The Adrenal Glands/ Adrenal Disorders Flashcards
The adrenal gland is made up of what two distinct areas?
The cortex and the medulla
What are the three layers of the cortex called?
What are each responsible for?
Zona glomerulosa - mineralcorticoids
Zona fasiculata -glucocorticoids
Zona reticularis- androgens
The adrenal medulla is a modified what?
It is made up of what kind of cells?
Sympathetic ganglion
Chromaffin cells
Steroid hormones are synthesised from what?
Cholesterol
Are steroid hormones lipid or water soluble?
Lipid soluble
Steroid hormones bind to what kind of receptors?
How do they exert their affect?
Nuclear (intracellular) receptors
They modulate gene transcription
How do corticosteroids exert their actions by regulating gene transcription?
They diffuse across the PM, bind to glucocorticoid receptors which leads to dissociation of chaperone proteins
Receptor ligand complex translocates to the nucleus
Receptors bind to GREs or other TFs
Which is the most abundant mineralcorticoid?
Aldosterone
Where is aldosterone synthesised and released?
Zona glomerulosa of the adrenal cortex
What is the carrier protein commonly used by steroid hormones?
Albumin protein
Aldosterone plays a key role in what process?
Regulation of plasma Na+ and K+ (blood volume)
Regulation of arterial BP
Where does the main action of aldosterone occur?
What does it do here?
In distal tubules and collecting ducts of the nephron
It promotes expression of Na/K pump (promoting the reabsorption of Na and excretion of K)
=water retention
In the RAAS, what molecule cleaves angiotensinogen to angiotensin I?
Where is this produced and in response to what?
Renin
Kidney in response to hypotension and hypovolaemia
What is responsible for the conversion of Angiotensin I to Angiotensin II?
Where does it have its effects?
Angiotensin converting enzyme (ACE)
In lung endothelial cells
Angiotensin II acts on what 3 things to produce its affects?
What are these affects?
Arterioles- vasoconstriction
Adrenal cortex- release aldosterone to increase expression of Na/K pump
Posterior pituitary- produce ADH to translocate aquaporin channels and aid reabsorption
What is hyperaldosternism?
What are the two types? How are they defined?
Over production of aldosterone
Primary - defect in adrenal cortex
Secondary - over activity of RAAS
What is the most common cause of hyperaldosteronism?
Bilateral idiopathic adrenal hyperplasia
What is the best way to distinguish between primary and secondary hyperaldosteronism?
The alsoterone:renin ratio
Primary- high (low renin)
Secondary- low (high renin)
What is an example of secondary hyperaldosteronism?
Renal artery stenois
What are the signs of hyperaldosteronism?
High blood pressure LV hypertrophy Stroke Hypernataemia Hypokalaemia
What is the treatment for hyperaldosteronism?
Surgery- if from tumour
Spironolactone (mineralcoricoid antagonist)
Which is the most abundant corticosteroid?
Cortisol
Where is cortisol synthesised and released?
In response to what?
From the Zona fasiculata of the adrenal cortex
In response to ACTH
How does negative feedback control the release of cortisol?
Cortisol feeds back to the hypothalamus and anterior pituitary to inhibit CRH and ACTH
What is the carrier protein that is used to transport cortisol?
Transcortin
What are the actions of cortisol?
Catabolic effects: -proteolysis -lipolysis -gluconeogenesis + (inhibits GLUT4- glucose sparing effect) Resistance to stress Anti-inflammatory Depression of immune system
What is Cushing’s syndrome?
A condition caused by chronic excessive exposure to cortisol
What are the endogenous and exogenous causes of Cushing’s syndrome?
Endogenous:
- Bengin pituitary tumour (Cushing’s disease)
- Excess cortisol production by adrenal tumour (Adrenal Cushing’s)
- Small cell lung cancer (V rare)- secretes ACTH
Exogenous:
-Prescribed glucocorticoids
What are the signs and symptoms of Cushing’s syndrome?
Plethoric moon-shaped face Dorsocervical fat pad "buffalo hump" Abdominal obesity Purple striae Acute weight gain Hyperglycaemia Hypertension
Apart from Cushing’s syndrome, what are steroid drugs such as Prednisolone and Dexamethasone used to treat?
Asthma IBD RA Other auto-immune conditions Suppression of immune rejection
What is Addision’s disease?
What is it now most commonly caused by?
Chronic adrenal insufficiency
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
How does Addison’s cause hyperpigmentation?
- More POMC is produced through reduced negative feedback on anterior pituitary which produces melanin
- ACTH activates melanocortin receptors
What is “Addisonian Crisis”
A life threatening emergency due to adrenal insufficiency
What factors can precipitate an Addisonian crisis?
Severe stress Salt deprevation Infection Trauma Cold exposure Abrupt steroid withdrawl
What are the symptoms of Addisonian crisis?
Nausea Vomiting Pyrexia Hypotension Vascular collapse
What is the treatment for someone in an Addisonian crisis?
IV fluid replacement
IV cortisol
The innermost layer of the adrenal cortex secretes what?
Androgens
The chromaffin cells of the adrenal medulla lack what feature?
Axons
What do the chromaffin cells of the medulla release upon stimulation by the sympathetic nervous system?
Adrenaline (about 80%)
Noradrenaline (about 20%)
Adrenaline and Noradrenaline are both derivatives of which amino acid?
Tyrosine
What do the chromaffin cells of the adrenal medulla only secrete around 20% noradrenaline?
20% of the cells lack N-methyl transferase which is an enzyme needed to convert noradrenaline into adrenaline
What are the actions of adrenaline on the heart?
What receptors are activated?
Increased heart rate
Increased contractility
Beta1 receptors: GalphaS –>activation of adenylyl cyclase–> cAMP–> PKA –> Target Proteins
What receptors are activated by adrenaline in the lungs?
What affect does this have on them?
How?
Activation of beta2 receptors
Causes bronchodilation
Through GalphaS–>Adenylyl cyclase activation–>cAMP–>PKA–>Target proteins
What affect does adrenaline have on blood vessels?
Which GPCR subunit is involved?
What are the downstream pathways of receptor activation ?
Vasoconstriction (if alpha1-skin,gut): GalphaQ–>Activates phospholipase C–> DAG IP3—>PKC and Ca2+ release via IP3 receptor–>Target proteins
Vasodilation (if beta2-skeletal muscle):Galphai–>Inhibits Adenylyl cyclase–> decreased cAMP, PKA
How does adrenaline increase the heart rate?
PKA activation leads to phosphorylation of HCn channels and L-type Ca2+ channels with potentials opening
Increasing the SLOPE of the upstroke of the action potential
What is Phaeochromocytoma?
A chromaffin cell tumour that secretes catecholamines (mainly noradrenaline)
What are the characteristics of Phaeochromocytoma?
Severe hypertension /hypotension Headaches Palpitations Anxiety Weight loss Elevated blood glucose Collapse
Why it is VITAL to decrease long-term use of steroids gradually over time and not just stop abruptly?
The steroids suppress the individuals HPA axis and therefore lose the negative feedback that is required to damped cortisol production leadings to excess secretion and potentially sudden death- addisonian crisis
How do you test for adrenocortical function?
- Plasma cortisol (bear in mind time of day)
- ACTH levels
- 24 hours excretion of cortisol and its breakdown products
- dynamic function tests: dexamethasone suppression tests and ACTH stimulation tests
A normal response on a Synacthen test would usually exclude what?
Why?
Addison’s disease
No response to the administered ACTH as the tumour/ectopic ACTH secretion does not respond ????
