01/26/2018

7:30-10:00 The Microcirculation and the Lymphatic System

MWF Physiology
Anatomy Bldg Richie Gaye Limbungan, M.D.


OUTLINE

I. Introduction
Microcirculation and Capillary System
II. Structure of the
III. Flow of Blood in the Capillaries – Vasomotion
IV. Exchange of Water, Nutrients and other Substances
V. Interstitium and Interstitial Fluid
VI. Hydrostatic and Colloid Osmotic Pressure
VII. Capillary Filtration Coefficient
VIII. Lymphatic System

INTRODUCTION


Purposeful Functions of the Microcirculation

• Transport of nutrients to the tissues
• Removal of cell excreta of metabolism
• Capillaries: Basic structure of microcirculation
Structure of the Capillary Wall


STRUCTURE OF THE MICROCIRCULATION • Composed of a unicellular layer of Endothelial cells
AND CAPILLARY SYSTEM • Surrounded by a thin basement membrane outside the capillary
• Total thickness: 0.5 micrometer
• Internal diameter: 4 to 9 micrometers
Organization of Microcirculation
o Barely large enough for RBC and other blood cells to
squeeze through
1. Nutrient artery branches out six to eight times
2. Arteries become small enough to become Arterioles
Pores in the Capillary Membrane
3. Arterioles branch out 2 to 5 times becoming Metarterioles

4. Capillaries originate from Metarterioles
Intercellular Cleft:
• Thin slit, curving channels between two adjacent endothelial cells
Arterioles:
• Each is interrupted periodically by short ridges of protein
• Highly muscular
attachments
• 10-15 micrometers in diameter
o The protein attachments hold the endothelial cells together
• Fluid can percolate freely
Metarterioles:
• Has uniform spacing of 6 to 7 nanometers (60 to 70 angstroms)
• Terminal arterioles
o Slightly smaller than the diameter of an albumin
• No continuous muscular coat

Precapillary Sphincter:
• Junction between the metarteriole and the capillary
• Opens and closes the entrance of the capillary

NOTE: The Metarterioles and the Precapillary Sphincters are in

close contact with the tissues. Therefore, the local conditions of the
tissues can cause a direct effect on the vessels to control local
blood flow in each small tissue area

Venules:
• Larger than arterioles
• Much weaker muscular coat compared to the arteries

NOTE: Pressure in venules is much weaker than the capillaries

giving the venules ability to contract despite a weak muscle

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 Plasmalemmal Vesicles:
• Caveolae (small caves)
• From Oligomers of proteins called Caveolins
o Associated with Cholesterol and Sphingolipids
• Believed to play a role in Endocytosis
o Process by which the cell engulfs material from outside the cell
• Transcytosis of macromolecules across the interior of the
endothelial cells
• Caveolae at the surface appear to imbibe small packets of plasma
or extracellular fluid that contain plasma proteins
• Some vesicles may coalesce to form vesicular channels all the
way through the endothelial cell
EXCHANGE OF WATER, NUTRIENTS, AND OTHER SUBSTANCES
AND INSTERSITIAL FLUID
Diffusion through the Capillary Membrane
Diffusion:
• The most important means by which substances are transferred
between the plasma and the interstitial fluid
• Results from thermal motion of the water molecules and dissolved
substances in the fluid

Special Types of Pores in Certain Organs

Brain:
• Mainly tight junctions that only allows extremely small molecules
(water, oxygen, carbon dioxide)

Liver:
• Opposite type of pore compared to the brain
• The clefts are wide open
o Almost all dissolved substances pass through

Gastrointestinal Capillary Membrane:

• Midway in size of the liver and muscle

Glomerular Capillaries of the Kidneys:
• Fenestraes penetrate all to the way to the middle of the
endothelial cell
o Small molecules and Ionic substances can filter through the
glomeruli without passing through the clefts
FLOW OF BLOOD IN THE CAPILLARIES – VASOMOTION o Carbon Dioxide
Vasomotion:
• Intermittent contraction of the metarterioles and precapillary
sphincters
• Blood does not usually flow continuously to the capillaries
• Blood flows intermittently in the capillaries, turning on and off
every few seconds or minutes
Regulation of Vasomotion
Oxygen:
• Most important factor affecting the degree of opening and closing
of the metarterioles and precapillary sphincters
NOTE: When the rate of oxygen usage by the tissue is great so that
tissue oxygen concentration decreases below normal, the
intermittent periods of capillary blood flow occur more often,
and the duration of each period of flow lasts longer, allowing the
capillary blood to carry increased quantities of oxygen to the
tissues
Lipid-Soluble Substances Diffuse Directly through the Cell
Membranes of the Capillary Endothelium
• Any lipid soluble substance can diffuse directly through the cell
membrane without having to go through the pores
o Oxgen
• Rates of transport are faster that the rates of lipid-insoluble
substances (e.g. Sodium and Glucose)
Water-Soluble Substances Diffuse through Intercellular Pores in
the Capillary Membrane
• The velocity of thermal molecular motion in the clefts is so great
that it allows diffusion of water and water-soluble substances
through the cleft pores
• Water molecules, Sodium Ions, Chloride Ions and Glucose
Effect of Molecular Size on Passage through the Pores
• The width of the capillary intercellular cleft-pores is about 20
times the diameter of the water molecule
o Water is the smallest molecule that normally passes through the
capillary pores
• The permeability of the capillary pores for different substances
varies according to their molecular diameters
NOTE: The capillaries of various tissues have extreme differences
in their permeabilities

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Effect of Concentration Difference on Net Rate Diffusion through interstitium
the Capillary Membrane
• The net rate of diffusion of a substance is directly proportional
to the concentration difference of the substance between the
two sides of the membrane.
NET RATE OF DIFFUSION ≈ CONCENTRATION DIFFERENCE
• The greater the difference between the concentrations of any
given substance on the two sides of the capillary membrane, the
greater the net movement of the substance in one direction
through the membrane.
INSTERSTITIUM AND INTERSTITIAL FLUID • Tends to force fluid and its dissolved substances through the
Interstitium: Spaces between the cells
Interstitial Fluid: Fluid in between the cells
Structure of the Interstitium spaces into the blood
• Collagen Fiber Bundles
o Extend long distances in the interstitium
o Extremely strong
o Provide most of the tensional strength of the tissues
• Proteoglycan Filaments
o Extremely thin coiled or twisted molecules
o Composed of 98% uronic acid; 2% protein
o Cannot be seen with a light microscope
o Form a mat of very fine reticular filaments, “brush pile”
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“Gel” in the Interstitium
• Fluid is derived by filtration and diffusion from the capillaries
• Contains almost the same constituents as the plasma except for
much lower concentration of proteins
o Proteins do not easily pass through the pores of the capillaries
• Entrapped mainly in the minute spaces among the proteoglycan
filaments
• Also called Tissue Gel
• Difficult for the fluid to flow easily through the tissue gel
o Due to large number of proteoglycan filaments
• Fluid mainly diffuses through the gel
o Moves molecules one after another by kinetic energy, thermal
motion
• Diffusion through the gel allows rapid transport through the
“Free” Fluid in the Interstitium
• Fluid that is free of the proteoglycan molecules
• Present in small rivulets or small vesicles
• Normal amount present in tissues is usually 1%
• During Edema: small packets and rivulets expand until half or
more of the edema fluid becomes freely flowing independent of
the proteoglycan filaments
HYDROSTATIC AND COLLOID OSMOTIC PRESSURE
Hydrostatic Pressure:
capillary pores into the interstitial spaces
Osmotic Pressure:
• Colloid osmotic pressure
• Tends to cause fluid movement by osmosis from the interstitial
• Prevents significant loss of fluid volume from the blood into the
interstitial spaces
Lymphatic System:
• Returns to the circulation the small amounts of excess protein and
fluid that leak from the blood into the interstitial spaces
Hydrostatic and Colloid Osmotic Forces Determine Fluid
Movement through the Capillary Membrane
Starling Forces:
• Four primary forces that determine the direction of fluid
movement
• Ernest Starling
1. Capillary Pressure (Pc): tends to force fluid outward
2. Intersitial Fluid Pressure (Pif): tends to force fluid inward
•Inward if positive
•Outward if negative
3. Capillary Plasma Colloid Osmotic Pressure (πp): tends to
cause osmosis of fluid inward
4. Interstitial Fluid Colloid Osmotic Pressure (πif): tends to
cause osmosis of fluid outward
 NOTE: If the Net Filtration Pressure (sum of all forces) is positive,
there will be net fluid filtration across the capillaries. If it is negative,
there will be a net fluid absorption from the interstitial spaces into
the capillaries.

