Interpreting Clinical Laboratory Data 2/11/2024 Efrata A. 1 Out line • Introduction • Diagnostic tests (General principle) – Electrolytes , – Renal Function tests , Liver function tests – Hematology – Urine analysis – Cardiovascular tests, Endocrine function test , Lipid panels – Diagnostic imaging 2/11/2024 Efrata A. 2 Why Bother? • Pharmacist is a member of the health care team and must ensure safe and effective drug therapy • Need for information – Patients details Disease History, Medication History, Laboratory data 2/11/2024 Efrata A. 3 As a pharmacist • You should be able to: - Recognize normal ranges for common lab results in adults and children - Identify causes for abnormal values and interpret their clinical significance - Identify circumstances for false negative and false positive - Utilize laboratory data to monitor disease states 2/11/2024 Efrata A. 4 Introduction Laboratory findings, both normal and abnormal, can be helpful in assessing clinical disorders, establishing a diagnosis, assessing drug therapy, or evaluating disease progression. In addition, baseline laboratory tests are often necessary to evaluate disease progression and response to therapy or to monitor the development of toxicities associated with therapy. 2/11/2024 Efrata A. 5 Uses of lab data for pharmacist Ensure drug and dose is appropriate for each patient Monitor Adverse drug reactions Assess need for additional or alternative therapy Monitor response to therapy Prevent misinterpretation from drug interference 2/11/2024 Efrata A. 6 General Principles: Reference ranges • Reference ranges: aka “normal ranges”. – Fall inside pre-determined values • Abnormal ranges Fall outside pre-determined ranges Various factors affect lab results: age, disease state, lab factors, drugs etc Not all abnormal values need to be treated Remember: ALWAYS TREAT THE PATIENT NOT THE LAB VALUE!! 2/11/2024 Efrata A. 7 Factors affecting Lab results • Patient-related factors – e.g., age, gender, weight, time since last meal • Laboratory based issues Spoiled specimen Taken at wrong time Incomplete collection Technical error Faulty reagents • Dietary effect • Medication – e.g., thiazides can increase the serum uric acid concentration 2/11/2024 Efrata A. 8 Electrolytes 2/11/2024 Efrata A. 9 Sodium (Normal: 135–145 mEq/L) • Sodium is the predominant cation of extracellular fluid (ECF). • Only a small amount of sodium (∼5 mEq/L) is in intracellular fluid (ICF). • Along with chloride, potassium, and water, sodium is important in establishing serum osmolarity and osmotic pressure relationships between ICF and ECF. 2/11/2024 Efrata A. 10 Sodium (Normal: 135–145 mEq/L) • Extracellular cation (95% in ECF) • Na+ balance is regulated by renal: Aldostrone (Na+ reabsorption) Natriuretic hormone (Na+ excretion) Antidiuretic hormone (reabsorption of free water) 2/11/2024 Efrata A. 11 Hyponatremia • can result from dilution of the sodium concentration in serum or from a total body depletion of sodium. • Some clinical conditions (e.g., cirrhosis, congestive heart failure, renal impairment), as well as the administration of osmotically active solutes (e.g., albumin, mannitol), are commonly associated with dilutional hyponatremia. • Sodium-depletion hyponatremia can be caused by mineralocorticoid deficiencies, sodium-wasting renal disease, or replacement of sodium-containing fluid losses with non saline solutions. 2/11/2024 Efrata A. 12 Hypernatremia • can be caused by the loss of free water, loss of hypotonic fluid, or excessive sodium intake. • Free water loss is uncommon, except in the presence of diabetes insipidus. 2/11/2024 Efrata A. 13 Case 1 • M.C, a 61-year-old woman with no known drug allergies (NKDA) is hospitalized with a chief complaint of increasing shortness of breath (SOB) and orthopnea during the past week. She has been treated previously for heart failure and has not taken any medication during the past 2 weeks. M.C. has severe (4+) pedal edema and is in respiratory distress. Laboratory tests were ordered and reported back as follows: – – – – – – – Sodium (Na), 123 mEq/L Potassium (K), 4.1 mEq/L Chloride (Cl), 90 mEq/L Carbon dioxide (CO2), 28 mEq/L Blood urea nitrogen (BUN), 30 mg/dL Serum creatinine (SCr), 1.3 mg/dL Fasting glucose, 260 mg/dL Should M.C. be given sodium chloride to return her serum sodium concentration to a normal value? 