Interpretation of Laboratory Tests. Katarzyna Kostka-Jeziorny, M.D.; Ph.D.

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1 Interpretation of Laboratory Tests Katarzyna Kostka-Jeziorny, M.D.; Ph.D.

2 Reference ranges ("normal ranges") Because reference ranges are typically defined as the range of values of the median 95% of the healthy population, it is unlikely that a given specimen, even from a healthy patient, will show "normal" values for all the tests in a lengthy profile. Therefore, caution should be exercised to prevent overreaction to miscellaneous, mild abnormalities without clinical correlate.

3 Sodium (Na) Normally mmol/l Hypernatremia means sodium levels in blood higher than normal. Commonly this is due to loss of sodium that can be related with excessive sweating, diarrhea, diuretics intake, kidney disease, or Addison s disease Hyponatremia means sodium levels in blood lower than normal. This can be due to excessive water intake or fluid retention and typically due to edema

4 Chloride (Cl) Normally meq/l Increased: Diarrhea, hyperalimentation Decreased: Vomiting, renal disease, diabetic ketoacidosis

5 Potassium (K) Potassium is an electrolyte, a positively charged molecule. It works with other electrolytes, such as sodium, chloride, and bicarbonate (total CO2) in order to regulate the amount of fluid in the body, stimulate muscle contraction, and maintain a stable acid-base balance. Only a very small part of the body`s potassium is present in the blood. Because of this, minor changes can have significant consequences. Abnormal concentration can alter the function of neuromuscular tissue. Potassium testing is used to detect concentrations that are too high (hyperkalemia) or too low (hypokalemia).

6 Potassium (K) Typical cause of hyperkalemia is kidney disease. Also many drugs can decrease potassium excretion from the body and result in this condition. Hypokalemia can occur with diarrhea and vomiting or with excessively sweating. Potassium test may be ordered at regular intervals to monitor drugs that can cause kidneys to lose potassium, particularly diuretics, resulting in hypokalemia. Also if you have a condition or disease, such as acute or chronic kidney failure, that can be associated with abnormal potassium levels.

7 Normally meq/l Potassium (K) Hemolysis may falsely elevate level High potassium levels (hyperkalemia) can be due to : acute or chronic kidney failure Addison's disease hypoaldosteronism injury to tissue infection diabetes dehydration excessive dietary potassium intake

8 Potassium (K) Low potassium levels (hypokalemia) can be due to : dehydration vomiting diarrhea Hyperaldosteronism deficient potassium intake

9 Examples of medications that can increase blood potassium levels Angiotensin Converting Enzyme Inhibitors- ACE inhibitors nonsteroidal anti-inflamatory drugs (NSAIDs) Angiotensin II Receptor Blockers (ARBs) Potassium-sparing diuretics (spironolactone, eplerenone)

10 Examples of medications that can decrease blood potassium levels diuretic medications hydrochlorothiazide, furosemid (Lasix) prednisone aminoglycosides like gentamicin or tobramycin

11 Blood Urea Nitrogen (BUN) Normally 5-20 mg/dl Increased: Renal failure, CHF Decreased: Starvation, liver failure BUN : Creatinine > 20 suggests dehydration BUN : Creatinine > 30 suggests GI bleed

12 Blood Urea Nitrogen (BUN) The following are possible reasons why this test may be done: Acute kidney failure Acute post-streptococcal glomerulonephritis Community acquired pneumonia Dehydration Diabetes with ketoacidosis Diabetic hyperosmolar non-ketotic state Kidney failure Systemic infection

13 BUN Appart from kidney disorders, this test can be influenced by other conditions such as: Results increased in: o Febrile illness o High protein diet Results decreased in: o Low protein diet o High carbohydrate diet

14 Creatinine Creatinine is a waste product produced in the muscles from the decomposition creatine. Creatine is part of the cycle that produces energy needed to contract the muscles. Almost all creatinine is filtered out by the kidneys. Consequently blood levels measure of how well the kidneys are working. Also Creatinine levels serve to monitor treatment for kidney disease.

