MLTS 2410 - Exam 1: Ch. 7, 11, 12

Carbohydrates

• most abundant organic molecules found in nature

• stored in the liver as glycogen, serve as source of glucose

• primary source of food and energy

What group of organic compounds are included in carbohydrates?

• sugars

• glycogen

• starches

NOTE: all contain the chemical compounds carbon, oxygen, hydrogen

What are two forms of the glucose molecule?

1. aldehyde

2. ketone

Aldehyde

• molecule containing the carbonyl group at the end of the carbon chain (first or last carbon)

• monosaccharide called aldose

Ketone

• molecule containing the functional group on an internal carbon

• monosaccharide called ketose

In a carbohydrate chain, what are the number of sugar units?

• monosaccharides

• disaccharides

• polysaccharides

Monosaccharides

• one-unit, simple sugars

• glucose, fructose, galactose, xylose, ribose

Disaccharides

• two units or monosaccharides

• maltose, lactose, sucrose

Polysaccharides

greater than 20 monosaccharides

In plants, what are carbohydrates stored as?

• starch

• cellulose

In animals, what are carbohydrates stored as?

glycogen

What are the two chemical properties of carbohydrates?

• reducing carbohydrates

• nonreducing carbohydrates

Reducing Carbohydrates

• to reduce, carbohydrate must have ketone or aldehyde group

• used in many methods in the determination of carbohydrates

• reducing agents = all monosaccharides and many disaccharides

In reduced carbohydrates, what are some examples of some reducing agents?

• glucose

• maltose

• fructose

• lactose

• galactose

Nonreducing Carbohydrates

• do not have ketone or aldehyde group and will not reduce

• ex. sucrose

What are four pathways carbohydrates are channeled?

1. converted to liver glycogen and stored

2. metabolized completely to CO₂ and H₂O to provide immediate energy

3. converted to keto acids, AA, proteins

4. converted to fats (triglycerides) and stored in adipose tissue

What are processes are involved in glucose metabolism?

• glycogenesis

• glycogenolysis

• gluconeogenesis

• glycolysis

Glycogenesis

conversion of glucose to glycogen for storage

Glycogenolysis

• involves the breakdown of glycogen to form glucose and other intermediate products

• process that regulates glucose levels b/w meals

Gluconeogenesis

• formation of glucose from noncarbohydrate sources, such as AA, glycerol, or lactate

• occurs during long-term fasting

Glycolysis

metabolism of glucose molecule to pyruvate or lactate for production of energy

What hormones regulate carbohydrate metabolism?

• insulin

• glucagon

• ACTH / growth hormone

• epinephrine

• cortisol

• T3 and T4

• somatostatin

Insulin

• inhibits release of glucose from liver—hypoglycemic agent

• source: beta-cells of Islets of Langerhans of pancreas

• action on glucose: decreases, released when glucose is elevated

Glucagon

• primary hormone responsible for increase

• source: alpha-cells of Islets of Langerhans of pancreas

• action on glucose: increase, released during stress and fasting

ACTH / Growth Hormone

• source: anterior pituitary

• increases glucose

Epinephrine

• inhibits insulin

• source: adrenal medulla

• action on glucose: increases, released during physical and emotional stress

Cortisol

• source: adrenal cortex

• increases glucose

T3 and T4

• source: thyroid gland

• increases glucose

Somatostatin

• source: delta-cells of Islets of Langerhans of pancreas

• increases glucose

C-Peptide

• primarily used to evaluate hypoglycemia; reflects pancreatic insulin secreting; diagnosing insulinomas (pancreatic tumor)

• released in equal amounts to insulin (1:1)

• used for detection of exogenous insulin administration

Leptin

• hormone that regulates body weight, metabolism, and reproductive function

• increased concentrations found in obese individuals

Fasting Blood Sugar (FBS)

measures the amount of glucose in your blood after a minimum 8 hr. fast

What is the reference interval for glucose?

74-100 mg/dL

Hypoglycemia

• men: < 55 mg/dL

• women: < 45 mg/dL

Hyperglycemia

≥ 126 mg/dL

What is the FPG (FBS) range for prediabetes / impaired fasting glucose?

100-125 mg/dL

Diabetes Mellitus (DM)

• primary cause of blindness (due to nerve damage) and end-stage renal disease

• group of diseases characterized by hyperglycemia due to defects in insulin production, insulin action, or both

What are the four categories ADA classifies diabetes mellitus into?

1. type 1

2. type 2

3. gestational

4. prediabetes

Type 1 Diabetes Mellitus

• immune-mediated diabetes

• insulin-dependent diabetes mellitus (IDDM)

• caused by destruction of the beta cells of the islets of Langerhans in the pancreas

• absolute insulin deficiency

• ketonemia and ketonuria

What are the signs and symptoms of type 1 diabetes mellitus?

