Return to: Medical School : AHC : U of M Home

PrintPrint

Rotation Summaries - Clinical Pathology

Clinical Chemistry - University of Minnesota and Affiliated Hospitals

These three units are coordinated within each hospital. Thus, questions or requests for information or time off should be addressed to each coordinator.

Unit One (Jasbir Singh, VA Coordinator)

Laboratory Operations, Instrumentation, QA and QC, Management, Regulations, TDM - kinetics, Diagnostic Enzymology, Bilirubin, GI, Electrolytes, Acid-Base, Renal Function, Cathecholamines, EIA/RIA principles

Unit Two (Fred Apple, HCMC Coordinator)

Laboratory Operations, Forensic Toxicology/Drug Analysis, Cardiac Markers, Tumor Markers, Lipids/Risk Factors, Triple Test, Pregnancy Testing, Fetal Lung Maturity, Predictative Value, ROC Curves, Point of Care Testing

Unit Three (Michael Steffes, University Coordinator)

Laboratory Operations, Proteins, Endocrinology, Anemia (iron, B12, folate, ferritin), Diabetes including glucose bedside testing, UA and Body Fluids, Biochemical Genetics, Amino and Organic Acids, Serology

Introduction

The Clinical Chemistry rotation provides a 3-month experience for all Department of Laboratory Medicine and Pathology residents, clinical chemistry postdoctoral fellows, and incoming chemical pathology fellows. As part of this basic rotation, the residents/fellows rotate through all general and special chemistry at the VA Medical Center, Hennepin County Medical Center and University of Minnesota Medical Center, Fairview. Interaction with faculty located at these institutions provides a perspective on laboratory organization and design and the practice of clinical chemistry as seen in a variety of different settings.

The Introduction to Clinical Chemistry rotation is organized to both teach the fundamental principles of clinical chemistry and to provide extensive experience with the day-to-day clinical application of those fundamentals. The fundamental principles are taught through a structured list of teaching objectives that are arranged into three separate Units. A description of each Unit with a list of teaching objectives and laboratory exercises is found in the next section of this manual. A Unit Coordinator and other specified faculty and senior fellows are assigned to each Unit to teach and instruct the residents/fellows through direct interaction. Each Unit Coordinator is responsible for arranging the day-to-day scheduling during her/his Unit, how and when the laboratory exercises will be performed, when the resident will meet with Unit faculty, etc. Depending on the faculty and the Unit, this interaction usually includes the following:

At least one week prior to the start date of each unit, the resident(s)/fellow(s) should review the section of this manual that describes the requirements for the next scheduled Unit. They then should contact the Coordinator to receive information regarding appointments for the didactic sessions and to complete any necessary arrangements for laboratory demonstrations and exercises.

Prior to the start date of each Unit the resident should review the Specific Learning Objectives and review the Required Reading Assignment listed in each Unit. If she/he is familiar with the material, she/he need not read the reading assignment word-for-word. However, if the material is not familiar, she/he should make every attempt to master it before meeting with the faculty for the didactic sessions throughout the Unit. This will allow for much more efficient use of time during the didactic sessions and will minimize the possibility of not having a chance to discuss with the faculty any section that is confusing or needs extraction of the key, most clinically relevant points in the subject matter under consideration. The Additional/Optional Readings are just that (i.e., optional) for the resident/fellow particularly interested in that area or having a case or clinical question posed to them as part of their consultative responsibilities during the rotation. There is no expectation that a resident/fellow will read all of these Additional/Optional Readings during the Introduction to Clinical Chemistry rotation.

The clinical applications are taught primarily through performance of a variety of assigned clinical responsibilities which are intended to provide extensive contact with attending and house staff physicians from clinical services. This includes:

Laboratory exercises are designed not only to illustrate technical aspects of clinical laboratory testing, but also interesting clinical results and potential clinically important interferences. In some cases the laboratory exercises involve actual performance of an "experiment" by the resident/fellow. Other times she/he merely observes a laboratory test being performed to gain some familiarity on the analytical time and complexity of a variety of representative tests. However, we recognize that our residents possess a wide variety in previous laboratory experience. Thus, the faculty has agreed that no laboratory exercise is required. At the beginning of each Unit, the resident(s)/fellow(s) should clearly state which experiments they plan to do or not do so that the technologists who assist with the laboratory exercises do not waste time preparing for something the resident(s)/fellow(s) do not intend to do.

