Carbohydrates Student PDF

Carbohydrates  Introduction Three general types of compounds provide chemical energy to our cells Lipids=Fats Amino acids = Proteins Carbohydrates= Sugars, starches Primary source of energy for brain, erythrocytes, retinal cells Brain has no glucose reserve...

Carbohydrates  Introduction Three general types of compounds provide chemical energy to our cells Lipids=Fats Amino acids = Proteins Carbohydrates= Sugars, starches Primary source of energy for brain, erythrocytes, retinal cells Brain has no glucose reserve capability Stored primarily as liver and muscle glycogen 2  Description and Classification of Carbohydrates Contain C, H and O –ose = sugar Classification Number of sugar units The size of the base carbon chain Location of the CO functional group Stereochemistry of compound  Description and Classification of Carbohydrates, 2 Classification based on: Size of base carbon chain Triose-3carbons Tetrose-4 Pentose-5 (DNA) Hexose-6 (Glucose) Location of CO functional group Aldose: terminal functional group; aldehyde group Ketose: carbonyl group in middle; linked to two other carbons; ketone group  Number of Sugar Units Monosaccharides-single sugar unit Can contain trioses, tetroses, pentoses, and hexoses Examples: glucose, fructose, and galactose Most simple-cannot be reduced Disaccharides: two sugar units Examples: maltose, lactose and sucrose (table sugar) Oligosaccharides: 3-10 sugar units Polysaccharides: >10 sugar units Complex carbohydrates Examples: starch, glycogen and cellulose  Chemical Properties of Carbohydrates Reducing carbohydrates To reduce, carbohydrate must have ketone or aldehyde groups All monosaccharides/many disaccharides=reducing agents Ex: glucose, maltose, fructose, lactose, galactose Nonreducing carbohydrates Do not have ketone/aldehyde group and will NOT reduce Ex: sucrose-table sugar Sucrase hydrolyzes sucrose to glucose Carbohydrates Metabolism Begins in mouth Salivary amylase cuts up polysaccharides into smaller sugars. Monosaccharides are absorbed by gut and transported to liver Glucose is only carbohydrate directly used for energy or stored as glycogen Once glucose enters cell, shunted into 1 of 3 metabolic pathways Converted to glycogen and stored in liver Converted to keto-acids, amino acids, and proteins and stored in muscle Converted to fats and stored in adiposeMajor targets organs of tissue insulin: Liver Muscle Ultimate goal Adipose tissue Metabolized to CO and H O  Glucose Breakdown Glycolysis  The conversion of glucose and other hexoses into lactate or pyruvate Breakdown of glucose for energy production Glycogenesis  The conversion of glucose to glycogen Usually in liver & muscle Excess glucose is converted and stored as glycogen High concentrations of glycogen in liver and skeletal muscle Glycogen is a quickly accessible storage form of8 glucose  Glucose Formation Glycogenolysis The breakdown of glycogen to form glucose Occurs when plasma glucose is decreased Occurs quickly if additional glucose is needed Controlled by hormones & enzymes Gluconeogenesis  The formation of NEW glucose from non- carbohydrate sources: amino acids, glycerol & fatty acids Happens in starvation and weight loss Occurs mainly in the liver Protects the body- especially the brain When Glucose is Created or stored  Carbohydrate Metabolism Lipogenesis Conversion of carbohydrates to fatty acids Fat is another energy storage form Not as quickly accessible as glycogen Lipolysis Decomposition of fat 11  Regulation of Plasma Glucose If plasma glucose is : Glycogenolysis (Brief Fast) The liver releases glucose into the plasma Quick response due to enzyme glucose-6- phosphatase Gluconeogenesis and lipolysis (Longer fast) Longer response If plasma glucose is  : Glycogenesis Liver stores glucose as glycogen  Insulin Only hormone to decrease glucose level Synthesized in the Beta cells of the Islets of Langerhans in the pancreas