdomen, between the
superomedial kidney and the
diaphragm. They are retroperitoneal,
with parietal peritoneum covering
their anterior surface only [2].
The right gland is pyramidal in
shape, contrasting with the semi-
lunar shape of the left gland.
Perinephric (or renal) fascia encloses the adrenal glands and the kidneys. This fascia attaches the
glands to the crura of the diaphragm. They are separated from the kidneys by the perirenal fat [7].
The adrenal glands sit in close proximity to many other structures in the abdomen:
Right adrenal gland Left adrenal gland
Anterior Posterior Anterior Posterior
 Inferior vena cava
 Right lobe of the liver
 Right crus of the
diaphragm
 Stomach
 Pancreas
 Spleen
 Left crus of the diaphragm
1.1 Anatomy of the Adrenal Glands
An adrenal gland is made of two main parts:

5. The adrenal glands consist of an outer connective tissue capsule, a cortex and a medulla. Veins
and lymphatics leave each gland via the hilum, but arteries and nerves enter the glands at numerous
sites [1].
The outer cortex and inner medulla are the functional portions of the gland. They are two separate
endocrine glands, with different embryological origins:
 Cortex – derived from the embryonic mesoderm.
 Medulla – derived from the ectodermal neural crest cells.
The cortex and medulla synthesise different hormones.
1.1.1 Cortex
The cortex is yellowish in colour. It secretes two cholesterol derived hormones – corticosteroids
and androgens. Functionally, the cortex can be divided into three regions (superficial to deep):
 Zona glomerulosa – produces and secretes mineralocorticoids such as aldosterone.
 Zona fasciculata – produces and secretes corticosteroids such as cortisol. It also secretes
a small amount of androgens [4].

6. Zona reticularis – produces and secretes androgens such as dehydroepiandrosterone (DHES). It
also secretes a small amount of corticosteroids [1].
The function of these three zones can be remembered by the mnemonic "Salt, Sugar, Sex," as they
correlate to the function of the hormones produced in each layer of the adrenal cortex. The names
of these zones can also be recalled by remembering "GFR" for glomerulosa, fasciculata, and
reticularis.
The adrenal medulla synthesizes catecholamines. Catecholamines are made from the precursor of
dopamine and combined with tyrosine, thus resulting in norepinephrine. Once norepinephrine has
been created, it is then methylated via phenylethanolamine N-methyltransferase (PNMT), which
is only present in the adrenal medulla [9].
1.1.2 Medulla
The medulla lies in the centre of the gland, and is dark brown in colour. It contains chromaffin
cells, which secrete catecholamines (such as adrenaline) into the bloodstream in response to stress.
These hormones produce a ‘flight-or-fight‘ response. Chromaffin cells also secrete enkephalins
which function in pain control. The adrenal medulla is located inside the adrenal cortex in the
center of an adrenal gland. It produces “stress hormones,” including adrenaline [3].
The adrenal cortex and adrenal medulla are enveloped in an adipose capsule that forms a
protective layer around an adrenal gland.
1.2 Vasculature

7. The adrenal glands have a rich blood supply via three main arteries:
Superior adrenal artery – arises from the inferior phrenic artery
Middle adrenal artery – arises from the abdominal aorta.
Inferior adrenal artery – arises from the renal arteries.
Right and left adrenal veins drain the glands. The right adrenal vein drains into the inferior vena
cava, whereas the left adrenal vein drains into the left renal vein. As the adrenal glands produce
various systemically-important hormones, they require significant blood supply and are extremely
well vascularized [13]. The blood supply is tightly controlled by neuroendocrine and paracrine
mechanisms, which is one method of regulating the systemic levels of adrenal hormones.
Variations in adrenal artery origin are very common. The superior adrenal artery can come off the
abdominal aorta, celiac axis, or, more rarely, an intercostal artery. The superior adrenal artery is
also commonly found as multiple arteries [1].
1.3 Innervation
The adrenal glands are innervated by the coeliac plexus and greater splanchnic nerves.
Sympathetic innervation to the adrenal medulla is via myelinated pre-synaptic fibres, mainly from
the T10 to L1 spinal cord segments. The function of the adrenal gland is mediated by both synaptic
stimulation and hormonal stimulation. Adrenocorticotropic hormone (ACTH) secreted from the
anterior pituitary gland activates the adrenal cortex. Subsequently, ACTH activates the respective
cortical zones to generate corticosteroids. However, the adrenal medulla is innervated by

