Endocrinology Session 5 Flashcards
What are the components of the adrenal gland?*
- Capsule
- Cortex
- Medulla
What are the 3 zones of the adrenal cortex and what do they produce?*
- Zona glomerulosa (mineralocorticoids; aldosterone)
- Zona fasciculata (glucocorticoids; cortisol)
- Zona reticularis (glucocorticoids and androgens)
What do the chromaffin cells of the medulla produce?
- Adrenaline 80%
- Noradrenaline 20%
(Cell bodies that secrete catecholamines into the bloodstream)
What are the adrenal glands?
Multifunctional endocrine glands that have a combined weight of 6-8g
What are the properties of steroid hormones?
- Synthesised from cholesterol
- Lipid soluble
How do steroid hormones work?
Bind to receptor of the nuclear receptor family (as cross the plasma membrane readily) and modulate gene transcription
What are the types of steroid hormones?
Glucocorticoids, mineralocorticoids, androgens, oestrogens, progestins
How do corticosteroids act?*
- Diffuse across plasma membrane
- Bind to glucocorticoid receptors
- Binding = dissociation of chaperone proteins
- Receptor-ligand complex translocates to nucleus
- Dimerises with other receptors
- Receptors bind to glucocorticoid response elements on DNA or other transcription factors
How is aldosterone carried?
Serum albumin (main) and transcortin
What does the connective tissue capsule contain?
Capsular plexus - many blood vessels
What is the function of aldosterone?
Regulating Na+, K+ and arterial BP
- Upregulation of epithelial sodium channels in collecting duct for more reabsorption
What is the main action of aldosterone?
Distal tubules and collecting ducts - promotes the expression of the Na/K pump that promotes Na+ reabsorption
Na+ is osmotically active, so water will follow and more water will be reabsorbed
What is the renin-angiotensin-aldosterone system?*
- Renin cleaves angiotensinogen into angiotensin I
- Angiotensin I cleaved by ACE in lung endothelial cells to Angiotensin II
- Angiotensin II acts on arteries to cause vasoconstriction
- Angiotensin II acts on the adrenal cortex/zona glomerulosa to release aldosterone, which increases Na+ and water reabsorption in kidney
- Angiotensin II acts on posterior pituitary to release ADH which adds more aquaporin channels in kidney and promotes reabsorption
What does the RAAS cause?
Increased blood pressure and blood volume
What causes the kidney to release renin in the first place?
Hypotension and hypovolaemia - decrease in renal perfusion which activates baroreceptors due to increased sympathetic tone = more renin released
What is hyperaldosteronism?
Overproduction of aldosterone
What are the causes of primary hyperaldosteronism?
Defects in the adrenal cortex:
- Bilateral idiopathic adrenal hyperplasia (common)
- Conn’s syndrome (aldosterone-secreting adenoma)
- Low renin levels
What are the causes of secondary hyperaldosteronism?
Overactivity of RAAS:
- Renin producing tumour
- Renal artery stenosis
- High renin levels
What are the signs of hyperaldosteronism?
- High blood pressure
- Left ventricular hypertrophy
- Stroke
- Hypernatraemia
- Hypokalaemia
What are the treatments for hyperaldosteronism?
- Adenomas - surgery
- Spironolactone - mineralocorticoid receptor antagonist
What are the features of cortisol?
- Synthesised in response to ACTH
- Negative feedback to hypothalamus inhibits CRH and ACTH release
How is cortisol carried?
Transcortin (carrier protein)
What are the catabolic effects of cortisol?
- Increased protein breakdown in muscle
- Increased lipolysis
- Increased gluconeogenesis in liver
What are the other effects of cortisol?
- Anti-inflammatory (meds for allergic reactions)
- Depression of immune response
Regulates gene transcription.
What is the hypothalamic-pituitary-adrenal axis?*
Production of cortisol in response to ACTH which is released from the anterior pituitary gland in response to CRH release from the hypothalamus (regulated by negative feedback)
When is CRF secreted?
In response to physical, chemical and emotional stressors (eg. temperature, hypoglycaemia)
Why should time always be taken into account when measuring cortisol levels?
Blood cortisol levels vary throughout the day (peak in morning, fall at night)
What is the effect of cortisol on MUSCLE?*
Inhibition of insulin-induced GLUT4 in muscle
- Prevents glucose uptake
- Less glucose utilisation so more protein degradation
What is the effect of chronic high levels of cortisol on FAT?
