LIFELABS GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
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LifeLabs Gastrointestinal Laboratory Diagnostic Services According to the Canadian Digestive Health Foundation, every year, more than 20 million Canadians struggle with digestive disorders, including lactose intolerance, celiac disease and gastro-esophageal reflux disease, and nearly 30,000 individuals die from these disorders. Inflammatory Bowel Disease (IBD) is diagnosed in 1 in every 150 Canadians, making Canada the country with the highest incidence of IBD world-wide. In addition, functional bowel diseases such as the irritable bowel syndrome (IBS) are common and a significant cause of morbidity. LifeLabs’ gastrointestinal test menu will support your clinical decision making for various common GI presentations such as chronic diarrhea and abdominal pain in specific disease conditions such as IBD, liver diseases, colorectal cancer and celiac disease. As well, we offer gastrointestinal pathology services to confirm diagnoses indicated by laboratory tests. LifeLabs’ medical experts, including specialists that focus on gastrointestinal pathology are available for professional consultations about test selection and rare or complex testing. Our gastrointestinal pathology services are designed to meet your specific needs, including specimen collection kits and requisition forms for better practice efficiency.
What’s Included? Assessment of Chronic Diarrhea 3 GI Tract Infections and Pathogen investigations 12 Stool Culture 3 Bacterial Gastroenteritis-Bacterial Stool Culture 12 C - Difficile Testing 4 Viral Gastroenteritis - Viral Stool Culture 13 Fecal - Ova & Parasite 4 Fecal - Antigen Testing by PCR 4 Assessment of Nutritional Deficiencies and Imbalances 13 Thyroid Stimulating Hormone (TSH) 4 Vitamin Levels Assessment 14 Free T3 and Free T4 4 Iron Levels Assessment 14 Ferritin 5 Electrolytes 14 C Reactive Protein (CRP) 5 Trace Mineral Assessments 14 Celiac Disease Antibody 5 Elastase Stool 14 Fecal Calprotectin 5 Celiac Disease Testing 14 Assessment of Inflammatory Bowel Disease 6 Assessment of Epigastric Pain 15 IBD & IBS Differential Diagnosis Tests 6 Lipase 15 Electrolytes 6 Helicobacter pylori Antigen and Urea Breath Test 15 Nutritional Evaluation - Iron & Vitamin Studies 7 Liver Function Tests 16 pANCA and ASCA Tests 7 Differential Diagnosis of Esophagitis 16 GI Histology 7 Peptic Ulcer Disease (PUD) Tests 16 Diagnosis and Monitoring of Malabsorption 8 Assessment of Liver Function 17 Vitamin B-12 9 Alanine Aminotransferase (ALT) 17 Prothrombin Time (PT) and INR 9 Albumin 17 Albumin 9 Alkaline Phosphatase (ALP) 18 Total Protein and A/G Ratio 9 Bilirubin - Total or Direct 18 Lactose Tolerance Test 9 Hepatitis C 18 25-Hydroxy Vitamin D 9 Hepatitis B 18 Celiac Disease Tests 10 Detecting Autoimmune Liver Disease 19 Tissue Transglutaminase IGA Antibody 10 Anti-Mitochondrial Antibody (AMA) 19 Deamidated Gliadin IgG Antibodies 11 Antinuclear Antibody (ANA) 19 Anti-Endomysial Antibodies (EMA), IgA Class 11 Smooth Muscle Antibodies 19 Consideration of Genetic Testing 11 Management of GI Malignancies 19 Fecal Immunochemical Test (FIT) 19 Carcinoembryonic Antigen (CEA) 20 Cancer Antigen 19-9 20 Why Choose LifeLabs? Over 360 LifeLabs locations We accept walk-ins , Quick turn-around time offer gastrointestinal sample as well as appointments for all (TAT) allows for fast decision- collection services blood tests making in treatment management Electronic reporting Launchpad – Consultations with direct results integration into an online physician portal with 24/7 with our team of pathology specialists most EMR’s remote access to results when required 2 LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
Assessment of Chronic Diarrhea Most diarrheal episodes in developed countries are acute and self-limited and are usually due to infections. In immunocompetent patients, acute infectious diarrhea typically resolves within 1-4 weeks. Therefore, chronic diarrhea is defined as diarrhea that lasts longer than 4 weeks.1 It is estimated that 1%–5% of adults suffer from chronic diarrhea.2 Since chronic diarrhea can occur due to many underlying causes, differential diagnosis is the key to effective patient management. In primary care settings, history, physical examination, assessment of diet, medications, previous surgeries and / or radiation therapy can indicate the cause of chronic diarrhea. However, laboratory tests of blood and stool, with histology and other non-laboratory testing is necessary when no obvious cause is evident. LifeLabs offers several stool-based laboratory tests to aid in the assessment of chronic diarrhea. STOOL CULTURE Cultures of stool samples use special nutrient media A stool culture is typically ordered to rule out any that selectively allow pathogens to grow while inhibiting infectious causes of chronic diarrhea, or when a patient growth of bacteria that are normally present in the has prolonged signs and symptoms and/or infections that digestive tract (normal flora). Stool cultures may detect do not resolve without treatment. several different bacteria, but typical investigations are for the most common intestinal pathogens, such as Campylobacter, Salmonella s and Shigella species, and Y enterocolitica in the presence of clinical signs of colitis or if fecal leucocytes are found.4 LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES 3
