Download Microcirculation

Microcirculation
Roland Pittman, Ph.D.
OBJECTIVES:
1. Associate the structure and function of the microcirculation.
2. State the determinants of diffusion of small solutes across the capillary wall.
3. Compare and contrast the permeability of the capillary wall to water-soluble and
lipid-soluble solutes.
4. State the four pressures that determine capillary exchange of water, according to
Starling’s hypothesis of fluid exchange.
5. Quantify the exchange of fluid between the intravascular and interstitial spaces
according to Starling’s hypothesis.
6. Identify the characteristics of the lymphatic system, including the determinants of
lymph flow.
SUGGESTED READING ASSIGNMENT
R. M. Berne, B. M. Koeppen, M. N. Levy, and B. A. Stanton, Physiology, 5th Ed., St.
Louis: Mosby, pp. 368-379, 2004.
L. S. Costanzo, Physiology, 3rd Ed. Philadelphia: W.B. Saunders, pp. 163-166, 2006.
I.
STRUCTURE AND FUNCTION OF THE MICROCIRCULATION
A.
Structure: Types of microvessels
Figure 1. Composite schematic drawing of the microcirculation. The circular structures on
the arteriole and venule represent smooth muscle fibers; branching solid lines represent
sympathetic nerve fibers. The arrows indicate the direction of blood flow.
B. Function
The primary function of the circulatory system is to exchange substances
between blood and tissue. The exchange processes take place in the
microcirculation. The classes of vessels playing a role there are the arterioles
(resistance vessels which regulate flow), capillaries (the primary exchange
vessels) and venules (exchange and collecting vessels). The amount of flow
through the capillaries appears to be regulated to maintain adequate tissue
oxygenation. This regulation appears to be accomplished in part by the
elaboration of tissue metabolites which affect the flow of blood through
precapillary vessels.
II.
TRANSCAPILLARY EXCHANGE OF SOLUTES
A.
Diffusion
This passive mechanism of transport is a rapid and efficient mode of
exchange over the small distances (tens of :m) between the blood supply
(capillaries) and tissue cells.
Figure 2.
Fick's first law describes the net rate of transfer of a substance from a
location of higher concentration to one of lower concentration:
ΔN/Δt = DA (Δc/Δx) = PA Δc
ΔN/Δt = number of moles of substance exchanged per unit time
D = diffusion coefficient for substance through the capillary wall
A = surface area available for diffusion (α number of perfused capillaries)
Δc = concentration difference across capillary wall = c(blood) - c(ISF)
Δx = thickness of the capillary wall (~ 1 :m)
P = permeability of the capillary wall defined as D/Δx
B. Permeability characteristics of the capillary wall
1. The wall is composed of a single layer of endothelial cells about l :m
thick.
2. For lipid soluble substances (e.g., oxygen), the entire wall surface is
available for diffusion.
3. For water soluble substances (e.g., glucose), there are small aqueous
pathways equivalent to cylindrical pores 80 to 90 Å in diameter
through which they may pass. Total pore area is about 1/1000 (i.e.,
0.1%) of the surface area of a capillary.
4. The permeability of the wall to a particular substance depends upon
the relative size of the substance and the pore ("restricted" diffusion).
Figure 3.
C. The amount of a substance which is exchanged can be increased by the
opening of more capillaries - this increases the surface area available for
exchange. Normally only a fraction (about 1/3 to 1/2) of the capillaries in a
given tissue are being perfused at any given moment. During times of
increased demand for nutrients (e.g., heart and muscle tissue during exercise)
more can be opened. Whether a given capillary is open or closed depends on
the contractile state of a region of smooth muscle (probably a terminal
arteriole) located near the entrance to a capillary.
III.
TRANSCAPILLARY EXCHANGE OF WATER
A.
The processes whereby water passes back and forth across the capillary
wall are called filtration and absorption. The flow of water depends upon
the relative magnitude of hydraulic and osmotic pressures across the
capillary wall.
