hematology oncology part 2 Flashcards
1
Q
infection in hereditary spherocytosis?
A
Parvovirus B19 leading to aplastic crisis
2
Q
MCV in spherocytosis?
A
Normal to decreased
3
Q
spherocytosis diagnosis?
A
Positive osmotic fragility test.
4
Q
hemolysis type in G6PD?
A
extravascular and intravascular
5
Q
G6PD presentation
A
Back pain + hemoglobinuria a few days following oxidant stress.
6
Q
pyruvate kinase deficiency from codebook
A
- Coded character: Piratte swinging around bathroom + /pyruvate kinase deficiency. Tyrion pissing on the baby/autosomal recessive. Solid, rigid RBC on the floor/defect in pyruvate kinase causes decreased ATP production, leading to rigid RBCs. Baby bleeding out in the sink/presentation = hemolytic anemia in a newborn. /Pyruvate kinase requires all the same cofactors as alpha-ketoacid dehydrogenase (TLCFD).
- Location: BG first floor bathroom
7
Q
pyruvate kinase pathophys
A
defect in pyruvate kinase leads to decreased ATP leading to rigid RBCs, leading to extravascular hemolysis
8
Q
classic pyruvate kinase presentation
A
hemolytic anemia in a newborn
9
Q
Don’t confuse HbS with HbC
A
ok
10
Q
hemolysis type in HbC
A
extravascular
11
Q
HbC on labs (homozygote)
A
hemoglobin crystals inside RBCs and target cells
12
Q
One disease smoking is protective for?
A
ulcerative colitis
13
Q
etiology of PNH
A
Acquired mutation in a hematopoietic stem cell.
14
Q
cancer and PNH?
A
PNH patients are at increased risk of acute leukemias
15
Q
PNH triad
A
Coombs negative hemolytic anemia + pancytopenia + venous thrombosis.
16
Q
treatment for PNH?
A
eculizumab
17
Q
eculizumab MOA
A
terminal complement inhibitor
18
Q
sickle cell etiology
A
point mutation causing replacement of glutamic acid with valine in beta chain
19
Q
hemolysis type in sickle cell anemia
A
Extravascular + intravascular hemolysis.
20
Q
what can precipitate sickling?
A
1) hypoxemia
2) high altitude
3) acidosis
4) dehydration
21
Q
newborns and sickle cell anemia
A
usually asymptomatic because of increased HbF
22
Q
epidemiology of sickle cell in AA’s
A
8% of African Americans carry an HbS allele
23
Q
other thing sickle cell pts are at increased risk for?
A
stroke
24
Q
Immunoglobulin in warm AIHA?
A
IgG (warm weather is Great)
25
when is warm AIHA seen?
1) Chronic anemia such as SLE and CLL
| 2) alpha-methyldopa
26
Immunoglobulin in cold AIHA?
IgM and complement (cold weather is Miserable)
27
when is cold AIHA seen?
1) acute anemia triggered by cold
2) CLL
3) mycoplasma infections
4) mononucleosis
28
pathophys of cold AIHA and cold
RBC agglutinates cause painful, blue fingers and toes with cold exposure.
29
Duodenum supply
Supplied proximally by a branch of the common hepatic (gastroduodenal). This is proximal to the 2nd part of the duodenum. Distal to 2nd part is SMA (inferior pancreaticoduodenal). So inferior pancreaticoduodenal supplies 3rd and 4th sections.
30
Where is collateral circulation in duodenum?
Superior and inferior pancreaticoduodenal arteries form an anastomotic loop between the celiac trunk and the SMA.
31
Anatomic location distinguishing foregut from midgut?
2nd part of the duodenum
32
Coombs positive?
AIHA
33
Direct coombs test
Anti-Ig antibody added to patients blood. RBCs agglutinate if RBCs are coated with Ig.
34
Indirect Coombs test
Normal RBCs added to patient's serum. If serum has anti-RBC surface Ig, RBCs agglutinate when Coombs reagent added.
35
When is microangiopathic anemia seen?
1) DIC
2) TTP/HUS
3) SLE
4) malignant HTN
36
When is macroangiopathic anemia seen?