Secretion controlled by: Increased blood glucose level Facilitates glucose entry into cells Cell membranes need insulin to be present for glucose to enter Promotes glycolysis Speeds up utilization of glucose in cells 13  Glucagon Primary hormone responsible for increasing glucose Referred to as a hyperglycemic agent Synthesized in alpha cells of the islets of Langerhans Action Increases plasma glucose concentration Increases glycogenolysis in liver & gluconeogenesis 14  Epinephrine & Cortisol Epinephrine Glucocorticoids: Cortisol Origin: adrenal cortex Origin: adrenal medulla Stimuli Stimuli Anterior pituitary’s Physical or emotional ACTH stress. Action: Adrenal tumors Increases blood Action: glucose Immediate release of Promotes glucose gluconeogenesis Inhibits insulin from breakdown of secretion & release proteins Promotes lipolysis Inhibits the entry of  Growth Hormone (GH) and Adrenocorticotropic Hormone (ACTH) Origin: anterior pituitary gland Stimuli Decreased glucose stimulates its release Increased glucose inhibits its release Action: Increases plasma glucose levels Inhibits insulin secretion Inhibits entry of glucose into muscle cells ACTH stimulates the adrenal cortex to release cortisol and increases plasma glucose levels by converting liver glycogen to glucose and promoting gluconeogenesis. 16  Thyroxine & Somatostatin Thyroxine Somatostatin Origin: thyroid gland Origin: Delta cells of Stimuli the islets of Pituitary gland’s TSH Langerhans in the pancreas Action Increases Action: absorption of Inhibits insulin glucose from intestines Promotes conversion of liver  Hyperglycemia Increase in plasma glucose levels due to hormone imbalance Reference Range Increased plasma glucose: > 100 mg / dl Glucose reference range: 74 - 100 mg / dl  Physiologic Abnormalities of Diabetes Hyperglycemia Increase blood glucose Diet, fat metabolism, protein destruction/wasting Ketosis From fat metabolism, ketonemia, ketonuria Hyperlipidemia Increase blood lipids from faulty glucose metabolism. Decreased blood pH - metabolic acidosis Urine abnormalities Glycosuria – glucose present Polyuria - increase in urine volume Loss of electrolytes - washing out with the urine 19  Diabetes in the US 2003: 18.2 Million or ~6.3% 2007: 23.6M or ~7.8%. 5.7 M undiagnosed 2011: 25.8 M or ~8.3%: 7M undiagnosed 2014: 29.1M or ~9.3%: 8.1M undiagnosed 2017: 30.3M or ~9.4% 7.2 M undiagnosed 2019: 34.2M or ~10.5% 7.3M undiagnosed 7th leading cause of death listed on 2015 death certificates 2018-National Direct medical costs: $237 billion Indirect medical costs: $90 billion Total medical cost: $327 billion  Diabetes WHO and ADA classifies diabetes into the following: Type 1 diabetes Type 2 diabetes Other (secondary diabetes) Gestational diabetes mellitus (GDM)  Type 1 Diabetes Insulin Dependent Diabetes Mellitus ( IDDM ) 10-20% of diabetes cases Demographics Non-Hispanic Whites/ Non-Hispanic Blacks Children & adolescents Pathology Disease triggered by viral illness or environmental factors that destroys beta cells in pancreas. Absolute Insulin deficiency Defect in secretion, production or action of Autoimmune destruction of islet beta – cells in 22 pancreas Auto-antibodies may be present  Type 1 Diabetes CLASSIC TRIAD Polyphagia (increased food uptake) Polydipsia (thirst) Polyuria ( increased urine production) Other symptoms Mental confusion Rapid weight loss Hyperventilation Diabetic ketoacidosis 23  Diabetic Ketoacidosis Leads to  in the blood pH: metabolic acidosis Blood levels of ketone acids rise Urine dipstick positive for ketones/acetone Blood pH  below 7.3 inducing hyperventilation Signs: Dehydration Anorexia Nausea /vomiting Polyuria Tachypnea Coma  Type 1 Diabetes - Laboratory Findings Hyperglycemia- plasma levels > 100 mg/dL Glucosuria- plasma glucose > 180 mg / dl (renal threshold is exceeded)  insulin  glucagon which causes Gluconeogenesis Lipolysis (breakdown of fat produces