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Understanding the
physiological concept
of Microcirculation
 Dr.Amrit Kour
 PG 1st
Year
R.G.G.P.G.Ayurvedic College
and Hospital, Paprola
The Microcirculation
• Microcirculation means circulation at micro level(with small
blood vessels).
• The most purposeful function of the microcirculation is transport
of nutrients to the tissues and removal of cell excreta.
• The small arterioles control blood flow to each tissue area, and
• local conditions in the tissues in turn control the
• Diameters of the arterioles.
• Thus, each tissue, in most cases, controls its own blood flow in
relation to its individual need.
Structure of the Microcirculation and
Capillary System
 The microcirculation of each organ is
organized specifically to serve that organ’s
needs.
 So, exact morphology varies from organ to
organ depending upon the functions of
organs.
 Structure of an ideal microcirculation unit,
 Arteriole at one end
 Venule at other end
 A network of capillaries in between.
Arteriole
 Arteriole arise from the branching of arteries.
 Each nutrient artery entering an organ
branches six to eight times before the arteries
become small enough to be called arterioles,
 Internal diameters = 10 to 15 micrometers.
 The arterioles are highly muscular, and their
diameters can change by many times.
 The metarterioles (the terminal arterioles) do
not have a continuous muscular coat,
 Walls of arterioles contain a single continuous layer of smooth
muscle cells.
 Smooth muscle cells receive innervations mainly from sympathetic
nervous system.
 So, the tone of arterioles is mainly under the control of nervous
system .
 At the point where each true capillary originates from a
metarteriole - smooth muscle fibers usually encircle the capillary
– Called Precapillary Sphinctres.
 These Precapillary Sphincters control the entry of blood into the
capillaries.
 It does not receive innervations.
microcirculation - COMPONENTS- STRUCTURE - FUNCTIONS - IMPORTANCE
Venules
 Venules are larger than the arterioles.
 Like arterioles, wall of venules is also lined by
layer of smooth muscle cells but it is not
continuous.
 So, venules are having weaker muscular coats.
 The pressure in the venules is much less than
that in the arterioles,
 but still It can contract to considerable extent
despite having weaker muscles.
 Venules converge to form veins and then larger
vena cava.
Note – Metarterioles and precapillary sphincters do not
receive innervations, so they are not under the control of
Nervous System.
But they are in very close contact with the cells they
serve.
 So, they respond directly to the local conditions .
Therefore, the local conditions of the tissues—such as the
concentrations of nutrients, end products of metabolism,
and hydrogen ions—can cause direct effects on the vessels
to control local blood flow in each small tissue area.
Capillaries
• The internal diameter of the capillary is 4 to 9
micrometers, barely large enough for red blood cells
and other blood cells to squeeze through.
• Small size of the capillary lumen, brings surface of
RBCs close to the wall of capillaries – helps in rapid
gaseous exchange.
• The wall of the capillary is composed of
• 1. unicellular layer of endothelial cells
• 2. thin basement membrane on the outside of the
capillary.
• The total thickness of the capillary wall is only about
0.5 micrometer.
Two pathways for filtration
• For the purpose of filtration mainly two pathways are
there-
• 1. Pores in the Capillary Membrane
• 2. coated pits on the surface of endothelial cells.
‘Pores’ in the Capillary
Membrane
 Intercellular clefts – spaces between the two adjacent endothelial cells.
 Proteins are also present in the intercellular clefts which attach the adjacent
endothelial cells together.
 Free fluid can also pass easily through these protein spaces.
 The cleft normally has a uniform spacing with a width of about 6 to 7
nanometers, slightly smaller than the diameter of an albumin protein
molecule.
 So, this width allows the movement of most of the solutes except plasma
proteins like albumin.
 Therefore, permeability decreases with increase in molecular size.
2. Coated pits on the surface of endothelial cells.
 Endothelial cells have coated pits- that perform receptor mediated
endocytosis.
 These pits capture small amount of fluid from the lumen.
 Vesicle is formed that travel to the opposite side and release the
contents in the interstitium by exocytosis.
 This is known as transcytosis.
 Plasma proteins enter the interstitium in this way.
Types of capillaries with different permeability
1.Continuous capillary 2.Fenestrated capillary 3.Discontinuous capillary
Structure is very similar with the
general structure of capillary.
They have average permeability.
 In these capillary, endothelial
cells are thin and have perforations
called fenestrae.
Increased permeability of these
capillaries.
large gaps between the endothelial
cells are also present.
These are also called as sinusoidal
capillaries.
Present In Most of the organs of
body e.g skeletal muscles,lungs,
skin, nervous system etc.
