Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
Hematopoiesis Masatoshi Kida, MD Dept. of Pathology University of Vermont
Hematopoiesis general <ul><li>myeloid tissue </li></ul><ul><li>lymphoid tissue </li></ul>
Hematopoiesis general <ul><li>myeloid tissue </li></ul><ul><li>bone marrow </li></ul><ul><li>lymphoid tissue </li></ul>
Hematopoiesis general <ul><li>myeloid tissue </li></ul><ul><li>bone marrow </li></ul><ul><li>erythrocytes </li></ul><ul><l...
Hematopoiesis general <ul><li>myeloid tissue </li></ul><ul><li>bone marrow </li></ul><ul><li>erythrocytes </li></ul><ul><l...
Development of Blood Cells <ul><li>3 wk : formation of blood islands from yolk sac </li></ul><ul><li>6 wk : liver becomes ...
Development of Blood Cells <ul><li>3 wk : formation of blood islands from yolk sac </li></ul><ul><li>6 wk : liver becomes ...
pluripotent stem cell committed stem cells Hematopoiesis lymphoid stem cell trilineage myeloid stem cell
Hematopoiesis Proliferative potential differentiation
Normal Marrow Composition granulocytes & precursors erythroid precursors Lymphocytes, monocytes unidentified or disintegra...
Normal Marrow <ul><li>myeloid to erythroid ratio = 3 : 1 </li></ul><ul><li>dominant myeloid cells </li></ul><ul><li>myeloc...
Myeloblast <ul><li>cell division: + </li></ul><ul><li>~2% of nucleated cells in BM </li></ul><ul><li>size: 8-13   m diame...
Promyelocyte <ul><li>cell division: + </li></ul><ul><li>~5% of nucleated cells in BM </li></ul><ul><li>size:  20   m  dia...
Myelocyte <ul><li>cell division: + </li></ul><ul><li>5-20% of nucleated cells in BM </li></ul><ul><li>cytoplasm: specific ...
Metamyelocyte <ul><li>no more cell division </li></ul><ul><li>~22% of nucleated cells in BM </li></ul><ul><li>size:  10-18...
Granulocyte maturation <ul><li>stem cell:  <0.1% </li></ul><ul><li>myeloblasts:  ~2% promyelocytes:  ~5% </li></ul><ul><li...
Lifespan of blood cells <ul><li>RBC 120 days </li></ul><ul><li>platelet 10 days </li></ul><ul><li>granulocytes circ : 9 ho...
Hematopoietic Microenvironment <ul><li>stem cell(s) </li></ul><ul><li>stromal cells </li></ul><ul><li>growth factors </li>...
Hematopoietic Response hypoxia infection antigen hemorrhage RBC granulocyte/monocyte lymphocyte platelet
Hematopoietic Microenvironment Stromal cells : fibroblasts endothelial cells adipocytes Growth Factors
Hematopoietic Growth Factors ( SCF, IL-6, GM-CSF , etc.) <ul><li>glycoprotein hormones </li></ul><ul><li>secreted by </li>...
Basal Hematopoiesis G-CSF SCF: stem cell factor GM-CSF: granulocyte-macrophage colony-stimulating factor G-CSF: granulocyt...
Antigen-amplified hematopoiesis TNF  IL-3 GM-CSF IL-4 IL-1 TNF  IL-1 SCF IL-6 GM-CSF G-CSF Ag Ag
Hematopoietic Growth Factors (IL-6, GM-CSF, SCF, etc.) <ul><li>Bacterial & viral products </li></ul><ul><li>monocyte </li>...
Hematopoiesis GROWTH FACTORS ERYTHROPOIESIS GRANULOPOIESIS MEGAKARYOPOIESIS LYMPHOPOIESIS generation of each specific line...
Erythropoiesis <ul><li>erythropoietin-independent stage: </li></ul><ul><ul><li>GM-CSF </li></ul></ul><ul><ul><li>SCF </li>...
<ul><li>early phase: </li></ul><ul><li>Neutropoiesis: </li></ul><ul><li>Monopoiesis: </li></ul><ul><li>Eosinopoiesis: </li...
Megakaryopoiesis <ul><li>may also play a role </li></ul>GM-CSF IL-3 SCF IL-6
Lymphopoiesis <ul><li>B-cells: </li></ul><ul><ul><li>initial stage: </li></ul></ul><ul><ul><li>later stage: </li></ul></ul...
