HemeOnc Flashcards
(209 cards)
1
Q
membrane of RBC contains what channel?
A
chloride bicarbonate antiport which is imp for allowing it to transport CO2 from periphery to lungs for elimination
2
Q
anisocytosis vs poikilocytosis
A
varying sizes vs varying shapes of the RBCs
3
Q
platelets contain
A
dense granules (ADP, calcium), and alpha granules (vWF, finbrinogen)
4
Q
how much of platelets is stored in the spleen?
A
one third
5
Q
life span of platelets
A
8-10 days
6
Q
vWF receptor
A
Gp1b
7
Q
Fibrinogen receptor
A
Gp11b/111a
8
Q
neutrophils
A
phagocytic, multilobed nucleus, large, spherical, azurophilic granules contain hydrolytic enzymes , lysozyme, myeloperoxidase, and lactoferrin
9
Q
what is lactoferrin used for?
A
binds iron and inhibits growth of phagocytosed bacteria and some fungi
10
Q
monocyte
A
large kidney shaped nucleus; extensive frosted glass cytoplasm; differentiates into macrophages in tissues
11
Q
macrophages are activated by
A
gamma-interferon
12
Q
cell surface marker for macrophages
A
CD14
13
Q
eosinophil
A
bilobate nucleus, defends against helminthic infxns (major basic protein), produces histaminase and arylsulfatase (helps limit rxn following mast cell degranulation)
14
Q
causes of eosinophilia
A
NAACP: neoplastic, asthma, allergic processes, collagen vascular diseases, parasites (invasive)
15
Q
basophil
A
mediates allergic rxn, bilobate nucleus, densely basophilic granules containing heparin, histamine, and leukotrienes (LTD4); MN: basophilic - staining readily with BASIC stains
16
Q
Mast cell
A
mediates allergic rxn, degranulation - histamine, heparin, and eosinophil chemotactic factors; can bind the Fc portion of igE to membrane; involved in type 1 hypersensitivity rxns
17
Q
what prevents mast cell degranulation?
A
cromolyn sodium
18
Q
dendritic cells
A
professional APCs; express MHC II and Fc Receptor on surface
19
Q
lymphocyte
A
round densely staining nucleus; small amt of pale cytoplasm; B lymphocytes produce antibodies; T lymphocytes manifest the cellular immune response as well as regulate B lymphocytes and macrophages
20
Q
plasma cell histo
A
off center nucleus, clock face chromatin distribution, abundant RER and well developed golgi apparatus; produced from B cells; will then produce large amts of antibody specific to a particular antigen
21
Q
costimulatory signal necc for t cell activation
A
cd28
22
Q
AB blood group
A
has both A and B antigens on RBC surface; no antibodies in plasma; universal recipient
23
Q
O blood group
A
neither A nor B antigen on RBC surface; both antibodies in plasma; universal donor
24
Q
treatment for mom at first delivery
A
Rho (D) immunoglobulin to prevent future erythroblastosis
25
vit K deficiency causes
decreased synthesis of factors 2, 7, 9 and 10; proteins C and S
26
how is vit K activated?
epoxide reductase
27
role of activated protein C (APC) and protein S
cleaves and inactivates 5a and 8a
28
vWF carries what factor?
factor 8
29
what is the extrinsic pathway of coagulation?
7 --> 10 --> 5 -->2 --> fibrinogen---> fibrin mesh
30
role of 5a and 8a
5a converts 10a to 2a; 8a converts 9a to 10a
31
antithrombin inactivates what factors?
