Clinical Biochemistry

1001411

Course Coordinators Adel M. Assiri, PhD. Department of Biochemistry

Faculty of Medicine

Umm Al-Qura University

Tel: (02) 5270000 Ext 4495

aassiri64@hotmail.com

When you have questions, concerns, or suggestions, please contact Prof. Assiri by e-mail, call

for an appointment, or catch them before or after class or lab.

Course title: Clinical Biochemistry 1001411

Credit hours: 4 credit hours

Program(s) in which the course is offered - Bachelors Degree of Medicine Program

Level/year at which this course is offered: Fourth year

Pre-requisites for this course: - Finishing Biochemistry course (10011211) in the second year

Course Description, Objectives, and Format The students will be able to:

1- Understand the biochemical basis of diseases, correlate symptoms, signs, and complications to biochemical events.

2- Understand the biochemical nature of the therapeutics approaches in the field of medicine.

3- To select the biochemical tests appropriate to the diagnosis and management of the disease.

4- Be able to interpret the laboratory data properly, which means that in assessing the significance of a test result, the students should consider the clinical circumstances and the possible contribution of any analytical or biological variation. Therefore, in future during their clinical practice they should use the laboratory intelligently and selectively.

Topics to be Covered No of Weeks

Contact hrs.

Overview of Clinical Chemistry Lecture No 1- THE BIOCHEMISTRY OF DISEASE Review of clinical aspects of carbohydrates, Lipids, Proteins and Amino Acids metabolism, Enzymes Integration of Metabolism Genetic Metabolism

1 2

Lecture No 2 – THE CLINICAL CHEMISTRY LABORATORY AND ORGAN SYSTEMS The placeof clinical biochemistry in medicine Interpretation of the laboratory data of: Cardiovascular Circulatory System Respiratory Tract Liver Renal System Digestive System Endocrine System Bone Central Nervous System

1 2

Diabetes and Other Carbohydrate Disorders Lecture No 3 – DIABETES MELLITUS Glucose Challenge Test and Other Diagnostic Tests Tests of Diabetes Control and Disease Progression

1 2

Lecture No 4 – LABORATORY RESULTS IN TYPE 1 DIABETES Hypertension and Microalbuminuria Glycated Hemoglobin Hypoglycemia

1 2

Lecture No 5 – OTHER CARBOHYDRATE METABOLIC DISORDERS Glycogen Storage Disorders Fructosuria GALACTOSEMIA Additional Testing to Aid Interpretation of Carbohydrate Disorders

1 2

Hemoglobin Production Disorders and Testing Lecture No 6- HEME SYNTHESIS ABSORPTION, TRANSPORT, AND STORAGE OF IRON How Is Iron Absorbed in the Body? How Is Iron Stored in the Body? How Is Iron Transported in the Body? ASSESSING IRON LEVELS AND FORMS Iron Deficiency Practice Calculation: UIBC and % Saturation of Iron Interpretation of Iron Results

1 2

Topics to be Covered No of Weeks

Contact hrs.

Assessment of Renal Function Lecture No 7- Basic renal functions. CREATININE METABOLISM GLOMERULAR NEPHRITIS NEPHROTIC SYNDROME AZOTEMIA TYPES AND ASPECTS OF RENAL FAILURE CALCULATION OF FRACTIONAL EXCRETION OF SODIUM

1 2

Lecture No 8- RENAL CONTROL OF ACID-BASE BALANCE THE ROLE OF ELECTROLYTES Sodium, Potassium, Chloride, Bicarbonate RENAL TUBULAR ACIDOSIS ELECTROLYTE ANALYSIS Calculation of Anion Gap, Use of Anion Gap Electrolyte Critical Values Abnormal Sodium Levels, Abnormal Potassium Levels RENAL IMPACT ON WATER AND ELECTROLYTES PHYSIOLOGY: HORMONAL AND RENAL CONTROL OF ELECTROLYTES AND MINERALS Water and Electrolytes KIDNEY STONES

1 2

METABOLIC BONE DISEASE Lecture No 9- Disorder of Calcium and Phosphate Metabolism. Review of normal physiology and metabolism of bone, calcium, phosphate and magnesium. Clinical disorders of calcium, phosphorus, magnesium metabolism, their etiology, pathophysiology, metabolic abnormalities, complication and management. Metabolic disorders of bone, biochemical markers of bone turnover, biochemical profile in various clinical disorders of bone.

