The microcirculation & lymphatic system Capillary fluid exchange Interstitial fluid Lymph flow local and humoral control of tissue blood flow 7/28/2018

THE MICROCIRCULATION 7/28/2018

THE MICROCIRCULATION components & function Arterioles Metarterioles precarpillary sphincters & venules Function Transport of nutrients to tissues Removal of cell excreta 7/28/2018

Microcirculation structure Arterioles Highly muscular Diameter changes many fold Metarterioles (terminal arterioles) No continuous muscular coat Smooth muscle fibers encircles the vessel at intermittent points 7/28/2018

Microcirculation structure cont. Precarpillary sphincter Opens and close entrance to capillary Venules Weaker muscular coat 7/28/2018

Structure of capillary wall Composed of unicellular layer of endothelial cells Surrounded by very thin basement membrane Thickness = 0.5 micrometer Internal diameter=4.9 micrometer Enough for RBC and other cells to squeese through Slit pores(intercellular clefts) Present in the capillary membrane Responsible for exchange of water molecules Most water soluble ions Small solutes 7/28/2018

Specific types of capillary wall Brain Tight junctions Allows only extremely small molecules (H2O, CO2,O2) Liver Clefts wide open Allows almost all disolved subatances of plasma to pass from blood into the liver Git Pores between those of muscles and liver Glomerular tufts Small oval windows called fenestrae Disallow large protein molecules to filter through 7/28/2018

vasomotion Flow of blood in the capillary is intermittent Regulator Caused by intermittent contraction of metarterioles and precarppilary sphincter (vasomotion) Regulator Oxygen concentration in the tissues Transport of materials between blood & interstitial fluid is through diffusion Determinants Solubility Lipid soluble substances Direct Water soluble substances & non lipid soluble through intercellular pores Molecular size Concentration gradient 7/28/2018

Starling forces Filtration across capillaries Capillary pressure (Pc) force fluid outward Interstitial fluid pressure (Pif) force fluid inwards (ve+) & outwards (-Ve) Capillary plasma colloid osmotic pressure osmosis inwards Interstitial fluid colloid osmotic pressure (Iiif outward force Net filtration pressure (NFP)=Pc-Pif-P+2if 7/28/2018

Transport of substances through capillary membrane At arterial end of capillary pressure is higher than interstitial fluid pressure which causes filtration. At venous end of capillary plasma colloid osmotic pressure is lower than interstitial pressure which cause reabsorbtion. 7/28/2018

THE LYMPHATIC SYSTEM 7/28/2018

Lymphatic system Represents an accessory route through which fluid can flow from the interstitial space into the blood Carry proteins – large particulate matter away from tissue space Neither of which can be removed by absorption directly into the blood capillaries Failure to retain proteins to the blood Leads to death within 24 hours 7/28/2018

Formation of lymph Lymph fluid Derived from interstitial fluid that flows into the lymphatics Lymphatic system is also a major route for absorption of nutrients from git esp fats Large particles such as bacterial are removed and destroyed from the lymph nodes 7/28/2018

Lymph flow Is directly proportional to interstitial fluid pressure Factors increasing interstitial fluid pressure increase lymph flow as well Elevated capillary pressure Decreased plasma colloid osmotic pressure Increased interstitial fluid colloid osmotic pressure Increased permeability of the capillary 7/28/2018

Lymphatic pump Pumping by the lymphatic system is the basic cause of the negative interstitial fluid presure i.e it is scavenger system that removes excess fluid , excess protein molecules, debris and other matters from the tissue spaces On entrance of the fluid in the terminal lymphatic capillaries The lymph vessel walls automatically contract for few seconds and pump the fluid into the blood circulation The overall process creates the slight negative pressure 7/28/2018

