Module 2 - Carbohydrates Flashcards
1. Classify carbohydrates into major groups 2. Describe digestion and absorption of carbohydrates 3. Describe metabolism of monosaccharides 4. Describe the regulation of blood glucose 5. Describe analytical techniques for the assessment of glucose in blood and urine 6. Describe diabetes mellitus 7. Describe disorders of carbohydrate intolerance and hypoglycemia
Define carbohydrates
Organic molecule consisting primarily of carbon, hydrogen, and oxygen
Contain either an aldehyde group or ketone group
What are the 3 types of carbohydrates?
Monosaccharides
Oligosaccharides
Polysaccharides
Define monosaccharide
Simple sugar that when hydrolyzed are broken down into molecules that are no longer carbohydates
Define oligosaccharide
Carbohydrates composed of 2-10 monosaccharides
Define polysaccharides
Carbohydrates composed of >10 monosaccharides
Define isomer
Molecules with the same formula but different arrangements
What is the most common form of glucose in the body?
B-D (beta-D)
What are disaccharides?
Two monosaccharides bonding by a glycosidic bond
What are examples of disaccharides?
Sucrose (glucose + fructose)
Lactose (glucose + galactose)
Maltose (glucose + glucose)
What is sucrose?
Glucose + fructose
What is lactose?
Glucose + galactose
Found in milk
What is maltose?
Glucose + glucose
Major degradation product of starch
What are 2 examples of polysaccharides?
Glycogen and starch
What is glycogen?
Major form of stored carbohydrate in animals
Very compact structure, large amount of energy
What is starch?
Major form of stored carbohydrate in plants
Branched = amylopectin Unbranched = amylose
How is starch digested?
Amylase breaks it into glucose
Where is amylase secreted?
Saliva and pancreatic juice
How are disaccharides digested?
Broken down into their 2 components by disaccharidases secreted in pancreatic juices
How is each disaccharide broken down?
Sucrose -> sucrase
Lactose -> lastase
Maltose -> maltase
What happens if there is a deficiency in an enzyme needed to break down a disaccharide?
Malabsorption
Nausea, vomiting, cramping (lactose intolerance)
Why must disaccharides be broken down?
Only monosaccharides can be absorbed
How are monosaccharides absorbed?
Glucose and galactose are absorbed by active transport
Fructose is absorbed by diffusion
What happens once monosaccharides are absorbed?
They move into the duodendal mucosal cells and are transported to the liver to be converted to glucose
What metabolic pathways can glucose go through during metabolism?
Glycogenesis
Anaerobic glycolysis
Aerobic glycolysis
Pentose shunt
What is glycogenesis?
Storage of excess glucose in cells
What is anaerobic glycolysis?
In anaerobic conditions (like in muscles) glucose is converted to pyruvate then lactate creating minimal ATP (2)
What is aerobic glycolysis?
Glucose is converted to pyruvate then further oxidized through the Kreb’s Cycle to produce lots of ATP (36) and reduced coenzymes like NADH
Define cellular respiration
Cabohydrate metabolism
Conversion of glucose into energy
ATP is stored in the bonds broken in glycolysis
What is the Pentose Shunt?
A reaction off the Embden-Meyerhof pathway (anaerobic) that creates NADPH
Define gluconeogensis
Synthesis of new glucose from non-carbohydrates like lactate, amino acids, etc
What cells can perform gluconeogensis?
Mostly liver and renal tubular cells
What is the problem with gluconeogensis?
Energy expensive
6 ATP to make 2 pyruvate
What substances can liver cells use for gluconeogensis?
Lactate
Pyruvate
Amino acids
Glycerol
Describe gluconeogenesis using lactate
Lactate made anaerobically in RBC’s and muscles diffuses into the liver
The liver can convert the lactate back into pyruvate and then into glucose
Describe gluconeogensis using glycerol
Glycerol formed from triglyceride hydrolysis can be converted in the liver back into glucose
What is the typical fasting blood glucose level?
