Hematology Lecture Notes PDF

HEMATOLOGY (Lecture) WEEK 3: Hematopoiesis MESOBLASTIC/ YOLK PHASE INTRODUCTION As early as the 19th day of gestation in the...

HEMATOLOGY (Lecture) WEEK 3: Hematopoiesis MESOBLASTIC/ YOLK PHASE INTRODUCTION As early as the 19th day of gestation in the blood islands of the yolk sac of the human Hematopoiesis is the production of embryo. different cells. Confined to erythropoiesis (PRIMITIVE HEMATOPOIETIC TISSUES HEMATOPOIESIS) producing primitive cells Organs and tissues areas in which blood containing embryonic hemoglobins: cell production or regulation occurs. ➔ Ery-RED -RBC, WBC, Platelets, etc. ➔ Poiesis-formation/red blood cell production Adults: restricted to the bone marrow ➔ embryonic hemoglobins-hemoglobin within the cortical bones of the body. present in the embryo Fetus: different organs ➔ Portland: 2 zeta + 2 gamma - Mesoblastic phase: Yolk sac (start Gower I: 2 zeta + 2 epsilon to form in mom’s womb; weeks) Gower II: 2 alpha + 2 epsilon - Hepatic phase: Liver (spleen, HEPATIC PHASE thymus, lymph nodes) On the 3rd month, yolk sac discontinues its - Medullary phase: bone marrow role, fetal liver becomes active (cortical bones of the bone; outside) (erthrocytes AND granulocytes in - Medulla; inside production) By the end of the 4th month, primitive cells are disappearing, with an increase in the more definitive erythroblast, granulocytes and megakaryocytes. - Granulocytes- eosinophil, basophils, neutrophils Also active are the spleen, thymus and lymph nodes START OF DEFINITIVE HEMATOPOIESIS producing producing definitive erythroblasts containing fetal hemoglobins: Hemoglobin F (2 alpha + 2 gamma) Hemoglobin A1 (2 alpha + 2 beta) STAGES OF HEMATOPOIESIS Hemoglobin A2 (2 alpha 2 delta) MEDULLARY/ MYELOID PHASE Between 5th and 6th month gestation, the bone marrow becomes the primary site of hematopoiesis. At birth, BM becomes the primary source of cell production. Hematopoiesis occurs in most bones but primarily in the flat bones of the sternum, ribs, vertebrae, skull, pelvis In ADULT, the principal source of production is the sternum and other flat bones. NORMAL CELL MATURATION 1. Nuclear Maturation -mas maraming napproduce sa bone marrow Loss of nucleoli Decrease in diameter of nucleus HEMATOLOGY (Lecture) Condensation of nuclear chromatin Possible change in shape of nucleus Possible loss of the nucleus Most reliable indicator of maturity: Chromatin pattern CHROMOSOME PARTS: Heterochromatin: (darker color in the chromosome; side parts) - More condensed - Silenced genes (methylated) - Gene poor (high AT content) - Stains darker Euchromatin: (middle part) - Less condensed ERYTHROPOIESIS - Gene expressing ➔ Process by which erythroid precursor cells - Gene rich (higher GC content) differentiate to become mature RBC - Stains lighter ➔ ERYTHROPOIETIN: primary regulator - produced in the KIDNEY ➔ HYPOXIA: primary stimulus (low oxygen level of blood cell) ➔ Retics: 1-2 days in BM + 1 day in PB - Reticulocytes- baby form of RBC BLASTS ➔ blast -baby (youngest) form ➔ Large size ➔ Basophilic cytoplasm ➔ Absence of granules ➔ Large nucleus ➔ High N/C ratio (dahil malaki ang nucleus) ➔ Presence of nucleoli 2. Cytoplasmic maturation ➔ Fine chromatin - Decrease in basophilia - Increase in the proportion of cytoplasm - Appearance of cytoplasmic granules PRONORMOBLAST ➔ Rubriblast/ Proerythroblast ➔ Diameter = 14-20 um ➔ Deeply basophilic cytoplasm ➔ Non-granular w/ fine chromatin HEMATOLOGY (Lecture) ➔ N/C ratio = 8:1 (nuclear–cytoplasmic ratio) ORTHOCHROMIC NORMOBLAST ➔ With 1-2 nucleoli ➔ Orthochromic Erythroblast/ Metarubricyte ➔ Diameter = 7-12 um ➔ Pink cytoplasm w/ small pyknotic nucleus ➔ N/C ratio = 1:2 ✓ LAST NUCLEATED STAGE MOBLAST BASOPHILIC NORMOBLAST ➔ Basophilic Erythroblast/ Prorubricyte ➔ Diameter = 12-17 um ➔ Intensely basophilic cytoplasm ➔ Chromatin slightly coarse RETICULOCYTE ➔ N/C ratio = 6:1 ➔ Polychromatophilic Erythrocyte ➔ Nucleoli not usually visible ✓ INDEX OF BONE MARROW ACTIVITY ✓ LAST STAGE WITH HEMOGLOBIN SYNTHESIS ➔ Diameter = 7-10 um ➔ Pink to slightly pinkish gray cytoplasm ➔ Contains fine basophilic reticulum of RNA which is only visible with SUPRAVITAL STAIN ➔ Brilliant Cresyl Blue ➔ New Methylene Blue POLYCHROMATIC ERYTHROBLAST ➔ Polychromatic Erythroblast ✓ LAST STAGE CAPABLE OF MITOSIS ✓ HEMOGLOBIN SYNTHESIS BEGINS ➔ Murky blue-gray to pink-gray ➔ cytoplasm ➔ Diameter = 10-15 um ➔ N/C ratio = 4:1 Light blue dots reticulocytes Darker blue dots called fine reticulum of RNA MATURE ERYTHROCYTE ➔ Red Blood Cells/ Discocyte ➔ Diameter = 6-8 um ➔ Non-nucleated, round and biconcave with a central pallor 1/3 of its size HEMATOLOGY (Lecture) ➔ Pink in color (Salmon-pink) Bg^b: HLA-B17 ✓ NOT CAPABLE OF HGB SYNTHESIS Bg^c: HLA-A28 ✓ Highest in the MORNING ✓ Life span: 120 days (4 months) Visible with SUPRAVITAL STAIN (RHH) Reticulum of reticulocytes Heinz bodies HbH RBC COLOR- SALMON PINK Must know! ➔ Up to 16 orthochromic normoblasts are produced from a single pronormoblast. ➔ LAST STAGE CAPABLE OF MITOSIS: PN (polychromatic normoblast) ➔ LAST NUCLEATED STAGE: ON (orthochromic normoblast) ➔ INDEX OF BM ACTIVITY: Reticulocytes ➔ HEMOGLOBIN SYNTHESIS - START: PN - ON BITE CELLS (parang may kagat dahil nag - END: PE (polychromatic denature yung hemoglobin) erythroblast) Salmon pink circle-mature RBC Lighter color on the RBC is central pallor (immature PHYSIOLOGIC VARIATIONS RBC) ➔ Males:↑RBC ↑Hct ↑Hgb HEINZ BODIES (mature RBC; darker color na - Due to female menstruation and parang blue; may hemoglobin na hindi male testosterone natanggal kaya parang may filling) ➔ Older males: ↓ Hgb - Older males have higher chances of having Gl bleeding and colon cancer than older women ➔ RBC, Hct, Hgb: - ↑upon STANDING from a recumbent position - ↑in the MORNING - ↑with HIGH ALTITUDE - ↑in SMOKERS Must know! EMBRYONIC HEMOGLOBINS ➔ Portland = 2 zeta + 2 gamma ➔ Gower 1 = 2 zeta+ 2 epsilon (FIRST TO APPEAR) - RBC (Tuldok) inclusions are called ➔ Gower 2 = 2 alpha + 2 epsilon precipitated chains of beta hemoglobin. LEUKOPOIESIS FETAL HEMOGLOBINS ➔ White blood cells ➔ HbF = 2 alpha + 2 gamma LEUKO-white ➔ HbA = 2 alpha +2 beta Poiesis- production or formation of cells ➔ HbA₂ = 2 alpha + 2 delta ➔ Clear colored ➔ HLA on RBC: BENNETT-GOODSPEED Bg^a: HLA-B7 HEMATOLOGY (Lecture) WBC MATURATION SERIES ➔ Granulocytes 1. Myeloblast (blast-pinaka baby) 2. Promyelocyte (pro-second) 