1 2

Assessment of Liver Function Lecture No 10- TESTS FOR LIVER FUNCTION BILIRUBIN METABOLISM HYPERBILIRUBINEMIA Obstructive Jaundice Hepatitis

1 2

Lecture No 11- NEONATAL HYPERBILIRUBINEMIA Physiological Jaundice of the Newborn PATHOPHYSIOLOGY OF LIVER ENZYMES ANALYTICAL ASPECTS OF LIVER ENZYMES Interpretation of Alkaline Phosphatase Results Liver Function of the Elderly or Pediatric Patient CLINICAL SIGNIFICANCE OF ALKALINE PHOSPHATASE

1 2

Topics to be Covered No of Weeks

Contact hrs.

Lecture No 12- OTHER LABORATORY TEST RESULTS THAT CORRESPOND WITH LIVER DISORDERS Proteins and Amino Acids Interpretation of Total Serum Protein Levels Cerebrospinal Fluid Proteins Interpretation of Serum Albumin Levels Other Serum Proteins Nephelometry Cirrhosis and Hepatitis AMMONIA METABOLISM Hepatic Encephalopathy

1 2

Assessment of Cardiovascular Disorders Lecture No 13- THE FIRST THREE PATIENTS IN THE EMERGENCY DEPARTMENT ACUTE MYOCARDIAL INFARCTION, Biomarkers of AMI LIPIDS AND LIPOPROTEINS The Role of HDL Physiological Changes in Lipid and Lipoprotein Levels Diabetes and Cardiac Disease National Cholesterol Education Program C-Reactive Protein Primary and Secondary Hyperlipoproteinemia Apoproteins, Hypoalphalipoproteinemia, Hyperbetalipoproteinemia Abnormalities With Apoprotein E Abetalipoproteinemia

1 2

Lecture No 14- NATRIURETIC PEPTIDES WHY WOMEN AND MEN EXPERIENCE DIFFERENT RISK FOR HEART ATTACKS DELAYED DIAGNOSIS OF AMI DIFFERENCES IN ELDERLY PATIENTS Lipoprotein (a) Homocysteine

1 2

Assessment of Respiratory Disorders Lecture No 15- COLLECTION AND HANDLING OF ARTERIAL BLOOD GASES ASSESSMENT FOR ARTERIAL BLOOD GASES Calculations in Arterial Blood Gas Anaylsis Arterial Collection, Venous Versus Arterial Samples ACID-BASE STATUS Metabolic Acid-Base Disturbances, Respiratory Acid-Base Disturbances Approach to Interpreting Acid-Base Disturbance VENTILATION AND PCO2 RELATIONSHIP OXYGENATION STATUS Oxygen-Carrying Capacity and Content

1 2

Topics to be Covered No of Weeks

Contact hrs.

Shift to the Right

Lecture No 16- RESPIRATORY DISORDERS Chronic Bronchitis, Acute-on-Chronic CO2 Retention, Fetal Lung Maturity Respiratory Distress Syndrome ANALYSIS OF OXYGENATION, TOXIC GASES Cyanide Poisoning, Carbon Monoxide Poisoning Distribution of Gases via Circulation of Erythrocytes Pathological Effects of Carbon Monoxide, Analysis of Carboxyhemoglobin Indirect Analysis of CO in a Venous Whole Blood Sample Determining p50

