WINDSOR UNIVERSITY SCHOOL OF MEDICINE

1. WINDSOR UNIVERSITYSCHOOL OF MEDICINE Autoregulation and Capillary Dynamics Dr.Vishal Surender.MD.

2. Autoregulation • • Autoregulation is the process by which the various organs and tissues of the body self-regulate blood delivery. • This process can be compared to water flow regulation. A pumping station pumps water to individual houses via water pipes, just as the heart pumps blood to individual organs via blood vessels. Similarly, as long as mean arterial pressure is normal, the various organs and body tissues of the body can regulate the amount of blood that enters them according to their needs at any given time.

3. Blood flow regulation occurs at arterioles and within capillary beds. Metabolic Control of Blood Flow • The build-up of certain chemical signals locally acts as a metabolic control that causes the terminal arterioles to dilate, bringing more blood into the local area. These chemical signals also cause the precapillary sphincters to relax. High 02 Low 02 High CO2 Low CO2 High pH (low acid) Low pH (high acid) Adequate nutrients Lack of nutrients Normal Body Temperature Fever

4. Myogenic Factors • Local physical factors acting on the vascular smooth muscle act as autoregulatory stimuli that affect arterioles. • Increased mean arterial pressure further stretches arteriolar walls, causing their smooth muscle to contract, constricting the arterioles. This myogenic control keeps blood flow in the capillary beds constant in spite of changing mean arterial pressure.

5. Capillary Wall Anatomy • • Several structural characteristics of capillaries aid the transport process: • 1. Capillary endothelial cells have fenestrations, which are pores that may be opened or covered by a very delicate membrane, allowing for passage of fluids and small solutes. • 2. Clefts between cells also allow movement of materials between the blood and tissue cells. • 3. Cytoplasmic vesicles move material across the capillary wall by bulk transport.

6. Passage of substances across the capillary wall 1. Lipid‑soluble substances ‑can cross the membranes of capillary endothelial cells by simple diffusion. ‑include O2 and CO2. 2. Small water‑soluble substances ‑can cross via the water‑filled clefts between the endothelial cells. ‑include water, glucose, and amino acids. ‑Generally, protein molecules are too large to pass freely through the clefts. 3. Large water-soluble substances ‑can cross by pinocytosis. Most solutes move across the capillary wall by diffusion, which is the movement of solutes from an area of higher concentration to lower concentration.

7. Bulk Fluid Flows • Bulk fluid flows, which have little to do with nutrient and gas exchanges, also occur at capillary beds. • Note that fluid leaves the capillaries at the arterial end and returns to the capillary at the venule end. • Bulk fluid flows are important in determining the relative amount of fluid in blood and tissue spaces. • Interstitial fluids, including any plasma proteins which have escaped from the blood stream, enter the lymph capillaries. These leaked fluids and plasma proteins are carried back to the blood stream by the lymphatic system.

8. Filtrationis the process by which fluid is forced through a membrane (capillary wall) because of a difference in pressure on the two sides, i.e. there is net flow of fluid out of the capillary • Absorptionis said to occurwhen there is net flow of fluid into the capillary • The rate of filtration at any point along a capillary depends upon a balance of forces called the Starling Forces: • Capillary hydrostatic pressure (Pc) • Interstitial fluid hydrostatic pressure (Pif) • Plasma colloid osmotic (oncotic) pressure (p ) • Interstitial fluid colloid osmotic (oncotic) pressure (if )

9. • Fluid flows represent the balance between hydrostatic and osmotic pressures acting at capillary beds Hydrostatic Pressure Example • Hydrostatic pressure is the pressure exerted on a fluid on the walls of its container. Capillary Hydrostatic Pressure • In capillaries, hydrostatic pressure is exerted by blood. Thus, capillary hydrostatic pressure (HPc) is equivalent to the blood pressure in the capillaries.

10. Filtration Pressure • Capillary hydrostatic pressure (HPc) is also called filtration pressure because it forces fluid out of the capillaries. Because of friction encountered in the capillaries, the capillary hydrostatic pressure (HPc) is lower at the venule end of the bed. • At arterial end HPc = 35 mm Hg • At venous end HPc = 15 mm Hg Interstitial Fluid Hydrostatic Pressure • In theory, the hydrostatic pressure of the interstitial fluid (HPif) in the tissue spaces opposes the capillary hydrostatic pressure (HPc). • HPif = 1 mm Hg • Normally, however, there is very little fluid in the tissue spaces because fluid is quickly picked up by the lymphatic capillaries, so the hydrostatic pressure of the interstitial fluid (HPif) is very low.

