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Flashcards in Hematology Deck (93):
1

Most common cancer of childhood
Immature B cells or T cells
Occurs before age 15 but most are age 1-3 yr
Cells: TdT+

Acute Lymphoblastic Leukemia

2

poor outcome in adult ALL

t(9;22) Philadelphia
Good outcome in child: t(12;21)

3

contains Major Basic Protein
Phagocytic for antigen-antibody complexes
Produces histaminase -> limits reaction following mast cell degranulation

Eosinophils

4

monocyte in the tissue

macrophage

5

mediates allergic reaction due to granule contents
heparin, histamine & leukotrienes

Basophil

6

mediates local allergic reaction
Binds Fc portion of IgE
Degranulates releasing histamine, heparin & eosinophilic chemotactic factors

Mast cell
Tx: cromolyn sodium

7

dendritic cell in skin

Langerhans cell

8

Functions as link between innate and adaptive immune systems.
Expresses Fc and MHC II
Highly phagocytic

dendritic cell

9

Where does B cell mature?

bone marrow

10

costimulatory signal required for T cell activation

CD28

11

chromatin distribution described as "clock-face"

plasma cell

12

Which antibodies cross the placenta?

IgG

13

Age: > 60 yr
CD20+, CD5+ B-cell neoplasm
smudge cells in peripheral smear
typically asymptomatic at diagnosis but may present with fatigue, anorexia, weight loss

Small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL)

14

complication of CLL

hypogammaglobulinemia -> infection is most common cause of death

15

Late adulthood painless lymphadenopathy
t(14;18)
BCL2 gene product overexpression -> inhibition of apoptosis
tumor arises in germinal centers
incurable with waxing & waning course

Follicular lymphoma

*note when any leukemia involves the lymph NODE it is referred to as LYMPHOMA

16

proliferation of large B cells that grow diffusely in sheets
high-grade
late adulthood
dysregulation of BCL6 (required for normal germinal center formation) -> p53 silenced -> no apoptosis

Diffuse Large B-cell Lymphoma

17

tumor of mature B cells
extranodal mass in child or young adult
African form: mandible
Sporadic form: abdomen (ileocecum & peritoneum)
Translocation of c-MYC: t(8;14)
associated with EBV
starry sky

Burkitt lymphoma

18

Age: 65-70 yr
destructive plasma cell tumors involving axial skeleton
Most commonly involves: vertebral column, ribs, skull, pelvis, femur, clavicle and scapula
Lytic, punched out vertebral & skull lesions on xray-> fracture risk
free Ig light chain excretion in urine (Bence Jones proteinuria)
Hypercalcemia: confusion, weakness, lethargy, constipation, polyuria (renal dysfunction)

Multiple Myeloma
cause of death: infection
2nd most common cause of death: renal insufficiency
CRAB: hyperCalcemia, Renal insuff, Anemia, Bone lesions/Back pain

19

hyperviscosity syndrome caused by excess secretion of IgM
no lytic bone lesions

Waldenstrom macroglobulinemia

20

asymptomatic plasma cell dyscrasia
precursor to multiple myeloma (1-2%)

MGUS => monoclonal gammopathy of undetermined significance

21

proliferation of small B cells in males age 50s-60s
t(11:14)
cyclin D1 overexpression -> promotes G1/S transition -> proliferation
expansion of mantle zone
symptoms related to spleen and gut in 50%

Mantle Cell Lymphoma

22

Arise in tissues involved in chronic inflammatory disorders of infectious or autoimmune etiology (Hashimoto, Sjogren, H pylori gastritis)
Memory B cell origin
More common in southern Europe than US
Ex: MALToma

Marginal Zone Lymphoma

23

B cell neoplasm of middle-aged white males
TRAP
"dry tap" due to marrow fibrosis

Hairy Cell Leukemia
cells have hairy cytoplasmic processes
Tx: cladribine

24

T cell tumors that home to the skin
Early stages have eczema-like lesions
Cells can spread to the blood and cause Sezary syndrome -> lymphocytes with cerebriform nuclei