3.3-6.0 mmol/L
What is triggered when blood glucose levels are low?
Production and release of glucagon by pancreas alpha cells
What is triggered when blood glucose levels are high?
Production and release of insulin by pancreas beta cells
What does glucagon do?
Binds to liver cells, activating glycogenolysis
Also increases gluconeogenesis
Increases blood glucose levels
What happens during glycogenolysis?
Glycogen is broken down and glucose is released into the blood to raise the blood glucose level
What does insulin do?
Stimulates extra-hepatic uptake of glucose from the blood
Also induces glycogenesis, glycolysis, etc
Lowers blood glucose levels
What other hormones raise blood glucose?
Cortisol
Epinephrine
Growth hormone
How does cortisol raise blood glucose?
Stimulates liver to increase glucoeneogenesis and glycogenolysis
How does epinephrine raise blood glucose?
Stimulates glycogenolysis in response to stress
How does growth hormone increase blood glucose?
Increases gluconeogenesis and glycogenolsis and inhibits glucose uptake by cells
What is the renal threshold?
The maximum concentration of a substance in the blood that can be re-absorbed from the urine
Why is there usually no glucose in the urine of healthy people?
The kidneys completely re-absorb the glucose
What is the renal threshold of glucose?
10 mmol/L
What is the difference of glucose in whole blood vs serum/plasma?
Whole blood glucose is around 10% lower
Why must the plasma/serum be separated from the cells within 1-2 hours for accurate glucose measurements?
The cells will use the glucose if not separated and decreased the result
How much glucose is lost per hour if cells are not separated from the serum/plasma?
About 5%
How can CSF glucose levels be used?
Identify bacterial meningitis
Lower glucose levels
What are the 2 popular methods for measuring glucose?
Glucose oxidase
Hexokinase
What are the basics of the glucose oxidase method?
Very specific, reacts with only B-D Glucose
Conversion of glucose (with oxygen consumption) to glucoinc acid and hydrogen peroxide
What are the 2 ways to measure the glucose oxidase test end products?
- Polaropgraphically (disappearance of oxygen)
2. Colormetric (colored endproduct)
How does the polarographic glucose oxidase method work?
Measures the disappearance of oxygen with an O2 electrode
How does the colormetric glucose oxidase method work?
Hydrogen peroxide + peroxidase = colored oxidized chromogen
What is the problem with the colormetric glucose oxidase method?
Subject to positive and negative interference
What causes negative interference in the Trinder’s Reaction for glucose?
Increased uric acid, bilirubin, and ascorbic acid causes decreased values
Because they are also oxidized by peroxidase instead of the chromogens
What causes positive interference in the Trinder’s Reaction for glucose?
Strong oxidizing substances
Oxidize the chromogens past the point the glucose would
Write the formula for the Trinder’s Reaction for glucose
Glucose + H2O + O2 –(glucose oxidase)> glucoinc acid + H202
H202 + chromagen –(peroxidase)> oxidized chromogen + H2O
What is the colormetric glucose oxidase test also called?
Trinder’s Reaction
Is the glucose oxidase or hexokinase method more accurate?
Hexokinase
Why is the hexokinase method more accurate for glucose measurement?
It is more specific and has less interference
How does the hexokinase method work?
Glucose is converted to G6P by hexokinase
G6P and NADP are converted to 6PG and NADPH
NADPH measured photometrically is equal to glucose in the sample
Write the reactions for the hexokinase method
Glucose + ATP –(hexokinase)> G6P
G6P + NADP –(G6P dehydrogenase)> NADPH
NADPH = Glucose
What samples can be used in the hexokinase method?
Serum, plasma, urine, CSF, and serous fluids
Are there interferences with the hexokinase method?
Gross hemolysis
Markedly elevated bilirubin
What method do glucose meters use to measure glucose?
Glucose dehydrogenase
How does the glucose dehydrogenase method work?
