Heme/Onc Flashcards
1
Q
What are the dense granules of thrombocytes?
A
ADP, Ca+2
2
Q
What are the alpha granules of thrombocytes?
A
vWF, fibrinogen, fibronectin
3
Q
Where is 1/3 of platelet pool synthesized?
A
Spleen
4
Q
Which leukocytes are granulocytes?
A
Neutrophils, eosinophils, basophils
5
Q
Which leukocytes are mononuclear cells?
A
Monocytes (macrophage in tissue), Lymphocytes (T and B cells)
6
Q
In an acute inflammmatory response, which leukocyte is predominant?
A
Neutrophil
7
Q
List 5 chemotactic factors for neutrophils
A
IL-8, LTB-4, kallikrein, platelet-activating factor, C5a
8
Q
Which cytokine activates macrophages in tissues?
A
gamma-interferon
9
Q
which leukocyte is important in granuloma formation?
A
macrophage
10
Q
How do macrophages initiate septic shock?
A
CD14 binds Lipid A from bacterial LPS
11
Q
Which cells do macrophage present antigens to/
A
CD4 (via MHC II)
12
Q
List the causes of eosinophilia (NAACP)
A
Neoplasia, Asthma, Allergies, Chronic Adrenal Insufficiency, Parasites
13
Q
Basophilia can be a sign of which hematologic problem?
A
CML (myeloproliferative disease)
14
Q
Which leukocyte produces major basic protein?
A
Eosinophil
15
Q
Describe Type I hypersensitivity reaction (allergic response)
A
Mast cell binds Fc portion of IgE, IgE cross-links, degranulation, release of histamine, heparin, tryptase and eosinophil chemotactic factors
16
Q
Cromolyn sodium is used to prevent
A
Degranulation of mast cells (allergic prophylaxis)
17
Q
Which cell serves as the link between innate and adaptive immunity?
A
Dendritic cell
18
Q
Which MHC do dendritic cells express?
A
MHC II
19
Q
Which blood cell is affected in multiple myeloma?
A
plasma cell
20
Q
Which blood cells make up the majority of circulating lymphocytes
A
T cells
21
Q
Which blood type is a universal donor of plasma?
A
AB
22
Q
Which blood type is universal recipient of plasma?
A
Type O
23
Q
What is the purpose of administering RhoGAM to mothers/
A
prevents maternal anti-d IgG production in Rh- mothers against Rh+ positive fetus (prevents hemolytic disease of newborn)
24
Q
What is ABO hemolytic disease of newborn
A
Hemolytic anemia of A, B, or AB fetus in type O mother. Presents as mild jaundice in first 24 hours of birth, treatment is phototherapy or exchange transfusion
25
Why can ABO hemolytic disease of newborn happen in first pregnancy and not Rh disease?
Anti-ABO antibodies are formed early in life while anti-D IgGs usually form after exposure to Rh
26
Which aspects of inflammation does PGE4 mediate?
Vasodilation, increased vascular permeability, pain and fever
27
Leukotrienes are primarily involved in which inflammatory response?
Anaphylaxis
28
What is the immediate response of mast cells in acute inflammation?
Release histamine to increase vasodilation of arterioles and vascular permeability
29
What is the delayed response of mast cells in acute inflammmation?
production of arachidonic acid metabolites, especially Leukotrienes
30
Which factors are involved in the Classical pathway for Complement activation?
IgM and IgG bound to antigen (bind C1)
31
Which factors activate the alternative pathway
microbial products
32
Which factors activate the Mannose-binding lectin pathway
MBL binds mannose on microorganisms to activate complement
33
Which complement factors are part of the MAC complex
C5b, C6-C9
34
Which complement protein is chemotactic for neutrophils
C5a
35
Which complement protein is an opsonin for phagocytosis?
C3b
36
Describe the function of Hageman factor (Factor XII)
Activates coagulation and fibrinolysis, complement and kinin system
37
Which inflammatory molecules are responsible for redness and warmth?
Histamine, Prostaglandins D2, E2 and I2, and bradykinin (vasodilators)
38
What are the key mediators of swelling in inflammmation?
Histamine (endothelial cell contraction) and tissue damage
39
Key mediators of pain in inflammation
Bradykinin and PGE2 (sensitize sensory nerve endings)
40
Key mediators of fever in inflammation?
Pyrogens that cause macrophage to release IL-1 and TNF (increase COX in perivascular cells of hypothalamus)
41
Which prostaglandin mediates fever in the hypothalamus?
PGE2
42
What are the features of autosomal recessive integrin deficiency? (CD18)
Delayed separation of umbilical cord, increased circulating neutrophils and recurrent bacterial infections that lack pus formation
43
What are the features of Chediak-Higashi syndrome?
Increased risk of pyogenic infections, neutropenia, giant granules on leukocytes, albinism, peripheral neuropathy, defective primary hemostasis
44
Which cellular mechanism is defective in Chediak-Higashi syndrome?
Cell-trafficking and phagolysosome formation
45
Which enzyme is defective in Chronic Granulomatous Disease?
NADPH Oxidase (converts O2 --> Superoxide radical)
46
People with CGD are prone to infections by which organisms?