1 2

Assessment of Nutrition and Digestive Function Lecture No 17- NUTRITION NITROGENOUS BIOMARKERS OF NUTRITIONAL STATUS VITAMINS TRACE ELEMENTS NUTRITIONAL DISORDERS VITAMIN A METABOLISM Vitamin A Night Blindness VITAMIN-RELATED MACROCYTIC ANEMIA Testing Strategies for Macrocytic Anemia

1 2

Lecture No 18- PHYSIOLOGICAL AND NUTRITIONAL CHANGES WITH AGE PREDIABETES AND METABOLIC SYNDROME

1 2

Lecture No 19- DIGESTIVE DISORDERS THE GASTROINTESTINAL TRACT MALABSORPTION GASTRIC FLUID ANALYSIS ZOLLINGER-ELLISON SYNDROME CYSTIC FIBROSIS GASTRIC FLUIDS AND ELECTROLYTE LEVELS OTHER ELECTROLYTE DISTURBANCES RESULTING FROM GASTROINTESTINAL DISTURBANCES Intestinal Loss Bulimia Nervosa

1 2

Endocrine Disorders and Function Lecture No 20- Classification of Hormones Hormone Receptors Feedback Control THE PITUITARY GLAND THE ADRENAL GLANDS Cortisol Synthesis, Cortisol Activity DISEASES OF THE ADRENAL CORTEX

1 2

Topics to be Covered No of Weeks

Contact hrs.

Hypocortisolism ROLE OF ALDOSTERONE, Disorders Involving Aldosterone GROWTH HORMONE, Disorders of Growth Hormone Secretion Lecture No 21- ADRENAL MEDULLARY HORMONES DISORDERS OF ADRENAL MEDULLARY HORMONES Pheochromocytomas, Neuroblastomas LABORATORY TESTING FOR ADRENAL MEDULLARY DISORDERS ROLE OF ENDOCRINE GLANDS IN THYROID FUNCTION Thyroid-Stimulating Hormone: Pituitary Hormone Thyroid Hormone Metabolism, Hypothyroidism

1 2

Lecture No 22- TESTING FOR THYROID DISORDERS Thyroid Function Testing Enzyme-Multiplied Immunoassay Technique (EMIT) Historical Methods of Thyroid Testing HYPERTHYROIDISM DISORDERS OF WATER BALANCE MINERAL METABOLISM PREANALYTICAL VARIATIONS IN HORMONE TESTING

1 2

Reproductive Endocrinology and Fetal Testing Lecture No 23- PREGNANCY, Markers of Pregnancy, Problems in Early Pregnancy Trophoblastic Neoplasm, Multiple Fetuses and Pregnancy Hormones PREGNANCY TESTS AND EARLY MARKERS OF PROBLEMS SEX STEROIDS Protein and Peptide Reproductive Hormones ENDOCRINE GLANDS INVOLVED IN REPRODUCTION

1 2

Lecture No 24- OVERVIEW OF NORMAL FEMALE REPRODUCTIVE PHYSIOLOGY The Role of Inhibins THE FEMALE REPRODUCTIVE CYCLE NORMAL MALE REPRODUCTIVE PHYSIOLOGY HORMONAL CHANGES IN MENOPAUSE FEMALE INFERTILITY Treatment for Infertility, Infertility of Multiple Causes ALPHA FETOPROTEIN Down Syndrome

1 2

Lecture No 25- FETAL SCREENING MULTIPLES OF THE MEDIAN Example Calculation of MoM Alpha Fetoprotein Levels and Fetal Disorders OTHER SIGNIFICANT BIRTH DEFECTS AND INBORN ERRORS OF METABOLISM REFERENCE RANGES IN NEONATES

1 2

Topics to be Covered No of Weeks

Contact hrs.

