Hem/Onc Flashcards
1
Q
Source of energy for erythrocytes
A
Glucose (90% glycolysis, 10% HMP)
2
Q
RBC transporter that allows RBCs to export bicarb and transport CO2 from periphery to lungs
A
Cl-/HCO3- antiporter
3
Q
ANisocytosis
A
Varying sizes of RBC
4
Q
Pikilocytosis
A
Varying shapes of RBC
5
Q
Life span of plts
A
8-10 d
6
Q
Dense granule of plts contents
A
ADP, Ca2, Serotonin
7
Q
Alpha granule of plts contents
A
vWF, fibrinogen, fibronectin
8
Q
Storage of plt pool
A
1/3 in spleen
9
Q
Low platelets/plt fxn –>
A
Petiechiae
10
Q
vWF receptor
A
GpIb (attach)
11
Q
Fibrinogen receptor
A
GIIb/IIIa (aggregate)
12
Q
Blue color in retics…
A
Residual rRNA
13
Q
Neutrophil specific granule contents
A
Leuk Alk PHos, collagenase, lysozyme, lactoferrin
14
Q
Azurophilic granule contents
A
In neuts – proteinases, acid phos, MPO, b-glucuronidase
15
Q
Hypersegmented neuts in
A
Vit B12/folate def
16
Q
More band cells means
A
More myeloid proliferation (CML, bacterial infxn)
17
Q
Neutrophil chemotactic agents
A
C5a, IL8, LTB4, kallikrein, PAF
18
Q
Activates macs
A
Gamma interferon
19
Q
Lipid A binds…
A
From bacteria LPS binds CD14 on macs –> septic shock
20
Q
Eosinophils produce
A
Histaminase, MBP (helminthotoxin), eosinphil peroxidase, eosinophil cationic protein, eosinophil derived neurotoxin
21
Q
Causes of eosinophilia
A
Neoplasia, Asthma, Allergic process, Chronic adrenal insufficiency, Parasites
22
Q
Basophil granules contain
A
Heparin (anticoag), histamine (vasodilator)
23
Q
Basophils can synthesize
A
Leukotrienes – not preformed!
24
Q
Basophilia can mean
A
Myeloproliferative disease, like CML
25
Mast cell from same precursor as
Basophils
26
Mast cell releases
Histamine, heparin, tryptase, and eosinophil chemotactic factors
27
Drug that prevents mast cell degranulation and use
Cromolyn sodium -- asthma prophylaxis
28
B cell markers
CD19, CD20,CD21
29
T cell markers
Tc: CD3, CD8
Th: CD3, CD4
T reg: CD3, CD28
30
Majority of circulating lymphs are...
T cells (80%)
31
Plasma cell cancer
Multiple myeloma
32
Fetal erythropoesis
```
Yolk sac (3-8wks)
Liver (6wk-birth)
Spleen (10-28 wks)
Bone marrow (18wk-adult)
Young Liver Synthesizes Blood
```
33
Embryonic globins
L and E
34
Fetal hemoglobin
a2gamma2
35
Adult hemoglobin
a2b2
36
Why does HbF have a higher affinity of O2?
Less avid binding of 23 BPG --> can extract oxygen from maternal hemoglobin across placenta
37
HbA2
a2d2 -- small amounts in adult
38
ABO abs are
IgM
39
Rh abs are
IgG
40
Presentation of ABO hemolytic disease in newborn (rare)
Mild jaundice in neonate w/in 24 hrs of birth -- tx phototherapy or exchange transfusion
41
Order of furthest migration on a gel for hemoglobins
A (normal hemoglobin B chain -- HbA)
F (normal hg gamma chain -- HbF)
S (sickle cell hemoglobin B chain -- HbS)
C (Hemoglobin C B chain -- HbC)
42
Intrinsic (contact activation) pathway
Collagen/basement membrane/activated platelets --> 12>11>9 and 8...
43
Tissue factor (extrinsic) pathway
7>...
