CHM 2311 Clinical Biochemistry Fall 2024 PDF

CHM 2311 Clinical Biochemistry Fall 2024 BScN Program  Clinical Biochemistry and General Interpretation of Results 1. Defining Terms Health X Disease Influence of culture Pixabay.com Normal X Abnormal Affected by v...

CHM 2311 Clinical Biochemistry Fall 2024 BScN Program  Clinical Biochemistry and General Interpretation of Results 1. Defining Terms Health X Disease Influence of culture Pixabay.com Normal X Abnormal Affected by various physiological factors Sex, age, timing, posture, exercise, etc. 2. Usefulness of Biochemical Tests The importance of biochemical tests Why are biochemical tests used? Medical history + clinical examination + concentrations = diagnosis 3. Clinical Chemistry Departments Routine biochemistry Therapeutic drug monitoring (TDM) and toxicology Arterial blood gases (ABG) https://youtu.be/4nYHPM7BHIM?si=Fau3heCfmtZu_FJb Pixabay.com 4. Specimen Collection Specimen – correct collection client Identification analyses specified reason for analyses Pixabay.com Nurses and specimen collection 5. Sampling errors that affect the quality of specimens Blood sampling difficulties May lead to hemolysis Prolonged stasis during venepuncture Long tourniquet placement False variations in several measurable analytes Insufficient specimen Small volume for requested tests Pixabay.com 5. Sampling errors that affect the quality of specimens (cont.) Errors in timing Duration of the collection Incorrect specimen container Type of tube Inappropriate sampling site “drip arm” artefact Pixabay.com Incorrect specimen storage  6. How biochemical results are expressed Most biochemical analyses are quantitative Many biochemical results are reported as concentrations (commonly mol/L) Units (mmol/L, mg/dL, %, etc.) Concentration amount of solute amount of solvent 7. Reference interval “Normal” results X “reference” interval (range) Calculation of reference intervals Every hospital/laboratory “should” generate their own reference intervals Reference intervals are chosen arbitrarily to include 95% of the values found in the population Reference intervals are merely a guide (overlap) 8. False-positive and false-negative results Diagnostic cut-off is a way of separating healthy and diseased populations “Less than perfect approach” True-positive and true-negative results Sensitivity how often patients with the disease are correctly identified Specificity how often healthy subjects are correctly identified 9. Health care providers and lab test requests No clinical chemistry test is 100% sensitive and 100% specific How does a health care provider determine which laboratory tests to order for an individual? Medical history + physical examination + objective test results Sensitive or specific test first? 10. Variation of Biochemical test results - patient monitoring Reasons to request biochemical investigations Repeated biochemical tests similar results markedly different results Variation- is it random? 1. Preanalytical variation 2. Analytical variation 3. Intrinsic biological variation Other biological variation 10.1 Variation of Biochemical test results - patient monitoring 1. Preanalytical variation Time of the day Posture Fasting status Time in transit to the lab https://brooksandkirk.co.uk/how-to-standardise-as-an-assessor-or-quality-assurer/ 10.2 Variation of Biochemical test results - patient monitoring 2. Analytical variation Temperature Pipetted volume of reagent/sample Not feasible to analyse every sample repeatedly Internal quality control (IQC) 10.3 Variation of Biochemical test results - patient monitoring 3. Intrinsic biological variation Or “within-subject variation” Random fluctuation around a homeostatic set point Samples from the same individual ❖Other biological variation Some tests vary in nonrandom ways E.g., Cortisol, hormones involved in ovulation 11. Analytical aspects of biochemical tests Biochemical results need to be reliable Precision Reproducibility of an analytical method Accuracy How close the measure value is to the “true value” Quality assurance QC samples are utilized to confirm reliability 12. Point-of-care testing Blood tests Urine tests Advantages of results at point-of-care General problems ✓Cost ✓Responsibility 13. The routine urinalysis Screening tool for renal/metabolic diseases Glucose Bilirubin Urobilinogen Ketones Specific gravity pH Proteins Blood Nitrite Leukocyte esterase 14. Fecal analysis Tests to help diagnose disorders