Hematology Granulopoiesis White blood cell production

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Haematology 3: AHHMX3A
JRTAGNEWAMBO
Granulopoiesis
• LU2

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CONTENTS
The contents of this presentation is confidential. ©VUT
1. Outline the blood cells
2. Myeloid maturation sequence
3. Normal functioning of WBCs
4. Lymphocytes
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3. • Red blood cells or erythrocytes
• White blood cells or leucocytes
• Platelets or Thrombocytes
• Plasma
• Blood cells varies in size and shape
• Pale centre, bi concave, lack nucleus
• (mature red cells)
• Described as normocytic/normochromic
• +/- 7,2 um or 7,5 um and 2.0 um thick at rim.
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4. It is the formation of WBC from the pluripotent stem cells of myeloid and lymphoid
progenitor cells.
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Leukopoeisis

5. • Composed of 1% of blood, found in
spleen, liver and lymph nodes.
• Produced in the BM, forming part of
the immune system to fight
infections
• Myeloid progenitor cells is
composed of monocytes,
macrophages, granulocytes
(neutrophils, eosinophils and
basophils) and antigen presenting
cells (dendritic cells)
• Lymphoid progenitor cells consist of
T-cell, B-cell and natural killer cells.
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White blood cells (Leucocytes)

6. • Formation of blood granulocytes and monocytes
takes place in the bone marrow from a common
precursor cell.
• Whereby myeloblasts, promyelocytes and
myelocytes (granulopoietic series progenitor cells)
form a proliferative or mitotic pool of cells.
• Meanwhile metamyelocytes, band and segmented
granulocytes forms a post mitotic maturation.
• Band and segmented neutrophils are held in the
bone marrow in a greater amount as a storage
compartment (reserve pool).
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Granulopoiesis

7. • Lobulated (3-4 lobes), having a large to round
cytoplasm eosinophilic granules.
• Originates in the BM composed of 70% of
peripheral WBC.
• Function in phagocytosis of microorganisms
• Surface of cells having receptors for the Fc
portion of antibody and compliment.
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Neutrophils

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Formation of Neutrophils

9. Lobulated (2 lobes), large round eosinophilic granules.
Function in allergic reactions, parasitic infection
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Eosinophil

10. Bilobed (2 lobes) with large, bluish-black
granules (cytoplasm).
Rarely seen as an isolated condition, which
is present sometimes in myxodema,
chicken box and smallpox
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Basophil

11. • One round, fine lacey chromatin
with 1-3 nucleoli, having a blue-
grey basophilic granule.
• Main function is phagocytosis
and antigen presentation.
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Monocytes

12. • Growth factors are involved in the process of maturation
including interleukin 1,3, 5, 6, 11, granulocyte macrophage
colony stimulating factor (GM-CSF), granulocyte CSF (G-CSF)
and monocyte CSF (M-CSF)
• The proliferation and differentiation of granulocyte are
stimulated by these growth factors, affecting the function of the
mature cells (by phagocytosis, superoxide generation and
cytotoxicity and production of other cytokins).
• Elevated plasma levels of granulocyte and monocyte are caused
by response triggered following infection (which speed up the
production of growth factors from stromal cells and T
lymphocytes).
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Control of granulopoiesis

13. 1. Chemotaxis; Which involves
cell mobilization and
migration.
-Whereby phagocytes are
attached to bacteria or attracted to
the site of inflammation, releasing
chemotactic substances from
damaged tissues.
-Or by complement component
and by the interaction of
leucocyte which adhere to
molecules with the ligands
situated on the damaged tissues.
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Functions of Granulocytes

14. 2.Phagocytosis; is the process whereby foreign material such as
bacteria, fungi, dead or damaged cells are eaten up (phagocytosed).
-By identifying or recognizing foreign particle, with the assistance
of opsonization with immunoglobulin or complement.
-Opsonization of the body cells (normal), helps in the destruction
by macrophages of the reticuloendothelial system.
-Macrophages plays an essential role in antigen presentation
(processing and presenting foreign antigens on human leucocyte
antigen) to the immune system.
-Chemokines are cytokines (chemotactic) acts on neutrophils (as
macrophage inflammatory protein.
-Meanwhile RANTES acts on basophils, monocytes, eosinophil
and NK
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Function of Granulopoiesis

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Granulopoiesis

16. 3. Killing and digestion; take place by oxygen-dependent and oxygen
independent pathways.
-Oxygen dependent pathways, superoxide, hydrogen peroxide and activated
oxygen are generated from oxygen and reduced to nicotinamide adenine
dinucleotide phosphate.
-Neutrophils (hydrogen peroxide reacts with myeloperoxidase to kill bacterial
with intracellular halide.
-Non-oxidative microbial mechanism is involved in microbicidal proteins
(lysozyme elastase).
-They also act in conjunction with a fall in pH in the phagocytic vacuoles
whereby lysosomal enzymes are released.
-
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Function of Granulopoiesis

17. -Lactoferrin factor is an iron binding protein
which is present in the granules of neutrophil.
Proving a bacteriostatic function, preventing
or depriving bacterial from iron and
generating free radicals.
-Nitric oxide is generated through the nitric
oxide synthase from L-arginine, thus another
mechanism or mode of action where by
phagocytes kill microbes.
-The undigested bacterial residual products are
discharges or excreted by exocytosis
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Function of Granulopoiesis

