Transcript Microcirculation

Microcirculation, lymphatic
system, specific blood circulatory
systems (fetal circulation)
Romana Šlamberová, MD PhD
Department of Normal, Pathological and
Clinical Physiology
Introduction
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Slides from the lecture.
Respecting the copyrights it was not
possible to publish pictures showed at the
lecture at our website.
© 2006, Romana Slamberova, MD PhD
Microcirculation (1)
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The microcirculation is
the blood flow through
blood vessels smaller
than 100 µm (i.e.
arterioles, capillaries,
and venules).
Function:
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Transport of cells, oxygen
and other substances
to/from the tissues
Regulation of body
temperature
Capillary Hydrostatic Pressure
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This pressure drives fluid out of the capillary (i.e., filtration),
and is highest at the arteriolar end of the capillary and lowest
at the venular end.
Depending upon the organ, the pressure may drop along the
length of the capillary (axial pressure gradient) by 15-30
mmHg.
The axial gradient favors filtration at the arteriolar end (where
PC is greatest) and reabsorption at the venular end of the
capillary (where PC is the lowest).
The average capillary hydrostatic pressure is determined
by arterial and venous pressures (PA and PV), and by the ratio
of post-to-precapillary resistances (RV/RA).
PC is more sensitive to changes in PV than by changes
in PA.
Capillary Osmotic Pressure
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Osmotic pressure is the hydrostatic pressure produced by a
solution in a space divided by a differentially permeable
membrane due to a differential in the concentrations of solute.
Because the capillary barrier is readily permeable to ions, the
osmotic pressure within the capillary is principally determined
by plasma proteins that are relatively impermeable.
Therefore, instead of speaking of "osmotic" pressure, this
pressure is referred to as the "oncotic".
Albumin generates about 70% of the oncotic pressure. This
pressure is typically 25-30 mmHg.
The oncotic pressure increases along the length of the capillary,
particularly in capillaries having high net filtration (e.g., in renal
glomerular capillaries), because the filtering fluid leaves behind
proteins leading to an increase in protein concentration.
Microcirculation (2)
The total length of capillaries in an average adult human is approximately 42 000 km
(25,000 miles), this is approx. equator of Earth.
Endothelium (1)
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The endothelium (0.5 μm) is
the layer of thin specialized
epithelium, comprised of a
single layer of flat cells that line
the interior surface of blood
vessels, forming an interface
between circulating blood in the
lumen and the rest of the vessel
wall.
Space between cells 6-7 nm
(little bit less than albumin)
Endothelial cells line the entire
circulatory system, from the
heart (endocardium) to the
smallest capillary.
Both blood and lymphatic
capillaries are composed of a
single layer of endothelial cells.
Endothelium (2)
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Function
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vasoconstriction and vasodilation, and hence the control
of blood pressure
blood clotting (thrombosis & fibrinolysis)
formation of new blood vessels (angiogenesis)
inflammation and swelling (oedema)
transit of white blood cells
Pathology
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Atherosclerosis (patients with diabetes mellitus,
hypertension and hyperlipidemia)
Arterioles
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An arteriole is a small diameter (<20 μm, up to 5-9 μm) blood
vessel that extends and branches out from an artery and leads to
capillaries.
Arterioles have thin muscular walls (usually only one to two layers of
smooth muscle) and are the primary site of vascular resistance.
In a healthy vascular system the endothelium, inner lining of
arterioles and other blood vessels, is smooth and relaxed.
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This healthy condition is promoted by the ample production of nitric
oxide in the endothelium.
The mean blood pressure in the arteries supplying the body is a
result of the interaction between the cardiac output (the volume of
blood the heart is pumping per minute) and the vascular resistance,
usually termed total peripheral resistance.
Any pathology which constricts blood flow, such as stenosis, will
increase total peripheral resistance and lead to hypertension.
Total peripheral resistance
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Total peripheral resistance refers to the
cumulative resistance of the thousands of arterioles
in the body, or the lungs, respectively.
It is approximately equal to the resistance of the
arterioles, since the arterioles are the chief resistance
vessels in the body.
Total Peripheral Resistance = Mean Arterial
Pressure / Cardiac Output.
The total peripheral resistance of healthy lung
arterioles is typically about 0.15 to 0.20 that of the
body, so pulmonary artery mean blood pressures are
typically about 0.15 to 0.20 of aortic mean blood
pressures.
Capillary (1)
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Capillaries, are the smallest of a body's blood vessels,
measuring 5-10 μm (erythrocytes?).
