mineralocorticoid disorders and endocrine hypertension W7

Question 1

3 main physiological factors regulating blood pressure?

Answer 1

cardiac output
vascular tone
extracellular fluid volume

Question 2

3 adrenal hormone systems that regulate blood pressure

Answer 2

sympathetic
renin-angiotensin
HPA axis

Question 3

what hormones can increase cardiac output

Answer 3

catecholamines
cortisol potentiation

Question 4

what hormones can increase vascular tone?

Answer 4

angiotensin 2
aldosterone
catecholamines
cortisol potentiation

Question 5

what hormones can increase extracellular fluid

Answer 5

aldosterone
cortisol

Question 6

what is renin released in response to

Answer 6

JG cell baroreceptors
macula densa cell Na+ sensing
carotid arch baroreceptors

Question 7

rapid vs long term effects of RAS and aldosterone?

Answer 7

vasculature - rapid (seconds)
adrenal - rapid (minutes)
kidney - 6-48 hrs

Question 8

renin angiotensin system effect on vasculature? when does this occur?

Answer 8

vasoconstriction
postural
regulation of BP

Question 9

renin angiotensin system effect on adrenal glands?

Answer 9

increased aldosterone synthesis
increased catecholamine synthesis

Question 10

renin angiotensin system effect on kidneys?

Answer 10

increased Na+ and water reabsorption via RAAS

Question 11

long term effects of RAS on vasculature?

Answer 11

smooth muscle
increased cell hyperplasia
increased cell hypertrophy
long-lasting change in vascular tone

Question 12

RAS long term affects on CNS?

Answer 12

increased thirst
increased salt appetite
increased ADH release

Question 13

RAS long term effects on adrenal gland?

Answer 13

increased aldosterone synthase enzyme expression
increased glomerulosa cell proliferation

Question 14

common cause of endocrine hypertension?

Answer 14

excess production of aldosterone

Question 15

conn’s syndrome?

Answer 15

unilateral adrenal tumour
aldosterone-producing adenoma

Question 16

Conn’s syndrome presentation?

Answer 16

high aldosterone
MR activation (mineralocorticoid receptor)
high Na+
low K+
ECF expansion (extracellular fluid)
hypertension
low renin (RAS)

Question 17

types of primary hyperaldosteronism?

Answer 17

Conn’s syndrome
Bilateral adrenal hyperplasia (most common)

Question 18

bilateral adrenal hyperplasia presentation?

Answer 18

same as Conn’s syndrome:
high aldosterone
MR activation (mineralocorticoid receptor)
high Na+
low K+
ECF expansion (extracellular fluid)
hypertension
low renin (RAS)

Question 19

treatment of Conn’s syndrome?

Answer 19

surgical:
venous sampling and/or CT scan
unilateral adrenalectomy

Question 20

treatment of bilateral adrenal hyperplasia?

Answer 20

pharmacological
anti-hypertensives eg MR antagonists
spironolactone, eplerenone

Question 21

what is glucocorticoid-remediable aldosteronism (GRA)

Answer 21

autosomal dominant genetic disorder (chromosome 8)
ACTH-driven hyperaldosteronism

Question 22

glucocorticoid-remediable aldosteronism (GRA) pathophysiology?

Answer 22

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.

Question 23

presentation of glucocorticoid-remediable aldosteronism (GRA)

Answer 23

high aldosterone
MR activation
High Na+
low K+
ECF expansion
hypertension
low renin (RAS)

same as other causes of primary hyperaldosteronism!!

Question 24

treatment of glucocorticoid-remediable aldosteronism (GRA)

Answer 24

synthetic glucocorticoids (inhibit ACTH production, downregulate function of hybrid gene

Question 25

renin-secreting JG cell tumour presentation?

Answer 25

high plasma renin, high aldosterone
MR activation, high Na+, low K+
ECF expansion, hypertension

Question 26

what is a JG cell

Answer 26

juxtaglomerular cell - responsible for production, storage, and release of renin

Question 27

treatment of renin-secreting JG cell tumour?

Answer 27

surgical removal

Question 28

what type of hyperaldosteronism is renin-secreting JG cell tumour?

Answer 28

secondary hypoaldosteronism

Question 29

cortisol overproduction - Cushing’s syndrome/disease presentation?

Answer 29

weight gain, stretch marks, easy bruising, proximal muscle weakness
diabetes mellitus, menstrual irregularities, depression

Question 30

Cushing’s Syndrome vs Cushing’s disease?

Answer 30

Cushing’s syndrome = adrenal tumour
Cushing’s disease = pituitary tumour

Question 31

Cushing’s syndrome/disease phenotype?

Answer 31

hypertension due to multiple effects of elevated plasma cortisol
high cortisol, high Na+, low K+, low renin and low aldosterone

Question 32

how to differentiate cushings syndrome with cushings disease

Answer 32

cushing’s syndrome = low plasma ACTH
cushing’s disease = high plasma ACTH

Question 33

what are the 3 mechanisms by which elevated plasma cortisol causes hypertension

Answer 33

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)

Question 34

how does glucocorticoids inhibiting vascular nitric oxide production lead to hypertension?

Answer 34

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

Question 35

how does glucocorticoids potentiating catecholamine action in heart and vasculature lead to hypertension?

Answer 35

increases adrenaline activation leading to increased vasoconstriction and cardiac output

Question 36

how does glucocorticoids inappropriately activating the kidney MR lead to hypertension?

Answer 36

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

Question 37

what is apparent mineralocorticoid excess?

Answer 37

mutation of 11β-HSD2 causing loss of function.

Question 38

apparent mineralocorticoid excess phenotype?

Answer 38

high local kidney cortisol, low RAS
MR activation, high Na+, low K+
ECF expansion, hypertension

Question 39

treatment of apparent mineralocorticoid excess?

Answer 39

pharmacological:
MR antagonists
low sodium diet, K+ suppliments

Question 40

pheochromocytoma?

Answer 40

in adrenal medulla
chromaffin cell tumour
secrete catecholamines
noradrenaline and/or adrenaline

Question 41

symptoms of pheochromocytoma?

Answer 41

palpitations, headache, episodic sweating
racing heart, anxiety (~50%)
hypertension - sustained/paroxysmal (~50%)
diabetes mellitus (40%)

Question 42

diagnosis of pheochromocytoma?

Answer 42

24 hours urinary metanephrines and catecholamines

Question 43

treatment of pheochromocytoma?

Answer 43

alpha-blockers, beta-blockers, surgical resection

Question 44

4 types of drugs involved in RAS and aldosterone action

Answer 44

MR receptor antagonists
renin inhibitors
ACE inhibitors
all receptor antagonists