Other Carbohydrate Metabolic Disorders

how is hypoglycemia characterized

blood glucose levels below 70 mg/dL

when do symptoms of hypoglycemia occur?

levels fall below 60mg/dL

what levels does the brain functions get affected?

below 50mg/dL

what are the two types of hypoglycemia?

reactive and fasting

what is reactive hypoglycemia also known as

postprandial type

what causes reactive hypoglycemia?

by a stimulus

injecting insulin at the wrong time, too much insulin, not eating enough between meals or skipping meals, exercising more than normal,

alcohol inhibits glyconeogensis and glycogenesis

how is reactive hypoglycemia diangosed by?

Whipple’s triad

what is Whipple’s triad?

low blood glucose

classic symptoms of hypoglycemia

relief of symptoms after plasma glucose level is raised

what is fasting hypoglycemia also known as

postabsorptive type

is fasting hypoglycemia common?

no, after fasting is rare

how does fasting hypoglycemia occur?

occurs as a response to insulin-producing tumors of the pancrease (insulinomas) or other tissues, hepatic dysfunction, glucocorticoid deficiency, sepsis, or low glycogen stores.

what is glucocorticoid deficiency?

A condition where the adrenal glands do not produce enough cortisol

since cortisol increase glucose in blood stream

when is hypoglycemia diagnosed?

after 72hr fasting in hospital

when do people with true fasting hypoglycemia show low glucose level?

within 12 hours after fasting begins

S/S of hypoglycemia

heart papitations, shakiness/dizziness, anxiety, sweating, hunger/tingling sensation around mouth, irritability

what effects to the brain when glucose is too low?

confusion, indifferences, abnormal behavior, inability to complete routine tasks

visual disturbances, dobule vision or blurred

seizures, loss of consciouness (uncommon)

are glycogen storage dieases rare?

yes, due to enzyme defects and accumulation of glycogen

what is the most common glycogen storage disorder

type I: glucose-6-phosphate

what is glucose-6-phosphate

an enzyme that converts glycogen into glucose

what is glucose-6-phosphate deficiency known as

von Gierke’s diease

what % of people are effected by glucose-6-phosphate deficiency

25%

what is glucose-6-phosphate deficiency?

accumulation of glycogen in the liver and skeletal muscle, causing ineffective glycogenolysis, hypoglycemia during fasting states, growth retardation, ketosis, lactic acidosis, and hepatomegaly

what is the treatment of glucose-6-phosphate deficiency?

first to treat the hypoglycemia,

eat more carbohydrate meals so the body does not use glycogenolysis

eat corn starch

continous night feeding

reduce exercise in childern

where does galactose come from?

break down of lactose

what is the most common defect in galactose metabolism?

galactose-1-phosphate uridyltransferase

what happens when galactose-1-phosphate uridyltransferase is defected

lead to accumulation of galactose in plasma, urine, and tissues

what are consequences of galactose-1-phosphate uridyltransferase defect

failure to thrive, liver problems, kidney problems, CNS problems, hypoglycemia

is the a cure for galactose-1-phosphate uridyltransferase defect?

no cure due to being a autosomal recessive disorder

whati is treatment for galactose-1-phosphate uridyltransferase defect?

remove galactose and lactose from diet

what are some testing methods for galactose?

blood test

urine test: clinatest

genetic testing

where does frutose comes from

break down of glucose in fruits

what are the 3 enzymes that can be defective in frutose?

fructokinase, fructose-1-phosphate aldolase, fructose-1,6-diphosphatase

which of the 3 fructose enzyme defect is least severe?

fructokinase

pass into the urine (frutosuria)

which of the 3 fructose enzyme defect is most severe?

fructose-1-phosphate aldolase, fructose-1,6-diphosphatase

serious consequences when there is dietary intake of fruits, honey, and syrup (corn)

ketosis, lactic acidosis, liver failure

how is frutose enzyme defect diagnosised?

chromtography; separate and measure individual carbohydrates (clinatest)

fructose-1-phosphate aldolase-B is responisble for degrading what?

fructose-1-phosphate to DHAP

what is the function of fructokinase?

Degrades fructose to fructose-1-phosphate

Fructokinase is the 1st enzyme in fructose metabolism, converting fructose into fructose-1-phosphate.

a deficiency in fructokinase causes which condition?

fructosuria

deficiency in aldolase B causes which condition, and what is a key consequence?

frutosemia or hereditary fructose intolerance

Glucose production is inhibited, fructose accumulates in liver, kidneys, and blood, and ATP available for cellular use is reduced.

what is the fuction of fructose-1,6-dipphosphatase?

Converts fructose-1,6-diphosphate to fructose-6-phosphate, enabling gluconeogenesis from amino acids, glycerol, or lactate

A deficiency in fructose-1,6-diphosphatase leads to which set of clinical findings?

hypoglycemia, lactic acidosis, glyceroluria

What clinical conditions are lactate measurements useful for evaluating?

useful for carbohydrate disorders, including diabetes mellitus and glycogen storage diseases.

Lactate results directly from what reaction?

Lactate is a by-product of glucose metabolism formed directly from the conversion of pyruvate and NADH by lactate dehydrogenase (LD)

Which enzyme catalyzes the conversion between pyruvate and lactate?

Lactate dehydrogenase (LD)

In which tissues/cells is the pyruvate-lactate reaction prevalent?

erythrocytes, brain, liver, kidneys, and skeletal muscle.

When do blood lactate levels accumulate?

accumulate/rise when the liver becomes saturated with lactate, since it can no longer clear it efficiently.

what conditions are associated with increased lactate production?

increase oxygen demand

loss of blood

shock

cancer

strenous exercise

lactate is produced from pyruvate in _________________ conditions

anaerobic

acetyl-CoA is produced from pyruvate in _________________ conditions

aerobic

What type of method is commonly used to measure lactate?

enzymatic spectrophotometric methods.

Which enzyme converts lactate and O2 into pyruvate and H2O2?

Lactate oxidase

Which enzyme converts H2O2 and a non-colored chromogen into a colored dye?

Peroxidase

At what wavelength is the red colored dye measured in the spectrophotometric lactate method?

540 nm, and its intensity is proportional to the patient's lactate levels.

What alternative method can be used to measure hydrogen peroxide (and thus lactate)?

amperometric electrode measurement of hydrogen peroxide.

H2O2 forms in proportion to lactate and generates a measurable current.

In the amperometric electrode method, what does hydrogen peroxide generate, proportional to lactate levels?

generates a measurable electrical current.

not common

What specimen types can be used to measure lactate?

venous plasma, venous or arterial whole blood (green top), and also in CSF.

What pre-analytical factors can affect accurate lactate results?

Exercise prior to collection, or interference with blood flow (e.g., prolonged tourniquet use)

How should a lactate specimen be handled to ensure accurate results?

collecting in the correct tube to reduce glycolysis, delivering the specimen to the lab on ice, and immediately separating plasma from cells.

Lactate accumulation leads to a process similar to what condition, and in what patient population is it relatively common?

similar to ketoacidosis, and is relatively common in chronically ill patients.

Lactate accumulation is associated with which patient groups?

diabetic patients as well as congestive heart failure patients.

common in older adults

What is the mortality significance of prolonged elevated lactate?

very high mortality rate when present for more than a short time.