Hematology and Oncology Flashcards
Leukemia
Lymphoid or myeloid neoplasm with widespread involvement of bone marrow. Tumor cells are usually found in peripheral blood.
Unregulated growth and differentiation of WBCs in bone marrow -> marrow failure -> anemia (decreased RBCs), infections (decreased mature WBCs) and hemorrhage (decreased platelets)
Lymphoma
Discrete tumor mass arising from lymph nodes.
Neutrophils
Acute inflammatory response cells. Numbers increase in bacterial infections. Phagocytic. Multilobed nucleus. Specific granules contain leukocyte alkaline phosphatase (LAP), collagenase, lysozyme and lactoferrin. Azurophilic granules (lysosomes) contain proteinases, acid phosphatase, myeloperoxidase, and beta-glucuronidase.
Erythrocytes
Carry O2 to tissues and CO2 to lungs. Anucleate and lack organelles; biconcave, with large surface area-to-volume ratio for rapid gas exchange. Life span of 120 days. Source of energy is glucose (90% used in glycolysis, 10% used in HMP shunt). Membranes contain Cl/HCO3 antiporter, which allow RBCs to export HCO3 and transport CO2 from the periphery to the lungs for elimination.
Thrombocytes (platelets)
Involved in primary hemostasis. Small cytoplasmic fragments derived from megakaryocytes.
Life span of 8-10 days. When activated by endothelial injury, aggregate with other platelets and interact with fibrinogen to form platelet plug. Contain dense granules (Ca, ADP, Serotonin, Histamine) and alpha granules (vWF, fibrinogen, fibronectin, platelet factor 4), Approximately 1/3 of platelet pool is stored in spleen.
Monocytes
Found in blood, differentiate into macrophages in tissues.
Large, kidney-shaped nucleus. Extensive “frosted glass” cytoplasm.
Macrophages
Phagocytose bacteria, cellular debris, and senescent RBCs. Long life in tissues. Differentiate from circulating blood monocytes. Activated by gamma-interferon.
Can function as antigen-presenting cell via MHC II. Important cellular component of granulomas (eg, TB, sarcoidosis).
Eosinophils
Defend against helminthic infections (major basic protein). Bilobate nucleus. Packed with large eosinophilic granules of uniform size. Highly phagocytic for antigen-antibody complexes.
Produce histamine, major basic protein (MBP, a helminthotoxin), eosinophil, peroxidase, eosinophil cationic protein, and eosinophil-derived neurotoxin.
Basophils
Mediate allergic reaction. Densely basophilic granules contain heparin (anticoagulant) and histamine (vasodilator). Leukotrienes synthesized and released on demand.
Mast Cells
Mediate local tissue allergic reactions. Contain basophilic granules. Originate from same precursor as basophils but are not the same cell type. Can bind the Fc portion or IgE to membrane. Activated by tissue trauma, C3a and C5a, surface IgE cross-linking by antigen (IgE receptor aggregation) -> degranulation -> release of histamine, heparin, tryptase, and eosinophil chemotactic factors.
Dendritic Cells
Highly phagocytic antigen-presenting cells (APCs). Function as link between innate and adaptive immune systems. Express MHC class II and Fc receptors on surface.
Lymphocytes
Refer to B cells, T cells and NK cells. B cells and T cells mediate adaptive immunity. NK cells are part of the innate immune system. Round, densely staining nucleus with small amount of pale cytoplasm.
Natural Killer Cells
Important in innate immunity, especially against intracellular pathogens. Larger than B and T cells, with distinctive cytoplasmic lytic granules (containing perforin and granzymes) that, when released, act on target cells to induce apoptosis. Distinguish between healthy and infected cells by identifying cell surface proteins (induced by stress, malignant transformation, or microbial infections).
B Cells
Mediate humoral response. Originate from stem cells in bone marrow and matures in marrow. Migrate to peripheral lymphoid tissue (follicles of lymph nodes, white pulp of spleen, unencapsulated lymphoid tissue). When antigen is encountered, B cells differentiate into plasma cells (which produce antibodies) and memory cells. Can function as an APC.
