UNIT 04 Carbohydrates - Cagayan State University PDF

Republic of the Philippines Cagayan State University Andrews Campus, Tuguegarao City, 3500 Cagayan  (078) 844-7631; http://www.csu.edu.ph COLLEGE OF ALLIED HEA...

Republic of the Philippines Cagayan State University Andrews Campus, Tuguegarao City, 3500 Cagayan  (078) 844-7631; http://www.csu.edu.ph COLLEGE OF ALLIED HEALTH SCIENCES Department of Public Health UNIT 04: CARBOHYDRATES The size of the base carbon chain OUTLINE a) Trioses- monosaccharides with three carbon atoms I. General Description of Ex: Glyceraldehyde Carbohydrates b) Tetroses- - monosaccharides with four  Classification of Carbohydrates carbon atoms  Fate of Glucose Ex: b-erythrose  Regulation of Carbohydrate c) Pentoses- monosaccharides with five carbon Metabolism atoms Ex: fructose II. Clinical Significance d) Hexoses- - monosaccharides with six carbon  Hyperglycemia atoms  Hypoglycemia Ex: glucose The location of the CO function group III. Laboratory Methods a) Aldose- monosaccharides with aldehyde in their structure I. GENERAL DESCRIPTION OF CARBOHYDRATES b) Ketose- carbon structure has ketone group CARBOHYDRATES  Are compounds containing C, H, and O The number of sugar units  Contain C=O and –OH functional groups  Some are reducing substances a) Monosaccharides - glucose, fructose, and Glucose, maltose, fructose, lactose, galactose and galactose b) Disaccharides - maltose, lactose, and sucrose  Glucose - primary source of energy for c) Oligosaccharides - raffinose and stachyose humans d) Polysaccharides - starch and glycogen The stereochemistry of the compound CLASSIFICATION OF CARBOHYDRATES a) D series (prefix D-) – most common in nature  Classification based on 4 properties: - Main energy source a) the size of the base carbon chain - Form is cyclic or linear b) the location of the CO function group - Can rotate clockwise order c) the number of sugar units b) L series (prefix L-)- less frequent d) the stereochemistry of the compound - Rotation is counter clockwise order - Form is alpha and beta forms N. Catral CC-Lec PH 4-A  Republic of the Philippines Cagayan State University Andrews Campus, Tuguegarao City, 3500 Cagayan  (078) 844-7631; http://www.csu.edu.ph COLLEGE OF ALLIED HEALTH SCIENCES Department of Public Health FATE OF GLUCOSE THE EMBDEN-MEYERHOF PATHWAY FOR ANAEROBIC GLYCOLYSIS Most of our ingested carbohydrates are polymers, such as starch and glycogen. ↓ Salivary amylase and pancreatic amylase are responsible for the digestion of these polymers to dextrins and disaccharides, which are further hydrolyzed to monosaccharide by maltase Sucrose- sucrose to glucose and fructose Lactase- lactose to glucose and galactose ↓ Monosaccharides are absorbed by the gut and transported to the liver by the hepatic portal venous blood supply. ↓ Three possible metabolic pathways 1. First step of all pathways- Glucose is converted to glucose-6-phosphate using the high-energy molecule, ATP (enzyme hexokinase) 2. Embden-Meyerhof pathway 3. Hexose Monophosphate Shunt 4. Glycogenesis  Glycolysis- conversion of glucose to pyruvate and lactate Anaerobic glycolysis- because oxygen is not a concern N. Catral CC-Lec PH 4-A  Republic of the Philippines Cagayan State University Andrews Campus, Tuguegarao City, 3500 Cagayan  (078) 844-7631; http://www.csu.edu.ph COLLEGE OF ALLIED HEALTH SCIENCES Department of Public Health PATHWAYS IN GLUCOSE METABOLISM GLUCAGON “Lysis”- breakdown  “Hyperglycemic agent” “Genesis”-synthesis or formation  Is synthesized by the α-cells of islets of Langerhans in the pancreas  Is released during stress and fasting states  Regulates glucose by increasing glycogenolysis and gluconeogenesis REGULATION OF CARBOHYDRATE METABOLISM  The two main hormones that control blood REGULATION OF CARBOHYDRATE glucose are insulin and glucagon. METABOLISM Insulin and glucagon are produced by pancreas  Other hormones that affect CHO metabolism: INCREASE GLUCOSE INSULIN  “Hypoglycemic agent” 1. Epinephrine – inhibits insulin  Is synthesized by the β-cells of islets of secretion, increases glycogenolysis Langerhans in the pancreas