Additional experience with practical problems related to laboratory operations and management is gained through involvement with basic issues of laboratory management, such as:

Goals and Objectives

Unit One (Jasbir Singh, VA Coordinator)

Laboratory Operations, Instrumentation, QA and QC, Management, Regulations, TDM - kinetics, Diagnostic Enzymology, Bilirubin, GI, Electrolytes, Acid-Base, Renal Function, EIA/RIA principles

  1. Introduction to Reporting of Laboratory Results
    1. Be familiar with chemistry specimen processing, data handling, record keeping, telephone answering and stat procedure system.
    2. Be familiar with the reporting units (SI and conventional), and enzymatic units.
  2. Laboratory Management

    Specific Learning Objectives

    1. Understand the following:
      1. Laboratory accreditation - HCFA, JCAHCO, CAP
      2. Internal quality control programs-materials available, methods.
        1. What is the precision of the method?
        2. How are "action" and "warning" limit defined?
        3. How large is the analytical imprecision compared to the reference range?
        4. Would a more precise analytical method be useful clinically?
      3. External quality control programs (proficiency testing)-CAP, others.
      4. Understand the impact of CLIA '88 on hospital and physician office laboratories.
    2. Be able to describe the concept of a quality assurance program, as opposed to a quality control program, as defined by the JCAHCO. Understand the concept of a quality assurance "indicator" and understand how to develop, perform, and utilize these indicators as part of an on-going quality assurance program.
    3. Know the general principles of the clinical laboratory administrative structure for optimum direction and management.
    4. Know the principles for laboratory design.
    5. Understand the following personnel matters:
      1. Registration, certification, licensure of various levels of laboratory personnel (CLA, MLT-non-degree, MLT-degree, MT, clinical chemists, pathologists) and agencies involved (ASCP, NCA, ABCC, ABP).
      2. Importance of position descriptions and performance evaluations.
      3. Ways of handling personnel problems with unionized and non-unionized employees.
      4. Productivity measurements (work-units).
    6. Understand principles concerning:
      1. What test should be offered and when they should be made available.
      2. What analytical methods should be used - analytic, economic and other considerations.
      3. Instruments selection-financing (lease, purchase, "free" for reagent use.) routine vs. STAT, sample size.
      4. Instrument maintenance - in-house availability or vendor service, service contracts.
      5. Reagent selection - kits, price, delivery, ordering, inventory, quality control in-house and by the vendor.
      6. Laboratory safety including state and federal regulations.
    7. Understand the importance of good communications with other areas of the hospital (e.g., medical and nursing staff, hospital administration, medical records, etc.).

    Required Reading

    1. Tietz Textbook of Clinical Chemistry 4th Edition. Burtis C.A. , Ashwood E.R. and Bruns D. E. Editors. Chapter 19.
    2. Clinical Chemistry Theory, Analysis and Correlation. 2nd Edition Kaplan, L.A. and Pesce, A.J. Editors. Chapters 18 and 19.
    3. Naito H.K. et al. Matrix effects on Proficiency Testing Materials, Impact on accuracy of Cholesterol Measurement in Laboratories in the Nation's Largest Hospital System. Arch Pathol Lab Med 117: 345-351, 1993.
    4. Westgard et al. A Muti-Rule Shewhart Chart for Quality Control in Clinical Chemistry. Clin Chem 27: 493-501, 1981.
  3. Introduction to Clinical Laboratory Instrumentation

    Specific Learning Objectives

    1. Describe functions of the principal components of and major differences between the following instruments using a block diagram:
      1. A simple single-beam spectrophotometer
      2. A Fluorometer
      3. A Nephelometer
      4. Several major automated instruments used in the VA clinical chemistry laboratories (e.g., Architect 2000, Abbott AxSym, Hitachi 911.)
    2. Describe Beer's Law, stray light, bandwidth, and Allen's correction.
    3. Know the importance of a spectrophotometer bandwidth.
    4. Describe the main clinical use of fluorescence polarization spectroscopy. Why is it useful?
    5. Describe the principles of flame emission and atomic absorption spectroscopy and the clinical uses of each?

    Required Reading

    1. Clinical Chemistry Theory, Analysis and Correlation. 2nd Edition Kaplan, L.A. and Pesce, A.J. Editors. Chapters 3 and 14.
    2. Tietz Textbook of Clinical Chemistry 4th Edition. Burtis C.A., Ashwood E.R. and Bruns D. A. Editors. Chapter 3
  4. Therapeutic Drug Monitoring

    Specific Learning Objectives

    1. List five reasons for performing drug analysis
    2. Know the definition and Clinical utility of the following pharmacokinetic terms
      • Volume of distribution
      • Half-life
      • Clearance
      • Loading dose
      • Steady state
      • Bioavailability
      • Therapeutic Concentration
      • Peak
      • Trough
    3. Review the pharmacokinetics of the following drugs through case review and problems
      • Theophylline
      • Vancomycin
    4. Know the principles that are involved in the measurement of therapeutic drugs by:
      • Fluorescent Polarization Immunoassays (FPIA)
      • Enzyme Multiplied Immunoassays (EMIT)
      • Cloned Enzyme Donor Immunoassay (CEDIA)
      • Kinetic Interaction of Microparticles in solution (KIMS)
      • High performance Liquid Chromatography (HPLC)
      • Gas Chromatography (GC)
    5. Know the advantages and disadvantages of measuring drug concentrations by immunoassay techniques compared to those that use HPLC or GC.
    6. Know the circumstances wherin determinations of serum free drug concentrations are necessary
    7. Describe the mechanism of toxicity, relevant serum drug concentrations and treatment for the overdose of salicylate and acetaminophen.

