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hematology > lecture 9 > Flashcards

lecture 9 Flashcards

1
Q

Both hereditary and acquired disorders are associated with morphologic abnormalities of:

A

neutrophils

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2
Q

what part of the cell could be defected/ abnormal?

A
  • nucleus
  • cytoplasm
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3
Q

nuclear defects include:

A
  • hyposegmentation
  • hypersegmentation
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4
Q

cytoplasmic abnormalities include:

A
  • inclusions
  • hypogranular cytoplasm
  • hypergranular cytoplasm
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5
Q

how long does it take for a blast to mature into a segmented neutrophil? and where?

(normally)

A
  • 7-10 days
  • in the BM
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6
Q

in septecemia, what happens to the BM function and nb of neutrophils?

(all details)

A
  • BM is stimulated to produce neutrophils at a faster rate
  • neutrophils are released from BM before they are completely mature
  • cytoplasm will contain more RNA and primary granules
  • residual RNA occur in small islets called Dohle bodies
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7
Q

what are the dohle bodies?

A
  • residual RNA in small islets
  • small light blue staining areas in the neutrophil cytoplasm (near cytoplasmic membrane)
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8
Q

what are the toxic granules?

A
  • primary granules which persisted in large numbers have been called by mistake “toxic granules
  • but these are in fact the promyelocyte granules which have persisted till the late stage because the neutrophil didn’t have enough time to lose them, or due to skipped divisions during the development of the neutrophil
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9
Q

what happens to the maturation time, nb of divisions, and neutrophil release under certain reactive or stressful conditions?

A
  • maturation time may be shortened
  • divisions may be skipped
  • release into the blood may occur prematurely
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10
Q

what happens when the damage to the neutrophils is more severe?

A
  • enzymes within granules are released into the cytoplasm
  • causes severe vacuolization of cytoplasm (holes) as a result of active phagocytosis
  • clear, unstained, round areas in cytoplasm
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11
Q

list the different congenital conditions of neutrophils

A
  • hereditary hypersegmentation
  • pelger-huet anomaly
  • may-hegglin anomaly
  • alder-reilly anomaly
  • chediak-higashi anomaly
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12
Q

hereditary hypersegmentation key points

A
  • autosomal dominant condition
  • hypersegmentation above 5 segments
  • rare
  • entirely harmless
  • not associated with any disease
  • seen in all neutrophils
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13
Q

what is pelger-huet anomaly?

A
  • autosomal dominant condition
  • hyposegmentation of neutrophils
  • patient could be homozygout or heterozygout
  • entirely harmless
  • neutrophils function normally
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14
Q
  1. what are the 2 states in pelger-huet anomaly?
  2. what difference do they have?
  3. what do they have common?
A
  1. heterozygout and homozygout
  2. homozygout –> nucleus rounded/ unsegmented
    heterozygout –> nucleus bilobed (all neutrophils have no more than a bilobed nucleus)
  3. in both states, chromatin is coarsely clumped
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15
Q

what causes pelger-huet anomaly?

A
  • mutation in the gene that controls the segmentation of neutrophils
  • results in failure of neutrophils to segment
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16
Q

why is it practically important to recognize pelger-huet anomaly?

A
  • so that it is not confused with a shift to the left
  • these cells are fully mature cells that look morphologically immature because they are unsegmented or hyposegmented
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17
Q

what is may-hegglin anomaly?

A
  • autosomal dominant condition
  • inherited abnormality of granulocyte and monocyte morphology
  • characterized by:
    1. large gray-blue staining inclusions in the cytoplasm
    2. variable leukopenia, thrombocytopenia, & giant platelets with low nb of granules
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18
Q

may-hegglin anomaly affects neutrophils only

(T/F)

A

false, all granulocytes and monocytes

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19
Q

what problems do people with may-hegglin could develop?

A
  • some may develop hemorrhagic problems of variable severity
  • at higher risk of infection

most people do not experience clinical symptoms

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20
Q

are the inclusions of may-hegglin anomaly similar to dohle bodies? if yes, how are they similar and how do they differ?

A

similarities:
* they are similar in appearance & composition
* they mainly consist of RNA derived from RER

differences:
* may-hegglin inclusions are larger & discrete
* they may be round or spindle-shaped
* found in large % of cells, not just neutrophils

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21
Q

RNA found in dohle bodies and May-hegglin inclusions are derived from the smooth endoplasmic reticulum

(T/F)

A

false, rough

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22
Q

what is alder-reilly anomaly?

