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White Blood Cell disorders

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kesapoju's version from 2017-11-05 21:40

Benign Qualitative White Blood Cell Disorders

Question Answer
Pathogenesisdefects in leukocyte structure or function
Clinical findingsunusual pathogens; frequent infections and growth failure in children; lack of an inflammatory response; severe gingivitis
Job's syndromeautosomal recessive disorder of neutrophils, characterized by abnormal chemotaxis leading to 'cold' soft tissue abscesses due to Staphylococcus aureus; patients have red hair , a leonine face, chronic eczema, and increased IgE
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Unusual benign leukocyte reactions

Question Answer
Leukemoid reactionsabsolute leukocyte count usually >50,000 cells/mm3; may involve neutrophils, lymphocytes, or eosinophils
Etiology of leukemoid reactionsperforated appendicitis (netrophils); whooping cough (lymphocytes); cutaneous larva migrans (eosinophils)
Pathogenesis of leukemoid reactionsexaggerated response to infection
Leukoerytrhoblastic reactionimmature bone marrow cells enter the peripheral blood
Pathogenesis of leukoerythroblastic reactionbone marrow infiltrative disease (fibrosis, metastatic breast cancer)
Peripheral blood findings of leukoerythroblastic reactionsmyeloblasts, progranulocytes; nucleated RBCs, tear drop RBCs if fibrosis is present
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Benign Quantitative WBC disorders

Question Answer
Neutrophilic leukocytosisabsolute neutrophil count > 7000 cells/mm3
Etiology of neutrophilic leukocytosisinfection, sterile inflammation with necrosis, drugs
Pathogenesis of neutrophilic leukocytosisincreased bone marrow production or release of neutrophils; decreased activation of neutrophil adhesion molecules
Neutropeniaabsolute neutrophil count <1500 cells/mm3
etiology of neutropeniaaplastic anemia, immune destruction, septic shock
Pathogenesis of neutopeniadecreased production, increased destruction, activation of neutrophil adhesion molecules
Eosinophiliaabsolute eosinophil count >700
Etiology of eosinophiliaType 1 hypersensitivity reaction, invasive helminthic infection, polyarteritis nodosa, Addison's disease
pathogenesis of eosinophiliarelease of eosinophil chemotactiv factor from mast cells; no sequestering of eosinophils in lymph nodes
etiology of eosinopeniahypercortisolism: corticosteroids sequester eosinophils in lymph nodes
basophiliaabsolute basophil count >100
etiology of basophiliachronic myeloproliferative disorders
lymphocytosisabsolute lymphocyte count >4000 in adults or >8000 in children
etiology of lymphocytosisviral, bacterial, drugs, Grave's disease
pathogenesis of lymphocytosisincreased production; decreased entry into lymph nodes
example of decreased lympohcytes entering lymph nodeslympohcytosis-promoting factor produced by Bordetella pertussis
etiology of atypical lymphocytosisinfections, drugs (phenytoin)
pathogenesis of atypical lymphocytosisantigenically stimulated lympohcytes; prominent nucleoli and abundant blue cytoplasm
Infectious mononucleosiscaused by Epstein-Barr virus
pathogenesis of monoprimarily transmitted by kissing (EBV initially replicates in oropharynx); Infection spreads to B cells in lymph nodes
EBV in B cellsattaches to CD21 receptors; causes cell proliferation and increased synthesis of IgM; virus remains dormant, recurrences may occur
Clinical findings of monosevere fatigue, exudative tonsillitis, hepatosplenomegaly (spleen can rupture in contact sports); generalized painful lymphadenopathy, rash develops if treated with ampicillin
lab findings of monoatypical lymphocytosis (antigenically stimulated T-cells; usually more than 20% of total WBC); positive heterophil antibody test; antiviral capsid antigen antibodies; anti-early antigen antibodies; anti-Epstein Barr nuclear antigen antibodies; increased serum transaminases from hepatitis
heterophil antibody testinitial screening test; detects IgM antibodies against horse, sheep, and bovine RBCs
antiviral capsid antigen (VCA) antibodiesdevelops early in infection, persists for life
anti-early antigen (EA) antibodiesincreased with chronic infections
anti-Epstein Barr nuclear antigen (EBNA) antibodiesdevelops late in infection; persists for life
jaundice in monorare; due to hepatitis
lymphopeniaabsolute lymphocyte count <1500 in adults or <3000 in children
etiology of lymphopeniaHIV; DiGeorge (T-cell); SCID; Immune destruction; corticosteroids (apoptosis); radiation
pathogenesis of lymphopeniaincreased destruction; decreased production: Bruton's agammaglobulinemia
monocytosisabsolute moncyte count >800
etiology of monocytosischronic infection, autoimmune disease, malignancy
pathogenesis of monocytosisresponse to chronic inflammation or malignancy
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Leukemias

