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Applied Anatomy
Physiology &
Pathology of
Lymphoreticular
system
Dr. Khaing zay aung
16. 2. 2015
The lymphatic system comprises:
 Lymphatic chanals
 Lymphoid organs &
(lymph nodes, Peyer’s patches, spleen, thymus &
tonsils)
 Circulating elements
(lymphocytes and other mononuclear immune cells)
Developmental Anatomy
 6 to 7 week of fetal life
 The origin of the lymphatic vessels
is unclear
 May arise from sac like outgrowth
of the endothelium of the veins
6 primary lymph sacs
2 JUGULAR
2 ILIAC
1 RETROPERITONEAL
1 CISTERNA CHILI
 These lymph-sacs are developed by the
confluence of numerous venous capillaries
 Which at first lose their connections with
the venous system
 But subsequently, on the formation of the
sacs, regain them
 Two main chanals
 The rt and lt thoracic ducts
 They join the jugular sacs with the
cisterna chili
 Drain into the venous system at the
junction of the internal jugular vein
and the subclavian vein
 Numerous anastomoses produce many
variations in the final form of the thoracic
duct.
Development of thymus
Develops from the third and
fourth pharyngeal pouches
The stroma arises out of the
endodermal and also
ectodermal in origin
5. Bud of thymus
Development of tonsils
 The tonsil buds appear with the formation
of the pharyngeal pouches
 Located in the throat region
 Palatine, lingual and unpaired pharyngeal
tonsils
8.Tonsilar buds
 The lymphatic tissues of the intestine,
Payer’s patches, appear later than tonsils.
 The second half of the pregnancy
Development of the lymphnodes
 The origin of the lymphatic vessels is
unclear
 May arise from sac like outgrowth of
the endothelium of the veins
 The primary lymph nodes develop in
regions that are occupied by lymphatic
sacs.
Development of spleen
 From the thickening of the visceral
mesothelium
 Within it there is an accumulation of the
mesenchymal cells
 Along the leftward shift of the stomach, it
resided on the left side of the abdomen
 During the first trimester, macrophages and
precursor cells of erythropoiesis enter into
the spleen
 After 15 wks of gestation, the white pulp and
red pulp appears
Development of lymphocytes
 Largest part of the lymphocyte
development occurs in bone marrow,
thymus and the primary lymphatic organs
 Large number of immunocompetent
lymphocytes are produced that colonize
the secondary lymphatic organs,
lymphnodes, tonsils, MALT and spleen
 Distinguish into two types; T & B
lymphocytes
Anatomy of lymphatic system
 the lymphatic system parallels the
cardiovascular system
 One way system
 Convey lymph from end organs to the
cardiovascular system
 Lymph contains nutrients, oxygen,
hormones, fatty acids, toxins and waste
products.
Functions
 Worked together with the immune system
 As immune surveillance that Produce,
maintain, and distribute lymphocyte
 Alternative route of Collection and
transportation of fluid , nutrient ,
proteins and hormones
 Part in maintenance of normal blood
volume
(There is a small net movement of fluid
from the plasma into the interstitial fluid
along every systemic capillary. The total
volume is 3.6 l/day.)
Collection of lymph
Formation of lymph
 ISF forms at the arterial end of the capillaries
 Most of it returns to its venous ends and venules; the
rest (10—20%) enters the lymph capillaries as lymph.
 As it flows through the lymph nodes, however, it comes
in contact with blood and tends to accumulate more
cells (particularly lymphocytes) and proteins.
Lymphatic vessels
 Blind ended tubes
 Endothelial lined (single layer)
 Lymphatic capillaries coalesce to form
larger meshlike network of tubes ka
lymphatic vessels
The lymphatic system
Lymphatic capillaries
 Absent in bone, bone marrow, teeth,
CNS
 Enter lymphatic collecting vessels
 Lacteals – specialized lymph capillaries
present in intestinal mucosa
 Absorb digested fat and deliver chyle
to the blood
Lymphnodes
 Beanshaped structures
 Throughout the lymphatic system
 App: 600 to 700
 Concentrated in the neck, axilla, groin,
mediastinum & mesenteries of the GI
tract.
 Main line of defense by 2 types of cell
lines
 T & B lymphocytes
 A lymph node has an outer capsule of
connective tissue from which trabeculae
pass into the deeper tissue.