    Required Reading

    1. Clinical Chemistry Theory, Analysis and Correlation. 2nd Edition Kaplan, L.A. and Pesce, A.J. Editors. Chapters 5, 6, and 11.
    2. Tietz Textbook of Clinical Chemistry 4th Edition. Burtis C.A., Ashwood E.R. and Bruns D.A. Editors. Chapter 33
    3. Friedman H and Greenblatt D.J. Rational Therapeutic Drug Monitoring. JAMA 256 (16): 2227-2233, 1986
    4. Levy R.H. and Moreland T.A. Rationale for Monitoring Free Drug Levels. Clinical Pharmacokinetics 9 (suppl 1): 1-9, 1984.
    5. Salgia, A.D.T. and Kosnik.S.D. When Acetaminophen use becomes toxic. Postgraduate Medicine 105: 81-90, 1999
  5. Electrolyte/Acid-Base Balance

    Specific Learning Objectives

    1. Understand the general operation of the following:
      • Flame photometer
      • Atomic absorption
      • Blood gas and pH instruments
      • Osmometer
    2. Understand the theoretical basis and application of ion-selective electrodes; understand the analytical difference between direct and indirect potentiometry, ion-specific electrodes on different instruments
    3. Know the flame emission methods for Na+ and K+, the atomic absorption methods for Ca++ and Mg++, the major methods for Ca++, phosphorus, Cl-, CO2 and HCO3-, the flame, atomic absorption and electrode methods for lithium.
    4. Understand the analytical principles and the quality control for blood gas measurements.
    5. Understand the pathophysiology of water regulation, extracellular fluid sodium content, ventilation and oxygenation.
    6. Understand the pathophysiology of hyponatremia, hypernatremia, hypokalemia, hyperkalemia, hypercalcemia, hypophosphatemia, hypomagesemia.
    7. Understand the pathophysiology of acid-base disturbances. Be familiar with the tables and nomograms for acute and chronic disorders.
    8. Know the causes of hypoxemia; learn to calculate the arterial/alveolar pO2 difference.
    9. Become familiar with the kinetics and affects of CO on oxygen saturation of hemoglobin. Know the principles of measuring saturated hemoglobin and methemoglobin by oximeter.

    Required Reading

    1. Clinical Chemistry Theory, Analysis and Correlation. 2nd Edition Kaplan, L.A. and Pesce, A.J. Editors. Chapters 13, 20, and 21.
    2. Cowell DC & McGrady PM: Direct-measurement ion-selective electrodes: Analytical error in hyponatremia. Clin. Chem. 1985;31:2009-2012.
    3. Apple FS, Koch DD, Graves S, and Ladenson J: Relationship between direct-potentiometric and flame-photometric measurement of sodium in blood. Clin. Chem. 1982;28:1931-1935.
    4. Ladenson.J.H. AppleF.S. and Koch D.D. Misleading Hyponatremia Due to Hyperlipemia: A Method-dependent Error. Annals Internal Med 95: (1981)
  6. Renal Function

    Specific Learning Objectives

    1. Know the major methods for urea and creatinine measurements.
    2. Know the relationship between urea and creatinine in prerenal and renal azotemia.
    3. Know the relationship between serum creatinine and creatinine clearance and how methods (Jaffe vs. enzymatic creatinine) will affect these results.
    4. Know uric acid metabolism.
    5. Know the usual causes of hyperuricemia and their management.
    6. Discuss the ways of distinguishing prerenal, renal and post-renal failure.
    7. Know how to evaluate polyuria.

    Required Reading

    1. Clinical Chemistry Theory, Analysis and Correlation. 2nd Edition Kaplan, L.A. and Pesce, A.J. Editors. Chapters 22
  7. Basic Enzymology, Liver Function Test and Gastrointestinal Disease

