Haematology 1.

Introduction to Haematopoiesis
C. Riedinger

Chapter 1

Introduction to Haematopoiesis

Haematology 1. Introduction to Haematopoiesis

C. Riedinger

Table of Contents
Chapter 1......................................................................................................................0
Introduction to Haematopoiesis...................................................................................0
Table of Contents........................................................................................................1
1. Introduction to Haematology...............................................................................2

a)
b)

1.1. Bone Marrow Function [1], [2].........................................................................2

1.2. Haematopoiesis [2], [1].....................................................................................2
1.3. Control of Haematopoiesis................................................................................3
1.4. Histological Features of the Bone Marrow........................................................3
1.4.1. Investigations of the Bone Marrow...........................................................3
1.4.2. Normal Bone Marrow...............................................................................3
1.4.3. Bone Marrow Aplasia................................................................................4
1.4.4. Bone Marrow Infiltration..........................................................................5
1.4.5. Bone Marrow Hyperplasia........................................................................5
MYELOPROLIFERATIVE DISORDERS (~CYTHAEMIA!)...................................5
MYELODYSPLASIA (~CYTOPENIAS!)..............................................................6

Bibliography................................................................................................................7

Haematology 1. Introduction to Haematopoiesis

C. Riedinger

1. Introduction to Haematology
1.1.

Bone Marrow Function [1], [2]

4% of adult body mass

main functions: haematopoiesis, 1* lymphoid organ, bone formation and

maintenance

consists of 2 types of tissue:

o red marrow => haematopoietic tissue (cells of myelopoiesis and
erythropoiesis) + supportive stromal tissue (incl. osteoblasts and
osteoclasts)
o yellow marrow => fat cells

in adults haematopoietic tissue in central skeleton and proximal long bones

(=half of marrow), extramedullary haematopoiesis in liver and spleen if marrow
dysfunction or excessive demand for blood cells

in children all bones!

in fetus initially haematopoiesis by yolk sac (since week3), later liver (3m) and
spleen

1.2.
-

Haematopoiesis [2], [1]

formation of the cellular components of the blood from HCSs involving

proliferation, differentiation and apoptosis

from common progenitor cell: pluripotent haematopoietic stem cell HSC

produces two main multipotent progenitor cells:

o common lymphoid progenitor cells
o myeloid progenitor cells

common lymphoid progenitor: B, T and NK precursors and cells

common myeloid progenitors: different commited precursors forming colony

forming

units,

differentiating

into

precursors:
o myeloblasts => myelocytes
o proerythroblasts => erythrocytes

morphologically

recognisable

late

Haematology 1. Introduction to Haematopoiesis

C. Riedinger

o megakaryoblasts => *cytes => thrombocytes

-

properties of HSCs
o not sessile!
o can be mobilised, e.g. under stress
o Can reach the liver and spleen to perform extramedullary haematopoiesis
o can harvest from blood for transplantation!

> a million RBCs + a few white cells and platelets produced per second!

capacity adjusted to demand

1.3.
-

Control of Haematopoiesis

short term: haematopoietic growth factors

o stem cell factor / c-KIT ligand => early commited progenitors
o erythropoietin EP, GM-CSF, G-CSF (G=granulocyte), thrombopoietin =>
commited progenitors

Growth factors:
o glycoproteins
o produced by stromal cells, T cells, liver and kidney

Erythropoietin:
o produced mainly by peritubular fibroblasts in the kidney
o in response to decrease oxygen, hypoxia increases production
o signals via JAK 2 => transcription, avoids apopotosis
o controls amount of RBCs produced

1.4.
1.4.1.
-

Histological Features of the Bone Marrow

Investigations of the Bone Marrow

marrow aspirate + smear, by microscopy and immunochemistry with lineage

specific antibodies and markers

bone marrow biopsy, shows architecture

1.4.2.

Normal Bone Marrow

o network of thin-walled sinusoids with endothelium, BM and adventitial cells

Haematology 1. Introduction to Haematopoiesis

C. Riedinger

o interstitium of haematopoietic and fat cells

pathological features:
o distorted architecture (cancer of granulomatous disease) => release of
immature precursors into peripheral blood = leukoerythroblastosis
o hypoblastic more fat!
o Hyperplastic less fat!
o infiltration/granulomatous disease: fibrosis

1.4.3.

Bone Marrow Aplasia

markedly hypocellular bone marrow

devoid of haematopoietic cells

often only fat cells and fibrous stroma

scattered lymphocytes and plasma cells remain

dry tap, i.e. marrow aspirate with little material => best detected on biopsy

QuickTime and a
decompressor
are needed to see this picture.

Haematology 1. Introduction to Haematopoiesis

C. Riedinger

causes:
o can be congenital
o acquired causes: drugs, radiotherapy, radiation, autoimmune conditions,
post viral infection

1.4.4.
-

Bone Marrow Infiltration

tumours that cause bone mets: (not necessarily the same??)

o breast carcinoma
o lung carcinoma
o kidney carcinoma
o thyroid carcinoma
o prostate carcinoma
o neuroblastoma in childhood

tumours that cause bone marrow infiltration:

o multiple myeloma with bone marrow involvement
o chronic leukaemias

osteolytic or osteosclerotic lesions

may induce extramedullary haematopoiesis

http://medtextfree.wordpress.com/2011/12/27/chapter-40-anemia-associatedwith-marrow-infiltration/

1.4.5.
a)
-

Bone Marrow Hyperplasia

MYELOPROLIFERATIVE DISORDERS

(~CYTHAEMIA!)

Chronic diseases caused by clonal proliferation of bone marrow stem cells

leading to excess production of one or more haemaopoietic lineages
o Polycythaemia rubra vera
o Essential thrombocythaemia
o Myelofibrosis

replacement of haematopoietic marrow by progressive fibrosis

compensated by extramedullary haematopoiesis

may all transform to ALL

Haematology 1. Introduction to Haematopoiesis

C. Riedinger
-

JAK2 mutation

Distinguish 1* from reactive!

b)
-

MYELODYSPLASIA

(~CYTOPENIAS!)

Clonal haemopoietic stem cell disorder characterised by peripheral blood

cytopenias usually affecting >1 lineage, usually in association with
hypercellular marrow, indicating ineffective haematopoiesis

Bone marrow usually hypercellular but can also be hypocellular/fibrotic

Clonal proliferation: myeloproliferative and myelodysplastic disorders,

probably also myeloma and ALL

Reactive proliferation: refers to increased demand of cells or bone marrow

destruction leading to the requirement of extramedullary haematopoiesis? How
about the effects of increased erythropoietin at high altitude?

Haematology 1. Introduction to Haematopoiesis

C. Riedinger

Bibliography