Hematology/Oncology Flashcards
In what organelle (within erythrocyte) does heme synthesis take place
Mitochondria
What deficiency is associated with warfarin skin necrosis
Protein C/ S deficiency- warfarin inhibits these factors since dependent on vitamin K and get a hypercoagulable state, this leads to microvascular occlusion and hemorrhagic skin necrosis ( Factor 7 and protein C have the shortest half lives)
Benefits of COX 2 inhibitors vs. having COX 1 inhibition?
COX 2 inhibition have potent anti-inflammatory with out GI ulceration side effects, COX 1: inhibits platelet aggregation and can lead to GI ulceration
How are myoglobin and hemoglobin related
Structurally analogous, myoglobin is not sigmoid and would be similar to 4 beta monomers—> most left shift curve possible and myoglobin is momomeric
What features are associated with hair cell leukemia?
Dry tap (unsuccessful bone marrow aspiration), lymphocytes with cytoplasmic projections, TRAP positive stain
What are the atypical cells seen on blood smear in EBV infection?
CD8+ T cells, although EBV preferentially infects B cells
What does von Willebrand factor bind to?
Platelet glycoproteins (Gp1b) and collagen
What is dactylitis and what disease is it associated with?
Painful swelling of hands and feet, Sickle cell disease
What does haptoglobin do?
Binds circulating hemoglobin and reduced free renal excretion of free hemoglobin preventing tubular injury
5 Ps Acute intermittent porphyria and what enzyme is deficient and what is treatment?
Painful abdomen Port wine urine Polyneuropathy Psychological disturbances Precipitated by drugs ( alcohol, starvation)
Porphobilinogen deaminase
Tx: glucose and heme which INHIBIT ALA-synthase (rate limiting step)
What is extramedullary hematopoiesis and what are bone marrow signs?
Presence of erythroid precursors in liver and spleen, EPO hyperplastic marrow
Atypical venous thrombosis in adults <50, which no aPTT response after giving protein C
20% FACTOR V Leiden—> factor V resistance to protein C so—> hypercoagulable
Heme oxygenase
( found in macrophages) Converts heme into biliverdin( green color after bruise), CO, ferrous iron and then bilverdin is broken down by biliverdin reductase to yellow bilirubin which is then transported by albumin to liver
Burkitt lymphoma
t(8;14), cMYC overexpression=transcription activator
Mantle cell lymphoma
t(11;14), cyclin D1 overexpression=promoter of G1–>S phase
Follicular lymphoma
t(14;18), BCL2 overexpression=INHIB apoptosis
Chronic myelogneous leukemia (CML)
t(9;22), ABL gene from chr 9–> INC tyrosine kinase activity
Polycythemia vera (describe dz and associated mutation with function)
Myeloproliferative disorder characterized by UNCONTROLLED RBC production, mutation in JAK2 ( cytoplasmic tyrosine kinase)= hematopoietic cells more sensitive to growth factors, also see: splenomegaly, aquagenic pruritus(histamine from basophils), facial plethora, gout (inc cell turnover)
Aplastic anemia triad
Low hemoglobin, thrombocytopenia, ABSENT hematopoietic stem cells in bone marrow( high lipid content), would see and INC in EPO if also have normal renal function
How can you treat hemophilia?
Give thrombin because no factor 8 or 9 to convert factor 10 into factor 2 (thrombin)
CD 14 is a cell marker for and what disease can it be seen in that has caseating granulomas
Monocyte macrophage lineage with pale pink granular cytoplasm and secondary TB
Why is amyloid associated with multiple myeloma?
