Embryology and anatomy of Lymphatics. Function and diagnostic tests of lymphatics.

Presenter : Dr Shirin Joshi

Chairperson : Prof.Dr N K Ray.

History

• Hippocrates (ca. 460-ca. 360 B.C.)- Described axillary lymph nodes and "white blood" in the nodes

• Erasistratus (310-250 B.C.)- Described lymphatics of small bowel.

• Marinus (fl. A.D. 50)-Described mesenteric lymph nodes

• Bartholomeus Eustachius- From dissecting a horse, described thoracic duct ("vena alba thoracica")

• Sayegh et al.- Used term "sentinel node" to mean the node first visualized following injection of dye (lymphangiography)

Embryology

• During the 5th week of gestation, two paired and two unpaired endothelial sacs arise as outgrowths from the venous channels. These sacs form the primordia of the lymphatic system.

• The first primordial lymph sacs to appear are the paired jugular sacs in the neck. They are located bilaterally at the junction of the subclavian and internal jugular (precardinal) veins.

• The next sac to appear is unpaired and located at the mesenteric root in the retroperitoneal space. Later the unpaired cisterna chyli develops dorsal to the mesenteric sac. The final paired sacs, two posterior (iliac) sacs, appear at the junction of the sciatic and femoral veins. In short, it may be said that embryologically the lymph system originates and terminates in the venous system.

Development of the lymphatic vessels. A. Human embryo at nine weeks, showing the primitive lymph sacs and the developing vessels. B. Ventral view of the formation of the single thoracic duct from the primitive paired lymphatic plexus.

• By the end of the ninth week, these six lymphatic sacs are linked together by multiple endothelial channels to form a complicated network of lymphatic vessels (Fig. 29-1).

• During early fetal development mesenchymal cells invade these sacs, converting them into groups of lymph nodes

• At first, the nodes are represented by unencapsulated lymphoid tissue located within the meshwork of lymphatic channels. Later, the lymphoid mass separates into smaller portions allowing the inward growth of blood vessels and the lymphatic network.

• Each mass, together with portions of the surrounding network, becomes enclosed by a capsule of connective tissue.

• Embryologically, lymphocytes are derived from the primitive stem cells in the mesenchyme of the yolk sac.

• From a functional standpoint, there are two types of lymphocytes: T cells and B cells. The progeny of the lymphopoietic stem cells found in the bone marrow that are destined to become T cells exit the marrow and settle in the thymus where their differentiation is completed. Ultimately T cells enter the circulation as the long-lived small lymphocytes.

• B cells originate in marrow, gut-associated lymphatic tissue, and the spleen. T cells are responsible for cellular immunity; B cells are responsible for the synthesis of antibodies.

• Six sacs can be considered. The right and left jugular sacs lie near the junction of the posterior cardinal and subclavian veins ( ie at the future junction between the internal jugular and subclavian veins)

• The right and left( or iliac ) sacs lie around the corresponding common iliac vein.

• The retroperitoneal sac ( unpaired ) lies in relation to the root of the mesentry.

• The sixth sac ( unpaired ) is the cisterna chyli

• It lies in the midline some distance caudal to the retroperitoneal sac.

• Lymphatic vessels are formed either by extension from the sacs or may form de novo and extend into various tissues

• Ultimately all the sacs except cisterna chyli are invaded by connective tissue and lymphocytes and are converted into groups of lymph nodes.