Present in the glomerular
capillaries of the kidneys.
Most permeable.
They are found in the sinusoids
of the liver, plasma proteins can
pass.
In the bone marrow,large gaps
help newly formed cells to enter
into the circulation.
These tight junctions allow only
the small molecules like oxygen,
water, carbon dioxide etc. to pass
through them.
microcirculation - COMPONENTS- STRUCTURE - FUNCTIONS - IMPORTANCE
Flow of Blood in the Capillaries—Vasomotion
 Blood usually does not flow continuously through the capillaries.
 Instead, it flows intermittently, turning on and off every few seconds
or minutes.
 The cause of this intermittency is the phenomenon called vasomotion.
 Vasomotion - means intermittent contraction of the metarterioles and
precapillary sphincters (and sometimes even the very small arterioles
as well).
Regulation of Vasomotion.
• Intermittent contraction of the metarterioles and precapillary
sphincters depends upon the concentration of oxygen in the
tissues.
• When a tissue is metabolicaly active
• Amount of usage of oxygen by the tissue will be more
• oxygen concentration decreases below normal
• Intermittent periods of capillary blood flow will
occur more often with increased duration
•
• allowing the capillary blood to carry increased
quantities of oxygen (as well as other nutrients) to
the tissues.
Average Function of the Capillary System
• Despite the fact that blood flow through each capillary is
intermittent, so many capillaries are present in the tissues
that their overall function becomes averaged.
• That is, there is an average rate of blood flow through
each tissue capillary bed,
• an average capillary pressure within the capillaries, and
an average rate of transfer of substances between the
blood of the capillaries and the surrounding interstitial
fluid.
Capillary exchange of nutrients and waste
products
 Note- capillary wall is highly permeable, so that both I.C.F and the plasma are continuously
mixing with each other.
 So, they have almost same composition.
 Main difference in the composition of I.C.F and plasma is due protein concentration.
 Capillary wall is not permeable to proteins, so proteins remain in the plasma only.
 Therefore, concentration of proteins is higher in plasma.
Intracellular fluid compartment Extracellular Fluid compartment
2/3rd
of body fluid.
28L of body fluid.
Interstitial fluid- 11L
Plasma- 3L
Total 14L of E.C.F .
1/3rd
of total body fluid.
• This mixing of capillary and interstitial fluid – helps in
the exchange of substances.
• Cells in our body, use nutrients like glucose, Carbon
Dioxide, oxygen for their function.
• So, concentration of nutrients is less in the interstitial
fluid.
• Capillary fluid contain normal amount of nutrients.
Diffusion Through the Capillary Membrane
 DIFFUSION - Is the Most Important Means of Transfer of
Substances Between Plasma and Interstitial Fluid.
 Electrolytes, nutrients, and waste products of metabolism all
diffuse easily through the capillary membrane.
 The proteins are the only dissolved constituents in the plasma
and interstitial fluids that do not readily pass through the
capillary membrane.
Water-Soluble, Non–Lipid-Soluble Substances Diffuse Through
Intercellular Pores in the Capillary Membrane.
• Many substances needed by the tissues are soluble in water but
cannot pass through the lipid membranes of the endothelial cells;
• these include water molecules, sodium ions, chloride ions, and
glucose.
• because of high thermal velocity of molecules in the fluid –
rapid diffusion of water and water-soluble substances through
these cleft pores.
Effect of Molecular Size on Passage Through the Pores.
 The width of the capillary intercellular cleft pores, 6 to 7 nanometers.
 The diameters of plasma protein molecule is slightly greater than the
width of the pores.
 Other substances, such as sodium ions, chloride ions, glucose, and
urea, have intermediate diameters.
 Therefore, the permeability of the capillary pores for different
substances varies according to their molecular diameters
microcirculation - COMPONENTS- STRUCTURE - FUNCTIONS - IMPORTANCE
Diffusion through capillary pores depends upon -
• 1. Depends upon size of the molecules.
• With increasing molecular weight permeability decreases.
• 2. Permeability also depends upon the types of capillary.
• Continuous capillary in the cerebral microcirculation -
average permeability.
• Fenestrated capillaries in the glomerulus of kidneys – high
permeability.
• Discontinuous/ sinusoidal capillaries in the liver – very
high permeability.
Lipid-Soluble Substances Diffuse Directly Through
the Cell Membranes of the Capillary Endothelium.
 If a substance is lipid-soluble, it can diffuse directly through the
cell membranes of the capillary without having to go through the
pores.
 Such substances include oxygen and carbon dioxide.
 Rates of transport of Lipid-Soluble Substances is faster than the
lipid-insoluble substances, such as sodium ions and glucose,
which can go only through the pores.