Forms from accumulation of mono colonial immunoglobulin light chains
What enzyme deficiency can present similar to glucose 6 phosphate dehydrogenase deficiency
Glutathione reductase deficiency: if don’t have, can’t use NADPH to reduce glutathione to get rid of free rads
Basophillic stippling and microcytic hypochromic anemia are associated with
Lead poisoning ( can also see abdominal pain and blue lead lines in teeth)
B cells mature in the _____ and undergo what process there
Bone marrow, VDJ recombination
What process are B cells undergoing in the follicles
Isotype switching and requires interaction of CD40 receptors on B cells with CD40 ligand of activated T cells (CD154)
Peru ate kinase deficiency leads to ______ anemia. How does the spleen react to this
Hemolytic, red pulp hyperplasia because has to work overtime to get rid of lysed RBCs
The anal canal drains to which lymph nodes
Superficial inguinal
Lymph from superior bladder drains into
External iliac nodes
Lymph from prostate drains into
Internal iliac nodes
Lymph from upper 1/3 rectum drains into
Inferior mesenteric nodes
Myeloblasts stain positive for
Peroxidase
Sickling in sickle cell disease is promoted by situations with ______ oxygen, ______ acidity, _____ blood volume, _____ levels of 2,3 bisphosphoglycerate
Low oxygen, increased acidity, low blood volume, increased
Patients who receive more than 5-6 L of blood transfusion have high levels of _____ in the blood and this can chelate ____ and leads to parathesias
Citrate, calcium
What is the translocation associated with APML and how do you treat?
15;17
15: PML
17: RARA
Tx with all trans retinoic acid
Methemoglobinemia happens because _____ cause poisoning by inducing the conversion of oxidized Fe3+ state. The _____ of oxygen remains unchanged
Nitrates, partial pressure (amount of oxygen dissolved in the plasma)
Inhibition of proteasomes may lead to an _____ of proapoptotic proteins
Excess
G6PD deficiency can lead to hemolytic anemia. What conversion is inhibited
Glucose 6 phosphate to 6 phosphogluconate
Hemoglobin F does not bind to 2,3 bisphosphoglycerate and as a result has a _____ affinity for O2 than Hemoglobin A
higher, this allows HbF to extract lots of oxygen from mom
Hemoglobin S leads to ______ interactions that cause sickling
hydrophobic, glu switched for a valine (nonpolar)
Clinical features of back pain at night, not relieved by rest or analgesics, advanced age, and systemic symptoms suggest what kind of cause
metastasis to bone
DIC is associated with sepsis and how does it affect aPTT and PT, platelets, fibrinogen
BOTH PROLONGED (ONLY ONE THAT does this when compared to ITP and TTP) -dec platelets, dec fibrinogen
The key growth factors for angiogenesis are?
VEGF: vascular endothelial growth factor, fibroblast growth factor
The ________ in basement membranes poses a physical barrier to the sprouting of new blood vessels
laminin
In a post menopausal women with microcytic anemia, need to rule out ________
occult blood loss (Ex: from GI malignancy)
Renal cortical cells sense hypoxia and respond by synthesizing and releasing _______. This leads to an elevated hematocrit
EPO, esp in sleep apnea
how does uremic platelet dysfunction affect PT, aPTT, bleeding time, platelet count?
platelet count=dec, everything else normal
Pure red cell aplasia is associated with ______, lymphocytic leukemia, parvovirus B19
thymomas and have preserved myeloid and megakaryotic elements
Factor V Leiden is a defect in ______ and predisposes you to _______ events
protein C, thrombotic
_______ defiiciency is a megaloblastic anemia that can occur in weeks in alcholics
folate
PT is affected by _____ and if levels are really low sometimes vitamin K supplementation still won’t help because not enough around to be activated
factor 7
bony pain in and older man who smokes is ______ cancer
prostate
how does vwF disease affect PTT, bleeding time, PT
PTT: prolonged, PT: normal, bleeding time: prlonged
_________ is the most common indolent non-Hodgkin lymphoma in adults. It typically has a waxing and waning course
follicular lymphoma
Tumor cells detach from neighboring cells with dec expression of
E-cadherin
Tumor cells adhere to the basement membrane which is facilitated by inc expression of
laminin
Tumor cells invade the basement membrane with inc expression of
proteolytic enzymes (metalloproteinases, cathepsin D protease)
The major chronic pathologic changes in the spleen of patients with sickle cell results from?
microvessel occulsion
-this leads to a fibrotic, shrunken, brown (excess hemosiderosis from extravascular hemolysis of RBCs)
________ is defined by a hematocrit leve >52% in men and 48% in women
erythrocytosis
Erythrocytosis with and increase in RBC mass indicates
absolute erythrocytosis
Erythrocytosis with a normal RBC mass indicates
relative erythrocytosis
Primary erythrocytosis is associated with ____ levels and is caused by
low EPO, myeloproliferative disorders (like polycythemia vera)
Secondary erythrocytosis is associated with ___ levels and is caused by
high EPO, chronic hypoxia (COPD, high altitude, smoking)
Activating mutations of the KRAS gene lead to constuitive activation of the _________ pathway leading to?
