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PLURIPOTENT HEMATOPOIETIC STEM CELL
PRECURSOR TO WHITE AND RED BLOOD CELLS
DIFFERENTIATE INTO UNIPOTENTIAL STEM CELL (CFU) AND THEN TO SPECIFIC BLOOD CELL LINES
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MONOPHYLETIC THEORY
SINGLE TYPE OF STEM CELL GIVES RISE TO ALL TYPES OF BLOOD CELLS IN BODY
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COLONY-FORMING CELLS (CFU)
DIFFERENTIATED PLEURIPOTENTIAL CELLS
CHANNELED INTO SPECIFIC CELL LINE
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MAJOR SITES OF HEMATOPOIESIS DURING DEVELOPMENT
- MESOBLASTIC PHASE
- 3RD-9TH WEEK OF GESTATION - "BLOOD ISLANDS" DERIVED FROM MESODERM YOLK SAC
- PRIMITIVE BLOOD VESSLE FORMATION
- PRIMITIVE ERYTHROBLASTS
- HEPATIC PHASE
- 4TH WEEK TO BIRTH - MIGRATION OF PRIMITIVE ERYTHROBLASTS FROM YOLK SAC TO LIVER
- DEFINITIVE ERYTHROPOIESIS IN SPLEEN, LYMPH NODES AND THYMUS
- MYELOID PHASE
- 4TH-5TH MONTH OF GESTATION - MEDULLARY (MYELOID) HEMATOPOIESIS WITH EARLY SKELETAL DEVELOPMENT
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AGE RELATED CHANGES OF BONE MARROW
AT BIRTH, MARROW IS ACTIVE IN HEMATOPOIESIS AND HEPATIC ACTIVITY IS MINIMAL
INFANT'S LUNGS REPLACE PLACENTA, 02 SATURATION INCREASES, AND ERYTHROPOIESIS PRODUCTION DECREASES (RBC's)
THROUGH EARLY PUBERTY, MARROW IN MOST OF SKELETON IS RED
BY EARLY ADULTHOOD ONLY VERTABRAE, RIBS, STERNUM, SKULL, PELVIS, AND PROXIMAL EPIPHYSEAL AREAS OF HUMERUS AND FEMUR HAVE RED MARROW. OTHER BONES FILLED WITH ADIPOSE YELLOW MARROW
YELLOW CAN CONVERT BACK TO RED IF DEMAND IS HIGH, EXTRAMEDULLARY (LIVER, SPLEEN, ETC) CAN KICK IN ALSO
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STRUCTURE OF BONE MARROW
FOUND BETWEEN TRABECULAE OF SPONGY BONE
- HIGHLY CELLULAR LOOSE CONNECTIVE TISSUE COMPOSED OF:
- HEMATOPOIETIC CORDS OF MATURING BLOOD CELLS ALONG WITH A SUPPORTIVE STROMA (esp RETICULAR CELLS AND MACROPHAGES)
VASCULAR COMPARTEMENTS - ONCE MATURED, BLOOD CELLS MOVE TO ADJACENT SINUSOIDS AND TRAVERSE ENDOTHELIAL LINING TO GET INTO CIRCULATIONAND VASCULAR COMPARTMENTS
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ERYTHROPOIETIN
GLYCOPROTEIN
STIMULATES STEM CELL DIFFERENTIATION - PROERYTHROBLASTS
PRODUCED IN KIDNEYS (MAYBE OTHER ORGANS)
PRODUCED IN RESPONSE TO CHANGES IN O2, BLOOD FLOW, HEME [ ], HEME/O2 SATURATION, etc
RENAL INSUFFICIENCY OFTEN ASSOCIATED WITH DECREASED ERYTHROPOIETIN LEADING TO ANEMIA
ELEVATED ERYTHROPOIETIN PRODUCTION SEEN WITH RENAL CELL CARCINOMAS, HEPATOCARCINOMAS, etc.
INCREASED ERYTHROPOIESIS CALLED POLYCYTHEMIA
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ERYTHROPOIESIS
RBC FORMATION 3-7 DAYS
ERYTHS MAKE UP 25-30% OF MARROW CELLS
ERYTHS OFTEN SURROUND MACROPHAGE CREATING ERYTHROBLASTIC ISLAND
DEVELOPING ERYTHROBLASTS THOUGHT TO RECEIVE IRON FROM THE MACROPHAGE AS THE FORMER DEVELOP
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PRONORMOBLAST
ERYTH
UNIPOTENT CELL DERIVED FROM PLURIPOTENT STEM CELL
NUCLEUS - REDDISH BLUE; CHROMATIN MORE DEFINED THAN MYELOBLAST
FREE RIBOSOMES AND NO CYTOPLASMIC GRANUALS
MITOTIC
GROWS INTO BASOPHILIC NORMOBLAST
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BASOPHILIC NORMOBLAST
ERYTH (FROM PRONORMOBLAST)
NUCLEUS - COARSENING OF CHROMATIN PATTERN (DARKER STAIN)
CYTOPLASM - INC AMOUNTS OF HEME BEGIN TO IMPART REDDISH TINGE
MITOTIC
GROWS INTO POLYCHROMATOPHILIC NORMOBLAST
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POLYCHROMATOPHILIC NORMOBLAST
ERYTH (FROM BASOPHILIC NORMOBLAST)
NUCLEUS - CHECKERBOARD PATTERN
CYTOPLASM - RED/BLUE
LAST ERYTH STAGE CAPABLE OF MITOSIS
GROWS INTO ORTHOCHROMATIC NORMOBLAST
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ORTHOCHROMATIC NORMOBLAST
ERYTH (FROM POLYCHROMATOPHILIC NORMOBLAST)