ketones) Ketoacidosis  blood pH ( acidosis ) 25  Na + …  K + …  HCO3 _ and TCO2  anion gap and osmolality Development of Diabetic Ketoacidosis  Type 2 Diabetes (NIDDM) Non – Insulin Dependent Diabetes Mellitus (NIDDM) Most common form of diabetes Demographics Adult onset Patients usually > 20 years old American Indians and non-Hispanic blacks 27  Type 2 Diabetes Develops gradually Disorder in insulin resistance and relative deficiency of insulin Plasma glucose is unable to enter cells Contributory factors Obesity Lack of exercise Diet Genetics Drugs, such as diuretics, psychoactive 28 drugs Increases in hormones that  Type 2 Diabetes - Laboratory Findings Hyperglycemia Glucosuria Insulin is present Glucagon is not elevated No lipolysis and no ketoacidosis Absence of ketones Excess glucose is converted to triglycerides Increased plasma triglycerides Normal /  Na + / K+  BUN & Creatinine  renal function 29  osmolality due to high glucose levels Major Complications of Diabetes  Secondary Diabetes Genetic defects of beta cell function Genetic defects in insulin action Genetic syndromes Pancreatic disease Endocrinopathies Drug or chemical induced 31  Gestational Diabetes Glucose intolerance associated with pregnancy’s hormonal and metabolic changes Glucose returns to normal after pregnancy,  risk for diabetes later on in life Infants are at increased risk for: Respiratory complications Hypoglycemia after birth 32 Generally increased birth  Diabetes Screening Beginning at age 45 every 3 years Testing earlier if patient is overweight and meets criteria: Physically inactive Family history High-risk minority population History of GDM High blood pressure Low HDL Elevated triglycerides Women with PCOS 33  Established Criteria for Diagnosing Diabetes: ADA and WHO 1. Symptoms of diabetes plus random plasma glucose concentration > 200 mg/dL Random is defined as any time of day 2. Fasting plasma glucose > 126 mg/dL Fasting is defined as no caloric intake for at least 8 hours 3. 2-Hour glucose > 200 mg/dL during an oral glucose tolerance test 4. A HgbA1C > 6.5%, if confirmed on repeat measurement Two criteria required for diagnosis!  Prediabetes or Impaired Glucose Tolerance Fasting glucose between 100- 125mg/dl 2 Hr GTT results between 140-199 mg/dl HgbA1C results between 5.7-6.4% According to 2022 CDC Diabetes Report: 96 million people have prediabetes 35 15-30% will develop type 2 diabetes  GDM Testing Moms screened between 24-28 weeks Test with 2-hour GTT Perform in am following 8 hour fast 75gram glucose load given to patient Measurements taken at fasting, 1 hour and 2 hours Diagnosis: Fasting > 92mg/dl One hour > 180mg/dl Two hour > 153mg/dl 36  Hypoglycemia Plasma glucose level falls below 60 mg/dL Glucagon is released when plasma glucose is between 65-70 mg /dL Epinephrine, cortisol, and growth hormone released from adrenal gland to increase glucose metabolism and inhibit insulin Treatment Varies with cause. Small, frequent meals, (5-6/day) Low in carbohydrates, high in protein  Hypoglycemia Symptoms Lab Findings Increased hunger  plasma glucose Sweating Insulinoma  glucose Nausea  insulin level Vomiting Dizziness Whipple’s Triad Shaking Low plasma glucose Blurring of speech Symptoms of hypoglycemia and sight Alleviation of symptoms Mental confusion with glucose ingestion  Galactosemia Resulting from : Galactose-1-phosphate uridyltransferase deficiency Enzyme that converts galactose to glucose, patients cannot change either galactose or lactose into glucose Effects: Failure to thrive Can lead to mental retardation, cataracts, death Check children for reducing  Glucose - Laboratory testing Considerations Reference values depend on: Type of specimen Venous/capillary Serum, plasma, whole blood How was it collected? Fasting, random, after a meal Reference glucose value (serum/plasma) 74-100 mg/dL *Required BOC 40 Reference Range  Glucose - Specimen Collection Serum Plasma