Carbohydrates PDF - Compiled Notes in Clinical Chemistry

CARBOHYDRATES socdh A. CLASSIFICATION OF CARBOHYDRATES twi 1. Number of sugar units - polysaccharides, disaccharides, monosaccharides noutisus th lonih 2. Number of carbons trioses, tetroses, pentoses, hexoses 3. Location of the CO fu...

CARBOHYDRATES socdh A. CLASSIFICATION OF CARBOHYDRATES twi 1. Number of sugar units - polysaccharides, disaccharides, monosaccharides noutisus th lonih 2. Number of carbons trioses, tetroses, pentoses, hexoses 3. Location of the CO functional group - aldoses and ketoses aldo hero ½ Stereochemistry of the compound - D and L enantiomers. oN 0of CH2QH 025 HO- HO--H -OH HO- HO- -H HO-H CH2OH CH2OH CH2OH CH2OH CH2OH Light CO)CH2OH D-glyceraldehyde D-Erythrose L-Ribose D-Glucose D-Galactose tnoy Hayog Aldose  COMPILED NOTES IN CLINICAL CHEMISTRY RODERICK D. BALCE 15 B. GENERAL PROPERTIES Form glycosidic bonds with other carbohydrates and with noncarbohydrates Modify proteins and their function by glycosylation Some are reducing substances (sugars with hemiacetal group) tept ieng C. HORMONAL REGULATION OF GLUCOSE METABOLISM LSIED VIOLES - cellube phake (. Glucose Lactate Fatty acid Aroollss Ghyolysis Pyruyate Acetyl CoA TCA cycle Glycogen Glucose-6-PO, fatty Ruds mitachodra Aniad acid$ Effect on PG Modes of action Hormone Source Insulin PROHOIES 14,3,4 ; IMMIbiS $,47 Glucagon PAALLEAS ALPHA CEUS DULTA LELLS Somotostatin AOLENAL loflEy PIbMOTES 644 Cortisol Mioous POHOTES 544 Epinephrine MOOENAI PiLOMOIES CORTISOL SECRENOM CAIMULMES S &6 ACTH INHIBNS CUAL CIASVLIN AULAGORIST) 1H1(L610 PROMOTES INIBUMALAGRAPION OF GWGE,14S Thyroxine HoH0L0606 To GH CINSLIN ANTAGOUS) hPL PLACEAVA Cpcut in pgunb) D. DISORDERS OF GLUCOSE METABOLISM 1. HYPOGLYCEMIC DISORDERS a. Types Post-absorptive/Fasting- occurs after 10 hours without food; secondary to hyperinsulinism (insulinoma), hormonal deficiencies, genetic disorders, autoimmunity or drug-induced Post-prandial/Alimentary/Reactive - occurs usually within 4 hours after eating a meal b. Symptoms - tgin ho ngont at fba g0-gwalal Atoronic Myiob Sete Neurogenic -Tremulolisness, palpitations, anxiety, diaphoresis, hunger, and paresthesias nblelt Shan ic rcativd - Neuroglycopenic - dizziness, tingling, blurred vision, behavioral changes, seizure, and coma Wlain L40mglolL C. Diagnosis relief Whipple's triad of hypoglycemia: symptoms of hypoglycemia, low plasma glucose level, and of symptoms with correction of hypoglycemia a Tmlal doniny Pstrg) Diagnostic Criteria for Insulinoma: thingy ton cauline( Hagiddl -7 Jo ngidil Change in glucose level e.25 mg/dL (under controlled fasting condition) coincident with: 1 insulin (241.7 pmol/L) T proinsulin (≥5 pmol/L) 1 c-peptide (20.2 nmol/L) Lttort bodies J B-hydroxybutyrate ($2.7 mmol/L) peijod Proinsulin 2. DIABETES MELLITUS a. ADA Classification I. Type 1 -1; cell destruction eading to absolute insulin deficiency a) immune-mediated (Auloiamine) II. Type - insulin resistance with progressive insulin deficiency III. Other types a) genetic defects of B cell function The b) genetic defects in insulin action ~c) diseases of the exocrine pancregs (pancreatitis, pancreatectomy, pancreatic cancer/neoplasia, 202 cystic fibrosis, hemochromatosis, fibrocalculouspancreatopathy d) endocrinopathies