18. • Made up of T cell, B cells and natural killer cells (NK).
• Produced by lymph nodes, spleen, thymus and BM
• They moves to the lymph nodes and spleen where they interact with antigen and triggers an
immune response.
• Composed of 20% of peripheral blood cells
• T cells (matures in the BM)and NK cells function in cell-mediated immunity
• B cells ( matures in the thymus but is form also in the BM)differentiate into plasma cells
secreting antibodies
• Lymphoblast is the earliest recognisable cell, followed by prolymphocyte and later mature
lymphocytes.
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Lymphocytes

19. • Lymphocytes size varies from 10-
20um round and occupies 80% of
cell having basophilic and agranular
cytoplasm.
• Prolymphocytes have 10-16um,
round, dense chromatin. With an
abundant cytoplasm than blast.
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Lymphocytes

20. • NK cells are antibody dependent
cells mediated cytotoxicity
(cytotoxic CD8+) , with large cells
having cytoplasmic granules.
• Expressed as CD16, CD 56 and CD
57, killing cells with low
expression of viral infection or
malignant cells (HLA class 1
molecules).
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Lymphocytes

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Lymphocytes

22. • Plasma cells are B cells which are
activated, producing specific
immunoglobulins during the
process of an immune response.
• Having an eccentric round nucleus
appearing as a clock face chromatin
pattern with a perinuclear halo and
basophilic cytoplasm.
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Lymphocytes

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Lymphocytes

24. Video

25. • Neutrophilia (increased count); caused by bacterial
infections, inflammation and tissue necrosis
-Acute haemorrhage, polycythaemia vera, CML, drugs, ET,
pregnancy, smoking, asplenia, post operative and vigorous
exercise.
Neutropenia ( decreased count); caused by autoimmune SLE,
kotsmann’s, certain drugs, alcoholism, hypersplenism, aplastic
anaemia, felty’s syndrome, large granular lymphocytic
leukaemia, viral infection, splenomegaly and BM failure.
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Granulopoiesis

26. •Lymphocytosis (increased count); caused by
infectious mononucleosis, CLL, ALL, viral
infections, smoking, chronic infection and non
Hodgkin lymphoma.
Lymphocytopenia (decreased count); caused by
acute bacterial infection, Hodgkin lymphoma, severe
burn and immune deficiency syndrome.
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Granulopoiesis

27. • Monocytosis (increased count); caused by
chronic bacterial infection such as typhoid, TB,
AML, CML, Hodgkin lymphoma, connective tissue
disease, SLE and protozoan infections.
Monocytopenia (decreased count); caused by ill,
certain drugs, HIV, vitamins deficiencies, bacterial
infection and arthritis.
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Granulopoiesis

28. •Eosinophilia (increased count); caused by allergic disease, asthma,
parasitic disease, psoriasis (skin disease), graft vs host disease,
vasculitis, Hodgkin lymphoma and chronic eosinophilic leukaemia.
Decreased count is caused by steroid and corticosteroids intake or
administration.
Basophilia (increased count); caused by PV, CML, smallpox,
chickenpox, hypersensitivity reactions and ulcerative colitis.
Decreased count is caused by severe allergies, stress, pregnancy and
hyperthyroidism.
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Granulopoiesis

29. video

30. video

31. video

32. • Chediak higashi syndrome; rare autosomal recessive
condition associated with abnormally large leukocytes
granules resulting from lysozymes fusion
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Neutrophil morphological
abnormalities

33. •May-Hegglin anomaly; Autosomal dominant inherited disease associated
with mild thrombocytopenia with giant platelets
Basophilic inclusions of 2-5um, RNA, spindle shaped, randomly distributed in
cell.
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Neutrophil morphological abnormalities

34. •
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Neutrophil morphological abnormalities

35. • Pelger-Huet anomaly; Autosomal dominant inherited disease (AML,
myelodysplasia), having coarse clumping of chromatin, bilobed (dumb bell
shaped) nucleus.
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Neutrophil morphological abnormalities

36. •• Hypersegmentation neutrophil; More than 5 lobed nucleus, common with
megaloblastic anaemia.
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Neutrophil morphological abnormalities

37. • Dohle body; Small pale blue/grey cytoplasmic inclusion situated towards the
periphery of the cell.
Commonly seen with infection, inflammation, pregnancy, burns, AML and
myelodysplasia
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Neutrophil morphological abnormalities

38. •Toxic granulation; Darker and larger cytoplasmic granules seen with
infection and pregnancy.
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Neutrophil morphological abnormalities

39. •
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Neutrophil morphological abnormalities

40. • •Gaucher’s disease; uncommon autosomal recessive disorder (lipid storage
disease).
• Straited cytoplasm resembling the skin of onions (BM aspirate).
• Accumulation of glucosylceramide in RE cells as a result of glucocerebroside
deficiency.
• The 3 types are; type 1- chronic adult, type-acute infantile neutropathic type
and type 3- subacute neutropathic childhood/adolescent onset.
• Gene mutation, common in Ashkenazi Jews.
• Splenomegaly, hepatomegaly, bone pain and pathological features,
osteoporosis, anaemia, leucopenia and thrombocytopenia.
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Monocytes morphological abnormalities

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Monocytes morphological abnormalities

42. • •Niemann-Pick disease; Inherited disease having foaming
cells with packed cytoplasm having small droplets of lipid
and large granules containing ceroid (stains green-blue).
• Accumulation of sphingomyelin, lipids in RE cells
(sphingomyelin efficiency), hepatosplenomegaly, lung and
nervous system involvement.
• Retarded physical and mental development, cherry red spot
in retina off affected infants and pancytopenia.
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Monocytes morphological abnormalities

43. QUESTIONS?
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