Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
J.
Basophilia
1. Causes: CMPDs (PCV, CGL, etc.)
K. Monocytosis
i. Causes:
1. Chronic infection (TB)
2. Autoimmune disease (SLE, rheumatoid arthritis)
3. Malignancy
2. Benign Qualitative WBC disorders
A. The oxygen dependent myeloperoxidase system (MPO system) is the most
potent of all the bactericidal mechanisms (also discussed in inflammation
notes) -- see diagram.
i. Opsonized bacteria coated by IgG and C3b are easily phagocytized
by neutrophils and monocytes, which contain receptors for IgG and
C3b on their cell membrane.
ii. Bacteria are enclosed within a phagosome (vacuole in the cytoplasm)
iii. Lysosomes empty their enzymes (MPO and others) into the
phagosomes, which is now called a phagolysosome
iv. After phagocytosis has occurred, NADPH oxidase, located in the leukocyte
cell membrane, converts molecular oxygen from the surrounding
tissue into singlet oxygen, which is a free radical that generates the
energy referred to as the respiratory burst
v. Singlet oxygen Is converted Into hydrogen peroxide by superoxide
dismutase (SOD)
vi. In the presence of MPO, a lysosomal enzyme present within the
phagolysosome, peroxide plus chloride ions are converted into HOCI
(bleach), which ultimately destroys the bacteria.
vii. The excess peroxide is either neutralized by
viii. Catalase derived from peroxisomes in the cell or by glutathione
(GSH) in the HMS
B. Types of tests
i. Peroxidase stains of leukocytes are used to demonstrate whether
MPO is present in the leukocyte granules. MPO is in the primary, or
azurophilic granules commonly seen with regular Wright- Giemsa stained
peripheral smears.
ii. The respiratory burst mechanism in the oxygen dependent MPO
system is evaluated with the nitroblue tetrazolium (NBT) dye test
(colorless dye converted to colored dye in PMNs if system is working) or the
chemiluminescence assay (detects energy given off from free radical
formation).
C. Qualitative disorders
i. Primary or acquired MPO deficiencies are common (neonates) and
result in susceptibility to infections.
ii. Chediak Higashi syndrome is an autosomal recessive disease with a
primary defect in the polymerization of microtubules in leukocytes,
which interferes with their emigration through tissue in response to
chemotactic agents
1. In addition, the leukocytes contain giant lysosomes in their
cytoplasm that are unable to properly release their lysosomal
enzymes into the phagosomes, thus impairing bactericidal function as
well.
iii. Chronic granulomatous disease (CGD) is a sex- linked recessive
disease characterized by the absence of NADPH oxidase
1. The respiratory burst mechanism is impaired, so peroxide is
unavailable for the reaction with chloride ions to generate
HOCl
Hypoxemia (COPD)
Ectopic erythropoietin
N
N
Stress polycythemia
N
N
N
Dehydration
N
N
N
D. D. Myeloproliferative: Chronic granulocytic! myelogenous leukemia (CGL or
CML)
i. 1. 30% of all leukemias between 30-50 years old; male dominant
cancer.
ii. 2. causes: radiation, benzene
iii. 3. clinical:
1. a. in~ 3 years, progress into an acute blast crisis with
myeloblasts (majority) or lymphoblasts (20-30%---do marker
studies)
2. b. massive hepatosplenomegaly; infarcts common
3. c. soft tissue collections of leukemic cells called chloromas
iv. 4. laboratory
1. a. WBC counts 50,000 to 200,000 cells/L
2. b. peripheral blood with mature and immature WBCs
(myelocyte most abundant cell); increased basophils and
eosinophils; myeloblasts < 10% blasts; pseudo- Pelger Duet
cells
3. c. bone marrow: hypercellular fibrotic with < 10% blasts.
4. d. Ph chr positive (#22---95 % cases); t 9;22 translocation of cabl oncogene from 9 to 22 with fusion near the break cluster
region (bcr) of chr 22
5. e. positive bcr study In almost all cases
6. f. low leukocyte alkaline phosphatase score (LAP score; see
PRV discussion).
7. g. thrombocytosis (only leukemia with thrombocytosis).
8. h. anemia (marrow infiltration by leukemic cells).
v. 5. treatment: alkylating agents; Philadelphia chromosome is not lost with
treatment.
E. E. Myeloproliferative: Agnogenic myeloid metaplasia
i. 1. age: over 50 years old
ii. 2. primary stem cell disorder originating in the spleen with reactive
marrow fibrosis from megakaryocytes secreting platelet derived
growth factor, which stimulates marrow fibrosis
1. a. extramedullary hematopoiesis in spleen, liver and other
sites
iii. 3. clinical:
1. a. massive splenomegaly (extramedullary: hematopoiesis) with LUQ
pain due to Infarctions and size of spleen.
iv. 4. laboratory:
1. a. WBC count 10,000 to 50,000 cells/L.
2. b. leukoerythroblastic smear; tear drop RBCs (damaged when
getting out of fibrosed sinusoids); pseudo-Pelger Duet cells;
basophilia
3. c. thrombocytosis
4. d. bone marrow: fibrosed; numerous megakaryocytes; "dry
tap"--cannot aspirate marrow because it is fibrosed
5. e. LAP score increased
v. 5. no specific treatment; can progress to acute leukemia as terminal
event; usually die in 5 years.
F. F. Myeloproliferative: Essential thrombocythemia
i. 1. age: over 50 years old
ii. 2. clinical:
1. a. rule out other causes of thrombocytosis (iron deficiency,
malignancy, etc.).
2. b. commonly causes bleeding (patients do not function properly--qualitative defects), which leads to Iron deficiency
iii. 3. laboratory
1. a. platelet count> 600,000 cells/L
2. b. bone marrow with increased dysplastic megakaryocytes
3. c. absolute neutrophilic leukocytosis
iv. 4. treat with alkylating agents; compatible with long life.
G. G. Myelodysplastic syndrome (MDS)
i. 1 . stem cell disorder predominantly in the elderly (over 60) with an
increased risk for developing acute leukemia
ii. 2. laboratory:
1. a. chromosome abnormalities common: 50% have a 5q anomaly
2. b. dimorphic RBC population (microcytic and macrocytic);
siderocytes (iron in RBCs) in peripheral blood (sometimes
called Pappenheimer bodies--best visualized with Prussian
blue stain)
3. c. pancytopenia common
4. d. bone marrow commonly has ringed sideroblasts
(sideroblastic anemia) and increased myeloblasts
4. Malignant White Blood Cell Disorders: Leukemia
A. A. Leukemia: Overview
i. 1. leukemias are malignant neoplasms of hematopoietic stem cells
within the bone marrow which ultimately replace the marrow and spill
over into tile peripheral blood in the majority of cases
ii. 2. predisposing factors for leukemia include:
1. a. chromosomal abnormalities: trisomy 21 in Down's syndrome
2. b. RNA oncogenic viruses: HTLV-l in T cell leukemia
3. c. chromosomal instability syndromes (increased mutations):
ataxia telangiectasia, Bloom's syndrome
4. d. ionizing radiation: atomic bomb; acute leukemia is the MC
malignancy associated with irradiation
5. e. drugs/chemicals: benzene; alkylating agents