carbohydrates

General structure of carbs + formula

• composed of carbons, oxygen and hydrogens

• Formula:

  • (CH2O)n

Monosaccharides vs disaccharides vs polysaccharides

Mono:

• contain 3,4,5,6 or more carbons

Dis:

• two monosaccharides linked together w/ loss of a molecule of water

Poly:

• many monosaccharides linked together

Specific commotion of lactose

Glucose + galactose

Specific combination of maltose

Glucose + glucose

Specific combination of sucrose

Glucose + fructose

Specific combination of glycogen

Glucose (x many)

Specific combination of starch

Amylose + amylopectin

Reducing sugars + clinical significance

• any sugar containing a hemiacetal

• Can use a clinitest and urine dip stick

  • See if glucose and galactose are present

Two analytically important reducing sugars

1. Glucose

2. Galactose

Starch digestion

Starts in the month by salivary amylase enzyme and stops in the stomach

Intestine digestion

Small intestine (duodenum)

Hydrolysis disaccharides to monosaccharides (lactose, maltose, sucrose)

• enzymes for this: Lactase, Maltase, Sucrase and Lipase

*liver converts galactose and fructose to glucose

Glycolysis (anaerobic and aerobic)

Break down of glucose forming either lactate or pyruvate

Aerobic:

• pyruvate to Acetyl CoA to ATP

• In liver

Anaerobic:

• More lactate produced

• In RBCs and skeletal muscles

Starting and ending material for glycolysis

Starting = glucose

Ending = pyruvate/ lactate

Glycogenesis starting and ending material

Starting= glucose

Ending = glycogen

Glycogenolysis starting and ending products

Starting =gylcogen

Ending= glucose

Glyconeogenesis starting and ending products

Starting = AA, fatty acids, glycerol, lactate (non-carbohydrates)

Ending = glucose

Kreb cycle

Site insulin produced at

Beta cells in islets of langerhans in pancreas

Function of proinsulin and C-peptide

Proinsulin:

• storage of pre proinsulin

C-peptide

• necessary to ensure correct folded structure of insulin (measured in labs)

Insulin affect on glucose concentration

Decreases it

Insulin action on the membranes

Attaches to receptors which then allow glucose to enter the cell and decrease glucose lvls in blood

Major factor the regulates insulin’s release

Blood glucose concentration

Insulin’s affect on carbohydrate metabolism

Increased glycolysis

Decrease glyconeogenesis

Decrease glycogenolysis

(Makes more glycogen and decreases glucose production)

Insulin affect on protein metabolism

Increase protein synthesis

Decrease protein degradation

Increase amino acid uptake

Insulin affect on lipid metabolism

Decrease lipolysis

Increase storage of fatty acids and triglycerides

Decrease fatty acid oxidation

Glucagon

Produce in alpha cells of pancreatic langerhans

Increase blood glucose

Growth hormone

Produce ingredients anterior pituitary gland

Increases blood glucose

Epinephrine

Produced in adrenal medulla

Increase blood glucose

Cortisol

Produced in adrenal cortex

Increases blood glucose

Thyroid hormone

Produced in thyroid gland

Increase blood glucose

Somatostatin

Produced in delta cells of pancreatic langerhans

No effect on glucose

Inhibits growth hormone, insulin and glucagon

Somatomedins

Produced in liver

No effect on glucose

Hyperglycemia

Too much glucose in blood

Glucose greater than or equal to 100 mg/dL

Hypoglycemia

Too little glucose in blood

Less than 50 mg/dL (adults)

9 complications of diabetes

1. Nethropathy

2. Neuropathy

3. Heart disease and stroke

4. Hyper tension

5. Blindness or retinopathy

6. Amputation

7. Dental disease

8. Complications of pregnancy

9. Life threatening events

4 clinical symptoms used for diabetic diagnosis

1. Polyuria (lots of urinating)

2. Polyphagia (lots of eating)

3. Polydipsia (thirsty)

4. Unexplained weight loss

3 specific diagnostic criteria for diabetes

1. Fasting blood glucose >126 mg/dL

2. 2hr post-prandial glucose >200 mg/dL with 75g glucose load (drink)