Redistribution of fat in abdomen, supraclavicular fat pads and face (less glucose utilisation so more lipolysis)
How do glucocorticoids affect the LIVER?*
- Increased glycogen storage and gluconeogenesis
- More insulin due to more insulin, so more liver glycogen stores
What are the net effects of glucocorticoids?
- Increased glucose production
- Breakdown of protein
- Fat redistribution
What is Cushing’s syndrome caused by?
Chronic, excessive exposure to cortisol
What are the external causes of Cushing’s syndrome?
Prescribed glucocorticoids (common)
What are the endogenous causes of Cushing’s syndrome?
- Benign, pituitary ACTH secreting adenoma (C. Disease)
- Excess cortisol produced by adrenal tumour
- Non-pituitary adrenal tumour producing ACTH (eg. small cell lung cancer)
What are the signs and symptoms of Cushing’s syndrome?
- Moon-shaped face
- Buffalo hump
- Abdominal obesity
- Purple striae (increased proteolysis due to weaker integrity of the skin)
- Acute weight gain
- Hyperglycaemia
- Hypertension
What are the examples of steroid drugs?
Prednisolone, dexamethasone
What are the properties of steroid drugs?
- Have anti-inflammatory and immunomodulatory effects
- Used to treat disorders, eg. asthma, IBD, RA
- Immunosuppression after organ transplants
- Same side effects as higher levels of cortisol
Why should steroids be reduced gradually and not stopped abruptly?
The body will stop making some of its own steroids = sharp fall in blood glucose and BP
What is Addison’s disease?
Chronic adrenal insufficiency
What can cause Addison’s disease?
- Complication of TB
- Destructive atrophy from autoimmune response
- More common in women
- Rare: cancers, trauma, infections
What are the signs and symptoms of Addison’s disease?
- Postural hypotension
- Lethargy
- Weight loss
- Anorexia (related to an increase in beta-endorphins?)
- Increased skin pigmentation
- Hypoglycaemia
What causes hyperpigmentation in Addison’s disease?*
- Decreased cortisol causes more CRH and ACTH production (neg. feedback)
- More POMC needed to synthesise ACTH
- Increased ACTH, so increased POMC
- POMC can also produce more MSH
- Alpha-MSH stimulates melanocytes in the skin to produce more melanin - more pigment
ACTH ITSELF CAN ALSO ACTIVATE MELANOCORTIN RECEPTORS
What is Addisonian crisis?
Acute medical emergency whereby the adrenal glands stop working and there is not enough cortisol in body
What can precipitate Addisonian crisis?
- Severe stress
- Infection
- Trauma
- Cold exposure
- Overexertion
- Abrupt steroid withdrawal
What are the symptoms of Addisonian crisis?
- Nausea and emesis
- Hypotension
- Pyrexia
- Vascular collapse
What is the treatment for Addisonian crisis?
- Fluid replacement
- Cortisol
What androgens are secreted from the zona reticularis and what do they do?
- DHEA and androstenedione
Male: DHEA converted to testosterone in testes
Female: promote libido, converted to oestrogens by other tissues (only oestrogen source post-menopause)
PROMOTE AXILLARY AND PUBIC HAIR GROWTH
What is the adrenal medulla?*
Modified sympathetic ganglion of ANS - chromaffin cells have no axons
What conversions happen in the adrenal medulla?
- Tyrosine - (tyrosine hydroxylase) > Levodopa
- Levodopa - (DOPA decarboxylase) > Dopamine
- Dopamine - (Dopamine B-hydroxylase > NAd
- NAd - (N-methyl transferase) > Ad
Why can’t some chromaffin cells make adrenaline?
Lack N-methyl transferase
What are the actions of adrenaline (fight or flight)?**
- Increase in HR and contractility
- Bronchodilation (B2)
- Vasoconstriction (a1) and vasodilation (B2)
- Renin secretion in kidney
- Glycolysis and glycogenolysis (muscle, + gluconeogenesis in liver)
- More glucagon secretion
- Lipolysis
What is a phaeochromocytoma?*
Tumour of the chromaffin cells = rare, catecholamine-secreting tumour that secretes noradrenaline and can cause lifethreatening hypertension
What are the symptoms of a phaeochromocytoma?*
- SEVERE HYPERTENSION
- Headaches
- Palpitation
- Excessive sweating/diaphoresis
- Anxiety
- Weight loss
- Hyperglycaemia
