Hematopoiesis

hemapoiesis

hematopoiesis is also known as

blood cell formation

define hematopoiesis

CD 34

classical marker of hematopiesis

19th day of embryonic development after fertilization

hematopoiesis is considered to start around

1. polyphyletic theory

2. monophyletic theory

2 related theories (origin of hematopoietic progenitor cells)

polyphyletic theory

each blood cell linages is derived from own unique stem cell

monophyletic theory

all blood cells are derived from a singe progenitor stem cell—pluripotential stem cell

monophyletic theory

most widely accepted theory among experimental hematologists

1. mesoblastic / megaloblastic

2. hepatic

3. intramedullary / medullary / myeloid

3 phases of of hematopoiesis

yolk sac

chief site of mesoblastic / megaloblastic hematopoiesis

fetal liver w/ spleen, thymus, lymph nodes

chief site of hepatic hematopoiesis

bone marrow

chief site of intramedullary / medullary / myeloid hematopoiesis

primitive erythroblasts

1st blood cells developed in mesoblastic / megaloblastic hematopoiesis

first 2-8 weeks of life

when are the 1st blood cells developed in mesoblastic / megaloblastic hematopoiesis

• Gower-1

• Gower-2

• Portland

primitive erythroblasts are important in early embryogenesis of producing embryonic hemoglobin—necessary for delivery of oxygen to embryonic tissues

it occurs intravascularly (within developing blood vessels)

how does yolk sac hematopoiesis differs from fetal and adult stage hematopoiesis?

Hemoglobin F (fetal hemoglobin)

predominant hemoglobin during the hepatic phase

thymus

first fully developed organ in the fetus

thymus

major site of T cell production

increases

size of the thymus ____ during fetal development

kidneys, spleen

produce B cells

before the 5th month of fetal development

when does hematopoiesis starts in the bone marrow

by the end of 24 weeks gestation

when does the bone marrow becomes the chief sites of hematopoiesis

• lymph nodes — lymphocytes

• spleen — lymphocytes

• thymus — lymphocytes

• liver — only in certain diseases, healthy / normal liver should not make blood cells

hematopoietic tissues of adults are located NOT ONLY in the bone marrow

bone marrow

in adult hematopoiesis, it contains developing erythroid, myeloid, lymphoid, and megakaryocytic cells

bone marrow

considered to be a primary lymphoid organ w/ functions equivalent to that of Bursa of Fabricius (birds)

• RBCs — 2.5 billion

• granulocytes — 1 billion

• platelets — 2.5 billion

bone marrow is estimated to be capable of generating how much blood cells per kilogram of body weight DAILY

retrogression

process of replacing red (active) marrow → yellow marrow (adipose tissue)

5-7 years of age

between what age do adipocytes become more abundant → start to occupy the spaces in the long bones previously dominated by active marrow

RSVP

• ribs

• sternum, skull, shoulder blade

• vertebrae

• pelvis, proximal ends of long bones

in retrogression, red marrow in the adult is restricted to

healthy / normal

red marrow = yellow marrow

equal amounts

• red marrow: 50%

• yellow marrow: 50%

in normal / healthy adults, what is the amount of red and yellow marrow

certain disease

red marrow > yellow marrow

increased demand (e.g., excessive blood loss and hemolysis)

yellow marrow → reverts back to active marrow in what cases

red marrow

hematopoietically active marrow (mainly fat cells / adipocytes) → can create blood cells

yellow marrow

hematopoietically inactive marrow → cannot create blood cells

• primary lymphoid organs

• secondary (peripheral) lymphoid organs

lymphoid development occurs in

• bone marrow — B lymphocytes

• thymus — T lymphocytes

primary lymphoid organs

atrophy

thymus’ size increases during fetal development until puberty → undergo ____ with aging

bone marrow

lymphoid cells fated to become B cells undergo their early stages of differentiation where

• spleen

• lymph nodes

major secondary / peripheral lymphoid organs

• tonsils

• appendix

• Peyer’s patches

• MALT (mucosa associated lymphoid tissue)

minor secondary / peripheral lymphoid organs

spleen

largest secondary lymphoid organ

• trapping and concentration of foreign substances

• antibody production & induction of antigen-specific T lymphocytes

2 major functions of secondary / peripheral lymphoid organs

induction of antigen-specific T lymphocytes

the process where naive T cells are activated and transformed into specialized effector or memory cells after recognizing a specific target peptide

spleen

major organ → synthesize and release antibody in the circulation

lymph nodes

small, ovoid, bean-shaped structures (normally <1 cm diameter) found in different areas throughout the body

lymphoma

cancer / solid tumor neoplasm of lymphoid tissue

splenectomy

removal of spleen

increased incidence of bacterial sepsis caused primarily by:

• SMH

  • Streptococcus pneumoniae

  • Neisseria meningitidis

  • Haemophilus influenzae

splenectomy has more adverse effects in children → often leads to

splenomegaly

enlargement of spleen

tonsils

to detect and respond to antigens in the respiratory and alimentary secretions

Peyer’s patches

clusters of lymphocytes distributed in the lining of the small intestine—detect substances that diffuse across the intestinal epithelium

mucosal-associated lymphoid tissue

general term for the unencapsulated lymphoid tissues present in regions underlying the mucosal areas

infectious agents or in pathologic myelofibrosis of the bone marrow

liver can maintain hematopoietic stem cells and progenitor cells to generate various blood cells as a response to

posterior and anterior superior iliac crest

preferred areas for blood marrow aspiration in adults

anterior medial surface of the tibia

preferred areas for bone marrow aspiration in children <2 y/o

• posterior & anterior superior iliac crest — adults

• sternum

• anterior medial surface of the tibia — children <2 y/o

• spinous process of the vertebrae, ribs, other red-marrow containing bones

bone marrow collection sites

• recommended: ≥500 cells

• preferrably: 1000 cells

  • 500 cells on each of 2 slides

marrow differential preferred number of cells to be counted

myeloid-to-erythroid ratio

M:E ratio stands for

bone marrow aspirate

disturbs bone marrow architecture → used only for analysis of individual cell morphology

10 years

bone marrow smears retention

bone marrow aspirate

bone marrow sample that is spread as a smear on a slide, stained, and examined for hematologic or systemic disease

bone marrow biopsy

bone marrow removed intact without disturbing the bone architecture → analysis of bone marrow architecture

bone marrow biopsy

a cylinder of gelatinous red marrow → fixed in formalin, sectioned, stained

bone marrow biopsy

gives a better picture of the real structure of bone marrow

extramedullary hematopoiesis

blood cell production outside of the bone marrow

liver and spleen

extramedullary hematopoiesis occurs mainly in

hepatomegaly and splenomegaly

extramedullar hematopoiesis is accompanied but what organ manifestations

when it creates other blood cells other than lymphocytes

spleen is part of normal hematopoiesis, but when does it produce extramedullary or abnormally

• bone marrow becomes dysfunctional

  • aplastic anemia

  • infiltration by malignant cells

  • overproliferation of a cell line (leukemia)

• bone marrow incapable of meeting demands

  • hemolytic anemias

when does extramedullary hematopoiesis take place

M:E ratio

proportion of myeloid cells to nucleated erythroid precursors in the bone marrow aspiratem

• monocytic and lymphoid precursors

• plasma cells

excluded from myeloid cell count — because the ratio specifically intends to compare granulocytic cells (and sometimes monocytic cells) against nucleated red blood cell precursors to measure active turnover of blood-producing cells

1.5:1 to 3.3:1

M:E ratio in a healthy adult

10:1

M:E ratio in leukemia