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Prof.Dr. Ümmühan İşoğlu-Alkaç
İ.Ü. İstanbul Tıp Fakültesi Fizyoloji Anabilim Dalıalkac@istanbul.edu.tr
YU Medical Faculty, 09.10.2013
Microcirculation and Lymphatic System
Microcirculation and the
Lymphatic System
Structure of the microcirculation
and capillary system
• The arterioles are highly muscular …
• Metarterioles (the terminal arterioles) do not have a
continuous muscular coat, but smooth muscle fibers encircle
the vessel at intermittent points
• Precapillary sphincter between the metarteriole and capillary
• The venules are larger than the arterioles and have much
weaker muscular coat
• Local conditions of the tissues and regulation of blood flow
Structure of the microcirculation and
capillary system
Structure of the capillary wall
• Total thickness of the capillary wall is only about 0.5 µm, 500-900 m2 , 4-9 µm, funct.cell:20-30 µm
Special types of pores and certain organs
1) In the brain, junctions between the capillary endothelial
cells are mainly “tight” junctions that allow only
extremely small molecules such as water, O2, CO2 for
passage
2) In the liver, the opposite is true.
3) The pores of the gastrointestinal capillary membranes
are midway between those of the muscle and liver
4) In the glomerular structure of the kidney, there are small
oval windows on the capillary walls called “fenestrae”
(fenestrated capillaries)
Liver, Bone Marrow, Spleen
Flow of Blood in the Capillaries-
Vasomotion
• Blood usually does not flow continuously through the
capillaries
• It flows intermittently every few seconds or minutes
• This phenomenon is called “vasomotion”
• The most important factor to affect the degree of
openning and closing of the metarterioles and
precapillary sphincters is the oxygen concentration
• Average function of the capillary system…
Exchange of water, nutrients and other substances
between the blood and interstitial fluid
• Diffusion through the capillary membrane: the most
important means for transport of substances between the
plasma and interstitial fluid
• Lipid soluble substances can diffuse directly through the cell
membranes of the capillary endothelium (e.g. O2 and CO2)
• Water-soluble, non-lipid-soluble substances diffuse only
through intercellular pores in the capillary membrane (e.g.
water molecules, Na ions, Cl ions and glucose)
• Effect of concentration difference on net rate of diffusion through
the capillary membrane
Exchange of water, nutrients and other substances
between the blood and interstitial fluid
Effect of molecular size on passage through the pores
Substance Molecular Weight Permeability
Water 18 1.00
NaCl 58.5 0.96
Urea 60 0.8
Glucose 180 0.6
Sucrose 342 0.4
Inulin 5,000 0.2
Myoglobin 17,600 0.03
Hemoglobin 68,000 0.01
Albumin 69,000 0.001
The Interstitium and Interstitial Fluid
• Interstitium and interstitial fluid (12 lt, ~1/6¨, -2 --- -3 mmHg)
• Two major types of structures
– Collagen fiber bundles
– Proteoglycan filaments
• Proteoglycan filaments: 98% hyaluronic acid and 2% protein
• “Gel” in the interstitium: because of large number of
proteoglycan filaments, it is difficult for fluid to flow easily
through tissue gel
• Interstitial fluid is the same as plasma except it contains low
concentrations of proteins
• Formation of edema… (%1 free fluid)
The Interstitium and Interstitial Fluid
Fluid filtration, hydrostatic and oncotic pressures
• The hydrostatic pressure in the capillary tends to force
fluid and its dissolved substances through the
capillary pores into the interstitial spaces
• Conversely, colloid osmotic pressure (oncotic
pressure) of the plasma proteins tends to cause fluid
movement by osmosis from the interstitial spaces into
the blood
• This oncotic pressure prevents significant loss of fluid
volume from blood
• Lymphatic system and recovery of proteins from the
interstitial space
Fluid filtration, hydrostatic and oncotic pressures
• Starling Powers:
• The hydrostatic pressure
• Kolloid osmotic pressure
(oncotic pressure)
Four primary hydrostatic and colloid osmotic forces
determine fluid movement through the capillary membrane
1) Capillary hydrostatic pressure (Pc)
2) Interstitial fluid (hydrostatic) pressure (Pif)
3) The capillary plasma colloid osmotic (oncotic)
pressure
4) Interstitial fluid colloid osmotic (oncotic) pressure
Net filtration pressure
• The net filtration pressure is positive, under
normal conditions
Capillary and Interstitial Hydrostatic Pressures
• Capillary hydrostatic pressure:
– Arterial end of capillary: 30 mmHg
– Venous end of capillary: 10 mmHg
• Interstitial fluid (hydrostatic) pressure:
• The true interstitial fluid pressure is negative,
averaging about -3 mmHg
• Pumping by the lymphatic system is the basic
cause of negative interstitial pressure
Plasma Colloid Osmotic (Oncotic) Pressure
• Proteins in the plasma cause oncotic pressure
– Non-permeability of plasma proteins
• Normal values: plasma oncotic pressure of normal
human plasma is about 28 mmHg
• 19 mmHg of this is caused by molecular effects of
dissolved proteins and 9 mmHg by Donnan effect (i.e.
