the lymphatic system

The Lymphatic System

Chapter 20

Introduction The lymphatic system supports the

function of the cardiovascular and immune systems of the body

The lymphatic system consists of two semi-independent parts– A network of lymphatic vessels– Lymphoid organs scattered throughout the

body

Introduction The lymphatic vessels transport fluids

that have escaped from the cardio-vascular system

The main components of the immune system (lymphocytes, lymphoid tissue, and lymphoid organs) fight infections and confer immunity to disease

The Lymphatic System An elaborate system of lymphatic vessels

runs throughout the body These vessels collect a fluid called lymph

from the loose connective tissue around blood capillaries and carry this fluid to the great veins at the root of the neck

The Lymphatic System Because lymph flows

only toward the heart, the lymphatic vessels form a one-way system rather than a full circuit

The Lymphatic System There are several

orders of vessels– Lymph capillaries– Lymphatic

collecting vessels– Lymph nodes– Lymph trunks– Lymph ducts

The Lymphatic System Recall that all blood

capillaries are surrounded by a loose connective tissue that contains tissue fluid or interstitial fluid

The fluid arises from blood filtered through the capillary walls

The Lymphatic System Tissue fluid consists of

small molecules of blood plasma, water, various ions, nutrient molecules, and respiratory gases

The Lymphatic System Tissue fluid is

continuously leaving and re-entering the blood capillaries

For complex reasons slightly more fluid arises from the arteriole end than re-enters the venule end

This amounts to about 3 liters a day

The Lymphatic System The lymphatic

vessels function to collect this excess fluid and return it to the bloodstream

Any blockage of the lymphatic vessels causes the affected body region to swell with excess tissue fluid resulting in edema

The Lymphatic System The lymphatic vessels also perform another

related function Blood proteins leak slowly from blood

capillaries into the surrounding tissue fluid Lymph vessels return leaked proteins to the

bloodstream This is important because proteins in blood

generate osmotic forces that are essential for keeping water in the bloodstream

Lymph Capillaries

Lymph capillaries are permeable vessels that receive the tissue fluid

They are located near blood vessels in the loose connective tissue

Like blood capillaries their walls consists of a single layer of endothelial cells

Lymph Capillaries Lymph capillaries

are very permeable The permeability

results from the structure and arrangement of the endothelial cells

They have few intercellular junctions

Lymph Capillaries In lymph capillaries

the adjacent edges of cells overlap to form easily opened mini- valves

These valves open to allow tissue fluid to enter the lymphatic capillary

Collagen filaments anchor the cells to the connective tissue

Lymph Capillaries The minivalves work because the collagen

filaments anchor portions of the cell wall to the surrounding connective tissue

Any fluid pressure in the volume of the tissue fluid separates the minivalves

This opens gaps in the wall of the capillary allowing fluid to enter

Once in the lymphatic capillary, it cannot leak out, because backflow pressure forces the minivalve flaps together

Distribution of Lymphatic Vessels Lymph capillaries are widespread,

occurring almost everywhere blood capillaries occur

Lymph capillaries are absent from bone and teeth, bone marrow, and the entire central nervous system

Lymph Capillaries Once interstitial fluid enters the

lymphatic ducts it is called lymph Although the high permeability of lymph

capillaries allows the uptake of large quantities of tissue fluid and protein molecules it also allows bacteria, viruses, or cancer cells in the loose connective tissue to enter these capillaries with ease

Lymph Capillaries These pathogenic agents can then travel

throughout the body via the lymphatic vessels

However, most pathogenic agents are destroyed in the lymph nodes by various antibodies before reaching the general circulation

Cancer cells can be the most problematic and can actually use lymph nodes as a site to metastasize further

Lymph Capillaries Lymph

capillaries are widespread, occurring almost everywhere blood capillaries occur

Lymph Capillaries Lymph capillaries are absent from bone

and teeth, from bone marrow, and from the entire CNS

In the CNS excess fluid drains into the cerebrospinal fluid and then returns it to the blood at the superior sagittal sinus