Glucose and NAD make gluconolactone and NADH
NADH is measured photometrically and is equal to glucose
Write the reaction for the glucose dehydrogenase method
Glucose + NAD –(GDH)> Gluconolactone + NADH + H
NADH measured
Describe the 2 hour GTT
Patient fasts
Patient drinks a 75g glucose drink
Glucose level taken 2 hours later
Describe the gestational diabetes screen
No fasting
Patient drinks 50g glucose drink
Glucose level taken after 1 hour
What are the normal fasting and non fasting glucose levels?
Fasting 3.3-6.0 mmol/L
Non-fasting 3.3-11.0 mmol/L
What is the difference of glucose values in an arterial sample?
15% higher
What is the normal glucose result after a 2 hour GTT?
< 7.8 mmol/L
What is the normal glucose result after a gestational diabetes screen?
< 11.0 mmol/L
When might a GTT be indicated after a gestational diabetes screen?
If result is between 7.8-11.0 mmol/L
What are the critical glucose levels?
= 2.5 mmol/L
>/= 25.0 mmol/L
What is the difference for CSF glucose levels compared to serum/plasma?
CSF levels are about 60% of serum levels
What are the criteria for DM diagnosis?
2 of the following on different days
- Fasting glucose > 7.0 mmol/L
- 2h PP > 11.1mmol/L
- Random glucose > 11.1 mmol/L
- HbA1C >/= 6.5%
What are pre-diabetes results?
- Fasting glucose between 6.1-7.1 mmol/L
2. 2h GTT between 7.8-11.1 mmol/L
Define hyperglycemia
Elevated blood glucose
What causes hyperglycemia other than diabetes?
Hypoinsulinemia
Hyperadrenalism
Hyperpituitarism (acromegaly)
Pheochomocytoma
Define diabetes mellitus
Metabolic disorders characterized by hyperglycemia due to:
insufficient insulin secretion
Defective insulin action
Target tissue insulin resistance
What are lab findings in diabetes mellitus?
Hyperglycemia Glycosuria Increased urine SG Increased serum and urine osmolality Ketonemia Ketonuria Acidosis Abnormal electrolytes
What are complications of diabetes mellitus?
Hyperlipidemia
Heart and vascular disease
Kidney and retina damage
Nerve damage/loss of sensation in extremities
Describe type 1 diabetes
Absolute insulin deficiency with hyperglycemia and frequently ketoacidosis
10-20% of diabetes usually early onset
Usually insulin dependent
What might cause insulin deficiency?
Autoantibodies against pancreatic beta cells causing destruction
Other autoantibodies (against insulin, etc)
What are symptoms of type 1 diabetes?
Polyuria, polydipsia (thirsty), polyphagia (hungry), weight loss
Describe type 2 diabetes
Insulin resistance
Secreted insulin is less effective than normal in activating glucose uptake
80-90% of diabetes, later onset, less severe
Usually controlled with diet and exercise
Describe gestational diabetes
Glucose intolerance induced by pregnancy
Increased metabolic demand, insulin can only raise so much
High blood glucose transfers to fetus which can lead to after birth hypoglycemia
What are insulin levels like in type 1 diabetes?
Low levels
What are insulin levels like in type 2 diabetes?
Usually high levels
How is DM monitored?
HbA1C (glycosylated hemoglobin)
Fructosamine (glycosylated albumin)
Urine microalbumin
How does HbA1C monitor DM?
Blood glucose slowly binds to HbA proportional to glucose levels
So levels can be used to monitor blood glucose over time (2-3 months)
What is the normal range of HbA1C?
4.0-6.0% of Hb
Diabetic target <7.0%
How does fructosamine monitor DM?
Albumin becomes glycosylated over time but has a shorter lifespan
Monitors 1-3 week glucose levels
How does urine microalbumin monitor DM?
Damage to glomerular membrane causes increased urine albumin
Allows for early intervention
Why are ketones produced in type 1 DM?
Glucose is not entering cells to lipolysis is done for energy
This leads to fatty acids being taken in by the liver and being converted to cholesterol and ketones
What are the 3 ketones?
