Hem Onc Flashcards

1
Q

2 derivatives of HSCs?

A
  1. Myeloids

2. Lymphoids

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2
Q

What do RBCs derive from?

A

Myeloid line of HSCs

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3
Q

Do RBCs have nucleus?

A

No

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4
Q

What does Wright giemsa stain for?

A
  • Ribosomal RNA in cytoplasm of reticulocytes

- As have just lost nucleus, have lots of this

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5
Q

Movement of CO2 into RBC?

A
  1. Moves into cell and converted to bicarb

2. Moves out in exchange for Cl

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6
Q

What is anisocytosis? Poikilocytosis?

A

Anisocytosis: Varying sizes of RBCs
- Think, aniso sounds like “anysize”
Poikilocytosis: varying shapes

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7
Q

Size of RBC relative to lymphocytes?

A

About same size

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8
Q

What is a thrombocyte?

A

AKA platelet

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9
Q

What is megakaryocyte?

A

Progenitor cell of platelet that is of myeloid lineage

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10
Q

Lifespan of platelet?

A

8 - 10 days: this is why you have to wait this long for platelet to fully regain function post aspirin use as it is binding COX in platelet

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11
Q

Where are 1/3 of body’s platelets found?

A

Spleen: this is why you can have low platelet count if you have splenomegaly
*Reverse is true if you have no spleen

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12
Q

2 granules in platelets and what is contained in them?

A
  1. Dense: ADP, Ca

2. Alpha: vWF, fibrinogen

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13
Q

What does clopidogrel block?

A

ADP receptor on platelet

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14
Q

What does GP1B receptor on platelet bind?

A

VwF

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15
Q

What does GP2b/3a bind?

A

Fibrinogen

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16
Q

Another name for leukocytes?

A

WBCs

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17
Q

2 classes of leukocytes?

A
  1. Granulocytes: myeloid lineage derived from myeloblasts

2. Monocytes: same lineage as above

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18
Q

Which are the granulocytes?

A
  1. Neuts
  2. Basophils
  3. Eosinophils
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19
Q

What is a band neutrophil?

A

Immature neut with one large nucleus as it has not yet had chance to break up into bilobed nucleus

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20
Q

When are neuts hypersegmented?

A

B12 deficiency anemia

*Neuts with > 6 lobes

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21
Q

What is released to activate macs?

A

INF-gamma from T helper cells

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22
Q

What is TNF alpha?

A
  • Released from macs to encourage granuloma formation
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23
Q

What is cell marker for macrophage?

A

CD14

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24
Q

What is CD 14 the cell marker for?

