the bone marrow, haematopoiesis (blood formtion) and blood
TRANSCRIPT
The bone marrow,
haematopoiesis (blood
formtion) and blood
Ivan Varga,
2020, March 13
On-line documents for histology
lectures: introductory notesDear students,
until now, it hasn´t been our custom to publish any of histology lectures in freely accessible
on-line form on the website of our faculty and there has been a good reason for that. The
most important elements of each one of the histology lectures are high quality schematic
pictures, drawings and photomicrographs. The source of these didactic materials is
commonly some internationally acceted textbooks, however, any further spread of these
materials to wider public requires a consent from the publisher/copyright owner. Therefore,
the lecture you will obtain is a version with significantly reduced number of figures. The only
graphic materials I have been able to use come from a textbook which I co-authored, so I
have the "copyright" to share them. Only other option has been to use free-access
documents from the web. It is important to point out that any figure without proper
commentary loses its educational value, so for the purpose of your self-study, I must refer to
other textbooks we have written for you. Please feel free to contant me via an e-mail if you
have any other queries. I hope, that the epidemiological situation will allow us to continue the
in-person education as soon as possible, so we can get back to "classic" lectures followed
by discussion, which represent the highest form of teaching and manifestation of creativity
within the university education.
With best personal wishes, prof. RNDr. Ivan Varga, PhD. [email protected]
www.fmed.uniba.sk/en/science/
Is the hematopoiesis important
during the whole life?
Blood cells have relativelly short lifespan
Erythrocytes – 120 days
Thrombocytes – 10 - 12 days
Leukocytes – only few days in the
blodstream, migrate to the connective tissue
Which organ is responsible for
hematopoiesis?
It´s depend on the period of development
Yolk sac - embryo
Liver and spleen - fetus
Bone marrow
Yolk sac
Blood
A special type of connective tissue (develops from embryological mesenchyme)
The volume of blood in healthy adult human is about 4.5 – 6 liters
Is composed of blood cells suspended in a fluid matrix called plasma
Blood cells / elements: Red blood cells (erythrocytes)
White blood cells (leukocytes)
Platelets (thrombocytes)
Blood cells
leukocytes
erythrocytes
platelets
artery
Functions
Transport of oxygen, carbon dioxide, nutrients
and hormones
Maintance of acid-base balance
Removal of waste products of cell metabolism
Temperature control of the body
Defense against infection (immune function)
Blood plasma
yellowish fluid in which blood elements are
suspended,
components :
water – 90%
inorganic salts – 3%
organic – proteins (albumins, globulins,
fibrinogen) – 7%
after coagulation (some components leave
plasma) called serum
Histological examination of blood
Prepare a blood film by drawing out a
small drop of blood into a thin film
Pappenheim method for staining is
commonly used
The stains are applied to a
thin dried and fixed
film of blood on a
glass slide
Blood smearThrombocyte
Erythrocyte
Neutrophil
granulocyte
Lymphocyte
Eosinophil granulocyte
Balko J, Tonar Z, Varga I. Memorix Histology. Prague: Triton 2018
Blood cell production
(hematopoiesis)
Blood elements are highly specialized
corpuscles („cells“) and can not divide
Most of them have relatively short life span
Are formed in a special type of connective
tissue called bone marrow
Bone marrow
Hematopoietic tissue is derived from mesenchyme
In adults, the red bone marrow is located in flat bones (skull, ribs, sternum, pelvis, vertebrae) and ends of long bones
Yellow bone marrow characteristic for adult long bones does not form blood but it stores fat
Bone marrow
Medulla ossium rubra - red
Medulla ossium flava - yellow
Cellulae haemopoieticae
precursoriae – hematopoietic
stem cells