A
  • autosomal recessive trait
  • inherited abnormality of granulocyte, monocyte, & lymphocyte morphology
  • presence of abnormally large azurophilic and basophilic granules
  • resembling severe toxic granulation in the cytoplasm
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23
Q

does the alder-reilly bodies (inclusions) affect function?

A

no

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24
Q

alder-reilly anomaly is in association with what type of disease?

A
  • storage diseases in which protein-carbohydrate complexes called mucopolysaccaride accumulate in the cytoplasm of tissues & blood cells
  • due to lack of lysosomal enzymes that break down these complexes
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25
Q

what is the chediak-higashi anomaly?

A
  • autosomal recessive condition
  • inherited abnormality of granulocyte function
  • characterized by abnormal killing
  • important anomaly but very rare
  • very serious
  • characteristic feature: granules of all granular cells tend to fuse & form large granules
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26
Q

chediak-higashi anomaly is associated with what conditions?

A
  • associated with increased susceptibility to infections and bleeding tendencies
  • normal platelet counts, but abnormal platelet function
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27
Q

how are granules fused in neutrophils, lymphocytes, and promyelocytes?

(in chediak-higashi anomaly)

A

in neutrophils:
* fusion of primary and secondary granules to form extremely coarse structures
* instead of having fine granules, we will have 10-15 huge granules

lymphocytes:
* fusion of nonspecific granules onto a single huge solitary granule

promyelocyte:
* primary granules fuse to form 3-4 clumps surrounded by vacuoles (strictly characteristic)

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28
Q

what happens to the function of granulocytes when the granules are fused?

(in chediak-higashi anomaly)

A
  • they are unable to degranulate and release their digestive enzymes when exposed to bacterial infections –> poor bacterial killing
  • children are prone to repeated bacterial infections
  • eventually die from 1 of those infections
  • who survive the recurrent infections develop an “accelerated” phase of the disease: a progressive lymphoma like disease
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29
Q

what are downy cells?
when do they occur?
what are the 3 types?

A
  • abnormal lymphocytes
  • in some disease conditions such as viral infections
  • the 3 types are:
    1. atypical lymphocyte
    2. blast-like lymphocyte with hyperbasophilic cytoplasm
    3. plasmacytoid lymphocyte
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30
Q

what congenital conditions (anomalies) have an autosomal dominant trait?

A
  • hereditary hypersegmentation
  • pelger-huet anomaly
  • may-hegglin anomaly
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31
Q

what congenital conditions (anomalies) have an autosomal recessive trait?

A
  • alder-reilly anomaly
  • chediak-higashi anomaly
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32
Q

pelger-huet is an inherited abnormality of granulocyte function

(T/F)

A

false, chediak-higashi

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33
Q

alder-reilly anomaly affects granulocytes and monocytes only

(T/F)

A

false, and lymphocytes

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34
Q

what cells does may-hegglin anomaly affect?

A

granulocytes and monocytes

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35
Q

WBC anomalies can be divided into 2 broad categories:

A
  1. quantitative or numerical anomalies
  2. qualitative or morphological anomalies
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36
Q

what is the normal range for WBC count?

A

4,000-11,000/mm^3

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37
Q

what is leukocytosis?

A
  • WBC count above normal range
  • increase in one or more cell types, or by the presence of abnormal cell types
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38
Q

leukocytosis is usually a sign of what conditions?

A
  • inflammatory response
  • infections
  • parasitic infections
  • exercise
  • epilepsy
  • emotional stress
  • pregnancy
  • labour
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39
Q

what are the 5 principle types of leukocytosis?

A
  1. neutrophilia
  2. lymphocytosis
  3. monocytosis
  4. eosinophilia
  5. basophilia
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40
Q

what is the most common form of leukocytosis?

A

neutrophilia

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41
Q

cytosis always refers to:

A

elevation in cell count

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42
Q

if WBC count drops below 4,000/mm^3, we call the condition:

A

leukopenia

(penia refers to depression in cell count)

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43
Q

decrease in neutrophils, lymphocytes, all cell types, we call these conditions:

A
  • neutropenia
  • lymphopenia
  • pancytopenia
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44
Q

does the decrease in eosinophils, basophils, or monocytes cause leukopenia?

