3/11 hematology Flashcards
1
Q
Pyruvate kinase deficiency (E)
- inheritance pattern?
- whats it causes?
A
- Autosomal recessive.
- rigid RBCs (lack of ATP) => extravascular hemolysis.
2
Q
Why do RBCs need:
- NADH
- NADPH
A
- NADH: reduce naturally occuring MetHb => Hb.
- NADPH: reduce glutathione.
3
Q
2,3-BPG level in PK deficiency?
A
- inc. 2,3-BPG
- PK is deficient to the substrates upstream of it will build up, which includes 2,3 BPG.
- This will shift oxy-Hb to the right and O2 will be unloaded easier. So these pts have a hard time carrying oxygen.
4
Q
HbC defect
- whats the mutation?
- what type of hemolysis?
A
- Glutamic acid-to-lysine mutation at residue 6 in β-globin.
- extravascular hemolysis.
5
Q
Whats worse, HbSC or HbSS?
A
HbSS is worse.
-full sickle cell.
6
Q
Whats the problem in paroxysmal nocturnal hematuria (PNH)?
A
- Mutation in PIGA gene.
- Impaired synthesis of GPI anchor needed to flank the decay-accelerating factor that protects RBC/WBC/platelets against complement.
*DAF degrades C3 convertase.
7
Q
PNH
- inheritance pattern?
- inc. incidence in what disease?
A
- Acquired mutation in a hematopoietic stem cell.
- Increased incidence of acute leukemias.
8
Q
PNH
- Coombs + or -?
- Sxs:
A
- Coombs (-)
- hemolytic anemia, pancytopenia, and venous thrombosis.
*these pts have a history of infection due to the lack of WBCs.
9
Q
PNH
-why do you get venous thrombosis?
A
-when platelets are destroyed they release their components into serum which causes a hypercoag. state.
10
Q
PNH
- Tx:
- CD55 =
- CD59 =
A
- eculizumab.
- CD55 = DAF
- CD59
11
Q
glutamic acid => _____ @ residue 6 on beta chain.
- HbC:
- Sickle Cell:
A
- HbC: lysine
- SS: valine
12
Q
the O2-dissociation curve shifted to the ____ for Hb-S
A
RIGHT
13
Q
Absent spleen
-what happens to platelet & WBC count?
A
-both increase.
-About one third of all circulating platelets are pooled
in the spleen, and granulocytes are marginated in splenic
sinusoids, so that when the spleen is absent, the WBC and platelet counts increase.
14
Q
Sickle cell
-common presentation in kids?
A
dactylitis
15
Q
Sickle Cell
- most common way it kills adults?
- Tx:
A
Acute chest syndrome
–occlusionin lungs. Precip by pneumonia.
-Tx: hydroxyurea (inc. HbF).
16
Q
Do HbC and HbS bind 2,3-BPG considering their beta-chains are mutated?
A
Yes, they still do.
17
Q
Warm agglutinin
- which Ab?
- seen in which diseases?
- caused by which drugs?
A
- IgG
- SLE, CLL
- alpha-methyldopa
18
Q
Cold agglutinin
- which Ab?
- seen in which diseases?
- caused by which drugs?
A
-IgM
-CLL, Mycoplasma pneumonia infections, or infectious mononucleosis.
-
19
Q
Why do you see spherocytes in autoimmune hemolytic anemia?
A
Spleen will take off the attached IgG or IgM and the piece of membrane its attached to. Too little membrane leads to a spherocyte.
20
Q
Most important test for autoimmune hemolytic anemia?
A
Direct Coomb’s test will be (+).
21
Q
Indirect Coombs test
-aka?
A
Antibody screen
-screen plasma for Abs
22
Q
How does CLL cause IgG Autoimmune hemolytic anemia?
A
-Neoplastic B cells do NOT turn into plasma cells,
so you get a hypogammaglobinemia and most pts
will end up dying via ifx. The ones that do
make immunoglobulin will make them against the pts
own RBCs => autoimmune hemolytic anemia.
23
Q
Why do you get neutropenia in a severe infection?
A
Most neutrophils are in tissues and not serum, so you can get a neutropenia.
24
Q
What are the most vulnerable cells in the body to radiation?
A
Lymphocytes
25
Acute intermittent porphyria
- inheritance pattern?
- affected enzyme?
- what builds up?
- auto dom.
- Porphobilinogen deaminase (PORD) (aka uroporphyrinogen 1 synthase).
