11. Control Of BP Flashcards
What is hypertension?
Sustained increase in blood pressure
Normal or ideal adult BP is between 90/60mmHg and 120/80mHg
What is the BP in stage 1 hypertension?
> = 140/90 mmHg
What is the BP in stage 2 hypertension?
> =160/100 mmHg
What is the BP in severe hypertension?
> = 180 systolic or >= 110 diastolic
What causes hypertension?
In about 95% of cases, cause is unknown (primary hypertension)
Where the cause can be defined it is secondary hypertension e.g. renovascular disease, chronic renal disease, hyperaldosteronism, Cushing’s syndrome
Why is it important to treat hypertension?
Silent killer
Although it can be asymptomatic, can have unseen damaging effects on heart and vasculature, leading to heart failure, MI, stroke, renal failure, retinopathy
What is the medium and loner term control of blood pressure?
Complex interaction of neurohumoral responses
Directed at controlling sodium balance and thus extracellular fluid volume
What are the 4 parallel neurohumoral pathways that control circulating volume and hence BP?
Renin-angiotensin-aldosterone system
Sympathetic nervous system
Antidiuretic hormone (ADH)
Atrial natriuretic peptide (ANP)
Where is renin released from?
Granular cells of juxtaglomerular apparatus (JGA)
What are the factors that stimulate renin release?
Reduced NaCl delivery to distal tube
Reduced perfusion pressure in kidney (detected by baroreceptors in afferent arteriole)
Sympathetic stimulation to JGA increases release of renin
What is the renin-angiotensin-aldosterone system?
Angiotensinogen converted to angiotensin 1 by renin
Angiotensin 1 converted to angiotensin 2 by ACE (angiotensin converting enzyme)
Angiotensin causes vasoconstriction, stimulates Na+ absorption at kidney and stimulates aldosterone
What are the 2 types of Ang 2 receptors?
AT1 and AT2
Main actions via AT1 receptor
G-protein coupled receptor
What are the actions of aldosterone on the kidney?
Acts on principal cells of collecting ducts
Stimulates Na+ and therefore water reabsorption
Activatesapical na+ channels and apical K+ channel
Also increases base lateral Na+ extrusion via Na/K/ATPase
What does bradykinin convert to?
Peptide fragments using angiotensin converting enzyme (ACE)
Where s bradykinin mainly found?
In the lungs
Describe ACE inhibitors
ACE inhibitors prevent ACE from working and therefore angiotensin 1 cannot convert to angiotensin 2 and bradykinin cannot convert to peptide fragments
E.g. captopril, lisinopril, perindopril, enalapril
How does the sympathetic nervous system control blood volume and therefore BP?
High levels of sympathetic stimulation reduce renal blood flow - vasoconstriction, decrease GFR and decrease Na+ excretion
Activates apical Na/H-exchanger and basolateral Na/K ATPase in PCT
Stimulates renin release from JGcells - leading to increased Ang 2 levels and increased aldosterone levels, therefore increased Na+ reabsorption
Describe direct sympathetic stimulation
Acts on arteriolar to reduce renal blood flow - vasoconstriction
Stimulates granule cells of afferent arteriole to release renin via renin-Ag-aldosterone axis
Stimulates Na+ reabsorption from PCT
What is ADH release stimulated by?
Increases in plasma osmolarity or severe hypovolaemia
Stimulated with low BP as low blood volume
What is the role of ADH?
Stimulates Na+ reasborption - acts on thick ascending limb, stimulates apical Na/K/Cl co-transporter
Increases water absorption in distal nephron
How do natriuretic peptides control circulating volume and therefore BP?
Atrial natriuretic peptide promotes Na+ excretion
Synthesised and stored in atrial myocytes
Released from atrial cells in response to stretch
Low pressure volume sensors in atria
Reduced effective circulating volume inhibits release of ANP to support BP
What are the actions of ANP?
Causes vasodilation of afferent arteriole
Increased blood flow increases GFR
Also inhibits Na+ reabsorption along nephron
Acts in opposite direction to other neurohumoral regulators - causes natriuresis (loss of Na+ into urine)
If circulating volume is low ANP release is inhibited - supports BP
What are prostaglandins?
Acts as vasodilator
Enhance glomerular filtration and reduce Na+ reabsorption
Protective function
Act as bidder to excessive vasoconstriction produced by SNS and RAA system
Important when levels of Ang 2 are high
What is dopamine?
Formed locally in kidney from circulating L-DOPA
Receptors present on renal blood vessels and cells of PCT and TAL
Causes vasodilation and increases renal blood flow
Reduces reabsorption of NaCl
What is renovascular disease?
Occlusion of renal artery (stenosis) causes fall in perfusion pressure in kidney
Decrease perfusion pressure leads to increased renin production
Activation of renin-angiotensin-aldosterone system
Vasoconstriction and Na+ retention at other kidney
What are the adrenal causes for secondary hypertension?
Conn’s syndrome - aldosterone secreting adenoma
Cushing’s syndrome - excess secretion of glucocorticosteroid cortisol
Tumour of adrenal medulla - secretes catacholamines
What are the non-pharmacological approaches to treating hypertension?
Exercise
Diet
Reduced Na+ intake
Reduced alcohol intake
How do you treat hypertension by targeting the renin-angiotensin-aldosterone system?
ACE inhibitors - prevents production of Ang2 from Ang1
Ang2 receptors antagonists
Blocking production or action of Ang2 has diuretic and vasodilator effects
What can a build up of bradykinin cause?
Can cause dry cough
How do you treat hypertension with vasodilators?
L-type Ca channel blockers - reduce Ca2+ entry to vascular smooth muscle cells, relaxation of vascular smooth muscle
Alpha 1 receptors blockers - reduce sympathetic tone, can cause postural hypotension
How do you treat hypertension with diuretics?
Thiazides diuretics - reduce circulating volume
Inhibit Na/Cl co-transporter on apical membrane of cells in distal tubule
When are beta blockers used to treat hypertension?
If there are other indications such as previous MI
