Heme/Onc Flashcards
1
Q
Anisocytosis =
A
varying sizes
2
Q
Poikilocytosis =
A
varying shapes
3
Q
Plts contain?
- stored in?
A
dense granules (ADP, Ca), alpha granules (vWF, fibrinogen) - 1/3 in spleen
4
Q
vWF R? Fibrinogen R?
A
GpIb
GpIIb/IIIa
5
Q
Leuk’s
- 2 types?
- nl #
A
Granulocytes (N, Eo, Baso)
Mononuc (monocytes, lymph’s)
- 4-10k
6
Q
Hyperseg’d poly’s =
Seen in?
A
5+ lobes in N’s
VitB12/folate defic
7
Q
Eo’s produce what 2 substances?
Nuc is?
A
Histaminase and arylsulfatase (limit rxn post-mast cell degran)
- bilobed
8
Q
Baso’s secrete?
A
heparin (anticoag)
hist (vasodil)
LTD4
9
Q
Cromylyn sodium =
A
prevents mast cell degranulation
10
Q
VitK
- active form?
- cofactor for
A
reduced by epoxide reductase
- 2, 7, 9, 10, C, S
11
Q
Warfarin =
- how long until it works?
- which is the last factor to go away?
A
inhib’s epoxide reductase -> no VitK -> no factors 2, 7, 8, 10, C, S
- full anticoag in 3-4d
- prothrombin has longest t 1/2
12
Q
vWF carries/protects which CF?
A
VIII
13
Q
Heparin =
A
act’s antithrombin, which inact’s 2, 7, 9, 10, 11, 12
14
Q
Factor V Leiden mutation =
A
Factor V is resistant to inhib by act’d PrC -> more clotting
15
Q
Bernard-Soulier synd =
- sx
- labs
- dx by
A
AR; no GpIb -> vWF can’t bind plts for plt plug (intrinsic cascade)
- thrombocytopenia, giant plts (“big suckers”)
- incr’d BT
- Ristocetin cofactor assay (causes plts to clump only if vWF is there and its Rs work!)
16
Q
What do plts have in them?
A
vWF, fibrinogen
Arachidonic acid -> via COX to TXA2 (more clotting)
17
Q
Glanzmann’s thrombasthenia =
- periph smear shows?
A
AR; no GpIIb/IIIa, so plts can’t be linked together via fibrinogen -> less clotting
- no plt clumping, incr’d BT but nl plt ct
18
Q
Aspirin =
A
inhib’s COX, so not TXA2 syn
19
Q
Ticlopidine =
A
inhib’s ADP-induced exp’n of GPIIb/IIIa on plts -> no plt X-linking by fibrinogen and no clots
20
Q
Clopidogrel =
A
inhib’s ADP-induced exp’n of GPIIb/IIIa on plts -> no plt X-linking by fibrinogen and no clots
21
Q
Abciximab =
A
inhib’s GPIIb/IIIa on plts directly -> no plt X-linking by fibrinogen and no clots
22
Q
What are these RBCs seen in: acanthocyte (spur cell) basophilic stippling bite cell elliptocyte macro-ovalocyte ringed sideroblasts schistocyte, helmet cell spherocyte Teardrop cell Target cell
A
- liver dz, abetalipoproteinemia
- “BASte the ox TAiL” -> Thalassemias, Anemia of chronic dz, Lead poisoning
- G6PD defic
- hereditary elliptocytosis
- megaloblastic anemia, marrow failure
- sideroblastic anemia (Fe in mito -> bad)
- DIC, TTP/HUS, traumatic hemolysis (metal heart valve)
- hereditary spherocytosis, autoimm hemolysis
- BM infiltration (forced out of BM home…tear tear)
- “HALT, said the hunger to the Target” -> HbC dz, Asplenia, Liver dz, Thalassemia
23
Q
Heinz bodies =
- seen in
A
ox’n of Hgb sulfhydryl gps -> denatured Hgb that precipitates and hurts mem -> bite cells
- G6PD defic, similar bodies in a-thalassemia
24
Q
Howell-Jolly bodies =
- seen in
A
baso nuc remnants in RBCs, usu removed by spleen
- hyposplenia or asplenia, post-mothball ingestion (naphthalene)
25
```
Anemia in:
kids? why?
adult male?
adult female?
preg female? why?
```
< 11.5 (high phos -> incr'd 2,3BPG -> R shift OBC -> more O2 released, so don't need as high Hgb)
< 13.5
< 12.5
< 11 (2x incr in pl vol than RBC mass)
26
Hemochromatosis =
HFE gene prod -> binding of pl transferrin to mucosa cell R -> incr'd transferrin reab'n by GI cells -> more mucosal cell Fe so more released into the pl to bind w/ transferrin -> high pl Fe
27
Plummer-Vinson synd
- caused by?
- manifestations?`
chronic Fe defic -> eso web (dysphagia for solids but not liquids), achlorhydia, atrophic glossitis, koilonychia (spoon nails), pica
28
Hepcidin =
Antimicrobial peptide released by liver in response to inflamm (acute phase rct) -> enters Mphage in BM -> prevents release of Fe to transferrin bc binds ferroportin on intestinal mucosa cells and Mphage so Fe can't get out -> incr'd ferritin syn and Fe stores but little released
29
Fanconi synd =
| sx?
renal tubular damage (from Pb)
| - RTA type II (prox loss of bicarb), aminoaciduria, phosphaturia, glucosuria
30
Stages of Fe defic:
```
No Fe stores
Decr'd serum ferritin
Decr'd serum Fe
Incr'd TIBC
Decr'd Fe sat'n
Normocytic normochromic anemia
Microcytic hypochromic anemia
```
31
```
Decr'd MCV
Decr'd serum Fe
Incr'd TIBC
Decr'd % sat
Decr'd serum ferritin
Incr'd RDW
Decr'd RBC count
Hb electrophoresis nl
```
Fe defic bc sm RBC, less Fe so incr'd TIBC, decr'd ferritin bc less stored, incr'd RDW bc diff in sizes
32
```
Decr'd MCV
Decr'd serum Fe
Decr'd TIBC
Decr'd % sat
Incr'd serum ferritin
Nl RDW
Decr'd RBC count
Hb electrophoresis nl
```
ACD (anemia of chronic dz) - diff than Fe defic bc decr'd TIBC from incr'd serum ferritin, nl RDW
- first is normocytic normochromic anemia -> can become microcytic hypochromic
33
Decr'd MCV
Nl serum Fe, TIBC, % sat, serum ferritin, RDW
Incr'd RBC count
a-thal or b-thal minor
| Hgb electrophoresis nl in a-thal trait
34
```
Decr'd MCV
Incr'd serum Fe
Decr'd TIBC
Incr'd % sat
Incr'd serum ferritin
Nl RDW
Decr'd RBC count
```
Also have?
Lead poisoning bc have enough Fe, everything is nl, but decr'd RBC ct
AND
ringed sideroblasts (bc can't turn Fe into heme, NZ doesn't work) and coarse basophilic stippling (ribosomes)
35
Lead poisoning -> inhibits? interferes w/?
| - high risk in?
inhibits ferrochelatase and ALA DH -> decr'd heme syn (ringed sideroblasts bc have Fe in mito but no heme)
inhib's ribonuclease so can't brkdwn ribo's in RBCs -> basophilic stippling
interferes w/ growing cartilage -> see deposits in bones and lines on gums (Burton's lines)
- houses built before 1978
36
Sx of lead poisoning?
Trtmt?
LEAD:
Lead Lines on gums (Burton's lines) and on metaphyses of long bones on XR
Encephalopathy and Erythrocyte basophilic stippling
Ab colic and sideroblastic Anemia
Drops - wrist/foot
Trtmt by chelation: EDTA and succimer for adults, succimer (EDTA, dimercaprol) for kids
37
How is VitB12 ab'd?
Eaten ->
Pepsin (from pepsinogen via gastric acid from parietal cells) frees it from pr's ->
Binds R-binders from salivary gl's ->
Panc NZs in duo free B12 -> binds IF (from parietal cells) in duo ->
B12-IF reab'd in term ileum -> B12 binds transcobalamin II -> secreted into pl -> used or stored in liver for 6-9yrs
38
Folic acid
- circ'ing form?
- reab'n blocked by?
- supply in liver lasts?