3. Myelocyte 4. Metamyelocyte LEUKOCYTE CLASSIFICATION 5. Band form/ stab 6. Mature granulocyte MYELOBLAST ➔ Diameter = 15-20 um ➔ Basophilic cytoplasm ✓ EARLIEST RECOGNIZABLE GRANULOCYTIC PRECURSOR USING LIGHT MICROSCOPE ✓ ONLY NONGRANULATED WBC PRECURSOR ➔ N/C ratio = 4:1 NORMAL MYELOID (Neutrophilic) MATURATION ➔ Round or slightly oval nucleus ➔ With fine chromatin ➔ 2-5 nucleoli PROMYELOCYTE ➔ Diameter = 15-21 um ➔ LARGER than its immediate precursor ➔ Basophilic cytoplasm ✓ Contains PRIMARY/NONSPECIFIC granules Maturation or granulopoiesis takes up to 14 ➔ N/C ratio = 2-3:1 days (2 weeks) to produce mature ➔ With slightly coarser chromatin granulocytes. ➔ 2-3 nucleoli GRANULOPOIESIS ➔ Production of mature granulocytes ➔ Takes about 14 days HEMATOLOGY (Lecture) BAND FORM ➔ Stab/ Staff ➔ Diameter = 9-15 um ✓ YOUNGEST WBC TO APPEAR IN THE PB ✓ ELONGATED/ BAND-SHAPED/ SAUSAGE-SHAPED NUCLEUS/very manipis ➔ More than ½ of the diameter of the nucleus With coarse and clumped chromatin MYELOCYTE ➔ Diameter = 12-18 um ➔ N/C ratio = 1:1 ➔ No nucleoli ✓ Contains SECONDARY/SPECIFIC Granules ➔ With coarse chromatin ✓ LAST STAGE CAPABLE OF MITOSIS ✓ YOUNGEST STAGE WHEREIN SPECIFIC GRANULOCYTE CAN BE IDENTIFIED MATURE NEUTROPHIL ➔ Neutrophil myelocyte: ROSE-PINK granules ➔ Segmented Neutrophil/ Segmenters ➔ Eosinophil myelocyte: ORANGE RED ➔ Diameter = 9-15 um granules ➔ PINK to ROSE VIOLET granules ➔ Basophil myelocyte: DARK ➔ Granules contain ACP, acid hydrolase, PURPLE/BLUE-BLACK muramidase, lysozyme, collagenase, plasminogen actiovator, aminopeptidase and lactoferrin which are essential for phagocytosis ➔ Nucleus has 2-5 lobes (5: hyperlobed) ➔ With coarse and clumped chromatin ➔ Phagocytic ➔ Highest in the AFTERNOON METAMYELOCYTE ✓ JUVENILE LEUKOCYTE ➔ Diameter = 10-15 um ➔ N/C ratio = decreased ✓ Contains TERTIARY/GELATINASE granules ✓ YOUNGEST STAGE NOT CAPABLE OF MITOSIS ✓ PREDOMINANT CELL IN THE ADULT BM* ➔ INDENTED or KIDNEY-SHAPED NUCLEUS ✓ Less than ½ of the diameter of the nucleus ➔ With coarse and clumped chromatin NEUTROPHILS ➔ PRIMARY DEFENSE against infection ➔ MOST COMMON and MOST ABUNDANT of the WBCS ➔ Pseudoneutrophilia (pseudo-false; philia-increase) falsely increase - Caused by a shift of marginated cells to the circulatory pool due to exercise, extreme temperatures, HEMATOLOGY (Lecture) nausea, vomiting, pregnancy, labor, EOSINOPHIL rage, panic and stress ➔ Act as phagocytes and modulate ➔ Neutrophilia inflammatory responses - Bacterial Infection ➔ Plays a role in allergic disorders and - Inflammation/injury parasitic infections - Leukemia and other BM disorders ➔ Dampen hypersensitivity and - Response to medications inflammatory reactions (chemotherapy) ➔ Leave the blood when adrenal corticosteroid hormones increase (Thorn et al.) ➔ Eosinophilia (philia-increase) -Allergic disorders (Hay fever, asthma) - Parasitic infections - Scarlet fever - Skin inflammation (Psoriasis, eczema) - Eosinophilic leukemia and other BM ➔ Neutropenia disorders - Chemical toxicity (benzene) ➔ Eosinopenia (penia-decrease): ACTH - BM replacement (adrenal corticosteroid hormone) - Nutritional deficiencies administration - Cytotoxic drugs ➔ Agranulocytosis - WBC count: