8/11- Leukocytes: Benign Leukocyte Disorders Flashcards Preview

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Flashcards in 8/11- Leukocytes: Benign Leukocyte Disorders Deck (79):
1

What are 3 causes of eosinophilia?

?

2

What are 3 causes of benign neutrophilic leukocytosis?

?

3

Which of the following cells would be considered granulocytes: A. Neutrophils B. Lymphocyte C. Eosinophil D. Basophil E. Monocyte

A, C, D

4

Which of the following neutrophil functions is effective in chronic granulomatous disease?

A. Chemotaxis

B. Migration

C. Phagocytosis

D. Intracellular killing

?

5

Name four common causes of neutropenia

?

6

Name three characteristics of neutrophilic leukemoid reaction

?

7

The leukocytosis seen in peripheral blood of pts with infectious mononucleosis are composed largely of which of the following:

A. B cells

B. T cells

C. Monocytes

D. Neutrophils

E. Eosinophils

?

8

Where do granulocytes originate? Mature?

Granulocytes (BEN) grow up and mature in the bone marrow 

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9

What is this? 

Q image thumb

Neutrophil

10

Morphologic characteristics of neutrophils?

- Size

- Nucleus

- Chromatin

- Nucleoli

- Cytoplasm

- 10-15 um

- Segmented nucleus with 2-5 lobes (connected by filaments)

- Clumped chromatin

- No nucleoli

- Pale pink cytoplasm with many specific (pink to lilac) granules 

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11

What kind of granules do neutrophils contain?

Contain primary (general to granulocytes) and secondary (specific) granules

12

When do primary granules form? What do they contain?

Primary granules form at promyelocyte stage

Contain:

- Myeloperoxidase

- Lysozyme

- Elastase

13

When do secondary (specific) granules form? What do they contain?

Myelocyte and metamyelocyte stages

Contain:

- Lactoferrin

- Lysozyme

- Collagenase

14

What are the main roles of neutrophils?

- Important roles in response to infection and acute inflammation

Specific jobs:

- Chemotaxis

- Phagocytosis

- Killing of microorganisms

15

What is this? 

Q image thumb

Eosinophil

16

Morphologic characteristics of eosinophils?

- Size

- Nucleus

- Chromatin

- Nucleoli

- Cytoplasm

- 10-15 um

- Segmented nucleus with 2-3 lobes (connected by a thin filament)

- Dense and compact chromatin

- No nucleoli

- Cytoplasm filled by uniform, coarse spherical orange-red refractile granules 

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17

What kind of granules do eosinophils contain?

Also have 2 types of granules (electron dense, crystalloid containing)

Both contain:

- Peroxidase

- Major basic protein

- Histamine

- Collagenase

- Acid phosphatase

18

Functions of eosinophils?

Shared functions with neutrophils:

- Chemotaxis

- Phagocytosis

- Killing of microorganisms

Special abilities:

- Killer (effector) cells in antibody-dependent damage to parasites

- Allergic responses to foreign bodies (like catheters)

19

What is this? 

Q image thumb

Basophil

20

Morphologic characteristics of basophils?

- Size

- Nucleus

- Chromatin

- Nucleoli

- Cytoplasm

- 10-15 um

- Segmented nucleus, often obscured by granules

- Clumped chromatin

- No nucleoli

- Cytoplasm is filled with coarse, dense, dark granules 

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21

What granules do basophils contain?

- Histamine

- Heparin

22

Functions of basophils?

Along with mast cells, basophils play important roles in immediate-type hypersensitivity reactions

23

Morphologic characteristics of monocytes?

- Size

- Nucleus

- Chromatin

- Nucleoli

- Cytoplasm

- 12-20 um (larger than granulocytes)

- Round to oval, indented nucleus

- Chromatin is slightly clumped, rope-like

- No nucleoli

- Cytoplasm is gray-blue with scattered vacuoles

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24

Where do monocytes grow up and mature?

- Grow up in bone marrow

- Circulate in blood and mature into macrophages/histiocytes in the tissues

25

What is this? 

Q image thumb

Monocyte

26

What enzymes are contained within monocytes?

- Collagenase

- Elastase

- Coagulation system proteins

- Hydrolytic enzymes

27

Roles of monocytes?

- Phagocytose particulate material and kill microorganisms (like neutrophils)

Unique functions:

- Chronic inflammatory response

- Present antigen to T cells

- Destroy old RBCs in the bone marrow, spleen, and liver

- Produce cytokines important in hematopoiesis

(Growth factors such as G-CSF, M-CSF)

28

What is this? 

