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Histology of Circulatory System

By: Daniel T.

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Objectives
After the end of this chapter, the
students will be able to:
• List the general function of circulatory
system
• Describe the difference between
cardiovascular system and lymphatic
system
• Identify the histology of heart and blood
vessels
• Identify the functional histology of
lymphoid organs

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Circulatory System
• Ensures continuous uninterrupted movement of all
body fluids (blood, lymph & CSF) throughout the body.
• Functions:
– Transport oxygen, nutrients and hormones to the
body tissues
– Transport CO2 & other metabolic wastes away from
the tissues
– Deliver blood and immune cells throughout the
body
– Regulates body temperature

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Circulatory System
• It contains two subsystem :

– Cardiovascular System/Blood Vascular System &

– Lymph Vascular System

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Cardiovascular System/Blood Vascular System
 Cardiovascular system is consists of:
• Heart: propels blood through the system
• Arteries: series of vessels efferent from
the heart that becomes smaller as they
branch into various organs.
– Carry blood to the tissues.
• Capillaries: smallest vessels
– Site of O2, CO2, nutrient and waste
product exchange between blood and
tissues
– Form a complex anastomosing
tubules called microvasculature or
microvascular bed.
• Veins: result from the convergence of
venules into a system of larger channels
that continue enlarging as they approach
the heart.
– Return blood from tissue to the heart

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Lymphatic Vascular System
• Begins in the lymphatic capillaries, closed ended tubules that
anastomose to form vessels of steadily increasing size.
• These vessels terminate in the blood vascular system , emptying
into the large veins near the heart.
• One of the functions of the lymphatic system is to return the
fluid of the tissue spaces to the blood.
• Lacks pump and includes three vessel types:
– Lymphatic capillaries
– Lymphatic vessels
– Lymphatic Duct
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Circulatory System
• Closed cardiovascular system - blood never leaves the
network of arteries, veins and capillaries.

• The lymphatic system is an open system.

• The internal surface of all components of the blood


and lymphatic systems is lined by a single layer of a
squamous epithelium, called endothelium.

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Heart
• Hollow muscular organ

• Has four chambers: 2As: receive; 2Vs:


pump

• Right side carry poorly oxygenated blood


while the left side carry well oxygenated
blood

• Atria and ventricles communicate via


atrioventricular orifice

• Valves (one-way-flow)

• Surrounded by a fibro-serous sac =


Pericardium
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Walls of the heart
 Has three tunics (coats):
1. Endocardium:
• Innermost layer
• Homologous to intima of the vessels
• Has three components:
– Endothelium- single layer of squamous epithelium,
underlain by a thin, continuous basal lamina.
– Subendothelial connective tissue- with elastic fibers and
smooth muscles.
– Subendocardium- layer of areolar tissue with small blood
vessels, nerves and in the ventricles branches of the impulse
conducting system.
• Merges with the myocardium
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Walls of the heart
2. Myocardium
• Middle layer, homologous to the tunica media of
vessels
• Constitute the main mass of the heart
• Consist mainly of cardiac muscle fibers.
• Responsible for the pumping action of heart
• Contains the impulse conducting system and parts of
the cardiac skeleton.
• Much thicker in walls of ventricles, particularly the left,
than in the atrial walls.

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Myocardium

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Walls of the heart
Atrial cardiac muscle:
• Arranged in overlapping network giving the inner
surface of the atria a woven appearance
• Have granules containing atrial natriuretic factor
• Have less extensive T- tubule system
• Have more gap junctions
• Conduct impluses at a higher rate
• Contract more rhythmically than the ventricular
muscles

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Walls of the heart
Ventricular layers of cavity
• Comprises complex layers of cells that wound helically
around the ventricular cavity
• This arrangement and in wringing out the heart during
contraction which maximizes the percentage of blood
in the cavity that is expelled during contraction

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1. contractile cells (specialized muscle: cardiomyocytces)
•contract to propel blood into aorta for distribution to the body tissues.
•Pumping action of the heart.
•Unlike skeletal muscle fibers, cardiac musculature is not a syncytium.

2. Impulse-generating + conducting cells


Responsible for electrical signal that initiates the heartbeat.

Trabeculation is most marked in ventricles.

Elastic fibers are scarce in myocardium of ventricles,


plentiful in atrial myocardium.

In both ventricles raised mounds of cardiac muscle


(papillary muscles) protrude into ventricular lumina &
point towards the AV valves.

Papillary muscles are the sites of attachment of


chordae tendinae.

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Walls of the heart
3. Epicardium
• Outermost layer
• Corresponds to the visceral layer of the pericardium.
• Is a simple squamous epithelium (mesothelium) supported
by a layer of loose connective tissue containing blood
vessels and nerves.
• The adipose tissue that generally surrounds the heart
accumulates in this layer
• The Epicardium is reflected back at the great vessels
entering and leaving the heart

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Epicardium
Low power view of epicardium of the ventricle.

ad = adipose tissue
bv = blood vessel
nv = nerve
Myo = myocardium

High power view of epicardium

ad = adipose tissue
bv = blood vessel
meso = mesothelium
nv = nerve The nuclei of the mesothelial cells
can be distinguished (albeit with
difficulty) at this magnification.
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Cardiac Valves
• Controls the direction of blood flow through the heart
• Regardless of their location, the valves are similar in
histologic structure.
• The valves are attached to the annuli fibrosi.
• Has connective tissue core covered by endocardium
• Scattered smooth muscle cells are present on the atrial
side of the valves
• Elastic fibers are prominent on the ventricular side

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Cardiac Skeleton
• Fibrous skeleton of the heart
• Made up of dense irregular
fibrous connective tissue
• Located at the level of four
cardiac valves.
• Functions:
– Anchor and support heart
valves
– Insertion for bundles of
cardiac muscle fibers
– Coordinate the heartbeat by
acting as electrical insulation
between atria and ventricles

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Cardiac Skeleton
 Has three major components:
• Annuli fibrosa:
– Rings of dense connective tissue
– Surround and reinforce the valve openings in the atrioventricular
canals and at the origins of the aorta and pulmonary artery
• Trigona fibrosa:
– Are two triangular dense connective tissue masses mainly around
the cuspal area of aortic valve
– Link the aortic root to the atrioventricular annuli
– Occasionally containing some cartilage and in old age may undergo
calcification.
• Septum membranaceum:
– Is a fibrous plate forming the top of the muscular interventricular septum
– Provides attachment for septal leaf of the tricuspid valve.

