Adrenal Medulla And Hypertension Flashcards
Where are catecholamine made?
Sympathetic nervous system and the medulla
What are catecholamines involved in?
Fight and flight
What are 2 branches of the autonomic nervous system?
Parasympathetic and sympathetic
What influence does the sympathetic nervous system have?
Dilates pupils, decreases saliva, dilates lung airways, increases heart rate, decrease gut movement, increases secretion of Noradrenaline and adrenaline, decreases bladder, increasing sweating and vessel contraction, increases BP
What does the parasympathetic nervous system do?
Decreases Dilation of pupils, increases saliva, decrease dilation of lung airways, decreases heart rate, increase gut movement, increases bladder, decreases vessel contraction, decreases BP
Biochemical markers of deficiency in catecholamines?
Low BP
Bowel habit disruption, diarrhoea.
Impaired urinary continuance and sexual arousal
Less sweating
Low glucose and low hypoglycaemic awareness
Eventually cardiovascular instability
You can also get selective adrenal catecholamine loss - what is this? is it serious?
When adrenal is damaged but isn’t too serious as there is normally other places catecholamines (particularly noradrenaline) can be released
Does adrenaline have a role in maintaining glucose?
Yes
Does adrenaline maintain glucose on its own and if not what does it do it with?
No - cortisol, growth hormone and glucagon
What does a profound loss of cortisol do to adrenaline?
Decreases adrenaline
Catecholamines -what are these products and do they have alpha or beta characteristics?
Adrenaline - alpha
Noradrenaline - beta
What does adrenaline have a role in?
Excess is, raising glucose and delivering it to tissue
Where do catecholamines act on?
9 receptors - alpha and beta adrenergic receptors
What drugs can block alpha affects
Doxazosin
Phenyoxybenzamine
What drugs block beta affects?
Propranolol
What happens if you get catecholamine excess? More alpha
Vasoconstriction - high BP, pale skin
Reduced gut activity and blood flow - nausea, butterfly’s
Headaches
What happens if you get catecholamine excess? More beta?
Heart racing - palpatations
Tendency to crease glucose
Phychological arousal - on edge, anxious, fearful
Overbreathe (airways dilation)
If you have intermittent excess catecholamines what symptoms do you get?
blood pressure variable
postural drops in blood pressure on standing
get attacks of panic+palpitations
What causes increase catecholamines?
Phaeochromocytoma (paraganglioma = outside adrenal, only some make cathechoamines)
Drugs – eg antidepressants (tricyclic, MAOIs), some cold cures (ephidrine, pseudoephedrine)
Physiological – severe stress/illnes
What are concerning signs of a phaeochromocytoma?
Headache, sweating, palpitations, high blood pressure, panic attacks and fear
What do you tests to see if someone has phaeochromocytoma
Metanephrons
What are the inactive forms of adrenaline and noradrenaline?
Normetadrenaline and metadrenaline
What is the pathway of release of catecholamine and metanephrines?
Dopamine goes into vesicles which gather at the membrane and are released by nerve signal.
In the alternative pathway the vesicles break spilling adrenaline and noradrenaline back into the cytoplasm and COMT turns them into metanephrones - this is bad
How would you diagnose a phaeochromocytoma?
24 urine to screen for metanephrines,
To localise it use MRI/CT or abdomen and pelvis.
MIGB scans
Venous sampling
How do you manage a phaeochromocytoma?
- Initiate alpha blockade with phenyoxybenzamine
- Then beta blockade with propranolol
- surgery
After you remove consider if the phaeochromocytoma was part of a syndrome - what are these syndromes?
Von Hippel Lindau cerebellar - retinal, ± renal/pancreatic tumours/cysts
MENII - medullary carcinoma thyroid, hyperparathyroidism, mucosal neuromas etc
Paragangliomas - SDHB, SDHC, SDHD. Paragangliomas in neck imprinting ect.
Neurofibromatosis - skin neurofibromas, multiple pigmented patches
Hypertension - what is too high?
Over 140/90
Is BP constant?
No
When will BP alter?
Normally lower at night
can be affected with how its measured,
What tests are done to diagnose hypertension?
Should allow several readings over 5 minutes while person relaxingif seems raised should ideally average
assessments over few weeks
Is hypertension important?
Yes as it is a risk factor for CVD
What are the 3 main CVD’s
Coronary heart disease - includes MI
Cerebrovascular disease - dementia, stroke
Arterial disease - peripheral vascular disease, renal impairment, renal artery stenosis, abdominal aortic aneurysms.
What are risk factors for CVD?
Hypertension, hyperglycaemia smoking, family history, poor history, obesity, insulin resistance, kidney disease, dyslipidaemia
What is hypercholesterolanemia?
High cholesterol
What two diagnostic tests are needed to make a hypertension diagnosis?
Clinical BP and ABPM/Home BP
How many grades of hypertension is there and a d what are these called?
Normal BP, High normal BP, Hypertension, Grade 1, grade 2 and grade 3
What is white coat hypertension?
Only hypertension due to the white coat affect
What are some key signs of hypertension that isn’t blood pressure?
Target organ damage (heart, eyes, kidneys)
Life threatening symptoms (confusion, chest pain, heart failure an AKI)
Accelerated hypertension
What grades of hypertension would get treatment?
Grade 1 (some people
Grade 2 - 3 all people
What guidance would you give people with hypertension and an increased risk of CVS? What advice gets given to everyone?
➔advice about lifestyle changes to moderate BP (aim for weightin ideal range, limit salt intake, regular exercise etc)
➔BP kept under review (may be just x1-2/year if mild)and
➔may warrant drug treatment eventually if remain hypertension
What guidance would you give someone high risk of hypertension?
