Physiology of

Microcirculation
Dr Anupama
The Blood Vessels and the Cardiovascular
System
• Arteries: blood from heart
– Strong & Elastic
– Conduct blood to capillaries
– Sphincters
• Capillaries: exchange with cells
• Veins
– Return blood to heart
– Valves
The microcirculation refers to the smallest blood
vessels in the body:
• the smallest arterioles
• the metarterioles
• the precapillary sphincters
• the capillaries
• the small venules
Functional element of microcirculation
• Microcirculatory part of vascular system
performs all blood functions.
• There are such types of vessels: arterioles,
metarterioles, capillaries and venuls.
• Mean diameter of these vessels is less than
100 mcm.
• Arterioles, capillary bed venuls and lymphatic
capillaries compose functional element of
microcirculation
Functional element of microcirculation
• Main processes as blood-tissue exchange or
lymph production are performed there.
• Mean diameter of capillaries is 3-6 mcm.
• The length of capillary vessel is near 750 mcm.
• Capillaries perform exchange in surface near
14000 mkm2.
• Blood flow velocity in capillaries consists near 0.3
mm/s, which permits passing erythrocytes
through capillary in 2-3 s.
 Endothelial cells—capillary
• are active elements of capillary bed.
• produce enzymes as antithrombin III
• endothelial relaxing factor,
• endothelial contracting factor,
• which may activate function of hormones and
neurotransmitters on vessel's wall or cause some
physiological effects.
• contain microfibrills,
• composed from actin, myosin and other contractive
elements.
• Such structures are directed along cell basis and binds
to cytoplasm in places of intracellular contacts.
 Endothelial cells—capillary
• When microfibrills contracting two kinds of effects may
be produced:
• both increasing intracellular split after contraction and
increasing cell height and its' prominence inside the
vessel.
• Capillary wall has small splits and a lot of pores.
• In kidneys glomeruls, intestinal epithelium, capillaries
are fenestrated.
• This specialty permits passing through endothelial cells
water, ions and other large molecules as aminoacids or
fructose.
• In red bone marrow, liver and spleen capillaries have
interrupted walls, which let passing even blood cells.
 Interstitial spaces
• Intracellular substance surrounds microcirculatory bed and
lymphatic capillaries.
• Intracellular substance is composed by net of collagen and
elastic fibers, which form small cavities filled in by gelatin-
like substance including proteins, ions and water.
• Intracellular space has filter system and reabsorbtive
system.
• Filter system in composed by capillary bed. Reabsorbtive
system includes lymphatic capillaries and venules.
• Due to convection and diffusion in fluid surroundings,
intracellular fluid streams from blood capillaries to
lymphatic capillaries.
 Transport of substances through capillary
membrane
• are lipid soluble as O2 or CO2 and water-soluble as ions or
glucose.
• Substances of molecule size more than 6-7 nm cannot diffuse
through intra-endothelial pores.
• The greater the concentration difference of a given substance on
two sides of capillary membrane, the greater will bi net rate of
diffusion.
• Forces that determine fluid movement through capillary
membrane are capillary pressure, interstitial fluid pressure,
plasma colloid osmotic pressure and interstitial fluid colloid
osmotic pressure.
• At arterial end of capillary pressure is higher than interstitial fluid
pressure, which causes filtration.
• At venous end of capillary plasma colloid osmotic pressure is
lower than interstitial pressure, which cause reabsorbtion.
 Structure and function of blood vessels

• 5 main types
– Arteries – carry blood AWAY from the heart
– Arterioles
– Capillaries – site of exchange
– Venules
– Veins – carry blood TO the heart

Copyright 2009, John Wiley & Sons, Inc.

 Basic structure

– 3 layers or tunics
1. Tunica interna (intima)
2. Tunica media
3. Tunica externa
– Modifications account for 5 types of blood vessels
and their structural/ functional differences

Copyright 2009, John Wiley & Sons, Inc.

Copyright 2009, John Wiley & Sons, Inc.
 Structure
• Tunica interna (intima)
– Inner lining in direct contact with blood
– Endothelium continuous with endocardial lining of heart
– Active role in vessel-related activities
• Tunica media
– Muscular and connective tissue layer
– Greatest variation among vessel types
– Smooth muscle regulates diameter of lumen
• Tunica externa
– Elastic and collagen fibers
– Vasa vasorum
– Helps anchor vessel to surrounding tissue

Copyright 2009, John Wiley & Sons, Inc.

