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CLINICAL CHEMISTRY

I. PROTEINS AND TUMOR MARKERS


PROTEINS: PLASMA, URINARY, CSF
TUMOR MARKERS: PSA, APP, CEA, B-HCG, CA 15-3, CA 125, CA 19-9
II. NONPROTEIN NITROGENOUS COMPOUNDS
III. CARBOHYDRATES
IV. LIPIDS AND LIPOPROTEINS
V. ENZYMES

PROTEINS AND TUMOR MARKERS

PROTEINS
Macromolecules made up of amino acids, with each AA being linked to another via a peptide bond

Functions:
o Energy production: Proteins can be broken down into AA that can be used in the citric acid cycle to produce
energy
o Water distribution: Maintain the colloidal osmotic pressure between different body compartments
o Buffer: The ionisable R groups of the individual AA provide buffering capacity by binding or releasing H+ ions
as needed
o Transporter: Binding of proteins to hormones, free Hgb, lipids, drugs, Ca, unconjugated bilirubin allows
movement of these and other molecules in the circulation
o Antibodies: Function as receptors for hormones so that the hormonal message can activate cellular components;
some hormones are protein in nature e.g. ACTH, FSH, TSH
o Structural proteins:Collagen is the fibrous component that maintains the structure of body parts
o Enzymes: catalysts that accelerate chemical reactions

PLASMA TOTAL PROTEIN
1. REGULATION
The liver synthesizes most of the plasma proteins. Plasma cells synthesize the Igs.
Proteins are synthesized from AA.
When proteins degrade, their constituent AA undergoes deamination with the formation of ammonia, which is
converted to urea to excretion in the urine.
Some cytokines released at the site of injury or inflammation cause the liver to increase synthesis of the acute-
phase reactant proteins (nonspecific response to inflammation that may be caused by autoimmune disorders,
infections, tissue injury from tumors, MI, trauma, or surgical procedures)
Some proteins will decrease in concentration negative acute-phase proteins, e.g. prealbumin (transthyretin),
albumin, and transferrin.
Immunoglobulins humoral Ab produced in response to foreign Ag for the purpose of destroying them
Reference ranges: Total protein 6.5 8.3 g/dL

Changes in total protein concentration:
Hypoproteinemia caused by urinary loss, GIT inflammation, liver disorders, malnutrition, inherited
immunodeficiency disorders, and extensive burns
Hyperproteinemia caused by dehydration, increased protein production (gammopathies) and chronic
inflammatory disease associated with paraprotein production.