A

Macrophage

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25
Protein specific to eosinophils?
Major basic protein
26
States in which eosinophilia is seen?
``` "NAACP" Neoplasia Allergy Asthma Chronic adrenal insufficiency Parasites ```
27
Difference between histo of basophils and eos?
Basophils have granules that obscure the nucleus
28
What do basophils release?
1. Heparin 2. Leukotrienes 3. Histamine 4. Vasoactive amines
29
What do mast cells mediate? How?
Allergic reactions 1. Allergen binds IgE 2. Mast cell binds FC portion IgE 3. Upon enough IgE binding, IgE cross links and cells degranulate
30
What do mast cells release?
1. Histamine 2. Heparin 3. Eosinophil chemotactic factors
31
What type of hypersensitivity do mast cells regulate?
Allergic: 1. Asthma 2. Hay fever
32
Medicine blocking mast cell degranulation?
Cromolyn sodium
33
What are dendritic cells derived from?
The monocyte, just like the macrophage
34
Which are the APCs?
1. Dendritic - best 2. Macs 3. B cells
35
What is main inducer of primary / humoral immunity?
Dendritic cells
36
What are the derivatives of lymphoid lineage?
1. NK - only innate cell of lymphoid origin 2. B cells 3. T cells
37
What do NK cells do?
Recognize infected cells that do not have MHC attached or Ig attached - Induce apoptosis in these cells
38
What are the B cell markers?
1. CD19 | 2. CD20
39
What are CD 19/20 cell markers for?
B cells
40
What do CD8s mainly regulate?
Viral infx
41
What does chromatin in clockface distribution indicate?
Plasma cells
42
Do eosinophils or mast cells act in asthma?
Eosinophils
43
When are where are RBCs made in fetus?
``` "Young liver synthesizes blood" Yolk sac: 3 - 8 Liver: 6 - birth Spleen: 10 - 28 Bone marrow: 18 - life ```
44
What is a type II hypersensitivity?
Rxn against antigen that is on a cell surface as would be seen in a blood transfusion
45
Difference between anti AB and RH antibodies?
RH: IgG *****Crosses Placenta***** AB: IgM ***Does NOT cross placenta*** - If you are blood type O, you naturally have anti A/B antibodies: same goes for A/B blood type - With RH, regardless of if you are +/- you only develop the antibody if you have been exposed to the antigen
46
Are proteins positively or negatively charged?
Negative, as such RBCs move towards cathode in electrophoresis
47
Which unit is mutation in in sickle cell?
Beta globin, Alpha globin chains are normal
48
Mnemonic for where HgB types fall on electrophoresis?
``` "A Fat Santa Claus" HgA Fetal Sickle HgC disease ```
49
What is job of intrinsic and extrinsic pathway?
Extrinsic: initiation of clot Intrinsic: Amplification of clot
50
Starting point of extrinsic pathway?
Factor VII: activated by Tissue Factor (thromboplastin)
51
What is first step in common pathway?
Factor X
52
What are intrinsic and extrinsic paths measured with?
Intrinsic: PT/INR Extrinsic: PTT
53
What sets off factor XII in intrinsic path?
1. Platelets 2. HMWK 3. Collagen 4. Basement membrane
54
Steps in intrinsic path?
XII XI IX VIII - ***VIII is cofactor for IX
55
What is required for both intrinsic / extrinsic paths to function that must be added before testing?
Ca
56
What is cofactor for X in common pathway?
Factor Va
57
Another name for factor II?
Thrombin - activated by X/V complex
58
What does thrombin do?
Break fibrinogen into fibrin which can now bind GP2a/3b on platelets causing them to stick
59
What does factor XIII do?
Activated by thrombin to stabilize thrombin meshwork
60
What is kallikrein? What does it do?
- Activated by factor XII 1. Enhances inflammation by converting HMWK to bradykinin 2. Converts plasminogen to plasmin: plasmin activates C3 turning on complement * **TPA is better at this
61
Functions of bradykinin?
Increased: 1. Pain 2. Permeability 3. Dilation
62
What does antithrombin act on?
1. X | 2. IIa
63
How does heparin work?
Potentiates antithrombin
64
What are the hemophilias and which is more common?
A: VIII deficiency - more common B: IX deficiency
65
Which factors produced by liver?
II, VII, IX, X - Activated in vitamin K dependant process * VIII: made in endothelial cells
66
What is vitamin K necessary for?
Synthesis of: II, VII, IX, X, C, S
67
Enzyme activating Vitamin K and drug that blocks this action?
Vitamin K epoxide reductase: warfarin blocks this action
68
Warfarin Heparin effect monitored by what?
Warfarin: extrinsic Heparin: intrinsic
69
Why do babies get vitamin K shot?
- Important source of vitamin K is enteric flora and babies lack this so they need shot
70
What do proteins C/S do?
Cleave and inactivate factor V/VIII
71
What is factor V leiden?
Having factor V molecules that are resistant to cleavage of factor C and thus you are hypercoagulable
72
What to think if young person with DVT and no risk factors?
Factor V leiden | ***Especially if person is white
73
What is secondary hemostasis?
The process of the coagulation paths with the goals of activating thrombin so that it can convert fibrinogen to fibrin
74
2 important factors of VwF?
1. Bind platelet to collagen | 2. Protect factor VIII
75
What does TXA2 do?
1. Increases aggregation | 2. Constricts to slow down blood
76
What leads to expression of GP2b/3a receptor?
Binding of ADP to platelets
77
Role of COX in platelets?
Generaties TXA2 from arachidonic acid in cell walls
78
What is bernard Soulier?
Deficiency in GP1b receptor | - Platelet can no longer ADHERE to collagen in damaged endothelium
79
When disease has mechanism similar do bernard Soulier?
VwF disease
80
What is ristocetin?
- Induces binding of VwF to GP1b | - If ristocetin test is negative, you are either lacking VwF or its receptor
81
What does negative agglutination test indicate?
- VwF disease | - Ristocetin should induce VwF binding so if test is negative you are missing VwF
82
What is glanzmann's thrombasthenia?
Deficiency of GP2b/3a
83
First thing that occurs when endothelial layer of vessel is damaged?
Vessel constricts mediated by: 1. Endothelin 2. Neural stimulation
84
Where is VwF coming form?
1. Platelets | 2. Endothelial cells - majority
85
What is weibel palade body?
Found in vessel endothelial cell holds: 1. VwF 2. P selectin
86
What is P selectin?
Found in weibel palade body serving as speed bump in atherosclerosis
87
Signs of issues in primary hemostasis?
Mucosal and skin bleeding
88
What are mucosal and skin bleeding indicative of?
Disorder in primary hemostasis
89
Main risk in sever thrombocytopenia?
Intracranial bleeding
90
Petechiae sign of qualitative or quantitative issue with platelets?
Quantity
91
What is increased bleeding time indicative of?
Platelet issues
92
What is ITP?
- Autoimmune disease w/ IgG against platelet antigens: usually IIa/IIIb - IgG is produced by spleen and macs in spleen will eat the bound platelets * ***Since IgG can cross placenta
93
Difference in ITP in kids and adults?
Kids: acute, self resolving after viral Adults:
94
PT/PTT in ITP?
