The Adrenal Glands Flashcards
True or False:
The adrenal glands are outside of the renal fascia
False
Encapsulated within renal fascia
How many layers does the adrenal cortex have?
3
What are the layers of the adrenal cortex?
Zona glomerulosa, zona fasiculata, zona reticularis
What is produced in the zona glomerulosa of the adrenal cortex?
Mineralocorticoids (eg aldosterone)
What is produced in the zona fasiculata of the adrenal cortex?
Glucocorticoids (eg cortisol)
What is produced in the zona reticularis of the adrenal cortex?
Glucocorticoids + small amounts of androgens
What is produced in the adrenal medulla?
Adrenalne and noradrenaline
What are chromaffin cells?
They are neuroendocrine cells found mostly in the medulla of the adrenal glands
What are corticosteroids?
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex
What is an example of a mineralocorticoid?
Aldosterone
What is an example of a glucocorticoid?
Cortisol
What are steroid hormones synthesised from?
Cholesterol
What is the adrenal cortex derived from in embryonic development?
Mesoderm
What is the adrenal medulla derived from in embryonic development?
Neural crest cells
How do corticosteroids exert their actions?
By regulating gene transcription
Outline how corticosteroids regulate gene transcription
1) Diffuse across plasma membrane
2) Bind to glucocorticoid receptors
3) Chaperone proteins on receptors dissociate
4) Receptor-ligand complex translocates to nucleus
5) Dimerisation with other receptors can occur
6) Receptors bind to glucocorticoid response elements (GREs) or other transcription factors
What is a hormone response element?
A hormone response element (HRE) is a short sequence of DNA within the promoter of a gene that is able to bind a specific hormone receptor complex and therefore regulate transcription
Where is aldosterone synthesised and released by?
Zona glomerulosa of adrenal cortex
What carrier proteins bind to aldosterone?
Serum albumin and transcortin
What is the role of aldosterone?
RAAS
In distal tubules and collecting ducts - promotes expression of Na+/K+ pump to promote reabsorption of Na+ and excretion of K+, influencing water retention, blood volume and thus blood pressure
Outline the RAAS
1) Renin released from kidney cleaves angiotensinogen (released from liver) into angiotensin I
2) ACE in lungs cleaves angiotensin I into angiotensin II
3) Angiotensin II stimulates aldosterone release from adrenal cortex, vasoconstriction of arterioles and ADH release from the posterior pituitary
4) ADH release -> translocation of aquaporin channels in nephron aids reabsorption of water back into blood
4) Aldosterone increases expression of Na+/K+ pump in collecting ducts - increased reabsorption of Na+
How is the RAAS initiated?
Input eg hypotension, hypovolaemia
Decrease in renal perfusion, drop in blood pressure, increased sympathetic tone from baroreceptor activation leads to more renin release from kidney
What is primary hyperaldosteronism due to?
Defect in adrenal cortex
eg bilateral idiopathic adrenal hyperplasia, conn’s syndrome, aldosterone secreting adenoma
Describe the renin and aldosterone levels in primary hyperaldosteronism
Low renin - high aldosterone
What is secondary hyperaldosteronism due to?
Over activity of the RAAS
eg renin producing tumour, renal artery stenosis
Describe the renin and aldosterone ratio in secondary hyperaldosteronism
High renin levels
Low aldosterone:renin ratio
What are some signs of hyperaldosteronism?
High BP, LV hypertrophy, stroke, hypernatraemia, hypokalaemia
How can hyperaldosteronism be treated?
Surgery, spironolactone (mineralocorticoid receptor antagonist)
What is cortisol synthesised and released by?
Zona fasiculata
What is cortisol synthesised and released in response to?
CRH (corticotropin-releasing hormone) released from hypothalamus -> ACTH (Adrenocorticotropic hormone) released from anterior pituitary -> cortisol released from adrenal cortex
What is cortisol’s carrier protein in plasma?
Transcortin
What are the catabolic effects of cortisol?
Increased protein breakdown in muscle
Increased gluconeogenesis in liver
Increased lipolysis in fat
Aside from catabolic effects, what are the other actions of cortisol?
Resistance to stress, anti-inflammatory effects (inhibits macrophage activity+mast cell degranulation), depression of immune response
Why is cortisol perscribed to organ transplant patients?
It depresses the immune respnse
Outline the HPA axis
Stressor (eg pain, fever, hypoglycaemia, low BP):
1) Hypothalamus releases CRH to anterior pituitary
2) Anterior pituitary releases ACTH to adrenal cortex
3) Adrenal cortex releases cortisol to target tissues
What are the net effects of glucocorticoid actions on metabolism?
