First Aid - Hematology Flashcards
(154 cards)
1
Q
Dense granules of platelets contain..
A
ADP and Calcium
2
Q
Alpha granules of platelets contain…
A
vWF and fibrinogen
3
Q
Where is 1/3 of platelet pool stored?
A
spleen
4
Q
Hypersegmented polys =
A
folate/b12 deficiency
5
Q
increased band cells means…
A
increased myeloid proliferation (in repsonse to things like bacterial infections or CML)
6
Q
Which cytokine activates macrophages?
A
IFN-gamma
7
Q
Important macrophage cell marker
A
CD14
8
Q
Functions of eosinophils
A
Anti-helminthic
Antigen-antibody opsonin phagocytosis
histaminase and arylsulfatase production to limit mast cell degranulation effects
9
Q
What do basophils secrete to mediate allergic reactions?
A
heparin, histamin, leukotrieneds
10
Q
Important B-cell markers
A
CD19, CD20
11
Q
What are all the cells that act as APCs?
A
Macrophages, Dendritic (langerhan cells, B-lymphocytes
12
Q
Important T-cell markers
A
CD3, CD4, CD8
13
Q
What is the costimulatory signal necessary for T-cell activation?
A
CD28
14
Q
What are the markers for T-cell PRECURSORS
A
CD1a; CD2, 3, 4, 5, 7, 8
15
Q
Which antibody isotype causes hemolytic disease of hte newborn
A
IgG
16
Q
Hemolytic disease of the newborn is when…
A
Mom has preformed antibodies against a blood type that her new baby has.
17
Q
What type of antigens are attacked in hemolytic disease of the newborn
A
Rh+ cells
A,B, AB –> usually only by type O mothers, who form IgG rather other bood type moms, who tend to form IgM
18
Q
What is the hageman factor?
A
Factor XII in the intrinsic pathway
19
Q
What does vWF act as a carrier protein for?
A
Factor VIII
20
Q
What is thrombin time?
A
TT = rate of conversion of fibrinogen to fibrin. Different form PTT and PT
21
Q
Where is Factor VIII synthesized and stored?
A
synthesized in liver; stored in endothelium
22
Q
How does Vitamin K play into coagulation factors?
A
Vitamin K must be reduced by epoxide reductase before it can act as the cofactor for maturation of coagulation factors 2, 7, 9, 10, C, S.
(epoxide reductase is the enzyme warfarin inhibits
23
Q
Factor V leiden mutation does what…?
A
makes factor V that is resistant to cleavage/inactivation by Protein C. = procoagulant state.
24
Q
What does TXA2 do in coagulation?
A
decreases blood flow by vasoconstriction , increases platelet aggregation
25
What does ADP do in coagulation?
induces GP2b/3a expression on platelet surface
26
What is seen under a crystal violet stain
Heinz bodies
27
What are howell jolly bodies?
remnants of nucleus. found in RBCs
supposed to be removed from RBC by splenic macrophages - so if you're asplenic... womp womp, no howell jolly body removal for you.
28
What do you think when you see erythroid precursors in liver or spleen?
Extramedullary hematopoiesis
29
What promotes extramedullary hematopoiesis
EPO
| hyperplastic marrow cell invasion of extramedullary organs
30
Plummer-Vinson Syndrome
Triad of iron deficiency anemia, esophageal webs, atrophic glossitis
31
koilonhychia (spoon nails)- where do you see it?
IRON DEFICIENCy
32
alpha-thalassemias - Asians vs Africans
Asians are Cis
| Africans are trans
33
Alphat thalassemia - all the gene cominations
1-2 deletiosn = no anemia
3 = HbH disease (beta tetramers)
4 gene deletions = HbBarts (gamma tetramers) incompatible with life. hydrops fetalis
34
What is the genetic abnormality with beta thalassemia?
mRNA splice site point mutation = mrNA processing screw up
35
Why is beta thal asmptomatic at birth?
HbF for the next 6 months
36
What is beta thalassemia intermedia?