A

no, since they are normally present in low nbs

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45
Q

if leukopenia is severe enough to result in almost complete disappearance of neutrophils, we call the condition:

A

agranulocytosis

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46
Q

what is agranulocytosis?

A
  • almost complete disappearance of neutrophils
  • extremely dangerous condition
  • person cannot react to infections
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47
Q

what cells have the greatest impact on the total WBC count?

A

neutrophils, since they normally constitute the largest % of cells

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48
Q

what is the life span of neutrophils? (from myeloblast to death)

A

9-10 days

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49
Q

the neutrophil spends its life in 3 main areas of the body:

A
  • passing from the BM
  • to peripheral blood
  • into the tissues

movement does not reverse

50
Q

neutrophil population in the BM can be subdivided into 2 groups:

A
  • mitotic pool
  • post-mitotic pool (maturation & storage pool)
51
Q

the mitotic pool refers to:

A

cells undergoing proliferation & differentiation (myeloblasts, promyelocytes, myelocytes)

52
Q

cells stay in the mitotic pool for how long? how many divisions do they undergo?

A
  • for few days
  • 4-5 divisions
53
Q

at what stage is the cell no longer capable of mitosis?

A

metamyelocyte stage

spends its time in maturation

54
Q

under certain reactive or stressful conditions, what happens to the maturation time and nb of divisions?

(+ release)

A
  • maturation time may be shortened
  • division may be skipped
  • released into the blood prematurely
55
Q

how long to cells spend in the maturation and storage pool?

A

5-7 days maturing

56
Q

what type of cells make up the post-mitotic pool?

A

fully differentiated mature neutrophils

57
Q

once in the peripheral blood, neutrophils are divided into 2 pools, what are they:

A
  • 50% of neutrophils circulate freely –> making up the circulationg pool
  • other 50% adhere to the walls of blood vessels –> making up the marginating pool
58
Q

cells in the marginating pool are not included in the WBC count

(T/F)

A

true

58
Q

cells in the marginating pool are not included in the WBC count

(T/F)

A

true

59
Q

the number of neutrophils counted in a WBC count and differential count represents 100% of the neutrophils in PB

(T/F)

A

false, represents only half the nb actually present in PB since cells in the marginal pool are not included in the WBC count

60
Q

do neutrophils in circulating and marginal pools change pools or remain in the same pool?

A

neutrophils are continually changing between the marginal and circulating pools

(marginating cells can enter circulating pool, & vice versa)

61
Q

what is neutrophilia? (>? /mm^3)

A
  • increase in the nb of neutrophils
  • > 8,000 /mm^3
62
Q

what is the ANC?
what is the formula of it?

A
  • aboslute neutrophil count (ANC) is the measure of the nb of neutrophil granulocytes present in blood
  • AC= WBC (/mm^3) x % neutrophils /100
63
Q

conditions associated with neutrophilia may be divided into 3 categories:

A
  1. physiologic
  2. pathologic
  3. hereditary
64
Q

what causes physiologic neutrophilia?

give examples of common physiologic causes (conditions)

A

caused by a shift of marginating cells to the circulating pool in relation to hormonal release
* pregnancy
* physical exercise
* emotional stress
* newborns

65
Q

physiologic neutrophilia is not characterized by any significant increase in __?

A

immature cells

66
Q

physiologic neutrophilia is transient, lasting only a few hours

(T/F)

A

true

its a very rapid phenomenon

67
Q

1 physiological cause of neutrophilia is newborns

(T/F)

A

true

68
Q

what 2 hormones causes the shift of marginating cells into the circulation

A
  1. adrenalin (epinephrine)
  2. hydrocortisone

nb of neutrophils almost double

69
Q

what causes pathologic neutrophilia?

give examples of certain conditions

A

any pathologic condition that stimulates increased marrow output of neutrophils
* infections
* inflammation
* metabolic disorders
* malignancy
* CSFs, ILs

70
Q

pathologic neutrophilia is accompanied by:

A

a shift to the left (increased % of immature cells)

71
Q

mobilization of the maturation/storage compartment can occur within days in pathologic neutrophilia (shift to the left)

(T/F)

A

false, can occur within hours

72
Q

in more severe conditions, for neutrophilia to be sustained, ____BM production must occur, up to ____as a response to ____accompanied by ____release of cells, and ____.

