Lactose Intolerance a2 Grp 3

LACTOSE INTOLERANCEA 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.

REPORTER: BUNDALIAN, EDER B.

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

WHAT IS LACTOSE INTOLERANCE?

most common carbohydrate maldigestion syndrome

results from insufficient levels of enterocyte lactase, which hydrolyzes ingested lactose to glucose and galactose

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.

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 Intolerancegenetic lactose maldigestionHypolactasia (adult-type) lactase deficiency lactase non-persistencebegins at the ages of two to three years

Secondary Lactose Intolerancegastrectomy, celiac disease, intestinal

inflammationoccur at any age- common in infancy

CLASSIFICATION… CONT’D

Congenital Lactose Intoleranceselectively adult type lactase enzyme synthesis reduceddominant allelesautosomal recessive traitmutation on chromosome 2- shutdown in lactase

production

DIGESTION, ABSORPTION AND UTILIZATION OF LACTOSE


UDP-Glucose

UDP-glucose-4-epimerase

galactosyltransferase



REPORTER: BROWN, SHEENA MAY B.

PATHOPHYSIOLOGY of Lactose Intolerance

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

REPORTER: BURGOS, NIKKI ANNE C.

Clinical Manifestation of Lactose Intolerance

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

Small doseYoung subject

Normal gastric emptyingNormal small intestine

transitNo GI surgery

Intake with mealTOLERANCE

Large doseElderly subject

Rapid gastric emptyingFast small intestine transitPrevious gastric or small

intestinal surgeryLactose consumed alone

INTOLERANCE

Primary AdultLactase Deficiency

Figure 1. Characteristics of different presentations of lactase deficiency

MOLECULAR PERSPECTIVELactase 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.


The galactose 1-phosphate is then transferred to uridylic acid (UMP) in a reversible reaction by galactose 1-phosphate uridyltransferase:


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.



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.

REPORTER: BUMALAY, MARIVIC O.

Diagnosis of Lactose Intolerance

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

Quantitation of small bowel lactase activity

Intestinal Biopsy

Hydrogen Breath Test

Lactose Tolerance TestsBlood Glucose TestLactose-Ethanol Load Test

Stool Acidity TestUrinary 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 availableo Most invasiveo 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 doseo After 6 hours, sensitivity is increased by 40-60%

Advantage:o A convenient, non-invasive, cost-effective, and

reliable testo Efficacy:

Preferred over Lactose Tolerance Test Test Sensitivity: 90% (Powell, 2000)

Disadvantages:o Long, boring test - 3 – 8 hourso 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

LACTOSE HYDROGEN BREATH 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 testo Blood Glucose Testo Urinary Galactoseo 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 DIAGNOSIS1. 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.

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Lactose Intolerance a2 Grp 3