- methylTHF
- EtOH, OCPs; phenytoin blocks intestinal conjugase which converts it into ab'able form
- 3-4mo
39
```
Lab findings in VitB12 defic:
Decr'd...
Incr'd...
See in periph bl?
See in BM?
```
Determine cause by?
- Decr'd serum B12
- Incr'd serum homocysteine and methylmalonic acid
- pancytopenia, oval macrocytes, hyperseg'd Ns (>5 lobes)
- megaloblastic nucleated cells w/ open (lacy) chromatin pattern
- Schilling test (PO radioactive B12 +/- IF or panc extract)
40
VitB12 defic -> demyelination of what?
Post columns (decr'd vibratory sensation and proprioception)
Lat corticospinal tract (spasticity)
Dorsal spinocerebellar tract (ataxia)
41
Haptoglobin =
acute phase rct, combines w/ Hgb to form complex that Mphage eat -> decr in serum haptoglobin
42
Target cells =
| sign of?
excess RBC mem
| - hemoglobinopathy (like HbS) or EtOH excess (incr'd choles -> incr'd cell mem)
43
5 ox'ing drugs:
CD-NPS
| chloroquine, dapsone, nitrofurantoin, primaquine, sulfonamides
44
Hemolytic anemias:
extravasc hemolysis -> ?
IV hemolysis -> ?
EV: Mphage phagocytosis, unconj'd hyperbilirubinemia -> jaundice, incr'd LDH
IV: decr'd serum haptoglobin, hemoglobinuria, incr'd LDH
45
Does the hemolysis occur EV or IV? What type of defect (intrinsic vs. extrinsic)
- Hereditary spherocytosis
- PNH
- Sickle cell
- G6PD
- Pyr kinase defic
- IgG-mediated
- C'-mediated
- IgM-mediated
- MHA (macroangiopathic hemolytic anemia)
- Malaria
- EV (intrinsic defect)
- IV (intrinsic)
- EV (intrinsic)
- IV (intrinsic) or EV
- EV (intrinsic) (PK defic)
- EV
- IV or EV
- IV usu, some EV
- IV (extrinsic) (MHA)
- IV (extrinsic)
46
Hereditary spherocytosis:
- defect in?
- aplastic crisis from?
- (+) ? test
- AD: ankyrin, band 3, pr 4.2, spectrin
- Parvov. B19 infec
- (+) osmotic fragility test (bc bad mem)
47
What yields hemolytic anemia in a newborn?
| Which is an acq'd defect -> hemolytic anemia?
Pyr kinase defic
| PNH
48
HbC =
| - if you have HbSC?
Glu -> Lys mutation at residue 6 in b-globin
| - you have milder dz than HbSS
49
PNH triad?
- Flow cytometry shows?
- Trtmt
```
Hemolytic anemia
Pancytopenia
Venous thrombosis
- CD55/59 (DAF, protectin) are NOT on RBCs on flow cytometry
- Eculizumab (term C' inhib)
```
50
Sickle cell trtmt?
Hydroxyurea bc incr's HbF, which doesn't sickle; BM transplant
51
Direct vs. Indirect Coomb's tests?
| - (+) direct Coomb's test in?
Direct: anti-Ig Ab added to pt's bl -> RBCs aggregate if coated w/ Ig
Indirect: nl RBCs added to pt's serum and add anti-IgAb -> RBCs aggregate if anti-RBC Ig in pt's serum
- AIHA (hot and cold)
52
When do you see schistocytes on periph bl smear?
W/ micro/macro-angiopathic hemolysis
53
Drug-induced hemolytic anemia, MoA for:
- Pn
- Quinidine (Class IA anti-arrhythmic)
- a-methyldopa (a-agoinst)
- a-Pn IgG attaches to RBC mem
- drug-IgM imm complex deposits on RBC -> IV hemolysis
- drug alters Rh Ag on RBCs -> autoAbs to new Rh
54
Infectious mononucleosis
- caused by? infects how?
- sx?
- imm response is what?
- test for it how?
