Hematology/Oncology Flashcards
Fluctuating sizes of lymph nodes = _____ lymphoma
Follicular
What is 5-HIAA and what is its clinical utility?
A serotonin metabolite. Increased levels will be found in the urine in the setting of carcinoid syndrome.
What is carcinoid syndrome? What are presenting symptoms?
Carcinoid tumors arise from enterochromaffin (endocrine) cells of the intestinal mucosa. When they metastasize to the liver they bypass destruction and thus release their products into the systemic circulation. Most notably: serotonin (5-HT), bradykinin, and prostaglandins.
Symptoms:
Skin flushing, telangiectasias, watery diarrhea, bronchospasm, dyspnea, valvular fibrous plaques
Does CO cause methemoglobin?
NO!
Methemobloginemia is caused by drugs (dapsone, nitrites), enzyme deficiencies, and hemoglobinopathies
Ondansetron, granisetron, and dolasteron are all examples of ________ used in the treatment of _________. How do they work?
5-HT3 (serotonin) receptor antagonists
Treat chemotherapy-induced vomiting.
They work by:
- Blocking the vagus-mediated n/v from Gi tract stimulus
- Central blockage of serotonin receptors in the area protstrema and NTS
What are the 3 drug classes useful in treating chemotherapy-induced vomiting?
- Serotonin receptor antagonists (e.g. ondansetron)
- NK1 receptor antagonists (e.g. arepitant)
- Dopamine receptor antagonists (e.g. metoclopramide)
Why do you get splenomegaly in the setting of pyruvate kinase deficiency?
PK converts PEP to pyruvate in the glycolytic pathway. RBCs do not have mitochondria and thus rely on lactate (made from pyruvate) for glycolysis and thus ATP generation.
Absence of PK reduces ATP -> echinocyte formation and hemolysis. Hemolyzed RBCs are destroyed and eaten up in the spleen by the reticuloendothelial system in the RED PULP. Chronic hemolysis leads to red pulp hyperplasia and splenomegaly.
Etoposide targets Topoisomerase ___, preventing the repair of the double stranded breaks it makes when it relieves positive and negative supercoiling.
II
What lab findings are indicative of hemolytic uremic syndrome (HUS)?
Anemia and thrombocytopenia
Decreased hemoglobin and haptoglobin
Increased serum LDH and indirect (unconjugated) bilirubin
^massive hemolysis overwhelms conjugation abilities
_______ syndrome is characterized by dysphagia due to esophageal web formation, iron deficiency anemia, spoon nails, and a shiny smooth red tongue.
Plummer-Vinson
Tx: iron supplementation
How would nephrotic syndrome end up causing renal vein thrombosis and a varicocoele?
Nephrotic syndrome causes loss of many proteins, including anticoagulant antithrombin III -> hypercoaguable state and renal vein thrombosis.
RVT will cause impaired LEFT gonadal venous drainage -> varicocoele.
_______ balance pro- and anti-apoptotic proteins. When inhibited, proapoptotic proteins build up causing apoptosis. Bortezomib is an example of an inhibitor of these and is used in the tx of _________.
Proteasomes
Multiple Myeloma
Patients with beta thalessemias generate more Hemoglobin ____ to compensate. What is the main deficiency in beta thalessemias?
Hemoglobin A2 (alpha2delta2) is upregulated to compensate.
Occasionally increased HbF
Thalessemias occur due to a variety of DNA mutations affecting the transcription, processing, and translation of beta-globin mRNA (most commonly due to aberrant precursor mRNA splicing or premature chain termination during translation).
What do lead-poisoned RBCs look like? What are symptoms of lead poisoning?
Basophilic stipling
Microcytic hypochromic anemia
Constipation
Mental status change
HER2 ___ (+/-) breast cancers are associated with poorly differentiated, rapidly growing tumors.
HER2 +
HER2 oncogene encodes for a human epidermal growth factor receptor with tyrosine kinase activity in the intracellular domain.
Anti-HER2 monoclonal Abs (e.g. trastuzumab) are now available.
Integrin is important for bridging cell membranes with both INTRA and EXTRAcellular filaments. Intracellular filaments include:
Extracellular include:
Intracellular: actin and keratin
Extracellular: fibronectin, collagen, laminin
TMP-SMX is the drug of choice for PJP. However, in patients with sulfa allergies, dapsone is used instead. What does dapsone put them at risk for?
