THE THYMUS

DR. MUSTAFA SAAD (2019)

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• The thymus is a soft, lobulated organ with two lobes
located in the mediastinum. It’s one of the two primary
lymphatic organs.

• Each lobe is covered by its own capsule, and the two lobes
are joined together in the midline by connective tissue.

• The thymus grows until it reaches its largest size about

puberty. At this time, it’s located in the superior and
anterior mediastinum and may, even, extend superiorly into
the neck up to the thyroid gland.

• After that, it undergoes involution where the thymic tissue

is replaced by fatty-areolar tissue. 2
 Fig.1: Relations of
the thymus.
Important relations
1) Anterior relations
• Body of sternum
• Manubrium of sternum
• Sternothyroid and sternohyoid
muscles

2) Lateral relations
• Pleurae and lungs
3) Posterior relations
• Pericardium (to which it may be attached)
• Arch of aorta and its main branches
• Left brachiocephalic vein (which may be embedded in the
thymus) 3

• Trachea
Fig.2: Inferior view of a cross section through the chest at
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the level of T4 vertebra showing relations of the thymus.
Blood supply

Arterial supply: (Fig.1)

• Mainly from the internal thoracic artery
• Sometime from the inferior thyroid artery

Venous drainage
• To the left brachiocephalic, internal thoracic, and
inferior thyroid veins.
• One or more veins often emerge medially from each
lobe of the thymus to form a common trunk opening
into the left brachiocephalic vein. 5
Lymphatic drainage
• The thymus has no afferent lymphatics.
• Efferent lymphatics leave the organ.
• They ultimately end in nearby lymph nodes.

Nerve supply
• The thymus receives sympathetic nerve fibers which are
vasomotor.

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 Histology of the thymus
• Each lobe of the thymus is covered
by a connective tissue capsule.
From the capsule, several septa
pass into the gland dividing it into
several incomplete lobules.

• Each lobule is formed of an outer

darker region called the cortex,
and an inner lighter region called
the medulla. Since the division into
lobules is incomplete, there’s
continuity between the cortex and
medulla of adjoining lobules.
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Fig.3: Histology of the thymus. Ca=capsule,
Se=septa, Lo=lobule, C=cortex, M=medulla.
The Cortex

• Contains:
• Numerous T-lymphocytes precursors (lymphoblasts) at
various stages of maturation.
• Epithelial reticular cells
• Macrophages
• Antigen presenting cells

• Lymphoblasts originate in the fetal liver or bone

marrow and travel through blood to reach the thymus.
Here they enter the cortex and become known as
thymocytes.
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The epithelial reticular cells

• The thymus is peculiar in that its supporting framework is

formed of a network of cells rather than fibers. These cells
are called the epithelial reticular cells.

• They are stellate in shape with multiple processes, a large

lightly stained nucleus, and keratin intermediate filaments
(indicating their epithelial origin). The processes of these
cells are connected to each other by desmosomes and tight
junctions to form a network. In the spaces of this network,
the maturing lymphocytes are located.

• These cells, also, line the capsule and the septa and they
form part of the blood-thymus barrier. 9
 Fig.4: Left side, vessels in the thymus.
Note the loops. Right side, the epithelial
reticular cells. Note how they surround
the arteries in the cortex.

Fig.5: The supporting network of the

thymus is formed of epithelial cells 10

connected to each other by desmosomes.

The blood-thymus barrier

• Arteries enter the thymus by passing through the capsule and,

then, the septa. When they reach the corticomedullary junction,
capillaries are sent to the cortex and medulla. The capillaries of
the cortex form loops which will join venules that either pass to
the medulla or to the capsule (left side of Fig.4).

• A barrier separates the blood from the thymic tissue preventing

antigens in blood from coming in contact with the maturing
lymphocytes.

• This barrier is found in the cortex but not in the medulla of the
thymus.
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• The blood-thymus barrier is formed of:

1. Capillary endothelium. This is continuous and with tight

junctions between the cells.
2. Thick basal lamina of the endothelial cells.
3. Pericytes surrounding the capillaries.
4. Perivascular connective tissue containing macrophages.
5. Basal lamina of the epithelial reticular cells.
6. The epithelial reticular cells with tight junctions between
the cells.