Anti-hypertensive drug treatment
What other situations would you start someone on anti-hypertensives?
ii) Established Cardiovascular disease– e.g. past heart attack (MI), stroke (CVA), definite angina etc
iii)Target organ damage– e.g. heart ➔enlarged, kidney➔protein in urine, retinal damage (back of eye)
iv)Especially vulnerable to raised blood pressure- e.g. diabetes, chronic kidney disease (especially proteinuria:albumin/creatinine>70)
v)If at high Cardiovascular Disease (CVD) risk-usually 10-year CVD Risk, less if other increased CVD risk factors- e.g. Family history- relatives (especially close/many/young) with CVD eve
What are some BP target exceptions?
In cases of chronic kidney disease, diabetes or people who are frail and it could be risky lowering BP
What is resistant hypertension?
If blood pressure is high and the 3x drugs (ACE inhibitor or angiotensin, calcium blockers or thiazide-like diuretic) doesn’t help it
What would you do if someone had resistant HT?
Specialist, spironolactone drug and look for secondary causes
What causes hypertension?
Genetics
Fetal programming - if you are born underweight
Environment - diet, salt, stress
What is seen in all hypertension?
Impairment in the kidney regulation of body salt balance
What is secondary hypertension?
Hypertension with a clear cause that can be fixed by fixing the cause
What is primary hypertension associated with?
Metabolic syndrome
What is primary hypertension rick factors?
Western diet, high salt, low K, high Caroline, low fibre, physical inactivity, alcohol, stress
What is secondary hypertension associated with?
Endocrine
Renovascular
Renal
Drugs
Coarctation
Others-e.g. Sleep Apnoea
Endocrine Secondary hypertension - what specific things can cause this?
Mineralocorticoid-salt retention
Phaeochromocytoma etc
Others:
Thyroid dysfunction
Cushing’s syndrome(incl GC drugs)
Hyperparathyroidism
Acromegaly
Endocrine drugs such as oral contraceptives
What would you ask when investigating secondary hypertension?
History and examination - does this suggest a specific secondary HT e.g. hypokalaemia, alkalosis
Drugs - oestrogen containing pill, liquorice, glucocorticoids
Cushings, acromegalic appearance
- is there young/severe/resistant HT for example is it caused by target organ damage
What are the biochemical tests you would ask about when investigating secondary hypertension?
Recent glucose, HbA1c, potassium, HC, calcium, thyroid function test,
1) aldosterone and renin
2) 24hr urine metadrenaline
3) renal ultrasound (only if you suspect a renal disease)
adrenal related endocrine hypertension - what causes mineralocorticoid excess?
Bilateral hyperplasia
Unilateral (Conn’s) tumour
Rarities eg GRA (FH1), FH2+3, low 17alpha OHase and 11βOHase
What is the rare mineralocorticod excess conditions?
Resemblance to Aldo excess but Aldo suppressedeg SAME, Liddle’s syndrome, activating MR mutations
What is primary aldosteronism?
Aldosterone excess,-driven by a primary adrenal abnormality (raised renin-angiotensin or body K+) -above physiological requirements (BP high)
It isn’t suppressed by sodium loading
How do you diagnose aldosteronism?
Screening hypertensives ➔measure aldo/renin ratio (ideally off all interfering medication)
When should you diagnose someone with primary aldosteronism?
If they have all:
➔ ARR >40 [pmol/miU/L] if renin assay = direct renin concentration (DRC)
➔Aldosterone >300-400pmol/L (sitting) (ie >upper part normal range or supranormal
➔Aldosterone that is abnormally resistant to suppression – often by assessing ARR when on high salt intake- but may require salt-loading/saline infusion tests
What are the two common causes of primary aldosteronism?
BAH
Conns tumour
What is conns tumour?
Unilateral aldosterone producing adenoma– potentially benefitting from surgery
What is BAH?
bilateral adrenal hyperplasia,– often shows adrenal hyperplastic nodules not tumours), increases with age– not helped by surgery
What is rare causes of primary aldosteronism?
FH, GRA
how do you treat primary aldosteronism?
Drugs (spironolactone, Eplerenone)
If conns tumour once sure of location do a adrenalectomy (surgery)
How would you distinguish conns tumour and BAH?
Adrenal venous sampling = best but invasive and difficult
Imaging - adrenal CT/MRI
- look for non functional nodules (useful in people under 40 but people over that age tend to have these naturally)
What are the controversial tests to distinguish a conns tumour and BAH?
Potassium level, BP, 18OH cortisol, novel imaging and C-metomidate PET-CT scan.
What is venous sampling/ how is it done?
Catheter put in and thread into adrenal to collect fluid
What are the trends of age with Conn’s tumour, BAH and GRA?
Conns tumour - Rare in childhood but has a slow increase
BaH - over age 40
GRA - born with it
What causes glucorticoid remediable aldosteronism (GRA)?
The 11-OHase accidentally combines with a aldosterone which means when you are given glucocorticoids it releases aldosterone
What can you suppress GHA with?
Dexamethasone
Is GHA autosomal recessive?
No dominant
What is GRA also called?
Fh1
What is the biochemistry of GRA?
Potassium normal
18OH cortisol high
How is GRA tested for?
Genetic test showing the abnormal chimeric gene present
How is GRA managed?
Combination of dexamethasone and eplerenone/amiloride
What are some other mineralocorticoid disorders affecting BP?
11 beta HSD2 deficiency
Mutations promoting ENaC half life
Inactive MR mutations
Inactivating ENaC mutations
Hypertension form activating MR mutations
Aldosterone excess and deficiency
