Heme - FA Anat/Phys/Patho p.396-421 Flashcards
1
Q
Life span of RBC?
A
120 days
2
Q
Life span of platelet?
A
8-10 days
3
Q
Normally leukocyte count range?
A
4000–10,000 cells/mm3.
4
Q
Membrane of RBC contains — antiporter,
A
Cl-/HCO3
5
Q
Name the vWF receptor?
A
GpIb
6
Q
Erythrocytosis = — = —- hematocrit
A
polycythemia incr
7
Q
Dense granules in Platelets contain —- and α granules contain —.
A
ADP, Ca2+
vWF, fibrinogen, fibronectin, platelet factor 4
8
Q
Normal Basophils %?
A
(0–0.75%)
9
Q
Poikilocytosis =
A
varying shapes
10
Q
Name Fibrinogen receptor?
A
GpIIb/IIIa.
11
Q
Neutrophyls specific granules contain 4 components: “CALL”
A
ALP collagenase lysozyme lactoferrin (traps iron)
12
Q
What are Azurophilic granules?
A
lysosomes
13
Q
Anisocytosis =
A
varying sizes (seen in thalasemia, spherocytosis)
14
Q
Azurophilic granules contain what 4 components?
A
- proteinases
- acid phosphatase
- myeloperoxidase
- β-glucuronidase (in liver)
15
Q
Important neutrophil chemotactic agents:
A
C5a, IL-8, LTB4, kallikrein, platelet-activating factor
16
Q
How does gram neg bacteria initiate septic shock?
A
Lipid A from bacterial LPS binds CD14 on macrophages
17
Q
Incr in myeloid proliferation is observed by the incr of what cells during infection or CML?
A
band cells (immature neutrophils)
18
Q
Macrophages are activated by
A
γ-interferon.
19
Q
Which 2 cells are packed with basophylic granules?
A
Basophyls Mast cell
20
Q
Monocytes differentiates into —- in tissues.
A
macrophage
21
Q
Macrophages are antigen-presenting cell via —.
A
MHC II.
22
Q
Extensive “frosted glass” cytoplasm referrers to what type of cells?
A
monocyte
23
Q
Basophilia is uncommon, but can be a sign of what path?
A
myeloproliferative disease, particularly CML.
24
Q
Which cells expresses MHC class II and Fc receptors on surface?
A
Dendritic cell, macrophage
25
Which kind of Leukocyte produces histaminase and major basic protein?
eosinophil
26
Round, densely staining nucleus with small amount of pale cytoplasm describes what type of cells?
lymphocyte
27
Name the 5 causes of eosinophilia
* Acute interstitial nephritis (eosinphilia and eosinophiluria) - Diuretics, NSAIDs, Penicillins/cephalosporins, PPI, Rifampin
* Neoplasia - ex/ hodgkins
* Asthma
* Aspergillus
* Allergic processes
* Chronic adrenal insufficiency,
* Churg Strauss
* Parasites (invasive)
28
--- is a costimulatory signal necessary for T-cell activation.
CD28
29
Which type of cells have abundant RER, and well developed Golgi apparatus?
plasma cells
30
Which Leukocyte contains Heparin?
basophil, mast cells
31
“Clock-face” chromatin distribution refers to what type of cells?
plasma cells
32
mothers exposed to fetal Rh+ blood (often during delivery) may make what type of Ab? How are they diff from anti-A/B Ab?
anti-D IgG. - can cross placenta
Anti-A & Anti-B Ab are IgM and can't cross placenta
33
---- administration to Rh− pregnant women during -----, which prevents maternal anti-Rh IgG production.
RhoGAM third trimester
34
Hemophilia C has a deficiency of what factor? And what is the genetic inheritance?
XI (AR)
35
Name 3 LMWHs?
dalteparin, enoxaparin, Fondaparinux
36
---- activates bradykinin; --- inactivates bradykinin
Kallikrein (HMWK) activates bradykinin;
ACE inactivates bradykinin
37
The LMWH have the greatest eefficacy on which factor?
Factor Xa
38
Which 3 tissue factors require Ca2+ and phospholipid?
Thromboplastin (III) (produced from fetus during abortion) Va VIIIa
39
Which 4 tissue factors are inhibited by vitamin K antagonist warfarin?
II VII IX X
40
Heparin has the greatest eefficacy on which factor?
IIa (thrombin)
41
Which 2 coagulation factors are cofactors?
Va VIIIa
42
T or F? Plasmin activates but is not part of coagulation cascade.
