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CARBOHYDRATES

Carbohydrates have been named as such because of the general


empirical formula of monosaccharides, Cn (H2O)m, which shows the same
proportion of hydrogen and oxygen with that of water. They have been
described before as hydrates of carbon, thus the name carbohydrates. The
true nature of carbohydrates however, is that of polyhydroxy aldehydes and
polyhydroxyketones and their derivatives.
Functions
1. Energy
2. Storage
3. Structural
4. Molecular Recognition
Nomenclature and Classification
According to:
1. Number of Carbons (for simple sugars)
2. Number of Basic Units
3. Location of C=O
4. Steroechemistry
CARBOHYDRATE METABOLISM
The body normally has its way of regulating the digestion, absorption,
assimilation, storage, and utilization of carbohydrates. They have to be
digested and absorbed in the simplest form. Glucose is the carbohydrate
readily utilizable by the body for energy. It enters glycolysis in order to
produce ATP. The body stores glycogen, which can release glucose when
needed. There are various processes and regulatory hormones that control
the bodys utilization of carbohydrates and maximize its use.
Important Processes
1. Glycolysis- the utilization of glucose for energy
2. Glycogenesis- the synthesis of glycogen from glucose for storage
3. Glycogenolysis- the breakdown of glycogen to release glucose for
energy
4. Gluconeogenesis the utilization of non carbohydrate compounds for
energy

5. Lipolysis- the breakdown of fats, which can eventually be used for


energy
6. Lipogenesis- the synthesis of fats
Regulatory Hormones
1. Insulin- a peptide hormone produced by the pancreatic islet cells;
synthesized from pre proinsulin and proinsulin; lowers blood glucose by
promoting its cellular uptake
2. Glucagon- a hormone produced by the pancreatic islet cells;
increases blood glucose by promoting glycogenolysis and
gluconeogenesis
3. Somatostatin- a hormone produced by the pancreatic islet cells
4. Others: Incretin, Epinephrine, Thyroxine, Growth Hormone, ACTH,
Cortisol
CLINICAL CONDITIONS
Hyperglycemia- an increased blood glucose level
Diabetes- a disorder characterized by hyperglycemia
Types
Diabetes insipidus- due to ADH deficiency
Diabetes mellitus- disorder of glucose metabolism
Diabetes Mellitus
Cardinal Signs- polyphagia, polydipsia, and polyuria
Types
1. Type 1- involves autoimmune cell destruction leading to absolute
insulin deficiency; represents about 5-10% of all diabetes mellitus
cases; used to be known as insulin- dependent diabetes mellitus;
usually of juvenile onset; ketosis- prone; patients usually thin
2. Type 2- involves an insulin resistance or insulin secretory defect that
leads to relative insulin deficiency; represents about 90-95% of all
cases of diabetes mellitus; used to be known as non- insulindependent diabetes mellitus; usually of maturity onset; ketosis is rare;
patients are often obese; involvement of lifestyle factors
3. Gestational Diabetes Mellitus- glucose intolerance associated with
pregnancy; due to metabolic and hormonal changes; increased risk of
perinatal complications and development of diabetes in later years

4. Other Specific Types- secondary conditions that may be associated


with drugs, chemicals, genetic defects, and other endocrine disorders

METHODS OF GLUCOSE MEASUREMENT


Non Enzymatic
1. Alkaline Copper Reduction- involves the conversion of cupric ions
into cuprous ions in the presence of reducing sugars like glucose;
used in the methods such as Benedicts. Fehlings. Folin Wu,
Nelson Somogyi and Neocuproine
2. Alkaline Ferric Reduction- involves the reduction of ferric ions into
ferrous ions; used in the method Hagedorn Jensen

3. Condensation with Phenols


4. Condensation with Aromatic Amines- used in the Ortho Toluidine
Method

Enzymatic
1. Glucose Dehydrogenase- glucose is converted by glucose
dehydrogenase into gluconolactone with the simultaneous
conversion of NAD into NADH; a chromophore is produced at the
end of the series of reactions
2. Glucose Oxidase- this is the most specific enzyme for D
Glucose; involves the conversion of glucose into gluconic acid
with H2O2 production
Colorimetric Glucose Oxidase- involves a second reaction using
Peroxidase
Saifer Gernstenfield- uses O- dianisidine as chromogen
Trinder- used phenylphenazone as chromogen

Polarographic Glucose Oxidase- measures the rate of consumption of


oxygen as glucose is converted to gluconic acid using a polarographic
oxygen electrode
3. Hexokinase- reference method for glucose

LABORATORY DIAGNOSIS
1. RBG- uses randomly collected samples; especially useful in cases of
hypoglycemia, insulin shock, and hyperglycemic coma; a value 200
mg/dl with signs and symptoms can be used to diagnose diabetes
2. FBG- requires an 8- hour fast; useful for diabetes diagnosis

3. 2 hr. PPBS- useful for monitoring glycemic control; blood glucose is


determined 2 hours after a meal
4. Oral Glucose Challenge Test (OGCT)- useful for screening for
gestational diabetes; uses a 50g glucose load; no fasting required
5. Oral Glucose Tolerance Test (OGTT)- useful for both diabetes mellitus
and gestational diabetes diagnosis; uses either a 75g (for DM and
GDM) and a 100g (for GDM) glucose load; blood samples are taken in a
series
Intravenous glucose tolerance tests are sometimes given for patients
with gastrointestinal and absorption problems
6. HBA1C- useful measure of glycemic control for the past 2- 4 months
7. Fructosamine useful for measuring glycemic control for the past 3-6
weeks; also called glycosylated albumin
8. Microalbumin- useful for detecting early renal damage especially in
diabetic patients
9. Urine Glucose becomes positive when blood glucose has reached the
renal threshold of about 160- 180 mg/dl

Analyte
Fasting Blood
Glucose
Random Blood
Glucose
OGCT
OGTT (Fasting)
OGTT (1st hour)
OGTT (2nd hour)
OGTT (3rd hour)
HbA1c

REFERENCE INTERVALS
Conventional Unit Conversion Factor
70-100 mg/dl
0.056

SI Unit
3.9-5.6 mmol/l

0.056
<130 mg/dl
DM 70-100 mg/dl
GDM <95 mg/dl
DM <140 mg/dl
GDM <180 mg/dl
DM <140 mg/dl
GDM <155 mg/dl
GDM <140 mg/dl
4-5.6%

0.056
0.056
0.056
0.056
0.056
0.01

<7.2 mmol/l
3.9-5.6 mmol/l
<5.3 mmol/l
<7.8 mmol/l
<10.0 mmol/l
<7.8 mmol/l
<8.6 mmol/l
<7.8 mmol/l
0.04-0.056

NONPROTEIN NITROGENOUS COMPOUNDS


Nonprotein nitrogenous compounds result from the metabolism
of nucleic acids, amino acids, and proteins in the body. There are
about 15 different nonportein compounds amounting to
approximately 250-400 mg/l. They include urea, amino acids, uric
acid, creatinine, creatine, and uric acid. Whole blood NPN is higher

than that of plasma because of the presence of glutathione in the red


blood cells.
UREA
- end product of protein catabolism
- synthesized in the liver
- >90% excreted through the kidneys
- around half of the total urinary solids
- affected by renal function, diet, level of protein metabolism and state of
hydration
- part of the B:C Ratio
- increased in azotemia (prerenal, renal, or postrenal)
- decreased in poor nutrition, high fluid intake, overhydration, pregnancy,
severe liver disease, as effect of some hormones
- Analytical Techniques
Direct Method- used in the Fearon Reaction where urea reacts with
diacetylmonoxime to form a chromogen diazine
Indirect Method- used in the Urease Reaction where the ammonia
produced can be measured by acidimetric titration, Berthelot Reaction
or Nesslerization