LYMPHATIC SYSTEM COMPONENTS

LYMPHATIC VESSELS

• BUD FROM VEINS IN EMBRYO

• SIMILAR HISTOLOGY

• THREE TUNICS

– TUNICA INTERNA

– TUNICA MEDIA

– TUNICA EXTERNA

• THINNER WALLS THAN VEINS

• MORE VALVES THAN VEINS

COLLECTING VESSELS

• FORMED BY CONVERGENCE OF LYMPHATIC CAPILLARIES

• OFTEN TRAVEL ALONGSIDE VEINS

• OFTEN SHARE CONNECTIVE TISSUE SHEATH WITH VEINS

• NUMEROUS LYMPH NODES (ORGANS) OCCUR ALONG LENGTH

LYMPHATIC TRUNKS

• FORMED BY CONVERGENCE OF COLLECTING VESSELS

• SIX EXIST, EACH DRAINING MAJOR PORTION OF BODY

– LUMBAR TRUNK

– INTESTINAL TRUNK

– INTERCOSTAL TRUNK

– BRONCHOMEDIASTINAL TRUNK

– SUBCLAVIAN TRUNK

– JUGULAR TRUNK

COLLECTING DUCTS

• FORMED BY CONVERGENCE OF LYMPHATIC TRUNKS

• RIGHT LYMPHATIC DUCT

• THORACIC DUCT

LYMPHATIC TISSUE

• DIFFUSE

• AGGREGATES OF LYMPHOCYTES AND MACROPHAGES

• POPULATE MANY ORGANS

• ESPECIALLY PREVALENT IN PASSAGES OPEN TO EXTERIOR

– RESPIRATORY

– DIGESTIVE

– URINARY

– REPRODUCTIVE

LYMPHATIC ORGANS

• WELL-DEFINED

• CONNECTIVE TISSUE CAPSULES

• SITES OF LYMPHOCYTE AND MACROPHAGE CONCENTRATION

• LYMPHATIC ORGANS LYMPH NODES

• TONSILS

• THYMUS

• SPLEEN

• LYMPH NODES

• HUNDREDS IN BODY

• MOST EMBEDDED IN CONNECTIVE TISSUE

• VARIOUS SITES OF CONCENTRATION

• LYMPH NODES

• BEAN-SHAPED

• < 3 CM LONG

• ENCLOSED IN FIBROUS CAPSULE WITH EXTENSIONS (TRABECULAE)

• TRABECULAE COMPARTMENTALIZE INTERIOR

• LYMPH NODES

• STROMA

• CONNECTIVE FUNCTION

• RETICULAR FIBERS

• COLLAGEN, GLYCOPROTEIN

• PHAGOCTIC RETICULAR CELLS

• MACROPHAGES

• LYMPH NODES

• PARENCHYMA

• PHYSIOLOGICAL FUNCTION

• LYMPHOCYTES AND MACROPHAGES

• DIVIDED INTO

• OUTER CORTEX

• INNER MEDULLA

• LYMPH NODES

• STROMA

• CONNECTIVE FUNCTION

• PARENCHYMA

• PHYSIOLOGICAL FUNCTION

• CORTICAL SINUS

• SPACE BETWEEN CAPSULE AND PARENCHYMA

• LYMPH NODES

• OUTER CORTEX OF PARENCHYMA

• LYMPHATIC NODULES

• GERMINAL CENTERS IN NODULES PRODUCE B-LYMPHOCYTES DURING INFECTION

• OTHER CELLS MAINLY T-LYMPHOCYTES

• INNER MEDULLA OF PARENCHYMA

• LOOSE SYSTEM OF IRREGULAR SPACES (MEDULLARY SINUSES)

• MACROPHAGES CONCENTRATED

•

TONSILS

• DEEP PITS (TONSILLAR CRYPTS)

• PITS LINED BY LYMPHATIC NODULES

• INGESTED/INHALED MATTER ENTERS CRYPTS

• LYMPHOCYTES PRESENT IN AND BEYOND CRYPTS

THYMUS

• BETWEEN STERNUM AND AORTIC ARCH

• HOUSES DEVELOPING LYMPHOCYTES

– T-LYMPHOCYTES

• SECRETES HORMONES REGULATING ACTIVITY OF LYMPHOCYTES

• LARGE IN FETUS, EARLY CHILDHOOD

• SMALL IN ADULTS

• BEGINS SHRINKING AT ~14 YEARS OLD

THYMUS

• ENCLOSED IN FIBROUS CAPSULE WITH EXTENSIONS (TRABECULAE)

• TRABECULAE COMPARTMENTALIZE INTERIOR (PARENCHYMA)

• EACH LOBULE POSSESSES CORTEX AND MEDULLA

– POPULATED WITH LYMPHOCYTES

THYMUS

• SECRETES HORMONES

– THYMOPOIETIN AND THYMOSINS

– STIMULATE DEVELOPMENT AND ACTIVITY OF T-LYMPHOCYTES

• NECESSARY FOR THE DEVELOPMENT OF IMMUNITY

SPLEEN

• INFERIOR TO DIAPHRAGM

• DORSAL TO STOMACH

• FUNCTIONAL, BUT DISPENSIBLE

– LIVER, BONE MARROW DUPLICATE

• BLOOD PRODUCTION IN FETUS

– ALSO IN ADULTS WITH EXTREME ANEMIA

• BLOOD RESERVOIR IN ADULT

– VERY PERMEABLE CAPILLARIES

– ALLOW RBCs TO LEAVE BLOOD

SPLEEN

• FILTERS BLOOD ~LIKE LYMPH NODES

• ERYTHROCYTE GRAVEYARD

– SMALL CAPILLARIES

– MACROPHAGES PHAGOCYTIZE REMAINS

– MACROPHAGES PHAGOCYTIZE BACTERIA, DEBRIS, ETC.