8. preganglionic nerve fibers (type B) arising from the intermediolateral cell column of the spinal
cord's lateral horn from the T5–T8 spinal cord segments [9].
These nerve fibers form the greater splanchnic nerve without entering the paravertebral
sympathetic ganglion chain. Some of the nerve fibers from the greater splanchnic nerve synapse
at the celiac ganglion. The blood vessels supplying the adrenal glands will then receive their
innervation from the celiac ganglion's postsynaptic fibers. On the other hand, some fibers of the
greater splanchnic nerve circumvent the celiac ganglion and directly enter the adrenal gland to
synapse at the chromaffin cells' membranes. This is the reason why the adrenal medulla acts as a
neuroendocrine junction between the two physiological segments. The chromaffin cells release
their neurohormones directly into the bloodstream to produce a widespread sympathetic response
and apparently act as a special type of postsynaptic neuron [5] .

9. 1.4 Lymphatics
Lymph drainage is to the lumbar
lymph nodes by adrenal
lymphatic vessels. These vessels
originate from two lymphatic
plexuses – one deep to the
capsule, and the other in the
medulla.The venous drainage
from the adrenal glands is
dependent on the side of the
gland. The left adrenal gland is
anatomically further away from
the inferior vena cava, and
therefore the left adrenal vein drains into the left renal vein. The right adrenal vein is much closer
to the inferior vena cava and drains directly into this large vessel. Variations in adrenal venous
drainage are common, particularly on the left side. There are reports of venous connections
between the left adrenal vein and the left genital vein, and the inferior phrenic vein. Double left
adrenal veins are also common. [2]
2. Embryology
The adrenal gland is composed of two embryologically distinct tissues that contain two different
forms of signaling chemicals. One is the outer cortex of mesodermal origin, which produces steroid
hormones [4]. The other is a medulla that is derived from neuroectoderm and secretes
catecholamines. In the 5th week of development, an isolated cluster of cells emerges within the
urogenital ridge, identified as the adrenal-gonadal primordial germ cells. Mesothelial cells
penetrate the mesenchymal layer and form fetal adrenal cortex and Leydig cells [16].

10. Consequently, large acidophilic cells differentiate to form a primitive cortex. Smaller cells then
migrate and engulf these acidophilic cells; they will proceed to form the definitive cortex. During
the 7th week of development, neural crest cells formed at the apex of the neural folds migrate into
the adrenal primordium via a ventral pathway. These cells enter the gland from the medial face
and then differentiate into chromaffin cells centrally arranged in cords and masses. The cortex
engulfs and gradually encapsulates the whole medulla in the later stages of embryonic
development [7].
At a molecular level, many factors were described to be essential for the development of adrenal
glands. The most essential among them are steroidogenic factor-1, CITED-2, β-catenin, and others
[2].
3. Hormones of the Adrenal Glands
The role of the adrenal glands in your body is to release certain hormones directly into the
bloodstream. Many of these hormones have to do with how the body responds to stress, and some
are vital to existence. Both parts of the adrenal glands — the adrenal cortex and the adrenal medulla
— perform distinct and separate functions [3].
Each zone of the adrenal cortex secretes a specific hormone. The key hormones produced by the
adrenal cortex include:
3.1 Cortisol

11. Cortisol is a glucocorticoid hormone produced by the zona fasciculata that plays several important
roles in the body. It helps control the body’s use of fats, proteins and carbohydrates; suppresses
inflammation; regulates blood pressure; increases blood sugar; and can also decrease bone
formation. This hormone also controls the sleep/wake cycle. It is released during times of stress to
help your body get an energy boost and better handle an emergency situation.
3.1.1 How Adrenal Glands Work to Produce Cortisol
Adrenal glands produce hormones in response to signals from the pituitary gland in the brain,
which reacts to signaling from the hypothalamus, also located in the brain [4]. This is referred to
as the hypothalamic pituitary adrenal axis. As an example, for the adrenal gland to produce cortisol,
the following occurs:
 The hypothalamus produces corticotropin-releasing hormone (CRH) that stimulates the
pituitary gland to secrete adrenocorticotropin hormone (ACTH).

