MODULE 2 UNIT 4: LEUKOCYTOSIS Flashcards

1
Q

are a heterogenous group.

A

Leukocytes

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2
Q

2 types of Leukocytes

A

granulocytes and agranulocytes

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3
Q

The granulocytes together with the monocytes share the (?) while the lymphocytes have their (?).

A
  1. same lineage with the red cells (CFU-GEMM)
  2. own (CFU-L)
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4
Q

pertains to the production and development of the three granulocytes.

A

Ganulopoiesis

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5
Q

Give the three granulocytes.

A

neutrophils, eosinophils and basophils

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6
Q

Give the three granulocytes.

A

neutrophils, eosinophils and basophils

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7
Q

The maturation sequence is almost similar for the three types of cells, except for the (?) that influence production and differentiation.

A

cytokines

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8
Q

Maturation Sequence of Neutrophil Development

A

I. Stem cell pool
II. Mitotic pool
III. Maturation pool
IV. Neutrophil

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9
Q

Pluripotential hematopoietic stem cell

A

Stem cell pool

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10
Q

Mitotic pool
Progenitors:

A

a. CFU-GEMM (Common Myeloid Progenitor)
b. CFU-GM (Granulocyte-Macrophage Progenitor)
c. CFU-G

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11
Q

Mitotic pool
Precursors:

A

d. Myeloblast
e. Promyelocytes
f. Myelocytes

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12
Q

Maturation pool
Precursors:

A

a. Metamyelocytes
b. Neutrophilic band

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13
Q

MYELOBLAST

Size (um)
N:C ratio
Nucleus Shape
Chromatin
Nucleoli
Staining
Granules

A

14 to 20
8:1 to 4:1
Round to oval
Homogenous, delicate, fine euchromatin
2 to 4
Slightly basophilic
No Granules

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14
Q

PROMYELOCYTE

Size (um)
N:C ratio
Nucleus Shape
Chromatin
Nucleoli
Staining
Granules

A

16-25
3:1 to 2:1
Round to oval
Heterochroma tin Slightly coarse
1-3
Basophilic
Formation of PRIMARY/ Azurophilic granules

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15
Q

PROMYELOCYTE

Size (um)
N:C ratio
Nucleus Shape
Chromatin
Nucleoli
Staining
Granules

A

16-25
3:1 to 2:1
Round to oval
Heterochroma tin Slightly coarse
1-3
Basophilic
Formation of PRIMARY/ Azurophilic granules

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16
Q

MYELOCYTE (“Dawn of Neutrophilia”)

Size (um)
N:C ratio
Nucleus Shape
Chromatin
Nucleoli
Staining
Granules

A

12-18
1:1
Oval or round
Coarser and condensed
NONE
Mixture of basophilic and acidophilic
Formation of SECONDARY / Specific granules “Dawn of Neutrophilia ”

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17
Q

METAMYELOCYTE

Size (um)
N:C ratio
Nucleus Shape
Chromatin
Nucleoli
Staining
Granules

A

15-18
1:1
KIDNEY-SHAPED
Coarse & clumped
NONE
Beige/ salmon
Formation of TERTIARY/ Gelatinase granules

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18
Q

BAND/STAB

Size (um)
N:C ratio
Nucleus Shape
Chromatin
Nucleoli
Staining
Granules

A

9-15
1:1 to 1:2
Elongate/ band (C or S)
Coarse & clumped
NONE
Beige/ salmon
Continuous formation of tertiary granules Formation of SECRETORY GRANULES (vesicles)

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19
Q

Cellular Activity of MYELOBLAST

A

0-3% of nucleated cells in BM

  • Classification:
    Type I blasts: No visible granules
    “Granular blasts” Rare in normal marrow

Type II blasts: < 20 visible primary or azurophilic granules

Type III blasts: >20 visible primary or azurophilic granules

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20
Q

Cellular Activity of PROMYELOCYTE

A

1-5% BM Hof/ Paranuclear halo surrounding the nucleus

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21
Q

Cellular Activity of MYELOCYTE (“Dawn of Neutrophilia”)

A

6-17% BM
LAST STAGE CAPABLE OF MITOSIS

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22
Q

Cellular Activity of METAMYELOCYTE

A

3-20% BM

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23
Q

Formed during the promyelocyte stage
Last to be released (Exocytosis)

A

Primary (Azurophilic) Granules

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24
Q

Contain:
• Myeloperoxidase
• Acid-β- glycerophosphate
• Cathepsins
• Defensins
• Elastase
• Proteinase-3
• Others

