Capillaries Capillaries lack smooth muscle, but contraction/relaxation of circular smooth muscle in upstream metarterioles and precapillary sphincters determine the volume of blood each capillary receives.

Capillaries: Exchange Plasma and cells exchange materials across thin capillary wall Capillary density is related to metabolic activity of cells Capillaries have the thinnest walls Single layer of flattened endothelial cells Supported by basal lamina 25,000 miles of them in adult

Capillary cross-section Capillary walls are a single endothelial cell in thickness. The capillary is the primary point exchange between the blood and the interstitial fluid (ISF). Intercellular clefts assist the exchange. Graphic is confusing since ALL of lumen is red (but plasma is clear)– accompanying photo shows an RBC.

Two Types of Capillaries Figure 15-16a

Two Types of Capillaries Figure 15-16b

Velocity of Blood Flow Velocity of flow depends on total cross-sectional area of the vessels Figure 15-17

Blood velocity example When a continuous stream moves thru consecutive tubes, the velocity of flow decreases as the sum of the cross-sectional areas of the tubes increases. Six balls in per minute mandates six balls out per minute. Therefore, the velocity of the balls in the smaller tubes is slower.

Slow blood velocity helps exchange There are many, many capillaries, each with slow-moving blood in it, resulting in adequate time and surface area for exchange between the capillary blood and the ISF.

Capillary Exchange Exchange by paracellular pathway (except in brain) or transendothelial transport (ie ions, glucose) Small dissolved solutes and gasses by diffusion is determined by concentration gradient (ie O2, CO2) Large solutes and proteins by vesicular transport In most capillaries, large proteins are transported by transcytosis--except liver with fenestrated capillaries

Capillary Exchange Bulk flow Mass movement as result of hydrostatic or osmotic pressure gradients Absorption: fluid movement into capillaries Net absorption at venous end Filtration: fluid movement out of capillaries Caused by hydrostatic pressure Net filtration at arterial end

Diffusion A substance diffuses across a capillary wall only i. if the capillary wall is permeable to the substance and there is a concentration gradient for the substance. Stated in an equation this is Fick's law: J = -PS(Co - Ci) where J = quantity of substance moved per unit time P = capillary permeability of the substance S = capillary surface area Ci = concentration inside capillary Co = concentration outside capillary Proteins are prevented from crossing the walls of most capillaries. i. Most of the large protein in the blood is serum albumin. ii. Permeability of some capillary walls to serum albumin is very low (for example, in muscle). iii. Permeability of some capillary walls to serum albumin is higher (for example, in liver). Permeability of all capillary walls to water and gasses is extremely high. Some capillary beds are extremely tight to solutes, even small ones. (For example, the capillaries in the brain allow very few solutes to diffuse out of the capillary and into the extracellular space. Any material, other than gasses, that is exchanged across the capillary walls must be carried by protein transporter molecules that recognize specific solutes, such as glucose. This is called the blood-brain barrier.)

Bulk Flow In addition to solute movement by diffusion, the likelihood that material will move across the capillary wall and the direction in which it will move can be influenced by the hydrostatic pressure difference between the inside and the outside of a capillary affects . a. Solutes in the blood that are small enough to get through the pores in capillary walls can be carried across the walls along with bulk water flow driven by hydrostatic and osmotic gradients. This mechanism operates in addition to diffusion. b. In most cases, the hydrostatic pressure outside the capillary is essentially 0 mm Hg. c. Therefore, normally all along capillaries there is a hydrostatic pressure gradient pushing fluid and dissolved materials out into the tissues. The Starling hypothesis: The net direction in which fluid moves across the walls of capillaries depends upon a balance between the net hydrostatic pressure across the capillary wall and the net osmotic pressure across the capillary wall. 1. The net hydrostatic pressure depends upon the blood pressure within the capillary and upon the pressure within the tissue surrounding the capillary (which normally is very low but which can become elevated in abnormal conditions). 2. Factors that contribute to the osmotic pressure (π) a. π =  RT (Ci - Co) where  = the reflection coefficient (depends on the % of solute that is prevented from crossing the capillary wall; 0 = all crosses, 1 = none crosses) R = the gas constant T = absolute temperature Ci = solute (albumin) concentration inside the capillary Co = solute (albumin) concentration outside the capillary b. If you need to review the concepts of osmotic pressure and osmosis, please do so. You must understand osmosis to do well in the next part of the course. Briefly, given two compartments containing solutions of different solute concentration and separated by a semi-permeable membrane that allows only solvent through, π is the pressure required to precisely counteract the tendency for solvent to move into the compartment with higher solute concentration. In reality, if a little of the solute can cross the membrane, an osmotic pressure will still develop.  reflects how impermeable the membrane is to the solute.) c. When the osmotic pressure depends on the concentrations of albumin and other large proteins, as it does across the capillary wall, this osmotic pressure is called the oncotic pressure.