Lymphatic pump All favour movement into the interstitium thus increasing interstitial fluid volume interstitial fluid pressure and lymph flow all at the same time Maximum lymph flow rate Increased tissue pressure not only increases entry of fluid into the lymphatic capillaries but also compress the outside surfaces of the larger lymphatics thus impeding flow Achieved at 1 or 2mmHg 7/28/2018

Interstitial fluid pressure vs lymph flow 7/28/2018

Lymphatic capillary pump cont.. Intrinsic Intermittent contraction of the lymph vessel walls Each segment of lymph vessel when stretched with fluid contract; thus act as a pump Generates pressure 50-100mmHg 7/28/2018

Lymphatic capillary pump cont.. Extrinsic External intermittent compression of the lymphatics enhances pumping activity Any external factor that intermittently compress the lymph vessel 7/28/2018

Lymphatic pump cont.... Contraction of the surrounding skeletal muscles During exercise lymphatic pump becomes very active flow increase 10-30 fold Movements of the parts of the body During period of rest flow is sluggish , almost to zero Pulsations of arteries adjacent to the lymphatic's Compression of tissues by objects outside the body 7/28/2018

Determinants of lymph flow Is the product of interstitial fluid pressure x activity of the lymphatic pump LF=Pif x LPA (lymphatic Pump Activity) Role of the lymphatic system Controls Interstitial fluid protein concentration Interstitial fluid volume Interstitial fluid pressure Increase proteins interstitium increased oncotic pressure increase fluid volume increase fluid pressure increased lymph flow 7/28/2018

Significance of –Ve interstitial fluid pressure Holds tissue together-which is actually a partial vacuum When the tissue lose their negative pressure fluid accumulates in the spaces oedema 7/28/2018

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summary . Functions of lymph: 1. support of constant level of volume and components of tissue fluid; 2. transport of nutritive substances from digestive tract in venous system; 3. barrier-filter function. 4. take place in immunology reactions 7/28/2018

CONTROL OF BLOOD FLOW BY THE TISSUES 7/28/2018

mechanisms Local control In response to specific needs of the tissues Oxygen delivery to the tissues Nutrient delivery (glucose, amino acids, fatty acids) to the tissues Removal of carbondioxide from the tissues Removal of hydrogen ions from the tissues Maintenance of proper concentration of the ions in the tissues Transport of various hormones and other substances to different tissues 7/28/2018

Importance of local control Avoid overworking of the heart Keep the workload on the heart minimum Tissues may suffer from oxygen nutritional deficiency Mechanisms Acute control Rapid changes in local Vasodilation & Vasoconstriction Arterioles Metarterioles Precarpillary sphincter Occurs within seconds-minutes to provide very rapid maintenance of appropriate local tissue blood flow 7/28/2018

Mechanism cont..... Long term control Slow controlled changes over a period of days, weeks or months Provides better control Mechanism The actual blood vessels supplying the tissues Increase or decrease in Physical sizes Numbers 7/28/2018

Acute control Effect of tissue metabolism on local blood flow Theory Decrease in oxygen availability Increased blood flow Theory Vasodilator theory Oxygen lack theory Vasodilator Role of adenosine Increased metabolism leads to increase in rate of formation of vasodilator substances diffuse to precarppilary sphincters, metarterioles and arterioles to cause dilation 7/28/2018

Vasodilator theory cont... Example Adenosine, CO2, adenosine phosphate compounds, histamine, potassium ions, hydrogen ions etc Released in response to oxygen deficiency Oxygen deficiency leads to degradation of ATP which leads to increase of adenosine Oxygen lack theory(nutrient lack theory) Vessels do relax therefore naturally dilate Role of other nutrients Lack of glucose, a.a, fatty acids Beriberi (vit. B deficiency)- thiamine, niacin, riboflavin Vitamin required for oxygen induced phosphorylation required to produce ATP Vasodilatation 7/28/2018

Tissue unit area Figure showing a tissue unit area explaining acute local feed back control of blood flow Shows metarteriole passing through the tissue and a side arm carpillary with its sphincter for controling carpillary blood flow 7/28/2018

