MICROCIRCULATION AND LYMPHATICS LEARNING OBJECTIVES At the end of lecture the student should know : • About the component of microcirculation • About the Structure and function of capillaries • About different pressure acting on capillary membrane and the conditions that can alter these pressure • About the mechanism and direction of exchange of fluid at the arterial and venous end of capillary • About the structure and function of lymphatic vessels • About the mechanism of lymphatic flow MICROCIRCULATION • The microcirculation is the blood flow through blood vessels smaller than 100 µm Components of microcirculation • Meta arterioles • Arterioles • Capillaries • Postcapillary venules • Arteriovenous shunts(in skin low resistance connections between arterioles veins) ARTERIOLES • • • • • • Small diameter (<20 μm, up to 5-9 μm) blood vessels Extends and branches out from an artery Leads to capillaries Thin muscular walls The primary site of vascular resistance. Total peripheral resistance approximately equal to the resistance of the arterioles, since the arterioles are the chief resistance vessels in the body • Total Peripheral Resistance = mean arterial pressure/cardiac output. VENULES • Blood vessel that allows deoxygenated blood to return from the capillary beds to the larger blood vessels • Have three layers: – An inner endothelium composed of squamous epithelial cells that act as a membrane – A middle layer of muscle and elastic tissue (poorly developed so that venules have thinner walls than arteriole) – An outer layer of fibrous tissue. CAPILLARIES • • • Smallest of a body's blood vessels, measuring 5-10 μm Connect arteries and veins Closely interact with tissues • "CAPILLARY BED" the network of capillaries supplying an organ. • Usually carries no more than 25% of the amount of blood it could contain This amount can be increased through autoregulation (i.E. Active muscle cells) by inducing relaxation of smooth muscle. • STRUCTURE OF CAPILLARIES • • • • • • • • Walls composed of a unicellular layer of endothelium Surrounded by a basement membrane 0.5 micrometer thick Lipids soluble substances and gases can pass easily through diffusion Pores or intercellular cleft represents 1/1000th of total surface area Allows for the passage of water soluble molecules except for proteins Plasmalemmal vesicles– play a minor role in transporting material from one surface of capillaries to other Capillary permeability can be increased by the release of certain cytokines. TYPES OF CAPILLARIES Continuous – Have a sealed epithelium – only allow small molecules, water and ions to diffuse – Example blood brain barrier Fenestrated – Have openings that allow larger molecules to diffuse – Examples-- Renal glomeruli,GIT Sinusoidal – Special forms of fenestrated capillaries – Have larger openings in the epithelium allowing RBCs and serum proteins to enter – Example liver, lymphoid tissue, endocrine organs, and hematopoietic organs (bone marrow, spleen) VASOMOTION Changes in capillary blood flow caused by intermittent constriction and dilation of regional arterioles • Oxygen concentration in tissue is the most important factor regulating circulation • Under basal condition – 1-10 % of the capillaries are operational • During High metabolic activities – More capillaries – More oxygen and metabolites to tissues FUNCTIONS OF ENDOTHELIUM] • Vasoconstriction and vasodilation, and hence the control of blood pressure by secreting certain substances • Kinins – Arteriolar dilation – Increase capillary permeabilty • Endothelium derived relaxing factor – Identified as NO – Continuous vasodilating effect • Endothelins – Initial vasodilation followed by vasoconstriction (potent and lasting) – Positive ionotropic and chronotropic – Effects on myocardium – Mode of action By activating specific receptors OTHER FUNCTIONS OF ENDOTHELIUM – Blood clotting (thrombosis & fibrinolysis) – Formation of new blood vessels (angiogenesis) – Inflammation and swelling (oedema) – Transit of white blood cells CAPILLARY FUNCTIONS • Exchange – 700 meter square area – xchange of substances in capillaries and post capillary venules • Mechanism of exchange • Diffusion • Filtration (bulk flow) DIFFUSION • Principal mechanism of microvascular exchange • Rate of diffusion is directly proportinal to • Inversely proportional to – Thickness of membrane – Molecular weight • Lipid soluble – through endothelial cell membrane. • Water soluble – through intercellular pores • Size Dependent INTERSTITIUM • Spaces between the cells • Fluid in this space– interstitialfluid • 2/3rd of ECF, 1/6th of TBW • Composed of – Collagen fiber bundles – Proteoglycan filaments Permeability (Relative to Water) – Change in concentration – Surface area – Solubility 1.2 Water 1 0.8 0.6 0.4 Albumin 0.2 0 10 100 1000 Molecular Weight (Daltons) 10000 100000 INTERSTITIAL FLUID • Interstitial fluid---same composition as of plasma except for lower concentration of proteins • Composed of – Interstitial gel – Free fluid • Gel--- fluid that is entrapped in the small spaces among proteoglycan filaments – Difficult to flow easily • Free fluid----fluid that is free from proteoglycan – Can flow easily – In the formof free fluid vesicle and rivulets BULK FLOW FILTRATION AND REABSORPTION • FILTRATION – Movement of fluid from plasma into interstitium • REAPSORPTION – Movement of fluid from interstitium to palsma • STARLING FORCES • Hydrostatic and osmotic forces that determines direction of flow STARLING FORCES NFP= Pc – Pif –Πp+ Πif • NFP is net filtration forces • Pc is capillary hydrostatic pressure that forces the fluid outwards • Pif is interstitial fluid hydrostatic pressure – If positive favors reapsorption – If negative then favour filtration • Πp is plasma colloid osmotic pressure or oncotic pressure – Tends to favor reapsorption • Πif isinterstitial fluid colloid osmotic pressure – Favours filtration CAPILLARY HYDROSTATIC PRESSURE • Pressure in capillaries that favors the outward fluid movement • At arterial end : 30 mm Hg • At venous end : 10 mm Hg • The gradient favors fitration at arterial end and reabsorption at venous ends • Mean capillary pressure is sum of two 17 mmhg • 30 – 45 mmHg in most tissues • In kidneys 50 – 60mmHg CAPILLARY HYDROSTATIC PRESSURE • In the presence of blood flow capillary pressure must exceed the venous pressure • Depends on arterial blood pressure pre and postcapillary resistance venous pressure (most important) FACTORS AFFECTING CAPILLARY HYDROSTATIC PRESSURE Direction of change in variable resistance Increase in arterial pressure Decrease in arterial pressure Increase in TPR Decrease in TPR Increase in venous pressure Decrease in venous pressure Venous constriction Venous dilation INTERSTITIAL FLUID HYDROSTATIC PRESSURE • Slightly negative • Promotes filtration • Intrapleural space -8mmHg • Epidural space -4 to -6mmHg • Average pressure in subcutaneous interstitial fluid is -3mmHg • Due to pumping of fluid by lymphatic system • Rises if the interstitial fluid volume increases e,g edema • Positive pressure prevents filtration from capillaries Capillary flow Capillary pressure Pc PLASMA OSMOTIC COLLOID PRESSURE • Ions cross the capillary membrane easily • Osmotic pressure within the capillary is principally determined by plasma proteins that are relatively impermeable. • Referred to as the "oncotic“ • Tends to favor reapsorption • Average value 28mmhg – 19mm hg comes from protein – 9mm hg by DONNAN effect i.E. Osmotic pressure exerted by sodium potasium and other ions held in plasma by proteins • Albumin generates about 70% of the oncotic pressure. • Increases along the length of the capillary, – Because the filtering fluid leaves behind proteins leading to an increase in protein concentration. INTERSTITIAL FLUID COLLOID OSMOTIC PRESSSURE • Proteins cannot pass through endothelium into interstitium • Only a very small amount leaks through pores • Total protein AMOUNT is more than in plasma • Interstitial fluid volume is high , CONCENTRATION is much lower than in plasma • 3gm/dl of protein exerts a pressure of 8mmhg • Favors filtration of fluid FILTRATION COEFFEICENT • Rate of filtration perminute per mmHg for entire body • 6.67 ml/min/mmHg • Depends on number of microvessels receiving blood flow and permeablity of vessels substances raise the K – Hypercapnia – Hypoxia – No – Increased H+ AND K+ conc. – Histamine Bradykinin – Adenosine – Other – MOVEMENT OF FLUID AT ARTERIAL END OF CAPILLARY • Pressures moving fluid out of the capillary: – Capillary pressure – Pressure of intestitial fluid – Oncotic pressure of ISF 30 3 8 41 • Pressures moving fluid into the capillary: – Oncotic pressure of plasma 28 • Together 41-28=13 mmHg in direction out of the capillary (0.5 % of plasma) MOVEMENT OF FLUID AT VENOUS END OF CAPILLARY • Pressures going out of the capillary: – Capillary pressure – Pressure of intestitial fluid – Oncotic pressure of ISF 10 3 8 21 • Pressures going into the capillary: – Oncotic pressure of plasma 28 • Together 28-21=7 mmHg in direction into the capillary (0.5 % of plasma) MOVEMENT OF FLUID THROUGHOUT CAPILLARY • Pressures going out of the capillary: – Mean Capillary pressure – Pressure of intestitial fluid – Oncotic pressure of ISF 17.3 3 8 28.3 • Pressures going into the capillary: – Oncotic pressure of plasma 28 • Together 28-28.3= 0.3 mmHg in direction out of the the capillary (0.5 % of plasma) NET MOVEMENT • Net filtration pressure= 13mmHg • Net reabsorption pressure = 7 mmHG th • Capillaries at their venous ends absorb 9/10 of fluid filtered at arterial end • Remaining is absorbed by lymphatics LYMPHATIC FLOW Lymph vessels – endothelial tubes – permeable to fluid and high molecular weight compound Only mechanism for – returning albumin and other interstitialmacromolecules to the circulatory system • Recovers 200 gm proteins daily • Excess fluid is removed from interstitium to maintain a gel state • Normal lymph flow 2L/day for entire body • Highest rate in GI tract and liver MECHANISM OF LYMPH FLOW • Lymphatic fluid is pumped out of the tissues by contraction of large lymph vessels and skeletal muscle • Flow towards the heart because of one way valves in vessels • This fluid is then transported to progressively larger lymphatic vessels culminating in the right lymphatic duct (for lymph from the right upper body) and the thoracic duct (for the rest of the body); these ducts drain into the circulatory system at the right and left subclavian veins. 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