L11: Control of BP Flashcards
What is hypertension?
Sustained high blood pressure (mmHg)
What is normal blood pressure considered to be?
Between 90/60mmHg - 120/80mmHg
- Continuum–> no cut of score
- Closer to the upper limit more at risk
What are the difference classifications of high blood pressure?
Stage 1 hypertension–> >140/90mmHg
Stage 2 hypertension –> >160/100mmHg
Severe hypertension–> >180 systolic or >110/120 diastolic
What causes hypertension?
Primary hypertension–> 95%
–> Cause unknown
Secondary hypertension–> 5%
–> Cause defined–> important to identify cause and treat
–> E.g. renovascular disease, chronic renal disease, hyperaldosteronism, Cushings disease
Why is it important to treat hypertension?
Silent killer
Assymptomatic but can have unseen damaging effects (heart and vasculature–> HF, Stroke, Renal failure and retinopathy)
3rd biggest risk factor for premature death
affects >1/4 people
What disease are caused by hypertension?
HF Stroke Coronary Heart Disease MI Left Ventricular Hypertrophy Aortic Aneurysm Peripheral vascular disease Retinopathy Hypertensive encephalopathy Chronic kidney failure Cerebral Haemorrhage
How does it lead to these diseases?
Hypertension–> ↑ afterload–> LVH (–> HF) and ↑Myocardial oxygen demand (–>Myocardial ischemia and MI)
Hypertension–> arterial damage–> arthersclerosis and weakened vessels–> cerebrovascular disease, stroke, aneurysm, nephrosclerosis and renal failure and retinopathy
What areas of the body are usually the target for hypertensive disease?
Brain (ischemia, haemorrhage), Heart (left ventricular hypertrophy), Arteries (atherosclerotic plaques), Eyes Kidneys --> should be checked--> clinical history and physical examination
How effective are the interventions?
For every 10mmHg reduction in blood pressure
- -> 17%↓ CHD
- -> 27%↓ stroke
- -> 28%↓ HF
- -> 13%↓ in all case mortality
What is blood pressure?
Pressure= Flow X Resistance BP= CO X TPR (CO= SV x HR)
How is blood pressure regulated?
Short and long term regulation –> baroreceptor reflex
–> adjust para- and sympathetic output to heart to alter CO and peripheral vessel to alter TPR
What is the baroreceptor reflex?
Reflex that controls acute changes in BP
BP↑–> baroreceptors detect stretch–> medulla–> efferent vessels ↓BP via vasodilation, decreased HR and CO
Opposite for BP↓
Where are the baroreceptors located?
Aortic Arch
Carotid sinus
What is the problem with sustained high blood pressure and the baroreceptor reflex?
Baroreceptor reflex resets
Elevated blood pressure no longer causes stretch and AP firing
How is the blood pressure controlled in the medium and long term?
Neurohumoral Response
Control sodium balance and thus extracellular fluid volume
–> plasma part of ECF volume
–> control Na+ control H2O and ECF volume so plasma volume (BP)
What are the 4 neurohumoeral pathways controlling circulation and hence volume?
1) Renin-Angiotensin-Aldosterone system
2) Sympathetic nervous system
3) Antidiuretic Hormone
4) Atrial Natriuretic Peptide
How does the renin-angiotensin-aldosterone system work?
LOW BP
Renin released from glands of Juxaglomerular appartus
Converts angiotensinogen –> angiotensin 1
Angiotensin 1–> angiotensin 2 by ACE
Angiotensin 2–> vasoconstriction, stimulates Na+ reabsorption from kidneys, stimulates aldosterone (adrenal cortex)–> Na+ reasborption from kidneys
What causes renin to be released?
Reduced NaCl delivery to renal tubules- macula densa detect
Reduced perfusion pressure across kidneys–> baroreceptors detect
Sympathetic stimulation to JGA
Released from granular cells/JGA cells–> afferent arterioles–> in response to reduced perfusion pressure
What are the angiotensin 2 receptors? Where does angiotensin act and what does it do?
Two types AT1 and AT2
Main action via AT1
GPCR –> increase BP
Aterioles–> vasoconstriction
Kidney–> Stimulates Na+ reabsorption
Sympathetic NS–> Increased release of NA
Adrenal Cortex–> Stimulates release of aldosterone
Hypothalamus–> Increased thirst sensation (stimulate ADH release)
How does aldosterone work?
AngII–> Aldosterone release from adrenal cortex
Actions:
- Principle cells of collecting duct
- Stimulate Na+ reabsoprtion–> H2O follows
- Activates apical Na+ channel (epithelial Na Channel (ENaC)) and apical K+ channels
- ↑ basolateral Na+ extrusion via Na/K ATPase
How does ACE impact on bradykinin? What is significant about this?