Its beta thal major that happens to have mild clinical presentation
37
How do beta thalassemics compensate for their messed up hemoglobin?
they make HbF (a2g2 for thal major) and HbA2 (a2d2) for thal minor
38
Special cells in beta thal major
target cells, schistocytes
39
What genetic mutation is beta thal intermedia associated with?
kozak sequence = mutaiton tha tprevents mRNA binding to ribosome
40
Clinical symptom difference between folate and B12 deficeincy
Folate deficienty = NO NEUROLOGIC SYMPTOMS
| B12 = subacute combined degeneration leads to posterior column, lateral corticospinal and dementia symptoms)
41
Why folate deficeincy in alcoholics?
poor B9 ABSORPTION
42
What happens to your CBC when you treat B12 deficeincy?
give B12 supplement. Early spike in reticulocyes. older reticulocytes are slow to mature because they had a B12 deficient chidlhood. so you have a big proliferaiton of reticulocytes
43
Alcoholics and B12 vs Folate defiency
usually alcoholics dont' get B12 , they gete B9 deficeincy
44
old people and B12 deficeincy
old people w/ chornic anemia w/o other identifiable causes
| Old people = gatric catrophy = low H+ = low release of B!2 from food.
45
What is haptoglobin?
binds free hemoglobin to prevent renal excretion
46
What happens to haptoglobin in hemolytic anemias?
drops because hemolysis produces so much Hb the haptoglobin can't handle it.
47
Explain the blood smear appearance of anemai of chronic disease
starts off as normocytic but over time you have less and less iron and you become microcytic and hypochromic.
48
Aplastic anemia presents as...
triad of severe anemia, thrombocytopenia and absent stem cells in marrow
49
Is there splenomegaly in aplastic anemia?
no
50
Marrow tap for aplastic anemia
dry. normal cell morphology but hypocellular marrow with fatty infiltration.
low reticulocyte count
51
Distinction of aplastic anemia from myeloplastic syndromes?
Marrow tap is dry in aplastic anemia.
52
Where are haptoglobin/Hemoglobin complexes cleared?
Liver
53
What is pure RBC aplasia associated with?
No RBC but normal WBC and Plateets associated with 1) Thymoma 2) lymphocytic leukemia. Can result from PArvo B19
54
General principle of inheritance patterns with protein mutations.
Structural protein defects = dominant (ankyrin in spherocytosis)
Enzymatic defects = REcessive (G6PD)
55
INheritance pattern of Hereditary spherocytosis
Autosomal dominant
56
Defect in hereditary spherocytosis
ankyrin, band 3, spectrin mutaitons
| defective cytoskeleton = loss of plasma membrane = spherocytosis
57
Clinical findings of hereditary spherocytosis
Splenomegaly. Increased risk of aplastic crisis w/ Parvo B19, pigmented gallstones, jaundice and anemia
58
Diagnostic testing for hereditary spherocytosis
positive osmotic fragility test
| Increased MCHC
59
Treatment of hereditary spherocytosis
splenectomy - RBCS work find its jsut he spleen keeps clearing them cuz their ugly.
60
Inheritance pattern of G6PD
X-linked recessive
61
What triggers hemolysis in G6PD?
Oxidant stresses like:
Sulfadrugs = sulfonamids, antimalarials, bactrim
infections
Fava beans
62
Clinical presentation of G6PD
Back pain followed by hemoglobinuria a few days later
| Jaundice, or could be asymptomatic
63
Labs and smear for G6PD deficeincy
Heinz bodies, bite cells, reticulocytosis
| decreased haptoglobin
64
Pyruvate kinase deficeincy inheritance pattern
autosomal recessive
65
Pathophysiology of pyruvate kinase deficeincy
bad pyruvate kinase = low ATP = dead RBC = splenomegaly due to work hypertrophy
66
Clinical presentation of pyruvate kinase deficeincy
hemolytic anemia of hte newborn.... as in anemia from destroying RBC when you're newly born. not antibody mediated??? check with weinstein
67
Whats HbC defect
Same as SCA except mutation = Glu to Lys NOT Glu to Val. milder disease than SCA
68
PNH pathophysiology
DAF (CD55) and GPI protect RBC from complement damage. It's deficeincy in this disease.