Lymph Collecting Vessels From the lymph

capillaries, lymph enters lymphatic collecting vessels which accompany blood vessels

Lymph Collecting Vessels In general, the

superficial lymphatic collecting vessels in the skin travel with superficial veins

Deep lymphatic collecting vessels of the trunk and digestive viscera travel with the deep arteries

Lymph Collecting Vessels Lymphatic collecting vessels are narrow

and delicate and are usually not seen in a laboratory dissection

The vessels have the same tunics as blood vessels but their walls are always thinner

The thinness reflects the fact that lymph flows under very low pressure and have no pump to move the lymph along

Lymph Collecting Vessels To direct the flow of

lymph, lymphatic collecting vessels contain more valves than do veins

At the base of each valve, the vessel bulges, forming a pocket in which lymph collects and forces the valve shut

Lymph Collecting Vessels Because of these

bulges, each collecting vessel resembles a string of beads

This distinctive appearance, which characterizes the larger lymph ducts as well allow MD’s to recognize lymph vessels in X-rays

Lymph Collecting Vessels Unaided by pressure from a pump,

lymph is propelled through lymph vessels by a series of weaker mechanisms

The action of contracting skeletal muscle and the pulsation of nearby arteries push on lymph vessel, squeezing lymph through them

Lymph Collecting Vessels The muscular tunica media of the lymph

vessels also contacts to help propel the lymph

Additionally, the normal movements of the limbs and trunk keep the lymph flowing

Despite these mechanisms, the transport of lymph is slow

People who are inactive or who stand for long times often develop edema

Lymph Nodes Lymph nodes, which

cleanse the lymph of pathogens are bean shaped organs situated along lymphatic collecting vessels

The term lymph gland is not correct because they are not glandular in their function

There are about 500 lymph gland in the body

Lymph Nodes Large clusters of

superficial lymph nodes in the cervical, axillary, and inguinal regions

The superficial cervical nodes along the jugular and carotid arteries receive lymph from the head and neck

Lymph Nodes Axillary nodes in the

armpit filter lymph from the upper limbs

Lymph Nodes The inguinal nodes in

the superior thigh filter lymph from the lower limb

Lymph Nodes Nodes in the

mediastinum such as the deep tracheobronchial nodes receive lymph from the thoracic viscera

Lymph Nodes Deep nodes along the

abdominal aorta, called aortic nodes, filter lymph from the posterior abdominal wall

Lymph Nodes Finally, deep nodes

along the iliac arteries, called iliac nodes, filter lymph from the pelvic organs and the lower limbs

Lymph Nodes The microscopic

anatomy of a lymph node suggests its role as a body filter

The node is surrounded by a fibrous capsule of dense connective tissue

Lymph Nodes Fibrous strands of

connective tissue called trabecule extend inward to divide the node into compartments

Lymph Nodes Lymph enters the

convex aspect of the node through several afferent lymphatic vessels and exits from the indented region on the other side, the hilus, through efferent lymphatic vessels

Lymph Nodes Between the

afferent and efferent vessels, lymph percolates through lymph sinuses

These large lymph capillaries are spanned internally by a crisscrossing network of reticular fibers

Lymph Nodes The reticular fibers are

covered by star-shaped endothelial cells

Many macrophages live on this fiber network, phagocytizing pathogens and foreign particles in the lymph that flows through the sinuses

Lymph Nodes Most lymph passes through several nodes It is usually free of pathogens by the time

it leaves its last node and enters the lymph trunks on its way to the great veins in the neck

Lymph Nodes Along with its

lymph sinuses, a lymph node also contains tadpole shaped masses of lymphoid tissue

This tissue is divided into outer (cortex) and inner (medulla) regions and are part of the immune system

Lymph Trunks After leaving the

lymph nodes, the largest lymphatic collecting vessels converge to form lymph trunks

These trunks drain large areas of the body

Lumbar Trunks The paired lumbar

trunks lie along either side of the aorta in the inferior abdomen

They receive all lymph draining from the lower limbs, pelvic organs and some of the anterior abdominal wall