Q image thumb

Lymphocyte

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29

What are the main types of lymphocytes?

- B cells

- T cells

- NK cells

30

Where do lymphocytes originate/mature?

- Originate in bone marrow

- B cells mature in bone marrow

- T cells mature in thymus

31

Morphologic characteristics of lymphocytes?

- Size

- Nucleus

- Chromatin

- Nucleoli

- Cytoplasm

- 7-15 um (roughly same size as RBC)

- Round, oval, occ notched nucleus

- Diffusely dense/coarse chromatin

- Not visible nucleoli

- Cytoplasm is scant to moderate, pale to dark (reactive lymphocytes have more cytoplasm) 

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32

Functions of lymphocytes

- Chronic inflammatory response (T, B, NK)

- Humor immunity (B cells, plasma cells)

T cells have different types:

- T helper (CD4) recognize antigen and stimulate B cells

- T suppressor/cytotoxic (CD8) regulate other lymphocytes and kill tumor cells or virus-infected cells

33

Where are lymphocytes found after maturity?

- Lymph nodes and other lymphoid tissues (spleen, thymus)

- Circulate as part of immune surveillance (T more than B)

34

How WBC are analyzed in lab

- Total number

- Differential (how many of each type)

35

What are some quantitative WBC disorders?

How are they expressed?

Too many

- Leukocytosis

- Lymphocytosis

Too few:

- Neutropenia

- Leukopenia

Expressed as either % of total or absolute number (no/volume)

Can also describe in terms of a relative or absolute increase

36

What are some qualitative WBC disorders?

Function- not working well

Morphology

- Nuclear or cytoplasmic changes

- May or may not work well

- more than one cell lineage may be affected

37

Inherited WBC disorders?

(think syndromes with people's names)

- Pelger-Huet anomaly

- Fanconi anemia

- Chediak-Higashi

38

Acquired WBC disorders?

- Result of some external stimuli: infection, stress, drugs, immune

39

Reactive WBC disorders? Benign or malignant?

Reactive (benign):

- Infection

- Congenital (inherited)

- Drugs

- Immune

40

Neoplastic WBC disorders?

- Leukemias

- Lymphomas

- Myeloproliferative disorders (neoplasms)

- Myelodysplastic syndromes

41

Describe relative vs. absolute increases in WBCs in terms of numbers/percentages.

Which is more important?

Relative increase

- Overall WBC NOT high but percentage is higher than normal

Absolute increase

- WBC is high, but percentage is normal

- WBC is normal/high and percentage is high

Absolute counts are more significant

42

What are leukemoid reactions?

- What cells involved

- WBC levels

- Reactive (benign, not neoplastic) increase in WBC count (leukocytosis)

- Usually refers to granulocytes (typ neutrophils, but may be eos)

- Immature forms of 1+ cell lines in the peripheral blood (left shift)

- May resemble a form of leukemia, but is due to some other cause

- Usually WBCs > 20-30,000/mm3

- May be between 50-100,000/mm3

- Very rarely > 100,000/mm3

43

What are some causes of neutrophilia?

Reactive:

- Infections (bacterial)

- Inflammation/necrosis

- Drugs, hormones, toxins (e.g. steroids, Cushing's)

- Strong physical/emotional stimuli (trauma)

Neoplastic:

- Myeloproliferative neoplasms

44

What are some causes of eosinophilia?

- Associated with what cytokine?

- Associated with IL-5

Reactive causes:

- Infections (parasites, fungal)

- Allergy

- Drugs

- Collagen vascular diseases

- Addison's disease

Neoplastic:

- Myeloproliferative neoplasms

- Some T cell lymphomas/leukemias

45

What are some causes of basophilia?

- Rare

- Usually associated with a myeloproliferative neoplasm (Chronic myelogenous leukemia, CML)

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46

What are some causes of moncytosis?

Reactive:

- Neutropenia

- Collagen vascular diseases

- Immune disorders

- infections (viral, TB, syphilis, bacterial endocaditis)

Neoplastic

- Myeloproliferative neoplasms

- Leukemias

47

What are some causes of lymphocytosis?

- Associated with what cytokine?

- Associated with IL-7

Reactive:

- Infections (viral, pertussis, TB, rickettsial)

- Infectious mononucleosis (EBV, CMV)

- Autoimmune disorders

- Drugs

Neoplastic:

- Lymphomas/leukemias

48

Case)

- 14 yo female with fever, sore throat, malaise, cervical lymphadenopathy

CBC:

- WBC = 18.1 K

- Hct = 45%

- Plts = 305K

- Differential: 35% neutrophils, 58% lymphocytes, 12% monocytes

Differential diagnosis?

