Heme/Onc Flashcards
Platelet disorder (defect in platelet plug) where you have decreased GpIb.
Bernard-Soulier syndrome
No Gp1b = no platelet adhesion.
Mild thrombocytopenia and Big Suckers (big platelets).
Defect in platelet plug where you have decreased GpIIb/IIIa.
Glanzmann’s Thrombasthenia
Defect in platelet AGGREGATION
On blood smear, you will see no platelet clumping.
Autoimmune issue where the autoantibody will attack GPIIb/IIIa proteins.
Idiopathic thrombocytopnic purpura (seen with SLE at times)
Note: These autoantibodies are made in the spleen and the platelet/antibody complex is consumed in the spleen by splenic macrophages. So, you get DECREASED number of platelets, and INCREASED megakaryocytes.
Also, you see with SLE
Primary platelet disorder in which there is a deficiency of ADAMTS 13 due to autoimmune destruction. ADAMTS 13 is a vWF metalloprotease:
TTP (Thombotic thrombocytpenic purpura).
*Decreased degradation of vWF multimer. Will get increased vWF multimers and therefore increased platelet aggregation and thrombosis, AND DECREASED platelet survival.
Will see SCHISOTOCYTES and neurologic and renal symptoms, fever, thrombocytopenia, microangiopathic hemolytic anemia.
Treatment: get rid of the autoantibody with plasmaphoresis and corticosteroids.
What casues HUS?
E. Coli H0175H7 tonxin (undercooked beef in children). The toxin damages the GI endothelium causing platelet aggregates, which will cause shearing of RBC’s as they pass by. This looks a lot that TTP (schisotocytes, neurologic and RENAL symptoms, thrombocytopenia, microangiopathic hemolytic anemia).
What will the bleeding time of the primary platelet disorders be? What about PT/PTT?
Bleeding time: increased
PT/PTT: normal–>no problem with the coagulation cascade.
Note: primary platelet issues are Bernard-Soulier syndrome, Glanzmann’s thrombasthenia, ITP, TTP/HUS.
Hemophilia A is an X-linked RECESSIVE (so males get it) deficiency of Factor ?
VIII
Will have increased PTT. (draw out the way that Pathoma did).
Hemophilis B is a deficiency of what clotting factor?
B
Bleeding into deep tissue (blood and joints) and re bleeding after surgical procedures describes what type of problem?
Coagulation cascade problem (as opposed to a problem with primary hemostasis, like platelets).
Remember that platelet problems will present with mucosal bleeding, not deep bleeding.
Vitamin K deficiency causes coagulation cascade problems.
What factors need Vitamin K?
II, VII, IX, X, protein C and protein S
Vitamin K is necessary to gamma carboxylate these factors.
Note: Vitamin K increases PT and PTT.
How does coumadin work?
Blocks Epoxide reductase (which is the made the the liver).
epoxide reductase is the enzyme necessary to activate vitamin K so that it can gamma carboxylate factors II, VII, IX, IX, protein C and protein S.
How can you tell difference between Hemophilia A and an autoantibody against Factor VIII.
Do a mixing study. If you mix good blood with the broken blood of Hemophilia A, it will clot. If there are autoantibodies, it won’t matter.
PTT measures intrinsic or extrinsic pathway.
PTT (XII, XI, IX, VIII)–>intrinsic pathway. HEP works on this pathway to prevent clotting
PT measures intrinsic or extrinsic pathway?
PT (VII)–>extrinsic pathway. Coumadin works on this pathway.
How does liver injury affect coagulation?
Factors are made in liver. So is epoxide reductase, which is necessary to activate vitamin K. So, liver injury decreases coagulation.
Note: Use PT to test for liver issues.
What issue will increase both bleeding time and PTT?
vWB disease.
It is mixed platelet and coagulation disorder.
vWF factor is necessary to stabilize Factor VIII (increase PTT). It is also necessary for platelet adhesion (increased BT).
Diagnosed with RISTOCETIN. If there is a disorder of vWF, there will be NO aggregration upon test.
