Review of Organic Chemistry & Biomolecules Primordial Biomolecules Water is the “cradle of life” - All organisms are about 2/3 water. Pathway metabolites are simple. Of the 21 metabolites involved in glycolysis, gluconeogenesis and TCA cycle, all are 6 carbons - “Small is better” Three major biomolecules/ fuels/nutrients : Carbohydrate Lipid Protein Early ( 18 hr) starvation fuel: Carbohydrate (liver glycogen) Late starvation fuel: Lipid (adipose tissue) and protein (muscle) Other biomolecules include: DNA/RNA, vitamins, xenobiotics (alcohol, etc.)

Laboratory Diagnosis of Rhabdomyolysis Definition of Rhabdomyolysis ‘Skeletal muscle injury, reversible or irreversible, that alters the integrity of the cell membrane sufficiently to allow the escape of cell contents into the extracellular fluid, and leakage into the cell of water, Na+, Cl-, and Ca++. Skeletal muscle is the largest organ in the body 40% of body weight Potential for extracellular fluid loss is large Potential for K+, PO4- -, enzymes, proteins, purine release is large ...

Essential Thrombocythemia Followed by Acute Leukemia Does therapy lead to leukemic transition or is it a failure of accurate diagnosis? 63 yo male admitted with Appendicitis Diagnosed with Essential Thrombocythemia 1992. Treated with Chlorambucil to keep platelet count less than 600,000K 1999 diagnosed with AML; cytogenetics normal Offered induction therapy with 7+3. Pt refused. Continued on Chlorambucil. Stable AML x 2 years WS labs. WBC: 14.0, 45% Segs, 7% Bands, 15%Blasts Plts: 693K PCR for BCR/ABL + Objectives Establish the diagnostic criteria for Essential Thrombocythemia (ET) Discuss the natural history of ET Discuss the evidence supporting the treatment of ET Discuss acute Leukemia following ET Diagnostic Criteria for ET Platelet count 600,000 Hematocrit,40 or normal RBC mass Normal serum ferritin and MCV No Philadelphia Chromosome or bcr/abl gene rearrangement Absence of collagen Fibrosis on bone marrow No cytogenetic or morphologic evidence for a myelodysplastic syndrome No cause for reactive thrombocytosis Presenting Features Vasomotor symptoms...

Laboratory Evaluation of Renal Disease Blood Tests Blood Urea Nitrogen (BUN) Plasma Creatinine (Cr) Urine Tests Urinalysis ‘Dip Stick’ Sediment Renal Blood Tests (BUN, Cr) The function of the glomerulus is plasma filtration Thus, one measure of renal function is the glomerular filtration rate or GFR Assessment of Glomerular Filtration Creatinine is a product of muscle creatine metabolism Creatinine is released into the blood at a constant rate Assessment of Glomerular Filtration Creatinine is not protein bound and is filtered at the glomerulus Thus it is a useful measure of blood clearance Glomerular Filtration Rate (As measured by Creatinine Clearance) Urine Flow (ml/d) x Ucr (mg/dL) CrCl....

Renal Function Tests Why Test Renal Function? To identify renal dysfunction. To diagnose renal disease. To monitor disease progress. To monitor response to treatment. To assess changes in function that may impact on therapy (e.g.Digoxin, chemotherapy). Renal Functions Production of urine Elimination of metabolic end products (Urea/Creatinine) Elimination of foreign materials (Drugs) Control of volume & composition of ECF Water and electrolyte balance Acid/Base status Endocrine Functions Vit D, Epo, Renin Renal Functions Production of urine: - Excretion of water soluble waste : - End products of metabolism (urea, creatinine) Foreign materials (drugs etc) Control of volume & composition of ECF Water and electrolyte balance Acid/Base status Renal functions Endocrine functions: - Vitamin D Erythropoietin Renin/angiotensin/aldosterone axis Signs and Symptoms of Renal Failure Symptoms of Uraemia (nausea, vomiting, lethargy) Disorders of Micturation (frequency, nocturia, retention, dysuria) Disorders of Urine volume (polyuria, oliguria, anuria) Alterations in urine composition (haematuria, proteinuria, bacteriua, leujocyturia, calculi) Pain Oedema (hypoalbuminaemia, salt and water retention) Biochemical Tests of Renal Function Urinalysis Appearance Specific gravity and osmolality pH Glucose Protein Urinary sediments? Measurement of GFR Clearance tests Plasma creatinine Tubular function tests Role of Biochemical Testing Presentation of patients:...