Carbohydrates CHO

Carbohydrates (CHO)

JEANNIE LIMAYO, RMT MPH DTA

BCM 314

Carbohydrates

• Are hydrates of aldehyde or ketone derivatives based on the location of the CO functional grp.

• Monosaccharide, disaccharides, oligosaccharides, polysaccharides- CHOs.

• Glycol aldehyde-is the simpliest CHO• Glucose, maltose, fructose, lactose and

galactose- reducing substances/sugars.

• The presence of a double bond and a negative charge in the enol anion makes glucose an active reducing substance.

• Sucrose- most common non-reducing sugar• Non-reducing sugar do not contain an active

ketone or aldehyde group.• Glucose is the only CHO to be directly used for

energy or stored as glycogen.

Pathways in Glucose Metabolism

• Glycolysis – metabolism of glucose molecule to pyruvate or lactate for production of energy


• Gluconeogenesis- formation of glucose 6-phosphate from noncarboydrate sources


• Glycogenolysis – breakdown of glycogen to glucose for use of energy


• Glycogenesis – conversion of glucose to glycogen for storage


• Lipogenesis – conversion of carbohydrates to fatty acids


• Lipolysis – decomposition of fat

Carbohydrates Classification

• CLASSIFICATION is based on 4 different properties– Size of the base carbon chain– Location of the CO function group– Number of sugar units– Stereochemistry of the compound

CLASSIFICATIONS OF CARBOHYDRATES:

• Based on the number of carbons in the molecule (Generic classifications)– 3 carbons compound (Trioses) e.g. glyceraldehyde– 4 carbons compound (Tetroses)– 5 carbons compound (Pentoses)* (Note: *most

important)– 6 carbons compound (Hexoses)*

CLASSIFICATIONS OF CARBOHYDRATES:

• Based on the location of CO functional group– Hydrates of aldehyde or ketone– Aldose – functional group: aldehyde – Ketose – functional group: ketone

• anomeric carbon – carbon in the functional group

MODELS TO REPRESENT CARBOHYDRATES

• FISHER PROJECTION– Has the aldehyde or ketone at the top of the

drawing– Carbons are numbered starting at the aldehyde or

ketone end– Straight chain or cyclic (linked in hemiacetal form)

MODELS TO REPRESENT CARBOHYDRATES

• HAWORTH PROJECTION– Cyclic form– More representative of the actual structure– Formed when the functional group (ketone or

aldehyde) reacts with an alcohol group on the same sugar to form a ring (hemiacetal ring)

Pancreas

• Functions: an endocrine and exocrine organ in the control of the CHO metabolism

• As an exocrine gland, it produces and secretes an amylase responsible for the breakdown of ingested complex CHO.

• As an endocrine gland, it secrets the hormones; insulin, glucagon and somatostatin from different cells residing in the islets of langerhans in the pancreas.

INSULIN• The primary hormone responsible for the entry of

glucose into the cell.• Synthesized by the beta cells of the islets of

langerhans in the pancreas• It is normally released when glucose levels are high.• It is the only hormone that decreases glucose levels

– hyploglycemic agent • Stored from sources such as liver, fat and muscles.• Has a reciprocal relationship with glucagon.• Promotes glycogenesis, lipogenesis and glycolysis;

decreases glycogenolysis.

GLUCAGON

• The primary hormone responsible for increasing glucose – hyperglycemic agent

• Synthesized by the alpha cells of the islets of langerhans in the pancreas

• It is released during stress and fasting states.• It enhances catabolic functions during fasting

periods; promotes glycogenolysis and gluconeogenesis

Other hormones that tend to increase glucose concentration1. Cortisol and corticosteroids (Glucocorticoids) Secreted by the cells of the zona fasciculata and

zona reticularis of the adrenal cortex Decreases intestinal entry of glucose into the cell It promotes gluconeogenesis and lipolysis

2. Cathecolamines It is released from the chromaffin cells of the

adrenal medulla Inhibits insulin secretions and promotes

glycogenolysis and lipolysis.