    Specific Learning Objectives

    1. Residents should have a knowledge of the following basics:
      1. The Michaelis-Menten equation.
      2. Zero- and first-order kinetic portions of this equation.
      3. Principles used in the measurement of serum or urine enzyme activity
      4. Principles used in the measurement of an organic molecule's concentration using an ezymatic method.
    2. Know the factors involved in clinical interpretation of enzyme tests:
      1. Tissue distribution, intracellular location, isozymic forms of the commonly measured serum enzymes.
      2. Mechanisms of release and duration of release from damaged cells and tissues.
      3. How rates of enzyme clearance from plasma effect serum enzyme concentrations..
      4. Which enzymes rise primarily because of induced enzyme synthesis rather than release from damaged cells.
    3. Be familiar with the analytical methods used in the determination of enzyme activity, enzyme mass, and isoenzymes:
      1. Electrophoretic
      2. Spectrophotometric
      3. Immunoenzymatic
    4. Know the normal anatomy, physiology and biochemistry of the liver:
      1. Micro and macroanatomy of the liver and biliary tract.
      2. Metabolism of carbohydrates, lipids and proteins in the liver.
      3. Hormonal influences in the liver (e.g. insulin, glucagon).
      4. Synthesis of specific plasma proteins.
      5. Bile acid synthesis and excretion.
      6. Urea synthesis and excretion.
      7. Drug metabolism in the liver.
      8. Metabolism and excretion of bilirubin.
    5. Understand the etiology and diagnosis of the major types of jaundice:
      1. Pre-hepatic (hemolysis, ineffective erythropoiesis).
      2. Hepatic (pre-microsomal, microsomal, post-microsomal, intrahepatic obstruction.
      3. Post-hepatic (gallstones, stricture, carcinoma of the pancreas or biliary tree).
    6. Be familiar with the basic liver function tests:
      1. Hepatocellular serum enzyme indicators (serum AST, ALT).
      2. Obstructive jaundice indicators (serum conjugated bilirubin, alkaline phosphatase, 5'-nucleotidase, gamma-glutamyltransferase).
    7. Know the macro and microanatomy of the upper and lower gastrointestinal tract and the specialized functions of each region.
    8. Understand the pathogenesis, diagnosis and management of acute and chronic pancreatitis.
    9. Know the difference between malabsorption and maldigestion and how the laboratory is used to distinguish them.
    10. Understand the pathogenesis of diarrhea, the techniques for evaluation and the interpretation of stool testing.

    Required Reading

    1. Clinical Chemistry Theory, Analysis and Correlation. 2nd Edition Kaplan, L.A. and Pesce, A.J. Editors. Chapters 23, 25 and 26
    2. Tietz Textbook of Clinical Chemistry 4th Edition. Burtis C.A., Ashwood E.R. and Bruns D.A. Editors. Chapter 21
    3. Singh J. and Bowers L. Serum Bilirubin Species: Analysis and Clinicl Utility. Lab Medicine 16: 597-601 (1985)
    4. Shiau YF: Clinical and laboratory approaches to evaluate diarrheal disorders. CRC Crit Rev Clin Lab Sci 1987;25:43-69.
    5. Wong, ECC. The Clinical Chemistry Laboratory and Acute Pancreatitis. Clin Chem 1993;39(2):234-243.
    6. Moseley RH. Evaluation of Abnormal Liver Function Test. Medical Clinics of North America 1996;80(5):887-906.
    7. Lott JA, Dumas BT. "Direct" and Total Bilirubin Test: Contemporary Problems. Clin Chem 1993;39(4):641-647.

Unit Two (Fred Apple, HCMC Coordinator)

Laboratory Operations, Forensic Toxicology/Drug Analysis, Cardiac Markers, Lipids/Risk Factors, Triple Test, Pregnancy Testing, Fetal Lung Maturity, Predictive Value, ROC Curves, Point of Care Testing

  1. During the 4 week rotation, laboratory medicine residents and fellows should be able to accomplish the objectives outlined in the enclosed schedule.
  2. Dr. Fred Apple will supervise the residents and fellows. Each resident will be responsible for the following.
    1. Residents will be on (beeper) call to answer questions that arise in the toxicology or chemistry laboratory that require test approval, Stat assays, clinician interaction, etc. A call schedule will be completed and given to Linda Moyer for hospital (HCMC) circulation. Arrangements for coverage for off time should be discussed with Dr. Apple.
    2. Meet for 3 to 5 hours per week at scheduled times to discuss specific topic of the week, problems and questions that arise during the week.
    3. Friday mornings, 9:30 - 10:30 a.m. Chem/Tox call rounds (QA Monitor); presentation of all beeper calls and cases followed up during the week by resident and staff on call. Following this, discuss, review and follow up on cases concerning interesting problems related to the previous week's teachings and discussions with lab supervisors and managers (keep notebook and current literature file).
    4. Present interesting case with bottom line on role of laboratory (10-15 minutes) at Wednesday noon, Staff-Resident Conference pertaining to topic of week (or previous week) as per schedule.
    5. Review sendout requests from triage (follow up at Friday call meeting) will be paged when necessary.
    6. Tuesdays, 2:30-3:30, Toxicology ME Rounds, ME Conference Room; will present articles at journal club as per schedule.
    7. Review daily cardiac troponin I results. Follow up with chart review for interesting cases. Always complete investigative patient form and present 1 or 2 cases as unknowns every Friday morning at call review.
  3. Residents will be required to review any toxicology results and follow up on unusual and/or abnormal results generated by the tox staff, and to keep records of consultation.
  4. Paula Toupal, Clinical Chemistry supervisors (x 7-3016) and Julie Kloss, Toxicology Laboratory supervisor (x 7-3018), will be your key contact people regarding these lab areas. They will (often) call you with questions and cases.
  5. Residents will be required to review and follow up on abnormal/interesting quad testing cases; discussion with genetics counselor will be scheduled monthly in Carol L.'s office. Follow up at Friday call review.
  6. Residents will be required to enter interesting case follow-ups into the computer case format, documenting and recording appropriate information as designed, on a weekly basis.
WEEK ONE: A. General Introduction to Laboratory Operations, Instrumentation, Laboratory Management

Monday through Friday (Weekends): These items should be reviewed daily while on service (go over with Dr. Apple).

