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TSB PHYS 2 The Microcirculation and the Lymphatic System: Capillary Fluid Exchange, Interstitial Fluid, and Lymph Flow

Are arterioles surrounded by a continuous sheet of smooth muscle?
What is the transition between arterioles and capillaries?
Where do you find pre-capillary sphincters?
Close contact to tissue so local environment can control regional blood flows.
Can pre-capillary sphincters recognize O2 levels?
Yes, thats how they know when to open. They can respond to all sorts of things
Understand the structure of the mesenteric capillary bed.
What is the exchange area of a capillary bed?
500 square meters
How many cells are close to a capillary?
Almost every single one is within 20-30 microns of a capillary
What are the pores to the extravascular region?
1) Intracellular clefts

2) Plasmalemmal vesicles
How big are intracellular clefts?
-6-7 nm, which is slightly smaller than albumen but 20x the diameter of H2O.
-represent 1/1000 of total surface area, but most H2O molecules and small solutes diffuse with ease.
What are plasmalemmal vesicles?
Small packets of plasma or ECF that move through the endothelial cells. Of little importance quantitatively.
What is a vesicular channel?
A little coalescence of plasmalemmal vesicles.
What are some other names for intracellular clefts?
Slit pores and tight junctions
What are fenestrae?
Basically windows in the epithelial cell
Understand the structure of tight junctions, gap junctions, close junctions, and pinocytic vesicles.
425 or slide 5

426 or slide 6
What are the 4 pathways of capillary exchange?
1) Transcellular (lipophilic substances)
2) Clefts (6-7 A - hydrophilic substances)
3) Fenestrae (large proteins)
4) Pinocytotic vesicles (large hydrophilic molecules)
What does the term "pore" refer to?
All H2O channels including intercellular spaces (clefts), fused pinocytotic vesicles, and aquaporins.
How do water soluble molecules get through the capillary?
Via pores. although pores are only 1/1000 of surface area, velocity of thermal motion in the clefts is enormous.
What are some common water soluble molecules?
H2O, NaCl, other ions, and glucose.
How much exchange has occurred by the end of a capillary?
80 fold!
Where do lipid soluble molecules cross capillaries?
They diffuse directly thru cell membranes, they're transcellular.
What are some common lipid soluble molecules?
O2, CO2, NO, CO
Understand capillary exchange pathways.
428 or slide 8
What is bulk flow?
Movement of molecules and water across a pore, its like they are being filtered.
What is the diffusion rate determined by?
1) Net movement is down a concentration gradient
2) Area = 2πrl x number of open capillaries
3) Diffusion coefficient - determined by molecule and capillary type
When is exchange flow dependent?
When diffusion is very rapid

430 or slide 10
When is exchange difusion limited?
When large molecules are involved
Understand surface area exchange.
431 or slide 11
What happens to diffusion and bulk flow as pore radius increases?
They both increase

432 or slide 12
At what radius does diffusion become important?
10 A
At what radius does bulk flow become important?
5 A
What is the pore radius in most capillaries?
greater than 10 A
What type of movement predominates for water movement in capillaries?
Bulk flow, the pore width is 20x the diameter of H2O
What is bulk flow filtration determined by?
1) Hydrostatic pressure
2) Osmotic pressure
What does bulk flow filtration depend on?
Relative permeability of muscle capillary pores to different size molecules.
What is bulk filtered fluid important for?
Fluid balance and glucose transport
What is diffusion most important for?
O2 and CO2 exchange
Do tight junctions have a continuous epithelium?
Where do you find tight junctions?
Brain, lungs, and striated muscle
How big are tight junctions?
50-100 A
Do wide clefts have a continuous endothelium?
No, its discontinuous
Where do you find wide clefts?
Liver, spleen, and bone marrow
What are wide clefts often called?
Open fenestrae and closed fenestrae
How big are wide clefts?
5000 A
Diffusion coefficients in specific organ systems are determined by what?
Capillary pores
Describe brain pores.
Very closed (tight junctions) allowing only very small molecules such as H2O, CO2, and O2.
Describe liver pores.
Pores are very open allowing almost all dissolved substances of the plasma including proteins.
Describe intestinal pores.
Intermediate between liver and brain.
Describe kidney glomerular tufts.
Fenestrae (windows/open pores) penetrate through the middle of endothelial cells so large amounts of small molecular and ionic substances filter through the glomeruli without passing through clefts (pores) between the endothelial cells.
Capillary beds control flow and what else?
Describe some characteristics of blood flow in capillaries (4).
1) Blood flow is intermittent

2) Vasomotion causes intermittency - metarterioles and precapillary sphincters contract/relax

3) Tissue oxygen concentration detrmines vasomotion; low O2 relaxes, high O2 contracts sphincters

4) There are billions of individual capillaries so despite intermittent opening and closing we generally consider an average rate of flow, an average capillary pressure, and average rate of transfer of substances
What happens to flow when the heart is contracting?
It basically stops at the peak of systole
How much free fluid is in the interstitial space?
Very little, its usually bound up to proteins and what not
What are the two types of solid structures in the interstitial fluid?
1) Collagen fiber bundles, which provide strong/tensile strength