and lipolysis  Normally released when glucose levels are - Produced by adrenal medulla high  Is responsible for the entry of glucose into the 2. Glucocorticoids (cortisol) – decreases cell regulates glucose by increasing intestinal entry into the cell, increases glycogenesis, lipogenesis, and glycolysis and gluconeogenesis and lipolysis inhibiting glycogenolysis - Cortisol is produced by adrenal cortex 3. Growth hormone - decreases the entry of glucose into the cells and increases glycogenolysis N. Catral CC-Lec PH 4-A  Republic of the Philippines Cagayan State University Andrews Campus, Tuguegarao City, 3500 Cagayan  (078) 844-7631; http://www.csu.edu.ph COLLEGE OF ALLIED HEALTH SCIENCES Department of Public Health - its release from the pituitary gland  Old Classification is stimulated by decreased o National Diabetes Group, 1979 glucose levels and inhibited by  Type 1, insulin-dependent increased glucose diabetes mellitus (IDDM)  Type 2, non-insulin- 4. Adrenocorticotropic hormone – its dependent diabetes mellitus release is stimulated by decrease (NIDDM) levels of cortisol. o International Expert Committee on - ACTH stimulates the adrenal the Diagnosis and Classification of cortex to release cortisol and Diabetes Mellitus, 1995 increases plasma glucose by  Type 1 and Type 2 glycogenolysis and  New Categories of Diabetes (ADA/WHO): gluconeogenesis. o Type 1 diabetes - Produced by pituitary gland o Type 2 diabetes o Other specific types of diabetes 5. Thyroxine - by increasing o Gestational diabetes mellitus (GDM) glycogenolysis, gluconeogenesis, and intestinal absorption of glucose. - Also known as T4 TYPE 1 DIABETES (Tetraiodothyronine)  Insulin Dependent DM, Juvenile Onset DM, 6. Somastotatin - by the inhibition of Brittle Diabetes, Ketosis-Prone Diabetes insulin, glucagon, growth hormone,  Result of cellular-mediated autoimmune and other endocrine hormone destruction of the β-cells of the pancreas, - Produced by the delta cells of causing an absolute deficiency of insulin pancreas secretion  Antibodies associated with type 1: o Islet cell autoantibodies (ICA) o Insulin autoantibodies (IAA) II. CLINICAL SIGNIFICANCE o Glutamic acid decarboxylase A. Hyperglycemia- Elevated blood glucose level autoantibodies (GADA) B. Hypoglycemia- - Low blood glucose level o Tyrosine phosphatase IA-2 and IA-2B autoantibodies o Zinc transporter 8 antibody (ZnT8)  Constitutes only 5% to 10% of all cases of DIABETES MELLITUS diabetes  Risk factors  A group of metabolic diseases characterized o genetic, autoimmune, environmental by hyperglycemia resulting from defects in insulin secretion, insulin action, or both N. Catral CC-Lec PH 4-A  Republic of the Philippines Cagayan State University Andrews Campus, Tuguegarao City, 3500 Cagayan  (078) 844-7631; http://www.csu.edu.ph COLLEGE OF ALLIED HEALTH SCIENCES Department of Public Health  Characteristics: o Adult onset, milder symptoms than o abrupt onset, insulin dependence, in type 1, ketoacidosis is rare and ketosis tendency  Risk factors  Signs and symptoms: o Genetic, obesity, sedentary lifestyle, o Polydipsia, polyphagia, polyuria, race/ethnicity, PCOS, dyslipidemia, rapid weight loss, hyperventilation, hypertension mental confusion, and possible loss  Complications: Macrovascular and of consciousness microvascular  Complications  Uses hypoglycemic agents to regulate blood o microvascular problems sugar level (metformin)  nephropathy  neuropathy OTHER SPECIFIC TYPES OF DIABETES  retinopathy; increased incidence of heart disease) o Associated with secondary conditions  Management: Parenteral administration of o Genetic defects of β-cell function or insulin insulin action  Latent Autoimmune Diabetes of Adulthood o Pancreatic disease or injury (LADA) / Type 1a o Endocrine disease o a slower autoimmune β-cell Such as Cushing’s Syndrome- high destruction that can occur in adults cortisol production  Idiopathic Type 1 diabetes Pheochromocytome- catecholamine o has no known etiology secreting tumor ( increased o is strongly inherited production in epinephrine and o does not have β-cell autoimmunity norepinephrine) o requires