Catalase-positive (S. aureus, Pseudomonas, Serratia, Nocardia, Aspergillus)
47
Which test is used to screen for CGD
Nitroblue tetrazolium (leukocytes turn blue if normal, stay colorless if NADPH oxidase is defective)
48
MPO deficiency increases risk of which infections?
Candida infections
49
What are the anti-inflammatory cytokines produced by macrophages?
IL-10 and TGF-beta
50
Which cytokine from macrophages recruits additional neutrophils?
IL-8
51
Which leukocytes mediate abscess formation?
Macrophages via fibrosis
52
Which T cells are involved in chronic inflammation?
CD4+ T cells activated by MHCII of macrophages
53
Which cells express MHC I and what do they present?
All nucleated cells, intracellular antigens (viruses)
54
Which cells express MHC II and what do they present?
Antigen-presenting cells (dendritic, macrophage), extracellular antigens (parasites, bacteria, etc)
55
Which two interactions activate CD4+ helper T cells?
B7 on APC to CD28 on T cell and MHCII on APC to TCR (+CD3) on T cell
56
What are the two subsets that helper T cells divide into?
TH1 and TH2
57
Which cytokines are secreted by TH1 cells?
IFN-gamma to activate macrophage and promote B cell class-switch to IgG, IL-2 to activate CD8+ T cells (and inhibit TH2)
58
Which cytokines do TH2 cells secrete and what is their function?
IL-4 (B cell class switch to IgE); IL-5 (recruit eosinophils); IL-13 (B cell class switch); IL-10 (inhibit TH2)
59
What is the second activation signal for CD8+ T cells?
IL-2 secreted by TH1 cells
60
How do CD8+ T cells kill infected cells? (2 ways)
Secrete perforin and granzyme to activate apoptosis; express FasL to bind Fas on target cells and activate apoptosis
61
List 3 ways to activate apoptosis
cyt c, Fas-FasL, granzyme via CD8+
62
Which two signals activate B cells to become plasma cells?
CD40 on B binds CD40L on helper T cell; BCR-MHCII
63
What 2 cytokines released by helper T cell promote B cell class switch?
IL-4 and IL-5
64
Describe what a granuloma looks like
epithelioid histiocytes (macrophage with abundant pink cytoplasm) surrounded by giant cells and rim of lymphocytes
65
Difference between caseating and non-caseating granulomas
Non-caseating granulomas lack central necrosis; caseating granulomas are characteristic of tuberculous and fungal infections
66
Which cytokine induces helper T cells to turn into TH1 subtype?
IL-12
67
Describe how granulomas form
Macrophage ingest pathogen and present to CD4 T cell on MHC II--> macrophage secrete IL-12 to differentiate T cell into TH1 cell--> TH1 cell secretes IFN-gamma to activate macrophages into epithelioid histiocytes and giant cells
68
List the clinical presentation of DiGeorge syndrome
T-cell deficiency (thymic aplasia), hypocalcemia (parathyroid aplasia), abnormalities of heart, great vessels and face
69
What are three major causes of SCID?
Cytokine receptor defects (most common); ADA deficiency (leads to oxidative death of lymphocytes); MHC II deficiency (cannot activate T cells and cytokine production)
70
X-linked agammaglobulinemia is a mutation in which enzyme?
Bruton tyrosine kinase
71
What is the defect in X-linked Agammaglobulinemia?
Pre- and pro-B cells cannot mature to plasma cells (complete lack of immunoglobulins)
72
Presentation of X-linked Agammaglobulinemia
presents after 6 months of life with recurrent bacterial, enterovirus and Giardia infections
73
Why does X-linked agammaglobulinemia present after 6 months?
Infant no longer has protective maternal IgGs
74
Patients with Common variable immunodeficiency are at increased risk of which diseases?
Autoimmmune diseases and lymphoma
75
What is the difference in presentation between X-linked agammaglobluinemia and common variable immunodeficiency?
CVID arises in late childhood (not after 6 months) and blood tests show low Ig count
76
Which protein is mutated in hyper-IgM syndrome?
CD40L (on helper T cells) or CD40 receptor (on B cells)
77
What is the Ig presentation of hyper-IgM syndrome?
elevated IgM, low IgA, IgG and IgE (recurrent pyogenic infections) at mucosal sites
78
Which gene is mutated in Wiskott-Aldrich syndrome?
WASP (XLR)
79
Clinical presentation of Wiskott-Aldrich Syndrome?
Eczema, thrombocytopenia (low platelet count), and recurrent infections
80
What is the major cause of death in Wiskott-Aldrich syndrome?
Bleeding
81
Patients who are prone to Neisseria infections are deficient in which immune component?
Complement C5-C9 (MAC complex)
82
What causes hereditary angioedema (inflammation around orbitals)
C1 deficiency (persistent vasodilation)
83
What does central tolerance lead to?
T cell apoptosis or generation of regulatory T cells
84
Which mutation leads to autoimmune polyendocrine syndrome (hypoparathyroidism, adrenal failure, chronic candida infections)
AIRE
85
Which 2 autoimmune conditions are polymorphisms in CD25 associated with?
MS and T1DM
86
What is a the phenotype of Treg cells?
CD3+ CD4+ CD25+ FOXP3+
87
IPEX syndrome is a mutation in which protein?
FOXP3 on Treg cells
88
Describe symptoms of IPEX syndrome
Immune dysregulation
Polyendocrinopathy
Etneropathy
X-linked
89
What type of Hypersensitivity reaction is SLE?