inhibits thrombin and factors 7a, 9a, 10a, 11a, and 12a; activated by heparin
32
role of tPA
converts plasminogen to plasmin --> cleavage of fibrin mesh
33
platelet plug formation
vWF binds to exposed collagen upon damage; platelets then bind to vWF via Gp1b receptor at injury site; platelets then release ADP and Ca2+; ADP helps platelets adhere to endothelium; ADP binding induces GpIIb/IIIa expression at platelet surface; fibrinogen binds to these receptors and links platelets
34
ticlopidine and clopidogrel inhibit
ADP induced expression of GpIIb/IIIa
35
proaggregation factors
TXA2 (released by platelets) to decrease blood flow and increase platelet aggregation
36
antiaggregation factors
PGI2 and NO (released by endothelial cells) to increase blood flow and decrease platelet aggregation
37
aspirin inhibits
cyclooxygenase (TXA2 synthesis)
38
abciximab inhibits
GpIIb/IIIa
39
decreased ESR can be indicative of
polycythemia, sickle cell anemia, congestive heart failure, microcytosis, hypofibrinogenemia
40
acanthocyte
spur cell; asso with liver disease, abetalipoproteinemia
41
howell jolly bodies
basophilic nuclear remnant found in RBCs, seen in pts with functional hyposplenia or asplenia
42
ddx for microcytic anemia
IDA, ACD, thalasssemias, lead poisoning, sideroblastic anemia
43
nonmegaloblastic anemia
liver disease, alcoholism, reticulocytosis
44
extrinsic hemolytic anemias
autoimmune, AIHA, MAHA, infxns
45
intrinsic hemolytic anemias
rbc membrane defect; hereditary spherocytosis; rbc enzyme def: G6PD, PK; HbC, sickle cell anemia, paroxysmal nocturnal hemoglobinuria
46
intravascular hemolysis findings
decreased haptoglobin, increased LDH, hemoglobin in urine (PNH), mechanical destruction (aortic stenosis, prosthetic valve)
47
extravascular hemolysis findings
macrophage in spleen clears RBC, increased LDH plus increased UCB which causes jaundice; examples are hereditary spherocytosis, sickle cell anemia
48
nonhemolytic anemias
Anemic of chronic disease, aplastic anemia, kidney disease
49
pancytopenia, normal cell morphology but hypocellular bone marrow with FATTY infiltration, dx?
aplastic anemia
50
causes of aplastic anemia
radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites); viral (parvo, EBV, HIV, HCV), fanconi's anemia ; idiopathic (may follow acute hepatitis)
51
treatment of aplastic anemia
withdrawal of offending agent, immunosuppressive regimens (antihyymocyte globulin, cyclosporine), allogeneic bone marrow transplanation, RBC and platelet transfusion, G-CSF or GM-CSF
52
anemia of chronic disease
inflammation causes increased hepcidin (released by liver, binds ferroportin on intestinal mucosal cells and macroophages thus inhibiting iron transport) caused decreased release of iron from macrophages
53
anemia of chronic disease lab findings
decreased iron, decreased TIBC, increased ferritin
54
pathogenesis of hereditary spherocytosis
less membrane causes small, round RBCs with no central pallor --> premature removal of RBCs by spleen
55
findings of iron def
microcytosis, hypochromia --> plummer vinson syndrome (IDA, esophageal web, atrophic glossitis)
56
4 gene deletion in alpha thalassemia causes
Hb Barts, incompatible with life (hydrops fetalis)
57
3 gene deletion in alpha thalassemia causes
HbH disease
58
beta thalassemia defect
point mutation in splice sites and promoter sequences; decreases beta globin synthesis;
59
beta thalassemia is prevalent where?
in mediterranean populations
60
how to confirm diagnosis of beta thalassemia minor?
increased HbA2 on electrophoresis
61
dif between beta thalassemia minor vs major
heterozygote, beta chain is underproduced vs homozygote, beta chain is absent , severe anemia requiring blood transfusions
62
both major and minor beta thalassemias cause an increase in what kind of hemoglobin
HbF
63
chipmunk facies
assso with beta thalassemia major due to marrow expansion (crew cut on skull xray ) --> skeletal deformities
64
why is lead toxic?