-Porphobilinogen (and everything upstream = δ-ALA,
coporphobilinogen)
26
Acute intermittent porphyria
| -Sxs:
Symptoms (5 P’s):
- Painful abdomen
- Port wine–colored urine
- Polyneuropathy
- Psychological disturbances
- Precipitated by drugs, alcohol, and starvation
27
Acute intermittent porphyria
| -Tx:
-glucose and heme, which inhibit ALA synthase.
28
-red urine that darkens on exposure to light or
| air = what disease?
Acute intermittent porphyria
| -key feature of acute porphyrias are red urine that darken on exposure to light or air due to oxidation of excess PBG.
29
Porphyria cutanea tarda
- affected enzyme?
- what builds up?
- Sxs:
- Uroporphyrinogen decarboxylase
- Uroporphyrin (tea-colored urine)
- Blistering cutaneous photosensitivity.
30
Most common porphyria?
Porphyria cutanea tarda
31
ALAD
| -contains which metal cofactor?
Zn
32
What activates factor 12 (hageman factor)
| -first step of which pathway?
SEC
- subendothelial collagen
- intrinsic pathway
33
What activates factor 7?
| -first step of which pathway?
Thromboplastin (aka tissue factor)
| -extrinsic pathway
34
Extrinsic
| -PT or PTT?
PT
35
Intrinsic
- PT or PTT?
- mnemonic?
-Intrinsic has more factors so measured using PTT which has more letters than PT.
36
Hemophilia A pt not respond to factor 8. What could be the problem?
15% of patients with hemophilia A eventually develop an inhibitor to factor VIII = giving the pt normal plasma (w/factor 8) will not solve the problem.
37
What drug causes release of vWF & factor 8 from endothelial cells?
DDAVP (desmopressin)
| -remember, DDAVP does not have the V1-vasoconstrictive properties as normal ADH.
38
Bernard-Soulier syndrome
- problem?
- mnemonic?
- genetic Gp1b deficiency.
| - Craig (Bernard) is a 1beta male
39
Glanzmann thrombasthenia
- problem?
- what does blood smear show?
- platelet GpIIb/IIIa deficiency.
| - blood smear shows no platelet clumping.
40
Immune thrombocytopenia
- Abs against what?
- possible trigger?
- labs?
- GpIIb/IIIa
- viral illness
- inc. megakaryocytes on bone marrow biopsy.
41
Thrombotic thrombocytopenic purpura
- problem?
- leads to what?
- which systems hit the hardest?
- Inhibition or deficiency of ADAMTS 13 (vWF metalloprotease) which degrades vWF multimers.
- lots of platelet microthrombi forming.
-CNS and renal hit the hardest. But mostly CNS (HUS will be mostly renal).
42
Thrombotic thrombocytopenic purpura
| -Tx:
Exchange transfusion and steroids.
43
Thrombotic thrombocytopenic purpura & HUS
| -is coagulation system activated?
NO
44
Thrombotic thrombocytopenic purpura
- PT time: inc or dec?
- PTT time: inc or dec?
both normal!
| -NO activation of coag cascade in TTP or HUS!
45
HUS
- PT time: inc or dec?
- PTT time: inc or dec?
both normal!
| -NO activation of coag cascade in TTP or HUS!
46
Uremia
| -effect on platelets?
-disrupts platelet function: adhesion & aggregation problems.
47
TTP & HUS
| -LDH: inc or dec?
- inc LDH due to microangiopathic anemia.
| - you'll see schistocytes.
48
von Willebrand disease
- inheritance pattern?
- Tx:
- auto dom
| - DDAVP, which releases vWF stored in endothelium.
49
DIC
| -what gets depleted?
- coag factors AND platelets.
| - can't make a thrombus w/o platelet plug first!
50
DIC
- causes
- mnemonic?
STOP Making New Thrombi
- Sepsis (gram-negative)
- Trauma
- Obstetric complications
- acute Pancreatitis
- Malignancy
- Nephrotic syndrome
- Transfusion
51
DIC labs
- fibrin split products:
- fibrinogen:
- factor 5:
- factor 8:
schistocytes
- inc. fibrin split products (d-dimers).
- dec. fibrinogen.
- dec. factors 5 & 8.
52
Rattlesnake bite
| -can lead to what?
DIC
53
Prothrombin gene mutation
| -where is the gene mutation?
3′ untranslated region
54
If you give heparin but PTT does NOT increase.
| -Think of what?
Antithrombin deficiency
55
How do you acquire an antithrombin deficiency?
Nephrotic syndrome
56
Skin and subcutaneous tissue necrosis after warfarin administration: think what?
Protein C deficiency
57
Warfarin causes transient deficiency of what?
Protein C
| -bc it has a short half life. Shorter than 1972
58
Which factor has a shorter half life than protein C?
