The Adrenal Glands Flashcards
Where are the adrenal glands located?
Ad = on top of
Renal = kidneys
What are the 2 main sections of the adrenal glands?
Adrenal Cortex
Adrenal Medulla
What is the capsule?
The outer fibrous protective layer of the adrenal glands
What are the 3 layers of the adrenal CORTEX?
Zona Glomerulosa
Zona Fasiculata
Zona Reticularis
Acronym to remember the the order of layers of the cortex (outermost to innermost)
GFR
Zona Glomerulosa
Zona Fasiculata
Zona Reticularis
What is the function of the Zona Glomerulosa?
Produce Mineralocorticoids
(Aldosterone)
What is the function of the Zona Fasiculata?
Produce Glucocorticoids
(Cortisol)
What is the function of the Zona Reticularis?
Produce a small amount of Androgens (sex hormones)
Also some glucocorticoids
What is good way to remember which hormones are produced by each layer of the cortex?
The Deeper you go the sweeter it gets
Salt
Sugar
Sex
What is the function of the medulla and what type of cells does it contain?
Produces Adrenaline and Noradrenaline
Contains Chromaffin cells which are responsible for this
What are corticosteroids?
Steroid hormones made in the adrenal cortex
What are all of the corticosteroids and steroid hormones made in the gonads synthesised from?
Are they water soluble or lipid soluble?
They are all synthesised from cholesterol
All lipid soluble hormones
How do steroid hormones affect their target tissues?
They regulate gene transcription
How do Corticosteroids regulate gene transcription?
Diffuse across plasma membrane
Bind to Glucocorticoid receptors
Receptor ligand complex translocates to nucleus
Receptor binds to glucocorticoid response elements (GREs) or other transcription factors
What type of corticosteroid hormone is Aldosterone?
Where is it produced?
How is it transported in the blood and why?
Mineralocorticoid
Zona Glomerulosa (salt)
Associated with a carrier protein mainly serum Albumin sometimes Transcortin
It must be transported with a carrier protein since it’s lipophilic, it’s insoluble in water
Where is the receptor for aldosterone and how does it exert its actions?
Intracellular
Regulates gene transcription
What is the role of aldosterone?
Regulates plasma Na+, K+ and so arterial blood pressure
What does aldosterone cause? So how does it regulate Na+, K+ and BP
Increases BP
Causes increased expression of Na+/K+ Pump in the distal tubules and collecting duct of nephron
3 Na+ pumped out of tubule into the blood and 2 K+ pumped into the tubule to be excreted
This causes more Na+ and water to reabsorbed into the blood increasing blood pressure
What is the RAAS system and what is its purpose?
The Renin-Angiotensin-Aldosterone System
System of blood pressure Regulation by regulating blood volume, sodium re absorption, potassium secretion and blood vessel tone
What is hypotension?
Lower BP than normal
What is hypovolaemia?
Fall in blood volume
What is produced when less blood is delivered to the kidneys? (Hypotension or hypovolaemia)
Renin
What is the function of Renin?
It cleaves Angiotensinogen to Angiotensin I
What is the function of ACE (Angiotensin Converting Enzyme)? Where is it found?
Cleaves Angiotensin I to Angiotensin II
Angiotensin II is the functional Hormone
ACE is located in the capillaries of the lungs
Describe how Angiotensinogen is converted to Angiotensin II in the RAAS
Angiotensinogen is cleaved by Renin which is produced due to low BP this makes Angiotensin I
Angiotensin I cleaved by ACE in the lungs converting it into the active Angiotensin II
What does Angiotensin II do?
Vasoconstriction of Arterioles (Increases BP)
Stimulates Adrenal cortex (Zona Glomerulosa) to produce Aldosterone. Aldosterone increases expression of Na+/K+ pump in nephrons
Stimulates posterior pituitary to secrete more ADH (more aquaporins translocated in nephrons)
What is the disease associated with being deficient in the enzyme 21-hydroxylase?
Condition called Congenital Adrenal Hyperplasia (CAH)
What are the 2 types of Hyperaldosteronism?
What is the difference between the 2?
