Adrenal Glands Flashcards
What are the four zones of the adrenal gland from top to bottom?
- Zona Glomerulosa (mineralocorticoids e.g. aldosterone)
- Zona Fasciculta (glucocorticoids e.g cortisol)
- Zona Reticularis (glucorticoids and small amount of androgens)
- Medulla (chromaffin cells- adrenaline, noradrenaline)
What is the clinical signicance of 21-hydroxylase deficiency?
sex hormone overproduction
How do corticosteroids exert their actions?
- Corticosteroids readily diffuse across plasma membrane
- Bind to intracellular glucocorticoid receptors.
-Binding causes dissociation of
chaperone proteins (e.g. heat
shock protein 90),
-Receptor ligand complex
translocates to nucleus
-Receptors bind to glucocorticoid
response elements (GREs), or
other transcription factors
How does aldosterone exert its effects?
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.
What is the difference between primary and secondary hyperaldosteronism?
primary= defect in adrenal cortex (e.g d8e to bilateral idiopathic adrenal hyperplasia or Conn’s syndrome)
secondary= overactivity of RAAS (e.g rare renin producing tumour or renal artery stenosis)
best way to distinguish is measuring renin: aldosterone levels . primary has low renin levels.
What are the signs of hyperaldosteronism and what is the treatment?
- high blood pressure
- LV hypertrophy
- stroke
- hypernatraemia
- hypokalemia
treatment depends on type of hyperaldosteronism. aldosterone producing adenomas can be removed via surgery. spironolactone can be given (mineralocorticoid receptor antagonist)
What are the actions of cortisol?
- Increased protein breakdown in muscle
- Increased gluconeogenesis in liver
- Increased lipolysis in fat
• Resistance to stress (increased supply of glucose, raise blood
pressure by making vessels more sensitive to vasoconstrictors)
- Anti-inflammatory effects (inhibits macrophage activity + Mast cell degranulation)
- Depression of immune response (prescribed to organ transplant patients)
How is cortisol release regulated?
stress (e.g pain, fever, hypoglycaemia, low bp stimulates CRH release at hypothalamus. CRH stimulates ACTH release at AP. ACTH stimulate cortisol release at zona fasiculata. Cortisol is transported in the blood by transcortin and the cortisol receptor exerts its actions by regulating gene transcription.
Describe the effect of glucocorticoids on metabolism
Net effects are increased glucose production and breakdown of protein as well as redistribution of fat.
In muscle, cortisol inhibits GLUT4 translocation of glucose (glucose sparing).
In fat, chronic high levels of cortisol can result in redistribution of fat (moon face/buffalo hump).
What is Cushing’s syndrome?
-chronic excessive exposure to cortisol e.g via external causes such as prescribed glucocorticoids or endogenous causes such as Cushings disease, or adrenal cushings)
causes:
-Plethoric moon- shaped face -“Buffalo hump” -Abdominal obesity -Purple striae -Acute weight gain -Hyperglycaemia -Hypertension
What are some steroid drugs?
e.g prednisolone, dexamethasone
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.
Note, steroid dosage should be reduced gradually and not stopped suddenly.
What is Addison’s disease?
chronic adrenal sufficiency
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
- Hypoglycaemia
Why is hyper pigmentation seen in Addison’s?
-initial biosynthetic precursor is proopiomelanocortin (POMC).
Post-translational processing of POMC at different sites produces biologically active peptides including ACTH, MSH (Melanocyte Stimulating Hormone) and endorphins.
-The MSH sequence is contained within the ACTH sequence in POMC giving ACTH some MSH-like activity when present in excess (e.g as in Addisons)
What is an Addisonian crisis?
- clinical emergency that must be treated with intra-venous cortisol and fluid replacement (dextrose in normal saline) to avoid death.
- life threatening emergency due to adrenal insufficiency precipitated by severe stress, infection, trauma, over exertion etc).
- symptoms include nausea, vomiting, pyrexia, vascular collapse
What are the adrenal 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.