A

Primary (Azurophilic) Granules

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25
Q

Formed during myelocyte and metamyelocyte stages
Third to be released

A

Secondary (Specific) Granules

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26
Q

Contain:
• β2- microglobulin
• Collagenase
• Gelatinase
• Lactoferrin
• Neutrophil gelatinase- associated lipocalin
• Transcobalamin I
• Others

A

Secondary (Specific) Granules

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27
Q

Formed during metamyelocyte and band stages
Second to be released

A

Tertiary Granules

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28
Q

Contain:
• β2- microglobulin
• Collagenase
• Gelatinase
• Lysozyme
• Acetyltransferase

A

Tertiary Granules

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29
Q

Formed during the band and segmented neutrophil stages
First to be released (fuse to plasma membrane)

A

Secretory Granules (Secretory Vesicles)

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30
Q

Contain (attached to the membrane):
• CD11b/ CD18
• Alkaline phosphatase
• Vesicle-associated membrane-2
• CD10, CD13, CD14, CD16
• Cytochrome b558
• Complement 1q receptor
• Complement receptor-1

A

Secretory Granules (Secretory Vesicles)

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31
Q

are also known as polymorphonuclear cells (PMNs) or segmenters.

A

Neutrophils

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32
Q

Neutrophils are the cells that respond to (?).

A

bacterial infection

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33
Q

Neutrophils average size ranges from (?) microns.

A

9 to 15 microns

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34
Q

The nucleus presents with (?) lobes with highly condensed chromatin.

A

2-5 lobes

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35
Q

The cytoplasm will contain continuously forming (?) secretory granules.

A

pink to rose-violet

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36
Q
  • Normal values:
    o Bone marrow:
    o Relative value in peripheral blood:
    o Absolute value:
A

o Bone marrow: 7-30% of nucleated cell population
o Relative value in peripheral blood: 50-70% of WBCs
o Absolute value: 1.7-7.5 x 109/ L

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37
Q

Neutrophil kinetics:
o Production:
o Mitotic pool:
o Maturation pool:
o Once in the peripheral blood, neutrophils are divided randomly into a (?) and a (?). The ratio of CNP and MNP is roughly equal.
o Majority of the MNP are in the (?) of the lungs.

A

o Production: 0.9-1.0 x 109 cells/ kg per day
o Mitotic pool: 2.11 x 109 cells/ kg
o Maturation pool: 5.6 x 109 cells/ kg
o Once in the peripheral blood, neutrophils are divided randomly into a circulating neutrophil pool (CNP) and a marginated neutrophil pool (MNP). The ratio of CNP and MNP is roughly equal.
o Majority of the MNP are in the capillaries of the lungs.

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38
Q

Transit time:
o HSC to myeloblast:
o Myeloblast to maturation pool:
o Neutrophil half-life in blood:
o It takes about (?) from the blast stage to the release of mature granulocytes.

A

o HSC to myeloblast: 6 days
o Myeloblast to maturation pool: 4 to 6 days
o Neutrophil half-life in blood: 6-8 hours
o It takes about 14 days from the blast stage to the release of mature granulocytes.

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39
Q

Neutrophil Function: a. Phagocytosis Steps

A

Chemical signals from damaged cells leading to chemotaxis → Margination (sticking to capillary endothelium) → Diapedesis → Recognition of pathogen→ Attachment (Toll-like receptor of phagocyte attaching to PAMPs) → Ingestion → Pathogen in phagosome → Formation of phagolysosome→ Digestion & killing

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40
Q

Respiratory burst through the activation of NADPH oxidase. H2O2 and peroxidase are produced

A

Oxygen dependent Digestion

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41
Q

The pH within the phagosome becomes alkaline and then neutral, the pH at which digestive enzymes work.

A

Oxygen independent Digestion

42
Q

▪ Nuclear & organelle membrane dissolves → DNA release → DNA + cytoplasmic enzymes → Cell membrane ruptures → NET release

A

NETs

43
Q

▪ Extracellular threadlike structures believed to represent chains of nucleosomes from DNA

A

NETs

44
Q

▪ Have enzymes from neutrophil granules

A

NETs

45
Q

▪ Have been shown to be able to trap and kill gram-positive and gramnegative bacteria as well as fungi

A

NETs

46
Q

NETs are generated at the time that neutrophils die as a result of antibacterial activity

A

“NETosis”

47
Q

• Transcobalamin I/R binder (needed for Vitamin B12 absorption)
• Variety of cytokines

A

Secretory Function

48
Q

Maturation Sequence of Eosinophil Development

A

I. Pluripotential hematopoietic stem cell
II. Progenitors
III. Precursors
IV. Eosinophil

49
Q

Eosinophil Development
Maturation Sequence
II. Progenitors:

A

a. CFU-GEMM (Common Myeloid Progenitor)
b. CFU-Eo

50
Q

Eosinophil Development
Maturation Sequence
III. Precursors:

A

a. Myeloblast
b. Promyelocytes
c. Myelocytes
d. Metamyelocytes
e. Eosinophilic band

51
Q

o Not fully characterized

A

A. Eosinophilic myeloblasts

52
Q

o Cytochemical identification only

A

B. Promyelocytes

53
Q

o PRIMARY GRANULE: Charcot-Leyden crystal protein

A

B. Promyelocytes

54
Q

o Similar to neutrophil myelocytes

A

Myelocytes

55
Q

o Large, pale, reddish-orange SECONDARY GRANULES

A

Myelocytes

56
Q

o Resemble their neutrophil counterpart

A

Metamyelocytes & Band Forms

57
Q

o Formation of SECRETORY GRANULE/ VESICLE

A

Metamyelocytes & Band Forms

58
Q

o Two other organelles are also present: Lipid bodies and Small lysosomal granules

A

Metamyelocytes & Band Forms

59
Q

Formed during the promyelocyte stage

A

Primary Granules

60
Q

Contain:
• Charcot-Leyden crystals

A

Primary Granules

61
Q

Formed throughout remaining maturation stages

A

Secondary (Specific) Granules

62
Q

Contain:
• Major basic protein (core)
• Eosinophil cationic protein (matrix)
• Eosinophil- derived neurotoxin (matrix)
• Eosinophil peroxidase (matrix)
• Lysozyme (matrix)
• Catalase (core and matrix)
• β-Glucuronidase (core and matrix)
• Cathepsin D (core and matrix)
• Interleukins 2,4, and 5 (core)
• Interleukin- 6 (matrix)
• Granulocyte- and Macrophage colony-stimulating factor (core)
• Others

A

Secondary (Specific) Granules

63
Q

• Acid phosphatase
• Arylsulfatase B
• Catalase
• Cytochrome b558
• Elastase
• Eosinophil cationic protein

A

Small Lysosomal Granules

64
Q

• Cyclooxygenase
• 5-Lipoxygenase
• 15-Lipoxygenase
• Leukotriene C4 synthase
• Eosinophil peroxidase
• Esterase

A

Lipid Bodies

65
Q

Carry proteins from secondary granules to be released into the extracellular medium

A

Storage Vesicles

66
Q

can also be classified as larger or smaller granules

A

Eosinophil specific granules

67
Q

MAJOR BASIC PROTEIN, Acid hydrolase, Peroxidase, Phospholipase, Cathepsin, Eosinophil cationic protein, Eosinophil-derived neurotoxin

A

Larger granules

68
Q

Arylsulfatase, Peroxidase, Acid phosphatase

A

Smaller granules

69
Q

Eosinophils have bilobed nucleus measuring around (?) microns.

A

9-15

70
Q

They possess refractile, orange-red granules and are involved in allergic and parasitic infections.

A

Eosinophils

71
Q

Eosinophils
- Normal values:

o Relative value:
o Absolute value:

A

o Relative value: 1-3% of WBC in peripheral blood
o Absolute value: 0-0.3 x 109/ L

72
Q

Production of eosinophil from last myelocyte division:

A

3.5 days

73
Q

Eosinophil kinetics:

o Turnover of eosinophils:
o Large storage pool:
o Half-life in circulation:
o Survival in tissues:

A

o Turnover of eosinophils: 2.2 x 108 cells/ kg
o Large storage pool: 9-14 x 108 cells/ kg
o Half-life in circulation: 18 hours
o Survival in tissues: 2-5 days (columnar epithelial cells of the respiratory, genitourinary, and gastrointestinal tracts)

74
Q

Eosinophil Function:
a. Eosinophil degranulation

A

i. Classical exocytosis
ii. Compound exocytosis
iii. Piecemeal degranulation

75
Q

▪ Granules move to plasma membrane → Fuse with cell membrane → Emptying of contents to extracellular fluid (ECF)

A

Classical exocytosis

76
Q

▪ Granules fuse together within eosinophils → Fuses with cell membrane → Emptying to ECF

A

Compound exocytosis

77
Q

▪ Secretory vesicles remove specific CHONs from 20 granules → Secretory vesicles migrate to plasma membrane → Emptying to ECF

A

Piecemeal degranulation

78
Q

Eosinophils delete double-positive thymocytes, act as antigen-presenting cells, promote proliferation of effector T cells, initiate Type 1 or Type 2 immune response and regulate mast cells