Type III (Antigen-Antibody complexes)
90
Deficiency of which complement proteins associated with SLE?
C1q, C4 and C2 (needed to clear Ab-Ag complexes)
91
Which antibodies are highly specific for SLE?
Anti-Sm (mitochondrial) and Anti-dsDNA
92
Which antiphospholipid antibodies are elevated in SLE?
anticardiolipin, anti-beta2-glycoprotein I, and lupus anticoagulant (falsely-elevated PTT)
93
What is a complication of antiphospholipid syndrome?
recurrent miscarriages
94
What is antihistone antibody specific for?
Drug-induced lupus
95
anti-SSA/Ro and anti-SSB/La associated with which disorder
Sjogren syndrome
96
What type of HS reaction is Sjogrens
Type IV Lymphocyte-mediated damage with fibrosis
97
Which malignancy commonly presents with Sjogrens
Rheumatoid arthritis
98
What risks exists for babies with mother's who have anti-SSA?
neonatal lupus, congenital heart block
99
B cell (marginal) zone lymphoma risk is increased in which condition?
Sjogren's
100
What is the diagnostic criteria for Sjogren's?
Lymphocytic sialedenitis on lip biopsy
101
What are the two types of scleroderma and what are their antibodies?
```
Limited type (CREST syndrome): anti-centromere
Diffuse type (any organ, especially lungs): anti-Scl70 (DNA Topoisomerase I)
```
102
What is primary intention?
Wound edges brought together, minimal scar formation
103
What is secondary intention wound healing?
Edges not approximated--granulation tissue fills defect; myofibroblasts contract--scar formation
104
Deficiencies that cause delayed wound healing?
Vitamin C (hydroxylation of proline and lysine of procollagen-- collagen cross-linking)
Copper (cofactor for lysyl oxidase to cross-link collagen)
Zinc (cofactor for collagenase)
105
How do disorders in primary hemostasis typically manifest?
Mucosal or skin bleeding
106
What is the most common symptom of primary hemostasis disorders
epistaxis
107
List symptoms of mucosal and skin bleeding common to primary hemostasis disorders
epistaxis (nosebleeds), hemoptysis, GI bleeds, petechiae, purpura, easy bruising, echhymoses
108
What is Immune Thrombocytopenic Purpura?
Splenic generation of autoantibodies against platelets (IgG)
109
What are the two forms of ITP?
Acute (in children, usually after viral infection)
| Chronic (in women, usually pregnant, secondary to autoimmune dz, can lead to ITP in kids)
110
Lab findings of ITP?
thrombocytopenia (<50k), normal PT/PTT, megakaryocytosis
111
What is treatment of ITP for refractory cases?
Splenectomy
112
What types of cells can be seen in microangiopathic hemolytic anemia?
Schistocytes (helmet cells)
113
What are two major causes of Microangiopathic Hemolytic Anemia?
HUS and TTP
114
Mutation in which enzyme causes thrombotic thrombocytopenic purpura (TTP)
ADAMTS13
115
What is the function of ADAMTS13?
Cleaves vWF multimers (polymeric vWF cause abnormal aggregation and microthrombi)
116
How is deficiency of ADAMTS13 acquired?
Autoimmunity (autoantibody), more common in females
117
What causes hemolytic uremic syndrome (HUS)?
endothelial damage by drugs or infection
118
What is the most common cause of HUS?
E Coli O157:H7 (undercooked beef); verotoxin damages endothelial cells
119
Clinical findings of HUS/TTP
Skin/mucosal bleeding, hemolytic anemia (schistocytes), fever
120
Clinical finding specific to HUS
Renal insufficiency (elevated Creatinine/BUN)
121
Clinical finding specific to HUS
CNS involvement (hydroencephaly, confusion, etc)
122
Lab findings of HUS/TTP
Thrombocytopenia, longer bleeding time, normal PT/PTT, anemia with schistocytes, megakaryocytosis
123
What is the treatment for TTP/HUS?
Plasmapharesis (protein removal) and corticosteroids
124
What is the defect in Bernard-Soulier syndrome?
defective GPIb so platelet cannot adhere to endothelial cell
125
What is the defect in Glanzmann thrombasthenia?
GPIIb/IIIa deficient so platelet aggregation is impaired
126
How does aspirin affect platelet aggregation?
Inhibits COX irreversibly, impairing aggregation
127
What are the clinical features of secondary hemostasis disorders (coagulation cascade)
Deep tissue bleeding into muscles and joints; rebleeding after surgeries
128
Which pathway/factors does prothrombin time measure?
Extrinsic: 7; Common: 2, 5, 10, fibrinogen
129
Which pathway/factors does partial thromboplastin time measure?
Intrinsic (12, 11, 9, 8) and common (2, 5, 10, fibrinogen)
130
How is Hemophilia A inherited?
XLR or de novo
131
Which factor is deficient in Hemophilia A?
VIII of intrinsic pathway
132
Lab findings of Hemophilia A
Increased PTT; normal PT
Decreased Factor VIII
Normal platelet count and bleeding time
133
Symptoms of Hemophilia A
Deep tissue bleeding; rebleeding after surgical procedures
134
Which factor is deficient in Hemophilia B (Christmas disease)?
