Adrenal Gland

Question 1

Describe the vascular drainage of the adrenal glands

Answer 1

Left adrenal vein drains into renal vein. Right adrenal vein drains into Inferior Vena Cava. Both adrenals have many arteries stemming from abdominal aorta but only one vein.

Question 2

Describe microanatomy of the adrenal glands and functions

Answer 2

Adrenal gland composed of an adrenal cortex and adrenal medulla. The adrenal medulla secretes catecholamines such as adrenaline. The adrenal cortex consists of three zones , listed from outside in: Zona glomerulosa, Zona fasciculata and Zona reticularis. Zona glomerulosa is the first layer and relatively thin, secreting aldosterone. Zona fasciculata is the largest zone (appears thickest) and secretes cortisol mainly. Zona reticularis is relatively thin and does not have a clear function in humans except secreting small amounts of sex hormone. The adrenal cortex secretes corticosteroids.

Question 3

Describe secretions of adrenal glands in detail

Answer 3

The adrenal medulla secretes mainly catecholamines, mostly epinephrine (80%) and norepinephrine. Dopamine is a precursor of both these molecules and so a small amount of dopamine is also secreted. The adrenal cortex secretes corticosteroids such as mineralocorticoids (aldosterone), glucocorticoids (cortisol) and sex steroids.

Question 4

Describe the organisation of blood vessels in the adrenal gland

Answer 4

Capsule has capsular plexus which forms from the divisions of the suprarenal artery on the surface of the adrenal gland. The cortical capillaries branch through the layers of the zones. These then branch to form the medullary capillaries in the medulla and link to the central vein.

Question 5

What is a steroid?

Answer 5

A hormone whose precursor is cholesterol. The precursor of mineralocorticoids. glucocorticoids and sex steroids is cholesterol.

Question 6

What is an enzyme and its function?

Answer 6

Protein that catalyses a specific reaction. Various enzymes are present in cells. Specific enzymes catalyse the synthesis of particular alterations to the molecule.

Question 7

Describe process of aldosterone formation and the enzymes involved

Answer 7

Cholesterol undergoes side-chain cleavage by side chain cleavage enzymes, forming pregnenolone. Pregnenolone is then acted on by 3 beta Hydroxy Steroid Dehydrogenase to form progesterone. 21 Hydroxylase then removes a hydroxyl group from carbon 21 on progesterone forming 11 deoxycorticosterone. This is acted on by 11 hydroxylase, forming corticosterone. Finally, 18 hydroxylase acts to produce aldosterone.

Question 8

Describe process of cortisol formation and the enzymes involved

Answer 8

Progesterone is acted on by 17 hydroxylase to form 17-hydroxyprogesterone. This is acted on by 21 hydroxylase, forming 11-deoxycortisol. Finally 11 hydroxylase acts to produce cortisol.

Question 9

What does aldosterone do?

Answer 9

Stimulates Na+ reabsorption in distal convoluted tubule and cortical collecting duct in kidney (and in sweat glands, gastric glands, colon). Stimulates K+ and H+ secretion, also in distal convoluted tubule and cortical collecting duct. Does this by controlling ATPase activity. As Na+ is responsible for blood pressure, aldosterone therefore indirectly controls blood pressure as well. If sodium is reabsorbed, water is also reabsorbed which increases blood volume.

Question 10

When is renin released?

Answer 10

When blood pressure falls, it is detected by various receptors in the juxtaglomerular apparatus in the kidneys and Macula Densa. It is detected by:

1. Decreased renal perfusion pressure (normally associated with decreased arterial BP detected by baroreceptors in arteriole)
2. Increased renal sympathetic activity (direct to JGA cells detected by beta 1-adrenergic receptors)
3. Decreased Na+ load to top of loop of Henle (detected by macula densa cells)

Question 11

How does renin act?

Answer 11

The liver releases angiotensinogen into the bloodstream. Renin cleaves this to form angiotensin-1. Angiotensin I is then converted to angiotensin II by angiotensin-converting enzyme (ACE). This conversion occurs mainly in the lungs where ACE is produced by vascular endothelial cells, although ACE is also generated in smaller quantities within the renal endothelium. Angiotensin-2 has many different impacts on receptors across the body but when it binds to those in the adrenal cortex, it stimulates the release of aldosterone.

Question 12

What are the effects of angiotensin II on the adrenals?