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 13

Fig.6: Components of the blood-thymus barrier.

The Medulla

• Contains:
• Many mature T-lymphocytes (the number of cells here
are less than that in the cortex)
• Epithelial reticular cells arranged as a network
• Epithelial reticular cells arranged as corpuscles

• The thymic (Hassall’s) corpuscles are formed of

epithelial reticular cells arranged in concentric circles.
These cells are filled with keratin and may, even, be
calcified. They are characteristic of this organ and their
function is not exactly known.
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Fig.7: Above, the thymic cortex. The dark nuclei
are those of lymphoblasts. The large pale-staining
nuclei (E) are those of the epithelial reticular
cells. Right, the thymic medulla. The circular 15
structures (HC) are thymic (Hassall’s) corpuscles.
Functions of the thymus
• The thymus is the site where T-lymphocyte become mature; that’s,
it’s the site where T-lymphocytes acquire their specific surface
antigens and become functional.

• The thymus is the site where only lymphocytes functional against

foreign antigens are allowed to survive. This is done by:
• Positive selection: if the lymphocytes do bind to antigens, they
survive.
• Negative selection: if the lymphocytes don’t bind to self-
antigens, they survive.

• These two tests are carried out by antigen presenting and the
epithelial reticular cells. By this way, about 95% of lymphocytes
do not survive and are destroyed by macrophages. This is why the
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thymus is called the ‘graveyard of lymphocytes’

• The surviving lymphocytes pass to the medulla, leave the thymus by
passing into the circulation, and go to the secondary lymphatic organs
where they will perform their functions.

• The epithelial cells (1)isolate the developing lymphocytes from the

surrounding environment, (2) form part of the blood-thymus barrier, and
(3)secrete hormones that stimulate the maturation of the lymphocytes.

• After puberty, the thymic tissue is gradually replaced by fatty and areolar
tissue, thus becoming yellow in color. The remaining thymic tissue,
however, continues to function.

Fig.8: An involuted thymus. Note that

the dimensions of the capsule does not
change much. The thymic tissue,
however, is replaced by fatty tissue.
C=capsule, A=adipose tissue, Co=cortex, 17

M=medulla.
Development of the thymus

• The endoderm of the third pharyngeal pouch grows to form a

dorsal bud and a ventral bud.

• The thymus develops

from epithelial cells
derived from the
endoderm of the ventral
bud of the third
pharyngeal pouch and
from mesenchyme into
which the epithelial
tubes grow.
Fig.9: Development of the thymus from the 18

third pharyngeal pouch.

• Some cells of the epithelium become arranged around a
central point forming the thymic corpuscles. Other cells of
the epithelial cords spread apart but retain connections with
each other to form an epithelial reticulum.

• The mesenchyme between the epithelial cells forms thin

incomplete septa between the lobules. Lymphocytes
(derived from hematopoietic stem cells) soon appear and
fill the spaces between the epithelial cells.

• The surrounding mesenchyme will form the capsule.

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Clinical thymus

• Myasthenia gravis: is a condition characterized by the formation

of antibodies against acetylcholine receptors of skeletal muscles
that leads to weakness of these muscles. Many patients with this
disease have an enlarged thymus, and removal of this organ have
been shown to be beneficial in some cases.

• Agenesis of the thymus: this will greatly impair the immune

system and often leads to early death from infections.

• Ectopic parathyroid in the thymus: the inferior parathyroid gland

also forms from the third pharyngeal pouch. It eventually
separates from the thymus. Sometime, parathyroid tissue may
remain in the thymus. This is usually not significant. 20
THE SPLEEN
DR. MUSTAFA SAAD (2019)

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➢ The spleen is the largest single mass of lymphoid tissue in the
body. Due to its high content of blood, it’s reddish in color.

➢ It’s situated in the left hypochondriac region between the

stomach and the diaphragm.

➢ It’s variable in size and shape. Usually, it’s wedge-shaped with

an average length of 12cm and an average width of 7cm.