Diffusion Through the Capillary Membrane Is
Proportional to the Concentration Difference
Between the Two Sides of the Membrane.
 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.
 For example, the concentration of oxygen in capillary blood is normally greater
than in the interstitial fluid.
 Therefore, large quantities of oxygen normally move from the blood toward the
tissues in the interstititum.
 Opposite to the concentration of carbon dioxide is greater in the tissues than in
the blood, which causes excess carbon dioxide to move into the blood and to be
carried away from the tissues.
INTERSTITIUM AND INTERSTITIAL FLUID
 spaces between cells, which collectively are called the interstitium.
 About one sixth of the total volume of the body consists of interstitium.
 The fluid in these spaces is called the interstitial fluid.
 The structure of the interstitium –
 It contains two major types of solid structures:
 (1) Collagen fibers
 (2) Proteoglycan filaments. With fluid trapped within them.
 Collagen fiber bundles are very strong and provide most of the tensional strength of the
tissues.
 Proteoglycan filaments are extremely thin, coiled or twisted molecules - composed of about
 98% hyaluronic acid &
 2% protein.
microcirculation - COMPONENTS- STRUCTURE - FUNCTIONS - IMPORTANCE
 This combination of proteoglycan filaments and fluid
entrapped within them has the characteristics of a gel; it is
therefore called tissue gel.
 So, it is a gel like structure.
 Because of large number of filaments, fluid cannot flow freely
as it does in open space in capillary rather it diffuses through
gel.
 This diffusion is also fast enough .
 So, passage through interstitium is also fast.
Free Fluid in the Interstitium.
 In the interstitium, there are small areas of free fluid where
proteoglycan are absent.
 The amount of free fluid present in most normal tissues is usually
less than 1%.
 But when the tissues develop edema, these small pockets
expand. So, percentage of free fluid also increases.
FLUID FILTRATION ACROSS CAPILLARIES
It is determined by
Capillary filtration coefficient (Kf) and Net Filtration
Pressure (NFP).
Filtration = Kf X NFP
Net Filtration Pressure (NFP)
 NFP is determined by Starling Forces.
 Starling Forces-
 Theses are the driving forces that move the fluid across the
capillary.
 They include-
 Hydrostatic Pressure and colloidal osmotic pressure in the
capillary as well as in the interstitium.
 Sum of these forces, determine whether there will be net
filtration or net absorption.
1. Hydrostatic Pressure
 It is the pressure which is exerted by the fluid.
 Hydrostatic Pressure in the capillaries-
 Pushes the fluid out of the capillary.
 At the arterial end = 30mmHg
 At the venous end = 10mmHg
 Hydrostatic Pressure in the Interstitium-
 Positive hydrostatic pressure in the interstitium , tend to move the fluid
back into the capillaries.
 But due to fluid removal by the lymphatics, it is negative in the loose
tissues like lungs and subcutaneous tissues.
 So, being negative, it pulls the fluid out of the capillary.
 It is -3mmHg
2. Colloidal osmotic Pressure
 It is the pressure exerted by the proteins.
 Colloidal osmotic pressure in the capillaries is exerted by the plasma proteins.
 It pushes the fluid inward.
 It is about 28mmHg.
 Colloidal osmotic pressure in the interstitium –
 Although capillary walls are highly impermeable to the proteins but some
proteins may leak through the pores and by the means of transcytosis.
 These proteins and proteoglycans contribute to the colloidal osmotic pressure in
the interstitium.
 It tends to pull the fluid in the interstitium.
 It is 8mmHg.
Small ions like sodium and calcium freely move
across the capillary wall, so they do not contribute to
the osmotic driving forces.
 The net filtration pressure (NFP) is calculated as follows:
 NFP= Pc- Pif − ∏p + ∏ if
 If the sum of these forces—the net filtration pressure— is
positive, there will be a net fluid filtration across the capillaries.
 If the sum of the Starling forces is negative, there will be a net
fluid absorption from the interstitial spaces into the capillaries.
Analysis of the Forces Causing Filtration
at the Arterial End of the Capillary
 At arterial end
 capillary Hydrostatic Pressure = 30mmHg
 Interstitial Hydrostatic Pressure = -3mmHg
 Plasma colloidal osmotic pressure = 28mmHg
 Interstitial colloidal osmotic pressure = 8mmHg
 Total outward forces= 30+3+8 = 41mmHg
 Total Inward forces = 28mmHg.
 So, NFF = 13mmHg – being positive, it favours filtration of the
fluid.
Analysis of Reabsorption at the Venous End
of the Capillary.