Creatinine and Creatine


-involved in muscle metabolism
- increased creatinine during decreased GFR
- Analytical Techniques
Jaffe Reaction creatinine reacts with picric acid in alkaline solution to
form a red tautomer creatinine picrate

Enzymatic- uses creatininase or creatinine amidohydrolase


URIC ACID
- end product of purine metabolism
- formation through xanthine oxidase
- hyperuricemia: leukemia, lympnoma, MM, drugs, diet, obesity,
hypertriglyceridemia, renal disease, gout, Lesch Nyhan Syndrome

- hypouricemia: Fanconis, Wilsons, Hodgkins, bronchogenic CA,


xanthinuria
- Analytical Techniques
Caraway- involves the chemical reaction of uric acid with alkaline
phosphotungstate in a protein- free solution with tungsten blue as the
end product
Uricase- uses uricase to convert uric acid into allantoin

AMMONIA
- byproduct of protein catabolism
- converted to urea
- increased in liver disease, Reyes Syndrome
- Analytical Techniques
Isothermal Diffusion
Enzymatic- uses the enzymatic reaction of ammonia with
ketoglutarate in the presence of glutamine dehydrogenase
AMINO ACIDS
- basic units of proteins
- 20 biologically significant
- essential vs nonessential
- amphoteric
- aminoacidurias may be overflow or due to inborn errors of metabolism
- Amino Acidopathies
Phenylketonuria (PKU)- inherited deficiency of phenylalanine
hydroxylase needed for the conversion of phenylalanine to tyrosine;
increased phenylalanine and phenylpyruvic acid in plasma and urine; diet
should lack phenylalanine to prevent cerebral damage
MSUD- deficiency of branched chain alpha keto acid dehydrogenase
that results to the accumulation of the branched chain amino acids
isoleucine, leucine, and valine
Transient Neonatal Tyrosinemia- most common amino acid disorder in
the neonatal period; due to an imbalance of elevated serum tyrosine
levels from protein intake and delayed maturation of the hepatic enzyme
parahydroxyphenylpyruvate dioxygenase
Secondary Aminoaciduria- may occur in cirrhosis and chronic liver
diseases
Renal Aminoaciduria- due to diminished tubular reabsorption; may be
acquired due to kidney damage or an inborn error of metabolism

Homocysteinuria- accumulation of homocysteine; clinical risk factor for


the development of coronary artery diseases
- Analytical Techniques:
Screening: TLC, Tandem MS, Photometric, Guthrie Test, Flourometric
Quantitative: Capillary Electrophoresis, GLC, HPLC, Ion Exchange LC,
Tandem MS, Molecular
Analyte
Blood Urea
Nitrogen
Creatinine
Creatine
Uric Acid

Ammonia

REFERENCE INTERVALS
Conventional Unit Conversion Factor
8-23 mg/dl
0.357
F- 0.5-1.0 mg/dl
M- 0.6-1.2 mg/dl
F- 0.2-0.7 mg/dl
M- 0.1-0.4 mg/dl
F- 2.7-7.3 mg/dl
M- 4.0-8.5 mg/dl

<114 ug/dl

88.4
76.25
0.059

0.59

SI Unit
2.9-8.2 mmol/l
F- 44-88 umol/L
M- 53-106 umol/L
F- 15-53 umol/l
M- 8-31 umol/l
F 0.16-0.43
mmol/L
M 0.24-0.51
mmol/L
< 67 umol/L

PROTEINS
Definition- polymers of amino acids produced by living cells
Composed of amino acids in varying numbers and sequences
Approximately 16% nitrogen content
Functions:
1. maintenance of plasma colloid osmotic pressure
2. transport of water- insoluble substances
3. antibodies
4. hormone structure
5. nutrients for building materials
6. catalyst
7. clotting
Classifications
A. Structure- primary, secondary, tertiary, quarternary
B. Shape- globular, fibrous
C. Solubility
D. Composition- simple, conjugated
E. Electrophoretic Mobility
SPECIFIC PLASMA PROTEINS

are proteins found in blood plasma

They serve many different functions, including:


- circulatory transport molecules for lipids, hormones, vitamins and
metals
- enzymes, complement components,protease inhibitors, and kinin
precursors
- regulation of acellular activity and functioning and in the immune
system

MAJOR PLASMA PROTEINS COMPONENTS


1. Prealbumin
- Called thyroxine binding prealbumin.
- Responsible in the metabolism of vitamin A by complexing with the
retinol binding protein
- Is rich in tryptophan (tryptophan rich pre albumin
- Quantitation is a marker of nutritional status
2. Albumin
- Protein in highest concentration in serum
- Major contributors to oncotic pressure (known also as colloid osmotic
pressure) of plasma
- General transport or carrier protein
- Measurement of albumin concentration are vital in the interpretation of
calcium and magnesium levels
3. Alpha 1 globulins
Alpha 1 antitripsin
- generally known as serum trypsin inhibitor
- It protects tissues from enzyme of inflammatory cells, especially
elastase
- In its absence, elastase is free to break down elastin, which contributes
to the elasticity of the lungs
- resulting in respiratory complications such asemphysema, or COPD in
adults and cirrhosis in adults or children
Alpha 1 fetoprotein
- a major plasma protein produced by the yolk sac and the liver during
fetal life
- AFP levels decrease gradually after birth, reaching adult levels by 8 to
12 months
- it is principally increased in open neural tube defects & decreased in
Down Syndrome
4. Alpha 2 Globulins
Haptoglobin
- It functions to bind free plasma hemoglobin

allows degradative enzymes to gain access to the hemoglobin while at


the same time preventing loss of iron through the kidneys
Alpha 2 Macroglobulin
- Largest major non immunoglobulin in plasma
- It is produced by the liver
- major component of the alpha-2 band in protein electrophoresis
5. Beta Globulins
Transferrin
- is a blood for iron delivery
- Transports ferric ion from the iron stores of intracellular or mucosal
ferritin to bone marrow
- Glycoprotein that binds iron very tightly but reversibly
- A deficiency is associated with atransferinemia.
6. Fibrinogen
- a soluble plasma glycoprotein that is synthesised by the liver
- fibrinogen can form bridges between platelets
-

MINOR PLASMA PROTEIN COMPONENTS


Ceruloplasmin
- the major copper-carrying protein in the blood
- plays a role in iron metabolism
- Mutations in the ceruloplasmin gene can lead to iron overload in the
brain, liver, pancreas, and retina.
- Lower-than-normal ceruloplasmin levels may indicate:
Menkes disease (Menke's kinky hair syndrome)
Wilsons disease (a rare copper storage disease)
Gc- Globulin
- Group-specific component globulin
- Congenital absence of this protein may be a lethal mutation, owing to
impairment of vitamin D transport
Hemopexin
- binds heme with the highest affinity of any known protein
- protects the body from the oxidative damage that free heme can cause
- Low hemopexin levels are one of the diagnostic features of a hemolytic
anemia
C- Reactive Protein
- is a protein found in the blood, the levels of which rise in response to
inflammation
- It is thought to assist in complement binding to foreign and damaged
cells and enhances phagocytosis by macrophages (opsonin mediated
phagocytosis)
PROTEASE INHIBITORS
Alpha 1 antichymotripsin- highly specific in neutralizing chymotrypsin
Inter a trypsin inhibitor- prevent autodigestion of tissue by endogenous
cellular enzyme

