Circulation and blood pressure (L13 + 15)

Question 1

What is fluid flow through blood vessels governed by?

Answer 1

Physical laws: Blood flow (cm^3) = change in pressure/resistance

Question 2

What is Poiseuille’s Law?

Answer 2

Flow = π x r^4 x ΔP / 8 x η x L
The flow of liquid is related to the viscosity of the fluid, the pressure gradient across the tubing, the length of the tubing, the diameter of the tubing.

Question 3

Why is the diameter of a vessel very important?

Answer 3

Because flow and resistance depend on the change in pressure, but also the radius, especially in small arteries and particularly arterioles which is where blood first meets high resistance. The vessel diameter is a key control point of this resistance.

Question 4

Explain the idea of collapsing blood vessels.

Answer 4

Blood vessels are not rigid and tissue pressure will collapse vessels is the blood pressure falls (critical closing pressure). The relationship between flow and pressure is not linear in elastic tubes because for flow to increase, the pressure inside must exceed the pressure outside for the tube to be fully open.

Question 5

What does the law of Laplace state?

Answer 5

Applies to open vessels - states that the transmural pressure (pressure across the wall of the blood vessel) (P) = tension of the blood vessel / radius of the blood vessel. Tension = P x r (the internal radius) / W (wall width)

Question 6

What are aneurysms and how does Laplace’s law apply?

Answer 6

Ballooning of the blood vessel due to a weakness in the wall. The pressure from within the artery causes it to locally balloon out. The tension across the vessel depends on the radius of the aneurysm. The smaller the aneurysm, the higher the pressure, but the wall is thicker. So as the aneurysm gets bigger, the wall gets thinner and it is more likely to burst

Question 7

What is compliance? How is it worked out?

Answer 7

Compliance is a measure of give a blood vessel has (how much internal pressure it takes to expand it). Compliance = Change in volume/change in pressure

Question 8

Why are veins more compliant than arteries?

Answer 8

They have a less thick wall so expand more easily. This means they store blood (capacitance vessels) which can also lead to post-mortem blood pooling.

Question 9

Why is the fact that your vessels are elastic important?

Answer 9

The fact out arteries and veins are elasticated means that blood can flow continuously. If the tubes were rigid, blood flow would stop with every heartbeat. But because they are elastic, tension is stored when the blood flows through elastic recoil so it can be pulsated continuously in between heart beats.

Question 10

Explain the different types of flow through vessels and how can they be worked out?

Answer 10

Flow through blood vessels can be laminar or turbulent (similar to in the airways.) The type of flow can be found using Reynold’s number, which is equal to ρ (fluid density) x vessel diameter x mean velocity / η (viscosity)
if Reynolds number is less than 2000 you get a laminar flow and if it’s over 3000 you get turbulent flow.

Question 11

What happens to blood pressure and velocity at the arterioles and why?

Answer 11

Blood pressure decreases across arterioles because there becomes many more of them. The mean pressure is about 35mmHg compared to 120mmHg in the aorta. Blood velocity also decreases because diametre deceases.

Question 12

Explain blood flow through the capillaries

Answer 12

5% of total blood volume is contained within capillaries. Velocity through capillaries is low (0.07 cm/s). Capillaries have a large total surface area because they are a major site for nutrient exchange.
Precapillary sphincters direct flow and the vessels can be inactive (collapsed) when less exchange is needed

Question 13

What is tissue fluid and how is it formed?

Answer 13

Fluid between tissues. Net fluid transfer from capillaries to tissue is by a balance of filtration and absorption. Filtration occurs through cells (aquaporins - transcellular) and between cells (paracellular).
The fluid formation depends on a change in pressure ( a hydrostatic pressure difference between the capillary and interstitial fluid). A difference in COP =a difference in colloid osmotic pressure. CFC = capillary fibrillation coefficient (what dictates the ease of flow across the vessel wall). Blood hydrostatic pressure is normally higher than tissue fluid hydrostatic pressure (which may be negative). Thus, the change in pressure is outwards. COP is caused by impermeable proteins e.g. albumin. If the plasma pressure is high, and the tissue fluid is low (thus the change in COP is about equal to COP of plasma), the change of COP is in. This balance causes a net production of tissue fluid.

Question 14

What are the similarities and differences between different types of vessels?

Answer 14

Veins have much larger lumens than that of arteries of the same size. All vessels have an endothelium and basement membrane layer. Arteries have a thick elastic layer (tunica media) and veins have a larger tunica externa but not as much elastic tissue. Smaller veins and venuoles contain valves to help with the blood flow in the right direction.

