NONMALIGNANT LEUKOCYTE DISORDERS. Changes in leukocyte concentration and morphology often reflect...
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Transcript of NONMALIGNANT LEUKOCYTE DISORDERS. Changes in leukocyte concentration and morphology often reflect...
NONMALIGNANT LEUKOCYTE DISORDERS Changes in leukocyte concentration
and morphology often reflect disease processes and toxic challenge.
The type of cell affected depends upon its primary function: In bacterial infections, neutrophils are
most commonly affected In viral infections, lymphocytes are most
commonly affected In parasitic infections, eosinophils are most
commonly affected.
NONMALIGNANT LEUKOCYTE DISORDERS Neutrophil disorders
The peripheral neutrophil concentration depends upon Bone marrow production and release The rate of neutrophil movement into the tissues The proportion of circulating to marginating
neutrophils Most benign quantitative abnormalities occur in
response to physiologic or pathologic processesNeutrophilia – an increase in neutrophils
Immediate – may occur without tissue damage or other pathologic stimulus. Results from a simple redistribution of cells from the
marginal pool to the circulating pool
NONMALIGNANT LEUKOCYTE DISORDERS
May occur after violent exercise, epinephrine administration, anesthesia, or anxiety
Is also called shift neutrophilia Acute neutrophilia – this occurs 4-5 hours after a
pathologic stimulus Results from an increased flow of cells from the
bone marrow to the peripheral blood Bands and metamyelocytes may be seen
Chronic neutrophilia – this follows acute neutrophilia The bone marrow starts to throw out younger and
younger cells (a shift to the left)
NONMALIGNANT LEUKOCYTE DISORDERS
Conditions that are associated with neutrophilia are: Bacterial infections (most common cause)
This usually causes an absolute neutrophilia (10-19 x109/L)
In severe infections, the bone marrow stores may be depleted and this can result in neutropenia (typically seen in typhoid fever and brucellosis)
Tissue destruction or drug intoxication (tissue infarctions, burns, neoplasms, uremia, gout)
NONMALIGNANT LEUKOCYTE DISORDERS
Leukemoid reaction – this is an extreme neutrophilia with a WBC count > 30 x 109/LMany bands, metamyelocytes, and myelocytes
are seenOccasional promyelocytes and myeloblasts may
be seen.This condition resembles a chronic myelocytic
leukemia (CML), but can be differentiated from CML based on the fact that in leukemoid reactions:
There is no Philadelphia chromosomeThe condition is transientThere is an increased leukocyte alkaline
phosphatase score (more on this later)Leukemoid reactions may be seen in tuberculosis,
chronic infections, malignant tumors, etc.
NONMALIGNANT LEUKOCYTE DISORDERS
Leukoerythroblastic reaction – in this condition nucleated RBCs and neutrophilic precursors are both found in the peripheral bloodThe WBC count may be increased, normal, or
decreasedThis is associated with myelopthesis (proliferation
of abnormal elements in the bone marrow) Reactive states
With hemorrhage or hemolysis of RBCs, there is increased production of RBCs in the bone marrow and sometimes the granulocyte production also increases.
Corticosteroid therapy
NONMALIGNANT LEUKOCYTE DISORDERS
Neutropenia – this may result from Decreased bone marrow production
The bone marrow will show myeloid hypoplasia with a decreased M:E ratio
The bone marrow storage pool, and peripheral and marginating pools are all decreased
Immature cells may be thrown into the peripheral blood and those younger than bands are ineffective at phagocytosis. This can lead to overwhelming infections.
This may be due to stem cell failure, radiotherapy, chemotherapy, or myelopthesis.
Ineffective bone marrow production The bone marrow will be hyperplastic Defective production is seen in megaloblastic anemias
and myelodysplasic syndromes where the abnormal cells are destroyed before they are released from the bone marrow
NONMALIGNANT LEUKOCYTE DISORDERS
Increased cell loss Early in an infection there is a transient decrease
due to increased movement of cells into the tissues Could be due to an immune mechanism such as
production of anti-leukocyte antibodies or PNH Hypersplenism Pseudoneutropenia – alterations may occur in the
circulating to marginating pools. This may be seen in: Early in any infection: Viral infections Bacterial infections with endotoxin production Hypersensitivity reactions
NONMALIGNANT LEUKOCYTE DISORDERS
Periodic or cyclic – is an inherited autosomal dominant disorder in which every 21-30 days there are several days of neutropenia with accompanying infections. This is followed by asymptomatic periods.
