LACTOSE INTOLERANCE

A CONFERENCE REPORT

Group 3 – Section A2

BORRICANO, Jayne Nicholei C.

BRIONES, Ana Leslie M.
BROWN, Sheena May B.
BUENAVENTURA, Arthur R.
BUMALAY, Marivic O.
BUNDALIAN, Eder B.
BURGOS, Nikki Anne C.
OBJECTIVES
 
 The main objective of this paper is to be able to define lactose
intolerance and to understand the mechanisms involved in its progress.
It also emphasizes measures to aid in the diagnosis and proposes ways to
reduce and manage symptoms of lactose intolerance.

Specifically, at the end of the discussion, students are expected to:

(1) identify the food sources of lactose;
(2) understand how the body normally digest and utilize lactose;
(3) define lactose intolerance and to differentiate it from lactase deficiency;
OBJECTIVES
 
(4) enumerate the three distinct clinical syndromes of lactase
deficiency;
(5) differentiate the different types of lactose intolerance;
(6) recognize the different clinical manifestations of lactose intolerance;
(7) determine the laboratory tests or procedures that can be done to
diagnose lactose intolerance; and
(8) discuss the significance of the different procedures used in its
diagnosis as well as the different interventions that can be done.
 Definition of Lactose Intolerance
Lactose Intolerance vs Lactase Deficiency
Food Sources of Lactose
Distinct Clinical Syndromes of Lactase Deficiency
Different Types of Lactose Intolerance
Digestion, Absorption and Utilization of Lactose

REPORTER: BUNDALIAN, EDER B.

WHAT IS LACTOSE INTOLERANCE?

 most common carbohydrate maldigestion syndrome

 resultsfrom insufficient levels of enterocyte lactase,

which hydrolyzes ingested lactose to glucose and
galactose
LACTOSE INTOLERANCE VS. LACTASE
DEFICIENCY

 A diagnosisof lactase deficiency is made when the

amount of lactase in the intestine is reduced.

 A diagnosisof lactose intolerance is made only when

the reduced amount of lactase causes symptoms.
FOOD SOURCES OF LACTOSE

 Milk and milk products

 bread and other baked goods
 waffles, pancakes, biscuits, cookies, and mixes to make them
 processed breakfast foods such as doughnuts, frozen waffles
and pancakes, toaster pastries, and sweet rolls
 processed breakfast cereals
 instant potatoes, soups, and breakfast drinks
 potato chips, corn chips, and other processed snacks
OTHER FOOD SOURCES
 processed meats, such as bacon, sausage, hot
dogs, and lunch meats
 margarine
 salad dressings
 liquid and powdered milk-based meal
replacements
 protein powders and bars
 candies
 non-dairy liquid and powdered coffee creamers
 non-dairy whipped toppings
CLINICAL SYNDROMES OF LACTASE
DEFICIENCY

 Congenital- This is very rare inborn error of

metabolism transmitted in an autosomal recessive
pattern.

 Primary- This is the most common type.

 Secondary - This type is caused by lactase activity in

the small intestines as a result of disease or damage to
the villous structure or its function.
CLASSIFICATION OF LACTOSE
INTOLERANCE
 Primary Lactose Intolerance
 genetic lactose maldigestion
 Hypolactasia
 (adult-type) lactase deficiency
 lactase non-persistence
 begins at the ages of two to three years

 Secondary Lactose Intolerance

 gastrectomy, celiac disease, intestinal
inflammation
 occur at any age- common in infancy
CLASSIFICATION… CONT’D
 Congenital Lactose Intolerance
 selectivelyadult type
 lactase enzyme synthesis reduced
 dominant alleles
 autosomal recessive trait
 mutation on chromosome 2- shutdown in lactase
production
DIGESTION, ABSORPTION AND
UTILIZATION OF LACTOSE
DIGESTION, ABSORPTION AND
UTILIZATION OF LACTOSE
DIGESTION, ABSORPTION AND
UTILIZATION OF LACTOSE

UDP-
glucose-4-
epimerase

UDP-Glucose
galactosyltransferase
DIGESTION, ABSORPTION AND
UTILIZATION OF LACTOSE
PATHOPHYSIOLOGY of Lactose Intolerance

REPORTER: BROWN, SHEENA MAY B.