Question 15

Explain what is meant by a basal tone and autoregulation

Answer 15

Vessels have a resting tension, like with muscles. Their tension is myogenically regulated (stretch evokes a contraction). This low-level control is designed to give a constant flow (auto-regulation). The vessels respond to changes in factors so that they can maintain blood flow to important structures and organs, even if perfusion changes. Local factors like partial pressure of oxygen and co2, temp, potassium conc and lactate conc and things like bradykinins (known as metabolite regulators) can also impact the diameter of the vessel. E.g. increased co2 production makes the vessel dilate to increase blood flow. - no input from medullar needed for autoregulation, the vessel does it all by itself

Question 16

Explain the role of extrinsic control of vessels through the autonomic system.

Answer 16

Most vessels (not capillaries and venules) have tonic sympathetic adrenergic constrictor input (alpha adrenergic receptors). Precapillary vessels in skeletal muscle, heart, lung and kidneys have sympathetic ACh neurones, which cause vasodilation and increase blood flow to a tissue. The exception is erectile tissue/glands which have para. ACH vasodilators. Sympathetic constrictors are very important, they divert blood into the capillary beds.

Question 17

Explain how innervation from the autonomic system varies between vessels.

Answer 17

Innervation to vessels int eh brain is low because you never really need to decrease blood to this area. Muscles with a weaker sympathetic tine cause smooth muscle relaxation and the blood pressure dilates the vessel. Whereas, the innervation to cutaneous vessels is high, so blood flow to those areas can be controlled. , e.g. to direct blood to the surface of the skin to reduce heat

Question 18

Explain the humoral ways blood vessels are regulated.

Answer 18

Hormones made by the adrenal medulla e.g. adrenaline
- Causes vasoconstriction in the skin/viscera, but vasodilation in the skeletal muscle and liver- this is so blood is concentrated to certain areas in the fight/flight response when it’s needed most. (muscle, liver, heart etc) In this response, however, it is the nervous system response rather than autoregulation that has the biggest influence because it is faster. Kinins e.g. bradykinin is a vasodilatory peptide (released when using ACE inhibitors to treat hypertension)
Angiotensin II are vasoconstrictors which increas BP: they’re formed by enzymes e.g. renin in the kidney acting on precuroses when BP falls.

Question 19

What local agents help control blood vessels?

Answer 19

Prostaglandins can be produced by tissues in response to hypoxia (causes vasodilation), Serotonin (produced by platelets) causes vasoconstriction (helps reduce bleeding during a cut). Histamine released from mast cells during allergic reactions causes vasodilation (BUT bronchoconstriction) - why you go red when you have an allergic reaction - its aim is to flush blood into the area to hopefully get rid of the allergen.

Question 20

Explain how Endothelium-derived relaxing factor causes relaxation.

Answer 20

It is another local agent involved in the extrinsic control of blood vessels. its basically NO produced by endothelial cells after stimulation e.g. ACh. It stimulates cGMP in the muscle which causes relaxation of smooth muscle. Sildenafil (Viagra) inhibits cGMP breakdown, which increases relaxation in the penis. Nitroglycerin causes an increase of NO which causes vasodilation - this increases flow and blood supply (used to treat angina - pain caused by decreased blood flow to the heart) endothelium-derived hyperpolarizing factors are also released on stimulation by ACh. They do the same thing as EDRFs, but their pathway is very complex.

Question 21

Explain the central control of blood vessels.

Answer 21

Done by interlinked CNS centres in the brain - especially the medulla. It receives multiple inputs from the body and will alter blood flow accordingly. The emotional response also plays a part in this. And your brain also ‘knows’ when you’re going to exercise. Neurones in the medullary centres regulate cardioexcitation, cardioinhibition, and vasomotor output.
E.g. the carotid sinus is innervated by the glossopharangeal nerve. Stretch of the sinus will result in activation of the nerve. This signal will be sent to the cardioinhibitory centre. It will the be passed down parasympathetic efferents to causes a decrease in the heart rate. A similar signal is also sent to the vessels to cause vasodilation. This reduces blood pressure

Question 22

Explain the kind of things medullary neurones react to.

