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Heme > Chapter 8 Essential Hematology (WBCs) > Flashcards

Chapter 8 Essential Hematology (WBCs) Flashcards

1
Q

What 2 categories can white blood cells be divided into?

A

Phagocytes and immunocytes.

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2
Q

What are the 3 types of granulocytes?

A
  1. Neutrophils
  2. Eosinophils
  3. Basophils
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3
Q

The WBC phagocytes consist of what cell types?

A

Granulocytes and monocytes.

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4
Q

Which WBCs are normally found in peripheral blood?

A

Only mature phagocytes and lymphocytes.

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5
Q

Which cell types are the immunocytes of the WBCs?

A

The lymphocytes, their precursors, and plasma cells.

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6
Q

What is the normal range of total leukocytes?

A

4-11x10^9/L

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7
Q

What is the normal range of neutrophils?

A

2.5-7.5x10^9/L

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8
Q

What is the normal range of lymphocytes?

A

1.5-3.5x10^9/L

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9
Q

What is the normal range of monocytes?

A

0.2-0.8x10^9/L

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10
Q

What is the normal range of eosinophils?

A

0.04-0.4x10^9/L

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11
Q

What is the normal range of basophils?

A

0.01-0.1x10^9/L

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12
Q

Characteristics of neutrophils?

A

Dense nucleus with 2-5 lobes. Pale cytoplasm with an irregular outline containing many fine pink-blue (azurophilic) or grey-blue granules.

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13
Q

What are the 2 categories of neutrophilic granules?

A
  1. Primary: appear at promyelocyte stage

2. Secondary: appear at myelocyte stage and predominate in the mature neutrophil

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14
Q

What is the lifespan of neutrophils in the blood?

A

6-10 hours

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15
Q

List the cell stages of the neutrophil in order.

A
  1. Myeloblast
  2. Promyelocyte
  3. Myelocyte
  4. Metamyelocyte
  5. Band neutrophil
  6. Mature neutrophil
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16
Q

What are the characteristics of the myeloblast?

A

Cell of variable size. Large nucleus with fine chromatin. 2-5 nucleoli. Basophilic cytoplasm with NO granules.

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17
Q

What are the characteristics of the myelocyte?

A

Nuclear chromatin more condensed and nucleoli not visible.

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18
Q

What are the characteristics of the metamyelocyte?

A

Non-dividing cells. Indented or horseshoe-shaped nucleus. Cytoplasm filled with primary and secondary granules.

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19
Q

Can band neutrophils be seen in peripheral blood?

A

Yes

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20
Q

How can you distinguish band neutrophils from mature neutrophils?

A

Bands do not contain the clear, fine filamentous connections between nuclear lobes as seen in mature neutrophils.

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21
Q

What are the characteristics of monocytes?

A

Larger than other peripheral blood leukocytes. Large central oval or indented nucleus with clumped chromatin. Abundant cytoplasm stains blue and contains many fine vacuoles (gives a ground glass appearance). Cytoplasmic granules often present.

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22
Q

What are the 2 monocyte precursors found in the bone marrow?

A
  1. Monoblasts

2. Promonocytes

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23
Q

What are the characteristics of eosinophils?

A

Similar to neutrophils except cytoplasmic granules are coarser and stain red. Rarely more than 3 nuclear lobes.

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24
Q

T or F. The blood transit time for eosinophils is longer than for neutrophils.

A

T

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25
Q

What are the 3 roles of eosinophils?

A
  1. Allergic responses
  2. Parasite defense
  3. Removal of fibrin formed during inflammation
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26
Q

What are the characteristics of basophils?

A

Many dark cytoplasmic granules which overlie the nucleus and contain heparin and histamine. IgE on surface. Become mast cells once they enter tissue.

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27
Q

In granulopoiesis, which cells are proliferative? Non-dividing?

A

Proliferative: myeloblasts, promyelocytes, myelocytes.

Non-dividing: metamyelocytes, band and segmented granulocytes

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28
Q

T or F. Large numbers of band and segmented neutrophils are held in the marrow as a reserve pool or storage compartment.

A

T

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29
Q

In the bone marrow, are myeloid cells or erythroid cells more abundant?

A

Myeloid cells: 2-12x more.

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30
Q

T or F. Normally, the bone marrow contains 10-15x the number of granulocytes found in peripheral blood.

A

T

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31
Q

What are the 2 pools of granulocytes found in the bloodstream?

A
  1. Circulating pool: included in blood count

2. Marginating pool: not included in blood count

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32
Q

How many days do granulocytes spend in the tissues before they are destroyed?