12.  ACTH then stimulates the adrenal glands to make and release cortisol hormones into the
blood.
 Normally, both the hypothalamus and the pituitary gland can sense whether the blood has
the appropriate amount of cortisol circulating. If there is too much or too little cortisol,
these glands respectively change the amount of CRH and ACTH that gets released. This is
referred to as a negative feedback loop.
 Excess cortisol production can occur from nodules in the adrenal gland or excess
production of ACTH from a tumor in the pituitary gland or other source [1].
3.2 Aldosterone
This mineralocorticoid hormone produced by the zona glomerulosa plays a central role in
regulating blood pressure and certain electrolytes (sodium and potassium). Aldosterone sends
signals to the kidneys, resulting in the kidneys absorbing more sodium into the bloodstream and
releasing potassium into the urine. This means that aldosterone also helps regulate the blood pH
by controlling the levels of electrolytes in the blood. [11]
3.3 DHEA and Androgenic Steroids

13. These hormones produced by the zona reticularis are weak male hormones. They are precursor
hormones that are converted in the ovaries into female hormones (estrogens) and in the testes into
male hormones (androgens). However, estrogens and androgens are produced in much larger
amounts by the ovaries and testes [7].
3.4 Epinephrine (Adrenaline) and Norepinephrine (Noradrenaline)
The adrenal medulla, the inner part of an adrenal gland, controls hormones that initiate the flight
or fight response. The main hormones secreted by the adrenal medulla include epinephrine
(adrenaline) and norepinephrine (noradrenaline), which have similar functions [8].
Among other things, these hormones are capable of increasing the heart rate and force of heart
contractions, increasing blood flow to the muscles and brain, relaxing airway smooth muscles, and
assisting in glucose (sugar) metabolism. They also control the squeezing of the blood vessels
(vasoconstriction), helping maintain blood pressure and increasing it in response to stress [2].

14. Like several other hormones produced by the adrenal glands, epinephrine and norepinephrine are
often activated in physically and emotionally stressful situations when your body needs additional
resources and energy to endure unusual strain [4].
4. Adrenal Gland Disorders
The two common ways in which adrenal glands cause health issues are by producing too little or
too much of certain hormones, which leads to hormonal imbalances. These abnormalities of the
adrenal function can be caused by various diseases of the adrenal glands or the pituitary gland.
4.1 Adrenal Insufficiency
Adrenal insufficiency is a rare disorder. It may be caused by disease of the adrenal glands (primary
adrenal insufficiency, Addison’s disease) or by diseases in the hypothalamus or the pituitary
(secondary adrenal insufficiency). It is the opposite of Cushing syndrome and is characterized by

15. low levels of adrenal hormones. The symptoms include weight loss, poor appetite, nausea and
vomiting, fatigue, darkening of skin (only in primary adrenal insufficiency), abdominal pain,
among other [7].
The causes of primary adrenal insufficiency may include autoimmune disorders, fungal and other
infections, cancer (rarely), and genetic factors.
Although adrenal
insufficiency usually
develops over time, it can
also appear suddenly as an
acute adrenal failure
(adrenal crisis). It has
similar symptoms, but the
consequences are more
serious, including life-
threatening shock,
seizures, and coma. These
may develop if the
condition is left untreated
[16] .
4.1.2 Congenital Adrenal Hyperplasia
Adrenal insufficiency can also result from a genetic disorder called congenital adrenal hyperplasia.
Children who are born with this disorder are missing an essential enzyme necessary to produce
cortisol, aldosterone or both. At the same time, they often experience excess of androgen, which
may lead to male characteristics in girls and precocious puberty in boys [18].
Congenital adrenal hyperplasia can remain undiagnosed for years depending on the severity of the
enzyme deficiency. In more severe cases, infants may suffer from ambiguous genitalia,
dehydration, vomiting and failure to thrive.