1) prosthetic heart valves
| 2) aortic stenosis
37
macroangiopathic anemia on smear...
schistocytes, just like microangiopathic
38
Intrinsic vs. extrinsic distinction
Intrinsic to the RBC (structural defect or error in biochem process). Extrinsic to the RBC
39
Iron deficiency
1) serum iron
2) transferrin/TIBC
3) ferritin
4) % transferrin saturation (serum iron/TIBC)
1) down
2) increased
3) decreased
4) way down
40
Chronic disease
1) serum iron
2) transferrin/TIBC
3) ferritin
4) % transferrin saturation (serum iron/TIBC)
1) decreased
2) decreased
3) increased
4) no change
41
Pregnancy/OCP use
1) serum iron
2) transferrin/TIBC
3) ferritin
4) % transferrin saturation (serum iron/TIBC)
1) no change
2) increased
3) no change
4) decreased
42
Hemochromatosis:
1) serum iron
2) transferrin/TIBC
3) ferritin
4) % transferrin saturation (serum iron/TIBC)
1) increased
2) decreased
3) increased
4) way increased
43
When do you get severe infections with neutropenia?
less than 500 cells
44
neutropenia definition
less than 1500 cells
45
Causes of neutropenia
1) sepsis/postinfection
2) drugs (chemo)
3) aplastic anemia
4) SLE
5) radiation
46
lymphopenia definition
less than 1500 cells in adults; less than 3000 cells in children
47
Causes of lymphopenia
1) HIV
2) DiGeorge
3) SCID
4) SLE
5) corticosteroid
6) radiation
7) sepsis
8) postoperative
48
eosinopenia definition
eosinophils less than 30 cells
49
Causes of eosinopenia
1) Cushing syndrome
| 2) corticosteroids
50
Corticosteroids and neutrophils/eosinophils mechanism
1) decrease activation of neutrophil adhesion molecules, impairing migration out of the vasculature to sites of inflammation.
2) Sequester eosinophils in lymph nodes and cause apoptosis of lymphocytes.
51
What is a left shift?
A shift to more immature cell in the maturation process
52
When is a left shift usually seen?
With neutrophilic in the acute response to infection or inflammation.
53
What is a leukoerythroblastic reaction? When is it seen?
Left shift with immature RBCs.
1) severe anemia
2) marrow response (fibrosis, tumor taking up space in marrow).
54
accumulated substrate in lead poisoning
1) protoporphyrin
| 2) delta-ALA
55
How are adults exposed to lead?
batteries, ammunition
56
lead poisoning presentation in adults
Headache + memory loss + demyelination
57
defective enzyme in AIP?
porphobilinogen deaminase
58
accumulated substrate in AIP?
1) porphobilinogen
2) delta-ALA
3) coporphobilinogen (in urine)
59
what can precipitate AIP?
1) CYP-450 inducers
2) alcohol
3) starvation
60
Treatment for AIP?
Glucose and heme, which inhibit ALA synthase
61
Defective enzyme in porphyria cutanea tarda
Uroporphyrinogen decarboxylase
62
accumulated substrate in porphyria cutanea area?
Uroporphyrin (tea-colored urine)
63
Most common porphyria?
porphyria cutanea tarda
64
ferrochelatase action + site of action
Final step of heme synthesis: protoporphyrin --> heme (incorporation of iron into protoporphyrin)
65
What step does uroporphyrinogen decarboxylase catalyze?
uroporphyrinogen III --> coproporphyrinogen III
66
difference between left and right GI
Right side is microsatelite instability/mismatch repair pathway.
Left side is more APC pathway.
67
What is protective against progression to GI cancer with APC pathway?
aspirin.
68
Heme synthesis pathway
FA 395
69
What step does porphobilinogen catalyze?
Porphobilinogen --> hydroxymethylbilane
70
What step does delta-aminolevulinic acid dehydratase catalyze?
delta-aminolevulinic acid --> porphobilinogen
71
Rate limiting step of heme synthesis?
delta-aminolevulinic acid synthase
72
What step does delta-aminolevulinic acid (ALA) synthase catalyze?
