mineralocorticoid disorders and endocrine hypertension W7 Flashcards
3 main physiological factors regulating blood pressure?
cardiac output
vascular tone
extracellular fluid volume
3 adrenal hormone systems that regulate blood pressure
sympathetic
renin-angiotensin
HPA axis
what hormones can increase cardiac output
catecholamines
cortisol potentiation
what hormones can increase vascular tone?
angiotensin 2
aldosterone
catecholamines
cortisol potentiation
what hormones can increase extracellular fluid
aldosterone
cortisol
what is renin released in response to
JG cell baroreceptors
macula densa cell Na+ sensing
carotid arch baroreceptors
rapid vs long term effects of RAS and aldosterone?
vasculature - rapid (seconds)
adrenal - rapid (minutes)
kidney - 6-48 hrs
renin angiotensin system effect on vasculature? when does this occur?
vasoconstriction
postural
regulation of BP
renin angiotensin system effect on adrenal glands?
increased aldosterone synthesis
increased catecholamine synthesis
renin angiotensin system effect on kidneys?
increased Na+ and water reabsorption via RAAS
long term effects of RAS on vasculature?
smooth muscle
increased cell hyperplasia
increased cell hypertrophy
long-lasting change in vascular tone
RAS long term affects on CNS?
increased thirst
increased salt appetite
increased ADH release
RAS long term effects on adrenal gland?
increased aldosterone synthase enzyme expression
increased glomerulosa cell proliferation
common cause of endocrine hypertension?
excess production of aldosterone
conn’s syndrome?
unilateral adrenal tumour
aldosterone-producing adenoma
Conn’s syndrome presentation?
high aldosterone
MR activation (mineralocorticoid receptor)
high Na+
low K+
ECF expansion (extracellular fluid)
hypertension
low renin (RAS)
types of primary hyperaldosteronism?
Conn’s syndrome
Bilateral adrenal hyperplasia (most common)
bilateral adrenal hyperplasia presentation?
same as Conn’s syndrome:
high aldosterone
MR activation (mineralocorticoid receptor)
high Na+
low K+
ECF expansion (extracellular fluid)
hypertension
low renin (RAS)
treatment of Conn’s syndrome?
surgical:
venous sampling and/or CT scan
unilateral adrenalectomy
treatment of bilateral adrenal hyperplasia?
pharmacological
anti-hypertensives eg MR antagonists
spironolactone, eplerenone
what is glucocorticoid-remediable aldosteronism (GRA)
autosomal dominant genetic disorder (chromosome 8)
ACTH-driven hyperaldosteronism
glucocorticoid-remediable aldosteronism (GRA) pathophysiology?
2 genes involved in protein synthesis close on chain - 95% identical but gene promotors are different.
hybrid gene created during meiosis, much more active gene.
presentation of glucocorticoid-remediable aldosteronism (GRA)
high aldosterone
MR activation
High Na+
low K+
ECF expansion
hypertension
low renin (RAS)
same as other causes of primary hyperaldosteronism!!
treatment of glucocorticoid-remediable aldosteronism (GRA)
synthetic glucocorticoids (inhibit ACTH production, downregulate function of hybrid gene
renin-secreting JG cell tumour presentation?
high plasma renin, high aldosterone
MR activation, high Na+, low K+
ECF expansion, hypertension
what is a JG cell
juxtaglomerular cell - responsible for production, storage, and release of renin
treatment of renin-secreting JG cell tumour?
surgical removal
what type of hyperaldosteronism is renin-secreting JG cell tumour?
secondary hypoaldosteronism
cortisol overproduction - Cushing’s syndrome/disease presentation?
weight gain, stretch marks, easy bruising, proximal muscle weakness
diabetes mellitus, menstrual irregularities, depression
Cushing’s Syndrome vs Cushing’s disease?
Cushing’s syndrome = adrenal tumour
Cushing’s disease = pituitary tumour
Cushing’s syndrome/disease phenotype?
hypertension due to multiple effects of elevated plasma cortisol
high cortisol, high Na+, low K+, low renin and low aldosterone
how to differentiate cushings syndrome with cushings disease
cushing’s syndrome = low plasma ACTH
cushing’s disease = high plasma ACTH
what are the 3 mechanisms by which elevated plasma cortisol causes hypertension
glucocorticoids inhibit vascular
nitric oxide production by eNOS
glucocorticoids potentiate catecholamine action in heart and vasculature
glucocorticoids can inappropriately activate the kidney MR (mineralocorticoid receptors)
how does glucocorticoids inhibiting vascular nitric oxide production lead to hypertension?
glucocorticoids inhibit eNOS (converts arginine to nitric oxide).
nitric oxide usually causes vasodilation (leading to decreased BP)
elevated plasma cortisol (a glucocorticoid) reduces eNOS mediated vasodilation leading to increased blood pressure
how does glucocorticoids potentiating catecholamine action in heart and vasculature lead to hypertension?
increases adrenaline activation leading to increased vasoconstriction and cardiac output
how does glucocorticoids inappropriately activating the kidney MR lead to hypertension?
increased plasma cortisol exceeds capacity of 11β-HSD2 to convert cortisol to cortisone. active cortisol inappropriately activates the kidney MR receptor. this increases Na+ and water retention causing ECF expansion and hypertension
what is apparent mineralocorticoid excess?
mutation of 11β-HSD2 causing loss of function.
apparent mineralocorticoid excess phenotype?
high local kidney cortisol, low RAS
MR activation, high Na+, low K+
ECF expansion, hypertension
treatment of apparent mineralocorticoid excess?
pharmacological:
MR antagonists
low sodium diet, K+ suppliments
pheochromocytoma?
in adrenal medulla
chromaffin cell tumour
secrete catecholamines
noradrenaline and/or adrenaline
symptoms of pheochromocytoma?
palpitations, headache, episodic sweating
racing heart, anxiety (~50%)
hypertension - sustained/paroxysmal (~50%)
diabetes mellitus (40%)
diagnosis of pheochromocytoma?
24 hours urinary metanephrines and catecholamines
treatment of pheochromocytoma?
alpha-blockers, beta-blockers, surgical resection
4 types of drugs involved in RAS and aldosterone action
MR receptor antagonists
renin inhibitors
ACE inhibitors
all receptor antagonists
