Leucopoiesis

Question 2

What is leucopoiesis divided into?

Answer 2

-Granulopoeisis
-Lymphopoiesis
-Monopoiesis

Question 3

Look at leucopoeisis diagram

Question 4

What is the maturation process of neutrophils

Answer 4

Myloblast - promyelocyte - myelocyte - metamyelocyte - band neutrophil - neutrophil

Question 5

What is the maturation process of monocytes

Answer 5

Myeoblast - promonocyte - monocyte - immature macrophage - macrophage

Question 6

When is granulopoeisis seen to start taking place?

Answer 6

Little activity until 4-5 months gestation
Myeloblast in bm to mature granulocyte in peripheral blood takes 6-10 days

Question 7

Neutrophils appearance?

Answer 7

-Nucleus that divides into 2-5 lobes - separated by a thin strand of nuclear material
-Chromatin in nucleus is lumpy
-Cytoplasm is v pale blue ad packed w lilac staining granules
-About 2-3 times the size of the red cell
-Represent 40-75% of white cells
-Ref range is 2.0-7.0 x 10*9/L
-In females, proportion of N have v small lobe (drumstick lobe) protuding from nucleus which represents the inactive X chromosome
-Only spend 10 hours in the blood before passing to the tissues

Question 8

What enzymes do neutrophils have?

Answer 8

Myeloperoxidase, alkaline phosphatase, acid phosphatase, hydrolases
Contain Lactoferrin and Lysozyme

Question 9

What is the primary func of neutrophils and what are the stages?

Answer 9

Kill bacteria and certain fungi
-Chemotaxis
-Opsonisation/Adhesion
-Ingestion/Phagocytosis
-Killing phase

Question 10

Look at migration of N to tissue

Question 11

What are chemotaxi ns?

Answer 11

Proteins derived from activation of plasma protein pathways such as the coagulation, complement, fibrinolytic and kinin systems

Question 12

What is opsonisation?

Answer 12

The process by which the surface of the bacteria is modified to allow phagocytosis

Question 13

Phagocytosis in the neutrophil?

Answer 13

-The bacterium is enclosed in a phagocytic vacuole into which the N discharges its granules

Question 14

N killing of bacteria stage?

Answer 14

-Involves an oxygen dependent and independent system
1) The oxygen dependent system relies on myeloperoxidase, hydrogen peroxide, superoxides and hydroxyl radical formation
2) The oxygen independent system involves a fall in pH, the direct action of lysozyme on the bacterial wall and the bactericidal property of cationic proteins from primary N granules

Question 15

When are the primary granules in Neutrophils synthesised and what are examples of whats in these granules?

Answer 15

-Primary granules are synthesised during the promyelocyte stage where the level is highest - as cell matures, conc of primary granules falls
Contain : myeloperoxidase, bacterial permeability inducing factor, lysozyme, elastase, acid hydrolases

Question 16

What CD markers are seen onm premature N and on mature N?

Answer 16

CD34 and CD33 are seen on premature N
CD11b/CD18 are seen on mature cells

Question 17

What is the role of myeloperoxidase enzyme?

Answer 17

-Plays role in nonspecific elinmination of bacteria, viruses and fungi
-Involved in conversion of hydrogen peroxide to form hychlorus acid which has anti microbial properties

Question 18

Role of bacterial permeability inducing factor?

Answer 18

Bind specifically to lipopolysaccharides (gram neg) increasing bacterial membrane permeability and death

Question 19

Role of lysozyme?

Answer 19

-Enyzme that can degrade the bacterial cell wall, very effective at destroying Gram Pos bacteria but may require cofactors (Lactoferrin or hydrogen peroxide) to destroy Gram Neg organisms

Question 20

What does Elastase kill?

Answer 20

Gram Neg bacteria, fungi, enterotoxins

Question 21

Examples of acid hydrolases?

Answer 21

Enzymes such as acid phosphatase, ß-galactosidase, ß-gluconoridase, esterases wtc

Question 22

Purpose of secondary granules?

Answer 22

Provide distinctive staining patterns that are used in the identification of granulocytes and their precursors

Question 23

What do secondary granules contain?

Answer 23

-Lactoferin - has bacteriostatic and bacteriosidal - binds to iron and prevents its uptake by microorganisms
-Lysozyme found in both primary and secondary

Question 24

What do tertiary granules include?

Answer 24

-Gelatinase - capable of digesting denatured collagen as well as intacxt collagen
This digestion allows neutrophils to migrate through the blood vessel basement membrane and enter tissue fluid

Question 25

What are the myeloblast, promyeloblast and myelocyte stages called?

