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Lactose Intolerance

Lactose Intolerance
Definition of Lactose Sources of Lactose Absorption of Lactose Definition of Lactose Intolerance - Types of Lactose Intolerance - Clinical Manifestations and their Molecular Basis - Tests and Procedures in Diagnosing Lactose Intolerance - Management

- Galactose
- Metabolic Reactions of

Galactose - Biochemical Effects of Galactosemia - Laboratory Procedures in Diagnosing Galactosemia - Treatment of Galactosemia

To define what is lactose

To identify the sources of lactose

To understand the process of digesting lactose To define what is lactose intolerance To understand the molecular basis behind the

condition To identify the different types of lactose intolerance to galactosemia To know the different tests and procedures in order to diagnose lactose intolerance To identify treatments of lactose intolerance

Identify the metabolic reactions that galactose undergo Identify the reason behind some patients failure to

metabolize galactose and develop galactosemia. Identify the biochemical effects of galactosemia and their corresponding clinical manifestations and their molecular explanation Identify the laboratory procedures that can be done to diagnose galactosemia and their corresponding rationale Discuss the treatment of galactosemia Determine reason why galactosemic patients can tolerate milk and other galactose-containing products once they are adults

What is Lactose?

Sources of Lactose
Lactose is found in milk and all foods made with milk, like: Ice cream Sherbet Cream Butter Cheese Cottage cheese Yogurt

Sources of Lactose
Lactose is added to some boxed, canned, frozen, and other prepared foods, like: Bread Cereal Lunch meats Salad dressings Mixes for cakes, cookies, pancakes, and biscuits Frozen dinners Non-dairy coffee creamer

Absorption of Lactose

Absorption of Lactose

Hydrolysis of Lactose

Absorption of Lactose

Lactose Intolerance
It is the inability to metabolize lactose

because of the deficiency of the enzyme lactase. May lead to diarrhea and intestinal discomfort. Lactase deficiency can occur in several ways: Primary Lactase Deficiency Secondary Lactase Deficiency Congenital Lactase Deficiency

Primary Lactase Deficiency


most human beings, lactase activity begins to fall after weaning, and is almost completely lost by late adolescence, leading to lactose intolerance.

Secondary Lactase Deficiency


in these cases are secondary to intestinal diease or damage to the intestinal villi structure or its function.

Congenital Lactase Deficiency

Congenital or hereditary lactose

intolerance, which is the rarest form, is characterized by an infant's inability to produce lactase.

Lactose Intolerance: The Molecular Basis of Its Clinical Manifestations

The resultant in vivo fermentation produces: - copious amounts of gas (a mixture of hydrogen, carbon dioxide, and methane), - acidic by products, and - other osmotically active molecules

Clinical Manifestations

Bloating or meteorism
Abdominal cramps Decreased stool pH Diarrhea

Laboratory Procedures for Diagnosis of Lactose Intolerance

Initial diagnosis of lactose intolerant would

be made by using trial of lactose withdrawal.

If this does not result in complete relief of

symptoms, the following could be performed:

Hydrogen Breath Test.

standard, simple and non-invasive procedure. Principle: fermentation produces hydrogen that is absorbed in the colon. 15-20% of the hydrogen is exhaled through the lungs. Method: 8 hours fasting, asked to drink lactose load patients breath will be measured for its hydrogen content at regular intervals usually up to 2 hours.


Oral Lactose Tolerance Test. measurement of serum glucose level after the ingestion of a lactose load Principle: lactose is not hydrolysed into galactose and glucose. expected that the serum glucose level of the patient will not rise after lactose load ingestion. Method: 8 hours of fasting patient will be asked to drink a lactose load of 50g. after 2 hour period for blood extraction. The blood will be analysed for serum glucose level.

Stool Acidity Test:

to detect lactose intolerance among infants. Principle: Lactose metabolism by bacteria due to lactase deficiency produces by products, lactic acid, that causes acidity of the stools. Method: patient is instructed to drink lactose rich fluid. Afterwards, the stool is measured for its acidity.