Osmotic pressure caused by Na, K and other cations
held in the plasma by proteins)
• About 80% of plasma oncotic pressure results from
Albumin, 20% from globulin and almost none from
fibrinogen
Interstitial Fluid Colloid Osmotic (Oncotic)
Pressure
• Although size of the usual capillary pore is smaller
than the molecular sizes of the plasma proteins, this
is not true for all pores. Therefore, small amounts of
proteins leak into the interstitial space
• Presence of these proteins cause interstitial fluid
oncotic pressure (8 mmHg)
Exchange of Fluid Volume Through the
Capillary membrane
• The average capillary pressure at the arterial ends of
the capillaries is 15 to 25 mmHg greater than at the
venous ends.
• Because of this difference, fluid filters out of the
capillaries at the arterial end, but it is reabsorbed at
the venous end.
Analysis of the forces causing filtration at the arterial end of the capillary
Forces tending to move fluid outward:
Capillary pressure (arterial end of capillary) 30
Negative interstitial free fluid pressure 3
Interstitial fluid colloid osmotic pressure 8
total outward force 41
Forces tending to move fluid inward:
Plasma colloid osmotic pressure 28
Summation of forces:
Outward 41
Inward 28
net outward force (at arterial end) 13
Analysis of reabsorption at the venous end of the capillary
Forces tending to move fluid inward:
Plasma colloid osmotic pressure 28
total inward force 28
Forces tending to move fluid outward:
Capillary pressure (venous end of capillary) 10
Negative interstitial free fluid pressure 3
Interstitial fluid colloid osmotic pressure 8
total outward force 21
Summation of forces:
Inward 28
Outward 21
net inward force 7
Starling Equlibrium for Capillary Exchange
Mean forces tending to move fluid outward:
Mean capillary pressure 17.3
Negative interstitial free fluid pressure 3.0
Interstitial fluid colloid osmotic pressure 8.0
total outward force 28.3
Mean force tending to move fluid inward:
Plasma colloid osmotic pressure 28.0
total inward force 28.0
Summation of mean forces:
Outward 28.3
Inward 28.0
net outward force 0.3
Net Filtration
• Outward forces: 28.3 mmHg
• Inward forces: 28 mmHg
• This slight excess of filtration is called net filtration: 0.3 mmHg
• 2 ml / min in the body
• Abnormal imbalance of forces at the capillary membrane
• If the mean capillary pressure rises above 17 mmHg, the net
force increases.
• As a result fluid will accumulate in the interstitial space and
edema will result.