Intestinal Trunk The unpaired

intestinal trunk lies near midline on the posterior abdominal wall

It receives fatty lymph (chyme) from the stomach, intestines, and other digestive organs

Brachiomediastinal Trunks These paired

trunks ascend near the sides of the trachea

They collect lymph from the thoracic viscera and thoracic wall

Subclavian Trunks These are paired

trunks located near the sides of the trachea

These trunks receive lymph from the upper limbs

They also drain the inferior neck and the superior thoracic wall

Jugular Trunks These trunks are

located in the neck at the base of each internal jugular vein

These trunks drain lymph from the head and neck

Lymph Ducts The lymph trunks drain into the largest

vessels the lymph ducts The number of ducts in an individual

may vary from two to only only duct

Thoracic Duct The thoracic duct

is present in all individuals

Its most inferior part, located at the union of the lumbar and intestinal trucks is the cisterna chyli which lies on the bodies of vertebrae L1 + L2

Thoracic Duct The thoracic duct

ascends along the vertebral bodies

In the superior thorax, it turns left and empties into the venous circulation at the junction of the internal jugular and left subclavian veins

Right lymphatic Duct Some people have

a short right lymphatic duct formed by the union of the right jugular, subclavian, and broncho-mediastinal trunks

Right lymphatic Duct When present, this

duct empties into the neck veins at or near the junction of the right internal jugular and subclavian veins

The right lymphatic duct drains the upper quarter of the body

Right lymphatic Duct In individuals

without a right lymphatic duct, the three trunks empty separately into the neck veins

Lymphatic Vessels In summary, the lymphatic vessels….

– Return excess tissue fluid to the bloodstream– Return leaked proteins to the blood– Carry absorbed fat from the intestine to the

blood through lacteals

Immune System The immune system is central to the

body’s fight against disease Unlike the body’s other defense systems,

it recognizes and attacks specific foreign molecules

It destroys pathogens more and more effectively with each new exposure

Immune System The immune system centers around the

key defense cells from lymphocytes But it also includes lymphoid tissue, and

the lymphoid organs these include…– Lymph nodes, spleen, thymus, tonsils,

aggregated lymphoid nodules in the small intestine, and appendix

Lymphocytes Infectious microorganisms that penetrate

the epithelial barriers of the body enter the underlying loose connective tissues, where they are attacked by the inflammatory response, by macrophages and finally, by lymphocytes of the immune system

Lymphocytes are white blood cells and that each lymphocyte recognizes and attacks its own type of foreign molecule, called an antigen

Lymphocytes B lymphocytes multiply to become

plasma cells that secrete antibodies Cytotoxic (CD8+) T lymphocytes destroy

antigen bearing cells by penetrating their membranes and inducing programmed cell death

Lymphocytes B and T cells continuously travel in the

blood and lymph streams to reach infected connective tissues throughout the body, where they fight infection

They repeatedly enter and exit these connective tissues, including the often infected lymphoid tissue, by squeezing through the walls of capillaries and venules

Lymphocytes This repeated movement of activated

lymphocytes between the circulatory vessels and the connective tissues, called recirculation, ensures that lymphocytes reach all infection sites quickly

Lymphocyte Activation Immature lymphocytes go through

several stages before they are able to attack antigens

Most lymphocytes pass through these stages during infancy and childhood, by many do so in adulthood as well

Lymphocyte Activation

This illustration provides an overview of lymphocyte activation

Lymphocyte Activation Lymphocytes

originate in the bone marrow from lymphoid stem cells, some of which travel in the bloodstream to the thymus in the thorax and become T lymphocytes (T is for Thymus)

Lymphocyte Activation Other

lymphocytes stay in the bone marrow and become B lymphcytes

Lymphocyte Activation These new T and B lymphocytes divide

rapidly and generate many lymphocyte families (clones), each of which is able to recognize one unique type of antigen (this is called gaining immunocompetence)

Lymphocyte Activation Young T or B

lymphocytes travel through the bloodstream to an infected connective tissue, where it binds to its specific antigen, an encounter called antigen challenge

