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Hematology and Oncology Flashcards

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1
Q

Leukemia

A

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)

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2
Q

Lymphoma

A

Discrete tumor mass arising from lymph nodes.

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3
Q

Neutrophils

A

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.

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4
Q

Erythrocytes

A

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.

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5
Q

Thrombocytes (platelets)

A

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.

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6
Q

Monocytes

A

Found in blood, differentiate into macrophages in tissues.

Large, kidney-shaped nucleus. Extensive “frosted glass” cytoplasm.

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7
Q

Macrophages

A

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).

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8
Q

Eosinophils

A

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.

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9
Q

Basophils

A

Mediate allergic reaction. Densely basophilic granules contain heparin (anticoagulant) and histamine (vasodilator). Leukotrienes synthesized and released on demand.

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10
Q

Mast Cells

A

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.

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11
Q

Dendritic Cells

A

Highly phagocytic antigen-presenting cells (APCs). Function as link between innate and adaptive immune systems. Express MHC class II and Fc receptors on surface.

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12
Q

Lymphocytes

A

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.

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13
Q

Natural Killer Cells

A

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).

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14
Q

B Cells

A

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.

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15
Q

T Cells

A

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%).

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16
Q

Plasma Cells

A

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.

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17
Q

Cisplatin, carboplatin, oxaliplatin

A

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

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18
Q

Etoposide, teniposide

A

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

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19
Q

Irinotecan, topotecan

A

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

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20
Q

Hydroxyurea

A

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

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21
Q

Bevacizumab

A

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

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22
Q

Erlotinib

A

EGFR tyrosine kinase inhibitor
Clinical Use: non-small cell lung cancer
Adverse Effects: rash, diarrhea

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23
Q

Cetuximab, panitumumab

A

Monoclonal antibodies against EGFR
Clinical Use: Stage IV colorectal cancer (wild-type KRAS), head and neck cancer
Adverse Effects: rash, elevated LFTs, diarrhea