Acetone
Acetoacetic acid
B-hydroxybutyric acid
What happens when ketones accumulate?
Ketones are excreted without taking their H so blood pH decreases creating ACIDOSIS
Na and K leave with ketones creating dehydration and electrolyte imbalance
What are findings in ketoacidosis?
Hyperglycemia Acidosis Ketonuria Glycosuria Dehydration Electrolyte imbalance
SEVERE = DIABETIC COMA
What is diabetes insipidous?
Decreased secretion of antidiuretic hormone causing polyphagia and polyuria
Define hypoglycemia
Decreased glucose levels too low to fuel body
When does hypoglycemia happen most often?
When diabetics take insulin to lower blood sugar
too much insulin, missed meal, eating too little
Define hyperinsulinemia
Hyper secretion of insulin
due to hyperactive beta cells in pancreas
or
Beta cell tumors
Define hypoadrenalism
Addison’s Disease
Lack of epinephrine and glucocorticoids = decreased glycolysis, glycogenolysis, and gluconeogensis
How does hypothyroidism affect glucose?
Decreases glycolysis
How do liver problems affect glucose?
Drugs and chemicals can poison liver
Inhibition of gluconeogenesis
Ethanol induced glycogen depletion
What is galactosemia?
Genetic disorder resulting in enzyme deficiency and unable to convert galactose
Increased galactose can cause growth and mental issues
Must prohibit all sources of galactose
What is lactose intolerance?
Decreased levels of lactase result in lactose accumulation and metabolism by gut bacteria causing cramping and GI symptoms
When is a lactate test used?
Sepsis, heart or lung failure, liver failure
What do lactate levels show?
Elevated tissue hypoxia (acid base and oxygenation status)
Low O2 = anaerobic glycolysis producing higher levels of lactate
List the 3 main classifications of carbohydrates
Monosaccharides
Oligosaccharides
Polysaccharides
List the 3 main dietary monosaccharides
Glucose
Galactose
Fructose
Define isomer
Molecules with the same molecular formula but different structural arrangement
State the most common form of glucose in the body
B-D Glucose
List the 3 common disaccharides and the monosaccharides that make them
Lactose - galactose and glucose
Sucrose - glucose and fructose
Maltose - glucose and glucose
Name the enzyme that digests starch and its two sources in the body
Amylase
Saliva and pancreatic juices
State which class of carbohydrate is absorbed
Monosaccharides
Name the molecule that stores energy in high energy phosphate bonds
ATP
Briefly describe anaerobic glycolysis (embden meyerhof)
Non-O2 dependent
Glucose split into 2 pyruvate and minimal ATP
Pyruvate converted to lactate
State which step of glycolysis is not reversible in most cells, including the name of the enzyme that catlyzes this step.
Also indicate which tissue can reverse this step.
