Adrenal glands Flashcards
Where are the adrenal glands found?
Sits right above each kidney
What are the 3 parts of the adrenal glands?
- Capsule
- Cortex
- Medulla
What are the 3 zones of the adrenal cortex?
hint: girls fart rainbows
1) Zona glomerulosa (outer)
2) Zona fasiculata (middle)
3) Zona reticularis (inner)
What is the broad name for the hormones of the adrenal cortex?
Corticosteroids
What are the three subdivions of corticosteroids?
1) Mineralocorticoids (aldosterone)
2) Glucocorticoids (cortisol, corticosterone, oestrogen)
3) Androgens (testosterone and oestrogen)
Describe the characteristics of steroid hormones
- Lipid soluble
- Synthesised from cholesterol in adrenal glands and gonads
- Bind to receptors of nuclear receptor family
- Modulate gene transcription
What is (most commonly) deficient in congenital adrenal hyperplasia?
21-hydroxylase
Briefly describe the mechanism of corticosteroids
1) Readily diffuse across plasma membrane and bind to glucocorticoid receptors
2) Binding leads to chaperone proteins dissociating
3) Receptor ligand complex translocates to nucleus
4) Receptors bind to glucocorticoid response elements or other transcription factors
What are chaperone proteins (give an example)?
Proteins that assists conformational folding and unfolding e.g. heat shock protein 90
Where is Aldosterone produced?
Zona glomerulosa of the adrenal cortex
What is the carrier protein for aldosterone?
(mainly) serum albumin and to some extent transcortin
What is the effect of aldosterone to the body and how does it do so?
- Regulation of plasma Na+, K+ and arterial blood pressure
- Upregulates expression of Na+-K+ ATPase increasing the concentration gradient
- Also upregulates epithelial sodium channels (ENaCs)
- Greater reabsorption of Na+ and water retention
- Acts on DCT and collecting tubules of the nephron
What is aldosterone a central component of?
The renin-angiotensin-aldosterone system (RAAS)
What is the renin-angiotensin-aldosterone system (RAAS)?
A system of hormones involved in the regulation of plasma sodium concentration and arterial blood pressure
Describe the mechanism of RAAS
- Decrease in blood pressure (renal perfusion) or in plasma Na+ concentration stimulates the kidneys to release RENIN
- RENIN cleaves ANGIOTENSINOGEN (produced in the liver) giving ANGIOTENSIN 1
- ANGIOTENSIN 1 is further cleaved into ANGIOTENSIN 2 by ANGIOTENSIN-CONVERTING ENZYME (ACE)
- ANGIOTENSIN 2 increases blood pressure
How does angiotensin 2 increase blood pressure?
- Potent vasoconstrictor
- Stimulates adrenal cortex to release aldosterone
- Stimulate posterior pituitary to release ADH
What is hyperaldosteronism?
Too much aldosterone produced
What are the signs of hyperaldosteronism?
- High blood pressure
- Left ventricular hypertrophy
- Stroke
- Hypokalaemia
- Hypernatraemia
What is the treatment for hyperaldosteronism?
Treatment is dependant on which type
- Aldosterone-producing adenomas = surgery
- Spiranolactone (mineralocorticoid receptor antagonist)
What are the two types of hyperaldosteronism?
1) Primary = defect in adrenal cortex
- Most common cause: bilateral idiopathic adrenal hyperplasia
- Aldosterone secreting adrenal adenoma (Conn’s syndrome)
- Low renin levels
2) Secondary = over activity of the RAAS
- Renin producing tumour
- Renal artery stenosis
- High renin levels
Differentiate based on renin levels
What type of hormone is cortisol and where is it produced?
Cortisol is a glucocorticoid produced from the zona fasiculata of the adrenal cortex
How is cortisol transported in the blood stream?
Transcortin (90%) and serum albumin (10%)
What stimulates the release of cortisol?
ACTH from the anterior pituitary (which is stimulated by CRH)
-ACTH binds to corticotropin receptors (melanocortin receptor/MC2) which is a GPCR
What effects does cortisol have on the body?