- EBV (less commonly CMV) first rep's in epi cells in oropharynx -> spreads to B cells in LNs (attaches to CD21 on B cells) -> incr'd syn of IgM [atyp lymphocytosis!]; also goes to liver (-> hepatitis)
- severe fatigue, exudative tonsilitis, HSM (periart lymphatic sheath in spleen enlarged) (spleen can rupture), painful lymphadenopathy (incr'd CD8 T cells in paracortex of LN), rash if trted w/ Amp
- atyp CD8 T cells (big nuc and lots of blue cyto), which are reactive T cells
- Monospot test: pos. heterophil Ab test (detects IgM Abs to animal RBCs) is screening test -> confirm w/ VCA test (viral capsid Ag)
55
How to tell acute vs. chronic leukemia?
Do BM aspirate w/ blast count:
Acute has >20% blasts in BM
Chronic has >10% blasts in BM
56
ALL
- Age
- Markers?
- Can manifest at?
- Better prog w/?
- <15yo
- CALLA (CD10) and TdT
- B cell types goes to CNS/testes, T cell type (CD10-) can be mediastinal mass
- t(12;21)
57
SLL/CLL = ?
- Age
- Periph bl smear shows?
- Assoc'd sx?
- Diff btwn SLL and CLL?
Virgin B cell leukemia (no pl cells, no Igs and incr'd risk for infec)
- >60yo
- smudge cells
- asymp, autoimm hemolytic anemia (IgG and IgM), lymphadenopathy in old ppl
- SLL is confined to LNs, CLL has leukemic phase (incr'd periph bl lymphocytosis or BM involvement)
58
Hairy cell leukemia = ?
- Age
- Stains?
- Sx? Pos/neg
- Trtmt
Mature B-cell tumor
- Middle-aged men
- TRAP(+)
- Splenomegaly from prolif of B cells in red pulp, trapped in BM -> fibrosis and dry tap; NO lymphadenopathy
- Purine (adenosine) analogs = Cladribine (2-CDA)
59
Adult T cell leukemia
- Markers?
- Sx?
- Due to?
- Assoc'd w/?
- CD4+ Tdt-
- skin infiltration (RASH); lytic bone lesions -> hyperCa
- act'n of TAX gene -> inact'n of p53
- HTLV-1
60
AML
- Age?
- Periph smear shows?
- stain is (+) for?
- M3 AML subtype =
- What do you usu see w/ M3?
- 15-59yo, avg 65yo
- incr'd circ'ing myelobl's (-> Ba, Eo and N)
- peroxidase
- t(15;17) -> PML, trt w/ all-trans retinoic acid to induce differentiation of myeloblasts
- DIC, Auer rods (when released in trtmt can cause DIC)
61
CML
- Age
- Cause?
- Periph bl smear shows?
- Sx?
- Labs show?
- Trtmt?
- 30-60yo
- Philadelphia chr, t(9;22), bcr-abl gene
- Basophlilia w/ NO Auer rods
- HSM, painless lymphadenopathy, thrombocytosis sometimes present (only leuk w/ this!!!)
- Low leuk alk phosphatase (via high in leukemoid rxn to infec)
- Imatinib (sm-molec inhib of bcr/abl TK)
62
```
Where do you see these translocations?
t(9;22)
t(8;14)
t(11;14)
t(14;18)
t(15;17)
```
- CML
- Burkitt's lymphoma (c-myc act'n)
- Mantle cell lymphoma (NHL, cyclin D1 act'n)
- Follicular lymphoma (NHL, bcl-2 act'n)
- PML (M3 type of AML)
63
Where are these found:
B cells
T cells
Histiocytes
- LN germinal follicles, periph areas of white pulp of spleen
- LN paracortex (parafollicular), periart sheath in spleen, thymus
- LN subcapsular sinuses, skin (as Langerhans cells)
64
Hodgkin's lymphoma
- arises from?
- characterized by?
- age of onset? M/F?
- which is assoc'd w/ EBV?
- worst prog w/?
- best prog w/?
- sx?
- single gp of nodes w/ contiguous spread, usu starts in neck region
- Reed-Sternberg cells (binuc/bilobed, owl's eyes, CD30+, CD15+), secrete cytokines to bring in other cells which define type of HL
- bimodal: yg adults and >55yo; M>F except nodular sclerosing F>M
- mixed cellular
- lymphocyte mixed or depleted forms
- lymphocyte-rich type
- constitutional, low-gr F that comes and goes, night sweats, wt loss
65
Non-Hodgkin's lymphoma
- arises from?