2/11/2024 Efrata A. 14 Potassium (Normal: 3.5–5.0 mEq/L) • Potassium is the major intracellular cation in the body. • Because the majority of potassium is sequestered within cells, a serum potassium concentration is not a good measure of total body potassium • The clinical manifestations of potassium deficiency (e.g., fatigue, drowsiness, dizziness, confusion, electrocardiographic changes, muscle weakness, muscle pain) correlate well with serum concentrations. • During depletion K+ moves from the ICF into the ECF to maintain serum concentration 2/11/2024 Efrata A. 15 Potassium • Serum potassium concentrations, therefore, can be misleading when interpreted in isolation from other considerations, and assumptions should not be made as to the status of total body potassium concentration based solely on a serum concentration measurement. • When the serum concentration decreases by a mere 0.3 mEq/L, the total body potassium deficit is approximately 100 mEq – ↓ 0.3 mEq/L =100 mEq the total body K+ deficit • The kidneys are responsible for about 90%of daily potassium loss (∼40–90 mEq/day), and the remaining 10% of potassium excretion each day is managed by the gastrointestinal (GI) system and the dermatologic system (i.e., sweating). 2/11/2024 Efrata A. 16 Causes for Hypokalemia • Prolonged intravenous therapy with potassium-free solutions in a patient unable to obtain potassium in foods (e.g., nothing by mouth [NPO] patient). • Patients who are on thiazide or loop diuretics • Vomiting and Severe diarrhea, • Insulin and stimulation of β2-adrenergic receptors • Treatment - replacement (IV or PO) – KCl (IV) – KCl, phosphate, or acetate (PO) 2/11/2024 Efrata A. 17 Causes for Hyperkalemia • decreased renal excretion of potassium, • excessive exogenous potassium administration (especially when combined with a potassium-sparing diuretic), or • excessive cellular breakdown (e.g., hemolysis, burns, crush injuries, surgery, infections). • Metabolic acidosis also can induce hyperkalemia as hydrogen ions move into cells in exchange for potassium and sodium. – During Metabolic acidosis, for every 0.1 decrease in pH from 7.4, the serum potassium concentration will be falsely elevated by about 0.6 mEq/L • Use of ACE inhibitors, and K-sparing diuretics 2/11/2024 Efrata A. 18 Treatment for Hyperkalemia o Check ECG o Na+ polystyrene sulfonate (Kayexalate) PO or rectal o Loop diuretics o Hemodialysis (if severe) o IV calcium (to antagonize cardiac effect of K) o regular insulin (shift) + dextrose (for insulin) o Albuterol 2/11/2024 Efrata A. 19 Case 2 • M.C. also has type 1 diabetes mellitus, and is hospitalized a couple of months later for ketoacidosis. Her fasting blood glucose is 802 mg/dL, her urine output is 140 mL/hour, and her urine is positive (4+) for glucose and ketones. M.C.’s blood pH is 7.1, and her serum potassium concentration is 4.1 mEq/L. • Although M.C.’s serum potassium concentration is normal, why is her serum potassium of concern? 2/11/2024 Efrata A. 20 Chloride (Normal: 96 – 106 mEq/L) •Major anion involved in extracellular fluid balance and makes up about two-thirds of the inorganic anion in plasma. • Chloride is measured routinely along with other electrolytes, sodium, potassium, and carbon dioxide and results are used to calculate the anion gap. 2/11/2024 Efrata A. 21 Chloride Con’t … • When chloride is selectively depleted, most common seen in vomiting, nasogastric suction, and in patients who developed a metabolic alkalosis. • The anion gap is much increased. • Cl- exchanged with bicarbonate to maintain acid/base balance 2/11/2024 Efrata A. 22 Bicarbonate • HCO3 - Reference range (2- 28 mEq/L) • Bicarbonate ions are controlled by kidney Increase in Bicarbonate concentration of the serum –Metabolic alkalosis exchange with chlorine Decrease in serum bicarbonate –Metabolic acidosis 2/11/2024 Efrata A. 23 Anion Gap • Reference range : 5 - 12 mEq/mL , or < 16 mEq/mL • represents the contribution of unmeasured acids like lactate, phosphates, sulfates, and proteins • Anion gap = (Primary cation – primary anion) • Elevated anion gap shows metabolic acidosis • Low anion gap E.g - Hypoalbuminemia, Hyperviscosity of multiple myeloma 2/11/2024 Efrata A. 24 Magnesium (Normal: 1.5–2.4 mEq/L) • Magnesium is primarily an intracellular electrolyte • metabolic role in the phosphorylation of adenosine triphosphate (ATP) • Hypomagnesemia – Primary cause is Malnourishment – Should be corrected before attempting to correct hypokalemia or hypocalcemia • Hypermagnesemia – Causes • Excessive ingestion of magnesium-containing antacids • reduced renal function – can slow conduction in the heart, prolong PT intervals, and widen the QRS complex 2/11/2024 Efrata A. 25 Calcium • Normal reference; CaT = 