Microcirculation

Microcirculation & Lymphatics
 Submitted to: Mam Shazia
 Submitted by: Ayesha Saddiqa &
Maryam Jamil

MicrocirculationMicrocirculation
 The microcirculation is the blood flow through
blood vessels smaller than 100 µm (i.e.
arterioles, capillaries, and venules).
 Function:
 Transport of cells, oxygen and other substances to/from
the tissues
 Regulation of body temperature

Capillary Hydrostatic PressureCapillary Hydrostatic Pressure
 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 PressureCapillary Osmotic Pressure
 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.

MicrocirculationMicrocirculation
The total length of capillaries in an average adult human is approximately 42 000 km
(25,000 miles), this is approx. equator of Earth.

EndotheliumEndothelium
 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.

EndotheliumEndothelium
 Function
 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
 Atherosclerosis (patients with diabetes mellitus,
hypertension and hyperlipidemia)

ArteriolesArterioles
 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.
 This healthy condition is promoted by the 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 resistanceTotal peripheral resistance
 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 pressure are
typically about 0.15 to 0.20 of aortic mean blood
pressures.

CapillaryCapillary
 Capillaries, are the smallest of a body's blood vessels,
measuring 5-10 μm .
 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.

CapillaryCapillary
 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 signaling 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.

EndothelinEndothelin
 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 oxideNitric oxide
 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:
 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

Capillary pressuresCapillary pressures
 Middle pressure 25 mm Hg
 30-40 mm Hg by arterioles
 10-15 mm by venules
 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


Arterial end of capillaryArterial end of capillary
 Pressures going out of the capillary:
 Capillary pressure 30
 Pressure of interstitial fluid 3
 Oncotic pressure of ISF 8
41
 Pressures going into the capillary:
 Oncotic pressure of plasma 28
 Together 41-28=13 mmHg in direction out
of the capillary (0.5 % of plasma)

Venous end of capillaryVenous end of capillary
 Pressures going out of the capillary:
 Capillary pressure 10
 Pressure of interstitial fluid 3
 Oncotic pressure of ISF 8
21
 Pressures going into the capillary:
 Oncotic pressure of plasma 28
 Together 28-21=7 mmHg in direction into
the capillary (0.5 % of plasma)

Types of capillariesTypes of capillaries
 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.

Continuous capillary
 one of the two major types of capillarie
s, found in muscle, skin, lung, central n
ervous system,
and other tissues, characterized by the
presence of an uninterrupted endotheliu
m and a continuous basal lamina, and b
yfine filaments and numerous pinocytoti
c vesicles.

Fenestrated capillary
 one of the two major types of capillarie
s, found in the intestinal mucosa, renal
glomeruli,pancreas, endocrine glands, a
nd other tissues, and characterized by t
he presence of circular fenestrae or por
es thatpenetrate the endothelium; these
pores may be closed by a very thin dia
phragm.

Sinusoidal capillariesSinusoidal capillaries
 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.

VenuleVenuless
 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:
 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 systemLymphatic system
 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:
 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

LymphLymph
 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.

Lymph node
 A lymph node is an oval or kidney-
shaped organ of the lymphatic system,
distributed widely throughout the body
including the armpit and stomach and
linked by lymphatic vessels. Lymph
nodes are major sites of B, T, and
other immune cells.

Lymph node
 Lymph nodes are important for the
proper functioning of the immune
system, acting as filters for foreign
particles and cancer cells. Lymph
nodes do not deal with toxicity, which is
primarily dealt with by
the liver and kidneys.

Clinical significance
 They become inflamed or enlarged in various
infections and diseases which may range
from trivial throat infections, to life-
threatening cancers. The condition of the
lymph nodes is very important in cancer
staging, which decides the treatment to be
used, and determines the prognosis. When
swollen, inflamed or enlarged, lymph nodes
can be hard, firm or tender.

Lymphatic circulationLymphatic circulation
 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.

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.

Fatty Acid Transport SystemFatty Acid Transport System
 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 organsLymphoid organs
 The thymus, spleen, lymph nodes, peyer's patches, tonsils,
vermiform appendix, and red bone marrow are accessory
lymphoid tissues that comprise the lymphoid organs.
 These organs contain a net that support circulating B- and T-
lymphocytes and other immune cells like macrophages and dendritic
cells.
 Another sub-component of the lymphatic system is the
reticuloendothelial system.
 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.

ThymusThymus
 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.

SpleenSpleen
 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:
 Blood reservoir
 Destruction of old red blood cells
 Immune functions
 Blood cells production in embryogenesis

Fetal circulationFetal circulation
 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.
 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 circulationFetal circulation
 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 ofPostnatal development of
circulationcirculation
 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 andDifferences between fetal and
adult circulatory systemsadult circulatory systems
 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 hemoglobinFetal hemoglobin
 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 hemoglobinFetal hemoglobin
 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
 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.

Microcirculation

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