15 Creatinine Creatinine blood test is usually ordered together with a blood urea nitrogen (BUN) test to check kidney function. Creatinine may be ordered routinely as part of a comprehensive or basic metabolic panel, when someone has non-specific health complaints, is acutely ill, and/or when a doctor suspects kidney dysfunction. The creatinine blood test may be ordered, along with the BUN test, at regular intervals when the patient has a known kidney disorder or has a disease that may affect kidney function or be exacerbated by dysfunction.

16 Creatinine Both may be ordered when a CT scan is planned, prior to and during certain drug therapies, and before and after dialysis to monitor the effectiveness of treatments. Its concentration is measured by means of analysis of a blood sample drawn from the vein in the arm. Also you may be asked to collect a complete 24-hour urine sample in addition.

17 Creatinine Normally < 1.1 mg/dl Measures blood flow through kidneys Increased: Renal failure, false positive seen in diabetic ketoacidosis Decreased: Muscle wasting, liver disease

18 egfr (Estimated Glomerular Filtration Rate) The egfr is a calculated estimation of the glomerular filtration rate and is based on the serum creatinine level. Calculation also takes into account the age, gender, height, and weight, even sometimes the race. Compared to serum creatinine, egfr detects more reliably the kidney disease in its early stages

19 GFR Measured clearance rather than calculated (egfr) is recommended for: Patients with known kidney damage Patients very old Patients very young Patients with high overweight problems Patients with unusual dietary intakes such as vegetarians Patients taking drugs that can affect renal function. The most commonly used equation for calculating the egfr is called the MDRD (Modification of Diet in Renal Disease study) equation.

20 egfr Reference range values egfr ml/min/1.73 sq.m normal range egfr < 60 ml/min/1.73 sq.m suggests moderate kidney problem. egfr < 15 ml/min/1.73 sq.m means severe kidney failure. Abnormal findings Low GFR values can be caused by any kidney disease and also high blood pressure and diabetes

21 Uric acid (UA) Uric acid is produced by the breakdown of purines, chemicals that come from nucleic acids (DNA). They enter the circulation from digestion of foods or from normal metabolism in the body cells. Uric acid is removed by the kidneys and expulsed in the urine and also excreted in the feces. The excesive presence of uric acid in blood can cause the condition called gout an inflammation that occurs in joints when crystals derived from uric acid form in the joint fluid.

22 Uric acid Common reasons for accumulation of uric acid are an inherited tendency to overproduce uric acid or inapropiated kidney function that results in low ability to excrete uric acid. Purpose of the test: To detect high levels of uric acid in blood, which could be a sign of the condition gout, or to monitor uric acid levels when undergoing chemotherapy or radiation treatment. It is prescribed when monitoring certain chemotherapy or radiation therapies for cancer or when there are symptoms of gout such as joint pain.

23 Abnormal findings Uric acid Higher than normal uric acid levels can be due to over production of uric acid or due to the body being unable to clear away it. In any case this lead to formation of uric acid crystals in the joints, which leads to the joint inflammation and pain characteristic of gout. Uric acid can also form crystals or kidney stones that can damage the kidneys. Low values can be associated with some kinds of liver or kidney diseases, exposure to toxic compounds, and rarely as the result of an inherited metabolic defect.

24 Uric acid (UA) Reference range values mg/dl (SI: mmol/l = x mg/dl) Male Female

25 Glucose Slight increase normal with aging High levels of glucose frequently indicate DM/prediabetes. Some other possible diseases that can result in elevated glucose levels include: Acromegaly Acute stress Chronic renal failure Cushing syndrome Drugs such as: corticosteroids, tricyclic antidepressants, diuretics, epinephrine, estrogens, lithium, salicylates, Excessive food intake Hyperthyroidism Pancreatic cancer / Pancreatitis

26 Glucose Low blood glucose levels (hypoglycemia) can be cause by: Adrenal insufficiency Drinking alcohol Drugs, such as acetaminophen and anabolic steroids Extensive liver disease Hypopituitarism Hypothyroidism Insulin overdose Insulinomas Starvation

27 Hemoglobin A1c Glycohemoglobin is a blood test that checks the amount of glucose bound to hemoglobin. Only a small percentage of hemoglobin in the blood (4% to 6%) has glucose bound to it. People with diabetes or other conditions that increase the blood glucose levels have more glycohemoglobin. The glycohemoglobin A1c test checks the long-term control of blood glucose levels in people with diabetes. Most doctors think the glycohemoglobin A1c level is the best way to check how well a person is controlling diabetes.