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Impulse generation and conducting system
of the heart
• Consists of structures that
makes atria + ventricles to
beat in succession and
• Thus, permit the heart to
function as an efficient
pump.
• These structures are:
 Sinoatrial node (pacemaker)
 Atrioventricular node
 Atrioventricular bundle (of
His)
 Purkinje fibers
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Impulse generation and conducting system
of the heart
 Sinoatrial node:
• Small cell mass in the right atrium’s
median wall, near the opening of the
superior vena cava
• Has the fastest intrinsic rhythm,
hence, they set pace for the rest of
the heart.
• Intercalated discs are lacking
between cells of the sinoatrial nodes
• Impulse generated in the SA node
travel slowly through ordinary atrial
cardiac muscle to the AV node.
• Slow conduction allows the atria to
complete their contraction before
ventricles begin theirs.
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Impulse generation and conducting system
of the heart
 Atrioventricular node
• A cell cluster on the right side
of the interatrial septum just
above TV.
• As an impulse leaves the AV
node, it passes rapidly along
the atrioventricular bundle
• The slowest conducting fibers
in the heart.

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Impulse generation and conducting system
of the heart
 AV Bundle:
• Located in the membranous
part of the IV septum and
penetrate the annulus fibrous
skeleton
• The bundle divides into two
trunks that pass into the
ventricles.

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Impulse generation and conducting system
of the heart
 Purkinje fibers (cells):
• Larger modified cardiac muscle cells.
• Contain more sarcoplasm
• Sparse myofibrils located peripherally
• The fibers are rich in glycogen and
mitochondria and often binucleated.
• Intercalated discs are uncommon, but
numerous desmosomes along cell
boundaries.
• Purkinje fibers are the fastest
conducting fibers in the heart.

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The SA node sends out a
stimulus, which cause the
atria to contract.
When this stimulus reaches
the AV node, it signals the
ventricles to contract.
Impulses pass down the two
branches of the
atrioventricular bundle to the
Purkinje fibers, and
thereafter the ventricles
contract.

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Cross section of Purkinje fibres

bv = blood vessel
CT = connective tissue
n = Purkinje cell nucleus

Regular cardiac fibres in cross section

bv = blood vessel
n = nucleus of blood vessel

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Blood Vessels

The blood vessels contains:

• Anatomically: outer wall & the interior lumen, a


central fluid containing hollow space surrounded by
the wall.

• Histologically: three basic layers or tunics (L. tunica,


coat) in the wall:
 Tunica intima (internal)
 Tunica media (middle)
 Tunica adventitia (externa)

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Structural Plan of Blood Vessels
• Consist of concentric layers or "tunics" of different tissue types

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Tunica Intima
• Innermost layer, bordering the lumen
• It consists:
A. Endothelium
• A single layer of extremely flattened endothelial cells (simple
squamous epithelium) lining the lumen.
• Supported by a basal lamina & a delicate fibroelastic collagenous
CT.
• The nucleus causes that part of the cell to bulge into the capillary
lumen.
B. Subendothelial CT layer
• Is a thin loose areolar CT layer containing occasional smooth muscle
cells formerly known as myointimal cells.
C. An internal elastic lamina.
• Thin elastic tissue layer
• In arteries, the intima is separated from the media by an internal
elastic lamina.

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Elastic artery
Muscularr artery prepared
stained by Weigert's
by HE staining
method

The tunica media of a muscular artery contains predominantly smooth muscle, whereas the tunica media of an elastic artery
is formed by layers of smooth muscle intercalated by elastic laminas. The adventitia and the outer part of the media have
small blood vessels (vasa vasorum) and elastic and collagenous fibers. 31
Cross sections of
small arteries.
A: The elastic
lamina is not
stained and is seen
as a pallid lamina
of scalloped
appearance just
below the
endothelium
(arrowhead).
Medium
magnification.
B: A small artery
with a distinctly
stained internal
elastic lamina
(arrowhead).
Low magnification.
(From a
preparation of the
late G Gomori.)

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Tunica Media
• An intermediate muscular or elastic tissue wall
• Consists primarily of concentric layers of helically arranged
smooth muscle cells.
• Interposed among these cells are variable amounts of:
– Elastic fibers and lamellae
– Reticular fibers
– Proteoglycans, and
– Glycoproteins
• In arteries, the media has a thinner external elastica lamina,
which separates it from the tunica adventitia.
• Arteries generally have thicker media than veins

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Tunica Adventitia
• Outermost layer
• Attaches the vessel to the neighboring tissue
• Consists principally of collagen type I and elastic fibers.
• It becomes loose CT near the outer portion of the vessel.
• In large vessels, it contains:
– Vasa vasorum : blood vessels of the blood vessels,
which supply the vessel wall.
– Nervi vascularis : nerves of the blood vessels, which
supply the vessel wall.
• In veins, it is the thickest layer.

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Vasa Vasorum
• Large vessels usually have vasa
vasorum ("vessels of the vessel"),
which are arterioles, capillaries, and
venules that branch profusely in the
adventitia and the outer part of the
media.
• Vasa vasorum provide metabolites
to the adventitia and the media,
since in larger vessels the layers are
too thick to be nourished solely by
diffusion from the blood in the
lumen.
• Vasa vasorum are more frequent in (vasa vasorum)
veins than in arteries.
• In arteries of intermediate and large
diameter, the intima and the most
internal region of the media are
devoid of vasa vasorum.
• These layers receive oxygen and
nutrition by diffusion from the Transverse section showing part of a muscular
blood that circulates into the lumen (medium caliber) artery. Small blood vessels (vasa
of the vessel. vasorum) are observed in the tunica adventitia. 35
Types of Blood Vessels
A. Arteries
• Carry blood away from the heart
• Delivers oxygenated blood with the exception of the
pulmonary and umbilical arteries.
• Have thicker tunica media than do veins.
• In cross- sections through paired vessels, arteries appear
more round than veins, with thicker walls and smaller
lumens.
• Classified into three types:
– Elastic (large or conducting) arteries
– Muscular (Medium, Distributing) arteries
– Small arteries or arterioles (< 0.5 mm in φ ).
• NB: These types are all continuous with one another.
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Elastic Arteries
• Larger diameter arteries in the body
• Conduct blood away from the heart
• Tunica intima is very thick and rest on basement
membrane of elastic fibers
• Endothelium rest on thin basal lamina underlain by thick
subendothelial connective tissue
• Internal lamina may be present
• The connective tissue fibers of the subendothelial layers
are longitudinally arranged.
• Tunica media contains abundant elastin as concentric,
fenestrated membranes that increase in number with age.