Factor IX
135
How to distinguish between Coagulation Factor Inhibitor and Hemophilia A?
In CFI, PTT does not correct after mixing normal plasma with patient's plasma (bc antibodies impair VIII function, there is no deficiency)
136
What is von Willebrand Disease?
Genetic vWF deficiency, most common inherited coagulation disorder
137
How is the most common type of vWF disease inherited?
AD
138
Lab findings of vWF disease?
Increased bleeding time, increased PTT (decreased VIII deficiency), abnormal ristocetin test (impaired agglutination)
139
Describe the ristocetin test
Induces platelet agglutination by having vWF bind platelet GPIb; checks for vWF disease
140
Treatment for von Willebrand disease?
Desmopressin (ADH analogue that stimulates vWF production from Weibel-Palade bodies of endothelial cells)
141
Where is Vitamin K produced
gut flora
142
How does vitamin K deficiency lead to hemorrhage?
Vitamin K is needed to gamma carboxylate factors (activate) 2, 7, 9, 1 and Proteins C and S, all of which are needed for coagulation; deficiency keeps them inactive, so coagulation can't occur
143
Who is at greatest risk of Vitamin K deficiency?
Newborns (sterile gut)
Pts with Malabsorption syndromes
Pts on long-term broad-spectrum antibiotics
144
How does liver failure lead to thrombocytopenia and abnormal hemostasis?
Decreased production of coagulation factors (monitor PT)
145
Laboratory findings of disseminated intravascular coagulation
thrombocytopenia (decreased platelet count)
increased PT/PTT
decreased fibrinogen
hemolytic anemia (schistocytes)
146
Which test confirms DIC dx?
Elevated D-dimer (split products of fibrin)
147
How is a clot removed?
fibrin broken down via plasmin, coagulation factors destroyed, platelet aggregation inhibited
148
What activate plasmin from plasminogen?
tPA
149
What inactivates plasmin?
alpha2-antiplasmin
150
What do disorders in fibrinolysis resemble?
DIC
151
How to distinguish disorders in fibrinolysis from DIC?
D-dimers in DIC, only fibrinogen split products in fibrinolysis disorder
152
Treatment for disorder in fibrinolysis?
aminocaproic acid
153
Labs for disorder in fibrinolysis?
increased bleeding time (clotting factors destroyed by overactive plasmin), increased PT/PTT
154
What is the most common site for thrombi development?
Deep veins below the knee
155
How to distinguish thrombus from postmortem clot?
Lines of Zahn and attachment to vessel wall
156
What is Virchow's triad?
3 risk factors for thrombosis: disruption of blood flow, endothelial cell damage, hypercoagulable state
157
3 main causes of endothelial damage
atherosclerosis, vasculitis, homocysteine
158
How do folate and B12 deficiency increase the risk of thrombosis?
Lead to mild elevation in homocysteine, which damages endothelial cells and can promote clotting cascade
159
Which congenital disorder leads to high levels of homocysteine with homocysteinuria?
Cystathionine beta synthase deficiency
160
Clinical features of cystathione beta synthase deficiency?
vessel thrombosis, mental retardation, lens dislocation, long slender fingers, death at young age
161
Three main sites of DVTs?
Deep veins of legs, hepatic and cerebral veins
162
What clinical feature is an indication of hypercoagulable state?
Recurrent DVTs, DVTs at a young age
163
Which disorder is the most common inherited cause of hypercoagulable state?
Factor V Leiden (cannot be inactivated by Protein C or S bc lacks cleavage site)
164
How does PTT behave in ATIII deficiency with Heparin dosing?
does not increase like it should
165
How are oral contraceptives related to a hypercoagulable state?
Estrogen increases synthesis of coagulation factors
166
On histology, what do you find in an atherosclerotic embolus?
Cholesterol clefts
167
What increases the risk of fat embolus?
Bone fractures
168
Laprascopic surgery increases the risk of which embolus?
Gas embolus
169
How does an amniotic fluid embolus present?
SOB, neuro symptoms, DIC; characterized by squamous cells and keratin debris from fetal skin
170
A saddle embolus that causes sudden death likely originated from which part of the body?
Deep veins below the knee
171
What are the presenting signs and symptoms of anemia?
Weakness, fatigue, and dyspnea
Pale conjunctiva and skin
Headache and lightheadedness
Angina
172
List 4 microcytic anemias
Iron-deficiency anemia, sideroblastic anemia, thalassemia, anemia of chronic disease
173
Where does iron absorption occur in gut?
Duodenum
174
Why does iron deficiency cause microcytic anemia?
Low iron = low hemoglobin so RBCs divide and extra time to maintain hemoglobin concentration
175
Which two hookworms are linked to iron-deficiency anemia?
Ancylostoma duodenalle; Necator americanus
176
What are the lab values of early stages of iron deficiency?
Low ferritin (stored iron is depleted first), increased TIBC (measure of transferrin molecules in blood)
177
What are lab values for iron-deficiency anemia after ferritin is depleted?
decreased serum iron, decreased % saturation (% of transferrin bound by iron)
178
Lab findings of iron-deficiency anemia
microcytic, hypochromic RBCs with increased red cell distribution width; decreased ferritin, increased TIBC, decreased % saturation, decreased serum iron; increased free erythrocyte protoporphyrin
179
How does Plummer-Vinson Syndrome present?