inhibits ferrochelatase and ALA dehydratase causing a decrease in heme synthesis; inhibits rRNA degradation;
65
etiologies of megaloblastic anemia caused by folate deficiency
malnutrition (alcoholics), malabsorption, impaired metabolism (methotrexate, trimethoprim), hemolytic anemia, pregnancy
66
findings of megaloblastic anemia caused by folate def
hypersegmented neutrophils, glossitis, decreased folate, increased homocysteine but normal methylmalonic acid
67
etiologies of megaloblastic anemia caused by b12 def
insufficient intake (vegans), malabsorption (crohn's dz), pernicious anemia, D latum (fish tapeworm)
68
findings of megaloblastic anemia
increased homocysteine AND methylmalonic acid; peripheral neuropathy with sensorimotor dysfunction, posterior columns (vibration/proprioception); lateral corticospinal (spasticity); dementia
69
MN for lead poisoning
Lead lines on gingivae (burton's lines) and on epiphyses of long bones; Encephalopathy and Erythrocyte basophilic stippling, Abdominal colic and sideroblastic ANEMIA, DROPS (wrist and foot drop),
70
treatment for lead poisoning
Dimercaprol and EDTA are 1st line of treatment; use succimer for kids ("it sucks to be a kid who eats lead)
71
hereditary spherocytosis
defect in proteins interacting with RBC membrane skeleton and plasma membrane (ankyrin, band3, protein 4.2, or spectrin)
72
clinical findings of hereditary spherocytosis
splenomegaly, aplastic crisis, howell jolly bodies after splenectomy
73
hereditary spherocytosis lab findings
positive osmotic fragility test
74
G6PD deficiency
x linked, defect in g6pd causes a decrease in glutathione which causes increased RBC susceptibility to oxidant stress--> hemolytic anemia
75
fava beans
causes hemolytic anemia:oxidant stress --> G6PD deficiency
76
G6PD deficiency lab findings
blood smear with RBCs with Heinz bodies and bite cells
77
pt presents with back pain followed by hemoglobinuria a few days later, what do you think it is?
g6pd deficiency
78
pyruvate kinase deficiency
autosomal recessive, defect in PK causes decrease in ATP which causes rigid RBCs
79
hemolytic anemia in a newborn think
pyruvate kinase def
80
crew cut on skll x ray due to marrow expansion from increased erythropoiesis caused by 2 conditions
sickle cell anemia and thalassemias
81
pathogenesis OF sickle cell anemia
deoxygenated HbS polymerizes. Low O2 or dehydration precipitates sickling --> anemia + venoocclusive disease
82
complications in homozygotic SCD
aplastic crisis, autosplenectomy, salmonella osteomyelitis, painful crisis (vaso-occlusive), dactylitis (painful hand swelling), acute chest syndrome, renal papillary necrosis, microhematuria, splenic sequestrations
83
defect in sickle cell anemia
HbS point mutation causes a single amino acid replacement in beta chain (substitution of glutamic acid with valine) at pos 6
84
heterozygotic SCD has resistance to
malaria
85
treatment for SCD
hydroxyurea (increases HbF) and bone marrow transplantation
86
HbC defect
glutamic acid to lysine mutation at position 6 in chain mutation
87
paroxysmal nocturnal hemoglobinuria
increased complement - mediated RBC lysis from Impaired synthesis of GPI anchor, decay accelerating factor in the RBC membrane; increased urine hemosiderin
88
autoimmune hemolytic anemia (warm agglutinin)
IgG; chronic anemia seen in SLE, in CLL, and with certain drugs (methyldopa); MN: Warm weather is GGGGreat
89
cold agglutinin autoimmune hemolytic anemia
acute anemia triggered by cold, seen in CLL, mycoplasma pneumoniae, mononucleosis; MN: Cold ice cream...MMMM
90
erythroblastosis fetalis
autoimmune hemolytic anemia seen in newbornes due to Rh or other blood antigen incompatibility
91
direct coomb's test
anti-Ig antibody added to patient's RBCs agglutinate if RBCs are coated with Ig
92
indirect coomb's test
normal RBCs added to pt's serum agglutinate if serum has anti-RBC surface iG
93
microangiopathic anemia pathogenesis
RBCs are damaged when passing thru obstructed or narrowed vessel lumina, seen in DIC, TTP-HUS, SLE, malignant HTN
94
schistocytes (helmet cells) seen in
microangiopathic anemia and macroangiopathic anemia
95
macroangiopathic anemia
prosthetic heart valves and aortic stenosis can cause hemolytic anemia secondary to mechanical destruction
96
increased serum iron can be seen in what conditions
hemochromatosis, lead poisoning
97
in anemia of chronic disease
decrease in serum iron, decrease in TIBC, increase in ferritin
98
iron deficiency lab values
decreased serum iron, increased transferrin/TIBC, decreased ferritin , major decrease in % transferrin saturation
99
dif bw lab values for hemochromatosis vs lead poisoning
both will have increased serum iron, decreased transferrin/TIBC and increased % transferrin saturation but there is an increase in ferritin in hemochromatosis
100
lead poisoning affects what enzymes that are needed for heme synthesis
ferrochelatase, ALA (aminolevulinic acid) dehydratase
101
lab findings for anemia caused by pregnancy or OCP use
will only see an increase in transferrin and a decrease in % transferrin saturation
102
transferrin vs ferritin
transport iron in blood vs primary iron storage protein of body
103
what is the accumulated substrate of lead poisoning?