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Elastic Arteries…
• Several circular layers of elastic muscle fibers lie
between elastic membranes of media.

• Tunica adventitia is thin relative to vessel diameter

• Adventitia contain elastic and type I collagen fibers.

• Lamina that may be hard to distinguish

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Wall of the Elastic Artery
Most arteries have
continuous layer of elastin,
called the internal elastic
lamina, at the boundary
TI between the media with the
intima.
In routine histological
sections, the internal elastic
lamina of transversely-
sectioned arteries typically
displays a distinctive
TM sinusoidal appearance,
resulting from postmortem
contraction of the artery's
smooth muscle in the
absence of normal blood
pressure.

TA TI = T. Intima;
TM = T. media;
TA = T. adventitia
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Transverse section showing part
of a large elastic artery showing a
well-developed tunica media
containing several elastic
laminas.
Pararosaniline
toluidine blue (PT) stain.
Medium magnification.

(vasa vasorum)

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Muscular Arteries
• Most named arteries in the human body (radial, brachial,
femoral, popliteal…)
• Regulate BP by contracting or relaxing the smooth muscle
in the media.
• Tunica intima:
– Contains typical endothelium
– Has a very thin subendothelial layer and
– A prominent internal elastic lamina
– Prominent internal elastic lamina appears as wavy,
refractile line between intima and media.

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Muscular Arteries
• Tunica media:
– Is thick, contains up to 40 layers of smooth muscle
interspersed with elastic, reticular fibers, and
proteoglycans.
– An external elastic lamina is present only in the larger
muscular arteries.
• Tunica adventitia:
– Is relatively thin
– Contains mostly collagen fibers that surround the artery
– Lymphatic capillaries, vasa vasorum, and nerves are
also found and
– These structures may penetrate to the outer part of the
media.

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Transverse section showing part of a muscular (medium caliber) artery. Small blood 43
vessels (vasa vasorum) are observed in the tunica adventitia.
Arterioles
• Are small unnamed branches of artery
• Less than 0.5 mm in diameter and have relatively narrow
lumens.
• Are the site for blood pressure regulation.
• Indicate the beginning of an organ’s microvasculature
where exchanges between blood and tissue fluid occur.
• They branch to form anastomosing networks or beds of
capillaries that surround the parenchymal cells of the
organ.
• Smooth muscle fibers act as sphincters closing arterioles
and producing periodic blood flow into capillaries.
• Are referred to as peripheral resistance vessels.

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Arterioles
• Tunica intima:
– Is lined by endothelial cells

– The subendothelial layer is very thin

– In the very small arterioles, the internal elastic lamina is absent

• Tunica media:
– Composed of 1 or 2 circularly arranged layers of smooth muscle cells.

– No external elastic lamina

• Tunica Adventita
– In both arterioles and small arteries, the tunica adventitia is very thin.

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Cross section through an arteriole and its accompanying venule from the myometrium of
mouse uterus. Note the elongated, large nucleus (arrowhead) of a pericyte surrounding the
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venule wall. Toluidine blue stain. High magnification. (Courtesy of TMT Zorn.)
Meta- Arterioles
• Microvessels
• Smaller branches of arterioles
• Intermediate between capillaries and arterioles
• Pre-capillary sphincters, rings of smooth muscles
surround meta- arterioles at capillary origins.
• This sphincters allow blood to enter the bed of
capillaries in a pulsatile manner for maximally efficient
exchange.
• Its distal portion, sometimes called a thoroughfare
channel
– Lacks any smooth muscle cells
– Merges with the postcapillary venule
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Meta- Arterioles
• True Capillaries:
– Smallest branches from the metarteriole and
thoroughfare channel.
– Lacks smooth muscle cells (although pericytes may
be present)
– The precapillary sphincters regulate blood flow to
it.

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Fig: Microvascular bed
structure and perfusion.

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Arterioles (A), capillaries (C), and
venules (V) comprise the
microvasculature where, in almost
every organ, molecular
exchange takes place between
blood and the interstitial fluid of
the surrounding tissues. Lacking
media and adventitia tunics and
with diameters of only 4-10μm,
capillaries (C) in paraffin sections
can be recognized by nuclei
adjacent to small lumens or by
highly eosinophilic red blood
cells in the lumen. 200X H&e.

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B. Capillaries
• Smallest vascular channels

• Average diameter: 4 -10µm

• Comprise over 90% of all blood vessels in the body.

• Are often referred to as exchange vessels.

– O2, CO2, substrates, and metabolites are transferred


from blood to the tissues and from the tissues to blood.

• Blood reach to it by small arteries called pre- capillary and


leave it through small venules called post venules
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Capillaries
• Structure:
– Composed of a single layer of endothelial cells rolled
up as a tube and surrounded by a thin basal lamina.
– The cells attach to one another at their borders by
junctional complexes including tight and gap junctions.
– 4 to 10 μm diameter and 50μm long.
• Functions:
– Are the site of normal exchange of materials between
blood and tissue.
– May be sites of exit of WBCs from blood into tissues
under some conditions, although this is probably more
frequent in venules.

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Photomicrograph of the capillary network in the retina. Vertically crossing the image is an
arterial (A) with a clearly visible layer of circularly arranged smooth muscle cells (SM). The
arterial is crossed perpendicularly by a venule (V). Note the extensive network of capillaries
connecting both vessels. Nuclei of endothelial cells (E) are clearly visible within capillaries
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Capillaries
• Cells of the capillaries include:
1. Endothelial cells:
– Chief structural components of capillaries
– Lined by simple squamous epithelial cells
– Mesenchymal in origin
– Joined by intercellular junctions to form a tube
– Functions:
Convert angiotensin I to angiotensin II
Inactivates bioactive compounds such as bradykinin and
serotonin
Break down of lipoproteins
Prevent clot formation
Participate in capillary transport
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Capillaries
2. Pericytes or adventitial cells:
– Small msenchymal cells scattered along capillaries
– With long cytoplasmic processes partly surrounding the
endothelial layer
– Functions:
Produce their own basal lamina, which may fuse with
that of the endothelial cells.
Have contractile function (possess myosin, actin &
tropomyosin)
 Have great potential for transformation into other
cells: Reserve cells.
 Participation in repair process.