Equation of Net filtration Pressure:

Interstitial Fluid Hydrostatic Pressure

Negative Interstitial Fluid Pressure:
• Pressure is less than the atmospheric pressure
• Loose subcutaneous tissues
Capillary Filtration Coefficient:
• Measure of the capacity of the capillary membranes to filter water Positive Interstitial Fluid Pressure:
for a give NFP • Greater than atmospheric pressure
• Usually expressed as ml/min per mmHg NFP • Encapsulated tissues (kidneys)

Methods of Measurement:
Rate of Capillary Fluid Filtration:
1. Micropipette:
• Same type of pipette used in the measurement of capillary
pressure
• Pressure that is measured is probably the pressure in a free
fluid pocket
Capillary Hydrostatic Pressure
• Loose Tissue: -2 to +2 mmHg
Methods of Measurement:
2. Implanted Perforated Hollow Capsules:
1. Direct Micropipette Cannulation of the Capillaries: • Loose Subcutaneous Tissue: -6 mmHg
• Gives off an average mean capillary pressure of 25 mmHg • Smaller capsules tend give off a smaller pressure: -2 mmHg
• Capillary pressure can be measured through the capillaries of
exposed tissues of animals and in large capillary loops of the 3. Cotton Wick inserted into the Tissue
eponychium at the base of the fingernail in humans
Interstitial Fluid Pressures in Tightly Encased Tissue
• 30 to 40 mmHg in the arterial ends of the capillaries

• 10 to 15 mmHg in the venous ends
• Interstitial Fluid pressures are almost always positive
• Glomerular Capillaries of the Kidneys: 60 mmHg
• Considerably less than the pressures exerted on the outside of
• Peritubular Capillaries of the Kidneys: 13 mmHg
the tissues by their encasement
• The capillary hydrostatic pressures in different tissues are high
variable, depending on the tissue and physiologic condition
Pressure Inside Pressure Outside
CSF Flow +4 to +6 mmHg +10 mmHg
2. Isogravimetric Method
Kidneys +6 mmHg +13 mmHg
• Indirect measurement of functional capillary pressure
• Gives off a pressure averaging 17 mmHg
• The capillary pressure is kept constant while: • The normal interstitial fluid pressure is negative with respect to
o Decreasing the arterial pressure the pressure that surrounds each tissue
o Increasing the venous pressure • Intrapleural Space Pressure: -8 mmHg
• Exactly balances all the forces tending to move fluid into or out • Joint Synovial Space Pressure: -4 to -6 mmHg
of the capillaries • Epidural Space Pressure: -4 to -6 mmHg
o Gives off a lower pressure compared with the capillary
pressure measured directly with a micropipette Interstitial Fluid Pressure in Loose Subcutaneous Tissue:
• Usually subatmospheric
• In normal conditions: -3 mmHg

Pumping by the Lymphatic System

• Basic cause of the negative interstitial fluid

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 • When the fluid enters the terminal lymphatic capillaries, the lymph Analysis of the Forces Causing Filtration at the Arterial End of
vessel walls automatically contract for a few seconds and pump the Capillary:
the fluid into the blood circulation