protoporphyrin (blood)
104
acute intermittent porphyria: affect enzyme, accumulated substrate
porphobilinogen deaminase; accumulated substrates are porphobilinogen, ALA, uroporphyrine (urine)
105
symptoms of acute intermittent porphyria
painful abdomen, red wine colored urine, polyneuropathy, psychological disturbances,
106
treatment of acute intermittent porphyria
glucose and heme,w hich inhibit ALA synthase
107
porphyria cutanea tarda: affected enzyme and accumulated substrate
uroporphyrinogen decarboxylase; uroporphyrin (tea colored urine)
108
porphyria cutanea tarda symptoms
blistering cutaneous photosensitivity, most common porphyria
109
decreased heme causes what to ALA synthase activity
increases ALA synthase activity and vice versa
110
PT
tests function of factors 1, 2, 5, 7, and 10
111
PTT
tests function of all factors except 7 and 13
112
hemophilia A or B causes prolonged
PTT but not PT
113
vit K deficiency causes prolonged
PT and PTT
114
clinical manifestations of hemophilia a or b
macrohemorrhage, hemarthroses (bleeding into joints), easy bruising
115
platelet abnormalities can result in
microhemorrhage: mucous membrane bleeding, epistaxis, petechiae, purpura, increased bleeding time, possible decreased platelet count
116
bernard soulier disease
decrease in platelet count, increase in bleeding time, defect in platelet plug formation, decrease in Gp1b which causes a defect in platelet to vwf adhesion
117
Glanzmann's thrombasthenia
increase in bleeding time, defect in platelet plug formation, decrease GPIIb/IIIa --> defect in platelet to platelet aggregation
118
idiopathic thrombocytopenic purpura
decrease in platelet count, increase in bleeding time, decrease platelet survival
119
ITP defect
anti GpIIb/IIIa antibodies --> platelet/Ab complex is consumed by splenic macrophages ; labs show an increase in megakaryocytes
120
thrombotic thrombocytopenic purpura
decrease platelet survival; defect in ADAMTS 13 (vWF metalloprotease) which decreases degradation of vWF multimers
121
pathogenesis of TTP
increase large vWF multimers --> increased platelet aggregation and thrombosis
122
symptoms of TTP
pentad: neurologic and renal symptoms, fever, thrombocytopenia, microangiopathic hemolytic anemia
123
labs of TTP
schistocytes, increased LDH
124
most common inherited bleeding disorder
von willebrand's disease
125
mechanism of von willebrand's disease
defect in platelet plug formation: decreased vWF causing a defect in platelet to collagen adhesion
126
treatment for von willebrand' disease
DDAVP (desmopressin) which releases vWF stored in endothelium
127
DIC levels for PC, BT, PT and PTT
decrease in platelet count, increase bleeding time, increase in PT and PTT as well
128
causes of DIC
MN: STOP Making New Thrombi = sepsis (gram neg), trauma, obstetric complications, acute Pancreatitis, Malignancy, Nephrotic syndrome, Transfusion
129
DIC labs
schistocytes, increased fibrin split products (D-dimers), decreased fibrinogen, decreased V and VIII
130
factor V leiden disease
production of mutant factor V that cannot be degraded by protein C.