Normal, this is a platelet issue, coagulation cascade has not been touched
95
Last ditch therapy for ITP?
Remove spleen as this is both source of IgG and platelet destruction
96
What is microangiopathic hemolytic anemia?
1. Pathologic formation of microthrombi in small vessels 2. RBCs lysed as they traverse = schistocytes 3. Thrombi formation drops platelet levels
97
2 disorders in which microangiopathic hemolytic anemia is seen?
1. TTP | 2. HUS
98
What is TTP?
"Thrombotic thrombocytopenic purpura" - Caused by decreased in ADAMTS13 increasing VwF multimers - Leads to abnormal platelet adhesion and microthrombi * Can be genetic or autoimmune
99
What does decreased ADAMTS13 cause and why?
TTP - Normally degrades VwF multimers - Since low in disease, multimers aggregate and activate paltelets
100
What is HUS?
"Hemolytic uremic syndrome" Platelet microthrombi caused by endothelial damage from: 1. Drug 2. E-coli 0157
101
Main location of disease process in TTP and HUS?
1. HUS: kidney | 2. TTP: brain
102
What is blood smear with large platelets and and mild thrombocytopenia indicative of?
Bernard Soulier: BS is for "big suckers" Enlarged: immature Low levels: Don't live as long without GP
103
Uremia impact on platelets?
Messes up both adhesion and aggregation
104
What is required for activation of clotting factors?
1. Ca 2. Phospholipid surface: surface of platelets 3. activating substance
105
Signs of problems with secondary hemostasis?
Deep bleeds: 1. Rebleeds after surgery 2. Muscle bleeds 3. Joint bleeds
106
What activates factor XII, VII?
XII: Subendothelial collagen VII: Tissue thromboplastin
107
Disease similar to hemophilia A?
"Coagulation factor inhibitor" - Usually vs factor VIII - Will appear same with increase PTT however factor VIII levels are normal
108
What is the mixing study?
Distinguishes hemophilia A from coag inhibitor: - Mix patient with normal plasma 1. If Hemophilia A: normal VIII in sample corrects and coagulation occurs 2. If inhibitor: donor serum will not correct
109
What is failed mixing study indicative of?
Coagulation factor inhibitor
110
Lab results in VwF diseased?
1. Increased bleeding time: primary disease 2. Increased PTT: remember that VwF also protects factor VIII from degradation and VIII 3. Abnormal ristocetin: ristocetin usually induces VwF function
111
Treatment for VwF disease?
Desmopressin: increase VwF release from weibel palade bodies
112
What is desmopressin used to treat?
VwF disease
113
Another name for warfarin?
Coumadin
114
What is HIT?
"Heparin induced thrombocytopenia" - Hep binds to platelet factor IV on surface - Ptn develops antibodies to this = platelet destruction - Platelet fragments can lead to thrombosis
115
What is DIC?
- Pathologic activation of coag cascade - Forms microthrombi - Consumes platelets and clotting factors
116
When is bleeding from IV sites seen?
DIC
117
How do obstetric complications cause DIC?
- Amniotic fluid contains Tissue thromboplastin with activates factor VII
118
When are Auer rods seen?
Acute promyelocytic anemia
119
Lab findings in DIC?
1. Increased bleeding time 2. Decreased PT/PTT 3. Decreased fibrinogen 4. Increased D dimer
120
3 actions of plasmin?
1. Cleaves fibrin 2. Cleaves fibrinogen 3. Blocks aggregation 4. Destroys clotting factors
121
What inactivates plasmin?
A-2-antiplasmin
122
Risk of radical prostectomy?
- Release of urokinase which activates plasmin
123
Effect on cirrhosis on plasmin?
- Decreased A-2-antiplasmin leading to over activation of plasmin
124
Lab findings in disease of fibrinolysis?
1. Elevated PT/PTT: plasmin cleaves coags 2. Increased bleeding time: plasmin inhibits aggregation 3. Increased fibrinogen split products WITHOUT D dimer: D dimer is from fibrin and not clots are actually present
125
What does aminocaproic acid do?
Treats diseases of fibrinolysis as blocks activation of plasminogen
126
What does PGI2 do?
- Block platelet aggregation | - Released by endothelium
127
What is heparin like molecule?
- Released from endothelial activating antithrombin III | - Inactivates thrombin
128
What is thrombomodulin?
- Anticoag released by endothelium - Takes thrombin and causes it to activate protein C instead of thrombin - C then inactivates V and VIII
129
How do we get elevated homocysteine and what is the risk?
Causes endothelial damage = thrombosis 1. B12/folate deficiency 2. CBS deficiency "cystathionine beta synthase"
130
How does B12/folate deficiency lead to elevated homocysteine?
- Can no longer convert homocysteine to methionine
131
Interaction of B12/folate?
1. Folate enters body as THF and is methylated 2. To work in DNA gives methyl to B12 3. B12 then gives methyl to homocysteine making it methionine = elevated homocysteine
132
Presentation and cause of homocystinuria?
Deficiency in CBS 1. Thrombosis 2. Lens dislocation 3. Long, slender fingers 4. Mental retardation
133
What is following indicative of: 1. Thrombosis 2. Lens dislocation 3. Long, slender fingers 4. Mental retardation
Homocystinuria
134
Function of factor C and S?
Inactive Factor V and VIII | - THink that if you double the S = 8, and if you put the Cs on top of each other you kind of have a 5
135
Associated risk with C/S deficiency?
1. Warfarin skin necrosis | * Also remember that this is just a hypercoagulable state in general as C/S normally inactivate 5/8
136
What happens in Factor V leiden?
Factor V can no longer be inactivated by C/S
137
What is PTT not rising with standard Hep dose seen in?
Antithrombin III deficiency
138
How does heparin work?
Activates antithrombin III
139
Presentation of fat embolism?
1. Petechiael rash on chest | 2. Dyspnea
140
What causes gas embolism and presentation?
Gas embolism: 1. Dyspnea 2. Bone pain - infarct of bone if chronic 3. Muscle pain
141
What is squamous cells and keratin debris in lung indicative of?
Amniotic embolism
142
Does inner or outer rectum drain to inguinals?
Outer
143
What do superficial inguinals drain? Exceptions?
1. Cutaneous from umbilicus down 2. External genitals 3. Anus below dentate Exceptions (deep inguinal): 1. Glans penis 2. Posterior calf
144
Where does upper rectum drain lymph?
Inferior mesenteric
145
Does sickle cell trait present?
No
146
Benefit of sickle cell trait?
Protection from plasmodium falciparum
147
Function of BRCA1/2?
DSDNA breaks
148
Why does blood transfusion cause hypocalcemia?
- Contains citrate which is an anticoag and also chelates Ca | * Ca is required for coagulation pathway so this makes sense
149
Where does VDJ rearrangement occur?
Bone marrow
150
Where does isotype switching occur?
Germinal centers
151
What does isotype switching allow for?
Isotype: changing of IgM to other Igs
152
What does G6PD do in RBCs?
- Maintains NADPH levels - Low NADPH = cannot keep glutathione reduced - Cells at higher risk for damage
153
When is 14:18 translocation seen?
Follicular lymphoma = BCL 2 overexpression, a protooncogene