• HIGHLY VASCULAR

• VULNERABLE TO TRAUMA AND INFECTION

SPLEEN

• TWO TISSUE TYPES IN PARENCHYMA

– RED PULP

• SINUSES FULL OF ERYTHROCYTES

– WHITE PULP

• AGGREGATES OF LYMPHOCYTES AND MACROPHAGES

Cisterna Chyli

• The cisterna chyli as "atypical" and "unusual.( Gray's Anatomy7)

• Cisterna chyli is present in 25 percent of individuals as a dilatation of the thoracic duct. (Woodburne and Burkel,8 quoting Nelson)

• it as being present in 50 percent of cases.( Lee McGregor's Synopsis of Surgical Anatomy10 )

• The cisterna chyli is an elongated and sometimes dilated sac about 5 cm in length.

• It is located in the shadow of the right side of the aorta and behind the right diaphragmatic crus at the surface of L2 (variably, T12-L2).

• It receives the right and left lumbar trunks, the intestinal trunk, and the lowest intercostal vessels

The general plan of the lymphatic system

• Each of the lumbar trunks is a short vessel which leaves the para aortic glands to enter the cisterna

• The lumbar trunks convey the lymph from the lower limbs, the pelvis including its viscera, kidneys and adrenals, and deep lymphatics of the abdominal walls.

• The left lumbar trunk reaches the cisterna by passing behind the aorta.

• The intestinal trunk passes from the pre-aortic nodes to the cisterna.

• It conveys lymph from – stomach, pancreas, spleen, most of liver and intestines.

Thoracic duct

• The thoracic duct is the largest lymphatic channel in the body.

• It collects lymph from the entire body except the right hemithorax (thoracic wall, right lung, right side of the heart, part of the diaphragmatic surface of the liver, lower area of the right lower lobe of the liver), right head and neck, and right upper extremity.

• The volume of flow through the thoracic duct is between 60 and 190 cc/hr.

• It commences from the upper end of the cisterna chyli. Length – 45cms

• The thoracic duct has a short abdominal course and continues up through the chest to terminate in the neck.

• Abdominal course: leaving the cisterna, the duct passes through the aortic orifice of the diaphragm, having the azygous vein on its right

• Thoracic course: it runs in the posterior mediastinum, behind it are the verterbrae, right intercostal arteries, hemi azygous and accessory hemi azygous veins.

• In the front are the esophagus, diaphragm and pericardium.

• On reaching the 7th thoracic verterbra it crosses to the left.

• It reaches the left at the level of 5th verterbra after crossing behind the esophagus.

• It then runs up along the left border of the esophagus medial to the pleura and behind the left subclavian artery into the neck.

• Cervical course: the duct forms an arch which reaches as high as the 7th cervical vertebra.

• The duct arches behind the carotid system and in front of the vertebral system.( ie behind the common carotid artery, internal jugular vein and vagus nerve and in front of verterbral artery , vein and sympathetic trunk.

• As the duct arches to the left it also crosses the scalenus anterior and phrenic nerve and the transverse cervical and suprascapular arteries.

• Termination :

• It usually ends as a single vessel by entering the junction of the left internal jugular and subclavian veins.

• The opening is guarded by valves to prevent regurgitation of blood into the duct.

Variations of the entry of the thoracic duct into the venous system. a. A single thoracic duct and a simple junction. b. Plexiform ramification of the final segment of a thoracic duct, but with a simple junction. c. Delta-like entry of the thoracic duct. d. Duplication of the final segment of the thoracic duct and two separate junctions. e. Ampullary enlargement of the thoracic duct with multiple terminal branches.

Tributaries

• Abdomen : the duct receives on either side a trunk from the lateral intercostal lymph nodes of the lower six spaces

• Thorax: it receives 1. a trunk from either side draining the upper lumbar nodes which pierces the crus of the diaphragm to join the duct

• 2. Efferents from the posterior mediastinal nodes

• 3.Efferents from the lateral intercostal nodes of the upper six left spaces.

