endocrinology of blood pressure control

7/30/2019 Endocrinology of Blood Pressure Control

1/25

ENDOCRINOLOGY OF BLOOD

PRESSURE CONTROL


2/25

The control of blood pressure (BP) is complex,

involving neural, cardiac, hormonal and many

other mechanisms.


3/25

BP is dependent upon cardiac output and

peripheral resistance.

Although cardiac output can be increased in

endocrine disease (e.g. hyperthyroidism), the

main role of hormonal mechanisms is control

of peripheral resistance and of circulating

blood volume


4/25

The oral contraceptive pill is a common

endocrine cause of mild hypertension.


5/25

Endocrine causes of hypertension


6/25

The renin-angiotensin-aldosterone

axis

Angiotensinogen, an alpha2-globulin of

hepatic origin, circulates in plasma. The

enzyme, renin, is secreted by the kidney in

response to decreased renal perfusion

pressure or flow; it cleaves the decapeptide

angiotensin I from angiotensinogen.


7/25

Angiotensin I is inactive but is further cleaved

by angiotensin-converting enzyme (ACE;

present in lung and vascular endothelium)

into the active peptide, angiotensin II, which

has two major actions (mediated by two types

of receptor, AT1 and AT2).


8/25

The AT1 subtype which is found in the heart,

blood vessels, kidney, adrenal cortex, lung and

brain mediates the vasoconstrictor effect. AT2

is probably involved in vascular growth.

Angiotension II:

causes rapid, powerful vasoconstriction

stimulates the adrenal zona glomerulosa toincrease aldosterone production (over hours or

days).


9/25

As BP increases and sodium is retained, the

stimuli to renin secretion are reduced.

Dietary sodium excess also suppresses renin

secretion, whereas sodium deprivation or

urinary sodium loss will increase it.


10/25

The renin-angiotensin system can be blocked

at several points with renin inhibitors,

angiotensin-converting enzyme inhibitors

(ACEI) and angiotensin II receptor antagonists

(A-IIRA).


11/25

The latter two are useful agents in treatment

of hypertension and heart failure but have

differences in action: ACEIs also block kinin

production while A-IIRAs are specific for the

AT-II receptor


12/25


13/25

Atrial and brain natriuretic

factors/peptides (ANP and BNP)

Atrial natriuretic peptides, a family of varying

length forms, are secreted from atrial granules

in response to atrial stretch. They produce

marked effects on the kidney, increasingsodium and water excretion and glomerular

filtration rate and lowering BP, plasma renin

activity and plasma aldosterone


14/25

Brain natriuretic peptide is found in the

ventricle as well as the brain and has

moderate sequence homology with ANP;

normally its circulating level is much less thanfor ANP but may exceed it in congestive

cardiac failure


15/25

ANP and BNP appear to play a significant role

in cardiovascular and fluid homeostasis, but

there is no evidence of primary defects in

their secretion causing disease


16/25

RENIN (AND ANGIOTENSIN)

DEPENDENT HYPERTENSION

Many forms of unilateral and bilateral renal

diseases are associated with hypertension.

The classic example is renal artery stenosis:

the major hypertensive effects of this andother situations such as renin-secreting

tumours are directly or indirectly due to

angiotensin II.


17/25

Angiotensin II receptor antagonists (e.g.

losartan, valsartan, candesartan and

irbesartan) are effective in hypertension and

congestive cardiac failure, similar toangiotensin-converting enzyme inhibitors

(ACEI). They produce much the same clinical

effects, though with fewer side-effects (e.g. nocough and less hyperkalaemia).


18/25

THE ADRENAL MEDULLA

The major catecholamines, noradrenaline

(norepinephrine) and adrenaline

(epinephrine) are produced in the adrenal

medulla, although most noradrenaline isderived from sympathetic neuronal release.


19/25

Phaeochromocytoma

Phaeochromocytomas, tumours of the

sympathetic nervous system, are very rare

(less than 1 in 1000 cases of hypertension).

Ninety per cent arise in the adrenal, while

10% occur elsewhere in the sympathetic chain


20/25

Pathology

Oval groups of cells occur in clusters and stain

for chromogranin A. Twenty-five percent are

multiple and 10% malignant, the latter being

more frequent in the extra-adrenal tumours.

Malignancy cannot be determined on simple

histological examination alone.


21/25

Clinical features

Symptoms Anxiety or panic attacks

Palpitations

Tremor

Sweating Headache

Flushing

Nausea and/or vomiting

Weight loss

Constipation or diarrhoea

Raynaud's phenomenon

Chest pain

Polyuria/nocturia


22/25

Signs

Hypertension - intermittent or constant

Tachycardia plus arrhythmias

Bradycardia

Orthostatic hypotension

Pallor or flushing

Glycosuria

Fever (Signs of hypertensive damage)


23/25

The clinical features are those of

catecholamine excess and are frequently, but

not necessarily, intermittent. The diagnosis

should particularly be considered whencardiovascular instability has been

demonstrated, and in severe hypertension in

pregnancy.


24/25

Diagnosis

Measurement of urinary catecholamines and

metabolites

Resting plasma catecholamines

CT scans

MRI


25/25

Treatment

Tumours should be removed if this is possible;

5-year survival is about 95% when not

malignant. Medical preoperative and

perioperative treatment is vital and includescomplete alpha- and beta-blockade with

phenoxybenzamine (20-80 mg daily initially in

divided doses), then propranolol (120-240 mgdaily), plus transfusion of whole blood to re-

expand the contracted plasma volume

endocrinology of blood pressure control

Documents