LACTOSE INTOLERANCE

Section E-1 Group 7

SOLIS, Ianne Robin SONACO, Angela Baye B. SUAREZ, Jaennes S. SUAYBAGUIO, Carl Angelo M. SUING, Essel Marie L.

Outline
Case Introduction Definition of Lactose Intolerance and Lactase Food Sources of Lactose Normal Digestion and Utilization of Lactose Definition and Differentiation of Lactose and Lactase Deficiency

Distinct Clinical Syndromes of Lactase Deficiency

Characteristic Clinical Manifestations of Lactose Intolerance Laboratory Tests/Procedures to Diagnose Lactose Intolerance Therapy & Treatment for Lactose Intolerance Case Discussion and Application

Case Introduction
SALIENT FEATURES 54 y/o, female Chief complaint: Abdominal distension & bloating after meals Associated w/: flatulence Episodic diarrhea (30mins-4hours after meals) Mild suprapubic cramping & urgency before BM relieved by defecating (-) Nausea/Vomiting (-) Skin rash Past Medical History: (-) DM (-) Prev GI surgery (-) History of foreign travel (-) Radiation exposure (+) Osteoporosis-15months ago - dietary calcium intake (3cups of milk/day) Physical examination: -Unremarkable Stool examination: - (-) for occult blood Flexible sigmoidoscopy - normal

Lab Tests:
Hemoglobin = 15 g/dL (normal = 14-16 g/dL) Hematocrit = 46% (normal = 44-50%) Serum albumin = 4.5 g/dL (normal = 3.8-4.8g/dL) Serum cholesterol = 210 mg/dL (normal = <200 mg/dL) Serum beta-carotene = 35.7 ug/dL (normal = 20-60 ug/dL) Stool ova and parasites = (-) negative giardia and amoeba

Fecal leukocytes = (-) negative

Thyroid stimulating hormone (TSH) = 1mclU/ml (normal = 0.6-4.6 mclU/ml)

Lactose
Lactose (galactosyl-P- 1,4-glucose) in the milk of mammals (including humans) is the major dietary source of galactose. Lactose is hydrolyzed in the intestine by lactase. Galactose produced by hydrolysis of dietary lactose is mostly in the form of the alpha-isomer.

Lactase
Lactase is the enzyme needed to digest Lactose in the intestine, with the absence of Lactase, the Lactose cannot be digested and absorb in the body. And if Lactose cant be digested Lactose Intolerance could happen to a person

Food Sources of Lactose

Milk, 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 potato chips, corn chips, and other processed snacks margarine salad dressings

Digestion of Lactose

Lactose
Stomach
Small Intestines (Brush border of Proximal Jejunum)

Beta-Glycosidase Complex

Beta-Glycosidase Complex
Lactase
Cleaves via Beta 1,4 Glycosidic bond

Glucosyl Ceramidase
Split Glucose and Galactose from Ceramides

Lactose to Glucose and Galactose

Active Secondary Simporter

Glucose and Galacose + SGLT1

Absorption in the intestinal epithelium

GLUT5

Glucose and Galactose + GLUT 2

Exit to the blood capillaries

 Once broken down into the simple form of sugars, they are now readily adsorbed. Glucose and galactose are taken into the enterocyte by cotransport with sodium using the same transporter. Lactase has two activities. It hydrolyzes phlorizin, a disaccharide found in roots and bark of plants of the family Rosaceae and some seaweeds and it also hydrolyzes galactoside or put simply, lactose.

 Lactase hydrolyses (binds water chemically H2O) the linkage. Once lactose is hydrolysed by the interaction of the lactase enzyme, the enzyme then moves onto the next lactose molecule and does the same each time.

 The result of the hydrolysed lactose disaccharide is the formation of glucose and galactose as seen in the image above. These monosaccharides are readily adsorbed by the transport mechanism of the enterocytes in the small intestine.

Transport Mechanism

Lactose Intolerance

Lactose
Stomach (Small Intestine)

Absence of Glycosidase Complex

Goes down to large intestine

Normal flora ferment the lactose to lactate

Producing gases and flatulence

Attracts water to large intestine causing osmotic Diarrhea and bloating

Differences of Lactose Intolerance and Lactase Deficiency

Lactose Intolerance Is usually a disease of adults and is most often associated with an inadequate amount of an enzyme lactase in the small intestines, which is essential to digest lactose. Without enough lactase, there is lactose intolerance Lactase Deficiency Not enough of an enzyme called lactase in the small intestine to digest lactose

Lactoferrin
also known as lactotransferrin Found in milk, saliva, tears, and nasal secretion Human Colostrum has the highest concentration Component of Immune system (antimicrobial) Provide antibacterial activity to infant

3 Distinct Clinical Syndromes of Lactase Deficiency:

Congenital Very rare inborn error of metabolism Autosomal recessive pattern Alactasia Primary, adult lactase deficiency or hypolactasia Most common type Begins to fall after weaning Almost completely lost by late adolescence Also called Late Onset Lactase Deficiency Other type is Developmental Lactase Deficiency

Secondary Disease or damage to the small intestine villous structure or its function e.g. Celiac disease, Cystic Fibrosis, Short gut syndrome (small bowel resection), Parasitic infection, - Gardia, Zollinger Ellison Syndrome, Whipples disease

Clinical Manifestations of Lactose Intolerance:

Meteorism Borborygmi Flatulence Abdominal pain/Colicky pains Dyspepsia Bloating/Fullness Nausea Diarrhea