 Beneath the capsule is a space, the
subcapsular sinus into which the afferent
lymphatics drain after penetrating the
capsule.
 Lymph from the subcapsular sinus passes
via the medullary cords to the hilum of
the lymph node from which the efferent
lymphatics drain.
 Both afferent and efferent vessels have
valves which allow only forward flow.
 The node consists of an outer cortex and an
inner medulla and contains lymphatic
sinuses.
 Three distinct microanatomical
regions within a lymph node.
Cortex
Paracortex
Medulla
1. Cortex: which contains either primary
or secondary lymphoid follicles;
2. Paracortex: which is the T-cell
dependent region of the lymph node; and
3. Medulla: which contains the medullary
cords and sinuses and also contains
lymphocytes which are much less densely
packed than in the cortex, together with
macrophages, plasma cells and a small
number of granulocytes.
Cortex
 consists of primary lymphoid follicles which
are unstimulated follicles, spherical in
shape, containing densely packed
lymphocytes.
 Secondary follicles are present after
lymphocytes have been stimulated
antigenically.
 These follicles have an outer ring of small
B lymphocytes surrounding the germinal
centre, which contains largely dividing
lymphoblasts, macrophages and dendritic
cells.
 Antigen is trapped upon the surface of the
dendritic cells and presented to ‘virgin’ B
lymphocytes in the presence of T helper
cells.
 These B cells subsequently undergo a series
of morphological and functional changes.
 The function of germinal centre is to
generate immunoglobulin-secreting plasma
cells in response to antigenic challenge.
Paracortex
 T-cell-dependent region of the lymph node.
 When a T cell response occurs there is marked
proliferation of cells in this area.
 contains large number of T lymphocytes with
a predominance of helper/inducer cells.
 The cluster of differentiation (CD4) is
expressed by helper/inducer T cells.
Medulla
 Lymph enters the marginal sinus of the node and drains
to the hilum through the sinuses which converge into
the medullary region.
 The sinuses are lined by macrophages which
phagocytose foreign or abnormal particles from the
lymph passing through the node, i.e. the filtering
function.
 Between the sinuses in the medulla lie
the medullary cords which contain
numerous plasma cells.
 The medullary cords are one of the main
sites of antibody secretion within the
lymph node.
Waxing and waning of lymph
nodes
 Enlargement on infections occurs in the
corresponding areas
 Inflammation – swollen glands
 Lymphadenopathy– chronic or excessive
enlargement of lymph nodes
 They received the metastasizing cancer cells
 Spread along the lymphatics
 Nodal status is important
Lymphatic vessels
2 main lymphatic ducts
 Right lymphatic duct
drains the upper rt quardrant
 Thoracic duct
drains the remaining tributaries
They have one way valves to prevent any
back flow.
Cisterna chyli
 It is a lymphatic sac at the base of the
thoracic duct
 Anterior to the body of L1 or L2
 Formed by the convergence of the lumbar
lymphatic trunks and intestinal lymphatic
trunks
Cisterna chyli
Thoracic Duct
 Main lymphatic duct of the body
 Originates from the cisterna chili
 Enters into the thorax via the aortic
foramen of the diaphragm
 Situated in the posterior mediastinum
 Receives lymph from the left side of the
head & neck, lt upper limb & lt chest wall
 Empty into the junction of the lt
subclavian vein and internal jugular vein
Area of body drained by thoracic duct
area of body drained by the right lymphatic duct
Thymus
 Bilobed lymphoid organ
 Located in the superior
mediastinum
 maximum absolute size during
puberty between 30 and 40 g
 It regresses after the puberty
 Two lobes covered by capsules
 Fibrous septa – divided 2 mm area of lobules
on each lobe
 Each lobule
 dense cortex
 Pale medulla
 Lymphoid stem cells in cortex
 Divided rapidly and daughter T cells become
matured
 Migrated into Medulla -
 T cells sensitive to normal tissue are destroyed
Spleen
 Largest lymphoid organ
 75-250 g
 Lies in lt hypochondrium with its long axis
along the 10th rib
 Mainly over the 9th , 10th and 11th ribs
 There is a notch in its inferolateral
surface
 Blood supply is from the tortious splenic
artery from the coeliac axis
 Which gives off branches to stomach and
pancreas within the gastrosplenic
ligament
 Divides into superior and inferior
branches
 Splenic vein is formed by several
tributaries within the splenic substance
 Joins with the superior mesenteric vein to
form portal vein behind the neck of the
pancreas
 Efferent lymphatics in white pulp joins
with the arterioles
 Emerge as nodes at the hilum
 Drains via the retropancreatic nodes to
the coeliac nodes
Tonsils
 Aggregates of lymphnodes under the
epithelial lining of the oral and
pharyngeal areas
 Pharyngeal tonsils
 On the roof of the nasopharynx
 Also called the adenoids
 Palatine tonsils &
 Lingual tonsils- at the base of posterior
surface of tongue
 These are collectively known as
Waldeyer’s ring
 Bld supply is principally from the tonsilar
artery which is the branch of the facial
artery
 Entering at the lower pole of the tonsil
 Also from lingual, ascending palatine and
ascending pharyngeal arteries
 Lymphatic drainage is nodes around the
internal jugular vein to the
jugulodigestric or tonsillar nodes
Physiology
Functions of LYMPHATIC SYSTEM
 The principal function of the lymphatic
system is the return of protein rich fluid to
the circulation through the lymphatic venous
junctions in the jugular area.