A

Regulation of immune responses

79
Q

can trigger mast cell degranulation

A

▪ Major basic protein & other cytokines

80
Q

is needed for mast cell survival

A

▪ Nerve growth factor

81
Q

In the peripheral blood, eosinophil concentration correlates with severity of disease

A

Hallmark of allergic disorders

82
Q

They secrete HISTAMINASE, IL-5 that function for airway inflammation and mucosal cell damage, and eosinophil-derived fibrogenic growth factors that function for airway remodeling

A

eosinophil concentration

83
Q

Maturation Sequence Basophil Development

A

I. Pluripotential hematopoietic stem cell
II. Progenitors
a. CFU-GEMM (CMP)
b. CFU-Baso
III. Immature basophil
IV. Mature basophil

84
Q

Formed throughout remaining maturation stages

A

Secondary (Specific) Granules

85
Q

Secondary (Specific) Granules

A

• Histamine
• Platelet-activating factor
• Leukotriene C4
• Interleukin-4
• Interleukin-13
• Vascular endothelial growth factor A
• Vascular endothelial growth factor B
• Chondroitin sulfates (e.g. Heparin)

86
Q

possess unsegmented or bilobed nucleus with condensed chromatin.

A

Basophils

87
Q

The (?) almost obscure the nuclear material of the cell.

A

blue-black water-soluble granules

88
Q

Basophils are further characterized by:

A

Normal values
Basophil kinetics
Basophil functions

89
Q

Normal values
Relative value:
Absolute value:

A

0-2%
0-0.2 x 109/ L

90
Q
  • Basophil kinetics:
A

Poorly understood
Life span of 60 hours

91
Q
  • Basophil functions
A

(ALLERGIC OR HYPERSENSITIVITY REACTION)

92
Q

Basophils possess (?). They regulate Th2 response (IL-4 & IL ), induce B cells to synthesize IgE, mediate allergic processes (production of HISTAMINE, Granzymes B, retinoic acid) and promote angiogenesis (Vascular endothelial growth factor production)

A

surface IgE receptors

93
Q

are erroneously called tissue basophils.

A

Mast cells

94
Q

They are not true leukocytes; they are cells from the BM that uses blood as transit system to gain access to tissues where they mature.

A

Mast cells

95
Q

They function as effector cells in allergic reactions by stimulating IgE receptors and inflammatory reactions by an IgE receptor-independent process.

A

Mast cells

96
Q

They can also act as antigen presenting cells that induce Th2 differentiation.

A

Mast cells

97
Q

They are known for their anti-inflammatory and immunosuppressive functions

A

Mast cells

98
Q

MONOPOIESIS Maturation sequence (Table 2-2):

A

I. Pluripotential hematopoietic stem cell
II. Progenitors:
a. CFU-GEMM (CMP)
b. CFU-GM
c. CFU-M
III. Precursors:
a. Monoblasts
b. Promonocyte
IV. Monocyte
V. Tissue spaces: Macrophage

99
Q

Size (um): 12-20
N:C ratio: 4:1 to 3:1
Nucleus Shape: Round to oval
Chromatin: Delicate
Nucleoli: 1-2
Cytoplasm Staining: Basophilic
Cytoplasm Granules: No Granules
Cellular Activity
Carries out 2 mitotic divisions in 60 hours to produce 8 monocytes
Can carry out 4 mitotic divisions in 60 hours under increased demand

A

MONOBLAST

100
Q

Size (um): 12-18
N:C ratio: 3:1 to 2:1
Nucleus Shape: Slightly indented or folded
Chromatin: Delicate
Nucleoli: > 1
Cytoplasm Staining: Blue-gray
Cytoplasm Granules: Formation of AZUROPHILIC GRANULES
Cellular Activity
Carries out 2 mitotic divisions in 60 hours to produce 8 monocytes
Can carry out 4 mitotic divisions in 60 hours under increased demand

A

PROMONOCYTE

101
Q

LARGEST CELL IN PERIPHERAL BLOOD

A

MONOCYTE

102
Q

Size (um): 15-20
N:C ratio: 2:1 to 1:1
Nucleus Shape: Oval or round KIDNEY/ HORSE-SHOE May be folded, showing brain-like convolutions
Chromatin: Looser (Lace-like/ Stringy
Nucleoli: NONE
Cytoplasm Staining: Blue-gray
Cytoplasm Granules: Many fine azurophilic granules having GROUNDGLASS APPEARANCE (frosted)
Cellular Activity
Enter tissues and mature to macrophages

A

MONOCYTE