Lactose Intolerance a2 Grp 3
-
Upload
kristian-cada -
Category
Documents
-
view
719 -
download
1
Transcript of 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
DIGESTION, ABSORPTION AND UTILIZATION OF LACTOSE
UDP-Glucose
UDP-glucose-4-epimerase
galactosyltransferase
DIGESTION, ABSORPTION AND UTILIZATION OF LACTOSE
DIGESTION, ABSORPTION AND UTILIZATION OF LACTOSE
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.
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.
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.
Thank You for Listening!