44
Combined pathway
X & V>2>1> cross linking via 13
45
Require calcium/phospholipid
```
9 to 9a,
9a+8a to X-->Xa,
7-->7a-->+cofactor to catalyze X-->Xa
Xa+Va to catalyze II-->IIa
13 to crosslink
```
46
Kinin cascade
HMWK > activates 12
| via kallikrien-->bradykinin --> vasodilation, permeability and pain
47
Inhibited by Warfarin
2,7,9,10 C,S
48
Hemophilia A def
Factor 8 -- XR
49
Hemophilia B
Factor 9 -- XR
50
Hemophilia C
Factor 11 --AR
51
Vit K in coagulation
Reduced via epoxide reductase to become cofators in gamma glutamyl carboxylation to make mature/active coag cascade components
52
VIt K def
Low fact II, 7, 9, 10, pC, pS
53
vWF carries/protects
Factor 8
54
Protein C cleave and inactivates
Va and 8a w/ help of pS
55
Antithrombin inhibits activated
2,7,9,10,11,12; principal targets are thrombin and Xa
56
Heparin acts by
Enhancing activity of antithrombin
57
Factor V leiden mutation
Factor V that cannot be inhibited by protein C --> hypercoagulability
58
Plasminogen-->
via tPA to plasmin --> fibrinolysis -- cleavage of fibrin mesh, destruction of coag factors
59
Platelet plug formation
Endothelial damage --> transient vasoconstriction (neural stim reflex and endothelin released) --> vWF binds exposed collagen (from Weibel Palade bodies of endothelial cells and a granules of plts --> plts bind vWF via GpIb and undergo conformational change --> release ADP (helps plts adhere, binds P2Y12 receptor to induce GpIIbIIIa expresion on plt), Ca, and TXA2 --> Fibrinogen binds GpIIb/IIIa receptors to link platelets
60
Proaggregation factors
TXA2 from plts, slower blood flow, increased platelet agg
61
Antiaggregation factors
PGI2 and NO from endothelial cells, faster blood flow, less platelet aggregation
62
How does aspirin cause anticoag?
Irreversible inhib of COX in plts --> no TXA2 synthesis
63
These inhibit GpIIb/IIIa direction
Abiciximab, eptifibatide, tirofiban
64
Action of ristocetin
Activates vWF to bind GpIb -- failure of assay with vWD and Bernard Soulier syndrome
65
Inhibit P2Y12 receptor
Clopidogrel, prasugrel, ticlodipine
66
Deficiency of GpIb on plt -->
Bernard-Soulier syndrome
67
Def of vWF
vWD
68
Inside endothelial cells
vWF and factor 8, thromboplastin, tPA, PGI2
69
Acanthocytes seen in
Liver disease, abetalipoproteinemia (states of cholesterol dysregulation)
70
Basophilic stippling seen in
Lead poisoning, sideroblastic anemias, myelodysplastic syndromes
71
Basophilic stippling sample
Periperal smear
72
Ringed sideroblast sample
Bone marrow
73
Basophilic stippling is
Aggregation of residual ribosomes
74
Dacrocyte aka
Teardrop cell
75
Acanthocytes aka
Spur cell
76
Dacrocyte seen in
Bone marrow infilitration (myelofibrosis) -- due to mechanical squeezing out of its home
77
Degmacyte aka
Bite cell
78
Degmacyte seen in
G6PD def
79
Echinocyte aka
Burr cell
80
Echinocyte seen in
ESRD, liver disease, PK def
81
Ddx from acanthocyte to echinocyte
Echinocyte has more uniform and smaller projections
82
Elliptocyte seen in
Mereditary elliptocytosis, usually asymptomatic -- caused by mutations in genes encoding RBC membrane proteins (spectrin)
83
Macroovalocytes seen in
Megaloblastin anemia (w/ hypeseg PMNs)
84
Ringed sideroblast seen in
Sideroblastic anemia, excess iron in mitochondria
85
Schistocyte seen in
Microangiopathic hemolytic anemias (DIC,TTP/HUS, HELLP), mechanical hemolysis
86
Schitocyte is a
Fragmented RBC, eg helmet cell
87
Sickle cell seen in/caused by
Sickle cell anemia -- occurs w/ dehydration, deoxygenation, and high altitudes
88
Spherocytes seen in
Hereditary spherocytosis, drug/infxn induced hemolytic anemia
89
Target cells seen in
HbC disease, Asplenia, Liver disease, Thalassemia (HALT)
90
Heinz bodies seen in
G6PD def (precipitated hemoglobin due to SH grp reduction to S-S -- phagocytes eat leading to bite cells
91
Howell Jolly bodies seen in
Fxnal hyposplenia or asplenia
92
HJ bodies are made up of
Basophilic nuclear remnants in RBCs --normally removed by splenic macrophages
93
Causes microcytic anemia
```
Sideroblastic anemia (cause be caused by Cu def)
ACD
Lead poisoning
Thalassemias
Iron def (late)
SALTI
```
94
Causes megaloblatic macrocytic anemia
Folate def
B12 def
Orotic aciduria
95
Causes nonmegaloblastic macrocytic anemia
Liver disease
Alcoholism
Diamond-BLackfan anemia
96
Causes nonhemolytic normocytic anemia (normal or low retic)
