Contrl Of Blood Pressure - The Patient With Hypertension Flashcards
What is the ideal normal blood pressure
- BP is measured in millimetres of mercury (mmHg)
* The normal or ideal adult blood pressure is considered to be between 90/60mmHg and 120/80mmHg
What is hypertension
• Sustained increase in blood pressure
Stage 1 hypertension >= 140/90 clinic or >= 135/85 home
Stage 2 hypertension >=160/100 clinic or >=150/95 home
Severe hypertension >= 180 systolic or >= 110 diastolic
What causes hypertension?
• In around 95% of cases the cause is unknown - combination of genetic, lifestyle, environmental, combination etc
– ‘essential’ or primary hypertension
• Where the cause can be defined it is referred to as secondary hypertension – examples • renovascular disease • chronic renal disease • hyperaldosteronism • Cushing’s syndrome
• With secondary hypertension – important to identify and treat the underlying cause or will struggle to reduce bl
Why is it important to treat hypertension?
• Hypertension – the silent killer
• Although hypertension may be asymptomatic, it can have unseen damaging effects on
– heart and vasculature
– potentially leading to heart failure, MI, stroke, renal failure and retinopathy
Describe the relationship between blood pressure and ratio of actual to expected mortality
Mortality increases are blood pressure increases - relationship particularly strong with systolic
Name some diseases attributable to hypertension
Coronary heart disease Heart failure Stroke Cerebral haemorrhage Chronic kidney failure Hypertensive encephalopathy Retinopathy Peripheral vascular disease Aortic aneurysms Left ventricular hypertrophy Myocardial infarction Coronary heart disease
All vascular
Describe how hypertension can lead to various diseases
Pls see slide for diagram
How can organ damage be assessed
By clinical history ad physical examination - brain, eyes, heart, kidneys, arteries
What is the effect of intervention?
Every 10mmHg reduction in blood pressure results in: • 17% reduction for coronary heart disease
• 27% reduction for stroke
• 28% reduction for heart failure
• 13% reduction in all-cause mortality
How is blood pressure regulated?
• Pressure = flow x resistance
• mean arterial BP = CO x TPR
• CO = SV x HR
- if bp falls, heart can combat by increasing stroke volume or heart rate
• Both short and long term regulation
• Short term regulation
– baroreceptor reflex
– adjust sympathetic and parasympathetic inputs to the heart to alter cardiac output
– adjust sympathetic input to peripheral resistance vessels to alter TPR
What is the baroreceptor reflex
Nerve endings in the carotid sinus and aortic arch are sensitive to stretch.
Increased arterial pressure stretches these receptors.
Decreased pressure stretches less
Increases stretch detracted by baro receptors - feedback to medulla - reduce sympathetic - reduce vasocostrition - relative bradycardia
• The baroreceptor reflex works well to control acute changes in BP
• Produces rapid response to changes in BP
• Does not control sustained increases because the threshold for baroreceptor firing resets
Happens in seconds to minutes
Describe medium and longer term contorl of blood pressure
• Complex interaction of neurohumoral responses
• Directed at controlling sodium balance and thus extracellular fluid volume
• Plasma is part of the extracellular fluid compartment
– control of extracellular fluid volume controls plasma volume
– water follows Na+ therefore controlling total body Na+ levels controls plasma volume
What are 4 parallel neurohumoral pathways which control circulating volume and hence BP?
- Renin-angiotensin-aldosterone system
- Sympathetic nervous system
- Antidiuretic hormone (ADH)
- Atrial natriuretic peptide (ANP)
Control BP in part by controlling sodium balance and extracellular fluid volume
What is the renin-angiotensin-aldosterone system
• Renin is released from granular cells of juxtaglomerular apparatus (JGA)
• Factors that stimulate renin release: a) Reduced NaCl delivery to distal tubule b) Reduced perfusion pressure in the kidney causes the release of renin detected by baroreceptors in afferent arteriole
c) Sympathetic stimulation to JGA increases release of renin
What stimulates renin release
Decreased circulating volume
Decreased NaCl delivery to the macula densa
Sympathetic stimulation to juxtaglomerular apparatus
Decreased renal perfusion pressure (sensed by renal baroreceptors)
Renin is released from the granular cells of the afferent arteriole in response to reduced perfusion pressure
What are the precursors of angiotensin and what is its role?
Angiotensinogen —-(renin)—> angiotensin I —-(angiotensin converting enzyme ACE)—> angiotensin II
Causes vasoconstriction, stimulates Na+ reabsorption at kidney, stimulates aldosterone from adrenal cortex
Wat are the 2 types of angiotensin II receptors
• Two types of Ang II receptors identified
– AT1 and AT2
• Main actions via AT1 receptor
• G-protein coupled receptor
What are the sites and actions of angiotensin ii receptors
Arterioles - vasoconstriction
Kidney - stimulates Na+ reabsorption at the kidney
Sympathetic NS - increased release of NA
Adrenal cortex - stimulated release of aldosterone
Hypothalamus - increases thirst sensation (stimulates ADH release)
Describe the action of aldosterone on the kidney
AngII stimulates aldosterone release from the adrenal cortex Actions of aldosterone:
• acts on principal cells of collecting ducts
• stimulates Na+ and therefore water reabsorption
• activates apical Na+ channel (ENaC, Epithelial Na Channel) and apical K+ channel
• also increases basolateral Na+ extrusion via Na/K/ATPase
What is the effect of ACE on bradykinin
Breaks it down into peptide fragments
What are ace inhibitors?
