Amyloidosis and porphyria

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Amyloidosis and porphyria

  1. 1. DAPM RV DENTAL COLLEGE DEPARTMENT OF ORAL AND MAXILLOFACIAL PATHOLOGY
  2. 2. REFERENCES <ul><li>Shafer’s textbook of oral pathology- </li></ul><ul><li>Shafer , Hine , Levy. </li></ul><ul><li>Oral and Maxillofacial Pathology- Neville, Damm, Allen, Bouquot. </li></ul><ul><li>Textbook of Biochemistry- DM Vasudevan and Sreekumari </li></ul>
  3. 3. REFERENCES <ul><li>Pathologic Basis of Disease – Robbins and Cotran </li></ul><ul><li>Essential Pathology for Dental Student- Harsh Mohan. </li></ul><ul><li>Pathologic outlines.com </li></ul><ul><li>Wikipedia.org </li></ul><ul><li>Emedicine .medscape.com </li></ul>
  4. 4. AMYLOIDOSIS <ul><li>DEFINITION : </li></ul><ul><li>Term used for a group of diseases characterized by extracellular deposition of a fibrillar protein called amyloid . </li></ul><ul><li>First described by ROKTINASKY in 1842 </li></ul><ul><li>( Pathologic Basis Of Disease- Robbins And Cotran) </li></ul>
  5. 5. AMYLOIDOSIS <ul><li>Named by Virchow </li></ul><ul><li>Amylon = starch </li></ul><ul><li>Oid = like </li></ul><ul><ul><ul><ul><li>Synonym = beta fibrillosis </li></ul></ul></ul></ul><ul><ul><ul><ul><li>(Pathologic Basis Of Disease- Robbins And Cotran) </li></ul></ul></ul></ul>
  6. 6. COMPOSITION
  7. 7. COMPOSITION <ul><li>FIBRIL PROTEIN </li></ul><ul><li>By electron microscopy , the fibrils are non branching filaments, delicate. </li></ul><ul><li>lying singly or 1-4 laterally aligned . </li></ul><ul><li>Each fibril is composed of protofibrils. </li></ul><ul><li>By X ray crystallography, the fibrils have a cross beta-pleated sheet configuration. </li></ul><ul><li>( Essential Pathology for Dental Students- Harsh Mohan) </li></ul>
  8. 8. COMPOSITION <ul><li>P COMPONENT </li></ul><ul><li>By electron microscopy, it has a pentagonal profile . </li></ul><ul><li>Has a internal diameter = 4nm </li></ul><ul><li>External diameter = 9nm </li></ul><ul><li>Chemical analysis, it is a glycoprotein resembling the serum alpha one glycoprotein. </li></ul><ul><li>( Essential Pathology for Dental Students- Harsh Mohan) </li></ul>
  9. 9. CHEMICAL NATURE OF AMYLOID <ul><li>Chemically analysis of the fibril protein revealed two types of amyloids : </li></ul><ul><li>AL (amyloid light chain ) protein. </li></ul><ul><li>AA ( amyloid associated ) protein. </li></ul>
  10. 10. AL( Amyloid light chain ) PROTEIN <ul><li>Consists of poly peptides. </li></ul><ul><li>Produced by immunoglobulin secreting protein. </li></ul><ul><li>Molecular weight = 7500 to 23,000 </li></ul><ul><li>Either lambda or kappa light chains form the AL protein. </li></ul><ul><li>Lambda chains are two times more common. </li></ul><ul><li>(Pathologic Basis of Disease- Robbins and cotran ) </li></ul>
  11. 11. AA (Amyloid associated) Protein <ul><li>Consists of polypeptides </li></ul><ul><li>Derived from Serum Amyloid Protein. </li></ul><ul><li>SAA circulates in association with HDL. </li></ul><ul><li>Synthesized in the liver. </li></ul><ul><li>Molecular weight= 8500 </li></ul><ul><li>(Pathologic Basis of Disease- Robbins and cotran ) </li></ul>
  12. 12. Amyloid fibril structure obtained by cryo-electron microscopy with a cross-β structure modeled into the electron density map based on J.L. Jimenez et al.,  EMBO J , 18: 815–21, 1999
  13. 13. CLASSIFACATION OF AMYLOIDOSIS
  14. 14. ORGAN LIMITED AMYLOIDOSIS
  15. 15. AMYLOIDOSIS OF KIDNEY SOURCE: Pathologic outlines.com
  16. 16. AMYLOIDOSIS OF HEART SOURCE: Pathologic outlines.com
  17. 18. SAGO SPLEEN SOURCE: Altas of pathology
  18. 19. LARDACEOUS SPLEEN SOURCE: Altas of pathology
  19. 20. AMYLOIDOSIS IN LIVER
  20. 21. SYSTEMIC AMYLOIDOSIS
  21. 22. SYSTEMIC AMYLOIDOSIS
  22. 23. PRIMARY and MYELOMA ASSOCIATED <ul><li>CLINICAL FEATURES </li></ul><ul><li>Age : older adults, above 65 years. </li></ul><ul><li>Slight male predilection. </li></ul><ul><li>SIGNS AND SYMPTOMS </li></ul><ul><li>Fatigue, weight loss, paresthesia, hoarseness, edema and orthostatic hypotension. </li></ul><ul><li>(Textbook of oral and maxillofacial Pathology- Neville, Second Edi.) </li></ul>