Antithrombin III- neutralize thrombin, which normally becomes activated


intravascularly from prothrombin during clot formation
Antiplasmin- maintains homeostasis by balancing clot formation against
dissolution
C1 esterase inhibitor- capable of inhibiting activated complement
components C1r and C1s plus some other coagulation factor
Protein C
Plasminogen activator inhibitor-1- prevent activation of plasminogen,
thereby blocking fibrinolysis at an early step
ACUTE PHASE REACTANTS
- Acute phase reactant proteins share the property of showing elevations
in response to inflammation
- Inflammation must be neutralize by enzyme inhibitors to limit their
extent of destruction
- The elevation of acute phase reactants is likely a response to the
cytokines
- Total physiologic response includes induction of fever, recruitment of
leukocyte, and catabolism of muscle
PROTEINS DETERMINATION
1. Kjeldahl Technique- reference method; involves acid digestion to
release ammonium ions from nitrogen- containing compounds
2. Refractive Index- can be accurate for measuring serum proteins as
dissolved solute for levels >2.5 g/dl
3. Specific Gravity- can be estimated using copper sulfate solutions
4. Spectrophotometry- proteins in solution absorb ultraviolet light at 280
nm, owing mostly to tryptophan, but also to tyrosine and phenylalanine
5. Turbidimetric- often used for CSF and urine samples; proteins
precipitate with TCA or SSA or other acids
6. Colorimetry
Biuret Method- copper salts in alkaline solutions form a purple complex
with two or more peptide bonds

Folin Ciocalteau- also called phenol reagent; phosphotungstomolybdic


acid oxidizes phenolic compounds like tyrosine, tryptophan, or histidine
to give a deep blue color
Lowry Assay- involves the Biuret Method followed by phenol reagent

Coomassie Brilliant Blue


Ninhydrin- produces a violet color upon reaction with primary amines
7. Dye- Binding- binding to dyes like bromphenol blue, methyl orange,
HABA (hydroxyazobenzene benzoic acid), bromcresol purple, or
bromcresol green are commonly used for albumin quantitation
8. Electrophoresis- separates serum proteins into albumin, 1 globulins,
2 globulins, globulins, and globulins

9. Nephelometry
10.
Immunoassay
Analyte
Total Protein
Albumin
Globulin
A/G Ratio
Serum Protein
Electrophoresis

REFERENCE INTERVALS
Conventional Unit Conversion Factor
6.0-7.8 g/dl
10
3.2-4.5 g/dl
10
2.3-3.5 g/dl
10
1.3-3.0
% Total Protein
Albumin- 52-65%
0.01
1- 2.5-5%
0.01
2- 7-13%
0.01
- 8-14%
0.01
- 12-22%
0.01

SI Unit
60-78 g/l
32-45 g/l
23-35 g/l
1.3-3.0
Fraction Total
Protein
0.52-0.65
0.025-0.055
0.07-0.13
0.08-0.14
0.12-0.22

LIPIDS AND LIPOPROTEINS


Lipids- organic compounds that are actually or potentially esters of fatty
acids and dissolve only in organic solvents
Functions:
1. Metabolic fuel
2. Material for membrane construction
3. Metabolic pathways

CLASSIFICATION
1. Fatty acids- long chain hydrocarbons
- Short chain, medium chain or long chain
- Saturated, monounsaturated or polyunsaturated
- Even or odd numbers of carbons
- Cis or Trans configuration
2. Glycerol esters
TAG- prevalent glycerol ester in the plasma and adipose tissues; has 3
fatty acids attached to glycerol
Phospholipids- has a phosphoric acid head group in one of the carbons
of glycerol and 2 fatty acids
Over 90% phosphatidylcholine and sphingomyelin, 3-6%
ethanolamine and serine, and 4-9% lysophosphatidylcholine
3. Sterol Derivatives
Cholesterol- source of primary and secondary bile acids, steroid
hormones and Vitamin D; Has CPPP nucleus; 60-70% esterified and
30-40% unesterified
4. Sphingosine Derivatives (Sphingolipids)
Ceramide- with fatty acid bound to sphingosine; CNS cell membrane
structure; sphingomyelin, galactosylceramide, glucosylceramide
Terpenes- with 5 branched chain units; intermediates in the production
of cholesterol; includes the fat- soluble vitamins
MAJOR LIPID CONSTITUENTS IN THE PLASMA
1. Cholesterol
2. Phospholipids
3. TAG
LIPOPROTEINS
Lipoproteins transport all the essential cholesterol and lipids in the plasma;
for the packaging, solubility, and metabolism of lipids
Apolipoproteins- the protein moiety of lipoproteins; influences enzymes in
lipid metabolism; helps bind lipoproteins to cell surface receptors
General Lipoprotein Structure

MAJOR LIPOPROTEIN CLASSES


1. Chylomicrons
2. Very Low Density Lipoproteins (VLDL)
3. Low Density Lipoproteins (LDL)
4. High Density Lipoproteins (HDL)

MINOR LIPOPROTEIN CLASSES


1. Lipoprotein A- associated with increased risk for cardiovascular
diseases; also called sinking pre lipoprotein
2. Intermediate Density Lipoproteins (IDL)
3. Lipoprotein X- abnormal lipoprotein associated with obstructive liver
disease
4. VLDL- increased in Type II Hyperlipoproteinemia; also called floating
lipoprotein

Lipoproteins are generally made up of the protein portion called


Apolipoprotein, and the lipid portion composed of cholesterol,
triglycerides, and phospholipids. The different types of lipoproteins
differ in the amount of these different components.

APOLIPOPROTEINS
1. Apo A- Apo A1 and Apo A2
2. Apo B- Apo B48 and Apo B 100

3. Apo C- Apo C1, Apo C2 and Apo C3


4. Apo D
5. Apo E
Presence in Lipoproteins
1. Chylomicrons- Apo B 48, Apo A1, Apo A IV, Apo C1, Apo C2, Apo C3,
Apo E
2. VLDL- Apo B 100, Apo C, Apo E
3. LDL- Apo B 100, Apo C
4. HDL- Apo A1, Apo A2, Apo C and Apo E
LIPOPROTEIN METABOLISM
1. Lipid Absorption Pathway
2. Exogenous Pathway
3. Endogenous Pathway
4. Reverse Cholesterol Transport Pathway
Enzymes Important in Lipoprotein Metabolism
1. Lipolytic Enzymes
LPL- derived mainly from adipose tissue, skeletal, and heart muscles;
hydrolyzes TAG in chylomicrons and VLDL; phospholipids and Apo CII
as cofactors
Hepatic TAG Lipase- secreted by hepatocytes; most active in the
hydrolysis of phospholipids and TAG in HDL2
2. LCAT- synthesized in the liver; normally present in the plasma;
transfer of fatty acids from lecithin to cholesterol; Apo A1 as
cofactor
ADULT REFERENCE RANGES IN LIPIDS
ANALYTE
REFERENCE RANGE
Total Cholesterol
140-200 mg/dl
HDL Cholesterol
40-75 mg/dl
LDL Cholesterol
50-130 mg/dl
TAG
60-150 mg/dl
NCEP ATP: CHD RISK FACTORS
1. POSITIVE RISK FACTORS
Age
Family History
Cigarette Smoking
Hypertension
LDL 160 mg/dl with 1 risk factor
LDL 130 mg/dl with 2 risk factors
LDL 100 mg/dl with CHD or risk equivalent
HDL < 40 mg/dl
Diabetes Mellitus (CHD Risk Equivalent)
Metabolic Syndrome (Multiple Metabolic Risk Factors)

