Unit 1: Nonmalignant Leukocyte Disorders Flashcards
Congenital Defects of Leukocytes
SCID
Wiskott-Aldrich Syndrome
22q11 Syndromes
Chediak-Higashi Syndrome
Chronic Granulomatous Disease
What 3 conditions can go on to develop non-Hodgkin’s Lymphoma?
-SCID (Severe Combined Immunodeficiency Syndrome)
-Wiskott-Aldrich Syndrome (WAS)
- 22q11 Syndromes
So-called “hematopoietic variant” causes death in first few mos. of life
SCID
Pts. have few or no T cells, & B cells have abnormal function. (Also affects granulocytes.)
SCID
SCID is caused by a mutation to the_____ receptor
IL-2
SCID:
______ curative in some (but not all) cases; this disease
has been major focus of gene therapy trials in past.
BMT
-Rare sex-linked recessive mutation
-Both B- & T-cells have abnormal function.
-Boys seldom survive beyond adolescence
Wiskott-Aldrich Syndrome (WAS)
Wiskott-Aldrich Syndrome (WAS) manifests a ______ defect.
CD 43
Wiskott-Aldrich Syndrome (WAS) is characterized by…
recurrent infections, eczema, & thrombocytopenia.
What is the prognosis with 22q11 Syndromes?
Death rate high – most do not survive > 1 yr
Includes multiple immunodeficiency disorders
Involve the absence or decreased size of thymus and T-lymphs
22q11 Syndromes
______ deletion associated with cardiac
defects, developmental delays, psychiatric disorders, short stature, hypocalcemia, thrombocytopenia and large platelets, cytopenias, and increased risk of malignancy
22q11
What is the treatment for 22q11 Syndromes?
thymic tissue transplantation or T-cell transplantation
Chediak-Higashi Syndrome:
-Rare, autosomal ___________
-Patients don’t usually survive past childhood
recessive
Characterized by gigantic, fused, primary
and secondary granules
Chediak-Higashi Syndrome
Chediak-Higashi Syndrome:
Peroxidase ___________ lysosomes in granulocytes ,
monocytes, and lymphocytes.
positive
Chediak-Higashi Syndrome:
Mutation in _________ gene
CHS1 LYST
Chediak-Higashi Syndrome:
Abnormal _______ granules in platelets but usually normal sized
Dense means
dense
Dense with energy so ATP ADP serotonin and
Giant granules in all WBCs =
Chediak -Higashi
Chediak-Higashi Syndrome:
prone to….
infections and bleeding issues
Chediak Higashi Syndrome:
Granules are normal, but they ____________ , so
WBCs kill ineffectively
Pts. have recurrent infections & syndrome is eventually fatal.*
are fused together
Granular fusion in other body cells such as melanocytes affect their function, so bizarre problems
such as partial cutaneous albinism result
-Known to affect other species! (Ex., killer whales,
cats, mice, mink & cattle!)
Chediak Higashi Syndrome
-Rare, inherited (60% X-linked, 40% autosomal recessive)
-Really a syndrome representing several different genetic diseases
Chronic Granulomatous Disease (CGD)
Chronic granulomatous representing several
Chronic granulomatous diseases
Question- various defects cause
Question 2- WBC’s have special difficulty
FYI cat and bacteria don generate enough what
WBCs to have ineffective killing ability, due to inability to produce superoxide and H2O2.
WBC’s have special difficulty with catalase pos bacteria
FYI cat + bacteria don’t generate enough H2O2 to trigger MPO activity so the bacteria can fly under the radar and flourish
Chronic granulomatous diseases
Question- bacteria thus can breed inside
Phagolysosomes, causing chronic infections characterized by granuloma formation
Chronic granulomatous diseases
Question- what is a granuloma
A granuloma is a tissue accumulation of macrophages usually surrounded by lymphocytes due to unresolved inflammation
Chronic granulomatous diseases
Question- most patients experience what
Fungal and bacterial infections of the lungs, skin, lymph nodes, and liver.
Chronic granulomatous diseases
Question- neutrophil count is normal until
Infection, then increases
Chronic granulomatous diseases
Question- test for CGD
Is Nitroblue tetrazolium slide test (NBT)- no reaction form CGD neutrophils.