Lactose Ethanol Load Test.

does not only break down to glucose, but also galactose. Some deem that galactose levels more accurately reflect lactase activity Principle: Blood galactose level is measured by inhibiting the liver to metabolize galactose into glucose by ingestion of ethanol prior to intake of lactose load. Method: Ethanol load of 300mg/kg is given to the patient before the intake of lactose load Blood galactose levels are taken


Intestinal Biopsy.

tissue sample from the distal duodenum or jejunum will be obtained through endoscopy for lactase quantification. This laboratory procedure is the most accurate however; this is also the most invasive among the tests mentioned above

Lactose Intolerance Management

No treatment is available for lactose intolerance

Amount of lactose that can be tolerated varies from

person to person, and may change with age

1. Avoidance of Dietary Lactose

Patients should be educated with regards to which

food contain lactose and how much they contain Patients are advised to read labels carefully If unavoidable, divide into several meals combined with solid and dietary fibers

2. Substitution of food to maintain nutrient intake

Alternative products is encouraged


soy milk, almond milk, or rice milk could be used as alternatives

3. Regulation of calcium intake

Large amount of lactose also contain a high

amount of calcium Calcium supplements and food substitution are highly recommended Some of the foods that have high calcium include salmon, shrimp, broccoli, and green leafy vegetables.

4. Use of enzyme substitute

Lactase additives


What is Galactose?

1. A monosaccharide sugar that is less sweet

than glucose. 2. A product from the digestion of the disaccharide, lactose. 3. An epimer of glucose meaning glucose and galactose is mostly equal but except in carbon number 4.

Food sources of Galactose


Plums(raw) Kiwi fruit

Celery Cherries( sweet , raw) Peaches(raw)

Galactose Metabolism

It is formed by the digestion of lactose. The

enzymes of carbohydrate metabolism are specific enough that galactose must be changed to glucose before it can enter glycolysis. It is the fourth carbon epimer of glucose.

Conversion of Galactose to Galactose -1-phosphate

Uses ATP by donating the third phosphate in the

galactose forming galactose-1-phosphate An enzyme called Glucokinase catalyzes this If Glucokinase is diminished or lacking, the process will stop here. (No product of glucoseGalactosemia 2)

Conversion of Glucose-1-phosphate to glucose-6-phosphate

It is catalyzed by the enzyme glucose 1-p-

uridyltransferase Exchange occurs Problems with the enzyme will cause not to proceed to the next step of conversion(No product of glucose-Galactosemia 1)

Glucose 6 phosphate converted to glucose

Glucose can be used for energy

The reversible process of the conversion of UDP galactose to UDP Glucose

UDP glucose originates from glucose metabolism

A cycle

Role of Galactose in Lactose and Other Galactolipid formation

The UDP-galactose goes a different route and

serves as a donor of galactose units to a number of pathways including the synthesis of lactose, glycoproteins, glycolipids, and cosaminoglycans.


A rare genetic metabolism disorder that affects an individual's ability to metabolize the sugar galactose properly.

Different types of galactosemia

1. Galactosemia I (severe)

2. Galactosemia II
3. Galactosemia III

classic galactosemia

is caused by defects in both copies of the gene that

codes for an enzyme called galactose-1-phosphate uridyl transferase (GALT).

Newborns with galactosemia I appear normal at birth,

but begin to develop symptoms after they are given milk for the first time. Symptoms include vomiting, diarrhea, lethargy (sluggishness or fatigue), low blood glucose, jaundice (a yellowing of the skin and eyes), enlarged liver, cataracts.

Signs and symptoms

Upon ingestion of milk vomiting and diarrhea occur

Jaundice and hepatomegaly

Mental retardation

is caused by defects in both copies of the

gene that codes for an enzyme called galactokinase (GALK). Galactosemia II is less harmful than galactosemia I. Babies born with galactosemia II will develop cataracts at an early age unless they are given a galactose-free diet.

Signs and Symptoms



is caused by defects in the gene that codes

for an enzyme called uridyl diphosphogalactose-4-epimerase (GALE). is very rare. Has two types, Type 1 rare Type 2 - benign

Type 2 (Benign Form)

- have high levels of galactose-1-phosphate

that show up on the initial screenings for elevated galactose and galactose-1phosphate. - no symptoms and requires no special diet


Newborn Screening
Galactose-1-Phosphate Uridyltransferase Galactokinase

Molecular Gene Testing Galactosemia Gene Analysis Panel Gene Analysis: Known Mutation Galactose-1-Phosphate Uridyltransferase Phenotyping


Dietary Restrictions

Nourishing infants
Birth 4 months Choosing a formula

4 months 6 months Starting baby foods

6 months 8 months Increasing variety of food

8 months 1 year Cup drinking

Calcium Vitamin D

Why can patients with Galactosemia tolerate milk and other Galactose-containing products once they are adults?

