Lecture 2

renewal, proliferation, differentiation, and maturation of all blood cell lines

formation, development, and specialization of all functional blood cells that are released from bone marrow into circulation

1. mesoblastic
2. hepatic
3. medullary

yolk sac and AGM

aorta-gonad-mesonephros

liver and spleen

bone marrow

9th day after fertilization

cells from mesoderm migrate to yolk sac to make primitive erythroblasts

intravascular

embryonic hemoglobins:
Gower I, Gower II, Portland

begins at 5-7 gestational weeks

extravascular

liver

recognizable clusters of developing erythroblasts, granulocytes, and monocytes

mainly HbF, small amt of HbA development
(HbF = fetal hemoglobin)

3rd month of fetal development

thymus (t cells), spleen and kidney (b cells)

begins between the 4th and 5th month of fetal development

HSC and mesenchymal cells migrate to core of bone,
mesenchymal produce stromal cells
myeloid development is apparent
by wk 24, BM is primary hematopoietic site

mesenchymal cells produce stromal cells that support developing hematopoietic cells

(M:E) of 3:1 to 4:1 (normal adult levels)

HbF and HbA

Erythropoietin (EPO)
granulocyte colony-stimulating factor (G-CSF)
granulocyte-mq colony stimulating factor (GM-CSF)

bone marrow
lymph nodes
spleen, liver
thymus

erythroid, myeloid, megakaryocytic, and lymphoid cells develop in the BM

primary lymphoid organ
secondary lymphoid organ

BM for T cells and B cells,
thymus for T cell development

spleen
lymph nodes,
mucosa-associated lymphoid tissue (MALT)

trabecular radiate out from the cortex into central cavity forming honeycomb structure

haematopoietically active marrow

all bones

adipocytes increase in number
(adding yellow marrow to what was previously all red)

haematopoietically Inactive marrow
mostly fat cells or adipocytes

ratio of red to yellow marrow will decrease with age

hypOcellular

hypErcellular

erythrocytes
megakaryocytes
granulocytes

produce platelets

help body fight bacterial infections

hematopoietic microenvironment

megakaryocytes

erythroblastic island surrounding the mq

mq produces iron to make Hb

close to sinusoid bc it's a parent cell that produces platelets rupture and releases platelet to sinuses

farther away → more mature
close → less mature

3.4-5.9% body weight
1600-3700 g
30-50mL/KBW

all bones

fat replaces red in long bones
(yellow is hematopoietically INactive)

only flat bones (skull, vertebrae, pelvic, sternum) will be haematopoietically active

Posterior iliac crest (spine of pelvis)
Anterior superior iliac crest (spine of the pelvis)
sternum

cytologic typing / flow cytometry

hematopoietic cell proportions (M:E)

Cellularity (hypo / hypercellular)
certain disease state

low power examination
high power examination (ID cells)

Prussian blue iron stain examination

cellularity and cell density

BM aspirate or imprint examination (?)

pt history, CBC
cellularity, megakaryocytes, maturation, addt'l hematologic cells
stromal cells
differential count
M:E, iron stores, diagnosis

eosinophils, basophils, mast cells, lymphocytes, monocytes, and histocytes

# and morphology of osteoblasts, osteoclasts, trabeculae, fibroblasts, adipocytes, and endothelial cells
appearance of sinuses;
presence of amyloid, granulomas, fibrosis, necrosis

ID of iron deficiency, iron overload

diagnosis of leukemias / lymphomas
-genetic : acute leukemias via deletions, translations, polysomy; remission studies

PCR for diagnostic pt mutations, minimal residual disease studies

staining for diagnostic mutations;
minimal residual disease studies

immunophenotyping, usually of malignant hematopoietic cells, clonality;
minimal residual disease study

major site of hematopoiesis during 2nd trimester of fetal development

2 lobes beneath diaphragm of abdomen cavity;
optimal for gathering, xferring, and eliminating substances thru bile duct

Kupffer cells (mq)
endothelial cells

remove senescent cells and foreign debris
(destroy cell debris and engulf sick RBCs)

line the sinusoids of liver

porphyrias, hemolytic anemias,
extramedullary hematopoiesis, storage diseases
hepatitis, cirrhosis

indiscriminate filter of circulating blood

largest lymphoid organ lies beneath diaphragm, behind the fundus of the stomach in upper L quadrant of abdomen;
surrounded by peritoneum

white pulp
red pulp
marginal zone

follicles containing lymphocytes, mq, dendritic cells,
germinal centers (B cells), T cells in periarteriolar lymphatic sheath (PALS)

cords of Billroth, splenic mq, culling and pitting functions

loosely connected mq, creating a sponge-like matrix that acts as a filter; increase dmg and stress of RBCs to remove abnormal RBCs

cells are phagocytized with subsequent degradation of cell organelles

splenic mq remove inclusions or damaged surface membrane from circulating RBCs

surrounds the white pulp
memory B cells, mq, CD4+ T cells

microvascular
environment
splenomegaly

spleen becomes enlarged

Hereditary spherocytosis (HS)
ITP (immune thrombocytopenic purpura)
AIHA (autoimmune hemolytic anemia)

autosplenectomy (?)

when there is excessive destruction of RBcs and corticosteroids cannot suppress hemolysis

storage disorder resulting in cytopenias

Repeated infarcts caused by sickled RBCs trapped in small-vessel circulation of spleen causing tissue dmg and necrosis

Filters lymph, running in parallel with blood circulation

bean shaped structure with outer cortex and inner medulla

adenitis
malignant tumors
lymphoma vs lymphocytic leukemia

infection of inflammation of lymph node

lymphoma - involve lymph node
lymphocytic leukemia - bone marrow / stem cell

primary lymphoid organ for cell development
produces T cells
pre T cells migrate to thymus to develop into CD4+ / CD8

2 lobes further divided into lobules
located at the anterior mediastinum;
subdivided into cortex and medulla

T lymphocytes
other cells

nondevelopment → lack of T cells
failure to thrive, infections, death in infants
adults not affected bc they developed T cells for life

capable of self renewal
pluripotent
able to reconstitute hematopoietic system of a lethally irradiated host

undifferentiated hematopoietic stem cell (HSC)
differentiated (committed) progenitor cell

CMP (CFU-GEMM) or CLP

colony forming unit--granulocyte, erythrocyte, monocyte, megakaryocyte

Unipotential and bipotential

CFU-E, CFU-M, CFU-G, CFU-Eo, CFU-Baso, CFU-Meg, CFU-PreB, CFU-PreT

CFU-GM

not morphologically recognizable

monophyletic
polyphyletic

one stem cell that can produce all blood cells

each cell type has its own stem cell

long term self renewing stem cell → short term → pluripotent hematopoietic stem cell

becomes common myeloid progenitor (CMP) or
common lymphoid progenitor (CLP)

neutrophils, monocytes, mq, eosinophil, basophil, mast cell, erythrocytes, platelets

B cell / T cell, plasma cell

granulocyte-monocyte progenitor
eosinophil basophil progenitor
megakaryocyte-erythrocyte progenitor
mast cell

myeloblast and monoblast

myeloblast (2)

pronormoblast and megakaryoblast

neutrophil

monocyte → mq

eosinophil or basophil

erythrocyte

megakaryocyte → platelets

dendritic cell
Pre-B
Pre-T
natural killer cell

B lymphoblast → B cell → plasma cell

T lymphoblast → T cell

positive and negative influence

TGFB, TNF-a, interferons

IL-3, IL-5

IL-7

in early stage progenitors

KITLG, FTL3L, GM-CSF, Il-1, IL-3, IL6, IL-11