Control of BP Flashcards
What is hypertension?
Sustained increase in BP
What is BP measured in?
mmHg (millimetres of mercury)
Normal BP
90/60mmHg –> 120/80mmHg
Stage 1 hypertension
> 140/90mmHg
Stage 2
> 160/100mmHg
severe hypertension
> 180 systolic or >110 diastolic
Primary hypertension
Cause unknown (90%)
Secondary hypertension
Cause known eg:
Renovascular disease, chronic renal, hyperaldosteronism, cushings
Treatment for secondary hypertension
Treat underlying cause!!!
Why is hypertension known as silent killer?
No symptoms until BP is measured
What effect does hypertension have on body?
Damages heart and vasculature
lead to heart failure, MI, stroke, renal failure and retinopathy
arterial damage hypertension
Atherosclerosis/weakened vessels
= stroke, aneurysm, nephrosclerosis/renal failure, retinopathy
Increase afterload from hypertension (amount of force needed to eject blood)
LV hypertrophy and Increased myocardial oxygen demand
= heart failure, myocardial ischaemia, MI
Target organ damage for cardiovascular disease
Brain (ischaemia/haemorrhage) Eyes (retinopathy) Heart (LV hypertrophy, MI) Kidneys (atrophy from damaged vessels) Arteries (calcified atheroma)
Exams for CVD
Check back of eyes (retinopathy?) Listen for heart murmurs Urine sample Palpate kidneys (atrophy?) ECG Palpate arteries/listen for bruit
What does intervention achieve?
Reduced risk of: Coronary heart disease (17%) Stroke (27%) Heart failure (28%) All-cause mortality (13%)
Blood pressure equations
BP = CO x TPR
CO = SV x HR
Medium and long term control of blood pressure
Neurohumoral response
Controlling of sodium balance
How is blood pressure controlled with Na+?
Water follows Na+
If increase Na+, increase plasma volume
(then increase stroke volume)
4 neurohumoral pathways controlling BP
RAAS (renin-angiotensin-aldosterone system)
SNS (Sympathetic nervous system)
ADH (Antidiuretic hormone)
ANP (anti natriuretic peptide)
where is renin released from?
Kidneys - granular cells of juxtaglomerular apparatus (JGA)
What stimulates renin release?
Reduced salt (NaCl) delivery to distal tubule
Reduced perfusion pressure to kidney (baroreceptors)
Sympathetic stimulation to JGA
what does renin do?
Cleaves angiotensinogen to angiotensin 1
What happens to angiotensin 1?
Cleaved to angiotensin 2 by ACE (angiotensin converting enzyme)
What effects does angiotensin 2 have?
Vasoconstriction Na+ reabsorption in kidney Increase aldosterone release Increase thirst sensation (hypothalamus) Increase NA release (sympathetic NS)
what does angiotensin 2 act on?
Angiotensin 2 receptors (AT1 and AT2)
Main action on AT1
What does aldosterone do?
Stimulates Na+ reabsorption in collecting ducts (so water too)
Activates Na+ channel (epithelial Na+ channel ENaC) and apical K+ channel
Increases Na+ extrusion via Na+K+ATPase
What other effects does ACE (angiotensin converting enzyme) have?
Breaks down bradykinin (vasodilator) into peptide fragments
What happens if using an ACE inhibitor?
Angiotensin 1 is not cleaved into angiotensin 2
Bradykinin not broken down = vasodilation
What can occur if there is accumulation of bradykinin?
Dry cough (in lungs)
examples of ACE inhibitors
Captopril
Lisinopril
Perindopril
effects of sympathetic nervous system
Vasoconstriction
= reduced renal blood flow
= Decrease GFR (decrease Na+ excretion)
Stimulates renin release
activates Na+ H+ exchanger and Na+K+ATPase
ADH stimulated by
Increases in plasma osmolarity
Severe hypovalaemia
ADH function
Form concentrated urine
Retain water in body
What does ADH also stimulate
Na+ reabsorption (Na/K/Cl cotransporter in thick ascending limb)
Vasoconstriction
Atrial Natriuretic peptides function (ANP)
Counteract other methods
Promotes Na+ excretion
Where is ANP synthesised and stored?
Atrial myocytes
When is ANP released?
In response to stretch (high BP so needs to lower BP)
What inhibits ANP?
Reduced effective circulating volume
reduced filling = reduced stretch = less ANP
Actions of ANP
Vasodilation
Increased blood flow increases GFR
Inhibits Na+ reabsorption = natriuresis (loss of Na+ in urine)
Prostaglandins
Vasodilators
enhance GFR = reduced Na+ reabsorption
When are prostaglandins important?
Buffer excess vasoconstriction from SNS/RAAS
When Angiotensin 2 levels are HIGH
= protect
Dopamine
Vasodilation and increase renal blood flow
(receptors present on renal BV, PCT cells)
Reduces reabsorption of NaCl
How doe dopamine reduce absorption of NaCl?
Inhibits NH exchanger and Na+K+ATPase in PCT
How does renovascular disease cause hypertension?
Occlusion of renal artery (renal artery stenosis)
Lower perfusion to kidney
Increased renin production
=RAAS system activated (Vasoconstriction and Na+ retention)
How does renal parenchymal disease cause hypertension?
Loss of vasodilator substances (eg dopamine)
Na+ and water retention due to low GFR
Adrenal causes of hypertension
Conns syndrome
Cushings
Phaechromocytoma
Conns syndrome cause of hypertension
Aldosterone secreting adenoma
= hypertension and hypokalaemia
(Na+ reabsorbed, K+ secreted out)
Cushings causing hypertension
High levels of glucocorticoid cortisol
At high concentrations, acts on aldosterone receptors
Phaeochromocytoma cause of hypertension
Tumour of adrenal medulla
secretes catecholamines (noradrenaline and adrenaline)
= surge in BP via SNS
Treating hypertension non pharmacological
Exercise Diet Reduced Na+ intake Reduced alcohol (failure to implement = drugs work less effectively)
Drug targets for RAAS
Ace inhibitors
Angiotensin 2 receptor antagonists
= diuretic and vasodilator effects
Angiotensin receptor blockers example
Losartan, Valsartan
Vasodilator treatments
L type Ca2+ blockers (Ca2+ cannot enter smooth muscle cells = no contraction)
a1 receptor blockers (reduces sympathetic tone = relaxation of smooth muscle cells lower BP)
L type Ca2+ blockers eg
Verapamil, Nifedipine
a1 receptor blocker example
Doxazosin
Diuretics treatment
Thiazide diuretics = reduce circulating volume
(inhibits Na/Cl cotransporter)
Aldosterone antagonists (spironolactone)
Beta blockers treatment
Blocking b1 receptors reduces sympathetic output
reduce HR and force of contraction
Not usually used (only if previous MI)
Main drug types for hypertension
Renin inhibitors ACE inhibitors Angiotensin 2 antagonists Aldosterone antagonists Beta blockers