C- DIFFICILE TESTING This test detects the presence of an infection caused C. difficile infection is the most common cause of diarrhea in people who develop diarrheal by toxin-producing Clostridium difficile bacteria, when symptoms while hospitalized. C. difficile toxin is persistent diarrhea is present. This typically occurs as detected in the stools of up to 20-30% of those a result of prolonged use of broad-spectrum antibiotics with antibiotic-associated diarrhea and greater which eliminate the regular, healthy flora found in than 95% of those with pseudomembranous the digestive tract, leading to an over-production colitis.5 of C. difficile and its toxins. This may lead to severe inflammation of the colon and chronic diarrhea. FECAL – OVA & PARASITE The fecal ova and parasite test includes evaluation for cysts and trophozoites of intestinal protozoa and larvae, eggs, and adults of intestinal helminths. Chronic diarrhea is accompanied generally by blood or mucus in the loose stools, nausea and / or abdominal pain. The ova and parasite examination includes a macroscopic examination to determine fecal consistency, abnormalities (blood, excessive mucus), and the presence of larval or adult worms or proglottids, as well as a microscopic examination of protozoal trophozoites and cysts. To aid diagnosis, an ova and parasite exam may be done in conjunction with or following a GI pathogens panel that simultaneously tests for multiple disease-causing bacteria, viruses, and parasites. Other tests that may be done include a stool culture and antigen tests to identify specific microbes. FECAL – ANTIGEN TESTING BY PCR / MICRO-STOOL PARASITE This test is done by polymerase chain-reaction (PCR) technique and detects the protein structures on parasites found in the stool. This is test is sensitive and specific to the parasites being investigated, including Giardia lamblia, Entamoeba histolytica and Cryptosporidium parvum known for causing significant diarrhea. In addition to Complete Blood Count (CBC), LifeLabs offers several other blood tests to aid in the assessment of chronic diarrhea. THYROID STIMULATING HORMONE (TSH) TSH is the test of choice to screen for thyroid dysfunction6. When the thyroid produces too much thyroid hormone (hyperthyroidism), it can lead to hypertension, weight loss, difficulty sleeping and sometimes, chronic diarrhea. TSH may be ordered at regular intervals when an individual is being treated for a known thyroid disorder. FREE T3 AND FREE T4 Free T3 and T4 may be ordered along with thyroid stimulating hormone test (TSH) to evaluate thyroid function. T3 levels are obtained in suspected cases of hyperthyroidism, either because the patient has typical symptoms or when the TSH levels are lower than normal and free T4 levels are not elevated10 4 LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
FERRITIN Ferritin is present in small concentrations in blood. The serum ferritin concentration normally correlates well with total- body iron stores, making its measurement important in the diagnosis of disorders of iron metabolism7. The ferritin test may be ordered, along with other iron tests, when a routine complete blood count (CBC) shows that a person’s hemoglobin and hematocrit are low and their red blood cells are smaller and paler than normal (microcytic and hypochromic), suggesting iron deficiency anemia even though other clinical symptoms may not have developed yet8. Iron deficiency anemia may in turn be caused by the inability of the body to absorb iron from foods eaten, such as in celiac disease, another common cause of chronic diarrhea. C REACTIVE PROTEIN (CRP) C-reactive protein (CRP) is an acute phase reactant, a protein made by the liver and released into the blood within a few hours after tissue injury, the start of an infection, or other cause of inflammation. The level of CRP can jump as much as a thousand-fold in response to inflammatory conditions9, and its rise in the blood can precede pain, fever, or other clinical indicators. The test measures the amount of CRP in the blood and can be valuable in detecting inflammation due to acute conditions or in monitoring disease activity in chronic conditions, to detect flare-ups and / or to determine if treatment is effective. High CPR levels may indicate the presence of inflammatory bowel disease (IBD). For more information, see section on IBD. CELIAC DISEASE ANTIBODY Celiac disease is an autoimmune disorder characterized by an inappropriate immune response to gluten. One of the most common symptoms of celiac disease is chronic diarrhea, usually accompanied by abdominal pain and weight loss. Celiac disease tests detect the autoantibodies in the blood which are produced as part of the immune response. For more information, see section on ‘Celiac Disease Testing’. FECAL CALPROTECTIN* Calprotectin is a protein released by the neutrophil white blood cell. When there is inflammation in the gastrointestinal tract, neutrophils move to the area and release calprotectin, resulting in an increased level in the stool. Thus, calprotectin is a surrogate marker for mucosal inflammation in the intestines.14. Fecal Calprotectin will help evaluate the level of intestinal inflammation and will differentiate between irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) in the primary care setting. When used for this differential The 2018 clinical practice guidelines from the diagnosis, fecal calprotectin has sensitivity and specificity British Society of Gastroenterology state that in both of approximately 85% and high negative predictive patients with typical symptoms of functional bowel value (>96%) for IBD. disease, normal physical examination and normal screening blood tests and calprotectin levels, a In IBD patients, Fecal Calprotectin is used to monitor positive diagnosis of IBS can be made.16 disease activity and response to therapy, thus allowing *The fecal Calprotectin test is an uninsured test in all provinces of Canada physicians to adjust treatment to achieve remission. LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES 5
