Flashcards in Hematology/ Oncology Missed Questions Deck (243):
In a-fib, what regulates the number of atrial impulses that reach the ventricle?
The AV node refractory period determines the number of impulses that reach the ventricle and determines ventricular contraction rate.
What is hepcidin?
An acute phase reactant synthesized by the liver that acts as the central regulator of iron homeostasis
What is ferroportin?
A transmembrane protein responsible for transferring intracellular iron to circulation.
Describe the two paths for iron once inside the intestinal cells.
1. it may bind to ferritin to be stored within an enterocyte. It is excreted in the stool as enterocytes slough off and are replaced; 2. It may enter circulation through ferroportin; free iron in circulation is transported by transferrin.
How is hepcidin synthesized?
By hepatic parenchymal cells. Synthesis is increased in inflammatory conditions and is lowered in states of hypoxia and erythropoiesis.
How do low hepcidin concentrations affect iron absorption?
Low hepcidin levels increase intestinal iron absorption and stimulate iron release by macrophages.
In Burkitts lymphoma, what gene is translocated and what is its function?
Translocation of the c-myc oncogene on the long arm of chromosome 8 with the Ig heavy chain region on chromosome 14. C-myc is a nuclear phosphoprotein that functions as a transcription factor which controls cell proliferation, differentiation, and apoptosis.
What is deficient in a patient with acute intermittent porphyria?
Porphobilinogen (PBG) deaminase deficiency
How does acute intermittent porphyria present?
Acutely with GI and neurologic symptoms, most commonly abdominal pain, vomiting, peripheral neuropathy, neuropsych derangements. Key feature is reddish urine that darkens on exposure to light and air due to oxidation of excess PBG.
What is the target of treatment and prevention of acute porphyria attacks?
Inhibition of ALA synthase (rate limiting enzyme of heme synthesis) to reduce formation of toxic intermediate metabolites. Avoid CYP450 inducers, alcohol, smoking; tx with IV heme administartion and carbohydrate loading such as dextrose infusion.
How does CO affect PaO2?
It does not affect this value. It only affects the amount of oxygen that can bind to hemoglobin and PaO2 in CO poisioning is typically normal.
What side effects are associated with ticlopidine?
Neutropenia, fever, mouth ulcers.
Auer rods are found in what type of cells?
Myeloblasts in AML
What is the mechanism of Heparin?
It increases the effect of antithrombin III.
What is measured to monitor the therapeutic effect of heparin?
aPTT (activated partial thromboplastin time).
What is protamine sulfate used to treat?
Heparin toxicity (not effective in LMW heparins)
What is the function of aminocaproic acid treatment?
To inhibit fibrinolysis.
To what drug class does enoxaparin belong?
Low molecular weight heparin. It functions by binding and activating antithrombin III.
How does antithrombin III produce an anticoagulant effect?
By reducing thrombin production through binding to factor Xa to stop the conversion of prothrombin to thrombin.
What adverse effects are associated with Non-nucleotide RT inhibitors?
Abrupt flulike symptoms, abdominal pain, jaundice, fever may indicate hepatic failure and encephalopathy. These effects are most common within the first 6 weeks of therapy. Stevens- Johnson syndrome has also been observed.
How are nonnucleoside reverse transcriptase inhibitors (NNRTIs) activated?
They do not require activation via intracellular phosphorylation.
Name the three most common NNRTI drugs.
Nevirapine, efavirenz, delavirdine.
HIV fusion inhibitor drugs function by what mechanism?
Selective binding to HIVs transmembrane envelope protein gp41
What is the mechanism of action of enfuvirtide?
Binds to the heptad repeat 1 (HR1) of gp41 preventing gp41 from undergoing conformational changes necessary for viral membrane fusion with the target cellular membrane. This denies HIV genome entry into uninfected CD4+ T cells.
What is the mechanism of action of aspirin?
Irreversible inhibition of COX1 and COX2 through acetylation of the COX enzymes. At low doses, aspirin inhibits COX1 alone but at high doses it inhibits both COX 1 and COX2.
What drug is used to terminate early (<6 weeks gestational age) ectopic pregnancies?
What does methotrexate inhibit?
Competitive and irreversible inhibition of dihydrofolate (DHF) reductase. This causes accumulation of dihydrofolic acid polyglutamate within treated cells.
Where in the prostate does prostate adenocarcinoma typically originate?
The peripheral zone of the prostate and can thus be detected on digital rectal examination as an asymmetric nodular enlargement of the prostate.
What is characteristic of a peripheral blood smear in a patient with lead poisioning?