- Pt has lymphocytosis

DDx:

Reactive

- Lymphocytic leukemoid reaction- infectious mononucleosis

Neoplastic: leukemia

- Acute lymphoblastic leukemia

- Chronic lymphocytic leukemia

49

What would be seen on PBS with these possible causes of lymphocytosis:

- Lymphocytic leukemoid reaction- infectious mono:

- Acute lympohblastic leukemia:

- Chronic lymphocytic leukemia:

- Lymphocytic leukemoid reaction- infectious mono: reactive lymphocytes

- Acute lympohblastic leukemia: blasts

- Chronic lymphocytic leukemia: mature neoplastic B lymphocytes

50

What does this show? Details?

What does it suggest in terms of our previous DDx? 

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Reactive ("atypical") lymphocytes

- Large

- Low N/C ratio (lots of cytoplasm)

- +/- coarse chromatin, nucleoli

- Heterogenous population

This is infectious mononucleosis

(pt then had positive Monospot test and EBV serologies)

51

What are the clinical features and lab date of infectious mononucleosis?

Clinical features:

- Adolescents and young adults

- Fever, tonsillitis

- Cervical adenopathy

- Mild hepatitis, moderate splenomegaly

Lab data:

- Mono-spot test: heterophil anti-sheep RBC Abs

- EBV titers: IgM, IgG

- Absolute lymphocytosis with atypical lymphs

- May see WBC as high as 80E9 C/L

52

What is neutropenia (defined/levels)/

- Blood absolute neutrophil count less than 2 standard deviations below the normal population mean

- Absolute neutrophil count (ANC) < 1000 is worrisome; ANC < 500 is most serious

53

Consequences of neutropenia?

Increased risk of bacterial or fungal infections

- Risk inversely proportional to degree of neutropenia

- Chronic gradual process less dangerous than acute drop in counts Ulceration of oral cavity

- Also skin, GI, GU tract Symptoms related to infection

- Fever, chills, malaise

54

Pathogenesis behind neutropenia?

Production problem

- Reduced or ineffective production in the bone marrow

- Congenital or acquired

Accelerated removal from the circulation

- Immune – antibody mediated

- Splenic sequestration

- Increased utilization – overwhelming infection

55

Causes of neutropenia?

Inherited:

- Congenital neutropenic syndromes

- Cyclic neutropenia Reactive:

- Nutritional deficiencies (B12, folate)

- Drugs

- Severe infections

- Autoimmune

Neoplastic:

- Acute leukemia

- Myelodysplastic syndrome

- Large granular lymphocyte (LGL) leukemia

- Tumor (or other infiltrative process) in the bone marrow

56

What is the mechanism behind drugs causing neutropenia?

Marrow suppression as expected side effect: drugs directly toxic to marrow

- Chemotherapy agents (antimetabolites, alkylating agents) Idiosyncratic reactions

- Marrow or granulocyte suppression

- Immunologically mediated

57

What are some characteristics of congenital neutropenias?

- Rare inherited syndromes (e.g. Kostmann Syndrome or agranulocytosis: AR, elastase mutation)

- May be primary problem or just one of many features of another syndrome

- Usually present in infancy or childhood

58

How should neutropenia be managed in acute and chronic situations?

Acute (often have signs of fever or infection)

- Supportive measures

- CBC, blood cultures (fluids, broad spectrum antibiotics)

- Consider bone marrow exam if etiology not apparent

Chronic (often asymptomatic)

- Serial CBCs to determine if chronic or cyclic

- Morphologic examination of blood and bone marrow

- Test for immune rheumatological or nutritional causes [Whether acute or chronic, some etiologies will respond to G-CSF therapy]

59

Causes of leukopenia?

Monocytopenia

- Aplastic anemia

- Hairy cell leukemia

Lymphopenia

- HIV

- Immune deficiency

- Infections

- Drugs (immune suppressive agents)

- Autoimmune diseases

- Malnutrition

60

What are some broad characteristics of qualitative WBC changes?

- May be inherited or acquired

Inherited:

- Usually part of a syndrome

- May or may not affect WBC function

- Some associated with increased infections (Chediak Higashi)

Acquired:

- Much more common than inherited

- May be reactive or neoplastic

- Reactive: infecitons, trauma, pregnancy, drugs

- Neoplastic: myelodysplasia, myeloproliferative neoplasms, acute myelogenous leukemia

61

What are some toxic changes of WBCs?