PATHOPHYSIOLOGY
 Lactose intolerance occurs due to a deficiency of lactase
 Non-hydrolyzed lactose increases the osmotic pressure
in the small intestine, thereby drawing water into the
lumen.
 Stimulation of peristalsis and shortening the transit time

 Lactose in the colon is fermented by the intestinal flora,

producing gas and SCFA
 Bloating, flatulence, cramps, pain, and diarrhea
PATHOPHYSIOLOGY
PATHO… CONT’D
PATHO… CONT’D
PATHO… CONT’D
Clinical Manifestation of Lactose Intolerance

REPORTER: BURGOS, NIKKI ANNE C.

CLINICAL MANIFESTATION OF LACTOSE
INTOLERANCE

 Symptoms of lactose intolerance develop in only a subset of

patients with hypolactasia and include meteorism, borborygmi,
flatulence, distension, dyspepsia, fullness, colicky pains, loose
stools, and diarrhea.

 Gastric emptying time and small intestine transit time.

 Patients with irritable bowel disease are more sensitive to intestinal

distension.

 Gastric surgery can bring on symptoms of previously subclinical

lactase
CLINICAL MANIFESTATION OF LACTOSE
INTOLERANCE

Primary Adult
Lactase Deficiency

Small dose Large dose

Young subject Elderly subject
Normal gastric emptying Rapid gastric emptying
Normal small intestine Fast small intestine transit
transit Previous gastric or small
No GI surgery intestinal surgery
Intake with meal Lactose consumed alone
TOLERANCE INTOLERANCE

Figure 1. Characteristics of different presentations of lactase deficiency

 MOLECULAR PERSPECTIVE
Lactase catalyzes the following reaction in the intestinal lumen:
MOLECULAR PERSPECTIVE

 The monosaccharide products are actively transported from

the lumen and transferred to the portal circulation.

 In the liver, glucose is phosphorylated at C6 and stored as

glycogen. Galactose, however, is phosphorylated at the C1
position.
MOLECULAR PERSPECTIVE

 The galactose 1-phosphate is then transferred to uridylic acid (UMP) in a

reversible reaction by galactose 1-phosphate uridyltransferase:
MOLECULAR PERSPECTIVE

 The interconversion of UDP-galactose and UDP-glucose is catalyzed by

the enzyme UDP-galactose-4-epimerase, historically called
galactowaldenase because it accomplishes a Walden inversion on C4.

 NAD+ acts as a true coenzyme in this reaction.

 The C4 is oxidized to a carbonyl and subsequently reduced back to the

alcohol; the configuration of the hydroxyl group is randomized, and the
NAD+ is regenerated.
MOLECULAR PERSPECTIVE
MOLECULAR PERSPECTIVE

The net of the last 3 reaction is:

D- Galactose + ATP  D-Glucose 1-phosphate + ADP

 The glucose moiety of glucose 1-phosphate can be directly incorporated into

glycogen; alternatively, glucose 1-phosphate can be isomerized to glucose 6-
phosphate.

 Glucose 6-phosphate, in turn, can be metabolized through glycolysis or the

pentose phosphate pathway, or it can be hydrolyzed to free glucose

 The inability to convert galactose to glucose leads to an accumulation of

galactose (galactosemia), which can cause mental retardation and even death.
 Diagnosis of Lactose Intolerance

REPORTER: BUMALAY, MARIVIC O.