Methemoglobinemia.
Occurs most often in G6PD-deficient patients.
What are common precipitating factors for G6PD deficiency anemia?
- Infection
- Drugs (dapsone, antimalarials, sulfa drugs)
- DKA
- Favism (ingestion of fresh fava beans)
What do bite cells indicate?
Oxidant-induced RBC damage, e.g. G6PD deficiency
KRAS is a _______ while
APC, BRCA1, RB, and TP53 are all tumor _______
KRAS = proto-oncogene
The rest are examples of tumor suppressors.
What is the most common tumor in HIV-positive individuals?
Kaposi’s Sarcoma caused by HHV-8
Presents as multiple blue-violet or brownish dermal plaques that start on the feet and legs and spread proximally.
Cytokeratins are commonly used immunohistochemical markers for __________ tumors.
Epithelial-derived tumors (e.g. breast cancer)
Angiogenesis is primarily driven by what 2 factors?
VEGF (vascular endothelial growth factor)
and
Fibroblast growth factor (FGF)
How is G6PD deficiency inherited? In which ancestry is it most common?
X-linked (therefore more common in males)
Commonly found in people of African, Asian, and Mediterranean descent.
In question stems, hemolysis caused by sulfa drugs (bactrim, TMP/SMX) is often due to __________.
G6PD deficiency
G6PD is an enzyme in the pentose phosphate shunt necessary for maintaining NADPH (and therefore reduced glutathione needed to relieve RBC oxidative stress)
How does desmopressin (DDAVP) stop bleeding in hemophilia and Type I vWF disease patients?
Increases circulating factor VII and endothelial secretion of vWF to stop bleeding.
How is von Willebrand’s disease inherited?
Autosomal dominant
HHV8/Kaposi’s Sarcoma can cause __ cell lymphoma
B
What seen on peripheral smear is indicative of EBV (mono) infection?
“Downey cells” - atypical lymphocytes with abundant pale blue cytoplasm with a basophilic rim often indented by surrounding RBCs.
If the question stem says someone is generally unwell with a sore throat and “GENERALIZED” lymphadenopathy, think _____.
EBV (mono)!
EBV is associated with a higher incidence of which 3 cancers?
Hodgkin’s Lymphoma (mixed cellularity esp)
Non-Hodgkin’s Lymphoma: Burkitt lymphoma
Nasopharyngeal carcinoma
_____ patients who are improperly treated with amoxicillin or ampicillin (i.e. a penicillin when the Dr. mistakenly thinks it is strep) will break out in a maculopapular rash.
Mono
Weirdly it is not an allergic rxn. The actual cause is unknown.
How does the monospot test work?
Rapidly diagnoses mono in the clinic. You’ll see clumping of IgM when mixed with sheep EBV serum (??)
EBV + HIV = ?
Oral hairy leukoplakia
Immune thrombocytopenia purpura (ITP) is a group of disorders of IgG antibodies against ____________.
glycoprotein IIb/IIIa receptors on platelets -> thrombocytopenia because platelets are unable to adhere to one another
The classic (adult) ITP patient is?
A young woman with easy bruising and nosebleeds over a few months but no other symptoms/abnormalities
Heparin-Induced thrombocytopenia most commonly results from _______ heparin.
unfractionated
What is this describing? : IgG antibodies bind to platelets -> degranulation and destruction -> platelet factor 4 released -> ironically end up with platelet aggregation, clotting and at risk for DVT, PE, and arterial thrombus
Heparin-induced thrombocytopenia (probably from unfractionated heparin administration)
How should you treat HIT?
Direct thrombin inhibitors
e.g. bivalrudin, dabigatran, agatroban
Decreased haptoglobin is indicative of ________ .
Intravascular hemolysis.
Haptoglobin binds the circulating free hemoglobin
_____ is the #1 cause of AKI in children.
HUS
You should NEVER treat EHEC HUS with what?
Antibiotics! Abs kill off EHEC bacteria with shiga-toxin that upon killing would spill out and make the HUS way worse
What are the pentad of symptoms associated with TTP? What is the defect?
Thrombocytopenia Hemolytic anemia AKI Neuro sx Fever
Defect = Abs against AdamsTST13 which cleaves vWF
Bernard-Soulier = deficient ___
Glanzmann thrombasthenia = deficient ___
Bernard-Soulier = deficient Ib
Glanzmann thrombasthenia = deficient gIIb/IIIa
Wiskott-Aldrich is an x-linked deficiency in cytoskeletal proteins (WASP) needed to make what cell types?