Conversion of glucose to G6P by hexokinase is not reversible
EXCEPT by liver cells
Define glycogenesis and glycogenolysis
Glycogenesis: excess glucose converted to glycogen
Glycogenolysis: breakdown of glycogen back to G6P
Define gluconeogenesis and state the main disadvantage
Synthesis of new glucose from non-carbohydrate sources (lactate, amino acids, glycerol, fatty acids)
Energy expensive, not efficient
List four non-carbohydrate sources for gluconeogensis
Lactate
Amino acids
Glycerol
Fatty acids
Name which hormone is released in response to low blood glucose
Glucagon
Name which hormone is released in response to high blood glucose
Insulin
State the main action of glucagon and the primary target tissue
Raises blood glucose by acting on liver to break down glycogen to produce more glucose
State the main action of insulin and the primary target tissue
Lowers blood glucose by acting on extra-hepatic cells to increase glucose uptake
List the 3 other hormones involved in glucose regulation and state whether they act to raise or lower blood glucose
Cortisol/ACTH - Raise glucose by glycogenolysis and gluconeogenesis
Epinephrine - Raise glucose by glycogenolysis
Growth hormone - Raise glucose by glycogenolysis and gluconeogensis and inhibiting uptake
Define renal threshold
Maximum level of substance in the blood that can be fully re-absorbed by the kidneys
State the renal threshold of glucose and whether is is normally found in urine
10 mmol/L
Not normal in urine
State the difference in glucose values between serum/plasma and whole blood
10% less in whole blood
State the length of time required for a patient to fast
8 hours minimum
State the preferred handling requirement for serum/plasma samples
Spun in 1-2 hours after collection and separated from cells
Refrigerated
State the collection preservative that should be used if glucose testing is significantly delayed
Sodium fluoride
State the role of glucose measurement in CSF
Help detect bacterial meningitis
Decreased glucose
List the two main methods for measuring glucose
Glucose oxidase
Hexokinase
State the form of glucose that glucose oxidase is specific for
B-D glucose
Describe the two measurement techniques that can be used in glucose oxidase methods, and which is more susceptible to interferences
Amperometrically - measure O2 disappearance by O2 electrode
Colormetrically - measure oxidized chromogens by H2O2
Aperometric has more interference by bilirubin, ascorbic acid, and uric acid
State what is actually being measured in the hexokinase method, including wavelength
Measuring NADPH at 340nm
Describe the 2h PP glucose test and an advantage over the OGTT
Patient drinks 75g glucose
Glucose level taken after 2 hours
Advantage is no fasting required
Provide the reference range for fasting serum/plasma glucose and for a 2h PP
Fasting 3.3-6.0 mmol/L
2h PP = < 6.7 mmol/L
State the approximate difference in values from serum for arterial/capillary and CSF samples
Arterial 15% more
CSF 60% of serum level
List 3 causes of hyperglycemia in DM
- Insufficient insulin secretion
- Defective insulin action
- Target tissue insulin resistance
List the typical findings in DM
Clinical and lab
Polyuria, polyphagia, polydipsia, weight loss, confusion
Hyperglycemia, glycosuria, increased serum and urine osmolality, ketonemia, ketonuria
Describe the disorder in type 1 DM
Insulin deficiency due to decreased secretion
May be due to autoantibodies against pancreatic B cells
Describe the disorder in type 2 DM
Insulin resistance
May be due to target tissues not as responsive
or
Secreted insulin less effective
Compare and contrast type 1 and 2 DM with regards to:
cause blood insulin level onset control frequency of ketoacidosis
TYPE 1: C: insulin deficiency, maybe autoantibodies BIL: low O: early C: insulin FOK: frequent
TYPE 2: C: insulin resistance BIL: usually high O: late C: diet and exercise FOK: rare
List the complications associated with DM
Hyperlipidemia causing:
artherosclerosis
Damage due to glycation of proteins:
vascular, heart, kidney, retina, nervous
List the criteria for diagnosing DM
Two on different days
Fasting glucose > 7.0 mmol/L
2h PP glucose > 11.1 mmol/L
Random glucose > 11.1 mmol/L
HbA1C >/= 6.5%
State the analyte useful for long term monitoring of blood glucose levels, and the time frame it is useful for
HbA1C
2-3 months
State the testing performed on urine for diabetic patients and what it is used for
Urine microalbumin
Glomerular damage monitoring
Briefly describe the formation of ketones in type 1 DM
Low glucose, not entering cells
Lipolysis for energy creates fatty acids that are converted to ketones and cholesterol
List the common findings in ketoacidosis
Hyperglycemia Acidosis Ketonuria Glycosuria Dehydration Electrolyte imbalance
State the most common cause of hypoglycemia
Diabetics taking insulin
overdose, missed meal, not eating enough
State the disorder in galactosemia
Enzyme deficiency = unable to convert galactose
State the disorder in lactose intolerance
Decreased lactase = lactose accumulation in GI
Which of the folloing promotes gluconeogenesis?