- Toxic granulation

- Dohle bodies

- Vacuoles in cytoplsam

- Leukocytosis (sometimes leukopenia)

- "left shift"- circulating bands and immature myeloid precursors in addition to mature granulocytes

62

What is this? Describe 

Q image thumb

Dohle bodies (a toxic change)

- Rounded, oval, or rod-shaped pale grayish-blue inclusions in neutrophil ctoplasm (1-5 um long)

- Represents stacks of RER or denatured aggregates of free ribosomes

63

Dohle bodies are associated with what conditions?

- Normal pregnancy

- infections

- Pts with various neoplasms

- Severe burns

- Trauma

- G-CSF therapy

- Kwashiorker

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64

What is this?

Q image thumb

Toxic granulation (a toxic change)

- Fine or coarse reddish-violet granules scattered throughout neutrophil cytoplasm

- Primary (azurophilic) granules

- Result from altered maturation of neutrophil granules

65

Toxic granulation is associated with what conditions?

- Severe infections

- Other inflammatory states

- Pregnancy

- Trauma

- Burns

- G-CSF therapy 

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66

What is this? 

Q image thumb

Vacuoles in the cytoplasm (a toxic change)

- Clear round spaces in cytoplasm

- Sites of digestion of phagocytized material

- Occur in many cases of septicemia

67

Vacuoles in the cytoplasm is associated with what conditions?

- Infections

- Acute alcohol poisoning

- Carnitine deficiency

- Kwashiorkor

- (may be an artifact of prolonged storage in EDTA)

68

What are these? 

Q image thumb

The "toxic changes"

69

What is seen here? When is it seen? 

Q image thumb

Hyposegmentation

- Inherited: Pelger-Huet anomaly

- "Pseudo Pelger-Huet" change: associated with myelodysplasia and AML, drugs, infection (mycoplasma, HIV), rarely in bone marrow transplant pts

70

What is seen here?

Q image thumb

Hypersegmentation (6 or more nuclear lobes)

71

What does hypersegmentation typically mean?

Associated with what?

Usually means megaloblastic myelopoeisis

- Most unequivocal morphologic finding (may precede RBC changes)

- Impaired DNA synthesis

Associations:

- Nutritional deficiencies (B12, folate)

- Alcoholism

- Drugs (corticosteroids, folate antagonists)

- Rarely in renal insufficiency, sepsis, MDS, MPN

72

What are the main duties of the neutrophil?

- Chemotaxis – follow the scent

- Migration – move out of the blood, into & through the tissues

- Phagocytosis – bind & ingest the offending agent

- Killing & digestion of said offending agent (organisms/foreign materials)

**Impairment in 1 or more of these activities results in increased infections**

73

What is chronic granulomatous disease (CGD)?

Problem with killing and digestion

- Defective oxidative respiratory burst (can't make H2O2- hydrogen peroxide)

- Affects neutrophils and monocytes

- Especially catalase positive microorganisms (live happily within neutrophils, safe from Abx: Staph, Aspergillus, Candida)

Body makes granulomas to help fight/contain the bugs it can't kill

- Recurrent abscesses, infections

Rare disorder

- Most cases are X-linked recessive

74

How can CGD be diagnosed?

Measuring respiratory burst

75

Treatment for CGD?

Only curative measure is bone marrow transplant

Aggressive supportive measures:

- Cultures & radiographic imaging as soon as infection suspected

- Drainage of abscesses

- Prolonged use of antibiotics

76

What is seen here? Describe the condition

Q image thumb

Pelger-Huet Anomaly

- Autosomal dominant inheritance

- Incidence 1 in 5000

- Marked reduction in number of neutrophil lobes

- Usually normal neutrophil number & function

- Heterozygotes – most patients [2 lobes (pince-nez appearance) in 50-75% of their neutrophils]

77

What is seen here? Describe the condition

Q image thumb

May-Hegglin Anomaly

- Rare

- Autosomal dominant inheritance

- MYH9 disorder

- Intracytoplasmic inclusions in granulocytes and monocytes (Look like giant Döhle bodies)

- Giant platelets

78

What is seen here? Describe the condition

Q image thumb

Chediak-Higashi Syndrome

- Rare

- Autosomal recessive

- Reduced & abnormally large granules (Giant, often round; Red, blue, or greenish-gray)

- Partial oculocutaneous albinism

- Recurrent infections

79

What is seen here? Describe the condition 

Q image thumb

Alder-Reilly Anomaly

- Also known as Alder’s anomaly

- Autosomal recessive

- Seen in mucopolysaccharidoses

- Abnormally course azurophilic granules in neutrophils and sometimes lymphocytes & monocytes