B-cell maturation
B-cell transformation
Lymph node
Spleen
T-cell transformation
Markers <ul><li>Stem cell: CD34, c-kit rhodamine, Hoechst dyes (pale) </li></ul><ul><li>B-cell: CD19, CD20, (CD22), CD79a ...
RBC variation and irregularity
anisocytosis poikilocytosis <ul><li>anisocytosis (aniso = unequal) </li></ul><ul><li>various sizes </li></ul><ul><li>poiki...
elliptocytes <ul><li>- heredirary elliptocytosis </li></ul><ul><li>- iron def. anemia </li></ul><ul><li>myelofibrosis with...
spherocytes <ul><li>- hereditary spherocytosis </li></ul><ul><li>- acquired hemolytic  anemia (e.g. AIHA) </li></ul><ul><l...
leptocytes (target cells) <ul><li>- liver disease  </li></ul><ul><li>(obstructive jaundice) </li></ul><ul><li>- post splen...
schistocytes (cell fragments) <ul><li>indication of hemolysis </li></ul><ul><li>- megaloblastic anemia </li></ul><ul><li>-...
acanthocytes (irregular surface spicules) <ul><li>irregularly spiculated  cells </li></ul><ul><li>with bulbous/rounded  en...
echinocytes (crenated cells, burr cells) <ul><li>regularly contracted cells with smooth surface undulation </li></ul><ul><...
bite cells <ul><li>Removal (“bites”) of membrane by splenic macrophages </li></ul><ul><li>- G6PD deficiency </li></ul>
dacrocytes (teardrop cells) <ul><li>- thalassemia </li></ul><ul><li>- myelofibrosis </li></ul>
drepanocytes (sickle cells) <ul><li>- sickle cell anemia </li></ul>
rouleaux <ul><li>lined up RBCs in a row </li></ul><ul><li>- multiple myeloma </li></ul>
basophilic stippling <ul><li>irregular basophilic granules </li></ul><ul><li>(remnants of RNA) </li></ul><ul><li>fine stip...
sideroblast/siderocyte <ul><li>inorganic iron-containing granules (Pappenheimer bodies) </li></ul><ul><li>- sideroblastic ...
Howell-Jolly body <ul><li>remnant of nuclear chromatin </li></ul><ul><li>single: </li></ul><ul><ul><li>megaloblastic anemi...
Heinz bodies <ul><li>denatured hemoglobin </li></ul><ul><li>- G6PD deficiency </li></ul>
leukemoid reaction <ul><li>an excessive leukocytic response </li></ul><ul><li>leukocytosis of 50 x10 9 /L or higher  with ...
leukemoid reaction hemolysis hemorrhage malignancy Hodgkin disease myelofibrosis TB burns eclampsia parasite infectious ly...
leukoerythroblastic reaction solid tumors lymphomas myeloprolif dis acute leukemias benign hematologic conditions hemolysi...
reactive WBC proliferations <ul><li>leukocytosis </li></ul><ul><ul><li>(1) increased  PMN </li></ul></ul><ul><ul><ul><li>i...
increased  PMN <ul><li>(1) increased bands (“left shift”) </li></ul><ul><li>(2) reactive morphologic changes </li></ul><ul...
reactive WBC proliferations <ul><li>leukocytosis </li></ul><ul><ul><li>(2) increased  eosinophils </li></ul></ul><ul><ul><...
reactive WBC proliferations <ul><li>leukocytosis </li></ul><ul><ul><li>(3) increased  monocytes  (monocytosis) </li></ul><...
reactive WBC proliferations <ul><li>leukocytosis </li></ul><ul><ul><li>(4) increased  lymphocytes  (lymphocytosis) </li></...
infectious mononucleosis <ul><li>- one of causes of lymphocytosis </li></ul><ul><li>- a virus-induced disease </li></ul><u...
<ul><li>(1) EBV invades B-cell via CD21 (CR2) </li></ul><ul><li>(2) cytotoxic (CD8) T-cells respond against invaded B-cell...
<ul><li>(3) heterophil antibody production </li></ul><ul><ul><li>(heterophil antibody : antibody against other species) </...
<ul><li>patient population: </li></ul><ul><ul><li>adolescents and young adults </li></ul></ul><ul><ul><li>(“kissing diseas...