 Water
 Electrolytes
 low molecular weight molecules
(polypeptides, cytokines, growth factors)
 Macromolecules - fibrinogen, albumin,
globulins, coagulation and fibrinolytic
factors
 From the interstitial fluid (ISF) return to
the circulation via the lymphatics
 Intestinal lymph (chyle) transports
cholesterol, long-chain fatty acids,
triglycerides and the fat-soluble vitamins (A,
D, E and K) directly to the circulation,
bypassing the liver.
 Lymphocytes and other immune cells also
circulate within the lymphatic system.
Innate immunity
 Also called natural or native immunity
 Defense mechanisms that are present
before the infection
 First line of defence
 Always ready
Innate immunity consists of:
• physical barriers
• secretions with antibacterial activity, including
lactoferrin;
• phagocytic cells: monocytes, macrophages and
neutrophils;
• NK cells (lymphocytes capable of non
MHC restricted killing);
 soluble mediators which can enhance the
activity of innate and specific responses:
 C-reactive protein (CRP)
 mannose-binding lectin (MBL)
 cytokines
 soluble enzymatic cascades such as the
complement system
 The innate immune system is non-adaptive,
i.e. it cannot adapt its receptors to
recognize an organism which has evolved
and mutated its antigens to evade binding.
 It does not develop memory
 It does not possess antigen specificity
through the specialized and mutable antigen
receptors of immunoglobulins.
Adaptive immunity
 Also called acquired or specific immunity
 Mechanisms that are stimulated by
microbes
 Capable of recognizing nonmicrobial
substances called ‘antigens’.
 These are more effective than innate
ones
 Mediated by lymphocytes and antibodies
which amplify and focus non-specific
responses and provide additional effector
functions
 These cells are organised into lymphoid
tissues
 Cellular (cell mediated) immunity refers
to lymphocyte-mediated effector
responses (T helper (Th) and cytotoxic
cells) of the specific immune response
 Cellular immunity refers to lymphocyte-
mediated effector responses (T helper
and cytotoxic T cells) of the specific
immune response
 Humoral immunity often refers to the
antibody arm of the specific immune
response.
 Antibodies are usually not produced without
some cell-mediated response to the same
antigen
 T and B lymphocytes possess infinitely
variable antigen receptors which can
clonally expand.
 Antigen receptors which can be secreted
into interstitial fluid and onto mucosal
surfaces are called antibodies.
 Antibodies can activate complement and
also enhance opsonization of antigen to
facilitate phagocytosis.
 Both innate and adaptive mechanisms
exponentially amplify the immune response
 since clonal expansion of lymphocytes
increases the number of cells reactive with
an antigen.
 Cytokines and complement components
recruit other immune effector mechanisms
and antibodies activate complement and
phagocytes.
 The specific adaptive immune response is thus
flexible and adaptable.
 Capable of responding to antigens which
have not been previously encountered
 Including those generated in organisms by
the selecting pressures of an effective
adaptive immune response.
 Many pathogens have specific
adaptations/mutations to evade previous
immunological memory responses (e.g.
influenza antigen variability) or to suppress
the normal mechanisms of immune
destruction.