➢ It has:
o 2 surfaces: diaphragmatic and visceral
o 2 border: superior and inferior
o 2 extremities (poles): anterior and posterior
o A hilum on the visceral surface where vessels, nerves, and
lymphatics enter or leave the spleen. 22
 23

Fig.10: The spleen in its normal position.

➢ The diaphragmatic surface,
faces superiorly, laterally, and
posteriorly. It is convex, smooth,
and related to the diaphragm.
The diaphragm separates the
spleen from the left lung, left
costodiaphragmatic recess of the
pleura, and the left 9th – 11th ribs.
The axis of the 10th rib runs
along the axis of the spleen.

Fig.11: Lateral view of the diaphragmatic surface of the

spleen and its relation to the ribs. Note the relation between
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the spleen and the mid-axillary line and the 10th rib.
➢ The visceral surface, faces inferomedially. It is irregular with
several impressions created by the relation of this surface to
various abdominal organs:
o Gastric impression: between the hilum and the superior
border. Related to the posterior surface of the stomach.
o Renal impression: between the inferior border and a ridge of
splenic tissue called the intermediate border. This
impressions is related to the left kidney which is medial to
the spleen.
o Colic impression: at the anterior extremity. Related to the
left colic flexure and the phrenicocolic ligament which are
just inferior to the spleen.
o Pancreatic impression: a shallow impression near the hilum
created by the tale of the pancreas which is medial to the
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spleen.
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Fig.12: The visceral surface of the
spleen and its various features.
➢ The superior border, separates the diaphragmatic surface from
the gastric impressions. It usually has one or two notches.

➢ The inferior border, separates the diaphragmatic surface from

the renal impression.

➢ The posterior extremity, directed medially towards the vertebral

column.

➢ The anterior extremity, broad and rarely extends beyond the

mid-axillary line (Fig.10).

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The spleen and the peritoneum
➢ The spleen is an intraperitoneal organ: it’s completely
surrounded by peritoneum except at the hilum.

➢ Folds of peritoneum connect the spleen to nearby organs:

1. The gastrosplenic (gastrolienal) ligament: connects the
greater curvature of the stomach to the spleen. Through it
pass the short gastric and the left gastroepiploic vessels.

2. The splenorenal (lienorenal) ligament: connects the spleen

to the left kidney. Through it pass the splenic vessels and
the tail of the pancreas.

3. Other ligaments that attaches the spleen to the diaphragm

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and the left colonic flexure.

Fig.13: Inferior view of a section through the abdomen showing the
gastrosplenic and the splenorenal peritoneal folds.
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Blood supply

Arterial supply:
➢ From the splenic artery.
➢ The largest branch of the celiac artery.
➢ It is very tortuous.
➢ Passes to the left posterior to the stomach and the
upper border of pancreas, then anterior to the kidney
and suprarenal gland to reach the hilum of the spleen
through the splenorenal ligament.
➢ At the hilum, it divides into several branches that enter
the spleen.
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Venous drainage
➢ The splenic vein is formed at the hilum by the union of
several smaller veins.
➢ This vein traverses the splenorenal ligament and then
passes to the right behind the tail and body of the
pancreas.
➢ Behind the neck of the pancreas, it unites with the
superior mesenteric vein to form the portal vein.

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Fig.14: Blood supply of the spleen. (A) Arterial supply by the
splenic artery. (B) Venous drainage through the splenic vein. 32
Lymphatic drainage
➢ Lymphatic vessels leave the spleen through the hilum.
➢ The lymph will ultimately drain into the celiac lymph
nodes.

Nerve supply
➢ The spleen receives sympathetic nerve fibers which
supply the vessels.
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Histology of the spleen

➢ The spleen is surrounded by a dense connective tissue

capsule covered by mesothelium. From the capsule, several
trabeculae pass to divide the parenchyma of the spleen into
splenic pulps.

➢ The capsule also contains some smooth muscles.

➢ Attached to the capsule and trabeculae is a network of

reticular fibers with the reticular cells that form them. This
network provides support for the splenic tissue.

