The Adrenal Glands Flashcards
The adrenal glands
Top layer of cortex - Zona glomerulosa - mineralcortocids (e.g. aldosterone)
Middle layer of cortex - Zona fasiculata - glucocorticoids (e.g. cortisol)
Deepest layer of cortex - zone reticularis - glucocorticoids + small amounts of androgens
Layer of Medulla - chromaffin cells - adrenaline (~80%), Noradrenaline(~20%)
The steroid hormones
Synthesised from cholesterol in adrenal glands and gonads
Lipid soluble hormones
Bind to receptors of the nuclear receptor family to modulate gene transcription Glucocorticoids Mineralocorticoids Androgens Oestrogens Progestins
Corticosteroids exert their actions by regulating gene transcription
Corticosteroids readily diffuse across plasma membrane
Bind to glucocorticoid receptors.
Binding causes dissociation of chaperone proteins (e.g. heat shock protein 90),
Receptor ligand complex translocates to nucleus
Dimerisation with other receptors can occur
Receptors bind to glucocorticoid response elements (GREs), or other transcription factors
Aldosterone
Most abundant mineralocorticoid
Synthesised and released by Zona glomerulosa of adrenal cortex
Steroid hormone = lipophilic. Carrier protein = mainly serum albumin and to a lesser extent transcortin
Aldosterone receptor is intracellular & exerts its actions by regulating gene transcription
Plays central role in regulation of plasma Na+, K+ and arterial blood pressure.
Main actions in distal tubules and collecting ducts of nephron where it promotes expression of Na+/K+ pump promoting reabsorption of Na+ and excretion of K+ thereby influencing water retention, blood volume & therefore blood pressure.
On of the Central components of renin-angiotensin-aldosterone system (RAAS)
Hyperaldosteronism - Too much aldosterone produced
Primary - Defect in adrenal cortex - Bilateral idiopathic adrenal hyperplasia - most common
or Aldosterone secreting adrenal adenoma (Conn’s syndrome)
Or Low renin levels (high aldosterone:renin ratio)
Secondary - due to activity of the RAAS Renin producing tumour (Rare) e.g juxtaglomerular tumour. Renal artery stenosis High renin levels and remain high (low aldosterone:renin ratio)
Signs - High bp Left ventricular hypertrophy Stroke Hypernatraemia Hypokalaemia
Treatment - depends on type - aldosterone producing adenoma removed by surgery
Spironolactone acts as a mineralcorticoid receptor antagonist
Cortisol
Most abundant corticosteroid & accounts for ~95% of glucocorticoid activity
Synthesised and released by Zona fasiculata in response to ACTH
Negative feedback to hypothalamus inhibits CRH & ACTH release
Steroid hormone - Transported by a carrier protein in plasma = transcortin
Cortisol receptor exerts its actions by regulating gene transcription
Actions:
Increased protein breakdown in muscle
Increased lipolysis in fat
Increased gluconeogenesis in liver
Resistance to stress (increased supply of glucose, raise blood pressure by making vessels more sensitive to vasoconstrictors) reactions
Anti-inflammatory effects (inhibits macrophage activity + Mast cell degranulation)
Depression of immune response (prescribed to organ transplant patients)
Glucocorticoid actions on metabolism
Increased Glucose leads to increased
Cushing’s Syndrome
Signs and symptoms Plethoric moon shaped face Buffalo hump Abdominal obesity Purple striae - mainly on abdomen Acute weight gain Hyperglycaemia Hypertension
Causes - endogenous and exogenous
Exogenous - overdosing/over use of prescribed glucocorticoids (most common cause)
Endogenous - a benign pituitary adenoma secreting excess ACTH (now called Cushing’s disease), or excess cortisol produced by adrenal tumor, or non pituitary adrenal tumours producing ACTH e.g. small cell lung cancer (very rare)
Steroid drugs
e.g. Prednisolone, Dexamethasone Anti-inflammatory & immunomodulatory effects Used to treat inflammatory disorders e.g. Asthma Inflammatory bowel disease Rheumatoid arthritis Other auto-immune conditions
Also used to supress immune reaction to organ transplantation
Side-effects are the same as the effects of higher levels of cortisol, plus can also have mineralocorticoid effects
IMPORTANT POINT !! Steroid dosage should be reduced gradually and not stopped suddenly - this is done because due to the large amount of cortisol in the body, it stops producing it endogenously, therfore if you stop completely then your body will have a sudden drop in cortisol
Addison’s disease
Chronic adrenal insufficiency
First identified by Thomas Addison in 1855 while working at Guy’s.