Normal neutrophils reduce the yellow nitroblue to a dark blue reaction
CGD cell have no
Reaction with NBT
Normal neutrophils have
Reaction with NBT
Chronic granulomatous diseases
Question- survival rate based on type of
Mutation
CGD can’t kill what type of bacteria?
catalase pos
Morphological abnormalities of leukocytes
Question- nuclear abnormalities-
Pelger huet anomaly
Twinning
Morphological abnormalities of leukocytes
Question- cytoplasmic abnormalities
- may-haggling anomaly
- Alder Reilly anomaly
- lysosomal storage diseases
Pelger-huet anomaly
Question- is what type of disorder
- Benign autosomal dominant disorder
Pelger-huet anomaly
Question- decreased what and most obvious in
Nuclear segmentation in all WBC’s and most obvious in neutrophil’s
Pelger- huet anomaly may be in what forms
Two forms
1.) bi-lobed nuclei in 55-93% of sets of heterozygotes ( peanut, dumbbell-shaped)
2.) mostly unsegmented, round nuclei in sets of homozygotes ( found in all sets and much rarer)
More common form of Pelger huet anomaly
bi-lobed nuclei in 55-93% of sets of heterozygotes ( peanut, dumbbell-shaped)
Less common form of Pelger-Huet anomaly
2.) mostly unsegmented, round nuclei in sets of homozygotes ( found in all sets and much rarer)
Pelger-Huet anomaly
Question- segs are still
N. In function and can preform phagocytosis
Pseudo Pelger- huet anomaly
Question- true pelger- huet is
Inherited and the # of affected cells is greater than pseudo
Pseudo Pelger- huet anomaly
Question- Pseudo pelger huet is acquired with=
is seen in conjunction=
Lower percentage of affected cells.
Seen in conjunction with myelodysplastic syndromes (MDS), AML, CML, HIV infections
Pseudo Pelger- huet anomaly
Question- Pseudo PHA neutrophils are
Often hypogranular, while true PHA neutrophils have normal granulation
Pelger huet=
Dumbbell Segs
Twining and associated with
A nucleus with axial symmetry ( mirror image)
Associated with malignancies and chemotherapy
Neutrophil hypersegmentation and associated with
Greater then 5 lobes
Associated with megaloblastic anemias
Neutrophil hypersegmentation can be inherited (true or false)
Inherited (rare-myelokathexis)
Cytoplasmic abnormality defects- Mary- hegglin anomaly
Question- what type of disorder is this and its characterized by what
It’s a rare autosomal dominant disorder and is characterized by leukopenia, variable thrombocytopenia, and giant plts. ( with abnormal function)
Cytoplasmic abnormality defects- Mary- hegglin anomaly
Question- what type of inclusion do Mary hegglin anomaly have and Inclusions are a combination of what
Gray blue RNA inclusions ( look like Dohles but larger) in all WBCs.
Inclusions are a combination of rods and granules that are ribosomal hence Dohle like
Cytoplasmic abnormality defects- Mary- hegglin anomaly
Question- mutation in what gene on what chromosome
MYH9 gene on chromosome 22q12-13
Cytoplasmic abnormality defects- Mary- hegglin anomaly
Question- most pts have no=
But blank show variable=
Clinical abnormalities
But 1/3 sow variable hemorrhagic problems, depending upon plt count ( approximately 40,000-80,000 plts/uL)
Alder-Reilly anomaly
Question- what type of disorder and decreased what
Is a Rare inherited disorder
Decreased degradation of mucopolysaccharides results in deposition of lipids in the cytoplasm of most cells.
Alder-Reilly anomaly
Question- structural abnormality of the blank
Myeloperoxidase gene
Alder-Reilly anomaly
Question- characterized by
Clusters of large 1 prime, non- specific, azure Philip granules resembling severe toxic granulation
Alder-Reilly anomaly
Question- these granules can be seen in
All types of WBC’s, but not toxic granulation only in neutrophils
Alder-Reilly anomaly
Question- sometimes nucleus is
Totally obscured by granules
Alder- Reilly=
Pseudo toxic gran
Alder-Reilly anomaly
Question- so how would you know this wasn’t real toxic granulation
- no neutrophila
- no Dohle bodies
- no left shift
- occurs in wrong cells ( lymph’s and monos)
Lysosomal storage disease in monocytes/ macrophages
Question- group of rare what inheritance
Rare autosomal recessive disorders
Lipidoses
Lipidoses
Question- what type of deficiency and causes what
Inherited enzyme deficiency causes inability to degrade lipids, causing enlarged cytoplasm filled with wast-stuffed lysosomes
Lipidoses
Question- adult type lipidoses mostly found in
Ashkenazi Jewish populations
Lipidoses
Question- types of disorders
There are four major disorders
- Gaucherie disease
- Niemann- pick disease
- Familial sea blue histiocytosis
Gaucher’s disease
Question- is the most common and causes accumulation of what of what spring olio is