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➢ Within the spaces of the reticular network, the splenic pulps
are seen to be formed of two morphologically different
regions: (1)white pulp and (2)red pulp. The difference in
appearance is due to difference in functions.

➢ These regions take their names from their appearance in a

fresh section of the spleen.

Fig.15: Diagram showing the white

and red pulps of the spleen. These
are named after their appearance in
a fresh section of the spleen. 35
Fig.16: Histology of the spleen. Note how there is no
distinct boundaries between the white pulp (W) and the red
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pulp (R). C=capsule, T=trabecula.
The White Pulp

➢ Branches of the splenic artery enter through the hilum. They,

then, pass through the trabeculae as the trabecular arteries.

➢ Trabecular arterioles from these arteries leave the trabeculae to

enter the white pulp of the spleen.

➢ As they do so, they’ll become surrounded by a sheath, formed

mainly of T-lymphocytes, known as the Periarteriolar
Lymphoid Sheath (PALS). The arteriole is now called the
central arteriole.

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Fig.17: Diagram showing the blood flow through the spleen. Note the PALS
and the lymphoid nodules in the white pulp. In the red pulp, note the sinusoids
and the two types of circulation.
➢ If the B-lymphocytes in the PALS are activated (by antigens),
they’ll form a typical lymphoid nodule. This also contains
macrophages and mast cells and may form a germinal center.

➢ In such a nodule, the arteriole occupies an eccentric position,

but is still called the central arteriole.

➢ Surrounding these nodules is a marginal zone of sinuses.

➢ Eventually, the central arteriole leaves the white pulp to enter

the red pulp losing its lymphoid sheath.

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Fig.18: The white pulp (W) of
the spleen. The image above is
a longitudinal section through a
central arteriole (arrow head).
Note the darkly colored PALS.
The image below is a cross
section through a lymphoid
nodule. Note the eccentric
position of the central arteriole
and small marginal sinuses. In
both images, the white pulp is
surrounded by red pulp (R).

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The Red Pulp

➢ When the central arterioles enter the red pulp, they will give
rise to several, short, and straight penicillar arterioles.

➢ The penicillar arterioles will give rise to capillaries that are

surround by a sheath of antigen presenting cells (like
macrophages) (see Fig.16).

➢ The red pulp is formed of splenic cords and splenic sinusoids.

➢ The splenic cords are formed of reticular fibers and reticular

cells. In the spaces between the fibers, we find T and B
lymphocytes, other leukocytes, macrophages, platelets, and
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erythrocytes.
➢ The splenic sinusoids of the red pulp:

1. Are lined by a special type of endothelial cells called stave

cells. These cells are
⁃ Elongated.
⁃ With large nuclei.
⁃ Arranged in a direction parallel to the blood flow.
⁃ Have narrow slits between them.

2. Have a highly discontinuous basal lamina.

3. Are sparsely wrapped by reticular fibers.

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Fig.19: The splenic red pulp is formed of splenic cords (C) and splenic sinusoid (S). The
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enlarged image on the right shows the large nuclei of the stave cells that line these
sinusoids (arrows).
Circulation through the splenic red pulp

➢ Two types of circulations are present in the red pulp of the

spleen:

1. Closed circulation, in which the capillaries open into the

sinusoids. Thus blood is always inside a blood vessel.

2. Open circulation, in which the capillaries are of the open type

and blood spills into the parenchyma of the splenic cords.
Platelets, leukocytes, and viable erythrocytes re-enter the
circulation by passing through the slits between the stave cells
of the sinusoids. Senescent or abnormal erythrocytes cannot
squeeze through these slits and remain in the parenchyma to be
engulfed by macrophages. 44
➢ Blood from the sinusoid will drain into small red pulp veins.
These veins will converge as the trabecular veins in the
trabeculae. These in turn will form the splenic vein at the hilum.