 Arteries
– 3 layers of typical blood vessel
– Thick muscular-to-elastic tunica media
– High compliance – walls stretch and expand in
response to pressure without tearing
– Vasoconstriction – decrease in lumen diameter
• Vasodilation – increase in lumen diameter

Copyright 2009, John Wiley & Sons, Inc.

 Elastic Arteries

– Largest arteries
– Largest diameter but walls
relatively thin
– Function as pressure
reservoir
– Help propel blood forward
while ventricles relaxing
– Also known as conducting
arteries – conduct blood to
medium-sized arteries

Copyright 2009, John Wiley & Sons, Inc.

 Arteries
• Muscular arteries
– Tunica media contains more smooth muscle and fewer elastic
fibers than elastic arteries
– Walls relatively thick
– Capable of great vasoconstriction/ vasodilatation to adjust rate
of blood flow
– Also called distributing arteries
• Anastomoses
– Union of the branches of 2 or more arteries supplying the same
body region
– Provide alternate routes – collateral circulation

Copyright 2009, John Wiley & Sons, Inc.

 Arterioles
– Abundant microscopic vessels
– Metarteriole has precapillary sphincter which
monitors blood flow into capillary
– Sympathetic innervation and local chemical
mediators can alter diameter and thus blood flow
and resistance
– Resistance vessels – resistance is opposition to
blood flow
– Vasoconstriction can raise blood pressure

Copyright 2009, John Wiley & Sons, Inc.

 Capillaries
• Capillaries
– Smallest blood vessels connect arterial outflow and venous
return
– Microcirculation – flow from metarteriole through
capillaries and into postcapillary venule
– Exchange vessels – primary function is exchange between
blood and interstitial fluid
– Lack tunica media and tunica externa
• Substances pass through just one layer of endothelial cells and
basement membrane
– Capillary beds – arise from single metarteriole
• Vasomotion – intermittent contraction and relaxation
• Throughfare channel – bypasses capillary bed

Copyright 2009, John Wiley & Sons, Inc.

 Microcirculatory bed and functional types of
capillaries
• Depending on structure
• it distinguished three types of capillaries:
• somatic,
• visceral and sinusoidal.
• Capillaries walls are composed from one layer of endothelial cells
and basal membrane.
 Types of Capillaries
• 3 types
1. Continuous
– Endothelial cell
membranes from
continuous tube
2. Fenestrated
– Have fenestrations or
pores
3. Sinusoids
– Wider and more
winding
– Unusually large
fenestrations

Copyright 2009, John Wiley & Sons, Inc.

Arteries, Capillaries, and Venule

Copyright 2009, John Wiley & Sons, Inc.

 Veins
– Structural changes not as distinct as in arteries
– In general, very thin walls in relation to total
diameter
– Same 3 layers
• Tunica interna thinner than arteries
• Tunica interna thinner with little smooth muscle
• Tunica externa thickest layer
– Not designed to withstand high pressure
– Valves – folds on tunica interna forming cusps
• Aid in venous return by preventing backflow

Copyright 2009, John Wiley & Sons, Inc.

 Veins

• Portal vein – blood passes through second

capillary bed
– Hepatic or hypophyseal
• Venules
– Thinner walls than arterial counterparts
– Postcapillary venule – smallest venule
– Form part of microcirculatory exchange unit with
capillaries
– Muscular venules have thicker walls with 1 or 2
layers of smooth muscle

Copyright 2009, John Wiley & Sons, Inc.

Venous Valves

Copyright 2009, John Wiley & Sons, Inc.

 Blood Distribution

– Largest portion of
blood at rest is in
systemic veins and
venules
• Blood reservoir
– Venoconstriction
reduces volume of
blood in reservoirs
and allows greater
blood volume to flow
where needed

Copyright 2009, John Wiley & Sons, Inc.

 Capillary exchange
• Movement of substances between blood and
interstitial fluid
• 3 basic methods
1. Diffusion
2. Transcytosis
3. Bulk flow

Copyright 2009, John Wiley & Sons, Inc.

 Diffusion
– Most important method
– Substances move down their concentration gradient
• O2 and nutrients from blood to interstitial fluid to body cells
• CO2 and wastes move from body cells to interstitial fluid to blood
– Can cross capillary wall through intracellular clefts, fenestrations
or through endothelial cells
• Most plasma proteins cannot cross
• Except in sinusoids – proteins and even blood cells leave
• Blood-brain barrier – tight junctions limit diffusion

Copyright 2009, John Wiley & Sons, Inc.