Plasma Colloid Osmotic Pressure

Plasma Proteins:
• Cause colloid osmotic pressure
• The only dissolved constituents in the plasma and interstitial fluids
that do not readily pass through the capillary pores
• Responsible for the osmotic pressures on the two sides of the
capillary membrane

Oncotic Pressure:
• Other name for Plasma Colloid Osmotic Pressure
• Osmotic pressure that occurs at the cell membrane

Normal Value:
• 28 mmHg
o 19 mmHg caused by molecular effects of the dissolved protein
o 9 mmHg caused by the Donnan Effect • The net filtration pressure of 13 mmHg tends to move fluid
outward of the capillaries
Donnan Effect:
• Extra osmotic pressure caused by sodium, potassium and other Analysis of Reabsorption at the Venous End of the Capillaries:
cations held in the plasma by the proteins

Effect of Different Plasma Proteins on Colloid Osmotic

Pressure:
• 80% results from Albumin
• 20% results from Globulins

Interstitial Fluid Colloid Osmotic Pressure
• The total quantity of protein in the entire 12 liters of interstitial
fluid of the body is slightly greater than the total quantity of
protein in the plasma itself
o Small amounts of protein leak into the interstitial spaces through
the pores and by transcytosis in small vesicles
• Average Interstitial Fluid Colloid Osmotic Pressure: 8 mmHg
Exchange of Fluid Volume through the Capillary Membrane • The amount of fluid filtering outward almost equals the fluid that
• Average Capilllary Pressure at the Arterial ends of the Capillaries
is 15 to 25 mmHg greater that at the venous ends
• Fluid filter out of the capillaries at the arterial ends
• Fluids are reabsorbed at the venous ends
• Less reabsorption pressure is required to cause inward
movement of fluid
o Venous capillaries are more numerous and more permeable
compared to arterial capillaries
Starling Equilibrium for Capillary Exchange
• A state of near equilibrium exist in most capillaries
reabsorbed
• The slight disequilibrium is accounted for the fluid that us
returned to the circulation by the lymphatics

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 • Lymph from the left side of the head, left arm, and parts of the
chest region also enters the Thoracic Duct before it empties into
the veins
• Lymph from the right side of the neck and head, the right arm,
and parts of the right thorax enters the Right Lymph Duct, which
empties in the blood venous system at the juncture of the right
subclavian vein and internal jugular vein

Net Filtration:
• Slight excess of filtration
• Fluid that must be returned to the circulation through the
lymphatics
• Normal rate: 2 mL/min (except kidneys)

CAPILLARY FILTRATION COEFFICIENT

• Expressed the net fluid filtration rate for each mmHg imbalance
• Capillary filtration coefficient of Average Tissue:
0.01 mL/min/mmHg/100 g of Tissue
• Very small in brain and muscle
• Moderately large in Subcutaneous tissue
• Large in the intestines
• Extremely large in the liver and glomerulus of the kidney

Effect of Abnormal Imbalance of Forces at the
Capillary Membrane Terminal Lymphatic Capillaries and Their Permeability

• If the mean capillary pressure rises, the net force tending to • One tenth of the fluid enters the lymphatic capillaries and returns
cause filtration of fluid in the tissue spaces also rises to the blood through the lymphatic system
o Failure to prevent excess fluid accumulation in the spaces • Total quantity is normally 2 to 3 liters per day
results to edema • Fluid is usually of high molecular weight
• If the capillary pressure falls very low, net reabsoprtion of fluid • The endothelial cells of the lymphatics are attached by anchoring
into the capillaries will occur instead of net filtration filaments to the surrounding connective tissue
o Blood volume will increase at the expense of the interstitial fluid • At the junction of the adjacent endothelial cell overlaps the edge
volume of another adjacent cell, forming a valve
• Lymphatics have valves at the very tips of the terminal lymphatic
LYMPHATIC SYSTEM capillaries as well as in their larger vessels up to the points where
thy empty into the blood circulation
• Accessory route through which fluid can flow from the interstitial
spaces into the blood
• Lymphatics can carry proteins and large particulate matter away
from the tissue spaces
o Neither can be removed by absorption directly into the
capillaries
• Death if failure to return the proteins into the blood from the
interstitial spaces