Mycosis Fungoides

25

-Endemic to southern Japan, West Africa and Caribbean basin
-associated with HTLV-1 -> encodes Tax which activates NF-kappaB
-Skin lesions (rash), generalized lymphadenopathy, hepatosplenomegaly, peripheral blood lymphocytosis and hypercalcemia
Rapidly fatal (months-1 yr)

Adult T cell Leukemia/Lymphoma

26

○ Large multimeric glycoprotein that stabilizes factor VIII and protects it from degradation
○ Synthesized by endothelial cells and megakaryocytes
○ Concentrated in the endothelium of blood vessels and released in response to stress hormones of endothelial damage

• Von Willebrand factor

27

extrinsic coagulation pathway vs. intrinsic coagulation pathway

• Extrinisic pathway is initiated by trauma & tissue factor exposure
• Intrinsic pathway is activated when factor XI is converted the factor XIa by thrombin

28

serine protease that degrades fibrin

plasminogen -> plasmin

29

vitamin K antagonist

warfarin

30

oxidation of Hb sulfhydryl groups
Denatured Hb precipitates
Seen with G6PD deficiency

Heinz bodies

31

Seen with functional asplenia -> normally removed
basophilic nuclear remnants

Howell-Jolly bodies

32

triad of iron deficiency anemia, esophageal webs and atrophic glossitis

Plummer-Vinson syndrome

33

homozygote with absent beta chain
marrow expansion causing "crew cut" on skull xray
chipmunk facies
extramedullary hematopoiesis
increased risk of parvo B19 aplastic crisis

beta-thalassemia major

34

deficiency of ADAMTS13 (which can be inherited or acquired)
decreased degradation of vWF multimers

Thrombotic Thrombocytopenic Purpura

35

Bleeding due to defective platelet aggregation (platelet plug) in response to ADP, collagen, epinephrine or thrombin because of deficiency or dysfunction of GpIIb-IIIa,
AR

Glanzmann Thrombasthenia

36

defect in platelet plug formation due to deficiency of GpIb
AR

Bernard-Soulier syndrome

37

antibodies to GpIIb/IIIa with splenic macrophage consumption of platelet/antibody complex
Bone marrow bx: increased megakaryocytes

Immune thrombocytopenia (ITP)

38

Hypercoagulability in whites with increased risk of cerebral vein thrombosis, especially with oral contraceptive use

Factor V Leiden
resists degradation by activated protein C

39

inactivates factor V

protein C
PROC mutations causes deficiency
protein S enhances protein C cleavage of factor V

40

X-linked intrinsic coagulation pathway defect
hemarthroses, easy bruising, increased PTT
classically affected male and carrier females

Hemophilia A: deficiency factor VIII
Hemophilia B: deficiency factor IX
cure: liver transplant

41

see normal bleeding time but decreased synthesis of factors 2, 7, 9, 10, protein C & S

vitamin K deficiency

42

which chromosome for ABO blood groups?

chromosome 9

43

when is Rhogam given?

28-32 weeks

44

inhibits ferrochelatase and ALA dehydratase therefore decreases heme synthesis
inhibits rRNA degradation -> basophilic stippling seen
symptoms: Burton lines on xray, encephalopathy, abdominal colic, sideroblastic anemia, wrist & foot drop

lead poisoning
ALA dehydratase contains zinc and is therefore sensitive to inhibition by lead
Tx: EDTA and dimercaprol; succimer in children

45

glutamic acid -> valine change in codon for beta globin
AR hemolytic condition
painful swelling in hands and feet
splenic infarct at low O2 tensions

sickle cell anemia
HbS is less soluble so RBC less deformable when moving through capillaries
heterozygote advantage for malaria