Fig.20: The two circulations of the splenic red 45

pulp. Note the features of the sinusoids.
How macrophages recognize
senescent or abnormal RBCs?
a. These RBCs are enlarged or
have a rigid cell membrane;
thus, they cannot squeeze
through the narrow slits
between the stave cells.
b. Such RBCs express certain
markers on their surface.
These markers are recognized
by the macrophages and the
process of phagocytosis
Fig.21: Macrophages of splenic red
begins. pulp destroying effete red blood cells.
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Functions of the spleen

➢ The spleen has both immune and blood related functions

occurring in the different pulps of the spleen.

a) Immune functions: occur in the white pulp

1. Antigen presentation
2. Activation of lymphocytes
3. Production of antibodies
4. Removal of various antigens from blood

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b) Blood related functions: occur in the red pulp
1. Removal and destruction of senescent, damaged, or
abnormal erythrocytes from the blood. The spleen is thus
considered the ‘graveyard of erythrocytes’.
2. Retrieval of iron and hemoglobin from the destroyed red
blood cells. These substances will be reused for the
formation of new RBCs or excreted.
3. Destruction of antigens in blood.

→ Because of these functions, the spleen is considered a ‘Filter of

Blood’.

c) Formation of blood during fetal life.

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d) Storage of blood.
Development of the spleen

➢ During the fourth week of development, the formation of

alimentary tract begins. The developing stomach is attached
to the anterior body wall by a double-layer of peritoneum
called the ventral mesogastrium, and it’s attached to the
posterior body wall by a double-layer of peritoneum called
the dorsal mesogastrium.

➢ The spleen develops from mesenchymal cells between the

two layers of the dorsal mesogastrium.

➢ The spleen begins to develop during the fifth week, but it

does not acquire its characteristic shape until early in the fetal
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period.
Fig.22: Above, the spleen develops
within the dorsal mesogastrium. To the
right, note the peritoneal folds that
connects the spleen to the stomach and
the posterior abdominal wall.
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➢ The fetal spleen is lobulated, but the lobules normally disappear
before birth. The notches in the superior border of the adult
spleen are remnants of these fetal lobules.

➢ The developing spleen divides the dorsal mesogastrium into

three part:
1. The part between the stomach and the spleen, this will
form the gastrosplenic ligament.
2. The part surrounding the spleen, this is the peritoneal
covering of this organ.
3. The part between the spleen and the posterior abdominal
wall, this will form the splenorenal ligament.

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Clinical spleen

➢ The spleen is a small organ about the size of a clenched fist.

Its anterior extremity does not, usually, cross over the mid-
axillary line. Because of this, the normal spleen cannot be
palpated. The notches of the superior border assist in
identifying a palpable enlarged spleen.

➢ Wandering spleen: The ligaments of the spleen provide the

spleen with little mobility. Sometimes, these ligaments may
be long and mobility of the spleen increases. This is called a
‘wandering spleen’. These elongated ligaments may be
twisted leading to the compression of the vessels they contain
which will affect the blood supply to the spleen. 52
➢ Enlargement of the spleen (splenomegaly): In many
infectious diseases or in conditions with abnormal RBCs, the
spleen will be overworked and it will hypertrophy.

➢ Accessory spleen: One or more small, fully functional,

splenic masses may exist in addition to the main organ. These
can be found in one of the peritoneal folds, commonly near
the hilum.

➢ Splenic rupture: Although protected by the ribs, the spleen is

frequently injured. Severe blows on the left side may fracture
one or more ribs, resulting in sharp bone fragments that can
lacerate the spleen. Rupture of the spleen causes severe
intraperitoneal hemorrhage. 53
➢ Hypoxia and the spleen, when a person is exposed to
hypoxic conditions (high altitude, for example), the body
responds by several coping mechanisms. One of these is by
the spleen. Under hypoxic conditions, the smooth muscles in
the capsule of the spleen contract pushing the blood stored in
the spleen back into the circulation. In this way, more
oxygen-carrying RBCs re-enter the circulation and provide
the required oxygen to the various parts of the body.

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 Thank You
Did you know?

❑ The Bajau people (sea nomads) of south-east Asia are known for their long
period breath-hold diving. Research have shown that the spleens of these
people are larger than those of others that don’t dive in such a way. Is this
enlarged spleen what gives them the ability to dive for such long times?

❑ Refer to this article: Physiological and Genetic Adaptations to Diving in

Sea Nomads.
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