T Cells
Mediate cellular immune response. Originate from stem cells in the bone marrow, but mature in the thymus. Differentiate into cytotoxic T cells (express CD8, recognize MHC I), helper T cells (express CD4, recognize MHC II), and regulatory T cells. CD28 (costimulatory signal) necessary for T-cell activation. Most circulating lymphocytes are T cells (80%).
Plasma Cells
Produce large amount of antibody specific to particular antigen. “Clock face” chromatin distribution and eccentric nucleus, abundant RER, and well-developed Golgi apparatus. Found in bone marrow and normally do not circulate in peripheral blood.
Cisplatin, carboplatin, oxaliplatin
Cross-link DNA
Clinical Use: Testicular, bladder, ovary, GI and lung carcinomas
Adverse Effects: Nephrotoxicity (including Fanconi syndrome), peripheral neuropathy, ototoxicity. Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride (saline) diuresis
Etoposide, teniposide
Inhibit topoisomerase II -> Increased DNA degradation (cell cycle arrest in G2 and S phases).
Clinical Use: Solid tumors (particularly testicular and small cell lung cancer), leukemias, lymphomas
Adverse Effects: Myelosuppression, alopecia
Irinotecan, topotecan
Inhibit topoisomerase I and prevent DNA unwinding and replication
Clinical Use: Colon cancer (irinotecan); ovarian and small cell lung cancers (topotecan)
Adverse Effects: Severe myelosuppression, diarrhea
Hydroxyurea
Inhibits ribonucleotide reductase -> DNA Synthesis (S-phase specific)
Clinical Use: Myeloproliferative disorders (eg, CML, polycythemia vera), sickle cell disease (increased HbF)
Adverse Effects: Severe myelosuppression, megaloblastic anemia
Bevacizumab
Monoclonal antibody against VEGF. Inhibits angiogenesis.
Clinical Use: Solid tumors (eg, colorectal cancer, renal cell carcinoma), wet age-related macular degeneration.
Adverse Effects: Hemorrhage, blood clots and impaired wound healing
Erlotinib
EGFR tyrosine kinase inhibitor
Clinical Use: non-small cell lung cancer
Adverse Effects: rash, diarrhea
Cetuximab, panitumumab
Monoclonal antibodies against EGFR
Clinical Use: Stage IV colorectal cancer (wild-type KRAS), head and neck cancer
Adverse Effects: rash, elevated LFTs, diarrhea
Imatinib, dasatinib, nilotinib
Tyrosine kinase inhibitors of bcr-abl (encoded by Philadelphia chromosome fusion gene in CML) and c-kit (common in GI stromal tumors)
Clinical Use: CML, GI stromal tumors (GISTs)
Adverse Effects: Fluid retention
Rituximab
Monoclonal antibody against CD20, which is found on most B-cell neoplasms
Clinical Use: Non-Hodgkin lymphoma, CLL, ITP, rheumatoid arthritis, TTP, AIHA
Adverse Effects: Increased risk of progressive multifocal leukoencephalopathy
Bortezomib, carfilzomib
Proteasome inhibitors, induce arrest at G2-M phase and apoptosis.
Clinical Use: Multiple myeloma, mantle cell lymphoma
Adverse Effects: Peripheral neuropathy, herpes zoster reactivation
Tamoxifen, raloxifene
Selective estrogen receptor modulators (SERMs) - receptor antagonists in breast and agonists in bone. Block the binding of estrogen to ER (+) cells.
Clinical Use: Breast cancer treatment (tamoxifen only) and prevention. Raloxifene also useful to prevent osteoporosis.
Adverse Effects: Tamoxifen - partial agonist in endometrium, which increases the risk of endometrial cancer.
Raloxifene - no increase in endometrial carcinoma (so you can’t relax), because it is an estrogen receptor antagonist in endometrial tissue.