- Increased proteolysis
- Increased lipolysis
- Increased gluconeogenesis
- Increased resistance to stress (increase supply of glucose, raise blood pressure by making vessels more sensitive to vasoconstrictors)
- Anti-inflammatory effects (inhibit macrophages)
- Depression of immune response (for organ transplant)
What are the effects of glococorticoids on metabolism?
- Increased glucose production (decrease utilisation, prevent glucose uptake by GLUT4 in muscles)
- Breakdown of proteins
- Redistribution of fat (abdomen, dorso-cervical fat pad)
What is Cushing’s syndrome?
chronic excessive exposure to cortisol
What are external causes of Cushing’s syndrome?
Prescribed glucocorticoids
What are endogenous causes of Cushing’s syndrome?
- Benign pituitary adenoma secreting ACTH (Cushing’s disease)
- Excess cortisol from adrenal tumour (Adrenal cushing’s)
- Non-pituitary-adrenal tumours producing ACTH e.g. small cell lung cancer
What are the signs and symptoms of Cushing’s syndrome?
- Plethoric moon-shaped face
- Buffalo hump
- Abdominal obesity
- Purple striae
- Acute weight gain
- Hypertension
- Hyperglycaemia
What are steroid drugs and give examples
Anti-inflammatory and immunomodulatory drugs for conditions such as asthma, rheumatoid arthritis and organ transplant. Examples: prednisolone and dexamethasone
Why should dosage of steroid drugs be reduced gradually and not stopped completely?
Cortisol is a steroid thus steroid drugs have similar effects to cortisol. Abrupt withdrawal is a life threatening emergency (Addisonian crisis)
What is Addison’s disease?
Chronic adrenal insufficiency
-used to be caused by TB, now is destructive atrophy from immune response
What are the signs and symptoms of Addison’s disease?
- Lethargy
- Weight loss
- Postural hypotension
- Anorexia
- Hypoglycaemia
- Increased skin pigmentation
Why do you get increased skin pigmentation in Addison’s disease?
1) Decreased cortisol
2) Negative feedback to anterior pituitary
3) More POMC required to synthesis ACTH
4) ACTH has alpha-MSH that synthesises melanin
What is Addisonian crisis?
A life threatening emergency due to adrenal insufficiency
What can trigger addisonian crisis?
- Severe stress
- Salt depravation
- Infection
- Trauma
- Cold exposure
- Over exertion
- Abrupt steroid drug withdrawal
What are the symptoms of addisonian crisis?
- Nausea
- Vomiting
- Pyrexia
- Hypotension
- Vascular collapse
What is the treatment for addisonian crisis?
- Fluid replacement
- Cortisol
What hormones does the zona reticularis of the adrenal cortex produce?
Androgens
- Dehydroepiandosterone (DHEA)
- Androstenedione
What is DHEA converted to in males?
Testosterone in testes
What happens to adrenal androgens in females?
Converted to oestrogen
-only source after menopause
What is the adrenal medulla?
The central most part of the adrenal glands
-A modified sympathetic ganglion of autonomic nervous system
What are the main cells in the adrenal medulla and what chemical messengers do they produce?
Chromaffin cells
- Adrenaline (Epinepharine)
- Nor-adrenaline (Norepinepharine)
- Dopamine
Describe the synthesis of adrenaline and noradrenaline in chromaffin cells
Tyrosine -> (Levodopa) -> Dopamine -> Noradrenaline -> Adrenaline
-20% of chromaffin cells dont have N-methyl transferase (converts noradrenaline to adrenaline)
What are adregenic receptors?
G-protein coupled receptors
- Adenylyl cyclase
- CAMP
- Protein Kinase A
What is the effect of adrenaline on the body?
Fight or flight response
- inc. heart rate (B1)
- inc. heart contractility (B1)
- bronchodilation (B2)
- Vasoconstriction (A1)
- Vasodilation (B2)
- inc glycolysis and glycogenolysis (A1 B2)
- inc. lipolysis (B2)
What is a phaeochromocytoma?
A rare catecholamine-secreting tumour (mainly noradrenaline)
-dark stains with chromium salt
What are the characteristics of phaeochromocytoma?
- Severe hypertension
- Headaches
- Diaphoresis (excessive sweating)
- Palpitations
- Anxiety
- Weight loss
- Elevated blood glucose
