LACTOSE INTOLERANCE

A CONFERENCE REPORT

Group 3 ² 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 from insufficient levels of enterocyte lactase, which hydrolyzes ingested lactose to glucose and galactose

results

LACTOSE INTOLERANCE VS. LACTASE DEFICIENCY
A

diagnosis of lactase deficiency is made when the amount of lactase in the intestine is reduced.

A

diagnosis of 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. This is the most common type.

Primary-

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
y

Primary Lactose Intolerance
y
y

genetic lactose maldigestion

Hypolactasia y (adult-type) lactase deficiency y lactase non-persistence y begins at the ages of two to three years
y

Secondary Lactose Intolerance
gastrectomy, celiac disease, intestinal inflammation y occur at any age- common in infancy
y

CLASSIFICATION« CONT·D
y

Congenital Lactose Intolerance
y y y y y

selectively adult 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
UDPglucose-4epimerase

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 Young subject Normal gastric emptying Normal small intestine transit No GI surgery Intake with meal

Large dose Elderly subject Rapid gastric emptying Fast small intestine transit Previous gastric or small intestinal surgery 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

Positive for LI
Strict lactosefree diet Symptoms unrelieved

Complete resolution of symptoms Recurrence after subsequent introduction of dairy food

Further evaluation for other GI disorder

SPECIFIC TESTS
DIRECT Enzyme Assay Quantitation of small bowel lactase activity Intestinal Biopsy INDIRECT Hydrogen Breath Test Lactose Tolerance Tests
Blood Glucose Test 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:
Gives definitive diagnosis o Secondary causes of lactase deficiency (e.g. sprue) can be detected
o 

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:
Use of specialized procedures not always available o Most invasive o Used for research purposes only
o

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:
Long, boring test - 3 ² 8 hours o Results cannot determine whether a person will be symptomatic if lesser quantities of lactose is consumed
o 

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

LACTOSE HYDROGEN BREATH TEST
Preparation
‡ Procedure is scheduled at least 10 days after last dose of antibiotics ‡ Discontinue laxative use 1 day prior to procedure ‡ Low residue, Low fat diet 24 hours before procedure ‡ 8-12 hours fasting prior to procedure ‡ No smoking or strenuous exercise and sleeping 30 minutes before procedure ‡ Avoid alcohol consumption, and smoking 48 hours before test

Initial Procedure

‡ Measure baseline breath hydrogen ‡ Ingestion of lactose solution² 2 g/kg BW ‡ Classic 25 to 50 g lactose (equivalent to 32 oz of milk) ‡ Physiologic: 12 g lactose (equivalent to 8 oz milk)

Sample Collection and Analysis

‡ Serial 10-15 min samples taken for 3 to 8 hours after ingestion ‡ H2 concentration determined by gas chromatography

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 y Sensitivity 76 %
y 

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:
y y

Extremely accurate Needs just one blood sample ² 40 minutes after lactose ingestion

Disadvantages:
y

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 ² 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
y

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

y

y

GOLDEN STANDARD DIAGNOSIS FOR LACTOSE INTOLERANCE
Used to increase accuracy of diagnosis and avoid false positive test result  combination of the three diagnostic indicators: 

Hydrogen breath test o Blood Glucose Test o Urinary Galactose o Development of GI symptoms
o 

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:
from Cebu

54 year old woman

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 ² 15 months ago (+) osteoporosis: advised to increase her dietary calcium intake, average milk consumption: 3 cups (24oz) per day ² last 6 months

CASE PRESENTATION
Physical STOOL:

Examination: normal

negative for occult blood SIGMOIDOSCOPY: normal

FLEXIBLE

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

CASE PRESENTATION
Laboratory

Exams:

serum - 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 ² 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
y

DIETARY CHANGES
± REDUCTION OF LACTOSE IN THE DIET

y

LACTASE ENZYME ADAPTATION - INGESTION OF ANY MILK CONTAINING FOODS DURING
MEAL

y

y

CALCIUM AND VITAMIN D SUPPLEMENTS THE SAME MANAGEMENT AS IN GALACTOSEMIA

y

SIMILARITY OF TREATMENTS BETWEEN LACTOSE INTOLERANCE AND GALACTOSEMIA
y

LACTOSE IS A DISACCHARIDE THAT CONSISTS OF A MOLECULE OF -GALACTOSE ATTACHED BY A (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.

y

y

THE END. Thank You for Listening!