8.5–10.5 mg/dL , Cai = 4.5 to 5.6mg/dL • Resides primarily in the bone (99%) • 40% is bound to plasma proteins (especially albumin) • 5% to 15% is complexed with phosphate and citrate, • 45% to 55% is in the unbound, ionized form • The total serum calcium will decrease by 0.8 mg/dL for each decrease of 1.0 g/dl in serum albumin concentration (4.0g/dl) 2/11/2024 Efrata A. 26 Calcium Hypercalcemia • Metastasis • Hyperparathyroidism • Meds - Lithium, Thiazides 2/11/2024 Hypocalcaemia • Vit D deficiency, • Pancreatitis, • Loop diuretics and • Alcoholism Efrata A. 27 Glucose (Normal: 70–110 mg/dL) Glucose level is controlled by homeostatic mechanisms FBG can fluctuate acutely based on either meals or insulin use Hgb A1c is an average blood glucose concentration over the life span of circulating RBCs. Every 1% reduction in the elevated A1c reduced the risk of microvascular complications • Hyperglycemia - Diabetes mellitus • Hypoglycemia - Missed meal in a patient receiving insulin 2/11/2024 Efrata A. 28 Uric Acid (Normal: 2.0 to 7.0 mg/dL) • Uric acid is an end product of purine metabolism. • It serves no biological function, is not metabolized, and must be excreted renally. • Gout is usually associated with increased serum concentrations of uric acid. • Increased uric acid (Leads to Gout) – decrease in excretion – excessive urate production - Diuretics (thiazides, loops), Neoplastic therapy • Low serum uric acid concentrations – hypouricemic drugs (e.g., high dosages of salicylates) 2/11/2024 Efrata A. 29 Albumin (3.5 – 5 g/dl) • Synthesized by the liver • Hypoalbuminema associated with Edema • Causes malnutrition, malabsorption, impaired synthesis by the liver Direct loss from the blood • Used for therapeutic monitoring of drugs and electrolytes that are highly protein bound 2/11/2024 Efrata A. 30 Renal function test 2/11/2024 Efrata A. 31 Blood Urea Nitrogen (BUN) (Normal: 8–18 mg/dL) • Urea nitrogen is an end product of protein metabolism. It is produced solely by the liver, is transported in the blood, and is excreted by the kidneys. • The serum concentration of urea nitrogen (i.e., BUN) is reflective of renal function because the urea nitrogen in blood is filtered completely at the glomerulus of the kidney, and then reabsorbed and tubularly secreted within nephrons. • Acute or chronic renal failure is the most common cause of an elevated BUN. • Causes of elevated BUN – renal failure – high protein intake – increased protein catabolism – hydration status 2/11/2024 Efrata A. 32 BUN : SCr (normal=15:1) >20:1 If - decreased blood flow to the kidney (dehydration) - increased protein in the blood <15:1 if - 2/11/2024 renal failure significant malnourishment severe liver disease muscular individuals, renal dialysis Efrata A. 33 Case 1 • Why is the BUN abnormal for M.C. (from question 1)? – Blood urea nitrogen (BUN), 30 mg/dL – Serum creatinine (SCr), 1.3 mg/dL 2/11/2024 Efrata A. 34 Creatinine (Normal: 0.6–1.2 mg/dL) • Creatinine is derived from creatine and phosphocreatine (major constituents of muscle). • Less affected by exogenous factor • determined primarily by an individual's muscle mass or lean body weight • A doubling of the SCr level roughly corresponds to a 50% reduction in the GFR. 2/11/2024 Efrata A. 35 Creatinine Clearance (Normal: 90- 130 mL/min) • measure of a patient's GFR (glomerular filtration rate) • Important for dose adjustment • To calculate measured CrCl - 24-hour urine is collected [Urine conc.(mg/dL)] × [Total urine volume(mL/min)] / SCr(mg/dL) 2/11/2024 Efrata A. 36 Cockcroft-Gault method – Estimated CrCl 2/11/2024 Efrata A. 37 Case 2 • A 24-hour CrCl determination was ordered for E.S., a 63-yearold, 60-kg man. The following data were returned from the clinical laboratory: total collection time was 24 hours; total urine volume, 1,000 mL; urine creatinine concentration, 42 mg/dL; and SCr, 1.7 mg/dL. Determine both the measured and the estimated CrCl for E.S. based on the given data, and compare and contrast these results. 