They connect arteries and veins, and most closely interact
with tissues.
Capillaries have walls composed of a single layer of cells, the
endothelium.
This layer is so thin that molecules such as oxygen, water and
lipids can pass through them by diffusion and enter the
tissues.
Waste products such as carbon dioxide and urea can diffuse
back into the blood to be carried away for removal from the
body.
Capillary permeability can be increased by the release of
certain cytokines.
Capillary (2)
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The "capillary bed" is the network of capillaries
supplying an organ.
The more metabolically active the cells, the more
capillaries it will require to supply nutrients.
The capillary bed usually carries no more than 25%
of the amount of blood it could contain, although this
amount can be increased through autoregulation (i.e.
active muscle cells) by inducing relaxation of smooth
muscle.
Any signalling molecules they release (such as
endothelin for constriction and Nitric oxide for
dilation) act on the smooth muscle cells in the walls
of nearby, larger vessels, e.g. arterioles.
Endothelin
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Endothelin is a 21-amino acid vasoconstricting
peptide that plays a key part in vascular
homeostasis = one of the strongest
vasoconstrictors.
In a healthy individual a delicate balance between
vasoconstriction and vasodilation is maintained by
endothelin, calcitonin (vasoconstrictors) and by
nitric oxide, prostacyclin (vasodilators).
Overproduction of endothelin can cause pulmonary
artery hypertension.
Nitric oxide
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The chemical compound nitric oxide is a gas with chemical
formula NO.
In the body, nitric oxide (the 'endothelium-derived relaxing
factor', or 'EDRF') is synthesized from arginine and oxygen by
various nitric oxide synthase (NOS) enzymes and by sequential
reduction of inorganic nitrate.
Function:
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The endothelium (inner lining) of blood vessels use nitric oxide to signal
the surrounding smooth muscle to relax, thus dilating the artery and
increasing blood flow.
Nitric oxide is a key biological messenger, playing a role in a variety of
biological processes (vessel dialatation, neurotransmission, penile
erections, hair growth / loss).
"Nitro" vasodialators such as nitroglyceric are converted to nitric oxide.
Immune system: generated by macrophages, toxic to bacteria and
other human pathogens.
Capillary pressures
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Middle pressure 25 mm Hg
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Oncotic pressure 28 mm Hg
19 mm Hg because of proteins
 9 mm Hg because of some cations
Because of differences in capillary pressures by arterioles and venules
 Venous end has lower pressure, but there is higher permeability therefore 90 % of liquid that goes out at arterial end comes back at
venous end.
Balance disorder
 Increase of capillary pressure of 20 mmHg increases filtration pressure
cca 68x
 Lymphatic system is not able to accomodate the increase of IC liquid =
results in oedemas
 The oposite – when capillary pressure is lower, the IC liquid decreases
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30-40 mm Hg by arterioles
10-15 mm by venules
Arterial end of capillary
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Pressures going out of the capillary:
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30
3
8
41
Pressures going into the capillary:
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Capillary pressure
Pressure of intestitial fluid
Oncotic pressure of ISF
Oncotic pressure of plasma
28
Together 41-28=13 mmHg in direction out
of the capillary (0.5 % of plasma)
Venous end of capillary
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Pressures going out of the capillary:
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10
3
8
21
Pressures going into the capillary:
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Capillary pressure
Pressure of intestitial fluid
Oncotic pressure of ISF
Oncotic pressure of plasma
28
Together 28-21=7 mmHg in direction into
the capillary (0.5 % of plasma)
Types of capillaries
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Continuous - Continuous capillaries have a
sealed epithelium and only allow small
molecules, water and ions to diffuse.
Fenestrated - Fenestrated capillaries (as their
name implies "fenster") have openings that
allow larger molecules to diffuse.
Sinusoidal - Sinusoidal capillaries are special
forms of fenestrated capillaries that have larger
openings in the epithelium allowing RBCs and
serum proteins to enter.
Sinusoidal capillaries
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A sinusoid is a type of a capillary with a fenestrated
endothelium.
Located in: liver, lymphoid tissue, endocrine organs,
and hematopoietic organs (bone marrow, spleen).
Their highly permeable nature, which is due to larger
inter-cellular clefts allows small and medium-sized
proteins such as albumin to enter and leave the blood
stream.
Some spaces are large enough for blood cells to pass.
Liver sinusoids are equipped with Kupffer cells that
can take up and destroy foreign material such as
bacteria entering the sinusoids.
