Physiology - Haemodynamics and Microcirculation PDF

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Lecture on Haemodynamics and Microcirculation. Fifth part of the 7 part Physiology lecture series...

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Regulation of MAP! ! • MAP = CO x TPR! ◦ (Mean arterial pressure = cardiac output x total peripheral resistance)! • CO = HR x SV! • Therefore ! # MAP = HR x SV x TPR! ! Darcy's Law •

Flow in the steady state is linearly proportional to the pressure difference between two points - a pressure gradient drives blood flow! • Darcy's law concerns fluid flow (volume/time), which is not the same as fluid velocity (distance/time)! • Mean velocity = flow / total cross sectional area! • Total cross sectional area increases as the blood enters the microcirculation, mean velocity falls progressively! • Total flow is not altered - it remains equal to the CO at each level of the vascular system! ! Flow • Laminar flow - occurs in normal arteries and veins! • Turbulent flow - occurs in the ventricles and sometimes the ascending aorta (of healthy subjects)! • Single-file flow - occurs in the capillaries! ! Resistance (don't memorise equations)

Resistance to laminar flow! ◦ Resistance (R) to steady flow along a straight, cylindrical tube is proportional to tube length (L) and fluid viscosity (n) and inversely proportional to tube radius raised to the 4th power (r^4)! ! ! ! ! ! • Q - flow! • P1-P2 - pressure gradient! ! ! ! ! ◦ From the equation you can see that flow is extremely sensitive to vessel radius. A small increase in radius will decrease the resistance a lot! ‣ This is why arterioles are the main site of resistance in the circulation! ! Resistance in series and parallel circuits! • Collectively all the vessels are arranged in series! • With the exception of the aorta and pulmonary trunk, each vessel is arranged in parallel with other vessels of the same type! • Therefore, the resistance to blood flow are arranged in both series and parallel circuits! • Increased resistance if more series units added! • Decreased resistance if more parallel units added! ! Compliance of vessels! ! ! • The distending pressure acting on a vessel is the pressure inside minus the pressure outside! • The compliance of a vessel - the change in volume per unit change in distending pressure! • Veins have higher compliance/capacitance than arteries as they are thin walled and easily stretched! ◦ Therefore they can accommodate large increases in blood vol in response to a small increase in blood pressure (I.e. good at storing volume!

◦ Veins therefore act like volume reservoirs unlike arteries which act as pressure reservoirs! ! Forces ! • The distending pressure acts on vessel walls causing it to stretch! • Unless the force is balanced by force within the vessel wall, it will rupture! • The necessary tension to withstand transmural pressure is influenced by radius and wall thickness! • Tension - T! • Transmural pressure - Pt! • Vessel radius - r! • Wall thickness - u! ! • Wall tension increases with internal pressure and vessel radius! • Wall tension decreases with increasing wall thickness! • In large arteries Pt and r are large, so the wall needs to be thick to compensate! • In veins Pt is low but r is large. Since the walls are thin, significant tension is still generated ! • In capillaries Pt and r is small, this allows the walls to be thin otherwise they'd be vulnerable to damage! • Likelihood in vessel rupture is greatest in elastic arteries ! ◦ Aortic rupture is a relatively common, and usually fatal, medical emergency! ! Microcirculation Microcirculation - the circulation of blood through the smallest blood vessels (arterioles, capillaries and venules)! • There is a met arteriole running through the capillary bed! • Density of the capillary networks in the capillary bed is highest in metabolically active tissues such as the skeletal muscle! • Blood flow in capillaries is not uniform and depends on the contractile state of there arteriolar smooth muscle! ! Autoregulation! ! • Autoregulation - the intrinsic adjustment of blood flow to a tissue or specific vascular bed such that the flow meets the local requirements at any given time! • Changes in local blood flow! ◦ By change in arteriole diameter! ◦ Altering the contraction of precapillary sphincters! • These intrinsic control mechanisms can be classified as either metabolic or myogenic! ! Metabolic control •

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Clear relationship between the rate of metabolism and the rate of blood flow! In vitro, this relationship is observed when perfusion pressure (pressure of blood entering the capillaries) is kept constant! ◦ characterised as an intrinsic property of microcirculation!