Iron def (early)
ACD
Aplastic anemia
CKD
97
Causes intrinsic hemolytic normocytic anemia
RBC membrane defect (hereditary spherocytosis), RBC enzyme def (G6PD, pyruvate kinase), HbC disease, Paroxysmal nocturnal hemoglobinuria, Sickle cell anemia
98
Causes extrinsic hemolytic normocytic anemia
Autoimmune, microangiopathic, macroangiopathic, infxns
99
Iron def causes
Chronic bleeding (GI loss, mnorrhagia), malnutrition, absorption disrders, GI surg, increased demand (e.g. preg), --> lowers the final step in heme synth
100
Labs in iron def anemia
Low iron, high TIBC, low ferritin, high free erythrocyte protophyrin; microcytosis, hypochromasia (central pallor)
101
Sx of IDA
Fatigue, conjunctival pallor, pica, spoon nails (koilonychia); glossitis, cheliosis
102
Plummer Vinson
IDA, esophageal webs, dysphagia
103
Alpha thalassemia caused by
Alpha globin deletions --> less alpha synthesis
104
Alpha thalassemia genetics
Cis -- Asian pops
Trans -- African pops
4 allele deletion --> no alpha globin, excess gamma globin --> Hb Barts (gamma4) --> hydrops fetalis
3 allele delition --> HbH disease -- very little alpha globin --> excess b globin makes HbH
2 allele deletion --> less clinically severe anemia
1 allele deletion --> no anemia (clinically silent)
105
HbH disease sx
Hemolytic anemia, jaundice (hyperBR), high LDH, low hapto
106
B thalassemia genetics
Point mutations in splice sites and promoter sequences --> less B globin synthesis (esp in Mediterranean pops)
107
B thalassemia minor
Heterozygote -- less B change produced, usually asymptomatic -- diagnosis by high HbA2 (>3.5%) on EP
108
B thalassemia major
Homozygote -- no B chain --> severe mycrocytic hypochromic anemia w/ target cells and increased anisopoikilocytosis req blood transfusion (2o hemochromatosis) -->
a. marrow expansion (crew cut on xray) --> skeletal deformities, chipmunk facies,
b. extramedullary hematopoesis -_> hepatosplenomegaly, higher risk of parvo aplastic crisis
High HbF (alpha2g2) -- protective in infant so only symptomatic after 6 mths when fetal hb declines
109
HbS/B thalassemia heterozygote
Mild-mod sickle cell depending on amt of B globin prodxn
110
Lead poisoning inhibs
Ferrochetalase and ALA DHase --> less heme synth and increased RBC protophyrin;
also inhib rRNA degradation --> retaining aggregates of rRNA --> basophilic stippling
111
Sx of lead poisoning (and Tx)
Lead lines on gingivae (Burton lines) and metaphyses of long bones on Xray
Encephalopathy and Erythrocyte basophilic stippling
Abdominal colic and sideroblastic Anermia
Drops -- wrist/food; Dimercaprol and EDTA are 1st line tx
112
In kids tx
Succimer
113
Siderblastic anemia causes
Genetics (x linked defect in ALA synthase), acquired (myelodyslastic syndromes), reversible (EtOH, lead, B6 def, Cu def, isoniazid)
114
Labs in sideroblastic anemia
Increased iron, normal or low TIBC, high ferritin; ringed sideroblasts w/ iron laden Prussian blue stained mitochondria in bone marrow; peripheral smear --> basophilic stippling of RbCs
115
Tx of sideroblastic anemia
Pyridoxine (B6 -- cofactor for ALA synthase)
116
Megaloblastic anemia
Impaired DNA synth --> maturation of nucleus of precursor cells in bone marrow delayed relative to maturation of cytoplasm
See RBC macrocytosis, hyperseg neuts, glossitis
117
Folate deficiency causes
Malnutrition (alcoholics), malabsorption, drugs (methotrexate, TMP, phenytoin), increased req (e.g. hemolytic anemia, preggers)
118
Labs in folate def
High homocystein, normal MMA; NO NEURO SYMPTOMS
119
Vitamin B12 def causes
Insufficient intake (veganism), malabsoprtion (Crohns), pernicious anemia, Diphyllobothrium latum (fish tapeworm), gastrectomy
120
Vit B12 def labs
High homocysteine, high MMA
121
Vit B12 sx
NEURO! REversible dementia, SCD due to involvement in fatty acid pathways and myelin synth --> spinocerebellar tract, LCST, dorsal column
122
Schilling test
Dietary vs malabsorption
123
Liver can store folate or B12 longer
B12 -- takes several years
124
Orotic aciduria mechanism
Inability to convert orotic acid to UMP (de novo pyrimidine synth pathway) due to defect in UMP synthase
125
Orotic aciduria genetics
AR
126
Orotic aciduria presentation
In children -- failure to trive, developmental delay, megaloblastic anemia refractory to folate and B12
NO HYPERAMMONEMIA! (vs OTC def!)