Glycine + succinyl-CoA --> delta-aminolevulinic acid
73
What regulates ALA synthase?
Decreased heme increases ALA synthase activity; increased heme decreases.
74
Why is iron toxic?
Cell death due to peroxidation (oxidative degradation of membrane lipids).
75
iron poisoning symptoms
Nausea + vomiting + gastric bleeding + lethargy + scarring leading to GI obstruction
76
Extrinsic pathway components
I,II,V,VII, and X
77
PT related to
extrinsic pathway
78
INR
Calculated from PT. 1 = normal, greater than 1 = prolonged.
79
What does PTT test?
Function of common and intrinsic pathway (all factors except VII and XIII).
80
hemophilia inheritance
A and B are x-linked excessive. **hemophilia C is autosomal recessive.
81
hemophilia A deficiency of...
VIII
82
hemophilia B deficiency of...
IX
83
hemophilia C deficiency of...
XI
84
treatment for hemophilia
Desmopressin + factor VIII for A, IX for B, XI, for C
85
Vitamin K deficiency labs
Increased PT + increased PTT
86
Bernard-Soulier: PC, BT
PC normal or decreased
| BT increased
87
Bernard-Soulier mechanism
Defect in platelet plug formation. Large platlets.
| Decreased GpIb receptor leads to defect in platelet to vWF adhesion.
88
Glanzmann thrombasthenia: PC, BT
PC normal
| BT increased
89
Glanzmann thrombasthenia mechanism
Defect in platelet plug formation.
| Decreased GpIIb/IIIa leads to defect in platelet-to-platelet aggregation.
90
Glanzmann thrombasthenia labs
no platelet clumping
91
HUS: PC, BT
PC decreased
| BT increased
92
Difference in presentation between HUS in kids and adults
In kids, usually caused by 0157:H7 and presents with diarrhea; in adults no diarrhea and STEC infection not required.
93
HUS treatment
plasmapheresis
94
HUS very similar to
on the same spectrum as TTP; similar presentation
95
Immune thrombocytopenia: PC, BT
Decreased PC, Increased BT
96
Immune thrombocytopenia pathophys
Anti-GpIIb/IIIa antibodies lead to splenic macrophage consumption of platelet-antibody complex. Often with viral illness.
97
Immune thrombocytopenia treatment
IVIG + splenectomy for refractory ITP
98
TTP: PC, BT
Decreased PC, increased BT
99
what is ADAMTS 13?
vWF metalloprotease
100
TTP pathophys
Inhibition or deficiency of ADAMTS 13 leads to impaired degradation of vWF multimers. Large vWF multimers leads to increased platelet adhesion and increased platelet aggregation and thrombosis.
101
TTP labs
1) shistocytes
| 2) increased LDH
102
TTP treatment
Plasmapheresis + steroids
103
TTP symptoms
Pentad of neurologic and renal symptoms + fever + thrombocytopenia + microangiopathic hemolytic anemia.
104
vW labs
Increased BT
| Increased PTT
105
underlying problem in vW
defect in platelet to vWF adhesion
106
vW inheritance
Autosomal dominant
107
DIC
1) PC
2) BT
3) PT
4) PTT
1) decreased
2) increased
3) increased
4) increased
108
DIC labs
1) shistocytes
2) Increased fibrin degradation products (D-dimers)
3) decreased fibrinogen
4) decreased factors V and VIII
109
causes of DIC
```
STOP Making New Thrombi
Sepsis
Trauma
Obstetric complications
Pancreatitis
Malignancy
Nephrotic syndrome
Transfusion
```
110
Antithrombin deficiency
Inherited deficiency of antithrombin. No direct effect on PT, PTT, or thrombin time but diminishes increase in PTT following heparin administration.
Can also be acquired from nephrotic syndrome through loss in urine, which decreases inhibition of factors IIa and Xa.
111
Mutation in factor V leiden
Point mutation --> Arg506Gln mutation near cleavage site.
112
protein C or S etiology
Decreased ability to inactivate factors Va and VIIIa
113
Common protein C deficiency presentation
thrombotic skin necrosis with hemorrhage after administration of warfarin.