Coarse basophilic stippling on the background of hypochromic microcytic anemia. Basophilic stippling is the result of ribosome aggregation.
What is inhibited in lead poisioning?
delta-ALA dehydratase. This causes reduced incorporation of iron into heme and decreased hemoglobin synthesis.
What occurs in clotting after platelet activation?
Release of mediators (such as ADP and thromboxane A2) and conformational change of glycoprotein IIb/IIIa to bind fibrinogen and form a crosslinked plug.
What is the mechanism of action of Abciximab?
A glycoprotein IIb/IIIa inhibitor. It inhibits its binding to fibrinogen.
What conditions is Abciximab used to treat?
Unstable angina, acute coronary syndrome (esp in patients undergoing percutaneous coronary intervention).
What is Glanzmann thrombasthenia?
Disorder characterized by defective glycoprotein IIb/IIIa on platelet surfaces causing mucocutaneous bleeding. No platelet clumping on peripheral smear.
Which proteins drive angiogenesis?
Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Proinflammatory cytokines (like IGF-1 and INF-y) can indirectly promote angiogenesis through increased VEGF expression.
What does ki-67 fraction measure?
Proliferation index (ie mitotic index)
What condition is characterized by burr cells, helmet cells, and RBC fragments?
Traumatic hemolysis which can result from either microangiopathic hemolytic anemia or mechanical damage (i.e. prosthetic valve).
What are Burr cells?
Erythrocytes with short, evenly spaced projections. They can occur as an artifact or in association with uremia, pyruvate kinase deficiency, microangiopathic hemolytic anemia, or mechanical damage.
What distinguishes benign lymph node enlargement from malignant enlargement?
Benign enlargement in response to antigenic stimulation is associated with a polyclonal proliferation of lymphocytes; malignancy is associated with a monoclonal lymphocytic proliferation.
What findings are seen on light microscopy of GBM?
Pseudopalisading tumor cells around areas of necrosis. Necrosis and hemorrhage are also seen on gross examination.
What is the key metabolic difference between methotrexate and 5-FU?
Methotrexate prevents reduction of folic acid to tetrahydrofolate while 5-FU binds tetrahydrofolate and thymidylate synthetase in a stable reaction intermediate form thereby decreasing the amount of thymidylate synthetase available for thymidine synthesis.
How does leucovorin (N5-formyl-tetrahydrofolate) rescue cells from MTX toxicity?
It is a tetrahydrofolate derivative that does not require reduction by dihydrofolate reductase before acting as a cofactor for thymidylate synthase. It thus bypasses the dihydrofolate reductase step inhibited by methotrexate.
What is a common point in the mechanism of action of MTX and 5-FU?
Both effectively inhibit thymidylate formation. The effects of methotrexate can be overcome by folinic acid or leucovorin supplementation however.
Myeloblasts stain positive for what?
Peroxidase (or myeloperoxidase) in auer rods.
Describe the appearance of a myeloblast nucleus.
Folded/ bilobed nuclei containing multiple nucleoli. They contain auer rods.
What are the clinical manifestations associated with hereditary spherocytosis?
Anemia, jaundice, splenomeagly with increased risk of pigmented gallstones and aplastic crisis (parvovirus B19 infection). These sx are caused by splenic sequestration.
What test is diagnostic for hereditary spherocytosis?
Osmotic Fragility Test.
What is the pattern of inheritance for hereditary spherocytosis?
What types of proteins are BRCA1 and BRCA2?
DNA repair genes.
What laboratory abnormalities are characteristic of multiple myeloma?
Erythrocyte rouleaux formation on peripheral smear and Bence-Jones proteins in the urine.
What reduces the risk of non-hereditary ovarian cancer?
OCPs. They decrease the total number of times that a woman ovulates in her lifetime and thus with fewer ovulatory cycles, there is less need for ovarian surface repair
What is the most prominent adverse effect of Cisplatin?
Nephrotoxicity (acute tubular injury)
What preventative measures must be undertaken for a patient on cisplatin?
Amifostine- a thiol based cytoprotective free radical scavenging agent used to decrease cumulative nephrotoxicity. Also, chloride diuresis (via IV NS) keeps cisplatin in the nonreactive state.
Hemolytic anemia due to intravascular erythrocyte destruction results in what laboratory findings?
Increased serum indirect bilirubin, free hemoglobin in serum and urine, and increased LDH. It also causes decreased serum haptoglobin.
What is haptoglobin?
A serum protein that binds to free hemoglobin and promotes its uptake by the reticuloendothelial system.
When do haptoglobin levels characteristically decrease?