Both increase risk of thromboembolic events (eg, DVT, PE) and “hot flashes”
Trastuzumab
Monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase receptor. Helps kill cancer cells that overexpress HER-2 through inhibition of HER-2 initiated cellular signaling and antibody-dependent cytotoxicity.
Clinical Use: HER-2 (+) breast cancer and gastric cancer
Adverse Effects: Dilated cardiomyopathy. “Heartceptin” damages the heart.
Dabrafenib, vemurafenib
Small-molecule inhibitors of BRAF oncogene (+) melanoma. Vemurafenib is for V600E-mutated BRAF inhibition. Often co-administered with MEK inhibitors (eg, trametinib).
Clinical Use: Metastatic melanoma.
Rasburicase
Recombinant uricase that catalyzes metabolism of uric acid to allantoin
Clinical Use: Prevention and treatment of tumor lysis syndrome
Iron deficiency
microcytic (small), hypochromic anemia
decreased iron due to chronic bleeding (eg, GI loss, menorrhagia), malnutrition, absorption disorders, GI surgery (eg, gastrectomy), or increased demand (eg, pregnancy) -> decreased final step in heme synthesis.
Labs: decreased iron and ferritin
Symptoms: fatigue, conjunctival pallor, pica (persistent craving and compulsive eating of nonfood substances), spoon nails (koilonychia)
alpha-thalassemia
microcytic, hypochromic anemia
alpha-globin gene deletions on chromosome 16 -> decreased alpha-globin synthesis. cis deletion (deletions occur on same chromosome) prevalent in Asian populations; trans deletion (deletions occur on separate chromosomes) prevalent in African populations.
beta-thalassemia
microcytic, hypochromic anemia
Point mutations in splice sites and promoter sequences on chromosome 11 -> decreased beta-globin synthesis. Prevalent in Mediterranean populations.
beta-thalassemia minor
microcytic, hypochromic anemia
beta chain is underproduced. usually asymptomatic. Diagnosis confirmed by increased HbA2 on electrophoresis
beta-thalassemia major
microcytic, hypochromic anemia
beta chain is absent -> severe microcytic, hypochromic anemia with target cells and increased anisopoikilocytosis requiring blood transfusion (secondary hemochromatosis). Marrow expansion (“crew cut” on skull x-ray) -> skeletal deformities (eg, “chipmunk” facies). Extramedullary hematopoiesis -> hepatosplenomegaly. Increased risk of parvovirus B19-induced aplastic crisis. Increased HbF, HbA2. HbF is protective in the infant and disease becomes symptomatic only after 6 months, when fetal hemoglobin declines.
HbS/beta-thalassemia heterozygote
microcytic, hypochromic anemia
mild to moderate sickle cell disease depending on amount of beta-globin production
alpha-thalassemia minima
microcytic, hypochromic anemia No anemia (silent carrier)
alpha-thalassemia minor
microcytic, hypochromic anemia
Mild microcytic, hypochromic anemia; cis deletion may worsen outcome for the carrier’s offspring
Hemoglobin H disease (HbH); excess beta-globin forms B4
Moderate to severe microcytic hypochromic anemia
Hemoglobin Barts disease; no alpha-globin, excess gamma-globin forms gamma4
Hydrops fatalis; incompatible with life
Lead Poisoning
Microcytic, hypochromic anemia lead lines on gums and long bones peripheral neuropathy (wrist drop/foot drop)
Sideroblastic Anemia
Microcytic, hypochromic anemia
Anemia
A hemoglobin (Hb) concentration below the reference range for the age and sex of an individual
Microcytic Anemia
Small RBCs
MCV < 80
Macrocytic Anemia
Large RBCs
MCV > 100
megaloblast or not
Macrocytic, Megaloblastic Anemia
Impaired DNA Synthesis
Folate Deficiency
B12 (cobalamin) Deficiency
Orotic Aciduria
Folate Deficiency
Megaloblastic Anemia
normal methylmalonic acid
alcoholism, poor nutrition
B12 Deficiency
