The Adrenal Glands and their Disorders Flashcards
Describe the structure of the adrenal glands.
A capsule, then the cortex, then the medulla. From outside in the cortex has the Zona glomerulosa, the Zona fasiculata and the Zona reticularis. The medulla is made up of chromaffin cells.
Mineralocorticoids (aldosterone), glucocorticoids (cortisol etc) and androgens (converted in other tissues to sex hormones), are all part of which group?
The corticosteroids.
Steroid hormones are made from ____________ in the adrenal glands and _______. They are _______ soluble and bind to those in the _________ receptor family to modulate gene transcription.
Cholesterol
Gonads
Lipid
Nuclear
How do steroid hormones modulate gene transcription?
Corticosteroids really diffuse across the plasma membrane and bind to glucocorticoid receptors, resulting in the dissociation of chaperone proteins (e.g. Heat shock protein 90). The receptor-ligand complex translocates to the nucleus, where dimerisation with other receptors may occur. Receptors bind to glucocorticoid response elements (GREs-DNA in promoter region) or other transcription factors (protein production produces end effect).
Aldosterone is the most abundant ______________ and is synthesised and released by the Zona ___________. It is carried mainly by serum ________ (and to a lesser extent transcortin). It is a central component of the ______. Its intracellular receptors exert actions by ___________ gene transcription to regulate plasma ____/____ and arterial _______ __________.
Mineralocorticoid Glomerulosa Albumin RAAS Regulating Na+/K+ Blood pressure
How does aldosterone regulate plasma Na+/K+ and arterial blood pressure?
It promotes NaKATPase expression in distal tubules and collecting ducts of nephrons, which promotes the reabsorption of sodium (and potassium excretion). This influences water retention, so blood volume and therefore pressure.
How does the RAAS go from inputs of hypotension/volaemia to outputs of increased blood pressure and volume?
Decreased renal perfusion, blood pressure and increased sympathetic tone from the baroreceptor reflex, lead to increased renin release from the kidney. The liver constitutively releases angiotensionogen into the blood, which renin converts to AngI. Then, ACE from lung endothelial cells cleaves this to AngII. Angiotensin II, vasoconstricts arterioles, promotes aldosterone release from the adrenal cortex and ADH from the posterior pituitary.
How does ADH help raise blood volume and pressure when its release is stimulated by the RAAS?
Translocation of aquaporin channels and water reabsorption in nephrons.
What are the different types of Hyperaldosteronism and how can you tell the difference clinically?
Primary (defect in adrenal cortex) - most common is bilateral idiopathic adrenal hyperplasia. There’s also Conn’s syndrome (adenoma). Low renin, high aldosterone.
Secondary (overactivity of RAAS-more rare) - renin producing tumour, renal artery stenosis. Low aldosterone in comparison to renin.
What are the signs of Hyperaldosteronism?
High blood pressure (in a young person), LV hypertrophy, a stroke, hypernatraemia, hypokalaemia. Elevated aldosterone independent of the RAAS (primary).
Once it’s been confirmed with a scan, how do you treat primary Hyperaldosteronism?
Bilateral hyperplasia - aldosterone agonists.
Conn’s adenoma - surgery.
100% cure for low K+, but 70% for high BP, as damage already done.
Cortisol is the most abundant ___________, with ___% of the glucocorticoid activity. It is synthesised and released by the Zona __________ in the adrenal cortex in response to ______. With negative feedback it inhibits this, as well as ______. Its carrier protein is ___________.
Corticosteroid 95 Fasiculata ACTH CTH Transcortin
Cortisol has catabolic effects, what are these?
Increased proteolysis in muscle, increased gluconeogenesis in the liver and increased lipolysis in fat.
As well as its catabolic effects, what other effects does cortisol have on the body?
Anti-inflammatory (inhibits macrophages and mast cell degranulation), depression of the immune response (organ transplants) and resistance to stress - increased blood glucose and raised BP by making vessels more sensitive to vasoconstrictors.
Cortisol inhibits insulin-induced ________ translocation in muscle (preventing the _________, and so having a glucose sparing effect). It also causes the redistribution of fat to the _________, supraclavicular and _______-__________ fat pads and the face (moon). The increased blood glucose means increased levels of ______ and so ___________ stores in the liver.
GLUT4 Uptake Abdominal Dorso-cervical Insulin Glycogen
What is Cushing’s syndrome?
A chronic excessive exposure to cortisol.
How may Cushing’s syndrome be caused?
Most commonly from external causes (prescribed glucocorticoids for their anti-inflammatory/immune suppressing qualities), and more rarely from endogenous causes: benign pituitary adenoma secreting ACTH (Cushing’s disease-with pigmentation), excessive cortisol from an adrenal tumour or an ectopic (non pituitary-adrenal) ACTH producing tumour (and/or CRH e.g. Small cell lung cancer).
What are the signs and symptoms of Cushing’s syndrome?
Redistribution of fat, acute weight gain with purple striae, hyperglycaemia and hypertension.