Assessment of Inflammatory Bowel Disease (IBD) Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to host intestinal microflora, often manifested in the form of inflammation of the digestive tract11. The two major types of inflammatory bowel disease are ulcerative colitis (UC), which is limited to the colonic mucosa, and Crohn’s disease (CD), which can affect any segment of the gastrointestinal tract from the mouth to the anus, involves “skip lesions,” and is transmural12. There is a genetic predisposition for IBD, and patients with this condition are more prone to the development of malignancy. The World Gastroenterology Organization indicates that diarrhea with the presence of mucus/blood in the stool, constipation, possible rectal bleeding, tenesmus, abdominal cramping and nausea are symptoms that maybe associated with inflammatory damage of the digestive tract13. Along with Complete Blood Count, Stool Culture, C-Difficile and C-Reactive Protein, LifeLabs offers several other laboratory tests in the diagnosis and management of IBD. IBD & IBS DIFFERENTIAL DIAGNOSIS TESTS The fecal calprotectin test can be used to differentiate IBD See section on Chronic Diarrhea for more information on from IBS (Irritable Bowel Syndrome) – a non-inflammatory fecal calprotectin. condition, in the work up of a patient with chronic diarrhea. ELECTROLYTES The electrolyte panel measures the blood levels of the main conditions, and often, in ulcerative colitis (UC). electrolytes in the body: sodium (Na+), potassium (K+), chloride (Cl-), and bicarbonate (HCO3-; sometimes reported Electrolyte tests are commonly ordered at regular intervals as total CO2). Electrolyte measurements may be used to to monitor treatment of certain conditions, including help investigate conditions that cause electrolyte imbalances hypertension, heart failure, lung diseases, and liver and such as dehydration, kidney disease, lung diseases, heart kidney disease. 6 LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
The incidence of gallstones and kidney stones is increased in Crohn’s disease because of malabsorption of fat and bile salts.17 Gallstones are formed because of increased cholesterol concentration in the bile, which is caused by a reduced bile salt pool. Patients who have Crohn’s disease with ileal disease or ileal resection are also likely to form calcium oxalate kidney stones. NUTRITIONAL EVALUATION – IRON & VITAMIN STUDIES Vitamin B-12 deficiency can occur in patients with blood loss18. Hence, serum iron tests are often required Crohn’s disease who have significant terminal ileum to detect iron deficiency. Additional tests to consider in disease or in patients who have had terminal ileum determining nutritional status are albumin, prealbumin resection, so the Vitamin B-12 test may be ordered to and transferrin. assess status. Active IBD is a source of gastrointestinal pANCA and ASCA TESTS Perinuclear antineutrophil cytoplasmic antibodies combination of positive p-ANCA and negative ASCA has (p-ANCA) have been identified in about 60%-80% of high specificity for ulcerative colitis, whereas the inverse patients with ulcerative colitis, and anti-Saccharomyces pattern—positive ASCA, negative p-ANCA—is more cerevisiae antibodies (ASCA) have been found in in specific for Crohn’s disease. about 60%-70% of patients with Crohn’s disease19. The GI HISTOLOGY The typical histologic findings of ulcerative colitis include intestinal wall is involved with inflammation in Crohn’s expansion of chronic inflammation in the mucosa and, disease. Biopsy specimens may demonstrate granulomas in active cases, the presence of acute inflammation. In (approximately 50% of the time).21 severe cases, mucosal ulcers may be detected. The entire LifeLabs offers comprehensive pathology services to confirm a diagnosis. Our experienced gastrointestinal pathology team includes medical doctors, nationally recognized GI pathologists, specialists, and technicians who are available for professional consultations about test selection and rare or complex testing. LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES 7
Diagnosis and Monitoring of Malabsorption Malabsorption occurs due to an impaired transport of nutrients from the intestine to the blood thereby compromising a patient’s ability to digest or absorb necessary nutrients from their diet. Malabsorption can be nutrient-specific (due to a specific food allergy or intolerance) or non-specific, which can occur when a diffuse disorder like celiac disease or Crohn’s disease affects the intestine, and impairs the absorption of almost all nutrients. Malabsorption can occur when any of the three stages of digestion, namely, the luminal phase (the breakdown of proteins, fats and carbohydrates by stomach acids, pancreatic enzymes and bile), the mucosal phase (the absorption of nutrients by intestinal cells) or the postabsorptive phase (transportation, usage and storage of nutrients) gets impaired22. Symptoms generally include diarrhea, stearorrhea, weight loss, fatigue, flatulence and may rarely include edema, anemia and bone disorders. There are many possible causes of malabsorption, including Biliary Atresia, Cholestasis, pancreatic cancer, lymphoma, stomach cancer, celiac disease, cystic fibrosis, congestive heart failure, lactose intolerance, hyperthyroidism, gastrointestinal infections, Crohn’s disease, liver disease, pancreatic disease and pancreatic insufficiencies, scleroderma, bariatric surgeries and Zollinger-Ellison syndrome, among others23. Laboratory work up of malaborption focuses on differential diagnoses of its possible causes. Along with Complete Blood Count (CBC), C–Reactive Protein, electrolytes and tests to evaluate iron levels, LifeLabs offers the following tests for assessment of malabsorption: 8 LifeLabs DIABETES LABORATORY TESTING SERVICES