Diagnostic Tests

Breath Hydrogen Test

After an overnight fast, patient exhales through a breath analyzer Water solution of 50 grams of lactose (32 oz of milk) is then ingested End-expiratory samples are taken at 30-minute intervals and compared with zero-time level

Hydrogen breath >20 ppm above zero-time level Hypolactasia

Oral Lactose Tolerance Test

Ethanol (300 mg/kg) is administered 15 minutes before oral lactose
40 minutes after lactose ingestion, blood sample is taken Blood galactose level of <0.3mmol/L (5mg/dL) Hypolactasia

Lactose-Ethanol Load Test

Ingestion of 50g lactose

Serum glucose is measured in fasting state, then every 30 minutes thereafter 2 hours following lactose ingestion
Blood glucose rise of less than 1.1 mmol/L (20mg/dL) Hypolactasia Blood glucose rise greater than 1.7 mmol/L (30 mg/dL) lactose persistence Blood glucose incremental rise of 1.1 - 1.7 mmol/L inconclusive

Quantitation of Small Bowel Lactase Activity

Tissue sample obtained from distal duodenum by endoscopy or jejuna biopsy Most accurate, but also most invasive method Seldom used clinically to make the diagnosis of lactase deficiency

Therapy
Amount of lactose that can be toleratedvaries from person to persons Complete lactose restriction to confirm all symptoms are indeed related to the Lactose Intolerance Dietary management
Avoiding lactose-containing products Alternative products Lactase supplementation Division into several meal

 Treatment of lactose intolerance should not be aimed at reducing malabsorption but rather at improving digestive symptoms. Reduction of lactose intake rather than exclusion is recommended because long-term effects of lactose restriction may help improve gastrointestinal complaints but can lead to other damages.
Long-term effects of a diet free of dairy products may be a concern as you are significantly decreasing the amount of calcium. Low calcium levels are leading to an increase in fractures and orthopaedic problems.

Age group

Amount of calcium to consume daily, Age group in milligrams (mg) 210 mg 270 mg 500 mg 800 mg 1,300 mg 1,000 mg 1,200 mg

06 months 712 months 13 years 48 years 918 years 1950 years 5170+ years
Recommended calcium intake by age group

Source: Adapted from Dietary Reference Intakes, 2004, Institute of Medicine, National Academy of Sciences.

 To help in planning a high-calcium and low-lactose diet, the table that follows lists some common foods that are good sources of dietary calcium and shows how much lactose they contain.
Vegetables Calcium Content Calcium-fortified orange 308-344 mg juice, 1 cup Sardines, with edible 270 mg bones, 3 oz. Salmon, canned, with 205 mg edible bones, 3 oz. Soymilk, fortified, 1 cup 200 mg Broccoli (raw), 1 cup 90 mg Orange, 1 medium 50 mg Pinto beans, 1/2 cup 40 mg Tuna, canned, 3 oz. 10 mg Lettuce greens, 1/2 cup 10 mg Lactose Content 0 0

0 0 0 0 0 0 0

 Recent research shows that yogurt with active cultures may be a good source of calcium for many people with lactose intolerance, even though it is fairly high in lactose. Evidence shows that the bacterial cultures used to make yogurt produce some of the lactase enzyme required for proper digestion.

SUMMARY Lactose intolerance is the inability or insufficient ability to digest lactose, a sugar found in milk and milk products. Lactose intolerance is caused by a deficiency of the enzyme lactase, which is produced by the cells lining the small intestine. Not all people with lactase deficiency have digestive symptoms, but those who do may have lactose intolerance. Most people with lactose intolerance can tolerate some amount of lactose in their diet. People with lactose intolerance may feel uncomfortable after consuming milk and milk products. Symptoms can include abdominal pain, abdominal bloating, gas, diarrhea, and nausea. The symptoms of lactose intolerance can be managed with dietary changes. Getting enough calcium and vitamin D is a concern for people with lactose intolerance when the intake of milk and milk products is limited. Many foods can provide the calcium and other nutrients the body needs. Milk and milk products are often added to processed foods. Checking the ingredients on food labels is helpful in finding possible sources of lactose in food products.

SALIENT FEATURES 54 y/o, female Chief complaint: Abdominal distension & bloating after meals Associated w/: flatulence Episodic diarrhea (30mins-4hours after meals) Mild suprapubic cramping & urgency before BM relieved by defecating (-) Nausea/Vomiting (-) Skin rash Past Medical History: (-) DM (-) Prev GI surgery (-) History of foreign travel (-) Radiation exposure (+) Osteoporosis-15months ago - dietary calcium intake (3cups of milk/day) Physical examination: -Unremarkable Stool examination: - (-) for occult blood Flexible sigmoidoscopy

Lab Tests:
Hemoglobin = 15 g/dL (normal = 14-16 d/dL) Hematocrit = 46% (normal = 44-50%) Serum albumin = 4.5 g/dL (normal = 3.8-4.8g/dL) Serum cholesterol = 210 mg/dL (normal = <200 mg/dL) Serum beta-carotene = 35.7 ug/dL (normal = 20-60 ug/dL)

Stool ova and parasites = (-) negative giardia and amoeba

Fecal leukocytes = (-) negative Thyroid stimulating hormone (TSH) = 1ulU/ml (normal = 0.6-4.6 ulU/ml)

Sources:
Laboratory Manual and Conference Guide Lecture Guide in Biochemistry, vol. 1 Harpers Illustrated Biochemistry 28th ed Biochemistry 5th ed, Stryer Biochemistry 4th ed, Lehninger Lippincott Biochemistry 3rd ed Medical Biochemistry: Human Metabolism in Health and Disease, 2009