Hematology/Oncology Flashcards
Erythrocytosis
Anisocytosis
Poikilocytosis
Reticulocyte
- Erythrocytosis = polycythemia = increased RBCs
- Anisocytosis = varying sizes
- Poikilocytosis = varying shapes
- Reticulocyte = immature RBC
Spectrin
supplies the biconcavity/flexibility of RBCs
1/3 of platelets are stored in?
Spleen (lifespan = 8-10 days)
Causes of polycythemia/erythrocytosis?
- Any time have increased EPO (hypoxia, renal cell carcinoma, HCC, pheochromocytoma, hemangioblastoma)
- Down’s babies at birth
- Polycythemia vera –> have increased RBCs, but normal EPO
Barr bodies
=inactivated X in neutrophils
–>seen in all women + KF men
When do you see hypersegmented polymorphic neutrophils?
-Vitamin B12/Folate deficiency
Neutrophil chemotactic factors?
- Leukotriene B4
- IL-8
- C5a
CD14 = cell marker for?
Macrophages
Causes of Eosinophilia?
- DNA-CAAPA:
- Drugs
- Neoplastic
- Asthma (and Churg-Strauss)
- Collagen Vascular diseases
- Allergic processes
- Addison’s (adrenal insufficiency)
- Parasites (invasive)
- Acute Interstitial Nephritis
Phagocytes:
- in brain
- in tissue
- in liver
- in joints
- brain = microglia
- tissue = macrophages
- liver = kupffer cells
- joints = A-cells
Mast cells vs Basophils?
Both are similar, mediate allergic rxn
- Basophils in Blood
- Mast cells in tissue
-mast cells are involved in type 1 hypersensitivity rxns
Langerhans cells
- dendritic cells on skin and mucous membranes
- act as professional APCs
- possess Birbeck granules = racquet-shaped intracytoplasmic granules
Main inducers of primary antibody response?
Dendritic cells = professional APCs
clock-face chromatin
Plasma cells (B cells differentiate into plasma cells; plasma cells produce lots of antibody specific to a particular antigen)
plasma cell neoplasm?
Multiple Myeloma –> make a whole bunch of one particular type of B cell, all making one type of antibody (so see monoclonal antibody spike)
CD3
on ALL T-cells
- ->Th also have CD4
- ->Cytotoxic also have CD8
anti-AB antibodies (Ig type?)
-IgM –> don’t cross placenta
anti-Rh antibodies (Ig type?)
=IgG –> can cross placenta and cause hemolytic disease of newborn (erythroblastosis fetalis) if fetus is Rh+
Blood type A (example)
- have A antigen on RBC surface
- B antibody in plasma
erythroplastosis fetalis
- cause?
- symptoms?
- hypersensitivity type?
- how to prevent?
- type 2 hypersensitivity rxn
- cause: Rh- mother exposed to Rh+ fetal blood during delivery; makes anti-Rh IgG –> can cross placenta in subsequent pregancies, causing hemolytic disease of newborn in next fetus who is Rh+
- Symptoms in infant: hepatosplenomegaly, severe anemia, jaundice, demise/death
- Treat/Prophylaxis = give mother Rhogam = Rho (D) Ig at first delivery to prevent all future erythroblastosis
Deficiency of Factor VIII?
Hemophilia A
“Aight”
Deficiency of Factor IX?
Hemophilia B
“Benine”
Vitamin K deficiency?
decreased synthesis of “diSCo 1972”
- proteins C and S
- Factors X, IX, VII, II (10, 9, 7, 2)
*Vitamin K normally catalyzes carboxylation of glutamic acid residues on proteins involved with blood clotting
Vitamin K antagonist?
Warfarin
–>acts by inhibiting Epoxide Reductase (vitamin K–>activated vitamin K)
Antithrombin inhibits?
Antithrombin inhibits:
- thrombin
- factors VIIa, IXa, Xa, XIa, XIIa
Drug that activates antithrombin?