- usu involves?
- age of onset?
- may be assoc'd w/?
- sx?
- mult periph nodes, extranodal involvement or starts extranodal; non-contiguous spread
- B cells, some have T cell origin though
- 20-40yo
- HIV, immsupp'n
- less constitutional sx than HL
66
Burkitt's lymphoma =
- assoc'd w/? presents as?
- age of onset
- genetics
- histo shows?
NHL
- EBV, jaw lesion in Africa or GI/para-Ao'ic nodes in America
- yg adults
- t(8;14) -> act's c-myc
- "starry sky" of lymph's w/ star Mphage clearings
67
Diffuse large B cell lymphoma =
- age of onset
- derives from
- common?
NHL
- older adults, 20% in kids
- germinal center
- Yes, most common adult NHL
68
Mantle cell lymphoma =
- age of onset
- genetics
- marker
- prognosis
NHL
- older males
- t(11;14), act'n of cyclin D1
- CD20+ B cells, and CD5+
- poor
69
Follicular lymphoma =
- age of onset
- genetics
- prognosis
NHL
- adults
- t(14;18), act's bcl-2 (anti-apoptosis gene)
- hard to cure, indolent course
70
Mycosis fungoides/Sezary syndrome =
- marker
- course
- why might you mistake it for MM?
Mature T cell neoplasm, CD4+
- Starts as skin rash -> plaque -> nodular masses
- Sezary when reaches leukemic spread (see cells w/ cerebriform nuc)
- has lytic bone lesions w/ hyperCa, like MM, but also has RASH
71
MM =
- on histo?
- Sx?
- cell makes?
- Light chains can do what?
- RBCs looks like?
- bone lesions are ? why?
monoclonal pl cell (IgG > IgA) ca from bone
- fried egg appearance
- CRAB: hyperCa, Renal insuff, Anemia, Bone lytic lesions and Back pain
- monoclonal M pr
- become amyloid (1* amyloidosis), make BJ pr's in urine
- Rouleaux formation
- lytic bc pl cells make IL-1 = osteocl act'ing factor
72
Waldenstrom's macroglobulinemia =
- don't have?
- does have?
has M spike on electrophoresis like MM
- no lytic bone lesions
- does have hyperviscosity sx and BJ pr
73
MGUS =
- sx?
- progresses to?
- does not have?
monoclonal gammopathy of undetermined significance = monoclonal expansion of pl cells w/ M spike
- asymp
- MM at rate of 1-2% per yr
- BJ pr
74
Langerhans cell histiocytosis =
- presents as?
- do the cells work?
- marker?
- characteristic look on EM?
prolif d/o of DCs (Langerhans histiocytes)
- in kid as lytic bone lesions and skin rash
- cells are functionally immature, don't stim T cells via Ag presentation (not func'ing APCs)
- S-100 (neural crest origin) and CD1a
- Birbeck granules (tennis rackets)
75
PT
- measures what?
- use for?
- Extrinsic coag system
| - Pt's on Warfarin, eval liver func, defect F VII defic
76
PTT
- measures what?
- use for?
- intrinsic coag system
| - Pt's on heparin (not needed for LMWH)
77
D-dimer assay
- detects what?
- use for?
- X-linked insol fibrin monomers in fibrin clot
| - evidence of degradation of fibrin clot: CA thrombosis, screening for PE or DIC
78
4 anti-thrombi mech's in sm vessels?
1) heparin-like molec's that enhance AT III activity which neutralizes Ser protease coag factors (7, 11, 9, 10)
2) PGI2 (prostacyclin)
3) prC/S (inact F V and F VIII)
4) tPA (act's plasminogen to plasmin)
79
3 pro-thrombus mech's in sm vessels?
1) TXA2 (made by plts, inhib'd by COX inhib's)
2) vWF (made in Weibel-Palade bodies in endo cells and megakaryocytes, carried in plts)
3) FIII = TF = tissue thromboplastin (released by injured tissue, act's F VIII)
80
Where is F VIII:c made?
What stabilizes it?
What does it act on?