RBC lysed by complement = anemia
69
Why is PNH calle dparoxysmal nocturanl hemoglobinuria
Sleep = shallow breaht = mild acidosis = increased complement = increased lysis of RBC bec/ RBC can't defend themselves w/ their mutation = hemolysis = peeing blood in the morning rom the hemolysis
70
CLinical presentaiton of PNH
triad of hemolytic anemia, pancytopenia and venous thrombosis (including Budd chiari)
71
Labs for PNH
CD55/59 negative RBCS
72
Autosplenectomy - you should think of...
Sickle cell anemia. REcurrent ischemia and infarction. Almost all SCA adults have this.
73
What is splenic sequestration?
This thing with SCA. vasoocclusion of splenic outflow = pooling of blood in spleen = hypovolemia/splenic rupture = medical emergency.
Rarely seen seen in adults bec/ they have autosplenectomized by then
74
What does the spleen look like with autosplenectomy
bronw from hemosiderosis. firm and shrunken
75
Crew cut on skull x-ray - you should think off..
1) Sickle cell anemias 2) Thalassemia = Marrow expansion for more erythropoiesis.
76
Most common cause of osteomylitis? What about in people with sickle cell anemia?
```
Normal = Staph aureus
SCA = Salmonella
```
77
Major complications of Sickle cell DISEASE
```
aplastic crisis (Parvo B19)
Autosplenectomy (infected by capsuled bacteria)
SPlenic sequestration
Salmonella osteomyelitis
Vaso-cclusive pain
Renal papillary necrosis
```
78
What are the presentaiton sof vaso-occlusive pain in Sickle cell anemia?
Dactylitis (pain in hands)
Acute chest syndrome
Avascular necrosis (of femoral head?)
79
Therapeutic strategy for sickel cell disease
Hydroxyurea = increase HbF
Marrow transplant
Gardos-Channel blockers (Ca-dependent K-efflux channels. Keeps ions in the cell to maintain hydration of cell)
80
What physiology/clinical stuf distinguishes sickle cell TRAIT from DISEASE
Trait: no sickling (except in renal papilla), no target cells or sickle cells
81
Asplenics are at risk of what?
Infection by encapsulated bacteria:
S. Pneumo; Haemophilus Influenza; Neisseria Menigitis; E. Coli; Salmonella, Klebsiella, GBS
SHiNE SKis
relevant to SCA with autosplenectomy
82
Direct vs Indirect Coombs test
```
Direct = Is there Ig already bound to the RBC?
Indirect = Do you have anti-RBC Igs in your serum?
```
83
Agglutination in Immune hemolytic anemias – why is it called warm or cold? whats the difference between the two?
```
Warm = IgG binds in warm central body.
Cold = IgM binds in cold extremities of body
```
84
What causes warm agglutin IHA
Warm immune hemolytic anemia = SLE, CLL, Drugs (a-methyl dopa, peniccilins/cephalosporins)
85
What causes cold agglutin IHA?
Cold immune hemolytic anemia = Mycoplasma, Mononucleosis
86
What causes microangiopathic anemia
DIC, TTP/HUS, SLE and malignant hypertension
87
Lab finding sin microangiopathic anemia
whatever results form increased Hb in serum
88
Hepcidin does....what?
Master regulator of body e Levels. Made in liver and controls ferroportin activity in enterocytes. (Ferroportin = basolateral iron channel in enterocytes)
89
Coarse basophilic stippling
Lead poisoning
90
Brutons Lines
Blue lead lines in the gums of the tooth
| Lead poisoning
91
Clinical appearance of lead poisonign in adults
headache, memory loss, weakness, abdominal pain, constipation
92
Why is there no sideroblastic anemia with lead poisoning, acute intermittent porphyria or porphyria cutanea tarda?
Because they dont' inhibit heme synthesis at a step that occurs in the mitochondria. (except lead poisoning which inhibits a mitochondrial step that's AFTER a cytoplasmic step - ferrochelatase)
93
Affected enzyme in porphyria cutanea tarda
Uroporphyrinogen decarboxylase
94
Blood smear appearance with acute intermittent porphyria
NORMAL.
