Control Of Blood Pressure

Question 1

What is hypertension

Answer 1

Sustained increase in blood pressure

BP is measure in millimetres of mercury (mmHg)

The normal or dial adult blood pressure is considered to be between 90/60mmHg and 120/80 mmHg

Question 2

What causes hypertension

Answer 2

In around 95% of cases the cause in unknown - this is know as essential/ primary hypertension

Where the cause can be defined it is referred to as secondary hypertension - examples:

Question 3

Why is it key to treat hypertension

Answer 3

Hypertension = the silent killer

Although hypertension may be asymptomatic, it can have unseen damaging effects on heart and vasculature, and it can potentially lead to heart failure, MI, stroke, renal failure and retinopathy

Diseases attributable to hypertension:
They are all vascular diseases - which drives the pathology e.g. Stroke, heart failure, retinopathy, aortic aneurysm, LV hypertrophy, MI, chronic kidney failure

If you have sustained high bp, your heart is working under an increased system - so muscle in heart increases in size in left ventricle - Eventually this could lead to failure of heart

Question 4

Effect of intervention

Answer 4

Lowering blood pressure compared to not (lowering by any means) increases you changes of survival and having non/fatal endpoints

Effect of intervention - Every 10mmHG reduction in BPG 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 bp regulated - Pressure = flow x resistance
Mean arterial BP = CO xTPR
CO = SV x HR

Both short and long term regulation is achieved in the body
Short term regulation - uses baroreceptor reflex
adjust sympathetic and parasympathetic inputs to heart to alter cardiac output
adjust SNS input to peripheral resistance to alter TPR

Question 5

Baroreceptors reflex

Answer 5

The barorecptor 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 barorecptor firing resets

Question 6

Medium and longer term control of blood pressure

Answer 6

Complex interaction of neurohumoral responses

Directed at controlling sodium balance and thus extracellular fluid volume

Plasma is part of the extracellular fluid compartment

Question 7

4 parallel neurohumoral pathways controlling circulating volume and hence BP

Answer 7

1. Renin-angiotensin-aldosterone system
2. Sympathetic nervous system
3. Antidiuretic hormone (ADH)
4. Atrial natriuretic peptide (ANP)
   Control BP in part by controlling sodium balance and extracellular fluid volume

Question 8

The Renin-angiotensin - aldosterone system (RAAS)

Answer 8

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 	- which is detected by baroreceptors in afferent arteriole
c) Sympathetic stimulation to JGA increases release of renin

Decreased circulating volume stimulates renin release:
Due to -
Sympathetic stimulation occur to the juxtaglomerular apparatus
Decreased NaCl delivery to the macula densa
decreased renal perforation pressure (sensed by renal baroreceptors)
Leads to Renin in being released from the granular cells of the afferent arterioles

Angiotensin 2 receptors - Two types of Ang II receptors identified

Question 9

Brazilian viper

Answer 9

Bothrops envenomings may be followed by shock, with or without a defined cause; hypovolemia due to blood or plasma loss; activation of hypotensive substances, pulmonary oedema, and disseminated intravascular coagulation

Family of peptides, which were initially named bradykinin potentiating factors.

Question 10

2. SNS

Answer 10

High levels of sympathetic stimulation reduce renal blood flow due to

Question 11

3. Antidiuretic hormone (ADH)

Answer 11

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

Question 12

Actions of Atrial natriuretic peptide (ANP)

Answer 12

Atrial natriuretic peptide (ANP) promotes Na+ excretion

Synthesised and sorted 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/increase BP
reduced filing if the heart - less stretch -less ANP released

actions - 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 increasing BP

Question 13

Other methods of regulating BP

Answer 13

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 - good indicator of hypertension - if inhibited could help increase BP

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

Question 14

when BP gets too high

Answer 14

When blood pressure is too high:
We have looked at a number of mechanisms which help maintain circulating fluid volume and therefore BP

Considered some stabilizing influences

But when arterial BP becomes too high, we can apply these principles to the understanding of secondary causes and the treatment of Hypertension

Secondary hypertension: Renovascular disease:
Occlusion of the renal (renal artery stenosis) artery causes a fall in perfusion pressure in that kidney
Decreased perfusion pressure leads to increased renin production
Activation of the RAAS - as pressure in the kidney is low (normal elsewhere)
Vasoconstriction and Na+ retention at other kidney + overall BP increase in body

Secondary hypertension: Renal parenchyma 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 due to too much water reuptake

Secondary hypertension: adrenal causes:
Conn’s syndrome

Question 15

Treating hypertension

Answer 15

Treating hypertension: non-pharmacological approaches -
Exercise
Diet
Reduced Na+ intake
Reduced alcohol intake
Although Lifestyle changes can only have limited effect
Failure to implement lifestyle changes could limit the effectiveness of antihypertensive therapy

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

Treating hypertension: vasodilators:
L-type Ca channel blockers (eg Verapamil, Nifedipine)