2. NEGATIVE RISK FACTORS


HDL 60 mg/dl
LDL < 100 mg/dl
LIPID DISORDERS
- Collectively called dyslipidemias
- Are associated with CHD and arteriosclerosis
1. Arteriosclerosis- lipid deposition, mainly cholesteryl esters on artery
walls; initially fatty streaks, which can eventually develop into
plaques that can occlude blood flow or rupture (resulting to
thrombosis); leads to PVD, CAD, or CVD; associated with increased
LDL or decreased HDL
Tx: Bile acid sequestrants, Statins, Niacin, Fibric acid derivatives,
Ezetimibe
2. Hyperlipoproteinemia- dyslipidemia characterized by increased
lipoproteins; may be hypercholesterolemia, hypertriglyceridemia, or
combined hyperlipidemia
Hypercholesterolemia- most closely linked to heart disease; may be
familial or secondary
Hypertriglyceridemia- may be familial or secondary; generally a result of
an imbalance between the synthesis and clearance of VLDL in the
circulation; many patients with CHD have moderately increased TAG and
low HDL; can cause acute and recurrent pancreatitis when severe
Combined Hyperlipoproteinemia- increased Total Cholesterol and TAG;
may be familial [FCH, Type III Hyperlipoproteinemia (VLDL:TAG >0.30)]
3. Lp (a) Elevation- increases the risk for CHD and CVD; has an extra
apolipoprotein called apo (a) that has a high degree of homology
with plasminogen
4. Hypolipoproteinemia- low lipoprotein levels
Hypoalphalipoproteinemia-HDL Cholesterol < 40 mg/dl (isolated);
extreme risk of premature CHD
Tangier Disease- HDL Cholesterol about 1-2 mg/dl and Total Cholesterol
about 50-80 mg/dl
Acute Transitory Hypoalphalipoproteinemia- during physiologic stress
Hypobetalipoproteinemia
Andersen Disease (GSD IV)
Bassen Kornzweig Syndrome (Abetalipoproteinemia)
Familial Hypobetalipoproteinemia (FHBL)
LIPID AND LIPOPROTEIN ANALYSES
Specimen Considerations- fasting; sudden position changes
Total Cholesterol
1. Chemical Methods

Abell- Kendall- reference method; involves the Liebermann Burchard


Reaction
Reagents: Glacial HOAc, Acetic Anhydride, C. H2SO4
Other Methods that Involve LBR: Ferro- Ham; Pearson,
Stearn and
McGavach
Salkowski Reaction- uses iron salt (red)
Paratoluene Sulfonic Acid Reaction (green)
Tsugaeff Reaction (red)
2. Enzymatic Methods
Triglycerides
1. Chemical Methods
Hantzch Condensation (Van Handel and Silversmith)- reference
method
2. Enzymatic Methods
Lipoproteins
1. Analytical Ultracentrifugation- based on density; reference method
2. Electrophoresis- Agarose gel is the most commonly used support
medium; Oil Red O, Fat Red 7B and SBB as stains
3. Standing Plasma Test- for detection of increased chylomicrons; patient
plasma is allowed to stand overnight undisturbed in a refrigerator;
development of a floating creamy layer indicates increased chylomicrons
4. Polyanion Precipitation- lipoproteins are prsipitated using anions such
as heparin sulfate, dextran sulfate, phosphotungstate with the help of
divalent cations such as calcium, magnesium, and manganese
Formula for LDL Derivation
1. Friedewalde Formula
VLDL is obtained when TAG is divided by 2.175 (mmol/L) or 5.0 (mg/dl)
2. De Long Formula
VLDL is obtained when TAG is divided by 2.825 (mmol/L) or 6.5 (mg/dl)
! LDL is eventually derived as follows:
LDL-C= Total Cholesterol (HDL-C + VLDL)
Analyte
Total Lipids
Total Cholesterol
Triglycerides
Phospholipids
Free Fatty Acids

REFERENCE INTERVALS
Conventional Unit Conversion Factor
400-800 mg/dl
0.01
150-250 mg/dl
0.026
10-190 mg/dl
0.0113
150-380 mg/dl
0.01
9-15 mmol/l
1

SI Unit
4-8 g/l
3.88-6.47 mmol/l
0.11-2.15 mmol/l
1.5-3.8 g/l
9-15 mmol/l

ENZYME MEASUREMENTS
Concentration- can be determined by immunologic techniques
Activity- evidenced by increase in product formation, decrease in amount of
substrate, or changes in coenzyme concentration
Methods
1. Fixed Time/ End Point
2. Kinetic/ Continuous Monitoring
Units
1. International Units
2. Katal- SI Unit
Enzymes of Clinical Significance and their EC Nomenclature
1. Lactate Dehydrogenase (LD)
EC 1.1.1.27
2. Alanine Aminotransferase (ALT)
EC 2.6.1.2
3. Aspartate Aminotransferase ( AST) EC 2.6.1.1
4. Creatine Kinase (CK)
EC 2.7.3.2
5. Alkaline Phosphatase (ALP)
EC 3.1.3.1
6. Acid Phosphatase (ACP)
EC 3.1.3.2
7. Amylase (AMS)
EC 3.2.1.1
8. Lipase (LPS)
EC 3.1.1.3
9. Gamma Glutmayl Transferase (GGT)
EC 2.3.2.2
10.
5 Nucleotidase (5 N)
EC 3.1.3.5
11.
Leucine Aminopeptidase (LAP)
EC 3.4.11.1
12.
Acetylcholinesterase (ACE)
EC 3.4.15.1
13.
Pseudocholinesterase (PCHE)
EC 3.1.1.8
14.
Aldolase (ALD)
EC 4.1.2.13
Creatine Kinase
Abbreviation: CK, CPK
Systematic Name: ATP: Creatine N-phosphotransferase
Clinical Significance: MI, skeletal muscle disorders
Functions: ATP regeneration
Reaction Catalyzed

CK Isoenzymes and Tissue Sources


1. CK1/ CK BB- bladder, brain, colon, lung, prostate, stomach,
thyroid, uterus

2. CK2/ CK MB- heart, skeletal muscles


3. CK3/ CK MM- heart, skeletal muscles
Assay Methods
1. Tanzer- Gilvarg Method

2. Oliver- Rosalki Method

Lactate Dehydrogenase
Abbreviation: LD, LDH
Systematic Name: L- Lactate: NAD+ Oxidoreductase
Clinical Significance: MI, Liver Disorder, Hemolysis, Megaloblastic
Anemia, CA
Functions: Hydrogen Transfer
Reaction Catalyzed