A

4-5 days

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33
Q

What are the myeloid growth factors involved in control of granulopoiesis?

A

IL-1, IL-3, IL-5, IL-6, IL-11, GM-CSF, G-CSF, and M-CSF.

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34
Q

What do they myeloid growth factors do?

A

Stimulate differentiation and proliferation as well as play a role in the function of mature cells.

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35
Q

In an infection, what 3 molecules stimulate stromal cells and T cells to increase production of growth factors which increase granulocyte and monocyte production?

A
  1. Endotoxin
  2. IL-1
  3. TNF
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36
Q

Endothelial cells and FBs increase production of what 2 molecules when stimulated by TNF and IL-1 from monocytes?

A
  1. GM-CSF

2. G-CSF

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37
Q

Clinical administration of G-CSF IV or subq does what?

A

Produces an increase in circulating neutrophils. Short-acting G-CSF given daily. Longer acting pegylated G-CSF given once every 7-14 days.

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38
Q

What are the 7 clinical indications of administering G-CSF?

A
  1. Post-chemo, radiotherapy, or stem cell transplant
  2. Acute myeloid leukemia
  3. Myelodysplasia
  4. Lymphomas
  5. Severe neutropenia
  6. Severe infection
  7. Peripheral blood stem cell harvesting
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39
Q

How many hours do monocytes circulate in the blood before entering tissues to mature and carry out their function?

A

20-40 hours

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40
Q

When monocytes enter the tissues, what do they become?

A

Macrophages (or histiocytes).

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41
Q

How long can monocytes live in tissue?

A

Several months to years.

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42
Q

What is one very important lineage of monocytes?

A

Dendritic cells: Ag presentation to T cells.

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43
Q

What 2 molecules are involved in the production and activation of dendritic cells?

A

GM-CSF and M-CSF

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44
Q

Monocytes become what in the kidney? Brain? Gut? Lung? Liver? Spleen? BM? Lymph node?

A 
Kidney: intraglomerular mesangial cells
Brain: microglia
Gut: serosal macrophages
Lung: alveolar macrophages
Liver: Kupffer cells
Spleen: sinus macrophages and APCs
BM: macrophages and APCs
Lymph node: macrophages and APCs
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45
Q

What are the 3 phases of neutrophil and monocyte function?

A
  1. Chemotaxis
  2. Phagocytosis
  3. Killing and digestion
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46
Q

What are the 2 classes of chemokines?

A
  1. CXC: act on neutrophils

2. CC: act on monocytes, basophils, eosinophils, and NK cells (ex. MIP-1a, RANTES)

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47
Q

What oxygen species are produced in oxygen-dependent pathways used by phagocytes? How are they produced?

A

Superoxide, H2O2. Generated from O2 and reduced NADPH.

48
Q

In neutrophils, what does H2O2 react with to kill bacteria?

A

MPO and intracellular halide.

49
Q

What are some examples of non-oxidative microbicidal proteins used by phagocytes?

A

Cathepsin G, lysozyme, elastase.

50
Q

Lactoferrin is present where and does what?

A

Neutrophil granules. Bacteriostatic (deprives bacteria of iron and generates free radicals).

51
Q

How is NO utilized by phagocytes?

A

Use it to kill microbes. Synthesized by NOS from L-arginine.

52
Q

In what condition are bi-lobed neutrophils found in the peripheral blood?

A

Pelger-Huet Anomaly. Sometimes unsegmented neutrophils present. Autosomal dominant.

53
Q

In what condition do neutrophils contain basophilic inclusions of RNA in the cytoplasm that resemble Dohle bodies?

A

May-Hegglin Anomaly. Associated mild thrombocytopenia with giant platelets. Autosomal dominant.

54
Q

In what condition are giant granules seen in neutrophils, eosinophils, monocytes, and lymphocytes accompanied by neutropenia, thrombocytopenia, and hepatosplenomegaly?

A

Chediak-Higashi syndrome. Autosomal recessive.

55
Q

In what disorders are abnormal leukocyte granulations and vacuolations seen?

A

Rare mucopolysaccharide disorders (ex. Hurler’s syndrome).

56
Q

T or F. Hypersegmented neutrophils are seen in megaloblastic anemia, Dohle bodies, and toxic changes in infection.

A

T

57
Q

In a proportion of neutrophils in normal females, what is seen?

A

“Drumstick” appears on the nucleus. Caused by the presence of two X chromosomes.

58
Q

Pelger cells are also seen in what 2 conditions?

A
  1. Acute myeloid leukemia

2. Myelodysplasia

59
Q

Neutrophil leukocytosis is defined as circulating neutrophil levels greater than?