Main cause at time was a complication of Tuberculosis.
Most common cause now is destructive atrophy from autoimmune response
Affects more women than men.
Exact reason for autoimmunity unknown.
Other, much rarer causes include fungal infection, adrenal cancer & adrenal haemorrhage (e.g. following trauma)
Signs & Symptoms - Postural hypotension, Lethargy, Weight loss, Anorexia, Increased skin pigmentation and Hypoglycaemia
Hyperpigmentation in addisons - Increased melanocyte stimulating hormone (MSH) as consequence of increased POMC in Addison’s leads to hyperpigmentation.
This occurs due to the low levels of circulating cortisol, therefore very little negative feedback is acting on Ant. Pit., hence keeps producing ACTH (using POMC)
As well as producing ACTH, it also produces MSH, hence leading to hyperpigmentation
ACTH itself can also activate melanocortin receptors on melanocytes so will also contribute to hyperpigmentation
Addisonian Crisis Life threatening emergency due to adrenal insufficiency Precipitated by - Severe stress Salt depravation Infection Trauma Cold exposure Over exertion Abrupt steroid drug withdrawal
Symptoms - Nausea
Vomiting
Pyrexia,
Hypotension - Vascular collapse -> could lead to heart problems
Treatment - Fluid replacement
exogenous Cortisol
Androgens
Innermost layer of adrenal cortex (zona reticularis) secretes weak androgens
Dehydroepiandrosterone (DHEA) and androstenedione
Partially regulated by ACTH and CRH
In male DHEA converted to testosterone in testes (after puberty this is insignificant since testes release far more testosterone themselves)
In female adrenal androgens promote libido and are converted to oestrogens by other tissues. After menopause this is only source of oestrogens.
Promote axillary and pubic hair growth in both sexes
Adrenal medulla
Adrenal medulla is a modified sympathetic ganglion of the ANS
Chromaffin cells in adrenal medulla lack axons but act as postganglionic nerve fibres that release hormones into blood:
Adrenaline (~80%), Noradrenaline (~20%)
~20% chromaffin cells lack N-methyl transferase enzyme and secrete noradrenaline
Adrenaline and Noradrenaline will then bind to adrenoreceptors around the body - 4 types - alpha 1, alpha 2, ß1 and ß2
Alpha 1 is a Gq PCR (PLC stim), alpha 2 is a Gi PCR(inhibits AC), and both ß1 and 2 are Gs PCR (AC stim)
Throughout the body there are different receptors -
In the heart there are ß1 receptors present - when adrenaline binds this causes an increase in heart rate and contractility
In the lungs - ß2 receptors are present - causing bronchodilation when bound to
In blood vessels there is both alpha 1 and ß2 receptors - in skin and gut its alpha1, therefore causing vasoconstiction, in muscles its ß2, therefore causing vasodilation
Phaechromocytoma - chromaffin cell tumor
Phaeo (dark) chromo (color) cyte (cell) oma (Tumour stains dark with chromium salts)
Rare, catecholamine-secreting tumour (mainly noradrenaline)
May precipitate life-threatening hypertension
Characteristics: - Severe hypertension Headaches Palpitations Diaphoresis (excessive sweating) Anxiety Weight loss Elevated blood glucose