Platelets
B cells
T cells
Increased alkaline phosphatase is indicative of osteo______ activity.
osteoblastic (i.e. bone formation)
Why is prothrombin time is a more sensitive test for liver damage than albumin levels?
The half-life of clotting factors is much much shorter (e.g. the shortest half life of factor VII is only 3-6 hours) while the half-life of albumin is 21 days so liver damage will show changes to the coagulation cascade much more readily.
How do you reverse heparin overdose?
Protamine (heparin-specific antidote)
NOT fresh frozen plasma because FFP contains antithrombin III -> enhances hep effect
What are the lab findings of SLE?
HA, thrombocytopenia, leukopenia
Hypocomplementemia (C3 and C4)
ANA pos
Anti dsDNA, Anti-smith
What does the spleen of an adult sickle cell patient look like?
Fibrosed and atrophied due to repeated infarction from sickled cells causing vasoclusive episodes.
Which leukemia can be treated with a vitamin A/retinoic acid derivative?
PML (acute myeloid leukemia with at t(15;17)
What positive lab test diagnoses hereditary spherocytosis?
Acidified glycerol lysis test
CD55 aka decay accelerating factor and CD59 aka MAC inhibitory protein are on ___ surfaces to prevent complement-mediated hemolysis
RBC
Cyanide toxicity is treated with inhaled ______
amyl nitrites which oxidize Fe2+ to Fe3+ generating methemoglobin which cyanide has a high affinity for so although it fucks up oxygen binding and delivery for a bit, it is better to have the cytochrome c oxidase working.
Target cells = _______ anemia
Microcytic
Hemoglobin H disease = ?
Alpha thalessemia intermedia - 3 out 4 alpha genes are deleted and thus lack of alphas sometimes leads to 4 betas becoming hemoglobin H. These guys will travel further on a gel and can sometimes precipitate and form inclusion inside in the cytosol -> extravascular hemolysis
Hemoglobin Barts = ?
4 gamma subunit Hgb formed in alpha thalessemia major (aka all 4 alpha subunits deleted)
Precipitates out -> massive hemolysis -> hydrops fetalis -> in utero death
Immediate Warfarin reversal is achieved with: ?
Fresh Frozen Plasma
If you end up with excessive bleeding from fibrinolytic administration, what can you give to reverse it?
Aminocaproic acid (lady capping the red paint in the sketchy)
OR
transexamic acid
Where is hepcidin made?
Liver: Hepatocytes in the parenchyma
Horse serum agglutination aka _______ aka _________.
Heterophile antibody test aka Monospot test
the rapid test for mononucleosis/EBV
What is hemoglobin A2?
A normal variant of hgb that inclues 2 alpha chains and 2 delta chains. Often higher than normal levels in patients with beta thalessemia
Older man + “dry tap” on bone marrow = ?
Likely Hairy Cell Leukemia
You’ll also see pancytopenia, massive splenomegaly, and TRAP pos.
could also be seen in late disease of primary myelofibrosis, given that the fibrotic marrow is the pathogenesis in both
Heme synthesis occurs where?
Mitochondria (first and final 3 steps) and cytoplasm (middle steps)
leucovorin aka ____
folinic acid
Enoxaparin = ?
LMWH
Why do you often see excessive bleeding in patients with significant renal dysfunction? What will you see on labs?
The accumulation of uremic toxins impair platelet aggregation and adhesion resulting in a qualitative platelet disorder. This causes prolonged bleeding time but platelet count, PT, and aPTT will all be normal!
What mnemonic is helpful to remember which cancers frequently metastasize to the bone?
“lead kettle”
PB/KTL
Prostate, breast, kidney, thyroid, lung
Rituximab is a mab against what?
CD20 (B-cells)
What is Gaucher disease and how does it present on bone marrow aspirate?
Gaucher disease is an AR lysosomal storage disease caused by Beta-glucocerebrosidase deficiencies. This leads to an accumulation of glucocerebroside (a glycolipid component of lymphocytes and RBCs)…
This build up leads to lipid-laden macrophages that make the cells look like “wrinkled tissue paper or crumpled newspaper”
