LIFELABS GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES

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LIFELABS GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
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.
LIFELABS GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
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
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
LIFELABS GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
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
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.

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LIFELABS GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
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
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
LIFELABS GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
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
LIFELABS GASTROINTESTINAL LABORATORY DIAGNOSTIC 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
LIFELABS GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
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
22 LifeLabs GASTROINTESTINAL LABORATORY DIAGNOSTIC SERVICES
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
CORPORATE OFFICES
LifeLabs
3680 Gilmore Way
Burnaby, BC
V5G 4V8

LifeLabs
100 International Blvd
Toronto, ON
M9W 6J6

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175 Galaxy Blvd., Suite 105
Toronto, ON
M9W 0C9

                              www.LifeLabs.com
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