hema 1 -MT113- LEC 5 HEMATOPOIESIS (ERYTHROID SERIES)

Hematopoeisis

process of making blood cells

What does hematopoiesis encompass?

-Formation of blood cells

-development of blood cells

-specilaziation of all functional blood cells (differentiation)

-cellular perforation

3 major phases of Hematopoeisis

Mesoblastic

Hepatic

Myeloid

Mesoblastic

Embryo (3-12 weeks of gestation)

Hepatic

Fetus (beginning of 6th week of gestation)

Myeloid

begining 5th month of gestation and continuing throughout adulthood

What is the first embryonic hematopoietic organ

The yolk sac

-external hematopoeisis

-primitive erythroblast

What embryonic organ becomes a major hematopoietic organ at 6 week

The liver

-helped by spleen

-granulocytes, megakaryocytes, erythroblasts

-predominant at 5 months

At 7 months, what becomes the major hematopoietic organ?

bone marrow

Where are the 4 sites of blood production in the fetus

yolk sack, liver, spleen, lymph node

Once a cell is filled matured, where does it travel to?

Hematopoietic tissue

What are the hematopoietic tissues in adults

Bone Marrow

Spleen

Lymph nodes

Thymus

Mononuclear-phagocyte system

Liver

3 Lymphoid Tissues

Spleen

Lymph nodes

Thymus

What helps in destruction of RBCs

Hematopoietic tissues

Medullary hematopoiesis

blood cell production in the bone marrow. NORMAL

Extramedullary hematopoiesis

blood cell production in hematopoietic tissue other than bone marrow. ABNORMAL

Examples of flat bones

cranium, hip, sternum...

What are the 2 types of bone marrow

red marrow

yellow marrow

Red marrow

Hematopoietically active

Myeloid:Erythroid ratio

M:E

myeloid:erythroid

-ratio of the # of Myeloid (white cell) elements to the # of nucleated erythroid (red cell) elements

yellow marrow

inactive

-100% fat

-in adults % amount roughly matches one's age

In a newborn, what percentage of bone marrow is active

80-90%

In young adults (~age 20) what percentage of bone marrow is active

60% red 40% yellow

In older adults (~age 55) what percentage of bone marrow is active

40% red 60% yellow

What are 3 different cell types found in bone marrow

stem cells

progenitor cells

precursor cells

Stem cells

-found in bone marrow

-pluripotent cells (give rise to all blood cells. Can become any type of blood cell)

Progenitor cell

committed cells (CFU-GEMM)

-decides what become what (not as many options as a stem cell)

-classified based on function

Precursor cells

mature into blast forms

BFU

blast forming unit

GEMM

Granulocyte, erythrocyte, monocyte, megakaryocyte

CFU

colony forming unit

What forms the bone marrow structure

Hematopoietic cells

blood vessels (vasculature)

stromal cells

Hematopoietic cells

-form the cords in bone marrow

-composed of developing blood cells

compartments of hematopoietic cells

-erythroblastic islands=red cells around a central macrophage

-white cells=in focal areas away from sinus

-megakaryocytes=adjacent to sinus

Blood vessels (vasculature) in bone marrow

Sinuses-large, thin walled veins lined with endothelial cells

Nutrient arteries

Stromal cells

-non hematopoietic cells

-adventitial reticular cells associated with a type of cell that produces fibers (fibroblasts)

-cytoplasm branches into the space occupied by hematopoietic cells (the cords)

Hematopoietic inductive microenvironment in stromal cells

provides the environment for the optimal growth orderly maturation and release of blood cells from the marrow

What are the 3 compartments of the bone marrow cords?

RBC, WBC, PLT

What do red cell precursors gather around

Macrophages

What cell is adjacent to the bone marrow sinus

stromal cells

Myeloid progenitor cell

(CFU-GEMM)

-granulocyte

-erythrocyte

-monocyte

-megakaryocyte

Lymphoid progenitor cells

(CFU-L)

- T-Lymphocyte

- B-Lymphocyte

- NK Cells

What changes during cell maturation

size

N:C ratio

What happens to cytoplasm during cell maturation

-less basophilic (due to loss of RNA)

-Granulocytes produce granules

-erythrocytes product hemoglobin

What happens to the nucleus during cell maturation

-becomes smaller

-chromatin condenses

-nuccleoli disappear

-granulocytes -> segmented

-erythrocytes -> nucleus is eccentric and then extruded

Erythropoietin (EPO)

-stimulates erythropoiesis (production of RBC)

-glycoprotein hormone

-made by kidney

-made in response to tissue hypoxia (initiates early release of reticulocytes and inhibition of cell death)

Order of Erythrocytic Developmental Series

Rubriblast

Prorubricyte

Rubricyte

Metarubricyte

Polychromatic erythrocyte

Erythrocyte

Rubriblast

Pronormoblast

Prorubricyte

Basophilic normoblast

Rubricyte

Polychromatophilic normoblast

metarubricyte

orthochromic normoblast

Pronormoblast

Rubriblast

-nucleus takes up most of the cell

-nucleoli present

-no granules

-basophilic

-Cell DOES divide

Basophilic normoblast

Prorubricyte

-nucleus is present

-nucleoli eventually disappear

-lacy texture

-BLUE

-size of cell decreased from first stage

-cell DOES divide

Polychromatic Normoblast

Rubricyte

-nucleus has checkerboard look

-cytoplasm is purple (stained Hgb)

