Spring 2016-17 Pharmacy Practice II Interpretation of lab data Ms. Beena Jimmy Lecturer(Pharmacy Practice) School of Pharmacy

Learning Objective To understand different lab investigations Normal values of various tests How to interpret the lab results

INTRODUCTION Lot of laboratory data will be associated with a patient Application for a pharmacist: - General understanding of lab data helps to understand the patient’s medical background and in order to separate that which is relevant to patient’s drug therapy - Advising on the choice of drug and dosage in patients with renal, hepatic, or cardiac failure - Detecting and preventing adverse drug reactions and interactions e.g. those involving oral anticoagulants. Monitoring the patient’s response to drugs Lab tests are used to detect disease, guide treatment, monitor response to treatment, and monitor disease progression.

A variety of factors can interfere with the accuracy of laboratory tests. 1- Patient-related factors (e.g., age, gender, weight, height, time since last meal) can affect the range of normal values for a given test. 2- Laboratory-based issues can also influence the accuracy of laboratory values. For example, a specimen can be spoiled A-because of improper handling or processing (e.g., hyperkalemia due to hydrolysis of a blood specimen); B-because it was taken at a wrong time (e.g., fasting blood glucose level taken shortly after a meal); C- because collection was incomplete (e.g., 24-hour urine collection that does not span a full 24-hour period); 3- because medications can interfere either with the testing procedure or by their pharmacologic effects (e.g., thiazides can increase the serum uric acid concentration, β-agonists can reduce serum potassium concentrations).

Renal function tests Why assessing kidney function? To diagnose and assess renal dysfunction, Classification of kidney disease, Dosing of medication BUN Serum Creatinine

Blood Urea Nitrogen (BUN) Normal range: 8-20mg/dL The BUN measures the amount of urea nitrogen in the blood. Urea is formed in the liver as the end product of protein metabolism and is transported to the kidneys for excretion. Nearly all renal diseases can cause an inadequate excretion of urea, which causes the blood concentration to rise above normal. The BUN is interpreted in conjunction with the creatinine test Causes of increased urea Renal failure High protein intake Gastrointestinal bleeding Dehydration Causes of decreased urea Liver failure Poor protein diet High carbohydrate Over hydration

Serum creatinine(Scr) Normal: 62 – 133 mmol/L or 0.7-1.5 mg/dL Eliminated by glomerular filtration and is a sensitive indicator for renal function Factors that affect SCr are muscle mass, sex, age, drugs, low protein diet An increased SCr almost always reflects a decreased GFR Increased serum creatinine: – Impaired renal function – Very high protein diet – Anabolic steroid users/body builders – Vary large muscle mass: giants – Athletes taking oral creatine - Medicines- Cimetidine, Trimethoprim

GFR and Various levels of kidney dysfunction Creatinine clearance Glomerular filtration rate (ml/min) helps in assessing kidney function/ no of functional nephrons • Cockroft-Gault formula is used for estimation of creatinine clearance- gold standard for drug dosing GFR and Various levels of kidney dysfunction Stage Description GFR (mL/min/1.73 m2) 1 Kidney damage with normal or ↑ GFR ≥90 2 Kidney damage with mild ↓ GFR 60-89 3 Moderate ↓ GFR 30-59 4 Severe ↓ GFR 15-29 5 Kidney failure <15 (or dialysis)

Blood glucose measurement 2 most common methods- fasting plasma glucose test (FBS) and 2-hour post prandial glucose test (PPBS) Elevated glucose levels may also be indicative of diabetes mellitus Glycosylated hemoglobin (HBA1C) is used to monitor long-term glucose control Fasting plasma glucose >7.0 mmol/L on at least 2 occasions is diagnostic of diabetes mellitus

Fasting is defined as no caloric intake for at least 8 hours Casual (Random) blood sugar is defined as blood sugar measurement at any time of day without regard to time since last meal. A random blood sugar measurement greater than 11.2 mmol/l is diagnostic criteria for diabetes mellitus (in presence of symptoms) Glycosylated hemoglobin (A1C): Normal range: 4-6% It is a component of the hemoglobin molecule. It is indicative of glucose control during the preceding 2-3 months.

Hematology Blood cells - WBC/leukocytes- Neutrophils, Lymphocytes, monocytes, eosinophils, basophils -RBC/ erythrocytes -Platelets/ thrombocytes Blood tests done to assess disorders of Hb, cell production, synthesis and function; also disorders of blood- anemia, leukemia, abnormal bleeding and clotting, infection, inherent disorders of cells

RBC count is the number of red corpuscles in a given volume of blood Haemoglobin (Hb) Normal value: Male – 13.6 – 17.5 g/dL; Female 12.0- 15.5 g/dL Used to screen for disease associated with anemia, severity of anemia, monitor response to treatment for anemia and to evaluate polycythemia Red blood cell count Normal value: M= 4.5–5.9 × 106 cells/μL ; F= 4.1–5.1 × 106 cells/μL RBC count is the number of red corpuscles in a given volume of blood Require B12, folate, iron (Hb) for its formation Increased (polycythaemia) in: living at altitude, chronic lung/heart disease, tobacco use/carbon monoxide, stress Decreased (anemia) in: B12/folate/iron deficiency, pregnancy, haemolysis

White blood cell count; Normal value: M= 4.4–11.4 × 103 cells/μL WBC count is an actual count of the number of leukocytes in a given volume of blood Increased in: Infection, inflammation, hematologic malignancies Drugs: Corticosteroids. Decreased in: Aplastic anemia Vitamin B12 or folate deficiency Drugs: Phenothiazines, Chloramphenicol

