Chemical Pathology - General Aspects - September 12, 2022 PDF

Chemical Pathology – General Aspects Dr. Donovan McGrowder Sub-Department of Chemical Pathology Department of Pathology  Introduction - Clinical Pathology  Clinical pathology is a medical specialty that is concerned with the diagnosis of disease based on the laboratory a...

Chemical Pathology – General Aspects Dr. Donovan McGrowder Sub-Department of Chemical Pathology Department of Pathology  Introduction - Clinical Pathology  Clinical pathology is a medical specialty that is concerned with the diagnosis of disease based on the laboratory analysis of bodily fluids such as blood and urine, as well as tissues, using the tools of clinical chemistry, haematology and anatomical pathology.  Introduction The Sections of Clinical Pathology are:  Anatomical Pathology - Histology and Cytology  Haematology  Blood Bank  Chemical Pathology  Chemical Pathology  Chemical Pathology is the area of clinical pathology that is generally concerned with analysis of bodily fluids for diagnostic and therapeutic purposes.  Chemical Pathology  Chemical Pathology can be categorized into sub- specialities of:  General or routine chemistry - commonly ordered blood chemistries (e.g., liver and kidney function tests).  Special chemistry - elaborate techniques such as electrophoresis, and manual testing methods.  Clinical endocrinology - the study of hormones, and diagnosis of endocrine disorders.  Chemical Pathology  Toxicology - the study of drugs of abuse and other chemicals.  Therapeutic Drug Monitoring - measurement of therapeutic medication levels to optimize dosage.  Urinalysis - chemical analysis of urine for a wide array of diseases, along with other fluids such as CSF.  Fecal analysis - mostly for detection of gastrointestinal disorders. Chemical Pathology Chemical Pathology – Laboratory Workflow Chemical Pathology – Laboratory Workflow  Types of Specimens Used in Clinical Chemistry  Tests in clinical chemistry are performed primarily on serum, plasma, urine and other body fluids. Do you want a footer? Vacutainer Blood Tubes  Types of Specimens Used in Chemical Pathology Laboratory  Serum is the yellow watery part of blood that is left after blood has clotted and all blood cells have been removed.  Serum is the supernatant fluid that can be collected after centrifuging the clotted blood. Electrolytes  Types of Specimens Used in Chemical Pathology Laboratory  Plasma, obtained by centrifuging the whole blood collected with an anticoagulant (EDTA), is employed for the parameters - fibrinogen, glucose,  Types of Specimens Used in Chemical Pathology Laboratory  Blood plasma is prepared by spinning a tube of fresh blood containing an anticoagulant in a centrifuge until the blood cells fall to the bottom of the tube. The blood plasma is then poured or drawn off.  Blood plasma has a density of approximately 1025 kg/m3, or 1.025 g/mL.  Test Panels  A set of commonly ordered tests are combined into a panel:  Basic metabolic panel (BMP) - 8 tests - sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, glucose, calcium.  Comprehensive metabolic panel (CMP) - 14 tests - above BMP plus total protein, albumin, alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino transferase (AST), bilirubin. CHEMICAL PATHOLOGY ELECTROLYTE PANEL  Electrolytes  Electrolytes Substances whose molecules dissociate into ions when they are placed in water. CATIONS (+) , ANIONS (-)  Medically significant/routinely ordered electrolytes include: sodium (Na) potassium (K) chloride (Cl) and CO (in its ion form = HCO - ). 2 3 Cobas – c6000 Analyzer  Calcium Metabolism  Calcium is the most abundant mineral in the body and its intake and output are normally balanced.  There is the movement of calcium between extracellular fluid, gut, bone and kidney.  Calcium metabolism or calcium homeostasis is the mechanism by which the body maintains adequate calcium levels.  Derangements of this mechanism lead to hypercalcemia or hypocalcemia, both of which can have important consequences for health.  Calcium Fractions  In the serum, calcium is present in three forms. They are: (i) Ionized (Ca2+) – physiologically active (50%). (ii) Protein-bound (approximately 80% to albumin) – 40%. (iii) Complexed (citrates, phosphates etc) 10%.  Calcium Reference Intervals  Serum total calcium reference range is 2.25 – 2.75 mmol/L.  Serum ionized calcium reference range is 1.1 – 1.4 mmol/L.  Serum albumin concentration should be measured along with serum total calcium.  The serum calcium concentration should be corrected taking into account the abnormal albumin concentration.  Causes of Hypercalcemia Common Uncommon Malignant disease, e.g. Renal failure some lung cancers Hyperparathyroidism Sarcoidosis Vitamin D toxicity Multiple myeloma (excessive intake)  Causes of Hypocalcemia Hypoparathyroid Nonparathyroid PTH Resistance Postoperative Vitamin D Pseudo- deficiency hypoparathyroidism Idiopathic Malabsorption Post radiation Liver disease Kidney disease Vitamin D resistance CHEMICAL PATHOLOGY RENAL FUNCTION TEST PANEL CHEMICAL PATHOLOGY RENAL FUNCTION TEST PANEL Renal Function Tests  Biochemical Tests of Renal Function  Glomerular Function Tests:  Measurement of GFR (clearance tests) – Creatinine clearance. – Serum creatinine – Serum blood urea nitrogen (BUN).  