 Transcytosis

– Small quantity of material

– Substances in blood plasma become enclosed
within pinocytotic vessicles that enter endothelial
cells by endocytosis and leave by exocytosis
– Important mainly for large, lipid-insoluble
molecules that cannot cross capillary walls any
other way

Copyright 2009, John Wiley & Sons, Inc.

 Bulk Flow
– Passive process in which large numbers of ions,
molecules, or particles in a fluid move together in
the same direction
– Based on pressure gradient
– Diffusion is more important for solute exchange
– Bulk flow more important for regulation of relative
volumes of blood and interstitial fluid
– Filtration – from capillaries into interstitial fluid
– Reabsorption – from interstitial fluid into
capillaries

Copyright 2009, John Wiley & Sons, Inc.

 NFP = (BHP + IFOP) – (BCOP + IFHP)

• Net filtration pressure (NFP) balance of 2

pressures
1. 2 pressures promote filtration
– Blood hydrostatic pressure (BHP) generated by
pumping action of heart
• Falls over capillary bed from 35 to 16 mmHg
– Interstitial fluid osmotic pressure (IFOP)
• 1 mmHg

Copyright 2009, John Wiley & Sons, Inc.

 NFP = (BHP + IFOP) – (BCOP + IFHP)

2. 2 pressures promote reabsorption

– Blood colloid osmotic pressure (BCOP) promotes
reabsorption
• Due to presence of blood plasma proteins to large to
cross walls
• Averages 36 mmHg
– Interstitial fluid hydrostatic pressure (IFHP)
• Close to zero mmHg

Copyright 2009, John Wiley & Sons, Inc.

 Starling’s Law
• Nearly as much reabsorbed as filtered
– At the arterial end, net outward pressure of 10
mmHg and fluid leaves capillary (filtration)
– At the venous end, fluid moves in (reabsoprtion)
due to -9 mmHg
– On average, about 85% of fluid filtered in
reabsorpbed
– Excess enters lymphatic capillaries (about 3L/ day)
to be eventually returned to blood

Copyright 2009, John Wiley & Sons, Inc.

Copyright 2009, John Wiley & Sons, Inc.
 Hemodynamics: Factors affecting blood flow

• Blood flow – volume of blood that flows through any

tissue in a given period of time (in mL/min)
• Total blood flow is cardiac output (CO)
– Volume of blood that circulates through systemic (or
pulmonary) blood vessels each minute
• CO = heart rate (HR) x stroke volume (SV)
• Distribution of CO depends on
– Pressure differences that drive blood through tissue
• Flows from higher to lower pressure
– Resistance to blood flow in specific blood vessels
• Higher resistance means smaller blood flow

Copyright 2009, John Wiley & Sons, Inc.

Arteries

endothelium
Smooth muscle cell layer

adventitia
 Veins
“Blood Reservoir”
70% of our blood volume
is on the venous side.
The Blood Vessels and the Cardiovascular
System

Figure 15-1: Functional model of the cardiovascular system

 Arterioles
• Major resistance vessels
• Arteriolar Resistance converts the pulsatile
systolic to diastolic pressure swings in the
arteries into the non-fluctuating pressure
present in the capillaries
• Radius supplying individual organs can be
adjusted independently to
– Distribute cardiac output among systemic organs,
depending on body’s momentary needs
– Help regulate arterial blood pressure
 Arterioles
• Mechanisms involved in adjusting arteriolar
resistance
– Vasoconstriction
• Refers to narrowing of a vessel
– Vasodilation
• Refers to enlargement in circumference and
radius of vessel
• Results from relaxation of smooth muscle layer
• Leads to decreased resistance and increased
flow through that vessel
Arteriolar Vasoconstriction and Vasodilation
Mechanisms for control of blood flow
to the various organs
• Blood flow to organ depends on the demands
of each organ.
a) Local control of blood flow is the primary
mechanism that matches the blood flow to
the metabolic needs of the organ.

b) Neural or Hormonal control is the other

mechanism.
 Arterioles
• Only blood supply to brain remains constant
• Changes within other organs alter radius of
vessels and adjust blood flow to organ
• Local chemical influences on arteriolar radius
– Local metabolic changes
– Histamine release
• Local physical influences on arteriolar radius
– Local application of heat or cold
– Chemical response to shear stress
– Myogenic response to stretch
 ARTERIOLES
• Many factors can increase or decrease the tone and can
cause vasoconstriction and vasodilation.
Causes of VASOCONSTRICTION
- Sympathetic Stimulation
- Epinephrine and Nor Epinephrine
- Angiotensin II
- Vasopressin
- Endothelin [from endothelial cells]
- O2