Megaloblastic Anemia high methylmalonic acid pernicious anemia (autoimmune disease against parietal cells in stomach) can't absorb B12 fish tape worm (D. latum) neurologic symptoms - dementia
Macrocytic, Non-Megaloblastic Anemia
Liver disease
Alcoholism
Diamond-Blackfan anemia
Reticulocytosis (immature RBCs - larger than RBCs)
Hemolysis
Destruction of RBCs
Non-hemolytic
Low production
Hemolytic
Increased destruction
Extrinsic Hemolytic Hemolysis
Antibodies
Mechanical trauma (narrow vessels)
RBC Infection
Intrinsic Hemolytic Hemolysis
Failure of membrane, hemoglobin or enzymes
Failure of membrane = Hereditary spherocytosis
Enzyme = G6PD
Hemoglobin = Sickle Cell Anemia
Hemolysis Consequences
Elevated plasma LDH (lactate dehydrogenase). Glycolysis enzyme. Converts pyruvate -> lactate
Elevated reticulocyte count
Elevated unconjugated (indirect) bilirubin
Reticulocytes
Immature RBCs
Usually 1-2% of RBCs in peripheral blood
Reticulocyte count in non-hemolytic anemia
DECREASES
Reticulocyte count in hemolytic anemia
INCREASES
Corrected Reticulocyte Count
Retic % * (Hct/Norm Hct 45)
Normal = 1-2%
Reticulocyte Production Index
RPI corrects for longer life of reticulocytes in anemia
Corrected Retic %/Maturation Time
MT is dependent on Hgb count
Intravascular Hemolysis
Destruction of RBCs inside blood vessels
Mechanical Trauma = narrowed vessels, mechanical heart valves
Extravascular Hemolysis (Liver)
Receives a large portion of cardiac output
Can remove severely damaged RBCs
Extravascular Hemolysis (Spleen)
Destroys poorly deformable RBCs
Cords of Billroth: Vascular channels that end blindly
Found in red pulp of spleen
RBCs must deform to pass through slits in walls of cords
Old “senescent” or damaged RBCs remain in the cords
Phagocytosed by the macrophages
Hemolysis Disorders -> increased splenic removal of RBCs
Haptoglobin
Plasma protein. Produced by the liver. Binds free hemoglobin.
Haptoglobin-hemoglobin complex removed by liver
Hemolysis = decreased serum haptoglobin (b/c it’s bound to the heme released from the destruction of RBCs)
Intravascular VERY LOW haptoglobin
Hemolysis (Urine Findings)
No bilirubin.
Positive hemoglobin (haptoglobin saturation = free excess hemoglobin “hemoglobinemia”)
Hgb may turn urine dark red/brown
No red cells + Hgb think hemolysis
Parvovirus B19
DNA Virus. Replicates in RBC progenitor cells.
Decreased erythropoiesis.
Healthy patients - RBC production returns in 10-14 days
Hemolysis Patients - increased RBC turnover, lack of erythropoiesis leads to severe anemia, pallor, weakness, lethargy
“Aplastic Crisis” in patients with chronic hemolysis
Autoimmune Hemolytic Anemia (AIHA)
Red cell destruction from autoantibodies
Red cell membrane removed in pieces by spleen
Warm AIHA (Autoimmune Hemolytic Anemia)
Antibodies bind at body temp 37 deg C
IgG antibodies against RBC surface antigens
Clinical Symptoms = anemia (fatigue, pallor, dyspnea, tachycardia) & extravascular hemolysis (jaundice, splenomegaly)
Diagnostic Findings = Spherocytes
Direct Antiglobulin Test (DAT)
or Coombs Test
RBCs + Anti-IgG Antibodies
Positive is agglutination occurs
Indicates patient’s RBCs covered with IgG
Tests for antibodies bound to RBCs
Indirect Antiglobulin Test
Indirect Coombs
Serum + RBCs
Tests for antibodies in the serum
Cold AIHA (Autoimmune Hemolytic Anemia)
Antibodies bind <30 deg C IgM antibodies agglutinate RBCs C3 is bound to RBCs = pos DAT Occurs in limbs, fingers, toes, nose, ears Purple discoloration
Microangiopathic hemolytic anemia (MAHA)
Shearing of RBCs in small blood vessels
Blood smear = schistocytes
Hodgkin Lymphoma
low grade fever, night sweats, weight loss
Localized, single group of nodes with contiguous spread.
