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 k\a

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 ltsubclavian 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 fibrinolyticfactors

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