Factor 7a
-so transient protein C deficiency wont affect extrinsic pathway, so extrinsic pathway will be properly inhibited by warfarin which is why we measure warfarin w/PT (for extrinsic pathway).
59
Why do we measure warfarin w/PT time?
Factor 7a has shorter half life than protein C
-so transient protein C deficiency wont affect extrinsic pathway, so extrinsic pathway will be properly inhibited by warfarin which is why we measure warfarin w/PT (for extrinsic pathway).
60
What activates factors 8 and 5?
thrombin
61
Factor 8a
| -speeds up which step?
9a activating 10
62
Factor 5a
| -speeds up which step?
10a activating 2(prothrombin)
| -thrombin having a sor of positive feedback here.
63
Alcoholics w/megaloblastic anemia
| -what deficiency?
folate
64
hypothyroidism
| -what kind of anemia can it causes?
Macrocytic
65
thrombocytopenia in setting of chronic liver disease due to what?
hypersplenism
66
Pt. w/ESRD that has a bleeding problem.
Uremic platelet disorder.
67
Cryoprecipitate
| -contents?
-fibrinogen, factor VIII, factor XIII, vWF, and fibronectin.
68
How can blood transfusions lead to hypocalcemia?
Citrate is a calcium chelator & is found in blood transfusions.
-hypocalcemia => tetany.
69
Non-hodgkins vs hodgkins
| -all neoplastic cells or also some inflammatory cells?
- non-hodgkins: entire mass = malignant cells
| - hodgkins: RS cells release cytokines and call in inflammatory cells as well.
70
Can you see circulating neoplastic cells in Hodgkin's lymphoma?
No
| -the finding of circulating neoplastic cells is extremely rare in Hodgkins.
71
Hodgkins vs non-hodgkins
| -which has better prognosis?
Hodgkins has better prognosis.
72
Hodgkins vs non-hodgkins
| -bimodal age distribution
Hodgkins
73
Hodgkins vs non-hodgkins
| -50% of cases associated with EBV
Hodgkins
74
Hodgkins vs non-hodgkins
| -Constitutional (“B”) signs/symptoms—low-grade fever, night sweats, weight loss.
Hodgkins
75
Hodgkins vs non-hodgkins
| -Localized, single group of nodes; extranodal rare; contiguous spread.
Hodgkins
76
Hodgkins vs non-hodgkins
-Multiple, peripheral nodes; extranodal
involvement common; noncontiguous spread
Non-Hodgkins
77
Painless lymphadenopathy
| -DDx:
-chronic inflammation, metastatic carcinoma, lymphoma, leukemia.
78
L. node pain w/alcohol consumption =
Characteristic of Hodgkins Lymphoma
79
RS cells
- which CD markers?
- which blood cell does it originate from?
- CD15+ and CD30+
| - B-cell origin.
80
RS cells: is this sufficient to diagnose Hodgkins disease?
Necessary but not sufficient for a diagnosis
| of Hodgkin disease.
81
Lymphocyte-rich form of Hodgkins
| -good or bad prognosis?
-the more lymphocytes the better the prognosis.
82
Lymphocyte mixed & depleted forms of Hodgkins
| -good or bad prognosis?
-poor prognosis.
83
Most common form of Hodgkins lymphoma
Nodular sclerosis variant
84
IL-5 calls in eosinphils which releases TGF-beta which causes fibrosis.
-this happens in which form of Hodgkins lymphoma?
Nodular sclerosis variant.
85
-erythroblastosis fetalis: Whats the kids liver going to look like?
-you will see extra-medullary hematopoiesis bc infant is trying to keep up w/the blood loss via hemolysis from
maternal IgGs that cross over!
-liver & spleen = two prominent sites of this.
86
Is there CD20 expression in Hodgkin's lymphoma?
No
| -even tho reed sternberg cells are derived from B cells, it is NOT CD20 positive!
87
Burkitt lymphoma
- whats the neoplastic cell?
- translocation?
- B cell, CD20+
| - t(8;14)—translocation of c-myc (8) and heavy-chain Ig (14)
88
Most common type of non-Hodgkin lymphoma in adults.
Diffuse large B-cell lymphoma
89
Diffuse large B-cell lymphoma
- translocation?
- nodal or extranodal?
- whats it look like?
- t(14;18)
- usually extranodal
- single large mass w/bunch of cells that look like lymphocytes.
90
Mantle cell lymphoma
- whats the neoplastic cell?
- translocation?
- B cell, CD20+
* CD5+
- t(11;14)—translocation of cyclin D1 (11) and heavy-chain Ig (14).