95
Why do RBC lose their heme synthesis ability?
no mitochondria
96
difference between liver heme and marrow heme?
liver heme for CYP450; marrow heme for hemoglobin
97
why do drugs trigger acute intermitten tporphyria attack
use up CYP450 for drug metabolism. Liver heme triggers d-ALAS activity in both liver and marrow = d-ALA accumulates
98
Prolonged bleeding after tooth extraction
Hemophilia or Von Willebrand's Disease
99
Prolonged bleeding from venous puncture sites
DIC
100
Inheritance of Hemophilia A and B
X-linked recessive
101
CLinical presentaiton of hemophilia
Macrohemorrhage (hemarthrosis = bleeding into joints; easy bruising) mucocutaneous bleeding
102
When do you get vitamin K deficiency?
First week of birth (don't get it in utero or breast milk)
malabsorptive disease
Liver disease
Broad spectrum antibiotics that kill colonic bacteria (which make vitamin K)
103
```
What are the defects in:
Bernard Soulier
Glanzmann's Thrombasthenia
ITP
TTP
```
```
Bernard = defect GP1B = poor adhesion
Glanzmann's = defect GP2b3a = poor aggregation
ITP = anti-Gp2b3a Abs = destroyed platelets
TTP = ADAMST13 mutation in vWF metalloprotease = less vWF degradation = too much platelet aggregation and consumption.
```
104
Difference in bleeding symptoms for coagulative disorders vs platelet disorders
```
coagulation = macrohemorrhage in large vessels (bleeding into joints, easy bruising) - Hemophilia, DIC, vWF
Platelet disorders = hemorrhage in superficial vessels (petechiae, mucous membrane pleeding) - glanzmans, bernard, ITP, TTP-HUS
```
105
Pathophysiology of uremic platelet dysfunction
uremia from renal failure = elevates plt inhibitory factors in blood = normally removed by kidney or dialysis = REsults in inability to undergo PRIMARY hemostasis. PT/PTT are unaffected
106
Hemolytic URemic Syndrome - platelet effects
Shiga toxin causes activation of platelets BUT NO COAGULATION FACTORs systemically
107
Why does vWF disease lead to increased PTT?
vWF carriers/protect factor VIII. vWF deficiency = messed up intrinsic pathway
108
Ristocetin is for... what?
activtaes Gp1b on platelets to cause adhesion. no adhesions = vWF disease
109
Treatment of vWF
DDAVP (desmopressin) = ADH analogue.
| FX: vWF release from endothelium. Diuresis. No vasoconstriction (which ADH does) Does not work in severe disease
110
What causes DIC?
STOP Making New Thrombi
| Sepsis. Trauma, Ob complications, Pancreatitis. Malignancy. Nephrotic syndrome. Transfusion.
111
How does Ob complication cause DIC?
dead fetus = placenta releases tissue factor to cause clotting in response to the necrotic tissue = consumes platelets = DIC
112
Labs and Smear for DIC
elevated D-dimer (from fibrinogen cleavage)
Decreased fibrinogen
Decreased Factor V and VII
Schistocytes
113
Most common hypercoagulability defect in WHITES
Factor V Leiden.
114
Fresh frozen plasma vs Cryoprecipitate
```
FFP = coagulation factors
Cryoprecipitate = cold soluble precipitates (fibrinogen, Factor 8, 13, vWF)
```
115
Electrolyte risk with packed RBCs
packed blood comes in citrate, which preserves the blood? but chelates Ca = hypocalcemia with transfusions - Clinically appears as parasthesias
116
What is Fresh frozen plasma for?
DIC, Cirrhosis, warfarin overdose
117
how to distinguish leukemoid reaction from CML
leukemoid rxn = when WBC proliferate as part of hteir normal reaciton to infection.