Lymphocyte Activation As a consequence of the antigen challenge

the lymphocyte becomes fully activated, gaining the ability to attack its antigen, proliferates rapidly, and produces mature lymphocytes that recirculate throughout the body seeking pathogens to attack

Lymphocyte Activation During the antigen challenge, an activating

lymphocyte interacts with several other cells types

The lymphocyte receives its antigen from an antigen presenting cell, such as a macrophage that has recently phagocytized the antigen, or a star shaped dendritic cell, a professional antigen gathered that patrols the body seeking antigens and carries them to places where lymphocytes gather

Lymphocyte Activation A distinct type of lymphocyte, called a

helper (CD4+) T lymphocyte, secretes chemical signals that greatly stimulate the proliferation of activating B and cytotoxic T lymphocytes

Helper T cells are important because their signals amplify and fine-tune the immune response

Lymphocyte Activation The importance of helper T lymphocytes

is illustrated by acquired immune deficiency syndrome (AIDS), a viral disease in which a drastic decline in the body’s helper T cells greatly weakens the immune system

Lymphocyte Activation As more activating T or B cells

proliferates within infected connective tissue, it produces two types of mature lymphocytes, effector and memory

Short lived effector lymphocytes attack the pathogen immediately and then die

Memory lymphocytes, by contrast, wait until the body encounters their antigen again - maybe decades later

Lymphocyte Activation When a memory lymphocyte finally

encounters its antigen, its proliferating response and its attack are most vigorous and rapid

Memory lymphocytes are the basis for acquired immunity

They guard against subsequent infections and prevent us from getting many diseases more than once

There are T and B varieties of memory lymphocytes

Lymph Nodes: Clinical Inflammation of a node is caused by a

large number of bacteria trapped in a node– Inflammation results in swelling and pain

Lymph nodes can become secondary cancer sites, particularly in metastasizing cancers that enter lymphatic vessels and become trapped– Cancer infiltrated nodes are swollen but not

painful

Lymphoid Tissue Lymphoid tissue is an important

component of the immune system because it– Houses and provides a proliferation site for

lymphocytes– Furnishes an ideal surveillance vantage point

for both lymphocytes and macrophages

Lymphoid Tissue Lymphoid tissue is the most important

tissue of the immune system The tissue is an often infected connective

tissue in which vast quantities of lymphocytes gather to fight invading microorganisms

This tissue had two general locations– Mucous membranes– Lymphoid organs

Lymphoid Tissue Mucous membranes

– Found within the digestive, respiratory, urinary and reproductive tracks where it is called mucosa-assocaited lymphoid tissue (MALT)

Lymphoid Organs– Lymph nodes, spleen, thymus, tonsils,

aggregated lymphoid nodules, and appendix

Lymphoid Tissue This tissue is the main battleground in

the fight against infection Lymphoid tissue is where most

lymphocytes become activated and most effector and memory lymphocytes are generated

Lymphoid Tissue Lymphoid tissue, a

type of loose connective tissue called reticular connective tissue, dominates all lymphoid organs except the thymus

The dark staining areas represent the connective tissue fibers

Lymphoid Tissue The structural features

of lymphoid tissue serves its infection fighting role

It is a reticular connective tissue whose basic framework is a network of reticular fibers secreted by reticular cells (fibroblasts)

Lymphoid Tissue Within the spaces

of this network reside the many T and B lymphocytes that arrive continuously from venules coursing through the tissue

Lymphocytes

Macrophage

Reticularfiber

Lymphoid Tissue Macrophages on

the fiber network kill invading microorganisms by phagocytosis and along with dendritic cells, they activate nearby lymphocytes by presenting them with antigens

Lymphocytes

Macrophage

Reticularfiber

Lymphoid Tissue Evident within

lymphoid tissues are scattered, spherical clusters of densely packed lymphocytes, called lymphoid nodules or follicles

These nodules often exhibit lighter staining germinal centers

Lymphoid Tissue Nodules derive from

the activation of a single B cell, whose rapid proliferation generates the thousands of lymphocytes in the nodule

