1a The Adrenal Gland Flashcards
What does the left adrenal gland drain into?
The renal vein
What does the right adrenal gland drain into?
The inferior vena cava
How many arteries and veins are there in the adrenal glands?
One central vein, many arteries
Where are the adrenal glands located?
Above the kidneys
What is the adrenal cortex composed of?
The zona glomerulosa
The zona fasciculata
The zona reticularis
What does the adrenal cortex secrete?
Corticosteroids
What is secreted in the zona glomerulosa?
Aldosterone
What is secreted in the zona fasciculata?
Cortisol
What are catecholamines?
Adrenaline and noradrenaline
Where are catecholamines secreted from?
The adrenal medulla
What is the relative percentages of adrenaline and nor-adrenaline produced?
80% ADRENALINE
20% NORADRENALINE
What is the precursor for all steroid hormones?
Cholesterol
How many carbons do cholesterol molecules have?
27
How is cholesterol turned into pregnenolone?
Side chain cleavage
What enzyme converst pregnenolone into progesterone?
3-Beta Hydroxy Steroid dehydrogenase
Which enzymes are specifically found in the zona glomerulosa?
Those involved in the synthesis of steroids like aldosterone and corticol from cholesterol
What are the numbers of Hydroxylases and the intermediate names that eventually take Progestone to Aldosterone?
21 Hydroxylase-> 11 deoxy- corticosterone
11 Hydroxylase -> corticosterone
18 Hydroxylase-> aldosterone
Where is the adrenal medulla derived from?
Ectodermal neural crest
What do the hydroxylase enzymes do?
Add an OH group to that position on the molecule
How is Adrenaline formed from its amino acid precursor
Tyrosine hydroxylated to form Dopa
Dopa decarboxylated to form Dopamine
Dopamine hydroxylated to form noreadrenaline
Noradrenaline methylated to form adrenaline
What is the precursor amino acid for Adrenaline and Noradrenaline?
Tyrosine
What are the numbers of hydroxylases that are required to take Progestone and convert it into Cortisol?
17 Hydroxylase
21 Hydroxylase
11 Hydroxylase
What is the function of aldosterone?
The major net effect is to conserve body sodium by stimulating its reabsorption into the blood
Explain how aldosterone works to increase sodium reabsorption
- Aldosterone binds to receptors on nucleus
- Causes the transcription of certain genes which results in Sodium ion channels and Na+/K+ Pumps being opened
- This results in an influx of Na+ from the urine, and more Na+ being pumped into blood
What affect does increase sodium reabsoprtion have on the blood pressure?
Increased Na+ into the blood, sets up a high concentration gradient for water, meaning water is reabsorbed into the blood also by osmosis
This water reabsorption raises blood volume and therefore raises blood pressure as well
What is the name of the renin secreting cells?
Juxtaglomerular cells
Which cells detect changes in blood pressure?
Cells in the macula densa
What is released and from where when the blood pressure drops?
Renin released from the juxtaglomerular apparatus
What regulates the release of aldosterone?
Angiotensin II
What effect does renin have on Angioteninogen?
Renin cleaves angiotensinogen to form angiotensin I
What enzyme is used to convert Angiotensin I to Angiotensin II?
Angiotensin converting enzyme ACE
What does angiotensin II do?
Acts on the zona glomerulosaof the adrenal cortex to stimulate the release of aldosterone
How is cortisol regulated?
ACTH = Adrenocorticotrophic hormone
What does cortisol do?
Prepares the body for stress
What are some of the metabolic effects of stress?
- Gluceoneogenesis
- Increased blood glucose concentration
- Increased lipolysis (fat metabolism)
- Enhanced effects of glucagon and catecholamines
What is the rhythm of cortisol release?
Diurnal release
Describe the hypothalamo-pituitary-adrenal axis?
