Confounding bias

Chronic Myeloid Leukemia (CML)

Quick Review Patient is often older, and can no symptoms or have B symptoms (night sweats, etc), fatigue, and weight loss (caused by early satiety due to enlarged spleen). On physical exam, an enlarged spleen can be palpated. CBC shows very high WBC count (typically >100,000) with elevated basophils on differential. Peripheral smear shows early, immature neutrophil precursors (myelocytes, metamyelocytes) as well as many basophils. It is important for CML to know the details of the genetic abnormality because it relates to the treatment. CML is due to a translocation of BCR and ABL on chromosomes 9 and 22 resulting a fusion BCR-ABL gene that produces a tyrosine kinase that is always active. The treatment of choice is a tyrosine kinase inhibitor e.g. imatinib. They work to suppress the tyrosine kinase and can induce disease remission. Relevant Images Immature neutrophil precursors on peripheral smear BCR-ABL translocation

Chemotherapy

Terminology Adjuvant therapy - given in addition to standard therapy Consolidation therapy - given after induction therapy with multidrug regimens to further reduce tumor burden Induction therapy - initial dose of treatment to rapidly kill tumor cells and send the patient into remission Maintenance therapy - given after induction and consolidation therapies or after the initial standard therapy to kill any residual tumor cells and keep the patient in remission Neoadjuvant therapy - given before the standard therapy for a particular disease Remission - less than 5% tumor burden Salvage therapy - given when standard therapy fails Adjuvant therapies in various cancers Metastasis to bone - bisphosphonates (e.g. zoledronic acid) are given to prevent lytic lesions and pathologic fractures as well as malignant hypercalcemia. Bisphosphonates work by inhibiting osteoclasts and thereby preventing bone breakdown. Breast cancer Tamoxifen , a selective estrogen recep...

Intracellular accumulations

Parenchymal cells may accumulate normal (water, proteins, etc) or abnormal (mutated proteins, infectious agents, etc) substances in their nuclei or cytoplams (typically in phagolysosomes). These substances can be produced by the cell (endogenous) or elsewhere but stored in the cell (exogenous). This can be harmless for the cell or toxic. Here are some examples of accumulations. Fatty Change or Steatosis Cholesterol & Cholesteryl esters Proteins Glycogen Pigments These can accumulate in the cell via 4 main pathways: Abnormal metabolism (can't remove endogenous substance) - e.g. fatty change in liver and heart Abnormal folding, transport, or degradation of endogenous proteins - e.g. α1-antitrypsin in liver cells Storage diseases: Defect in enzymes that metabolize lipids and carbs -> accumulation of endogenous lipids and carbohydrates in usually lysozymes Ingestion of indigestible materials - cell takes in exogenous substances that it can't metabolize or transport elsewher...

pathology

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