Control of capillary blood flow Flashcards
On the simplest level how is capillary flow regulated?
Arteriolar resistance
What are the 3 factors that regulate arteriolar resistance?
- Nerves
- Hormones and other vasoactive substances
- Local tissue metabolism
CO is proportional to what other measure?
Why is this?
VO2 (Volume of oxygen used per minute)
Blood flow is very well matched to metabolic demand
Why is VO2 used as a proxy for CO in studies of athletes?
It is proportional to CO
What equation is used to calculate flow in a capillary?
What is this simplified to?
Why can it be simplified?
Q = (PA - PV) / (Rpre + Rcap + Rpost)
Q α 1/Ra
Pressure gradient is fairly constant
Arteriolr resistance makes up 70% of total series and is the only directly regulated resistance
What is the purpose of LOCAL control of arteriolar resistance?
Matches local blood flow to local metabolici demand
What is the purpose of central autonomic contol of arteriolar resistance?
Controls TPR to maintain a constant ABP
What mechanisms of regulation are used in central control of arteriolar resistance?
Neuronal and endocrine
How is arteriolar smooth muscle arranged?
Radially
How is tension of vascular smooth muscle modulated?
Intracellular Ca2+ concentration
Phosphorylation of myosin light chain kinase
How is functional hyperaemia meausured?
Inflated cuff above arterial pressure around arm for 10 minutes
Cuff removed and an increase in blood flow through the arm is recorded
What metabolic factors promote vasodilatation of systemic arterioles?
Changes accompanying increased metabolism or normal metabolism with reduced blood flow:
-Reduced PO2
-Increased CO2
- Decreased pH
- Increased adenosine
- Increased extracellular K+
Why does a large increase in pressure only result in a small increase in flow to areas such as the brain, heart and kidney?
Resistance increases as vessels vasoconstrict
What are the direct and indirect effects of an increased ABP on vasoconstriction?
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
How was the role of the endothelium in regulating vasuclar responses first observed?
ACh could only dilate arteries when endothelium was intact
(whereas noradrenaline constricted them even if the endothelium had been removed)
What is the signalling pathway from the endothelium to vasuclar smooth muscle?
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
How does sildenafil (viagra) cause vasodilatation?
Inhibits cGMP-specific phosphodiesterase type 5 which reduces cGMP breakdown thus increasing MLCK inhibition
Why does endothelial dysfucnction lead to atherosclerosis and increased riskk of clots?
Endothelium containd pro-coagulants, anti-coagulants, fibrinolytics, antibacterials and growith factors
What is fibrinolysis?
A process that prevents blood clots from growing and becomming problematic
Where are α1 receptors not found?
Brain, heart and placenta
How does activation of an α1 receptor trigger Ca2+ release from the SR?
α1 receptor linked to the G-protein, Gαq
activates phospholipase C and raises IP3
What are eicosanoids?
arachidonic acid derivativesinvolved in clotting and inflammatory responses
What enzyme synthesises most eicosanoids?
Why is this of clinical significance?
Cyclooxygenase
This enzyme is inhibited by aspirin
Which prosaglandins are vasoconstrictory?
PG-F
Which prosaglandins are vasodilatory?
PGs I, D and E
What is thromboxane A2?
An eicosanoid produced by platelets that is reponsible for vasoconstriction and platelet aggregation
Which eicosanoid opposes thromboxane A2?
Prostacyclin (PG I2)
Why is aspirin used to treat myocardial infarction?
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
Where are prostaglandins produced?
Endothelium