<ul><li>complications: </li></ul><ul><ul><li>hepatic dysfunction (“hepatitis”) </li></ul></ul><ul><ul><li>splenic rupture ...
lymphadenopathy <ul><li>acute non-specific lymphadenopathy </li></ul><ul><ul><ul><li>tender enlargement of lymph nodes </l...
lymphadenopathy <ul><li>chronic non-specific lymphadenopathy </li></ul><ul><ul><ul><li>non-tender enlargement of lymph nod...
 
Upcoming SlideShare
Loading in …5
×

hematopoiesis_06-07.ppt

6,379 views

Published on

hematopoiesis_06-07.ppt

  1. 1. Hematopoiesis Masatoshi Kida, MD Dept. of Pathology University of Vermont
  2. 2. Hematopoiesis general <ul><li>myeloid tissue </li></ul><ul><li>lymphoid tissue </li></ul>
  3. 3. Hematopoiesis general <ul><li>myeloid tissue </li></ul><ul><li>bone marrow </li></ul><ul><li>lymphoid tissue </li></ul>
  4. 4. Hematopoiesis general <ul><li>myeloid tissue </li></ul><ul><li>bone marrow </li></ul><ul><li>erythrocytes </li></ul><ul><li>platelets </li></ul><ul><li>granulocytes </li></ul><ul><li>monocytes </li></ul><ul><li>lymphoid tissue </li></ul>
  5. 5. Hematopoiesis general <ul><li>myeloid tissue </li></ul><ul><li>bone marrow </li></ul><ul><li>erythrocytes </li></ul><ul><li>platelets </li></ul><ul><li>granulocytes </li></ul><ul><li>monocytes </li></ul><ul><li>lymphoid tissue </li></ul><ul><li>thymus </li></ul><ul><li>lymph nodes </li></ul><ul><li>spleen </li></ul>
  6. 6. Development of Blood Cells <ul><li>3 wk : formation of blood islands from yolk sac </li></ul><ul><li>6 wk : liver becomes hematopoietic organ </li></ul><ul><li>6-8 wk : spleen (until 8th month) </li></ul><ul><li>12-14wk : bone marrow (life-long) </li></ul>
  7. 7. Development of Blood Cells <ul><li>3 wk : formation of blood islands from yolk sac </li></ul><ul><li>6 wk : liver becomes hematopoietic organ </li></ul><ul><li>6-8 wk :spleen (until 8th month) </li></ul><ul><li>12-14wk : bone marrow (life-long) </li></ul><ul><li>Bone Marrow </li></ul><ul><ul><li>red marrow </li></ul></ul><ul><ul><li>yellow marrow </li></ul></ul>
  8. 8. pluripotent stem cell committed stem cells Hematopoiesis lymphoid stem cell trilineage myeloid stem cell
  9. 9. Hematopoiesis Proliferative potential differentiation
  10. 10. Normal Marrow Composition granulocytes & precursors erythroid precursors Lymphocytes, monocytes unidentified or disintegrated cells 60% 20% 10% 10%
  11. 11. Normal Marrow <ul><li>myeloid to erythroid ratio = 3 : 1 </li></ul><ul><li>dominant myeloid cells </li></ul><ul><li>myelocytes </li></ul><ul><li>metamyelocytes </li></ul><ul><li>granulocytes </li></ul><ul><li>dominant erythroid cells </li></ul><ul><li>polychromatophilic normoblasts </li></ul><ul><li>orthochromic normoblasts </li></ul>
  12. 12. Myeloblast <ul><li>cell division: + </li></ul><ul><li>~2% of nucleated cells in BM </li></ul><ul><li>size: 8-13  m diameter </li></ul><ul><li>cytoplasm: basophilic (many free ribosomes) no granules </li></ul><ul><li>nucleus: undifferentiated round to ovoid coarse nucleoli --> sieve-like appearance </li></ul>