insulin replacement - Epinephrine can reduce blood sugar levels Acromegaly- high growth hormone Hyperthyroidism- high T4 o Drug or chemical induced receptor TYPE 2 DIABETES abnormalities  Non-Insulin Dependent DM, Maturity Onset Dilantin and Pentamidine - Both are or Adult Type DM, Stable Diabetes, Ketosis- inducers of –cell dysfunction Resistant Diabetes, Receptor-Deficient DM  Dilantin- is an anti-epileptic  A result of an individual’s resistance to drug insulin with an insulin secretory defect  Pentamidine- anti-fungal drug (relative insulin deficiency) Thiazides- anti-diuretics  Constitutes the majority of the diabetes cases - Impair insulin action dysfunction  Characteristics: o Other genetic syndromes Down syndrome- extra chromosome particularly number 21 N. Catral CC-Lec PH 4-A  Republic of the Philippines Cagayan State University Andrews Campus, Tuguegarao City, 3500 Cagayan  (078) 844-7631; http://www.csu.edu.ph COLLEGE OF ALLIED HEALTH SCIENCES Department of Public Health GESTATIONAL DIABETES MELLITUS CRITERIA FOR TESTING PREDIABETES (GDM) AND DIABETES  Any degree of glucose intolerance with onset ADA recommendations or first recognition during the second or third  All adults beginning at the age of 45 years trimester of pregnancy should be tested for diabetes every 3 years  Risks for infants using either the hemoglobin A1c (HbA1c), respiratory distress syndrome fasting plasma glucose, or a 2-hour 75 g hypocalcemia- if fully developed ang oral glucose tolerance test (OGTT) unless parathyroid gland affected ang the individual has been diagnosed with production nang hormone diabetes - parathyroid hormone increases  It should be done in individuals who display blood calcium level overweight tendencies (BMI ≥ 25 kg/m2) and hyperbilirubinemia have additional risk factors.  Screening should be performed between 24 and 28 weeks of gestation LAB FINDINGS IN HYPERGLYCEMIA: 1. Decreased or absent insulin 2. Increased glucose in plasma and urine 3. Increased urine specific gravity- cause of presence of glucose in urine sample 4. Ketones in serum and urine (ketonemia and ketonuria) 5. Decreased blood and urine pH (acidosis)- because of formation of ketones 6. Electrolyte imbalance- sodium is low ; potassium is high. - Sodium ion and urine sample will CRITERIA FOR THE TESTING FOR TYPE 2 diluted leading to a decrease DM IN ASYMPTOMATIC CHILDREN: concentration of sodium in the urine and blood  Testing at the age of 10 years or at the onset of puberty, with follow up testing every 2 years  Overweight plus any two of the following risk factors: N. Catral CC-Lec PH 4-A  Republic of the Philippines Cagayan State University Andrews Campus, Tuguegarao City, 3500 Cagayan  (078) 844-7631; http://www.csu.edu.ph COLLEGE OF ALLIED HEALTH SCIENCES Department of Public Health o 2-hour OGTT using a 75 g glucose load (Note: 150 grams of CHO/day for 3 days) CRITERIA FOR THE TESTING AND DIAGNOSIS OF GDM TWO-STEP APPROACH  Initial measurement of plasma glucose at 1- hour post load (50g glucose load)  Plasma glucose value of ≥ 140 NOTE: mg/dL – a need to perform 3-hour OGTT using 100g glucose load 1. HbA1C ≥ 6. 5% using a method that is NGSP  Fasting: > 95 mg/dL (5.3 mmol/L) certified and standardized to the DCCT  1-hour plasma glucose: ≥ 180 mg/dL (10.0 assay a mmol/L)  HbA1C also known as glycosylated  2-hour plasma glucose: ≥ 155 mg/dL (8.6 hemoglobin; a test that measures long term mmol/L) glucose control for the previous two to three  3-hour plasma glucose: ≥ 140 mg/dL (7.8 months. mmol/L) 2. Fasting plasma glucose also known as fasting blood sugar 3. Random plasma glucose also known as HYPOGLYCEMIA random blood sugar  65 to 70 mg/dL (3.6 to 3.9 mmol/L) - glucagon and other glycemic factors are CRITERIA FOR THE TESTING AND released DIAGNOSIS OF GDM  50 to 55 mg/dL (2.8 to 3.1 mmol/L) - observable symptoms of hypoglycemia  International Association of the Diabetes appear and Pregnancy Study Groups  Classification: o All nondiabetic pregnant women should o Postabsorptive (fasting)- associated be screened for GDM at 24 to 28 weeks with insulinoma of gestation N. Catral