Familial – this is benign, chronic, and mild with rare clinical symptoms
Infantile genetic agranulocytosis – this is a rare, congenital, and often fatal disorder in which there is defective bone marrow production of neutrophils.
False – blood drawn into EDTA in which the cells stick to the side of the tube; disintegration of cells due to age from sitting in a tube for too long; cell clumping
NONMALIGNANT LEUKOCYTE DISORDERS
Morphologic and functional abnormalities of neutrophils Acquired, morphologic – these are reactive, transient
changes accompanying infectious states. They include Toxic granulation Dohle bodies Cytoplasmic vacuoles May also see ingested microorganisms
NONMALIGNANT LEUKOCYTE DISORDERS
Inherited functional and/or morphological abnormalities Pelger- Huet Anomaly – this is a benign, inherited,
autosomal dominant abnormality in which the neutrophil nucleus does not segment beyond the bilobular stage (“Prince-nez cells”). The cells may sometimes resemble bands, but the
chromatin is more condensed (mature). The cells function normally. Acquired or pseudo Pelger-Huet Anomaly is seen in
myeloproliferative and myelodysplastic states
NONMALIGNANT LEUKOCYTE DISORDERS
Alder-Reilly Anomaly – in this disorder all leukocytes contain large, purplish granules (due to partially degraded protein-carbohydrates) in the cytoplasm, but the cells function normally. This is seen in Hurler’s and Hunter’s syndromes in which
there is an incomplete breakdown of mucopolysaccharides
NONMALIGNANT LEUKOCYTE DISORDERS
Chediak-Higashi Anomaly – This is a rare autosomal recessive disorder in which
abnormal lysosomes are formed by the fusion of primary granules. These are seen as grayish-green inclusions
The cells are ineffective in killing microorganisms and affected individuals often die early in life from pyogenic infections.
NONMALIGNANT LEUKOCYTE DISORDERS
May-Hegglin Anomaly This is a rare, autosomal dominant disorder in which
the leukocytes contain large basophilic inclusions containing RNA that look similar to Dohle bodies.
It can be differentiated from an infection because toxic granulation is not seen.
The patients also have giant platlets that have a shortened survival time. Because of this, patients may have bleeding problems, but they usually have no other clinical symptoms
NONMALIGNANT LEUKOCYTE DISORDERS
Chronic granulomatous disease This is a lethal, sex-linked disorder affecting the
function of the neutrophil The neutrophil can function in phagocytosis, but it
cannot kill microorganisms because the cells have a defect in the respiratory burst oxidase system.
Affected individuals have chronic infections with organisms that do not normally cause infections in normal individuals
Myeloperoxidase deficiency This is a benign, autosomal recessive disorder
characterized by a lack of myeloperoxidase in the neutrophils
NONMALIGNANT LEUKOCYTE DISORDERS
Affected individuals may have occasional problems with Candida infections, but usually they have no problems with infections because they have other mechanisms to kill microorganisms
Leukocyte adhesion deficiency This is a rare, autosomal recessive disorder
characterized by the absence of leukocyte cell surface adhesion proteins
Because of the lack of the adhesion molecules, the leukocytes have functional defects in:ChemotaxisPhagocytosisRespiratory burst activationDegranulation
Affected individuals have frequent bacterial and fungal infections and mortality in childhood is high.
NONMALIGNANT LEUKOCYTE DISORDERS Eosinophil disorders
Eosinophilia may be found in Parasitic infections Allergic conditions and hypersensitivity reactions
Eosinophils have low affinity IgE Fc receptors and may be important in modulating immediate hypersensitivity reactions
Cancer Chronic inflammatory states
NONMALIGNANT LEUKOCYTE DISORDERS Basophil disorders
Basophilia Is associated with chronic myeloproliferative disorders
(discussed later) Inflammatory bowel disease Radiation exposure
Monocyte quantitative and qualitative disorders Associated with malignancies
NONMALIGNANT LEUKOCYTE DISORDERS
Inherited abnormalities of neutrophils are also seen in monocytes because they originate from a common stem cell: Chronic granulomatous disease (defective respiratory
burst) Chediak Higashi (abnormal lysosomes caused by
fusion of primary granules) Alder Reilly Anomaly (large purple-blue granules)
NONMALIGNANT LEUKOCYTE DISORDERS Macrophage disorders
Lipid storage diseases – the cells are unable to completely digest phagocytosed material Gaucher’s disease – is a recessive autosomal disorder
with a deficiency of glucocerebroside There is an accumulation of lipid in macrophages in
lymphoid tissue This leads to liver and spleen enlargement and
destructive bone marrow lesions Death occurs early in life
NONMALIGNANT LEUKOCYTE DISORDERS
Niemann-Pick Disease – This is an autosomal recessive disorder with a defect in sphingomyelinase It is often fatal by the age of 3
Tay Sachs and Sandhoffs diseases – these are autosomal recessive disorders with deficiencies in - hexosaminidase and and - hexosaminidase, respectively Gangliosides and other glycolipids and
mucopolysaccharides accumulate in tissues, especially in the CNS.