3. Growth hormones(Somatotrophic) Secreted by the anterior pituitary gland Decreases entry of glucose into the cell It promotes glycogenolysis and glycolysis.

4. Thyroid hormones Secreted by the thyroid gland. Promotes glycogenolysis, gluconeogenesis and

intestinal absorption of glucose.

5. Adrenocorticotropic hormones (ACTH) It stimulates release of cortisol from the adrenal

cortex It promotes glycogenolysis and gluconeogenesis.

6. Somatostatin Produced by the delta cells of the islets of

langerhans of the pancreas It is primarily inhibits the action of insulin and

glucagon.

Clinical conditions of carbohydrate metabolism

1. Hyperglycemia Increase in blood glucose levels Causes: stress, severe infection, dehydration or

pregnancy, pancreatectomy, hemochromatosis, insulin deficiency, abnormal insulin receptor.

FBS level= 126 mg/dL All adults older than 45 yrs.old should have a

measurement of FBS every 3 years unless the individual is diabetic.

Lab. findings in Hyperlgycemia

1. Increase glucose in plasma and urine

2. Increase urine specific gravity

3. Ketones in serum and urine

4. Decrease blood and urine pH(acidosis)

5. Electrolyte imbalance

2. Hypoglycemia Involves decreased glucose levels and can have

many causes. Warning signs and symptoms of hypoglycemia are all

related to CNS. 80 mg/dl to 5mg/dl (2.8-3.0 mmol/L) – observable

symptoms of hypoglycemia occur.

CLASSIFICATION:

1. Drug administration- insulin alcohol, salicylates, sulfonamides, pentamidine. Etc.

2. Critical illnesses- hepatic failure, sepsis, renal failure, cardiac failure, malnutrition

3. Hormonal deficiency- epinephrine, glucagons, cortisol, growth hormone

4. Endogenous hyperinsulinism- pancreatic beta cell disorder

5. Autoimmune hypoglycemia- insulin antibodies

6. Non beta cell tumors- leukemia, hepatoma, pheochromocytoma, lymphoma etc.

7. Hypoglycemia if infancy and childhood- galactosemia, GSD, Reye’s syndrome

8. Alimentary (reactive) hypoglycemia- post-gastric surgery

9. Idiopathic (functional) postprandial hypoglycemia

A diagnosis of hypoglycemia should not be mad unless a patients meets the criteria WHIPPLE’S TRIAD – low blood glucose concentration with typical symptoms alleviated by glucose administration.

Diabetes Mellitus(DM)

• A group of metabolic disorders characterized by hyperglycemia resulting from defects in insulin secretion, insulin or both.

• Fasting plasma glucose concentrations > 26 mg/dL on more than one testing are diagnostic DM.

• Glucosuria occurs when the plasma glucose levels exceeds 180 mg/dL (9.99mmol/L) with normal renal function

• In severe DM, the ratio of beta-hydroxybutyrate to acetoacetate is 6:1

Classification of DM:

A. Type 1 DM

Formerly known as:

Insulin Dependent Diabetes Mellitus (IDDM)

Juvenile Onset Diabetes Mellitus

Brittle Diabetes

Ketosis-Prone Diabetes• Is a result of cellular-mediated autoimmune destruction of the

beta cells of the pancreas.• Diabetic individuals have insulinopenia (absolute insulin

deficiency) because of loss of pancreatic beta-cells and depend on insulin to sustain life and prevent ketosis.

• 80-90% reduction in the vol. of the beta cell is required to induce symptomatic type 1 DM

• Signs and symptoms: polyuria, polydipsia, polyphagia, rapid wt. loss, hyperventilation, mental confusion and possible loss of consciousness.

• Complications: nephropathy, neuropathy, and retinopathy – microvascular disorders.

• Microalbumin of 50-200 mg/24hrs. – diabetic nephropathy

• Urine albumin excretion rate of 200 g/minute – overt diabetic nephropathy.