2/11/2024 Efrata A. 38 2/11/2024 Efrata A. 39 Aspartate Aminotransferase (AST) (Reference Range: 0–35 units/L) • The AST enzyme, formerly called “serum glutamic oxaloacetic transaminase (SGOT),” is abundant in heart and liver tissue and moderately present in skeletal muscle, the kidney, and the pancreas. • useful for identifying inflammation and necrosis of the liver • AST level is increased in more than 95% of patients after an MI • Peak AST ~ extent of myocardial damage • Alcoholic hepatitis: AST exceeds ALT (> 2:1 ratio) • Drugs also may increase AST (Acetaminophen, Erythromycin, Levlodopa, phenytoin, Niacin, Valproic acid) 2/11/2024 Efrata A. 40 Con’t … • Acute hepatic necrosis - both AST and ALT will be increased, even before the appearance of clinical symptoms • Parenchymal liver disease - 100 times greater than the usual upper limits of AST and ALT • AST serum concentration is usually higher than that of ALT in patients with cirrhosis 2/11/2024 Efrata A. 41 Alanine Aminotransferase (ALT) (Reference range 0 – 35U/L) • The ALT enzyme, formerly called “serum glutamic pyruvic transaminase (SGPT),” is found in essentially the same tissues that have high concentrations of AST. • Elevations in serum ALT are more specific for liver-related injuries • The ALT/AST ratio frequently exceeds 1.0 with – chronic liver disease, or – hepatic cancer. • ratios <1.0 tend to be observed with – viral hepatitis or acute hepatitis 2/11/2024 Efrata A. 42 Alkaline phosphatase (AP) (Reference range : 30 – 120 u/L) derived primarily from liver and bone elevated ALP – – – – – 2/11/2024 mild intrahepatic or extra hepatic biliary obstruction. Drug-induced cholestatic jaundice (e.g Sulfonamides) conditions of pronounced osteoblastic activity periods of rapid bone growth during pregnancy Efrata A. 43 Bilirubin • Total Bilirubin= 0.1–1.0 mg/dL Direct Bilirubin = 0–0.2 mg/dL • Bilirubin is a breakdown product of Hgb • Unconjugated (indirect) bilirubin is water insoluble and is highly bound to serum albumin 2/11/2024 Efrata A. 44 Bilirubin Hyperbilirubinemia • liver disease • Hemolysis or increased breakdown of red blood cells • Drugs - Antipsychotic - Sulfonamides (Infants) - kernicterus 2/11/2024 Efrata A. 45 Jaundice - Yellow discoloration secondary to accumulation of bile - may be noticeable • in the sclera (white) of the eyes at levels of about 2 to 3 mg/dL and • in the skin at higher levels. - Jaundice is classified conjugated jaundice or unconjugated jaundice depending upon whether the bilirubin is free or conjugated to glucuronic acid 2/11/2024 Efrata A. 46 HEMATOLOGY 2/11/2024 Efrata A. 47 Hematogenesis • All blood cells are produced in the bone marrow • Hematopoietic stem cell differentiates into: o Lymphoid progenitor cell that matures into lymphocytes in the lymphoid organs o Myeloid progenitor cells that mature into: - Neutrophils, Eosinophils, Basophils, Monocytes, - Reticulocytes and erythrocytes - Platelets 2/11/2024 Efrata A. 48 Complete Blood Count • • • • • • • • • Red blood cells (RBCs), Hemoglobin (Hgb), Hematocrit (Hct), Mean cell volume (MCV), Mean cell Hgb concentration (MCHC), Total white blood cells (WBCs) Platelets, Reticulocytes, Leukocyte differential. 2/11/2024 Efrata A. 49 Red Blood Cells (Erythrocytes) Males—Normal: 4.3 - 5.9 × 106/mm3 Females—Normal: 3.5 - 5.0 × 106/mm3 • RBCs are produced in the bone marrow and circulate in peripheral blood for about 120 days. • Primary function of RBCs is to transport oxygen to tissues • RBCs useful to detect anaemia 2/11/2024 Efrata A. 50 Con’t … •Causes of decrease in RBC count -Decreased production -Increased destruction (hemolysis) -Blood loss •Increased RBC count –living at altitude –chronic lung/heart disease –tobacco use/carbon monoxide 2/11/2024 Efrata A. 51 Hematocrit (Packed cell volume) Males—Normal: 39% to 49% Females—Normal: 33 to 43% • The percentage of RBCs to the blood volume • Hct are determined by centrifuging a capillary tube of whole blood and comparing the height of the settled RBCs to the height of the column of whole blood 2/11/2024 Efrata A. 52 Con’t … A decrease in Hct may result from • bone marrow suppressant drugs, • chronic diseases, • genetic alterations in RBC morphology • Hemolysis, • bleeding, An increase in Hct may result from • COPD, high altitude, • Dehydration, • polycythemia vera or polycythemia secondary to chronic hypoxia 2/11/2024 Efrata A. 53 2/11/2024 Efrata A. 54 Hemoglobin (Males— 14 to 18 g/dL, Females—12 to 16 g/dL) • Hgb is the oxygen-carrier • conditions that impact the number of RBCs will also affect Hgb concentration. • glycosylated Hgb (A1c) is used to monitor diabetes mellitus 2/11/2024 Efrata A. 55 RBC Indices • Are useful in classification of anaemia 2/11/2024 Efrata A. 56 Mean Cell Volume (MCV) • It is Volume occupied by a single RBC and detects changes in cell size • Microcytic anemia - Decreased MCV indicates a microcytic cell (<80 fL*) , usually due to iron deficiency anemia. • Macrocytic anemia (>100 fL) - A large MCV indicates a macrocytic cell, which can be due to: Vitamin B12 or folic acid deficiency Underlying disease states (e.g., habitual alcohol ingestion, chronic liver disease, anorexia nervosa, hypothyroidism, reticulocytosis, hematologic disorders). • MCV can be normal (Normocytic anemia) in a patient with a “mixed” (microcytic and macrocytic) anemia. 