HYPOGLYCEMIA
• Hypoglycemia involves decreased plasma glucose levels and can
have many causes—some are transient and relatively insignificant,
but others can be life-threatening.
• The plasma glucose concentration at which glucagon and other
glycemic factors are released is between 65 and 70 mg/dL (3.6 to
3.9 mmol/L); at about 50 to 55 mg/dL (2.8 to 3.1 mmol/L),
observable symptoms of hypoglycemia appear.
• The warning signs and symptoms of hypoglycemia are all related to
the central nervous system.
• The release of epinephrine into the systemic circulation and of
norepinephrine at nerve endings of specific neurons acts in unison
with glucagon to increase plasma glucose.
• Glucagon is released from the islet cells of the pancreas and inhibits
insulin.
• Epinephrine is released from the adrenal gland and increases
glucose metabolism and inhibits insulin.
• In addition, cortisol and growth hormone are released and increase
glucose metabolism.
• Symptoms of hypoglycemia are increased hu8nger, sweating,
nausea and vomiting, dizziness, nervousness and shaking, blurring
of speech and sight, and mental confusion.
• Laboratory findings include decreased plasma glucose levels during
hypoglycemic episode and extremely elevated insulin levels in
patients with pancreatic B-cell tumors (insulinoma).
GENETIC DEFECTS IN CARBOHYDRATE METABOLISM
• Glycogen storage diseases are the result of the deficiency of a
specific enzyme that causes an alteration of glycogen metabolism.
• The most common congenital form of glycogen storage disease is
glucose-6-phosphatase deficiency type 1, which is also called von
Gierke disease, an autosomal recessive disease.
• This disease is characterized by severe hypoglycemia that coincides
with metabolic acidosis, ketonemia, and elevated lactate and
alanine.
• A glycogen buildup is found in the liver, causing hepatomegaly.
• The patients usually have severe hypoglycemia, hyperlipidemia,
uricemia, and growth retardation.
• A liver biopsy will show a positive glycogen stain.
• Liver transplantation corrects the hypoglycemic condition.
• Other enzyme defects or deficiencies that cause hypoglycemia
include glycogen synthase, fructose-1,6-biphosphatase,
phosphoenolpyruvate carboxykinase, and pyruvate carboxylase.
• Glycogen debrancher enzyme deficiency does not cause
hypoglycemia but does cause hepatomegaly.
GALACTOSEMIA
• A cause of failure to thrive syndrome in infants, is a congenital
deficiency of one of the three enzymes involved in galactose
metabolism, resulting in increased levels of galactose in plasma.
• The most common enzyme deficiency is galactose-1-phosphate
uridyl transferase.
• Galactokinase, uridine diphosphate galactose-4-epimerase.
• Galactose must be removed from the diet to prevent the
development of irreversible complications.
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•
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If left untreated, the patient will develop mental retardation and
cataracts.
The disorder can be identified by measuring erythrocyte galactose1-phosphate uridyl transferase activity.
Laboratory findings include hypoglycemia, hyperbilirubinemia, and
galactose accumulation in the blood, tissue, and urine following milk
ingestion.
Another enzyme deficiency, fructose-1-phosphate aldolase
deficiency, causes nausea and hypoglycemia after fructose
ingestion.