LD Isoenzymes and Tissue Sources


1. LD1- HHHH; heart, kidneys, red blood cells
2. LD2- HHHM; heart, kidneys, red blood cells
3. LD3- HHMM; lungs, lymphocytes, pancreas, spleen
Assay Method

Aspartate Aminotransferase
Abbreviation: AST, SGOT
Systematic Name: L- Aspartate: 2- Oxaloglutarate Aminotransferase

Clinical Significance: MI, Liver Disorder, Skeletal Muscle Disorder


Functions: Synthesis & Degradation of Amino Acids in Intermediary
Metabolism
Reaction Catalyzed

Assay Methods
1. Karmen Method

Alanine Aminotransferase
Abbreviation: ALT, SGPT
Systematic Name: L- Alanine: 2- Oxaloglutarate Aminotransferase
Clinical Significance: Liver Disorder,
Functions: Synthesis & Degradation of Amino Acids in Intermediary
Metabolism
Reaction Catalyzed

Assay Methods

Alkaline Phosphatase

Abbreviation: ALP
Systematic Name: Orthophosphoric monoester phosphohydrolase
(alkaline)
Clinical Significance: Bone Disorder, Liver Disorder
Functions: Liberates inorganic phosphate from an organic phosphate
ester
Reaction Catalyzed

Assay Methods
1. Bowers and McComb

2. Others: Kay and Bodansky, King- Armstrong, Modified Roy

Acid Phosphatase
Abbreviation: ACP
Systematic Name: Orthophosphoric monoester phosphohydrolase
(acid)
Clinical Significance: Prostate CA
Functions: Liberates inorganic phosphate from an organic phosphate
ester
Reaction Catalyzed

Isoenzymes: Prostatic, RBC, Platelets


Assay Methods

Glutamyltransferase
Abbreviation: GGT, GGTP
Systematic Name: (5-Glutamyl)peptide: amino acid-5glutamyltransferase
Clinical Significance: Liver Disorder
Functions: Peptide and protein synthesis, regulation of tissue
glutathione levels, and transport of amino acids across cell membranes
Reaction Catalyzed

Assay Methods

Amylase
Abbreviation: AMY, AMS
Systematic Name: 1,4 D-Glucan Glucanohydrolase
Clinical Significance: Acute Pancreatitis
Functions: Catalyzes the breakdown of starch and glycogen
Reaction Catalyzed

Isoenzymes: P and S
Assay Methods
1. Amyloclastic
2. Saccharogenic
3. Chromogenic
4. Continuous Monitoring
Lipase
Abbreviation: LPS
Systematic Name: Triacylglycerol Acylhydrolase
Clinical Significance: Acute Pancreatitis
Functions: Catalyzes the partial hydrolysis of dietary TAG

Reaction Catalyzed

Assay Methods
1. Titrimetric
2. Turbidimetric

Glucose-6-Phosphate Dehydrogenase
Abbreviation: G6PD, G6PDH
Systematic Name: D- Glucose-6-Phosphate: NADP+ 1- Oxidoreductase
Clinical Significance: Drug- induced Hemolytic Anemia
Functions: NADPH production in the Pentose Phosphate Shunt
Assay Methods

Analyte
Amylase
Creatine Kinase
Glucose 6
Phosphate
Dehydrogenase
Glutamyltransfer
ase
Lactate
dehydrogenase
Leucine
aminopeptidase

REFERENCE INTERVALS
Conventional Unit Conversion Factor
SI Unit
16-120 Somogyi
1.85
30-220 U/L
units/dl
M- 55-170 U/L
1
M- 55-170 U/L
F- 30-135 U/L
F- 30-135 U/L
12002000
1
12002000 U/L
mU/mL packed
packed
erythrocytes
erythrocytes
540 U/L
1
540 U/L

(lactate
pyruvate) 100
190 U/L
Male 80200
U/mL (Goldbarg
Rutenberg)
Female 75185

100190 U/L at
37 C

0.24

19.248 U/L
1844.4 U/L

Lipase
5 Nucleotidase
Acid phosphatase
Alkaline
phosphatase
Aspartate amino
transferase
Alanine amino
transferase

U/mL (Goldbarg
Rutenberg)
14280 mU/mL
01.6 units at 37
C
0.130.63 U/L at
37 C
20130 U/L at 37
C
833 U/L at 37 C
436 U/L at 37 C

1
1

14280 U/L
01.6 units at 37
C
2.210.5 U/L at
37 C
20130 U/L at 37
C
833 U/L at 37 C

436 U/L at 37 C

16.67
1

SERUM CARDIAC MARKERS

1.
2.

3.

1.

2.

Enzymes
Angiotensin Sensitivity Test- first marker developed; obsolete
Lactate Dehydrogenase- not specific but isoenzymes LD1 and
LD2 are used; 2-4 times elevation from the upper limit of normal
that peaks at 48- 72 hours from chest pain onset and goes back
to baseline within 10 days; flipped LD pattern
Creatine Kinase- most specially CKMB
CK MB- rises 4-6 hours from the onset of chest pain, peaks within
12- 24 hours, and returns to baseline in 48- 72 hours
CK MB Mass/ CK Activity of >3 is associated with AMI.
Cardiac Proteins
Myoglobin- released upon cardiac damage; small and rapidly
cleared by the kidneys so it cannot be used as a long term
marker; not specific for AMI; rises within 1-4 hours from the onset
of chest pain, peaks within 6-9 hours, but declines to baseline
within 18- 24 hours; it cannot be used for those with renal
disease because of slower clearance; can be used to detect reinfarction if it elevates again in the next few days
Troponin Complex- includes Troponin C (least cardiac-specific),
Troponin I and Troponin T; not detectable in the serum of healthy
individuals
Troponin T- allows for both early and late AMI diagnosis;
increases a few hours after the onset of chest pain and peaks by

2.
3.
4.
5.

day 2, plateaus at 2-5 days, and remains elevated beyond 7 days


before returning to normal; 100% sensitivity 12 hours to 5 days
after chest pain; increases up to 200 times the upper limit of
normal
Troponin I- only found in the myocardium; very specific; rises 4-6
hours from the onset of chest pain, peaks in 12-18 hours and
returns to normal in 6 days depending on the size of the infarct
Other Cardiac Markers
Carbonic Anhydrase III- present in skeletal but not cardiac
marker; negative cardiac marker; released from damaged
muscle at a fairly fixed ratio to myoglobin
Glycogen Phosphorylase
Heart Fatty Acid Binding Protein- not cardiac- specific
Myosin Light Chains
Ischemia- modified Albumin

1.
2.
3.
4.
5.

Markers for Cardiovascular Risk


HDL- negative risk factor
HS- CRP
Fibrinogen
D Dimers
Homocysteine

1.