Acute control of local blood flow 1. Blood flow vs metabolism 2. Blood flow vs arterial o2 saturation 7/28/2018

Other local mechanisms Reactive hyperemia If you block flow for t sec/min/hour then unblock flow will increase 4-7 fold for t sec/min/hour Lack of flow decrease oxygen supply Thereby increasing vasodilators Active hyperemia When tissue becomes active the rate of blood flow increases exercising muscles 20 fold increase can be achieved git gland during hypersecretory period or brain during rapid mental activity 7/28/2018

Other mechanism cont.... Autoregulation Mechanisms Observations Due to increased arterial pressure Mechanisms Metabolic Myogenic Observations Increment of AP by 150% only increases blood flow by 30 % between 70-175 mmHg 7/28/2018

Effect of different levels of arterial pressure on blood flow through a muscle Solid red curve shows the effect if the arterial pressure is raised over a few minutes The dashed green curve shows the effect if the arterial pressure is raised slowly over a period of many weeks 7/28/2018

Autoregulation cont... Metabolic An increase of AP will increase nutrient delivery which will lead to vasoconstriction and flow return to normal Myogenic Increased pressure Increase stretch Increase contraction Decrease flow Decrease AP low stretch relax vessel & dilate increase flow Stretch increases calcium entry into the cells from ecf Opening and closing of ion channels 7/28/2018

Special mechanisms Large vessels Kidney Tubuloglomerular feedback Brain vasodilation in response to CO2 & H+ conc. Skin Blood flow control is linked to regulation of body temp. Large vessels When microvascular blood flow increases Upstream arteries (intermediate & larger arteries back upstream) There is a release from the endothelial cells lining the arteries and small arteries a substance called Endothelial derived relaxing factors (EDRF) Nitric Oxide is the principal agent 7/28/2018

Large vessels & EDRF cont... Mechanism of release Increased blood flow cause shear stress in endothelial cells which releases Nitric oxide which dilates the vessels (Increased the diameter s of upstream vessels) Meet demand increase to downstream vessels 7/28/2018

Long term blood flow regulation Important for chronically overactive tissue which requires chronically increased quantities of oxygen & other nutrients Arterioles and capillary vessels increase both in number and size with in a few weeks to match the needs of the tissue Mechanism Increase/decrease tissue vascularity Examples new growth tissue Scar tissue Cancerous tissue Slowly in old well established tissues 7/28/2018

Long term control cont.... Oxygen role Example Oxygen lack is associated with increased vascularity Example Retrolental fibroplasia (a.k.a retinopathy of prematurity) Neonate –born premature Exposed to high oxygen therapy-i.c.u normal blood vessels degrade and cease to develop. When the excess oxygen environment is removed the blood vessels rapidly begin forming again and grow into the vitreous humor of the eye from the retina Retinal detachment -blindness 7/28/2018

Long term regulation cont... Development of collateral circulation A phenomenon of long term local blood flow regulation When a blood vessel is blocked New vessels open up to supply the area Mechanisms involves both acute and long term local blood flow control Acute Rapid neurogenic and metabolic dilation followed chronically by mass fold growth and enlargement of new blood vessels over a period of weeks and months E.g thrombosis of one of the coronary arteries 7/28/2018

Humoral control of the circulation Means substances secreted or absorbed into the body fluids such as hormones or ions Vasocontrictor agents Norepinephrine/epinephrine Angiotensin II Vasopresin (ADH) Endothelium- a powerful vasocontrictor in damaged vessels Vasodilator agents Bradykinin Histamine (Basophils & mast cells) Damaged tissues Inflammed tissue Allergic reactions 7/28/2018

Humoral control of the circulation Vascular control by ions and other chemical factors Vasocontriction Ca2+ Vasodilation K+ Mg++ H+ Acetate Citrate CO2 7/28/2018