  1. Review Troponin I results
  2. Review protein ELP
  3. Review sendout and endocrine critical values for QA
  4. Review FLM logs - diabetics, twins only
  5. Review forensic toxicology reports (GC/MS) with Dr. Apple or Julie Kloss

Tuesday:

  1. * Chemistry Lab Tour - supervisors (x 7-3405)
  2. * Toxicology Lab Tour - Julie Kloss, supervisor (x 7-3018)
  3. * SendOuts - Joan Morgan, supervisor
  4. * Triage - , supervisor
  5. * Review major policies in Toxicology and Chemistry lab with Paula Toupal and Julie Kloss (Residents' Room has circulating policy book)

Wednesday:

  1. * Computer Introduction supervisor (x 7-6460); obtain password
  2. * Instrumentation Overview
    1. Chemistry -Paula Toupal
    2. Toxicology - Julie Kloss

Thursday:

  1. * Quality Control Review - Julie K. Tox

Friday:

9:30 - 10:30 Chem/Tox Rounds - Call Review/Case Review

* It is the resident's responsibility to arrange/schedule.

WEEK ONE: B. Diagnostic Efficacy of Lab Tests; Quality Control; Lab Test Evaluation
  1. Understand calculations for standard deviation and coefficient of variation; interpret data.
  2. Distinguish between the within-run versus day-to-day imprecision; describe percentage of people or observations that fall within + or - S.D., + or - 2 S.D., and + or - 3 S.D..
  3. Explain the clinical usefulness of quality control and quality assurance programs.
  4. Understand and calculate diagnostic sensitivity, specificity, predictive value (positive and negative result) (ref: Galen and Gambino: Beyond Normality).
  5. Familiarize yourself with use and interpretation of ROC (receiver operator characteristic) curves; find relevant examples in the literature for discussion.
  6. Normal Values/Reference Ranges
    1. Describe parametric and nonparametric techniques and the inherent statistical bias and problems.
    2. Review normal range book in chemistry; understand how we calculate normal ranges using parametric and nonparametric methods. Prepare to discuss how ranges were accepted.
    3. Describe conditions that affect the normal values.
  7. Read Chapter 9 in Gradwohls on Nonanalytical Sources of Variation. Utilize thischapter in resolving patient methodology problems.
  8. Be familiar with the S.I. units.
  9. Discuss throughout rotation the rationale of offering "panel" tests vs. "individual" test ordering. Review BC/BS and American College of Physicians guidelines. Understanding HCFA guidelines for panels and the need for documenting medical necessity.
  10. Review how new assay evaluation protocol is performed: precision, linearity, patient crossover, recovery, interferences, etc.

Laboratory Management

  1. Understand the following:
    1. Laboratory accreditation (JCAH, CLIA, CAP, State Health Department, CAP Forensic Tox, NIDA) review policies
    2. Internal quality assurance (QA) and quality control programs - monthly meeting should be attended
    3. External quality control programs (proficiency testing) - CAP, AACC, CDC, State Health Department, NIDA
  2. Know the laboratory organization hierarchy and laboratory design.
  3. Understand the following personnel matters (discuss with Chem and Tox managers and supervisors):
    1. Registration, certification, licensure of various levels of laboratory personnel (CLA, MLT, MT, clinical chemists, pathologists) and agencies involved (ASCP, ISCLT, NCA, ABCC, ABP)
    2. Position descriptions, performance evaluations
    3. Ways of handling personnel problems with union and non-union employees
    4. Productivity measurements (work-units)
  4. Understand principles of:
    1. Method selection - analytical, economic and other considerations
    2. Instrument selection - financing (lease, purchase, reagent rental), routine vs. Stat, sample size, random access
    3. Instrument maintenance - in-house availability or vendor service, service contracts
    4. Reagent selection - kits, price, delivery, vendor QC
    5. Review the bid process - use example, i.e. GC MS, Immunoassay analyzer.
    6. Purchasing
    7. It would be advantageous for the resident to undertake a mini project in this area. Discuss with Dr. Apple.
  5. Understand the importance of good communications. Meet with lab administrator, lab manager, laboratory staff and other parts of the hospital (medical and nursing staff, hospital administration, medical records, etc.).
  6. Be visible and always work on good communications.
WEEK ONE AND TWO: Markers for Detection of Myocardial Injury
  1. Review the pathophysiology and definitions of acute myocardial infarction, acute coronary syndrome, and unstable angina. Include review of WHO criteria, NACB guidelines, and ACC/AHA unstable angina guidelines.
  2. Review biochemistry of creatine kinase isoenzymes, myoglobin, and cardiac troponins I and T.
  3. Review methods for cTnI, cTnT and CK MB. Understand standardization issues and potential interferences with assays.
  4. Review protocols and assays used to rule in and rule out AMI in ischemic chest pain patients. Understanding time of markers and what markers are optimal as first line testing.
  5. Understand how markers, especially troponins, are used for early diagnosis, confirmation, reinfarction, reperfusion assessment.
  6. Be familiar with role of markers in cardiac surgery for ruling in AMI.
  7. Understand role of troponins for risk stratification in acute coronary syndrome patients; regarding the role of medical intervention with or without marker information.
  8. Discuss role for CRP and BNP as markers for risk stratification and detection of severity of heart failure, respectively.
WEEK THREE

