Adrenal Gland

Question 1

Where are the adrenal glands, how big are they, and what do they look like on a scan?

What is the orientation of this image? (i.e. which is the left adrenal gland, and which is the right one?

Answer 1

Just above the kidneys - 3-4 cm in size, look like triangles on CT scans

Question 2

Fill in the labels on this diagram of the blood supply to the adrenal gland:

Answer 2

The inferior vena cava (IVC) comes up from the legs, and travels up to the heart

Right adrenal gland has many arteries (57 according to Grey’s Anatomy), but only one vein, which drains into the IVC - important to note during surgeries, as all the arteries need to be clipped

Left adrenal gland also has many arteries supplying it blood, but one vein that drains into the renal vein, and the renal vein drains into the IVC

All the arteries supplying the adrenal glands enter from the outside, but their veins emerge from the inside (medulla portion)

Question 3

What is the advantage of the right adrenal gland having only one vein that drains into the IVC directly?

Why is it harder to cannulate the vein of the left adrenal gland?

Answer 3

Allows for clinicians to measure hormone secretions accurately, by cannulating that one vein

It’s vein drains into the renal vein, which drains into the IVC, so the cannula needs to turn 2 corners (shown in the diagram)

Question 4

Draw a diagram showing the position of the adrenal glands and their blood supply system:

Answer 4

Question 5

What are the 2 parts of the adrenal gland?

What are the names of the different zones of the adrenal cortex and what hormones do they each produce?

What hormone does the adrenal medulla produce?

What type of hormones does the adrenal medulla produce?

Answer 5

Adrenal cortex and medulla

The adrenal cortex is made up of 3 zones:

Zona glomerulosa (outermost zone) - set of enzymes that make the hormone aldosterone

Zona fasciculata (thick one) - makes the hormone cortisol (and some sex steroids)

Zona reticularis - also makes the hormone cortisol (and some sex steroids)

Adrenal medulla (inner most section) - secretes catecholamines i.e. makes adrenaline (and some noradrenaline)

Adrenal cortex (made up of the first 3 zones only, not the adrenal medulla) makes corticosteroids (so aldosterone, cortisol, testosterone and oestrogen)

Question 6

What are the adrenal hormones? Fill in the table:

Answer 6

Question 7

Fill in the labels in the diagram showing which zones of the adrenal cortex release which hormone:

In which organisms is the production of sex steroids more important?

Answer 7

More important in animals rather than humans

Question 8

Fill in the labels of the adrenal cortex under the microscope:

Describe the rest of the image?

How can the zones be seen more clearly?

Answer 8

Thin outer layer = capsule

ZG = aldosterone production

ZF = cortisol production

Medulla = adrenaline production

Using a stain with an Ab that binds ot the specific hormones

Question 9

How do all the hormones eventually filter into the renal vein?

Fill in the labels on this diagram:

Answer 9

One of many of the suprarenal arteries enter from the outside and pass through the capsule layer

Travel through the glomerulosa picking up the aldosterone, goes into the deeper zones to pick up the cortisol, eventually all the hormones drain into the central vein

The central vein then drains into the IVC

Question 10

Draw a diagram detailing the different zones of the adrenal cortex and what hormones they produce:

Answer 10

Question 11

What is the precursor for the production of corticosteroids from the adrenal cortex? What is the structure of it?

What is the length of the carbon chain / backbone in cholestrol i.e. how many carbons?

What is meant by the term steroids and what are different types of steroids and their effects?

Is adrenaline a steroid?

Answer 11

Cholestrol

27 carbons

Steroid = any of the molecules that come from cholestrol (must have cholestrol backbone, note the number of carbons)

Some steroids help build muscle (sex steroid), other steroids are prescribed for autoimmune conditions (cortisol), etc.

No, does not come from cholestrol

Question 12

Which zones of the adrenal gland follow which pathways in the diagram?

How are the end-products of each of the pathways produced?

Answer 12

The pathways from left to right: first pathway produces aldosterone from the zona glomerulosa, the second and third pathways are cortisol and sex steroids respectively from the zona fasciculata and zona reticularis

Specific enzymes catalyse the synthesis of speciific alterations to the molecules

Mineralocorticoid = controls mineral levels e.g. Na+, K+

Glocucorticoid = controls glucose, and so consequently BP

Question 13

Describe the pathway for the synthesis of aldosterone from cholestrol:

How many enzymes required from making the precursor to forming aldosterone? How is aldosterone production controlled to control mineral (Na+ / K+) levels?

