March 14 - Heme/onc Flashcards
Haldane effect
O2 affects affinity of hemoglobin for CO2/H+. Serves to increase CO2 delivery to lungs. Increase in PO2 increases CO2 and H+ offloading from Hb.
LMWH compared with UH
Better bioavailability Can give SC Less monitoring Longer half half Less easily reversible
Direct thrombin inhibitors
Argatroban, dabigatran, bivalirudin
Direct factor Xa inhibitors
Apixaban, rivaroxaban. Oral, don’t require monitoing but not as easily reversible.
Fondaparinux
Factor Xa inhibitor
Antiemetics used for chemo-induced vomiting
1) 5-HT3 antagonists: ondansetron and granisetron
2) Dopamine antagonists: metoclopromide, prochlorperazine
3) Neurokinin1 antagonists which prevent substance P release: aprepitant, fosaprepitant
Mutation in polycythemia vera (specifics)
Mutation in JAK2, which is involved in EPO signaling.
Normal pathway: EPO binds receptor. Receptor interacts with JAK2, which is a cytoplasmic tyrosine kinase receptor. Leads to downstream signling and activation of STATs.
Mutated pathway: JAK2 constitutively active resulting in overproduction of red cell.
Labs in sickle cell trait
Normal retic count, HGB, RBC indices and morphology
Integrins
Bind collagen, laminin, and fibronectin in the ECM to facilitate adhesion
Acute intermittent porphyria: presentation, pathophysiology, prevention, treatment of acute attacks
Presentation: episodes of abdominal pain, N/V, peripheral neuropathy, neuropsych derancements, red urine that darkens on exposure to light and air due to exccess PBG
Pathophys: AD defect in porphobilinogen deaminase in heme synthesis pathway. Causes early heme intermediates to accumulate and cause NS damage.
Prevention: avoid alcohol, smoking, and CYP inducing drugs which increase ALA synthase activity
Treatment : dextrose and IV heme which decrease ALA synthase activity
Cutaneous porphyrias
Caused by defect later in pathway than AIP. Photosensitivity
Heme synthesis pathway
Glycine and succinyl coA ALA Porphobiolinogen many steps Porphyrin IX Heme
Osteoblastic vs osteolytic bone mets: which cancers
Osteoblastic: prostate, small cell lung, hodgkin
Osteolytic: multiple myeloma, non-small cell lung, non-hodkin lymphoma, RCC, melanoma
Congenital parvovirus B infection, type of virus
Mom: arthritis
Fetus: hydrops fetalis due to interruption of erythropoiesis in bone marrow
Virus type: ssDNA
Congenital infections causing chorioretinitis
CMV or toxoplasma
Congenital infections causing sensorineural hearing loss
Rubella, CMV
Presentation of follicular lymphoma
Indolent, waxing and waning course. Painles LAD
Auer rods
Indicate myeloid differentation. Stain for peroxidase
RhoGAM: MOA
Anti-Rh(D) IgG pooled from donor plasma (polyclonal antibody). Binds to Rh-pos fetal RBCs that enter maternal circulation to prevent them from interacting with the maternal immune system and being sequestered in the spleen. Amount given is small enough that there is no significant transplacental fetal hemolysis.
IgG is given because that is what is produced against Rh antigens (vs IgM made against ABO)
Stop codons
UAA, UAG, UGA
Sickle cell mutation
Valine sub for glutamic acid
HMP shunt: location, products, key enzymes
In cytoplasm.
Produces ribose 5-phosphate and NADPH
Enzymes: transaldolase and transketolase
Blood cells in EBV infectious mono
Infects B cells by binding CD21 receptor
CD8+ cells clonally expand to kill the virus-infected cells. Appear larger than usual with abundant cytoplasm, eccentrically placed nuclei, membrane that appears to adhere to neighboring cells
Cyanide poisoning: pathophys, presentation, treatment
Pathophysiology: binds iron-containing cytochrome enzymes, inhibiting aerobic metabolism
Presentation: flushing, increased RR and HR, headache
Antidote: nitrites which induce formation of methemoglobin. Methemoglobin has high affinity for cyanide and sequesters it in blood
Beta thalassemia: mutation
Multiple mutaitons that affect mRNA
Abciximab
GPIIb/IIIa receptor antagonist. Used for acute coronary syndrome, especially if undergoing percutaneous intervention
Aspirin OD treatment
Alkalinize urine with sodium bicarb
ADP receptor inhibitors: names, MOA, kinetics
Names: clopidogrel, ticagrelor, ticlopidine
MOA: block ADP receptor preventing GIIb/IIIa expression
Kinetics: prodrugs with slow onset of action, with exception of ticagrelor
Phosphodiesterase III inhibitors: names, effects
Names: cilostazol, dipyridamole
Effects: inhibit platelet aggregation, vasodilate
Inflammatory carcinoma: presentation and pathophys
Presentation: itchy, generalized erythematous rash on breast with thick and coarse skin texture and breast edema. Underlying mass may or may not be present.
