Lecture 18 Flashcards
Where do you find the adrenal glands?
On top of the kidneys
What is the structure of the adrenal glands and where are they derived from?
Fibrous capsule around entire gland
Cortex (mesoderm origin-envelopes medulla)
-zona glomerulosa (produces mineralocorticoids)
-zona fasiculata (produces glucocorticoids)
-zona reticularis (produces glucocorticoids and some androgens)
Medulla (from neural crest cells)
-chromaffin cells (secrete mostly adrenaline, but also noradrenaline)
What are chromaffin cells?
Post ganglionic neuronal cells with no axon
- usually sympathetic
- secrete NA/A into bloodstream
Give an example of a mineralocorticoid:
Aldosterone
Give some examples of glucocorticoids:
- cortisol (main)
- corticosterone
- cortisone
Give some examples of androgens:
Sex hormones
-dehydroepiandrosterone
-androstenedione
These are converted to testosterone/oestrogen in peripheral tissues
What is the main function of corticosteroids?
Steroid hormones bind to intracellular receptors as they are lipid soluble and affect gene transcription
What are the steroid hormones derived from and where are they synthesised?
Derived from cholesterol
Synthesised in adrenal glands and gonads
Why is the enzyme 21-hydroxylase clinically important?
Deficiency in this causes congenital adrenal hyperplasia
- decreased cortisol and aldosterone= health problems
- increased androgens= early puberty and genital changes
Method of action of corticosteroids:
-readily diffuse across plasma membrane
-bind to glucocorticoid receptors
-binding causes dissociation of chaperone proteins
-receptor ligand complex translocates to nucleus
(dimerisation with other receptors can occur)
-receptors bind to glucocorticoid response elements (GRE’s) or transcription factors
Give an example of a chaperone protein:
Heat shock protein 90
How is aldosterone transported in blood?
Bound to serum albumin (sometimes to transcortin)
What is the role of aldosterone?
Regulation of gene transcription
Regulation of plasma Na+/K+/arterial blood pressure
-acts on collecting duct of nephron to promote expression of Na+/K+ pump
-promoting reabsorption of Na+ and excretion of K+
=influencing water retention, blood volume and therefore BP
(reabsorbing more Na+ causes more water to be reabsorbed)
What is the role of aldosterone inthe renin-angiotensin-aldosterone system? (RAAS)
Angiotensin 2 acts on the adrenal cortex to produce aldosterone when A2 receptors are activated
What are the types of hyperaldosteronism?
Primary: defect in adrenal cortex
- bilateral idiopathic adrenal hyperplasia (most common)
- aldosterone secreting adenoma (Conn’s syndrome)
Secondary: over activity of RAAS
- renin producing tumour
- renal artery stenosis: reduced blood supply stimulates production of renin
How do you distinguish between primary/secondary hyperaldosteronism?
Primary: low renin levels (high aldosterone:renin ratio)
Secondary: high renin levels (low aldosterone:renin ratio)
What are the signs and treatment for hyperaldosteronism?
Signs
- high BP
- left ventricular hypertrophy
- stroke
- hypokalaemia
- hypernatraemia (high calcium)
Treatment:
- aldosterone producing adenomas are removed by surgery
- drug called spironolactone used (mineralcorticoid receptor agonist)
When is cortisol released?
In response to ACTH, released by zona fasiculata
-negative feedback (increased cortisol) to hypoathalmus inhibits CRH/ACTH release
How is cortisol transported?
Bound to carrier protein in plasma called transcortin
What is the action of cortisol?
-increased proteolysis in muscle
-increased lipolysis in fat
(catabolic effects)
-increased gluconeogenesis in liver
-anti-inflammatory effects (useful for allergic reactions as inhibits macrophage activity/mast cell degranulation)
-depression of immune response (given to transplant patients)
Effect of glucocorticoids (cortisol) on metabolism:
Net effects
- increased glucose production
- breakdown of protein
- redistribution of fat (to abdomen, supraclavicular fat pads:buffalo hump, dorso-cervical fat pads: moon face)
- reduced sensitivity to insulin in muscles as cortisol inhibits GLUT4 translocation
- increased glycogen stores in liver
What is Cushing’s syndrome and its causes?