Answer 22

1. Local environment:
   - respond to pH change, increase in CO2, decrease in O2.
   - Increase in intercranial pressure e.g. due to swelling after brain injury - decreases blood flow to the brain
   - Cushing’s reflex leads to increase in vasoconstriction, this causes an increase in BP but also brachycardia (decrease in heart rate) - so risk of death in these patients is high.
2. Peripheral proprioceptors
   - Baroreceptors (stretch receptors)
   - Stretch receptors - in the carotid sinus / aortic arch detect high pressure
   - A sudden decrease in arterial pressure decreases baroreceptor firing, which activates sympathetic neurones and inactivates vagal neurones in the medulla. This increases cardiac output and systemic vascular resistance increases. This acts to increase arterial pressure.

• this is short term regulation of BP - long term is by the kidneys that regulate blood volume

Question 23

What is the prevalence of hypertension and what is it?

Answer 23

Kills up to 1 mill people per year. It is when blood pressure is abnormally high compared to the average for the age/sex of the patient.

Question 24

What are the different types of hypertension?

Answer 24

Essential hypertension

Secondary hypertension - a consequence of a clinical condition (so basically caused by another disease)

Question 25

What are the suspected risk factors/ causes of essential hypertension?

Answer 25

Mean arterial BP = cardiac output x total peripheral resistance. Cardiac output tends to decrease with age, whilst TPR increases, which may cause an increase in blood pressure. 
Cardiac dysfunction - EH patients have an increased response to stress and catecholamines.
Vessel abnormalities - Symp. nervous system abnormalities (too much stimulation causes too much vasoconstriction) - leading to increases pressure. 
Local factors e.g. low EDRF or smooth muscle ion channel defects.\Muscle hypertrophy/rigidity ( decreases elasticity of vessels) 
Kidney dysfunction (volume-induced hypertension)

Question 26

Are genes thought to be involved in essential hypertension?

Answer 26

Yes, EH is familial, suggesting genetic factors are involved. It correlates with how directly related you are, e.g. identical twins will both get it. EH also varies with race (higher incidence among african-Caribbean people in the US) It is estimated about a 30-50% genetic predisposition and then the rest is environmental factors. The best evidence for polymorphisms in angiotensinogen and ENaC.

Question 27

What environmental factors may cause EH?

Answer 27

Diet and obesity (metabolic syndrome), a western lifestyle, high salt intake and vitamin D deficiency.

Question 28

Explain how salt is involved in essential hypertension

Answer 28

The known single mutation in blood pressure diseases (hypertension and hypotension) affects sodium uptake (HIT). This has been shown in animal models like chimps and in humans:
- Reduce salt by 3g per day
This reduces MABP by 5mm/Hg. This is equivalent to a drug that reduces strokes. It must be NaCl, not sodium ion reduction

Question 29

What diseases can cause secondary hypertension?

Answer 29

Renal disease
- When nephron function is impaired
- Blood volume and BP are increased
- Hypertension also leads to more damage and kidney failure
Renal artery stenosis-
- Narrowing of tubes
- Renin production and blood pressure increases
Pheochromcytomas
- Chromaffin ADR is increased, which increases BP
Hormone imbalance
- Aldosterone increases sodium and therefore BP (water follows sodium)
- Can also cause mini adrenal tumours

Question 30

What are the consequences of hypertension?

Answer 30

Flushing, sweating, blurred vision
Arteriosclerosis, atherosclerosis - blockage of vessels
Aneurysms e.g. aortic diameter increase form 2.5 -3 cm, can cause it to burst
Stroke due to blockages in the brain (can be bleeding (with post bleeding) or thrombosis
Myocardial infarctions
Retinal damage - hypersensitivity retinopathy - hard to tell the difference between arterioles and venules so a funduscopic examination is inconclusive

Question 31

How can hypertension be treated?

Answer 31

Non-pharmacological:
Weight loss
Exercise
Diet (decrease salt, alcohol and caffeine)
Smoking decrease
Relaxation
Pharmacologically:
Diuretics: thiazides (increases sodium and cl- excretion, so lowers blood volume)
Sympatholytics:
alpha blockers, clonidine decreases CNA sympathetic output
Prazosin relaxes smooth muscle and decreases TRP
Beta-blockers:
Propranolol decreases heart rate and contractility
Calcium channel blockers:
Broad spectrum - Minoxidil decreases cardiac contractility and vascular muscle
Selective: Manidipine effects vascular smooth muscle
The RAA system:
ACE inhibitors like Moxeipril
AG-II receptor blockers (sartan family)
Dual approaches used using a diuretic and another drug.