VITAMIN B-12 Vitamin B-12 and folate tests measure vitamin levels intestine, bound by carrier proteins (transcobalamins), and in the liquid portion of the blood (serum or plasma) to enters the circulation. If a disease or condition interferes detect deficiencies. B-12 is normally released from food by with any of these steps, then B12 absorption is impaired, stomach acid and then, in the small intestine, is bound to and will be detected by this serum test. Vitamin B-12 is intrinsic factor (IF), a protein made by parietal cells in the diminished in bacterial overgrowth and tropical sprue. stomach. This B12-IF complex is then absorbed by the small PROTHROMBIN TIME (PT) AND INR Prothrombin time (PT) is a test that helps evaluate performed to investigate the bleeding. If the result is a person’s ability to appropriately form blood clots. prolonged and is suspected to be due to low levels of A deficiency of vitamin K is usually discovered when vitamin K, then vitamin K will often be given by injection. unexpected or excessive bleeding occurs. In such cases, If the bleeding stops and the PT returns to normal, then a a prothrombin time (PT/INR) is the main laboratory test vitamin K deficiency is assumed to be the cause. ALBUMIN Albumin is a protein found in the blood. Since albumin is ordered as part of a liver panel to evaluate liver function or produced by the liver, its level can decrease with loss of with a creatinine, blood urea nitrogen (BUN), or renal panel liver function; however, this typically occurs only when the to evaluate kidney function. liver has been severely affected. An albumin test may be TOTAL PROTEIN AND ALBUMIN / GLOBULIN RATIO Albumin makes up about 60% of the total protein. The A low total protein level can suggest a liver disorder, remaining 40% of proteins in the plasma are referred a kidney disorder, or a disorder in which protein is not to as globulins which include enzymes, antibodies, digested or absorbed properly. Low levels may be seen hormones, carrier proteins, and other types of proteins24. in severe malnutrition and with conditions that cause Protein malabsorption may cause hypoproteinemia and malabsorption, such as celiac disease or inflammatory hypoalbuminemia, which is indicated by the Albumin / bowel disease (IBD). Globulin, or A/G ratio. LACTOSE TOLERANCE TEST* A sensitive test for carbohydrate malabsorption is the flora digest the unabsorbed lactose, resulting in an hydrogen breath test, in which patients are given an oral elevated hydrogen content in the expired air. solution of lactose. In cases of lactase deficiency, colonic 25-HYDROXY VITAMIN D* When calcium is low and/or a person has symptoms usually is ordered to identify a possible deficiency in of vitamin D deficiency, such as bone malformation vitamin D. in children (rickets) and bone weakness, softness, or *provincial health plan coverage for 25-Hydroxy Vitamin D varies by province or by fracture in adults (osteomalacia), 25-hydroxyvitamin D specific clinical indications. The Lactose tolerance test is an uninsured test. LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES 9
Celiac Disease Tests Celiac disease (CD), also known as celiac sprue or gluten-sensitive enteropathy, is a chronic 1 out of 100 people in Canada have disorder of the digestive tract that results in an inability to tolerate gliadin, the alcohol- celiac disease25 soluble fraction of gluten. Gluten is a protein commonly found in wheat, rye, and barley. When patients with celiac disease ingest gliadin, an immunologically mediated inflammatory response occurs that damages the mucosa of their small intestines, resulting in maldigestion and malabsorption of food nutrients. Symptoms include weight loss, diarrhea, abdominal pain/distension, and occasionally, severe malnutrition. Weight-loss (or failure to thrive in children), muscle wasting and Dermatitis herpetiformis (DH) may also occur. Along with Complete Blood Count (CBC), C–Reactive Protein, electrolytes and tests to evaluate iron and vitamin levels, LifeLabs offers the following specific tests for the diagnosis of celiac disease: TISSUE TRANSGLUTAMINASE IgA ANTIBODY (TTG-IgA) When a susceptible person is exposed to gluten, the specific blood test for celiac disease and is the test person’s body produces autoantibodies that act against recommended by the Canadian Celiac Association. This constituents of the intestinal villi. Celiac disease blood test may also be used to monitor treatment effectiveness, tests measure the amount of particular autoantibodies in as IgA antibody levels should fall once gluten is removed the blood. The TTG-IgA test is the primary test ordered from the diet. to screen for celiac disease. It is the most sensitive and The joint recommendation from the Canadian Celiac Association (CCA), American College of Gastroenterology (ACG), North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and World Gastroenterology Organization (WGO) is to use TTG-IgA as the primary screening test in the diagnosis of celiac disease in adults and children26. 10 LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
DEAMIDATED GLIADIN IgG ANTIBODIES Around 2-3% of people with Celiac disease have an IgA deficiency26, which can lead to a false negative result of the tTG, IgA test. This is when a test to measure IgG is recommended. The Deamidated Gliadin IgG antibodies test may be positive in some people with celiac disease who are negative for anti-tTG, especially children less than 2 years old. ANTI-ENDOMYSIAL ANTIBODIES (EMA), IgA CLASS muscle fibers. IgA may be measured using the EMA or the TTG test. Almost 100% of people with active celiac disease and 70% of those with dermatitis herpetiformis will have the IgA class of anti-EMA antibodies27. CONSIDERATION OF GENETIC TESTING Genetics play an important role in celiac disease. The incidence of celiac disease in relatives of patients with celiac disease is significantly higher than in the general population. The prevalence in first-degree relatives of patients with celiac disease is approximately 10%. Concordance for the disease in monozygotic twins approaches 75% and is approximately 30% for first-degree relatives28. Genetic tests include the Human Leukocyte Antigen (HLA) markers DQ2 and DQ8. They are most useful for family members of individuals with the disease who fall into a high risk category. A negative result is generally useful to rule out celiac disease in individuals for whom results of other tests are inconclusive. A positive result, however, with confirmed serology may streamline the diagnosis and subsequent management of celiac disease. LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES 11