Malignancy Disorders and Testing Lecture No 26- LABORATORY TESTS TO SCREEN FOR DISEASE TUMOR MARKERS FOR COLORECTAL CANCER PROTEIN ELECTROPHORESIS MULTIPLE MYELOMA Waldenström’s Macroglobulinemia Amyloidosis Monoclonal Gammopathy of Undetermined Significance CA 125 MEDICAL DECISION LIMITS

1 2

Lecture No 27- THE CELL CYCLE MOLECULAR DIAGNOSTICS PROSTATE CANCER, Tumor Markers for the Prostate, Prostate Specific antigen Prostatic Acid Phosphatase, Other Prostate Tumor Markers Ectopic Hormone Production PANCREATIC CANCER, Pancreatic Tumor Markers

1 2

Therapeutic Drug Monitoring and Toxicology Lecture No 28- THERAPEUTIC DRUG MONITORING DRUG METABOLISM DRUG ACTION OF ANTIBIOTICS DRUG ACTION OF CARDIOACTIVE AGENTS TOXICITY OF CARDIOACTIVE DRUGS METHODS OF ANALYSIS FOR THERAPEUTIC DRUGS Complementary or Herbal Medicines’ Effect on Therapeutic Drug Monitoring ANTIEPILEPTIC DRUGS OTHER THERAPEUTIC DRUGS Psychoactive Drugs Antiasthmatic Drugs Antineoplastic Drugs Immunosuppressive Drugs

1 2

Lecture No 29- TOXICOLOGY ACETAMINOPHEN TOXICOLOGY, TOXICITY OF OTHER ANALGESICS ETHANOL AND ALCOHOL TESTING OTHER ALCOHOLS OSMOMETRY Volatile Organic Toxicity Screening THERAPEUTIC DRUG MONITORING AND TOXICOLOGY DRUG-OF-ABUSE TESTING HEAVY METAL TOXICITY Mercury Exposure

1 2

Topics to be Covered No of Weeks

Contact hrs.

Case Presentation (Clinical Session) As applications of laboratory tests for management of diseases or conditions many Case Scenarios will be presented and discussed with the students. In the hospital Diabetes and Other Carbohydrate Disorders 1. Diabetes Mellitus Type 1: The Emergency Department 2. Diabetes Mellitus Type 2 and the Diabetes Center 3. Gestational Diabetes Mellitus: The Prenatal Clinic 4. Transient Neonatal Hypoglycemia: The Big Baby Hemoglobin Production Disorders and Testing 1. Case of Iron-Deficiency Anemia: Iron-Poor Blood 2. Low Hemoglobin of Unknown Cause: Lead Poisoning from Paint in an Old House 3. Acute Variegate Porphyria: Darkening Urine Samples in the Laboratory 4. Problems With Glycated Hemoglobin Analysis Assessment of Renal Function 1. Glomerular Nephritis: Jennie 2. Nephrotic Syndrome Assessment: The Diabetic Patient 3. Azotemia Assessment: Out of Proportion 4. A Case of Renal Failure: A Review of the Laboratory Results 5. Renal Tubular Acidosis: A Matter of Balance 6. Hyperkalemia Due to Hemolysis: The Difficult Venipuncture 7. Pseudohyponatremia? A Problem With Analysis 8. Nephrogenic Diabetes Insipidus: Critical Values 9. Renal Calculi: Kidney Stones Assessment of Liver Function 1. Hyperbilirubinemia: A Yellow Serum Sample in a Rack of Tubes 2. Neonatal Hyperbilirubinemia: Why Is the Baby Yellow? 3. Elevated Hepatic Enzymes: The Standout Patient 4. Acute Inflammation of the Liver: The Out-of-Range Bilirubin Result 5. Acute Liver Failure: The STAT Ammonia 6. Quality Assurance in the Clinical Chemistry Laboratory: Why Are All of the Alkaline Phosphatase Results the Same? Assessment of Cardiovascular Disorders 1. Acute Myocardial Infarction: The Obese Smoker 2. Type 2 Diabetes With Cardiac Risk: Mildred Dodge, the Bonbon Eater

7 14

Topics to be Covered No of Weeks

Contact hrs.