Whole blood Point-of-care Results are 10-15% lower than plasma/serum Dilution by cells 41 Glucose - Other Specimen Types CSF specimens Analyzed ASAP Glucose level is 60-70% of pts current blood level. CSF glucose in Fasting (non-diabetic) @ 40- 70 mg/dL Decreased CSF glucose values suggestive of bacterial meningitis 24-hour urine A small amount of glucose is lost in the urine 42 daily Usually < 500mg/24 hr  Glucose - Laboratory testing, 2 Glucose preservation Perform testing < 1 hour after collection Separate plasma from cells < 1 hour Cells continue to utilize glucose at a rate up to 10 mg/dL per hour. Refrigeration slows the process. Collect blood in gray top tube Additive: sodium fluoride inhibits glycolysis Anticoagulant: potassium oxalate Test Methods: Enzymatic: 43 Glucose Oxidase or Hexokinase  Fasting Glucose Levels Fasting blood sugar (FBS) Most frequently ordered “screening” test for glucose metabolism Fasting values > 126 mg/dL indicative of diabetes FBS should be repeated on another day to confirm diagnosis Borderline diabetes may have a normal FBS & may need a challenge test to 44 demonstrate abnormality  Glucose Tolerance Test (GTT) Purpose – diagnose hyperglycemia / diabetes and evaluate patients with symptoms of hypoglycemia Phlebotomist Responsibilities: Confirm patient has been fasting and draw fasting (baseline) sample Administer glucose solution Schedule / collect timed blood specimens Patients must understand the importance of adhering to the scheduled blood collection times for accurate results Maintain consistency of tube type and specimen type Venipuncture vs. dermal puncture Monitor patient When collecting GTT specimens, observe the patient for symptoms of hyperglycemia or hypoglycemia  l a i dnarp t sop rh 2 t seT ecnare l oT esocu lG l arO ruoH- 2 Patient has FBS drawn Ingests a 75 gram load of glucose 2 hours later- draw glucose Glucose level should have returned to fasting/normal levels If glucose > 200 mg/dL on the test, a fasting or random glucose level, should be performed on a subsequent day to diagnose with diabetes Oral glucose tolerance test (GTT) Glycosylated Hemoglobin/Hemoglobin Glucose molecule attaches A1C nonenzymatically to the hemoglobin molecule Advantages: ◦ “Time average glucose” ◦ Not subject to temporary variability due to diet and exercise ◦ Does not require fasting Influenced by: ◦ Conditions that affect the life span of the RBC, such as sickle cell disease and hemolytic diseases  Hemoglobin A1C Specimen : EDTA whole blood Doesn’t need to be fasting Methods: Enzymatic Immunoassay, mass spectrometry, chromatography HPLC and electrophoresis Hemoglobin A1C reference range: 4.0 – 5.6 % *Normal Range for the ASCP BOC 6.5% Confirmed by repeat measurement For every 1% change in HbgA1C-35mg/dl change in HbA1C Target of 30mg/g is considered diagnostic If detected, should be confirmed if positive on 2 of 3 determinations over a 3- to 6-month period Specimen types: Random or spot-more convenient for patient Timed collections (24-hour or 4-hour) Normal urine dipsticks are insensitive to detect low concentrations of urine albumin Test with a microalbumin reagent strip  Lactose Tolerance Testing Lactose - disaccharide Lactose malabsorption or lack of enzyme (lactase) needed to breakdown lactose Often results in diarrhea, cramping, and gas Lab evaluation: Give patient lactose load Hydrogen Breath test Collect breath samples in bags at timed intervals Increased hydrogen levels are diagnostic Lactose Tolerance Test Similar to glucose tolerance test Timed specimens for glucose 54 Must be a rise of >30mg/dl of glucose over baseline to rule out lactase deficiency  Glucose and HbA1C Decision Levels – Fasting Glucose HbA1C: Monitoring Known Diabetics Normal < = 99 Acceptable Control mg/dL < = 7.0% Prediabetes 100 - 125 HbA1C for Diagnosis of Diabetes > = 126 Diabetes Mellitus mg/dL Normal = 6.5 Diagnosed Diabetes Cases Nationally 56