Beefy-red tongue, dysphagia, iron-deficiency anemia due to esophageal web and atrophic glossitis
180
Which enzyme is involved in anemia of chronic disease?
Hepcidin
181
Lab values of anemia of chronic disease?
increased ferritin (sequestered iron), decreased TIBC, decreased serum iron, decreased % saturation, increased FEP
182
Which vitamin deficiency can lead to sideroblastic anemia?
B6
183
What causes sideroblastic anemia?
Decreased protoporphyrin synthesis
184
What are sideroblasts?
RBCs with iron-laden mitochondria forming ring around nucleus
185
List three causes of acquired sideroblastic anemia
1. Lead poisoning
2. Alcoholism
3. B6 deficiency
186
How does lead poisoning cause sideroblastic (microcytic) anemia?
inhibits ALAD and ferrochelatase
187
How does alcoholism cause sideroblastic anemia?
Poisons mitochondria- site of protoporphyrin synthesis
188
How does B6 deficiency lead to sideroblastic anemia?
ALAS (rate-limiting step) can only function with B6 as a cofactor
commonly a side-effect of isoniazid therapy
189
Lab findings of sideroblastic anemia
increased ferritin, decreased TIBC, increased serum iron, increased %saturation
190
Which chromosome has beta globin genes?
Chromosome 11
191
Which chromosome has alpha globin genes
Chromosome 16
192
How many copies of beta globin are there?
2
193
How many copies of alpha globin gene are there?
4
194
Which genetic error causes alpha thalassemias?
gene deletion
195
Which genetic mutation causes beta thalassemias?
gene mutation
196
clinical presentation of alpha thalassemia where two genes are deleted?
mild anemia with increased RBC count; cis deletion in Asians, trans in Africans
197
Cis deletions of alpha globin are problematic because
increase rate of spontaneous abortions and inheritance in offspring
198
Clinical presentation when three genes of alpha globin are deleted
Severe anemia, beta chains form HbH that damage RBCs
199
Clinical presentation when four alpha genes are deleted
lethal in utero (hydrops fetalis); gamma chains form tetramer (Hb Barts)
200
Presentation of beta thalassemia minor?
usually asymptomatic with mild RBC increase
201
Histology and electrophoresis of beta thalassemia minor
microcytic, hypochromic RBCs with target cells
| slightly increased HbA2 and slightly decreased HbA
202
Parvovirus B19 causes aplastic anemia crisis in which patients?
Beta thalassemia, sickle cell patients
203
List major features of beta thalassemia major
Severe anemia a few months after birth, extravascular hemolysis, "crewcut" Xray and chipmunk facies, risk of secondary hemochromatosis
204
Blood smear of beta thalassemia major
microcytic, hypochromic RBCs with target cells and nucleated red blood cells
205
What causes the appearance of nucleated red blood cells in thalassemia?
Synthesis of RBCs in abnormal locations (liver, spleen, skull) allows nucleated ones to escape
206
What causes extravascular hemolysis in beta thalassemia
precipitation of alpha chains that damage RBC membranes
207
Electrophoresis of beta thalassemia major
Little to no HbA, Increased HbA2 and HbF
208
Two major causes of macrocytic anemia
B12 or Folate deficiency
209
What causes megaloblastic cells in macrocytic anemia
Impaired DNA synthesis leads to one less division (larger cells)
210
What causes hypersegmented neutrophils in macrocytic anemia
Impaired DNA synthesis leads to impaired division of granulocytic precursors
211
List 5 causes of folate deficiency
poor diet (alcoholism, elderly), pregnancy, cancer, hemolytic anemia, and methotrexate
212
Where is folate absorbed
Jejunum
213
List 5 clinical and lab findings of folate deficiency
```
Macrocytic RBCs with hypersegmented neutrophils
Glossitis
decreased serum folate
increased serum homocysteine
normal methylmalonic acid
```
214
Where is B12 absorbed
ileum
215
What is pernicious anemia?
Autoimmune destruction of parietal cells that leads to intrinsic factor deficiency
216
List 5 common causes of B12 deficiency
Pernicious anemia, pancreatic insufficiency, Crohn's, Diphyllobothrium latum (fish tapeworm) and veganism
217
How does B12 deficiency lead to spinal cord degeneration?
B12 is a cofactor for converting MMA to succinyl coA. Low B12 allows methylmalonic acid to buildup, which impairs spinal cord myelinization
218
Clinical findings of B12 deficiency macrocytic anemia
Macrocytic RBCs with hypersegmented neutrophils
Glossitis
Spinal cord degeneration
219
Lab findings of B12 deficiency
decreased serum B12
increased serum homocysteine
increased methylmalonic acid
220
What are reticulocytes?
Young RBCs released from bone marrow; bluish cytoplasm on smear due to residual RNA
221
How does reticulocyte count distinguish between hemolytic normocytic anemia and underproduction normocytic anemia?
RCT >3% implies hemolytic; RCT <3% implies marrow underproduction
222
List the clinical findings of extravascular hemolysis
splenomegaly, jaundice, RCT >3% due to marrow hyperplasia
223
Where does extravascular hemolysis occur
Spleen, liver, lymph nodes (reticuloendothelial system)
224
What causes jaundice in extravascular hemolysis
unconjugated bilirubin from broken down protoporphyrin overwhelms liver, which conjugates bilirubin into bile
225
What causes splenomegaly in extravascular hemolysis?