Clinical Significance of the Major Proteins
1. Prealbumin (transthyretin)
Indicator of nutritional status; transports thyroid hormones
Decreased in liver disorders, inflammation, malignancy, poor nutrition
Increased in steroid therapy, CRF, alcoholism
2. Albumin
Synthesized in the liver
Highest concentration of all plasma proteins
Binds many analytes for transport in blood, including unconjugated bilirubin steroids, ions such as Ca and
Mg, FA, and drugs
Significantly contributes to plasma osmotic pressure
Decreased in liver disorders, malabsorption, muscle-wasting diseases, severe burns, renal diseases
(nephrotic syndrome, glomerulonephritis), starvation, malnutrition
3. Alpha 1 Antitrypsin
Acute-phase reactant
A protease inhibitor that neutralizes trypsin-type enzymes that can damage structural proteins
Decreased in emphysema-associated pulmonary disease and severe juvenile hepatic disorders that may
result in cirrhosis
Increased in inflammatory disorders
4. Alpha 1 Fetoprotein (AFP)
Is synthesized during gestation in the yolk sac and liver of the fetus, peaking at 13 wks and declining at 34
wks.
Normally adult levels are very low.
Maternal serum AFP is measured between 15 and 20 wks AOG and is reported as multiples of the median
(MoM)
Increased level: neural tube defects, spina bifida, and fetal distress
Decreased level: Down syndrome, trisomy 18
In adults, increased levels of AFP can be indicative of hepatocellular carcinoma and gonadal tumors.
5. Alpha 1 Acid glycoprotein (orosomucoid)
Acute-phase reactant; bonds to basic drugs
Increased in inflammatory disorders such as RA, pneumonia and conditions associated with cell
proliferation
Decreased in nephrotic syndrome
6. Haptoglobin
Alpha 2 globulin that binds free hemoglobin; an acute-phase reactant
Increased in inflammatory conditions, burns, trauma
Decreased in intravascular hemolysis because of formation of a haptoglobin-hemoglobin complex for
removal by the liver
7. Ceruloplasmin
Ab acute phase reactant that is an a2-globulin, copper-containing protein with enzymatic activity
90% of serum copper is bound in ceruloplasmin
Increased in pregnancy, inflammatory disorders, malignancies, and with intake of oral estrogen and OCP
Decreased in Wilson disease, malnutrition, malabsorption, severe liver disease
8. a2-Macroglobulin
proteolytic enzyme inhibitor thatinhibits thrombin, trypsin, and pepsin
increased in nephrotic syndrome, contraceptive use, pregnancy, estrogen therapy
decreased slightly in acute inflammatory disorders and prostatic cancer, decreased markedly in acute
pancreatitis
9. Transferrin
-globulin that transport iron
decreased in infections, liver disease, and nephrotic syndrome
increased in iron-deficiency anemia and pregnancy
10. C-reactive protein (CRP)
-globulin acute-phase reactant
increased in tissue necrosis, RF, infections, MI, RA gout
11. Immunoglobulins (Ig): Antibodies
Five major classes: IgA, IgD, IgE, IgG, and IgM
Synthesized in plasma cells as an immune response
One of the Igs will be increased in a monoclonal gammopathy (e.g. multiple myeloma) generally
associated with increase in IgG, IgA, or IgM
IgG can cross the placenta.
Increased in liver disorders, infection, and collagen disease
Decreased in presence of increased susceptibility to infection and when a monoclonal
gammopathy is associated with an increase in another immunoglobulin
IgA levels increase after birth.
Increased in liver disorders, infections, and autoimmune diseases
Decreased in inhibited protein synthesis and hereditary immune disorders
IgM cannot cross the placenta; it is made by the fetus
Increased in various bacterial, viral and fungal infections and Waldenstrom
macroglobulinemia
Decreased in renal disease associated with protein loss and immunodeficiency disorders
IgD is increased in liver disorders, infections, connective tissue disorders
IgE is increased in allergies, asthma, and hay fever, parasitic infections

Proteins In Other Body Fluids
Urinary Proteins
Quantifications performed on 24-hour urine specimens
Reference range urine total protein: 1-4 mg/dL; <100 mg/day

Clinical significance of proteinuria
May result from tubular or glomerular dysfunction, multiple myeloma, Waldenstrom macroglobulinemia,
nephrotic syndrome
Bence Jones protein may be found in urine of patients with multiple myeloma
Glomerular membrane can be damaged in diabetes, amyloidosis, and collagen diseases.
Glomerular dysfunction can be detected in its early stages by measuring microalbumin in urine.
Microalbuminuria the quantity of albumin in urine is greater than normal, yet it undetectable by urine
dipstick method; generally precedes nephropathy
Reference range for urine albumin: < 30 mg/day
2. CSF
Reference range 15-45 mg/dL

Clinical Significance
Increased in viral, bacterial, and fungal meningitis, traumatic tap (bloodly), multiple sclerosis, herniated disk,
and cerebral infarction
Decreased in hyperthyroidism and with CNS leakage of CSF

TUMOR MARKERS

Tumor Marker Utilization
In general, tumor markers are not very useful in diagnosis.
Useful in tumor staging, monitoring therapeutic responses, predicting patient outcomes, and detecting cancer recurrence.