Lymph Channels of the Body

• Almost all tissues of the body have special lymph channels that
drain excess fluid directly from the interstitial spaces
• Exceptions:
o Superficial portions of the Skin
o Central Nervous System Formation of Lymph
o Endomysium of the Muscles
o Bones • Derived from interstitial fluid that flows into the lymphatics
• All lymph vessels from the lower part of the body empty into the • Lymph has almost the same composition as the interstitial fluid as
Thoracic Duct, which in turn empties into the blood venous in the first enters the terminal lymphatics
system at the juncture of the left internal jugular vein and left • Two –thirds of all lymph is normally derived from the liver and
subclavian vein intestines

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 Thoracic Duct Lymph:
• Mixture of lymph from all areas of the body
• Has protein concentration of 3 to 5 g/dL
Rate of Lymph Flow through the junction between the endothelial cells
• Resting Human: 100 mL/hour
• 20 mL/hr flows through other channels
• Estimated Lymph Flow: 120 mL/hour or 2 to 3 L/day
Effect of Interstitial Fluid on Lymph Flow:
• Normal lymph flow is very little at interstitial fluid pressures more
negative than the normal value of -6 mmHg
• As the pressure rises (atmospheric pressure), flow increases
more that 20-fold
• Any factor that increases interstitial fluid pressure also increases
lymph flow given that the lymph vessels are functioning properly
o Elevated Capillary Hydrostatic Pressure
o Decreased Plasma Colloid Osmotic Pressure
o Increased Interstitial Fluid Colloid Osmotic Pressure
o Increased Permeability of the Capillaries
Lymphatic Pump Increases Lymph Flow:
• When a collecting lymphatic or larger vessel becomes stretched
with fluid, the smooth muscle in the wall of the vessel
automatically contracts
• Each segment of the lymph vessel between successive valves
function as a separate automatic pump
Pumping Caused by External Intermittent Compression of
the Lymphatics:
• Any external factor that intermittently compresses the lymph
vessels can also cause pumping
o Contraction of surrounding skeletal muscles
o Movement of the parts of the body
o Pulsations of arteries adjacent to the lymphatics
o Compression of the tissues by objects outside the body
• Becomes very active during exercise
• Sluggish during periods of rest
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Lymphatic Capillary Pump:
• Each time excess fluid enters the tissue and causes the tissue to
swell, the anchoring filaments pull on the wall of the lymphatic
capillary and fluid flows into the terminal lymphatic capillary
• When the tissue is compressed, pressure inside the capillary
increases and causes the valves to close
• Pressure pushes the lymph forward into the collecting lymphatic
instead of backward through the cell junction
• At least part of the lymph pumping results from lymph capillary
endothelial cell contraction in addition to contraction of the larger
muscular lymphatics
Factor that Determine Lymph Flow:
1. Interstitial Fluid Pressure
2. The activity of the lymphatic pump
NOTE: The rate of lymph flow is determined by the product of
interstitial fluid pressure time the activity of the lymphatic pump
The Lymphatic System Play a Central Role
1. Concentration of Protein in the Interstitial Fluid
2. Volume of Interstitial Fluid
3. Interstitial Fluid Pressure
• Proteins tend to accumulate in the interstitial fluid, which in turn
increases the colloid osmotic pressure of the interstitial fluids
• Fluid is translocated osmotically outward through the capillary
wall by the proteins and into the interstitium
o Increases both interstitial fluid volume and interstitial fluid
pressure
• Increasing the interstitial fluid pressure greatly increases the rate
of lymph flow
Significance of Negative Interstitial Fluid Pressure
• Means for holding body tissues together
• When the tissues lose their negative pressure, edema ensues
SOURCES
• Guyton and Hall textbook of Medical Physiology