e) drug- or chemical-induced f0 infections uncommon forms of immune-mediated diabetes h) other genetic syndromes IV. Gestational - glucose intolerance during pregnancy that disappears post-partum but may convert to(type 2 DMjin 30-40% of cases within 10 years; due to metabolic and hormonal changes  COMPILED NOTES IN CLINICAL CHEMISTRY RODERICK D. BALCE 16 b. Characteristics of Type and Type Diabetes Mellitus Type Type Frequency Lip°lo 790% LF 7H) Age of onset CHILOHOOD/JUENILE ADULTHCOO Risk factors Autoimmunity Vauhsabs Family history of DM, high-risk minority population (e.g., African American, Latino, Native Genetic predisposition -> Hut-015/ American, Asian American, and Pacific Islander) (hlEliC) PILA PCOS, GDM or delivering a baby weighing(>9 lb, pre-diabetes (IFG, IGT, HbA1c 5.7-6.4%) CINSUN GLLAME) Obesity or overweight tendencies (BMI 2134)1m) habitually physically inactive, hypertension (BP 2 140/40), dyslipidemia (HDL 535 myldl history of CVD LHEIACoLIL STHDRIME Therapy Insulin injection Lifestyle changes, oral hypoglycemic agents;Gu1Foo may require insulin. Acute Diabetic ketoacidosis l1 (hlo Hytorg Hyperglycemic hyperosmolar non-ketotic coma complications /ynt teid) Copposk biuliions) Lab Findings Symptoms Polyuria, polydipsia, polyphagia (3Ps); pruritus, poor wound healing (sPs) Long-term Microvascular complications: BILPHLDPAIY CLELLINORTHY.ADAUMTHY Complications Macrovascular complications: CAD, CVA o/Hwpandri Intashon, Cun -shoke E. TESTS AND DIAGNOSTIC CRITERIA FOR DM Screening: All adults 245 years old ; individuals with 21 risk factor EVElY VAL US RPG/CPG FPG 2-hr PG (OGTT) Important conjunction with Fasting for at least CHO intake 2 Is0 aldan Foh Specimen considerations SYMPTONG OF DM gars (no food or 3 CAYS PLYOL drink except water) Fasting _1-14hs NON-PISTINIG MOS PEETELOEO Standard load Bo sAl.Ts ofhgOw Normal 100 -115 phldit CIFh) 40 -191 midl C(Gt) 57-6.4% Pre-diabetes 2 4.5% mnldl 7ill maldL F. TESTS AND DIAGNOSTIC CRITERIA FOR GDM All nondiabetic pregnant women should be screened for GDM at 24-28 weeks of gestation. One-Step Method Two-Step Method Step 1: 50 g C-h bLIC Step 2: 100 a ( G-h 0LIT) Glucose load 75g -blM) FPG: If the 1 -h PG ≥140 mg/dL, FPG: 205 mhldl Diagnostic Any 1 h PG: 2180 muldl criteria 1-h PG: 2190 proceed to Step 2. 2 h PG: 21s modt 2-h PG: -155 bot oliutmoe*Some use the 2130 or 135 mg/dL 140 mndl toff which have creater sensitivity _3-h PG G. TESTS FOR MONITORING GLYCEMIC CONTROL 1. WHOLE BLOOD GLUCOSE most commonly analyzed using POCT devices at home or at the patient's bedside; 3-4 times daily for type 1 DM. patients according to ADA guidelines Pc-poadial:70-150 myidl about 1o -15 % lower than plasma glucose; ADA glycemic goals Pt andral : Lip maldl 2. GLYCATED HEMOGLOBIN/ HbA1c vn Hb A with glucose irreversibly attached to one or both N-terminal valines of the B-chains 2-5 months provides an index of average blood glucose levels over the past unreliable in patients with Poor control: 711% eAG (28.7*A1c) - 46.7 ADA glycemic goal: 419le allbunin pond to lomglaatiuns 3. FRUCTOSAMINE riengats byyosbhed the past 1-3 weeks in cases when HbA1c is unreliable used to assess glycemic control over. has the advantage of using serum samples but is unreliable when serum albumin level is