 At the venous end –
 capillary Hydrostatic Pressure = 10mmHg
 Interstitial Hydrostatic Pressure = -3mmHg
 Plasma colloidal osmotic pressure = 28mmHg
 Interstitial colloidal osmotic pressure = 8mmHg
 Total outward forces= 10+3+8 = 21mmHg
 Total Inward forces = 28mmHg.
 So, NFF = -7 mmHg – being negative, it favours reabsorption of the
fluid.
Reabsorption pressure at the venous end is considerably
less (-7mmHg) than the filtration pressure at the arterial
end (13mmHg).
However at the venous end, capillaries are more
numerous and more permeable.
So, even this less pressure is sufficient for the
reabsorption of most of the filtered fluid.
Capillary filtration coefficient (Kf)
 In simple words, it is the permeability of the capillary.
 It depends upon –
 Number and size of the pores in the capillary.
 Number of capillaries.
 It is expressed as Net Fluid Filtration rate for each mmHg of the net
driving force.
 Average Capillary Filtration Coefficient (Kf) for the whole body =
6.67mL/min.
The Lymphatic System
• One of the important component of
the microcirculation.
• As we see, net fluid reabsorption is
less than net fluid filtration.
• So, there is some fluid and proteins
left in the interstitium.
• Proteins cannot enter into the
capillary due to their large size.
• So, lymphatic system reabsorb the
remaining filtered fluid including the
proteins.
Structure of Lymphatic Channels
• There are terminal lymphatic capillary (initial
capillaries)
• Merge to form progressively larger lymphatic
channels called collecting lymphatics.
 Like regular capillaries, terminal lymphatic capillaries also have
endothelial cells.
 But theses endothelial cells are attached to the surrounding tissues
by anchoring filaments.
 Edges of the adjacent endothelial cells overlap with one another.
 Theses are arranged in such a way, that free edge of the endothelial
cells, can only flap inwards.
 This allows the entry of fluid from interstitium into the lymphatics.
 But if the fluid tries to move out, flap closes and prevent the
backflow of fluid.
 Such micro valves are present all over the capillary.
Secondary valves are present in the larger capillaries,
which prevent the backflow within lymphatic system.
So, lymph flow only in forward direction and finally
emptied into veins.
microcirculation - COMPONENTS- STRUCTURE - FUNCTIONS - IMPORTANCE
Factors driving the flow of lymph
• 1. Interstitial fluid pressure- interstitial hydrostatic pressure = -
3mmHg.
• When interstitial hydrostatic pressure increases = more fluid enters
the lymphatics. So, flow increases.
• 2. Pressure above 0, start compressing the lymphatic channels.
This prevents further increase in the flow.
• 3. At a pressure of 2mmHg, increased entry of fluid and
compression of lymphatic channels balances out each other.
• After that there is no increase in the flow with increase in the
pressure.
microcirculation - COMPONENTS- STRUCTURE - FUNCTIONS - IMPORTANCE
Lymphatic capillary pump
Endothelial cells of the terminal lymphatic capillaries are
attached to the surrounding tissues by anchoring filaments.
So, when excess fluid enters the interstitium, anchoring
filaments pulls the endothelial cells of the terminal
lymphatic capillaries and the fluid flows into the terminal
lymphatic capillaries, through the junctions between the
endothelial cells.
So, when the tissue is compressed, pressure inside the
capillary increases, which closes the edges of the
endothelial cells.
Therefore, pressure pulls the fluid forward into the
collecting lymphatics and prevent the backflow.
Thus, lymphatic capillary pump- helps in the
absorption of interstitial fluid and also pushes the fluid
forward.
• Smooth muscles are present in the collecting lymphatics.
• When the collecting lymphatics receives fluid, it stretches and
contract – allows forward movement of fluid.
• Secondary valves present in the collecting lymphatics – prevent
the backflow of fluid.
Pumping Caused by External Intermittent
Compression of the Lymphatics.
 In addition to the pumping caused by intrinsic intermittent contraction of the lymph
vessel walls, any external factor that intermittently compresses the lymph vessel can
also cause pumping.
 In order of their importance, such factors are as follows:
 • Contraction of surrounding skeletal muscles
 • Movement of the parts of the body
 • Pulsations of arteries adjacent to the lymphatics
 • Compression of the tissues by objects outside the body .
 The lymphatic pump becomes very active during exercise, often increasing lymph
flow 10- to 30-fold.
 Conversely, during periods of rest, lymph flow is sluggish (almost zero).
• Lymphatic system functions as an overflow mechanism to
return excess proteins and excess fluid volume from the tissue
spaces to the circulation.