When significant quantities of hemoglobin are released into circulation (ex. intravascular hemolysis).
What are the lymphoblast types in precursor B-ALL?
TdT+, CD10+, CD19+.
What are the lymphoblast types in precursor T-ALL?
CD2, CD3, CD4, CD5, CD7, CD8, TdT, CD1a
What disorders characteristically present with petechial lesions?
How does Desmopressin acetate (DDAVP) ameliorate symptoms of hemophilia A?
Stimulates release of factor VIII and vWF from endothelial cells which temporarily increases factor VIII. It has no effect in hemophilia B.
What symptoms are associated with hemorrhagic disease of the newborn?
Cutaneous, GI, and intracranial bleeding due to vitamin K deficiency.
Patients with Polycythemia Vera have increased incidence of what conditions?
Peptic ulceration, itching, gouty arthritis, reversible moderate hypertension.
What type of protein is JAK2?
A non-receptor tyrosine kinase associated with the erythropoietin receptor (a type I cytokine receptor).
What are bence jones proteins?
Monoclonal light chains circulating in the serum or urine.
What is the most common mutation associated with primary hemochromatosis?
Mutation of the HFE protein which interacts with the transferrin receptor to increase endocytosis of the iron transferrin complex. This iron is added to the regulatory pool which controls expression of proteins involved in iron absorption.
What is the pathophysiology of iron deposition in hereditary hemochromatosis?
Mutated (inactivated) HFE proteins cause enterocytes and hepatocytes to detect falsely low iron levels which increases bodily iron accumulation through enterocyte increase of apical divalent metal transporter 1 (DMT1) which increases iron absorption from the intestinal lumen; and by hepatocyte decrease of hepcidin synthesis which causes increased ferroportin expression allowing for increased iron secretion into circulation.
What is the classic triad of symptoms in hereditary hemochromatosis?
Micronodular cirrhosis, diabetes mellitus, skin pigmentation.
For what conditions are patients with hereditary hemochromatosis at increased risk?
HCC, CHF, testicular atrophy/ hypogonadism.
What predisposes a patient on warfarin to warfarin-induced skin necrosis?
A protein C or protein S deficiency. This causes a relative hypercoaguable state with thrombotic occlusion of the microvasculature and skin necrosis due to rapid drop in protein C and factor VII levels.
Mutations to genes that code for epidermal growth factor receptors are associated with what cancers?
Non-small cell lung carcinoma (erbB1), breast cancer (erbB2 aka Her2/neu), some ovarian and gastric tumors
In what condition does a defective platelet derived growth factor play a role?
Chronic myelomonocytic leukemia
What is the mechanism of action of argatroban?
It is a direct thrombin inhibitor and binds directly tho the thrombin active site
Name the three direct thrombin inhibitors.
Hirudin, lepirudin, argatroban
What drugs are used to treat Heparin Induced Thrombocytopenia?
Direct thrombin inhibitors as they do not require antithrombin III for action.
What side effects are associated with Dapsone?
Fever, rash, methemoglobinemia, oxidative stress (hemolytic anemia in people with G6PD deficiency)
Name four triggers of G6PD deficiency anemia.
Infection, drugs (dapsone, antimalarials, sulfonamides, diabetic ketoacidosis, favism (fava beans).
When are bite cells most commonly seen?
Due to oxidant induced damage (i.e. in G6PD deficiency)
On crystal violet stain, how does G6PD deficiency present?
With Heinz bodies- small irregular, dark purple granules in RBCs. Peripheral smear will also show Bite cells (Caused by attempted removal by splenic monocyte macrophage system).
A prolonged PTT indicates a defect in what coagulation factors?
VIII, IX, XI, or XII.
Bleeding time is a measure of what?
In Hemophilia A and B, what do bleeding time labs show?
Isolated prolongation of PTT. PT, TT, and bleeding time are normal.
Deficiencies in what factors cause PT prolongation?
II, V, VII, X and fibrinogen.
What is the leading cause of blindness in developed countries?
Age related macular degeneration.
What is age related macular degeneration?
Degeneration of the central retina that presents as difficulty with driving, reading, watching TV, and other daily life activities. It can be classified as 'dry' or 'wet'.
What is dry age related macular degeneration?
Gradual loss of vision in one or both eyes due to subretinal drusen deposits or pigment changes. It usually progresses to wet AMD.
What is wet age related macular degeneration?
Abnormal blood vessels with subretinal fluid/ hemorrhage, gray subretinal membrane, neovascularization which lead to acute vision loss over a period of days to weeks. Caused by VEGF which causes retinal neovascularization.