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24
Q

Imatinib, dasatinib, nilotinib

A

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

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25
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
26
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
27
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"
28
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.
29
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.
30
Rasburicase
Recombinant uricase that catalyzes metabolism of uric acid to allantoin Clinical Use: Prevention and treatment of tumor lysis syndrome
31
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)
32
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.
33
beta-thalassemia
microcytic, hypochromic anemia Point mutations in splice sites and promoter sequences on chromosome 11 -> decreased beta-globin synthesis. Prevalent in Mediterranean populations.
34
beta-thalassemia minor
microcytic, hypochromic anemia | beta chain is underproduced. usually asymptomatic. Diagnosis confirmed by increased HbA2 on electrophoresis
35
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.
36
HbS/beta-thalassemia heterozygote
microcytic, hypochromic anemia | mild to moderate sickle cell disease depending on amount of beta-globin production
37
alpha-thalassemia minima
``` microcytic, hypochromic anemia No anemia (silent carrier) ```
38
alpha-thalassemia minor
microcytic, hypochromic anemia | Mild microcytic, hypochromic anemia; cis deletion may worsen outcome for the carrier's offspring
39
Hemoglobin H disease (HbH); excess beta-globin forms B4
Moderate to severe microcytic hypochromic anemia
40
Hemoglobin Barts disease; no alpha-globin, excess gamma-globin forms gamma4
Hydrops fatalis; incompatible with life
41
Lead Poisoning
``` Microcytic, hypochromic anemia lead lines on gums and long bones peripheral neuropathy (wrist drop/foot drop) ```
42
Sideroblastic Anemia
Microcytic, hypochromic anemia
43
Anemia
A hemoglobin (Hb) concentration below the reference range for the age and sex of an individual
44
Microcytic Anemia
Small RBCs | MCV < 80
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Macrocytic Anemia
Large RBCs MCV > 100 megaloblast or not
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Macrocytic, Megaloblastic Anemia
Impaired DNA Synthesis Folate Deficiency B12 (cobalamin) Deficiency Orotic Aciduria
47
Folate Deficiency
Megaloblastic Anemia normal methylmalonic acid alcoholism, poor nutrition
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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 ```
49
Macrocytic, Non-Megaloblastic Anemia
Liver disease Alcoholism Diamond-Blackfan anemia Reticulocytosis (immature RBCs - larger than RBCs)
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Hemolysis
Destruction of RBCs
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Non-hemolytic
Low production
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Hemolytic
Increased destruction
53
Extrinsic Hemolytic Hemolysis
Antibodies Mechanical trauma (narrow vessels) RBC Infection
54
Intrinsic Hemolytic Hemolysis
Failure of membrane, hemoglobin or enzymes Failure of membrane = Hereditary spherocytosis Enzyme = G6PD Hemoglobin = Sickle Cell Anemia
55
Hemolysis Consequences
Elevated plasma LDH (lactate dehydrogenase). Glycolysis enzyme. Converts pyruvate -> lactate Elevated reticulocyte count Elevated unconjugated (indirect) bilirubin
56
Reticulocytes
Immature RBCs | Usually 1-2% of RBCs in peripheral blood
57
Reticulocyte count in non-hemolytic anemia
DECREASES
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Reticulocyte count in hemolytic anemia
INCREASES
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Corrected Reticulocyte Count
Retic % * (Hct/Norm Hct 45) | Normal = 1-2%
60
Reticulocyte Production Index
RPI corrects for longer life of reticulocytes in anemia Corrected Retic %/Maturation Time MT is dependent on Hgb count
61
Intravascular Hemolysis
Destruction of RBCs inside blood vessels | Mechanical Trauma = narrowed vessels, mechanical heart valves
62
Extravascular Hemolysis (Liver)
Receives a large portion of cardiac output | Can remove severely damaged RBCs
63
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
64
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
65
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
66
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
67
Autoimmune Hemolytic Anemia (AIHA)
Red cell destruction from autoantibodies | Red cell membrane removed in pieces by spleen
68
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
69
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
70
Indirect Antiglobulin Test | Indirect Coombs
Serum + RBCs | Tests for antibodies in the serum
71
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 ```
72
Microangiopathic hemolytic anemia (MAHA)
Shearing of RBCs in small blood vessels | Blood smear = schistocytes
73
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
74
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
75
Reed-Sternberg Cells
"owl eyes" Hodgkin Lymphoma 2 owl eyes x 15 = 30 CD15+ and CD30+ B-cell origin
76
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) ```
77
Diffuse Large B-cell Lymphoma
Non-Hodgkin lymphoma **most common Neoplasm of mature B cells mutations in BCL-6
78
Follicular Lymphoma
Non-Hodgkin lymphoma Neoplasm of mature B cells t(14;18)- translocation of heavy chain Ig (14) and BCL-2 (18)
79
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+
80
Marginal Zone Lymphoma
Non-Hodgkin lymphoma Neoplasm of mature B cells t(11;18)
81
Primary Central Nervous System Lymphoma
Non-Hodgkin lymphoma Neoplasm of mature B cells EBV related; associated with HIV/AIDS
82
Adult T-cell Lymphoma
Non-Hodgkin lymphoma | Neoplasm of mature T cells
83
Mycosis fungoides/Sezary Syndrome
Non-Hodgkin lymphoma | Neoplasm of mature T cells
84
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
85
Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma | CLL
Leukemia - Lymphoid Neoplasm Most common adult leukemia CLL = Crushed Little Lymphocytes (smudge cells)
86
Hairy Cell Leukemia
Leukemia - Lymphoid Neoplasm | Adult males. Mature B-cell tumor. Cells have filamentous, hair-like projections
87
Acute Myelogenous Leukemia | AML
Leukemia - Myeloid Neoplasm Auer rods. Increased circulating myeloblasts (eosinophil, basophil, neutrophil) on peripheral smear.
88
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.
89
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
90
Essential Thrombocytopenia
Massive proliferation of megakaryocytes and platelets. Symptoms including bleeding and thrombosis.
91
Myelofibrosis
Obliteration of bone marrow with fibrosis due to increased fibroblast activity. Associated with massive splenomegaly and "teardrop" RBCs

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