Toxicology, Drug Analysis

(Always be familiar with where, how, and when assay/test is performed. Also be familiar with back-up procedures; assay down policies, etc.)

  1. Describe the operation, utility, and components of a gas chromatograph/mass spectrometer (GC-MS) in a toxicology laboratory.
  2. Describe screening and quantitative methods for the following. Review all policies and memos regarding test result interpretation.
    1. Volatiles: Ethanol, Methanol, Isopropanol, Acetone, Ethylene Glycol
    2. Pentobarb
    3. Phenytoin (Total/Free)
    4. CO
    5. Lithium
    6. Thiocyanate, cyanide
    7. Tricyclic antidepressants
    8. Chloramphenicol
    9. Arsenic
    10. Caffeine
    11. Digoxin
    12. Drugs of abuses including:
      Amphetamines
      Methadone
      Cocaine
      Cannabinoids
      Morphine
      LSH
      Benzodiazepines
      PCP
      Opiates
  3. Describe the mechanism of toxicity, relevant serum concentrations, and treatment for salicylate and acetaminophen overdose.
  4. Explain the pathophysiology of alcohol (ethanol) with respect to:
    1. Absorption, metabolism, elimination
    2. Blood, urine, breath analyses
    3. Forensic use of vitreous humor
    4. Review calculations in dram shop ethanol case (forensic)
  5. Know pathways of iron metabolisms; Iron OD-chronic vs acute.
  6. Review specimen handling/screening/quantitation in forensic cases.
  7. Become familiar with NIDA and CAP-TOX guidelines for drugs of abuse screening and confirmation; and what quality control procedures must be maintained.
  8. Review the mechanism for lead intoxication. Describe the methods used to measure lead and review the need for requested Stat lead levels. How are ZnEP and FEP used to screen for lead intoxication. Understand problems involved with collections.
WEEK FOUR:

Review methods, pathophysiology and clinical use of the following tumor markers:

  1. PSA (total, free)
  2. CEA
  3. Beta-hCG
  4. AFP
  5. CA 19-9
  6. CA-125
  7. LD
  8. Others

Fetal Monitoring - OB/GYN Testing

  1. Understand the protocol and technology used for screening for fetal lung maturity (FLM) using the Abbott FLM test. Under what circumstances do we obtain L/S ratios, PG, and DSL requests. Follow up on a daily basis all FLM requests with Labor and Delivery/OBGYN involving diabetes cases and twin pregnancies.

    Beware of other amniotic fluid tests: foam stability, OD 650 nm.
  2. Understand amniotic fluid and maternal serum alpha fetoprotein MSAFP, beta hCG and unconjugated estriol monitoring (triple test) and the protocols followed. Review the pathways for correcting results and reporting results as MoM. Determine effects of race, diabetes and weight on MoM. Follow up on abnormal cases on a monthly basis with genetics counselor. How are values used clinically for Down Syndrome and neural tube defects. Review data on inhibin.

Lipid

  1. Describe the methods used in quantifying serum total cholesterol, triglycerides.
  2. Describe the methods used to fractionate and quantitate the following: HDL-C, LDL-C, VLDL-C. Understand utility of calculated LDL-C; illustrate the electrophoretic migration of lipoproteins. What, if any, is the utility of this test?
  3. Describe the clinical utility of total cholesterol, HDL-C, LDL-C and VLDL-C and trigs. Become familiar with the NIH National Cholesterol Education guidelines and recommendations.
  4. Understand the methods and utilization of apolipoproteins for clinical diagnosis of lipid disorders; specifically A1, B100, and Lpa; and their use as markers for coronary artery disease.
  5. Review the pathophysiology, clinical significance and role for measuring homocysteine as a marker for CAD. Review technologies available for measurement.