Increased activity of spleen causes hyperplasia
226
Clinical findings of intravacular hemolysis
Hemoglobinemia, hemoglobinuria, hemosiderinuria, decreased serum haptoglobin
227
Why does haptoglobin decrease in intravascular hemolysis?
More of it is bound to Hemoglobin from lysed RBCs in blood vessels
228
List three disorders with predominant extravascular hemolysis
Hereditary spherocytosis, Sickle Cell Anemia and Hemoglobin C
229
How is hereditary spherocytosis diagnosed?
Osmotic fragility test
230
Why does splenectomy lead to RBCs with Howell-Jolly bodies?
Spleen removes extra genetic material in RBCs; without spleen, extra genetic material remains as Howell-Jolly bodies
231
Which globin chain is mutated in sickle cell anemia?
beta chain
232
What three factors promoted sickling of cells?
Hypoxemia, dehydration and acidosis
233
What are clinical features of sickle cell anemia
Extravascular hemolysis (jaundice, splenomegaly), intravascular hemolysis (hemoglobinuria), massive erythroid hyperplasia so crewcut/chipmunk faces, hepatomegaly
234
What is a common presenting sign of sickle cell anemia in infants
Dactylitis
235
Why are sickle cell patients prone to infections from encapsulated organisms?
Due to autosplenectomy (fibrotic spleen)
236
What is the mutation in Hemoglobin C disease?
beta globin glutamic acid replaced with lysine
237
How to RBCs protect themselves against Complement
GPI on RBCs anchors DAF (decay accelerating factor) and MIRL (membrane inhibitor of reactive lysis) to inactivate complement C3 convertase
238
What is paroxysmal nocturnal hemoglobinuria a defect in?
GPI
239
Why does intravascular hemolysis in PNH occur primarily at night?
We breathe shallow at night, leads to increase CO2, respiratory acidosis, activates complement
240
What is the screening test and confirmatory test for PNH
Sucrose test to screen; Acidified serum test for CD55 (DAF)
241
What is the main cause of death in PNH?
Thrombosis of hepatic, portal or cerebral veins
242
Which cell is specifically mutated in PNH? What does this increase the risk for
Myeloid cell --> Acute myeloid leukemia (AML)
243
How does G6PD present clinically?
Hemoglobinuria and back pain hours after exposure to oxidative stress
244
IgG mediated immune hemolytic anemia involves
extravascular hemoolysis
245
IgM mediated immune hemolytic anemia involves
intravascular hemolysis
246
What is IgG mediated immune hemolytic anemia associated with?
SLE, CLL, and penicllin and cephalosporins
247
What is IgM mediated immune hemolytic anemia associated with
Mycoplasma pneumoniae and infectious mononucleosis
248
Describe the direct Coomb's test
Add antibodies (IgG) to patient's RBCs. Agglutination confirms presence of IgG and IHA
249
Describe indirect Coomb's test
Add anti-IgG and test RBCs to patient's serum. Agglutination confirms serum antibodies
250
How does IgM cause intravascular hemolysis in IHA?
IgM binds and fixes complements in cold temperatures; residual C3b acts as opsonin for splenic macrophages
251
Three common causes of microangiopathic hemolytic anemia (intravascular hemolysis)
HUS/TTP, prosthetic heart valves, aortic stenosis
252
How do the fevers in P falciparum malaria and P vivax and ovale differ?
P falciparum-- fever everyday
| P vivax and ovale- fever every other day
253
List three major causes of anemia due to underproduction
```
Parvovirus B19 (infects progenitor RBCs and halts erythropoeisis)
Aplastic anemia (damage to hematopoetic stem cells; biopsy shows fatty marrow)
Myelophthisic process (replacement of marrow with metastatic cancer)
```
254
List two causes of neutropenia
```
Drug toxicity (damage to stem cells)
Severe infection (increased neutrophils in tissues, decreased circulating)
```
255
What is the treatment for neutropenia?
GM-CSF or G-CSF
256
4 causes of lymphopenia
Immunodeficiency
High cortisol state
Autoimmune destruction (SLE)
Whole body radiation
257
What characterizes immature neutrophils?
decreased CD16 (Fc receptors)
258
Which lymphoma exhibits eosinophilia?
Hodgkin Lymphoma
259
Which cancer has increased circulating basophils?
Chronic myeloid leukemia
260
What causes lymphocytic leukocytosis
Viral infections and bordatella pertussis infection
261
How does EBV cause splenomegaly
Increased T cell proliferation in periarterial lymphatic sheath of spleen (PALS)
262
Which T cells are predominant in infectious mononucleosis?
CD8+ T cells
263
List three complications of Infectious mononucleosis
1. Increased risk of splenic rupture
2. Rash if exposed to ampicillin
3. Increased risk of recurrence and B cell lymphoma
264
What is the marker for Lymphoblasts?
TdT (DNA Polymerase)
265
What are the markers for B-ALL
Tdt CD10, CD19, CD20
266
Who is at risk of developing Acute Lymphoblastic Leukemia?