Answer 13

1. Cholestrol’s side chain (C22) is cleaved to form pregnenolone
2. 3 beta hydroxy steroid dehydrogenase oxidises the alcohol group in pregnenolone to form a ketone group, producing progesterone
3. Hydroxylate (put an OH group on) position 21 using 21 hydroxylase forms the precursor to aldosterone (called 11 deoxycorticosterone)
4. Hydroxylate position 11 using 11 hydroxylase (forms corticosterone)
5. Hydroxylate position 17 using 17 hydroxylase to finally form aldosterone

3 enzymes - these enzymes can be controlled to regulate aldosterone production to control mineral levels

Question 14

What is the pathway for the synthesis of cortisol from cholestrol?

Answer 14

1. Cholestrol’s side chain (C22) is cleaved to form pregnenolone
2. 3 beta hydroxy steroid dehydrogenase oxidises the alcohol group in pregnenolone to form a ketone group, producing progesterone
3. Hydroxylate position 17 using 17 hydroxylase (to form 17 hydroxy-progesterone)
4. Hydroxylate position 21 using 21 hydroxylase (to form 11 deoxy-cortisol)
5. Hydroxylate position 11 using 11 hydroxylase to finally form cortisol

Question 15

What is the pathway for the synthesis of testosterone from cholestrol? (covered in the gonad lecture)

What is the difference between testosterone production and oestrogen production?

Answer 15

This is covered in the gonads lecture

V. small change between testosterone and oestrogren - therefore small errors in the pathways can have huge implications

Question 16

Fill in the missing labels in this diagram, summarising the 3 pathways to produce aldosterone, cortisol and testosterone from cholestrol:

Answer 16

Question 17

What is aldosterone important in controlling?

Where does aldosterone act?

Blood pressure is driven by which ion?

What is aldosterone’s mechanism of action?

What’s lost in the presence of aldosterone?

Answer 17

Blood pressure control

Aldosterone promotes Na+ and H2O reabsorption in the DCT to increase BP (also acts on sweat glands, and colon)

BP is dependent on Na+, and Na+ concentration in the blood (as it affects osmosis of water in / out of cells)

When BP falls, aldosterone production increases, and it travels via the bloodstream to the DCT cells. It is lipid soluble, it enters the cell and turns on genes that synthesise Na+ channels. Na+ channels attach on the lumen side of the DCT cell, and Na+/K+ pumps attach on the blood side of the DCT cell, which uses ATP to pump Na+ into the bloodstream from the urine - increases amount of Na+ being taken back into the blood, so water reabsorption also consequently increases (due to osmotic forces)

K+ and H+ lost

Question 18

What is renin and why is it released when BP falls? (e.g. when you lose blood)

Where is the low BP detected?

What hormone stimulates the production of renin?

How does renin perform its action?

Answer 18

Regulates aldosterone production / release - when BP drops, more renin is produced to stimulate more aldosterone produciton, so blood volume increases to restore normal BP

In the juxtaglomerular apparatus

Adrenaline

Renin converts angiotensinogen (an enzyme) to form angiotensin I, and then angiotensin converting enzyme (ACE) forms angiotensin II. Angiotensin II causes the constriction of vassels and also stimulates the renal gland to produce aldosterone

Question 19

What are the effects of angiotensin II on the adrenal glands?

Answer 19

Activates the series of enzymes (all the hydroxylases) that leads to the production of aldosterone from cholestrol

Question 20

Summarise what that actions of aldosterone are?

Answer 20

Controls BP, increases Na+ and H2O reabsorption, and lowers K+ and H+ in the blood

Question 21

What is cortisol regulated by?

What is cortisol and what is its action?

Answer 21

The pituitary gland - (unlike aldosterone = BP and kidney system), this is controlled by the hormone ACTH

Stress hormone - released when you feel threatened (i.e. fight or flight response)

Works by turning on gluconeogenesis (to increase plasma glucose), changes fat metabolism by breaking down fat, increases BP for higher blood flow

Question 22

Where are the 2 sets of negative feedback loops produced by cortisol?

Answer 22

When cortisol levels go up, it suppresses ACTH (adrenocorticotrohpin hormone) production, and the precursor of ACTH, CRH (corticotrophin hormone)

Question 23

Draw a simplistic diagram detailing the HPA axis?

Answer 23

HPA = Hypothalamo Pituitary Adrenal

Question 24

Fill in the missing labels of the HPA axis drawing:

Answer 24

CRH - stands for corticotrophin

ACTH - is also called corticotrophin

CRH comes down to the pituitary gland and causes the pituitary galnd to form ACTH

ACTH acts on the adrenal gland, so the adrenal cortex produces cortisol

There are 2 negative feedback loops of cortisol - one to the pituitary (ACTH production) and one to the hypothalamus (CRH production)

Question 25

What are the effects of ACTH on the adrenal gland? What molecule stimulates the pathway that leads to the production of aldosterone?