Heparin
Coagulase
Produced by S. aureus
–>can convert fibrinogen–>fibrin
tPA, Streptokinase, Urokinase:
All facilitate: plasminogen–> plasmin
so, stimulate breakdown of clots!
vWF receptor on platelets? Fibrinogen receptor on platelets?
- vWF –> GpIb
- Fibrinogen –> GpIIb/IIIa
***vWF and Fibrinogen are both inside platelets
ESR in pregnancy?
increased
Decreased ESR:
- polycythemia
- sickle cell anemia
- CHF
- microcytosis
- hypofibrinogenemia
Spur cell (Acanthocyte)
Liver disease, Abetalipoproteinemia
–>irregularly spiked RBCs
basophilic stippling
TAIL:
- Thalassemias
- Anemia of chronic disease
- Iron deficiency
- LEAD poisoning!
–>have denatured RNA within RBCs
type of anemia caused by folate or B12 deficiency?
Macrocytic, Megaloblastic anemia
iron deficiency anemia + esophageal web + atrophic glossitis?
Plummer-Vinson syndrome
“crew cut” on skull x-ray?
Bone Marrow expansion –> see in beta-thal major
- thalassemias
- Sickle cell disease
chipmunk facies
beta-thal major
Ringed sideroblasts
sideroblastic anemia = defect in heme synthesis (x-linked defect in ALA synthase gene)
-treat with B6 (Pyridoxine)
Lead poisoning symptoms: LEEAADDS
- Lead lines on gingivae (Burton’s lines) and on epiphyses of long bones on x-ray
- Encephalopathy
- Erythrocyte basophilic stippling
- Abdominal colic
- Anemia (sideroblastic anemia)
- Drops (wrist and foot drop)
- Dimercaprol and EDTA = treatment
- Succimer = treatment for kids
Dimercaprol
treatment for lead poisoning (also EDTA)
Succimer
=treatment for kids with lead poisoning (“SUCks to be a kid with lead poisoning”)
Hypersegmented neutrophils + glossitis +
increased homocysteine and:
-normal methylmalonic acid?
-increased methylmalonic acid?
- if normal methylmalonic acid: Folate deficiency
- if increased methylmalonic acid: B12 deficiency
***both cause megaloblastic macrocytic anemia (so have impaired DNA synthesis and ineffective erythropoiesis = pancytopenia)
Megaloblastic anemia that’s not correctable by vitamin B12 or Folate?
–> Orotic Aciduria
Pancytopenia =
- Anemia
- Neutropenia
- Thromboctyopenia
Fanconi’s anemia
DNA repair defect –> get aplastic anemia
NOT the same as Fanconi’s syndrome = proximal tubule reabsorption defect in kidneys!
Why anemia in kidney disease?
decreased EPO –> decreased hematopoiesis
Aplastic anemia
- Pancytopenia
- Normal cell morphology, but hypocellular bone marrow with fatty infiltration
Hemolytic anemia in a newborn?
Pyruvate kinase deficiency –> decreased ATP –> rigid RBCs
HbC defect
Glutamic acid-to-lysine mutation
*pts with HbSC (1 of each mutant gene) have milder disease than HbSS pts (full sickle cell)
older pt, unexplaned anemia:
must rule out colon cancer
reversible etiologies of sideroblastic anemia?
- alcohol
- lead
what vitamin should be supplemented in vegans/vegetarians?
B12 (may get deficiency –> megaloblastic anemia)
Hepcidin
released by liver, binds ferroportin on intestinal mucosal cells and macrophages
-increased in cases of inflammation: increased hepcidin–>decrease release of iron from macrophages
*this is what happens in anemia of chronic disease: decreased iron, decreased TIBC, increased ferritin
decreased iron + decreased TIBC + increased ferritin
anemia of chronic disease (inflammation–> increased hepcidin –> decreased release of iron from macrophages
Cause of hereditary spherocytosis?
- extravascular intrinsic hemolytic normocytic anemia
- caused by defect in proteins interacting with RBC membrane skeleton and plasma membrane (ankyrin, band 3, protein 4.2, spectrin)
- premature removal of RBCs by spleen –> splenomegaly, aplastic crisis; eventually need splenectomy
Labs for PNH (paroxysmal nocturnal hemoglobinuria)?
increased urine hemosiderin
complication of PNH?
thrombosis
Treatment for sickle cell anemia?