CC-Lec PH 4-A  Republic of the Philippines Cagayan State University Andrews Campus, Tuguegarao City, 3500 Cagayan  (078) 844-7631; http://www.csu.edu.ph COLLEGE OF ALLIED HEALTH SCIENCES Department of Public Health  Insulinoma- tumor in the beta cells of pancreatic islets GSD ENZYME DEFICIENT o Postprandial (reactive)- occurs 4 (Tissue Affected) hours after meals Ia (VON GIERKE) Glucose-6-phosphatase  Whipple triad Ib Glucose-6-phosphatase o Hypoglycemic symptoms translocase o Plasma glucose is low (< 50 mg/dL) II (POMPE) 1,4-glucosidase o Symptoms are relieved by IIIa (CORI De brancher (liver and administration of glucose or glucagon FORBES) muscle) IIIb De brancher (liver) IV (ANDERSEN) Amylopectinase/ glycogen  Symptoms: branching enzyme o increased hunger, sweating, nausea and V (MC ARDLE) Muscle phosphorylase vomiting, dizziness, nervousness and VI (HERS) Liver phosphorylase shaking, blurring of sight, and mental VII (TARUI) Phosphofructokinase confusion VIII Adenyl kinase  Laboratory findings: IXa Phosphorylase kinase o decreased plasma glucose levels (liver) o extremely elevated insulin levels in patients IXb Phosphorylase (liver and muscle) with pancreatic β–cell tumors (insulinoma) X Cyclic AMP-dependent kinase XI (FANCONI Glycogen transporter-2 GENETIC DEFECTS IN CHO METABOLISM BICKEL) 0 Glycogen synthase GLYCOGEN STORAGE DISEASES GALACTOSEMIA  Are the result of the deficiency of a specific enzyme that causes an alternation of  a cause of failure to thrive syndrome in glycogen metabolism infants, diarrhea, and vomiting  Von Gierke disease (glucose-6-phosphatase)  resulting in increased levels of galactose in is the most common form plasma o Management thru liver  Enzymes: transplantation o Galactose-1-phosphate  The liver forms (types I, III, IV, VI, IX, AND uridyltransferase (most common) 0) are marked by hepatomegaly and o Galactokinase hypoglycemia. o Uridine diphosphate galactose-4-  The muscle forms (types V and VII) are epimerase characterized by musclecramps, exercise  Lab test : Erythrocyte galactose-1-phosphate intolerance, fatigue, and weakness. uridyltransferase activity N. Catral CC-Lec PH 4-A  Republic of the Philippines Cagayan State University Andrews Campus, Tuguegarao City, 3500 Cagayan  (078) 844-7631; http://www.csu.edu.ph COLLEGE OF ALLIED HEALTH SCIENCES Department of Public Health  Lab findings:  FBS/FPG values have a diurnal variation o hypoglycemia, hyperbilirubinemia, and (FPG is higher in the morning than in the galactose accumulation in the blood, afternoon). tissue, and urine following milk  No to hemolysis ingestion  Essential fructosuria- o Fructokinase deficiency TESTS FOR GLUCOSE MEASUREMENT:  Hereditary fructose intolerance o Defect in fructose-1,6-biphosphate 1. Fasting Blood Sugar (FBS) or Fasting Blood aldolase B activity Glucose  Fructose-1,6-biphosphatase deficiency screening test for DM o defect in fructose-1,6-biphosphatase  taken after at least 8 hours of fasting III. LABORATORY METHODS GLUCOSE MEASUREMENTS SPECIMEN CONSIDERATIONS 2. Random Blood Sugar (RBS)  Glucose concentration in WB is 11% lower 3. 2-Hour Post Prandial Blood Sugar (PPBS) than in plasma. 4. Glucose Tolerance Test (GTT)  Glucose is metabolized at room temperature at a rate of 7 mg/dL/hour (0.4 mmol/L/ hour);  Oral Glucose Tolerance Test (OGTT) at 4° C, glucose decreases by approximately o 75g glucose load, plasma glucose is 2 mg/dL/hour (0.1 mmol/L/ hour). drawn 2 hours later  A serum specimen should be separated from o Not recommended for routine use the cells within 30 minutes (from Henry’s o Only the fasting and 2-hour sample be 21st ed). measured, except when the patient is o if longer than 30 minutes, add sodium pregnant fluoride o Adult dose is 75g; children 1.75g/kg of  If WB is refrigerated, 2 mg of sodium glucose (maximum dose is 75g) fluoride per milliliter of WB prevents glycolysis for up to 48 hours.  