the bone marrow, haematopoiesis (blood formtion) and blood

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. ivan.varga@fmed.uniba.sk

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

Thank you for your attention!

ivan.varga@fmed.uniba.sk