Normal adrenal function Flashcards
HI
Briefly describe the anatomy, location, innervation and vascularisation of the adrenal gland
Anatomy of Adrenal Glands
- Small (~5 g), bilateral organs.
- Located behind peritoneum, above and in front of the upper pole of each kidney (Supra-renal gland).
- Embryological origin: Mesoderm (~90%) forms cortex, Ectoderm (neural crest) (~10%) forms medulla (part of Sympathetic Nervous System).
- note that adrenal gland is essentially post-ganglionic ganglion of SNS
- instead of synapsing, it releases hormones into bloodstream
Anatomical Location
- Retro-peritoneal position.
- Under the diaphragm.
- At the upper pole of the kidney.
- Approximately 3-5 cm in length.
- Weighs about 5-10 grams.
Describe the regulation of adrenocortical hormone secretion
-
Glucocorticoid Secretion:
- Controlled by the pituitary gland.
-
Mineralocorticoid Secretion:
- Partial control by the pituitary gland.
- Predominantly regulated by extracellular potassium concentration and renin from the kidney.
List the functions of the adrenal gland
- Synthesis of:
- Mineralocorticoids (Aldosterone from Zona glomerulosa).
- Glucocorticoids (Predominantly Cortisol from Zona fasciculata).
- Androgens (DHEA and Androstenedione from Zona reticularis).
- Catecholamines (from adrenal medulla).
Note the features of the pathway of steroid hormone synthesis
![[Pasted image 20231025195109.png]]
- this diagram demonstrates that all steroid hormones have a similar chemical structure
- this is because they are derived from the same precursor: cholesterol
- mutations in proximal enzymes of the pathway are either incompatible with life or result in severe defects leading to death shortly after birth
- synthesis of hormones depends on enzymes present within the layer of the cortex
- Adrenal does not synthesize significant quantities of estradiol or testosterone under normal circumstances.
- Note also that the androgens produce have low affinity for androsterone (?)
- in neonates, adrenal gland is large
- secretes estriol which is essential for maintaining pregnancy
- facilitated by aromatase present in placenta
Describe the effect of circadian rhythm on secretion
Virtually all hormones, and certainly pituitary hormones, have a circadian pattern of secretion.
(Can be manipulated for therapeutic benefit e.g. tablet for CAH at 4 am).
Must interpret blood test results taken in afternoon with caution.
Best to take in morning.
Note changes in pattern of secretion occur with disease:
- Cushing’s results in constitutively active secretion, loss of diurnal pattern
Describe the biological actions of GCs
- Cortisol (Hydrocortisone).
- Analogue: Prednisolone.
- Bound in plasma to Corticosteroid Binding Globulin (CBG - made by liver, Transcortin). ^[note: free cortisol is detected in urine and saliva NOT blood]
- Target tissues: all cells and organs; the response depends upon tissue
Two broad effects - Metabolic effects - carbohydrate, protein and lipids
- Anti-inflammatory properties, and immune modulation.
Describe the metabolic effect of GCs
- GCC increase blood glucose concentration through their actions on glycogen, protein and lipid metabolism
- Hepatic glucose output increases through the activation of key enzymes of gluconeogenesis such as glucose-6-phosphatase and phosphoenolpyruvate carboxykinase
- In peripheral tissues (muscle and fat) cortisol inhibits glucose uptake and utilization
- In peripheral tissues cortisol causes catabolism of protein with released amino acids being used as gluconeogenic substrates
- In adipose tissue lipolysis is activated causing release of free fatty acids into the circulation
- GCC have a permissive effect on catecholamines and glucagon
The net result is insulin resistance and an increase in blood glucose
concentration
Note that at pharmacological levels, adverse effects are a result of the exaggeration of cortisol’s catabolic function:
- insulin resistance
- bone and muscle catabolism
- peripheral fat insulin ressistance
Describe the consequences of GC excess
- brain: depression and psychosis
- endocrine: decreased LH and FSH release, TSH release, GH secretion
- eye: glaucoma and cataracts
- GI tract: peptic ulcerations
- CVrenal: salt and water retention, HTN
- growth and development: decreased linear growth
- immune system: anti-inflammatory action, immunouppression
- skin/muscle/connective tissue: protein catabolism and collagen breakdown, skin thinning, muscular atrophy
- bone and Ca metabolism: ‘osteoporosis’: reduced mass and formation
- adipose tissue distribution: promotion of visceral obesity
- CH/lipid metabolism: overall diabetogenic effect: increased hepatic glycogen deposition, increased GNG, FFA production and increased peripheral insulin resistance
Describe the role of mineralocorticoids
- Regulation primarily by the renin-angiotensin-aldosterone pathway.
- ACTH is a minor stimulus
- Stimuli include hypovolemia and increased potassium.
- Principal actions involve sodium regulation in the kidney’s distal tubule.
- Similar to cortisol, aldosterone exerts its effects by binding a mineralocorticoid receptor which translocates to nucleus
- this upregulates ENaC, NA/K/ATPase and regulatory proteins to maintain ENaC and NA/K/ATPase
- cortisol can theoretically bind this receptor, but distal cells have an enzyme, 11b-HSD2 which converts cortisol to the inactive cortisone, which is then excreted ^[enzyme inhibited by licorice and in certain diseases, such as?]
Discuss the actions of glucocorticoids and mcs
- Most actions mediated through gene expression. Hundreds of such genes have been described. Hence why pharmacological agents have wide range of side effects
- Some actions occur rapidly, possibly through direct hormone actions.
- it is thought that there may be some directaction s of both classes of hormones. These are not well characterised and they are probably less important
Describe the adrenal androgens
- DHEA and Androstenedione secreted by the adrenal throughout life.
- Weakly androgenic; conjugated and excreted in urine.
Side notes:
- adrenarche and cytochrome B, cofactor for enzyme
- DHT problematic form
- - high ACTH can drive high adrenal androgens in an attempt to sort cortisol deficiency
Describe medulla and the hormones of the adrenal medulla
- Sympathetic nervous system and adrenal medulla form the sympatho-adrenomedullary unit.
- Major hormones:
- Adrenaline (Epinephrine).
- Noradrenaline (Norepinephrine).
- Dopamine.
- Synthesized from tyrosine.
- Very short half-life in circulation (1-2 minutes).
Adrenal Medullary Hormones (1)
- Action via specific cell surface receptors.
- Adrenaline: Predominantly β1 and β2.
- Noradrenaline: Predominantly α1 and β1.
- Actions relate to receptor:
- α1: Vasoconstriction and increased blood pressure.
- β1: Cardiac positive inotrope.
- β2: Vasodilation.
Adrenal Medullary Hormones (2)
- Metabolic actions:
- Stimulate glycogenolysis, gluconeogenesis, lipolysis.
- Stimulate amino acid uptake into muscle.
- Increase cellular uptake of potassium and phosphate to increases ATP generation in cells
- Stimulate release of glucagon, GH, and renin.
- Insulin secretion stimulated by β2 and inhibited by α2.
- Dopamine in hypothalamus inhibits prolactin secretion.