2/11/2024 Efrata A. 57 Mean cell hemoglobin (MCH) and Mean corpuscular hemoglobin concentration (MCHC) MCH - the weight of Hgb, while MCHC - the concentration of Hgb • The MCHC is a more reliable index of RBC Hgb than MCH. • Changes in Hgb content of RBCs alter their color, so: – Hypochromic: decrease in RBC Hgb, reflected by reduced MCHC, and may indicate iron-deficiency anemia. – Hyperchromic: elevated MCHC due to presence of greater amounts of Hgb. These are not commonly encountered. 2/11/2024 Efrata A. 58 2/11/2024 Efrata A. 59 Summary 2/11/2024 Efrata A. 60 Reticulocytes (Adults—Normal: 0.1% to 2.4% of RBCs) • immature erythrocytes • An increase in the number of reticulocytes implies an increased number of erythrocytes are being released into the blood in response to a stimulus. • BCs regenerate rapidly, so reticulocytosis is noted within 3-5 days after hemolysis or after a hemorrhagic episode • Helpful to identify cause of Anemia 2/11/2024 Efrata A. 61 Con’t … • Increase Retic count –Increase RBC production –Haemorrhage, sickle cell disease • Decrease count –Infection, alcoholism, renal disease 2/11/2024 Efrata A. 62 Erythrocyte Sedimentation Rate(ESR) (Males—Normal: 0 to 20 mm/hour, Females—Normal: 0 to 30 mm/hour) ESR: rate at which RBCs settle to bottom of a test tube by gravity and due to fibrinogen levels in the blood The ESR may be increased abnormally in acute and chronic inflammatory processes, acute and chronic infections, neoplasms, tissue necrosis, rheumatoid-collagen disease, dysproteinemias, nephritis, and pregnancy 2/11/2024 Efrata A. 63 White Blood Cells 2/11/2024 Efrata A. 64 White Blood Cells • White Blood Cells (Normal: 4–11 × 10*3/μL or 4–11 × 10*9/L) • five different types of cells formed from stem cells in the bone marrow - Neutrophils, Monocytes, Eosinophils, Basophils lymph nodes, thymus, or spleen - Lymphocytes “Never Let Monkeys Eat Bananas” 2/11/2024 Efrata A. 65 Neutrophils (Normal: 40% to 70% of WBC) “polys, segs, PMNs (polymorphonuclear neutrophils), granulocytes” essential in killing invading microorganisms Immature neutrophils (bands) also Cause of Neutrophilia •Pathologic (Bacterial infection, fungi, Inflammatory responses to tissue death) •Burns •Drugs (steroids, lithium) • Physiologic • Acute stress increase in blood during bacterial infection; this is known as “left shift” 2/11/2024 Efrata A. 66 Agranulocytosis and Absolute Neutrophil Count • Neutropenia is when <2,000 cells/mm3 • Agranulocytosis is severe neutropenia The % neutrophils indicates the severity of the infection the total WBC reflects the quality of the immune system ANC =WBC × (% neutrophils + % bands)/100 • ANC exceeds 1,000/mm3 - low risk of infection; • ANC is <500/mm3 - increased risk of infection • ANC <100/mm3 - “profound neutropenia” • The most common causes of neutropenia are metastatic carcinoma, lymphoma, and chemotherapeutic agents. 2/11/2024 Efrata A. 67 Lymphocytes: 20% to 40% of WBC • • • • Main function -antigen recognition and immune response T lymphocytes - cell-mediated immune responses B lymphocytes - Humoral antibody responses Therefore, diseases affecting lymphocytes manifest as immune deficiency disorders (e.g. HIV) or as autoimmune diseases. – elevated lymphocytes - lymphoma and viral infections 2/11/2024 Efrata A. 68 Con’t Lymphocytosis - Hepatitis, - viral infection (chickenpox, herpes) Lymphocytopenia • Acute infection • Burns, • trauma, • HIV 2/11/2024 Efrata A. 69 Monocytes: (0% to 11% of WBC) • Monocytes are formed in the bone marrow and are the precursors to macrophages and antigen-presenting cells (dendritic cells), which are found in the body's tissues. • Primary role is phagocytosis Monocytosis occurs if • subacute bacterial endocarditis, • malaria, • tuberculosis, • recovery phase of some infections 2/11/2024 Efrata A. 70 Eosinophils: 0% to 8% of WBC) Eosinophilia is commonly associated with • allergic reactions to drugs, • allergic disorders (e.g., hay fever, asthma, eczema), • invasive parasitic infections (e.g., hookworm, schistosomiasis, trichinosis), • collagen vascular diseases (e.g., rheumatoid arthritis), and • Malignancies (e.g., Hodgkin disease) 2/11/2024 Efrata A. 71 Basophils (Normal: 0 -3% of WBC) During infection or inflammation, basophils leave the blood and mobilize as mast cells to the affected site