The Adrenal Gland Flashcards
Explain adrenal gland anatomy
Situated superior pole of the kidney in the retroperitoneal space
Each weighing 4g in adults
What are the 2 endocrine glands in adrenal gland?
Adrenal medulla
Adrenal cortex
Describe the adrenal medulla
Modified sympathetic ganglion - neuroendocrine gland
Secretes catecholamines from postganglionic cell - mainly epinephrine and norepinephrine + dopamine
Describe the adrenal cortex
True endocrine gland and secretes mineralocorticoids, glucocorticoids and sex steroids
What are mineralocorticoids involved in?
Ex. aldosterone
Involved in regulation of Na and K
What are glucocorticoids involved in?
Ex. cortisol
Maintaining plasma glucose
What does the zona golmerulosa produce?
Aldosterone
What does the zona fasciculata produce?
Glucocorticoids
What does the zona reticularis produce?
Sex hormones
What are all steroid hormones derived from?
Cholesterol but different enzymes are found at different adrenal zones so different end products
What enzymes is involved in producing aldosterone and cortisol?
21-hydroxylase
What can defects in 21-hydroxylase cause?
Congenital adrenal hyperplasia resulting in deficiency in aldosterone and cortisol
So associated with disruption of salt and glucose balance
Accumulating steroid precursors are channelled into EX adrenal androgen production
Explain the hypothalamic pituitary adrenal pathway
Ex.
Hypothalamus produces CRH which acts on anterior pituitary stimulating release of ACTH
Acts on adrenal cortex which releases cortisol
Negative feedback loop and short loop by ACTH on CRH
Why does a deficit of 21-hydroxylase cause adrenal hyperplasia?
Lack of this enzyme inhibits synthesis of cortisol
So removes negative feedback on ACTH and CRH release
Increased ACTH secretion is responsible for enlargement
Babies come very ill within few days
Describe cortisol
Glucocorticoid hormone - 95% of plasma cortisol is bound to carrier protein - cortisol binding globulin (CBG)
Binds to cytoplasmic glucocorticoid receptors
Describe the binding of cortisol to receptors and its effect
All nucleated cells have cytoplasmic glucocorticoid receptors
Hormone receptor complex migrates to nucleus - binding to DNA via hormone response element to alter gene expression, transcription and translation
Describe cortisol release
Circadian rhythm, preceded by similar pattern of release of ACTH
Cortisol burst lasts longer as half life longer
Peak is at midnight and fluctuates during day due to stress stimuli
Why is cortisol essential for life?
Helps protect the brain from hypoglycaemia
Has permissive action on glucagon - glucagon inadequate alone to respond to hypoglycaemia
What is the actions of cortisol on glucose metabolism?
Gluconeogenesis
Proteolysis - breaks down muscle protein so gluconeogenic products
Lipolysis
Decreases insulin sensitivity of muscles and adipose tissue
All glucose counter regulatory effects - opposes insulin
How does cortisol effect gluconeogenesis?
Stimulates formation of gluconeogenic enzymes in liver and glucose production
How does cortisol stimulate lipolysis?
In adipose tissue
Increases FFA in plasma creating alternative fuel supply that allows BG conc. to be protected while also creating a substrate for gluconeogenesis - glycerol
How does cortisol supress immune system?
Reduces the circulating lymphocyte count which reduces antibody formation and inhibits inflammatory response (clinically good for asthma, UC and organ transplant)
What are some additional effects of cortisol - non-glucocorticoid?
Negative effect on Ca balance - decreases absorption from gut and increases excretion in kidneys
Impairment of mood and cognition
Permissive effects on norepinephrine
Suppression of immune system
What is Cushing’s disease?
Hypercortisolaemia - strongly associated with hypertension and permissive effect on norepinephrine
Most commonly due to adrenal cortex or pituitary gland tumour
What increases CRH release from hypothalamus?
Circadian rhythm and stress
What can be the effect of exogeneous cortisol?
Enhances negative feedback effects on hypothalamus and pituitary so reducing release of CRH and ACTH
Loss of trophic action of ACTH on adrenal gland causes enlargement - so insufficiently if withdrawal too fast
Describe aldosterone
Mineralocorticoid which acts on kidney to determine level of minerals reabsorbed/excreted
Increases reabsorption of Na ions and promotes excretion of K ions
What is aldosterone release from adrenal cortex controlled primarily by?
Renin angiotensin aldosterone system - RAAS
What does increased aldosterone do?
Release stimulates Na retention and K depletion which reduces blood volume and increases blood pressure
What does decreased aldosterone do?
Leads to Na loss and K increases in plasma which results in decreased blood volume and decreased BP
What is Cushing’s disease characterised by?
Wasting of extremities due to catabolic action of cortisol
But for unknown reasons fat is redistributed to face and trunk
Describe Addison’s disease
Hyposecretion of all adrenal steroid hormone
Due to autoimmune destruction of adrenal cortex
Addison’s crisis is life threatening hypotension and hypoglycaemia
What are the effects of Addison’s disease?
Hyperpigmentation due to XS MSH stimulation of melanocytes
MSH produced from same precursor as ACTH so as ACTH increase so does MSH
Hypotension - loss of permissible effects of cortisol and loss of ability to retain Na
Is hyper or hyposecretion of cortisol more common?
Hyper
How does stress increase vulnerability to infection via action of HPA?
CRH and ACTH release is promoted
Alcohol, caffeine and lack of sleep disinhibit the HPA axis so increase CRH and ACTH levels
This turns down immune system as increased cortisol
How does the adrenal medulla release their neurohormones?
Preganglionic sympathetic fibres terminate on postganglionic cells in medulla - do not have axons
Release neurohormone into blood directly
What is pheochromocytoma?
Rare neuroendocrine tumour found in adrenal medulla
Get EX catecholamines so increase HR, CO then BP
Diabetogenic as adrenergic effect on glucose metabolism
Responds to surgery
What does tertiary hypersecretion cause?
CRH levels high
ACTH levels high
Cortisol levels high
Hypothalamus pathology
What does secondary hypersecretion cause?
CRH levels low
ACTH levels high
Cortisol levels high
Pathology in anterior pituitary
What does primary hypersecretion cause?
CRH levels low
ACTH levels low
Cortisol levels high
Pathology in adrenal cortex