NUCLEUS - PYKNOTIC, OFTEN ECCENTRICALLY PLACED
CYTOPLASM - REDDISH PURPLE DUE TO HEME CONTENT
GROWS INTO RETICULOCYTE
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RETICULOCYTE
ERYTH (FROM ORTHOCHROMATIC NORMOBLAST)
NUCLEUS - NO LONGER PRESENT
CYTOPLASM - REDDISH PURPLE DUE TO HEME, MAY CONTAIN GRANULOFILAMENTOUS MATERIAL (POLYSOMES, ER)
RESIDUAL RNA AND MITOCHONDRIA IN CYTOPLASM
RELEASED INTO GENERAL CIRCULATION, CONTINUES DEVELOPMENT INTO ERYTHROCYTE
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ERYTHROCYTE
FROM RETICULOCYTE
BICONCAVE DISCS
EOSINOPHILIC CYTOPLASM DUE TO ABUNDANCE OF HEME
LITTLE, IF ANY, RESIDUAL RNA OR MITOCHONDRIA
LIFESPAN 100-120 DAYS
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MYELOBLAST
GRANULOPOIESIS (TOTAL 2-3 WEEKS)
UNIPOTENT CELL (MYOBLASTIC) DERIVED FROM A PLURIPOTENT STEM CELL
NUCLEUS - ROUND, LIGHT REDDISH PURPLE, FINE CHROMATIN PATTERN
CYTOPLASM - BLUISH, NONGRANULAR
MITOTIC
RER
GROWS INTO PROMYELOCYTE
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PROMYELOCYTE
GRANULOPOIESIS (FROM MYELOBLAST)
NUCLEUS - BLUE, DEVELOPMENT OF DISTINCT (PRIMARY AZUROPHILIC) GRANULES
MITOTIC
GROWS INTO NEUTROPHILIC MYELOCYTE
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NEUTROPHILIC MYELOCYTE
GRANULOPOIESIS
NUCLEUS - ROUND, OVAL OR SLIGHTLY INDENTED ON ONE SIDE
CYTOPLASM - "DAWN OF NEUTROPHILIA" FIRST APPEARANCE OF NEUTROPHILIC (SECONDARY) GRANULES ADJACENT TO NUCLEUS
LAST MYELOBLASTIC STAGE CAPABLE OF MITOSIS
GROWS INTO NEUTROPHILIC METAMYELOCYTE
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NEUTROPHILIC METAMYELOCYTE
GRANULOPOIESIS (FROM NEUTROPHILIC MYELOCYTE)
NUCLEUS - INDENTED "KIDNEY BEAN SHAPE"
CYTOPLASM - NUMEROUS NEUTROPHILIC (SPECIFIC) GRANULES OUTNUMBER AZUROPHILIC NONSPECIFIC GRANULES
RARELY SEEN IN CIRCULATION OF NORMAL INDIVIDUALS, MAY BE SEEN IN MYELOCYTIC HYPERPLASIA
GROWS INTO NEUTROPHILIC BAND
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NEUTROPHILIC BAND
GRANULOPOIESIS (FROM NEUTROPHILIC METAMYELOCYTE)
NUCLEUS - INDENTATION NOW HORSESHOE SHAPED, PYKNOTIC (VERY DENSE)
CYTOPLASM - NUMEROUS, EVENLY DISTRIBUTED NEUTROPHILIC GRANULES
GROWS INTO NEUTROPHIL
CAN BE FOUND IN NORMAL CIRCULATION
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NEUTROPHIL
GRANULOPOIESIS (FROM NEUTROPHILIC BAND)
NUCLEUS - SEPARATED INTO DEFINITE 2-4 LOBES LINKED BY THIN STRANDS (SEGMENTED), HIGHLY CONDENSED CHROMATIN
CYTOPLASM - NUMEROUS EVENLY DISTRIBUTED NEUTROPHILIC GRANULES, AZUROPHILIC GRANULES ARE STILL PRESENT BUT NOT EASILY IDENTIFIABLE
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PERCENTAGES OF WHITE CELLS IN BLOOD
- NEUTROPHILS 50-70%
- LYMPHOCYTES 20-40%
- MONOCYTES 2-8%
- EOSINOPHILS 1-4%
- BASOPHILS 0.5%
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BLOOD SERUM VS. PLASMA
SERUM: PLASMA MINUS FIBRIN CLOT (FORMED BY COAGULANTS)
PLASMA: PROTEIN-RICH FLUID SURROUNDING THE BLOOD CELLS
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HEMATOCRIT
PERCENTAGE OF WHOLE BLOOD SAMPLE OCCUPIED BY CELLS (Hct)
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SHIFT TO THE LEFT
UNUSUALLY LARGE NUBER OF IMMATURE WBC's PRESENT
SUGGESTS UNUSUAL DEMAND FOR GRANULOCYTES (SIGNIFICANT INFECTION OR LEUKEMIAS
SHIFT TO THE RIGHT SUGGESTS INCREASED NUMBER OF AGED CELLS, AS WIT HPERNICIOUS ANEMIA (ie HYPERSEGMENTED NEUTROPHILS)
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MEGAKARYOCYTES
BONE MARROW CELLS THAT MAKE PLATELETS
DERIVED FROM MEGAKARYOBLASTS CONTAINING SINGLE LARGE NUCLEUS WITH MULTIPLE NUCLEOLI
POLYPLOIDY WITH LARGE IRREGULAR MULTILOBAR NUCLEUS (30x DNA AS DIPLOID CELL)
FOUND NEAR SINUSOIDS, CYTOPLASMIC PROCESSES EXTEND THROUGH SINUS WALL AND RELEASE PLATELETS INTO CIRCULATION
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