A

7.5x10^9/L

60
Q

What is neutrophil leukocytosis often accompanied by?

A

Fever as a result of the release of leukocyte pyrogens.

61
Q

What are the 2 other characteristic features of reactive neutrophilia?

A
  1. Left shift (increase in bands) or presence of metamyelocytes and myelocytes
  2. Presence of cytoplasmic toxic granulations and Dohle bodies
62
Q

What are the 10 causes of neutrophil leukocytosis?

A
  1. Bacterial infections (esp pyogenic bac)
  2. Inflammation and tissue necrosis
  3. Metabolic disorders
  4. Neoplasms
  5. Acute hemorrhage or hemolysis
  6. Drugs
  7. Chronic myeloid leukemia
  8. Tx with myeloid growth factors
  9. Rare inherited disorders
  10. Asplenia
63
Q

What is the leukemoid reaction?

A

A reactive and excessive leukocytosis usually characterized by the presence of immature cells in the peripheral blood.

64
Q

What are the disorders associated with the leukemoid reaction?

A

Severe or chronic infections, severe hemolysis, or metastatic cancer.

65
Q

What differentiates the leukemoid reaction from CML?

A

Granulocyte changes such as toxic granulation and Dohle bodies.

66
Q

What is the leukoerythroblastic reaction characterized by?

A

The presence of erythroblast and granulocyte precursors in the blood.

67
Q

What causes the leukoerythroblastic reaction?

A

Metastatic infiltration of the marrow or certain benign or neoplastic blood disorders.

68
Q

What ethnic group has a normally low neutrophil count?

A

Blacks. Also Middle Easterners. Known as benign ethnic neutropenia.

69
Q

What causes benign ethnic neutropenia in people of West African origin?

A

Polymorphism in the DARC gene which leads to a loss of expression on red cells. DARC is used by the malaria parasite to enter red cells.

70
Q

What is Kostmann’s syndrome?

A

Autosomal recessive disease resulting in neutropenia. Presents in the first year of life with life-threatening infections. Mutation in neutrophil elastase gene.

71
Q

What is cyclical neutropenia?

A

Rare syndrome with 3-4 week neutropenia cycles. Monocytes tend to rise as neutrophils fall.

72
Q

What are the clinical features of severe neutropenia?

A

Infections (esp in mouth or throat). Painful ulceration of mouth, throat, skin, or anus. Septicemia. Normal flora may become pathogens.

73
Q

Bone marrow bx determines what in neutropenic patients?

A

At what stage of granulopoiesis does the damage extend to.

74
Q

Monocytosis is defined as a monocyte count above what?

A

0.8x10^9/L

75
Q

What are the 6 causes of monocytosis?

A
  1. Chronic bacterial infections
  2. Connective tissue diseases
  3. Protozoan infections
  4. Chronic neutropenia
  5. Hodgkin lymphoma, AML, and others
  6. Chronic myelomonocytic leukemia
76
Q

Eosinophilia is defined as an eosinophil count above what?

A

0.4x10^9/L

77
Q

What are the 4 most common causes of eosinophilia?

A
  1. Allergic diseases
  2. Parasites
  3. Skin diseases
  4. Drug interactions
78
Q

How is hypereosinophilic syndrome diagnosed?

A

Eosinophil count >1.5x10^9/L for over 6 months and associated with tissue damage.

79
Q

What 4 tissues are primarily damaged with hypereosinophilic syndrome?

A
  1. Heart valves
  2. CNS
  3. Skin
  4. Lungs
80
Q

What is the treatment for hypereosinophilic syndrome?

A

Steroids or cytotoxic drugs.

81
Q

What is chronic eosinophilic leukemia characterized by?

A

Chronic eosinophilia with a clonal cytogenetic or molecular abnormality.

82
Q

Basophilia is characterized by a basophil count above what?

A

0.1x10^9/L

83
Q

What is the usual cause of basophilia?

A

Myeloproliferative disorder (ex. CML or polycythemia vera).

84
Q

T or F. Reactive basophil increases are sometimes seen in myxoedema, during smallpox or chickenpox infections, and in ulcerative colitis.

A

T

85
Q

What are histiocytes?

A

Myeloid-derived tissue macrophages.

86
Q

What are the 2 types of dendritic cells?

A
  1. Langerhans cells

2. Lymphocyte-derived subset for Ag presentation

87
Q

Where are Langerhans cells found?

A

Skin and mucosa.

88
Q

What are Langerhans cells characterized by?

A

Large granules called Birbeck granules seen in electron microscopy sections.

89
Q

In what disease is there a clonal proliferation of CD1a+ cells?