ANTIGENS
 An antigen is any substance which can
elicit a specific immune response.
 Consists of many epitopes.
 An epitope is a specific sequence of a
protein or carbohydrate recognized by the
receptor molecules of the immune system
(antibody or T cell receptor)
 Antigens can be divided into
foreign - non-self, allogeneic,
xenogeneic, etc.
Autoantigens – self antigens
ANTIBODIES
 An antibody is a soluble protein immune
receptor produced by B lymphocytes,
consisting of two identical antigen-
binding sites .
 The antigen specificity of the antibody
resides in the antigen-binding variable
regions (the fragment antigen-binding,
Fab, portion).
 Antibodies are divided into different
isotypes (classes) which have different
functional attributes according to Fc
fragments
 Antibodies which bind to antigen or cells
and activate complement via the Fc region
thus recruit, activate, amplify and target
non-specific defense mechanisms.
Functions of the spleen
1. Haematological function
2. Immunological function
Haematological functions
 Site of quality control of erythrocyte
population
 Removes fragmented or damaged red
cells from circulation k/a culling
 Remodeling of surface of maturing
erythroctytes where by maintaining the
membrane surface area and volume ratio
 Removal of intraerythrocyte inclusions s/a
Heinz’s bodies, Howel-Jolly bodies k/a
pitting
 Clearance of particulate matter from the
circulation – imp function for the timely
immune response to blood borne antigens
 Sequestration of plalets
 Haemopoiesis
 Only in fetal life
 No bld formation in the after birth
 Revision of fetal pattern of haemopoiesis
in certain diseases
Immunological function
 Each population of lymphocyte is a
constant flux
 ¼ of body’s population of T lymphocytes
is in the spleen at a point time
 Humoral response following antigenic
stimulation involves co-operation
between T & B lymphocytes on the
surface of large dentritic cells
 Germinal centres ( secondary follicles)
later appear within the primary follicle
 Reach their maximum development in
about 8 wks following antigenic
stimulation
 Antibody response is relatively decreased
after splenectomy
 Also influence the opsonization of
pneumococci in non immune individuals
 Susceptible to them after splenectomy
Pathology
 Reactive lymphadenitis
 Tuberculous lymphadenitis
 Lymphoedema
 Lymphomas
Reactive Lymphadenitis
 Infections and nonmicrobial inflammatory
stimuli not only cause leukocytosis but
also involve the lymph nodes
 often associated with lymph node
enlargement (lymphadenopathy)
 may be acute or chronic
 histologic appearance of the nodes is
entirely nonspecific
Tuberculous lymphadenitis
 Especially neck glands
 Present as cervical lymphadenopathy
 Cold abscess
 Lymphnodes are rubbery and matted
together
 Eventually it can progress to collar stud
abscess formation & sinus
 Tissue diagnosis by excisional biopsy
 Granuloma formation with grossly
caseation necrosis
 Definitive Rx is antituberculous
chemotherapy
Lymphoedema
 Abnormal lymph swelling
 Caused by accumulation of increased
amount of high protein ISF
 Secondary to defective lymphatic
drainage in the presence of near normal
net capillary function
Pathophysiology
 Normal capillary function
 Oedema fluid is high protein content
 Results from
 Lymphatic aplasia
 Hypoplasia
 Dysmotility
 Obliteration by inflammation
 Infective or neoplastic process
 Surgical extirpation
Two main types
 Primary
 Unknown cause
 Thought to be congenital lymphatic
dysplasia
 Secondary
 Clear underlying cause
Aetiological classification of
lymphoedema
Primary
 Congenital (onset <2 years old):
 sporadic
 familial (Nonne–Milroy’s disease)
 Praecox (onset 2–35 years old):
 sporadic
 familial (Letessier–Meige’s disease)
 Tarda (onset after 35 years old)
Secondary
 lymphoedema
 Parasitic infection (filariasis)
 Fungal infection (tinea pedis)
 Exposure to foreign body material (silica
 particles)
 Primary lymphatic malignancy
 Metastatic spread to lymph nodes
 Radiotherapy to lymph nodes
 Surgical excision of lymph nodes
 Trauma (particularly degloving injuries)
 Superficial thrombophlebitis
 Deep venous thrombosis