28 Hemoglobin A1c A home blood glucose test measures the level of blood glucose only at that moment. Reference range values Blood glucose levels change during the day due to Glycohemoglobin A1c: diet, exercise, and the level of insulin in the blood. - Adults: 4.5%-5.7% It is - Children useful for below a diabetic 6 years to have old information % about - Children the long-term ages 6-12 control years of sugar old < levels. 8% The - Teens glycohemoglobin ages test years is one old blood <7.5% sample every 3 to 4 months, and the test does not change with any recent changes in medicines, diet or exercise.

29 ALT (Alanine aminotransferase ) It is an enzyme that is present in liver and heart. Also in the kidneys and muscles. Also present in high concentration into blood when heart or liver are damaged (hepatitis or heart attack for example). Some medications also increase ALT (statins) concentration in blood.

30 ALT Normally concentration in blood of ALT is low. When liver or heart suffer damage as a result, for example, of hepatitis virus or heart attack ALT is released into blood flux. This high level of ALT is previous to other visible effects as yellow color on the eyes and skin (jaundice), nausea, vomiting, dark urine, abdominal pain, abdominal swelling and unusual weight gain.

31 ALT This test is also prescribed to persons who: have a history of known or possible exposure to hepatitis viruses, drink too much alcohol have families with history of liver disease take drugs that might occasionally damage the liver. ALT concentration is compared to levels of other enzymes, such as alkaline phosphatase (ALP) and aspartate aminotransferase (AST), to determine what kind of health problem is present

32 AST (Aspartate Aminotransferase) Low levels of AST are normally found in the blood. When body tissue or an organ such as the heart or liver is diseased or damaged, additional AST is released into the bloodstream. The amount of AST in the blood is directly related to the extent of the tissue damage.

33 AST High levels of AST may be caused by: - Recent or severe liver damage, such as hepatitis caused by a viral infection or drug reaction. - Decay of a large tumor (necrosis). - Shock. Moderately high levels may be caused by: - Chronic diseases affecting the liver, such as cirrhosis. - Heart attack or heart failure. - Alcohol abuse. - High doses of vitamin A. - Kidney or lung damage. - Mononucleosis. - Duchenne muscular dystrophy. - Myositis.

34 AST Slightly high levels of AST may be caused by: - Fatty deposits in the liver. - Medicines, such as statins, antibiotics, chemotherapy, aspirin, narcotics, and barbiturates. - Alcohol abuse. AST levels are high when a disease first develops, which is often when tissue damage is most severe. Decreasing levels of AST in the blood may be a sign of recovery from the disease or injury.

35 AST/ALT Aspartate Aminotransferase: Normally 7-42 IU/L Increased: Liver disease, muscle trauma, burns Decreased: Vitamin B6 deficiency, dialysis AST > ALT in alcoholic hepatitis Alanine Aminotransferase: Normally 1-45 IU/L Increased: Liver disease, billary obstruction ALT > AST in viral hepatitis

36 Albumin Normally g/dl Best lab test for measuring protein Decreased: Malnutrition, nephrotic syndrome, alcoholic cirrhosis, inflammatory bowel disease, metastatic cancer, leukemia, Hodgkin s disease High albumin levels usually can mean: dehydration, presence of certain drugs: anabolic steroids, androgens, growth hormones, and insulin.

37 Bilirubin Normally mg/dl Bilirubin is a dark yellow substance included in the bile and the blood. Red blood cells (RBCs) normally degrade after 120 days in the circulation. Then, a component of the RBCs called hemoglobin breaks down into unconjugated bilirubin.