  23. 24. PRIMARY and MYELOMA ASSOCIATED <ul><li>SIGNS AND SYMPTOMS </li></ul><ul><li>Eventually, carpal tunnel syndrome, muco-cutaneous lesions, hepatomegaly and macroglossia. </li></ul><ul><li>Skin lesions are smooth, firm and waxy . </li></ul><ul><li>Lesions are associated with petechaiae and ecchymoses. </li></ul><ul><li>(Textbook of oral and maxillofacial Pathology- Neville, Second Edi.) </li></ul>
  24. 25. PRIMARY and MYELOMA ASSOCIATED <ul><li>Macro glossia has been reported in 10-40% cases . It may be diffuse or nodular enlargement of tongue. </li></ul><ul><li>Nodules may show ulceration and hemorrhage. </li></ul><ul><li>SITES: </li></ul><ul><li>Eyelid region, retroauricular region, neck and lips. </li></ul><ul><li>(Textbook of oral and maxillofacial Pathology- Neville, Second Edi) </li></ul>
  25. 26. Nodularity and ulceration of the tongue. Color atlas of Dental Medicine- Oral Pathology
  26. 27. Primary systemic amyloidosis: deep red nodules on the lips. Google images
  27. 28. Primary systemic amyloidosis: macroglossia, ecchymoses on the tongue. Google images
  28. 29. Patient exhibits a firm, waxy, smooth lesion near the eye. Google images
  29. 30. PRIMARY and MYELOMA ASSOCIATED <ul><li>Infrequently patients may complain of dry eyes and dry mouth which are secondary to amyloid infiltration and destruction of salivary and lacrimal glands. </li></ul><ul><li>(Textbook of oral and maxillofacial Pathology- Neville, Second Edi.) </li></ul>
  30. 31. SECONDARY AMYLOIDOSIS <ul><li>Develops as a result of long standing chronic inflammatory process like : Osteomyelitis </li></ul><ul><li>Tuberculosis </li></ul><ul><li>Sarcoidosis </li></ul><ul><li>SITES: Kidney, Liver, spleen, adrenals. </li></ul><ul><li>(Textbook of oral and maxillofacial Pathology- Neville, Second Edi.) </li></ul>
  31. 32. HEMODIALYSIS ASSOCIATED AMYLOIDOSIS <ul><li>Seen in patients who have under gone long term renal dialysis. </li></ul><ul><li>Due to accumulation of beta-2 microglobulin, an amyloid protein. </li></ul><ul><li>Deposits in the bones and joints . </li></ul><ul><li>Tongue involvement is common. </li></ul><ul><li>(Textbook of oral and maxillofacial Pathology- Neville, Second Edi.) </li></ul>
  32. 33. HEREDOFAMILIAL AMYLOIDOSIS <ul><li>Uncommon disease. </li></ul><ul><li>Inherited autosomal dominant trait. </li></ul><ul><li>These conditions appear as polyneuropathies, cardiomyopathy, cardiac arrhythmias, CCF and renal failure. </li></ul><ul><li>(Textbook of oral and maxillofacial Pathology- Neville, Second Edi.) </li></ul>
  33. 34. STAINING OF AMYLOID
  34. 35. Haematoxylin and Eosin <ul><li>Appears extracellular. </li></ul><ul><li>Homogenous. </li></ul><ul><li>structrureless. </li></ul><ul><li>eosinophilic hyaline material. </li></ul><ul><li>( Essential Pathology For Dental Students- Harsh Mohan) </li></ul>
  35. 36. Google images
  36. 37. IODINE STAIN <ul><li>Oldest method. </li></ul><ul><li>Lugol’s iodine is used. </li></ul><ul><li>It imparts mahogany- brown color to the amyloid containing area. </li></ul><ul><li>Addition of H2SO4 turns it violet. </li></ul><ul><li>( Essential Pathology For Dental Students- Harsh Mohan) </li></ul>
  37. 38. Google images
  38. 39. CONGO RED <ul><li>Stains it orange. </li></ul><ul><li>When viewed under polarized light it exhibits apple – green bifringerence due to cross beta </li></ul><ul><li>sheet configuration amyloid fibrils. </li></ul><ul><li>( Essential Pathology For Dental Students- Harsh Mohan) </li></ul>
  39. 40. Google images
  40. 41. CONGO RED <ul><li>Also used to differentiate between AA and AL amyloid. </li></ul><ul><li>AA amyloid fails to stain if previously treated with KMnO4. </li></ul><ul><li>Most reliable method. </li></ul><ul><li>( Essential Pathology For Dental Students- Harsh Mohan) </li></ul>