46

X-linked enzyme deficiency common in Mediterranean
hemolysis in response to bacterial & viral infections
Deficiency of reducing equivalents (NADPH) in RBC
drug-induced hemolysis

glucose 6 phosphate dehydrogenase deficiency
anemia with eating fava beans
Presents: back pain, hemoglobinuria a few days after oxidative stress
RBCs with Heinz bodies and bite cells on peripheral smear

47

first-line therapy for CML

imatinib
MOA: inhibitor of BCR-ABL tyrosine kinase

48

allosteric activator at low concentration, but is a competitive inhibitor for oxygen binding at higher concentration

carbon monoxide

49

has 1 polypeptide chain and 1 O2 binding site
binds O2 better at low O2 concentrations
heart and skeletal muscle

myoglobin

50

4 pyrrole rings linked by alpha-methylene bridges

heme

51

competitive inhibitors of O2 binding

CO and NO
both bind to the O2 binding site on heme

52

formed in RBCs from 1,3-bisphosphoglycerate &
binds to Hb in the central cavity formed by the 4 subunits and increases the energy required for conformational changes which facilitate O2 binding

2,3-BPG
levels of this increase at high altitudes in order to increase O2 delivery to the tissues
adjustment to high altitude occurs over approx lifespan of RBC

53

bind to Hb and cause a conformational change which releases O2

protons

54

What lab value predicts sickle cell crisis?

MCHC

55

decreases cell volume by increasing potassium and water efflux
reduced chance of malaria development because of decreased lifespan of RBC (40 days for homozygote) & inhibition of cell lysis for parasitized RBCs

HbC
Crystals form in O2-rich blood, so formation is more likely in the larger vessels and less likely to cause vascular occlusion.
Crystallization only occurs with ligand bound

56

hypersegmented neutrophils

folate and B12 deficiencies

57

B12 deficiency causes

dietary, malabosorption, pernicious anemia, Diphyllobothrium latum (fish tapeworm), proton pump inhibitors

58

hemoproteins

hemoglobin
myoglobin
CYPs
catalase
myeloperoxidase
NO synthase

59

cellular storage for iron

ferritin

60

iron transport in the plasma

transferrin

61

gene mutations which decrease hepcidin synthesis
chronic iron toxicity
increased iron absorption
iron deposition within the joints and tissues of the heart, liver and pancreas, causing organ damage and failure
slate-blue skin appearance

hemochromatosis

62

rate-limiting enzyme in porphyrin synthesis in the liver

ALA synthase

63

needed for hephaestin and ceruloplasmin activity (mobilization of iron)

copper

64

defect in hydroxymethylbilane gene
accumulation of ALA and PMB precursors causes abdominal pain, neurologic dysfunction but NOT photosensitivity
Painful abdomen
Port wine urine
Polyneuropathy
Psychological disturbances
Precipitated by drugs, alcohol & starvation

Acute Intermittent Porphyria
AD
Tx: glucose and heme -> inhibit ALA synthase

65

X-linked defect resulting in reduced catalytic activity of ALAS2
during the block in heme synthesis, iron delivery to the mitochondria continues so have accumulation of non-heme iron as ferrochelatase

sideroblastic anemia

66

Glycoprotein produced by the kidney in proportion to intracellular oxygen concentration

erythropoietin

67

○ Transfer of methyl group from N5-methyl-FH4 to homocysteine to form methionine
○ Rearrangement of methylmalonyl-CoA to form succinyl-CoA

functions of B12
if have deficiency see:
decrease in methionine and SAM
↑homocysteine in blood and methylmalonic acid in urine
Folate deficiency: ↑homocysteine but no methylmalonic acid in urine

68

deficiency of intrinsic factor

pernicious anemia

69

defect in UMP synthase causing inability to convert orotic acid to UMP (in the de novo pyrimidine synthesis pathway)
AR
megaloblastic anemia in children that cannot be cured with folate or B12

orotic aciduria

70

oxidized free Hb

methemoglobin

71

How do you test for folate deficiency?