B.
Fluid compartments of "average" adult (70 kg person)
1.
Extracellular space (19 L)
a.
b.
2.
3.
Plasma space (3 L)
Interstitial space (16 L)
Intracellular space (23 L)
Compartmental exchanges
Figure 4.
B. Why doesn't all the water leak out of the capillaries?
1. The effective "diameter" of a water molecule is about 2 Å, whereas the
effective "diameter" of the transendothelial pathways is about 80 Å.
2. The mean hydraulic pressure inside a capillary is about 25 mmHg
higher than that outside the capillary.
Figure 5.
In this diagram Ra and Rv represent the precapillary and postcapillary
resistances to blood flow, respectively. Since Rv/Ra is about 1/5, a given
change in Pv has much more impact on Pc than the same change in Pa.
3. Since the facts noted above in items 1 and 2 suggest that water should
leave the vascular system, why in reality is there no large net flow of
water from the vascular space to the interstitial space?
4. Proteins in plasma (primarily albumin and globulins) are too large to
cross the capillary wall which for them behaves like a semipermeable
membrane (i.e., the reflection coefficient, σ, is near 1) separating blood
from interstitial fluid. Thus, there is a net osmotic pressure established
between plasma and interstitial fluid and this tends to prevent the
leakage of water from the vascular compartment.
5. Note that the osmotic pressure of either plasma or interstitial fluid can
be written as the sum of three terms:
Π(total) = Π(electrolytes) + Π(nonelectrolytes) + Π(proteins)
Although small electrolytes and nonelectrolytes are osmotically active
particles, they can readily pass across the capillary wall (σ ≈ 0) and
their concentrations are approximately equal on both sides of the
capillary. Thus, no net osmotic pressure difference is created by these
substances and only the plasma proteins are responsible for the
observed net osmotic pressure. This quantity is generally referred to as
the colloid osmotic pressure or oncotic pressure.
6. Starling's hypothesis (1896) combines all this information and states
that in the steady state there is a delicate balance between hydraulic
and osmotic pressures which leads to little or no net flow of water.
Algebraically this is expressed by the following equation:
F = K {(Pc - PISF) - (Πpl -ΠISF)} = K {ΔP-ΔΠ}
F = rate of fluid flow across the capillary wall
K = capillary filtration coefficient, or hydraulic conductance
(α permeability to water x perfused capillary surface area)
Pc = capillary hydraulic pressure (32 mmHg to 15 mm Hg).
PISF = hydraulic pressure in ISF (0 mmHg)
Πpl = osmotic pressure due to plasma proteins (28 mmHg)
ΠISF = osmotic pressure due to proteins in ISF (5 mmHg)
If F > 0, water is filtered from blood into ISF.
If F < 0, water is absorbed into blood from ISF.
Figure 6. Schematic representation of the factors responsible for filtration and absorption
across the capillary wall and the formation of the lymph.
IV.
THE LYMPHATIC SYSTEM
A.
In 24 hours more fluid is filtered than is reabsorbed; 20 L/day are filtered
and 16 L/day are reabsorbed by the capillaries. The overflow is carried
back to the vascular system (via the superior vena cava) by the lymphatic
circulation.
B.
Characteristics of the lymphatic system
1.
2.
3.
C.
There are a large number of small vessels whose ends are closed.
Flap valves (similar to those in veins) provide for unidirectional
flow back to the cardiovascular system.
The smallest (terminal) vessels are very permeable, even to
proteins which occasionally leak from systemic capillaries.
Lymph flow is determined by:
1.
2.
Interstitial fluid pressure (↑ PISF → ↑ Qlymph)
The lymphatic "pump" (moves fluid from the extremities to the
central circulation)
a.
b.
c.
One-way flap valves (produce unidirectional flow)
Skeletal muscle contraction (periodically squeezes fluid in
lymphatics)
Tissue compression (squeezes fluid in lymphatics)
d.