Idiopathic Type 1 DM is a form of type DM that has no known etiology, is strongly inherited, does not have beta-cell auto antibodies and have episodic requirements for insulin replacement.

• Type 2 DM

Formerly known as: Non-insulin Dependent Diabetes Mellitus

Adult Type/maturity Onset Diabetes Mellitus

Stable Diabetes

Ketosis- Resistant Diabetes

Receptor-Deficient Diabetes Mellitus• Characterized by hyperglycemia du to an individual’s

resistance to insulin; there is relative insulin deficiency.• Associated with strong genetic predisposition and not

related to an autoimmune disease.• It has been described as a geneticist’s nightmare.• Has a milder symptoms as compared to type 1, however,

untreated type 2 DM will result to nonketotic hyperosmolar coma- overproduction of glucose (>500mg/dL), sever dehydration, electrolyte imbalance, and increased BUN and creatinine.

Risk factors

• Risk factors: obesity, family history, advanced age,

hypertension, lack of exercise, impaired glucose metabolism.

C. Other specific types of diabetes

1. Pancreatic disroders

2. Endocrine disorders –Cushing’s syndrome, pheochromocytoma, accromegaly and thyrotxicosis

3. Drugs or chemical inducers of beta cells dysfunction (dilantin and pentamidine)and impair insulin action (thiazides,glucocorticoids)

4. Genetic syndromes- down syndrome, klinefelter’s syndrome, leprechaunism etc.

D. Gestational DM(GDM)\• Characterized by impaired ability to metabolized CHO

usually caused by a deficiency of insulin,metabolic or abnormal changes occuring in pregnancy and disappearing after delivery but in some cases returning yrs. later

• Glucose intolerance with onset or first recognition during pregnancy

• Screening should be performed between 24 and 23 wks. Of gestation

• A plasma glucose concentration of 140 mg/dL or greater requires a full diagnostic glucose tolerance test (3hr GTT with 100g glucose)

GDM results:

FBS = >105 mg/dL

1 hr. = < 190 mg/dL

2 hrs. = 165 mg/dL

3 hrs. = 145 mg/dL

• GDM is diagnosed when any two of the above mentioned four values are met or exceeded.

• After giving birth, woman with GDM should be evaluated 6-12 wks. Postpartum

• Infants born to diabetic mothers are at increased risk for respiratory distress syndrome, hypocalcemia and hyperbilirubinemia.

4. Impaired Fasting Glucose• Characterized by fasting blood glucose

concentrations between normal and diabetic values.

5. Impaired Glucose tolerance• Characterized by fasting blood glucose

concentration less than those required for the diagnosis of DM, but the OGTT is between normal and diabetic values.

Diabetes Insipidus Deficiency of anti diuretic hormone released by

the posterior gland.

Clinical picture include:

1. Normoglycemia

2. Polyuria with low specific gravity

3. Polydipsia

4. Polyphagia - ocassional

Glucose Methodologies

• Fasting glucose in whole blood is 15% lower than in serum or plasma.

• Serum or plasma must be separated from the cells within one hour to prevent losses of glucose.

• At rm. Temp. (20-25C), glycolysis decreases glucose by 5-7%/hour (5-10mg/dL) in normal uncentrifuged coagulated blood.

• At refrigerated temp. (4 C) glucose is metabolized at the rate of about 1-2 mg/dL/hr.

• WBC and RBC metabolize glucose resulting to decrease value in clotted, uncentrifuge blood.

• CSF glucose concentration should be approximately 60% (40-60 mg/dL) of the plasma concentrations.

• Plasma glucose levels increase with age – fasting 2 mg/dL/decade; postprandial, 4mg/dL/decade; glucose challenge, 8-13 mg/dL/decade.