Characterized by Reed-Sternberg cells
Bimodal distribution: young adulthood and >55 years
Associated with EBV
Non-Hodgkin lymphoma
low grade fever, night sweats, weight loss
Multiple lymph nodes involved; extranodal involvement common; noncontiguous spread
May be associated with autoimmune diseases and viral infections
Reed-Sternberg Cells
“owl eyes”
Hodgkin Lymphoma
2 owl eyes x 15 = 30
CD15+ and CD30+ B-cell origin
Burkitt Lymphoma
Non-Hodgkin lymphoma Neoplasm of mature B cells "starry sky" Adolescents or young adults t(8;14)- translocation of c-myc (8) and heavy-chain Ig (14)
Diffuse Large B-cell Lymphoma
Non-Hodgkin lymphoma **most common
Neoplasm of mature B cells
mutations in BCL-6
Follicular Lymphoma
Non-Hodgkin lymphoma
Neoplasm of mature B cells
t(14;18)- translocation of heavy chain Ig (14) and BCL-2 (18)
Mantle Cell Lymphoma
Non-Hodgkin lymphoma
Neoplasm of mature B cells
t(11;14)- translocation of cyclin D1 (11) and heavy chain Ig (14), CD5+
Marginal Zone Lymphoma
Non-Hodgkin lymphoma
Neoplasm of mature B cells
t(11;18)
Primary Central Nervous System Lymphoma
Non-Hodgkin lymphoma
Neoplasm of mature B cells
EBV related; associated with HIV/AIDS
Adult T-cell Lymphoma
Non-Hodgkin lymphoma
Neoplasm of mature T cells
Mycosis fungoides/Sezary Syndrome
Non-Hodgkin lymphoma
Neoplasm of mature T cells
Acute Lymphoblastic Leukemia/Lymphoma (ALL)
Leukemia - Lymphoid Neoplasm
Most frequently occurs in children. T-cell ALL can present as mediastinal mass. Associated with Down Syndrome
Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma
CLL
Leukemia - Lymphoid Neoplasm
Most common adult leukemia
CLL = Crushed Little Lymphocytes (smudge cells)
Hairy Cell Leukemia
Leukemia - Lymphoid Neoplasm
Adult males. Mature B-cell tumor. Cells have filamentous, hair-like projections
Acute Myelogenous Leukemia
AML
Leukemia - Myeloid Neoplasm
Auer rods.
Increased circulating myeloblasts (eosinophil, basophil, neutrophil) on peripheral smear.
Chronic Myelogenous Leukemia
CML
Leukemia - Myeloid Neoplasm
Philadelphia chromosome t(9; 22) BCR-ABL and myeloid stem cell proliferation.
Presents with dysregulated production of mature and maturing granulocytes and splenomegaly.
Polycythemia vera
Disorder of increased RBCs, usually due to acquired JAK2 mutation
May present as itching after shower (aquatic pruritus). Rare but classic symptom is erythromelalgia (severe, burning pain and red-blue coloration) due to episodic blood clots in vessels of extremities
Essential Thrombocytopenia
Massive proliferation of megakaryocytes and platelets. Symptoms including bleeding and thrombosis.
Myelofibrosis
Obliteration of bone marrow with fibrosis due to increased fibroblast activity. Associated with massive splenomegaly and “teardrop” RBCs