91
CD5+.
| -which lymphoma?
mantle cell lymphoma
92
Follicular lymphoma
- whats the neoplastic cell?
- translocation?
- presentation?
- B cell, CD20+
- t(14;18)—translocation of heavy-chain Ig (14) and bcl-2 (18).
- Presents with painless “waxing and waning” lymphadenopathy.
93
Presents with painless “waxing and waning”
| lymphadenopathy.
Follicular lymphoma
94
Follicular lymphoma: two major cell types:
- centrocytes (small cleaves cells).
| - centroblasts (large, non-cleaved cells).
95
Follicular lymphoma
| -what can it progress to?
diffuse large B cell lymphoma
96
Adult T-cell lymphoma
- which cell?
- cause?
- presentation
- CD4 T cell, mature.
- Caused by HTLV-1 (associated with IV drug abuse).
- cutaneous lesions; especially affects populations in Japan, West Africa, and the Caribbean.
- Lytic bone lesions, hypercalcemia.
97
Why do chronic leukemias lead to lymphadenopathy?
bc mature lymphocytes like to go to lymph nodes.
98
Cutaneous lesions, lytic bone lesions, hypercalcemia.
| -which lymphoma?
Adult T-cell lymphoma
99
Mycosis fungoides/Sézary syndrome
- what is it?
- which cell?
- what is sezary syndrome?
Cutaneous T cell lymphoma: non-hodgkins lymphoma
- misnomer b/c it looks like a fungal ifx in the skin.
- tumor like infiltration of skin by neoplastic CD4 cell = mycosis fungoides
- its leukemic state (cells get into blood) = sezary syndrome
100
Multiple myeloma
- which cell?
- where?
- whats it make?
- Plasma cell.
- Arises in the marrow
- Large amounts of IgG (55%) or IgA (25%).
101
Most common 1° tumor arising within bone in the elderly (> 40–50 years old).
Multiple myeloma
102
Elderly male presenting w/lower back pain
| -DDx:
-MM, metastatic prostate cancer metastasizing to bone, AAA compressing on vertebral column.
103
Multiple myeloma
- amyloidosis: whats the protein?
- calcium levels?
- what do you call Ig light chains in urine?
- Ig light chain = AL amyloid
- hypercalcemia w/lytic bone lesions.
- bence jones protein
104
Proteinuria but negative for albumin
| -think what?
Bence jones proteins & multiple myeloma.
105
M spike
- what disease?
- what is it?
- MM
| - inc. prod of gammaglobulin
106
MM
| -what do cells look like?
-Numerous plasma cells with “clock face” chromatin and intracytoplasmic inclusions containing immunoglobulin.
107
MM
- Sxs
- mnemonic:
```
Think CRAB:
hyperCalcemia
Renal insufficiency
Anemia
Bone lytic lesions/Back pain
```
108
MM
- why do you get lytic bone lesions & hypercalcemia?
- which bones are most often affected?
- Plasma cells can produce osteoclast actvating factor. -Activates the RANK receptor.
- Particularly affects vertebrae & skull.
- Lead to bone pain & hypercalcemia.
109
Which IL is notoriously involved in MM?
IL-6
| -important growth factor for plasma cells.
110
What usually kills MM pts?
- infection
| - you look antigenic variation bc all plasma cells are monoclonal.
111
How does MM cause renal failure?
Infiltration of kidney by plasma cells, amyloid deposition, bence-jones casts in tubules, metastatic calcification due to hypercalcemia, and inflammation by macros & giant cells.
112
Waldenström macroglobulinemia
| -whats unique about it vs MM?
-M spike = IgM
-hyperviscosity symptoms (IgM = big molecule). Can
lead to visual & neuro deficits.
-no lytic bone lesions.
113
```
Hyperviscosity Sxs (headache, dizziness, blurry vision), and M-spike of IgM.
-which disease?
```
Waldenström macroglobulinemia
114
Monoclonal gammopathy of undetermined significance (MGUS)
- what is it?
- what is it a precursor for? what % advance?
-Monoclonal expansion of plasma cell. M spike. Bone
marrow with < 10% monoclonal plasma cells.
-Asymptomatic precursor to multiple myeloma
-1-2% per year advance to MM
115
Statistical precision
| -aka?
- reliability
| - reproducibility
116
Baby starts bleeding a few days after birth.
- more commonly in home births
- GI/umbilical/etc. bleed.
vitamin K deficiency aka hemorrhagic disease of newborn.
117
Post splenectomy
| -which cells are seen?
Howell-Jolly bodies, target cells.