Treat: Desmopressin: released vWF stored in endothelium (Weibel Palad bodies).
What is DIC?
What is the primary way to diagnose?
Widespread activation of clotting leads to deficiency in clotting factors, which creates a bleeding state.
Caused by something ELSE, like rattlesnake bite, gram - sepsis, trauma, Ob comlicaitons, Pancreatitis, Malignancy, Nephrotic syndrome, transfusion
STOP Make New Thrombi
DX: Increased fibrin split products (D-Dimers)
Increased BT Increased PT Increased PTT Decreased platelets Decreased fibrinogen
There are times when plasmin is activated and it should not be, which creates a clinical picture that looks a lot like DIC because there is an attack on clotting factors and fibrinogen. How do you distinguish the two?
Like DIC, you will have:
Increased PT
Increased PTT
Increased BT
But platelet count will be NORMAL.
And although you will have fibrinOGEN split products, you will NOT HAVE D-DIMERS.
The endothelium produces a molecule called thrombomodulin, which “modulates” thrombin. What exactly does it cause to happen?
Normally thrombin would convert fibrinogen into fibrin, which would stabilize a clot.
Thrombomodulin actually “modulates” thrombin to do something else. It activates Protein C, which will then go and inactivate some of the clotting factors. V and VIII.
What drug do you give a pregnant woman with DVT?
Heparin
Normally, warfarin is what you give to treat DVT, but it is teratogenic, so in pregnant ladies, you give heparin.
Note: Heparin increases Antithrombin III activity.
Drugs that end in dipine are what type of drugs?
Ca2+ channel blockers.
Immotile cilia due to an autosomal recessive mutation in a gene coding for the microtubule associated protein, dyne in.
Male infertility, recurrent sinusitus and bronchiectasis result.
Kartagener Syndrome
Cancer associated with Philadelphia chromosome
t(9:22) BCR-ABL
Chronic myelogenous leukemia
Cancers that down’s patients are most at risk for?
ALL and AML
What virus causes erythematous infectiosum (5th disease)?
Where does this virus replicate?
- Parvo B19 (tiny non-enveloped DNA virus).
2. In bone marrow, because it likes P antigen, which is found on erythrocyte precursors.
Prophylaxis drug for HIV patients with <200 T cell count.
Pentamidine–>to treat Pneumocytstis jiroveci
Heinz bodies, bite bells, microcytic anemia
- What causes it?
G6PD deficiency and oxidative damage of RBCs.
Can be induced by drugs that cause oxidative damage such as TMP-SMX and dapsone (both used as prophylactics in HIV patients with CD 4 < 200.
You are trying to figure out why a girl is having increased mucosal bleeding (gingival bleeding, long periods, etc) because she has iron deficiency anemia.
You do the ristocetin test. What does this tell yo?
Ristocetin is a test that activates GP1b receptors on platelets that bind to vWF on endothelial cells and ultimately cause platelet adhesion. If there is a deficiency of vWF, then the platelet adhesion/aggregation will be deficiency with this test.
Ristocetin tests for vWF.
Reg HbA:
Glutamate (- charged)
HbS, this is the change:
Gluatamate (-)—–>Valine (nonpolar)
HbC, this is the change:
Glutamate (-)—->Lysine (+)
Note: These are all missense mutations!
What will it look like if you have these three side by side on gel electrophoresis?
You will have this:
- HbA +
- HbS +
- HbC +
Why are the cells big in megaloblastic anemia?
No folate or B12, which PREVENTS DNA synthesis. The cells are big because there is not enough DNA to make the cells do their thing (divide and get smaller)
Note: Alcoholism can cause folic acid deficiency.
What happens on a molecular level in the RBC during hypoxia?
The RBC will sacrifice a net ATP to convert 1,3-bpg (which is used during glycolysis in the RBC…remember they do not have mitochondria) to make 2,3-BPG. 2,3-BPG allosterically DECREASES the affinity of Hb for oxygen so that it can get in the tissues quicker during hypoxia and chronic anemia.