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Types of Capillaries
Depending on the continuity of the endothelial cells
and the basal lamina:
• Capillaries are grouped into three histologic types :
1. Continuous capillaries
2. Fenestrated capillary
3. Sinusoid or discontinuous capillary

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Types of Capillaries
1. Continuous capillary
• Most common type of capillary
• Have many tight, well-developed
occluding junctions between
slightly overlapping endothelial
cell.
• Complete basal lamina
• Transport is thru diffusion or Fig: Continuous capillary
pinocytosis
• Locations: Muscle tissue, CT,
Nervous tissue, Exocrine glands &
lungs.
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Electron micrograph of continuous capillary, the nucleus (N) and the junctions between
neighboring cells (arrowheads). Numerous pinocytotic vesicles are evident (small arrows). The
large arrows show large vesicles being formed by infoldings of broad sheets of the endothelial59cell
cytoplasm
Types of Capillaries
2. Fenestrated capillary
• Characterized by the presence of small
circular fenestra on endothelial cells.
• Each fenestra is usually covered by a very
thin diaphragm
• The fenestrae allows more extensive
molecular exchange across the
endothelium
Fig: Fenestrated capillary
• Basal lamina is continuous and covers the
fenestrations.
• Also have pinocytotic vesicles
• Located in tissues where rapid interchange
of substances occurs b/n the tissues and the
blood.
• Locations: kidneys, intestine, choroid
plexus, & endocrine glands.
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Fenestrated Capillary EM
This electron micrograph shows a capillary with a fenestrated endothelium. These capillaries are far more permeable than those with continuous
endothelial linings. Identify the endothelial cells lining the capillary, and the fenestrae, or gaps, between the cells. Barely visible is an electron-dense
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line known as the diaphragm that functions as a filtration barrier. Fenestrated capillaries are prominent in the kidney, intestine and endocrine glands.
Types of Capillaries
3. Sinusoid or discontinuous capillary
• Endothelial cells have large fenestrae
without diaphragms
• The cells form a discontinuous layer
and are separated from one another
by wide spaces
• The basal lamina is also
discontinuous.
• Sinusoids are irregularly shaped
• Have diameters as large as 30–40µm Fig: Sinusoidal capillaries
• Blood flows slowly at this site
• Show macrophages among the
• Permits maximal exchange of endothelium cells
macromolecules as well as cells
between tissues and blood
• Locations: Liver, Spleen, Some
Endocrine Organs & BM
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Sinusoidal capillaries or sinusoids generally have much greater diameters than most capillaries
and are specialized not only for maximal molecular exchange between blood and surrounding
tissue, but also for easy movement of blood cells across the endothelium. The sinusoid (S) shown
here is in bone marrow contained in reticular tissue containing adipocytes (A) and masses of
hematopoietic cells (H). The endothelium is very thin and cell nuclei are more difficult to find
than in smaller capillaries. Ultrastructurally sinusoidal capillaries are seen to have large fenestrae
through the cells and large discontinuities between the cells and through the basal lamina.

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Microcirculation
Type of microcirculation
• The usual sequence
– Arteriole - metarteriole -
capillary – venule - vein
• An arterial portal system-
kidney glomerulus
– Capillary - efferent
arterioles-capillaries -veins
• A venous portal system - in
the liver
– Capillary – veins -
Capillary - veins

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Microcirculation
• Arteriovenous anastomosis
 Change in diameter of these
vessels regulate blood pressure,
flow, temperature, conservation
of heat in particular area.
 All are highly innervated by
autonomic innervation
• Glomus or glomera
 Arterioles are continuous with
venules
 Branched or highly convoluted
 No internal elastic lamina
 Thick smooth myocyte
 Location- skin of the
fingertips, nose, and lips and
in the erectile tissue of the
penis and clitoris
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Microcirculation
• Arteriovenous anastomosis
 AV shunts serve in
thermoregulation at the body
surface
 Closing an AV shunt in the
skin causes blood to flow
through the capillary bed,
enhancing heat loss
 Opening an AV shunt in the
skin reduces the blood flow
to the skin capillaries,
conserving body heat
 In erectile tissue such as the
penis, closing the AV shunt
directs blood flow into the
corpora cavernosa, initiating
the erectile response

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C. Veins
• Have thinner walls than arteries
• Carry non- oxygenated blood to the heart
• Blood passes through venous system by external
pressure due to muscle contraction, respiration and
valves found in veins.
• May contain erythrocytes in sectioned tissue.
• Have thicker adventitia which in larger veins may
contain longitudinal muscle.
• Contains valves that help maintain the unidirectional
flow of blood.

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Veins
• Valves:
– Are extensions of the intima into the lumen
composed of elastic CT.
– Have two semilunar folds of tunica intima that
project into the lumen
– Are lined on both sides by endothelium.
– Abundant in the veins of the lower limbs

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Vein with infoldings of the T. Intima = valves (V)
direct the venous blood toward the heart.

2 semilunar folds

They are composed of CT rich in elastic fibers and are


lined on both sides by endothelium.
are especially numerous in veins of the limbs. The
propulsive force of the heart is reinforced by
contraction of skeletal muscles that surround these
veins. 69
Veins
• Structurally classified according to their size as:
– Venules
– Small veins
– Medium-sized veins and
– Large veins

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Venules
• Receive blood leaving capillaries
• Are the primary site at which WBCs leave the circulation
• Tunica intima contains typical endothelium but lack valves
• The thin basal lamina is pierced by pericytes
• Tunica media is very thin
• Tunica adventitia is very thin that contains collagen
• Types of venules
– Postcapillary venules (Ø = 10 –25 µm).
– Collecting venules (Ø = 20-50 µm)
– Muscular venules (Ø = 50 – 100 µm)

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Venules
• Postcapillary venules:
– Transition from capillaries to venules
– The smallest venules (pericytic venules)
– They resemble capillaries but have more pericytes.
– Function = exchange.
– Endothelial cells are cuboidal in lymph nodes &
Peyer’s patches (high endothelial venules (HEVs)

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Venules
• Functions of Postcapillary venules:
Collect blood from capillaries.
Respond to vasoactive agents (e.g., histamine,
serotonin) by altering permeability.
Also a site of exchange of materials between
tissue fluid and blood.
Site of exit of WBCs from blood into tissue
(diapedesis).