154
Brain tumor that likes cerebellum?
1. Pilocytic astrocytoma: cystic with nodule on cyst 2. Medulloblastoma "meduloBLUEstoma" - Small and thick
155
Cancer Downs is at risk for?
ALL
156
When is reddish urine that darkens in light seen?
Acute intermittent porphyria
157
What does topoisomerase one / two do?
1: single stranded nicks to relieve supercoil 2: double stranded nicks
158
What is enoxaparin?
LMW heparin
159
What do the oxabans do?
Inhibit factor X: look anti X is in the name
160
Mechanism of aspirin?
Irreversibly inhibits COXI and II
161
What does red pulp of spleen do?
Filters: 1. Old and abnormal RBCs 2. Circulating bacteria
162
What is elevated HBA2 indicated of?
Betathalesemia
163
Mutation in CML?
BCR/ABL 9/22 | ***Causes constitutive kinase activity
164
How do some cancer cell become chemoresistant?
ATP dependent efflux pumps
165
What does P53 do?
Cuase mutated cells to arrest in G1/S
166
Presentation of vincristine toxicty?
Numbness and parasthesias
167
When is 15:17 mutation seen?
AML: mutation in retinoic acid receptor
168
What is wiskott aldrich?
1. Eczema 2. Thrombocytopenia 3. Recurrent infx
169
What is the following indicative of: 1. Thrombocytopenia 2. Eczema 3. Recurrent infx
Wiskott aldrich
170
Problem in spherocytosis?
Problem in RBC cytoskeletal abnormalities | - Usually defects in spectrin or ankyrin
171
Treatment of spherocytosis?
Splenectomy
172
What happens in positive and negative selection?
T cells Positive: bind self antigen = survive Negative: bind self antigen = death
173
What happens to hemoglobin and hematocrit during pregnancy?
- Total body volume greatly increases in pregnancy - Since HgB and hematocrit are [] dependant, these measures will drop - However, total RBC mass is the same and hasn't changed
174
Diagnosis and microcytic / macro anemia?
Micro: MCV 100
175
What is broad problem in microcytic anemia?
- For some reason there is decreased HbB causing erythroblasts to undergo extra division when making RBCs * **They are trying to keep [HgB] per RBC same so divide to make cell smaller to cope with lower HgB in body
176
What is responsible for giving the RBC its color?
HgB
177
What is heme composed of? Globin?
``` Heme: 1. Fe 2. Protoporphyrin Globin: 1. AAs ```
178
Causes of microcytic anemia
1. Low Fe 2. Anemia chronic disease: Fe stuck in macs 3. Sideroblastic anemia: low protoporphyrin 4. Thalassemia: decreased globin
179
Disease with decreased globin?
Globin: Thalassemia Protoporphyrin: Sideroblastic
180
What are heme and nonheme Fe?
Heme: from meat, > absorption | Non heme: plant
181
Where is Fe absorbed?
``` Duodenum "Iron First Bro" Iron Folate B12 ```
182
How is Fe absorbed from Gut?
- Enterocyte takes up Fe from gut and uses ferroportin to send it into blood if needed
183
What is ferroportin?
"When you look at the 'portin' use that to remember its a transporter" - Transporter in enterocyte that moves Fe from gut into blood
184
What is transferrin?
- Binds Fe in blood taking in from ferroportin and either takes it to liver or macs for storage
185
How is Fe stored?
- In cells bound to ferritin
186
That does TBC tell us?
- How much transferrin is in blood
187
Cause of Fe Deficiency anemia in adults in developing world?
- Hookworms
188
Fe2+ or 3+ more readily absorbable? How is 2 maintained
- 2+, think "Fe2 goes IN TWO the body" | - Acidity keeps Fe in 2+ state
189
How does gastrectomy lead to Fe anemia?
1. Stomach is a very acidic place 2. Acid keeps Fe in 2+ from 3. 2+ is more absorbable * **Thus, if we remove stomach and its acidic environment, we have more Fe3+ which is more absorbable
190
Relation to Ferritin and TIBC?
Inverse: 1. When ferritin goes up, TIBC goes down 2. When ferritin down, TIBC up * **Makes sense because if ferritin is low, Liver will realize body needs more Fe so will make more transferrin thus increasing TIBC
191
What is the first stage of Fe deficient anemia?
Normocytic: marrow wants to make normally pretty RBCs so will make them with normal Fe in then, but will just make fewer for them - Eventually this becomes microcytic
192
What is koilonychia?
"Spoon shaped nails" | - Seen in Fe deficient anemia
193
What is FEP?
"Free erythrocyte protoporphyrin" - Increased in Fe deficient anemia - Makes sense as normal proto but low Fe, so some proto in HgB will be unbound
194
Explain anemia of chronic disease?
- Hepcidin is an acute phase reactant which sequesters Fe into storage to bacteria can't use - Thus, macs can't give to erythroblasts - Hepcidin also suppresses EPO
195
What is hepcidin?
- Acute phase reactant responsible for anemia chronic disease as it functions to: 1. Sequester Fe to save from bacteria 2. Decrease EPO production
196
What is sideroblastic anemia?
- Defect in protoporphyrin synthesis = microcytic anemia
197
Steps in protoporphyrin synthesis?
1. Succinyl CoA converted to aminolevulinic acid (ALA): ALA synthase catalyzes - Rate limiting step with B6 as cofactor 2. ALA -> porphobilinogen: ALA-dehydrogenase ...... 10. Fe joined to protoporphyrin by ferrochelatase: occurs in mitochondria
198
Importance of B6 in sideroblastic anemia?
- B6 is cofactor for ALAS which converts SCoA into ALA: rate limiting step
199
What does ferrochelatase do?
Joins Fe to protoporphyrin
200
Mitochondrial significance on sideroblastic anemia?
1. Sidero is problem with protoporphyrin synthesis 2. Ferrochelatase combines Fe and proto in mitochondria of erythroblast 3. If mitochondria not making enough proto, Fe will still be entering cell and accumulate in mitochondria ringing nucleus "Ringed sideroblasts"
201
Normal cause of sideroblastic anemia?
Defect in ALAS: converts SuccCoA -> ALA which is rate limiting step in protoporphyrin synthesis
202
Acquired causes of sideroblastic?
1. Lead: denatures ALAD and ferrochelatase 2. Alcohol: mitochondrial poison 3. Deficient B6: ALAS cofactor
203
When is B6 deficiency seen?
Isoniazid treatment
204
What does Isoniazid treatment predispose for?
- B6 deficiency = sideroblastic anemia as B6 is cofactor for ALAS which is rate limiting enzyme in protoporphyrin synthesis
205
What findings in sideroblastic?
``` This is an Fe overloaded state: "imagine that as the Fe is accumulating and ringing the nucleus, it is leaking out into blood" Ferritin: increased TIBC: decreased Serum Fe: Increased % Sat: increased ```
206
What is thalassemia?
Decreased production of globin chains = decreased HbB = microcytic anemia
207
What are carriers of thalassemia protected against?
- Plasmodium falciparum
208
2 types of thalassemia?
Alpha: decreased A chains Beta: decreased B chains
209
Difference in HbA and HbA2?
HbA: 2 alpha and 2 beta chains HbA2: 2 alpha and 2 delta chains
210
Is the alpha or beta globin chain more important?
Alpha: is present in fetal, HbA, and A2 | - Beta chain is only present in HbA
211
Genetics of A-thalassemia?
- There are 4 alpha alleles on chromosome 16 | - DELETION leads to varying degrees of A thalassemia
212
Degrees of A-thalassemia?
1. 1 allele: asymptomatic 2. 2 alleles: cys or trans 3. 3 alleles: severe anemia HbH damages RBC
213
Explain cis and trans A thalassemia?
4 alleles for A chain on chromosome 16 Cys: knock out 2 alleles on some chromosome 1. Worse: can pass both to offspring 2. Seen in asians Trans: knock out 2 alleles on diff chromosome 1. Seen in africa 2. Less severe: lower risk of passing to offspring
214
What occurs in A-thalassemia with 3 alleles?
- B chains form tetramers (HbH) that damage RBCs | - Fetal HgB does not show issues
215
What is HbH?
- Tetramer of B globin seen in A thalassemia with 3 allele deletion - Damages RBCs - Not present in fetus
216
Genetics of beta thalassemia?
- 2 alleles on chromosome 11 - Due to MUTATIONS (A was due to deletion) 1. Beta null: one allele cant produce any 2. B+: decreased from one allele
217
What are target cells?
Blebs of hemoglobin in normally concave /pale central RBC 1. Decreased cytoplasm 2. Increased membrane * **Think like deflating basketball making its surface more malleable
218
What is B thalassemia minor?
- One normal B allele and one B+ - Slightly decreased HbA - Slight increase HbA2 (delta for beta)
219
What si B thalassemia major?
- Double B null - Fetal HbG is protective at birth - Rapid regression after - Alpha tetramers damage RBCs - Massive erythroid hyperplasia: in other organs
220
Which anemia is massive erythroid hyperplasia seen in? Presentation?
B Major 1. Expansion of skull and facial bones: "crew cut appearance on Xray" 2. HSM: spleen starts making again
221
When are circulating RBCs seen?
B major: being made in places other than marrow allowing nucleated cells to sneak out
222
2 most common causes macrocytic anemia?
1. B12 | 2. Folate
223
Broad problem in macrocytic anemia?
- Cells undergo one LESS division due to lack of DNA precursors
224
What takes methyl group from THF so it can participate in DNA synthesis?
B12 - B12 then gives methyl to homocysteine
225
What takes methyl group from B12?
Homocysteine - becomes methionine once it receives the methyl group
226
Presentation of B12/folate deficiency?
1. Megaloblastic anemia 2. HYPERsegmented neuts 3. MEGALOblastic change in all dividing cells: ie, epithelial cells of gut would be larger
227
Other cause of macrocytic anemia?
1. Alcohol 2. Liver disease 3. Drugs - 5 fu
228
Where is folate found?
- Green vegetabls and fruits | - Absorbed in jejunum "Iron First Bro"
229
How does methotrexate cause megaloblastic anemia?
Inhibits dihydrofolate reductase = folate deficiency
230
Presentation of folate deficiency?
1. Glossitis 2. Increased homocysteine 3. Normal methylmalonic acid: B12 converts this to succinyl CoA 4. Hypersegmented neuts
231
In megaloblastic anemia, what does normal methylmalonic acid tell us?
- B12 levels are normal: B12 converts this to succinyl CoA
232
What is R binder?
- Protein made by salivary gland to bind B12 in mouth - Cleaved in SI by proteases allowing to bind IF` from parietal cells in stomach - Absorbed in ileum when bound to IF
233
Folate of B12 deficiency take longer to develop?
B12: Body has very low folate stores | *There are large stores of B12 in liver
234
Cause of low B12 other than pernicious?
1. Pancreatic insufficiency: no R binder cleavage 2. Ileal damage in crohn's 3. Diphyllobothrium latum
235
Dietary cause of low B12?
Vegans
236
When is glossitis seen?
1. Plummer vinson | 2. Megaloblastic anemia
237
When is methylmalonic acid elevated?
B12 deficiency as B12 converts to succinyl CoA
238
What causes subacute combined degeneration? How?
B12: methylmalonic acid builds up in myelin of spinal cord
239
2 main classes of normocytic anemia?
1. Underproduction: low retic | 2. Peripheral destruction: normal retic
240
What do reticulocytes look like?
- Bigger than normal | - Slightly blue cytoplasm: RNA still in cytoplasm
241
What is normal retic count?
1-2% | - If there is anemia and marrow works, should be >3%
242
Why is retic falsely elevated in anemia?
- Retics are measured as % of total RBC - Anemia = low RBCs = inaccurate calc * *Need to adjust
243
How is the retic adjusted?
Multiply by hematocrit / 45
244
Where are RBCs destroyed in extravascular hemolysis?
RES system: 1. Liver 2. Lymph nodes 3. Macs in spleen
245
What does protoporphyrin become?
Unconjugated Bilirubin
246
Presentation of extravascular anemia?
1. Splenomegally 2. Unconjugated jaundice: liver can't keep up w/ spleen 3. Bili stones 4. Hyperplastic marrow
247
What is haptoglobin?
- When RBCs destroyed in vessels, haptoglobin binds HgB and takes it to spleen
248
Lab findings in intravascular hemolysis?
1. Decreased haptoglobin 2. Hemoglobinuria 3. Hemosiderinuria: Fe in tubular cells eventually is sloughed off into urine 4. Hemoglobinemia
249
What is going on in spherocytosis?
- Normally, cytoskeleton is anchored to membrane via ankyrin and spectrin giving RBC its its biconcave shape - Tethering is lost in sphero, leading to blebs coming off and transition to sphere shape
250
Why does spherocytosis cause anemia?
- Loss of biconcavity prevents spherocytes from moving through spleen - Spleen eats them = anemia
251
What is MCHC and when is it seen?
"Mean corpuscular hemoglobin []" | - Increased in spherocytosis as cell is shrinking in size as it blebs leading to greater []
252
Diagnosis in spherocytosis?
- Increased fragility in hypotonic solution in osmotic fragility test
253
Treatment of spherocytosis?
Splenectomy: RBCs still work fine spleen is just eating them 1. Howell Jolly bodies will still be seen
254
What are howell jolly bodies?
RBCs that still have a bit of nucleus left in them - Normally is spleens job to remove these but if spleen is gone you will see these * Appear as RBC with little blue spots in them
255
What causes sickle cell?
- Mutation in B chain of HgB replacing glutamic acid (hydrophilic) with valine (hydrophobic)
256
How does HbS causes disease?
- Polymerizes into needle like sickle cells when deoxygenated / stressed
257
How does hydroxyurea help in sickle cell?
HbF is protective in sickle cell | - Hydroxyurea causes this to form
258
Is sickle intra or extravascular?
Both: spleen eats them and some also rupture iin the vessels
259
What does sickle form target?
- Membrane damage dehydrates cell cytoplasm - This makes the basketball effect we talked about before where the membrane is now malleable - HgB can now move to center of cell making int darker instead of the area of pallor
260
What is dactylitis?
1. Swelling of bones in hands / feet due to vaso occlusive infarcts of bones * Common presentation of sickle cell in kids
261
What type of infx at risk for if now spleen?
1. Encapsulated organisms | 2. Salmonella paratyphi osteomyelitis
262
Most common cause of death in sickle?
1. Kids: encapsulated orgs | 2. Adults: acute chest syndrome
263