What is the first line drug to prevent DVT and pulmonary emboli?
What is its mechanism?
Warfarin
It inhibits epoxide reductase (so no active vitmin K). So, it inhibits vitamin K dependent-carboxylation of glutamic acid residues of clotting factors II, ViI, IX and X.
Parvo B19 (fifth disease–>erythema infectiosum) is a tiny little ss DNA virus (nonenveloped). Where does it replicate?
Bone marrow. It is highly tropic for erythroid precursor cells.
Malaria:
Chloroquine and mefloquine are used to treat erythrocytic forms of Plasmodia.
What do you need to give to kill P. vivax and P. ovale liver schizoint?
Primaquine
Heinz bodies and bite cells indicate a deficiency of
G6PD–>enzyme that helps during oxidative stress.
What is a complication (in the gallbladder) of any type of hemolytic anemia?
Pigmented gallstones.
Stop codons
UAA
UGA
UAG
Why does HbF bind oxygen with higher affinity?
Due to its inability to interact with 2,3-DPG.
Remember that during hypoxia, RBC will use an ATP to make 2,3-DPG from 1,3-DPG so that HbA can bind it, which lessens the Hb affinity to O2 so that it can release it in the tissues.
Three things that can cause Pure Red Cell Aplasia
- Thymoma
- Parvo B-19
- Lymphocytic leukemias
A deficiency of what in a patient can cause warfarin induced skin necrosis?
Protein C or S (these are natural anticoagulants). If they are not available AND warfarin is added (an anticoagulant), then you can get skin necrosis.
HbF has what globin subunit?
Gamma.
Keep in mind that most people have a tiny bit of delta.
End stage kidney disease causes uremia (urea and other waste problems in the blood). How does this affect the
PTT
PT
Platelet count
Bleeding time
It increases bleeding time only. There is a probl with the way the platelets function, not the number of platelets.
Protein C inactivates Factor V. If you add protein C to factor V and it dos not have a coagulatory effect, what is the problem?
Factor V Leiden mutation.
Patients with chronic hemolytic anemia (such as sickle cell) are predisposed to _____________ __________ deficiency and macrocytic changes due to increased erythrocyte turnover.
Folic acid
COX-2 inhibitor
Celecoxib
Antiplatelet coagulant drug that can rarely cause neutropenia and typically presents with fever and mouth ulcers.
Ticlopidine.
Note: It is not used very offer due to the serious side effects, but can be used when an individual can not tolerate aspirin or clopidogrel.
t(8;21)
AML
Note: Acute Promyelocytic Leukemia (M3 type of AML) is t(15;17).
AUER RODS SEEN IN BOTH
t(9;22)
Philadelphia chromosome
Bcr-Abl
CML
Increased tyrosine kinase
t(11;14)
Mantle Cell Lymphoma
Activation of cyclin D
t(8;13)
Burkett’s Lymphoma
C-MYC
Monoclonal antibodies against complement receptor on the surface of B-lymphocytes could prevent infection with which of the following viruses?
EBV
Note: EBV puts a person at greater risk for lymphomas.
CD21 is found on B-cells and nasopharyngeal epithelial cells.
How does Parvovirus B19 attach to erythrocytes?
P antigen on the RBC
EBV gp350 binds whats what?
CD21 on RBCs
HIV gp120 binds what?
CD4 on Tcells.
Note that there is a coreceptor (CCR5 or CXCR4)
Where does T-cell education undergo:
- Positive selection?
- Negative selection?
- Postive: In the cortex of thymus
2. Negative: In medulla of thymus
WHat is the final result of inositol phospholipid 2nd messenger pathway?
Gq: Increases cytoplasmic Ca2+ levels through IP3-mediated Ca2+ efflux from the endoplasmic reticulum.
What is the end result of the JAK/STAT pathways?
dimerize and translocate to the nucleus, activating transcription.
PI3/Akt/mTOR pathway is an intracellular signaling pathway important for antipoptosis, cellular proliferaiton and angiogenesis. Mutations in this pathway contribute to _______________.
cancer pathogenesis.