16. 4.1.3 Addison's disease
Addison's disease refers to primary hypoadrenalism, which is
a deficiency in glucocorticoid and mineralocorticoid
production by the adrenal gland. In the Western world,
Addison's disease is most commonly an autoimmune
condition, in which the body produces antibodies against cells
of the adrenal cortex. Worldwide, the disease is more
frequently caused by infection, especially from tuberculosis.
A distinctive feature of Addison's disease is
hyperpigmentation of the skin, which presents with other
nonspecific symptoms such as fatigue [11].
Fig: Characteristic skin color in Addison’s Disease
4.2 Overactive Adrenal Glands
Sometimes, adrenal glands may develop nodules that produce too much of certain hormones.
Nodules 4 centimeters or larger and nodules that show certain features on imaging increase
suspicion for malignancy. Both benign and cancerous nodules may produce excessive amounts of
certain hormones, which is referred to as a functional nodule [1]. Functional tumors, malignant

17. tumors or nodules greater than 4 centimeters are
recommended to be referred for surgical
evaluation [15].
4.2.1 Excess of Cortisol: Cushing Syndrome
Cushing syndrome results from excessive
production of cortisol from the adrenal glands.
The symptoms may include weight gain and
fatty deposits in certain areas of the body, such
as the face, below the back of the neck called a
buffalo hump and in the abdomen; thinning
arms and legs; purple stretch marks on the
abdomen; facial hair; fatigue; muscle weakness; easily bruised skin; high blood pressure; diabetes;
and other health issues [5].
Excess cortisol production can also be triggered by overproduction of ACTH by a benign tumor
in the pituitary gland or tumor elsewhere in the body. This is known as Cushing Disease. Another
common cause of Cushing syndrome is excessive and prolonged consumption of external steroids,
such as prednisone or dexamethasone, which are prescribed to treat many autoimmune or
inflammatory diseases (e.g., lupus, rheumatoid arthritis, asthma, inflammatory bowel disease,
multiple sclerosis, etc [6].
4.2.2 Excess of Aldosterone: Hyperaldosteronism
Hyperaldosteronism results from overproduction of aldosterone from one or both adrenal glands.
This is characterized by increase in blood pressure that often requires many medications to control.
Some people can develop low potassium levels
in the blood, which can cause muscle aches,
weakness and spasms. When the cause is
adrenal oversecretion, the disease is called
Conn syndrome [9].
Excess of Adrenaline or Noradrenaline:

18. 4.2.3 Pheochromocytoma
Pheochromocytoma is a tumor that results in excess production of adrenaline or noradrenaline by
the adrenal medulla that often happens in bursts. Occasionally, neural crest tissue, which has
similar tissue to the adrenal medulla, may be the cause of overproduction of these hormones. This
known as a paraganglioma [13].
Pheochromocytomas may cause persistent or
sporadic high blood pressure that may be difficult to
control with regular medications. Other symptoms
include headaches, sweating, tremors, anxiety and
rapid heartbeat. Some people are genetically
predisposed to developing this type of tumor [2].
4.3 Adrenal Cancer
Malignant adrenal tumors (adrenal cancer), such as
adrenocortical carcinoma, are rare and often have
spread to other organs and tissues by the time they
are diagnosed. These tumors tend to grow fairly
large and can reach several inches in diameter [3].
Cancerous adrenal tumors can be functional and release excess of one or more hormones
accompanied by corresponding symptoms, as listed above. Patients may also experience
abdominal pain, flank pain or a feeling of abdominal fullness, especially when the adrenal tumor
gets very large. Not all cancers found in adrenal glands originate from the gland itself. The majority
of adrenal tumors are metastasis, or cancer spread, from another primary tumor elsewhere in the
body[10].
5. Conclusion
The adrenal glands are like tiny factories in our bodies that make special chemicals called
hormones. These hormones help control many important things, like how we deal with stress, how

19. we use energy, and how our bodies keep the right balance of salt and water. The cortex makes
hormones like cortisol and aldosterone, which help us manage stress and keep our bodies in
balance [1]. The medulla makes adrenaline and noradrenaline, which make our hearts beat faster
and give us energy when we're in danger. Sometimes, the adrenal glands don't work as they should,
and that can cause health problems. We discussed conditions like Cushing's syndrome and
Addison's disease, which happen when these glands have trouble making the right hormones [5].
Understanding the adrenal glands is essential for our health because they play a big part in keeping
our bodies working well. Doctors and scientists are always studying them to help people stay
healthy and deal with life's challenges effectively [12].

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