11. Net Hydrostatic Pressure • Net hydrostatic pressure (Net HP) is equal to the capillary hydrostatic pressure (HPc) minus the hydrostatic pressure of the interstitial fluid (HPif). • Net HP = HPc - HPif • Net HP forces fluid out of the capillary. Venule Net Hydrostatic Pressure Arteriole Net Hydrostatic Pressure _14___ = ___15____ --___1____ ___34_ = 35_--__1__ Net HP at arteriole= HPc - HPif end

12. Osmotic Pressure • Osmotic pressure is the "pull" on water exerted by large nondiffusable solutes like proteins. • The higher the solute concentration, the more the solution pulls (or holds) water. • The movement of a solvent, such as water, through a membrane from a more dilute solution to a more concentrated solution is called osmosis.

13. Capillary Osmotic Pressure • Because of its high content of plasma proteins, capillary blood has a relatively high osmotic pressure (OPc) which tends to draw fluid into the capillary. • OPc = 25 mm Hg Interstitial Fluid Osmotic Pressure • Interstitial fluid contains few proteins because very few are small enough to fit through the capillary clefts. Hence, interstitial fluid osmotic pressure is very low, 3 mm of mercury in this example. Like leaked fluids, leaked proteins are gathered up by lymph capillaries. • OPif = 3 mm Hg

14. Net Osmotic Pressure • Net OP pulls fluids into the capillary. • The osmotic pressure in the capillaries of 25 mm Hg minus the osmotic pressure in the interstitial fluid of about 3 mm Hg is equal to the net osmotic pressure of 22 mm Hg. • Net OP = OPc– Opif

15. Net Force • Both net hydrostatic pressure and net osmotic pressure affect fluid flows at the capillary beds. Remember that hydrostatic pressure forces fluid out of the capillary blood and osmotic pressure pulls fluid into the capillary. • The net force determines the direction of fluid flow. It is equal to the net hydrostatic pressure minus the net osmotic pressure. • If net HP is higher than Net OP, fluid leaves the capillary. • If net HP is lower than Net OP, fluid enters the capillary.

16. Leave or Enter at Arterial End? • Net force (determines the direction of flow) Net Force = Net HP - Net OP • The net force at the arterial end of the capillary equals 34 mm Hg minus 22 mm Hg which equals 12 mm Hg. Since the net hydrostatic pressure is greater than the net osmotic pressure, at the arterial end of the capillary, the hydrostatic pressure wins out and fluid leaves the capillary at the arteriole end.

17. Leave or Enter at Venule End? • Net force (determines the direction of flow) = Net HP - Net OP • The venous net force in the capillaries equals 14 mm Hg minus 22 mm Hg which gives us --8 mm Hg.Since the net osmotic pressure is greater than the net hydrostatic pressure at the venule end, the osmotic pressure wins out and the fluid enters the capillary at the venous end of the fluid bed.

18. From the above examples it is evident that the reabsorption pressure causes about 90% of the fluid that has filtered out of the arterial ends of the capillaries to be reabsorbed at the venous end. The remaining 10% is drained by the lymphatic system

19. Lymph and Lymphatic system Fig. 8. The lymphatic system (green) in relation to the cardiovascular system (blue and red). The lymphatic system is a one-way system from interstitial fluid to the cardiovascular system

20. Lymph and Lymphatic system • The lymphatic system functions as an “overflow mechanism” to return to the circulation excess proteins and excess fluid volume from tissue spaces. This keeps interstitial fluid pressure from rising and promotes the turnover of tissue fluid. The normal 24-hour lymph flow is 2-4 L. The amount of protein returned in this fashion in one day is equal to 25-50% of the total circulating plasma proteins • The lymphatic capillaries lie in the interstitial spaces, close to the vascular capillaries

21. Interstitial Fluid Volume • The amount of fluid in the interstitial spaces depends upon: - the capillary pressure - the interstitial fluid pressure - the oncotic pressure - the capillary filtration coefficient - the number of active capillaries - the lymph flow - the total ECF volume - the ratio of precapillary to postcapillary venular resistance (precapillary constriction  filtration pressure, whereas postcapillary constriction  it • Changes of any of the above variables lead to changes in the volume of interstitial fluid

22. Edema is the accumulation of interstitial fluid in abnormally large amount Causes of interstitial fluid volume and edema • Increased filtration pressure - Arteriolar dilation - Venular constriction - Increased venous pressure (heart failure, incompetent valves, venous obstruction, increased total ECF volume, effect of gravity, etc) • Decreased osmotic pressure gradient across capillary - Decreased plasma protein level - Accumulation of osmotically active substances in interstitial space

23. 3.Increased capillary permeability - Substance P - Histamine and related substances - Kinins, etc. 4. Inadequate lymph flow (lymphedema), is combined with protein content - Radical mastectomy (in 10-30% of patients) - In filariasis: parasitic worms migrate into lymphatics and obstruct them (elphantiasis, edema of legs or scrotum)

24. Fig. 12. Filariasis causes the formation of edema and swelling of the afflicted areas. R. Rhoades & R. Pflanzer, Human Physiology