Excessive exposure to cortisol
- prescribed glucocorticoids
- benign pituitary adenoma secreting ACTH (Cushing’s disease)
- excess cortisol produced by adrenal tumour (Adrenal Cushing’s)
- non pituitary-adrenal tumours producing ACTH (small cell lung cancer)
What are the signs and symptoms of Cushing’s syndrome?
- plethoric moon shaped face
- buffalo hump
- abdominal obesity
- purple striae (weakened strength of skin due to proteolysis)
- acute weight gain
- hyperglycaemia
- hypertension
Give some examples of steroid drugs and what they are used to treat:
Prednisolone Dexamethasone -asthma -IBS -RA (inflammatory diseases) -used to supress immune reaction in transplant patients
What are the side effects of steroid drugs?
Same as those of higher cortisol levels
Important point about steroid dosage:
Dosage should be reduced gradually not stopped suddenly
What is Addison’s disease?
Chronic adrenal deficiency
- due to autoimmune response (attacking adrenal cortex)
- affects women more
- can be due to fungal infection/adrenal cancer/adrenal haemorrhage
What are the signs and symptoms for Addison’s disease?
- postural hypotension
- lethargy
- weight loss (due to reduced food intake due to alpha MSH)
- anorexia
- increased skin pigmentation
- hypoglycaemia
Why do you get hyperpigmentation in Addison’s disease?
- decreased cortisol
- negative feedback on anterior pituitary
- more POMC required to produce more ACTH and alpha-MSH
- alpha-MSH controls melanin synthesis
- ACTH can also activate melanocortin receptors on melanocytes
What is Addisonian crisis?
Life threatening emergency
- nausea
- vomiting
- pyrexia
- hypotension
- vascular collapse
What is the treatment for Addisonian crisis?
- fluid replacement
- cortisol
What is Addison’s crisis precipitated by?
- severe stress
- salt deprivation
- infection
- trauma
- cold exposure
- over-exertion
- abrupt steroid withdrawal
What are androgens and what are they regulated by?
Regulated partially by ACTH/CRH
-in men DHEA (dehydroepiandrosterone) is converted to testosterone in testes
-in women adrenal androgens promote libido and are converted to oestrogen by other tissues (after menopause this is the only source of oestrogens)
Promote axillary and pubic hair growth
What enzymes do the chromaffin cells that produce NA instead of adrenaline lack?
N-methyl transferase which converts NA to adrenaline
chromaffin cells release 20% NA and 80% adrenaline
What are the hormonal actions of adrenaline?
Fight/flight
- increase HR and contractility via B1
- bronchodilation via B2
- vasoconstriction via A1
- vasodilation via B2
- increased renin secretion via B1/B2
- glycolysis via A1/B2
- glycogenolysis via A1/B2
- lipolysis via B2
- glucagon secretion via A2
- insulin secretion via A2/B2
- glycogenolysis/gluconeogenesis via A1/B2
Give some examples of adrenergic receptors:
B1/B2
A1/A2
G-coupled
What is phaeochromocytoma?
Chromaffin cell tumour
- tumour stains dark with chromium salts
- mainly NA
What are the symptoms of phaeochromocytoma?
- severe hypertension (life-threatening)
- headaches
- palpitations
- anxiety
- weight loss
- elevated blood glucose
- diaphoresis (excessive sweating)
What are NA/adrenaline derived from?
Tyrosine
What are the differences between hormones from cortex/medulla?
Cortex: (cortisol/aldosterone/androgens) -endocrine -lipid soluble -nuclear receptors -slow response -death if none of these are present Medulla: (adrenaline/NA) -neurocrine -water soluble -GPCR's -fast response -no ill effects from lack of these
