Lecture 13 Flashcards
What is blood flow like in all tissues?
Enormous variation in blood flow possible within tissues (e.g. resting versus active muscle)
What tissue has the most blood flow at rest?
The kidneys
What tissue has the most blood flow at maximum?
Salivary glands
What determines flow in a vessel?
Poiseuilles law - resistance to steady laminar flow
What is the main determinant of flow?
Radius
What are the two types of vascular control?
Intrinsic and extrinsic control
What does intrinsic mean?
Within the vascular wall
What is intrinsic control?
Blood vessels automatically adjust their own vascular tone by dilating or constricting in response to change of environment
What is extrinsic control?
Includes, neuronal, humoral, reflex and chemical regulatory mechanisms . These regulate the heart and myocardial contractility, and vascular smooth muscle to maintain cardiac output
What does local control adjust?
Blood flow in a tissue, independent of neural and hormonal effects
What does local control do?
Ensures matching of blood supply with needs of tissue and regulates capillary filtration pressure
What is metabolic hyperaemia?
Flow in most tissues is proportional to metabolic rate of tissue
What is reactive hyperaemia?
Increased flow following occlusion response to ischaemia (post-Ischaemic)
What is autoregulation?
Keeps flow constant despite changes in perfusion pressure
What is hyperaemia?
Increase in blood flow
What happens in heart muscle, skeletal muscle and brain tissue?
Blood flow increases steeply with increased metabolic rate
What do metabolic vasodilators do?
Act locally on resistance vessels
What is a way to increase blood flow?
Increase vasodilation
What is adenosine?
A byproduct and breakdown of ATP
What mediates metabolic hyperaemia?
Adenosine and interstitial K+
What contains adenosine?
Lots of vascular tissue have adenosine receptors particularly found in skeletal muscles and myocardium
How do you get adenosine?
Increase in metabolism, breakdown of ATP to ADP and AMP, AMP breaks down into adenosine
What do muscle cell proteins produce (GS proteins)?
Adenosine 2A
What is the mechanism for adenosine 2A produced from muscle cell Gs proteins?
Causes a decrease in phosphorylation which causes relaxation and vasodilation and also decreases sensitivity to ca2+
What are A1 receptors coupled to?
Coupled to K+ ATP channels and this causes hyperpolarisation which causes vasodilation
When is interstitial K+ activated?
During skeletal muscle contraction of neural activity
What is the mechanism for interstitial K+?
Increase in firing builds up K+ outside of cell during repolarisation which causes hyperpolarisation of muscle cells which leads to vasodilation
What else mediates metabolic hyperaemia?
Acidosis and hypoxia
What are cerebral blood vessels sensitive to?
Changes in CO2
What are the mechanisms for acidosis?
Hyperpolarisation of smooth muscle cell membrane reducing open probability of ca2+ channels.
nitric oxide release from endothelial cells.
Cerebral blood vessels sensitive to PCO2.
Skeletal muscle and myocardium insensitive.
How does acidosis cause vasodilation?
Increase in metabolism, increase in PCO2 and lactic acid = vasodilation
How does hypoxia cause vasodilation?
Increase in metabolism, decreases PO2 causes vasodilation
What are cerebral blood vessels, skeletal muscle and myocardium sensitive to?
Hypoxia
What happens in a pulmonary vasculature?
Decrease in PO2 leads to vasoconstriction (hypoxia pulmonary vasoconstriction)
What does hypoxia and a build up of metabolites (PCO2, adenosine and Latic acid) generate?
Vasodilation and high flow when occlusion is removed
What is reactive hyperaemia?
Transient increase in organ blood flow after a period of occlusion/ ischaemia
What is increase in flow proportional to in reactive hyperaemia?
Duration of occlusion
What is magnitude and duration of increase flow dependent on?
Length of time of occlusion
What happens if you block off the flow to the tissue?
The tissue will become hypoxic and metabolic factors for hyperaemia are introduced, as the flow goes through the factors, they are washed away and acidosis and hypoxia disappears - blood flow returns to normal
What is auto regulation of blood flow?
Keeps the blood flow relatively steady
What does an increase in perfusion of pressure initially generate?
An increase in blood flow, followed by a rapid decrease in blood flow, towards control levels
Where does auto regulation occur?
In many vascular beds, a rapid response of constriction will prevent damage
What is the protective effect?
Autoregulation keeps flow almost constant within physiological pressure ranges
Who first described the myogenic response?
William baylis in 1902
What is a pressurised artery?
As long as the pressure is elevated the blood vessel will stay contracted
What is the myogenic response?
When there is increased internal pressure blood vessels contract, when there is decrease in pressure blood vessels dilate
What does the myogenic response do?
Managing flow in the vessel while an increase in pressure
What is an increase in pressure associated with?
A rapid decrease in vessel diameter
Why is the myogenic response a quick process?
So it will protect the downstream blood vessels
What is the myogenic response independent of?
It is independent of the endothelium and of endothelial derived signalling
What happens to the myocytes when there is an increase in pressure?
There is an initial stretch in the myocytes
What does an increase in stretch in the myocytes cause?
Opens the TRP non selective cation channels, Cl- channels and ENACs
How does ca2+ help with contraction in the myogenic response?
Depolarisation of smooth muscle cells increases ca2+ influx through L type calcium channels and causes contraction
What is the ca2+ role in the myogenic response impaired by?
Ca2+ channel blockers, gandolinium, Cl- channel blockers and amiloride
What are other mechanisms that could be involved in the myogenic response?
Proposer mechanosensors, calcium sensitisation pathways, depolarisation by 20-HETE
What is 20-HETE?
It is a vasoconstrictor derived from arachidonic acid which reduces KCa
What are some proposed mechanosensors?
Vascular smooth muscle cell-extracellular matrix adhesion through integrins, cell-cell adhesion through Cadherins, cytoskeleton components and membrane bound components
What can change in autoregulation?
You can change the set point, the presence of metabolic hyperaemia can shift the steady steady of blood flow to a high level
What does histamine do?
It is a inflammatory mediator, increases local blood flow and increases fluid movement into tissue
What are the two different types of histamine receptors?
H1 and H2
What does H1 receptor do in blood flow?
Increases vasoconstriction of venules and permeability of venules and capillaries
What does the H2 receptor do in blood flow?
Increases vasodilation in arterioles
What does serotonin do (5HT)?
Acts to increase vasoconstriction and permeability of venules and capillaries
Where is serotonin found?
Endothelium, platelets and central nervous system
What is thromboxane?
A vasoconstrictor and thrombotic agent released by platelets and endothelium
What does aspirin do?
It can inhibit COX platelets, providing protection against thrombosis
What are prostaglandins synthesised by?
Endothelium, fibroblasts, macrophages and leukocytes
What are PGFs?
Vasoconstrictor
What are PGEs and PGIs?
Vasodilators
What is another vasodilator?
Bradykinin
What is a vasoconstrictor?
Platelet activating factor
What is the hierarchy of vascular control?
Autoregulation of intrinsic myogenic response,
Intrinsic modulators of autoregulated flow,
Extrinsic factors that override intrinsic controls to meet the demands of the whole body
What are examples of intrinsic modulators?
Endothelial derived factors, metabolic and autacoids