• Neck : 1. the left jugular lymph trunk from the left side of the head and neck.

• 2. the left subclavian lymph trunk from the left upper limb

• 3. the left brochomediastinal trunk from the left side of the thorax.

Injury to the thoracic duct

• May be damaged in penetrating injuries of the chest or neck

• May lead to chylothorax which collapses the lung on the affected side.

• Treatment : conservative: aspiration

• Chest tube if recurrence.

• Ligation of the duct: only if lymph leak persists after 2-3 weeks of conservative mgmt.

• During operations in the chest , root of neck and upper abdomen eg: when mobilising the upper end of an aortic aneurysm, the major lymphatic ducts may be damaged.

• Ligature of the duct is done

Right lymph duct

• This is a short vessel 1.25 – 2.5 cm long which runs down on the scalenus anterior to join the junction of the right internal jugular and subclavian veins.

• It is formed by the union of the right jugular, subclavian and brochomediastinal trunks.

• These vessels may all open separately into the junction between the right subclavian and internal jugular veins.

The lymphatic watersheds of skin

• The lymphatic drainage of the skin and its appendages falls naturally into six great territories.

• A vertical line through the saggital plane of the body divides the lymphatic drainage of the skin into 3 areas in each side.

• 2 horizontal lines demarcate the areas from each other, one at the level of the clavicle and the other at the level of the umbilicus.

• The skin lymph flows in a direction away from them. Each line also represents the meeting place of two adjacent territories.

• The cancer situated anywhere on one of these lines may spread by 2 routes along the lymphatics running away from the watershed

• A cancer situated anywhere in the middle line of the surface of the body may spread in 2 directions because of lymphatic communication across midline.

• Cancer situated at the umbilicus may spread in 4 directions, towards both axillae and groins.

Functions

• The lymphatic system is composed of three elements:

• 1. Initial or terminal lymphatic capillaries, which absorb lymph

• 2. Collecting vessels, which serve primarily as conduits for lymph transport

• 3. Lymph nodes, which are interposed in the pathway of the conducting vessels, filtering the lymph and serving a primary immunologic role

FUNCTIONS

• TRANSPORT

– RETURNS FLUID TO BLOODSTREAM

– TRANSPORTS ABSORBED FAT FROM SMALL INTESTINE TO BLOOD

• IMMUNITY

• FLUID CONTINUALLY ENTERS TISSUE FLUID FROM CAPILLARIES

• ONLY ~85% OF THIS FLUID IS REABSORBED BY CAPILLARIES

• REMAINING ~15% RETURNED TO BLOOD VIA LYMPHATIC SYSTEM

– 2 – 4 LITERS OF WATER DAILY

– 25 – 50% OF PLASMA PROTEINS DAILY

• SIMILAR TO VENOUS RETURN

• LOW PRESSURE, LOW SPEED

• VALVES PREVENT BACKFLOW

• NO PUMP (HEART)

• RHYTHMIC CONTRACTION OF VESSELS

• ASSISTED BY

– SKELETAL MUSCLE PUMP

– ARTERIAL PULSATION

– THORACIC PUMP

– RAPID FLOW OF BLOOD IN SUBCLAVIAN VEINS

• The lymphatic system has three main functions.

• First, tissue fluid and macromolecules ultrafiltrated at the level of the arterial capillaries are reabsorbed and returned to the circulation through the lymphatic system. Every day, 50% to 100% of the intravascular proteins are filtered this way in the interstitial space. Normally, they then enter the terminal lymphatics and are transported through the collecting lymphatics back into the venous circulation.

• Second, microbes arriving in the interstitial space enter the lymphatic system and are presented to the lymph nodes, which represent the first line of the immune system.

• Last, at the level of the gastrointestinal tract, lymph vessels are responsible for the uptake and transport of most of the fat absorbed from the bowel.

• The terminal lymphatics have special structural characteristics that allow entry not only of large macromolecules but also of cells and microbes.

• Their most important structural feature is a high porosity resulting from a very small number of tight junctions between endothelial cells, a limited and incomplete basement membrane, and anchoring filaments (4-10 nm) tethering the interstitial matrix to the endothelial cells

• These filaments, once the turgor of the tissue increases, are able to pull on the endothelial cells and essentially introduce large gaps between them that allow for low-resistance influx of interstitial fluid and macromolecules into the lymphatic channels.