3. A1c level 5.7-6.4

Specific cause for type 1 diabetes

Beta cell destruction

Cause for beta cells in islets injury

1. Genetic factors

2. Environmental factors

3. Viral causes

4. Chemical causes

5. Autoimmune disease (main one)

Relative insulin concentration in type 1

Very decreased or absent

3 metabolic changes in type 1

1. Increase ketobodies

2. Hypoglycemia

3. Increase glycogenolysis, lipolysis and gluconeogenesis

Treatment for type 1

Insulin shots

2 general causes for type 2 diabetes

1. Progressive insulin resistance

2. Beta cell failure

2 factors that may predispose the patient

1. Genetic factors

2. Environmental Factors

Relative insulin concentration on type 2

Variable (depends on cause)

Treatment for type 2

Weight loss

Diet changes

Oral hypoglycemic agent

Gestational diabetes Mellitus

• a for of glucose intolerance diagnosed during pregnancy (~2%)

• Could result in long term type 2

• Determined by O’Sullivan test

Maturity-onset of youth (MODY)

• caused by a single gene defect

• Manifests before age 25

4 conditions that cause secondary diabetes

1. Pancreatic disease

2. Cystic fibrosis

3. Corticosteroids administration

4. Other hormonal disorders

Prediabetes/ impaired glucose tolerance criteria

• fasting plasma glucose 100-125 mg/dL

• 2hr post-prandial 140-199 mg/dL

Correlation between A1c and fasting blood lvls in diagnosis of prediabetes

You could eat well for a week and change the fasting glucose levels but A1c does not change as quickly so it will give you a more accurate diagnosis

Symptoms of diabetes mellitus

1. Acanthodii’s nigricans

2. Blurred vision

3. Slow wound healing

4. Hypertension

Double diabetes in adolescent diabetes

• you have both types of diabetes

  • Type 1 becomes overweight and becomes insulin resistant

  • Type 2 develops antibodies of beta cells

• Major factor is weight gain

Hypoglycemia lvls in adults, children, preterm infants and term infants

Adults : below 50

Children: below 50

Term: 30

Preterm: 20

Hypoglycemia

Release of epinephrine or adrenaline

Fasting blood sugar <50 mg/dL

Weakness, rapid pulse, epigastric discomfort

Severe hypoglycemia

Body needs 70-100 mg/dL a day

Only have <20-30 mg/dL

Give something ASAP (orange juice)

Fasting hypoglycemia

Rare but life threatening

Caused by certain drugs

<45 mg/dL

Reactive hypoglycemia

Post-prandial <45-50 mg/dL

1st must rule out fasting hypoglycemia

What is galactosemia caused by

Galactose-1-phosphate uriadylytransferase (GALT)

Symptoms of galactosemia

Fail to thrive on cow milk

Vomiting

Diarrhea

Galactosemia is diagnosed by

1. Screening urine via Benedict test (clinitest)

2. ID of super by paper chromatography

3. Direct assay of enzyme activity

What value makes a person a diabetic

Greater than 200

How do you calculate CSF plasma lvls

Times it by the plasma levels by 0.6 or 0.7

Draw OGTT curve

Normal and pre should never reach 200 but diabetic should

What causes lactose intolerance

Lactase deficiency

Symptoms of lactose intolerance

A nominal paiN, Diarrhea, and lactose in urine

What is the H2 test for lactose intolerance

Tests amount of produced H2 gas is measured after drinking lactose

What causes glycogen storage diseases

Deficiencies of specific enzyme in glycogen metabolism

Two forms of glycogen storage disease

1. Liver form (type 1,4,6)

2. Muscle form (type 2,3,5,7)

Liver form

Hepatomegsly, hypoglycemia, decrease insulin, increase glucagon

Muscle form

Appear in young adulthood during strenuous exercise

Vin gierke’s disease

Type 1 glycogen storage disease

Deficiency of glucose 6 phosphate (G-6-P)

