Endocrine Physiology - Adrenal

Question 1

Describe the anatomy of the adrenal gland

Answer 1

Bilateral, approximately triangular
Located at the superior pole of each kidney, around the level of T12

Retroperitoneal & encased in a protective fatty capsule.

Cortex (70%)
Zona Glomerulosa (15%) secretes aldosterone
Zona Fasciculata (50%) secretes cortisol
Zona Reticularis (5%) secretes sex steroids

Medulla
Essentially a modified sympathetic ganglion
Chromaffin cells, derived from neural crest
Secretes catecholamine neurohormones, ACh, Met-encephalin, Chromogranin A

Question 2

Describe the synthesis pathway for catecholamines

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Answer 2

Phenylalanine
Phenylalanine Hydroxylase
Tyrosine
Tyrosine Hydroxylase
L-DOPA
L Amino Acid Decarboxylase
Dopamine
Dopamine β Hydroxylase
Noradrenaline
PNMT
Adrenaline

norad:adrenaline secretion ratio is 20:80 in healthy adults

Question 3

How is noradrenaline eliminated

Answer 3

Two uptake processes

1: High affinity transport process sequesters NA into the nerve terminal from which it was released - mostly repackaged into vesicles, with some metabolism

2: Slower proces, NA passes into systemic circulation & degraded by catechol-O-methyltransferase (COMT) in the liver & other tissues

Question 4

Explain the hypothalamic-pituitary-adrenal axis & control of cortisol release

Answer 4

Cardiovascular/Respiratory
Sensitises blood vessels/airwayas to the effects of catacholamines

Catabolic
Gluconeogenesis
Protein catabolism
Lipolysis

Anti-inflammatory
Reduced white cell migration (neutrophils/macrophages)
Reduced cytokine production
Stabilisation of lysosome membranes
Reduces swelling

Miscellaneous
Mineralocorticoid activity
Increased sodium reabsorption & potassium excretion in DCT
Inhibits T4 to T3 conversion

Question 5

Explain the renin-angiotensin-aldosterone system

Answer 5

Juxtaglomerular apparatus has 3 types of cell
Juxtaglomerular cells in the afferent arteriole (protenin and convert it to renin)
Macula densa in the DCT
Mesangial (aka Lacis) cells next to glomerulus

Triggers for renin release:
Decreased renal blood supply
Decreased Na⁺ at the macula densa
β1-mediated sympathetic stimulation

Renin cleaves Angiotensinogen (secreted by liver into plasma) to Angiotensin I
Cleaved by ACE in the lungs to Angiotensin II

Angiotensin II acts on AT1 and AT2 G-Protein coupled receptors:

Profound arteriolar vasoconstriction (direct and indirect mechanisms), including inhibition of catecholamine reuptake
Triggers thirst reflex
Releases aldosterone
Releases ADH and reduces GFR to retain fluid
Releases ACTH as part of stress response
Negative feedback to reduce renin production

Question 6

What controls aldosterone release, and what are its effects?

Answer 6

Aldosterone acts to retain salt & water, acts primarily on DCT, as part of the renin-angiotensin-aldosterone system.

Juxtaglomerular apparatus detects low sodium in extracellular fluid around DCT, triggers release of renin.

Renin converts antiotensinogen (produced by the liver into the plasma) to angiotensin I.

This travels to the lungs where ACE (Angiotensin-converting enzyme) cleaves it to angiotensin II.

Angiotensin 2 has its own effects, but also triggers aldosterone release and production (as not much is stored in the adrenal zona glomerulosa).

Hyperkalaemia also directly stimulates aldosterone release.

Three main actions at DCT:
Increases NaKATPase pump (also in other tissues) - increases extracellular sodium, and intracellular potassium
Increases expression of sodium channels in DCT
Increases mitochondrial activity within these cells

Question 7

What problems are associated with hyperadrenalism?

Answer 7

Conn’s
Hyperaldosteronism
Increased salt/water retention leads to high BP and hypokalaemia
As sodium is reabsorbed in exchange for potassium & hydrogen, it leads to a metabolic alkalosis

Cushing’s
Hypercortisolism
Obesity, Moon facies, thin skin & poor wound healing
HTN and cardiac failure
Hypernatraemia, hypokalaemia, diabetes mellitus
Cushing’s syndrome describes hypercotisolism due to any cause
Cushing’s disease refers to the symptoms caused by an ACTH-secreting pituitary tumour

Derangement of sex steroid physiology can lead to virilisation, feminisation, or infertility.

Overactive medulla is seen in Phaeochromocytoma
Excess catecholamines lead to:
Profound HTN (requiring alpha & beta blockade)
Tachyarrhythmias
Vasoconstriction
Cardiomyopathies
Glucose intoleranceC

Question 8

What problems are associated with hypoadrenalism?

Answer 8

Adrenocorticoid deficiency is seen in Addison’s disease, diabetes, tuberculosis, amyloidosis, and thyroid disease

Hyperkalaemia and hyponatraemia
Hypoglycaemia and hypotension
Hypercalcaemia