FACTORS TO BE CONSIDERED…
 Symptoms of Lactose intolerance are non-specific
 Symptoms are directly related to the amount of lactose
ingested
 Focus on clinical symptoms is subjective

 1st diagnostic test should be a trial of lactose withdrawal

LACTOSE WITHDRAWAL
 SPECIFIC TESTS
DIRECT INDIRECT

Enzyme Assay Hydrogen Breath Test

Quantitation of small Lactose Tolerance

bowel lactase activity Tests
Blood Glucose Test
Intestinal Biopsy Lactose-Ethanol Load Test

Stool Acidity Test

Urinary Galactose
INTESTINAL BIOPSY
 obtained from the 3rd part of duodenum or proximal jejunum
during endoscopy procedure
 Normal:
 Abnormal findings: blunted, thickened villi with flattening of
the cuboid epithelium

 Advantages:
o Gives definitive diagnosis
o Secondary causes of lactase deficiency (e.g. sprue) can be detected

 Disadvantage: Invasive in nature

SMALL INTESTINE TISSUE ASSAY

 Obtained by endoscopy or special capsules that are passed

through the mouth or nose and into the small intestine

 Advantage:
o direct test for lactase deficiency

 Disadvantage:
o Use of specialized procedures not always available
o Most invasive
o Used for research purposes only
HYDROGEN BREATH TEST
 Based on the metabolism of undigested lactose by colonic
bacteria
 Amount of H2 or methane excreted in the breath is
roughly proportional to the degree of lactase deficiency.
However, it is not proportional to the severity of
symptoms
 Normal result: less than 12 ppm over fasting level
 Positive result: more than or equal to 20ppm after 1 hour of oral
lactose dose
o After 6 hours, sensitivity is increased by 40-60%

 Advantage:
o A convenient, non-invasive, cost-effective, and reliable test
o Efficacy:
 Preferred over Lactose Tolerance Test

 Test Sensitivity: 90% (Powell, 2000)

 Disadvantages:
o Long, boring test - 3 – 8 hours
o Results cannot determine whether a person will be symptomatic if
lesser quantities of lactose is consumed

 Factors affecting False Positive result:

 Bacterial overgrowth
 Ingestion of high fiber diet before test
 Intestinal motility disorder

• Factors that increase H2 secretion independent of lactose load

include: sleep deprivation, exercise, use of aspirin, gum, mouthwash
or smoking
 Factors affecting False Negative result:
o Absence of colonic bacteria
 Recurrent antibiotic use
 Increase colonic enema
TEST
BLOOD GLUCOSE TEST
 Oral Lactose Tolerance Test
 Measures glucose serum profile after ingestion of 50 g lactose

 Normal result: rise in BG more than 25mg/100ml

 Positive Result: increase in blood glucose concentration of less

than 1.1 mmol/L or 20 mg/dl above fasting level
 Advantage:
 Simple and easy to do
 Sensitivity 76 %
 Disadvantage:
 Requires collection of multiple samples of blood
 Inconvenient for the patient
 Invasive and indirect

 Factors affecting abnormal results:

 Variable gastric emptying time
 gastric emptying time (false positive result)
 Individual differences in glucose metabolism

 Efficacy:
 False positive result: 20%
 False negative result: 20%
TO CONFIRM POSITIVE RESULT…
 Repeat the test after patient drink an aqueous solution
containing half of carbohydrate dose as glucose and half as
galactose

 Normal: BG should rise at least 20-25 mg/dl from FBS

LACTOSE-ETHANOL LOAD TEST
 Measures blood galactose and a more specific test for lactase activity
 Administration of Ethanol 15 minutes before lactose ingestion
inhibits galactose metabolism
 Often combined with Blood Glucose Test

 Positive result: blood galactose level of less than 0.3 mmol/L

or 5mg/dl
 Advantages:
 Extremely accurate
 Needs just one blood sample – 40 minutes after lactose ingestion

 Disadvantages:
 Needs ethanol (alcohol) ingestion
STOOL ACIDITY TEST
 Required for clinical diagnosis
 Not specific but is a helpful marker for lactose (or CHO)
malabsorption
 Is usually combined with analysis for presence of reducing sugars
(lactose, glucose, galactose, and fructose) in the stool
 Normal: alkaline (7.0 – 8.0)
 Positive result: pH less than 5.6
presence of reducing sugar in stool
 Due to Lactic Acid, a fermentation product of bacterial digestion of
unabsorbed lactose

 Advantage:
 Used in infants and young children
 Disadvantage:
 Results cannot form a definitive diagnosis of Lactose Intolerance