- Hydroxyurea –> increases HbF
- Bone marrow transplant = ultimately
Coomb’s positive anemia?
autoimmune hemolytic anemia (ie warm agglutinin or cold agglutinin anemias)
microangiopathic anemia
- see schistocytes
- RBCs damaged when passing through obstructed or narrowed vessel lumina
- see in: DIC, TTP-HUS, SLE, malignant HTN; prosthetic valves, aortic stenosis…
rate limiter of heme synthesis?
ALA synthase (delta-aminolevulinic acid synthase)
effect of heme on ALA synthase activity
low heme–> increased ALA synthase
lots of heme–>decreased ALA synthase
Rate limiter of heme synthesis
ALA synthase (requires B6!)
tea-colored urine + blistering cutaneous photosensitivity?
- Porphyria cutanea tarda (most common porphyria)
- d/t deficiency of Uroporphyrinogen Decarboxylase (needed for heme synthesis); get accumulation of Uroporphyrin (hence the tea-colored urine)
painful abdomen + red-wine colored urine + polyneuropathy + psych disturbances; precipitated by drugs:
Acute Intermittent Porphyria
- d/t deficiency of Porphobilinogen Deaminase (aka uroporphyrinogen-I-synthase)
- accumulate Porphobilinogen, ALA, and uroporphyrin (in urine)
Treatment for Acute Intermittent Porphyria?
-Glucose and Heme –> inhibit ALA synthase
Defect in factors I, II, V, VII, X –>?
increased PT (extrinsic pathway defect)
Defect in all factors EXCEPT VII and XIII?
increased PTT
Defects in platelet plug formation?
increased BT (bleeding time)
Bernard-Soulier disease:
- defect
- labs (BT =bleeding time; PC=platelet count)
defect in Gp1b–> so vWF can’t bind platelets for platelet plug formation
- increased BT
- decreased PC
Glanzmann’s thrombasthenia:
- defect?
- BT/PC?
- defect in GpIIb/IIIa –> platelets can’t link to eachother, so no platelet aggregation for platelet plug formation
- increased BT
- no effect on PC
ITP = Idiopathic Thrombocytopenic Purpura:
- defect?
- labs?
- defect:have anti-GpIIb/IIIa antibodies–> antibodies bind platelets –> complex gets consumed by splenic macrophages
- increased BT
- decreased PC
- also have increased megakaryocytes (trying to make more platelets!)
TTP = Thrombotic Thrombocytopenic Purpura
- defect?
- labs?
deficiency of vWF metallprotease –> decreased degradation of vWF multimers: so: increased vWF multimers–> increased platelet aggregation and thrombosis–> decreased platelet survival
- increased BT
- decreased PC
- schistocytes
- increased LDH
Affect of aspirin on BT/PC?
increased BT
no effect on PC
(like Glanzmann’s)
All platelet disorders effects on BT/PC?
- all increase BT
- all decrease PC, except Glanzmann’s
most common inherited bleeding disorder?
von Willebrand’s disease
PC, BT, PT, PTT findings in von Willebrand’s disease?
- increased BT
- increased or normal PTT (depends on severity)
- normal PC and PT
-treatment for von-Willebrand’s disease?
DDAVP = Desmopressin (releases vWF stored in endothelium)
PC, BT, PT, PTT findings in DIC?
-other lab findings?
- decreased PC
- increased BT
- increased PT
- increased PTT
-also: schistocytes, increased D-dimers (fibrin split products), decreased fibrinogen, decreased factors V and VIII)
Causes of DIC?
“STOP Making New Thrombi”
- Sepsis
- Trauma
- Obstetric complications
- acute Pancreatitis
- Malignancy
- Nephrotic syndrome
- Transfusion
Factor V Leiden
most common cause of inherited hypercoagulability
-production of mutant factor V, that can’t be degraded by protein C
Cryoprecipitate
contains fibrinogen, factor, VIII, factor XIII
-used to treat coagulation factor deficiencies (if deficient in fibrinogen or factor VIII)
CD30+ and CD15+ cells of B-cell origin?