GI Tract Infections & Pathogen Investigations A variety of viruses, bacteria, and parasites can cause infections of the digestive system (gastrointestinal (GI) infections). The gastrointestinal pathogen tests simultaneously test for the presence of multiple disease-causing (pathogenic) microbes in a stool sample. GI infections are often caused by ingesting food or fluid that has been contaminated by bacteria, viruses or, more rarely, parasites. Infections can spread to other people through exposure to infected stool. Gastroenteritis has many causes, can range from mild to severe, and typically manifests with symptoms of vomiting, diarrhea, and abdominal discomfort. It is usually self-limited, but improper management of an acute infection can lead to a protracted course. The recommended laboratory tests include: Stool Antigen tests Stool Culture Ova & Parasite Exam to identify specific parasites to identify pathogenic bacteria to identify parasites by their protein structure BACTERIAL GASTROENTERITIS - BACTERIAL STOOL CULTURE / MICRO-STOOL C&S When the infection is bacterial in nature, the cause is generally linked to ingestion of certain foods, exposure to water and / or animals and travel. Assessment includes the stool pH, presence of reducing substances in the stool, fecal leucocytes and visual examination. Bacterial stool culture includes testing for the following species, among others: > Aeromonas species > Bacillus species > Campylobacter species > C difficile > C perfringens > E coli > Listeria species > Plesiomonas species > Salmonella species > Shigella species > Staphylococcus species > Vibrio species 12 LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
VIRAL GASTROENTERITIS – VIRAL CULTURE - STOOL Viral spread from person to person occurs by fecal-oral transmission of contaminated food and water. Some viruses, like noroviruses, may be transmitted by an airborne route. Sporadic gastroenteritis in infants is most frequently caused by rotavirus. Epidemic gastroenteritis occurs either in semi-closed communities (families, ships, vacation spots etc.) or as a result of food-borne or water-borne pathogens, like caliciviruses. Finally, sporadic gastroenteritis in adults is most frequently caused by caliciviruses, rotaviruses, astroviruses, or adenoviruses. Viral stool culture includes testing for the following species, among others: > Adenovirus > Rotavirus > Torovirus > Norwalk virus > Astrovirus > Calcivirus Other tests which may be considered to aid the GI pathogen work up are C - reactive protein to check inflammation, Stool White Blood Cell (WBC) and lactose tolerance test. Assessment of Nutritional Deficiencies and Imbalances Malnutrition is a condition in which there is a disparity between the amount of nutrients that the body needs for proper growth and health and the amount that it receives or takes in (absorbs). This occurs when a patient is unable to properly breakdown nutrients in the gastrointestinal tract. Imbalances are mostly associated with under-nutrition, but may also occur due to over-nutrition. Under-nutrition may be due to insufficient intake, increased loss, increased demand, or a condition or disease that decreases the body’s ability to digest and absorb nutrients from food. This may occur due to lack of nutritional support during pregnancy, very early childhood, acute conditions such as surgery, severe burns, infections or trauma, or chronic diseases that lead to malaborption. Malabsorption may occur with chronic diseases such as celiac disease, cystic fibrosis, pancreatic insufficiency, and pernicious anemia. An increased loss of nutrients may be seen with chronic kidney disease, diarrhea and excessive bleeding (see section on Malapsorption). Aside from fecal fat, Complete Blood Count (CBC), albumin and stool ova & parasite with possible stool culture, a healthcare provider can order additional laboratory tests to evaluate a patient’s blood and organ function, and to look for specific vitamin and mineral deficiencies. LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES 13
VITAMIN LEVELS ASSESSMENT An assessment of Vitamin B12 and folate, Vitamin A Vitamin A deficiency can present as night-blindness, (Retinol), Vitamins B and others can help the healthcare xerophthalmia, poor growth, and hair changes, whereas provider in determining the exact nutritional deficiency. Vitamin D deficiency can manifest itself as poor growth, While symptoms can be general poor health, many rickets and hypcalcemia29. A test for vitamin K can be vitamin deficiencies have specific symptoms. For example, done through INR (International Normalized Ratio). IRON LEVELS ASSESSMENT Tests to evaluate serum iron levels, as well as ferritin fatigue, decreased cognitive function, headaches, glossitis and transferrin are ordered especially when patient is and nail changes, and sometimes syncope. presenting symptoms consistent with anemia, such as ELECTROLYTES The electrolyte panel measures the blood levels of the used to help investigate conditions that cause electrolyte main electrolytes in the body: sodium (Na+), potassium imbalances such as dehydration, malabsorption, kidney (K+), chloride (Cl-), and bicarbonate (HCO3-; sometimes disease and liver disease, among others. reported as total CO2). Electrolyte measurements may be TRACE MINERAL ASSESSMENTS Tests for calcium, magnesium, zinc, selenium and dwarfism, hepatosplenomegaly, hyperpigmentation and iodine can help identify micronutrient deficiencies. For hypogonadism, acrodermatitis enteropathica, diminished example, a deficiency in zinc can be presented as anemia, immune response, and poor wound healing30. ELASTASE STOOL Elastase is an enzyme produced by special (exocrine) eliminated from the body in the stool. The level in the tissue in the pancreas. This test measures the amount stool is decreased when the exocrine tissues of the of elastase in stool to determine a possible exocrine pancreas are not producing sufficient elastase and other pancreatic insufficiency. In the digestive tract, elastase digestive enzymes. is not broken down by other enzymes and is eventually CELIAC DISEASE TESTING Celiac serology is a useful screening test and should be disease or if other autoimmune diseases, such as type I considered, especially if there is a family history of celiac diabetes mellitus, are present. 14 LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