Answer 12

Leads to activation of the following enzymes:
Side Chain Cleavage
3 Hydroxysteroid dehydrogenase
21 hydroxylase
11 hydroxylase
18 hydroxylase

Question 13

What are the physiological effects of cortisol?

Answer 13

Cortisol is part of a normal stress response. Metabolic effects include: peripheral protein catabolism, hepatic gluconeogenesis, increased blood glucose concentration, fat metabolism (lipolysis in adipose tissue), enhanced effects of glucagon and catecholamines. Weak mineralocorticoid effects. Renal and cardiovascular effects include: excretion of water load and increased vascular permeability.

Question 14

How is cortisol production regulated?

Answer 14

By ACTH, produced by corticotrophs in anterior pituitary gland. When cortisol levels are high, inhibits ACTH and corticotrophin-releasing hormone production in the adenohypophysis and hypothalamus respectively.

Question 15

What is the effect of ACTH on the adrenals?

Answer 15

Activation of the following enzymes: 
Side Chain Cleavage
3 Hydroxysteroid dehydrogenase
17 hydroxylase
11 hydroxylase
21 hydroxylase

Question 16

How do cortisol levels vary through the day?

Answer 16

Follow a diurnal pattern where they are lowest during sleep and increase gradually, hitting a peak at around 8:30 in the morning before gradually decreasing again.

Question 17

What is Addison’s disease?

Answer 17

Primary adrenal failure. Is an autoimmune disease where the immune system decides to destroy the adrenal cortex, caused most commonly by tuberculosis of the adrenal glands. As the adrenal gland does not produce steroid hormones, the pituitary starts secreting lots of ACTH and hence MSH (melanocyte-stimulating hormone) as they share the precursor proopiomelanocortin (POMC).

Question 18

What are the symptoms of Addison’s disease?

Answer 18

Hyperpigmentation of the skin, weakness, low blood pressure, weight loss, nausea, diarrhea, vomiting, constipation, abdominal pain and vitiligo.

Question 19

What causes the hyperpigmentation and vitilgo characteristic of Addison’s?

Answer 19

The hyperpigmentation is caused as POMC is a large precursor protein that is cleaved to form a number of smaller peptides, including ACTH, MSH and endorphins. When more ACTH needs to be produced, MSH is also produced which leads to over-stimulation of melanocytes which are the melanin-producing cells that provide color. Overproduction of melanocytes leading to more melanin will result in a person having a darker complexion than what is natural for them. Vitiligo is caused by autoimmune destruction of melanocytes.

Question 20

What are the symptoms of an adrenal crisis?

Answer 20

Fever, syncope, convulsions, hypoglycemia, hyponatremia, severe vomiting and diarrhea.

FSC HHVD

Question 21

What are the consequences of Addison’s?

Answer 21

Cortisol deficiency and aldosterone deficiency lead to salt loss. Hence, low blood pressure and eventual death.

Question 22

How is an Addisonian crisis treated?

Answer 22

1. Rehydrate with normal saline
2. Give dextrose to prevent hypoglycaemia which could be due to the glucocorticoid deficiency
3. Give hydrocortisone or another glucocorticoid

Question 23

What is Cushing’s syndrome and what can it be caused by?

Answer 23

Occurs due to an excess of cortisol or other glucocorticoid. Common causes:

1. Taking steroids by mouth (common)
2. Pituitary dependent Cushing’s disease (pituitary adenoma)
3. Ectopic ACTH (lung cancer)
4. Adrenal adenoma or carcinoma

Question 24

What are the symptoms of Cushing’s?

Answer 24

Thin skin
Proximal myopathy
Centripetal obesity (lemon on sticks)
Diabetes, hypertension and osteoporosis
Immunosuppression (reactivation of TB)
Moon face
Striae

Question 25

Where is the adrenal medulla derived from?

Answer 25

Ectodermal neural crest

Question 26

What is the precursor for adrenaline and noradrenaline?

Answer 26

Tyrosine, converted to DOPA and then dopamine. Dopamine forms norepinephrine and if a methyl group added to norep, forms epinephrine.

Question 27

Where are catecholamines stored?

Answer 27

Catecholamines stored in cytoplasmic granules & released in response to ACh from preganglionic sympathetic neurones

Question 28

What is the role of catecholamines and what is it degraded by?

Answer 28

‘Fight or flight response’ e.g. tachycardia, sweating, increased blood glucose, alertness, vasoconstriction. NA & Adr circulate bound to albumin. Degraded by two hepatic enzymes: monoamine oxidase & catechol-O-methyl transferase.