WBC Flashcards
• Affects both cellular and humoral immunity
• Patients exhibits : ⇣ T cells, poorly functioning B cells,
hypogammaglobulinemia
• Gamma chain deficiency : mutations in IL2RG gene
(IL 2,4,7,9,15,21)
Severe Combined Immunodeficiency disorder (SCID)
• X linked disease
➢Wiskott-Aldrich Syndrome (WAS)
Caused by one of 400 mutations in the WAS gene : (⇣ levels of
WASp proteins)
➢Wiskott-Aldrich Syndrome (WAS)
⇣ B cells, T, NK cells, neutrophils, monocytes are dysfunctional
Wiskott-Aldrich Syndrome (WAS)
• Absence or decreased size of thymus
• Low number of T lymphocytes
22q11 Syndromes
✓DiGeorge Syndrome
✓Sedlackova syndrome
22q11 Syndromes
✓Caylor cardiofacial syndrome
✓Shprintzen syndrome
✓Conotruncal anomaly face syndrome
22q11 Syndromes
• Antibody deficiency
Bruton tyrosine kinase Deficiency
mutation in the CHS1 LYST gene on chromosome 1q42.1-2 that encodes
for a protein that regulates the morphology and function of LYSOSOME-related organelles.
Chédiak – Higashi Syndrome
Inclusions that resembles the fused lysosomal granules in CHS
Pseudo Chédiak – Higashi
Congenital neutropenia (CN)
Low neutrophil count
Congenital defects of phagocytes
• defects of motility
• inability of neutrophils and monocytes to move from circulation to the site of inflammation (called extravasation)
Leukocyte Adhesion Disorders
only curative
treatment of Leukocyte Adhesion Disorders
Hematopoietic stem cell transplant
Types of Leukocyte Adhesion Disorders:
LAD I, II, III, SDS
Defects of respiratory burst
Chronic Granulomatous disease (CGD)
• caused by mutations in genes responsible for proteins
that make up the reduced form of (NADPH) oxidase
• patients experience life-threatening catalase-positive bacterial and fungal infections
Chronic Granulomatous disease (CGD)
warts, hypogammaglobulinemia, infections, and myelokathexis syndrome
WHIM syndrome
patients experience recurrent bacterial infections and are highly susceptible to human papillomavirus (HPV) infection, which leads to NEVER, which can be widespread and resistant
to treatmen
WHIM syndrome
characteristic spectacle-like (“pince-nez”) morphology with
the nuclei attached by a thin
filament
Pelger-Huët Anomaly
• decreased nuclear segmentation and distinctive coarse chromatin clumping pattern
• affects ALL leukocytes
• mutation in the lamin beta-
receptor gene.
Pelger-Huët Anomaly
• associated with severe bacterial infections, HIV, tuberculosis, and mycoplasma pneumonia
Pseudo- or Acquired Pelger-Huët Anomaly
NUMBER OFCELLS AFFECTED>68%TYPES OF WBC AFFECTED
: ALL WBC LINEAGES
(TRUE) Pelger Huët Anomaly
NUMBER OF
CELLS AFFECTED:
<35
TYPES OF WBC AFFECTED:
Neutrophil only
PSEUDO PHA
granulocytes with large, darkly
staining metachromatic cytoplasmic
granules (large azurophilic granules)
Alder-Reilly Anomaly
T/F: Leukocyte function is affected in
Alder-Reilly
FALSE; NOT
characterized by variable:
•thrombocytopenia
•giant platelets
•large Döhle
body-like inclusions in
neutrophils, eosinophils,
basophils, and monocytes
May-Hegglin
Anomaly
What gene is mutated in
chromosome mutation in the on chromosome 22q12-13.3
MYH9 gene
Enumerate Lysosomal Storage
Disorders
Mucopolysaccharides, Gaucher’s disease, Niemann Pick Disease
deficient activity of an enzyme necessary for the deg- radation of
dermatan sulfate, heparan sulfate, keratan sulfate, and/or chondroitin sulfate
Mucopolysaccharidoses
the most common of the lysosomal lipid storage diseases?
Gaucher’s Disease
defect or deficiency in the catabolic enzyme beta-glucocerebrosidase
Gaucher’s Disease
Gaucher Disease has three subtypes. What is the most common subtype?