• Therefore, the lymphatic system also plays a central role in
controlling the following:
• (1) concentration of proteins in the interstitial fluids;
• (2) volume of interstitial fluid; and
• (3) interstitial fluid pressure.
• In case of any abnormality with the lymphatic system –
• Proteins left in the interstitium increases
• Colloidal osmotic pressure increases
• Causes filtration of more fluids
• Increases interstitial fluid volume and pressure
• Resulting in EDEMA
Thank You

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microcirculation - COMPONENTS- STRUCTURE - FUNCTIONS - IMPORTANCE

  • 1. Understanding the physiological concept of Microcirculation  Dr.Amrit Kour  PG 1st Year R.G.G.P.G.Ayurvedic College and Hospital, Paprola
  • 2. The Microcirculation • Microcirculation means circulation at micro level(with small blood vessels). • The most purposeful function of the microcirculation is transport of nutrients to the tissues and removal of cell excreta. • The small arterioles control blood flow to each tissue area, and • local conditions in the tissues in turn control the • Diameters of the arterioles. • Thus, each tissue, in most cases, controls its own blood flow in relation to its individual need.
  • 3. Structure of the Microcirculation and Capillary System  The microcirculation of each organ is organized specifically to serve that organ’s needs.  So, exact morphology varies from organ to organ depending upon the functions of organs.  Structure of an ideal microcirculation unit,  Arteriole at one end  Venule at other end  A network of capillaries in between.
  • 4. Arteriole  Arteriole arise from the branching of arteries.  Each nutrient artery entering an organ branches six to eight times before the arteries become small enough to be called arterioles,  Internal diameters = 10 to 15 micrometers.  The arterioles are highly muscular, and their diameters can change by many times.  The metarterioles (the terminal arterioles) do not have a continuous muscular coat,
  • 5.  Walls of arterioles contain a single continuous layer of smooth muscle cells.  Smooth muscle cells receive innervations mainly from sympathetic nervous system.  So, the tone of arterioles is mainly under the control of nervous system .  At the point where each true capillary originates from a metarteriole - smooth muscle fibers usually encircle the capillary – Called Precapillary Sphinctres.  These Precapillary Sphincters control the entry of blood into the capillaries.  It does not receive innervations.
  • 7. Venules  Venules are larger than the arterioles.  Like arterioles, wall of venules is also lined by layer of smooth muscle cells but it is not continuous.  So, venules are having weaker muscular coats.  The pressure in the venules is much less than that in the arterioles,  but still It can contract to considerable extent despite having weaker muscles.  Venules converge to form veins and then larger vena cava.
  • 8. Note – Metarterioles and precapillary sphincters do not receive innervations, so they are not under the control of Nervous System. But they are in very close contact with the cells they serve.  So, they respond directly to the local conditions . Therefore, the local conditions of the tissues—such as the concentrations of nutrients, end products of metabolism, and hydrogen ions—can cause direct effects on the vessels to control local blood flow in each small tissue area.
  • 9. Capillaries • The internal diameter of the capillary is 4 to 9 micrometers, barely large enough for red blood cells and other blood cells to squeeze through. • Small size of the capillary lumen, brings surface of RBCs close to the wall of capillaries – helps in rapid gaseous exchange. • The wall of the capillary is composed of • 1. unicellular layer of endothelial cells • 2. thin basement membrane on the outside of the capillary. • The total thickness of the capillary wall is only about 0.5 micrometer.
  • 10. Two pathways for filtration • For the purpose of filtration mainly two pathways are there- • 1. Pores in the Capillary Membrane • 2. coated pits on the surface of endothelial cells.
  • 11. ‘Pores’ in the Capillary Membrane  Intercellular clefts – spaces between the two adjacent endothelial cells.  Proteins are also present in the intercellular clefts which attach the adjacent endothelial cells together.  Free fluid can also pass easily through these protein spaces.  The cleft normally has a uniform spacing with a width of about 6 to 7 nanometers, slightly smaller than the diameter of an albumin protein molecule.  So, this width allows the movement of most of the solutes except plasma proteins like albumin.  Therefore, permeability decreases with increase in molecular size.
  • 12. 2. Coated pits on the surface of endothelial cells.  Endothelial cells have coated pits- that perform receptor mediated endocytosis.  These pits capture small amount of fluid from the lumen.  Vesicle is formed that travel to the opposite side and release the contents in the interstitium by exocytosis.  This is known as transcytosis.  Plasma proteins enter the interstitium in this way.
