lymphoreticular system

lymphoreticular system UM 2 myanmar

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. 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

10. 8.Tonsilar buds

11. The lymphatic tissues of the intestine, Payer’s patches, appear later than tonsils. The second half of the pregnancy

12. Development of the lymphnodes

13. 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 .

14. 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

15. 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

16. Anatomy of lymphatic system the lymphatic system parallels the cardiovascular system One way system Convey lymph from end organs to the cardiovascular system

17. Lymph contains nutrients, oxygen, hormones, fatty acids, toxins and waste products.

18. 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.)

19. Collection of lymph

20. 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.

21. Lymphatic vessels Blind ended tubes Endothelial lined (single layer) Lymphatic capillaries coalesce to form larger meshlike network of tubes k\a lymphatic vessels

22. The lymphatic system

23. 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

24. 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

25. 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.

26. 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.

27. Three distinct microanatomical regions within a lymph node. Cortex Paracortex Medulla

28. Cortex : which contains either primary or secondary lymphoid follicles; 2. Paracortex : which is the T-cell dependent region of the lymph node; and 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.

29. 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 .

30. These follicles have an outer ring of small B lymphocytes surrounding the germinal centre , which contains largely dividing lymphoblasts , macrophages and dendritic cells.

31. 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.

32. 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.

33. 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.

34. 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.

35. 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

36. 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.

37. 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

38. Cisterna chyli

39. 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

40. Area of body drained by thoracic duct

41. area of body drained by the right lymphatic duct

42. Thymus Bilobed lymphoid organ Located in the superior mediastinum maximum absolute size during puberty between 30 and 40 g It regresses after the puberty

43. 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

44. Spleen Largest lymphoid organ 75-250 g Lies in lt hypochondrium with its long axis along the 10 th rib Mainly over the 9 th , 10 th and 11 th ribs There is a notch in its inferolateral surface

45. 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

46. 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

47. Efferent lymphatics in white pulp joins with the arterioles Emerge as nodes at the hilum Drains via the retropancreatic nodes to the coeliac nodes

48. 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

49. Palatine tonsils & Lingual tonsils- at the base of posterior surface of tongue These are collectively known as Waldeyer’s ring

50. 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

51. Physiology

52. 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 .

53. 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

54. 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.

55. Innate immunity Also called natural or native immunity Defense mechanisms that are present before the infection First line of defence Always ready

56. 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 );

57. 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

58. 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 .

59. Adaptive immunity Also called acquired or specific immunity Mechanisms that are stimulated by microbes Capable of recognizing nonmicrobial substances called ‘antigens’.

60. 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

61. 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.

62. 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 .

63. 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.

64. 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.

65. 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 )

66. Antigens can be divided into foreign - non-self , allogeneic, xenogeneic, etc. Autoantigens – self antigens

67. 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 ).

68. 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.

69. Functions of the spleen Haematological function Immunological function

70. 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

71. 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

72. Haemopoiesis Only in fetal life No bld formation in the after birth Revision of fetal pattern of haemopoiesis in certain diseases

73. 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

74. 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

75. Also influence the opsonization of pneumococci in non immune individuals Susceptible to them after splenectomy

76. Pathology Reactive lymphadenitis Tuberculous lymphadenitis Lymphoedema Lymphomas

77. 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

78. 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

79. Tissue diagnosis by excisional biopsy Granuloma formation with grossly caseation necrosis Definitive Rx is antituberculous chemotherapy

80. 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

81. 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

82. Two main types Primary Unknown cause Thought to be congenital lymphatic dysplasia Secondary Clear underlying cause

83. 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 )

84. 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

85. 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

86. 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

87. 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

88. 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 ”

89. Malignancies associated with lymphoedema Lymphangiosarcoma Kaposi’s sarcoma SCC Liposarcoma Malignant melanoma Malignant fibrous histocytoma BCC lymphoma

90. 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

91. 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

92. Investigations Routine tests CP, U&E, creatinine, LFT, T & DP, albumin, CRP Lymphangiography Lymphoscintigraphy CT MRI USG Limb volume measurement

93. Management Relief of pain Control of swelling Skin care Manual lymphatic drainage Multilayer lymphedema bandaging and compression garments Exercise Drugs

94. Surgery Bypass procedures Liposuction Limb reduction procedures

95. 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

96. 12 yrs old boy

97. 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

98. 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

99. 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)

100. 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

101. 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%).

102. 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

103. Treatment multimodality treatment program Resection - controversial Chemotherapy plus radiation therapy: CHOP (cyclophosphamide, hydroxy-daunomycin , Oncovin , prednisolone)

104. 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