Ideal Characteristic for Tumor Markers includes:
Measured easily
High analytical sensitivity of assay method
High analytical specificity of assay method
Cost-effective
Test result contributes to patient care and outcome

Prostate Specific Antigen (PSA)
Function:
1. Produced by epithelial cells of the prostate gland and secreted into seminal plasma
2. Glycoprotein protease that functions in liquefaction of seminal coagulum
Forms of PSA found in the blood
1. Enveloped by protease inhibitor, a2-macroglobulin; lacks immunoreactivity
2. Complexed to another protease inhibitor, a1-antichymotrypsin; immunologically detectable
3. Free PSA, not complexed to protease inhibitor, immunologically detectable
4. Total PSA assays measure complexed and free PSA dorms, as they are immunologically detectable
Specificity
1. A tissue-specific marker but not tumor specific
2. Small amount present in serum normally
3. Lacks specificity because serum level of PSA is increased in BPH as well as in adenocarcinoma of the prostate
Prostate cancer detection
1. Early detection guidelines endorse lower cutoff of PSA up to 2.5 ng/mL
2. PSA >2.5 ng/mL perform biopsy
3. PSA velocity is measurement of the rate of change per year.
a. Biopsy recommended when PSA rises more than 0.75 ng/mL/year even when PSA is <2.5 ng/mL.
4. Free PSA: Men with prostate cancer tend to have lower % free PSA (free PSA/total PSA) than men with benign
disease. Lower % free PSA is associated with a higher risk of prostate cancer.
5. PSA is used to monitor therapeutic response and to follow radical prostatectomy.
1-Fetoprotein (AFP)
Oncofetal glucoprotein antigen
1. Synthesized in liver, yolk sac, and GI tract of fetus
2. Fetal serum AFP peaks at 12-15 weeks of gestation with levels of 2-3 mg/mL.
3. At birth levels fall to 50 g/mL, and at 2 years of age only trace amounts are present.
4. Adult levels <20 ng/mL

Clinical Significance
Increased level of AFP in adults are associated with hepatocellular carcinoma, testicular, and ovarian
teratocarcinomas, pancreatic carcinoma, gastric and colonic carcinomas.
Increased levels in adults are also seen in non-malignant disorders, including viral hepatitis and chronic active
hepatitis
Useful in monitoring therapeutic response of cancer patient to treatment protocols
In pregnancy, increased maternal serum levels are associated with spina bifida, neural tube defects, and fetal
distress. Decreased levels of maternal serum AFP are associated with increased incidence of Down syndrome.

Carcinoembryonic antigen (CEA)
Oncofetal glycoprotein antigen
Normally found in epithelial cells of the fetal GI tract

Clinical Significance in adults
1. Increased levels of CEA are associated with adenocarcinoma of digestive tract and colorectal carcinoma.
2. Elevations are seen in other malignancies and noncancerous disorders.
3. Useful in monitoring therapeutic response of cancer patients to treatment protocols.

Enzyme immunoassay methods are used for measurement.

4. Human chorionic gonadotropin (hCG)
A glycoprotein composed of - and - subunits. The - subunit is unique and not common to other hormones; -
subunit is common to other hormones.
Normally secreted by the trophoblast cells of the placenta
Increased secretion is associated with trophoblastic tumors, choriocarcinoma, nonseminomatous testicular tumors,
and ovarian tumors.
Useful for monitoring the progress of patients
Immunoassay measurement is made of -hCG

5. CA 125
Mucin glycoprotein antigen
Marker for ovarian and endometrial cancer
Useful for monitoring the progress of patients

6. CA 19-9
Glycolipids blood group antigen-related marker
Marker for pancreatic, colorectal, lung, and gastric carcinomas
Useful for monitoring the progress of patients

7. CA 15-3
Mucin glycoprotein antigen
Useful for monitoring therapeutic response and for detecting recurrence of breast cancer in patients previously treated
Elevated levels observed in non-malignant diseases such as chronic hepatitis, tuberculosis, and SLE.


NONPROTEIN NITROGENOUS COMPOUNDS
UREA
CREATININE
URIC ACID
AMMONIA


1. UREA
Regulation of Urea
Major nitrogen-containing compound in the blood
Results from protein catabolism
Synthesized in the liver from the deamination of AAs
Excreted by the kidneys

Clinical Significance
Abnormal urea levels may be due to prerenal, renal or post renal d/o
Renal failure, GN, UTI, CHF, dehydration, increased protein catabolism
Severe liver disease, vomiting, diarrhea, malnutrition

Blood urea nitrogen (BUN) an older term still in use, terminology based on previous methodology where nitrogen was
measured. To convert BUN to urea: BUN x 2.14 = Urea

2. CREATININE
Regulation:
A waste product of muscle contraction that is formed from phosphocreatinine, a high energy comp.
Levels regulated by kidney excretion.
Measurements of creatinine in serum and urine (creatinine clearance) are used to assess the glomerular filtration rate
Levels not changed by diet or rate of urine flow
Creatinine is not reabsorbed by renal tubules.

