Medicine Notes Physiology and Pharmacology Notes
1st year Oxford notes and tutorial essays on Physiology and Pharmacology...
The following is a more accessible plain text extract of the PDF sample above, taken from our Physiology and Pharmacology Notes. Due to the challenges of extracting text from PDFs, it will have odd formatting:
The control of regional blood flow
Cardiac output is a global measure of flow and is a sum of all individual flow.
Local blood flow is determined by tissue and not the heart
Tissue blood flow = (arterial blood pressure – venous blood pressure) / resistance
a) blood flow can be controlled through changing pressure
-cardiac contraction: hormones, nerves, starling’s law
-water/salt balance: determines the volume in blood vessels changed by thirst, kidney, sweating
-vessels compliance and tension: affects the tension on the blood
However changes in blood pressure is often associated with pathology
b) Local blood flow is mostly controlled by changing resistance
-In blood vessels the tension exerted by smooth muscle in the tunica media is called the vascular tone-this regulates blood flow. Having a vascular tone allows vasodilation. Basal vascular tone is high in tissues capable of increasing their blood flow
-vascular tone regulates regional blood flow. Local blood flow changes through changes in resistance (arteriole) vessel radius. A small change in radius has a Highly non linear effect on resistance due to the r4 term in poiseuille’s Law. This allows tissues to alter blood flow over a wide range.
resistance: Poiseuille’s Law RESISTANCE =$\ \frac{8\ \times viscosity\ \times Length}{\pi\ \times \ {radius}^{4}}$
-Greatest fall in pressure occurs at arterioles which is known as resistance vessels- these are very long. Change in local blood flow occurs through changing the radius of arterioles.
-vasoconstriction: total peripheral resistance can be increased through a decrease in the size of radius. Due to poiseuille’s law a decrease in the radius by a factor of a half results in the resistance increasing by a factor of 16- this decreases local blood flow into capillaries leading to decrease in capillary perfusion. Blood builds up behind the site of vasoconstriction and leads to increase in arterial blood pressure.
-vasodilation: total peripheral resistance decreases due to relaxation of the smooth muscle basal tone-dilation of the blood vessels increases the local blood flow, increased capillary perfusion. If radius is increased by x 2 resistance decreases by /16-Arterial blood pressure decreases
-at rest all tissues have a basal blood flow but this flow in Salivary glands, skin and skeletal muscle can be increased by 20 fold through vasodilation.
Vascular tone is controlled by intrinsic and extrinsic mechanisms
Intrinsic regulatory mechanisms
-Bayliss myogenic response to arterial pressure
-endothelial secretions: nitric oxide, EDHF, prostacyclin, endothelin
-vasoactive metabolites generated by active tissue
-autacoids: vasoactive paracrine secretions such as histamine
-temperature: important in the skin
Extrinsic regulation
-vasomotor nerves: sympathetic
-vasoactive hormones: adrenaline, angiotensin, vasopressin
Control Hierarchy
Vascular tone regulation involves a hierarchy of control processes
-lowest level of intrinsic regulation is through the Bayliss myogenic response
-middle level is the modulation of the myogenic response by endothelial secretions, vasoactive metabolites, autocoids
These two levels of control provide for local tissue needs
-highest level of control is caused by extrinsic factors- modify and override the intrinsic controls to meet the needs of the whole animal
Myogenic responses to blood pressure changes
Arterial vessels contract when blood pressure is raised: Bayliss myogenic response
-myogenic response relies on the equation flow = pressure x r4
-when blood pressure is raised in an artery/arteriole the pressure at first distends the vessels. This is followed by a myogenic response of contraction- decrease in radius- constant flow
-when blood pressure falls it triggers a decrease in vascular tone/ vasodilation- increase in radius
-myogenic response is important:
-contributes to basal tone
-stabilises tissue blood flow and capillary filtration pressure if arterial pressure changes
-myogenic response well developed in the brain and kidney and myocardium but not the skin
Mechanism of the myogenic response
-when an arteriole smooth muscle is stretched due to the increase in arterial pressure, it increases tension in the wall of the arterioles
-this results in the opening of stretch activated TRP cation channels- non specific cation channels
-this leads to depolarisation in the arterial myocytes to around -40mv
- causing the activation of L type calcium channels- leading to a rise in cytosolic free calcium concentration and leading to contraction
Regulation by endothelium
Endothelium produces
vasoconstrictor: endothelin 1
vasodilator: NO, endothelium-derived hyperpolarising factor, prostacyclin
all four substancs are released as they are produced
roles of NO
Exp: vasodilatation of large arteries by acetylcholine changed into vasoconstriction when endothelial lining was rubbed away. Seen- agonists such as ACH stimulates endothelium to secrete vasodilator substance overrides the direct vasoconstriction action of ACH on arterial muscle
Formation of NO
-Nitric oxide is generated continuously by the constitutively expressed enzyme (endothelial nitric oxide synthase) Continuous modulation of basal tone -NO is produced continuously as NO synthase inhibitors reduce renal blood flow. Human vascular tone is the result of balance between tonic relaxation mediated by NO and tonic vasoconstriction mediated by TRP channels
-secreted by the endothelial cells due to shear stress (amount of force needed to move a unit area of blood) exerted by blood stream
-shear stress can be increased by raising blood viscosity- detected by endothelial glycocalyx – transduction activates enzyme phosphatidyl inositol 3 kinase- activation of protein kinase B- phosphorylates eNOS- activates endothelial NO synthase
-increase in NO causes local vasodilation- reduces shear stress
Evidence for the production of NO: Inhibitor L-NMMA reduces blood flow. Drugs such as glyceryl trinitrate are vasodilators...
Buy the full version of these notes or essay plans and more in our Physiology and Pharmacology Notes.
1st year Oxford notes and tutorial essays on Physiology and Pharmacology...
Ask questions 🙋 Get answers 📔 It's simple 👁️👄👁️
Our AI is educated by the highest scoring students across all subjects and schools. Join hundreds of your peers today.
Get Started