  13. 13. Promyelocyte <ul><li>cell division: + </li></ul><ul><li>~5% of nucleated cells in BM </li></ul><ul><li>size: 20  m diameter </li></ul><ul><li>cytoplasm: deep blue azurophilic granules abundant rER, free ribosome numerous mitochondria well developed Golgi </li></ul><ul><li>nucleus: round to ovoid occasionally indented prominent nucleoli </li></ul>
  14. 14. Myelocyte <ul><li>cell division: + </li></ul><ul><li>5-20% of nucleated cells in BM </li></ul><ul><li>cytoplasm: specific granules decreased in basophilia </li></ul><ul><li>nucleus: ovoid irregular shape disappearing of nucleoli dense and compact chromatin </li></ul>
  15. 15. Metamyelocyte <ul><li>no more cell division </li></ul><ul><li>~22% of nucleated cells in BM </li></ul><ul><li>size: 10-18  m diameter (slightly larger than mature PMN) </li></ul><ul><li>cytoplasm: prominent secondary granules </li></ul><ul><li>nucleus: slightly indented, kidney-shaped dense chromatin no nucleolus </li></ul>
  16. 16. Granulocyte maturation <ul><li>stem cell: <0.1% </li></ul><ul><li>myeloblasts: ~2% promyelocytes: ~5% </li></ul><ul><li>myelocytes: 5-20% </li></ul><ul><li>metamyelocytes: ~22% </li></ul><ul><li>granular leukocytes </li></ul>
  17. 17. Lifespan of blood cells <ul><li>RBC 120 days </li></ul><ul><li>platelet 10 days </li></ul><ul><li>granulocytes circ : 9 hours </li></ul><ul><li>tissue : days </li></ul><ul><li>lymphocyte circ : variable (hours to years) </li></ul><ul><li>tissue : weeks to years </li></ul>
  18. 18. Hematopoietic Microenvironment <ul><li>stem cell(s) </li></ul><ul><li>stromal cells </li></ul><ul><li>growth factors </li></ul><ul><li>stimulation </li></ul>
  19. 19. Hematopoietic Response hypoxia infection antigen hemorrhage RBC granulocyte/monocyte lymphocyte platelet
  20. 20. Hematopoietic Microenvironment Stromal cells : fibroblasts endothelial cells adipocytes Growth Factors
  21. 21. Hematopoietic Growth Factors ( SCF, IL-6, GM-CSF , etc.) <ul><li>glycoprotein hormones </li></ul><ul><li>secreted by </li></ul><ul><ul><li>bone marrow stromal cells </li></ul></ul><ul><ul><li>T-cells </li></ul></ul><ul><ul><li>monocytes </li></ul></ul><ul><li>regulate division and differentiation of hematopoietic cells </li></ul><ul><li>responsible for basal hematopoiesis and maintaining blood counts in normal ranges </li></ul><ul><li>greatly increased secretion in response to infection </li></ul>
  22. 22. Basal Hematopoiesis G-CSF SCF: stem cell factor GM-CSF: granulocyte-macrophage colony-stimulating factor G-CSF: granulocyte colony-stimulating factor SCF IL-6 GM-CSF
  23. 23. Antigen-amplified hematopoiesis TNF  IL-3 GM-CSF IL-4 IL-1 TNF  IL-1 SCF IL-6 GM-CSF G-CSF Ag Ag
  24. 24. Hematopoietic Growth Factors (IL-6, GM-CSF, SCF, etc.) <ul><li>Bacterial & viral products </li></ul><ul><li>monocyte </li></ul>IL-1 TNF  G-CSF M-CSF T-cell GM-CSF IL-3 Fibroblast Endothelial cell IL-6 GM-CSF G-CSF
  25. 25. Hematopoiesis GROWTH FACTORS ERYTHROPOIESIS GRANULOPOIESIS MEGAKARYOPOIESIS LYMPHOPOIESIS generation of each specific lineage of mature blood cells is regulated by a specific set of hematopoietic growth factors.