Primary
Secondary
Primary Hyperaldosteronism = issue with adrenal glands which produces too much aldosterone
Secondary Hyperaldosteronism = adrenal glands fine but TOO MUCH RENIN being produced which leads to too much aldosterone being produced
What causes Primary Hyperaldosteronism?
Give 2 examples of Primary Aldosteronism
Defect in the Adrenal cortex
Bilateral idiopathic adrenal hyperplasia
(Affecting both adrenal glands, unknown cause, increased number of cells)
Aldosterone secreting adrenal adenoma (CONNS SYNDROME)
What are the levels of renin like in Primary Hyperaldosteronism?
What is the ratio of aldosterone to renin?
Low renin
HIGH aldosterone:renin ratio
What causes Secondary Aldosteronism?
Give 2 examples of what may cause Secondary Hyperaldosteronism
Over activity of the RAAS due to too much RENIN being produced
Renin producing tumour
Renal artery stenosis (poor perfusion of kidneys leads to jutaglomerular cells making more renin)
What are the levels of renin like in Secondary Hyperaldosteronism?
What is the ratio of aldosterone to renin?
High renin
Low aldosterone:renin ratio
How can you distinguish between a primary and secondary cause of Hyperaldosteronism?
Use the aldosterone:renin ratio
High = Primary
Low = Secondary
Wha are the signs of Hyperaldosteronism?
High blood pressure (action of aldosterone)
Stroke
Hypernatraemia (aldosterone pumps more Na+ back into blood)
Hypokalaemia (aldosterone causes more K+ to be pumped out into the urine and lost)
How do we treat Hyperaldosteronism?
Depends on type
Aldosterone producing adenomas removed by surgery
Spironolactone = drug that inhibits mineralocorticoid receptors so acts as an aldosterone antagonist (Diuretic) helps treat the hypertension
What type of corticosteroid is Cortisol and where is it produced?
Glucocorticoid
Zona Fasiculata
How does Cortisol regulate its own production in negative feedback?
It inhibits the release of CRH (Corticotropin Releasing Hormone) from the hypothalamus which inhibits production of ACTH (Adrenocorticotropic hormone) by the anterior pituitary
Or it can directly act onto the anterior pituitary inhibiting the release of ACTH
How is cortisol transported in the blood?
How does the cortisol exert its action?
Carrier protein transcortin
Cortisol receptor regulates gene transcription
What actions does cortisol cause?
CATABOLIC EFFECTS
Increase proteolysis in muscle
Increased lipolysis
Increased Gluconeogenesis (liver)
Anti inflammatory effects
Depression of immune response (organ transplant patients )
It helps resist stress by increasing supply of glucose, raising BP
What are the net effects of Glucocorticoids on the body?
Increased glucose production (Gluconeogenesis)
Breakdown of protein
Redistribution of fat
How does hyperglycaemia occur when glucocorticoid levels are high?
Cortisol prevents skeletal muscle taking up glucose in response to insulin
Cortisol inhibits insulin-induced GLUT4 translocation in the muscle so glucose stays in blood
Increased Gluconeogenesis
What causes Cushing’s syndrome?
Chronic excess levels of exposure to cortisol (glucocorticoids)
What are the signs and symptoms of Cushing’s Syndrome?
Plethoric moon shaped face
Buffalo hump (redistribution of fat)
Abdominal obesity (redistribution of fat)
Thin arms and legs (redistribution of fat)
Purple striae
Hyperglycaemia
Hypertension
What causes the purple striae in Cushing’s syndrome?
The chronic excess of cortisol increases rates of proteolysis. This weakens skins integrity producing stretch marks
What are the 2 types of causes of Cushing’s Syndrome?
External causes (Exogenous)
Endogenous causes
External causes of Cushing’s Syndrome is most common. What is the most common external cause of Cushing’s?
Prescribed Gluocorticoids (Drugs)
What are the 3 rarer Enodgenous causes of Cushing’s Syndrome?
Benign Pituitary adenoma secreting ACTH
Excess cortisol produced by an adrenal tumour
Non pituitary-adrenal tumour producing ACTH OR CRH like small cell lung cancer (May be called Ectopic ACTH)
What are Prednisolone and Dexamethasone?
Steroid drugs (glucocorticoids)
What are Prednisolone and Dexamethasone used treat?