3. Apolipoprotein A Deficiency 4. Congestive Heart Failure: Joe Returns 5. Silent Myocardial Infarction: Woman at Risk 6. Medication Toxicity: Age-Related Drug Distribution 7. The Clot Thickens: Joe Returns Again Assessment of Respiratory Disorders 1. Arterial Blood Gas Collection and Specimen Handling: The Case of the Pink Patient With a Dark Blood Sample 2. Chronic Bronchitis: Blue Bloater or Pink Puffer Patient? 3. Acute Respiratory Failure: Pain Medication Made Things Worse 4. Neonatal Respiratory Distress: The Grunting Baby 5. Possible Carbon Monoxide Poisoning: The Nauseated Patient With Cherry Red Lips 6. Correlation of POC Blood Gas Analyzer With Bench-Top Instrument: Are We Comparing Apples to Oranges? Assessment of Nutrition and Digestive Function 1. Alcoholic Liver Disease: Nutritional Effects of Alcohol Substance Abuse 2. Dietary Assessment of the Elderly: Mrs. Jansen’s Anemia rediabetes and Metabolic Syndrome: Apples and Pears 4. Zollinger-Ellison Syndrome: The Gastrinoma 5. Pancreatic Insufficiency: The Patient With Cystic Fibrosis 6. Electrolyte Disturbance in Acute Vomiting: Does Mr. Vijay Have Metabolic Alkalosis? Endocrine Disorders and Function 1. Cushing’s Syndrome: The Woman With the Buffalo Hump 2. Addison’s Disease: The Man With Noticeable Pigments 3. Pheochromocytoma: A Red-Haired Woman With a Taste for Bananas 4. Neonatal Hypothyroidism: Repeat Thyroid Testing on a Baby 5. Graves Disease: The Woman With Prominent Eyeballs 6. Diabetes Insipidus: A Patient With Very Dilute Urine 7. Hyperparathyroidism: The Patient With Elevated Calcium Levels Reproductive Endocrinology and Fetal Testing 1. Pregnancy Testing: Yes or No? 2. Infertility and Polycystic Ovarian Disease: “String of Pearls” in a Bearded Lady 3. Preanalytical Error in Reproductive Testing: How Important Is the Timing? 4. Fetal Assessment for Open Neural Tube Defects and Down

Topics to be Covered No of Weeks

Contact hrs.

Syndrome: MoM Testing for Baby’s Health 5. Hemolytic Disease of the Newborn: Two Rh-Negative Mothers Malignancy Disorders and Testing 1. Multiple Myeloma: An Unusual Band in Protein Electrophoresis 2. Medical Decision-Making for Malignancy: Correlating Tumor Marker Results with Likely Disease 3. Ruling In or Ruling Out Breast Cancer: A Frightened Young Woman Has a Breast Lump 4. Screening for Prostate Cancer: What Was the Current PSA? 5. Ectopic Hormone Production due to Oat Cell Carcinoma: Is Hyperosmolar Urine due to SIADH? 6. Pancreatic Cancer: Searching for the Cause of High Amylase Levels Therapeutic Drug Monitoring and Toxicology 1. Therapeutic Ranges: Trouble for Baby Jones 2. Monitoring Digoxin Levels: A Confused Man in the ED 3. Antiepileptic Medication Testing: Why Is She Still Having Seizures? 4. Acute Acetaminophen Overdose: A Child Gets Into the Medicine Cabinet 5. Medical and Legal Alcohol Testing: Was Alcohol Involved in the Accident? 6. Volatile Organic Toxicity: Unexplained Intoxication 7. Decision-Making: For Which Drugs of Abuse Should We Test? 8. Mercury Poisoning: The Fish in the Sea Lectures Each lecture is accompanied by a PowerPoint presentation, animation. Information from the presentation and assigned reading is important for mastering the learning objectives which are the primary focus of exam questions.