I. CHEMICAL METHODS

A. Oxidation Reduction Methods

1. Alkaline Copper Reduction Methods Reduction of cupric ions to cuprous oxide in

hot alkaline solution by glucose.

a. Folin Wu Method

b. Nelson Somogyi Method

c. Neocuproine method

d. Benedict’s method- used for detection and quantitation of reducing substances in body fluids like blood and urine.

e. Citrate or tartrate as stabilizing agent

2. Alkaline Ferric Reduction Method (Hagedorn Jensen)

• Reduction of a yellow ferricyanide to a colorless ferrocyanide by glucose (inverse colorimetry)

3. Condensation Method

II. Enzymatic Method Acts on glucose but not on other sugars and not

on other reducing substances.

1. Glucose oxidase method

> Measures the beta-D glucose

a. Colorimetric Glucose Oxidase Method (saifer Gernstenfield Method)

b. Polarographic Glucose oxidase The enzymatic conversion of glucose is

quantitated by the consumption of oxygen Measure rate of oxygen consumption.

2. Hexokinase Method• Most specific glucose method ; reference

method

NOTES TO REMEMBER Ǚ

• Elevated amounts of bilirubin, uric acid and ascorbate – false decreased values of glucose(glucose oxidase method)

• Hemolysis affects hexokinase method – false low glucose value

• The enzymatic conversion of glucose to product is quantitated by a color change reaction at the last of a series of coupled chemical reactions (kinetic analysis)

3. Dextrostics• Important in establishing correct insulin amount

for next dose• Effective in reducing the rate of development of

diabetic complications

Samples for Glucose Measurement

1. RBS – random Blood Sugar

- requested during insulin shock, hyperglycemic ketonic coma

2. FBS – Fasting Blood Sugar

- NPO (Non-Per Orem) 6-8hrs.

3. 2-HR PPBS – 2 hour Post Prandial Blood Sugar

- below 110 mg/dL at 2 hours

4. GTT – Glucose Tolerance Test

Requirements:

CHO depletion and inactivity or bed rest impair glucose tolerance

GTT is unnecessary to do for women under 25 yrs. Old who have normal body wt. no family history of diabetes and are not member of an ethnic group with high prevalence of diabetes.

1. Patient should be ambulatory

- CHO depletion and inactivity or bed rest impair glucose tolerance

2. Fasting of 8-16 hrs.

3. Unrestricted diet of 150 gms. CHO/day for 3 days prior to testing.

4. The patient should not smoke and drink alcohol.

5. Glucose Load

- 75 gms (standard glucose load)

-100 gms

-1.75g of glucose/kg body wt. (children)

Procedure for GTT• The patient should avoid exercise, eating and

drinking (except water) and smoking during testing

• For nonpregnant women and adults, only the fasting and the 2 hour sample may be measured or accrdg. To the physician’s request

1. Collect the fasting blood sample

2. Instruct the patient to drink the glucose load within 5 mins.

3. Collect blood sample after 30 mins., 1 hour, 2 hours, 3 hours respectively.

Kinds of Glucose Tolerance Testa. Oral Glucose Tolerance Test

> Janney-Isaacson Method (single dose method)

>Exton Rose Method (divided oral dose or double method)

b. Intravenous GTT

> used for DM patients with GI disorders.

>determine glucose by getting blood samples every 10mins.for one hour

>0.5 g of glucose/kg body wt. (given within 3mins.) administered intravenously

>fasting sample is also required.

Indications

a. Those who are unable to tolerate a large CHO load.

b. Those with altered gastric physiology

c. Those who had undergone previous operation or surgery in the intestine.

d. Those with chronic malabsorption syndrome.

Criteria of Fasting Plasma Glucose (FPG)

1. Non-diabetic = <110mg/dl

2. Impaired PG = 110g/dl but <126mg/dl

3. DM = 126mg/dl

Categories of Oral Glucose Test

1. Normal GTT = 2hr PG <140mg/dl

2. Impaired GTT = 2hr PG 140mg/dl but < 200 mg/dl

3. DM = 2hr PG 200mg/dl

Diagnostic criteria for DM

1. RBS = 200 mg/dl (w/ symptoms of DM)

2. FBS = 126 mg/dl

3. 2-hr post glucose = 200 mg/dl

5. Glycosytated/glycated hemoglobin• Also called glycated hemoglobin• Largest subfraction of normal hemoglobin in both

diabetic and non-diabetic individuals.• A glucose molecule attached to one or both N-

terminus valines of the beta-polyp chains of normal adult hemoglobin

• A reliable method in the monitoring of long term glucose control

• It reflects the average blood glucose level over the previous 2-3mos.