Venules
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A venule is a small blood vessel that allows
deoxygenated blood to return from the capillary beds
to the larger blood vessels called veins.
Venules have three layers:
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An inner endothelium composed of squamous epithelial
cells that act as a membrane
a middle layer of muscle and elastic tissue (poorly
developed so that venules have thinner walls than
arterioles)
an outer layer of fibrous connective tissue.
Lymphatic system
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The lymphatic system is a complex network of
lymphoid organs, lymph nodes, lymph ducts,
and lymph vessels that produce and transport lymph
fluid from tissues to the circulatory system.
The lymphatic system is a major component of the
immune system.
Functions:
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removal of excess fluids from body tissues
absorption of fatty acids and subsequent transport of fat and
chyle to the circulatory system
production of immune cells (such as lymphocytes,
monocytes, and antibody producing cells called plasma cells)
Lymph
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Lymph originates as blood plasma that leaks from the
capillaries of the circulatory system, becoming interstitial fluid,
and filling the space between individual cells of tissue.
Plasma is forced out of the capillaries by hydrostatic pressure,
and as it mixes with the interstitial fluid, the volume of fluid
accumulates slowly.
Most of the fluid is returned to the capillaries by osmosis (about
90% of the former plasma).
The excess interstitial fluid is collected by the lymphatic
system by diffusion into lymph capillaries, and is processed by
lymph nodes prior to being returned to the circulatory system.
Once within the lymphatic system the fluid is called lymph,
and has almost the same composition as the original interstitial
fluid.
Lymphatic circulation (1)
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The lymphatic system acts as a secondary circulatory system, except
that it collaborates with white blood cells in lymph nodes to protect the
body from being infected by cancer cells, fungi, viruses or bacteria.
Unlike the circulatory system, the lymphatic system is not closed
and has no central pump; the lymph moves slowly and under low
pressure due to peristalsis, the operation of semilunar valves in the
lymph veins, and the milking action of skeletal muscles.
Like veins, lymph vessels have one-way, semilunar valves and
depend mainly on the movement of skeletal muscles to squeeze fluid
through them.
Rhythmic contraction of the vessel walls may also help draw fluid into
the lymphatic capillaries.
This fluid is then transported to progressively larger lymphatic vessels
culminating in the right lymphatic duct (for lymph from the right
upper body) and the thoracic duct (for the rest of the body); these
ducts drain into the circulatory system at the right and left subclavian
veins.
Lymphatic circulation (2)
 The thoracic duct, is an important part
of the lymphatic system—it is the largest
lymphatic vessel in the body.
 It collects most of the lymph in the body
(except that from the right arm and the
right side of the chest, neck and head,
which is collected by the right lymphatic
duct) and drains into the systemic (blood)
circulation.
 The thoracic duct drains into the left
subclavian vein.
 In an adult, the thoracic duct transports up to
4 L of lymph per day. When the thoracic duct
is blocked or damaged a large amount of
lymph can quickly accumulate in the pleural
cavity, this situation is called chylothorax.
The first sign of a malignancy
(intraabdominal) = enlarged Virchow's
node (lymph node in the left
supraclavicular area).
Fatty Acid Transport System
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Lymph vessels are present in the lining of the GIT.
While most other nutrients absorbed by the small
intestine are passed on to the portal venous system
to drain, via the portal vein, into the liver for
processing, fats are passed on to the lymphatic
system, to be transported to the blood circulation
via the thoracic duct.
The enriched lymph originating in the lymphatics of
the small intestine is called chyle.
The nutrients that are released to the circulatory
system are processed by the liver.
Lymphoid organs
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The thymus, spleen, lymph nodes, peyer's patches, tonsils,
vermiform appendix, and red bone marrow are accessory
lymphoid tissues that comprise the lymphoid organs.
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These organs contain a net that support circulating B- and Tlymphocytes and other immune cells like macrophages and dendritic
cells.
Another sub-component of the lymphatic system is the
reticuloendothelial system.
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When micro-organisms invade the body or the body encounters other
antigens, those are transported from the tissue to the lymph circulation.
The lymph nodes filter the lymph fluid and remove foreign material, such
as bacteria and cancer cells. Specialized cells called macrophages and
dendritic cells phagocytose pathogens and present antigens to
lymphocytes.
When these pathogens are recognized, the lymph nodes enlarge and
additional immune cells are produced to help fight the infection.
Thymus
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The thymus is an organ located
in the upper anterior portion of
the chest cavity.