of the digestive tract Macroscopic, microscopic and chemical examinations Role of the nurses Fecal investigation of gastrointestinal disorders Fecal Fat Test – malabsorption disorders https://www.cancercareontario.ca/en/types-of-cancer/colorectal/screening/fit-instructions Fecal calprotectin test – intestinal inflammation Fecal Pancreatic Elastase 1 Test– pancreatic insufficiency Trypsin test – pancreatic insufficiency Fecal immunochemical tests (FIT) – colon cancer screening 15. Blood Testing Pixabay.com 15. Blood Testing Electrolyte Abnormalities Specific Markers of Disease Enzymes Proteins Tumour Markers 15.1 Enzymes Properties Biological catalysts 3-D structure Enzymes act on specific substrates Cells contain a variety of enzymes Some tissues also generate enzymes upon stimuli Isoenzymes https://www.aatbio.com/catalog/gel-electrophoresis 15.2 Clinically relevant enzymes Markers of tissue/organ damage ❖ Why can enzymes be used as markers? Some are predominantly intracellular Some are found in one or a small number of tissues or organs 15.3 Clinically relevant enzymes 1. Alanine aminotransferase (ALT) Hepatocellular damage 2. Amylase and lipase Acute pancreatitis 3. Creatine kinase (CK) Skeletal muscle damage 4. Alkaline phosphatase (ALP) Cholestatic liver disease and bone disease 15.3 Clinically relevant enzymes 5. Gamma-glutamyl transpeptidase (GGT) Sensitive but not a specific marker of liver disease 6. Aspartate aminotransferase (AST) An indicator of hepatocellular damage, muscle damage or red cell damage (hemolysis) 7. Lactate dehydrogenase (LDH) Found in muscle, liver, kidney, brain and red blood cells 15.3.1 Aminotransferases and liver disease Clinically relevant aminotransferases 1. Alanine aminotransferase (ALT) 6. Aspartate aminotransferase (AST) Locations in the body Both in all major organs ALT- liver and kidney AST- heart, liver, skeletal muscle, and kidney https://www.google.com/search?sca_esv=556828901&rlz=1C5CHFA_enCA756CA756&q=rare+i n+nonliver+disorders.+Elevated+ALT+activity+persists+longer+than+that+of+AST+because+of+t he+longer+half-life+of+ALT+in+serum.&tbm=isch&source=lnms&sa=X&ved=2ahUKEwiNlLHZ6ty AAxVZj4kEHStYAGUQ0pQJegQIBxAB&biw=1440&bih=698&dpr=2#imgrc=I-nXXr8VsoH4IM Clinical significance ❖Evaluation of liver disease ❖Hepatic destruction  15.3.2 Enzymes in acute pancreatitis 2a. Amylase 2b. Lipase Locations in the body Locations in the body Clinical significance Elevation: Clinical significance acute pancreatitis acute pancreatitis Pixabay.com salivary gland concentrations elevated for inflammation longer periods renal insufficiency more specific biliary tract disorders ectopic pregnancy diabetic ketoacidosis 15.3.4 Enzyme in muscular damage 3. Creatine kinase (CK) “energy” Locations in the body Most tissues Highest activity in skeletal muscles and heart muscle Clinical significance Increases in total CK activity – skeletal and cardiac tissue pathologies Muscular dystrophy Acute rhabdomyolysis https://my.clevelandclinic.org/health/diseases/16818-heart-attack-myocardial-infarction Acute myocardial infarction (AMI) 15.3.5 Enzyme in liver and bone diseases 4. Alkaline phosphatase (ALP) Locations in the body Most organs Particularly in liver (most abundant), bones, small intestine, kidneys, and placenta Clinical significance Increases: cholestatic liver disease osteoblast-mediated bone disease Single increase – not diagnostic Growth spurts (transient) Pregnant women https://labpedia.net/alkaline-phosphatase-alp/ 15.3.6 Enzyme in hepatobiliary disease 5. Gamma- glutamyl transpeptidase (GGT) Location in the body Kidney, liver, pancreas, and intestine In serum: mainly hepatic origin Clinical significance https://www.niddk.nih.gov/health-information/liver-disease/biliary-atresia ❖Hepatobiliary disease ❖Elevated concentrations Note: Determination Hepatocellular carcinoma of GGT activity can Alcoholic hepatitis be useful in the Chronic alcohol drinkers context of elevated A sensitive but nonspecific marker of liver disease ALP activity 15.3.7 Enzyme in anemia and cancer 7. Lactate dehydrogenase (LDH) Location in the body Heart, liver, red blood cells, kidney, brain, lungs and skeletal muscle. Clinical significance Increases are seen in numerous disorders moderate to slight elevations- AMI, pulmonary embolism, leukemia, hemolytic anemia, liver and renal diseases significantly elevated concentrations- pernicious anemia, megaloblastic anemia, and some cancers *Usefulness!