Question Answer
Epidemiology of leukemiamalignant diseases of bone marrow stem cells; may involve all cell lines; more common in adults
persons newborn to 14ALL
persons 15 to 39AML
persons 40 to 60AML (>60%) CML (~40%; may occur in persons older than 60)
persons older than 60CLL
Pathogenesis of leukemiablock in stem cell differentiation; leukemic cells
block in stem cell differentiationmonoclonal proliferation of neoplastic leukocytes behind the block; acute leukemia: block occurs at early stage; chronic leukemia: block occurs at later stage; some evidence of maturation
Leukemic cellsreplace most of the bone marrow/normal hematopoietic cells; enter the peripheral blood; metastasize throughout the body
Clinical findings in acute leukemiaabrupt onset; fever usually from infection, bleeding from thrombocytopenia, fatigue from anemia; metastatic disease; bone pain and tenderness
metastatic disease in acute leukemiahepatosplenomegaly; generalized painless lymphadenopathy; CNS involvement (especially in ALL); skin involvement (especially in T-cell); testicles (especially in ALL)
peripheral WBC count in acute leukemiabelow 10,000 cells to >100,000 cells; blast cells usually present
lab findings in acute leukemianormocytic to macrocytic anemia: macrocytic if folate is depleted in production of leukemic cells; thrombocytopenia: usually less than 100,000; hypercellular bone marrow with >20% blasts, often completely replaced by blasts
Clinical findings in chronic leukemiainsidious onset; slightly more common than acute leukemia; hepatosplenomegaly; generalized painless lymphadenopathy
lab findings in chronic leukemiasimilar to that of acute leukemia; blast cells usually <10%; evidence of maturation of cells; (thrombocytosis coccurs in 40% of CML cases); hypercellular bone marrow with <10% blasts
ALL 5 YSR87%
AML 5 YSR21%
CLL 5 YSR75%
CML 5 YSR89%
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Neoplastic Myeloid Disorders

