Discuss the TNM classification of malignancy and colorectal cancer
T: extent/size of tumor (how far grown in wall colon-mucosa, muscularis properia, suberosa/serosa); N: spread to nearby lymphs; M: metastasis to distant organs
Discuss the clinical significance of APC-resistance assay and ratio in screening for factor V gene mutation
degree of abnormality of APC-assay correlates to heterozygosity (higher APC ratio) or homozygosity (low APC ratio) factor V Leiden mutation
Summarize the two main roles of vWF in the process of clot formation
1.primary hemostasis- PLT adhesion; 2.secondary hemostasis- vWF complexes VIII->prolong half-life VIII (prevent its degradation)->complex IX->activate X
Identify 3 specific gene mutations which can lead to the development of breast cancer
Discuss how Protein S and C work and their relevance in evaluating thrombophilia
Proteins S & C work together to prevent your blood from clotting too much; if low S&C = clot too much; P&C inactivate factors V/VIII = slow down clot formation
what are 3 drugs that can treat Factor V Leiden and briefly explain their MOA
1. Warfarin-block carboxylation of prothrombin/VII/X & proteins C/S->deactivates Vitamin K; 2. Dabigatran-inhibit thrombin; 3. Rivaroxaban-direct Xa inhibitor
why do patients with Ewing sarcoma present with generalized pain?
immune cells trigger inflammation->cytokines->inflammatory markers->activate nociceptors throughout body
What is the characteristic translocation associated with Ewing Sarcoma?
location at the chromosome 22 breakpoint of the t(11;22)(q24;q12) translocation; EWS (EWSR1) gene is involved in translocations in Ewing's sarcoma
Describe the process of plasmapheresis
liquid part of the blood, or plasma, is separated from the blood cells. Typically, the plasma is replaced with another solution--> returned to body
What are common symptoms of anemia you see in patients with CML?
Explain the significance of elevated LDH and Uric acid in the presentation of CML
LDH: high turn over of cells-excess cell lysis; Uric Acid-breakdown of cellular nucleic acid contents of leukemia cells
Contrast the pathogenesis of TTP with that of HUS
HUS: shiga toxin->ADAMTS 13 inhibition->failure to cleave vWF multimers; TTP: ADAMTS13 antibodies/congenital ADAMTS13 mutation->failure to cleave vWF multimers
What is the underlying pathogenesis of Von Gierk's (Type I) disease?
glucose-6-phosphatase deficiency (can't go from G6P to Glucose)
Describe the genetic pathogenesis of Chronic Myeloid Leukemia
Translocation of chromosome 9 segment onto Chromosome 22-> Philadelphia Chromosome w/ BCR-ABL fusion gene= hematopoeitic stem cell division unregulated
Discuss the role of factor V in blood clot formation (coagulant) & hemostatic (anticoagulant) regulation
Factor V synthesized in liver; Thrombin activates Factor V-> prothrombin to thrombin; Factor V cofactor aPC to degrade VIII/VIIIA= reduce thrombin formation
Why does a person with a G6P deficiency need to eat corn starch?
corn starch is a glucose polymer that is broken down slowly = control glucose levels
What does LMNA code for in and why is it so important in development of progeria?
LMNA codes for Lamina A-protein that acts as scaffolding on the inner side of the nucleus->farnesyl stays on lamina A->piles on=abnormal nuclear envelop
Describe how 5-flurouracil (5-FU) produces its chemotherapeutic effect