a. cortisol
b. insulin
c. calcitonin
d. somatostatin
e. epinephrine
a. cortisol
Glucose oxidase converts glucose into gluconic acid and
a. hydrogen peroxide
b. carbon dioxide
c. bicarbonate
d. water
e. ADP
a. hydrogen peroxide
Hexokinase catalyzes formation of ___ from glucose and ATP
a. NADPH
b. acetyl CoA
c. G6P
d. F6P
e. lactose
c. G6P
What’s the best specimen for glucose analysis?
a. serum
b. fluoride plasma
c. heparinized plasma
d. EDTA plasma
e. whole blood
b. fluoride plasma
Which of the following is secreted by the pancreas when there is hypoglycemia?
a. human growth hormone
b. glucagon
c. insulin
d. LH
e. epinephrine
b. glucagon
Which assay of glucose my be monitored by measuring the rate of oxygen disappearance?
a. glucose oxidase
b. hexokinase
c. o-toluidine
d. clinitest
e. benedict’s reaction
a. glucose oxidase
Which method is most specific for B-D glucose?
a. glucose oxidase
b. hexokinase
c. o-toluidine
d. clinitest
e. benedict’s reaction
a. glucose oxidase
G6PD is the coupling enzyme for which of the glucose assays?
a. glucose oxidase
b. hexokinase
c. o-toluidine
d. clinitest
e. benedict’s reaction
b. hexokinase
The term gluconeogensis referes to conversion of
a. glycogen into glucose
b. glucose into pyruvate
c. non-carbohyrates into glucose
d. fructose into glucose
e. fatty acids into ketones
c. non-carbohydrates into glucose
Which of the following is not a disaccharide
a. sucrose
b. maltose
c. lactose
d. galactose
d. galactose
Carbohydrates are
a. sweet to the taste
b. sugars
c. aldehydes
d. ketones
e. c and d
e. c and d
aldehydes and ketones
The pancreatic enzyme amylase acts upon
a. starches
b. disaccharides
c. monosaccharides
d. glycerol
e. fatty acids
a. starches
Insulin is synthesized and stored in the
a. adrenal cortex
b. adrenal medulla
c. alpha cells of the pancreas
d. beta cells of the pancreas
d. beta cells of the pancreas
In normal CSF the glucose concentration is approximately ___ of the plasma glucose level
a. 30%
b. 45%
c. 60%
d. equal to that
c. 60%
Which of the following methods estimates the urine sugar concentration by measuring the total reducing substances
a. copper sulfate
b. glucose oxidase
c. hexokinase
d. ferricyanide
a. copper sulfate
Which of the following chemicals is used in blood collection tubes to help preserve the integrity of the blood glucose concentration
a. citrate
b. EDTA
c. fluoride
d. oxalate
c. fluoride
In which of the following methods is the glucose concentration linked to a change in the oxygen concentration in the reaction mixture
a. copper sulfate
b. glucose oxidase
c. hexokinase
d. ferricyanide
b. glucose oxidase
Due to an enzyme deficiency which disaccharide accumulates in the intestine causing significant GI discomfort
a. glucose
b. galactose
c. lactose
d. maltose
c. lactose
Which form of diabetes manifests itself later in life and is associated with obesity, physical inactivity, and glycosuria
a. congenital
b. gestational
c. insulin dependent
d. non-insulin dependent
d. non-insulin dependent
The term ketone bodies refers to all of the following compounds except
a. acetic acid
b. acetoacetic acid
c. acetone
d. beta-hydroxybutyric acid
a. acetic acid
A patient with a severe uncontrolled case of DM shows all of the following conditions except
a. glycosuia
b. hyperglycemia
c. ketosis
d. metabolic alkalosis
d. metabolic alkalosis
Which of the following methods provides information about glucose metabolism over a 3 month period
a. fructosamin
b. glucose oxidase
c. glycosylated hemoglobin
d. oral glucose tolerance
c. glycosylated hemoglobin
Which hormone functions to increase the cellular uptake of glucose
a. catecholamines
b. cortisol
c. glucagon
d. insulin
d. insulin