131
most common cause of inherited hypercoagulability
factor V leiden
132
prothrombin gene mutation
mutation in 3' untranslated region associated with venous clots --> hypercoagulability
133
Antithrombin deficiency
inherited deficiency of antithrombin --> hypercoaguability, reduced increase in PTT after administration of heparin so cannot give heparin bc it works to activate antithrombin
134
protein C or S deficiency
decreased ability to inactivate factors V and VIII; increase risk of thrombotic skin necrosis with hemorrhage following adminstration of warfarin
135
cryoprecipitate contains
fibrinogen, factor 8 and factor 13, vWF
136
blood transfusion risks
hypocalcemia (citrate is a calcium chelator) and hyperkalemia (RBCs may lyse in old blood units)
137
when to give FFP
DIC cirrhosis, warfarin over-anticoagulation; will increase coagulation factor levels by about 20%
138
leukemoid reaction
increase WBC count with left shift and increase leukocyte alkaline phosphatase usually due to infection
139
reed sternberg cells characteristic of what neoplasm
hodgkin's lymphoma; binucleate/bilobed mirror images that look like "owl's eyes"
140
B symptoms
low grade fever, night sweats, weight loss
141
incidence of hodgkin's lymphoma vs nonhodgkin's lymphoma
hodgkin = bimodal (young and old, men) vs 20-40 years of age
142
viruses associated with hodgkin and nonhodgkin's lymphoma
EBV (50%) vs HIV
143
mediastinal lymphadenopathy is seen in hodgkin's or nonhodgkin's
hodgkin's lymphoma
144
hodgkin's vs nonhodgkins in terms of nodes and spreading
localized single group of nodes; contiguous spread vs multiple peripheral nodes; extranodal is common; noncontiguous spread
145
Reed Sternberg cell markers
CD30+ and Cd15+ B cell origin
146
nodular sclerosing hodgkin's lymphoma
(65-75% of all hodgkin's lymphoma); excellent prognosis, collagen banding, lacunar cells, found in M
147
lymphocyte predominant type of hodgkin's lymphoma
excellent prognosis, 5% of all hodgkin's lymphoma, occurs in <35 yo men
148
lymphocyte depleted type of hodgkin's lymphoma
poor prognosis, occurs in older males with disseminated disease
149
burkitt's lymphoma occurs in
adolescents or young adults
150
genetics of burkitt's lymphoma
t(8,14) c-myc gene
151
starry sky appearance
sheets of lymphocytes with interspersed macrophages = burkitt's lymphoma
152
diffuse large B cell lymphoma occurs in
older adults, 20% in children (a type of nonhodgkin's lymphoma)
153
most common adult NHL
diffuse large B cell lymphoma
154
mantle cell lymphoma occurs in
older males
155
genetics of mantle cell lymphoma, prognosis, marker
t(11,14), overexpression of cyclin D regulatory gene, poor prognosis, CD5+
156
follicular lymphoma occurs in whom? Prognosis?
adults, difficult to cure, indolent course, bcl-2 inhibits apoptosis
157
genetics of follicular lymphoma
t(14, 18), bcl-2 expression
158
adult T cell lymphoma caused by what virus?, clinical manifestations? Where is it most common?
HTLV-1 lesion, adults present with cutaneous lesions , in Japan, west africa, caribbean, aggressive
159
mycosis fungoides/Sezary syndrome occurs in whom? And what is the clinical manifestation?
adults; cutaneous patches/nodules
160
marker on mycosis fungoides/sezary syndrome
indolent Cd4+
161
fried egg appearance
multiple myeloma
162
multiple myeloma
monoclonal plasma cell cancer that arises in marrow and produces large amts of IgG or IgA
163
primary amyloidosis, lytic bone lesions, M spike on protein electrophoresis, Ig light chains in urine are associated with that?
multiple myeloma
164
bence jones protein
Ig light chains in urine, associated with multiple myeloma
165
rouleaux formation
RBCs stacked like poker chips in blood smear
166
mnemonic for clinical manifestations of multiple myeloma
CRAB: hypercalcemia, renal insufficiency, anemia, bone lytic lesions/back pain
167
multiple myeloma vs waldenstrom's macroglbulinemia
both have M spike = IgM (--> hyperviscosity) , but no lytic bone lesions in waldenstrom's
168
MGUS
monoclonal gammopathy of undetermined significance, monoclonal plasma cell expansion without the symptoms of multiple myeloma
169
Acute lymphoblastic leukemia/lymphoma occurs in
children
170
ALL markers
TdT+ (marker of pre-T and pre-B cells), CALLA+
171
where can ALL spread to?