The thymus plays an important
role in the development of the
immune system in early life, and
its cells form a part of the body's
normal immune system.
It is most active before puberty,
after which it shrinks in size and
activity in most individuals and is
replaced with fat.
Function: Production
(maturation) of T cells.
Spleen
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The spleen is located in the upper left part of the abdomen,
behind the stomach and just below the diaphragm.
The spleen is the largest collection of lymphoid tissue in the
body.
It is regarded as one of the centres of activity of the
reticuloendothelial system.
Its absence leads to a predisposition to certain infections.
Function:
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Blood reservoir
Destruction of old red blood cells
Immune functions
Blood cells production in embryogenesis
Fetal circulation (1)
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The circulatory system of a
human fetus works differently
from that of born humans,
mainly because the lungs are
not in use: the fetus obtains
oxygen and nutrients from
mother through the placenta
and the umbilical cord.
Blood from the placenta is
carried by the umbilical vein.
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About half of this enters the
ductus venosus and is carried to
the inferior vena cava,
while the other half enters the
liver proper from the inferior
border of the liver.
Fetal circulation (2)
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The blood then moves to the right atrium of the heart. In the fetus, there is
an opening between the right and left atrium (the foramen ovale), and most
of the blood flows from the right into the left atrium, thus bypassing
pulmonary circulation.
The majority of blood flow is into the left ventricle from where it is pumped
through the aorta into the body.
Some of the blood moves from the aorta through the internal iliac arteries to
the umbilical arteries, and re-enters the placenta, where carbon dioxide
and other waste products from the fetus are taken up and enter the
mother's circulation.
Some of the blood from the right atrium does not enter the left atrium, but
enters the right ventricle and is pumped into the pulmonary artery.
In the fetus, there is a special connection between the pulmonary artery and
the aorta, called the ductus arteriosus, which directs most of this blood
away from the lungs (which aren't being used for respiration at this point as
the fetus is suspended in amniotic fluid).
Postnatal development of
circulation
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With the first breath after birth, the pulmonary resistance is
dramatically reduced. More blood moves from the right atrium to the
right ventricle and into the pulmonary arteries, and less flows
through the foramen ovale to the left atrium.
The blood from the lungs travels through the pulmonary veins to the
left atrium, increasing the pressure there.
The decreased right atrial pressure and the increased left atrial
pressure pushes the septum primum against the septum secundum,
closing the foramen ovale, which now becomes the fosse ovalis.
This completes the separation of the circulatory system into the left
and the right.
The ductus arteriosus normally closes off within one or two days
of birth, leaving behind the ligamentum arteriosum.
The umbilical vein and the ductus venosus closes off within two
to five days after birth, leaving behind the ligamentum teres and
the ligamentum venosus of the liver respectively.
Differences between fetal and
adult circulatory systems
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The fetal foramen ovale - the adult fosse ovalis.
The fetal ductus arteriosus - the adult ligamentum arteriosum.
The extra-hepatic portion of the fetal left umbilical vein - the
adult ligamentum teres hepatis (the "round ligament of the
liver").
The intra-hepatic portion of the fetal left umbilical vein (the
ductus venosus) - the adult ligamentum venosum.
The proximal portions of the fetal left and right umbilical
arteries - the adult umbilical branches of the internal iliac
arteries.
The distal portions of the fetal left and right umbilical arteries the adult medial umbilical ligaments.
Fetal hemoglobin differs from adult hemoglobin.
Fetal hemoglobin (1)
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Fetal hemoglobin differs most
from adult hemoglobin in that
it is able to bind oxygen
with greater affinity than
the adult form, giving the
developing fetus better access
to oxygen from the mother's
bloodstream.
The P50 value for fetal
hemoglobin (i.e., the partial
pressure of oxygen at which
the protein is 50% saturated;
lower values indicate greater
affinity) is roughly 19 mmHg,
whereas adult hemoglobin has
a value of approximately
26.8 mmHg.
Fetal hemoglobin (2)
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At birth, fetal hemoglobin comprises 50-95% of the child's
hemoglobin.
These levels decline after six months as adult hemoglobin
synthesis is activated, while fetal hemoglobin synthesis is
deactivated.
Soon after, adult hemoglobin (hemoglobin A) takes over as the
predominant form of hemoglobin in normal children.
Neonatal jaundice tends to develop because of two factors
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the breakdown of fetal hemoglobin as it is replaced with adult
hemoglobin
the relatively immature hepatic metabolic pathways, which are
unable to conjugate bilirubin as fast as an adult.