This is usually fatal by the age of 4 Fabry’s, Wolman’s, and Tangier are examples of other
lipid storage diseases
NONMALIGNANT LEUKOCYTE DISORDERS
Lymphocyte disordersAcquired, quantitative
Is usually a self-limited reactive process to infection or inflammation
Both B and T cells are affected Function is normal, though the morphological
process may be heterogenous With intense proliferation, may have
lymphadenopathy or splenomegaly
NONMALIGNANT LEUKOCYTE DISORDERS
Lymphocytosis – may be relative (secondary to neutropenia) or absolute (usually seen in viral infections); if absolute it may or may not be accompanied by a leukocytosis Infectious mononucleosis (IM) –
This is caused by Epstein-Barr virus infecting B lymphocytes.
The infected B cells may eventually be killed by cytotoxic T cells, though some will continue to harbor the virus in a latent infection.
The reactive lymphocytes seen in the peripheral smear are cytotoxic T cells
The lymphocytosis is accompanied by a leukocytosis
NONMALIGNANT LEUKOCYTE DISORDERS
Cytomegalovirus infectionLeukocytosis with absolute lymphocytosis
Infectious lymphocytosisUnknown etiologyLeukocytosis with absolute lymphocytosis 60-97% normal appearing lymphocytesThe increased lymphocytes are mainly T lymphs
Bordetella pertussis infectionLeukocytosis with an absolute lymphocytosisDue to a redistribution of T lymphocytes from the
tissues to the circulationLymphocytes are small, normal appearing
lymphocytes
NONMALIGNANT LEUKOCYTE DISORDERS
Lymphocytic leukemoid reaction – Peripheral smear shows increased lymphocytes with
younger lymphocytes being seen Can occur with tuberculosis, chickenpox and the viral
diseases discussed above Plasmocytosis
Plasma cells are rarely seen in the peripheral blood, but they may be found under conditions of intense immune stimulation
Lymphocytopenia – caused by stress, drugs, irradiation, and some diseases
NONMALIGNANT LEUKOCYTE DISORDERS
Congenital qualitative or quantitative disorders – may affect both T and B cells or only one cell type. Most will severely compromise the immune system Severe combined immunodeficiency system
(SCIDS) This is a heterogenous group of disorders in which
both B and T cells are profoundly deficient In some cases there is no rearrangement of the B
cell and T cell receptor genes to produce immunocompetent cells
A bone marrow transplant or gene therapy are the only effective treatments
NONMALIGNANT LEUKOCYTE DISORDERS
Wiskott-Aldrich Syndrome Is a sex-linked progressive disorder characterized by
Eczema Thrombocytopenia Immunodeficiency due to progressive decrease in T cell
immunity There is also an intrinsic B lymphocyte abnormality
resulting in an inability to respond to polysaccharide antigens
Most children die before the age of 10 from bleeding and infections
Treatment is a bone marrow transplant
NONMALIGNANT LEUKOCYTE DISORDERS
DiGeorge syndrome This is characterized by absence or aplasia of the
thymus and parathyroid gland This results in decreased T lymphocytes and death
in the first year without thymic grafts X linked agammaglobulinemia
This is characterized by a block in B lymphocyte maturation leading to a decrease in B lymphocytes and no plasma cells
There is decreased IgM, IgA, and IgG Treatment is monthly injections with gammaglobulin
to prevent infections Ataxia telangiactasia
This is a cell mediated immune defect with thymic hypoplasia or dysplasia and depletion of T cells