  41. 42. METACHROMATIC STAIN <ul><li>Amyloid has a property of metachromasia. </li></ul><ul><li>Stains employed are : </li></ul><ul><li>Methyl Violet </li></ul><ul><li>Crystal violet </li></ul><ul><li>C. Gentian violet. </li></ul><ul><li>Imparts rose pink color. </li></ul><ul><li>( Essential Pathology For Dental Students- Harsh Mohan) </li></ul>
  42. 43. FLUORESCENT STAINS <ul><li>Stains like thioflavin S and T bind to amyloid </li></ul><ul><li>fluoresce yellow under U V light. </li></ul><ul><li>( Essential Pathology For Dental Students- Harsh Mohan) </li></ul>
  43. 44. DIAGNOSIS <ul><li>BIOPSY EXAMINATION. </li></ul><ul><li>IN VIVO CONGO RED TEST. </li></ul><ul><li>IMMNOELECTROPHORESIS. </li></ul><ul><li>BONE MARROW ASPIRATION . </li></ul>
  44. 45. TREATMENT AND PROGNOSIS <ul><li>No effective therapy. </li></ul><ul><li>Surgical debulking of tongue. </li></ul><ul><li>Treatment for primary amyloidosis with Prednisone and melphalan. </li></ul><ul><li>Most patients die of cardiac failure , arrhythmia or renal disease within few months or years of diagnosis. </li></ul><ul><li>(Textbook of oral and maxillofacial Pathology- Neville, Second Edi.) </li></ul>
  45. 47. INTRODUCTION <ul><li>This disease occurs due to inborn defect of porphyrin metabolism. </li></ul><ul><li>Porphyrias are a group of rare disorders passed down through families, in which an important part of hemoglobin, called heme, is not made properly </li></ul>
  46. 48. CLASSIFICATION
  47. 49. HEPATIC TYPE <ul><li>More common. </li></ul><ul><li>Defect of haem synthesis in the liver. </li></ul>
  48. 50. ACUTE INTERMITTENT PORPHYRIA <ul><li>Deficiency of UROPORPHYINOGEN I SYNTHETASE </li></ul><ul><li>Abdominal pain. </li></ul><ul><li>Vomiting </li></ul><ul><li>Cardiovascular abnormalities </li></ul>
  49. 51. HEREDITARY COPORPHYRIA <ul><li>Deficiency of enzyme coproporphyrinogen III oxidase. </li></ul><ul><li>Autosomal dominant. </li></ul><ul><li>Causes purple urine, photosensitivity, and attacks of abdominal pain. </li></ul><ul><li>Very rare. </li></ul>
  50. 52. Google images
  51. 53. VARIGATE PORPHYRIA <ul><li>South African porphyria. </li></ul><ul><li>Abdominal pain. </li></ul><ul><li>vomiting. </li></ul><ul><li>Diarrhea. </li></ul>
  52. 54. PORPHYRIA CUTANEA TARDA <ul><li>Most common. </li></ul><ul><li>SITES: f ace, hands, forearms, and lower legs. </li></ul><ul><li>Acute lesions consist of blisters, erosions and scars. These heal leaving areas of hyperpigmentation and hypopigmentation. Milia are pinpoint collections of a white, waxy substance just beneath the surface of the skin. </li></ul>
  53. 56. ERYTHROPOIETIC PORPHYRIA <ul><li>Common childhood porphyria. </li></ul><ul><li>Defective synthesis of heme in erythrocytes. </li></ul><ul><li>The enzyme deficiency occurs in the red blood cells </li></ul>
  54. 58. ERYTHROPOIETIC PROTOPORPHYRIA <ul><li>mild form of porphyria. </li></ul><ul><li>Severe photosensitivity. </li></ul><ul><li>Exposure to even indoor light sources can cause the rash. </li></ul><ul><li>Prolonged exposure lead s to edema and blistering. </li></ul>
  55. 59. CONGENITAL ERYTHROPIETIC PORPHYRIA <ul><li>Inborn-error of haem-porphyrin synthesis. </li></ul><ul><li>Autosomal recessive . </li></ul><ul><li>Also known as G ü NTHER’S DISEASE </li></ul><ul><li>Caused by deficiency of the enzyme uroporphyrinogen synthetase. </li></ul><ul><li>(Oral and maxillofacial pathology- Neville) </li></ul>
  56. 60. CLINICAL FEATURES <ul><li>No sex predilection. </li></ul><ul><li>The first sign is red coloration of urine by uroporphyrin. </li></ul><ul><li>Photosensitivity. </li></ul><ul><li>Hypertrichosis </li></ul>
  57. 61. ORAL MANIFESTATIONS <ul><li>Both deciduous and permanent dentition show pigmentation, usually brown. More intense in deciduous teeth. </li></ul><ul><li>Under Wood’s UV ray, teeth show a striking red fluorescence. </li></ul><ul><li>Ground sections show porphyrin pigments deposited in enamel, dentin and cementum. </li></ul>
  58. 64. TREATMENT <ul><li>No treatment is available. </li></ul><ul><li>Discolored teeth may be cosmetically restored with porcelain –veneered crown. </li></ul>
  59. 65. THANK YOU

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