Review Sessions Review sessions will be scheduled prior to each exam. The time and format for each session will be arranged via the students coordinators.

Course Learning Objectives The students will know the biochemical basis of diseases, and how to correlate symptoms, signs, and complications to biochemical events, and the biochemical nature of the therapeutics approaches in the field of medicine. Also the student will know the most important laboratory data properly, the significance of a test results. Our student will :

- Describe the development, structure and function of the healthy human body and each of his major organ systems at molecular levels.

- Recognize and discuss the implications of altered structure and function and chemistry of the body and its major systems that are seen in various diseases and conditions.

- Describe the molecular basis and maladies and the way in which they affect the body .

Teaching strategies to be used to develop knowledge The student will attend:

a- Regular 2 hour lecture per week b- 2 hour tutorial class/ month c- 4 hours clinical session per month Assignments for independent study will be followed once per month - Introductory lecture gives an overview of the content and significance of the course and

of its relationship to students’ existing knowledge. - Each subsequent lecture begins with a similar overview linking the particular content of

the presentation to the general overview. - Tutorials review the content of each lecture and clarify any matters not understood. - Individual assignments require use of library reference material and web sites to

identify information required to complete tasks.

Roles and Responsibilities of Students and lecturers Students are expected to:

1. Use all available resources to accomplish the learning objectives in each lecture and case-based discussion and exercise session, including:

a. Attending all lecture and case-based discussion sessions. b. Reading textbook assignments. c. Participating in lecture and case sessions by answering questions posed in class

and asking questions when information is unclear or more information is needed. d. Performing assigned exercises working individually or in groups, as directed.

e. Submitting completed assignments on or before the stated deadlines for timely feedback.

f. Optimizing their learning strategies by trying the suggested “tips” and/or other ideas, and working with others.

g. Asking for help from the course manager when they need it or even think they might need it.

2. Notify the course manager as soon as they can if they are seriously ill or have an emergency that prevents them from attending the case sessions or an exam.

3. Provide constructive feedback regarding the course on evaluation forms that will be provided at the end of the semester.

4. Adhere to the faculty academic and professional rules. 5. Recognize that the study of microorganisms is critically important to everyday life and is

totally fun. Lecturer is expected to:

- Explanations and examples given in lectures and practiced under supervision in tutorials and laboratory tasks. Transfer of learning encouraged by use of analytical tools in different applications and through discussion of potential application in other areas.

- Assignment tasks include some open ended tasks designed to apply predictive, analytical and problem solving skills

Learning Resources

1 Clinical Biochemistry (an illustrated colour text). Allan Gaw – Churchill Livingstone

2 Clinical Chemistry, 3rd edition-1998, By William Marshall. Mosby-London.

3 Clinical Chemistry: in Diagnosis & Treatment, 6th edition-1994; By Philip D Mayne. Arnold-London.

4 Clinical Chemistry, a laboratory perspective 1St edition 2007; By Wendey Arneson and Jean Brickell

5 Clinical Chemistry: Principle, Procedure, correlation, 3rd edition-1996; By Michael L Bishop. Lippincott- New York.

6 Davidson’s Principles & Practice of Medicine, 18th edition-1999; By C Haslett, ER Chilvers, JAA Hunter, NA Boon.Churchill Livingstone-London.

Methods of assessment of knowledge acquired - Mid semester examination: 60 minutes multiple choice test on studied topics with

results carrying 20% of final assessment. - 120 minutes multiple choice test on studied topics in mid- year exam with results

carrying 50% of final assessment. - Multiple choice knowledge item in final exam.

Schedule of Assessment Tasks for Students

Assessment task Week due Proportion of Final Assessment

1 First midterm exam 8 15 %

2 Seminar for search topics 16 10%

3 Mid year exam ( Final first term ) 17 25 %

4 Second mid term Exam 24 20 %

5 End of year Exam 34 30 %