epidermal growth receptor pathway (EGFR), increased cell proliferation and growth
-tumors with KRAS mutation are resistant to anti EGFR drugs
Large eosinophillic casts with Bence Jones proteins and a pt. w/ fatigue, back pain, elevated serum protein, and azotemia lead to?
multiple myeloma
SLE induced antiphospholipid syndrome is made by the presence of _________. How does this affect PTT and why? Will it be corrected with FFP?
lupus anticoagulant, prolongs PTT because it is an antiphospholipid antibody and it binds the reagent to the test, no
Which cancer is associated with auer rods and what’s the translocation
APML, t(15;17)
What precursor ALL has TdT+, CD 10, CD19
precursor B-ALL
What precursor ALL has TdT+, CD 2,3,4,5,7,8
precursor T-ALL
__-ALL is more likely to present with a large anterior mediastinal mass that can compress the great vessels, causing _________. It can also compress the esophagus/trachea leading to
T, superior vena cava syndrome (edema of face and arms), dysphagia, inspiratory stridor/dyspnea
___ thalasemia minor is common in people of Mediterranean descent. You can see inc level of which hemoglobin? What is the initial step in pathogenesis of this disorder?
beta, HbA2: b/c dec beta chain synthesis. mRNA of the beta globin gene is disrupted
Patients with sickle cell disease have inc requirement of what vitamin and what can this lead to?
folic acid (b/c of inc erythrocyte turnover), macrocytic anemia
If you have a low reticulocyte count that signifies a _____ response to anemia and lack of ________
inadequate, erythropoiesis
The most common for DIC in pregnancy is release of ___________ from an injured placenta into maternal circulation
tissue factor, DIC presents with bleeding from incision sites, and IV sites from MASSIVE consumption of platelets and clotting factors
Dysplasia is a _______ change in epithelial cells
reversible, once it invades BM=carcinoma and not reversible
Schistocytes can occur from mechanical trauma such as damage with ______
prosthetic valves
What does haptoglobin do? When do levels decrease?
binds free Hgb and promotes its uptake by the reticuloendothelial system, when lots of free Hgb is released into the serum such as in intravascular hemolysis
Paroxysmal nocturnal hemoglobinuria has an associated deficiency of which two CD proteins? It is associated with _______ anemia and _______thrombosis. What is its clinical triad? How does this affect the kidney
CD55/59. aplastic, hepatic vein,
- hypercoagulability, pancytopenia,hemolytic anemia
- hemosiderosis in the kidney from chronic hemolysis with breakdown of iron containing erythrocytes
Migratory ______ is suggestive for visceral cancer. Why does hypercoagulability develop?
thrombophlebitis, b.c adenocarcinomas produce a thromboplastin like substance capable of causing intravascular coagulations
How are these levels in multiple myeloma: RBCs, platelets, Ca, ESR, urine protein, serum protein, serum albumin
- dec RBCs and platelets(b/c plasma cells infiltrate the bone marrow)
- elevated Ca and ESR( systemic inflammation and proteolytic bone lesions)
- inc urine and serum protein but DEC serum albumin (b/c plasma cells make M protein–> rouleaux formation (stacks of RBCs) so get an inc in total SERUM protein but albumin typically dec
The gene for heavy chain of Igs is found on which chromosome?
14
_______calcemia is a common finding after blood transfusions and why? What are symptoms?
Hypocalcemia,
Citrate in the blood will bind calcium
Vague muscle weakness, irritability
Diffuse B cell lymphoma has cells that are ____ positive
CD5, presents with B symptoms
In sickle cell trait, only _____ of hgb is abnormal. And what is a symptom they might have?
35-40%, episodic hematuria (sickling of RBCs in the renal medulla from thromboembolic events)
Newborn born at homewith umbilical stump bleeding probably has a _______ deficiency
Vitamin K, so only PT and aPTT will be prolonged
-baby didn’t get vitamin K shot in the hospital
von willibrand disease leads to ____ PTT and ____ bleeding time
prolonged, prolonged
vWF is a cofactor for factor 8 as well
sporadic forms of _______ lymphoma can present with highly mitotic, basophilic lymphocytes surrounding clear zones of macrophages. most common presentation in north america is:
burkitt lymphoma, constipation, abdominal mass( enlarged LNs)
What is WAGR syndrome?