Bradykinin broken down into peptide fragments by ACE
Bradykinin–> Vasodilator further increase vasoconstriction
How do ACE inhibitors work? What are they used for?What is the significance of these with Bradykinin?
ACE inhibitors prevent the conversion of angiotensin 1- angiotensin 2 therefore reducing vasoconstriction–> reducing high blood pressure
Method for treating hypertension
Also inhibits conversion of bradykinin–> peptide fragment –> bradykinin builds up–> vasodilator so vasodilation of BV
How does the sympathetic system work to increase blood pressure?
Sympathetic stimulation–>reduced renal blood flow
- -> Vasoconstriction of arterioles
- -> Decrease GFR–> less Na+ excreted so less H2O excreted
Activated apical Na/H exchanger and basolateral Na/K ATPase in PCT (increase Na+ reabsorption)
Stimulate renin release from JGA cells–> increase angiotensin 2 levels via pathway–> increased aldosterone levels–> Increased Na+ reabsoprtion
How does antidiuretic hormone (ADH) increase blood pressure? What stimulates its release?
Formation of concentrated urine
Reabsorption of water in distal nephron (AQP2)
Stimulates Na+ reabsorption (thick ascending limb)–> stimuates apical Na/K/Cl co-transporter
Vasoconstriction (alternative name arginine vasopressin)
ADH release stimulated–> increase in plasma osmolarity or severe hypovolaemia (decreased volume)
How do natriuretic peptides decrease blood pressure? What causes it to be released?
ANP –> excretion of Na+ –> water follows
Stored in atrial myocytes–> released upon stretch–> low pressure volume sensors in the atria
How do natriuretic peptides increase blood pressure?
ANP released in response to stretch
Reduced circulating volume–> inhibits release for ANP–> supports increase in volume
What are the actions of ANP?
1- Vasodilation of afferent arterioles
2- Increased blood flow increase GFR
3- Inhibits Na+ reabsorption along nephron
4- Causes natriuresis (loss of Na+ in urine)
If BP low ANP release inhibited
What do prostaglandins do?
Vasodilators –> reduced BP
Important clinically rather than physiologically
Enhance glomerular filtration rate and reduce Na+
Protective function
Act as buffer–> excessive vasoconstriction produced by SNS and RAA system –> important when AngII↑
What does dopamine do?
Formed from L-DOPA
Locally–> kidney produced acts on renal blood vessels and cells of PCT and TAL
Vasodilaion and ↑ renal blood flow
Reduced NaCl reabsorption (Inhibits Na/H+ exchanger and Na/K ATPase)
How can secondary hypertension be treated?
Depends on cause
How is renovascular disease treated?
Occlusion of Renal artery–> stenosis
Fall in kidney perfusion pressure (JGA detects)
Leads to ↑ renin production –> angiotensin aldosterone system –> vasoconstriction and Na+ reabsorption–> ↑BP–> hypertension
therefore remove occlusion–> surgery, drugs to dissolve, stent etc…
What happens during renal parenchymal disease?
Caused initally by loss of vasodilator substances
Later stage–> Na+ and water retention–> inadequate glomerular filtration
Large Na+ loss –> body thinks its too much so reabsorbs it–> H2O follows
What are the adrenal causes of hypertension?
Conn’s Syndrome–> aldosterone secreting adenoma
Cushing’s syndrome–> Excess secretion of glucocoticoid cortisol–> high conc acts on aldosterone receptors–> Na+ and water retention
tumour–> Phaeochromocytoma–> secrete catecholamine–> NA and A–> over production leads to vasocontriction α1 receptors
What are the non pharmacological approaches to treating hypertension?
Exercise
Dietary advice
Lifestyle changes
Reduced NaCl intake
How does an ACE inhibitor reduce BP?
Prevent angiotensin 1 conversion to Angiotensin 2
AngII powerful vasoconstrictor–> inhibited no vasoconstriction
AngII also controls release of aldosterone–> Na+ reabsorption–> inhibited no aldosterone release therefore no Na+ reabsorption and reduced H2O uptake
Also used for bradykinin to peptide fragments conversion
Inhibited –> bradykinin builds up–> vasodilator
What other vasodilators can be used?
L-type Ca2+ channel blockers–> Verapamil and Nifedipine –> Reduce Ca2+ entry to SM cells–> relaxation of vascular SM
α1 receptor blockers–> Doxazosin
–> reduced sympathetic tone–> relaxation of vascular smooth muscle (Adrenaline at high levels= vasoconstriction)
Causes postural hypotension
How do diuretics work?
Thiazide
Inhibit Na/Cl transporter–> Na+ released –> H2O follows
Aldosterone antagonists–> spironolactone–> inhibit angiotensin effect (not first choice)
How do beta blockers work?
Block β1 receptors in heart–> reduce HR and contractility (sympathetic effects)
NOT used in hypertension alone
Only used if there are other indications such as MI