T
43
CD marker of macrophages
CD14
44
Eosinophils are activated by ___ to defend vs helminthic infection?
(+) by IL5 made by TH2 and Mast cells
45
Marker for mast cells?
Tryptase
46
What Rx is used to (-) mast cell degranulation?
Cromolyn sodium - used for asthma prophylaxis
47
hypersegmented neutrophils are seen in what path?
hypersegmented (% or more lobes) - seen in B12/folate def
48
costimulatory molecule for dendritic cell?
B7
49
Name 3 direct thrombin inhibitors? (DOC for HIT)
argatroban bivalirudin dabigatran
50
Name 2 direct Xa inhibitors?
apixaban, rivaroxaban
51
Fondaparinux inhibits which factor? (it causes HIT)
factor Xa
52
Thrombin converts what to what?
Fibrinogen to Fibrin monomers
53
phytomenadione or phylloquinone or phytonadione help mature which factors?
Vit K helps the maturation of clotting factors II, VII, IX, X, and proteins C and S.
54
Prolonged use of broad-spectrum antibiotics can cause what?
hemorrhagic disease due to vit K def ( enteric bacteria produce vit K)
55
Which complex activates protein C?
Thrombin-thrombomodulin complex
56
---- stabilizes platelet plug.
Fibrin mesh
57
Name the enzyme that produces reduced vit K?
epoxide reductase - inhibited by Warfarin
58
----- cleaves and inactivates Va, VIIIa
Protein C, with the aid of Protein S
59
Describe the Factor V Leiden mutation?
it produces a factor V resistant to inhibition by activated protein C.
60
Plasminogen ---\> plasmin
tPA
61
Basophils is incr in what path?
Chronic myelogenous leukemia (CML) polycythemia
62
Eosonophils are INC in what infections?
Aspergillus infection parasites
63
Which T cells recruit eosonophils?
Th2 cells
64
Eosinophylic infiltrate is see in what cardiac path?
Löffler syndrome (endomyocardial fibrosis with a prominent eosinophilic infiltrate), Eosinophilic granulomatosis with polyangiitis (Churg- Strauss)
65
Eosinophila in what 2 drugs?
Macrolides, NSAIDs
66
What vitamin in excess can alter the metabolism of vitamin K?
vit E
67
what blocks tPA?
Tranexamic acid (analog of lysine), Aminocaproic acid
68
VWF is stored in which cells?
1) Weibel Palade bodies in Endothelial cells - also P-selectin 2) Alpha granules in Platelets
69
What type of mutation in HbS and HbC?
Missense mutations in HbS - glutamic acid (neg aa) --\> valine (neutral) HbC - glutamic acid --\> lysine (postive)
70
Stimulate tPA?
Alteplase, Reteplase, streptokinase, tenecteplase
71
Inhibitor of plasmin?
alpha 2 anti-plasmin
72
How would you differentiate b/w Von Willebrand disease and Bernard Soulier syndrome after a positive ristocetin test?
BS syndrome: inc BT, PT and PTT (N) VW Disease: Inc BT, PT (N), Inc PTT, (vWF stabilizes Factor VIII therefore deficiency increase PTT)
73
Deficiency of Gp IIb/IIIa?
Glanzmann Thrombasthenia
74
Name the Pathology associated with peripheral blood smear presentation: Degmacyte
G6PD deficiency (Degmacyte = Bite cell)
75
Name the Pathology associated with peripheral blood smear presentation: Basophilic stippling
Lead poisoning
76
MOA of Aspirin?
irrev inhibits COX, stopping TXA2 synthesis
77
Rx that (-) ADP induced expression of GpIIb/IIIa via P2Y12-R
Clopidogrel, Prasugrel, Ticlopidine, Ticagrelor
78
Rx that inhibit GpIIb/IIIa directly (fibrinogen receptor)
Abciximab, Eptifibatide, Tirofiban, Lomifiban, Orbofiban
79
Risocetin - MOA?
activates vWF to bind GpIb
80
Name the Pathology associated with peripheral blood smear presentation: Dacrocyte
Myelofibrosis (Dacrocyte = Teardrop cell)
81
Name the Pathology associated with peripheral blood smear presentation: Schistocyte
DIC, TTP, HUS, Mechanical hemolysis (Schistocyte =Helmet cell)
82
Name the Pathology associated with peripheral blood smear presentation: Target cell
HALT HbC disease, Asplenia, Liver Disease, Thalassemia
83
Name two heme pathologies that show an X linked inheritance pattern?
