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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
Grading of lymphoedema
(Brunner)
 Subclinical
 excess interstitial fluid and histological
abnormalities in lymphatics and lymph nodes
but no clinically apparent lymphoedema
 Grade I
 Oedema pits on pressure and swelling largely
or completely disappears on elevation and bed
rest
 Grade II
 Oedema doesn’t pit and doesn’t reduce
upon elevation
 Grade III
 Oedema is associated with irreversible skin
changes e.g; fibrosis or papillae
Clinical features
 Characteristically involves foots
 Contour of ankle is lost
 Toes appears square
 Skin on the dorsum of the toes cannot be
pinched “Stemmer’s Sigh”
 Ulceration is unusual
 Ulceration and non healing bruises should
raise the suspicion of malignancy
 Lymphangiosarcoma was originally
described in post mastectomy oedema
 “Stewart-Treves” syndrome
 0.5% of patients
 Mean onset is 10 yrs
 Can develop in longstanding lymphedema
“20 yrs”
Malignancies associated with
lymphoedema
 Lymphangiosarcoma
 Kaposi’s sarcoma
 SCC
 Liposarcoma
 Malignant melanoma
 Malignant fibrous histocytoma
 BCC
 lymphoma
Filariasis
 Common cause of lymphedema worldwide
 Infectious disease caused by viviparous
nematodes “Wucheria bancrofti”
 Vector “mosquitos”
 Parasites enters the lymphatics via blood
 Lodges in lymphnodes
 Causing fibrosis and obstruction
 Either by direct damage or by immune
response of host
 Degree of lymphedema is often massive
referring to as elephantiasis
 Diethylcarbamazine destroys the
parasites but unable to reverse the
lymphedema
Investigations
 Routine tests
 CP, U&E, creatinine, LFT, T & DP, albumin, CRP
 Lymphangiography
 Lymphoscintigraphy
 CT
 MRI
 USG
 Limb volume measurement
Management
 Relief of pain
 Control of swelling
 Skin care
 Manual lymphatic drainage
 Multilayer lymphedema bandaging and
compression garments
 Exercise
 Drugs
 Surgery
 Bypass procedures
 Liposuction
 Limb reduction procedures
lymphomas
Hodgkin’s
lyphomas
Non Hodgkin’s
lymphomas
Hodgkin’s lymphomas
 Reed Stemberg giant cell
 Mainly arise from B lymphocytes
 Lymph node enlargement is often cervical
 Rubbery consistency
 Hepatosplenomegaly
 General symptoms of malignancies
 Diagnosed by lymph node histology and
bonemarrow aspirate and trephine biopsy
12 yrs old boy
Non Hodgkin’s lymphomas
 70% are B cell origin
 May present without typical lymphnode
enlargement
 Hepatosplenomegaly and other features
of malignancy
 Invx as in HL
 Treatment is mainly by chemotherapy
regimens
Thymic tumours
 May arise from either epithelium or
lymphoid tissue or both
 May present as
 Mediastinum mass
 Associated myasthenia gravis
 Associated immune deficiency states
 Treatment is by thymectomy
Gastric lymphoma
 Primary gastric lymphoma ~ 5% of all
gastric neoplasms
 most prevalent in the sixth decade of
life.
 most commonly occur in the gastric
antrum
 Primary gastric lymphomas are B cell-
derived
 arising from the mucosa-associated
lymphoid tissue (MALT)
 At an early stage, the disease takes the
form of a diffuse mucosal thickening,
which may ulcerate
 Presented as – pain, weight loss , bleeding
as s/s of Ca stomach
 Diffuse large B-cell lymphoma (55%)
 Associated with immunodeficiencies and H. pylori
infection
 Extranodal marginal cell lymphoma (MALT) (40%)
 Burkitt’s lymphoma (3%)
 associated with Epstein-Barr virus infections, highly
aggressive , younger age,
 Site – cardia or body of stomach
 Mantle cell and follicular lymphomas (each < 1%).
Management
 OGDS
 endoscopic biopsy ,not specify with endoscopic features
 Type of lymphoma
 Imaging
 EUS
 CT chest and abdomen
 H. pylori testing
 by histology and, if negative, confirmed by serology
Treatment
 multimodality treatment program
 Resection - controversial
 Chemotherapy plus radiation therapy: CHOP
(cyclophosphamide, hydroxy-daunomycin, Oncovin,
prednisolone)
 Early-stage MALT lymphomas
 Diffuse large B-cell lymphoma
 H. pylori eradication alone – Successful
eradication resulted in remission in more
than 75% of cases
 Follow up
 repeat endoscopy in 2 months to
document clearance of the infection as
well as biannual endoscopy for 3 years to
document regression
lymphoreticular system

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lymphoreticular system

  • 1. Applied Anatomy Physiology & Pathology of Lymphoreticular system Dr. Khaing zay aung 16. 2. 2015
  • 2. The lymphatic system comprises:  Lymphatic chanals  Lymphoid organs & (lymph nodes, Peyer’s patches, spleen, thymus & tonsils)  Circulating elements (lymphocytes and other mononuclear immune cells)
  • 3. 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
  • 4. 6 primary lymph sacs 2 JUGULAR 2 ILIAC 1 RETROPERITONEAL 1 CISTERNA CHILI
  • 5.  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
  • 6.  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.