Clinical Significance
Renal disease, renal failure

3. URIC ACID
Regulation
Major waste product of purine (adenosine and guanisine) catabolism
Synthesized in the liver
Elimination from the blood is regulated by the kidneys through glomerular filtration
Some excreted through the GI tract

Clinical Significance
Gout, renal d/o, tx of myeloproliferative d/o, lead poisoning, lactic acidosis, toxaemia of pregnancy, Lesch-Nyhan
syndrome
severe liver disease as a secondary d/o, tubular reabsorption d/o, drug induced

4. AMMONIA
Regulation
Ammonia produced from deamination of AAs
Hepatocytes convert ammonia to urea for excretion
With severe liver cell malfunction, blood levels of ammonia increase
Ammonia is neurotoxic

Clinical Significance
hepatic failure and Reye syndrome




CARBOHYDRATES

Glucose Metabolism
During fast, the blood glucose level is kept constant by mobilizing the glycogen stores in the liver.
During long fast, gluconeogenesis is required to maintain blood glucose levels because glycogen stores are used up in
about 24-48 hours.
Hypoglycemia: FBS < 50 mg/dL
Hyperglycemia: FBS> 200 mg/dL
Hormones Affecting Blood Glucose Levels
Insulin
Beta cells of the islets of Langerhans
Promotes entry of glucose into the liver, muscle, and adipose tissue to be stored as glycogen and fat
Inhibits the release of glucose from the liver
Somatostatin
Delta cells of the islets of Langerhans
Inhibits secretion of insulin, glucagon, and growth hormone
Results in an increase in plasma glucose level
Growth hormone and adenocorticotropic hormone (ACTH)
Secreted by the anterior pituitary
Raise blood glucose
Cortisol
Secreted by the adrenal glands
Stimulates glycogenolysis, lipolysis, and gluconeogenesis
Epinephrine
Secreted by the medulla of the adrenal glands
Stimulates glycogenolysis, lipolysis, and gluconeogenesis
Inhibits secretion of insulin
Physical or emotional stress causes increased secretion of epinephrine and an immediate increase in blood glucose
levels.
Glucagon
Secreted by the cells
Increases blood glucose by stimulating glycogenolysis and gluconeogenesis
Thyroxine
Secreted by the thyroid gland
Stimulates glycogenolysis and gluconeogenesis
Increase glucose absorption from the intestines

Renal Threshold for Glucose (RTG)
Glucose is filtrated by the glomeruli, reabsorbed by the tubules, and normally not present in urine.
If the blood glucose level is elevated, glucosuria occurs.
RTG varies between 160 and 180 mg/dL.
When blood glucose reaches this level or exceeds it, the renal tubular transport mechanism becomes saturated, which
causes glucose to be excreted into the urine.

ABNORMAL CARBOHYDRATE METABOLISM
Diabetes mellitus
Type 1 DM
Insulinopenia
Required tx with insulin to sustain life
An autoimmune disorder affecting cells
Peak incidence in childhood and adolescence, but may occur at any age
Primary sx include polyuria, polydipsia and weight loss
Ketosis-prone: Can produce excess ketones, resulting in diabetic ketoacidosis (DKA)
Type 2 DM
Defect in insulin secretion and cellular resistance to insulin
Generally responds to dietary intervention and oral hypoglycemic agents, but some may require insulin
therapy.
Associated with obesity and sedentary lifestyle
Sx include polyuria, polydipsia, and weight loss
Associated with age over 40, but becoming a significant problem in children and adolescents
Non-ketosis prone: without exogenous insulin or oral hypoglycemic medication, these individuals will have
an elevated glucose but will not go into DKA.
Gestational diabetes mellitus (GDM)
Onset of DM during pregnancy
Return to normal metabolism seen after childbirth
There is an increased chance that type 2 DM may develop later in life.