- CO2

- Cold
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 Arterioles
• Specific local chemical factors that produce
relaxation of arteriolar smooth muscle
– Decreased O2
– Increased CO2
– Increased acid
– Increased K+
– Increased osmolarity
– Adenosine release
– Prostaglandin release
 Arterioles
• Local vasoactive mediators
– Endothelial cells
• Release chemical mediators that play key role
in locally regulating arteriolar caliber
• Release locally acting chemical messengers in
response to chemical changes in their
environment
• Among best studied local vasoactive mediators
is nitric oxide (NO)
 Arterioles
• Extrinsic control
– Accomplished primarily by sympathetic nerve
influence
– Accomplished to lesser extent by hormonal
influence over arteriolar smooth muscle
• ARTERIES
• ARTERIOLES (pressure variability)
• METARTERIOLES (pressure variability)
• CAPILLARIES (microcirculation; low pressure)
• VENULES (microcirculation; low pressure)
• VEINS
Make Up of Blood Vessels: Arteries and
Arterioles

Figure 15-2: Blood vessels

 Metarterioles

• Bypass
capillaries
• Large cells
• Speed flow

Figure 15-3: Metarterioles

 Arteriole Resistance: Control of Local
Blood Flow
• Myogenic auto regulation
• Paracrines:
– Active hyperemia
– Reactive hyperemia
• Sympathetic nerves – CNS

• Not lecturing on it; but you are responsible for

this information.
 Capillary Blood Flow:
Greatest Total Cross Sectional Area

• Lowest Velocity
• Hydrostatic pressure
drops

Figure 15-17: The velocity of flow depends on the total cross-

sectional area
 Capillary Exchange:

• Filtration; leaves capillary

• Absorption; enters capillary
• Plasma (inside capillary)
• Interstitial fluid or ECF (outside capillary)
• Colloid osmotic pressure
• Created by proteins in the plasma (constant)
• Hydrostatic pressure- like holes in a garden hose.
• Decreases from artery to venous side!!!
 Capillary Exchange:
Colloidal Osmotic Pressure is Constant

Figure 15-18a: Fluid exchange at the capillary

 Net Out Flow Into ECF
• Net filtration – net absorption = net out flow
• About 2 L/day collected by lymph vessels

Figure 15-18b: Fluid exchange at the capillary

Capillary Exchange: Hydrostatic Pressure
Declines
• High on arterial side – bulk flow out
• Low on venous side – bulk flow in
• Fenestrations &/or leaky joints speed exchange

Figure 15-18a: Fluid exchange at the capillary

 SYMPATHETIC CONTROL OF
ARTERIOLE
• Sympathetic Control of Arterioles is important in
regulating blood pressure.
• Sympathetic ANS supplies arteriolar smooth
muscle all over body except brain.
• Increase sympathetic stimulation causes
arteriolar vasoconstriction.
• Decrease sympathetic stimulation causes
arteriolar vasodilation.
• There is no parasympathetic innervations to
arterioles.

66
CONTROL OF REGIONAL
BLOOD FLOW
 LOCAL CONTROL OF BLOOD FLOW

• A) Autoregulation – maintenance of
constant blood flow to an organ in spite
of fluctuations in BP.
E.g. brain – auto regulation is best
kidney – auto regulation is good
skeletal muscle – auto regulation is
poor
 LOCAL CONTROL OF BLOOD FLOW

• B) Active Hyperemia - When any tissue

becomes highly active [eg. Skeletal muscle
during exercise]. the rate of blood flow
through the tissue increases.

• C) Reactive hyperemia
When blood flow to a tissue is blocked for few
seconds and then is unblocked, the flow
through tissue increases almost 4-7 times
normal. The excess blood flow lasts long
enough to repay the tissue oxygen deficit that
has occurred during occlusion.
• Two basic mechanisms that explain local control of
blood flow
1. Myogenic theory
Increase in blood flow

Stretches the vessel

Contraction of vascular smooth muscle

Decrease blood flow back to normal
 2. Metabolic theory
Increase in rate of metabolism

Accumulation of vasodilator substances in active
tissues

Blood vessels dilate

Increase blood flow

Vasodilator metabolites
 O2 tension, H,  CO2 tension,  Temperature, K+,
lactate, Adenosine, Histamine.
• The term Microcirculation refers to the
functions of the capillaries and the
neighboring lymphatic vessels.

