Chapter 16 Microcirculation and Capillary Function

• The microcirculation transports nutrients to tissues and removes cell excreta
• Arterioles control blood flow to each tissue based on local conditions and individual needs
• Capillary walls are thin, made of permeable endothelial cells for easy exchange between tissues and blood
• Peripheral circulation has about 10 billion capillaries, totaling 500-700 square meters
• Functional cells are typically within 20-30 micrometers of a capillary

Microcirculation and Capillary Structure

• Microcirculation is organized based on specific organ needs
• Nutrient arteries branch multiple times into arterioles (10-15 micrometers diameter)
• Arterioles branch further, supplying blood to capillaries (5-9 micrometers diameter)
• Arterioles are muscular allowing diameter changes
• Metarterioles (terminal arterioles) have intermittent smooth muscle fibers
• Precapillary sphincters control entrance to capillaries
• Venules are larger and have weaker muscle coats than arterioles but can still contract

Capillary Wall Structure

• Capillary walls consist of a single endothelial cell layer
• Walls are surrounded by a thin basement membrane
• Total thickness is about 0.5 micrometers
• Internal diameter is 4-9 micrometers, allowing red and other blood cells to squeeze through

Pores in Capillary Membrane

• Intercellular clefts connect capillary interior to exterior
• Clefts are interrupted by protein attachments, allowing fluid percolation
• Cleft width is about 6-7 nanometers, slightly smaller than albumin
• Intercellular clefts account for 1/1000 of the capillary wall's surface area
• Rapid thermal motion of water molecules and small solutes facilitates diffusion through clefts

Plasmalemmal Vesicles (Caveolae)

• Minute vesicles present in endothelial cells contain caveolins, cholesterol, and sphingolipids
• Play a role in endocytosis and macromolecule transcytosis
• Appear to imbibe small packets of plasma or extracellular fluid containing plasma proteins
• Move slowly through the endothelial cell and may coalesce to form vesicular channels

Special Pores in Organ Capillaries

• Brain capillaries have tight junctions, allowing only water, oxygen, and carbon dioxide to pass
• Liver capillaries have wide-open clefts for almost all plasma substances to pass
• Gastrointestinal capillaries have pores midway in size between muscles and liver
• Kidney glomerular capillaries have fenestrae that allow tremendous amounts of small molecules and ions to filter through

Blood Flow and Vasomotion in Capillaries

• Blood flow through capillaries is intermittent due to vasomotion
• Vasomotion: intermittent contraction of metarterioles, precapillary sphincters, and small arterioles
• Oxygen concentration in tissues is the most important factor affecting vasomotion
• Low oxygen causes more frequent and longer flow periods, increasing oxygen supply
• Overall function of capillaries is averaged due to a large number of the vessels
• Average blood flow rate, capillary pressure, and substance transfer occur

Exchange of Substances Between Blood and Interstitial Fluid

• Tremendous numbers of water molecules and dissolved particles diffuse back and forth through the capillary wall
• Electrolytes, nutrients, and waste products of metabolism diffuse easily
• Proteins do not readily pass through the capillary membrane

Diffusion Through the Capillary Membrane

• Lipid-soluble substances diffuse directly through cell membranes
• Lipid-soluble substances (oxygen and carbon dioxide) transport faster than lipid-insoluble substances
• Water-soluble substances diffuse through intercellular pores
• Water, sodium, chloride, and glucose diffuse through these pores
• The rate of water molecule diffusion is 80 times greater than plasma flow rate

Molecular Size and Passage Through Pores

• Capillary intercellular cleft pores are 6-7 nanometers wide
• Plasma protein molecules have slightly greater diameters than the pores
• Permeability varies according to molecular diameters
• Permeability is 0.6 times less for glucose molecules than water molecules
• Permeability is slight for albumin molecules
• Capillary permeability varies in different tissues, some tissues require greater degrees of capillary permeability than other tissues

Concentration Differences and Diffusion

• Net movement is determined by the difference between the concentrations on the two sides of the capillary membrane
• Concentration of oxygen in the interstitial fluid outside the capillary is no more than a few percent less than its concentration in the plasma
• Diffusion rates of nutritionally important substances are so great that only slight concentration differences cause adequate transport