Assessment of Epigastric Pain Epigastric pain is felt in the upper abdominal section, usually in the area below the ribcage and is medically termed as dyspesia. It may occur along with other digestive symptoms such as heartburn, bloating and flatulence. When the pain occurs as result of overeating, alcohol consumption or during pregnancy, it is generally temporary and harmless. However, differential diagnosis is essential when symptoms become chronic and may be due to an underlying cause like inflammation, peptic ulcer disease, gastroesophageal reflux disease (GERD), lactose intolerance or an infection. Along with Complete Blood Count (CBC) LifeLabs offers the following diagnostic tests in the assessment and management of epigastric pain: LIPASE The lipase test is ordered when symptoms are suggestive the amylase test when the healthcare provider suspects of a pancreatic disorder, such as severe abdominal pain, acute pancreatitis. fever, loss of appetite, or nausea. It is often ordered with HELICOBACTER PYLORI ANTIGEN AND UREA BREATH TEST This test is ordered when symptoms are suggestive of an mucus, and increases the risk of developing ulcers (peptic ulcer, such as intermittent abdominal pain, unexplained ulcer disease), chronic gastritis, and gastric (stomach) cancer. weight loss, nausea and / or vomiting. Helicobacter pylori are a type of bacteria known to be a major cause of peptic LifeLabs offers two types of non-invasive H. Pylori tests- ulcer disease. H. pylori tests detect an infection of the the stool antigen test which detects the H. Pylori in a stool gastrointestinal tract caused by the bacteria. While most sample, and the urea breath test which detects carbon individuals with H. pylori remain asymptomatic, the presence dioxide in the breath after drinking a solution. of the bacteria affects the stomach’s ability to produce The joint recommendation from the American College of gastroenterology and Canadian Association of Gastroenterology is to perform the non-invasive H. Pylori test on patients < 60 when presenting symptoms of dyspepsia31. LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES 15
LIVER FUNCTION TESTS A wide range of laboratory tests may be ordered to (hepatitis), scarring (cirrhosis), bile duct obstructions, check the functioning of the liver in suspected dyspepsia. liver tumors, and liver dysfunction. See section on liver A variety of diseases and infections can cause acute function tests for more details. or chronic damage to the liver, causing inflammation DIFFERENTIAL DIAGNOSIS OF ESOPHAGITIS Esophagitis happens when the lining of the esophagus suppressed patients, CD4 count in patient with risk gets inflamed, accompanied by heartburn and / or factors for HIV and autoimmune disorder-specific work- dyspepsia, difficulty swallowing, coughing and burning ups may be considered when complications arising from sensation in the chest and throat. The common forms esophagitis (such as, upper GI hemorrhage) are observed. of esophagitis include reflux esophagitis, infectious Since many symptoms of esophagitis are similar to heart esophagitis, pill esophagitis, eosinophilic esophagitis, conditions like acute coronary syndrome, angina pectoris, and radiation and chemoradiation esophagitis. Candida myocardial infarction, a thorough differential diagnosis is esophagitis is the most common type of infectious necessary to rule out these conditions33. esophagitis32. A complete blood count (CBC) in immune- PEPTIC ULCER DISEASE (PUD) TESTS Peptic ulcers are sores that develop in the lining of help diagnose a peptic ulcer, identify the cause, detect the esophagus, stomach, or upper section of the small complications, and help determine appropriate treatment. intestine (duodenum). Epigastric pain is the most common The H. Pylori test can rule out a bacterial cause of symptom of both gastric and duodenal peptic ulcers. It inflammation. Serum iron tests can be done to check for is characterized by a gnawing or burning sensation and anemia and fecal immunochemical testing can be done to occurs after meals. A few different tests may be done to check for blood in the stool to rule out colon cancer. 16 LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
Assessment of Liver Function LifeLabs offers a range of tests to detect, evaluate and monitor liver disease or damage. A variety of diseases and infections can cause acute or chronic damage to the liver, causing inflammation (hepatitis), scarring (cirrhosis), bile duct obstructions, liver tumors, and liver dysfunction. Alcohol, drugs, some herbal supplements, and toxins can also pose a threat. A significant amount of liver damage may be present before symptoms such as jaundice, dark urine, light-colored stools, itching (pruritus), nausea, fatigue, diarrhea, and unexplained weight loss or gain emerge. Early detection is essential in order to minimize damage and preserve liver function. ALANINE AMINOTRANSFERASE (ALT) Alanine aminotransferase (ALT) is present primarily in liver a destruction of hepatocytes. Values are typically at cells. In viral hepatitis and other forms of liver disease least 10 times above the normal range. Levels may associated with hepatic necrosis, serum ALT is elevated even reach values as high as 100 times the upper reference before the clinical signs and symptoms of the disease appear. limit, although 20- to 50-fold elevations are most Although serum levels of both aspartate aminotransferase frequently encountered. In infectious hepatitis and (AST) and ALT become elevated whenever disease processes other inflammatory conditions affecting the liver, ALT affect liver cell integrity, ALT is a more liver-specific enzyme. is characteristically as high as or higher than aspartate Serum elevations of ALT are rarely observed in conditions aminotransferase (AST), and the ALT:AST ratio, which other than parenchymal liver disease. normally and in other condition is less than 1, becomes greater than unity. ALT levels are usually elevated before Elevated alanine aminotransferase (ALT) values are clinical signs and symptoms of disease appear34. seen in parenchymal liver diseases characterized by LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES 17