Reference range _165 -185 Jmolll MICROALBUMINURIA early indicator of diabetic nephropathy 10-260 1p-190 mg/24 h, or an persistent albuminuria in two out of three urine collections of ug/min, albumin-creatinine ratio of 10-500 ug/rg or 3.5-30 mg/mmol within a 3- to 6-month period AHD - Autirued  COMPILED NOTES IN CLINICAL CHEMISTRY RODERICK D. BALCE 17 H. METHODS OF GLUCOSE MEASUREMENT 1. SPECIMEN CONSIDERATIONS Use of NaF, or SST to prevent glycolysis. Otherwise, glycolysis will take place at a rate of TmbJUYA (A); 2U,1UhCgrc) b. Effect of dextrose contamination 10%% CONTAMINNION W/ 5% OEXTRUSC wIll 1Pl 1 (SuD m0 ldl) 2. CHEMICAL METHODS (Conmon lahiel Atruhon) Gcplon Gutdul's a. Copper Reduction (non-squike, Siyid to talph recny rolbs) 1) Folin-Wu olbrinttiyCu* + phosphomolybdic acid phosphomolybdénum Loodo - 2) olie in tobe Nelson-Somogyi~ Cu* + arsenomolybdic acid arsenomolybdenum 3) Neocuproine Cu' + neocuproine Cu-neocuproine complex noue cobrlts glucose b. Ferric Reduction Linnru toborn tu) ferricyanjde ferrocyanide duvrny in tolot intasihn C. Condensation wort sprutie glucose + o-toluidine Schiff's base (oyba.shi metsed) 3. ENZYMATIC METHODS Glucose oxidase B-D-glucose + O2 H2O Gluconic acid Detection Methods: Peroxidase-coupled Trinder reaction - subject to many interferences Peroxidase H2O2 + chromogen oxidized chromogen + H2O (4-Aninogheno1 4-amino matipuftel, Polarographic ~ measurement of the degree of O2 consumption using a pO2 (Clark) electrode; requires addition of molybdate and iodide or catalase and ethanol to prevent reformation of O2 Hexokinase b. Hexokinase Glucose + ATP Glucose-6-PO4 + ADP G-6-PD Glucose-6-PO4 + NADP 6-phosphogluconolactone + NADPH reference method; coupling reaction is highly specific effect of hemolyzed/icteric sample _ FALStLY OLC(UASEO Glucose Dehydrogenase TA 440nm C. Glucose Dehydrogenase Glucose NAD Gluconolactone + NADH + H+ Tetrazolium dye may be used to enable colorimetric-spectrophotometric measurement: Diaphorase NADH + tetrazolium dye NAD + formazan blue highly specific for glucose not subject to interference from substances normally found in serum not commonly used except in glucose POCT (glucometer) I. INBORN ERRORS OF CARBOHYDRATE METABOLISM 1. Galactosemia due to a deficiency of one of three enzymes involved in galactose metabolism: galactose-1-phosphate uridy! transferase (GALT), galactokinase (GALK), or uridine diphosphate galactose-4epimerase(GALE) affected children present with mental retardation, failure to thrive, and galactosuria 2. Glycogen Storage Diseases/Glycogenoses a. Hepatic glycogenoses usually manifest with hepatomegaly, hypoglycemia, and growth retardation on Gierke disease - most common; presents with hypoglycemia, lactic acidosis, and hyperuricemia b. Muscle glycogenoses - manifest with exercise intolerance, muscle cramps, fatigue, and weakness GSD Type Enzyme deficient 0 Glycogen synthase la Con Gaitrke) Glucose-6-phosphatase Glucose-6-phosphatase translocase Lysosomal acid alpha glucosidase Illa Cot - for b1s (Hepahe 4 Husule) Glycogen debranching enzyme Illb Glycogen debranching enzyme 2> 202: Andlegun Glycogen branching enzyme MeArdle Phosphorylase Hus Glycogen phosphorylase Phosphofructokinase IDB Phosphorylase kinase Famoni tickcl Glucose transporter 2