Answer 25

Mitotic maturation stages where daughter cells are produced

Question 26

What cells are pos for CD34 and CD33 and which for only CD33

Answer 26

Myeloblast AND PROMYELOCYTE CD34 and CD33 Myelocyte and metamyelocytes are pos for CD33 only

Question 27

Properties of Myeloblast?

Answer 27

-In normal bm 2-4% cells are myeloblasts -Shouldnt be in peripheral blood -Have a high nucleocytoplasmic ratio -Prominent nucleoli -Cytoplasm is pale blue -Size is 16 +/- µm in diameter -Acute/Chronic Myeloblastic Leukaemia if in blood

Question 28

Properties of Promyelocytes?

Answer 28

-Stage after myeloblast in granulocytic development -Shouldnt be in blood -Size around 20µm diameter -Occasional nucleolus -Cytoplasm is deep blue in colour -Contain primary granules

Question 29

Properties of Myelocytes?

Answer 29

-Smaller than promyelocyte, size around 15µm diameter -Shouldnt be in blood -Nucleoli are not visible -Secondary or specific granules present throughout cytoplasm - help identify granulocytic lineage -Gradual changes in the structural development of the myelocyte result in the metamyelocytes stage of maturation

Question 30

Properties of Metamyelocyte?

Answer 30

-Nucleocytoplasmic ratio is low - nucleus takes up alozt of cell -Contain distinctive primary and secondary granules -Nucleus becomes curved without being lobed and will mature in Band Neutrophils (Stab Cells)

Question 31

Hypersegmented vs Hyposegmented Neutrophils

Answer 31

-Neutrophils where more than 3% of cells have 5 or more lobes - hyper - right shift -N where have 2 or fewer lobes are hypo - Pelger-Huet

Question 32

What are examples of disorders associated with phagocytes?

Answer 32

-Neutrphilia - too many N - bacterial infec, CML, burns -Neutropenia - low N -Leukamoid rxn - leukaemia -Defects of phagocytic func -Eosinophilia - allergic rxn , parasitiuc infec -Basophilia - allergic rxn - lewukaemia -Monocytosis- fungal, bacterial, poarasitic

Question 33

What is Neutrophilia?

Answer 33

An increase in the circulating neutrophils to a level greater than 7.5x10*9/L - sometiems accompanied by fever

Question 34

What is reactive neutrophilia often associated with?

Answer 34

-A shift to the left (increase in no. of band Neutrophils and occassionally presence of Metamyelocytes in the blood) -The presence of cytoplasmic toxic granulation and Dohle bodies (black bodies circulating) -An elevated Neutrophil Alkaline Phosphatase Score

Question 35

What causes Neutrophilia?

Answer 35

-Bacterial infections -Inflammation of tissue and necrosis -Metabolic disorders - uraemia, eclampsia, acidosis, gout -Neoplasms -Acute haemorrhage, haemolysis -Drugs -Chronic myeloid leukaemia, myeloproliferative diseases -Treatment w myeloid growth factors (G-CSF, GM-CSF) -Asplenia -no spleen

Question 36

What is Leukaemoid Reaction?

Answer 36

-White cell count greater than 50x10*9/L with all cells of all stages of myeloid maturation appearing in peripheral blood -Blood film may look like Leukaemia but is a reactive response to severe infection, certain cancers, pharmaceuticals, growzth factors, haemorrhage, haemolysis -recovery from infection - wcc return to normal

Question 37

What is neutropenia?

Answer 37

-N levels fall below 0.5x10*9L - reoccurent infections -N levels fall below 0.2x10*9/L - risks are v serious especially when there is also a functionl defect -Can be selective or associated w general pancytopenia

Question 38

Causes of Neutropenia?

Answer 38

-Congenital - Kostmanns syndrome: mutation of gene encoding for Neutrophil Elastase -Acquired - drug induced: by direct toxicity or immune antibacterial drugs, anti inflammatory drugs -Infections - particularly viral infections -Some African and Middle East races appear to have lower N levels than Caucasian - 1.5x10*9/L

Question 39

Defects of Phagocytic Function?

Answer 39

i) Chemotaxis - rare congenital abnormality (lazy leucocyte syndrome), Acquired abnormalities (corticosteroid therapy or haematological malignancy) ii) Oponisation and Phagocytosis- congenital, acquired caused by hypogammaglobulinaemia or lack of complement iii) Killing- chronic granulomatous disease resulting from abnormal oxidative func, acquired conditions that interfere w killing func can happen in Acute ad Chronic Leukaemia