Erythrocyte sedimentation rate (ESR) Male: <10 mm/h, Female: <15 mm/h Sedimentation of erythrocytes increases when they combine with other plasma proteins; Increased in: Infections, anemia, pregnancy, chronic renal failure, multiple myeloma, various inflammatory disorders Decreased in: sickle cell anemia, liver disease, carcinomas, CHF, Drugs: high-dose Corticosteroids It helps to confirm a diagnosis supported by other tests and helpful in monitoring inflammatory conditions

Platelet Count (PLT) Normal: 150–450 × 103 cells /μL A count of the number of platelets (thrombocytes) per cubic milliliter of blood Increased in (Thrombocytosis->800,000/µL) Hematologic malignancies, Iron-deficiency anemia, Tuberculosis, Rheumatoid arthritis Decreased in (Thrombocytopenia- cause excessive bleeding- <150,000/µL) Drugs- heparin, anti-neoplastics, thiazides, cephalosporins Bone marrow suppression, liver failure and sepsis

Electrolytes- Plasma Sodium, Normal Range 136 – 145 mmol/L Sodium is the major cation in the extracellular space and determines the extracellular osmolality Causes of Hypernatremia: 1- Water depletion – due to insufficient water intake or excessive water loss e.g. vomiting, diarrhea 2- Sodium retention – due to excessive sodium intake or drugs e.g. steroids Causes of Hyponatremia Water retention – - In association with renal disease - In congestive heart failure

Serum Potassium, Normal range 3.5 – 5 mmol/L Potassium is the major intracellular cation Hyperkalaemia Causes: Chronic renal failure Excessive doses of potassium retaining diuretics Angiotensin Converting Enzyme Inhibitors Hypokalaemia Inadequate intake Gastro-intestinal loss- vomiting and diarrhea Renal loss Diuretic therapy *note – if a specimen is hemolyzed (such as by traumatic venipuncture or drawing blood with a needle that is too small) potassium levels may be “falsely” elevated.

Liver function tests Tests are to differentiate between liver function and liver injury Grouped into two broad categories- cholestatic disease & hepatocellular injury In cholestastic disease, there is an abnormality in the excreatory function of the liver In hepatocellular- inflammation & damage to the hepatocytes (due to viral infection of hepatocytes) They may overlap in severe conditions

Liver Function Test Albumin Bilirubin: Serum aminotransferases Total Bilirubin Direct Bilirubin (conjugated bilirubin) Serum aminotransferases Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Alkaline Phosphatase Prothrombin time

Tests of synthetic liver function One of liver function- synthesize proteins-albumin & clotting proteins- direct reflection of ability of the liver to synthesize them Inadequate protein synthesis- hepatic cirrhosis, scarring of liver due to alcohol abuse, inflammation or massive liver damage

Albumin Normal range: 3.5-5.5grams/dL3 or 35-50 g/l Synthesized in the liver and is responsible for maintaining oncotic pressure and binding of various drugs and hormones Long half-life, 20 days, serum values are slow to fall, hence albumin level may still not be affected in acute viral hepatitis or drug related toxicity Decreased: When liver is progressively damaged Albumin May also be decreased in malnutrition/mal absorption, protein loss from the body, severe burns severely ill hospitalized patients due to combination of IV fluids, poor nutrition, Increased in dehydration, in people who take anabolic steroids

Bilirubin Total bilirubin: 0.3-1mg/dL Used to determine liver’s ability to clear endogenous/exogenous substances from the circulation Indirect (unconjugated) bilirubin Elevated with hemolysis, hepatic disease Direct (conjugated) bilirubin Elevated with biliary obstruction and hepatocellular disease. Jaundice usually develops with a bilirubin ≥ 3 mg/dL Breakdown of erythrocytes also releases bilirubin into circulation,

Aminotransferases Normal is 0.8 Hepatic enzymes that are usually intracellular, but are released from hepatocytes with hepatocellular injury. Includes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) Normal Value: <35 IU/L AST/ALT ratio Normal is 0.8 In alcoholic hepatitis, is usually > 2 AST- not only in liver, but also in cardiac muscle, skeletal muscle, kidneys, brain, lungs.. ALT- more localized to liver, hence more specific to liver injury

Alkaline phosphatase (ALP) Normal value: 30-120IU/L Found in: Liver, Bone, Intestine, First trimester placenta, Kidney Children, aldoscents- high value ALP concentration 4 times normal- cholestatic disorder Increased in bone disorders, healing fracture, Vitamin-D deficiency, Hyperthyroidsm, Diabetes mellitus, renal failure

Prothrombin Time (PT) Normal value: 11.1-13.1 sec Short half-life, hence responds within 24 hrs to changes in hepatic status Related to synthesis of coagulation factors Liver is in charge of the synthesis of many clotting factors : Factor I (fibrinogen), Factor II (prothrombin), Factor V, Factor VII, Factor IX, Factor X, Factors XII and XIII Elevated PT may be reflection of decreased synthetic activity of liver. Prolongation of PT seen in other situations - Inadequate vitamin K in diet - Poor fat absorption - Poor nutrition - Use of drugs

Learning outcomes… Excessive laboratory tests can cause iatrogenic anemia! Every test ordered, including lab tests, on a patient should be assessed for its benefits, risks and true need. No laboratory test should ever be ordered unless it is medically necessary Interpretation of lab result is to be done with other patient disease conditions