Anti inflammatory and auto-immune conditions
Asthma
Inflammatory Bowel Disease
Rheumatoid arthritis
Organ transplant patiens
Why must you gradually reduce someone’s use of steroid drugs and not suddenly stop them?
Bodies endogenous production of corticosteroids inhibited by the influx of exogenous prescribed corticosteroids.
If you suddenly removed th drugs the person would not produce the corticosteroid hormone straight away
What is Addison’s disease?
Chronic cortisol deficiency due to chronic adrenal insufficiency
Zona Fasiculata doesn’t make enough cortisol
What is usually the cause of not enough cortisol being made by the Zona Fasiculata in Addison’s disease?
Autoimmune destruction of Zona Fasiculata cells
What are the signs and symptoms of Addison’s disease?
Hyperpigmentation of the skin (KEY)
Lethargy
Weight loss
Anorexia
Hypoglycaemia
Postural hypotension
What causes Hyperpigmentation in Addisons Disease?
To counteract the decreased levels of Cortisol, the body wants to make more ACTH so Cortisol production can be stimulated.
So more POMC I’d broken down (POMC = Precursor of ACTH)
POMC broken down to ACTH and MSH (Melanocyte Stimulating Hormone)
Stimulates more melanin production
What is an Addisonian Crisis?
Life threatening emergency due to adrenal insufficiency (not making enough cortisol) while being put under stress like trauma or infection
What is the treatment for an Addisonian Crisis?
Fluid replacement
Cortisol
What are the symptoms of an Addisonian Crisis?
Hypotension
Nausea
Vomiting
Pyrexia
VASCUAL COLLAPSE
What type of Corticosteroid hormone does the Zona Reticularis produce?
Androgens
Give 2 examples of androgens
DHEA
Androstenedione
What happens to DHEA in men and women?
Converted to testosterone in testes
Converted to oestrogens by tissues/ovaries
What is Special about the adrenal medulla?
It’s a modified ganglion of the autonomic nervous system
Describe the structure of chromaffin cells in the adrenal medulla
They don’t have axons but act as postganglionic nerve fibres releasing hormones into the blood
What amino acid are Adrenaline, noradrenaline and dopamine made from?
Tyrosine
Why do some Chromaffin cells secrete adrenaline and others secrete noradrenaline?
Some cells lack the enzyme N-Methyl Transferase which converts Noradrenaline into Adrenaline
What is Cushing’s Disease? (Different to Cushings Syndrome)
Term given to describe Cushing’s syndrome when it’s caused by a Bening Pituitary Adenoma secreting ACTH
What is adrenal Cushing’s?
When Cushing’s syndrome is caused by excess cortisol made by an adrenal tumour
How is Dexamethasone used to investigate possible Cushing’s disease?
When is it given and when is cortisol measured and why?
When are cortisol levels the highest?
Used in suppression test ASSESING ACTH RHYTHM
Dexamethasone given late at night, then measured early morning since Cortisol is highest in morning
Dexamethasone acts in the same way cortisol does
If cortisol levels not suppressed by low dose or high dose of Dexamethasone but ACTH levels are low likely a cortisol secreting adrenal adenoma
If cortisol levels not suppressed at low does but supressed at high dose may indicate a benign pituitary adenoma secreting ACTH (Cushings Disease) ACTH will be High
If not suppressed by low or high dose indicates Ectopic tumour making ACTH (ectopic Cushing’s ) ACTH will be high
Why might ACTH be supressed in Cushing’s syndrome?
Prescribed glucocorticoids taken (Exogenous Cushing’s)
Adrenal Cushing’s (excess cortisol made by adrenal tumour inhibiting ACTH production)
What is Phaeochromocytoma?
Phaeo =Dark
Chrome = Colour
Cyte = cell
Oma = tumour
Tumour of Chromaffin cells that secrete either adrenaline or noradrenaline
What does Phaeochromocytoma often cause?
Life threatening hypertension
Headaches
Palpitations
Elevated blood glucose
Palpitations
What type of molecules are adrenaline and noradrenaline?
Catecholamines
Compare Corticosteroids to Catecholamines
Please look in Endocrinology tab “comparing Corticosteroids and Catecholamines”
