Bone_marrow_and_blood_2020.pdf bone marrow ppt

Bone marrow

1. Thebone marrow,
haematopoiesis(blood
formtion) and blood
Ivan Varga,
2020, March13

2. On-line documents for histology
lectures: introductory notes
Dear 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, anyfurther spread ofthese
materials to wider public requires aconsent from the publisher/copyright owner. Therefore,
the lecture you will obtain is a version with significantly reduced number of figures. The only
graphic materialsI have been able to use comefrom 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 theepidemiological situation will allow usto 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 andmanifestation of creativity
within the university education.
With best personal wishes, prof. RNDr. Ivan Varga, PhD. [email protected]
www.fmed.uniba.sk/en/science/

3. 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

4. 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

5. 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)

6. Blood cells
leukocytes
erythrocytes
platelets
artery

7. 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)

8. 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

9. 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

10. Blood smear
Thrombocyte
Erythrocyte
Neutrophil
granulocyte
Lymphocyte
Eosinophil granulocyte
Balko J, TonarZ, Varga I. MemorixHistology. Prague: Triton2018

12. 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

13. Bone marrow
Hematopoietic tissue is derived from
mesenchyme
In adults, the red bone marrowis located
in flat bones (skull, ribs, sternum, pelvis,
vertebrae) and ends of long bones
Yellow bone marrowcharacteristic for
adult long bones does not form blood but it
stores fat

14. Bone marrow
Medulla ossium rubra-red
Medulla ossium flava-yellow
Cellulae haemopoieticae
precursoriae–hematopoietic
stem cells
Balko J, TonarZ, Varga I. MemorixHistology. Prague: Triton2018

16. Bone marrow, 20x
Balko J, TonarZ, Varga I. MemorixHistology. Prague: Triton2018

17. 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

18. 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

21. Regulation of hematopoiesis
Erythropoietin–cortexof thekidney
Thrombopoietin(megakaryocyte growth and
development factor)–liver, kidney
Cytokines(proteinsignalingmolecules) and
growthfactors–stromalcellsof bone marrow
Balko J, TonarZ, Varga I. MemorixHistology. Prague: Triton2018

22. Bone marrow examination
Bone marrow samples can be obtained by
aspirationand 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

24. 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 marrow50% : 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

25. 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

26. erythrocytes
eosinophil

28. 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

29. BASOPHILIC
ERYTHROBLAST
POLYCHROMATIC
ERYTHROBLAST
ACIDOPHILIC
(ORTOCHROMATIC)
ERSTHROBLAST
RETIKULOCYTE
ERYTHROCYTE
(NORMOCYTE)
Basophilia
(number of ribosomes)
Eosinophilia
(content of hemoglobin)
Development
of erythrocytes

30. Erythroblasticislet
Basophilic erythroblast Macrophage
Acidophilic erythroblast
Polychromatic erythroblast
Reticulocyte
Erythroblast´s cell nucleus after enucleation

31. Enucleation of erythroblast
Acidophilic
erythroblast
Balko J, TonarZ, Varga I. MemorixHistology. Prague: Triton2018

32. 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

33. 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

34. LEUKOCYTES –
white blood cells

35. 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

36. Classification of leukocytes
Accordingto thetype of cytoplasmic
granulesand theshapeof nuclei
leukocytesare classifiedinto:
Granularleukocytes–theycontainspecific
granulesand lobulatednuclei
Nongranular(agranular) leukocytes–theydo
notcontainspecificgranuleswithnon-
lobulatednuclei

37. Leukocytes –are classified into:
I. Granulocytes
Neutrophils
Eosinophils
Basophils
II. Agranulocytes
Lymphocytes
Monocytes

38. I. Neutrophils
60 -70% of total leukocyte population
Ø10 -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)

39. 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

41. Function of neutrophils
The first line of defense agains invading
microorganisms, especially bacteria
The bacteria are rapidly phagocytosed and
destroyed

42. Barr body

43. Young
neutrophil
neutrophil

44. 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

45. Eosinophils
At EM level –characteristic specific
granules with crystalloid electron dense
cores (aminoacid arginine)
These granules contain lysosomal
enzymes

48. 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

49. Eosinophils –antiparasitic response
Ascaris lumbricoides

50. Basophils
fewerthan1% of totalleukocyte population
Ø8 –10 µm
S-shapednucleus, whichisfrequentlymaskedby
thelargespecificgranulespresentin thecytoplasm
specificgranulesstainsdarkblueto black
thegranulescontainheparinand histamine

51. 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

54. II. Lymphocytes
make up 20 –30 % of total leukocyte
population
Ø6 –8 µm (small), 10-12 µm (medium),
12-18 µm (large)
dense nucleus with a lot of
heterochromatin
cytoplasm stains light blue

55. 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% nullcells

58. Monocytes
make up 3 –8% of total leukocyte population
the largest -Ø12 –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

60. monocyte

62. 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

63. 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

65. Platelets (thromboplastids)
Small, non-nucleated cell fragments
derived from megakaryocytes in the bone
marrow
Disk-shaped
Ø2-4 μm
lifespan of less than 14 days

67. MEGAKARYOCYTE

68. platelets

69. Summary of blood elements function
Erythrocytes
Hemoglobin Transport O
2 and CO
2
Neutrophils
Neutrophil granulesDestroy the
microorganisms by
fagocytosis
Eosinophils
Eosinophil granulesAllergy, 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 factorsBlod coagulation

70. Thank you for your attention!
[email protected]