Balko J, Tonar Z, Varga I. Memorix Histology. Prague: Triton 2018
Bone marrow, 20xBalko J, Tonar Z, Varga I. Memorix Histology. Prague: Triton 2018
Structure of the bone marrow
Stroma – network of reticular cells and reticular
fibers (reticular connective tissue)
Adipocytes, macrophages and fibroblasts are
also seen
Sinusoids are wide, numerous, fenestrated
blood capillaries
Haematopoietic stem cells and all stages in
maturation of blood elements
Pluripotential haematopoietic stem cells
Undifferentiated cells („stem cells“), they
can give rise to ALL the different types of
specialized blood elements
Differentiated to form progenitor cells in
two different ways:
Multipotential lymphoid stem cells
Multipotential myeloid stem cells
Regulation of hematopoiesis
Erythropoietin – cortex of the kidney
Thrombopoietin (megakaryocyte growth and
development factor) – liver, kidney
Cytokines (protein signaling molecules) and
growth factors – stromal cells of bone marrow
Balko J, Tonar Z, Varga I. Memorix Histology. Prague: Triton 2018
Bone marrow examination
Bone marrow samples can be obtained by
aspiration and trephine biopsy
Are usually performed on the back of the
hipbone, or posterior iliac crest
Bone marrow examination
is used in the diagnosis of a
number of conditions,
including leukemia,
multiple myeloma, lymphoma,
anemia
Cellularity of the bone marrow
Is the one of the most important factors in
evaluating the function of bone marrow
The ratio of hematopoietic cells to adipocytes
Normocellular bone marrow 50% : 50%
Hypocellular bone marrow – small number of
blood forming cells ca be found (after
chemotherapy, aplastic anemia, ...)
Hypercellular bone marrow – tumors originating
from hematopoietic cells
Red blood cells
Average number is about 5milion per cubic
mililiter in males, 4.5 milion per cubic mililiter in
females
Diameter 7.5 mikrometers = normocyte
Biconcave disc-shape (very large surface area,
ideal for exchange of gases)
Soft and elastic – can change its shape as it
passes through small capillaries
erythrocytes
eosinophil
Red blood cells
Without nucleus and organells
Only hemoglobin in cytoplasm
Function: transport oxygen from lungs to the
tissues, and carbon dioxide from the tissues to
the lungs
Hemoglobin + oxygen = oxyhemoglobin
Hemoglobin + CO2 = karbaminohemoglobin
BASOPHILIC
ERYTHROBLAST
POLYCHROMATIC
ERYTHROBLAST
ACIDOPHILIC
(ORTOCHROMATIC)
ERSTHROBLAST
RETIKULOCYTE
ERYTHROCYTE
(NORMOCYTE)
Basophilia
(number of ribosomes)
Eosinophilia
(content of hemoglobin)
Development
of erythrocytes
Erythroblastic isletBasophilic erythroblast Macrophage
Acidophilic erythroblast
Polychromatic erythroblast
Reticulocyte
Erythroblast´s cell nucleus after enucleation
Enucleation of erythroblast
Acidophilic
erythroblast
Balko J, Tonar Z, Varga I. Memorix Histology. Prague: Triton 2018
Physiological polycythemia
Any significant increase in the number of
red blood cells is called polycythemia
This occurs in persons living at high
altitudes, where oxygen concentration is
low
Excessive production of red blodd cells
by the bone marrow
Clinical notes
Anemia – significant decrease in blood
concentration of hemoglobin
Hemorrhagic anemia – it is due to loss of
blood (hemorrhage)
Aplastic anemia – due to damage to the red
bone marrow
Pernicious anemia – failure of absortion of
vitamin B12 (is essential for haematopoiesis)
Hemolytic anemia –abnormal shape of Ery,
they are very fragile, their lifespan is short
LEUKOCYTES –
white blood cells
Leukocytes – white blood cells
Are colorless because they contain no
hemoglobin
Each cell has a nucleus
In general, they protect the body in a number of
ways against infectious organisms
Perform their main functions outside the blood
stream after they have entered loose connective
tissue
Classification of leukocytes
According to the type of cytoplasmic
granules and the shape of nuclei
leukocytes are classified into:
Granular leukocytes – they contain specific
granules and lobulated nuclei
Nongranular (agranular) leukocytes – they do