How are dry and wet age related macular degeneration treated?
Dry and less advanced AMD: antioxidant vitamins and zinc; active and more-advanced wet AMD: anti VEGF inhibitors, laser therapy, phototherapy.
What type of oncogenic activity does Ras have?
What is Retinoblastoma (Rb) protein?
A regulator of the G1- S phase transition. It is active when it is hypophosphorylated (i.e. blocks transition to S phase)
What type of drug is raltegravir and what is its mechanism of action?
Integrase inhibitor in HIV which prevents the host cell from synthesizing HIV mRNA from DNA.
What type of protein is K-ras?
In a patient with folate deficiency anemia, what is seen on peripheral smear?
Pancytopenia and hypersegmented neutrophils.
How do platelets adhere to vessel collagen?
By glycoprotein Ia/IIa. Attachment is strengthened by binding of glycoprotein Ib/IXb with von Willebrand factor on the vessel wall.
What is extramedullary hematopoiesis?
Erythropoietin stimulated, hyperplastic marrow cell invasion of extramedullary organs.
What conditions cause extramedullary hematopoiesis?
Severe chronic hemolytic anemias (e.g. b-thalassemia)
What type of arthritis is typically seen in patients with SLE?
Symmetric, migratory arthritis.
What antibodies are produced by patients with SLE?
Anti ANA (sensitive); anti ds-DNA and anti-SM (specific)
What type of anemia may be present in patients with SLE?
Hemolytic anemia, thrombocytopenia, leukopenia.
What are keratins?
A broad group of intermediate filaments present in epithelial cells.
What do pathologists use keratin markers to detect?
Identification of poorly differentiated tumors or tumors with an unclear site of origin.
Name six types of tumors that stain positive for keratin.
Carcinomas, mesotheliomas, thymomas, sarcomas, trophoblastic tumors, desmoplastic small round cell tumors.
Describe the normal hemoglobin composition of adults.
HbA (a2b2) = ~97%; HbA2 (a2d2) =~2.5%; HbF (a2y2) = <1%.
What is Hemoglobin HbA1c?
A measurement of glycated hemoglobin.
How is Hemoglobin HbA1c formed?
Glucose attaches irreversibly to HbA inside erythrocytes by freely diffusing across the RBC membrane. This value reflects average blood glucose levels over the total erythrocyte lifespan.
What states influence HbA1c levels?
Changes in RBC survival.
What is the most common form of childhood brain tumor?
What is the most common location for pilocytic astrocytomas?
In the cerebellum of children (but they can develop in the cerebral hemispheres also).
How do pilocytic astrocytomas appear on imaging?
As a mass with both solid and cystic components.
How do pilocytic astrocytomas appear on microscopic examination?
Pilocytic astrocytes and Rosenthal fibers are seen.
What is the most common malignant childhood brain tumor?
How do medulloblastomas present on histology?
As sheets of small blue cells with hyperchromatic nuclei and scant cytoplasm.
Where are medulloblastomas most commonly located?
In the cerebellum of children.
What is the principle difference between a medulloblastoma and a pilocytic astrocytoma on imaging?
A medulloblastoma is a solid tumor; a pilocytic astrocytoma has both cystic and solid components.
What is the difference in possible secretory products between small cell carcinoma of the lung vs. squamous cell carcinomas of the lung?
Squamous cell produces PTHrP; Small cell produces ACTH and/or vasopressin.
Which type of NSAIDs do not impair platelet aggregation?
Selective COX2 inhibitors. (Platelets primarily express COX1).
What is the function of the Bcl-2 protein?
Bcl-2 inhibits apoptosis of tumor cells, promoting survival.
Why may excessive bleeding be seen in a patient with significant renal dysfunction?
Caused by an accumulation of uremic toxins in circulation which impair platelet aggregation and adhesion/
What laboratory characteristics are seen in a patient with abnormal bleeding secondary to renal failure?
Qualitative platelet disorder characterized by prolonged bleeding time with normal platelet count, PT, and aPTT. This can be improved with dialysis.
What is the characteristic histological appearance of plasma cells?
Abundant basophilic cytoplasm, eccentrically placed nuclei, wagon wheel/ clock face distribution of nuclear chromatin.
What bone marrow findings are diagnostic of multiple myeloma?
Greater than 30% plasma cells.
What type of anemia is seen in patients with multiple myeloma?
Normocytic and normochromic anemia due to bone marrow infiltration and replacement by malignant plasma cells. Suppression of normal hematopoiesis.
What causes osteopenia and bone resorption in a patient with multiple myeloma?