Subtype 1
deficiency of lysosomal hydrolase enzyme acid SPHINGOMYELINASE
Niemann-Pick Disease
neutrophils GREATER than ______ in adults or ____ in children
7.0x10^9/L and 8.5x10^9/L
- Neutrophilia
a decrease in the Absolute Neutrophil Count to less than ____ in white adults or ____ in
black adults
2.0x10^9/L or 1.3x10^9/L
-Neutropenia
Neutrophilia is can occur as a result of ______ shift in neutrophils
catecholamine-induced
Give the diagnostic values of the following:
Eosinophilia, and Eosinopenia
greater than 0.4x10^9/L
less than 0.09x10^9/L
What WBC is increased when a patient has chronic myeloid leukemia, allergic rhinitis, hypersensitivity to drugs or food, chronic infections, hypothyroidism,
chronic inflammatory conditions, radiation therapy, and bee stings?
Basophils
Basophilia is suspected when absolute basophil count greater than _____?
0.15x10^9/L
Diagnostic value for Monocytosis and Monocytopenia?
Monocytosis: greater than 1.0x10^9/L in adults and greater than 3.53x10^9/L in neonate
Monocytopenia: absolute monocyte count of less
than 0.2x10^9/L
Lymphocytosis vs Lymphocytopenia
Lymphocytosis: CHILDREN- greater than 10.0x10^9/L, whereas in ADULTS it is defined as a count greater than 5.0x10^9/L
Lymphocytopenia: less than 2.0 x10^9/L, whereas in adults it is de- fined as a count less than 1.0x10^9/L
Lymphocytosis vs Lymphocytopenia
Lymphocytosis: CHILDREN- greater than 10.0x10^9/L, whereas in ADULTS it is defined as a count greater than 5.0x10^9/L
Lymphocytopenia: less than 2.0 x10^9/L, whereas in adults it is de- fined as a count less than 1.0x10^9/L
first sign of recovery after
myelosuppression
Monocytosis
contagious illness caused by a virus called Epstein-Barr virus (EBV) also called as “kissing disease”
Infectious Mononucleosis
In Epstein-Barr virus (EBV) infection, there is typically an increase in the number of white blood cells called _____, specifically _____.
lymphocytes specifically B lymphocytes
General characteristics of Myelogenous leukemia (non-lymphocytic leukemia)
• Myeloperoxidase : positive (+)
• Sudan Black B : positive (+)
Presence of Auer rods
• Most common type of leukemia in adults
Acute Myelogenous Leukemias (AML)
• Based on CYTOGENETICS and
Molecular studies
• At least 20% blasts in bone marrow
to diagnose AML
WHO
• Based on MORPHOLOGY and
cytochemistry
• Based on Romanowsky-Stained
smears
• Pseudo-pelger-huet cells in the
granulocytic cell line
• Auer rods
French-American-British
(AML, Minimally Differentiated)
MO
● Blasts having CD13, CD33, CD34 and CD117
● NO EVIDENCE OF CELLULAR MATURATION of Blasts
● Auer Rods (-), Myeloperoxidase (-), Sudan Black B (-)
● Less than 5% of All AML
● Patients are usually infants or older adults
M0 (AML, Minimally Differentiated)
M1
(AML, Without Maturation)
● Blasts having CD13, CD33, CD34 and CD117 similar with those of M0
● 90% of Cells in BM are BLASTS
● Found in All Age Groups with Highest Incidence in Adults
● Has No Male or Female Predominance
M1 (AML, Without Maturation)
● Nuclear:Cytoplasmic Maturational Asynchrony
○ Morphologically - Nucleus appears more immature than Cytoplasm
○ Functionally - Leukemic Blasts exhibits Phagocytosis w/c is a property only of a Mature WBC
M1 (AML, Without Maturation)
● Auer Rods (+), Myeloperoxidase (+), Sudan Black B (+)
● Chloroacetate Esterase (+), Acetate Esterase (-)
M1 (AML, Without Maturation)
● Greater than 20% Type I and II Blasts in Bone Marrow
○ At least 10% Granulocyte @ Various Stages of Maturation
● Distinguished from M1 by Presence of Granulocytic Cells At or Beyond
the Promyelocytic Stage of Maturation
● Characteristic GINGIVAL BLEEDING
M2 (AML, With Maturation)
● Pseudo-Pelger-Huet (+) - Rod-Shaped or Dumbbell-Shaped or
Nonsegmented Nuclei