• polydipsia, polyuria, polyphagia

• mental confusion, hyperventilation, blurred vision

• loss of consciousness (due to increased glucose)

Type 2 Diabetes Mellitus

• most common and milder form

• adult onset, mostly over the age of 40 but becoming a problem w/ children

• insulin resistance and dyslipidemia

• risk factor for cardiovascular disease

• diet and exercise determines pathogenesis

What are the complications of diabetes mellitus?

• heat disease and strokes

• diabetic retinopathy

• end-stage renal disease

• nervous system damage (e.g., peripheral neuritis)

• susceptibility to infections (amputation of lower limbs)

What life-threatening health problems can diabetes mellitus increase a risk for?

• heart disease, leading cause of death

• high blood pressure present in 73% of diabetics

• heart disease and strokes occur 2-4 times more frequently

• 44% of new cases of end-stage renal disease

• 60-70% present nervous system damage

Gestational Diabetes (GDM)

• associated w/ pregnancy

• diagnosed when abnormal glucose concentrations are discovered for the first time during pregnancy

• occurs in 1-5% of pregnancies due to metabolic and hormonal changes

• most women revert to normal glucose metabolism after delivery

What are ADA’s four criteria for the diagnosis of diabetes mellitus?

• hgb A₁C (or glycosylate hgb)

• fasting glucose

• 2 hr. postload glucose

• random (casual) glucose

What is the normal fasting plasma glucose range?

FPG < 100 mg/dL

What is the fasting plasma glucose range for prediabetes / impaired fasting glucose?

FPG 100-125 mg/dL

What is the fasting glucose range for diabetes mellitus?

FPG ≥ 126 mg/dL

What is the normal 2-hour postload glucose (OGTT) range?

2-hour postload glucose < 140 mg/dL

What is the 2-hour postload glucose (OGTT) range for prediabetes / impaired glucose tolerance?

2-hour postload glucose 140-199 mg/dL

What is the 2-hour postload glucose (OGTT) range for provisional diabetes mellitus?

2-hour postload glucose ≥ 200 mg/dL (must be confirmed)

Glucose Tolerance Test (GTT)

• measures the body’s response to sugar

• 1 hr. (O’Sullivan) - ordered to rule out gestational diabetes; given a 50 g glucose load

• 2, 3, 4, 5 hr. tolerance test - given 75-100 g glucose load

How many times should people with diabetes monitor their blood glucose levels?

3-4 times

2-Hour Postprandial Test

• patient drinks standardized (75 g) glucose load

• glucose measurement is taken 2 hrs. later

What glucose tolerance test is not recommended by the ADA?

oral glucose tolerance test

Hypoglycemia

• decreased plasma glucose levels

• can be transient and relatively insignificant or can be life threatening

• occurs in healthy-appearing / sick patients, as a result of reaction to meds or of illness

• glucose level: 50-55 mg/dL

What is the range for men, women, and neonates with hypoglycemia?

• men: < 55 mg/dL

• women: < 45 mg/dL

• neonates: < 30

What are the symptoms of hypoglycemia?

• increased hunger

• sweating

• nausea

• vomiting

• dizziness

• nervousness

• shaking

• blurred speech / vision

• mental confusion

What amount of glucose is used as a cutoff for hypoglycemia?

≥ 70 mg/dL

What glucose tolerance test is used for those with hypoglycemia?

5 hr. GTT

What are the three criteria Whipple’s Triad set to diagnose hypoglycemia?

1. signs and symptoms of hypoglycemia

2. documentation of low plasma glucose at the time patient is experiencing the signs and symptoms, CBG or glucose levels < 55 mg/dL

3. alleviation of symptoms w/ the ingestion of glucose and an increase in plasma glucose

Glycogen Storage Diseases (GSDs)

affects the body’s ability and usage of glycogen

What are the glycogen storage diseases (GSDs)

• type I

• galactosemia

• lactase deficiency

Type I

• glucose-6-phosphatase deficiency, also known as von Gierke disease

• symptoms: hypoglycemia, hepatomegaly, hyperlipidemia, growth restriction

Galactosemia

• enzyme deficiency involved in galactose metabolism

• symptoms: failure to thrive, intestinal problems, jaundice increased galactose in blood, tissues, and urine from milk ingestion

Lactase Deficiency

• low or absent levels of the enzyme lactase in the small intestine

• lactose intolerance - body does not produce lactase; if not broken down, lactose ferments causing excess hydrogen

• H2 breath test

H3 Breath Test

measures the amount of hydrogen gas present in an individual after they consume a lactose solution

Glucose Oxidase

• catalyzes the oxidation of glucose to gluconic acid and hydrogen peroxide

• most automated analyzers use this reaction and POCT

• highly specific for β-D glucose

• increased levels of ascorbic acid and uric acid depress the glucose oxidase reaction (falsely decreased)

Describe the glucose oxidase reaction.