and release granules. These granules contain histamine, serotonin, prostaglandins, and leukotrienes An increase in basophils • allergic and anaphylactic responses, • chronic myeloid leukemia, • myelofibrosis, and • polycythemia vera. 2/11/2024 Efrata A. 72 Platelets (Thrombocytes) 2/11/2024 Efrata A. 73 Platelets • Thrombocytes (Normal: 150 to 450 × 103/mm3) • (<50,000) may lead to spontaneous hemorrhage Thrombocytopenia • decreased platelet production, • accelerated destruction, • dilution of blood samples secondary to blood transfusion • heparin 2/11/2024 Efrata A. • Thrombocytosis Malignancy, rheumatoid arthritis, iron-deficiency anemia, polycythemia vera, and Post splenectomy syndromes 74 Coagulation Studies • Tests below used to diagnose coagulation abnormalities or to monitor the effectiveness of anticoagulation therapy. Prothrombin time (PT) International normalized ratio (INR), and Activated partial thromboplastin time (aPTT) 2/11/2024 Efrata A. 75 Activated partial thromboplastin time (APTT) Reference Range: 20–39 seconds measures the intrinsic clotting system - factors VIII, IX, XI, and XII and the factors involved in the final common pathway of the clotting cascade (factors II, X, and V) used to monitor unfractionated heparin therapy 2/11/2024 Efrata A. 76 Prothrombin Time (PT) • Reference Range: 10–14 seconds • Prothrombin is synthesized in liver and converted to thrombin during the blood clotting process. • measures the activity of clotting factors VII, X, prothrombin (factor II), and fibrinogen • PT measured by recording the time required for the blood to clot after tissue thromboplastin is added to the patient’s blood sample 2/11/2024 Efrata A. 77 International Normalized Ratio (INR) • During initiation and maintenance of anticoagulant therapy (warfarin) • Reference range: 1.1 or less. Therapeutic goal 2-3 • variability observed between different laboratories 2/11/2024 Efrata A. 78 Urinalysis 2/11/2024 Efrata A. 79 Gross Appearance of the Specimen - A standard urinalysis begins with simple observation of the colour and the gross general appearance of the urine specimen. - First-morning urine specimen Normal - Clear and slightly yellow • Red - blood, phenolphthalein, beet root • Brown- blood, Primaquine, Metronidazole, Chloroquine, • Dark orange - Excessive excretion of urobilinogen ,rifampin or phenazopyridine • A blue to blue-green - methylene blue 2/11/2024 Efrata A. 80 Specimen pH (pH 4.6 – 8) Alkaline urine may indicate • an aged specimen, • systemic alkalosis, • failure of renal acidifying mechanisms, or • infection in the urinary tract 2/11/2024 Efrata A. 81 Specific Gravity (1.002 to 1.025) • Shows concentrating ability and hydration status • water intake should be restricted •Low specific gravity – CRF (concentration ability) or – Diabetes Insipidus (dilutional) •Elevated specific gravity seen with elevated protein levels (100 to 750 m g/dL) 2/11/2024 Efrata A. 82 Protein - Sign of renal injury a dipstick method – – – – – 0 (<30 mg/dL), 1+ (30–100 mg/dL), 2+ (100–300 mg/dL), 3+ (300–1,000 mg/dL), and 4+ (>1,000 mg/dL) • Protein > 150 mg/dL - refers to renal diseases • Greater than 300 mg/dL is clinically significant 2/11/2024 Efrata A. 83 Glucose - Urinary threshold - > 180 mg/dL - If glucose present (1) hyperglycemia that exceeds the renal threshold for plasma glucose (diabetes mellitus) or (2) defective renal tubular reabsorption - congenital defects •Drugs - thiazides, steroids, oral contraceptives 2/11/2024 Efrata A. 84 Nitrite • Gram –ve bacteria are capable of converting dietary nitrates into nitrites • If bacteria are present in the urine, there will be reduction of the normally occurring nitrates to nitrites. • Specific to presence of bacteria 2/11/2024 Efrata A. 85 Bilirubin –Normally no Bilirubin is detected in urine. –Even trace amounts are clinically significant. –Presence associated with liver diseases (hepatitis, obstructive biliary tract diseases) Drugs = phenazopyridine, phenothiazines 2/11/2024 Efrata A. 86 Ketones • Normal urine - negative with this test. • Detectable levels seen during –physiological stress such as fasting, –pregnancy, and –frequent strenuous exercise • Large amounts with ketoacidosis due to starvation and abnormal carbohydrate or lipid metabolism. 