● Hypogranular Neutrophils (+) - Leads to Deficient Phagocytosis,
Deficient Microbial Killing and Deficient Chemotaxis
● Auer Rods (+), MPO (+) and SBB (+)
● Aspects of DYSPLASIA are present
M2 (AML, With Maturation)
● AKA Hypergranular PROmyelocytic Leukemia
● Found in all age groups similar to M1 and M2
● Greater Predilection for Males
M3 (Acute Promyelocytic Leukemia)
APL
● Frequently more associated with Disseminated intravascular coagulopathy (DIC)
● Abnormal Promyelocytes with Heavy Granulation
● Presents with LEUKOPENIA
● Auer Rods (+) and Intensely Positive for MPO and SBB
● Faggot Cells (+)
● RENIFORM or Bilobed Nuclei
M3 (Acute Promyelocytic Leukemia)
(Microgranular Promyelocytic Leukemia)
M3m
● numerous granules present but can only be detected by electron
microscopy hence the term “MICROGRANULAR”
● Has WORSE Prognosis than M3 due to Initial High Blast Counts
M3m (Microgranular PROmyelocytic Leukemia)
M3m (Microgranular Promyelocytic Leukemia) is caused by a ________
Chromosomal Translocation t(15;17)
M4 (Acute Myelomonocytic Leukemia) AKA
Naegeli Monocytic Leukemia
● Positive for Myeloid Antigens - CD13 and CD33
● Auer Rods (+), MPO (+), SBB (+), Specific and Non-Specific Esterases (+)
M4 (Acute Myelomonocytic Leukemia)
M4 (Acute Myelomonocytic Leukemia) are POSITIVE for Monocytic Antigens - GIVE THE 6 ANTIGENS
CD4, 11b, 11c, 14, 36, 64
● Lysozyme - Muramidase > contained in LARGER amounts in Monocytes > excreted in large amounts in URINE when there is what kind of leukemia?
M4 (Acute Myelomonocytic Leukemia)
Diagnostically Important for M4 Leukemia
- 3x the Upper Limit is Significant
Serum or Urine Lysozyme
● Caused by a Problem in Chromosome 16
M4 (Acute Myelomonocytic Leukemia)
M4eo specific name
(Acute Myelomonocytic Leukemia w/ Eosinophilia)
● Increased Marrow Eosinophils
● Cells exhibit Large Basophilic Granules mixed with Smaller
Eosinophilic Granules
M4eo (Acute Myelomonocytic Leukemia w/ Eosinophilia)
● Uniquely exhibits Distinct Chloroacetate Esterase (+) and
PAS (+) which differentiates it from
normal eosinophils
M4eo
M4eo
Chloroacetate Esterase +/-
PAS +/-
BOTH POSITIVE
● AKA Schilling Leukemia
M5 (Acute Monocytic Leukemia)
● Presents w/ Highest Incidence of Organomegaly and Organ
Involvement of all AMLs
● Greater than 80% of Marrow Cells are Monoblasts, Promonocytes or Monocytes
M5 (Acute Monocytic Leukemia)
● Auer Rods (+), MPO (-), SBB (-), Specific Esterase (-)
Associated with problems in Chromosome 11, t(9;11)
M5 (Acute Monocytic Leukemia)
M5a vs M5b
M5a (Poorly Differentiated) and M5b
(Well Differentiated)
● Characterized by Large Blast Cells with Delicate, Lacy Chromatin in both blood and bone marrow
○ 1-3 Large, Prominent Vesicular Nucleoli are present
○ Voluminous Cytoplasm with 1 or More Pseudopods
M5a
(Acute Monocytic Leukemia, Poorly Differentiated)
● More than 80% of Monocytic Compartment Predominance are BLASTS
M5a
● Characterized by Presence of ALL STAGES OF MONOCYTE DEVELOPMENT (Monoblasts, Promonocytes and Monocytes)
M5b
● Associated with DIFFUSE ERYTHEMATOUS SKIN RASH
M5b
● Predominant Cell in BM in M5b
Promonocyte
DiGuglielmo’s syndrome
M6 (Acute Erythroleukemia)
● Variable WBC Count and Pancytopenia occurs
● Presence of Numerous Nucleated RBCs
● Mixed Populations of HYPOchromic and NORMOchromic RBCs
M6 (Acute Erythroleukemia)
frequently progresses to M1, M2 or M4 Leukemia
M6
● Alpha-Naphthyl Acetate Esterase (+)
● Auer Rods (+)
Defect in Chromosome 5 and 7
M6
Distinct Feature of M7
Myelosclerosis
(Acute MEGAakaryocytic Leukemia)
M7
● MPO (-), SBB (-) and Esterase (-)
● Alpha-Naphthyl Acetate Esterase (+)
●Alpha-Naphthyl Butyrate Esterase (-)
M7 (Acute Megakaryocytic Leukemia)
● Unique Cytochemistry for
MEGAkaryoblasts
● PAS (+)
M7
● CD41, CD42b and CD61
● Defect in Chromosome 21
M7