not contain specific granules with non-
lobulated nuclei
Leukocytes – are classified into:
I. Granulocytes
Neutrophils
Eosinophils
Basophils
II. Agranulocytes
Lymphocytes
Monocytes
I. Neutrophils 60 - 70% of total leukocyte population
Ø 10 - 12 µm
multilobed nucleus – the lobes are connected to each other by slender chromatin threads
the number of lobes increase with the age of the cell
in females – the nucleus present a characteristic small appendage – inactive second X chromosome (Barr body)
Neutrophils
The majority of leukocytes are neutrophils
(60 – 70% of total Leu population)
The nucleus is multilobulated (so they are
termed polymorphs)
the lobes are connected to each other by slender chromatin threads
the number of lobes increase with the age of the cell
Function of neutrophils
The first line of defense agains invading
microorganisms, especially bacteria
The bacteria are rapidly phagocytosed and
destroyed
Barr body
Young
neutrophil
neutrophil
Eosinophils
Constitute 1 – 5% of total leukocytes
Measure 10 – 14 mikrometers
The nucleus has only two lobes
The cytoplasm contains large specific
granules which stain pink with eosin
Eosinophils
At EM level – characteristic specific
granules with crystalloid electron dense
cores (aminoacid arginine)
These granules contain lysosomal
enzymes
Clinical notes - eosinophilia
Eosinophils are involved in antiparasitic
responses – they are able to kill larval
stages of parasitic worms
Eosinophils are found during allergic
reactions to phagocytose any antigen-
antibody complexes
Eosinophils – antiparasitic response
Ascaris lumbricoides
Basophils
fewer than 1% of total leukocyte population
Ø 8 – 10 µm
S-shaped nucleus, which is frequently masked by
the large specific granules present in the cytoplasm
specific granules stains dark blue to black
the granules contain heparin and histamine
Effect of histamine are:
Increase permeability of the capillaries
(causing oedema and decrease blood
pressure)
Contraction of the smooth muscle of the
bronci (causing respiratory distress)
Increase pancreatic secretrion
Attraction of eosinophils
II. Lymphocytes
make up 20 – 30 % of total leukocyte
population
Ø 6 – 8 µm (small), 10-12 µm (medium),
12-18 µm (large)
dense nucleus with a lot of
heterochromatin
cytoplasm stains light blue
Lymphocytes
in blood can be subdivided :
80% T-cells, cell mediated immunity
15% B-cells → differentiated into
plasma cells → produce antiboodies
(Ig), humoral immunity
5% null cells
Monocytes
make up 3 – 8% of total leukocyte population
the largest - Ø 12 – 20 µm
large, acentric, kidney-shape nucleus
dark, basophilic cytoplasm
from blood they migrate throught vessels into
the connective tissue, where they diferentiate
into macrophages
monocyte
Macrophage Development and
Distribution
System of phagocytic cells – mononuclear
phagocyte cells
Arise from common stem cell in the bone
marrow, precursors are monocytes
posses lysosomes,
are capable of phagocytosis
Stem cell in monocytes from macrophages in tissues
bone marrow bloodstream or organs
Connective tissue proper – macrophages
Liver – Kupffer cells
Lungs – dust cells (alveolar macrophages)
Kidney – mezangial cells
Thymus, spleen, lymphnode– different macrophages
Nervous tissue, brain – microglia
Bone – osteoclasts
Skin – Langerhans cells
Mononuclear phagocyte cells
Platelets (thromboplastids)
Small, non-nucleated cell fragments
derived from megakaryocytes in the bone
marrow
Disk-shaped
Ø 2-4 μm
lifespan of less than 14 days
MEGAKARYOCYTE
platelets
Summary of blood elements function
Erythrocytes Hemoglobin Transport O2 and CO2
Neutrophils Neutrophil granules Destroy the
microorganisms by
fagocytosis
Eosinophils Eosinophil granules Allergy, agains
parasites
Basophils Basophil granules
Heparin and histamine
Anticoagulation effect
Lymphocytes Immunoglobulins
(antibodies)
Interaction of
antibodies with
antigens
Monocytes Lysosomes with
enzymes
Destroy the
microorganisms by
fagocytosis
Platelets Coagulation factors Blod coagulation