A
  • increased
  • fivefold
  • cytokines
  • premature
  • a shift to the left

increase BM production occurs after few days

73
Q

what is the primary WBC that responds to bacterial infections?

A

neutrophils

74
Q

what is the most common cause of pathologic neutrophilia?

specify + what bacterias

A
  • bacterial infections
  • especially pyogenic infections
  • caused by streptococci, staphylococci, pneumococci
75
Q

more moderate neutrophilic responses are characteristic of infections caused by:

A
  • bacilli
  • viruses
  • rickettsiae
  • parasites
76
Q

in acute infections, leukocyte counts are:

A

15,000-20,000/mm^3

(>50,000/mm^3 occasionally occur)

77
Q

what is a leukemoid reaction?

A

an increase in WBC count with some immature cells

78
Q

leukemoid reaction is similar to what occurs in people with:

A

leukemia (CML)

however this reaction is due to an infection/disease and not cancer

79
Q

blood counts will return to normal when the underlying pathologic condition is not treated

(T/F)

A

false, when it is treated

80
Q

all bacterial infections result in neutrophilic leukocytosis (neutrophilia)

(T/F)

A

false, not all

81
Q

some bacterial infections result in neutropenia

(T/F)

A

true

82
Q

what type of bacterial infections result in neutropenia?

A

salmonellosis and brucellosis

83
Q

what types of inflammatory processes cause neutrophilia?

list all the examples

A
  • appendicitis
  • pancreatitis
  • colitis
  • myocardial infarction
  • surgical/traumatic wounds
  • gout (joint inflammation)
  • thermal injury (burns)
  • severe hemolysis
  • tissue destruction
  • rheumatoid arthritis
  • glomerulonephritis
  • hypersensitivity reactions
84
Q

tissue destruction is caused by:

(give examples)

A
  • a wide variety of chemicals (lead, mercury)
  • drugs (lithium)
  • venoms
85
Q

what are some examples of metabolic disorders associated with pathologic neutrophilia?

what do they do?

A
  • diabetes
  • renal dysfunction/ liver disease
  • produce circulating toxic substances that stimulate a neutrophilic response
86
Q

what are some examples of malignant neoplasms?

A
  1. rapidly growing neoplasms
  2. some leukemias, such as:
    * chronic myeloid leukemia (CML)
    * chronic neutrophilic leukemia (CNL)
87
Q

in hereditary neutrophilia, neutrophil counts are only mildly increased

(T/F)

A

false, mildly to markedly increased neutrophil counts

88
Q

when the infection or inflammation is over, the____ returns to _____ over the period of ______.

A
  • marrow proliferative activity
  • baseline
  • few days
89
Q

patients with neutropenia are more susceptible to:

A
  • bacterial or fungal infections
  • without medical attention, condition may become life-threatening and deadly (neutropenic sepsis)
90
Q

what is the most common cause of leukopenia?

A

neutropenia

91
Q

neutrophil count in neutropenia is:

A

<1800/mm^3

92
Q

causes of neutropenia are divided into 2 groups, what are they?

A
  1. decreased neutrophil production by the BM
  2. increased destruction/utilization of neutrophils elsewhere in the body
93
Q

decreased neutrophil production by the BM is due to:

(briefly)

A
  • aplastic anemia
  • cancer, particularly blood cancer
  • vitamin B12 or folate deficiency
  • infections
94
Q

what is aplastic anemia?

A
  • destruction or injury to the BM
  • results in hypoplastic or aplastic marrow (few BM cells)
  • associated with decrease in all cell types
95
Q

agents capable of causing marrow suppression (aplastic marrow) include:

A
  • ionizing radiation
  • chemicals
  • cytotoxic drugs (used in the treatment of malignancy that destroy or interfere with the mitosis of proliferating cells)
  • certain drugs
96
Q

how does cancer decrease neutrophil production by BM?

A
  • marrow replacement by tumors, leukemic cell, or fibrous tissue
  • result in pancytopenia
97
Q

how does vitamin B12 or folate deficiency decrease neutrophil production by BM?

A
  • affects all highly dividing cells of the body including all blood elements
  • causes pancytopenia
98
Q

how do infections decrease neutrophil production by the BM?