  26. 26. Erythropoiesis <ul><li>erythropoietin-independent stage: </li></ul><ul><ul><li>GM-CSF </li></ul></ul><ul><ul><li>SCF </li></ul></ul><ul><li>erythropoietin-dependent stage: </li></ul><ul><ul><li>erythropoietin </li></ul></ul>marrow stromal cells IL-3 (activated T-cells) hypoxia(liver, kidney)
  27. 27. <ul><li>early phase: </li></ul><ul><li>Neutropoiesis: </li></ul><ul><li>Monopoiesis: </li></ul><ul><li>Eosinopoiesis: </li></ul><ul><li>Basopoiesis,Mastpoiesis: </li></ul>Granulopoiesis G-CSF M-CSF GM-CSF SCF IL-3 IL-5 IL-3 GM-CSF SCF IL-3
  28. 28. Megakaryopoiesis <ul><li>may also play a role </li></ul>GM-CSF IL-3 SCF IL-6
  29. 29. Lymphopoiesis <ul><li>B-cells: </li></ul><ul><ul><li>initial stage: </li></ul></ul><ul><ul><li>later stage: </li></ul></ul><ul><ul><li>final proliferation and Ab secretion: </li></ul></ul><ul><li>T-cells: </li></ul><ul><li>CD8 cells: </li></ul><ul><li>CD4 cells: </li></ul>IL-7 SCF Fcg rec IL-4 IL-6 GM-CSF IL-6 IL-2 Ag TCR/CD3 CD28
  30. 30. B-cell maturation
  31. 31. B-cell transformation
  32. 32. Lymph node
  33. 33. Spleen
  34. 34. T-cell transformation
  35. 35. Markers <ul><li>Stem cell: CD34, c-kit rhodamine, Hoechst dyes (pale) </li></ul><ul><li>B-cell: CD19, CD20, (CD22), CD79a </li></ul><ul><li>T-cell: CD3, CD2, CD5, CD4/CD8 </li></ul><ul><li>NK-cell: CD16, CD57, CD56 </li></ul>
  36. 36. RBC variation and irregularity
  37. 37. anisocytosis poikilocytosis <ul><li>anisocytosis (aniso = unequal) </li></ul><ul><li>various sizes </li></ul><ul><li>poikilocytosis (poikilo = various) </li></ul><ul><li>various shapes </li></ul>
  38. 38. elliptocytes <ul><li>- heredirary elliptocytosis </li></ul><ul><li>- iron def. anemia </li></ul><ul><li>myelofibrosis with myeloid metaplasia </li></ul><ul><li>- megaloblastic anemia </li></ul><ul><li>- sickle cell anemia </li></ul><ul><li>- normal (<10% of cells) </li></ul>
  39. 39. spherocytes <ul><li>- hereditary spherocytosis </li></ul><ul><li>- acquired hemolytic anemia (e.g. AIHA) </li></ul><ul><li>- physical or chemical injury </li></ul><ul><ul><li>- heat </li></ul></ul>
  40. 40. leptocytes (target cells) <ul><li>- liver disease </li></ul><ul><li>(obstructive jaundice) </li></ul><ul><li>- post splenectomy </li></ul><ul><li>- hemoglobinopathies </li></ul><ul><li>(hypochromic anemias) </li></ul><ul><ul><li>thalassemia </li></ul></ul><ul><ul><li>Hgb C disease </li></ul></ul><ul><ul><li>Hgb H disease </li></ul></ul>beta thalassemia relative increase of cell membrane --> “target” formation
  41. 41. schistocytes (cell fragments) <ul><li>indication of hemolysis </li></ul><ul><li>- megaloblastic anemia </li></ul><ul><li>- severe burns </li></ul><ul><li>- traumatic hemolysis </li></ul><ul><li>- microangiopathic hemolytic anemia (helmet cells, triangular cells) </li></ul>“ helmet cell”
  42. 42. acanthocytes (irregular surface spicules) <ul><li>irregularly spiculated cells </li></ul><ul><li>with bulbous/rounded ends of spicules </li></ul><ul><li>- abetalipoproteinemia </li></ul><ul><li>- liver disease </li></ul>
  43. 43. echinocytes (crenated cells, burr cells) <ul><li>regularly contracted cells with smooth surface undulation </li></ul><ul><li>- uremia </li></ul><ul><li>- artifact </li></ul><ul><li>- hyperosmolarity </li></ul><ul><li>- discocyte-echinocyte transformation (may be associated with reduced ATP of RBCs) </li></ul>
  44. 44. bite cells <ul><li>Removal (“bites”) of membrane by splenic macrophages </li></ul><ul><li>- G6PD deficiency </li></ul>
  45. 45. dacrocytes (teardrop cells) <ul><li>- thalassemia </li></ul><ul><li>- myelofibrosis </li></ul>
  46. 46. drepanocytes (sickle cells) <ul><li>- sickle cell anemia </li></ul>