A

Langerhans’ Cell Histiocytosis (LCH)

90
Q

LCH affects what patient population?

A

Children in the first 3 years of life.

91
Q

What are the 3 signs of LCH?

A
  1. Hepatosplenomegaly
  2. Lymphadenopathy
  3. Eczematous skin
92
Q

In LCH, localized lesions occur where?

A

Skull, ribs, long bones, posterior pituitary (causing diabetes insipidus), CNS, GI tract, and lungs.

93
Q

The lesions seen in LCH include what cell types?

A

Langerhans cells, eosinophils, lymphocytes, neutrophils, and macrophages.

94
Q

What is Hemophagocytic Lymphohistiocytosis syndrome?

A

A rare disease characterized by increased numbers of histiocytes in the bone marrow which ingest red cells, white cells, and platelets.

95
Q

HLH syndrome is usually precipitated by what?

A

Viral (esp EBV or herpes), bacterial, or fungal infection.

96
Q

Patients with HLH syndrome present with what?

A

Fever and pancytopenia. Often with splenomegaly and liver dysfunction. The pt is often immunocompromised.

97
Q

What are the clinical features of HLH syndrome?

A

Fever, pancytopenia, multiorgan dysfunction, lymphadenopathy, hepatomegaly, splenomegaly, coagulopathy, and CNS signs.

98
Q

What is the treatment for HLH syndrome?

A

Tx of the underlying infection. Chemotherapy with etoposide, corticosteroids, cyclosporin, or rituximab.

99
Q

Sinus histiocytosis with massive lymphadenopathy is characteristic of what syndrome?

A

Rosai-Dorfman syndrome

100
Q

What are the clinical featuers of Rosai-Dorfman syndrome?

A

Painless and chronic cervical lymphadenopathy, fever, and weight loss.

101
Q

What are the 3 lysosomal storage diseases that result from a hereditary deficiency of enzymes required for glycolipid breakdown (lysosomal storage diseases)?

A
  1. Gaucher’s
  2. Tay-Sach’s
  3. Niemann-Pick
102
Q

What is Gaucher’s disease caused by?

A

Deficiency of glucocerebrosidase that results in an accumulation of glucosylceramide in the lysosomes of reticuloendothelial cells.

103
Q

Describe the 3 types of Gaucher’s disease.

A

Type 1: chronic adult type
Type 2: acute infantile neuronopathic type
Type 3: subacute neuronopathic type with onset in childhood or adolescence

104
Q

Which type of Gaucher’s disease is caused by a variety of mutations in the glucocerebrosidase gene?

A

Type 1. Single base pair substitution in codon 444 is particularly common in Ashkenazi Jews.

105
Q

What is the outstanding physical sign of Type 1 Gaucher’s disease?

A

Splenomegaly. Also: moderate liver enlargement, conjuctival deposits, osteoporosis.

106
Q

What causes the clinical manifestations seen in Gaucher’s disease?

A

Accumulation of glucocerebroside-laden macrophages in the spleen, liver, and bone marrow.

107
Q

T or F. Since Gaucher cells are metabolically active, they secrete proteins that cause secondary pathology.

A

T: pulmonary HTN, alveolar fibrosis, and cholesterol gallstones.

108
Q

Carriers of a Gaucher mutation have an increased incidence and earlier onset of what disease?

A

Parkinson’s

109
Q

Gaucher’s disease is also commonly associated with what 3 abnormalities involving blood cells?

A
  1. Anemia
  2. Leukopenia
  3. Thrombocytopenia
110
Q

How is Gaucher’s disease diagnosed?

A

Assay of white cell glucocerebrosidase and DNA analysis. Elevated levels of PARC, ACE, MIP-1-beta, and ferritin are also observed.

111
Q

How is Gaucher’s disease treated?

A

Replacement therapy of glucocerebrosidase.

112
Q

Deficiency of what enzyme causes Niemann-Pick disease?

A

Sphingomyelinase. Leads to accumulation of sphingomyelin and cholesterol in tissues.

113
Q

T or F. The majority of Niemann-Pick patients are infants who die in the first year of life.

A

T

114
Q

What are the clinical features of Niemann-Pick disease?

A

Massive hepatosplenomegaly, lung involvement, nervous system involvement, retarded physical and mental development.

115
Q

Cherry-red spots are commonly seen in the retina of infants affected with what disease?

A

Niemann-Pick disease

116
Q

T or F. Pancytopenia is a regular feature of Niemann-Pick disease.

A

T

117
Q

Marrow aspirates of patients with Niemann-Pick disease show what?

A

Foam cells of similar size to Gaucher cells.

Heme (38 decks)

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