Markers for CHF


1. Natriuretic Peptides

Analyte
Creatine Kinase
CK MB
Myoglobin
Troponin I
Lactate
dehydrogenase
Aspartate amino
transferase

REFERENCE INTERVALS
Conventional Unit Conversion Factor
M- 55-170 U/L
1
F- 30-135 U/L
<6% of total
<90 g/L
1
(lactate
pyruvate) 100
190 U/L
833 U/L at 37 C

SI Unit
M- 55-170 U/L
F- 30-135 U/L
<6% of total
<90 g/L
00.1 g/L
100190 U/L at
37 C
833 U/L at 37 C

EVALUATION OF LIVER FUNCTION


Liver- a complex organ responsible for many major metabolic
processes in the body; largest most versatile gland; 2 main lobes;
located at the right upper quadrant of the abdomen; blood supplies
come from the hepatic artery and the hepatic portal vein; lobule as
structural unit
Functions
1. Excretory and secretory
2. Metabolic
3. Synthetic
4. Detoxification
Bilirubin Synthesis

Liver Disorders
1. Jaundice- yellowish discoloration of the skin and sclera due to
increased bilirubin; prehepatic, hepatic, or posthepatic
2. Cirrhosis
3. Hepatitis
4. Biliary Obstruction
5. Tumors
6. Reyes Syndrome
7. Alcohol and Drug Related
Assessment of Liver Function
1. Bilirubin

2.
3.
4.
5.
6.
7.

Ehrlichs
Van Den Bergh Reactions
Evelyn Malloy Method
Jendrassik Grof
Icterus Index
Direct Spectrophotometry
Urobilinogen
Bile Acids
Enzymes- AST, ALT, ALP, 5N, LAP, LDH, GGT
Test Measuring Synthetic Activity- PT, APTT, Albumin, Globulin,
A/G
Ammonia
Older Tests: Vitamin K Response Test, Hippuric Acid Synthesis
Test

Analyte
Ammonia

Bile acids
Bilirubin
Direct
(conjugated)
Indirect
(unconjugated)
Total
Newborns total
Glutamyltransfer
ase
Lactate
dehydrogenase
Leucine
aminopeptidase

REFERENCE INTERVALS
Conventional Unit Conversion Factor
SI Unit
20120 g/dL
0.5872
1270 mol/L
(diffusion)
4080 g/dL
2347 mol/L
(enzymatic
method)
728 mol/L
1248 g/dL
(resin method)
0.33 mg/dL
10
330 mg/L
<0.3 mg/dL
0.11 mg/dL
0.11.2 mg/dL
112 mg/dL

17.10

<5 mol/L
217 mol/L
221 mol/L
17205 mol/L

540 U/L

540 U/L

(lactate
pyruvate) 100
190 U/L
Male 80200
U/mL (Goldbarg
Rutenberg)
Female 75185

100190 U/L at
37 C

0.24

19.248 U/L
1844.4 U/L

Isocitric
dehydrogenase

5 Nucleotidase
Alkaline
phosphatase
Aspartate amino
transferase
Alanine amino
transferase

U/mL (Goldbarg
Rutenberg)
50240 U/mL at
25 C (WolfsonWilliamsAshman
units)
01.6 units at 37
C
20130 U/L at 37
C
833 U/L at 37 C
436 U/L at 37 C

0.0166

0.834.18 U/L at
25 C

01.6 units at 37
C
20130 U/L at 37
C
833 U/L at 37 C

436 U/L at 37 C

ELECTROLYTES AND INORGANIC IONS


ANION GAP
Difference between the cation and anions routinely measured in
serum
[Na + K] [Cl + HCO3]
Increased in: uremia, ketosis, lactic acidosis, dehydration,
ingestion of toxins like methanol, salicylate, ethylene glycol, and
paraldehyde
Decreased in: Li toxicity, hypermagnesemia, multiple myeloma,
polyclonal gammopathy, Polymyxin B Treatment;
hypoalbuminemia
Electrolytes- inorganic substances that dissociate into ions
Functions
1. Control the osmosis of water between the fluid compartments.
2. Maintain acid- base balance.
3. Production of action potentials
4. Cofactors for enzymes
5. Maintenance of electrical neutrality
! The sum of cations should equal the sum of anions.
Cations- Sodium, Potassium, Calcium, Magnesium
Anions- Chloride, Bicarbonate, Phosphates

! Electrolyte Exclusion Effect


SODIUM

The most abundant extracellular cation


For the normal distribution of water and osmotic pressure in the
ECF
Regulated by: ADH, Aldosterone, ANP
Hyponatremia
Either due to water retention or sodium loss
Seen in overhydration, diuretic therapy, metabolic acidosis, Addisons
Disease, Diarrhea
May be artifactual: increased glucose, lipids and proteins
Hypernatremia
Can be due to excessive sodium intake or water depletion
Seen in dehydration, Cushings Syndrome, Insulin Therapy, profuse
sweating, diarrhea without adequate fluid replacement, Diabetes
Insipidus
Analytical Techniques
1. ISE- uses a glass membrane electrode
Types: Direct and Indirect
2. FES
3. Spectrophotometry
4. Colorimetric
5. AAS
POTASSIUM
Most abundant intracellular cation
Important for nerve impulse transmission and action potential
Levels controlled by aldosterone
Hypokalemia
Can be due to movement from ECF to ICF as seen in alkalosis
and insulin therapy
Can also be due to GI losses and renal losses
Hyperkalemia
Can be due to movement from ICF to ECF as seen in acidosis and
cell damage
Also seen in ARF and CRF and mineralocorticoid deficiency

Artifactual Hyperkalemia
Seen in hight platelet count, prolonged tourniquet application,
hemolysis, delayed separation, refrigeration
! Very high potassium levels can stop the heartbeat.
Analytical Techniques
! Serum vs Plasma
1. ISE
2. FES
3. Spectrophotometric: Lockhead and Purcell, Turbidimetric
4. AAS
CHLORIDE
Most abundant ECF anion
Also regulates osmotic pressure and water balance together with
sodium
Hypochloridemia
Metabolic alkalosis, respiratory acidosis
Hyperchloridemia
Metabolic acidosis, respiratory alkalosis
Analytical Techniques
1. Mercurimetric Titration- Schales and Schales
2. Mercuric Thiocyanate Methods- Skeggs Modification
3. Coulometric- Amperometric Titration
4. ISE
! Sweat Chloride Determination
CALCIUM

The 5th most abundant mineral in the body


Majority is in the skeleton in the form of hydroxyapatite crystals
Blood coagulation, neuromuscular conduction, cardiac and
skeletal muscle excitability
Regulation: PTH, Vit D, Calcitonin
Forms in the Blood: Free or Ionized (50%), Protein- Bound (40%),
and Complexed with Anions (10%)
Hypocalcemia

Hypoparathyroidism, steatorrhea, renal disease, pancreatitis

Hypercalcemia
Hyperparathyroidism, multiple myeloma, TB, antacids
Analytical Techniques
Total Calcium
1. Colorimetric- Clark and Collip
2. EDTA Titration
3. Spectrophotometric- O- Cresolphthalein, Alizarin, Arsenazo III
4. AAS
Ionized
1. Colorimetric
2. ISE
PHOSPHORUS
Found in bones, muscles, and ECF
Also influenced by PTH, Calcitonin, and Vit D
For structural support, energy generation, and storage
Analytical Techniques
1. Spectrophotometric- Fiske and Subarrow
MAGNESIUM
2nd most abundant cation in the ICF
4th most abundant cation in the body
As an activator of various enzymes
Forms in the Blood: Free or Ionized (2/3) and Protein Bound (1/3)
Analytical Techniques
1. AAS
2. EFP
3. Spectrophotometric- Calmagite Green, Formazan Dye, Methylene Blue
and others
4. Colorimetric- Titan Yellow
BICARBONATE (Total CO2)
2nd most abundant ECF anion
Chloride Shift
Acid- base balance
Analytical Techniques
1. Acid Titration and pCO2 Electrode
2. Akalinization and En

