HEMATOPOIESIS

MED 1103

HEMATOPOIESIS

Location
Prenatal
1.
2.
3.
4.

2 weeks 8 weeks: yolk sac produces blood islands

6 weeks birth: liver production
2nd trimester birth: spleen production
3rd trimester adulthood: bone marrow

Postnatal
1. exclusively in bone marrow
2. in disease states, spleen and
liver can produce blood cells

Bone Marrow
1. structure: reticular fibers, veins, arteries,
sinusoids, islands of cells
2. red marrow: active hematopoiesis
3. yellow marrow: fat in reticular cells,
inactive hematopoiesis

Production
1. greater than 109 (billion) cells produced daily
2. stem cells pleuripotent, low numbers, give rise to:
3. multipotential cells
a. colony forming units spleen (myeloid cell lines)
b. colony forming units lymphocytes (lymphoid cell lines)
4. progenitor cells committed to a single cell line, limited self renewal
5. precursor cells morphologically distinct, no self renewal
a. generally referred to as a "_____blast" which differentiates
to a "____cyte"
b. as cells develop; decrease in size, nuclei condense

MHSC

Prelymphocytes

CFU-LyB

CFU-Ly
Ly
m
ph
op
oi
es
is

CFU-LyT
CFU-Meg

PHSC

MKB

MKC

CFU-M

Promonocyte

CFU-N

Myeloblast

CFU-Ba

CFU-Ba

Myeloblast

CFU-Eo

CFU-Eo

Myeloblast

CFU-NM

My
e lo
po
is
ie s

CFU-GEMM
Myeloid stem cell

BFU-E

Stem Cells%

CFU-E

Progenitor Cells%

Proerythroblast
Precursor Cells%

Regulation
1. hematopoietic growth factors (colony stimulating factors)
glycoproteins
2. interleukins, granulocyte colony stimulating factor, erythropoietin, etc.
3. stem cell factor (steel factor) stromal cells of the bone marrow,
stimulates division
4. hematopoietic cells will die unless exposed to growth factors

ERYTHROPOIESIS

Erythropoiesis (erythrocyte formation)

1. ~ 2 x 109 erythrocytes per day in the bone marrow

2. controlled by cytokines and erythropoietin (kidney);
takes about 3 5 days to complete development
Rate is regulated by oxygen levels:
hypoxia (lower than normal oxygen levels) is detected by cells in the kidneys
kidney cells release the hormone erythropoietin into the blood
erythropoietin stimulates erythropoiesis by the bone marrow

Erythropoiesis (erythrocyte formation)

1. proerythroblast: 14 19 um, no hemoglobin, large nucleus,
basophilic cytoplasm
2. basophilic (early) erythroblast: 12 17 um, some hemoglobin,
condensing nucleus
3. polychromatophilic erythroblast: 12 15 um, "muddy" cytoplasm
4. orthochromatophilic (late) erythroblast (normoblast): 8 12 um,
increased hemoglobin
5. reticulocyte: 7 8 um, no nucleus, some ribosomes
(blue with cresyl blue stain)
6. erythrocyte: 7.5 um, only hemoglobin, no ribosomes

Identify the cells:

Identify the cells:

GRANULOCYTOPOIESIS

Granulocytopoiesis (granulocyte formation)

1. ~ 800,000 neutrophils, 170,000 eosinophils, 60,000 basophils per day
2. controlled by cytokines; takes about 11 days

Granulocytopoiesis (granulocyte formation)

1. myeloblasts: common precursor, 12 14 um,
no granules, cytoplasmic blebs
2. promyelocyte: 16 24 um, large nucleus,
azurophilic granules (not specific)
Neutrophilic, Eosinophilic or Basophilic:
3. myelocyte: 10 12 um, condensed rounded nucleus,
specific granules
4. metamyelocyte: kidneyshaped nucleus,
specific granules
5. band (stab): Cshaped nucleus, specific granules
6. mature form: neutrophil, eosinophil, basophil

Identify the cells:

Identify the cells:

THROMBOPOIESIS (platelet formation)

1. controlled by thrombopoietin
2. megakaryoblast: 25 40 um, endomitosis, polyploid ( ~ 32N)
3. megakaryocyte: 40 100 um, large multilobed nucleus
4. platelets are formed from fragments of megakaryocyte cytoplasm
(1000's per cell)
5. platelet demarcation channels

MONOCYTOPOIESIS (monocyte formation)

1. monoblasts: large, undifferentiated cells
2. promonocytes: 16 18 um, kidneyshaped nucleus,
azurophilic granules
3. monocytes: "sky" blue cytoplasm, kidney-shaped nucleus
4. enter the circulation, proceed to tissue spaces,
differentiate into macrophages

LYMPHOPOIESIS (lymphocyte formation)

1. colony forming units (CFU) lymphocyte
(B = bursa equivalent; T = thymus)
2. lymphoblasts: large, undifferentiated cells
3. prolymphocytes: mediumsized cells, condensing chromatin,
no cell surface antigens
4. some migrate from bone marrow to thymus,
divide and differentiate to Tcells
5. others remain in bone marrow, differentiate to
Bcells, migrate to lymph tissues