Heme/Onc 2 Flashcards
Cause of infectious mononucleosis (aka mono)
EBV
Symptoms of mono
Sore throat Malaise Lymphadenopathy Myalgias Splenomegaly Fever
What is seen on a peripheral blood smear of someone with mono?
Atypical lymphocytes —- activated CD8+ cytotoxic T-lymphs
They destroy virally infected B-lymphs — you see them ‘conforming’ to the border of a neighboring cell
I like to think it looks like they’re eating them OM NOM NOM
Describe the histo characteristics of reticulocytes
- Bluish cytoplasm (basophilic)
- rRNA precipitates
- all seen on Wright-Giema stain
- Slighly larger than mature RBCs
No mitos, nucleus, golgi, histones!
These are released into the bloodstream after tx for iron deficiency anemia (think super fast production so they don’t have time to mature in the BM)
Describe the spleen of a young adult with sickle cell disease
- After repeated splenic infarctions => splenic atrophy and fibrosis
- Think continual vasoocclusion
What are classic causes of megaloblastic anemia (think macrocytic w/ impaired DNA synthesis)?
- Vit B12 deficiency
- Folic acid deficiency
Pts w/ sickle cell and other chronic hemolytic anemias are predisposed to these b/c of increased erythrocyte turnover
What is ristocetin?
Activates vWF => binds GpIb
Ristocetin aggregation test measures in vitro vWF dependent platelet aggregation
Doesn’t work in vW disease or Bernard-Soulier Syndrome (deficiency GpIb receptors)
p53
- Tumor suppressor gene
- Controls cell division and apoptosis
Inactivated in many tumors!
Aplastic anemia
- Pancytopenia
- Low retic count
- Absent splenomegaly
- No lymphadenopathy
- Fat cells and stroma in bone marrow biopsy
Clinical
- Easy bruising
What’s the first thing you want to rule out when a pt comes in w/ findings for iron deficiency anemia?
BLOOD LOSSSSSS!
Especially occult loss from GI tract
What are the two most common cerebellar tumors (and brain tumors) in children?
1) Pilocytic astrocytomas
2) Medulloblastomas
How do you differentiate between pilocytic astrocytomas and medulloblastomas?
Get an MRI:
- Meds are only solid
- PAs are solid and cystic (come up white - liquid)
Both in cerebellum
What are the most common cancers in women? Excluding skin cancer
1) Breast
2) Lung
3) Colon
Mortality
1) Lung
2) Breast
3) Colon
What is increased in aplastic anemia?
Erythropoietin levels
What type of necrosis do you see in TB?
Caseous
Caseating granulomas of TB contains which type of immune cell?
- Large epithelioid macros
- Have pale pink granular cytoplasm
- Surface marker CD14 at periphery
CD14 is associated w/ all monocyte/macrophage cell lineage
Name the classes of adhesion molecules
- Integrins
- Cadherins
- Selectins
- Ig superfamily
How do integrins interact to ECM?
Bind collagen, fibronectin, and laminin
Argatroban
- Binds directly to thrombin active site
- Prevents conversion of fibrinogen to fibrin
Used to treat heparin-induced thrombocytopenia
Western blotting identifies…
Proteins
Northern blotting identifies…
specific RNA sequences
Southern blotting identifies…
specific DNA sequences
Which 2 substances drive angiogenesis?
- Vascular endothelial growth factor (VEGF)
- Fibroblast growth factor (FGF)
Raltegravir
- Integrase inhibitor
- Disrupts HIV genome integration into host cell’s chromosomes
- Therefore => it prevents host cellular machinery from being used to synthesize HIV mRNA
Pol gene mutations
- Happens due to HIV drug resistance
- These mutations create acquired resistance to HIV reverse transcriptase inhibitors and HIV protease inhibitors
What is methemoglobin?
Formed when Fe++ (ferrous) in heme is oxidized to Fe+++ (ferric)
Results from drug exposures (dapsone, nitrites), enzyme deficiencies, and hemoglobinopathies
Labs of CO poisoning
- Elevated carboxyHb
- Normal PaO2
- Normal methemoglobin
Life cycle of a B cell
- Precursors proliferate and mature in bone marrow
- Mature B cells migrate to lymphoid organs/peripheral tissues => exposed to Ags
- At first exposure => clone activated
- Some activated clones differentiate into plasma cells that release IgM (T-cell independent)
- Most activated clones go to lymphoid follicles (in lymph cortex) => creates germinal centers
- Isotype switching (IgM –> whatever) occurs in germinal centers
Describe isotype switching
- Occurs in response to new Ag
- Occurs in germinal center of lymphoid cortex
- Required CD40 receptor on B cells w/ CD40 ligand expressed by activated T cells
KRAS
- A proto-oncogene
- Activated in tumor cells
- Increases cellular response to mitogenic stimuli
How do you reverse the effects of heparin?
Protamine
- Binds hep => chemical inactivation
How do you reverse the effects of warfarin?
- Vit K
- Fresh frozen plasma
Paroxysmal nocturnal hemoglobinuria
TRIAD:
1) Hemolytic anemia
2) Hypercoagulability
3) Pancytopenia
- Acquired mutation in PIGA gene
- Deficiency in CD55 and CD59 complement inhibitor proteins
What is the fastest way to reverse Warfarin’s effects?
Fresh frozen plasma
Vit K facilitates clotting factor re-synthesis (takes time)
Why does a bruise turn green after several days?
- Heme is converted to biliverdin (verde) via heme oxygenase
- It’s then converted to unconjugated bilirubin via biliverdin reductase
How do you initiate hemolytic anemia in someone deficient in G6PD?
- Give them anti-malarial drugs! (they’re going to Africa usually)
Labs:
- Anemia
- Reticulocytosis
- Indirect hyperbilirubinemia
- Smear w/ Heinz bodies
X-linked recessive
What are Heinz bodies?
RBCs w/ dark, intracellular inclusions that stain w/ crystal violet
Isoniazid effects on heme production
- Inhibits pyridoxine phosphokinase => Vit B6 deficiency => deficiency in ∂-aminolevulinate synthase (RLS of heme synthesis)
Causes:
- Decrease Hb/HCT
- Decreased MCV
- Sideroblastic anemia
A “retained dead fetus” can cause what?
DIC and progressive hypofibrinogenemic
Must monitor fibrinogen and platelets to identify onset of DIC
Findings in DIC
- Prolonged PTT and PT
- Thrombocytopenia
- Microangiopathic hemolytic anemia
- Low fibrinogen
- Elevated D-dimers
- Low Factor 5 & 8 levels
Warfarin-induced skin necrosis
- Warfarin inhibits protein C/S => can cause necrosis
- Especially in people deficient in protein C/S
- Usually seen in first few days of admin