Analyte
Chloride

Calcium
Ionized
Total
Bicarbonate
Magnesium

Osmolality
Phosphorus,
inorganic

Potassium

Sodium

REFERENCE INTERVALS
Conventional Unit Conversion Factor
SI Unit
95103 mEq/L
1
95103 mEq/L
24 hr urine 140
1
140250
250 mEq/day
mmol/day
Sweat 460
1
mEq/L
460 mmol/L
44.8 mg/dL
0.2500
11.2 mmol/L
22.4 mEq/L
0.5000
3058% of total
0.01
0.300.58 of total
Plasma 2128
1
Plasma 2128
mmol/L
mmol/L
1.32.1 mEq/L
0.5000
0.651.05 mmol/L
1.83 mg/dL
0.4114
0.741.23 mmol/L
24 hr urine 68.5
0.5000
34.3 mmol/day
mEq/day
280295
1
280295
mOsm/kg
mOsm/kg
Adults 2.34.7
0.3229
0.741.52 mmol/L
mg/dL
1.292.26 mmol/
Children 47
mg/dL
3.85 mEq/L
1
3.85 mmol/L
24 hr urine 4080
1
4080 mmol/day
mEq/day
136142 mEq/L
1
136142 mmol/L
24 hr urine 75
1
75200 mmol/day
200 mEq/day
Sweat 1080
1
1080 mmol/L
mEq/L

BLOOD GASES AND ACID- BASE BALANCE


A certain amount of acids and bases need to be maintained by the boy
in order to keep the blood pH normal, and thus conducive to the
maintenance of the different metabolic processes. The lungs and kidneys
are very important organs in the maintenance of acid- base balance as well
as the correct function of the different buffer systems in the body.

Buffer Systems in the Body


1. Bicarbonate
Henderson Hasselbalch Equation
pH= 6.1 + log ___[HCO3-]__
pCO2 x 0.0307
2. Phosphate
3. Hemoglobin
4. Plasma Proteins
Lungs- important for the elimination and retention of CO2 by ventilation
Kidneys- important for excreting and reclaiming acids and bases through the
urine
Acid- Base Disorders
Acidosis and Acidemia- excess acids; low blood pH
Alkalosis and Alkalemia- excess bases; high blood pH
Compensation- may be primary or secondary; may be partial or full
Acidosis
Nonrespiratory- may be due to the administration of acid- producing
substances; diabetic ketoacidosis; starvation; renal tubular acidosis;
excess bicarbonate loss
Respiratory- COPD; bronchopneumonia; drugs like barbiturates,
morphine, and ethanol; mechanical airway obstruction, CHF
Alkalosis
Nonrespiratory- may be due to excess bicarbonate; administration of
bicarbonate- producing salts; excess acid loss through vomiting;
nasogastric suction; prolonged diuretic use
Respiratory- hypoxia; initial effect of salicylates; fever; hysteria
Assessment of Acid- Base Homeostasis
Specimen Collection- the ideal sample to be used is heparinized arterial
blood transported in ice
Blood Gas Analyzers
1. pO2- Clarke electrode (amperometric)
2. pH- glass membrane electrode sensitive to hydrogen
(potentiometric)
3. pCO2- Severinghaus electrode (potentiometric); modified pH
electrode
4. Bicarbonate
5. Oxygen Saturation (SO2)- Cooximeter
REFERENCE INTERVALS
Analyte
Conventional Unit Conversion Factor
SI Unit
pH
7.387.44
1
7.387.44

pCO2

pO2
Bicarbonate
Oxygen
Saturation

(arterial)
7.367.41
(venous)
3540 mm Hg
(arterial)
4045 mm Hg
(venous)
95100 mm Hg
(arterial)
21-28 mEq/L
94100%

7.367.41

0.1333

4.75.3 kPa
5.36 kPa

0.1333

12.713.3 kPa

1
0.01

21-28 mmol/L
Fraction
saturated:
0.941

TOXICOLOGY
Basic Techniques
Immunochemical Methods- homogeneous immunoassays; EMIT and FPIA
Chromatographic Techniques- TLC, HPLC, GC- MS
DRUGS OF ABUSE
Cocaine
derived from coca plant
prevalent form of cocaine is called crack a free-base form that passes rapidly
across the nasal membranes
half-life is 1-2 hours where as parent compound and its metabolites cleared from
the body within 2 days
normal administration of cocaine is nasal (inhalation or snorting)
Opiates (Morphine, Codeine, Heroin)
Clinical Significance
Morphine powerful analgesic, binding to receptors in the CNS; used in
treating acute CHF
Codeine - mild analgesic and as an antitussive
Heroin
- induces a pleasant, euphoric state and is highly addictive both
physically and physiologically
Amphetamines
It causes euphoria and increased mental alertness.
Competitive inhibitors of the enzyme monoamine oxidase which inactivates
adrenergic neurotransmitters by oxidatively removing their amino groups.
3,4-methylenedioximethamphetamine (MDMA or ecstacy) a derivative of
methamphetamine
CNS and respiratory stimulation and sympathomimetic activity
Loss of weight as a result of an anorectic effect
Psychic stimulation and excitability, temporary increase in mental and physical
activity
Benzodiapines
Minor tranquilizers

potentiate the effects of heroin


Induction of the secretion of GABA, a neurotransmitter that inhibits conduction in
dopaminergic neurons
A therapeutic drug to produce calming effects at higher doses
Phencyclidine (PCP)
Has numerous effects on a variety of different neural pathways
angel dust or angel hair
Physiologic effects appear to be analgesic and anesthetic and, paradoxically,
stimulatory
Barbiturates
derivatives of barbituric acid
Long acting as is Phenobarbital (used as anticonvulsant)
Short acting pentobarbital
Ultra- short acting with thiopental
Propoxyphene (Darvon)
It has pharmacologic properties very similar to opiates like morphine
It is taken orally that produce sedation and good feelings
Methaqualone (Quaalude)
sedative-hypnotic
anticonvulsant, antispasmodic, local anesthetic, antitussive, and weak
antihistamine
Half-life ranges from 20-60 hours
Chronic Usage- CNS depression with lethargy, respiratory depression, coma and
death
Marijuana (Cannabis)
Oldest and most widely used mind- altering drugs
hemp plant Cannabis sativa
Delta 9-tetrahydrocannabinol (THC)
half-life is 1 week, metabolites may be detected in the urine from 1-4 weeks
Lysergic Acid Diethylamide (LSD)
Semisynthetic indolalkylamine and hallucinogen
Sympathetic effects HPN, tachycardia, mydriasis, piloerection
Metabolism in the liver; excretion mainly the bile
Acute Toxicity- Illusions or hallucinations, panic reaction bad trip
THERAPEUTIC DRUG MONITORING
Cardiotropics
treat CHF and cardiac arrhythmias
Four classes of drugs that act on one or more phases:
Class I drugs block sodium influx in Ph.I
Class II beta receptor blockers