A

direct BM suppression by toxins derived from the infectious agent

99
Q

increased neutrophil destruction/ utilization due to:

(briefly)

A
  • infections
  • immune reactions (isoimmune/allo-immune, autoimmune, drug induced)
  • sequestration by the spleen
100
Q

how do infections increase neutrophil destruction/ utilization?

A
  • increased passage to the tissues or increased margination
  • any infection that overwhelms the marrow’s capacity to produce adequate nb of neutrophils
  • result in neutrophils being consumed or recruited to the tissues faster than they are released by the marrow
101
Q

what is the isoimmune or allo-immune neonatal neutropenia?

A
  • fetal-maternal incompatibility involving only the neutrophils
  • results from transplacental transfer of maternal IgG antibodies directed against fetal neutrophils
  • the first born child is commonly affected
102
Q

in autoimmune neonatal neutropenia, the first child is commonly affected

(T/F)

A

false, isoimmune or allo-immune

103
Q

what is autoimmune neutropenia?

A
  • when the body identifies neutrophils as enemies and makes antibodies to destroy them
  • most common in infants and children
104
Q

acquired autoimmune neutropenia has been described and is analogous to autoimmune hemolytic anemia and as common

(T/F)

A

false, not as common

105
Q

drug induced neutropenia is associated with:

A

the use of a wide variety of drugs

106
Q

sequestration by the spleen key points

A
  • sequestration or trapping by the spleen
  • splenic enlargement may lead to neutropenia
  • relatively mild
107
Q

what are the treatments of neutropenia?

(in details)

A
  • corticosteroids (reduce antibody production)
  • antibiotics (prevent infection)
  • colony-stimulating factors: G-CSF or GM-CSF
  • BM transplantation in severe cases
108
Q

in eosinophilia, the eosinophil count exceeds:

A

700/mm^3

109
Q

what are the main causes of eosinophilia?

A
  • parasitic infestation (parasites that have a tissue cycle)
  • allergic reactions (asthma, eczema)
  • certain cancers or leukemias
  • disorder called hypereosinophilic syndrome
110
Q

what is the hypereosinophilic syndrome?

A
  • disease characterized by a persistently elevated eosinophil count (>1500/mm^3)
  • for at least 6 months
  • no recognizable cause
111
Q

in basophilia, basophilic count is above:

A

200/mm^3

112
Q

what are the main causes of basophilia?

A
  • allergic reactions
  • cancers (MPD, CML)
113
Q

what is the lymphocyte counts in lymphocytosis in:
* adults
* children
* infants

A
  • adults: >4000 per microliter
  • children: >7000 per microliter
  • infants: >9000 per microliter
114
Q

lymphocytosis is associated with what type of conditions or disorders in each of:
* children
* elderly

A

in children:
* a feature of infection

in elderly:
* lymphoproliferative diorders (chronic lymphocytic leukemia, lymphomas)
* lymphadenopathy

115
Q

what are the causes of lymphocytosis?

A
  • acute bacterial infections
  • chronic bacterial infections
  • parasitic infections
  • viral infections
  • lymphoproliferative diorders (CLL)
116
Q

Viral infections tend to raise lymphocyte count but there are 2 special conditions where the lymphocyte count becomes very important:

(name them only)

A
  • infectious lymphocytosis
  • infectious mononucleosis
117
Q

what is the infectious lymphocytosis?

A
  • viral disease of children (1-10 years)
  • small lymphocytes increase very much
  • count can become very high
  • yet all lymphocytes appear normal
118
Q

what is the infectious mononucleosis?

A
  • viral infection
  • PB contains a micture of normal lymphocytes + atypical lymphocytes + increased nb of monocytes
  • increased WBC count (12,000-15,000/mm^3)
119
Q

monocyte count in monocytosis is above:

A

900/mm^3

120
Q

monocytosis often occurs in what condition:

(general)

A

chronic inflammation

121
Q

monocytosis is encountered in several conditions, what are they?

A
  • tuberculosis & brucellosis
  • bacterial infections
  • inflammatory diseases
  • parasitic infections
  • rickettsial diseases
  • fever of unknown origin
  • recovering phase of acute bacterial infections
  • infectious mononucleosis
  • malignancy (leukemia)

hematology (10 decks)

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