Leads to massive hepatomegaly

Liver form

Pompe’s disease

Type 2 glycogen storage disease

Deficiency in alpha 1,4 glucosidase

Muscle form

Blood sugar classification of FASTING

Normal: 70-99

Prediabetes: 100-125

Diabetes: greater than 126

Blood sugar classification of OGTT

Normal: less than 140

Prediabetes: 140-199

Diabetes: over 200

Blood sugar classification of POST-PRANDIAL

Normal:less than 140

Prediabetes: none

Diabetes: over 200

Blood sugar classification of RANDOM

Normal: 70-139

Prediabetes: 140-199

Diabetes: over 200

Blood sugar classification of A1c

Normal: less than 5.7%

Prediabetes: 5.7-6.4%

Diabetes: greater that 6.5%

Reference range for fasting glucose in everyone

Adult: 70-99

Children: same as adult

Preterm: 25-80

Term: 60-95

Why must test within 30 minutes of veniputure?

Glucose decrease up to 7% per hour or more when serum is left in contact 2/ cells

• RBCs metabolize glucose

Why oxalate sodium fluoride is preferred anticoagulant

Inhibits enolase a critical enzyme in glycolysis pathway

Whole blood glucose values

12-15% less than plasma values

Plasma glucose valuse

Adult 70-99

Oxygenated, deoxygenated, and capillary glucose values

Oxygenated and capillary are ~2-5 mg/dL higher than deoxygenated blood

Reason for prompt analysis of CSF glucose

Due to possible cellular utilization and resultant false report

Relationship between plasma and CSF glucose

CSF is 60-70% of concomitant plasma lvls

Clinical significance and specific renal threshold for urine glucose

Glucose appears in urine after blood exceeds renal threshold:160-180

Could point to Fanconi syndrome or pregnancy

Principle of measurement of Benedict’s copper reduction test

Based on reduction of the cupric ion in cupric sulfate

Significance of a positive test in a clinitest

Means there is a large amount of reducing sugars

Specific carbs detected by clinitest

Glucose and galactose

Hexokinase method reagents and products

Reagents used:

• glucose and atp

• G-6-P and NADP+

Products made:

• G-6-P and ATP

• 6-Phosphoglyconate, NADPH, H+

Hexokinase method usage

The reference method when protein-free filtrate is used

Measures absorbance at 340nm (NADPH)

Glucose oxidasse (Trinder”) reagents used and use of method

Reagents:

• glucose,water,oxygen (Step 1)

• Reduced chromogen and H2O2 (step 2)

Use:

• good for serum, plasma, urine and CSF

• Oxidized chromogen is propionate to glucose present

Prep instructions for OGTT

1. Minimum of 150g of carbs for 3 days prior to test

2. Fasting 10-16 hrs before test (water only)

3. Discontinue medication that alter glucose lvls

4. Normal amount of activity before and during test

3 indications for performing an intravenous glucose tolerance test

1. Malabsorption

2. Spruce )celiac disease)

3. GI surgery

Post-prandial procedure and use

Patient eat meal w/ 100g of carbs, rests until blood drawn at 2 hours

Used for preliminary diagnosis of DM

O’Sullivan test procedure and use

Used to screen for gestational DM

give 50g glucose load to fasting patient and draw after 1 hr

Metabolic pathway the leads to ketone body formation

Beta oxidation of free fatty acids

Specific starting products of ketone bodies

Fatty acids

3 ketone bodies and proportions in blood

1. Beta hydroxybutyric acid (78%)

2. Acetoacetic acid (20%)

3. Acetone (2%)