[HEMA] Chapter 3 - Hematopoiesis

Hematopoiesis

Is a continuous,  regulated process of blood cell production that includes cell renewal, proliferation, differentiation and maturation

Hematopoietic stem cell

A ______________ (multipotential stem cell, pluripotential stem cell, multipotent stem cell) is capable of cell-renewal (i.e., replenishment) and directed differentiation into all required cell lineages.

Yolk Sac

Sites of Hematopoiesis (Fetus) #1

Aorta-Gonad Mesonephros

Sites of Hematopoiesis (Fetus) #2

Fetal liver

Sites of Hematopoiesis (Fetus) #3

Bone Marrow

Sites of Hematopoiesis (Adult)

Mesoblastic Phase

Is considered to begin around the 19^th day of embryonic development after fertilization.

Gower-1,

Hemoglobin needed for mesoblastic phase #1

Gower-2

Hemoglobin needed for mesoblastic phase #2

Portland

Hemoglobin needed for mesoblastic phase #3

Hepatic Phase

Begins to happen at 5 – 7 gestational weeks.

Hepatic Phase

Extravascular hematopoiesis

spleen, thymus, kidneys and lymph nodes

The developing _________________ contribute to the hematopoietic process during this phase.

Hgb F

The predominant hemoglobin for Hepatic Phase is

Hgb A

Detectable amount of adult hemoglobin in hematic phase _______ is present.

medulla

Derived its name from its location – “__________” meaning inside the bones.

mesenchymal cells

The ___________, which are a type of embryonic tissue, differentiate into structural elements

Bone Marrow

By the end of 24 weeks gestation, the ___________ becomes the primary site of hematopoiesis. 

Granulocyte colony-stimulating factor (G-CSF)

Erythropoietin (EPO), ______________, and Hemoglobins A and F can be detected.

Extramedullary Hematopoiesis

Occurs when the BM cannot meet body requirements

Bone Marrow (BM), Liver, Spleen, Thymus, Lymph Nodes

Also called the Reticulo-Endothelial System (RES)

Bone Marrow

Contains developing erythroid, myeloid, megakaryocytic and lymphoid tissue.

Primary lymphoid

___________ tissue consists of the bone marrow and thymus is where T and B lymphocytes are derived.

Secondary lymphoid

_____________ tissue, where lymphoid cells respond to foreign antigens, consist of the spleen, lymph nodes, and mucosa-associated lymphoid tissue.

Red marrow

hematopoietically  active marrow consisting of the developing blood cells and their progenitors.

Yellow Marrow

hematopoietically inactive marrow composed primarily of adipocytes (fat cells), with undifferentiated mesenchymal cells and macrophages.

Newborn

80 – 90% BM is active RED Marrow.

Young adult

60% of BM is active. Hematopoiesis is confined to the proximal end of long bones, large flat bones, pelvis and sternum.

Older adult

40% is active; 60% is fat.

Normocellular

marrow has 30-70% hematopoietic cells

Hypercellular/Hyperplastic

>70% hematopoietic cells.

Hypocellular/Hypoplastic

<30% hematopoietic cells

Aplastic

marrow has few or no hematopoietic cells.

3:1 – 4:1

M:E Ratio (Myeloid: Erythroid) Ratio

Granulocyte, Erythrocyte, Megakaryocyte, Monocyte

CFU – GEMM

Erythrocyte

CFU – E

Megakaryocyte

CFU – Meg

Monocyte

CFU – M

Granulocyte, Monocyte

CFU – GM

Myeloid to Basophil

CFU – BASO

Myeloid to Eosinophil

CFU - EO

Myeloid to Neutrophil

CFU – G

T Lymphocyte

CFU – pre – T

B Lymphocyte

CFU – pre – B

Erythropoiesis

occurs in the BM and is a complex, regulated process for maintaining, adequate numbers of erythrocytes in the peripheral blood.

CFU-GEMM

The _____________ gives rise to the earliest identifiable colony of RBCs called burst-forming unit-erythroid (BFU-E). BFU-E’s under the influence of IL-3, GM-CSF, EPO, and KIT Ligand develop into colony forming unit-erythroid (CFU-E) colonies. The CFU-E has many EPO receptors and has an absolute requirement for EPO. 

burst-forming unit-erythroid (BFU-E)

The CFU-GEMM gives rise to the earliest identifiable colony of RBCs called ___________. BFU-E’s under the influence of IL-3, GM-CSF, EPO, and KIT Ligand develop into colony forming unit-erythroid (CFU-E) colonies. The CFU-E has many EPO receptors and has an absolute requirement for EPO.

colony forming unit-erythroid (CFU-E) colonies

The CFU-GEMM gives rise to the earliest identifiable colony of RBCs called burst-forming unit-erythroid (BFU-E). BFU-E’s under the influence of IL-3, GM-CSF, EPO, and KIT Ligand develop into ______________. The CFU-E has many EPO receptors and has an absolute requirement for EPO.

