HISTOLOGY & CELL BIOLOGY

BLOOD & HEMATOPOIESIS II

HEMATOPOIESIS

Blood Formation:
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
elo
ie
po
sis

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, loses 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

3.

H&E stain

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

DEFINITION: Pancytopenia due to the failure of bone marrow to produce blood cells
CAUSES OF BONE MARROW FAILURE
Approach:
Pancytopenia
1.Consider causes of peripheral destruction: hypersplenism, sepsis, immune...
Typically, these will be associated with a hypercellular marrow
2. Perform bone marrow investigation
a. Hypercellular marrow
bone marrow infiltration
-hematologic maligancies
leukemias
myeloma
lymphoma
-carcinoma
-storage disorders
myelodysplastic syndromes
B12 or folate deficiency
b. Hypocellular marrow
aplastic anemia (not enough elements making blood)
- congenital
- Fanconis anemia
- acquired
- idiopathic
- drugs/chemicals
- radiation
- viruses

Conceptual classification of pancytopenia

Pancytopenia

Increased destruction

sequestration

Immune destruction
sepsis

Hypersplenism

Decreased production

Myelodysplasia
Marrow infiltrate
B12 deficiency
Aplastic anemia
Drugs
Viruses
Radiation

A practical approach to pancytopenia

Pancytopenia
Review meds
Examine spleen
consider sepsis
Order: retics, B12,
ANA, SPE & abd U/S

Bone marrow
investigation

Hypocellular
Aplastic anemia
Drugs/chemicals
Viruses
Radiation
Fanconi anemia
idiopathic

Hypercellular
Peripheral destruction
Hypersplenism
MDS
Marrow infiltration
Hematologic malignancy
Solid tumor
Storage diseases
Other
Megaloblastic anemia
myelofibrosis

Other medical applications

RBC
Anemia

Increase or decrease in number

WBC
Inflammation, allergic reaction, hypersensitivity reactions, infections
four main types of leukemia are:

Hemorrhage,
Deficient erythropoiesis
Accelerated destruction of circulating RBCs
Deficiencies of Fe+, vit B12, folic acid

Acute lymphoblastic leukemia, or ALL, most common leukemia in

children. Adults can also get it.
Acute myelocytic leukemia, or AML., affects both children and adults.
Chronic lymphocytic leukemia, or CLL, most common leukemia in
adults, mostly those who are older than 55. Children almost never get
it.
Chronic myeloblastic leukemia, or CML, occurs mostly in adults.

Platelets
Bleeding problems- Increase vs decrease in numbers

Acknowledgement
L.C.

Junqueira and J. Carneiro, 2005, Basic

Histology, 11th Edition, Lange Medical Books,
New York.
Cormack DH, 2001, Essential Histology 2nd
Edition, Lippincott Williams & Wilkins,
Philadelphia.
MH Ross & W Pawlina, 2006, Histology: A text
and Atlas with correlated cell and molecular
biology, 5th Edition, Lippincott Williams &
Wilkins, Philadelphia.