Interstitium and Interstitial Fluid

• Interstitium: spaces between cells, about one sixth of the total body volume
• Interstitial fluid is the fluid in these spaces
• Contains two major solid structures: collagen fiber bundles and proteoglycan filaments
• Collagen fiber bundles are strong and provide tensional strength
• Proteoglycan filaments are thin, coiled molecules composed of hyaluronic acid and protein
• Fluid in the interstitium is derived from filtration and diffusion from the capillaries
• The interstitial fluid contains almost the same constituents as plasma except for lower concentrations of proteins

Gel in the Interstitium

• Fluid is entrapped in the minute spaces among the proteoglycan filaments
• Proteoglycan filaments and entrapped fluid have the characteristics of a gel, tissue gel
• Fluid mainly diffuses through the gel, moving molecule by molecule through kinetic thermal motion

Free Fluid in the Interstitium

• Most fluid in the interstitium is entrapped, small rivulets of free fluid and small free fluid vesicles are also present
• Dye injected show it coursing along the surfaces of collagen fibers or surfaces of cells
• Most normal tissues exhibit a slight amount of free fluid
• This expands tremendously during edema

Fluid Filtration Across Capillaries

• Hydrostatic pressure in capillaries forces fluid and dissolved substances into interstitial spaces
• Osmotic pressure from plasma proteins (colloid osmotic pressure) causes fluid movement into the blood
• Prevents significant fluid loss from blood

Starling Forces

• Capillary hydrostatic pressure (Pc) forces fluid outward
• Interstitial fluid hydrostatic pressure (Pif) forces fluid inward when positive, outward when negative
• Capillary plasma colloid osmotic pressure (Πp) causes osmosis of fluid inward
• Interstitial fluid colloid osmotic pressure (Πif) causes osmosis of fluid outward

Net Filtration Pressure

• Positive net filtration pressure leads to net fluid filtration across capillaries
• Negative balance leads to net fluid absorption from interstitial spaces to capillaries
• Formula: NFP = Pc – Pif – Пр+ Пif
• Rate of fluid filtration in a tissue is also determined by the number and size of the pores in each capillary and the number of capillaries which blood is flowing
• Capillary filtration coefficient (Kf) is a measure of capillary membrane capacity to filter water for a given NPF
• Filtration = Kf x NFP

Capillary Hydrostatic Pressure Measurement

• Direct micropipette cannulation reads 25 mm Hg
• Indirect functional measurement averages 17 mm Hg

Micropipette Method

• Measured 30-40 mm Hg in arterial ends, 10-15 mm Hg in venous ends, and 25 mm Hg in the middle
• Glomerular capillaries read 60 mm Hg
• Peritubular capillaries of the kidneys read 13 mm Hg

Interstitial Fluid Hydrostatic Pressure

• Measured with a micropipette, implanted perforated capsules, and a cotton wick inserted into the tissue
• Measurement varies in the method used and the tissue in which the pressure is measured

Interstitial Free Fluid Pressure Measurement

• Loose tissues measure -2 to +2 mm Hg but, on average, slightly less than atmospheric pressure

Implanted Perforated Hollow Capsules

• Measured at -6 mm Hg in normal loose subcutaneous tissue using 2-centimeter diameter capsules
• Capsules that are smaller capsule values are not greatly different from the -2 mm Hg measured by the micropipette

Interstitial Fluid Pressures in Tightly Encased Tissues

• Interstitial fluid pressures are positive in encased tissues
• Still less than the pressures exerted outside of the tissues by their encasements
• Intrepleural space: -8 mm Hg
• Joint synvoial spaces: -4 to -6 mm Hg
• Epidural space: -4 to -6 mm Hg
• Averages about -3 mm Hg in loose subcutaneous tissue

Pumping By The Lymphatic System

• Removes excess fluid, excess protein molecules, debris, and other matter from the tissue spaces
• Creates a slight negative pressure

Plasma Colloid Osmotic Pressure

• Proteins exert osmotic pressure because they don't pass through capillary pores