  • 7. Development of thymus Develops from the third and fourth pharyngeal pouches The stroma arises out of the endodermal and also ectodermal in origin
  • 8. 5. Bud of thymus
  • 9.
  • 10. 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
  • 12.  The lymphatic tissues of the intestine, Payer’s patches, appear later than tonsils.  The second half of the pregnancy
  • 13. Development of the lymphnodes
  • 14.  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.
  • 15. 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
  • 16. 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
  • 17.
  • 18. Anatomy of lymphatic system  the lymphatic system parallels the cardiovascular system  One way system  Convey lymph from end organs to the cardiovascular system
  • 19.  Lymph contains nutrients, oxygen, hormones, fatty acids, toxins and waste products.
  • 20. 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.)
  • 22. 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.
  • 23. Lymphatic vessels  Blind ended tubes  Endothelial lined (single layer)  Lymphatic capillaries coalesce to form larger meshlike network of tubes ka lymphatic vessels
  • 24.
  • 26. 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
  • 27. 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
  • 28.  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.
  • 29.  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.
  • 30.  Three distinct microanatomical regions within a lymph node. Cortex Paracortex Medulla
  • 31. 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.
  • 32. 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.
  • 33.  These follicles have an outer ring of small B lymphocytes surrounding the germinal centre, which contains largely dividing lymphoblasts, macrophages and dendritic cells.
  • 34.  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.
  • 35.
  • 36. 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.
  • 37. 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.
  • 38.  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.
  • 39.
  • 40.
  • 41.
  • 42.
  • 43.
  • 44.
  • 45. 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
  • 46. 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.
  • 47. 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
  • 49. 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
  • 50. Area of body drained by thoracic duct
  • 51. area of body drained by the right lymphatic duct
  • 52. Thymus  Bilobed lymphoid organ  Located in the superior mediastinum  maximum absolute size during puberty between 30 and 40 g  It regresses after the puberty
  • 53.  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
  • 54.
  • 55. 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
  • 56.  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
  • 57.  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
  • 58.  Efferent lymphatics in white pulp joins with the arterioles  Emerge as nodes at the hilum  Drains via the retropancreatic nodes to the coeliac nodes
  • 59.
  • 60. 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
  • 61.  Palatine tonsils &  Lingual tonsils- at the base of posterior surface of tongue  These are collectively known as Waldeyer’s ring
  • 62.  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
  • 63.
  • 65. 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.
  • 66.  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
  • 67.  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.
  • 68.
  • 69. Innate immunity  Also called natural or native immunity  Defense mechanisms that are present before the infection  First line of defence  Always ready
  • 70. 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);
  • 71.  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
  • 72.  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.
  • 73. Adaptive immunity  Also called acquired or specific immunity  Mechanisms that are stimulated by microbes  Capable of recognizing nonmicrobial substances called ‘antigens’.
  • 74.  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
  • 75.  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.
  • 76.  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.
  • 77.  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.
  • 78.  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.
  • 79. 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)
  • 80.  Antigens can be divided into foreign - non-self, allogeneic, xenogeneic, etc. Autoantigens – self antigens
  • 81. 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).
  • 82.  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.
  • 83.
  • 84. Functions of the spleen 1. Haematological function 2. Immunological function
  • 85. 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
  • 86.  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
  • 87.  Haemopoiesis  Only in fetal life  No bld formation in the after birth  Revision of fetal pattern of haemopoiesis in certain diseases
  • 88. 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
  • 89.  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
  • 90.  Also influence the opsonization of pneumococci in non immune individuals  Susceptible to them after splenectomy
  • 91.