38 Bilirubin Unconjugated bilirubin is transported to the liver, sugars are added to it, so it becomes water soluble, producing conjugated bilirubin. Conjugated bilirubin pass to the bile and then to the intestines, where a bacteria degrades it. Furtherwards it is excreted in the feces given them its brown color.

39 Bilirubin Bilirubin is found then in two variants: Indirect (or unconjugated) bilirubin. Insoluble in water. It travels through the bloodstream to the liver, where it is converted into direct or conjugated bilirubin. Direct (or conjugated) bilirubin. Soluble in water

40 Bilirubin With high bilirubin levels, the skin and whites of the eyes may appear yellow (jaundice). This must mean liver disease, blood disorders, or blockage of the bile ducts. Very high bilirubin levels in a newborn can cause brain damage, hearing loss, physical abnormalities, and death.

41 Bilirubin Reference range values mcmol/l Abnormal findings: high levels of Bilirubin in newborns are caused by: Accelerated breakdown of red blood cells due to a blood type incompatibility between the mother and her newborn. High levels of Bilirubin in adults and children are caused by: Liver damage/disease Gilbert s, Rotor s, Dubin-Johnson or Crigler-Najjar syndromes

42 Bilirubin High levels of unconjugated bilirubin are caused by: Pernicious anemias Transfusion reaction High levels of conjugated bilirubin means some kind of blockage of the liver or bile ducts, caused by : Hepatitis Liver trauma Cirrhosis Drug reaction Alcohol abuse

43 Alkaline Phosphatase Normally IU/L Alkaline phosphatase (ALP) is an enzyme. Different kinds of this protein are present on different parts of the body. The different forms of ALP are called isoenzymes. ALP is found especially in bone cells and liver cells. Smaller amounts of ALP are present in the placenta and in the bowels. Increased: Liver disease, billary obstruction, bone tumors, healing fracture, hyperparathyroidism, hyperthyroidism Decreased: Malnutrition, excessive vitamin D intake, pernicious anemia, zinc deficiency

44 Complete Blood Count WBC, H&H, Platelets most important Platelets normally 150, ,000 ul

45 White Blood Count Normally ,000 Increased: Infection, inflammation, leukemia Decreased: Bone marrow failure, vitamin B12 deficiency

46 Cause of Increased Differentials Basophils: Leukemia, s/p spleenectomy Eosnophils: Allergies, asthma, parasites Lymphocytes: Viral infections, leukemia Monocytes: Bacterial infections, protozoan infections, ulcerative colitis Neutrophils: Bacterial infection, noninfectious tissue damage, metabolic disorders

47 H & H Hematocrit: ~ 40-50% (lower in women, higher in men) The percentage of blood that is RBCs Decreased with anemia and blood loss Hemoglobin: ~ g/dl (lower in women, higher in men) Does not acurately reflect acute bleeding because plasma and RBC lost at same rate

48 Coagulation Studies INR: Higher with mechanical heart valves or history of thromboembolitic disease or atrial fibrillation INR is now the standard measure reported

49 Urinanalysis Urine is produced by the kidneys as product of filtering wastes and metabolic byproducts out of the blood. Anything that is not needed is excreted in the urine. Urine is generally yellow and relatively clear, but color, quantity, concentration, and content of the urine can be slightly different because of varying constituents. Many disorders can be diagnosed in their early stages by detecting abnormalities in the urine.

50 Urinanalysis A complete urinalysis consists of: 1. physical examination: urine's color, clarity, and concentration 2. chemical examination, which tests chemically for 9 substances that provide valuable information about health and disease 3. microscopic examination, which searches and counts the type of cells, casts, crystals, and other components (bacteria, mucus ) that can be present Its concentration is measured by means of analysis of a urine sample.

51 Urinanalysis reference range values Urinalysis Protein = Negative Glucose = Negative Ketones = Negative Hemoglobin = Negative Urobilinogen = Negative Nitrite = Negative ph = 5-6 Specific Gravity = RBC's 0-1 WBC's 0-2

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