Wilms tumor, Aniridia(partial or complete lack of the iris), Genital abnormalities, mental Retardation
unfractionated heparin is better at blocking ____ than regular heaprin
thrombin
-both affect factor Xa but unfractionated can also attack Xa AND thrombin
Rat poison has ______ in it so if someone overdoses good to treat with
warfarin, FFP to replace clotting factors
Cryoprecipitate has what factors
8,13,vWF,fibrinogen
Eculizimab blocks the conversion of ______
C5 and MAC complex
What is somatic hypermnutation
component of affinity maturation, its a randomized mutation process of variable regions, then follicular dendritic cells present antigen and B cells that prod the antibodies with highest affinity are positively selected
________ presents as hypoparathyroidism, adrenal insufficiency, chronic mucocutaneous candidiasis, skin dystrophy
AIRE gene dysfunction
________ presents with Bierbeck granules, painful bone lytic lesions, eczematous rash. Cells are ____ positive and express _____ protein
LangerHans histiocytosis, CD1a, S100
Hemolytic disease of the newborn typically results from ________
erythrocyte opsonization from maternal antibodies (hydros fetalis)
Mutations that cause production of hemoglobin with higher oxygen affinity ____ the ability of Hgb to release oxygen to the peripheral tissues so get a _______
compensatory erythrocytosis that helps maintain oxygen delivery
Hereditary spehrocytosis results in ____ membrane stability –>______ erythrocyte osmotic fragility
dec, inc
Sickle cell can cause _______ induced hemolysis due to Hgb S polymerizing and causing damage
hypoxia
Red blood cell fragments of burr and helmet cells are significant for
mechanical trauma
-look for “just got a heart valve”
isoniazid inhibits pyroxidine phosphokinase–> ___ deficiency. This is a cofactor for __________ and when dec can lead to ________anemia
B6, ALA synthase, sideroblastic
Lysing of RBCs in glycerol situation w/ inc osmotic fragility leads you to think
hereditary spherocytosis
__________ is a mutation in the HFE gene and typically interacts with the _______ receptor that acts as a sensor for iron stores. They’re at inc risk of developing __________ and _________
primary hemochromatosis, transferrin
- this causes receptors to detect falsely low levels
- hepatocellular carcinoma, liver failure
Integrins interact with the ECM by binding to which 3 proteins?
collagen, fibronectin, laminin
reticulocytes contain a bluish cytoplasm and why is it blue?
because of ribosomal RNA
_____ and ______ cause a WBC>50,000 with an inc in___________. How is the leukocyte (neutrophil) alkaline phosphatase leveL?
CML, leukemia reaction
- precursor forms( bands, metamyelocytes, myelocytes)
- CML: Dec (b/c WMCs are cytochemically abnormal), leukemoid rxn: inc
Phosphorylated Rb leads to _____ transcription
inc
erythroblastalis fetalis can lead to high levels of unconjugated bilirubin and SEVERE consequence of this is
kernicterus (can damage basal ganglia, thalamus)
Hereditary spherocytosis can lead to __________ unconjugated bilirubin—>
inc, gallstones
reverse anticoagulation (heparin use) with
protamine sulfate
replace warfarin overdose with
fresh frozen plasma
reverse low fibrinogen levels with
cryoprecipitate (fibrinogen, factor 7, vWF)
heparin doesn’t cross the placenta because its _____phillic
hydro (high water solubility)
What are three hematological abnormalities in PNH?
- hemolytic anemia (C5b-9 MAC formation),
- hypercoagulable state (complement attack on platelets–> release of thrombogenic molecules
- pancytopenia (aplastic anemia from lack of CD55,59)
________ are the only drugs used to treat brain tumors
nitrosureas
CA 19-9 is for ______ cancer
pancreatic
CA-125 is for _______ cancer
ovarian/endometrial cancer
abnormally large platelets on peripheral blood smear
Bernard Soulier (absence GP lb)
von willi brand disease you will see ___ PT, _____ platelet count, _____ PTT, ______ bleeding time
normal PT, normal platelet count, prolonged PTT (factor 8), prolonged bleeding time