  • 13. Types of capillaries with different permeability 1.Continuous capillary 2.Fenestrated capillary 3.Discontinuous capillary Structure is very similar with the general structure of capillary. They have average permeability.  In these capillary, endothelial cells are thin and have perforations called fenestrae. Increased permeability of these capillaries. large gaps between the endothelial cells are also present. These are also called as sinusoidal capillaries. Present In Most of the organs of body e.g skeletal muscles,lungs, skin, nervous system etc. Present in the glomerular capillaries of the kidneys. Most permeable. They are found in the sinusoids of the liver, plasma proteins can pass. In the bone marrow,large gaps help newly formed cells to enter into the circulation. These tight junctions allow only the small molecules like oxygen, water, carbon dioxide etc. to pass through them.
  • 15. Flow of Blood in the Capillaries—Vasomotion  Blood usually does not flow continuously through the capillaries.  Instead, it flows intermittently, turning on and off every few seconds or minutes.  The cause of this intermittency is the phenomenon called vasomotion.  Vasomotion - means intermittent contraction of the metarterioles and precapillary sphincters (and sometimes even the very small arterioles as well).
  • 16. Regulation of Vasomotion. • Intermittent contraction of the metarterioles and precapillary sphincters depends upon the concentration of oxygen in the tissues. • When a tissue is metabolicaly active • Amount of usage of oxygen by the tissue will be more • oxygen concentration decreases below normal
  • 17. • Intermittent periods of capillary blood flow will occur more often with increased duration • • allowing the capillary blood to carry increased quantities of oxygen (as well as other nutrients) to the tissues.
  • 18. Average Function of the Capillary System • Despite the fact that blood flow through each capillary is intermittent, so many capillaries are present in the tissues that their overall function becomes averaged. • That is, there is an average rate of blood flow through each tissue capillary bed, • an average capillary pressure within the capillaries, and an average rate of transfer of substances between the blood of the capillaries and the surrounding interstitial fluid.
  • 19. Capillary exchange of nutrients and waste products  Note- capillary wall is highly permeable, so that both I.C.F and the plasma are continuously mixing with each other.  So, they have almost same composition.  Main difference in the composition of I.C.F and plasma is due protein concentration.  Capillary wall is not permeable to proteins, so proteins remain in the plasma only.  Therefore, concentration of proteins is higher in plasma. Intracellular fluid compartment Extracellular Fluid compartment 2/3rd of body fluid. 28L of body fluid. Interstitial fluid- 11L Plasma- 3L Total 14L of E.C.F . 1/3rd of total body fluid.
  • 20. • This mixing of capillary and interstitial fluid – helps in the exchange of substances. • Cells in our body, use nutrients like glucose, Carbon Dioxide, oxygen for their function. • So, concentration of nutrients is less in the interstitial fluid. • Capillary fluid contain normal amount of nutrients.
  • 21. Diffusion Through the Capillary Membrane  DIFFUSION - Is the Most Important Means of Transfer of Substances Between Plasma and Interstitial Fluid.  Electrolytes, nutrients, and waste products of metabolism all diffuse easily through the capillary membrane.  The proteins are the only dissolved constituents in the plasma and interstitial fluids that do not readily pass through the capillary membrane.
  • 22. Water-Soluble, Non–Lipid-Soluble Substances Diffuse Through Intercellular Pores in the Capillary Membrane. • Many substances needed by the tissues are soluble in water but cannot pass through the lipid membranes of the endothelial cells; • these include water molecules, sodium ions, chloride ions, and glucose. • because of high thermal velocity of molecules in the fluid – rapid diffusion of water and water-soluble substances through these cleft pores.
  • 23. Effect of Molecular Size on Passage Through the Pores.  The width of the capillary intercellular cleft pores, 6 to 7 nanometers.  The diameters of plasma protein molecule is slightly greater than the width of the pores.  Other substances, such as sodium ions, chloride ions, glucose, and urea, have intermediate diameters.  Therefore, the permeability of the capillary pores for different substances varies according to their molecular diameters
  • 25. Diffusion through capillary pores depends upon - • 1. Depends upon size of the molecules. • With increasing molecular weight permeability decreases. • 2. Permeability also depends upon the types of capillary. • Continuous capillary in the cerebral microcirculation - average permeability. • Fenestrated capillaries in the glomerulus of kidneys – high permeability. • Discontinuous/ sinusoidal capillaries in the liver – very high permeability.
  • 26. Lipid-Soluble Substances Diffuse Directly Through the Cell Membranes of the Capillary Endothelium.  If a substance is lipid-soluble, it can diffuse directly through the cell membranes of the capillary without having to go through the pores.  Such substances include oxygen and carbon dioxide.  Rates of transport of Lipid-Soluble Substances is faster than the lipid-insoluble substances, such as sodium ions and glucose, which can go only through the pores.