G6PD Deficiency, Sideroblastic Anemia, Hemophilia A
84
Copper deficiency can lead to this heme pathology?
Microcytic Sideroblastic Anemia
85
Clinical presentation of a pt with Iron Deficiency Anemia
Conjunctival Pallor, Spooned Nails (koilonychia)
86
Describe the genetic defect in Alpha thalassemia? Which mutation is affiliated with which population?
Deletion in alpha globin gene (Ch 16). Cis deletion prevalent in Asians, Trans deletion prevalent in Africans
87
Describe the genetic defect in Beta thalassemia? Which mutation is affiliated with which population?
Point mutation in the beta globin gene promoter and splice sites (Ch 11). Prevalent in Mediterranean populations
88
What causes formation of Heinz bodies?
Oxidation of Hgb -SH groups to -S-S leads to Hgb precipitation = Heinz bodies
89
Crew cut on skull XR, Chipmunk Facies, Extramedullary hematopoiesis
B thalassemia major
90
Which virus can induce aplastic crisis (Clinical Presentation)? Name the heme pathologies associated with it.
Parvovirus B19 infection leads to slap cheek appearance in pts Patients with aplastic crisis: SCA, B Thalassemia
91
What is basophilic stippling?
Remnants of rRNA in RBCs due decreased degradation
92
Q. Clinical Presentation of Lead Poisoning?
Lead lines on gums (Burton lines) and long bone metaphyses Encephalopathy Abdominal colic Dropping of wrist and foot
93
Name the enzymes inhibited by Lead
Ferrochelatase, ALA Dehydratase
94
DOC for Lead poisoning in Adults?
Dimercaprol, EDTA
95
DOC for Lead poisoning in Children?
Succimer
96
What is the most common cause of Sideroblastic Anemia ? Is it Irreversible?
Alcoholism which is reversible if given B6 as Tx
97
Which three drugs are associated with folate deficiency?
Methotrexate, Trimethoprim, Phenytoin
98
Where do you see subacute combined degeneration of the spino cerebellar tract?
B12 def - along with lat corticospinal tract, dorsal column dysfunction
99
How do you differentiate Orotic aciduria from Ornithine transcarbamylase def?
There is no hyperammonemia with Orotic aciduria
100
Most common causes of macrocytic anemia that is not megaloblastic?
Alcoholism, liver disease,
101
Defective enzyme in Orotic aciduria? Substrate?
Orotic Acid --\> UMP, done by UMP synthase
102
Short stature, thumb and radial defects?
Diamond Blackfan anemia and Fanconi anemia
103
Two heme diseases with inc HbF?
B thalassemia major, Diamond blackfan anemia
104
dec haptoglobin, inc LDH, target cells seen in ?
intravascular hemolysis
105
Urine test shows Hgb, hemosiderin, and urobilinogen?
Intravacular hemolysis
106
iron def anemia, esophageal webs, dysphagia
Plummer Vinson syndrome
107
Which 3 GI issue can lead to iron def anemia?
GI bleed - colon cancer, etc
Malabsorption - gastritis, celiac disease,etc
108
Genetic mutation in B thalassemia?
Point mutation in splice site and promoter sequences - C replaces Guanine before AUG seq -- dec mRNA
109
Type of genetic defect in sideroblastic anemia?
X linked defect in delta- ALA synthase - req B6 as cofactor
110
Rx for Sideroblastic anemia
B6 (pyridoxine)
111
Inc risk of gallstones and BM hyperplasia with what type of hematological disordeR?
hemolysis
112
Iron, TIBC, ferritin - inc or dec in ACD (anemia of chronic disease)?
Dec FE, TIBC (indicator of transferrin) Inc Ferritin
113
What differentiates Diamond Blackfan from Fanconi Anemia?
Fanconi has cafe au lait spots
114
Is retic # inc or dec with aplastic anemia?
Dec
115
Most common congenital cause of Aplastic anemia?
Fanconi anemia
116
MCV and MCHC in heriditary spherocytosis ?
Inc MCHC (bc no central pallor) and normal to low MCV
117
Dec ATP production is a part of the pathogenesis of what heme disorder?
Pyruvate kinase deficiency - dec ATP will lead to rigid RBCs --\> extravasc hemolysis
118
What amino acid mutation in HbC disease?
glutamic acid to lysine in B globin chain
119
CD marker in Paroxysmal nocturnal hemoglobinuria?
CD 55/59
120
Tx for Paroxysmal nocturnal hemoglobinuria?