If suspect folic acid deficiency, give large histidine load and patient will excrete FIGLU in urine
see bright red tongue too!

72

proteins secreted by the salivary gland and gastric mucosa (parietal cells) & bind B12

haptocorrins

73

RBC proteins

• Spectrin, ankyrin, anion exchange protein (band 3), band 4.1, band 4.2 and actin all participate in the cytoskeleton, giving the RBC its biconcave shape
Function of band 3: exchange of chloride and bicarbonate ions

74

falsely elevated in anemia due to decrease in RBCs

reticulocyte count
a properly functioning marrow increases the RC to >3%
RC >3% suggests peripheral destruction

75

RBC destruction by macrophages of spleen, liver & lymph nodes (RES)

extravascular hemolysis
see: anemia with splenomegaly, jaundice, increased risk of gallstones
spherocytes in peripheral smear

76

hemolysis of RBCs within blood vessels

intravascular hemolysis
see: hemoglobinemia, hemoglobinuria, hemosiderinuria (iron), decreased serum haptoglobin
schistocytes and increased reticulocytes on peripheral smear

77

AD: Mutations which deplete band 3, RhAG, band 4.2, ankyrin or spectrin
small round RBCs with no central pallor
increased RDW
premature removal of RBCs by the spleen

Hereditary spherocytosis
tx: splenectomy

78

major energy source for RBC

glycolysis and pentose pathway shunt

79

highly condensed X chromosome

Barr body

80

Why does malaria grow poorly in G6PD deficiency?

ROS generation (glutathione depletion)

81

phenotypically "O" blood type but also have anti-H antibody

Bombay blood type

82

sugars that determine blood type

A: galactosamine
B: galactose

83

> 20% blasts in the bone marrow

leukemia
will also see decreases in normal blood cells (RBCs -> anemia; neutropenia; thrombocytopenia)
Blasts in the blood are larger than normal RBCs and have large nucleus, little cytoplasm, punched-out nucleolus

84

markers for myeloblasts vs lymphoblasts

Myeloblasts (AML): MPO -> look for Auer Rod**
Lymphoblasts (ALL): tDt

85

accumulation of myeloblasts in AML has what major risk

DIC
AML is a disruption to the Retinoic Acid Receptor (RAR)
Treat with ATRA -> causes myeloblasts to mature to neutrophils

86

subtype of myeloblastic leukemia in which presentation is swelling of the gums (blasts invade gums)
cells lack MPO

acute monocytic leukemia

87

causes of myeloblastic syndrome

prior exposure to alkylating agent or radiotherapy

88

neoplastic proliferation of naive B cells in older patient
coexistence of CD5 and CD20 is characteristic (CD5 is normally on T cells)
smudge cells

CLL

89

Why is there an increased risk of hyperuricemia & gout in myeloproliferative disorders?

high cell turnover

90

worst complication of CML

acute leukemia (can convert to ALL or AML)
CML has a characteristic increase in basophils**
t(9;22) generating BCR-ABL fusion protein with increased tyrosine kinase activity

91

proliferation of mature myeloid cells esp RBCs
Granulocytes & platelets also elevated
associated with JAK2 kinase mutation**
Symps: blurry vision, headache, flushed face (plethora), ITCHING after bathing (histamine release from extra mast cells), increased risk of venous thrombosis

Polycythemia Vera (PV)
Tx: phlebotomy (1st)
hydroxyurea (2nd)

92

causes of reactive polycythemia

hypoxia from lung disease
EPO production by renal cell carcinoma

93

neoplastic proliferation of megakaryocytes
assoc with JAK2 kinase mutation
progresses to marrow fibrosis
Slide: tear-drop RBCs, nucleated RBCs, immature granulocytes
Increased risk of infection, thrombosis, bleeding

Myelofibrosis

complications: splenomegaly from extramedullary hematopoiesis