  47. 47. rouleaux <ul><li>lined up RBCs in a row </li></ul><ul><li>- multiple myeloma </li></ul>
  48. 48. basophilic stippling <ul><li>irregular basophilic granules </li></ul><ul><li>(remnants of RNA) </li></ul><ul><li>fine stippling : </li></ul><ul><li>increased production of RBCs (reticulocytosis) </li></ul><ul><li>coarse stippling : </li></ul><ul><li>lead poisoning </li></ul><ul><li>impaired Hgb syntheisis </li></ul><ul><li>megaloblastic anemia </li></ul><ul><li>other sever anemias </li></ul>
  49. 49. sideroblast/siderocyte <ul><li>inorganic iron-containing granules (Pappenheimer bodies) </li></ul><ul><li>- sideroblastic anemia </li></ul><ul><li>abnormally trapped iron in mitochondria forming a ring around nucleus </li></ul><ul><li>- post splenectomy </li></ul>ring sideroblasts intermediate sideroblast siderocyte
  50. 50. Howell-Jolly body <ul><li>remnant of nuclear chromatin </li></ul><ul><li>single: </li></ul><ul><ul><li>megaloblastic anemia </li></ul></ul><ul><ul><li>hemolytic anemia </li></ul></ul><ul><ul><li>post splenectomy </li></ul></ul><ul><li>multiple: </li></ul><ul><ul><li>megaloblastic anemia </li></ul></ul><ul><ul><li>other abnormal erythropoiesis </li></ul></ul>
  51. 51. Heinz bodies <ul><li>denatured hemoglobin </li></ul><ul><li>- G6PD deficiency </li></ul>
  52. 52. leukemoid reaction <ul><li>an excessive leukocytic response </li></ul><ul><li>leukocytosis of 50 x10 9 /L or higher with shift to the left </li></ul><ul><li>or </li></ul><ul><li>lower counts with considerable numbers of immature granulocytes </li></ul><ul><li>quantitative or qualitative changes in lymphocytes or monocytes </li></ul>
  53. 53. leukemoid reaction hemolysis hemorrhage malignancy Hodgkin disease myelofibrosis TB burns eclampsia parasite infectious lymphocytosis pertussis TB neutrophilic eosinophilic lymphocytic
  54. 54. leukoerythroblastic reaction solid tumors lymphomas myeloprolif dis acute leukemias benign hematologic conditions hemolysis misc.
  55. 55. reactive WBC proliferations <ul><li>leukocytosis </li></ul><ul><ul><li>(1) increased PMN </li></ul></ul><ul><ul><ul><li>i. increased production </li></ul></ul></ul><ul><ul><ul><ul><li>a. acute inflammation </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>- pyogenic bacterial infection </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>- tissue necrosis </li></ul></ul></ul></ul></ul><ul><ul><ul><li>ii. increased release of stored RBCs from BM </li></ul></ul></ul><ul><ul><ul><ul><li>a. corticosteroids </li></ul></ul></ul></ul><ul><ul><ul><ul><li>b. stress </li></ul></ul></ul></ul><ul><ul><ul><ul><li>c. endotoxin </li></ul></ul></ul></ul>
  56. 56. increased PMN <ul><li>(1) increased bands (“left shift”) </li></ul><ul><li>(2) reactive morphologic changes </li></ul><ul><ul><li>a. Döhle bodies (aggregates of rough ER) </li></ul></ul><ul><ul><li>b. toxic granulations (prominent granules) </li></ul></ul><ul><ul><li>c. cytoplasmic vacuoles </li></ul></ul><ul><li>(3) increased leukocyte alkaline phosphatase (LAP) </li></ul> neoplasm (CML) : decreased LAP
  57. 57. reactive WBC proliferations <ul><li>leukocytosis </li></ul><ul><ul><li>(2) increased eosinophils </li></ul></ul><ul><ul><ul><li>i. allergies & asthma (type I hypersensitivity reaction) </li></ul></ul></ul><ul><ul><ul><li>ii. parasites </li></ul></ul></ul><ul><ul><ul><li>iii. drugs </li></ul></ul></ul><ul><ul><ul><li>iv. certain skin diseases </li></ul></ul></ul><ul><ul><ul><li>v. cancer (adenocarcinoma) </li></ul></ul></ul>