  • 27. Diffusion Through the Capillary Membrane Is Proportional to the Concentration Difference Between the Two Sides of the Membrane.  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.  For example, the concentration of oxygen in capillary blood is normally greater than in the interstitial fluid.  Therefore, large quantities of oxygen normally move from the blood toward the tissues in the interstititum.  Opposite to the concentration of carbon dioxide is greater in the tissues than in the blood, which causes excess carbon dioxide to move into the blood and to be carried away from the tissues.
  • 28. INTERSTITIUM AND INTERSTITIAL FLUID  spaces between cells, which collectively are called the interstitium.  About one sixth of the total volume of the body consists of interstitium.  The fluid in these spaces is called the interstitial fluid.  The structure of the interstitium –  It contains two major types of solid structures:  (1) Collagen fibers  (2) Proteoglycan filaments. With fluid trapped within them.  Collagen fiber bundles are very strong and provide most of the tensional strength of the tissues.  Proteoglycan filaments are extremely thin, coiled or twisted molecules - composed of about  98% hyaluronic acid &  2% protein.
  • 30.  This combination of proteoglycan filaments and fluid entrapped within them has the characteristics of a gel; it is therefore called tissue gel.  So, it is a gel like structure.  Because of large number of filaments, fluid cannot flow freely as it does in open space in capillary rather it diffuses through gel.  This diffusion is also fast enough .  So, passage through interstitium is also fast.
  • 31. Free Fluid in the Interstitium.  In the interstitium, there are small areas of free fluid where proteoglycan are absent.  The amount of free fluid present in most normal tissues is usually less than 1%.  But when the tissues develop edema, these small pockets expand. So, percentage of free fluid also increases.
  • 32. FLUID FILTRATION ACROSS CAPILLARIES It is determined by Capillary filtration coefficient (Kf) and Net Filtration Pressure (NFP). Filtration = Kf X NFP
  • 33. Net Filtration Pressure (NFP)  NFP is determined by Starling Forces.  Starling Forces-  Theses are the driving forces that move the fluid across the capillary.  They include-  Hydrostatic Pressure and colloidal osmotic pressure in the capillary as well as in the interstitium.  Sum of these forces, determine whether there will be net filtration or net absorption.
  • 34. 1. Hydrostatic Pressure  It is the pressure which is exerted by the fluid.  Hydrostatic Pressure in the capillaries-  Pushes the fluid out of the capillary.  At the arterial end = 30mmHg  At the venous end = 10mmHg  Hydrostatic Pressure in the Interstitium-  Positive hydrostatic pressure in the interstitium , tend to move the fluid back into the capillaries.  But due to fluid removal by the lymphatics, it is negative in the loose tissues like lungs and subcutaneous tissues.  So, being negative, it pulls the fluid out of the capillary.  It is -3mmHg
  • 35. 2. Colloidal osmotic Pressure  It is the pressure exerted by the proteins.  Colloidal osmotic pressure in the capillaries is exerted by the plasma proteins.  It pushes the fluid inward.  It is about 28mmHg.  Colloidal osmotic pressure in the interstitium –  Although capillary walls are highly impermeable to the proteins but some proteins may leak through the pores and by the means of transcytosis.  These proteins and proteoglycans contribute to the colloidal osmotic pressure in the interstitium.  It tends to pull the fluid in the interstitium.  It is 8mmHg.
  • 36. Small ions like sodium and calcium freely move across the capillary wall, so they do not contribute to the osmotic driving forces.
  • 37.  The net filtration pressure (NFP) is calculated as follows:  NFP= Pc- Pif − ∏p + ∏ if  If the sum of these forces—the net filtration pressure— is positive, there will be a net fluid filtration across the capillaries.  If the sum of the Starling forces is negative, there will be a net fluid absorption from the interstitial spaces into the capillaries.
  • 38. Analysis of the Forces Causing Filtration at the Arterial End of the Capillary  At arterial end  capillary Hydrostatic Pressure = 30mmHg  Interstitial Hydrostatic Pressure = -3mmHg  Plasma colloidal osmotic pressure = 28mmHg  Interstitial colloidal osmotic pressure = 8mmHg  Total outward forces= 30+3+8 = 41mmHg  Total Inward forces = 28mmHg.  So, NFF = 13mmHg – being positive, it favours filtration of the fluid.