Secretion of IL-1 (osteoclast activating factor) and IL-6 by neoplastic cells. This causes hypercalcemia.
What forms due to accumulation of monoclonal immunoglobulin light chains in a patient with multiple myeloma?
AL amyloid. This contributes to renal failure and amyloidosis of the heart, tongue, and nervous system.
What antineoplastic drug is an adenosine analog and reaches high intracellular concentrations due to resistance to adenosine deaminase?
What is the drug of choice in hairy cell leukemia and what drug class is it in?
Cladribine, a purine analogue.
To what receptors does von Willebrand Factor bind?
GP Ib-IX receptors on the platelet membrane
What test is used to measure vWF platelet aggregation?
Addition of Ristocetin; this produces poor platelet aggregation in patients with a vWF deficiency.
What is the pharmacologic treatment for vWF deficiency?
Desmopressin (DDAVP) which stimulates vWF release from the endothelium.
In a patient who ingested rat poison, what must be administered to prevent life threatening GI bleeding?
Fresh frozen plasma- this restores the clotting factors II, VII, IX, and X (vitamin K dependent factors) which are depleted by the poison. Vitamin K should also be given.
Most anemias produce increased production of what blood parameter as a compensatory response?
What is the classic triad of symptoms in aplastic anemia?
Low hemoglobin, absent hematopoietic cells in the bone marrow, thrombocytopenia.
In what conditions is an increased reticulocyte index seen?
Hemolytic or hemorrhagic anemia assuming normal bone marrow function. In aplastic anemia, it is low because there are few marrow progenitor cells.
What is erythropoietin?
A hormone secreted by the kidneys to induce RBC formation.
What cell surface glycoprotein may prevent the action of chemotherapeutic agents?
The human multidrug resistance (MDR1) gene codes for P-glycoprotein which is a transmembrane ATP dependent efflux pump protein that has broad specificity for hydrophobic compounds. It can reduce drug influx into the cytosol and can increase drug efflux from the cytosol preventing action of chemotherapeutic agents.
What drug can be administered to reverse methotrexate toxicity?
Folinic acid (leucovorin)
What is the function of leucovorin?
To rescue bone marrow, gastrointestinal, and other mucosal cells from toxicity following high dose methotrexate administration.
What is a principle difference between Hepatitis C and Hepatitis B viruses?
Hep C is an RNA virus, Hep B is a DNA virus.
Describe the difference in Hep. B and Hep C. liver toxicity.
Hepatitis B virus integrates its DNA into the host genome which increases risk for HCC. Hepatitis C is an RNA virus and lacks reverse transcriptase so does not integrate into the host genome.
In patients with B12 deficiency, what is the most common means of supplement administration?
Parenterally; oral supplementation only corrects the deficiency in patients with insufficient intake. For most patients (with gastric atrophy, intrinsic factor deficiency, or terminal illeal disease), parenteral administration is required.
Patients with repeated blood transfusions are likely to have buildup of what substance? And what form is this deposited in?
Iron buildup. Deposited as hemosiderin within tissues.
What symptoms are characteristic of paroxysmal nocturnal hemoglobinuria (PNH)?
Hemolytic anemia, hypercoaguability, pancytopenia.
What genetic mutation is associated with paroxysmal nocturnal hemoglobinuria?
Aquired PIGA gene mutation within a clonal population of multipotent hematopoietic stem cells. The gene is involved in glycosylphosphatidylinositol anchor (GPI) synthesis which is necessary for attachment of cell surface proteins including CD55 and CD59.
What is the function of CD55?
Decay accelerating factor.
What is the function of CD59?
MAC inhibitory protein.
What deficiencies are present in patients with paroxysmal nocturnal hemoglobinuria?
CD55 and CD59 deficiency and deficiency in complement-mediated hemolysis.
What complications are associated with paroxysmal nocturnal hemoglobinuria?
Budd chiari syndrome due to thrombotic complications, pancytopenia, aplastic anemia.
How is Paroxysmal Nocturnal Hemoglobinuria diagnosed?
Flow cytometry will show absence of GPI anchor and CD55 and CD59 deficiency.
Where are most coagulation factors synthesized?
In the liver.
What coagulation factor has the shortest half life?
Factor VII, part of the extrinsic pathway.
What coagulation factor is most likely to first become deficient in a patient with liver failure and what lab result will reflect this deficiency?
Factor VII deficiency resulting in prolonged PT.
What lab value must be monitored in a patient taking warfarin?
PT (or INR).
What is used to most rapidly reverse warfarin toxicity?
Fresh frozen plasma.
What is implicated by presence of erythroid precursor cells in the liver and spleen?