• Conversely, if the capillary pressure falls very low, net
reabsorption of fluid will occur and blood volume will
increase…
arterial end
venous end
Vasodilatator theory
• According to this theory, greater the rate of
metabolism or the less the availability of oxygen or
some other nutrients to the tissue, the greater the
rate of formation of vasodilatator substances
• Adenosine, CO2, adenosine phosphate compounds,
histamine, K ions and H ions
• Importance of adenosine in local vasodilatation
Oxygen lack theory for local blood flow control
• Vasomotion, metarteriole and precapillary sphincter
• Smooth muscle requires oxygen to remain contracted
Lymphatic System
• Consists of two semi-independent parts
– A meandering network of lymphatic vessels
– Lymphoid tissues and organs scattered
throughout the body
• Returns interstitial fluid and leaked plasma
proteins back to the blood
• Lymph – interstitial fluid once it has entered
lymphatic vessels
Lymphatic System: Overview
Lymphatic System
• Exceptions for the lymphatic system:
superficial portions of the skin, central
nervous system, endomyosium of muscles
and bones.
• But even these tissues have prelymphatics
through which interstitial fluid can flow
• Lymph vessels from lower parts of the
body – Thoracic Duct
Lymphatic System
• Lymph from the left side of the head, left
arm, and parts of the chest also goes into
thoracic duct
• Lymph from right side of the head, right
arm, and parts of the thorax enters the
right lymph duct which empties into the
venous blood at the right side (juncture of
jugular vein and right subclavian vein)
Lymphatic System: Overview
Lymphatic Capillaries
• Similar to blood capillaries, with modifications– Remarkably permeable– Loosely joined endothelial minivalves– Withstand interstitial pressure and remain open
• The minivalves function as one-way gates that:– Allow interstitial fluid to enter lymph capillaries– Do not allow lymph to escape from the capillaries
Lymphatic Capillaries
* Total quantity of lymph is normally only 2-3 liters/day
* This lymph is continually absorbed from the tissues by
lymphatic capillaries and returned to the blood circulation
Lymphatic Vessels
• A one-way system in which lymph flows toward the heart
• Lymph vessels include:– Microscopic, permeable, blind-ended
capillaries– Lymphatic collecting vessels– Trunks and ducts
Lymphatic Capillaries
• During inflammation, lymph capillaries can absorb:
– Cell debris
– Pathogens
– Cancer cells
• Cells in the lymph nodes:
– Cleanse and “examine” this debris
• Lacteals – specialized lymph capillaries present in
intestinal mucosa
– Absorb digested fat and deliver chyle to the blood
Rate of Lymph Flow
• Any factor increasing
interstitial fluid pressure
also increases lymph flow.
Such factors include
– Elevated capillary
pressure
– Decreased plasma colloid
osmotic pressure
– Increased interstitial fluid
colloid osmotic pressure
– Increased permeability of
the capillaries
• Maximum lymph flow rate
Lymphatic Pump
• Intrinsic intermittent contraction of the lymph vessel walls
• External factors:
– Contraction of surrounding skeletal muscles
– Movement of 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
Lymph Transport
• The lymphatic system lacks an organ that acts as a pump
• Vessels are low-pressure conduits
• Uses the same methods as veins to propel lymph– Pulsations of nearby arteries– Contractions of smooth muscle in the walls of
the lymphatics
www.youtube.com/watch?v=Kh-XdNnTZUo&feature=related
Lymphatic Pump
• Primary factors that determine the lymph flow:
– Interstitial fluid pressure
– Activity of the lymphatic pump
Interstitial Protein Concentration, Fluid Volume and Pressure
• The lymphatic system plays an important role in controlling
– protein concentrations in the interstitial fluid
– volume of interstitial fluid
– interstitial fluid pressure
• Significance of negative interstitial fluid pressure as a means for
holding the body tissues together
– Different tissues of the body are held together by connective
tissue fibers
– Skin sliding over the back of the hand and face
– It acts partially as a vacuum pump
– In its absence, edema develops.
Lymph Nodes
• Their two basic functions are:
– Filtration – macrophages destroy
microorganisms and debris
– Immune system activation – monitor for
antigens and mount an attack against them
Structure of a Lymph Node
http://trc.ucdavis.edu/biosci10v/bis10v/media/ch23/human_lymphatic.html
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