Newly produced B cells migrate away from the nodule to become plasma cells

Lymphoid Organs Lymphoid organs are

the lymph nodes, spleen, thymus, aggregated lymphoid nodules in the small intestine, and appendix

Lymphoid Organs Lymph nodes are

more than filters The regions of the

node between the lymph sinuses are tadpole shaped masses of lymphoid tissue

Lymphoid Organs As lymph moves

through the sinuses, some of the contained antigens leak out through the sinus wall into the lymphatic tissue

Most antigen challenges in the human body occur in the lymph nodes

Lymphoid Organs In the lymph nodes

antigens are destroyed and B and T lymphocytes are activated

The activation adds to the body’s supply of memory lymphocytes that offer long term immunity

Lymphoid Organs Lymph nodes have

two histologically distinct regions, an external cortex and a medulla

All the lymphoid nodules and most B cells occupy the lymphoid tissue of the most superficial part of the cortex

Lymphoid Organs Deeper in the cortex

the lymphocytes are primarily T cells, especially helper T cells that increase the activity of B cells in the nearby nodules

Lymphoid Organs Thin, inward

extensions from the cortical lymphoid tissue help define the medulla

These cord like medullary extensions contain both T and B lymphocytes, plus plasma cells

Spleen The soft, blood rich

spleen is the largest lymphoid organ

Its size varies greatly among individual, but on average it is the size of a fist

Lymph Nodes Dendritic cells nearly encapsulate the

follicles and abut the rest of the cortex, which primarily houses T cells in transit

The T cells circulate continuously between the blood, lymph nodes, and lymphatic stream, performing their surveillance role

Spleen The large splenic

vessels enter and exit the spleen on the anterior surface along a line called the hilus

Spleen The spleen has two main blood cleansing

functions– The removal of blood-borne antigens (its

immune function)– The removal and destruction of aged or

defective blood cells Additionally, the spleen is a site of

hematopoiesis in the fetus and stores blood platelets throughout life

Spleen The spleen is

surrounded by a fibrous capsule from which trabeculae extend inward

The larger branches of the splenic artery run in the trabeculae and send smaller arterial branches into the substance of the spleen

Spleen The arterial branches

are called central arteries because they are enclosed by thick sleeves of lymphoid tissue that collectively constitute the white pulp of the spleen

Spleen Blood borne antigens

enter this lymphoid tissue and are destroyed as they activate the immune response

Surrounding the white pulp is red pulp which has two parts– Venous sinuses– Splenic cords

Spleen Venous sinuses are

sinusoid capillaries that arise from the distal branches of the central arteries outside of the white pulp

Spleen Splenic cords consist

of reticular connective tissue that is exceptionally rich in macrophages

Whole blood leaks from the sinuses into this connective tissue where macrophages then phagocytize any defective blood cells

Spleen Red pulp is responsible for the spleen’s

ability to dispose of worn-out blood cells White pulp provides the immune

function of the spleen

Thymus The two lobed

thymus lies in the anterior thorax and inferior neck, just posterior to the sternum

Thymus The thymus is the site at which immature

lymphocytes develop into T lymphocytes The thymus secrets thymic hormones

such as thymopoietin which causes T lymphocytes to gain immunocompetence

Thymus Prominent in newborns, the thymus

continues to increase in size during childhood when it is most active

During late adolescence, it begins to atrophy gradually, as its functional tissue is slowly replaced with fibrous and fatty tissue

Thymus At age 20 it still has about 80% of its

functional tissue but at age 40 it typically retains only 5% of its functional tissue

By age only 2% of functional tissue remains and the thymus is a fatty mass that is difficult to distinguish from surrounding connective tissue

However, even as it atrophies, the thymus continues to produce immunocompetent cells throughout adulthood (reduced rate)

Thymus

Again, the thymus lies in the superior thorax

Thymus

The thymus contains numerous lobules arranged like fronds in the head of a cauliflower

Each lobule contains an outer cortex and an inner medulla

Thymus The cortex is packed with rapidly

dividing T lymphocytes gaining immunocompetence

The medulla contains fewer lymphocytes In addition, the medulla contain the

thymic (Hassall’s) corpuscles which seem to be collections of degenerating epithelial reticular cells