LIPIDS
• Commonly known as fats
• Functions
o Source of fuel
o Stability of cell membrane
o Steroid hormone production
• With special transport mechanism
• Phospholipid, Cholesterol, Trioglycerides, Fatty Acids and Fatsoluble vitamins (ADEK)
o Vitamin A – Retinol
o Vitamin D – Cholecarciferol
o Vitamin E – Alpha Tocopherol
o Vitamin K – Phytonadione
PHOSPHOLIPIDS
• Conjugated lipids
• Most abundant type of lipid
• Not an energy source
• Synthesis – liver and intestine
• Combination of 2 fatty acids and 1 glycerol
• Amphipathic
• Lungs (type II penumocytes)
• Reference range – 150-380 mg/dL
• Functions
o Surfactant – prevents the collapse of alveoli
o Cellular metabolism – permeability of cell membrane
o Blood coagulation
• Forms
o Lecithin/Phosphatidyl choline – 70%
o Sphingomyelin – 20%
o Cephalin – 10%
▪ Phosphatidyl ethanolamine
▪ Phosphatidyl serine
▪ Lysolecithin + inositol phosphatide
SPHINGOMYELIN
• Not derived from glycerol
• Sphingosine + fatty acids
• Essential component of cell membranes
• Niemann Pick Disease
o Accumulation of sphingomyelin in liver and spleen
o Deficiency in the enzyme sphingomyelinase
PHOSPHOLIPIDS
• For the assessment of fetal lung maturity
• Specimen – amniotic fluid
• Mature lung = L/S ratio ≥ 2
• Not part of the lipid panel
CHOLESTEROL
• Not a source of fuel
• Synthesized in the liver
• Transport and excretion – promoted by estrogen
• Should be measured in adults 20 years of age and older – at least
once every 5 years
• Reference range
o < 200 mg/dL = desirable
o 200-239 mg/dL = borderline high
o ≥ 240 mg/dL = high
• Functions
o Precursor of steroid hormones
o Fluidity of cell mebrane
o Bile acid formation
o Vitamin D formation
• Steroid hormone
o Progesterone
o Cortisol
o Aldosterone
o Androgen
o Estrogen
• Diagnostic significance
o Evaluate risk for atherosclerosis, myocardial and coronary
arterial occlusions
o Thyroid function test
o Liver function test
o Renal function test
o Monitor effectiveness of lifestyle change
• Sources
o Endogenous – liver
o Exogenous – diet
• Forms
o Cholesterol Ester – 70%
▪ Plasma and serum
▪ Bound to fatty acid
▪ LCAT – esterification
▪ Lecithin cholesterol acyl transferase
▪ Removal of fatty acid from lecithin
▪ Liver – synthesis
▪ Apo A-1 – activator of LCAT
o Free Cholesterol – 30%
▪ Serum, plasma, and RBC
▪ Non-esterified
▪ Hydrolysis
PATIENT PREPARATION
• Usual diet for 2 weeks prior to testing
• Fasting is not a requirement
• Sample: plasma or serum
MEASUREMENT
• Total cholesterol is measured rather than its forms
• Cholesterol increases with age, with women having lower values
than men before age 45
• Serum cholesterol increases at 2 mg/dL/year between 45 to 64
years old
METHODS FOR CHOLESTEROL
Chemical method
• Liebermann-Burchardt Reaction
o End color – green
o End product – cholestadienyl monosulfonic acid
o Reagent – LB reagent
• Salkowski Reagent
o End color – red
o End product - cholestadienyl disulfonic acid
o Reagent – Salkowski reagent
• Precautions
o Avoid hemolyzed sample – false increase
o Avoid icteric samples – false increase
o Avoid water contamination
o Precise and accurate timing for color development
Enzymatic method
• Routine
• Principle - H₂O₂ production
• Hemolysis – false increase
• Bilirubin – false increase and false decrease
CDC Reference Method
• Abell, Levy and Brodie method
• KOH
• Hexane
• LB reagent
Increased Cholesterol
• Hyperlipoproteinemia type II, III, IV
• Biliary cirrhosis
• Nephrotic syndrome
• Poor controlled diabetes mellitus
• Alcoholism
• Primary hypothyroidism
Decreased Cholesterol
• Severe liver disease
• Malnutrition
• Hyperthyroidism
• Malabsorption syndrome
TRIGLYCERIDES
METHODS OF TGL MEASUREMENT
LIPOPROTEINS
MAJOR LIPOPROTEINS
COMPOSITION
MINOR LIPOPROTEIN
ABNORMAL LIPOPROTEINS
LIPOPROTEIN METHODOLOGIES
Ultracentrifugation
Electrophoresis
Chemical Precipitation
= use of polyanions (Heparin) and divalent cations such as manganese
Immunochemical Methods
HDL Measurement
Beta Quantification
LIPID DISORDERS
Tangier’s Disease
Tay-Sachs Disease
Abetalipoproteinemia
Hypobetalipoproteinemia
= decreased LDL
= decreased cholesterol
Mixed Hyperlipoproteinemia
Dysbetalipoproteinemia
Hyperprebetalipoproteinemia
Combined Hyperlipoproteinemia
Hyperchylomicronemia
Hypercholesterolemia
AMINO ACIDS
Essential Amino Acids
Non-essential Amino Acids
AMINOACIDOPATHIES
= rare inherited disorder of amino acid metabolism