Question Answer
Neoplastic myeloid disordersneoplastic stem cell disorders; may involve one or more stem cell lines;
classifcations of neoplastic myeloid disorderschronic myeloproliferative disorders, myelodysplastic syndrome, acute myeloblastic leukemia
classifications of chronic myeloproliferative disorderspolycythemia vera, chronic myelogenous leukemia, myeloid metaplasia with myelofibrosis, essential thrombocythemia
general characteristics of chronic myeloproliferative disorderssplenomegaly, propensity for reactive bone marrow fibrosis (stent phase); propensity for transformation to acute leukemia
polycythemiaincreased Hb, Hct, and RBC count; plasma volume varies with type
RBC countRBC mass/plasma volume
Relative polycythemiamost common polycythemia; increased RBC count due to decrease in plasma volume; normal RBC mass, EPO, and SaO2; corrected by fluid replacement
Absolute polycythemiaincrease in bone marrow production of RBCs
Appropriate absolute polycythemiahypoxic stimulus for EPO release, decreased SaO2, increased RBC count, RBC mass, and EPO; normal plasma volume
inappropriate absolute polycythemiaectopic EPO production; Increased RBC count, RBC mass, and EPO; normal plasma volume and SaO2
Polycythemia verainappropriate absolute polycythemia; clonal expansion of myeloid stem cells
Pathogenesis of polycythemia veramost due to mutation of JAK2 gene on 9q (same mutation may manifest as myelofibrosis, myeloid metaplasia, or essential thrombocytopenia); increased production of RBCs, granulocytes, mast cells, and platelets
Clinical findings of polycythemia verahepatosplenomegaly; ruddy (plethoric) face; thrombotic veins (increased viscosity); impaired CNS circulation; signs of increased histamine release; gout
signs of increased histamine release in polycythemia verapruritis after bathing; peptic ulcer disease
lab findings in polycythemia veraincreased RBC count, RBC mass, and plasma volume; decreased EPO; normal SaO2; hypercellular bone marrow with fibrosis in later stages
Diagnosis polycythemia vera3 major criteria or first two major criteria and two minor criteria
Polycythemia vera major criteriaincreased RBC mass > 36 mL/kg, 32 in women; normal SaO2 (>92%); splenomegaly
Polycythemia vera minor criteriaabsolute leukocytosis: > 12,000; thrombocytosis: >400,000; increased serum leukocyte alkaline phosphatase: >100 score; increased vitmain B12 >900 pg/mL or B12 binding protein > 2200 pg/mL
Treatment of polycythemia veraphlebotomy to reduce hyperviscosity; hydroxyurea + phlebotomy; interferon-a
CML pathogenesisneoplastic clonal expansion of the pluripotential stem cell ; t9;22 translocation of ABL proto-oncogene (philadelphia chromosome): fuses with the break cluster region (BCR)
Clinical findings of CMLhepatosplenomegaly and genearlized painless lymphadenopathy; Blast crisis: usually occurs in ~5 years; increase in numbers of myeloblasts or lymphoblasts; myeloblasts do not contain Auer rods
lab findings of CMLperipheral WBC count 50,000 to 200,000; myeloid series in all stages of development; basophilia; normo/macrocytic (depending on folate); thrombocytosis in 40-50%, thrombocytopenia in the rest
bone marrow findings of CMLhypercellular; myeloblasts <10%
decreased leukocyte alkaline phosphatase score in CMLLAP is absent in neoplastic granulocytes and present in benign granulocytes
Treatment of CMLimatinib mesylate: oral tyrosine kinase inhibitor (< 35% PHiladelphia chromosome positive cells after treatment); allogenic stem cell transplant
epidemiology of CML40-60+ yo; risk factors: exposure to ionizing radiation and benzene
epidemiology of myelofibrosis and myeloid metaplasia (MMM)>50 yo; most common cause of splenomegaly in 50+ age group
pathogenesis of MMMclonal myeloproliferative disease; most due to mutation of JAK2 gene on 9q; ineffective erythropoiesis, dysplastic megakaryocytes, immature granulocytes, reactive myelofibrosis; EMH
clinical findings of MMMmassive splenomegaly with portal hypertension; splenic infarcts with left sided pleural effusions
Lab findings of MMMbone marrow fibrosis; normocytic anemia; tear drop cells; leukoerythroblastic reaction; LAP score normal to increased
peripheral WBC count in MMM10,000-50,000
platelet count in MMMvariable; platelets have abnormal morphology
treatment of MMMhydroxyurea, interferon-a
Pathogenesis of Essential thrombocytopenia (ET)clonal myeloproliferative disease with excess formation of dysplastic and defective platelets; most due to JAK2 on 9q
Clinical findings of ETbleeding: usually GI with concomitant iron deficiency; nonfunctional platelets; splenomegaly
Lab findings of ETplatelets >600,000 (often more than 1M); abnormal platelet morphology; mild neutrophilic leukocytosis; basophilia; hypercellular bone marrow with abnormal megakaryocytes
treatment for EThydroxyurea
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Myelodysplastic syndromes

Question Answer
epidemiologymen 50-80
pathogenesisacquired clonal disorders affecting stem cells; cytopenias and hypercellular marrow; frequently progresses to AML
Classificationsrefractory anemia; refractory anemia with ringed sideroblasts; chronic myelomonocytic leukemia; refractory anemia with excess blasts in transformation
lab findingssevere pancytopenia: normo/macrocytic (dimorphic: micro and macro); leukoerythroblastic reaction
bone marrow findingsringed sideroblasts; myeloblasts <20% (if more than 20%, disease is progressing to AML)
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Acute Myeloblastic leukemia

Question Answer
Epidemiologyusually occurs between 15 and 59
cytogenic abnormalities (example)t(15;17) in acute promyelocytic leukemia (M3)
Clinical findings of AMLDIC; gum infiltration common in acute monocytic leukemia (M5)
Auer rodssplinter-shaped to rod-shaped structures in the cytosol of myeloblasts (fused azurophilic granules); only present in AML
induction therapycytarabine + daunorubicin
consolidation therapyaggresive chemotherapy with or without radiation
maintenance therapycytarabine
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French-American-British Classification of Acute Myeloblastic Leukemia

Question Answer
M0Minimally differentiated AML; No Auer rods
M1AML without differentiation: 20%; Rare Auer rods
M2AML with maturation; Most common type (30-40% of cases); Auer rods present; 15-59-year-old age bracket
M3Acute promyelocytic; Numerous Auer rods; DIC is invariably present; t(15;17) translocation; Abnormal retinoic acid metabolism: high doses of all-trans-retinoic acid may induce remission by maturing cells
M4Acute myelomonocytic; Auer rods uncommon
M5Acute monocytic No Auer rods; Gum infiltration
M6Acute erythroleukemia Bizarre, multinucleated erythroblasts; Myeloblasts present
M7Acute megakaryocytic Myelofibrosis in bone marrow; increased incidence in Down syndrome in children < 3 years old
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