Endocrinology

Question 1

What are glucocorticoids, how are their regulated/secreted, what is their MOA and systemic effects

Answer 1

Glucocorticoids (cortisone, cortisol, corticosterone) are a class of steroid, lipid soluble molecules derived from cholesterol.
Released from Zona fasciculata.
Both anabolic, and catabolic. Maintain homeostasis

MoA: binding to intracellular receptors (GR alpha and beta) - found in all cells
work via mRNA transcription (therefore takes some time to work) to synthesis new enzymes involved in metabolism and the formation of lipocortin (negative feedback on HPA)

Negative feedback loop involving hypothalamus and pituitary
- CRH –> ACTH –> cortisol
- diurnal (high in AM)

Stimulus for CRH release is low cortisol, stress, pain, SNS.

Question 2

What are the effects of Glucocorticoids

Answer 2

They are metabolic:
Carbohydrates:
- increase gluconeogenesis, glycogenolysis
- decrease glycolysis, gluconeogenesis
- increase BGL

Fats:
- increase lipogenesis
- decrease lipolysis
redistribute fat from peripheral to central
- central fat deposition, peripheral wasting

Protein:
- increase protein catabolism

CVS:
- permissive effect on catecholamines (increase sensitivity)
- increase PNMT activity (conversion of noradrenaline to adrenaline in medulla)
Immune:
- Decreased pro-inflammatory cytokines (IL1/6 and TNF-alpha
- increased anti-inflammatory cytokines: (IL10/13)
- increase WCC but decreased activity
inhibits phsophlipase A = Bone: increased osteoclastic activity = increase bone fracture risk
CNS:
- behavioural change, mood change
- reduced PONV
- reduce cellular oedema
GIT:
- increase risk of PUD

Question 3

What are the equivalent doses of Hydrocortisone, Dexemethasone and prednisolone.
what is the ratio of glucocorticoid to mineralocorticoid effect.

Answer 3

4 Dex = 100mg hydro = 25mg pred

Dex: mainly GCC, little/no MCC
Hydro: 1:1 GCC to MCC
Pred: mainly GCC. 15:1 ratio to MCC

Fludrocortisone has the most mineralocorticoid effect (?200:1)

Question 4

What are the uses of corticosteroids

Answer 4

PONV
reduction in cellular swelling
stress dosing for adrenal suppression (Addisons, auto-immune disease dependant on steroids)
Anti-inflammatory effect
- bronchospasm, thyroid storm. Allergies
Minimise bronchopulmonary dysplasia in pre-term infants

Question 5

What is stimulation, site of release and MOA of mineralocorticoids

Answer 5

mineralcorticoids i.e aldosterone are released by the zone glomerulosa in adrenals glands in response to ACTH, hyperkalaemia, acidosis, and feedback from angiotensin

MoA: works intracellularly
- specifically in distal tubules of kidney and GIT where the cells contain 11-beta-hydoxysteroid dehydrogenase which attenuates the GC effect

Question 6

What are the effects of mineralcorticoids (aldosterone)

Answer 6

Upregulation of:
- basolateral Na/K/ATPase
- eNAC channels in renal tubular cells and sweat glands
- Na/H anti porter, H/K ATP-ase

Increased:
- Na+ and H20 reabsorption/retention
- increase. K+ and H+ secretion