Eculizumab - complement inhibitor
121
Pathogenesis of PNH?
Impaired synthesis of GPI anchor for decay accelerating factor that protects RBC from complement
122
Why are newborns normally asymptomatic in sickle cell?
They have higher hbF and lower HbS
123
Why is there a crew cut skull in thalassemia major and Sickle cell?
Marrow expansion due to inc erythropoiesis
124
What renal issue in Sickle cell and why?
Renal papillary necrosis - due to dec pO2 in papilla
125
Why give hydroxyurea in Sickle cell?
Inc the amount of HbF
126
Sickle cell osteomyelitis is assoc with which bact?
Salmonella paratyphi
127
What Ig is seen in Warm AIHA and Cold AIHA?
IgG and IgM
128
Which 3 pathologies are associated with cold agglutination AIHA?
Mycoplasma pneumoniae, Infectious Mono, CLL
129
Drug assoc with Warm AIHA?
methyldopa (alpha)
130
Microangiopathic hemolytic anemia seen in which diseases? (6)
DIC, TTP, HUS, SLE, Malig HTN, HELLP
131
Two diseases associated wtih macroangiopathic anemia?
Prosthetic heart valves and aortic stenosis
132
What is mixed with patients blood in Direct coombs test?
anti Ig antibody
133
What in patients serum will yield a positive result in indirect coombs test?
If serum has anti RBC surface Ig, RBC will agglutinate = pos result
134
What is the difference in Labs between ACD and Hemochromatosis?
Both have low TIBC and and high ferritin, but Hemochromatosis has high Fe levels and also high %transferrin sat'n therefore.
135
Neutropenia cut off point?
\<1500 cell/mm3
136
Lymphopenia cut off point?
\<1500 cell/mm3 (\<3000 cells/mm3 in children)
137
Which drug causes neutrophilia, inspite of eosinopenia and lymphopenia?
Corticosteroids (dec activation of neutrophil adhesion molecules, dec migration out, stay in blood - However, tend to keep eosinophils in l.n and cause lymphocyte apoptosis )
138
Enzymes def in lead poisoning?
ALA DH, and Ferro chelatase - "Dont eat DAH Fucking Lead!"
139
5 Ps of Acute intermittent porphyrias?
Painful stomach, Port wine colored urine, Polyneuropathy, Psych issues, Precipitated by drugs, etc
140
Tx for AIP? (2) Why?
Glucose and Heme, they inhibit ALA synthase
141
Enzyme def in AIP?
PBG deaminase
142
Which HIV drugs are CI with Acute Intermittent Porphyria?
NNRTIs - Nevirapine, Efavirenz (p450 inducer)
143
Def enzyme in Porphyria cutanea tarda?
UPG decarboxylase
144
Which is the most common Porphyria?
PCTarda
145
Which pathology is assoc with def in ALA synthase?
Sideroblastic anemia - S = synthase and sideroblastic
146
Which porphyria is assoc with photosensitivity?
PCT
147
What causes cell death due to peroxidation of membrane lipids?
Fe poisoning
148
Symptoms of Fe poisoning?
n/v, gastric bleeding, lethargy, scarring leading to GI obstruction
149
Drugs used for Fe poisoning?
Chelation - IV deferoxamine, oral deferasirox
150
Which factors are tested in PT?
Factors I, II, V, VII, and X
151
Which factors are not tested in PTT?
All factors except VII and XIII
152
Inheritance patterns of all three hemophilias?
Hemophilia A and B - XLR, and C is AR
153
Tx for Hemophilia A?
Desmopressin + factor VIII concentrate
154
Vitamin K def will have an increase in what lab tests?
PT and PTT, Bleeding time is Normal
155
What parts of the coag pathway are affected by Vit K def?
F II, VII, IX, X, and Prot C and S
156
Which 3 hemat diseases have an issue with platelet plug formation?
Both Bernard Soulier, Glanzmann thrombasthenia, vW disease
157
Which platelet disorder has normal platelet count?
Glanzmann , vW disease
158
With which heme disorder will you potentially see enlarged platelets?
Bernard Soulier - release of relatively immature platelets to replace loss.
159
Which heme disorder is associated with inc BUN ?
TTP, DIC, Hemolytic Uremic Syndrome, PNH, Sickle Cell, porphyria, Multple Myeloma
160
What enzyme activates vit K?
vit K epoxide reductase
161
Normal bleeding time?
2-7 min
162
Normal PT time?
11-15 sec
163
Normal PTT time?