Children (especially with Down Syndrome)
267
What is the translocation in children with B-ALL?
t(12;21) (TEL-AML1); good prognosis
268
What is the translocation in adults with B-ALL?
t(9;22); poor prognosis BCR-ABL (Philadelphia)
269
What are the markers for T-ALL
TdT, CD2 to CD28
270
What is the genetic mutation in T-ALL?
11q23
271
Children <5 yo with Down's are at increased risk of developing which WBC cancer?
Acute megakaryoblastic leukemia
272
Children >50 with Down's are at increased risk of developing which WBC malignancy
Acute Lymphoblastic Leukemia
273
What are the identifying features of Acute Myeloid Leukemia?
positive staining for MPO
Auer rods, CD13, CD 33
commonly arises in 50-60 yo adults
274
What is the translocation mutation in Acute Promyelocytic Leukemia?
t(15;17); RAR moves to 15 and inhibits blast maturation
275
How is Acute Promyelocytic Leukemia treated?
ATRA
276
What is the translocation mutation in Acute Monocytic Leukemia?
t(9;11)
277
What is characteristic about Acute Monocytic Leukemia?
Blasts infiltrate gums
278
How do myelodysplastic syndromes present?
Cytopenias, hypercellular bone marrow, abnormal maturation of cells and blasts <20%
279
Which AMLs lack MPO?
Acute Promyelocytic Leukemia and Acute Megakaryoblastic leukemia
280
What are the markers for Chronic lymphocytic Leukemia?
CD5, CD20 (naive B cells)
281
Smudge cells on a blood smear indicate which Leukemia?
CLL
282
List 3 complications of CLL
Hypogammaglobulinemia (prone to infections)
Hemolytic Anemia
Transformation into B cell lymphoma
283
What is the marker for Hairy Cell Leukemia?
TRAP+ of mature B cells
284
Clinical features of Hairy Cell Leukemmia
Splenomegaly, dry-tap bone marrow (fibrosis), pancytopenia, lymphocytes with cytoplasmic projections
285
Cladribine (2-CDA) treats which leukemia?
Hairy cell leukemia (inhibits ADA)
286
What is the prognosis of Adult T Cell Leukemia/Lymphoma?
Poor, death in a few months
287
Which cells proliferation in ATLL
Mature CD4 T cells
288
Who is at risk of acquiring ATLL
HTLV-1 infected people (Japan, Caribbean)
289
Clinical features of ATLL
Rash, generalized lymphadenopathy, lytic bone lesions with hypercalcemia
290
What does a smear for Mycosis Fungoides present?
CD4 Lymphocytes with cerebroid nuclei (Sezary Cells)
291
Clinical feature of Mycosis Fungoides?
Skin rash, plaques and nodules
292
Which cells proliferate in Myeloproliferative disorders?
Mature cells of myeloid lineage
293
Complications of Myeloproliferative disorders
Hyperuricemia (gout) due to high turnover of cells
| Progression to marrow fibrosis and acute leukemia
294
What is the translocation and mutation in Chronic Myelogenous Leukemia?
Philadelphia chromosome t(9;22) BCR:ABL leading to increased tyrosine kinase activity
295
Which cells are characteristically increased in CML?
Basophils
296
What is the first line treatment for CML?
Imatinib (blocks tyrosine kinase activity)
297
List two complications of CML
Can transform to AML or ALL since mutation is in pluripotent stem cells
298
Common clinical finding of CML
Splenomegaly
299
What are 3 distinguishing features of CML from leukemoid reaction
Negative LAP stain, Increased basophils, t(9;22)
300
Which mutation is associated with Polycythemia Vera?
JAK2 Kinase
301
Four symptoms of Polycythemia vera
Blurry vision and headache; increased risk of thrombosis; facial flushing; itching after bathing
302
Distinguishing feature of PV from reactive polycythemia
Decreased EPO, normal SaO2
303
What is the mutation in essential thrombocytopenia?
Jak2 Kinase
304
Clinical features of Myelofibrosis
Splenomegaly, Tear cells on smear, increased risk of infection, thrombosis and bleeding
305
Myelofibrosis is a mutation of Jak2kinase leading to proliferation of
megakaryocytes
306
Follicular cortex hyperplasia (B cell region) is associated with
rheumatoid arthritis and early stages of HIV
307
Paracortex hyperplasia (T cell region) is seen in
Viral infections and Mononucleosis
308
Hyperplasia of sinus histiocytes is seen in
cancers
309
List 5 Non-Hodgkin Lymphomas
Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Burkitt Lymphoma
310
Proliferation of small B cells CD20+ is characteristic of
Follicular cell Lymphoma
311
t(14;18)
Follicular Lymphoma
312
Bcl2 in follicular lymphomas
inhibits apoptosis of defective B cell, leads to monoclonality
313
Treatment of Follicular lymphoma
Rituximab (anti-CD20 antibody)
314
Four distinguishing features of Follicular lymphoma from hyperplasia
1. Disruption of architecture
2. Lack of tingible body macrophages
3. Bcl2 expression
4. Monoclonality
315
Which lymphoma is characterized by t(11;14)
Mantle cell lymphoma
316
Which gene is mutated in mantle cell lymphoma
Cyclin D1, promotes G1/S transition
317
Which gene is mutated in Burkitt Lymphoma
c-myc; promotes cell growth (transcription activation)
318
t(8;14) is which lymphoma
Burkitt
319
African vs sporadic presentation of Burkitt lymphoma
African child- extranodal mass on jaw
sporadic- extranodal mass on abdomen
due to EBV
320
Histology of Burkitt lymphoma
Starry sky
321
Gene mutation in diffuse large cell B lymphoma
BCL-6
322
Which infection is diffuse large B-cell lymphoma associated with
HIV
323
What are Reed-Sternberg cells?
