CVS 11 - Control of BP Flashcards
What is hypertension?
What causes hypertension (the classifications)?
Why is it important to treat hypertension?
- A sustained increase in blood pressure (ideal between 90/60 –> 120/80 mmHg)
- 95% of cases are unknown (essential/primary). Sometimes a cause can be identified (secondary) - e.g.: renovascular or chronic renal disease.
- Hypertension = the silent killer. Although can be asymptomatic - potential to cause HF, MI, renal failure etc. All vascular diseases.
- Increased BP increases risk of death significantly (especially as age increases).
Hypertension will lead to an increased afterload (working against a higher pressure system) + arterial damage. How do these factors lead to a number of heart problems?
1) Increased afterload = LV hypertrophy + HF or Increased myocardial oxygen demand + myocardial ischaemia/MI
2) Arterial damage can result causing atherosclerosis or weakened vessels. Both of these factors can precipitate aneurysms, renal failure, stroke, MI etc.
How is blood pressure regulated/controlled acutely?
Why does this system not control blood pressure after sustained increases?
Remember:
- MAP = CO x TPR
- CO = SV x HR
- Short term regulation via baroreceptor reflex.Nerve endings (stretch receptors) in carotid sinus and aortic arch stretch upon increased MAP.
- Increases PNS and decreases SNS inputs causing vasodilation and bradycardia (decreasing CO + TPR) thus reducing MAP.
- Sustained increases resets the threshold for baroreceptor firing.
What factors are responsible for medium and long-term control of BP?
- Complex interaction of neurohumoral responses, directed at controlling Na+ balance + therefore extracellular fluid volume.
1) RAAS
2) Sympathetic NS
3) Vasopressin (ADH)
4) ANP
- All control BP by controlling Na+ balance and extracellular fluid volume.
What stimulates renin release from the juxtaglomerular apparatus (JGA) granular cells?
1) Reduced NaCl delivery to distal tubule
2) Reduced perfusion pressure in the kidney
3) Sympathetic stimulation to JGA
- Essentially due to decreased circulating volume …
How does release of renin in response to decreased circulating volume increase bp?
1) Renin converts angiotensinogen to Ag1. ACE converts Ag1 into Ag2.
2) Ag2 causes vasoconstriction (Ag1 receptors on arterioles), stimulates Na+ reabsorption (Ag1 receptors in kidney) + stimulates aldosterone production (Ag1 receptors in adrenal cortex). Also stimulates ADH release from hypothalamus.
3) Aldosterone acts on principal cells of CD, stimulates Na+ and therefore water reabsorption + activated ENaC’
4) Therefore, vasoconstriction + reabsorption of Na+ via Ag2 + aldosterone increases circulating volume + TPR to increase BP.
How does the RAAS further potentiate its vasoconstriction effects?
- ACE (coverting Agl into Agll) breaks down bradykinin into peptide fragments.
- Bradykinin has vasodilatory effects, which are no longer possible due to breakdown.
How do ACE inhibitors work as anti-hypertensives?
Give an example of ACE inhibitors.
1) Prevents conversion of Agl –> Agll via inhibition of ACE.
2) Prevents Na+ reabsorption, vasoconstriction + increase of circulating volume achieved by Agll/aldosterone.
3) Also prevents bradykinin breakdown, which therefore has vasodilatory effects to reduce bp. Although build up of bradykinin = dry cough (use ARB’s if this is the case).
- Captopril, Enalapril etc.
By what 3 mechanisms does the sympathetic nervous system increase bp?
1) Reduced renal blood flow via vasoconstriction of renal arterioles, decreasing GFR and therefore Na+ excretion.
2) Activates apical Na/H exchanger and basolateral Na/K ATPase in proximal collecting tubule cells.
3) Stimulates renin release from JGA (increased Na+ reabsorption via RAAS).
What is the role of ADH?
What stimulates its release?
How does it increase BP?
- ADH forms concentrated urine by retaining water (increases water reabsorption through AQP2’s)
- Stimulated by increased plasma osmolarity or severe hypovolaemia.
- Stimulates Na+ reabsorption in the TAL + causes vasoconstriction.
How + where is ANP released?
How does ANP decrease bp?
- ANP is released by atrial myocytes in response to stretch.
- Causes vasodilation of afferent arterioles increasing GFR + inhibits Na+ reabsorption. Works opposite to the other neurohumoral regulators.
- Vice versa if BP decreases (ANP release inhibited).
How do 1) prostaglandins and 2) dopamine also play a role in maintaining blood pressure?
1) PG’s are vasodilators, enhancing GFR and reducing Na+ reabsorption. Act as a buffer to excessive vasoconstriction when Angll is high.
2) DA causes vasodilation of renal blood vessels increased GFR + reduces reabsorption of NaCl via inhibition of N/H exchanger + Na/K ATPase in principle cells of PCT + TAL.
List 3 root causes of secondary hypertension.
1) Renovascular disease - renal artery stenosis causes a fall in perfusion pressure to kidney, stimulating renin production + causing vasoconstriction plus Na+ retention.
2) Renal parenchymal disease - loss of vasodilator substances + Na+ retention to due inadequate GFR.
3) Adrenal causes - e.g.: Conn’s syndrome (aldosterone secreting adenoma) or phaeochromocytomas (catecholamine secreting tumour of the adrenal medulla)
What are the non-pharmacological approaches to treating hypertension?
- Exercise, diet, reduced Na+ intake.
- These could have limited effects, but also if not implemented could limit pharmacological interventions.
What 2 pharmacological agents that target the RAAS can treat hypertension?
1) ACE inhibitors (already covered)
2) ARB’s - prevents vasoconstrictive effects of Angll + prevents aldosterone release. Has diuretic and vasodilatory effects.