EPO

EPO serves as differentiation factor that causes the CFU-E to differentiate into pronormoblasts, the earliest visually recognized erythrocyte precursors in the BM.

myelopoiesis

Leukopoiesis can be divided into two major categories #1

lymphopoiesis

Leukopoiesis can be divided into two major categories #2

CFU-GEMM

__________ to differentiate into neutrophils, eosinophils and basophils includes GM-CSF, G-CSF, macrophage colony-stimulating factor (M-CSF), IL-3, IL-5, IL-11 and KIT Ligand.

macrophage colony-stimulating factor (M-CSF)

CFU-GEMM to differentiate into neutrophils, eosinophils and basophils includes GM-CSF, G-CSF, ___________, IL-3, IL-5, IL-11 and KIT Ligand.

IL-3

is a multi-lineage stimulating factor that stimulates the growth of granulocytes, monocytes, megakaryocytes and erythrocytes. 

Eosinophils

requires GM-CSF, IL-5 & IL-3.

Basophils

requirements for differentiation are less clear, but it seems to depend on presence of IL-3 and KIT Ligand.

LYMPHOID

_______________differentiation requires IL-2, 7, 12, 15 and to some extent IL-4, 10, 13, 14, 16.

megakaryopoiesis

Early influences on ______________ are GM-CSF, IL-3, 6, 11, KIT Ligand and TPO.

Erythron

is the term used to describe the total population of mature RBC and their precursors in blood, bone marrow and other sites.

Pronormoblast

Size: 14 to 20 um

Pronormoblast

N:C Ratio = 8:1

Pronormoblast

Nucleoli: present (1-2) usually very faint

Basophilic Normoblast

Other name for Prorubricyte

Basophilic Normoblast

Size: 12 to 17 um

Basophilic Normoblast

Nucleoli: 0-1

Basophilic Normoblast

N:C Ratio = 6:1

Basophilic Normoblast

is the last stage with a nucleolus.

Basophilic Normoblast

gives rise to 4 rubricytes.

Polychromatic Normoblast

Other name for Rubricyte

Polychromatic Normoblast

Size: 10 to 15 um

Polychromatic Normoblast

N:C Ratio = 4:1

Polychromatic Normoblast

Last stage capable of mitosis (cell division).

Polychromatic Normoblast

Each of these cells (rubricyte) gives rise to 2 metarubricytes.

Polychromatic Normoblast

First stage of Hgb synthesis (Hemoglobinizations)

Polychromatic Normoblast

Checkerboard Appearance
Muddy/Gray

Lymphocyte

Crushed Velvet
Sky Blue/Robin Egg Blue

Orthocromatic Normoblast

Orthocromatic Normoblast

Other name for Metarubricyte

NRBC

Other name for Orthocromatic Normoblast

Orthocromatic Normoblast

Size: 7 to 12 um

Orthocromatic Normoblast

N:C Ratio = 0.5:1

Orthocromatic Normoblast

Cytoplasm: Salmon pink or pale blue

Orthocromatic Normoblast

Nucleus = pyknotic (dense mass of degenerated chromatin)

Orthocromatic Normoblast

Last stage with a nucleus.

Reticulocyte

Size: 7 to 10 um

Reticulocyte

Young RBC’s containing residual RNA (last immature erythrocyte stage)

Reticulocyte

Spend 2 to 3 days in the bone marrow and 1 day in the peripheral blood before developing into a mature RBC.

Reticulocyte

Last stage of Hemoglobin synthesis (Hemoglobinazation)

SHIFT CELLS

seen in conditions with Increase RBC production.

STRESS RETICULOCYTES

• n in more severe condition (e.g. Anemia)

Mature Erythrocyte

RBC

600:1

Normal ratio of RBC to WBC is approximately

15:1

normal ratio of RBC to Platelets

mitochondria

Adult RBC contains no

10%

RBC Membrane: Carbohydrates

40%

RBC Membrane: Lipids

50%

RBC Membrane: Proteins

1%

Pronormoblast % in BM

1%-4%

Basopholic Normoblast % in BM