Answer 25

Stimulates the activation of the pathway that produces cortisol from cholestrol - turns on the relevant enzymes Angiotensin II

Question 26

What is the circadian pattern of cortisol production in the average human? Why is it important to note the pattern of cortisol production?

Answer 26

Diurnal: Low during midnight, starts rising at about 5am, peaks when person wakes (8:30am ish), then gradually lowers throughout the day Medications can be set to match the circadian rhythm, e.g. if a person needs to take cortisol supplements, it would be best to take them in the morning

Question 27

What is Addison's disease and what is it caused by? What did patterns in patients did Thomas Addison notice in the 18th century? How do the symptoms present clinically?

Answer 27

Primary renal failure (adreno-cortical failure) - caused by either an autoimmune condition which destroys the adrenal cortex or tuberculosis (TB), which kills the cells of the adrenal gland When the adrenal gland failed to produce cortisol and aldosterone, BGL (blood glucose levels) fell, hyperpigmentation (even in places where the sun does not hit, e.g. gums), hypoglycaemic, vomiting, dehydration, eventually death, vitiligo, and in the post mortums: atrophy or TB in the adrenal gland Lack of aldosterone = responsible for weight loss, low BP, low salt levels; Lack of cortisol = hypoglycaemia (as cortisol liberates glucose for energy, esp. in stressful situations); Increased POMC / MSH produciton = hyperpigmentation; vitiligo (if you have one autoimmune condition, you're likely to have another)

Question 28

What major precursor molecule does the adrenal gland make, so when it breaks down, it releases a molecule that causes the tanning? What is the action of this precursor? So why or how does this precursor resulting in hyperpigmentation in patients?

Answer 28

POMC (proopiomelanocortin) This large precursor that is broken down to produce ACTH and MSH (melanocyte stimulating hormone) When a patient has adrenal failure, the negative feedback loop causes the production of more ACTH. Therefore, more POMC molecules need to be broken down for ACTH production, so more MSH is also made as the side product

Question 29

What investigations are used for the diagnosis of Addison's disease? What is the treatment for Addison's disease?

Answer 29

Look at blood Na+ levels and K+ levels - symptoms = high K+ and low Na+ Look at hyperpigmentation - ACTH levels high due to disrupted negative feedback loop; not enough cortisol = no negative feedback loop on the pituitary so ACTH is not inhibited ACTH goes up because POMC goes up, as ACTH and MSH are cleaved off POMC (byproducts) ---- Give cortisol and aldosterone replacement - if replacing cortisol, levels are diurnal (so should be taken in the morning) ICU treatment = saline (to replace lost salt), glucose (as they are hypoglycaemic), give them the steroids they are missing (i.e. glucocorticoid etc.)

Question 30

What is Cushing syndrome? What are some causes of Cushing syndrome? What are the symptoms of Cushing syndrome?

Answer 30

Too much production of cortisol 1. Steroids by mouth; 2. pituitary adenoma = tumour - causes excess ACTH production 3. Ectopic (in the wrong place) ACTH - e.g. lung cancer tumours producing ACTH though its not suppose to 4. Adrenal adenoma / carcinoma - excess cortisol production Symptoms = weight gain (change in metabolism), depression, retain fat and lose protein, thin skin, muscle weaknesses, poor protein synthesis (poor wound healing, stretchmarks etc), depression (cortisol affects the brain), diabetic, high BP, moon face, difficulty climbing stairs (very thin legs but put on weight), steroid suppress immune system

Question 31

What type of hormones does the adrenal medulla produce? What is the precursor for these hormones? What is the pathway for the production of these hormones from its precurson?

Answer 31

Catechloamines e.g. adrenaline, noradrenal etc. An amino acid called tyrosine Tyrosine is hydroxylated to dopamine in the medulla, then the dopamine is activated by further oxidation to produce noradrenaline (NA) or with an extra added methyl group, adrenaline (A)

Question 32

What is the role of calcetamines? How do calcetamines travel in the bloodstream? How are calcetamines degrades / broken down (so their effects cease and don't last forever)?

Answer 32

Fight or flight response - increases heart rate, constricts blood vessels, increases blood glucose concentration and alertness, etc. The are bound to albumin By 2 enzymes: monoamine oxidase and catechol-O-methyl transferase