• 5 % of circulating blood volume is present

in the capillaries at any given time.

• This takes part into the exchange of

nutrients, gases and waste products
between the blood & tissues.
 The Microcirculation

● Important in the transport of nutrients to tissues

● Site of waste product removal
● Over 10 billion capillaries with surface area of 500-700 square
meters
● Solute and fluid exchange
• Arteriole  Meta arteriole  Capillaries 
Venules.

• Pre capillary sphincter is present at the junction

where the capillary arises from the Meta arteriole.
This opens and closes the entrance of capillary and
hence regulates the blood flow through the capillary.

• The capillary wall is thin & consists of a single layer

of endothelial cells on basement membrane. Pores
are present between the endothelial cells that allow
transport of substances including water.
 Types of capillaries

Classified according to the size of the pores

• Brain – the pores are very tight and allow only
very small molecules to pass thru.

• Kidney & Intestine - the pores are wider –

fenestrations

• Liver - the endothelium is discontinuous with

wide gaps between the cells.
 EXCHANGE OF SUBSTANCES ACROSS THE CAPILLARY
WALL

This occurs by.

• Simple diffusion Lipid soluble gases such as O2
& CO2 readily diffuse thru the endothelial
cells.

• Bulk Flow - the most important mechanism

for fluid transfer driven by Starlings forces.
 The rate of filtration at any point along the capillary depends
on a balance of forces – STARLINGS FORCES.

• 1. Capillary hydrostatic pressure

Arterial end = 37 mmHg
Venous end = 17 mmHg

• 2. Plasma colloid osmotic pressure = 25 mmHg

• 3. Interstitial hydrostatic pressure = 0 -1

• 4. Interstitial colloid osmotic pressure = 0 mmHg

Fluid movement = Kf [ (Pc – Pi) – ( Πc - Πi )
Kf = filtration coefficient
• Arteriolar end  fluid moves out into tissue spaces

• Venous end fluid enters into capillaries.

• Any decrease in plasma proteins (hypoproteinemia)

or increase in capillary hydrostatic pressure (cardiac
failure) causes edema. (abnormal increase in
interstitial fluid volume )

• Histamines, bradykinin increases capillary

permeability  edema.
 Starling’s forces across capillary wall

Filtration Absorption

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 Lymphatic circulation

• Lymphatic system is responsible for bringing

the interstitial fluid to vascular compartment.
• Normal 24 hrs lymph flow is 2-4 L

• Lymphatic capillaries lie in interstitial fluid

close to vascular capillaries ,these capillaries
merge into large lymphatic vessels &
eventually into largest vessel, thoracic duct
which empties into large veins .
84
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 Lymphatic circulation
• The interstitial fluid enter lymphatic capillaries
through loose junctions between endothelial
cells .
• Lymph flow back to the thoracic duct is
promoted by contraction of smooth muscle in
wall of lymphatic vessels & contraction of
surrounding skeletal muscle .
• Failure of lymphatic drainage can lead to
Edema .

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 What is Edema?

• Accumulation of fluid
beneath the skin or in a
body cavity

• Palpable swelling produced

by expansion of the
interstitial fluid volume
Edema; increase in hydrostatic
pressure

Abnormal
swelling
 Causes of Edema
• Increase capillary
pressure
– Increase vascular
volume
• Heart failure
• Kidney disease
• Pregnancy
• Environmental heat stress
– Venous obstruction
• Thrombosis
• Liver disease
• Decrease colloidal
osmotic pressure
– Increase loss of proteins
• Nephrotic syndrome
• Burns
– Decrease production
• Starvation, Malnutrition
• Liver disease
 Causes of Edema
• Increase capillary • Obstruction of
permeability lymphatic flow
– Inflammation – Surgical removal of
– Allergic reaction lymph nodes
– Tissue injury – Malignant
– Malignancy obstruction
– Infection ( filariasis)
 Lymphatic System: Structure and Roles
• Lymphatic structures
(overview)
– Capillaries with valves
– Lymph vessels
– Lymph nodes & organs

• Immune defense
• Transport of fats
• Collects excess ECF
– Returns to plasma
– Edema
Lymphatic System: Structure and Roles
(overview)

Figure 15-19: The lymphatic system

Lymph Node; Immune function