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Venules
• Collecting venules:
– Have a thin adventitia in addition to the pericytes
surrounding the intima.
– The adventitia consists of longitudinally arranged
collagen fibres with a few elastin fibres.
– Pericyte layer is continuous and there are
surrounding collagen fibers.
• Muscular venules:
– Pericytes replaced by smooth muscle cells (1-2
layers thick).
– Adventitia (fibrocartilagenous) is identifiable.
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Venule
This image of a venule shows several of its characteristic features. Identify its endothelium and narrow layer of
smooth muscle cells. The largest wall component of the venule is usually the adventitia composed of connective
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tissue.
Small veins
• Tunica intima formed of endothelium and does not
contain elastic fibers.

• Tunica media forms 2 layers of smooth muscles and it


is very thin

• Tunica adventitia is formed of collagen fibers that


connect the veins with surrounding structures

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Medium sized veins
• Formed by collection of small veins and drains into
large veins
• Structure is similar to small veins but tunica media is
thicker and contain elastic fibers.

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Large veins
• Have largest diameter
• Includes venae cava, renal, external iliac, azygus, portal, and
internal jugular veins
• Conduct blood flow toward the heart
• Tunica intima is well developed and includes thick layer of sub-
endothelial connective tissue
• Extensions of intima protrude into lumens of large veins as
valves
• Tunica media contains several layers of smooth
• Muscle cells and abundant reticular and collagen fibers.
• Elastin is sparse
• Tunica adventitia in best developed in large veins which contains
abundant collagen and longitudinal bundles of smooth muscle
that strengthen the vessel wall to prevent excessive dilatation. 79
Muscular artery (left) and accompanying vein right
80
Fig: Wall of large vein with valve
81
Blood and nerve supply of blood vessels
• Vasa vasorum
 In large vessels, more frequent in veins
 In the tunica adventitia and outer media
• Lymphatic vessels
 In veins deep to tunica media, in arteries in the tunica adventitia
• Nervi vasorum
 Adrenergic – vasomotor
 Cholinergic- vasodilator

82
Specialized Sensory Structures in Arteries
• Carotid sinus:
– Are slight dilatations of the internal
carotid arteries.
– Contains baroreceptors that function
in the control of blood pressure by
mediating changes in heart rate.
– The arterial media layer of the sinus
is thinner to allow it to respond to
changes in blood pressure
– The intima and the adventitia are
very rich in nerve endings.
– Are derived from the neural crest
cells.

83
Specialized Sensory Structures in Arteries
• Carotid Bodies:
– Encountered near the bifurcation of the common carotid
artery
– Are chemoreceptors, sensitive to blood CO2 and O2
concentrations.
– Richly irrigated by fenestrated capillaries that surround type
I and type II cells.
– Type II cells are supporting cells
– Type I cells contain numerous dense-core vesicles that
store dopamine, serotonin, and adrenaline.
• Aortic bodies :
– Located on the arch of the aorta are similar in structure and
function to carotid bodies
– Are derived from the neural crest cells.
84
85
Lymphatic system

86
Lymphatic system

Lymphatic Vessels Lymphoid Organs

87
Lymphatic System
• Consists of:
– The lymph
– Lymphatic vessels
– Lymphatic organs like the lymph nodes, thymus, spleen,
tonsils and
– Collections of lymphoid tissue in the GIT and respiratory
system
• Functions:
– It transports excess interstitial (tissue) fluid
– It serves as the route by which absorbed fats and some
vitamins are transported from the small intestine to the
blood
– Provide immunological defenses against disease causing
agents

88
Lymphatic Vascular System
• Collect excess interstitial fluid from the tissue spaces and return it to
the blood.
• This fluid is called lymph.
• It flows in only one direction, toward the heart (unlike the blood)
• Are absent from cartilage, bone , bone marrow, teeth, CNS, cornea,
internal ear, thymus, and fetal placenta
• Lymphatic Capillaries:
– Originate in the various tissues as thin, closed-ended vessels.
– Thin continuous endothelium (Like blood capillaries)
– Discontinuous basal lamina
– No pericyte
– Anchoring filaments (bundle of elastic filament) that maintain the
patency of the vessel
• The thin lymphatic capillaries converge into larger lymphatic
vessels
89
90
Diagram indicating more details
about lymphatics, including
the openings between the
endothelial cells. The openings
are held in place by anchoring
filaments containing elastin and
are covered by extensions of the
endothelial cells. Interstitial fluid
enters primarily via these
openings, and the endothelial
folds prevent backflow of lymph
into tissue spaces. Lymphatic
endothelial cells are typically
larger than those of blood
capillaries.

91
Lymph collecting vessels
• Similar with vein but thinner wall and wider lumen
• Form more numerous internal valves
• Lack a clear-cut separation between layers
• Vessels show dilated and nodular, or beaded, appearance
between the valves

a) Cross section shows a lymphatic vessel ( LV ) near a venule ( V ), whose wall is thick by comparison. Lymphatic
vessels normally do not contain red blood cells. X200. Mallory trichrome (b) Lymphatic vessel ( LV ) in muscle cut
92
longitudinally shows a valve. X200. PT.
Lymphatic Trunks
• Major lymphatic duct for each side of the body are:
– Thoracic duct on the left
– Right lymphatic duct on the right
• Structurally, similar to large veins
• Smooth mm in the middle layer arranged both
longitudinally (predominant) and circularly.
• The adventitia is relatively underdeveloped and
• Contain vasa vasorum and a rich neural network

93
Lymph Transport
• The lymphatic system lacks an organ that acts as a pump
• Lymphatic vessels are low-pressure conduits.
• The mechanisms that promote lymph return are:
– Milking action of active skeletal muscles
– Pressure changes in the thorax during breathing
– Valves to prevent backflow
– Pulsations of nearby arteries
– Contraction of smooth muscle in the walls of larger
lymphatic vessels.
• About 3 L/day lymph enters the bloodstream.

94
Lymphoid Tissue
• Is a connective tissue characterized by a rich supply of
lymphocytes.
• It exists free within the regular connective tissue or is
surrounded by capsules, forming the lymphoid organs.
• Because lymphocytes have very little cytoplasm,
lymphoid tissue filled densely with such cells stain dark
blue in H&E-stained sections.
• Basically made up of free cells, typically with a rich
network of reticular fibers (made principally of type III
collagen)

95
Lymphoid Tissue
• Lymphoid tissues are:
– Are where most lymphocytes become activated and
most effector and memory lymphocytes are
generated.
– The main battleground to fight against infection.