UDP Glucose-Pyrophosphorylase

Similarity in Management of Lactose Intolerance and Galactosemia

Galactosemia is an inborn error of

metabolism which is characterized by the inability of the afflicted individual to metabolize galactose into glucose. Galactose also comes from the hydrolysis of lactose. This being said, part of the management of galactosemia also involves dietary restriction of lactose.

Lactose is composed of glucose and galactose joined

together by a glycosidic bond. Lactose is mainly found in milk and other dairy products. Digestion, absorption and utilization of disaccaharides happen in the small intestine. For lactose: galactose and glucose are transported into the transport protein the sodium-dependent glucose cotransporter 1 (SGLT-1). It is then transported in the portal circulation via another transporter GLUT2

Lactose intolerance is the inability to metabolize

lactose because of the deficiency of the enzyme lactase. It has 3 types: Primary, Secondary and Congenital. - Non Absoprtion of Lactose causes 1. flatulence 2. abdominal cramps 3. bloating or meteorism 4. borborygmi 5. Decreased stool pH 6. diarrhea

- Laboratory procedures include 1. Hydrogen Breath Test 2. Oral Lactose Toelrance Test 3. Stool Acidity Test 4. Lactose Ethanol Load Test 5. Intestinal Biopsy - Management 1. Avoidance of dietary lactose 2. Substitution of food to maintain nutrient intake 3. Regulation of calcium intake 4. Use of enzyme substitution

Galactose is an alternative source of glucose

Galactose sources in food are mainly from dairy

products, but it could also be obtained in vegetables Galactose when broken down to glucose, can undergo GLYCOLYSIS for energy.

* Galactose metabolism is being influenced in the

liver by three enzymes namely: 1. Galactokinase 2. UDP galactose epimerase 3. Galactose 1-phosphate urydyltransferase * Galactosemia is a problem that makes the body unable to use galactose as energy because of lack of enzymes.

Several Lab tests can be done to diagnose


Newborn Screening GALT in the blood GALK in the blood GALT Gene Analysis Panel GALT Gene: Known Mutation GALT Phenotyping

Treatment Dietary Restrictions Supplements Proper monitoring Gene Counseling
Adults can tolerate galactose-containing substances because endogenous production of galactose decreases with age. UDP Glucose Pyrophosphorylase is ynthesized

Case Study
Cherry, a twenty-five year old Asian graduate student in computer science, had been experiencing occasional discomfort after meals. The discomfort reached a new peak last Friday evening about an hour after eating a cheeseburger and a large chocolate milk shake. Cherry spent much of that night in pain. She had abdominal cramps and diarrhea. She went to the clinic the next day. The doctor asked Cherry a number of questions and noted that Cherrys discomfort seemed to be associated with dining out. Cherry told the doctor that on most evenings she cooked for herself, usually preparing traditional Asian cuisine, and that she seldom experienced any discomfort after eating home. Cherry only experienced discomfort after dining out, especially, it seemed, after eating her favourite fast food meal, a double cheese burger and a chocolate shake. When asked if she used very much milk and cheese when preparing meals at home, Cherry told the doctor that she almost never cooked with any dairy product.

Case Study
The doctor recommended to have a test perform to verify the suspicion of having lactose intolerance. At the clinic lab, Cherry was given a lactose rich fluid to drink and had her blood glucose level measured several times over the course of two hours. Later, her doctor informed Cherry that her blood glucose level had not risen after drinking the lactose rich fluid and that was evidence that she was lactose intolerant.

Case Analysis
Cherry was diagnosed by the doctor with lactose

intolerance. The foods that cause her abdominal cramps and diarrhea are double cheese burger and chocolate milkshake. Both the double cheese burger and chocolate milkshake contain significant amount of lactose, thus a good source of lactose. Abdominal cramps happened because of the gas that is produced by the bacteria from the lactose metabolized. Diarrhea occurred because of the presence of osmotically active particles, the undigested lactose which holds water which leads to the said disease.

The doctor instructed Cherry to undergo lactose tolerance

test, to conclude whether she had lactose intolerance or not. The result from the examination was blood glucose did not rise suggesting lactose intolerance.

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