Increased glucose production, breakdown of protein, redistribution of fat
Why does cortisol release lead to increased glycogen storage?
Increases glucose -> increased insulin so liver glycogen stores increase
What are the effects of cortisol on muscle?
Increased protein degradation
Decreased protein synthesis
Decreased glucose utilisation
Decreased sensitivity to insulin
(Cortisol inhibits insulin-induced GLUT4 translocation in muscle so has glucose sparing effect)
What are the effects of cortisol on fat?
Redistribution of fat especially in abdomen, supraclavicular fat pads, dorso-verical fat pad and face
(Buffalo hump and moon face)
Decreases glucose utilisation
Decreases sensitivity to insulin
Increases lipolysis
What is Cushing’s syndrome?
Chronic excessive exposure to cortisol
What is the most common cause of Cushing’s syndrome?
Prescribed glucocorticoids
What are some endogenous causes of Cushing’s syndrome?
1) Pituitary adenoma secreting ACTH (Cushing’s DISEASE)
2) Excess cortisol produced by adrenal tumour (Adrenal Cushing’s)
3) Non pituitary-adrenal tumours producing ACTH+/CRH eg small cell lung cancer
What is Cushing’s disease?
An excess of cortisol in the blood level CAUSED BY a pituitary tumour secreting adrenocorticotropic hormone
What are the signs and symptoms of Cushing’s syndrome?
Moon-shaped face Buffalo hump Abdominal obesity Purple striae (proteolysis - skin weaker) Acute weight gain Hyperglycaemia Hypertension
What are some examples of steroid drugs?
Prednisolone, dexamethasone
What are steroid drugs often used to treat?
Inflammatory diseases, allergies, organ transplant, auto-immune conditions
What is an important point about stopping steroid medication?
Steroid dosage should be reduced gradually and not stopped suddenly
What is Addison’s disease?
Chronic adrenal insufficiency
What is the most common cause of Addison’s disease?
Destructive atrophy from autoimmune response
What are the signs and symptoms of Addison’s disease?
Postural hypotension, lethargy, weight loss, anorexia, increased skin pigmentation, hypoglycaemia
Why does Addison’s disease lead to increased skin pigmentation?
Decreased cortisol -> negative feedback on anterior pituitary reduced -> more POMC required to synthesise ACTH -> more a-MSH produced -> melanin synthesis
What are the symptoms of an Addisonian crisis?
Nausea, vomiting, pyrexia, hypotension, vascular collapse
What is an addisonian crisis?
A life threatening emergency due to adrenal insufficiency
What is an addisonian crisis often precipitated by?
Stress, salt depravation, infection, trauma, cold exposure, over exertion, abrupt steroid drug withdrawal
How is an addisonian crisis treated?
Fluid replacement, cortisol
What are some examples of androgens excreted by the zona reticularis?
DHEA and androstenedione
True or False:
The adrenal medulla is a modified sympathetic ganglion of the autonomic nervous system
True
How is noradrenaline converted to adrenaline?
N-methyl transferase
Why do 20% of chromaffin cells secrete noradrenaline as opposed to adrenaline (like the other 80%)?
20% lack the N-methyl transferase enzyme to convert NA into adrenaline
What type of receptors are adrenergic receptors?
GPCRs
What adrenergic receptors in the heart increase HR and contractility?
B1
What adrenergic receptors in the lungs cause bronchodilation?
B2
What adrenergic receptors in the blood vessels cause vasoconstriction?
a1
What adrenergic receptors in the blood vessels cause vasodilation?
B2
What adrenergic receptors in the kidney causes increased renin secretion?
B1, B2
What adrenergic receptors in the muscle cause increased glycolysis and glygogenolysis?
a1, B2
What adrenergic receptors in the pancreas increase glucagon secretion?
a2
What adrenergic receptors in the pancrease decrease insulin secretion?
a2, B2
What adrenergic receptors in adipose tissue increases liplysis?
B2
How does adrenaline increase HR?
1) B1 adrenergic receptor - G-alpha S subunit
2) GDP for GTP exchange, dissociation of alpha subunit
3) Stimulates adenylyl cyclase - cAMP
4) cAMP can directly activate HCN chanels - funny current
5) cAMP activates PKA - phosphorylation of HCN channels, phosphorylation of L-type Ca2+ channels - potentiates opening, creasing the slope of the upstroke of the AP
What is pheochromocytoma?
Chromaffin cell tumour
Catecholamine-secreting (mainly NA) tumour that may precipitate life-threatening hypertension
What are some characteristics of pheochromocytoma?
Severe hypertension, headaches, palpitations, diaphoresis, anxiety, weight loss, hyperglycaemia
What are catecholamines derived from?
Tyrosine