96
Lymphoid Tissue…
• Groups of lymphocytes are arranged as spheres,
called lymphoid nodules or lymphoid follicles, that
primarily contain B lymphocytes.
• After activation of lymphoid nodules, the central
portion of the nodule is the area of lymphocytes
proliferation and then stains lighter termed as
germinative center.
After completion of the immune response, the
germinative center may disappear.
The germinative centers contain follicular
dendritic cell that has many processes that bind
antigen on their surfaces, to be presented to B
lymphocytes.

97
98
Reticular tissue in a human lymph node.
Lymphoid Tissue
• Lymphoid nodules
– Measure up to 1 mm in diameter
– Found free in connective tissues anywhere in the body
or within lymphoid organs except in the thymus.
– Are not covered by a capsule
– This tissue has two general locations
Mucous membranes
Lymphoid organs

99
Lymphoid Organs
• Lymphoid organs are classified in to:
• Primary or central organs: Red bone marrow and thymus gland
• Secondary organs: Lymph node, Spleen, MALT
• B and T Lymphocytes are the major component of Lymphoid
Organs.
• Other cells: macrophages, dendritic cells, reticular cells

??

100
Lymphoid Organs
 Classification based on encapsulation or not:
• Encapsulated:
 Thymus
 Lymph nodes
Spleen
• Incompletely encapsulated:
 Tonsils
• Unencapsulated:(sometimes called diffuse lymphoid tissue)
 MALT (e.g. Peyer’s patches)
 Lymphoid tissue in appendix
 Temporary aggregations of lymphocytes and other immune system
cells
101
102
Lymph Nodes
• Are bean-shaped, encapsulated structures
• Measure about 2.5 cm in diameter
• Distributed throughout the body along the lymphatic
vessels.
• Found in the axilla and the groin, along the great vessels
of the neck, and in large numbers in the thorax and
abdomen, especially in mesenteries
• The nodes constitute a series of in-line filters of lymph.

103
Lymph Nodes
• LN are surrounded by a
connective tissue capsule.
• The capsule send trabeculae
into its interior.
• Has three major regions:
– Cortex: outer
– Paracortex: deeper
extension of cortex
– Medulla: central
 These regions are not
physically compartmentalized
like those of the thymus.

104
Lymph Nodes
 Cortex- outer part
• Components of cortex:
• Sub capsular sinus:
– Located deep to capsule
– Receives lymph from the
afferent lymphatics
– Cortical sinuses (or
trabecular sinuses) branch
internally among the
lymphoid nodules along
trabeculae.
– Lymph containing Antigen,
lymphocytes and APCs
passes through these sinus
and percolates easily into the
surrounding lymphoid
tissue.

105
Lymph Nodes
 Components of cortex…
• Lymphoid nodules:
– With or without germinal
centers.
– Fill most cortical areas
– Consist largely of developing
B lymphocytes
– Numerous macrophages - for
removal of newly formed
defective B cells.

106
Lymph Nodes
• Paracortex:
– Region between the cortex and
medulla
– Does not have precise
boundaries with the outer cortex
– Distinguished from outer cortex
by its lack of lymphoid nodules.
– Contains lymphoid tissue rich T
cells (Unlike outer cortex)
– High endothelial venules
(HEVs)
Specialized postcapillary
venules in this cortex.
Represent an important entry
point for most (90%)
circulating lymphocytes into
lymph nodes.

107
Lymph Nodes
 Medulla - centeral
• Has two major components:
• Medullary Cords:
– Branched cordlike masses of lymphoid tissue extending
from the paracortex.
– They contain T and B lymphocytes and many plasma cells.
• Medullary sinuses:
– Are dilated spaces lined by discontinuous endothelium that
separate the medullary cords.
– The lumens include a meshwork of processes from reticular
cells, which represent a final lymph filter.
– These sinuses contain many macrophages and sometimes
neutrophils if the lymph node is draining an infected region.
– They are continuous with the cortical sinuses and converge
at the hilum as the efferent lymphatic vessel.
108
• lymph node showing the cortex and the medulla and their primary components.
B:(1) Capsule; (2) lymphoid nodule with germinative center; (3) subcapsular sinus;
(4) intermediate sinus; (5) medullary cords; (6) medullary sinus; (7) trabecula
109
110
Medulla of lymph node

A: Photomicrograph of the medulla of a lymph node; the medullary sinuses are separated by medullary cords.
Lymphocytes clearly predominate in number over other cell types. A blood vessel within a medullary cord is also
seen. B: (1) Medullary cords; (2) medullary sinuses. H&E stain. Medium magnification. (Courtesy of PA
Abrahamsohn.)
111
Lymph Circulation in the lymph nodes
Afferent lymphatic vessels

Subcapsular sinuses

Intermediate sinuses

Medullary sinuses

Efferent lymphatic vessels


o During this passage, the lymph
perfuse in to the paranchyma for
uptake and digestion of foreign
materials by macrophages
112
Blood circulation in lymph nodes
• The major blood supply reaches the node through the
hilus, and give medullar and cortical branches

• Postcapillary venules (HEV) located in the paracortex,


lined by from cuboidal to columnar epithelium b/n
which leave B cells to the cortex and T cells that
circulate for monitoring the body parts.

113
Blood and lymph circulation in the lymph nodes

114
Thymus
• Is a lympho-epithelial bilobed organ.
• Located in the superior mediastinum, anterior to the
heart and great vessels.
• The primary lymphoid organ in which T cells are
produced.
• Fully formed and functional at birth.
• It remains large and very active in T-cell production
until puberty during which it normally undergoes
involution.

115
Thymus
Age Mass
 Birth  about 15 grams;
 Puberty  about 35 grams
 Twenty-five years  25 grams
 Sixty years  less than 15 grams
 Seventy years  as low as 5 grams

116
(a) The thymus, a bilobed organ located in the superior mediastinum, is most prominent and active before puberty, undergoing
gradual shrinkage (involution) and loss of activity in adults. (b) A child’s thymus, showing connective tissue of the capsule (C) and septa (S)
between thymic lobules, each having an outer cortex (Co) and incompletely separated medulla (M) of lymphoid tissue. (H&E; X40) (c) After
involution the thymus shows only small regions of lymphoid tissue, here still with cortex (Co) and medulla (M), and these are embedded in
adipose tissue (A). Age-related thymic involution reduces production of naïve T cells and may be involved with the decline of immune function in
the elderly. (H&E; X24)
117
Thymus
• It has a vascularized connective tissue capsule.
• The capsule sends septa into the parenchyma
• This septa divide the organ into many incompletely
separated lobules.
• Each lobule has:
– Cortex - peripheral dark zone
– Medulla - central light zone

118
Thymus
119
Thymus
Cortex:
• Contains an extensive population of T lymphoblasts (or
thymocytes), dispersed epithelial reticular cells, and
macrophages.
• Darkly stain: due to greater density of lymphoblasts and
small lymphocytes.
• Thymic epithelial cells (TECs)
– Contains both epithelial and reticular cell features.
– Have large euchromatic nuclei but are morphologically
and functionally diverse.