What does sickle do to kidney?
Renal papillary necrosis | - Hematuria and proteinuria
264
Where does sickle cell trait usually present?
Renal medulla: very hypoxic and hypertonic which promotes sickling - Leads to microinfarcts, microalbumin, and inability to [] urine
265
What does metabisulfite do?
Used to diagnose sickle cell trait | - Forces cells to sickle when added
266
How much HbA is there in sickle cell?
Zero: HbA is 2 alpha and 2 beta | - In sickle the issue is with both alleles of the beta chain so we have no beta
267
What is hemoglobin C disease?
- B globin mutation of glutamic acid for lyCCCCine | - Less severe with HbC crystals seen in smear
268
What are MIRL and DAF?
Both found on surface of RBC and serve to inactivate complement when it comes close to RBC: DAF: "Decay accelerating factor" MIRL: "Membrane inhibitor of reactive lysis" ***Both connected to RBC surface by GPI
269
What is GPI?
Connects both DAF and MIRL to RBC membrane protecting them from complement - Is deficient in PNH
270
What happens to acid base status at night? How does it cause PNH?
- Breathe shallow increasing CO2 creating respiratory acidosis in body - Acidosis can activate complement and this is what happens in PNH - Wake up with dark urine as activation of complement leads to RBC lysis
271
What is PNH?
"Paroxysmal nocturnal hemoglobinuria" - Defect in GPI = no DAF / MIRL to protect RBCs from complement activation caused by respiratory alkalosis while we sleep
272
How do we screen for PNH?
1. Place sucrose in serum to activate complement then check for lysis 2. Do same with acid 3. Screen for DAF / CD55
273
What other disease is at risk in PNH?
AML: makes sense as PNH is problem with myeloid precursors just like AML
274
How do RBCs protect selves from oxidative stress?
- Glutathione reduces free radicals and is oxidized - To used oxidized glutathione again, must be reduced by NADPH - G6PD is required to created NADPH
275
What does G6PD do?
Produces NADPH so glutathione can be reduced so cell can continue to protect self from oxidative stress
276
What is issue with G6PD in disease?
Has a reduced half life, 2 types: African: mildly reduced Mediterranean: greatly reduced = cells die much younger
277
What causes GRPD to manifest?
1. Sulfa drugs 2. Primaquine 3. Dapsone 4. Infections 5. Fava beans
278
Disease process in G6PD?
- Oxidative stress causes HgB to precipitate as heinz bodies - Spleen eats heinz bodies = bite cells
279
Presentation of G6PD?
1. Hemoglobinuria | 2. Back pain
280
What happens in IgG Hemolysis?
Extravascular hemolysis - IgG coats RBC, splenic macs eat it off - Spherocytes now form - IgG is bound in warm central body
281
IgG or IgM warm / cold?
IgM: cold, distal body, intravascular IgG: warm, central body, extravascular
282
When is cold agglutination seen?
1. Mycoplasma pneumonia | 2. Mono
283
What does coombs test diagnose?
Hemolytic anemia: | 1. Direct: presence of Ig on RBC
284
How does direct coombs work?
1. Anti IgG added to serum | 2. Will agglutinate if RBC is coated
285
What does indirect coombs do?
Does patient have IgG in serum 1. Anti IgG and test RBCs mixed with serum 2. Will agglutinate if patient had IgG in serum
286
Parvo B19 effect on RBCs?
- Hurts RBC progenitors halting erythropoiesis | - Anemia if already marrow stress
287
What is aplastic anemia?
- Damage to HSC = pancytopenia with low retic
288
2 useful uses of desmopressin?
1. Increase factor VIII and VwF in hemophilia A and VwF disease 2. Water resorption in diabetes insipidus
289
What does VwF increase stability of?
Factor VIII
290
Presentation of platelet issues?
1. Prolonged bleeding time 2. Easy bruising 3. Mucosal bleeding
291
What are metalloproteinases?
Zinc enzymes that degrade ECM allowing for tumor invasion
292
What is PD1?
"Programmed death receptor" - Found on surface of T cells - When bound by its ligand leads to cell death - If blocked can help cell fight cancer
293
Type of drug to treat chemo vomit?
5HT blocker
294
HSC marker?
CD34+
295
What do myeloblasts become?
1. Neuts 2. Basos 3. Eos
296
How do treat chemo induced neutropenia?
1. GCSF | 2. GMCSF
297
How would infection cause neutropenia?
Most neuts will be out of blood and in tissue in sever infx so they would not be measured on a blood test
298
What is not developed in digeorge?
3/4 pharyngeal pouch: lymphopenia as no thymus
299
How does cortisol cause lymphopenia?
Induces apoptosis in lymphocytes
300
Cell in body most sensitive to radiation?
Lymphocytes
301
2 things causing neutrophilic leukocytosis?
1. Tissue necrosis | 2. Bacterial infx
302
What is a left shift?
Immature neuts in blood: characterized by decreased FC receptors that would recognize Ig so they dont function as well
303
What does decreased CD16 mean?
Immature neuts in blood as this is for FC receptor
304
Marker for immature neuts?
Decreased CD 16
305
Cortisol impact on neuts?
Disrupts adhesion of marginated cells attached to vessels causing them to enter serum = neutrophilia
306
3 scenarios for eosinophilia?
1. Parasitic infx 2. Allergy 3. Hodgkin's lymphoma: caused by increased IL5
307
When is basophilia seen?
CML
308
Change in cell count in CML?
Basophilia
309
Change in cell count in CML?
Basophilia
310
Cells responsible for viral infx?
CD8
311
Bordetella pertussis impact on blood count?
Lymphocytosis: clocks T cells from leaving blood to enter nodes so count goes up
312
Mono impact on cell count?
Lymphocytosis of CD8
313
What is found in cortex and paracortex of nodes?
Cortex (outer most) - B cells | Paracortex - T cells
314
What is periarterial lymphatic sheath?
Area surrounding artery in spleen where T cells are found | - Area responsible for splenomegaly in mono
315
What does the monospot test do?
- Detects heterophile IgM antibodies seen in mono * **Does not detect CMV - Need to follow up test with test for EBV viral capsid antigen
316
What happens if you give penicillin to mono patient?
- Get a rash
317
What is hallmark of acute leukemia?
- MyeloBLASTS and lymphoBLASTS cannot mature to begin to pile up * **> 20% blasts in marrow is diagnostic
318
Acute presentation of leukemia?
1. Blasts are pushing out other cells in marrow: a. Anemia b. Thrombocytopenia c. Neutropenia 2. High blast count in serm
319
Blasts on histo?
Large basophilic cell with punched out nucleus (nucleolus)
320
Difference between AML and ALL?
ALL: Accumulation of LYMPHOblasts AML: accumulation of MYELOblasts
321
What is TDT positivity indicative of?
LYMPHOblasts: DNA polymerase only found in there nucleus
322
How to tell LYMPHOblast from MYELOblast?
AML: MPO+ = AUER rods ALL: TDT+
323
What is MPO positivity indicative of?
AML - in crystallized form becomes auer rod
324
When are auer rods seen?
AML - this is crystallized MPO on staining
325
Common person ALL found in?
> 5 yo kid with Down syndrome
326
Cancer seen in > 5 yo kid with Down syndrome?
ALL
327
How to tell B-ALL from T-ALL?