2/11/2024 Efrata A. 87 ENDOCRINE TESTS 2/11/2024 Efrata A. 88 Glucose • Normal: 70–110 mg/dL (fasting) • Hypoglycemia Too much insulin Not enough food Increased physical activity Illness Injury 2/11/2024 Efrata A. 89 Hypoglycemia • Early signs: headache, hunger, mild agitation • Blood sugar below 50 – 70 mg/dL Hallucinations or nervousness or outright hostility Cold sweat and tachycardia common but not required • Blood sugar below 20 – 50 mg/dL Convulsions and loss of consciousness As sugar drops the convulsions stop but coma persists 2/11/2024 Efrata A. 90 Hyperglycemic syndromes • Diabetic ketoacidosis (DKA) • Hyperglycemic hyperosmolar state (HHS) • Manifestations – dehydration, polyuria/polydipsia, altered mental status, nausea, emesis, abdominal pain 2/11/2024 Efrata A. 91 Medications that affect glucose • Beta blockers: Glycogenolysis & gluconeogenesis Also mask hypoglycemic symptoms • Phenytoin: suppress insulin secretion • Diuretics: cause hyperglycemia • Estrogen: contraceptives cause 43-61% increase; Progestrone only – no effect 2/11/2024 Efrata A. 92 Glucose Lab assessment Initial diagnosis and short-term monitoring – Fasting blood glucose – Two hrs Post Prandial – Oral Glucose Tolerance Test (OGTT) Long-term monitoring - Glycosylated hemoglobin (A1C) 2/11/2024 Efrata A. 93 Fasting Plasma Glucose • Normal: 80 – 110 mg/dl • Prediabetes (impaired fasting glucose) 110 < FPG < 126 mg/dl • Diagnosis of DM: FPG > 126 mg/dl (at two occasions) • FPG done after 8 hrs of fasting • ADA recommend Q3 years screening (>30 yrs of age if have risk factors) 2/11/2024 Efrata A. 94 Oral glucose tolerance test • Normal: < 140 mg/dL • Pre-diabetes : 2-hr post prandial glucose 140 – 200 mg/dL • DM: 2-hr post prandial glucose ≥200 mg/Dl – Commonly used to diagnosis gestational DM (pregnancy) – 75 G glucose solution given over 5 min following overnight fasting and blood drown at 0, 0-2 hr, and at 2 hrs. 2/11/2024 Efrata A. 95 Thyroid Function Test 2/11/2024 Efrata A. 96 TFT • Secretion of the thyroid hormones T4 (thyroxine (tetra-iodothyronine)) and T3 (tri-iodothyronine) is regulated by pituitary thyrotropin (TSH). • TSH secretion, in turn, is controlled through negative feedback by thyroid hormones. 2/11/2024 Efrata A. 97 TFT con’t … • Laboratory tests used to assess thyroid function: Serum TSH concentration - 0.5 to 5 μU/mL or mU/L Serum total T4 concentration - 4.6 to 11.2 mcg/dL Serum total T3 concentration - 75 to 195 ng/dL Serum free T4 concentration - Only 0.03 percent of serum total T4 2/11/2024 Efrata A. 98 Clinical use of TFT Screening: • Serum TSH normal: no further testing performed • Serum TSH high: free T4 added to determine the degree of hypothyroidism • Serum TSH low: free T4 and T3 added to determine the degree of hyperthyroidism 2/11/2024 Efrata A. 99 Clinical use of TFT Con’t … • Monitoring thyroxine therapy: Patients with primary hypothyroidism taking levothyroxine replacement therapy: serum TSH If serum TSH is high, the dose needs to be increased; If it is low, the dose needs to be reduced • Monitoring hyperthyroid patients Serum free T4 and T3 measurements (early) TSH (later) 2/11/2024 Efrata A. 100 Cardiac Function Tests • Cardiac biomarkers: useful for the evaluation, diagnosis, and monitoring of patients with suspected heart injury 2/11/2024 Efrata A. 101 Creatinine Kinase - 0 to 150 units/L • In tissues that use high energy (skeletal muscle, myocardium, brain) • The serum concentration of CK can be increased by: – Strenuous exercise, – IM injections of drugs that are irritating to tissue (e.g., diazepam, phenytoin) – Acute psychotic episodes – Crush injuries – Myocardial damage 2/11/2024 Efrata A. 102 Creatinine Kinase Con’t … • CK is composed of M and B subunits, which are further divided into three isoenzymes: MM, BB, and MB. CK – MM predominantly in skeletal muscle, CK – BB predominantly in the brain, and CK – MB predominantly in the myocardium. 2/11/2024 Efrata A. 103 Creatinine Kinase Con’t … • CK-MB = 0-1 units/L • Myocardial damage appears to correlate with the amount of CKMB released into the serum The higher the amount of CK-MB, the more extensive the myocardial injury • CK-MB typically begins to increase 3 to 6 hours after an acute myocardial infarction (MI), peaks at 12 to 24 hours Remains elevated only for 2 to 3-days 2/11/2024 Efrata A. 104 Troponin • Troponins are proteins that mediate the calcium-mediated interaction of actin and myosin within muscles. • There are two cardiac-specific troponins, cardiac troponin I (cTnI) and cardiac troponin T (cTnT). • Whereas, cTnT is present in cardiac and skeletal muscle cells, cTnI is present only in cardiac muscle • cTnI - < 1.5 ng/Ml or < 1.5 mcg/L 2/11/2024 Efrata A. 105 Troponin • Compared with the detection of CK-MB, the presence of troponin I is a more specific and sensitive indicator of