Unit Three (Michael Steffes, University Coordinator)

Laboratory Operations, Proteins, Endocrinology, Anemia ( iron, B12, folate, ferritin), Diabetes including glucose bedside testing, UA and Body Fluids, Biochemical Genetics, Amino and Organic Acids, Serology

Phone: 612-624-8164
Length of Unit: 4 weeks

In this unit the resident will meet with the laboratory directors and supervisors at the University of Minnesota Medical Center (UMMC-F) to review the basic organization and function of the general and specialized laboratories as they relate to the broad are of clinical chemistry. This will include a tour of each section with an explanation of the physical organization of the laboratory, a brief introduction to the available equipment and how it relates to the specific needs of each laboratory. Additional time will be spent with Dr. Donald Connelly reviewing applicable statistical techniques, medical decision making, and computer-related topics. Basic overview of the clinical laboratory and its relationships to the clinical services at UMMC-F will be presented by Dr. Steffes. Throughout the unit the resident will meet with Dr. Steffes to compare and contrast the organization of the various laboratories, basic laboratory management principles, and to discuss how the needs of the hospital determine the form of the laboratory.

Specific Learning Objectives

  1. Introduction to Reporting of Laboratory Results (all faculty)
    1. Be familiar with chemistry specimen processing, data handling, record keeping, telephone answering and stat procedure system.
    2. Be familiar with the S.I. fundamental units, concentration units, and enzymatic units.
  2. Hematologic Chemistry (John Eckfeldt)
    1. Know the basic physiology of the erythrocyte, including hemoglobin synthesis, iron, folate, and B-12 metabolism.
    2. Understand the pathophysiology and diagnosis of the common disorders of hemoglobin synthesis and metabolism.
    3. Know the biochemical, genetic, and physiologic abnormalities of the six major types of porphyria.
    4. Know the etiology of porphyrinuria caused by lead poisoning and how to use the laboratory to identify lead poisoning.
  3. Proteins Measurements (Michael Steffes)
    Specific Learning Objectives
    1. Understand electrophoresis profiles, immunoelectrophoretic patterns and immunofixation patterns as they relate to polyclonal, monoclonal and oligoclonal gammopathies and monoclonal proteins found in the urine (usually light chains).
    2. Understand the genetic variation of alpha-1-antitrypsin and its clinical significance.
    3. Understand the physiologic role of albumin; cause and clinical significance of hypoalbuminemia, bisalbuminemia and analbuminemia.
    4. Understand IgG subclass analysis and clinical significance.
    5. Understand the advantages and disadvantages of specific immunochemical methods (RIA, EIA, RID and nephelometry).
    6. Know the more common serum protein electrophoresis patterns (e.g., acute phase reaction, liver disease, renal disease, monoclonol gammopathies, etc.) and their significance to a degree needed to sign-out the daily serum protein electrophoresis and immunofixation gels.

Required Reading

  1. The presentation and associated manuscripts.

Additional/Optional Readings

  1. Beyond Normality. Galen RS and Gambino SR. John Wiley Biomedical: New York. 1975.

Exercises/Demonstrations

The following exercises and demonstrations can be performed this week as appropriate to the background and interests of the residents (see attached schedule). The results should be discussed with the technologists assisting with the exercises and with teaching coordinators for the week. In general, experiments are designed not only to illustrate technical aspects of clinical laboratory testing, but also interesting clinical results and potential clinically important interferences. Recall that at the beginning of each unit the resident should clearly state which experiments he/she plans to do or not do, so that the technologists who assist with the experiments do not waste time preparing for experiments the resident(s) do not intend to perform.

  1. Obtain a CAP Laboratory Inspection and Accreditation checklist and some time within the first month of the rotation inspect a laboratory section of the UMMC-F clinical chemistry laboratory.
  2. Perform a serum protein electrophoresis and immunofixation; observe hemoglobin isoelectric focusing.
  3. Become proficient at interpreting serum and urine protein electrophoresis and immunofixation patterns, and hemoglobin isoelectric focusing patterns.
  4. Tutorials on the computer in the laboratory

Exercise Objectives

  1. Become familiar with general chemistry laboratory equipment
  2. Become familiar with the laboratory inspection and accreditation process.

Computers are available in the Resident's Room. The chemistry resident should be familiar with it for word processing (e.g., Microsoft Word) and spreadsheet use (e.g., Microsoft Excel).

Endocrinology And Metabolism (University)

The didactics and reading assignments are designed to provide the resident with an up-to-date overview of the principles of endocrinology and metabolism with an emphasis on laboratory investigations. Residents are strongly encouraged to schedule time with the Senior Medical Technologist in the Endocrine Laboratory at UMMCF to observe analytical procedures for several different compounds; e.g., parathyroid hormone assay (PTH), and chemiluminescent assay (TSH). For each of these the resident should review the kit's package insert to understand the principle of the assay.