Pathophys: cancer cells obstructing lymphatic drainage
Cryoprecipitate vs fresh frozen palsma
FFP has all coag factors; cryoprecipitate only has cold-soluble proteins
5-fluorouracil: MOA
pyrimidine analog that inhibits DNA synthesis by inhibiting thymidylate synthetase
Leucovorin: MOA and effects
Tetrahydrofolate derivative that doesn’t require dihydrofolate reductase. USed to rescue normal cells from methotrexate. Can potentiate effects of 5-fluorouracil which uses THF as cofactor
Vinca alkyloids: MOA and toxicity
MOA: M phase specific, inhibit microtubule formation
Toxicity: peripheral neuropathy
G2 phase cancer drugs
Bleomycin and doxorubicin
Why mature RBCs can’t make heme
Heme occurs partly in cytoplasm, partly in mitochondria. Mautre red cells have lost their mitochondria
Warfarin induced skin necrosis
Complication seenin first few days of warfarin therapy due to transident hypercoagulable state
Hairy cell leukemia: presentation and diagnosis
Presentation: pancytopenia and massive splenomegaly in middle aged male
Diagnosis: often a dry tap due to bone marrow fibrosis, massive splenomegaly due to cancer in the reticuloendothelial system as well as the marrow
Ringed sideroblasts
Seen in myelodysplastic syndrome due to mitochondrial iron accumulaiton around the nucleus
Tumor lysis syndrome
Emergency seen during chemo treatment of leukemia/lymphoma. Destroy a ton of cells at once resulting in release of ions and nucleic acids into the blood. Prevent with aggressive hdyration and medications.
Rasburicase
Recombinant urate oxidase. Promotes conversino of uric acid to soluble metabolites that are excreted in urine.
Translocation seen in burkitt lymphoma
t(8;14), c myc and IgH
desmopressin: two uses
- Hemophilia A and von willebrand disease: increases factor VIII and vWF to stop bleeding
- Central DI: binds V2 receptors on renal tubular cells, increasing water reabsorption and decreasing urine production
Leukemoid reaction
Benign leukocytosis in response to severe infection, malignancy, acute hemolysis. Presents with normal to elevates leukocyte alk phosphatase and basophilic granules in neutrophils on smear
Myoglobin O2 binding curve
Monomeric without cooperative binding. Saturates at much lwoer pO2 than HGB (higher O2 affinity)
Basis for hemoglobin electrophoresis: looking for HbS and HbC
Distinguishes based on charge. HbA has neg charged glutamate, HbS has nonpolar valine. HbC has pos charged lysine. Thus, HbA migrates farthest, HbC migrates the least toward the pos end of gel.
6-mercaptopurine
Inactivated by xanthine oxidase. Azathioprine is pro-drug
Distinguishing three types of childhood brain tumors
- Pilocytic astrocytoma: low grade, usually in cerebellum, presents with headache and balance problems, solid and cystic components on imaging, rosenthal fibers on path
- Medulloblastoma: high grade, always in cerebellum, solid mass, sheets of small blue cells
- Ependymoma: obstructive hydrocephalus, rosettes
N-myc: what associated with
neuroblastoma, small cell lung cancer
Bleomycin MOA
Forms radicals that damage DNA and produce double strand breaks; acts in G2
Thyroid cancer with psammoma bodies
papillary carcinoma
cancer associated with myasthenic syndrome
small cell lung cancer
cancer associated with paraneoplastic hypercalcemia
squamous cell carcinoma
cisplatin toxicity
Nephrotoxicity, acoustic nerve damage. Prevent nephrotoxicity with aggressive hydration
von hippel lindau disease: cause and manifestationa
Caused by AD mutation on chromosome 3
Causes hemangioblastomas of retina, cerebellum, medulla; renal cell carcinoma
Meningioma vs ependymoma (path and population(
Meningioma: psammoma bodies, middle aged woman
Ependymoma: perivascular pseeudorosettes, kids
Sacrococcygeal teratoma
Most common fetal neoplasm, benign, primitive streak remnant
Wilms tumor
Arises from embryonic renal cells due to WT del on chromosome 11. Presents as large palpable flank mass that distorts renal calyces
Doxorubicin MOA
DNA intercalater
Raltegravir MOA
integrase inhibitor for HIV
DIC in pregnancy
mediated by tissue factor release from placental trophoblasts
Metalloproteinases
enzymes that degrade ECM and basement membrane