Periodic (~ 5/min) lymphatic smooth muscle contraction in
response to stretch
D.
Control of ISF protein concentration is one of the most important
functions of the lymphatic system.
E.
Edema formation: If more net fluid is filtered than can be handled by the
lymphatics, the volume of interstitial fluid increases. This fluid
accumulation is called edema. This circumstance is important clinically
since solute exchange (e.g., oxygen) decreases due to the increased
diffusion distances produced when the accumulated fluid pushes the
capillaries, tethered to the interstitial matrix, away from each other.
STUDY QUESTIONS
1. Which of the following will produce increased capillary hydraulic pressure?
1.
2.
3.
4.
Increased venous pressure.
Decreased venous resistance.
Increased arterial pressure.
Increased arterial resistance.
ANSWER: B (1 & 3)
You need to remember the four factors that determine capillary hydraulic pressure:
arterial and venous pressures and resistances. You can determine the effect of each
one either by the equation from class or by thinking intuitively about what would
happen as a consequence of each change.
2. Which of the following statements is/are true about capillary exchange of solutes?
1. Passage of water-soluble substances is generally restricted to small channels
between adjacent endothelial cells.
2. The aqueous channels that allow the passage of substances like glucose
comprise a surface area of about 10% of the capillary wall.
3. Lipid soluble substances can generally pass through the entire capillary wall.
4. Proteins generally pass across the capillary wall by active transport.
ANSWER: B (1 & 3)
You need to remember that small water-soluble molecules are restricted to pass
through aqueous channels between adjacent endothelial cells that make up about
0.1 % of the surface area of the capillary wall. Lipid soluble substances have access
to the entire capillary wall and proteins are generally restricted to the intravascular
space.
3. Which of the following will produce increased lymph flow?
A.
B.
C.
D.
E.
Decreased venous pressure.
Decreased venous resistance.
Decreased plasma protein concentration.
Increased arterial resistance.
Decreased interstitial fluid pressure.
ANSWER: C
Decreased venous pressure and decreased venous resistance will both result in lower
capillary hydraulic pressure, and hence less filtration and lower lymph flow.
Decreased plasma protein concentration will produce lower osmotic pressure in the
plasma and will produce more filtration and hence increased lymph flow. Increased
arterial resistance will lower capillary hydraulic pressure and lead to less filtration
and lymph flow. Decreased interstitial fluid pressure (the driving force for fluid
entry into the lymphatics) will lead to decreased lymph flow.
4. Consider a typical capillary in which the following values are observed:
hydraulic pressure at the beginning of a
capillary
hydraulic pressure at the end of a capillary
interstitial hydraulic pressure
interstitial colloid osmotic pressure
= 30 mm Hg
= 15 mm Hg
= 3 mm Hg
= 1 mm Hg.
For what value of plasma colloid osmotic pressure will there be absorption of fluid all
along the capillary?
A.
B.
C.
D.
E.
20 mm Hg.
22 mm Hg.
24 mm Hg.
26 mm Hg.
28 mm Hg.
ANSWER: E
In order to have fluid absorption all along the capillary, the net pressure at all
points along the capillary must be < 0. The pertinent combination of pressures is
[(PC – PISF) – (ΠPL - ΠISF)]. (PC – PISF) represents the net filtration pressure due to
the hydraulic pressures inside and outside the capillary, respectively. (ΠPL - ΠISF)
represents the net absorption pressure due to the protein osmotic (oncotic)
pressures inside and outside the capillary, respectively. To ensure that there will be
absorption all along the capillary, it is necessary to make sure that the net pressure
at the entrance to the capillary (arterial end) is < 0.
Plugging in the numbers, we require that (30 – 3) – (ΠPL – 1) = 27 + 1 - ΠPL < 0. So,
if ΠPL > 28, there will be absorption all along the capillary.