Specific Learning Objectives

  1. Introduction to Endocrine Testing
    1. Understand the different types of assays (e.g., EIA, immunometric, chemiluminescent, etc.) used to measure various hormones and some of the advantages and disadvantages of these systems.
    2. Be familiar with the instrumentation for immunoassays in the clinical laboratory, particularly the newer automated equipment.
  2. Adrenal Function
    1. Know the major hormones of the adrenal cortex.
      • Synthetic pathways
      • Regulation
      • Actions
    2. Know the laboratory tests to diagnose the major disease entities in
      • Cushing's syndrome
      • Adrenal insufficiency
      • Adrenal tumors
    3. Know the methods for measuring the main plasma steroids and their metabolites in the urine.
  3. Reproductive Endocrinology
    1. Know the structural features, functions and regulation of synthesis for the sex steroids. Know the differential diagnosis of:
      • Hirsutism and virilization
      • Feminizing disorders
      • Precocious puberty
    2. Know the hormonal changes associated with the different phases of the menstrual cycle.
    3. Know the endocrine changes in pregnancy and lactation.
    4. Know the diagnostic tests for normal pregnancy, tubal pregnancy and miscarriage, and the interpretation of quantitative ß HCG assays for these conditions.
    5. Know the diagnostic tests for infertility and the appropriate tests to follow patients on Clomiphene Citrate, Pergonal and patients undergoing in vitro fertilization.
  4. Thyroid
    1. Understand the physiologic control of thyroid hormones, their structure and function.
    2. Know the principal causes of hypo and hyperthyroidism.
    3. Understand the principles of assays for TSH, free T4, and total T3.
    4. Understand how TSH, T3, T4, and TBG change in hypo and hyperthyroidism, in non-thyroidal illness, and with age.
    5. Understand the diagnostic utility of anti-mitochondrial and anti-thyroglobulin antibodies and how they are assayed.
  5. Diabetes Mellitus
    1. Know the classification, diagnostic criteria, and prevalence of diabetes mellitus.
    2. Understand current thinking on the etiology of diabetes and its complications.
    3. Know the principles of glucose analysis in the chemistry lab and by home monitors.
    4. Know the significance of glycated hemoglobin and methods for its analysis.
    5. Understand the pathophysiology of diabetic ketoacidosis and the following: analysis of ketones, usefulness of anion gap and ketostix to follow treatment.
  6. Calcium Metabolism
    1. Know the roles of the major hormones involved in calcium metabolism:
      • Parathyroid hormone
      • Calcitonin
      • Vitamin D
    2. Know the metabolic pathway and sites for Vitamin D.
    3. Know the role that parathyroid hormone-like peptide play in hypercalcemia of malignancy and how this hormone is measured.

Required Reading

  1. American Diabetes Guidelines, first supplement of each year in Diabetes Care
  2. Tietz. Fundamentals of Clinical Chemistry. Burtis CA, Ashwood ER, eds. WB Saunders: Philadelphia, 1996:617-703.

Diabetes:

  1. Expert committee on the diagnosis and classification of diabetes mellitus. Report on the Diagnosis of Diabetes Mellitus, Diabetes Care 1997;20:1183-1197.
  2. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977-981.

Calcium Metabolism:

  1. Farus MJ (editor). Primer on the metabolic bone diseases and disorders of mineral metabolism (third edition). The American Society for Bone and Mineral Research. Lippincott-Raven. Philadelphia. 1996.
  2. Heaney RP. Pathophysiology of osteoporosis in osteoporosis. Watts NB (ed). Endocrinology and Metabolism Clinics of North America 1998;27:253-266.
  3. Blake GM, Fogelman I. Applications of bone densitometry for osteoporosis. ibid 267-288.
  4. Garnero P, Delmas PO. Biochemical markers of bone turnover. Applications for osteoporosis. ibid 303-324.
Biochemical Genetics/Molecular Genetics ( University)

Residents are expected to follow all in and outpatients currently followed by the metabolic/genetics clinic. A file folder of some representative papers will be given by Dr. Tsai at the beginning of the rotation. Residents will be asked to read additional papers with regard to disorders related to patients being seen that week. Residents should also attend the Thursday afternoon conference of the Pediatric Metabolic Clinic from 1:30-3:00 p.m. on 13th floor PWB 13-114.

In addition to biochemical genetics, Unit 6 covers fetal lung maturity testing and lipid and cardiovascular risk factors. The general objectives for each of these four units are as follows:

Specific Learning Objectives

  1. Biochemical Genetics ( University )
    1. Know methods for diagnosis of aminoacidopathies.
    2. Know methods for diagnosis of organic aciduria.
    3. Know methods for diagnosis of lysosomal storage disorders.
    4. Understand the usefulness of very long chain fatty acid in the laboratory diagnosis of peroxisomal defects.
  2. Molecular Genetics ( University )
    1. Understand the technique polymerase chain reaction and the potential usefulness of this methods for diagnosis of genetic disorders.

Laboratory Exercises

  1. Watch TLC of amniotic fluid and measurement of L/S ration and disaturated lecithin.

Objective

To become familiar with Laboratory analysis for fetal lung maturity prediction.

Biochemical Genetics:

  1. Watch gas chromatographic analysis of urinary organic acids and very long chain fatty acids.
  2. Watch analysis of plasma and urinary amino acids.

Objective:

  1. Become familiar with chromatographic methods used in the biochemical genetics laboratory.