114
Prothrombin etiology
mutation in 3' untranslated region leads to increased production of prothrombin and increased plasma levels and venous clots.
115
Transfusion therapy for severe anemia?
packed RBCs (to increase hb and O2 carrying capacity)
116
Transfusion therapy for acute blood loss?
packed RBCs
117
transfusion therapy for DIC?
fresh frozen plasma (in order to increase coagulation factor levels)
118
transfusion therapy for cirrhosis?
fresh frozen plasma (in order to increase coagulation factor levels)
119
What is cryoprecipitate?
Contains fibrinogen, factor VIII, factor XIII, vWF, and fibronectin.
120
When is cryoprecipitate used?
Coagulation factor deficiencies involving fibrinogen and factor VIII.
121
Electrolyte complications of blood transfusion
1) iron overload
2) hypocalcemia (citrate is a Ca2+ chelator)
3) hyperkalemia (RBCs may lyse in old blood units)
122
Leukemia?
Lymphoid or myeloid neoplasm with widespread involvement of bone marrow.
123
Where are tumor cells usually found in leukemias?
In peripheral blood.
124
Lymphoma?
Discrete tumor mass arising from lymph nodes.
125
Lymph node involvement in Hodgkin's vs. non-Hodgkin's lymphoma
Hodgkin's --> localized, single group of nodes with contiguous spread.
non-Hodgkin --> multiple lymph nodes involved; extra nodal involvement common; noncontiguous spread.
126
Prognosis in Hodgkin's?
Many have a relatively good prognosis.
127
non-Hodgkins' epidemiology
young adulthood and over 55 years; more common in men except for nodular sclerosing type.
128
Note
Don't assume Hodgkin's with constitutional B signs/symptoms
129
RS cell markers
CD15, CD30
130
Plasma cell description in MM
"fried egg" appearance. "clock-face" chromatin and intracytoplasmic inclusions containing immunoglobulin.
131
Immunoglobulin types in MM
mostly IgG (55%) but can also be IgA (25%)
132
Most common primary bone tumor in 40-50 age group?
multiple myeloma
133
Waldenstrom macroglobulinemia
Hyper viscosity syndrome with M spike leading to blurred vision and Raynaud's but no CRAB findings.
134
Rate of multiple myeloma development with MGUS
1-2% per year.
135
myelodysplastic syndromes etiology
stem-cell disorders involving ineffective hematopoiesis, leading to defects in cell maturation of all non lymphoid lineages.
136
myelodysplastic syndromes sequela..
Can transform to AML
137
Cause of myelodysplastic syndromes
1) de novo mutations
| 2) environmental exposure (eg radiation, benzene, chemo)
138
Common things in leukemias
1) anemia (decreased RBCs)
2) infections (decreased mature WBCs)
3) hemorrhage (decreased platelets)
4) lymphocytosis (malignant leukocytes in blood)
So don't attribute any one of these to one type.
139
Leukemia cutis
leukemic cell infiltration of skin
140
Prognosis of ALL in adults
BAD, worse than in kids
141
mediastinal mass presenting as SVC syndrome?
ALL
142
translocation associated with better prognosis in ALL?
T(12:21)
143
Leukemia most responsive to therapy?
ALL
144
ALL mets
CNS + testes
145
ALL markers
TdT marker of pre-T and pre_B cells, CD10 marker of pre-B cells
146
CLL/SLL markers
CD20+, CD5+ B-cell neoplasm
147
CLL/SLL presentation
often asymptomatic, slow progression.
148
Richter transformation
SLL/CLL transformation into an aggressive lymphoma, most commonly DLBCL
149
Dry tap on aspiration...
1) hairy cell leukemia
| 2) myelofibrosis
150
Hairy cell leukemia treatment
Cladribine + pentostatin
151
No increase in PTT following heparin administration think...
Antithrombin deficiency
152
What are the prothrombotic disorders?
1) antithrombin deficiency
2) Factor V Leiden
3) Protein C or S deficiency
4) Prothrombin gene mutation
153
transferrin saturation
serum iron/TIBC