Normal Values for Plasma Colloid Osmotic Pressure

• Plasma averages about 28 mm Hg
• 19 mm is caused by molecular effects of the dissolved pressure
• 9 mm is caused by the Donnan effect
• Albumin takes up 21.8 mm Hg, globulins take up 6.0 mm Hg, and fibrinogen takes up 0.2 mm Hg

Interstitial Fluid Colloid Osmotic Pressure

• Averages about 8 mm Hg

Fluid Volume Exchange

• Capillary pressure is greater at the arterial ends
• Fluid filters out of the capillaries at their arterial ends
• The capillaries reabsorb fluid at their venous ends

Filtration at the Arterial End of the Capillary

• Capillary hydrostatic pressure is 30 mm Hg
• Negative interstitial fluid hydrostatic pressure is 3 mm Hg
• Interstitial fluid colloid osmotic pressure is 8 mm Hg
• Total outward force is 41 mm Hg
• Plasma colloid osmotic pressure is 28 mm Hg
• Total inward force is 28 mm Hg
• Net outward force at arterial end is 13 mm Hg

Reabsorption at the Venous End of the Capillary

• Plasma colloid osmotic pressure is 28 mm Hg
• Total inward force is 28 mm Hg
• Capillary hydrostatic pressure is 10 mm Hg
• Negative interstitial fluid hydrostatic pressure is 3 mm Hg
• Interstitial fluid colloid osmotic pressure is 8 mm Hg
• Total outward force is 21 mm Hg
• Net inward force is 7 mm Hg

Starling Equilibrium for Capillary Exchange

• In normal conditions, most capillaries are in near-equilibrium
• fluid filtering outward from arterial ends equals fluid returned to the circulation by absorption
• the slight disequilibrium offsets the fluid eventually returned to the circulation by way of the lymphatics
• average the pressures in the arterial and venous capillaries to calculate mean the functional capillary pressure for the length of the capillary

Capillary Filtration Coefficient

• Causes a net imbalance of forces at the capillary membranes of 0.3 mm Hg
• This causes a net fluid filtration in the entire body of 2 ml/min
• The whole-body capillary filtration coefficient is also expressed as a rate filtration per minute per mm Hg per 100 grams of tissue
• Tissues are permeable and that protein concentration differs
• This permeability differs with brain and muscle, and subcutaneous tissue
• This permeability also differs between intestines, livers

Lymphatic System

• Accessory route for fluid to flow from the interstitial spaces into the blood
• They have proteins
• Particulate matter can be transported away from the tissue spaces
• The return of proteins is essential

Lymph channels

• Have special lymph channels that drain excess fluid directly
• The superficial portions include the skin, central nervous system, endomysium of tissues
• All lymph empties into the Thoracic duct
• Lymph goes to the left side of the head, the left arm, and other areas of the chest

Terminal Lymphatic Capillaries and Their Permeability

• Returning fluid by way of vascular systems is extremely significant to maintain high energy
• Substantive molecular weight such as proteins may not be absorbed by any way other than this
• One-tenth of the fluid enters rather than goes through venous capillaries
• The total lymph is 2 to 3 L per day

Formation of Lymph

• Lymph is derived in the initial stages as the fluid from other flows
• This is a great process from this as some interstitial fluid.

The Protein

• Protein concentration averages about 2 g/dl.
• Protein in liver and intestine goes as far as 6 g/dl.
• All lymphatic systems
• A single nutrient system
• Amount of lymph goes through the body ( 100hr)
• Only large portions have little amount of pressure

Lymphatic Vessels

• Valves exist in all tissue channels
• The smooth muscle contracts
• Each segment of the vessel has a separate pump
• Large vessels have 50 to 100 mm Hg
• The flow causes external compression

Factors of Flow

• Surrounded Skelton muscles
• Movement of the body
• Puslations
• Vessels also have contraction

Summary

• Product
• Pressure determines flow by the other side
• Insterstial Fluids

Lymphatic Systems

• Excess proteins are contained
• Fluid balance
• Concentrations
• It maintains the homeostasis
• A lot of protein can leak

Significance of Negative Pressure

• Tissues have high connections
• Fibers provide
• If you lose fibers you loose pressure
• It can have serious issues.