What lab findings are associated with DIC?
Prolonged PTT, prolonged PT, thrombocytopenia and microangiopathic hemolytic anemia, low fibrinogen, elevated fibrin split products (D dimer), low factor V and VIII levels.
What is the mechanism of action of 6-Mercaptopurine?
Purine analog that inhibits de novo purine synthesis after being converted to active metabolites by hypoxanthine-guanine phosphoribosyl transferase (HGPRT).
6-Mercaptopurine is inactivated by which enzyme?
Xanthine oxidase degradation in the liver.
What drug may increase concentration of 6-mercaptopurine?
Allopurinol (xanthine oxidase inhibitor)
6-mercaptopurine and 6-thioguanine are prodrugs that require activation by what enzyme?
Hypoxanthine-guanine phosphoribosyl transferase.
Name three drugs that cause aplastic anemia.
Carbamazepine, chloramphenicol, sulfonamides.
What is a major dose related side effect associated with chloramphenicol?
Dose related anemia, leukopenia, and/or thrombocytopenia
What is a major dose independent side effect associated with chloramphenicol?
Aplastic anemia- this may be fatal if not treated with bone marrow transplantation.
What lab findings are associated with iron deficiency anemia?
Decreased serum ferritin, increased serum transferrin, and increased total iron binding capacity. Also decreased blood hemoglobin and microcytic hypochromic RBCs.
What is ferritin?
Cellular iron storage protein. It is also an acute phase reactant and may be elevated in patients with infections or inflammatory disease.
What is transferrin?
Transports iron through the plasma. In normal iron states, approximately 1/3 of circulating transferrin is saturated with iron. Synthesis of transferrin is markedly increased in iron deficiency.
What cell marker is diagnostic of small cell carcinoma?
Neuroendocrine markers such as neuron specific enolase, chromogranin, synaptophysin, neurofilaments. They also contain neurosecretory granules in the cytoplasm.
What cell marker is used to diagnose sarcomas?
Vimentin, an intermediate filament found in cells of mesenchymal origin.
What cell marker is used to diagnose non-small cell carcinomas?
Expression of EGF receptors, mucin, and surfactant associated proteins.
What causes hemorrhagic cystitis?
Urinary excretion of the toxic metabolite acrolein.
What is filgastrim?
A G-CSF (granulocyte colony stimulating factor) used to stimulate the proliferation and differentiation of granulocytes in patients with neutropenia as can occur after chemotherapy.
What enzyme metabolizes pro-carcinogens?
Cytochrome P450 monooxygenase of hepatic microsomes and in the endoplasmic reticula of other tissues. This converts pro-carcinogens to carcinogens capable of causing DNA mutation.
What is the HER-2/Neu gene also called?
What cells appear as blue, enlarged red blood cells on Wright-Giemsa stain?
What cellular component of reticulocytes appear blue microscopically after application of the Wright-Giemsa stain?
What deficiencies are sickle cell patients particularly prone to?
Folic acid deficiency due to increased erythrocyte turnover.
What presentation is typical of T-ALL over B-ALL?
Large anterior mediastinal mass that may compress the great vessels causing superior vena cava syndrome. It may also compress the esophagus causing dysphagia and compression of the trachea leading to dyspnea and stridor.
What cell surface markers characterize pre-B lymphoblasts?
CD10, CD19, CD20.
What cell surface markers characterize pre-T lymphoblasts?
CD2, CD3, CD4, CD5, CD7, CD8.
What is the most common malignancy of childhood?
Acute Lymphoblastic Leukemia (ALL)
Which type of ALL is most common?
B-cell ALL (70-80%); T cell accounts for 15-17%
What is Rituximab?
A monoclonal antibody used in lymphoma immunotherapy to specifically target the CD20 surface immunoglobulin.
What is the most common indolent non-Hodgkin lymphoma in adults?
What is follicular lymphoma?
Follicular B cell lymphoma that has an indolent clinical course marked by remissions and recurrences. It most often presents with painless lymph node enlargement of abdominal discomfort from an abdominal mass.
What is overexpressed in follicular lymphoma?
What is the pathophysiology associated with G6PD deficiency?
An X-linked erythrocyte enzyme deficiency of the hexose monophosphate pathway. NADPH produced in RBCs is low which impairs glutathione- mediated inactivation of free radicals. This induces hemolytic episodes as induced by infections, medications, and other oxidants.
What type of anemia is implicated by schistocytes (fragmented RBCs) in a peripheral smear?
Microangiopathic hemolytic anemia
Name five causes of microangiopathic hemolytic anemia.