120
Thymus
• There are three major types of TECs in the cortex of the
thymus:
• Type I –Sub-capsular ERC
– Polymorpho nuclear with well defined nucleolus
– Separate cortex capsule and trabelulae
– Surround the vascular elements in the cortex
– Connected by tight junction to isolate cortex from
remainder of the body
• Type II ERC
– Large cell with pale nuclei
– Located in the midcortex
– Have long, wide, sheath-like processes that form
desmosomal junctions with each other
– Their processes form a cytoreticulum that subdivides the
thymic cortex into small, lymphocyte-filled compartments
121
Thymus
• Type III ERC-at the corticomedullar junction
– Have denser cytoplasm and nuclei
– Process connected by tight junction with each other and with
ERC of medulla
– Isolate cortex from medulla

122
Thymus
 The epithelial reticular cells :
• All the three type isolate cortex and prevent T cell from
contacting foreign antigens
• Type I & II present self antigen and MCH I & II to the
developing T lymphocytes
• About 98% T lymphocyte die by apoptosis and removed by
macrophages if,
– T cell receptor recognize self antigen
– CD4 or CD8 of the T lymphocyte can’t recognize MCH I &
II
• The remaining T cells survive and migrate to the medulla and to
the thymic dependant secondary lymphoid organs
– Paracortical zone of lymph nodes
– Periarterial sheath of spleen
– Some part of peyer’s patches of ileum
123
Thymus
• Macrophages:
– Present in small numbers,
scattered throughout the
cortex
– They are difficult to
distinguish from reticular
cells by light microscopy
unless phagocytosed
material can be seen in their
cytoplasm in electron
micrographs
The relationship between
– Lack of desmosomes epithelial reticular cells and
thymus lymphocytes
124
Thymus cortical zone showing epithelial reticular cells with visible nucleoli (arrowheads)
surrounded by dark-stained T lymphocytes 125
Blood–Thymus Barrier
Lymphocytes reaching the thymic
cortex are prevented from contact
with antigen by a physical barrier
called the blood– thymus barrier
Is crossed by some
macromolecule
Components:
• Capillary endothelium and its
basal lamina
• Perivascular connective tissue
sheath
• Type I epithelial reticular cells
and their associated basal lamina .

Schematic diagram of the blood–thymus barrier.


126
Thymus
 Medulla
• Contains epithelial reticular cells, many differentiated T lymphocytes,
and thymic corpuscles or Hassall corpuscles
• Epithelial reticular cells
– Type IV ERC
Are darker cell with course nuclei
Make barrier at corticomedullary junction with type III cells
– Type V ERC
Are polymorphous nuclei with conspicuous nucleolus
Make stroma of medulla
– Type VI ERC
Compose the most characteristic feature of the thymic medulla
Are large flattened pale staining cells that coalesce and make
Hassall corpuscles

127
Thymus
 Medulla…
• Thymic corpuscles
– Large aggregates of TECs,
sometimes concentrically
arranged.
– Function - Their cells secrete
several cytokines that control
activity of local dendritic cells
and the differentiation of
regulatory T cells.
– They sometimes calcify
– Size from 10 -100μm or more
in diameter, increase with age
128
Medullary zone of the thymus. Large numbers of epithelial reticular cells with their large and
light-stained nuclei are responsible for the light color of the thymus medulla. This zone also
contains mature T lymphocytes
129
Blood circulation
• The arteries to the thymus penetrate and follow the connective
tissue of the septa.

• Arteriolar branches from these vessels run along the


corticomedullary junction and provide arterioles and capillaries
to the medulla and capillaries to the cortex

130
Blood circulation
• Cortical capillaries
– Have a non fenestrated endothelium
– Loop back to drain into medullary venules
– Enveloped by a collar of connective tissue that
forms part of the blood thymic barrier- prevent
developing T cells from contacting blood-borne
macromolecules

131
Blood circulation
• Medullary capillaries
– Drain in to medulary venules
– Make no blood thymic barrier
• The thymus has only few efferent, but no afferent lymphatic
vessels.
• Thymic secretion :
– Several proteins that act as growth factors to proliferation
and differentiation of T cells
1. Thymosin alpha
2. Thymopoietin
3. Thymolin
4. Thymic humoral factor

132
Spleen
• The largest lymphoid organ.
• Located in the superolateral part of the LUQ, 9th -11th ribs.
• The only lymphoid organ involved in filtration of blood.
• Functions:
– Removal of blood-borne antigens: “white pulp”
– Removal & destruction of aged or defective blood cells: “red
pulp”
– Recycling iron to the bone marrow
– Stores platelets
– Storage of erythrocytes that can be released into circulatory
system when needed.
– In fetus: site of hematopoiesis
133
Spleen
• It is surrounded by a dense CT capsule.
• From which trabeculae emerge to penetrate the
parenchyma or splenic pulp.
• The connective tissue contains nerves, blood vessels,
lymph vessels, and smooth muscle.
• Blood vessels and nerves run through the hilum and
enter the spleenic pulp via the trabeculae.
• There are no lymph vessels in the pulp.