CNS and testes
172
genetics of ALL that provides a better prognosis
t(12, 21)
173
small lymphocytic lymphoma/chronic lymphocytic leukemia occurs in whom? And what are the differences?
adults >60 yrs of age; SLL same as CLL except CLL has an increase in peripheral blood lymphocytosis
174
smudge cells on PBS indicate
SLL/CLL
175
hairy cell leukemia
mature B cell tumor in the ELDERLY, cells have filamentous hairlike projections,
176
what kind of leukemia stains TRAP (tartrate, resistant acid phosphatase) +?
hairy cell leukemia
177
acute myelogenous leukemia seen in whom? PBS characteristic?
adults, auer rods
178
t(15,17)
M3 AML subtype
179
how to treat AML M3 type
ATRA (all-trans retinoic acid (vit A) which induces differentiation of myeloblasts
180
CML presentation
increased neutrophils, metamyelocytes, basophils, splenomegaly, may transform to aml or all, very low leukocyte alkaline phosphatase due to immature granulocytes
181
genetics of CML
philadelphia chromosome (t9,22, bcr-abl); MN: PHILADELPHIA CreaML cheese = CML
182
CML responds to what treatment
imatinib (anti-bcrabl antibody) which inhbiits bcr-abl tyrosine kinase
183
blast crisis is associated with what condition and why?
CML bc it may accelerate and transform to AML or ALL
184
ages of the four leukemias
ALL = 60
185
auer rods
peroxidase+ cytoplasmic inclusions in granulocytes and myeloblasts, commonly seen in acute promyelocytic leukemia (M3)\
186
why do you get DIC in AML M3
release of Auer rods
187
Ewing's sarcoma genetics
t(11,22)
188
langerhans cell histiocytosis
proliferative disorders of dendritic (langerhans) cells. Defective cells express S-100 and Cd1a; cells immature and cannot stimulate T lymphocytes via antigen presentation
189
birbeck granules/tennis rackets on EM
langerhans cell histiocytosis
190
polycythemia vera in relation to RBC, WBC, platelet levels
increase in all, positive JAK2 mutation
191
essential thrombocytosis
increase in platelets, possible Jak2 mutation (30-50%)
192
myelofibrosis
decrease in RBCs , psotive JAK2 mutation (30-50%)
193
CML (RBC, WBC, Platelet levels)
decrease in RBC, increase in white cell and platelets; philadelphia chromosome!
194
polycythemia vera ?
abnormal clone of hematopoietic stem cells that are increasingly sensitive to growth factors
195
tear drop cell
bone marrow infiltration as seen in myelofibrosis: MN: bone marrow is crying bc it is fibrosed
196
appropriate absolute polycythemia and associate diseases
increase in RBC mass, decrease in O2 sat, increase in EPO; lung disease, congenital heart disease, high altitude
197
inappropriate absolute polycythemia and associated cause
increase in RBC mass and EPO; due to RCC, wilms' tumor, cyst, HCC, hydronephrosis; ectopic erythropoietin
198
plasmin's role
converts fibrinogen to degradation products or fibrin to to fibrin split products (d dimers)
199
leucovorin
used to "rescue" bone marrow if methotrexate is given too much
200
3 pathologies that will give basophilic stippling of RBCs
MN: Baste the ox TAIL: thalassemias, anemic of chronic disease, Lead Poisoning
201
bite cell RBC is caused by what pathology
G6PD deficiency
202
schistocytes and helmet cells can be seen in what pathology?
DIC, TTP/HUS, traumatic hemolysis
203
target cells are seen in what conditions?
MN: HALT -said the hunter to his target: HbC disease, Asplenia, Liver Disease, Thalassemia
204
heinz bodies seen in what pathologies?
alpha thalassemia, G6PD deficiency, oxidation of iron from ferrous to ferric form leads to denatured Hb precipitation and damage to RBC membrane which leads to formation of BITE CELLS
205
sideroblastic anemia
defect in heme synthesis
206
treat sideroblastic anemia with
pyridoxine (b6 therapy)
207
sideroblastic anemia etiology
x linked defect in aminolevulinic acid (ALA) synthase gene; reversible etiologies are alcohol and lead
208
lab findings for sideroblastic anemia
increased iron, normal TIBC, increased ferritin
209
thrombotic thrombocytopenic purpura
decreased platelet survival due to deficiency of ADAMTS 13 (vWF metalloprotease) that decreases degradation of vWF multimers