• The collecting vessels ascend alongside the primary blood vessels of the organ or limb, pass through the regional lymph nodes, and drain into the main lymph channels of the torso. These channels eventually empty into the venous system through the thoracic duct

• There are additional communications between the lymphatic and venous systems.

• These smaller lymphovenous shunts mostly occur at the level of lymph nodes and around major venous structures, such as the jugular, subclavian, and iliac veins.

• Several structures in the body contain no lymphatics. Specifically, lymphatics have not been found in the epidermis, the cornea, the central nervous system, the cartilage, tendon, and muscle

• Routine tests

• These include a full blood count, urea and electrolytes, creatinine,

• liver function tests, thyroid function tests, plasma total

• protein and albumin, fasting glucose, urine dipstick including

• observation for chyluria, blood smear for microfilariae, chest

• radiograph and ultrasound.

• Lymphangiography

• Direct lymphangiography involves the injection of contrast medium into a peripheral lymphatic vessel and subsequent radiographic visualisation of the vessels and nodes.

• It remains the ‘gold standard’ for showing structural abnormalities of larger lymphatics and nodes

• However, it can be technically difficult,it is unpleasant for the patient, it may cause further lymphatic injury and, largely, it has become obsolete as a routine method of investigation.

• Indirect lymphangiography involves the intradermal injection of water-soluble, non-ionic contrast into a web space, from where it is taken up by lymphatics and then followed radiographically.

• It will show distal lymphatics but not normally proximal lymphatics and nodes

• Lymphoscintigraphy :For patients with edema of unknown etiology and a suspicion for lymphedema, lymphoscintigraphy is the diagnostic test of choice.

• When lymphoscintigraphy confirms that lymphatic drainage is delayed, the diagnosis of primary lymphedema is never made until neoplasia involving the regional and central lymphatic drainage of the limb has been excluded through CT or MRI.

• If a more detailed diagnostic interpretation of lymphatic channels is needed for operative planning, contrast lymphangiography may be considered.

• It cannot differentiate between primary and secondary lymphedemas; however, it has a sensitivity of 70% to 90% and a specificity of nearly 100% in differentiating lymphedema from other causes of limb swelling.

• The test assesses lymphatic function by quantitating the rate of clearance of a radiolabeled macromolecular tracer

• The advantages of the technique are that it is simple, safe, and reproducible with low exposure to radioactivity (∼5 mCi).

• It involves the injection of a small amount of radioiodinated human albumin or 99mTc-labeled sulfide colloid into the first interdigital space of the foot or hand.

• Migration of the radiotracer within the skin and subcutaneous lymphatics is easily monitored with a whole body gamma camera, thus producing clear images of the major lymphatic channels in the leg as well as measuring the amount of radioactivity at the inguinal nodes 30 and 60 minutes after injection of the radiolabeled substance in the feet.

•

• An uptake value that is less than 0.3% of the total injected dose at 30 minutes is diagnostic of lymphedema. The normal range of uptake is between 0.6% and 1.6%.

• In patients with edema secondary to venous disease, isotope clearance is usually abnormally rapid, resulting in more than 2% ilioinguinal uptake.

• Importantly, variation in the degree of edema involving the lower extremity does not appear to significantly change the rate of the isotope clearance.

•

• Computerised tomography

• A single, axial computerised tomography (CT) slice through the midcalf has been proposed as a useful diagnostic test for lymphoedema (coarse, non-enhancing, reticular ‘honeycomb’ pattern in an enlarged subcutaneous compartment), venous oedema (increased volume of the muscular compartment) and lipoedema (increased subcutaneous fat).

• CT can also be used to exclude pelvic or abdominal mass lesions.

• Magnetic resonance imaging

• Magnetic resonance imaging (MRI) can provide clear images of lymphatic channels and lymph nodes, and can be useful in the assessment of patients with lymphatic hyperplasia.

• MRI can also distinguish venous and lymphatic causes of a swollen limb, and detect tumours that may be causing lymphatic obstruction

• Pathological examination

• In cases in which malignancy is suspected, samples of lymph nodes may be obtained by fine-needle aspiration, needle core biopsy or surgical excision.

Skin biopsy will confirm the diagnosis of lymphangiosarcoma

REFERENCES

• SKADALAKIS ANATOMY

• SABISTON 18TH EDITION

• BAILEY AND LOVE S

• Mc gregor anatomy

• Internet