Eg captopril, lisinopril, perindopril, enalapril
Block ace - build up or angiotensin i and bradykinin
side effect = dry cough
How does the sympathetic nervous system control circulating volume
• High levels of sympathetic stimulation reduce renal blood flow
– Vasoconstriction of arterioles
– Decrease GFR
– decrease Na+ excretion
• Activates apical Na/H-exchanger and basolateral Na/K ATPase in PCT
• Stimulates renin release from JGcells
– leading to increased Ang II levels
– leading to increased aldosterone levels
• increased Na+ reabsorption
What is direct sympathetic stimulation?
via renin-Ang- aldosterone axis
acts on arterioles to reduce renal blood flow
stimulates granule cells of afferent arteriole to release renin
stimulates Na+ reabsorption from PCT
How does ADK affect circulating volume?
• Main role is formation of concentrated urine by retaining water to control
plasma osmolarity
– Increases water reabsorption in distal nephron (AQP2)
• ADH release is stimulated by increases in
– plasma osmolarity
– or severe hypovolaemia
• Also stimulates Na+ reabsorption
– Acts on thick ascending limb
– stimulates apical Na/K/Cl co-transporter
• Also called arginine vasopressin
– Causes vasoconstriction
How do natriuretic peptides affect circulating volume?
• Atrial natriuretic peptide (ANP) promotes Na+ excretion
• synthesised and stored in atrial myocytes
• released from atrial cells in response to stretch
• low pressure volume sensors in the atria
• reduced effective circulating volume inhibits the release of ANP to support BP
– reduced filling of the heart
– less stretch
– less ANP released
What are the actions of ANP
• Causes vasodilation of the afferent arteriole
• Increased blood flow increases GFR
• Also inhibits Na+ reabsorption along the nephron
• Acts in opposite direction to the other neurohumoral regulators
– Causes natriuresis (loss of sodium into urine)
• If circulating volume is low ANP release is inhibited
– This supports BP
What are the roles of prostaglandins?
- Act as vasodilators
- More important clinically than physiologically
- Locally acting prostaglandins (mainly PGE2) enhance glomerular filtration and reduce Na+ reabsorption
- May have important protective function
- Act as a buffer to excessive vasoconstriction produced by SNS and RAA system
- Important when levels of Ang II are high
What is dopamine?
- Dopamine is formed locally in the kidney from circulating L-DOPA
- Dopamine receptors are present on renal blood vessels and cells of PCT & TAL
- DA causes vasodilation and increases renal blood flow
- DA reduces reabsorption of NaCl – Inhibits NH exchanger and Na/K ATPase in principal cells of PCT and TAL
What is renovascular disease?
Secondary hypertension: Renovascular disease
• Occlusion of the renal artery (renal artery stenosis) causes a fall in perfusion pressure in that kidney
• Decreased perfusion pressure leads to increased renin production
• Activation of the renin-angiotensin-aldosterone system
• Vasoconstriction and Na+ retention at other kidney
What is renal parenchyma disease?
Secondary hypertension: Renal parenchymal disease
• Earlier stage may be a loss of vasodilator substances
• In later stage Na+ and water retention due to inadequate glomerular filtration
– volume-dependent hypertension
What are adrenal causes of secondary hypertension
Secondary hypertension: adrenal causes
• Conn’s syndrome – aldosterone secreting adenoma
– hypertension and hypokalaemia
• Cushing’s syndrome – excess secretion of glucocorticoid cortisol
– at high concentration acts on aldosterone receptors - Na+ and water retention
• primarily a tumour of the adrenal medulla – phaeochromocytoma – secretes catacholamines (noradrenaline and adrenaline)
How should hypertension be treated?
Applying Physiology to Treating hypertension
• For secondary hypertension – treat underlying cause
• Most cases no identifiable underlying cause
• You can work out possible targets for treating hypertension from the following equations
• BP = CO x TPR
• BP = SV x HR x TPR
What are non pharmacological approaches to treating hypertension?
Always start with these first
• Exercise
• Diet
• Reduced Na+ intake
• Reduced alcohol intake
• Lifestyle changes above can have limited effect
• Failure to implement lifestyle changes could limit the effectiveness of antihypertensive therapy
How can the RAAS system be targeted to treat hypertension?
Treating hypertension: targeting the renin-angiotensin- aldosterone system
• ACE inhibitors
– prevent production of Ang II from Ang I
• Ang II receptor antagonists (AII antagonists)
• Ang II is a powerful vasoconstrictor, has direct actions on the kidney and promotes the release of aldosterone, thus leading to NaCl and H2O retention
• blocking production or action of Ang II has diuretic and vasodilator effects
• Angiotensin receptor blockers ARBs
How can hypertension be treated with vasodilators?
• L-type Ca channel blockers (eg Verapamil, Nifedipine)
– reduce Ca2+ entry to vascular smooth muscle cells
– relaxation of vascular smooth muscle
• Can also use α1 receptor blockers (eg Doxazosin)
– reduce sympathetic tone (relaxation of vascular smooth muscle)
– can cause postural hypotension
How can hypertension be treated with diuretics?
• Thiazide diuretics
– reduce circulating volume
• Inhibit Na/Cl co-transporter on apical membrane of cells in distal tubule
• Other diuretics eg aldosterone antagonists (spironolactone)
will also lower BP
– not first line choice
Can beater blocked be used to treat hypertension?
• Less commonly used to treat hypertension
• Blocking β1 receptors in the heart will reduce effects of sympathetic output
– reduce heart rate and contractility
• Not used in hypertension alone
• Would only be used if there are other indications such as previous MI
Beat blockers lower bp relatively efficiently - dont seem to lower central blood pressure - dont have beneficial effects in reducing stroke etc
What methods should preferentially be used to treat hypertension?
A: ACE inhibitor/angiotensin inhibitor
C: calcium ion channel blocker
D: diuretic
What are the targets of action of commmonly used antihypertensives
See slide 47?