• 3-6% of Hgb is glycosylated; 18-20% is prolonged hyperglycemia.

• For every 1% change in the HbA value, 35mg/dL is added to plasma glucose.

• Older RBCs have higher HbA, iron deficiency anemia – high levels

• Not suitable for patients with shortened RBC lifespan disorders.

• Specimen for testing, EDTA whole blood• Preferred method, affinity chromatography

6. Fructosamine• Also called glycosylated or glycated

albumin/plasma protein ketoamine.• A reflection of short term glucose control (2-3wks)

• May be useful for monitoring diabetes individuals w/ chronic hemolytic anemias and hemoglobin variants.

• It should not be measured in cases of low plasma albumin.

Other clinical Disorders of Carbohydrate

Metabolism

1.Galactosemia

> A congenital deficiency; one of three enzymes involved in galactose metabolism

• Cause of failure to thrive syndrome in infants• 3deficient enzymes: galactose 1-phophate uridyl

transferase galactokinase and uridine diphosphate galastose 4-epimerase

• Cllinical features: jauncide, hepatomegally, easy bruisability,sepsis, cataract, hypotonia and sensory neural deafness.

• Diagnostic test: erythrocyte galactose- 1-PO4 uridyl transferase activity.

2. Essential fructosuria• An autosomal recessive disorder characterized by

fructokinase deficiency• Diagnostic indicator: (+) fructose in urine

3. Hereditary fructose intolerance• A defect of fructose 1-6-b phosphate aldolase B

activity in the liver, kidney and intestine.• Inability to convert fructose-1-phosphate and

fructose-1,6-phosphate into dihyroxyacetone phosphate,glyceraldehyde-3-phosphate and glyceraldehydes.

• Clinical features: irritability, seizures, and hepatomegaly

4. fructose-1,6-biphosphate deficiency• A defect in fructose-1,6-biphosphate results in

failure of hepatic glucose generation by glucoriogenic precursors such as lactate and glycerol.

• Clinical features: hypoglycemia, lactic acidosis convulsion and coma.

5. Glycogen Storage Disease (GSD)• Deficiency of a specific enzyme involved in the

metabolism of glycogen• Inherited as autosomal recessive trait

• Blood specimen are collected for 2hrs at 15 mins. Interval

• Von Gierke disease – most common GS

Notes to Remember

1. CSF glucose• It is abt. 60-70% of the blood plasma glucose

level• Any changes in blood sugar are reflected in the

CSF approximately one hour later because of the lag in CSF equilibrium time.

• A blood glucose specimen should be collected at least 60 mins. Before the lumbar puncture.

• Increased levels: diabetes• Decreased levels: bacterial meningitis, TB,

fungal and amebic meningitis.

• Reference value:40-70 mg/dL (adult)

60-80 mg/dL (child)• Normal CSF to glucose ratio: <0.5

2. C-Peptide test • Formed during the conversion of pro-insulin to

insulin.• The amount of circulating C-peptides provides

reliable indicators for pancreatic and insulin secretionS (beta cells functions)

• Used to monitor individual responses to pancreatic surgery.

• To evaluate hypoglycemia• Specimen: fasting blood

Test for ketone bodies:

1. Gerhard’s ferric chloride test- reacts only w/ acetoacetate

2. Nitroprusside test- 10x more sensitive to acetoacetate than to acetone

3. Acetest tablets- detects acetoacetate and acetone

4. ketosux- detects acetoacetate better than acetone

5. Ketosite assay- detects beta hydroxybutyrate; not widely used.

Thank You for Listening

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Carbohydrates CHO