! ! ! Factors:! ! • Oxygen ! ◦ When metabolic rate of tissue increase to the point that local consumption of oxygen exceeds delivery, a local hypoxia (deprivation of adequate oxygen supplies) occurs! ‣ Causes relaxation of nearby arteriolar smooth muscle!

! • Metabolic products! ◦ Products such as CO2, H+, K+ and adenosine diffuse from surrounding tissue and cause relaxation of vascular smooth muscle! ! • Endothelium-derived relaxing factors (EDRFs) - e.g. prostacyclin and nitric oxide! ◦ Substances synthesised within the vascular endothelium! ◦ Diffuse into the adjacent smooth muscle, where they usually mediate vasodilation! ! ! Myogenic Control An isolated, perfused organ displays an intrinsic ability to maintain a constant rate of blood flow through its vascular bed over a wide range of perfusion pressures! • Flow = pressure gradient / resistance! ◦ So graph indicates that increased pressure gradient must be met by an increase in resistance if flow is to remain constant!

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Single-unit smooth muscle responds to passive stretch with an opposing contraction! This response keeps tissue perfusion fairly constant in the face of most variations in systemic arterial blood pressure!

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! Long term autoregulations May develop over a period of weeks to months in response to nutritional and/or oxygen demands of a tissue exceeding delivery! ◦ Increase in number of microcirculatory vessels supplying blood to the tissue! ◦ Enlargement of existing vessels! Provoked in the heart by gradual, partial occlusion of a coronary vessel! Chronic exposure to high altitude (low partial pressure of oxygen) elicits a similar response throughout the body!

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! Transcapillary Solute Exchange Lipophilic solutes (including O2 and CO2) enter or leave the capillary via the transcellular route! Hydrophilic solutes can cross through the intercellular clefts, which have a diameter of around 0.006 um! While clefts can easily be traversed by water, ions and small organic solutes, albumin and other larger plasma proteins cannot!

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Exchange of fluid between capillaries and tissues • Fluid is continuously circulating between capillaries and the interstitium – "dynamic"! • Hydrostatic pressures result from capillary blood pressure:! ◦ Capillary hydrostatic pressure is greatest at the arterial end, lowest at venous end! ◦ Net gradient in favour of fluid filtration is greatest at the arterial end! • Osmotic pressures result from large, non-diffusible molecules – plasma proteins! ◦ Net gradient favours fluid absorption by the capillary – little variation over length! ! Starling Forces

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The net result acting over the length of the capillary is net movement of fluid out of the circulation at the arterial capillary end of and net movement of fluid into the circulation at the venous capillary end. ! However, this system does not exist in perfect equilibrium: overall, there is a net loss of fluid from the circulation of about 1.5ml.min-1.! If unchecked, this seemingly insignificant rate of fluid loss would completely empty the vascular system of plasma within 24 hours!! Returning this fluid (along with any leaked plasma protein) to the circulation is the responsibility of the lymphatic system!

! The Lymphatic System: [Small study topic]! ! • Subsystem of the circulatory system – drainage system! • Helps maintain fluid balance in the body – collects excess fluid/matter from tissues and deposits them into the bloodstream! • Also defends the body against infection – supplies lymphocytes! • Extracellular fluid in lymphatic system referred to as ‘lymph’! • Lymph drains into lymphatic trunks! ◦ Right lymphatic duct – drains UR portion of body via right subclavian vein! ◦ Thoracic duct – drains the rest of the body via the left subclavian vein! • Lymph transportation facilitated by muscle contractions! • Vessels contain valves to prevent backflow! • Lymph nodes punctuate vessels – remove foreign materials (e.g. infectious microorganisms)! • Main lymphoid organs: thymus and bone marrow! • Secondary lymphoid organs: lymph nodes, spleen, mucosa-associated tissues...