  • 92. Pathology  Reactive lymphadenitis  Tuberculous lymphadenitis  Lymphoedema  Lymphomas
  • 93. 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
  • 94. 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
  • 95.  Tissue diagnosis by excisional biopsy  Granuloma formation with grossly caseation necrosis  Definitive Rx is antituberculous chemotherapy
  • 96. 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
  • 97. 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
  • 98. Two main types  Primary  Unknown cause  Thought to be congenital lymphatic dysplasia  Secondary  Clear underlying cause
  • 99. 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)
  • 100. 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
  • 101. Grading of lymphoedema (Brunner)  Subclinical  excess interstitial fluid and histological abnormalities in lymphatics and lymph nodes but no clinically apparent lymphoedema  Grade I  Oedema pits on pressure and swelling largely or completely disappears on elevation and bed rest
  • 102.  Grade II  Oedema doesn’t pit and doesn’t reduce upon elevation  Grade III  Oedema is associated with irreversible skin changes e.g; fibrosis or papillae
  • 103. Clinical features  Characteristically involves foots  Contour of ankle is lost  Toes appears square  Skin on the dorsum of the toes cannot be pinched “Stemmer’s Sigh”  Ulceration is unusual  Ulceration and non healing bruises should raise the suspicion of malignancy
  • 104.
  • 105.  Lymphangiosarcoma was originally described in post mastectomy oedema  “Stewart-Treves” syndrome  0.5% of patients  Mean onset is 10 yrs  Can develop in longstanding lymphedema “20 yrs”
  • 106. Malignancies associated with lymphoedema  Lymphangiosarcoma  Kaposi’s sarcoma  SCC  Liposarcoma  Malignant melanoma  Malignant fibrous histocytoma  BCC  lymphoma
  • 107. Filariasis  Common cause of lymphedema worldwide  Infectious disease caused by viviparous nematodes “Wucheria bancrofti”  Vector “mosquitos”  Parasites enters the lymphatics via blood  Lodges in lymphnodes  Causing fibrosis and obstruction
  • 108.  Either by direct damage or by immune response of host  Degree of lymphedema is often massive referring to as elephantiasis  Diethylcarbamazine destroys the parasites but unable to reverse the lymphedema
  • 109.
  • 110. Investigations  Routine tests  CP, U&E, creatinine, LFT, T & DP, albumin, CRP  Lymphangiography  Lymphoscintigraphy  CT  MRI  USG  Limb volume measurement
  • 111. Management  Relief of pain  Control of swelling  Skin care  Manual lymphatic drainage  Multilayer lymphedema bandaging and compression garments  Exercise  Drugs
  • 112.  Surgery  Bypass procedures  Liposuction  Limb reduction procedures
  • 113.
  • 114.
  • 115.
  • 117. Hodgkin’s lymphomas  Reed Stemberg giant cell  Mainly arise from B lymphocytes  Lymph node enlargement is often cervical  Rubbery consistency  Hepatosplenomegaly  General symptoms of malignancies  Diagnosed by lymph node histology and bonemarrow aspirate and trephine biopsy
  • 118. 12 yrs old boy
  • 119. Non Hodgkin’s lymphomas  70% are B cell origin  May present without typical lymphnode enlargement  Hepatosplenomegaly and other features of malignancy  Invx as in HL  Treatment is mainly by chemotherapy regimens
  • 120. Thymic tumours  May arise from either epithelium or lymphoid tissue or both  May present as  Mediastinum mass  Associated myasthenia gravis  Associated immune deficiency states  Treatment is by thymectomy
  • 121. Gastric lymphoma  Primary gastric lymphoma ~ 5% of all gastric neoplasms  most prevalent in the sixth decade of life.  most commonly occur in the gastric antrum  Primary gastric lymphomas are B cell- derived  arising from the mucosa-associated lymphoid tissue (MALT)
  • 122.  At an early stage, the disease takes the form of a diffuse mucosal thickening, which may ulcerate  Presented as – pain, weight loss , bleeding as s/s of Ca stomach
  • 123.  Diffuse large B-cell lymphoma (55%)  Associated with immunodeficiencies and H. pylori infection  Extranodal marginal cell lymphoma (MALT) (40%)  Burkitt’s lymphoma (3%)  associated with Epstein-Barr virus infections, highly aggressive , younger age,  Site – cardia or body of stomach  Mantle cell and follicular lymphomas (each < 1%).
  • 124. Management  OGDS  endoscopic biopsy ,not specify with endoscopic features  Type of lymphoma  Imaging  EUS  CT chest and abdomen  H. pylori testing  by histology and, if negative, confirmed by serology
  • 125. Treatment  multimodality treatment program  Resection - controversial  Chemotherapy plus radiation therapy: CHOP (cyclophosphamide, hydroxy-daunomycin, Oncovin, prednisolone)
  • 126.  Early-stage MALT lymphomas  Diffuse large B-cell lymphoma  H. pylori eradication alone – Successful eradication resulted in remission in more than 75% of cases  Follow up  repeat endoscopy in 2 months to document clearance of the infection as well as biannual endoscopy for 3 years to document regression