Class III block repolarizing potassium currents, increasing the length of the
action potential
Class IV verapamil, slow calcium influx resulting in action potential
prolongation
DIGOXIN the digitalis glycosides are used to treat atrial arrhythmias atrial
flutter and fibrillation; rapid onset of action
Digoxin: half life 35-40 hrs; 0.5-2 ng/ml
Digitoxin: half life 4-6 days; 9-25 ng/ml
PROCAINAMIDE (Pronestyl) Class I antiarrhythmic drug used in treating
supraventricular or ventricular arrhythmias
Half life app 3.5 hrs; 4-10 ng/ml
QUINIDINE - Class I antiarrythmic; half-life is 5-12 hours; 2.3-5 mcg/ml
LIDOCAINE (Xylocaine) Class I antiarrythmic, can also be used as local
anesthetic; acute control and prevention of ventricular arrhythmias after
myocardial infraction; half-life is 2 hours; 1.2-5.5 mcg/ml
PROPRANOL- Class II anti-arrhythmic beta-receptor blocking drug; antagonizes
the effects of epinephrine on the heart, arteries, and arterioles of skeletal
muscles, and on the bronchus; used to treat sinus tachycardia, atrial
tachycardia and ventricular arrhythmias; toxic effects include bradycardia,
arterial insufficiency, hypotension, AV block, nausea, vomiting, pharyngitis,
bronchospasm, and thrombic thrombocytopenic purpura; half app 3 hrs; 50-100
ng/ml
AMIODARONE- Class III anti-arrhythmic; oral loading dose is 1200-1600mg/day
with a maintenance dose of 200-400mg/day; toxic effects include bradycardia,
heart block, fatal pulmonary fibrosis, hepatitis, visual field disturbances,
photodermatitis, and mainly hypothyroidism but sometimes hyperthyroidism;
half life rapid- 3-10 days, slow- 25-110 days; 1-2.5 mcg/ml
VERAPAMIL- Class IV anti-arrhythmic drug; oral dose is 120-480mg/day in three
to four divided doses; toxic effects include hypotension, ventricular fibrillation,
constipation, and peripheral edema; half life 2-8 hours; 80-400 ng/ml
Anticonvulsants
Used in the treatment of seizure disorders
PHENOBARBITAL- long-acting barbiturate, used in the treatment of generalized
tonic-clonic seizures and simple partial seizures with motor or somatosensory
symptoms for anxiety and insomnia; toxic side effects include nystagmus,
ataxia, stupor, respiratory depression, coma and hypotension; half life 4-6 days;
15-30 ug/ml
PHENYTOIN (DILANTIN)- for generalized tonic-clonic, simple partial, and complex
partial seizures; toxic side effects include nystagmus, ataxia, stupor, and coma;
half life app 24 hrs; 10-20 ug/ml

PRIMIDONE (MYSOLINE)- for generalized tonic-clonic, simple partial, & complex


partial seizures; side effects include sedation, dizziness, ataxia, and skin rashes;
not for patients with acute intermittent porphyria; half life app 12 hrs; 5-21 ug/ml
ETHOSUXIMIDE (ZARONTIN)- drug of choice for the absence seizures accompanied
by other types of seizures
CARBAMAZEPINE (TEGRETOL)- primary antiepileptic drug; for generalized tonicclonic seizures and simple partial and complex partial seizures; also used to treat tic
douloureux and glossopharyngeal neuralgia, and is the drug of choice in the
treatment of these neuralgias; toxic reactions include drowsiness, ataxia, dizziness,
nausea and vomiting, and light headedness
VALPROIC ACID (DEPAKENE)- commonly used in the treatment of generalized tonicclonic seizures, absence seizures, myoclonic seizures, and atonic seizures; toxic side
effects include sedation, gastric disturbances, hematologic reactions, ataxia,
somnolence, and coma.
Ethosuximide- 40-100 ug/ml; half life: acute- 60 hrs; chronic- 30 hrs
Carbamazepine- 4-12 ug/ml; half life 8-20 hrs
Valproic acid- 50-100 ug/ml; half life 8-15 hours
Antiasthmatics
THEOPHYLLINE- bronchodilator; 10-20 mcg/ml; half life app. 8.7 hrs
Antiinflammatory and Analgesics
Steroids- highly effective anti-inflammatory agents
Aspirin- cyclo-oxygenase inhibitor; antiinflammatory, antipyretic, and analgesic
Acetaminophen- analgesic and antipyretic
IMMUNOSUPPRESSIVES
Ciclosporin and tacrolimus
Rapamycin (Sirolimus)
Mycophenolate mofetil (MMF)
Others
Lithium
TCAs
Neuroleptic
Chemotherapeutic Agents
TOXINS
CYANIDE
Binds iron in the ferric state; cyanoferric complex; inactivate iron-containing
enzymes that cycle between the ferrous and ferric states
tissue and cellular hypoxia; binds cytochrome A3 and inhibits reoxidation
Diagnosis: odor of bitter almonds, altered mental status and tachypnea in the
absence of cyanosis, metabolic acidosis
CARBON MONOXIDE

CO intoxication produces tissue hypoxia; carboxyhemoglobin


Intoxication: respiratory, neurologic, and cardiac; dyspnea is a principal symptom;
headache, visual disturbances, tachycardia, syncope, tachypnea, coma, convulsions
and death
A co-oximeter is utilized to make the definitive diagnosis
ALCOHOL AND GLYCOLS
ETHANOL
METHANOL
ETHYLENE GLYCOL
ISOPROPYL ALCOHOL
ARSENIC
It is used in ant poisons, rodenticides, herbicides and weed killers, insecticides,
paints, wood preservatives, ceramics, and etc..
Fast absorption via the GI and lungs; slow absorption via the skin
The major excretion is through the kidneys. Arsenic can cross the placenta.
GI symptoms are the most
There may be the odor of garlic on the breath, and a metallic taste in the patients
mouth.
Analysis of urine, hair, and nails, using ion emission spectroscopy, is important for
the diagnosis of chronic arsenic poisoning.
MERCURY
Exist in four different forms:
Elemental or metallic
Mercurous
Mercuric
Alkyl mercury
IRON
Acute ipoisoning is common in young children
Large dosescause acute mucosal cell damage, and significant absorption of iron
occurs once the binding capacity transferrin is exceeded
Hepatotoxicity occurs within 1-2 days of ingestion and has been associated with
levels equal to or greater that 1700g/dl.
Vomiting appears to be an early manifestation of iron intoxication along with severe
gastroenteritis, melena, abdominal pain, hematemesis.
Occurs up to 6 hours after ingestion. For the next 10 hours, the patient may appear
to improve.
Definitive diagnosis: Serum Fe and TIBC
Emesis or gastric lavage is used to prevent iron absorption.
Chelation therapy with deferoxamine is also utilized if the acute intoxication is
severe.
LEAD
Serious effects on the CNS and PNS
inhalation or ingestion
Primarily CNS symptoms and GI symptomatology such as colic.

Bone- largest body compartment of lead; app96%; may act as reservoir


The half life is 32 years
The most sensitive screening: low ALAD activity in urine
ORGANOPHOSPHATES AND CARBAMATES
ORGANOPHOSPHATES- esters of phosphoric acid or thiophosphoric acid
CARBAMATES- synthetic derivatives of carbamic acid

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