  58. 58. reactive WBC proliferations <ul><li>leukocytosis </li></ul><ul><ul><li>(3) increased monocytes (monocytosis) </li></ul></ul><ul><ul><ul><li>i. chronic disorders </li></ul></ul></ul><ul><ul><ul><ul><li>a. collagen vascular diseases </li></ul></ul></ul></ul><ul><ul><ul><ul><li>b. inflammatory bowel disease (IBD) </li></ul></ul></ul></ul><ul><ul><ul><li>ii. infection </li></ul></ul></ul><ul><ul><ul><ul><li>a. TB </li></ul></ul></ul></ul>
  59. 59. reactive WBC proliferations <ul><li>leukocytosis </li></ul><ul><ul><li>(4) increased lymphocytes (lymphocytosis) </li></ul></ul><ul><ul><ul><li>i. viral diseases </li></ul></ul></ul><ul><ul><ul><ul><li>a. infectious mononucleosis </li></ul></ul></ul></ul><ul><ul><ul><li>ii. chronic inflammatory process </li></ul></ul></ul>
  60. 60. infectious mononucleosis <ul><li>- one of causes of lymphocytosis </li></ul><ul><li>- a virus-induced disease </li></ul><ul><ul><li>Epstein-Barr virus (EBV) </li></ul></ul><ul><ul><li>CMV </li></ul></ul>
  61. 61. <ul><li>(1) EBV invades B-cell via CD21 (CR2) </li></ul><ul><li>(2) cytotoxic (CD8) T-cells respond against invaded B-cells </li></ul>infectious mononucleosis pathophysiology CD8 T-cells Atypical lymphocytes (Downey cells) Monocyte-like appearance (“mononucleosis”) Peripheral condensation of cytoplasm (“ballerina skirt” appearance) [enlargement]
  62. 62. <ul><li>(3) heterophil antibody production </li></ul><ul><ul><li>(heterophil antibody : antibody against other species) </li></ul></ul><ul><ul><li>monospot test (Paul-Bunnell reaction) </li></ul></ul><ul><ul><ul><li>checking for heterophil antibody </li></ul></ul></ul><ul><ul><li>CMV-infectious mono: usually heterophil Ab neg </li></ul></ul>infectious mononucleosis
  63. 63. <ul><li>patient population: </li></ul><ul><ul><li>adolescents and young adults </li></ul></ul><ul><ul><li>(“kissing disease”) </li></ul></ul><ul><li>Sx: “triad” plus one </li></ul><ul><ul><li>Fever </li></ul></ul><ul><ul><li>Sore throat (gray-white memb. on tonsils) </li></ul></ul><ul><ul><li>Lymphadenitis (post auricular nodes) </li></ul></ul><ul><ul><li>Hepatosplenomegaly </li></ul></ul><ul><ul><li>self-limited clinical course (resolving in 4-6 wks) </li></ul></ul>infectious mononucleosis
  64. 64. <ul><li>complications: </li></ul><ul><ul><li>hepatic dysfunction (“hepatitis”) </li></ul></ul><ul><ul><li>splenic rupture </li></ul></ul><ul><ul><li>rash (if treated with ampicillin) </li></ul></ul>infectious mononucleosis
  65. 65. lymphadenopathy <ul><li>acute non-specific lymphadenopathy </li></ul><ul><ul><ul><li>tender enlargement of lymph nodes </li></ul></ul></ul><ul><ul><li>bacterial lymphadenitis </li></ul></ul><ul><ul><ul><li>usually focal involvemnt </li></ul></ul></ul><ul><ul><ul><li>may see PMNs within lymph nodes </li></ul></ul></ul><ul><ul><ul><li>stellate microabscesses = Cat-scratch Dz </li></ul></ul></ul><ul><ul><li>viral infection </li></ul></ul><ul><ul><ul><li>usually generalized involvement </li></ul></ul></ul><ul><ul><ul><li>reactive T-cell immunoblasts (LN & peripheral blood) </li></ul></ul></ul>
  66. 66. lymphadenopathy <ul><li>chronic non-specific lymphadenopathy </li></ul><ul><ul><ul><li>non-tender enlargement of lymph nodes </li></ul></ul></ul><ul><ul><li>follicular hyperplasia (B-cells) </li></ul></ul><ul><ul><ul><ul><li>rheumatoid arthritis </li></ul></ul></ul></ul><ul><ul><ul><ul><li>toxoplasmosis </li></ul></ul></ul></ul><ul><ul><ul><ul><li>early HIV infection </li></ul></ul></ul></ul><ul><ul><li>paracortical lymphoid hyperplasia (T-cells) </li></ul></ul><ul><ul><ul><ul><li>viral infection </li></ul></ul></ul></ul><ul><ul><ul><ul><li>drugs (Dilantin) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>systemic lupus erythematosus (SLE) </li></ul></ul></ul></ul><ul><ul><li>sinus histiocytosis (macrophages) </li></ul></ul>

×