2) Proteoglycan filaments, which 98% is hyaluronic acid + 2% protein. This equates to a mat of fine filaments often called a "brush pile"
What exactly is a tissue gel?
Proteoglycans and trapped fluid.
How well do things diffuse in a tissue gel compared to free fluid?
95-99% as rapidly
How much free fluid is normally present in the body?
Less than 1%
How much free fluid can be present in edema?
~50% can be free
Where does fluid pressure force fluids?
Into the interstitial spaces
Where does colloid osmotic pressure force fluids?
Into the blood
How does the micropippette method work for measuring capillary pressure?
You poke a pipette into the capillary and measure the pressure. This is also called the direct method.
What is the isogravimetric method?
-its indirect

1) take a piece of the gut and have an arterial supply to the gut.
2) you tie the gut and hang it on a scale.
3) start pressure at 100 mmHg and gradually lower the arterial pressure. As you do so the venous pressure goes up.
4) where venous and arterial pressure meet the scale will not move and it will represent a functional pressure

437 or slide 17
What is the typical functional pressure measured by the isogravimetric method?
17 mmHg
What exactly does the isogravimetric method measure?
The pressure that exactly balances all the forces tending to move fluid into or out of capillaries = normal state
Why does the pressure measured through the isogravimetric method seem to be closer to venous end pressure?
There are many more venous capillaries and they are several times more permeable.
What pressure is typically read for the direct micropipette method?
25 mmHg
Understand the measuring of interstitial fluid pressure.
438 or slide 18
What is the typical pressure of interstitial fluid?
Its negative, around -2 to -6 mmHg
If the interstitial fluid is negatively pressured what would that do to the fluids in the capillaries?
It will suck them out.
What is the starling landis equation do?
Factors that determine rate of fluid movement across the capillaries.
What does a reflection coefficient of 1 mean?
Not permeable
What does a reflection coefficient of 0 equal?
Completely permeable
What is responsible for the osmotic pressures across capillary membranes?
What are two other names for the osmotic pressure that occurs in the capillaries?
Colloid osmotic pressure

Oncotic pressure
What two proteins are primarily responsible for oncotic pressures?
Albumin 80%

Globulins 20%
What is the donnon effect?
Charged particles are attracted to proteins, and water is osmotically attracted to those charged particles which increases the amount of oncotic pressure.
How much does the donnon effect contribute to oncotic pressure?
In plasma ~ 19mmHg of COP is due to dissolved protein; this is increased by about 9 mmHg due to donnon. The grand total COP is 28 mmHg
What forces tend to move fluid outward at the arterial end?
Capillary pressure at the arterial end (30 mmHg)
Negative interstitial free fluid pressure (3 mmHg)
Interstitial fluid COP (8 mmHg)

Total outward force is 41 mmHg
What forces tend to move fluids back into the capillaries at the arterial end?
Plasma colloid osmotic pressure (28 mmHg)
What is the net force on fluids in capillaries in the arterial end?
13 mmHg outward force
What forces tend to move fluids inward at the venous end of a capillary?
Plasma COP (28 mmHg)
What forces tend to move fluids outward at the venous end of a capillary?
Capillary pressure (10 mmHg)
Negative interstitial free fluid pressure (3 mmHg)
Interstitial fluid COP (8 mmHg)

Total outward force of 21 mmHg
What is the net force on fluids in capillaries at the venous end?
There is a net inward force of 7 mmHg
Understand the big picture of forces on fluids in capillaries.
442 or slide 22
What are the mean forces tending to move fluid outward?
Mean capillary pressure (17.3 mmHg)
Negative interstitial free fluid pressure (3 mmHg)
Interstitial fluid COP (8 mmHg)
What are the mean forces tending to move fluid inward?
Plasma COP 28 mmHg
What are the net mean forces in capillaries?
There is a net outward force of .3 mmHg
What would be wrong with having a large difference in outward and inward forces?
You would have a very large amount of lymph flow
What does the lymphatic system carry?
Fluid, proteins, and other large molecules
Most fluid that is filtered in capillaries is reabsorbed where?
The venous ends of the capillaries.
What portion of fluid enters the lymphatic system capillaries?
1/10, ~ 2-4 l/day
What factors influence lymph flow?
1) Elevated capillary pressure
2) Decreased plasma COP
3) Increased interstitial fluid COP
4) Increase permeability of the capillaries
5) Lymph pump (note role of valves)
Where would you see a loss of COP?
When you lose protein
How does the lymph pump work?
-collecting lymphatics have myogenic responses
-contraction of surrounding muscles
-movement of body parts
-pulsations of adjacent arteries
-compression of tissues by external forces
What happens as your intersitial fluid pressure goes from negative to positive?
Your lymph flow goes through the roof, your compliance gets very high

444 or slide 24
Understand the objective questions, they'll be on the test.
See on angel.