- in liver and reticuloendo cells
- vWF prevents its degradation in pl
- when act'd, helps IXa act Xa
81
Factors consumed in a clot to produce serum are?
I, II, V, VIII
82
How do plts make a temp plug?
What changes in the stable plt plug?
How do you test formation of the temp plug?
- Adhesion -> release rxn (of ADP) -> TXA2 syn -> temp plug that is held together by fibrinogen (btwn GpIIb/IIIa Rs on plts)
- held together by fibrin monomers made by clotting cascade
- bl'ing time
83
INR =
standardizes PT for warfarin tx, nl is 2-3
84
How does renal failure -> prolonged bl'ing?
| - Reverse w/?
Inhib of plt phospholipid by toxic products -> plt aggregation defect (incr'd BT)
- dialysis and desmopressin acetate (incr's vWF release from endo cells)
85
Von Willebrand dz =
- dx by?
- trtmt
- assoc'd sx?
AD; plt adhesion defect bc no vWF -> decr'd VIII:c
Is combo plt and coag factor d/o (incr'd BT and nl/incr'd PTT)
- Ristocetin cofactor assay (causes plts to clump ONLY if vWF is there)
- DDAVP (desmopressin) bc incr's vWF release from endo cells; OCP (incr'd CFs and decr's ATIII)
- MVP, Marfans, angiodysplasia
86
Lead poisoning has what affect on heme formation?
| - sx?
Inhib's ferrochelatase and ALA DH -> accum of protoporphyrin and d-ALA
- microcytic anemia, GI and kidney dz
87
Acute intermittent porphyria =
- sx?
- trtmt?
AD; defect in porphobilinogen deaminase -> build-up of porphobilinogen, d-ALA, uroporphyrin (urine)
- 5P's = painful ab, port wine-colored urine (when exposed to sunlight), polyneuropathy, psych disturbances, precipitated by drugs (which enhance P450, like EtOH -> decr'd heme and thus more ALAS activity so more build-up)
- glc (carbs) + heme -> inhib ALA synthase
88
Porphyria cutaneous tarda =
| - sx?
no uroporphyrinogen decarboxylase -> incr'd uroporphyrin (tea-colored urine)
- blistering cut photosensitivity; most common porphyria
89
Hemophilia A/B =
defect in F VIII / F IX -> incr'd PTT
90
VitK defic ->
decr'd syn of F II, VII, IX, X, prC/S -> incr'd PT and PTT
91
ITP (idiopathic thrombocytopenic purpura) =
- occurs when?
- labs show?
IgG Abs to GpIIb/IIIa -> splenic Mphage eat Ab:plt complex -> decr'd plt ct
- 1-3wks post viral infec in kids, in adults usu 2* to SLE
- incr'd megakaryocytes
92
Thrombotic thrombocytopenic purpura (TTP) =
- occurs in who?
- labs show?
- sx?
no ADAMTS 13 (vWF metalloprotease) -> less degradation of vWF multimers -> have more vWF and more plt aggregation and thrombosis
- adult F (usu is Ab to ADAMTS13)
- schistocytes, incr'd LDH
- 5 sx: F, decr'd plt ct, neuro and renal sx, and microangiopathic hemolytic anemia w/ schistocytes (damaged by plt thrombi)
93
HUS =
- occurs in who?
- sx?
endo damage at art-cap jxn by Shiga-like toxin of O157:H7 E. coli (undercooked beef) -> plt thrombi, shearing of RBCs
- usu in kids y D; sx like TTP but less CNS sx: F, low plts, renal failure, microangiopathic hemolytic anemia w/ schistocytes
94
Causes of DIC =
"STOP Making New Thrombi"
Sepsis (Gm-), Trauma (rattlesnake bite), Obstetric comp's, acute Pancreatitis, Malig (APL, adenoca), Nephrotic synd, Transfusion
95
If given, what do these incr?
- Packed RBCs
- Plts
- FFP
- Cryoprecipitate
- Hb and O2 carrying capacity
- plt ct (~5000/unit)
- coag factors
- fibrinogen, F VIII, XIII, vWF and fibronectin
96
Leuk's:
| 60yo
ALL if <15yo
Hairy cell leuk, CML, or AML(PML) if adult
SLL/CLL or AML(PML) if older