ALBUMIN Albumin is a protein found in the blood. Since albumin is may be ordered as part of a liver panel to evaluate liver produced by the liver, its level can decrease with loss of function or with a creatinine, blood urea nitrogen (BUN), liver function; however, this typically occurs only when or renal panel to evaluate kidney function. the liver has been severely affected. An albumin test ALKALINE PHOSPHATASE (ALP) ALP activity occurs with all forms of cholestasis, synthesis is the hepatocytes adjacent to the biliary particularly with obstructive jaundice. The response canaliculi35. ALP may be significantly increased with of the liver to any form of biliary tree obstruction is obstructed bile ducts, cirrhosis, liver cancer, and also with to synthesize more ALP. The main site of new enzyme bone disease. BILIRUBIN – TOTAL OR DIRECT Bilirubin is eliminated by the liver, hence any increase In hepatobiliary diseases of various causes, bilirubin in bilirubin levels are suggestive of an underlying liver uptake, storage, and excretion are impaired to varying disorder. Unconjugated bilirubin may be increased degrees. Thus, both conjugated and unconjugated when there is an unusual amount of RBC destruction bilirubin is retained and a wide range of abnormal serum (hemolysis) or when the liver is unable to process concentrations of each form of bilirubin may be observed. bilirubin (i.e., with liver diseases such as cirrhosis or Both conjugated and unconjugated bilirubin are increased inherited problems). Conversely, conjugated bilirubin can in hepatocellular diseases such as hepatitis and space- increase when the liver is able to process bilirubin but is occupying lesions of the liver, and obstructive lesions not able to pass the conjugated bilirubin to the bile for such as carcinoma of the head of the pancreas, common removal; when this happens, the cause is often acute bile duct, or ampulla of Vater38. hepatitis or blockage of the bile ducts37. GAMMA-GLUTAMYL TRANSFERASE (GGT) GGT enzyme is present in low levels, but when the liver is injured, the GGT level can rise. GGT is usually the first liver enzyme to rise in the blood when any of the bile ducts that carry bile from the liver to the intestines become obstructed, for example, by tumors or stones. Both GGT and ALP are increased in liver diseases, but only ALP will be increased with diseases affecting bone tissue38. Therefore, GGT can be used as a follow up to an elevated ALP to help determine if the high ALP result is due to liver or bone disease. 18 LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES LifeLabs DIABETES LABORATORY TESTING SERVICES 18
HEPATITIS C TESTING Hepatitis C (HCV) is a virus that causes an infection of used to screen for past exposure and current infection. It the liver that is characterized by liver inflammation and detects the presence of antibodies to the virus, indicating damage. Hepatitis C tests are a group of tests that are exposure to HCV. LifeLabs also offers the HCV RNA tests performed to detect, diagnose, and monitor the treatment detect the presence of viral RNA, the amount of viral RNA of a hepatitis C viral infection. An HCV antibody test is present, or determine the specific subtype of the virus. HEPATITIS B TESTING Hepatitis B is an infection of the liver caused by the can identify a person who has a current active infection, hepatitis B virus (HBV). LifeLabs Hepatitis B blood tests was exposed to HBV in the past, or has immunity as a detect antigens, the antibodies that are produced in result of vaccination. Active HBV infection can present response to an infection, or detect or evaluate the genetic as jaundice, unexplained elevated levels of alanine material (DNA) of the virus. The pattern of test results aminotransferase (ALT), fever and / or fatigue. Other tests which may be considered in liver function evaluation include Prothrombin Time (PT) & INR, Iron studies, Copper RBC and Total Protein. LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES 19
Detecting Autoimmune Liver Disease ANTI-MITOCHONDRIAL ANTIBODY (AMA) The anti-mitochondrial antibody (AMA) test may be inflammation and scarring of the bile ducts inside the liver. ordered to help diagnose primary biliary cholangitis It is a slow-progressing disease that causes worsening liver (PBC). PBC is a chronic autoimmune disorder that causes destruction and blockage of the bile flow. ANTINUCLEAR ANTIBODY (ANA) Antinuclear antibodies (ANA) are a group of autoantibodies autoimmune disorder or rule out other conditions with produced by a person’s immune system when it fails to similar signs and symptoms. The ANA test may be positive adequately distinguish between the body’s own healthy with several autoimmune disorders, and is often included cells and those of an antigen. The ANA test detects in the work up of suspected auto-immune hepatitis. It can these autoantibodies in the blood. The ANA test is one lead to liver cirrhosis and, in some cases, to liver failure. of the primary tests for helping to diagnose a suspected SMOOTH MUSCLE ANTIBODIES (SMA) Smooth muscle antibodies (SMA) are autoantibodies, proteins antibody titers. The smooth muscle (SMA) or actin antibody produced by the body’s immune system that recognize test is primarily ordered along with antinuclear antibodies and attack its own actin, a protein found in smooth muscle (ANA) and liver kidney microsomal type 1 (LKM-1) antibodies and other tissues, especially the liver. This test detects and to help diagnose autoimmune hepatitis and to differentiate measures the amount (titer) of SMA (or antibody against between the two major types of autoimmune hepatitis, type 1 actin) in the blood. The production of smooth muscle or actin and type 2. They are usually ordered when a person presents antibodies is strongly associated with autoimmune hepatitis. with symptoms such as fatigue and jaundice along with It may also sometimes be seen in other forms of liver disease, abnormal findings on routine liver tests such as aspartate such as primary biliary cholangitis (PBC), but usually at lower aminotransferase (AST) and/or bilirubin. 20 LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