25-40 sec
164
Which two hematological disorders affect GpIIb/IIIa? How do they affect it?
Glanzmann - dec levels of GpIIb/IIIa
Immune Thrombocytopenia - anti GpIIb/IIIa antibodies
165
Which hemat disorder show inc megakaryocytes on bone marrow biopsy?
ITP
166
Which hemat disorder has a def of metalloprotease?
TTP - ADAMTS 13 = vWF metalloprotease
167
Schistocytes are seen in which platelet disorder? why?
TTP - due to microthrombi formation (inc vWF multimers --\> Inc platelet adhesion --\> Inc platelet aggregation and thrombosis) DIC, HUS
168
Which hemat disorders have neurological symptoms?
TTP - pentad of neuro/renal symptoms, fever, thrombocytopenia, fever, microangiopathic hemolyic anemia
B12 deficiency -
169
What is the difference between HUS in adults and children?
Children tend to have diarrhea, adults do not.
170
Most common cause of dec platelet #?
ITP
171
Which blood tests are elevated in vW disease?
BT inc, and PTT may be normal or Inc
172
Explain the Ristocetin test result of vW Disease?
No platelet aggregation, without vW.
173
Which two hemat diseases are treated with desmopressin?
Hemophilia A, vW disease (affiliated with FVIII)
174
Causes of DIC?
Sepsis, Trauma, Obstetric complications, acute Pancreatitis, Malignancy, Nephrotic syndrome, Transfusion, Snake Bite
175
Lab values of DIC?
Inc fibrin degradation, dec fibrinogen, Dec factors V and VIII
176
How does Antithrombin deficiency affect PT, PTT, and thrombin time? It can affect which of those values following an admin of which drug?
No direct effect on PT, PTT, or thrombin time. However, it can decrease the level of PTT increase following Heparin admin. (PTT is normally used to follow Heparin admin)
177
Nephrotic syndrome is associated with which two coagulation disorders?
DIC and Antithrombin deficiency
178
What type of mutation in FV Leiden?
guanine --\> adenine DNA point mutation, Arg506Gln
179
The mutation is FV Leiden def stops its degradation by what protein?
Prot C
180
Most common cause of hypercoagulability in Caucasians?
F V Leiden
181
What issue specific to women must one be concerned about in terms of FV Leiden def?
1) Inc risk of PE with OCP 2) Recurrent pregnancy loss
182
Prot C and S def will lead inability to inhibit which factors?
Factor Va and VIIIa
183
Be careful with prescribing which anti-coag when it comes to Prot C or S def?
Warfarin - inc risk of skin necrosis
184
location of Gene mutation of Prothrombin?
Mutation in 3' UTR
185
Risk associated with blood transfusion?
transfusion reactions, Fe overload (could lead to 2ndary hemochromatosis) hypocalcemia, hyperkalemia
186
Viruses associated with Hodgkins and Non Hodgkins lymphoma?
Hodkin - EBV
Non-Hodkin - HIV, EBV, HTLV
187
Which type of lymphoma is assoc with B symptoms? What are those symptoms?
low grade fever, night sweats, weight loss - Both Hodgkin's and non Hodgkin's
188
CD # of Reed-Sternberg cells?
CD15, CD30
189
What are the two genes affected in Burkitts? (not the translocation itself, but the products of them)
Chr 8 - c -myc Chr 14 - Ig heavy chain
190
Tingible body macrophages associated with?
Burkitts
191
What type of lesion is seen in the sporadic form of Burkitts?
Pelvis and abdomen lesions
192
Most common type of Non Hodgkin's in adults?
Diffuse large B cell lymphoma
193
Why can blood transfusions lead to tingling sensations and paresthesias?
hypocalcemia
194
Gene products of the genes translocated in Mantle cell lymphoma?
Chr 11 - cyclin D1 (G1--\> S) Chr 14 - Ig heavy chain
195
What are the gene products of the gene translocation of Follicular lymphoma?
Chr 14 - Ig heavy chain Chr 18 - bcl2
196
Which lymphoma presents with intermittent pain of lymph nodes?
Follicular lymphoma
197
What are the cell types in grades 1-3 of Follicular lymphoma?
Grade 1 - small cleaved cells Grade 2 - Mixed Grade 3 - large cells
198
Inc plasmin seen in which path?
Radical prostatectomy - release urokinase -- (+) plasmin
Liver cirrhosis - dec prod'n of alpha antiplasmin looks like DIC w/o a postive D-dimer