2. Inherited disorders of carbohydrate metabolism
Glycogen storage disease
Inherited diseases involving the deficiency of particular enzymes
Deficiencies cause defects in the normal metabolism of glycogen
Von Gierke, type I: G6PD
Pompe, type II: -1, 4-glucosidase deficiency

3. Galactosemia
A deficiency or absence of galactokinase, galactose 1-phosphate uridyl transferase, or uridyl diphosphate
galactose
Galactose is found in milk as a component of lactose, with galactosemia generally identified in infants.
Most commonly, galactose 1-phosphae uridyl transferase is deficient, which leads to excessive galactose in
blood and excretion in urine.

Laboratory Diagnosis
Fasting plasma glucose
Normal < 100 mg/dL
Impaired 100-125 mg/dL
Provisional Dx of DM is made when FPG 126 mg/dL.
The Dx must be confirmed by one of the three methods described in the following outline:
Diagnosis of DM:
A plasma glucose analysis that yields any one of the following results is diagnostic for the presence of DM,
provided that unequivocal hyperglycemia is apparent.
If unequivocal hyperglycemia is not apparent, the glucose result must be confirmed by repeat analysis on a
subsequent day using any one of the ff. 3 methods:
a. Physical sx and a casual plasma glucose level of 200 mg/dL
b. FPG level that is 126 mg/dL (fasting defined as no caloric intake for minimum of 8 hours)
c. Plasma glucose level of 200 mg/dL at 2-hr point of an OGTT.
GDM
A woman at high risk of GDM should have an initial screening early in the pregnancy, and if found
negative, retesting done 24-28 weeks of AOG
For women of average risk, testing should be performed at 24-28 AOG
For GDM, FPG 126 mg/dL or a casual plasma glucose 200 mg/dL is diagnostic
If unequivocal hyperglycemia is not apparent, retesting must be performed on a subsequent day.

Two-step approach: GCT + OGTT
Initial screening: Glucose Challenge Test
a. 50-g oral glucose load (time of day or time of last meal not relevant)
b. Plasma is tested at 1 hour, and if glucose threshold value 140 mg/dL, an OGTT is performed
c. Some experts recommended using a threshold value of 130 mg/dL
OGTT oral ingestion of 100 g of glucose
Must meet or exceed two or more of the ff criteria:
1. FPG > 95 mg/dL
2. 1-hr > 180 mg/dL
3. 2-hr > 155 mg/dL
Alternatively, a 75-g glucose load may be used and glucose measured through the 2-hour period.

OGTT
Patient preparation:
Unrestricted CHO-rich diet for 3 days before the test with physical activity, restrict medication on the
test day, 12-hr fast required, no smoking
Adult patient ingests 75 g of glucose in 300-400 mL of water and children 1.75 g/kg up to 75 g of
glucose. For assessment of GDM, 50 g, 75 g, or 100 g of glucose may be used (see previous)
Plasma glucose specimen is collected fasting at 10 min, before glucose load and 2-hr after. Urine
glucose may be measured.
Impaired fasting glucose: FPG is between 110 and 125 mg/dL
Impaired glucose tolerance (IGT): FPG 126 mg/dL and 2-hr plasma glucose level (OGTT) between
140-199 mg/dL
DM: FPG 126 mg/dL or the 2-hour glucose is 200 mg/dL
HbA1c
Glycated/glycosylated hemoglobin
HbA composed of 3 forms, HbA
1a
, HbA
1b
, and HbA
1c
, which are referred to as glycated or glycosylated
hemoglobin. HbA
1c
is the main form.
Glycated Hb is formed from the nonenzymatic, irreversible attachment of glucose to HbA
1a

Measurement of glycated Hb reflects blood glucose levels for the past 2-3 months.
Useful in monitoring effectiveness and tx and compliance of diabetic individual to tx protocol
Specimen collection: Nonfasting blood drawn in EDTA tubes
Reference range: 4-6 % HbA
1c