Reed-Sternberg cells
Most common Hodgkin’s lymphoma? Prognosis?
- Nodular Sclerosing
- Excelent prognosis (b/c Lymphocytes»>R-S cells)
- see collagen banding in lymph node
- mostly young adults
t(8;14) c-myc gene
Burkitt’s lymphoma (non-Hodgkin lymphoma; neoplasm of mature B cells)
Most common adult non-Hodgkin lymphoma?
Diffuse large B-cell lymphoma
–>20% of cases are in kids though
t(11;14); affects cyclin D regulatory gene
Mantle Cell Lymphoma
-affects older males; poor prognosis
t(14;18) bcl-2 overexpression
- Follicular Lymphoma
- affects adults
- indolent course, but difficult to cure
- bcl-2 inhibits apoptosis (normally; it’s a proto-oncogene)
Lymphoma caused by HTLV-1?
Adult T-cell lymphoma
- ->adults present with cutaneous lesions
- ->aggressive
Mycosis fungoides/Sezary syndrome
- mature T-cell lymphoma; adults present with cutaneous lesions
- indolent
Bence-Jones protein
Multiple Myeloma
-Ig light chains in urine (don’t see on urinalysis though)
Rouleaux formation
Multiple Myeloma
most common primary tumor arising within bone in elderly?
Multiple Myeloma
CRAB symptoms of Multiple Myeloma:
- hyperCalcemia
- Renal insufficiency
- Anemia
- Bone lytic lesions/Back pain
Down syndrome pts: increased risk of which cancers?
- ALL
- AML
stains TRAP positive (tartrate-resistant acid phosphatase)
Hairy cell leukemia
-mature B-cell tumor in elderly; cells have filamentous, hairlike projections
Age group affected by ALL?
<15 years old
- most responsive to therapy
- may spread to CNS and testes
- t(12;21) = better prognosis
Hallmark of Acute Leukemias?
- lots of blast cells (>20% blasts)
- rapid onset and progression
Auer rods
AML = t(15;17)
-responds to vitamin A
Which leukemia can be treated with Vitamin A?
AML
- t(15;17)
- auer rods
t(9,22), bcr-abl
Philadelphia chromosome
- CML
- 30-60 yrs old
- more mature cells (<5% blasts); insidious onset
- resonds to imatinib = bcr-abl tyrosine kinase inhibitor
Imatinib
treatment for CML
-inhibits bcr-abl tyrosine kinase
Teardrop cell
Myelofibrosis
- ->fibrosis of bone marrow (
- ->bone marrow is crying because it’s fibrosed :(
JAK2 mutations: positive/negative? Philadelphia chromosome? -polycythemia vera -essential thromboyctopenia -myelofibrosis -CML
- JAK2:
- positive in polycythemia vera, essential thrombocytosis, myelofibrosis
- negative in CML
- Philadelphia:
- only positive in CML
thombolytics mechanism? (streptokinase, urokinase, tPA, APSAC)
aid conversion of plasminogen–>plasmin, which cleaves thrombin and fibrin clots
Affect of aspirin on BT, PT, PTT
increased BT
-no effect on PT, PTT
Ticlopidine toxicity?
-Neutropenia (should monitor CBC during first few months of trtmt)
(Ticlopidine = ADP-receptor blocker, so inhibits platelt aggregation; like Clopidogrel)
Drug side effect = tinnitus?
Aspirin!
Raloxifene vs Tamoxifen: Which is better for osteoporosis prevention?
- both are SERMs
- ->antagonists in breast (treat breast cancer)
- ->agonists in bone (bone-building)
- Tamoxifen may increase risk of endometrial carcinoma, b/c it’s a partial endometrial agonist
- Raloxifene is an endometrial antagonist, so no increased risk of endometrial carcinoma; so, better choice for osteoporosis trtmnt