Both have elevated WBC with left shift, but CML has decreased leukocyte alkaline phosphate. leukemoid reaction has increased
118
Hodgkin's Lymphoma - age distribution
bimodal (30s and older than 50s)
119
Localization of hodgkins vs non-hodgkins
```
hodgkins = single gorup of nodes. extranodal is rare
non-hodgkins = peripheral nodes with common extranodal invovlement. usually involves B cells (except if of T-cell origin)
```
120
starry sky
burkitt's lymphoma
121
hstology of burkitts lymphoma
medium sized lymphocytes with high proliferation index - starry sky
122
histology of diffuse large b-cell
large sized lymphocytes with huge nuclei
123
histology of follicular lymphoma
B-cells in follicle center. MANY follicles aggregating that distort normal lymph node architecture
124
Clinical findings of Multiple Myeloma
CRAB = hyeprCalcemia; Renal insufficeincy (from infiltration and amyloid deposits), Anemia; Bone lesions/Back pain
125
Age range for multipel myeloma
>40-50 years old
126
Punched out lesions on x-ray
multiple myeloma
127
M-spike on electorphoresis
multiple myeloma
128
what pathologic processes are associated with multiple myeloma
```
Primary amyloidosis (accumulation of igG with apple green birefringence)
Increased susceptibility to infection
```
129
Age ranges of the leukemias
ALL = 60
Hairy Cell = Adults
AML = >65
CML = 30-60
130
Neoplasm of Lymphoblasts
ALL
131
T-ALL clinical manifestation
MEdiastinal mass = dysphagia, SVC syndrome, respiratory symptoms
132
ALL markers
TdT+,
| CALLA+(CD10) = good prognosis
133
Most common ALL
B-ALL = 80% of ALL
| No mediastinal mass so no compression syndromes
134
Downsyndrome and ALL
Risk is 10-20x higher after 5 years old
135
Neoplasm of naive mature lymphocytes
SLL/CLL = lymphocytic lymphocyma/Leukemia
136
Neoplasm of mature B-cells
Hairy cell leukemia
137
Markers for Hairy cEll LEukemia
TRAP positive
138
Smudge CEll
SLL/CLL
139
Clinical findings of SLL/CLL
lymphadenopathy, hepatosplenomegaly, anemia
140
pathologic findings of hairy cell leukemia
red pulp expansion leading to splenomegaly. The cells are TRAPped in the spleen (TRAP staining)
141
Neoplasm of myeloid blast cells
AML
142
Neoplasm that responds to all-trans retinoic acid (ATRA)
Promyelocytic Leukemia = M3 subtype of AML
143
CLinical manifestation fo AML
Anemia symptoms, Thrombocytopenia symptoms (bleeding from IV puncture sites), Neutropenia symptoms
144
Increased risk before 5 yo in down syndrome
M7 subtype of AML = M4Eo AML
145
Cell lineage and Cell differential of CML
increased neutrophils, metamyelocytes and basophils (terminally differentiated)
Acceleration = transformation to AML or ALL
146
```
t(9;22)
t(8;14/22/2)
t(11;14)
t(14;18)
t(15;17)
```
```
t(9;22) = CML (or ALL acc/to Pathoma)
t(8;14/22/2) = Burkitts (c-myc)
t(11;14) = mantle cell
t(14;18) = follicular lymphoma (Bcl-2)
t(15;17) = PML/M3AML (RAR/PML)
```
147
Genetics and cell signaling in Chromic myeloproliferative disorders?
V617F mutation - Jak/Stat mutation leads to hematopoietic signaling except with CML (which has 9;22)
148
Polycythemia vera
primary proliferation of Erythroblast = leads to constiutive activity of JAK2 receptors so that it can proliferate w/o EPO stimulation. differs from other polcythemias that are not primary/vera
149
POlcythemia - Appropriate absolute
Physiologically compensating for another disease (lugn disease, CHD, high altitude)
150
POlycythemia - inapporpriate absolute
Pathologic erythrocytosis secondayr to ectropic EPO (RCC, wilm's tmor, HCC, anabolic steroids)
151
Relative Polycythemia
Increased RBC councentration because odf dehydration
152
Myelofibrosis
fibrotic obliteration of boen marrow. Megakaryocytosis can lead to fibroblast proliferation = myelofibrosis
153
Essential Thrombocytosis
Abnormla clone of megakaryocyte precursor leads to overproduction of platelets.
154
Hemolytic Uremia Syndrome - presentation
Triad of Thrombocytopenia, microangiopathic anemia and renal failure. most common cause of acute renal failure in children