- Hypothalamus releases CRH = corticotrophin releasing hormone
- This acts on the corticotrophs in the anterior pituitary to release ACTH = adrenocorticotrophic hormone
- This ATCH acts on adrenal cortex to stimulate cortisol release
How many levels does cortisol negatively feed back on and where?
The hypothalamus and the pituitary
What happens when cortisol levels are high?
The negative feedback loops are engaged, so the pituitary and hypothlamus stop producting CRH and ACTH
What affect does ACTH have on the adrenal gland?
Increases the activation of the enzymes needed to produce cortisol (17, 21 and 11)
At what time are cortisol levels the highest?
8:30 am in the morning
If you wanted to measure a patients highest possible cortisol level, what time would be the best to test it?
8:30 am in the morning
What is Addisons disease?
A disorder where the endocrine system does not produce enough steroid hormones
What is primary adrenal failure?
An autoimmune disease where the immune system decides to destroy the adrenal cortex
What is the most common cause of primary adrenal failure?
TB
What happens to ACTH levels when a patient has primary adrenal failure?
The raise - this is because the body is not producting enough cortisol, therefore via negative feedback loops, the body works to increase ACTH production so it accumulates
What is MSH?
Melanin Stimulating Hormone
What affect does CRH have on MSH?
Increases the release of MSH
What happens to patients blood pressure when they have primary adrenal failure?
Low blood pressure as no aldosterone to regulate it
Why do patients with Addisons disease have a good tan?
POMC - proopiomelanocortin is a large precursor protein which is cleaved to form a number of smaller peptides, including ACTH, MSH and endorphins
What is the urgent treatment for Addisons crisis?
rehydrate with normal saline, give dextrose to prevent hypoglyceamia and hydrocortisone
What are some symptoms of Addisons disease?
Weight loss
Hyperpigmentation due to MSH
Autoimmune vitiligo
Constipating, vomiting, nausea, diarrhoea
Low Blood Pressure
What is cushings syndrome?
When you have an excess of cortisol
What happens to your weight in Cushing syndrome?
Weight increases - put on weight
What can cause too much cortisol?
A tumour of the adrenal = too much cortisol
pituitary tumour = excess ACTH
Ectopic ACTH secretion
Steroids by mouth
What happens to blood pressure in Cushings syndrome?
Blood pressure increases
What are some clinical signs of Cushing syndrome?
Thin skin, centripetal obesity, Red Stretch Marks, Easy bruising, high blood pressure, impaired glucose tolerance
What does the adrenal medulla produce?
Catecholamines eg Adrenaline and Noradrenaline
What is the medulla derived from?
The ectodermal neural crest
What is a precursor for Adr and NA synthesis?
Tyrosine
What are catecholamines stored in?
Cytoplasmic granules
When is adrenaline and noradrenaline released?
In respnose to ACh from preganglionic sympathetic neurones
Describe how adrenaline and nor adrenaline are produced?
Tyrosoine -> DOPA -> Dopamine -> Noradrenaline -> Adrenaline
What is the role ofcatecholamines?
mediate the fight or flight response
How do NA and Adrenaline circulate?
Bound to albumin
Which enzymes degrade NA and Adrenaline?
Monoamine oxidase and catechol-O-methyl transferase
Why are the adrenal androgens more important for women?
Women do not have Leydig cells which are found in the testes to produce testosterone, so rely heavily on the production of testosterone from the adrenal gland
What is DHEA?
Dehydroepiandrosterone - A hormone which is made by the adrenal gland
What happens to DHEA in peripheral tissues?
It is converted into Testosterone / Dihydrotestosterone using the enzyme 5-alpha reductase
Under what conditions would renin be released from the juxtaglomerular cells of the macula densa?
Low blood pressure, hyperkalaemia and hypoatrenemia (low sodium)
What does aldosterone do?
Bind to intracellular receptor in DCT cells and act as a transcription factor. Produce more NA/K ATPase and NA channels. Loose K+!!
Where is renin produced?
Lungs
