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.)

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:...

RENAL DISEASES The Nephron Consists of the glomerulus and its attached tubules. The functional unit of the kidney. Major Renal Syndromes Acute Nephritic Syndrome The Nephrotic Syndrome Rapidly Progressive Glomerulonephritis Asymptomatic Hematuria or Proteinuria Major Renal Syndromes (cont) Acute Renal Failure Urinary Tract Infection Nephrolithiasis Acute Nephritic Syndrome Sudden onset of hematuria with RBC casts and renal failure (days - weeks) RBC casts not listed in the book!! But this is critical!! Proteinuria (mild to moderate but NOT Nephrotic Range) Hypertension Hallmark Disease: Post Streptococcal Glomerulonephritis What is an RBC cast? The Nephrotic Syndrome Proteinuria ( 3.5gm/day) Hypoalbuminemia Edema Hyperlipidema Lipiduria Rapidly Progressive Glomerulonephritis Nephronal hematuria Renal failure developing over weeks to months Diffuse glomerular crescent formation. Asymptomatic Hematuria or Proteinuria Hematuria with or without RBC casts and/or Proteinuria usually 2.0gm/day NO RENAL FAILURE NO NEPHROTIC SYNDROME Acute Renal Failure Oliguria ( 400ml/day) Rarely anuria Recent Onset of Azotemia (hours/days) Chronic Renal Failure Uremia Final Common Path of All Chronic Renal Diseases Urinary Tract Infection Bacteriuria and Pyuria Dysuria, Frequency, Urgency Pyelonephritis or Cystitis WBC casts = Pyelonephritis The Book Misses this one!!..

Overview of the Newer Rheumatoid Arthritis Therapies Cyclooxygenase inhibition COX-2–Specific Inhibitor: Celecoxib 12-week, double-blind, randomized trial; 1103 patients with RA in a flare state Celecoxib (100, 200, or 400 mg bid) vs naproxen (500 mg bid) vs placebo Efficacy of celecoxib generally comparable to naproxen Efficacy of all doses of celecoxib similar and superior to placebo on ACR 20, HAQ Disability Index Safety of celecoxib comparable to placebo COX-2–specific at therapeutic doses Incidence of Endoscopic Gastroduodenal Ulcers After Celecoxib Treatment COX-2–Specific Inhibitor: Rofecoxib 52-week double-blind, randomized trial vs diclofenac; 693 patients with osteoarthritis (OA) of knee or hip 6-week double-blind, randomized trial vs ibuprofen; 809 patients with clinical and radiographic knee or hip OA Efficacy of rofecoxib once daily comparable to that of diclofenac or ibuprofen three times daily Safety of rofecoxib comparable to that of placebo COX-2–specific at therapeutic doses Rofecoxib vs Ibuprofen and Placebo:...