The number and size of these corpuscles increases with age

Thymus The thymus differs from other lymphoid

organs in two basic ways (First) – It functions strictly in lymphocyte

maturation and thus is the only lymphoid organ that does not directly fight antigens

– The blood-thymus barrier, keeps blood-borne antigens from leaking out of thymic capillaries and prematurely activating the immature thymic lymphocytes

Thymus The thymus differs from other lymphoid

organs in two basic ways (Second)– The tissue framework of the thymus is not a

true lymphoid connective tissue– The thymus arises like a gland from the

epithelium lining the embryonic pharynx– Its basic tissue framework consists of star

shaped epithelial cells rather that reticular fibers

Thymus The thymus differs from other lymphoid

organs in two basic ways (Second)– These epithelial reticular cells secrete the

thymic hormones that stimulate T cells to become immunocompetent

– The thymus has no lymphoid nodules because it lack B cells

The Tonsils The tonsils are perhaps the simplest

lymphoid tissue They are mere swellings of the mucosal

lining of the pharynx

The Tonsils

There are four groups of tonsils, palatine, lingual, pharyngeal, and tubal

The Tonsils The palatine tonsils lie directly posterior

to the mouth and palate on the lateral sides of the pharyngeal wall

These are the largest tonsils and the ones most often infected and removed during childhood (tonsillectomy)

The lingual tonsil lie on the posterior surface of the tongue

The Tonsils The pharyngeal tonsil (adenoids) lie on

the pharyngeal roof The tubal tonsils are just behind the

openings of the pharyngotympanic tubes into the pharynx

The Tonsils The four tonsils are arranged in a ring

around the entrance to the pharynx to gather and remove many pathogens that enter the pharynx in inspired air and swallowed food

The tonsils process the antigens, then set up immune responses

The Tonsils The tonsils

consist of an epithelium underlain by a connective tissue lamina propria

The Tonsils In the tonsils the

underlying propria consists of abundant mucosa associated lymphoid tissue (MALT) packed with lymphocytes and scattered lymphoid nodules

Germinalcenters

The Tonsils The overlying

epithelium invaginates deep into the interior forming blind ended structures called crypts that trap bacteria and particulate matter

The Tonsils The trapped

bacteria work their way through the epithelium into the underlying lymphoid tissue causing the activation of lymphocytes

The Tonsils The trapping of bacteria in the crypts

leads to many infections during childhood

But it also generates a great variety of memory lymphocytes for long-term immunity

The Tonsils By inviting an

infection, the tissue produces a wide variety of immune cells with a “memory” for the trapped pathogens

The early risk during childhood results in better health in adulthood

Aggregates of Lymphoid Follicles Many bacteria permanently inhabit the

hollow interior of the intestines and are constantly infecting the intestinal walls

To fight these invaders, MALT is especially abundant in the intestine

In two parts of the intestine, MALT is so large, permanent, and densely packed with lymphocytes that is said to form lymphoid organs: Aggregated lymphoid nodules and the appendix

Aggregates of Lymphoid Follicles Aggregated

lymphoid nodules (Peyer’s patches) are clusters in the walls of the distal part of the ileum of the small intestine

About 40 of these patches are present averaging about 1 cm and 1 cm wide

Peyer’s Patches

Aggregates of Lymphoid Follicles Aggregates of lymphoid follicles are ideally

situated to destroy bacteria thereby preventing these pathogens from breaching the intestinal wall

The Appendix The appendix is a

tubular offshoot of the first part of the (cecum) of the large intestine

The Appendix Lymphoid tissue is

also heavily concentrated on the walls of the appendix

Histological sections reveal that dense lymphoid tissue uniformly occupies over half the thickness of the wall of the appendix

The Appendix Beside destroying the microorganisms

that invade them, the aggregated lymphoid nodules and the appendix sample many different antigens from within the digestive tube and generate a wide variety of memory lymphocytes to protect the body