-last stage cell DOES divide

Orthochromic Normoblast

Metarubricyte

-nucleus is pyknotic

-transcription for hemoglobin in nucleus

-the nucleus is not centered (eccentric location)

- cell does NOT divide

Polychromatic erythrocyte

-no nucleus

-vital (supravital)

-blue spotted when stained with new methane blue

-contain hemoglobin

-purplish red when stained with wright stain

Erythrocyte

-no nucleus

-fully matured

-cytoplasm red

Which erythrocyte precursor has a nucleus with a checkerboard apperance

Polychromatic normoblast (Rubricyte)

What is the last RBC precursor that has a nucleus

Orthochromic Normoblast (Metarubricyte)

What stain is used to identify reticulocytes

New methylene blue

What are 2 types of Asynchronous erythropoiesis

Megaloblastic

Iron Metabolism

Megaloblastic

-nuclear lags behind cytoplasmic maturation

-Vit B12 of folic acid deficiency

-oval macrocytes

-Ex: pernicious anemia

-larger than normal RBC

Iron Metabolism

-cytoplasmic maturation lags ehind nuclear maturation (inefficent hgb synthesis)

-deficiency of iron or inability to use iron

-microcytic, hypochromic RBCs (smaller than normal RBC)

-Ex: iron deficiency anemia

Leukopoiesis

production of white blood cells

Which cells result from extramedullary hematopoiesis

Lymphoid Cells

Which cells result from intramedullary hematopoiesis

Myeloid cells

What cells does not stay in the bone marrow to mature

T-cells. They travel to hematopoietic tissues to finished developing

Myelopoiesis

the formation of myeloid progenitor cells

Lymphopoiesis

the formation of lymphoid progenitor cells

What cytokines are required for the granulocyte lineage

IL-3

KL

GM-CSF

G-CSF

What cytokines are required for the monocyte lineage

IL-3

KL

GM-CSF

M-CSF

Cytokines involved in myeloidpoiesis

IL-3

KL

GM-CSF

G-CSF

M-CSF

Primary granules

nonspecific

azurophilic (stain different with different types of stains)

Secondary granules

-specific

- made during myelocyte stage

Neutrophil Maturation Series

Myeloblast

Promyelocyte

Myelocyte

Metamyelocyte

Band (no segmented form)

Segmented (polymorphonuclear neutrophil)

Myeloblast

-first cell of the neutrophilic series

-large cell (15 micrometers)

-High N:C ratio (4:1)

-round nucleus with light/loose chromatin

-1-2 nucleoli

-no cytoplasmic granules

-1% of BM nucleated cells

Promyelocyte

-high N:C ratio (3:1)

-chromatin still loose, but early signs of clumping

-contains large nonspecific (primary) cytoplasmic granules

-3-4% of BM nucleated cells

Myelocyte

-11.9% BM nucleated cells

-medium cell size

-round nucleus with darker blue heterochromatin

-first accumulation of secondary granules

-compromises 11.9% of bone marrow nucleated cells

Metamyelocyte

-18% of BM nucleated cells

-nucleus is kidney shaped

-condensed heterochromatin

-prominent golgi apparatus

-cytoplasm stains more pink due to the abundance of secondary granules

Band neutrophil

- ~11% of B< nucleated cells

-same size as mature neutrophil

-N:C ratio 1:2

-nucleus is band or sausage-shaped without segmentation

-granulation mainly secondary

-0-3% in peripheral blood

Segmented Neutrophil

- "segs, polymorphonuclear cells, PMS, polys"

- N:C ration 1:3

-nucleus 3-5 segments connected by narrow filaments

-50-70% pf peripheral WBCs

Hyposegmentation

<3 segments

hypersegmentation

>5 segments

Whats unique about lymphocytes

-not 'end' cells but resting mature cells until they're needed to do a different job

-recirculate from tissue to blood and back and forth

-capable of recombine gene segments

-some develop outside bone marrow (T-cells)

Antigen-independent maturation

location: marrow and thymus

antigen-dependent maturation

location: secondary lymphatic organs like the spleen, lymph nodes, tonsils, & aggregates like the Peyer patches in the intestinal wall

Where are immature B lymphs commonly seen

newborn smears

What percentage of circulating Lymph cells are T-cells

85%

Lymphocyte Marrow Maturation

Lymphoblast

Prolymphocyte

Lymphocyte

Lymphoblast

10-18 um

-scanty cytoplasm

-basophilic cytoplasm

Prolymphocyte

- Pre-B cells

-difficult to distinguish from previous stage

-slightly more clumped chromatin

-nucleolus less prominent

Lymphocyte

-dense chromatin

-3 different sizes

- B cell (plasma cell)

- T cell

What affects the size of the lymphocyte cell

-activity of the cell

-location in the smear

-small, medium, large

Terminal deoxynucleotidyl transferase (TdT)

-nuclear enzyme

-found in the earliest lymphoid cell

B cells

-cytoplasmic immunoglobulin (pre-B cells)

-surface immunoglobulin (mature B cells committed to specific antibody production)

Cluster of Differentiation: CD 19, CD 10, CD 20, CD 21, CD 22, CD 23, CD 24

T-cells

-cluster of differentiation (CD) 2 (pre T-cell)

-other clusters of differentiation associated with T-cells

CD 3, CD 4, CD 8

CD4

helper/inducer T cell

CD8

cytotoxice/suppressor T cell

Do Lymphoblast contain Auer rods

no and the nucleus is not indented

Do Myeloblast contain Auer rods

yes its possible

- "thumb print" (or indentation) of nucleus possible