Glomerular Filtration Rate  The GFR provides a useful index of the number of functioning glomerular.  The GFR gives an estimate of the degree of renal impairment.  The GFR is the rate in millilitres per minute that substances are cleared from the circulation through the kidney’s glomeruli. GFR via Clearance Studies: Criteria for substance used in Clearance Studies  Criteria of suitable marker of clearance studies: i. freely filterable at the glomerular barrier, ii. not reabsorbed by the tubules, iii. not secreted by the tubules, iv. present at a stable plasma concentration, v. if exogenous – non toxic, vi. reliable assay procedure.  Determination of Clearance  Accurately times urine sample plus representative blood sample (s).  Clearance (C) = (U x V) P  Units = volume/unit time (mL/min) U is the urinary concentration of substance V is the rate of urine formation (mL/min) P is the serum concentration of substance - Serum & urine conc. must be in the same units. - Largest source of error is accuracy of urine collection.  GFR Determination using Inulin  Inulin is uniquely treated by nephrons in that it is completely filtered at the glomerulus but neither secreted nor reabsorbed by the tubules.  This property of inulin allows the clearance of inulin to be used clinically as a highly accurate measure of glomerular filtration rate (GFR)  Inulin Clearance - potentially most accurate approach - Gold Standard.  Tubular Function Tests  Tubular function tests: Urinalysis – Appearance – Specific gravity and osmolality – pH – Glucose – Protein  Urinalysis  Urinalysis is a physical and/or chemical examination of the urine.  It consists of a range of chemical and microscopic tests to screen for urinary tract infections, renal disease, and diseases of other organs that result in the appearance of abnormal metabolites (break-down products) in the urine.  Urinalysis can reveal diseases such as diabetes mellitus, various forms of glomerulonephritis, and chronic urinary tract infections.  Urinalysis  TYPES OF URINALYSIS:  Macroscopic Examination.  Chemical Analysis (Urine Dipstick). Urinalysis - Dipstick CHEMICAL PATHOLOGY LIVER FUNCTION TESTS PANEL  Liver Function tests  These tests can be used to: (i) detect the presence of liver disease, (ii) distinguish among different types of liver disorders, (iii) gauge the extent of known liver damage, and (iv) follow the response to  Liver function tests  Some liver function test are associated with: (i) functionality (e.g., albumin); (ii) cellular integrity (e.g., transaminase) and (iii) conditions linked to the biliary tract (gamma-glutamyl transferase and alkaline  Routine LFTs  Transaminases - Alanine and Aspartate aminotransferase (ALT & AST),  Alkaline phosphatase (ALP),  Bilirubin (direct and total)  Gamma glutamy transferase (GGT),  Albumin. Alkaline Alkalinephosphatase phosphatase (ALP) (ALP) Infancy - Puberty - Pregnancy - Intestinal isoenzymes - Hyperparathyroidism - Osteomalacia, rickets - Paget’s disease of bone - Osteomyelitis - Hepatitis - Cholestasis - Cirrhosis - Carcinoma of the bronchus  AlkalineAlkalinephosphatase phosphatase (ALP) Causes (ALP) of increased serum alkaline phosphatase enzyme activity: Infancy - Puberty - Physiological : Pregnancy - Intestinal isoenzymes - Bone disease: Hyperparathyroidism - Osteomalacia, rickets - Paget’s disease of bone - Osteomyelitis - Hepatitis - Hepatobiliary disease: Cholestasis - Cirrhosis - Others: Carcinoma of the bronchus  Males Female Phos.units Alk. s 4 8 12 16 20 (Years) CARDIAC MARKERS PANEL  Troponin I (or T)  Creatinine kinase (Total)  Creatnine Kinase – MB  Lactate dehydrogenase (LDH-1)  Myoglobin  Bro-Brain natriuretic peptide.  Cardiac Markers  CK - MB:  The CPK-MB test is a cardiac marker used to assist diagnoses of an acute myocardial infarction.  It measures the blood level of CK-MB, the bound combination of two variants (isoenzymes CKM and CKB) of the enzyme phosphocreatine kinase. Cardiac Markers Cardiac Markers CHEMICAL PATHOLOGY LIPID PROFILE  Lipid Profile  Total Cholesterol  Triglycerides  Low Density Lipoprotein - Cholesterol  High Density Lipoprotein- Cholesterol. Lipid Profile  MISCELLANEOUS TESTS  Glucose  Glycated hemoglobin (HbA1c)  Uric acid  Hormones: Adrenocor ticotropic hormone (ACTH), Thyroid Stimulating hormone  Major characteristics of type 1 DM and type 2 DM Feature Type 1 DM Type 2 DM Typical age of onset Children Middle-aged, elderly Onset Acute Gradual Habitus Lean Often obese Weight loss Usual Uncommon Ketosis-prone Usually Usually not Plasma insulin Low or absent Often normal; may be concentration elevated Family history of diabetes Less common Common HLA association DR3, DR4 none Major characteristics of type 1 (formerly insulin-dependent) and type 2 (formerly non insulin-dependent) diabetes mellitus.  Diagnostic blood glucose concentrations. If a patient is asymptomatic, two results in the diabetic range are required to establish a diagnosis of diabetes mellitus (WHO proposals). Diagnostic blood glucose concentrations (mmol/L) Diagnosis Sample Venous Venous Capillary plasma blood blood Normal Fasting