134
Spleen
• The spleen is filled with
reticular tissue containing
reticular cells and fibers,
many lymphocytes and
other blood cells,
macrophages, and APCs.
• The splenic pulp has two
components:
– White pulp
– Red pulp

135
 White pulp consists:
Spleen
 Periarterial lymphatic sheath(PALS)
 Contain branches of trabeculae arteries (central arteries or white
pulp arteries) enveloped by a sheath of T lymphocytes.
 Lymphoid nodules
 Found eccentric to the sheath
 Contain mainly B lymphocytes
 Marginal zone
• Found at the periphery of the lymphatic sheath
• Concentric layers of the reticular fibers and cells form that delimit
the lymphatic tissue from the red pulp
• Contain:
– Lymphoid tissue with mainly B lymphocytes, macrophages,
plasma cells and interdigitating dendritic cells
– Marginal sinus 136
137
• Marginal zone….
• Marginal sinus …
– Surround the lymphoid tissue
– Receive arterioles that radiate from central arterioles and pass in to
red pulp and recur in to marginal sinus

138
Marginal zone….
• The spaces between the endothelial cells of the marginal sinuses may
be as wide as 2 to 3 μm, it is here that blood-borne cells, antigens,
and particulate matter have their first free access to the parenchyma
of the spleen.
• The following events occur at the marginal zone:
– APCs sample the material traveling in blood, searching for
antigens.
– Macrophages attack microorganisms present in the blood.
– The circulating pool of T and B lymphocytes leaves the
bloodstream to enter its preferred locations within the white pulp
– Lymphocytes come into contact with the interdigitating dendritic
cells; if they recognize their epitope-MHC complex, the
lymphocytes initiate an immune response within the white pulp
– B cells recognize and react to thymus-independent antigens (such
as polysaccharides of bacterial cell walls). 139
 Red Pulp -composed of
• Splenic cords:
– Contain a network of reticular cells supported by reticular fibers
– Filled by:
T and B lymphocytes, Macrophages, Plasma cells, other
leukocytes, and red blood cells.
• Splenic sinusoids:
– Lined by unusual elongated endothelial cells called stave cells.
– Oriented parallel to the blood flow and sparsely wrapped in
reticular fibers.
– Surrounding the sinusoid is an incomplete basal lamina.
– Supported by reticular fibers.

140
Structure of the red pulp of the spleen, showing splenic sinusoids and splenic cords
with reticular cells and macrophages, some of which contain ingested material.
141
• Scanning electron micrograph of the red pulp of the spleen showing sinusoids, red
pulp cords, and macrophages (M). Note the multiple fenestrations in the endothelial
cells of the sinusoids.
142
• Blood circulation
– Branches of the splenic artery enter the spleen at the hilus,
divide, and pass within trabeculae into the interior of the
organ
– The trabecular arteries
Central arteries
Immediately become surrounded by the lymphatic tissue of the
periarterial lymphatic sheath (PALS).
Give radial branches surrounding lymphoid nodules
– Penicillar arteries
Straight vessels that run in the red pulp and has no investing
lymphoid layers
Give rise to pulp and sheath arterioles and capillaries
Terminal capillaries lead to red pulp sinus trabecular veins
spenic veins portal vein

143
144
The two type of Blood Circulation in the Spleen
 Closed
Terminal arterial capillaries open directly into the red pulp
sinusoids
 Open Circulation
Penicillar arteries open into the splenic cords, and the blood
passes through the space between the cells to reach the sinusoids

145
MUCOSA-ASSOCIATED LYMPHOID
TISSUE
• Is one of the largest lymphoid organs, containing up to
70% of all the body’s immune cells.
• The mucosa of the Digestive, respiratory, and
genitourinary tracts is a common site of invasion by
pathogens.
– Because their lumens open to the external environment.
• To protect against such invaders mucosal connective tissue
of these tracts contains:
– Large and diffuse collections of lymphocytes
– IgA- secreting plasma cells all comprise MALT
– APCs, and lymphoid nodules
• Lymphocytes are also present within the epithelial lining of such mucosae.

146
MUCOSA-ASSOCIATED LYMPHOID
TISSUE
• Most of the immune cells in MALT are dispersed diffusely in
the connective tissue; others are found in aggregates forming
large, conspicuous structures such as the tonsils, Peyer patches
in the ileum, and the appendix.
• Most of the lymphocytes here are B cells; among T cells, CD4+
helper T cells predominate.

147
Tonsils
• Tonsils do not filter lymph
• They have no afferent vessels , nor do they have an internal system of sinuses
for the filtering of lymph
• Tonsils contribute to the formation of lymphocytes
• Palatine Tonsils
– The two palatine tonsils are located in the lateral walls of the oral part of
the pharynx .
– They are lined with a squamous stratified epithelium infiltrated by
lymphocytes
– Each tonsil has 10–20 epithelial invaginations or crypts that penetrate the
tonsil deeply
– Separating the lymphoid tissue from subjacent structures is a band of
dense connective tissue, the capsule w/c acts as a barrier against spreading
tonsillar infections
– Contain 1o and 2o lymphoid nodules

148
Tonsils

149
• The palatine tonsil consists of diffuse lymphocytes and lymphoid nodules disposed under a
stratified squamous epithelium. One of the crypts of the tonsil is shown; the crypts often
contain dead epithelial and inflammatory cells. B:(1) Crypt; (2) stratified squamous
epithelium; (3) lymphoid nodules; (4) diffuse lymphoid tissue; (5) germinative center; (6)
capsule; (7) mucous glands
150
Tonsils...
• Pharyngeal Tonsil
– Is a single tonsil situated in the superior—posterior
portion of the pharynx.
– It is covered by ciliated pseudostratified columnar
epithelium and some stratified epithelium.
– No crypts, but small folds
– Thin capsule separates the pharyngeal tonsil from
underlying tissues and
– Small compound tubuloacinar mucoserous glands lie
beneath the capsule and empty onto the surface of the
folds
– Contain 1o and 2o lymphoid nodules
– Hypertrophied pharyngeal tonsils -are called adenoids
151
152
Tonsils...
• Lingual Tonsils
– Are smaller and more numerous than the palatine and
pharyngeal tonsils.
– Situated at the base of the tongue
– Covered by stratified squamous epithelium
– Each lingual tonsil has a single crypt
– The bases of the crypts receive ducts of mucous glands
• Tubal tonsils
– Two in number, each around the opening of pharyngo
tympanic tube.
– Are not well developed.

153
154
155
Important histologic comparisons of the major lymphoid
organs
Thymus MALT Lymph Nodes Spleen
Cortex/medulla Distinctly present Absent Present Absent
Lymphoid nodules Absent Present Present (in cortex Present (in white
only) pulp only)
Lymphatic vessels No afferents; few No afferents; Afferents at No afferents;
efferents in septa efferents capsule, emptying efferents in
present into subcapsular trabeculae
sinus; efferent at
hilum
Unique features Hassall (thymic) Crypts lined by Thin paracortical Minor white pulp
corpuscles in surface region component, with
medulla; mucosa in tonsils; between cortex and central
epithelial- reticular epithelial M cells in medulla, with high arterioles; major
cells mucosa over Peyer endothelial venules red pulp
in cortex and patches (HEV); component, with
medulla medullary cords many
and sinuses sinusoids

156
157

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