Control of capillary blood flow

Question 1

On the simplest level how is capillary flow regulated?

Answer 1

Arteriolar resistance

Question 2

What are the 3 factors that regulate arteriolar resistance?

Answer 2

1. Nerves
2. Hormones and other vasoactive substances
3. Local tissue metabolism

Question 3

CO is proportional to what other measure?

Why is this?

Answer 3

V_O2 (Volume of oxygen used per minute)

Blood flow is very well matched to metabolic demand

Question 4

Why is V_O2 used as a proxy for CO in studies of athletes?

Answer 4

It is proportional to CO

Question 5

What equation is used to calculate flow in a capillary?

What is this simplified to?

Why can it be simplified?

Answer 5

Q = (P_A - P_V) / (R_pre + R_cap + R_post)

Q α 1/R_a

Pressure gradient is fairly constant

Arteriolr resistance makes up 70% of total series and is the only directly regulated resistance

Question 6

What is the purpose of LOCAL control of arteriolar resistance?

Answer 6

Matches local blood flow to local metabolici demand

Question 7

What is the purpose of central autonomic contol of arteriolar resistance?

Answer 7

Controls TPR to maintain a constant ABP

Question 8

What mechanisms of regulation are used in central control of arteriolar resistance?

Answer 8

Neuronal and endocrine

Question 9

How is arteriolar smooth muscle arranged?

Answer 9

Radially

Question 10

How is tension of vascular smooth muscle modulated?

Answer 10

Intracellular Ca²⁺ concentration

Phosphorylation of myosin light chain kinase

Question 11

How is functional hyperaemia meausured?

Answer 11

Inflated cuff above arterial pressure around arm for 10 minutes

Cuff removed and an increase in blood flow through the arm is recorded

Question 12

What metabolic factors promote vasodilatation of systemic arterioles?

Answer 12

Changes accompanying increased metabolism or normal metabolism with reduced blood flow:

-Reduced P_O2

-Increased CO₂

• Decreased pH
• Increased adenosine
• Increased extracellular K⁺

Question 13

Why does a large increase in pressure only result in a small increase in flow to areas such as the brain, heart and kidney?

Answer 13

Resistance increases as vessels vasoconstrict

Question 14

What are the direct and indirect effects of an increased ABP on vasoconstriction?

Answer 14

DIRECT:

vasoconstriction via the mygogenic mechanism (increased pressure = increased resistance to prevent rapid rise in flow)

INDIRECT:

increased perfusion washes out local metabolites responsible for vasodilatation

Question 15

How was the role of the endothelium in regulating vasuclar responses first observed?

Answer 15

ACh could only dilate arteries when endothelium was intact

(whereas noradrenaline constricted them even if the endothelium had been removed)

Question 16

What is the signalling pathway from the endothelium to vasuclar smooth muscle?

Answer 16

ACh and bradykinin (a vasodilator peptide) stimulate NO production by the action of NO synthase on L-arginine in the endothelium

NO is lipophilic and so diffuses quickly, stimulating soluble guanylyl cyclase in the vascular smooth muscle

cGMP dependent protein kinase then phosphorylates MLCK, inhibiting it

Question 17

How does sildenafil (viagra) cause vasodilatation?

Answer 17

Inhibits cGMP-specific phosphodiesterase type 5 which reduces cGMP breakdown thus increasing MLCK inhibition

Question 18

Why does endothelial dysfucnction lead to atherosclerosis and increased riskk of clots?

Answer 18

Endothelium containd pro-coagulants, anti-coagulants, fibrinolytics, antibacterials and growith factors

Question 19

What is fibrinolysis?

Answer 19

A process that prevents blood clots from growing and becomming problematic

Question 20

Where are α1 receptors not found?

Answer 20

Brain, heart and placenta

Question 21

How does activation of an α₁ receptor trigger Ca²⁺ release from the SR?

Answer 21

α₁ receptor linked to the G-protein, Gα_q

activates phospholipase C and raises IP₃

Question 22

What are eicosanoids?

Answer 22

arachidonic acid derivativesinvolved in clotting and inflammatory responses

Question 23

What enzyme synthesises most eicosanoids?

Why is this of clinical significance?

Answer 23

Cyclooxygenase

This enzyme is inhibited by aspirin

Question 24

Which prosaglandins are vasoconstrictory?

Answer 24

PG-F

Question 25

Which prosaglandins are vasodilatory?

Answer 25

PGs I, D and E

Question 26

What is thromboxane A₂?

Answer 26

An eicosanoid produced by platelets that is reponsible for vasoconstriction and platelet aggregation

Question 27

Which eicosanoid opposes thromboxane A₂?

Answer 27

Prostacyclin (PG I₂)

Question 28

Why is aspirin used to treat myocardial infarction?

Answer 28

Asprin irreversibly blocks cyclo-oxygenase (COX-1) which is required by both thromboxane A2 and prostacyclin

Endothelial cells have nuclei but platlets don’t therefore the endothelium can synthesise more COX-1 to produce prostacyclin

Thromboxane A2 not produced so there is a reduced risk of clotting

Question 29

Where are prostaglandins produced?

Answer 29

Endothelium