127
Orotic aciduria lab
Orotic acid in urine
128
Tx of orotic aciduria
Uridine triacetate to bypass mutated enzyme
129
Nonmegaloblastic anemia
Macrocytic anemia where DNA synth is unimpaired --> RBC macrocytosis w/o hyperseg neuts
130
Nonmegaloblastic anemia causes
EtOH, liver disease
131
Diamond Blackfan anemia mechanism
Rapid onset anemia w/in first year of life due to intrinsic defect in erythroid progenitor cells (build up--> disrupt bone formation)
132
Diamond blackfan labs
High %HbF, but low total Hb
133
Diamond blackfan presentation
Short stature, craniofacial abnormalities, upper extremity malformations (triphalangeal thumbs)
134
Intravascular hemolysis findings
Low hapto, high schistocytes, hemoglobinuria, hemosiderinuria, urobilinogen in urine, high unconj bili
135
Causes of intravascular hemolysis
Mechanical, paroxysmal nocturanl hemoglobinuria, microangiopathic hemolytic anemia
136
Extravascular hemolysis findings
Macs in spleen clear RBCs -- spherocytes in peripheral smear; no hemoglobinuria or hemosiderinura but may have urobilinogen in urine
137
Most common causes of extravascular hemolysis
Hereditary spherocytosis and autoimmune hemolytic anemia
138
Anemia of chronic disease mechanism
Inflamm --> high hepcidin (binds ferroportin on intestine cells and macs to inhib iron transport --> less release of iron from macs and less iron absorption in gut
139
ACD assc
SLE, RA, neoplastic disorders, CKD
140
ACD findings
Low iron, low TIBC, high ferritin
141
Tx of ACD
Address underling cause, can consider transfusion or stimulation
142
Aplastic anemia causes
Failure/destruction of myeloid stem cells due to
Radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites)
Viral agents (parvovirus B19, EBC, HIV, hepatitis)
Fanconi anemia (DNA repair defects --> bone marrow failure, macrocytosis may be seen on CBC, also short statures, high incidence of tumors/leukemia, cafe au lait spots, thumb/radial defects
Idiopathic
143
Findings in aplastic anemia
Low retic, high EPO; pancytopenia w/ severe anemia, leukopenia, thrombocytopenia; normal cell morph but hypocellular bone marrow w/ fatty infiltration
DRY BONE MARROW TAP!
144
Sx of aplastic anemia
Fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infxn
145
Tx of aplastic anemia
W.drawal of offending agent, immunosuppressive regiments (antithymocyte globulin, cyclosporine), bone marrow allograft, RBC/plt transfusion, bone marrow stim (GM-CSF)
146
Hereditary spherocytosis
A type of intrinsic hemolytic anemia -- extravascular hemolysis due to defect in proteins interacting w/ RBC membrane skeleton and plasma membrane (anykyrin band 3, protein 4.2, spectrin) --> small, round RBCs w/ less surface area and no central pallor (high MCHC)-->premature removal by spleen
147
Hereditary spherocytosis genetics
AD
148
Sx and labs in hereditary spherocytosis
Sx: splenomegaly, aplastic crisis (parvoB19 infxn)
Labs: Osmotic fragility test pos (put in saline), NL/low MCV w/ abundance of cells
149
Tx of hereditary spherocytosis
Splenectomy
150
Most common enzymatic disorder of RBCs
G6PD def
151
Genetics of G6PD def
XLr
152
G6PD def mechanism
Extravascular and intravascular hemolysis due to defect in G6PD --> low glutathione -_> high RBC susceptibility to oxidant stress -_> hemolytic anemia under that stress (sulfa drugs, antimalarials, infxns, fava beans)
153
Sx of G6PD def
Back pain, hemoglobinuria a few days after oxidant stress
154
Labs in G6PD def
Heinz bodies and bite cells on blood smear
155
Pyruvate kinase
PEP--> Pyruvate and ATP
156
Pyruvate kinase def genetics
Ar
157
Pyruvate kinase def mechanism
Less PKase--> less ATP --> rigid RBCs-->extravascular hemolysis
Increases levels of 23 BPG-->lower Hb affinity for O2
158
Presentation of pyruvate kinase def
Hemolytic anemia in a newborn
159
Paroxysmal nocturnal hemoglobinuria pathophys and associations
Compliment mediated intravascularRBC lysis due to impaired synth of GPI anchor for DAF (protects RBC membrane from compliment)
Is an acquired mutation in hematopoetic stem cell
--> increased incidence of acute leukemias, assc w/ aplastic anemia
160
PNH fx
Red or pink urine (hemoglobinuria), Coombs neg hemolytic anemia, pancytopenia, venous thrombosis
161
PNH labs
CD55/59 neg RBCs on flow cyto
162
PNH tx
Eculizumab (terminal compliment inhibitor)
163
Sickle cell anemia mutation
HbS point mutation --> single amino acid replacement in beta chain (glutamic acid --> valine)
164
Type of hemolysis in sickle cell
Intra and extravascular