Large B cells with multilobed nuclei with prominent nucleoli; positive for CD15 and CD30
324
What causes fever, chill, weight loss and night sweat symptoms in HL?
RS cells secrete cytokines to recruit reactive lymphocytes, plasma cells, macrophages and eosinophils
325
Most common type of HL
Nodular sclerosis
326
Which HL has best prognosis
Lymphocyte rich
327
Which HL has worse prognosis
Lymphocyte depleted
328
Which cytokine may be abundant in multiple myeloma?
IL-6 (growth factor for plasma cells)
329
6 clinical features of MM
```
bone pain with hypercalcemia
elevated serum protein
Increased risk of infection
Rouleux formation of RBCs (chains)
AL Amyloidosis
Proteinuria
```
330
What is Waldenstrom Macroglobulinemia
B cell lymphoma with monoclonal IgM production
331
4 clinical features of Waldenstroms Macroglobulinemia
1. Generalized lymphadenopathy
2. M spike
3. Visual and neurologic deficits (retinal hemorrhage)
4. Bleeding
332
What is the histological presentation of Langerhans cell histiocytosis
Birbeck granules (tennis rackets) on EM
333
Marker for Langerhans Histiocytosis
CD1a+ and S100+
334
Letterer-Siwe Dz clinical presentation
Langerhans cell malignant proliferation
| Skin rash and cystic skeletal defects <2 yo
335
Which disease is included in differential of osteosarcoma of young adult?
Eosinophilic granuloma (benign proliferation of Langerhans cells)
336
Hand-Schuller-Christian disease
Scalp rash, lytic skull defects, diabetes insipidus, exhophthalmos <3; malignant Langerhans cell proliferation
337
Which congenital disorder would lead to atrophic lymph node paracortex
DiGeorge Syndrome (Thymic aplasia)
338
Which condition would lead to atrophic follicular cortex in lymph node?
Agammaglobulinemia
339
Two ways ionizing radiation treats cancer cells
DNA double strand breakage, free radical formation
340
Which clotting factors are produced by liver?
II, VII, IX, X (inactive form; activated by Vitamin K)
341
Test to confirm Vitamin K deficiency?
Supplementation with Vit K improves Prothrombin time
342
Which cells synthesize factor VIII?
Endothelial cells
343
Why might PTT be affected in von Willebrand disease?
vWF is needed to form VIII
344
Describe holiday heart syndrome
Atrial fibrillation after consumption of excessive alcohol (absent P waves)
345
What causes high QRS voltage on an EKG?
Ventricular hypertrophy (prolonged untreated hypertension)
346
Prolongation of QRS interval raises suspicions of
Fascicular or bundle branch block
347
Where are troponin and calmodulin found, respectively?
Troponin in cardiac and skeletal muscle, calmodulin in smooth muscle
348
Which muscles have T tubules and what is their function?
skeletal and cardiac muscle; allow depolarization and rapid release of intracellular calcium stores
349
What is the normal kappa:lambda light chain ratio
3:1
350
>6:1 kappa:lambda light chain ratio indicates
lymphoma
351
Three most common adult cancers by incidence
breast/prostate, lung, colorectal
352
Three most common adult cancers by mortality
Lung, breast/prostate, colorectal
353
What are oncogenes?
Mutated proto-oncogenes (transcription regulators) that lead to uncontrolled cell growth
354
How does intravascular hemolysis decrease haptoglobin levels?
Hemolysis causes an increase in free hemoglobin, which binds free haptoglobin and decreases its levels
355
Which antibiotic can cause pancytopenia?
Chloramphenicol
356
The majority of hemoglobin in neonates up to 6 months is
HbF (alpha2gamma2)
357
Bcr-abl codes for
Tyrosine kinase
358
Over-expression of Erb-B2 gene is associated with which cancers
Breast and ovarian
359
Microcytic anemia with normal ferritin and transferring levels suggest
alpha or beta thalassemia
360
Normal MCV, low hemoglobin, low tranfserring, high serum ferritin and CRP suggest
Anemia of chronic disease
361
Hypersegmented neutrophils are characterstic of which anemias
Megaloblastic anemias (folate or B12 deficiency)
362
Bcr-abl codes for
Tyrosine kinase
363
Over-expression of Erb-B2 gene is associated with which cancers
Breast and ovarian
364
Microcytic anemia with normal ferritin and transferring levels suggest
alpha or beta thalassemia
365
Normal MCV, low hemoglobin, low tranfserring, high serum ferritin and CRP suggest
Anemia of chronic disease
366
Hypersegmented neutrophils are characterstic of which anemias
Megaloblastic anemias (folate or B12 deficiency)
367
CD15 is a marker for
REed STernberg cells in Hodgkin Lymphoma
368
CD16 is a marker for
NK cells, neutrophils and macrophages (low affinity Fc receptor)