Lipidoses
Accumulation of unmetabolized sphingolipid glucocerebrosides
Gaucher’s disease
Question- gauche cells
Large macrophages with small eccentrically placed nuclei, and cytoplasm with characteristic crinkled appearance ( “ crumpled tissue paper)
Gaucher’s disease
Question- usually seen in the
Bone marrow and spleen, and do not affect erythropoiesis
Gaucher’s disease
Question- Gaucher’s cell are blank stain positive
Periodic Acid Schiff (PAS) stain pos due to glycogen content
Gaucher’s disease
Question clinical symptoms due to accumulation of lipids in macrophage of spleen and liver
Bone pain
Splenomegaly
Gaucher’s disease
Question clinical symptoms due to splenomegaly
Leukopenia
Thrombocytopenia
Variable anemia
Gaucher’s disease
Question other symptoms
FYI
Vacuolated what
Vacuolated lymph’s and neurological symptoms
FYI three types of this disease have been identified bc they differ in severity and age of onset
Gaucher’s disease
Question treatment
Infusion with (r) glucocerebrosidase
Gene therapy also being investigated
Neumann- pick disease
Question group of disorder ( 3 types ) due to lack of
This causes eventual permanent damage
Sphingomyelin in macrophages of b.m, spleen, liver, and brain
Death usually occur by age three from damage
Niemann-pick Disease (NPD)
Question- macrophages are and are call what
Nuclei
Large with small eccentric nuclei and cytoplasm has round, uniformly sized droplets of accumulated lipid
- thus called foam cell
Familial sea blue histiocytosis
Question unknown specific what deficiency
Enzyme deficiency causes this inherited, lipid storage disease
Familial sea blue histiocytosis
Question- enlarged tissue what
However these cells can also be seen in
Tissue Macrophages in spleen, liver, and b.m. Show numerous lipid granules that stain a striking blue-green with wrights stain
Can also be seen in CML and niemann pick disease
Familial sea blue histiocytosis
Question H0 is just a
Subtype of Niemann pick disease
Familial sea blue histiocytosis
Question clinical symptoms
- Hepatosplenomegaly
- thrombocytopenia ( thus bleeding problems)
Infectious mononucleosis ( IM) is acute vs chronic, contagious or non- contagious, transmitted by
Acute, contagious, and is transmitted by saliva
IM is caused by and characterized by what type of cell
FYI by age 10
Epstein Barr virus and characterized by reactive lymph’s in p.b. And Pos heterophile test
Differentiated T-cells
FYI- by age 10, 90% of population has anti-EBV Abs
IM clinical features
Incubation
3-7 wk incubation ( teen and young adults) with 1-3 wk duration
IM clinical features
Sudden onset of
Sudden onset of fever, pharyngitis and bilateral cervical lymphadenopathy.
IM clinical features
Nonspecific what
Malaise and fatigue
IM clinical features
Usually self
Self limiting ( thus relatively benign)
IM clinical features
Complication
Rare, but can include aplastic anemia, DIC, TTP, splenomegaly, cold agglutination disease, and hepatitis
Cold agglutination disease may trigger
A transient hemolytic anemia
IM lab features
WBC count usually
Elevated to 10-30*10^9/L
IM lab features
Absolute T cell what
Lymphocytosis ( > 5*10^9/L)
IM lab features
Greater then ___ reactive lymph’s in p.b
20%
IM lab features
Also may see some p.b…
Monocytosis, but monocytes are not the definitive cell type seen here
IM lab features
Type what lymph’s predominate
Old name
Type 2 lymph’s predominate
Old name was Downey cells
IM classical serological tests
-POS for heterophile Ab
-Ex, monosure, monoquik, monospot(old), monocheck ( very popular now)
-POS for specific EBV abs
- POS for PCR for EBV Ag
Cytomegalovirus infection
Most likely if
Monospot negative
Cytomegalovirus infection
Type of
Common herpes virus
Cytomegalovirus infection
Condition closely resembles what
IM
Cytomegalovirus infection
Shows absolute reactive
Lymphocytosis ( but negative heterophile)
Cytomegalovirus infection
Virus shed into
Urine, body fluids, and even WBC’s, so transmission in adults primarily venereal
Acute infective Lymphocytosis
Viral blank
Viral (coxsackie enterovirus) or non viral
Acute infective Lymphocytosis
Usually occurs in
Children 1-10yrs
Acute infective Lymphocytosis
Contagious but
Benign and self limiting
Acute infective Lymphocytosis
Usually what
Asymptomatic but can have fever, diarrhea, upper respiratory infections, abdominal pain
Acute infective Lymphocytosis
Characteristics extreme absolute
T-cell Lymphocytosis ( > 100,000/uL usually 40,000-50,000/uL).
Acute infective Lymphocytosis
However, lymph’s are
Small, uniform and non-reactive ( little cytoplasm)