HUS, TTP, DIC, malignant hypertension, metastatic carcinoma.
What is the the underlying pathophysiology of hemolytic uremic syndrome?
Endothelial cell injury causes isolated activation of platelets and formation of microthrombi. RBCs are damaged when passing through mucrovascular channels and appear as schistocytes. The coagulation system is not activated thus PT and PTT are normal
What is the characteristic pentad of symptoms in HUS and TTP?
Fever, neurologic manifestations, renal failure, thrombocytopenia, microangiopathic hemolytic anemia
What are the principle epidemiological differences between HUS and TTP?
HUS occurs primarily in children and has renal involvement; TTP occurs most often in adults with predominant neurological symptoms. Fever, thrombocytopenia, microangiopathic hemolytic anemia are common in both conditions.
What is the treatment for HUS and TTP?
What are metalloproteinases?
Zn containing enzymes that degrade extracellular matrix. They participate in normal tissue remodeling and in tumor invasion through the basement membrane and connective tissue.
What is Immune thrombocytopenic purpura (ITP)?
An autoimmune disease characterized by the immune destruction of platelets by anti-platelet antibodies. In children it is typically acute and self limited while in adults it is often insidious and chronic. Tx is immunosuppression (steroids).
What symptoms are associated with immune thrombocytopenic purpura?
Ecchymoses, petechiae, mucosal bleeding without signs and symptoms of TTP/HUS, pancytopenia, marrow failure or splenomegaly.
What condition is indicated by red blood cells without central pallor?
Spherocytes. Indicate spherocytosis.
What red cell index is most specific for spherocytosis?
Elevated mean corpuscular hemoglobin concentration (MCHC).
What differentiates the presentation of CML from leukemoid reaction?
Both cause elevation of WBCs but neutrophil alkaline phosphatase level is elevated or normal in a leukamoid reaction but is decreased in CML.
What is the difference in lab values between AML and CML?
In AML, myeloblasts are elevated; in CML, there are few blasts.
What is the most important criteria for determining cancer prognosis?
Tumor stage (extent of tumor expansion)
What is considered first line treatment for DVTs in pregnant women?
What is the underlying pathology associated with mealoblastosis?
A defect in DNA synthesis. In chronic alcoholics this can result from a nutritional deficiency of folate which impairs synthesis of purine and pyrimidine bases.
What do blast cells look like on peripheral smear?
Very large nucleated cells with scant cytoplasm.
What is required for diagnosis of AML?
Greater or equal to 20% myeloblasts in the peripheral blood or marrow.
What is a complication associated with massive transfusion of packed red blood cells (i.e. more than 5-6 L of blood)?
Chelation of serum calcium (and magnesium), causing hypocalcemia and parasthesias. This is caused by elevated plasma levels of citrate, a substance added to stored blood.
In a patient with an intrinsic pathway clotting defect, administration of what agent will induce blood clotting?
What lab findings are characteristic of HUS?
Decreased RBC count, hematocrit, and platelet count, increased bleeding time, LDH, BUN, and creatinine.
What is Polycythemia Vera?
A clonal myeloproliferative disease of pluripotent hematopoietic stem cells. JAK2 mutation renders hematopoietic stem cells more sensitive to growth factors.
How does polycythemia vera present?
With increased RBC mass, increased plasma volume, low erythropoietin levels; elevated WBC count, thrombotic events (blood hyperviscosity), peptic ulceration, pruritus, gouty arthritis.
What are common physical exam findings in a patient with polycythemia vera?
Plethoric, ruddy face and splenomeagly.
What is the treatment for polycythemia vera?
Serial phlebotomy to keep hematocrit < 45%.
What may cause increased hematocrit in patients with obstructive sleep apnea?
Release of erythropoietin into the bloodstream by peritubular cells in the renal cortex due to sensed hypoxia.
Where are erythrocytes produced?
Induced by erythropoietin, production occurs in the bone marrow.
What is hematocrit?
The percentage of the volume of whole blood that is composed of RBCs.
In patients with high risk of developing DIC and progressive hypofibrinogenemia, what should be carefully monitored?
Serum fibrinogen and platelet count.
What result in the Schilling test indicates dietary deficiency of vitamin B12?
Normal urinary excretion of radiolabeled vitamin B12 suggests normal absorption and thus B12 deficiency is due to poor intake.
What Schilling test result indicates pernicious anemia?
Diminished urinary excretion of radiolabeled B12. Normal excretion after administration of intrinsic factor is diagnostic of pernicious anemia. Low excretion of B12 after intrinsic factor administration indicates malabsorption syndromes like pancreatic insufficiency, bacterial overgrowth, short gut syndrome.