What are the side effects of the NSAID Ticlopidine (3rd line after aspirin and clopidogrel).
Neutropenia and ulcers in the mouth with fever.
What kind of drugs are:
Nevirapine, efavirenz, and delavirdine?
These are NONnucleoside reverse transcriptase inhibitors used to treat HIV. Note that they do not require activation via intracellular phosphorylation like the nucleoside reverse transcriptase inhibitors (like zidovudine).
What things things shift the oxygen dissociation curve to the left (making the Hb have greater affinity for O2, thus making release into the tissue more difficult)?
- Hypothermia
- Alkalosis
- Decreased 2,3-diphosphoglycerate (HbF)
Note: strenuous exercise, increased tissue Co2 levels and decreased pH will cuase a shift to the right.
What is the purpose of snRNPs?
They are synthesized by RNA polymerase II in the nucleus. They help REMOVE INTRONS from the RNA transcript and thus are necessary for synthesis of messenger RNA.
Note: Intron is not part of the protein. They are spliced out.
Besides measuring neural tube defects, what else is elevated alpha-fetoprotein helpful for?
Monitoring the trend to help distinguish between cirrhosis and hepatocellular carcinoma.
Deficiency of alpha1-antitrypin is associated with…..
Panacinar emphysema and cirrhosis.
Both Neimann Pick and Tay Sachs present similarly. What are some differences that might help you distinguish between the two?
Tay Sachs: hyperacussis, NO hepatosplenomegaly. (Lack fo B-hexosaminidase A, so GM2 gangliosides build up)
Neimann-Pick: HEPATOSPLENOMEGALY.
(lack of sphingomyelinase)
Disease where macrophages look like crumbled up tissue paper.
- What is the disease?
- Enzyme and waht builds up?
- Gaucher
2. B-glucocerebrosidase, glucocerebroside builds up.
Gargoylism, corneal clouding, hepatosplenomegatly and developmental delay.
Hurler syndrome…
A-L-iduronidase deficiency. Build up of dermatan & heparan sulfate.
Potassium levels (intracellular and extracellular) in individuals with diabetic ketoacidosis.
Intracellular-low
Extracellular-normal or high
Which of these diabetic drugs:
- Increase the sensitivity of target tissues to insulin
- Stimulates insulin release.
- Metformin–>increases sensivity to insulin
2. Glyburide (sulfonylurea)–>increases the release of insulin.
Where does iron absorption occur?
Duodenum and proximal jéjunum.
What type of vaccine is available for rabies?
Killed
Vincristine is a cancer drug which can be used to treat non-Hodgkin lymphoma. How does it cause neurotoxicity?
It interferes with microtubule formation in nerve axons.
These “vin” drugs inhibit microtubule polymerization after binding to B-tubulin. These drugs are M- phase specific agents.
What causes pathogenicity of most H. Influenza (type B)?
Capsule
How do interferons work (alpha and beta) against viruses?
They stimulate cells to cease permitting viral replication and begin to synthesize antiviral proteins that impair the translation of viral mRNA without impacting cellular mRNA.
How is hydroxyurea used to treat sickle cell disease?
It increases fetal hemoglobin (HbF) synthesis by an unknown mechanism. It is reserved for patients with frequent pain crises.
Note: another treatment for SS is by using of calcium-dependent (Gardos) potassium channel blockers that regulates the transport of potassium and water through the red blood cell membrane. When blocked, potassium and water efflux is reduced, preventing dehydration or erythrocytes and reducing the polymerization of HbS.
You see a vignette that appears to be marfan’s except you have medullary carcinoma of the thyroid, pheochromocytoma and oral and intestinal mucosal neuromas. What is the disorder
MEN2B (Multiple endocrine neoplasia).
Note: MEN2A is also associated with parathyroid hyperplasia, whereas MEN2B is not.
Why are calcineurin inhibitors used as immunosuppressants?
Calcineurin activates IL-2, which promotes growth and differentiation of T-cells.