myocardial damage • The concentration of cTnI increases within 2 to 4 hours of an acute MI, enabling clinicians to quickly initiate appropriate therapy. • Troponin also remains elevated for about 10 days compared to the 2- to 3day elevation typically observed with CK-MB • The use of troponin as a primary diagnostic test for acute MI is becoming widely accepted as a standard 2/11/2024 Efrata A. 106 Lipid Profile • Also known as lipid panel or cholesterol • Screen for abnormalities in lipids (dyslipidemia), a risk factor for cardiovascular disease • Tests for: 2/11/2024 Total cholesterol High density lipoprotein Low density lipoprotein Triglycerides Efrata A. 107 Lipid Profile • Total cholesterol – Ref values: < 200 mg/dL or 5.2 mmol/L – Consider other risk factors to interpret • Low density lipoprotein: bad lipid – Ref values: 70–160 mg/dL • High density lipoprotein: good lipid – Ref values: 40 mg/dL • Note: ↑ LDL or ↓ HDL are risk factors for cardiovascular disease. 2/11/2024 Efrata A. 108 Lipid Profile • Triglycerides - Ref values: <150mg/dL • ↑ by alcohol, saturated fats, drugs e.g., propranolol, diuretics, oral contraceptives 2/11/2024 Efrata A. 109 Thank you. 2/11/2024 Efrata A. 110 Diagnostic Imaging EKG • Electrocardiography obtains a tracing of the electrical activity of the heart. – – – – sinus node of the right atrium atrioventricular node bundle of His ventricles. • Prominent parts of the ECG: – P wave- atrial depolarization; – QRS complex- ventricular depolarization; and – T wave- ventricular repolarization. 2/11/2024 Efrata A. 112 One normal cardiac cycle 113 P-Q interval … 0.16 s Q-T interval 0.35 s interval between two successive QRS complexes …. 0.83 s 114 Conventional radiography (x-rays) • X-rays are a form of electromagnetic radiation, able to pass through the human body and produce an image of internal structures • The common terms ‘chest X-ray’ and ‘abdomen X-ray’ • As a beam of X-rays passes through the human body, some of the X-rays are absorbed or scattered producing reduction or attenuation of the beam 1. Air/gas: black, 2. Fat: dark grey, 3. Soft tissues/water: light grey, 4. Bone: off-white 5. Contrast material/metal: bright white. 2/11/2024 Efrata A. 115 CT scan • CT is an imaging technique whereby cross-sectional images are obtained with the use of X-rays. • In CT, water is assigned an attenuation value of 0 HU (Hounsfield units). • fat and air, have negative values • substances of greater density have positive values. 2/11/2024 Efrata A. 116 Ultra sound (US) • US imaging uses ultra-high-frequency sound waves to produce cross-sectional images of the body. • Solid organs, fluid-filled structures and tissue interfaces produce varying degrees of sound wave reflection and are said to be of different echogenicity. • In an US image, hyper echoic tissues are shown as white or light grey and hypo echoic tissues are seen as dark grey 2/11/2024 Efrata A. 117 Ultra sound (US)… con’t • Advantages of US over other imaging modalities include: – Lack of ionizing radiation, a particular advantage in pregnancy and paediatrics – Relatively low cost – Portability of equipment. 2/11/2024 Efrata A. 118 Ultra sound (US)… con’t Disadvantages and limitations of US - US is highly operator dependent. - US cannot penetrate gas or bone. - Bowel gas may obscure structures deep in the abdomen, such as the pancreas or renal arteries. 2/11/2024 Efrata A. 119 MRI • MRI uses the magnetic properties of spinning hydrogen atoms to produce images. • patient is placed within a large powerful magnet • white or light grey areas are referred to as ‘high signal’; dark grey or black areas are referred to as ‘low signal’. 2/11/2024 Efrata A. 120 Applications • Imaging modality of choice for most brain and spine disorders • Musculoskeletal disorders, including internal derangements of joints and staging of musculoskeletal tumours • Cardiac MR is an established technique in specific applications including assessment of congenital heart disease and aortic disorders • MR of the abdomen is used in adults for visualization of the biliary system, and for characterization of hepatic, renal, adrenal and pancreatic tumours • In children, MR of the abdomen is increasingly replacing CT for the diagnosis and staging of abdominal tumours 2/11/2024 Efrata A. 121 Hazards associated with medical imaging • Exposure to ionizing radiation • Anaphylactic reactions to iodinated contrast media • Contrast-induced nephropathy (CIN) • MRI safety issues • Nephrogenic systemic sclerosis (NSF) 2/11/2024 Efrata A. 122 Thank you.