Bulk Flow Total fluid transferred = k[(Pcap + πint) - (Pint + πcap)] where k = the filtration constant for the capillary wall Pcap = hydrostatic pressure inside the capillary Pint = hydrostatic pressure of the interstitial fluid πcap = osmotic pressure of the plasma (normally it's largely due to serum albumin) πint = osmotic pressure of interstitial fluid a. Notice that Pcap and int are the factors tending to move fluid out of the capillary; Pint and cap are the factors tending to move fluid into the capillary. b. Rearranging this equation algebraically allows the pressures along capillaries to be represented graphically (see accompanying graph). You should be able to use the equation in both forms. c. The classical model for fluid movement across the walls of a capillary shows filtration out of the capillary at the arterial end and reabsorption of fluid from the extracellular space at the venous end. i. Real capillaries vary greatly. ii. In some organs (kidney), there normally is a net filtration out of a capillary all along its length, due to a very high hydrostatic pressure. iii. In other organs (gut), hydrostatic pressure is low and there normally is net reabsorption into a capillary all along its length. d. In typical capillaries the combination of filtration at the arterial end and reabsorption at the venous end facilitates rapid mixing between the plasma and the extracellular fluid.

Filtration/Absorption Movement of fluid and solutes out of the blood is called filtration. Movement of fluid and solutes into the blood is called absorption. Absorption

Fluid Exchange at a Capillary Hydrostatic pressure and osmotic pressure regulate bulk flow Figure 15-18a

Bulk Flow Factors affecting the total amount of exchange across a capillary wall: 1. Once again: In most capillaries diffusion is the most important process leading to the exchange of materials. 2. In some capillaries, filtration also contributes to the exchange of some solutes. 3. The percentage of each solute that gets exchanged across capillary walls depends upon both the permeability of the capillary for the solute and on the amount of blood that enters the capillary. a. The structure of the capillary walls determines how permeable a capillary is. i. Most capillaries have small spaces between the endothelial cells, allowing some filtration. ii. Some capillaries (for example, in the gut walls and in the kidneys) have large spaces between the endothelial cells, allowing much more filtration. iii. Some capillaries (for example, in the brain and spinal cord) have no spaces between the endothelial cells, and all material must move through the cells in order to reach the interstitial fluid. This situation is called the blood-brain barrier. b. Transfer of solutes to which the capillary walls are highly permeable, is flow-limited. These solutes come into equilibrium across the capillary wall as soon as they enter the capillary, so the amount transferred across the wall depends largely upon how much material is brought to the capillary by the blood. c. Transfer of solutes to which the capillary walls are only slightly permeable is diffusion-limited; i.e., these solutes may never come into equilibrium across the capillary wall before the blood leaves the capillary and enters a venule. The amount transferred across the capillary wall is limited by the low permeability of the capillary wall; it us relatively unimportant how fast the blood delivers the material to the capillary. 4. Fluid that is filtered out of the capillaries and not reabsorbed eventually finds its way into blind-ended, filmy vessels, the lymphatics, that form a network leading back to the thoracic duct. The thoracic duct empties into the vena cava.

Lymphatic System Returning fluid and proteins to circulatory system Picking up fat absorbed and transferring it to circulatory system Serving as filter for pathogens

Fluid Exchange at a Capillary Figure 15-18b

Lymphatic System Figure 15-19

Edema Two causes Inadequate drainage of lymph Filtration far greater than absorption Disruption of balance between filtration and absorption Increase in hydrostatic pressure Decrease in plasma protein concentration (protein malnutrition produces ascites) Increase in interstitial proteins