  • 39. Analysis of Reabsorption at the Venous End of the Capillary.  At the venous end –  capillary Hydrostatic Pressure = 10mmHg  Interstitial Hydrostatic Pressure = -3mmHg  Plasma colloidal osmotic pressure = 28mmHg  Interstitial colloidal osmotic pressure = 8mmHg  Total outward forces= 10+3+8 = 21mmHg  Total Inward forces = 28mmHg.  So, NFF = -7 mmHg – being negative, it favours reabsorption of the fluid.
  • 40. Reabsorption pressure at the venous end is considerably less (-7mmHg) than the filtration pressure at the arterial end (13mmHg). However at the venous end, capillaries are more numerous and more permeable. So, even this less pressure is sufficient for the reabsorption of most of the filtered fluid.
  • 41. Capillary filtration coefficient (Kf)  In simple words, it is the permeability of the capillary.  It depends upon –  Number and size of the pores in the capillary.  Number of capillaries.  It is expressed as Net Fluid Filtration rate for each mmHg of the net driving force.  Average Capillary Filtration Coefficient (Kf) for the whole body = 6.67mL/min.
  • 42. The Lymphatic System • One of the important component of the microcirculation. • As we see, net fluid reabsorption is less than net fluid filtration. • So, there is some fluid and proteins left in the interstitium. • Proteins cannot enter into the capillary due to their large size. • So, lymphatic system reabsorb the remaining filtered fluid including the proteins.
  • 43. Structure of Lymphatic Channels • There are terminal lymphatic capillary (initial capillaries) • Merge to form progressively larger lymphatic channels called collecting lymphatics.
  • 44.  Like regular capillaries, terminal lymphatic capillaries also have endothelial cells.  But theses endothelial cells are attached to the surrounding tissues by anchoring filaments.  Edges of the adjacent endothelial cells overlap with one another.  Theses are arranged in such a way, that free edge of the endothelial cells, can only flap inwards.  This allows the entry of fluid from interstitium into the lymphatics.  But if the fluid tries to move out, flap closes and prevent the backflow of fluid.  Such micro valves are present all over the capillary.
  • 45. Secondary valves are present in the larger capillaries, which prevent the backflow within lymphatic system. So, lymph flow only in forward direction and finally emptied into veins.
  • 47. Factors driving the flow of lymph • 1. Interstitial fluid pressure- interstitial hydrostatic pressure = - 3mmHg. • When interstitial hydrostatic pressure increases = more fluid enters the lymphatics. So, flow increases. • 2. Pressure above 0, start compressing the lymphatic channels. This prevents further increase in the flow. • 3. At a pressure of 2mmHg, increased entry of fluid and compression of lymphatic channels balances out each other. • After that there is no increase in the flow with increase in the pressure.
  • 49. Lymphatic capillary pump Endothelial cells of the terminal lymphatic capillaries are attached to the surrounding tissues by anchoring filaments. So, when excess fluid enters the interstitium, anchoring filaments pulls the endothelial cells of the terminal lymphatic capillaries and the fluid flows into the terminal lymphatic capillaries, through the junctions between the endothelial cells. So, when the tissue is compressed, pressure inside the capillary increases, which closes the edges of the endothelial cells.
  • 50. Therefore, pressure pulls the fluid forward into the collecting lymphatics and prevent the backflow. Thus, lymphatic capillary pump- helps in the absorption of interstitial fluid and also pushes the fluid forward.
  • 51. • Smooth muscles are present in the collecting lymphatics. • When the collecting lymphatics receives fluid, it stretches and contract – allows forward movement of fluid. • Secondary valves present in the collecting lymphatics – prevent the backflow of fluid.
  • 52. Pumping Caused by External Intermittent Compression of the Lymphatics.  In addition to the pumping caused by intrinsic intermittent contraction of the lymph vessel walls, any external factor that intermittently compresses the lymph vessel can also cause pumping.  In order of their importance, such factors are as follows:  • Contraction of surrounding skeletal muscles  • Movement of the parts of the body  • Pulsations of arteries adjacent to the lymphatics  • Compression of the tissues by objects outside the body .  The lymphatic pump becomes very active during exercise, often increasing lymph flow 10- to 30-fold.  Conversely, during periods of rest, lymph flow is sluggish (almost zero).
  • 53. • Lymphatic system functions as an overflow mechanism to return excess proteins and excess fluid volume from the tissue spaces to the circulation. • Therefore, the lymphatic system also plays a central role in controlling the following: • (1) concentration of proteins in the interstitial fluids; • (2) volume of interstitial fluid; and • (3) interstitial fluid pressure.
  • 54. • In case of any abnormality with the lymphatic system – • Proteins left in the interstitium increases • Colloidal osmotic pressure increases • Causes filtration of more fluids • Increases interstitial fluid volume and pressure • Resulting in EDEMA