Management of GI Malignancies While a confirmed diagnosis of gastrointestinal cancers such as colon, anal, rectal, liver and gall-bladder, among others require several diagnostic staging procedures, some laboratory tests can help in initial diagnosis as well as subsequent management of GI malignancies. FECAL IMMUNOCHEMICAL TEST (FIT) The FIT tests stool samples for the presence of occult blood which may be suggestive of colon cancer. In Canada, BC Cancer Agency and Cancer Care Ontario colon cancer screening guidelines recommend the FIT test for periodic screening of individuals over 5039. Fecal immunochemical testing (FIT) has evolved as the preferred occult blood test for colorectal cancer screening due to the lack of specificity and sensitivity of guaiac-based methods. FIT specifically detects the presence of human hemoglobin, eliminating the need for dietary and medication restrictions. CARCINOEMBRYONIC ANTIGEN (CEA) CEA is ordered primarily to monitor cancer treatment, including response to therapy and recurrence as an indicator of the amount of cancer or size of tumor present (tumor burden) and to assist in cancer staging. CEA is occasionally used as follow up to a positive screening test for cancer, to compare whether the level falls to normal (indicating that the cancer was all likely removed) after treatment for the cancer. CANCER ANTIGEN 19-9 Cancer antigen 19-9 (CA 19-9) is a protein that exists on the surface of certain cancer cells. CA 19-9 t is shed by the tumor cells and can be detected by blood tests, as is hence a useful tumor marker to follow the course of cancer. CA 19-9 is elevated in about 70% to 95% of people with advanced pancreatic cancer, however, may also be elevated in other cancers such as gallbladder and bile duct cancers, colorectal cancers, gastric cancers and liver cancer, among others40. LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES 21
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References 1, 2, 3- Chronic Diarrhea: Diagnosis and Management Schiller, Lawrence R. et al. Clinical Gastroenterology and Hepatology , Volume 15 , Issue 2 , 182 - 193.e3 4. Guandalini et al. Diarrhea Work up, Pediatrics & General medicine, eMedicine, July 02, 2018 5. Bartlett, J. (2013 August 26). 5 Important Developments in C difficile Management, Medscape Multispecialty. http://www.medscape.com/viewarticle/809238 6. Thyroid Tests, National Endocrine and Metabolic Diseases Information Service. Available at http://endocrine.niddk.nih.gov/pubs/thyroidtests/index.aspx 7, 8- Ferritin. Medscape Drugs and Diseases - http://emedicine.medscape.com/article/2085454-overview 9. Teitel, A. 2013 February 11. C-reactive protein, MedlinePlus Medical Encyclopedia http://www.nlm.nih.gov/medlineplus/ency/article/003356 10. Subclinical hyperthyroidism By K Burman, Endocrinology Advisor, 2017, 2013 ©Decision Support in Medicine, LLC 11,12,13,17,18 - Row et al. IBD Work up, Drugs & Diseases, Gastroenterology, eMedicine, Oct 18, 2017 15, 16- Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition Arasaradnam RP, et al. Gut 2018;0:1–20. doi:10.1136/gutjnl-2017-315909 19 – Mitsuyama et al. Antibody Markers in the Diagnosis of IBD World J Gastroenterol. 2016 Jan 21; 22(3): 1304–1310. doi: 10.3748/wjg.v22.i3.1304 21. Rendi et al. Crohn’s Disease Pathology - https://emedicine.medscape.com/article/1986158-overview 22, 23 - National Institute of Health. 2014. MedlinePlus: Malabsorption, available at: https://www.nlm.nih.gov/medlineplus/ency/article/000299.htm. 24. Bertholf, R. (2014). Proteins and Albumin. Medscape Multispecialty, Lab Med. 2014;45(1):e25-e41. 25,26, Screening and Diagnosis of Celiac Disease, a summary from NASPGHAN, WGO and ACG guidelines, Canadian Celiac Association Professional Advisory Council, 25 May 2016 27,28 Goebel et al. Celiac Disease (Sprue), Drugs & Diseases, Gastroenterology, eMedicine, Oct 10, 2018 29. Lee et al. A review of Vitamin D deficiency in pediatric patients. J Pediatr Pharmacol Ther. 2013 Oct-Dec; 18(4): 277–291. doi: [10.5863/1551-6776-18.4.277] 30. Shashidhar et al. Malnutrition, Pediatrics and General medicine, eMedicine, July 19, 2017 31. ACG and CAG Clinical Guideline: Management of Dyspepsia, Am J Gastroenterol advance online publication, 20 June 2017; doi: 10.1038/ajg.2017.154 32, 33 Devuni et al. Esophagitis, Drugs & Diseases, Gastroenterology, eMedicine, Apr 27, 2017 34, 35, 38- Mayo Clinic Rochester 2018 Interpretive Handbook March 01, 2018 37. (August 26, 2015). Jaundice. MedlinePlus (U.S. National Library of Medicine). Available at https://www.nlm.nih.gov/medlineplus/jaundice.html 38. (Jan 2016) American Liver Foundation. Liver Function Tests. Available at http://www.liverfoundation.org/abouttheliver/info/liverfunctiontests 39. Cancer Care Ontario and BC Cancer Agency, Guidelines and Resources Colon Cancer Screening 40. American Cancer Society (5 April 2016 revised). Tests for Pancreatic Cancer. Available online at http://www.cancer.org/cancer/pancreaticcancer/detailedguide/pancreatic-cancer-diagnosis LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES 23
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