FBG should be obtained in the morning after an approximately 8- to 10-hour fast (not longer than 16 hours). N. Catral CC-Lec PH 4-A  Republic of the Philippines Cagayan State University Andrews Campus, Tuguegarao City, 3500 Cagayan  (078) 844-7631; http://www.csu.edu.ph COLLEGE OF ALLIED HEALTH SCIENCES Department of Public Health Glucose  Alkaline Copper Tartrate > Heat Cuprous ions a. Folin Wu Method Cuprous ions → Phosphomolybdate Phosphomolybdic Acid or Phosphomolybdenum Blue b.. Nelson Somogyi Method Cuprous ions → Arsenomolybdate Arsenomolybdic Acid or 5.Glycosylated Hemoglobin/Hemoglobin A1c Arsenomolybdenum Blue (HbA1c) c. Neocuproine Method (2,9-Dimethyl-1,10-  “Glycated hemoglobin” Phenantroline Hydrochloride)  Is a more reliable method of monitoring Cuprous ions + Neocuproine → Cuprous- long-term diabetes control over the previous Neocuproine Complex (Yellow or Yellow 2-3 month period Orange)  For every 1% increase in hba1c, there is a 35 mg/dl (2 mmol/l)change in plasma glucose d. Benedict’s Method (Modification of Folin-  SPECIMEN: Whole blood in EDTA Wu)  HbA1c results:  It is used for the detection and o Normal: 4%-6% (Henry’s 21st ed) quantitation of reducing substances in o Increased risk for diabetes: 5.7%-6.4% body fluids like body and urine. o Diabetes: ≥ 6.5%  It uses citrate or tartrate as stabilizing agent. METHODS FOR GLUCOSE Copper Sulfate (blue) + glucose + heat DETERMINATION → brick red precipitate 2. Alkaline Ferric Reduction Method (Hagedorn Jensen) I. CHEMICAL METHODS It involves reduction of a yellow ferricyanide to a colorless A. OXIDATION REDUCTION METHOD ferrocyanide by glucose 1. Alkaline Copper Reduction Method Inverse Colorimetry  Principle: Reduction of cupric ions to cuprous ions forming cuprous oxide in hot alkaline solution by glucose. N. Catral CC-Lec PH 4-A  Republic of the Philippines Cagayan State University Andrews Campus, Tuguegarao City, 3500 Cagayan  (078) 844-7631; http://www.csu.edu.ph COLLEGE OF ALLIED HEALTH SCIENCES Department of Public Health B. CONDENSATION METHOD  Ortho-toluidine (Dubowski Method) Glacial HAC Glucose + Aromatic Amines > Heat Glycosylamine + Schiff’s Base (green- colored end product) Chromogens = 3-methyl-2-benzothiazolinone hydrazone and N,N-dimethylaniline II. ENZYMATIC METHODS B. Polarographic Glucose Oxidase  Three enzyme systems are commonly used to  measures the rate of oxygen measure glucose: consumption which is proportional o glucose dehydrogenase to glucose concentration o glucose oxidase o hexokinase  Acts on glucose but not on other sugars and not on other reducing substances GLUCOSE DEHYDROGENASE METHOD MUTAROTASE  (3-(4,5-dimethylthiazol-2-yl)- 2,5 diphenyltetrazolium bromide HEXOKINASE METHOD  is the most specific glucose method; reference method  the rate of disappearance of NADPH is measured spectrophotometrically (340 nm) GLUCOSE OXIDASE METHOD A. Colorimetric Glucose Oxidase Method (coupling enzyme)  Saifer Gernstenfield method KETONES N. Catral CC-Lec PH 4-A  Republic of the Philippines Cagayan State University Andrews Campus, Tuguegarao City, 3500 Cagayan  (078) 844-7631; http://www.csu.edu.ph COLLEGE OF ALLIED HEALTH SCIENCES Department of Public Health  Ketonemia - accumulation of ketones in blood  Ketonuria - accumulation of ketones in urine  Are produced by the liver through metabolism of fatty acids acetone (2%), acetoacetic acid (20%), and 3-β- hydroxybutyric acid (78%)  Low level of ketone bodies is present in the body at all times  Levels increase: diabetes mellitus, starvation/fasting, high-fat diets, prolonged vomiting, and glycogen storage disease  Specimen: fresh serum or urine  Gerhardt’s test - ferric chloride reacts with acetoacetic acid to produce a red color  Sodium nitroprusside test – sodium nitroprusside reacts with acetoacetic acid to produce a purple color  Enzymatic test – using 3-hydroxybutyrate dehydrogenase ; detects 3-β-hydroxybutyric acid or acetoacetic acid MICROALBUMINURIA  Persistent albuminuria – urinary albumin to creatinine ratio of 30-299 mg/g creatinine in two out of three urine collections over a 3- to 6-month period  Useful to assist in diagnosis at an early stage and before the development of proteinuria  Random spot collection for albumin- creatinine ratio, 24-hour collection, timed 4- hour overnight collection N. Catral CC-Lec PH 4-A