What type of leukemia can be treated by all trans retinoic acid (ATRA)?
Acute promyelocytic leukemia.
What gene is fused in patients with APL?
PNL/RARa. The fusion prevents the gene from signalling for proper cellular differentiation.
Define anaplastic and describe the features of an anaplastic tumor.
Neoplastic cells that demonstrate a complete lack of differentiation. Tumors bear no resemblance to the tissue of origin and are composed of pleomorphic cells with large, hyperchromatic nuclei that grown in a disorganized fashion. Anaplastic tumors may also contain many abnormal mitoses and giant tumor cells.
What is pure red cell aplasia (PRCA)?
A rare form of marrow failure characterized by severe hypoplasia of marrow erythroid elements in the setting of normal granulopoiesis and thrombopoiesis.
What conditions are associated with pure red cell aplasia?
Thymoma (autoimmune condition), lymphocytic leukemias, parvovirus B19 infection.
What three lab findings are diagnostic of hemolytic anemia?
Elevated LDH, indirect billirubinemia, anemia.
What condition is diagnosed by a positive osmotic fragility test?
What is a complication of hemolytic anemia?
Pigmented gallstones (composed of calcium bilirubinate, bilirubin polymers, calcium salts)
In a lesion involving the jugular foramen, what are the symptoms of jugular foramen (Vernet) syndrome?
CN IX, X, XI dysfunction. Loss of taste from posterior 1/3 of tongue (IX), reduced parotid gland secretion (IX), loss of gag reflex (IX, X), dysphagia (IX, X), dysphonia/ hoarseness (CN X), soft palate drop with uvular deviation towards normal side (X), STM and trapezius paresis (XI).
What symptoms are common in a patient with von Willebrand disease?
Easy bleeding from mucosal sites including gingivae, nasal mucosa, GI tract, menorrhagia.
Name the two roles of von Willebrand Factor.
Carrier protein for factor VIII; Aids in platelet adhesion to injured blood vessels during clotting by binding platelet glycoproteins and exposed collagen on injured blood vessel walls.
Cytokeratin is used as an immunohistochemical marker of what type of tissues?
What is encoded by the HER2/neu oncogene?
A transmembrane glycoprotein with intracellular tyrosine kinase activity. It is a member of the family of epidermal growth factor receptors.
What factor, when administered in vitro to animals produces symptoms of cachexia?
What symptoms are associated with a factor V Leiden deficiency?
Va is resistant to inactivation by protein C, an antithrombotic. This causes hypercoaguability.
Follicular lymphoma is associated with what translocation and what gene expression abnormality?
t(14,18) translocation with Bcl2 overexpression. Bcl2 is a protooncogene (anti-apoptotic effects) causing cell immortality.
What are the side effects associated with Vincristine?
Neurotoxicity- peripheral neuropathy. This is the dose limiting side effect.
What is the mechanism of action of vincristine (and other vinca alkaloids)?
Inhibition of microtubule polymerization after binding to b-tubulin. M-phase specific agents.
How do reticulocyte count, hemoglobin, and erythrocyte count levels change in a patient with a vitamin B deficiency who is started on replacement therapy?
Reticulocyte count increases dramatically upon initiation and hemoglobin and erythrocyte count levels rise more gradually.
What are the major adverse effects associated with Ganciclovir?
Neutropenia, anemia, thrombocytopenia, impaired renal function.
What is the major side effect associated with zidovudine?
Bone marrow suppression (anemia, granulocytopenia, etc,)
What are fibronectins?
Large glycoproteins produced by fibroblasts and some epithelial cells. It binds to integrins, matrix collagen, and glycosaminoglycans and serve as a mediator of normal cell adhesion and migration.
How is integrin mediated adhesion of cells to the basement membrane and extracellular matrix mediated?
Through binding of integrins to fibronects, collagen, and laminin.
What is the mechanism of action of etoposide?
Inhibition of the sealing activity of topoisomerase II. It causes chromosomal breaks to accumulate in dividing cells and ultimately causes cell death.
What is the difference between the actions of topoisomerase I vs topoisomerase II?
Topoisomerase I makes single stranded nicks to relieve negative supercoiling, topoisomerase II induces transient breaks in both DNA strands simultaneously to relieve both positive and negative supercoiling.
What two conditions is etoposide most commonly used to treat?
Testicular cancer and small cell lung cancer.
What are the two most common organisms causing bacteriemia in sickle cell patients?
Streptococcus pneumoniae followed by hemophilus influenza