• glucose +O₂ +H₂O → gluconic acid + H₂O

• H₂O₂ + reduced chromagen → oxidized chromagen + H₂O

Hexokinase

• reference method for glucose

• amount of NADPH is measured and is proportional to the amount of glucose present

• not affected by ascorbic acid or uric acid

• gross hemolysis and elevated bilirubin levels cause a false decrease in results

Explain the methods to measure glucose.

• glucose can be measured from serum, plasma, or whole blood

• fasting blood glucose be obtained in the morning after 8-10 hr. fast

• sodium fluoride (gray top) prevents glycolysis

• serum or plasma must be refrigerated and separated from cells within 1 hr. to prevent loss of glucose

How much does glucose levels decrease per hour in whole blood?

10 mg/dL per hr. depending on the temp. and WBC count

How low is whole blood glucose than serum glucose?

10-15%

What is capillary specimen higher than?

venous sample

What are the reference interval for fasting glucose specimens?

• serum and plasma glucose levels are 74-100 mg/dL

*NOTE: fasting specimens should be collected after a fast of at least 8 hrs. but not greater than 16 hrs.

What is the cerebral spinal fluid glucose range?

50-80 mg/dL

How is urine glucose reported?

negative 1+, 2+, 3+, and 4+, corresponding to concentrations of 100 mg/dL to 2 g/dL

Ketones

• produced by liver through metabolism of fatty acids

• products of incomplete fate metabolism

• increase w/ carbohydrate deprivation or decreased carbohydrate use (diabetes, starvation / fasting, high-fat diets)

• ketones in urine, ketonuria, or serum, ketonemia are detected by using sodium nitroprusside

What are the three ketone bodies?

1. acetone (2%)

2. acetoacetic acid (20%)

3. 3-β-hydroxybutyric acid (78%)

What is the specimen requirement when testing for ketones?

• fresh serum or urine (Clinitest/Acetest)

• testing recommended for type I diabetic (ketoacidosis, pos. ketones)

*NOTE: causes the fruity odor of the breath in ketoacidosis

Glycosylated Hemoglobin / Hemoglobin A₁C (Hgb A₁C)

• depends on the concentration of serum glucose and the life span of RBCs (shortened = decreased Hgb A₁C)

• indicates the glucose concentration over the preceding 3 months

• most commonly detected glycosylated hgb

Hgb A₁C <5.7%

• usually performed two or more times a year to monitor treatment

• EDTA whole blood required for testing

• fasting not required

Albuminuria

• previously called microalbuminuria (microalbumin)

• increase in urinary albumin is an early sign of renal nephropathy, complication of diabetes mellitus

• marker of cardiovascular morbidity and mortality

• usually qualitative test (neg., 1+, 2+)

Albumin-Creatinine Ratio

• measured test w/ numerical values—preferred test method

• spot urine or random urine

Fructosamine

• glycated protein which may be used in place of Hgb A₁C in patients w/ hgb variants

• reflects the glucose level for the past 2-3 weeks

• iron therapy lowers hgb A₁C and fructosamine levels in diabetic and non-diabetic individuals

What is the role of the kidneys?

• maintain levels of substances

• retain critical components

• eliminate what is not essential

What do renal function tests test for?

• renal disease

• water balance

• acid-base disorders

Nonprotein Nitrogen (NPN)

comprises the product of catabolism of proteins and nucleic acids, which contain nitrogen but are not part of a protein molecule

What does protein breakdown into?

proteins → amino acids → ammonia → urea

What does creatine breakdown into?

creatinine

Urea (or Blood Urea Nitrogen)

• major nitrogen-containing metabolic product of protein catabolism in humans

• synthesized by liver from ammonia

• excreted by the kidneys

What is blood urea nitrogen formed from?

• exogenous source: protein in the diet

• endogenous source: protein from the breakdown of cells in the body

In a patient with a normal to increased glomerular filtration rate (GFR), explain the direct relationship between the urea and GFR.

40% of BUN reabsorbed; 60% excreted

In a well-hydrated patient, explain the direct relationship between the urea and GFR.

more BUN excreted, results in a lower serum BUN

In a dehydrated patient, explain the direct relationship between the urea and GFR.

• 70% of BUN reabsorbed; 30% excreted

• results in the patient’s serum BUN increased and urine BUN decreased

What is the normal range of urea in the urine?

6-20 mg/dL

What is clinical affected by BUN?

• uremia

• azotemia

Uremia

increased urea/BUN w/ renal failure

Azotemia

very high BUN and creatinine concentration w/ renal failure

What is azotemia classified into?

• prerenal

• renal

• postrenal