 Normal infant pH is lower compared to older children and

adolescents (5.0-5.5) due to physiologic overload of lactose in
their diet
 Some may have decreased fecal pH but not necessarily
increased CHO excretion in the stool.
 URINE GALACTOSE
 Reliable, quantitative, non-invasive technique for assessing
profiles of whole intestinal lactose activity (Bjarhason et al.
1990)

 Assayed spectrophotomerically using a commercial enzyme

kit

 Positive Result: 3-4 hour urine galactose was less than 20

mg
GOLDEN STANDARD DIAGNOSIS FOR
LACTOSE INTOLERANCE
 Used to increase accuracy of diagnosis and avoid false positive
test result
 combination of the three diagnostic indicators:
o Hydrogen breath test
o Blood Glucose Test
o Urinary Galactose
o Development of GI symptoms

 Confirmatory: 2 out of 3 positive results will indicate

hypolactasia
If maldigestion is confirmed, and sympotms are at least moderate 
diagnosis of Lactose Intolerance
CASE REPORT
CASE PRESENTATION
General Data: 54 year old woman from Cebu

Chief Complaints: Abdominal Distention

and bloating after meals
History of Present Illness:
 With increased flatulence and episodic diarrhea of 1
year’s duration; occur 30 minutes to 4hours after meals;
no aggravating factors and feels best early in the
morning before she eats

 Fasting for 8 hours results in complete relief of all

symptoms

 No nausea or vomiting

 Mild suprapubic cramping and urgency before bowel

movements; discomfort was promptly relieved by
defecating
CASE PRESENTATION
 PMH: (-) diabetes
(-) previous gastrointestinal surgery
(-) foreign travel
(-) skin rash
(-) previous radiation exposure
(+) low back pain: pathological compression
fracture of the lumbar spine – 15 months ago
(+) osteoporosis: advised to increase her
dietary calcium intake, average milk consumption:
3 cups (24oz) per day – last 6 months
CASE PRESENTATION
 Physical Examination: normal

 STOOL: negative for occult blood

 FLEXIBLE SIGMOIDOSCOPY: normal

CASE PRESENTATION
 Laboratory Exams:

Hemoglobin: 15 g/dL (normal, 14-16 g/dL)

Hematocrit: 46% (normal, 44-50 %)

Serum albumin: 4.5 g/dL (normal, 3.8 – 4.8 g/dL)

Serum cholesterol: 210 mg/dL (normal, < 200 mg/dL)

CASE PRESENTATION
 Laboratory Exams:

serum β- carotene: 35.7 µg/dL (normal, 20-60 µg/dL)

stool & ova parasites: negative for Giardia & amoeba

fecal leukocytes: negative

TSH:1 µlU/mL (normal, 0.6 – 4.6 µlU/mL )

DIFFERENTIAL DIAGNOSIS
1. Celiac disease

2. Infectious etiologies such as giardiasis and amoebiasis

3. Inflammatory mucosal disease such as ulcerative colitis or Crohn’s

disease

4. Hypothroidism or hyperthroidism

5. Colonic polyps and cancer

6. Lactose intolerance

7. Hypolactasia
MANAGEMENT OF LACTOSE
INTOLERANCE
 DIETARY CHANGES
– REDUCTION OF LACTOSE IN THE DIET

 LACTASE ENZYME

 ADAPTATION
- INGESTION OF ANY MILK CONTAINING FOODS DURING
MEAL

 CALCIUM AND VITAMIN D SUPPLEMENTS

 THE SAME MANAGEMENT AS IN GALACTOSEMIA

SIMILARITY OF TREATMENTS BETWEEN
LACTOSE INTOLERANCE AND GALACTOSEMIA
 LACTOSE IS A DISACCHARIDE THAT CONSISTS OF A
MOLECULE OF Β-GALACTOSE ATTACHED BY A Β(1-4)
LINKAGE TO GLUCOSE.

 THE MAJOR DIETARY SOURCE OF GALACTOSE IS

LACTOSE.

 TREATMENT OF GALACTOSEMIA REQUIRES REMOVAL OF

GALACTOSE (AND, THEREFORE, LACTOSE) FROM THE
DIET.
 THE END.

Thank You for Listening!