BOTH are TDT positive: B-ALL: CD 10, 19 20 T-ALL: CD2 - 8 (think T cells are usually 4 and 8)
328
What are the following markers for CD 10, 19 20?
B-ALL
329
B-ALL treatment?
Great response to chemo with prophylaxis needing for scrotum and CSF - think, BALL affects your BALLS - Chemo cannot cross barriers here so needs to be injected
330
Translocations in BALL?
19 - 21: kids, good prognosis | 9 - 22: Adults, poor prognosis
331
Cancer with CD 2 - 8 markers?
TALL
332
Presentation of TALL?
TTTHymic mass in TTTTeenager | ***Actually called a lymphoma since there is a mass whereas a leukemia means cancer is in serum
333
Common mutation in AML?
15 - 17 translocation | - RAR disruption = promyelocytic accumulation
334
What is 15 - 17 translocation seen in?
AML
335
Treatment for AML?
All trans retinoic acid causes cells to mature "ATRA"
336
What is ATRA treatment for?
AML
337
What should you think if patient has cancerous swelling of gums?
Acute MONOcytic leukemia
338
Cancer in down > 5 yo?
5: ALL
339
What are myelodysplastic syndromes?
CYTOpenias with Hypercellular bone marrows that can cause leukemias arising in background of radiation
340
What is chronic leukemia?
Malignant proliferation of MATURE circulating LYMPHOcytes | - Characterized by high WBC count
341
What is CLL?
- Proliferation of Naive B cells - Express CD 5 and 20 - Increased lymphocytes and smudge cells seen on smear
342
What is CD 5/20 indicative of?
CLL
343
When are smudge cells seen?
CLL
344
Complications of CLL?
1. HYPOgammaglobulinemia: B cells are not maturing to secrete Ig as they should * Most common cause of death = infx 2. Autoimmune hemolytic anemia: B cells are making messed up Ig that is attacking self 3. Transform to diffuse large B cell lymphoma
345
What is hairy cell leukemia?
- Malignant proliferation of mature B cells - TRAP positive - Hairy cytoplasmic processes
346
What is TRAP + indicative of?
Hairy cell leukemia, think "Look out, its a hairy TRAP!!!!!!!!"
347
Hairy cell presentation?
1. Splenomegally in red pulp: atypical 2. Absent lymphadenopathy 3. Dry tap on marrow aspiration Think, they are TRAPPED in spleen so can make it nodes or marrow
348
Hairy cell treatment?
2-CDA: adenosine deaminase inhibitor causing adenosine to accumulate to toxic levels in B cells
349
What is ATLL?
"Adult T cell leukemia / lymphoma" - Neoplasm of Mature CD4+ T cells - HTLV1 association in caribbean and japan
350
Cancer to think if HTLV1?
ATLL "Adult T cell leukemia / lymphoma"
351
Presentation of ATLL?
1. Rash: T cells like to go to spleen 2. Lymphadenopathy 3. Splenomegally 4. Lytic bone lesions and HYPER Ca
352
Blood cancer with lytic bone lesions?
ATLL
353
What is mycosis fungoides?
- Neoplasm of mature CD4+ T cells presenting with: 1. Skin rash, plaques, nodules 2. Pautrier microabscesses in skin 3. Sezary syndrome: cerebriform nuclei on smear
354
When are Pautrier microabscesses seen?
Mycosis fungoides
355
When is cerebriform nuclei on smear seen?
Mycosis fungoides
356
What is a myeloproliferative disorder?
- Accumulation of mature myeloid cells | - All myeloid cells are increased but classified on dominant form
357
Associated risks in myeloproliferative disorders?
1. Hyperuricemia / gout: developing lots of cells so turning over rapidly 2. Marrow fibrosis 3. Transform to acute leukemia
358
What is end result of purine degradation path?
Uric acid
359
What is CML?
"Chronic Myeloid leukemia" - Predominant proliferation of granulocytes - Basophils are characteristically overproduced
360
Mutation in CML?
- 9/22 BCR/ABL fusion = increased TK activity
361
What is imatinib treatment for?
CML
362
How to treat CML?
- Imatinib: blocks overexpressed TK activity
363
Worst CML complication?
Transformation to acute leukemia: AML or ALL
364
3 ways to distinguish CML from leukemoid rxn:
Leukemoid is natural increase granulocyte to infx. In CML we have: 1. LAP negative granulocytes 2. 19/22 translocation 3. Increased basophils
365
What is polycythemia vera?
Neoplastic proliferation of RBCs - Granulocytes and platelets also increased - JAK2 kinase mutation seen
366
What is JAK2 mutation seen?
1. Polycythemia vera 2. Essential thrombocythemia 3. Myelofibrosis
367
Symptoms of polycythemia vera?
Hyperviscosity of blood: 1. Blurry vision and headache 2. Thrombosis: bud chiari 3. Flushed face 4. Itching after bathing: mast cells degranulate in hot water
368
When is itching after bathing seen?
Polycythemia vera: mast cells degranulate in hot water
369
Most common cause of budd chiari?
Polycythemia vera
370
Treatment for polycythemia?
1. Phlebotomy | 2. Hydroxy urea
371
What is hydroxyurea used to treat?
Polycythemia vera | *Also useful in sickle cell as it causes HbF to form
372
Characteristics of reactive lung disease from polycythemia?
1. Low O2 | 2. Increased EPO
373
Mutation in essential thrombocythemia?
JAK2 kinase
374
What doesn't thrombocythemia not have risk for gout/hyperuricemia?
- Platelets do not have nucleus so not creating uric acid via purine degradation path when being demolished
375
What is myelofibrosis?
- Neoplastic proliferation of megakaryocytes - JAK2 mutation - Are secreting excess PDGF = marrow fibrosis
376
What is fibrosis of marrow seen in?
Myelofibrosis: driven by JAK2 mutation in megakaryocuytes
377
When is leukoerythroblastic smear seen?
Myelofibrosis: - The marrow is shot so extramedullary creation of cells occurs - Places outside of marrow cannot filter immature cells so we are seeing blasts of all types in the smear
378
When are tear drop cells seen?
Myelofibrosis
379
What is multiple myeloma?
- Malignant growth of PLASMA cells in bone marrow | - High IL6 often seen: important plasma cell growth factor
380
What is high IL6 indicative of?
Multiple myeloma: important plasma cell growth factor
381
What does multiple myeloma cause back pain with hyper Ca?
- Plasma cell releases osteoclast activating factor which turns on RANK on the osteoclasts - Lytic lesions seen in vertebrae and skull - Increased risk of fracture
382
Multiple myeloma presentation?
1. Increased fracture risk 2. Lytic bone lesions 3. Hyper Ca 4. Risk for infx: Increased Ig lacks antigen diversity 5. Primary AL amyloidosis: plasma overproduces light chain 6. Proteinuria: bence jones proteins 7. Renal failure: same as above
383
What does electrophoresis look like in multiple myeloma?
"M Spike" monocolona Ig - Spike in gamma region from increased IgG * **Most commonly is IgG or IgA
384
When is rouleaux formation seen?
Multiple myeloma from increased Ig causing RBCs to aggregate
385
When are bence jones proteins seen?
Multiple myeloma: these are the same excess light chains being excreted that are causing the amyloidosis
386
What to think if M spike seen but not other myeloma features?
MGUS "Monoclonal gammopathy of unexplained significance"
387
What is waldenstrom macroglobulinemia?
- B cell lymphoma with monoclonal IgM
388
What are langerhans cells?
Dendritic cells of skin
389
What is langerhans cell histiocytosis?
1. Neoplastic langerhan cell proliferation 2. Birkbeck / tennis racket cells on EM 3. CD1a/s100 positive
390
When are Birkbeck / tennis racket cells seen?
Langerhans cell histiocytosis
391
When are CD1a/s100 positive cells seen?
Langerhans cell histiocytosis
392
What is eosinophilic granuloma?
Benign proliferation of langerhan cells in bone | - Pathologic fracture in kid with no skin involvedment
393
What to think when pathologic fracture in kid with no skin involvement?
Eosinophilic granuloma
394
When are painful and painless lymphadenopathy seen?
Painful: acute infx being drained Painless: chronic infx, cancer, lymphoma
395
When are lymph node follicles enlarged?
1. RA | 2. Early HIV
396
When are lymph node para cortexes enlarged?
Viral infx: this is where T cells live
397
When are sinus histiocytes of nodes enlarged?
Draining tissue with cancer
398
What lives in medulla, cortex, and paracortex of LN?
Cortex: B cells Paracortex: T cells Medulla sinus histiocytes
399
What is lymphoma?
Proliferation of lymphoid cells that forms a mass | - Can be in node or outside
400
2 major types of lymphoma?
1. Hodgkins: 40% | 2. Non hodgkin's: 60%
401
Where is mantel found?
- Surrounds follicles which are found in cortex
402
Where is marginal zone found?
Surrounding mantle zone with surrounds the follicle which is found in cortex
403
3 lymphomas arising from small B cells?
1. Follicular 2. Marginal 3. Mantle
404
What is CD20 marker for?
B cells
405
What is follicular lymphoma?
- CD20 B cells making follicle like nodules | - Painless generalized lymphadenopathy throughout body
406
Genetics of follicular lymphoma?
- 14:18 translocation of heavy chain / BLC2 | - IgH is highly expressed so BCL2 now is overexpressed
407
What does BCL2 do?
- Stabilizes mitochondrial membrane preventing cytochrome C from leaving and killing - Overexpressed in follicular lymphoma = indestructible self reactive B cells which no longer can be killed
408
When is 14:18 translocation of BLC2 seen?
Follicular lymphoma: BCL2 stabilizes mitochondrial membrane preventing cytochrome C from leaving - Indestructible self reactive B cells which no longer can be killed
409
Follicular lymphoma treatement?
Rituximab: anti CD20 Ig
410
How to distinguish follicular lymphoma from hyperplasia seen in rxn to normal infx?
1. BCL2 expression in follicles 2. Monoclonality: polyclonal expansion is seen in infx 3. Lack of tingible body macs in germinal centers: you expect to see macs if infx
411
What is mantle cell lymphoma?
- Neoplastic CD20 B cells expand in mantle zone "area immediately adjacent to follicle"
412
Mutation driving mantle cell lymphoma
- 11:14 translocation placing Cyclin D next to IgH | - Overexpression of cyclin D allows cells to move from G1 - S phase when they should not
413
Where is the Ig Heavy chain found?
Chromosome 14
414
What does cyclin D do?
Help cell move from G1 - > S phase
415
Is marginal zone always present in LN?
- No, when there is infx and germinal centers form the marginal zone forms
416
What is marginal zone lymphoma associated with?
1. Hashimotos 2. Sjogren's 3. H pylori
417
2 forms of Burkitt lymphoma?
African: jaw mass Sporadic: abdominal mass
418
Burkitt's genetics?
- 8:14 translocation of cMYC oncogene which promotes cell growth - Starry sky appearance on histo
419
When is starry sky appearance seen?
Burkitt's
420
What is diffuse large B cell lymphoma?
- Large B cells that grow diffusely in sheets - Most common NHL - Very aggressive
421
What occurs in hodgkin's lymphoma?
- Reed sternberg cells secrete cytokines that dram in inflammatory cells leading to mass
422
What are reed sternberg cells?
- Found in hodgkin's lymphoma - CD15/30 + - Large B cell with prominent nucleoli and multilobed nuclei
423
What cell is CD15/30?
Reed sternber
424
Presentation of nodular sclerosis?
- Enlarging cervical/mediastinal node in young female | - Fibrosis dividing nodes with RS cells in lacunar areas
425
Lymphocyte rich or depleted have better prognosis?
Rich
426
What does IL5 do?
Call in eosinophils
427
When are Bite cells seen?
X linked G6PD deficiency
428
Inheritance of enzymes and proteins?
Enzymes: recessive Proteins: autosomal dominant
429
When are acanthocytes seen?
1. Liver disease | 2. Abetalipoproteinemia
430
When are target cells seen?
``` "HALT" when you reach the target Hemoglobin C disease Asplenia Liver Disease Thalassemias ```
431
When are Heinz bodies seen?
Heinz G6PD deficiency, which the spleen taking a bite out of them
432
2 main categories of microcytes?
1. Problem making heme | 2. Problem making globin
433
When is basophilic stippling seen?
Lead poisoning
434
How to treat lead poisoning?
1. Dimercaperil 2. EDT 3. Succinyl CoA
435
What to give in patient low in clotting factors?
Fresh frozen plasma`
436
What is cryoprecipitate?
Factor VIII, XIII, VwF, fibrinogen
437
What does TNF-alpha do?
Responsible for cachexia seen in cancer: causes appetite suppression and increased BMR which makes senses when you think about symptoms
438
What is start codon in translation?
AUG - "translation starts in august"
439
What does rituximab do?
Target surface CD120
440
Signs of carcinoid?
1. Flushing 2. Bronchospasm 3. Watery Diarrhea 4. Right heart valve plaques
441
What is increased 5 HIAA in urine indicative of?
Carcinoid: this is a metabolite of 5HT - think that they both start with 5 H so makes sense that is metabolite
442
Lab studies in hemolytic anemia?
1. Increased LDH | 2. Decreased Haptoglobin
443
Importance of folic acid in DNA synthesis?
Carbon donor required for purine and pyrimidine synthesis
444
Inheritance of G6PD?
X recessive
445
Mechanism of allopurinol?
Xanthine oxidase inhibitor
446
What does RB do and how is it regulated?
Regulates G-> S transition - Dephosphorylated: active, cell cant progress - Phosphorylated: inactive, done by cyclins, cell progreses
447
What reduces hemorrhagic cystitis seen in chemo?
MENSA
448
KRAS, APC, BRCA1, RB oncogene or tumor suppressor?
``` KRAS: Proto oncogene APC: suppressor BRCA1: suppressor RB: suppressor TP53: suppressor ```
449
Function of MYC?
Oncogene that is a transcription activator
450
Which opioid side effects do not go away?
1. Constipation | 2. Miosis
451
Disease process in inflammatory breast cancer?
- Cancer cells obstructing lymphatic draining to breast leading to peau d'orange presentation
452
What is fibronectin responsible for?
Cell adhesion
453
When is FFP administered?
Warfarin OD
454
Treatment of warfarin OD?
FFP | - K also works but takes days
455
Treatment of heparin OD?
Protamine sulfate | *****FFP does not work as it contains ATIII which will potentiate warfarin
456
What do POL gene mutations convey?
In HIV, this conveys proteases that are resistant "paul the black smith" - Also can render reverse transcriptase resistant