Effective treatment range < 7% HbA
1c


LIPIDS AND LIPOPROTEINS

LIPID STRUCTURE
1. FAs
Exist as short, medium, and long chains of molecules that are major constituents of triglycerides and phospholipids.
Minimal amounts bound to albumin and circulate free (unesterified)
2. Triglyceride (TG)
Formed from one glycerol molecule with 3 FA molecules attached viva ester bonds
Comprise 95% of all fats stored in adipose tissue
Transported by chylomicrons and VLDL (very low density lipoprotein)
Metabolism involves releasing the FA to the cells for energy, then recycling the glycerol into the TG
Lipase, lipoprotein lipase, epinephrine, and cortisol break sown TGs.
3. Cholesterol
Unsaturated steroid alcohol; exists in the esterified form. Where a FA forms an ester bond at carbon-3, & free
(unesterified) form
Precursor for synthesis of bile acids, steroid hormones, & vit. D
LDL is the primary carrier of cholesterol
4. Phospholipid
Composed of one glycerol molecule and 2 FA molecules attached via ester bonds
Found on the surface of lipid layers
Major constituents of cell membranes and outer shells of lipoprotein molecules

Classification of Lipoproteins (Lp)
1. Lipoproteins
are molecules that combine water insoluble dietary lipids and water-soluble proteins (apolipoproteins) so that
lipids can be transported throughout the body. Micelles are spherical and have an inner core of neutral fat.
2. Chylomicrons are the largest Lps and have the lowest density
Formed in the intestines and transport TGs after a meal, giving serum a turbid appearance.
Low density: chylomicrons will float to the top and form a creamy layer when plasma is stored overnight
Composed of 86% TG, 5% cholesterol, 7% phospholipid, and 2% apolipoprotein
Enter the circulation and are metabolized to remnant particles for uptake and further modification by the liver.
3. Very-low-density lipoprotein (VLDL)
Carries endogenous TGs synthesized in the liver
Composed of 55% TG, 19% cholesterol, 18% phospholipid, 8% apolipoprotein
Secreted into the blood by the liver for metabolism in peripheral tissues
4. Intermediate-density lipoprotein (IDL)
A transitional form, as it is formed from VLDL and then further modified in the liver to LDL
IDLs carry endogenous TGS cholesterol esters
Composed of 23% TG, 38% cholesterol, 19% phospholipid, 19% apolipoprotein
5. Low-density lipoprotein (LDL)
Major cholesterol carrier
Transports a large amount of endogenous cholesterol
LDL is easily taken up by cells, so elevated levels are associated with increased risk for atherosclerosis
Composed of 50% cholesterol, 22% phospholipid, 6% TG and 22% protein
Brings cholesterol to peripheral cells for membrane synthesis and formation of adrenal and reproductive
hormones.


6. High-density lipoprotein (HDL)
Synthesized in the intestine and liver cells
Recycled chylomicron and VLDL molecules
50% protein, 28% phospholipids, 19% cholesterol and 3% TG
Has apoproteins A-I, mainly, and A-II on its surface
Removes excess cholesterol from peripheral tissues and transports it to other catabolic sites (antiatherogenic effect)
7. Lp(a)
Composed primarily of cholesterol esters, phospholipids and apolipoprotein (a) and B-100
Elevated levels assoc. with increased risk for coronary heart disease, MI, and cerebrovascular disease

Clinical Significance
Abnormal lipid metabolism can be due to genetic defects or it can be acquired.
Abnormal lipid metabolism is associated with risk of CAD and other disorders.
The National Cholesterol Education Program established the Adult Treatment Panel III Classification (ATP III), which
sets cutoff values for cholesterol and triglyceride levels based on a 9- to 12- hour fast.

TOTAL CHOLESTEROL REFERENCE RANGE
Desirable Borderline High High
Total Cholesterol (mg/dL) < 200 200-239 240

HDL CHOLESTEROL REFERENCE RANGE
Protective against
Heart Disease
The Higher, the
Better
Major Risk Factor for
Heart Disease
HDL Cholesterol
(mg/dL)
60 40-59 <40

LDL CHOLESTEROL REFERENCE RANGE
Optimal Near
optimal
Borderline High Very High
<100 100-129 130-159 160-189 190

TRIGLYCERIDE REFERENCE RANGE
Normal Borderline High Very High
Triglyceride
(mg/dL)
<150 150-199 200-499 500

Clinical Significance
Cholesterol
linked to atherosclerosis, CAD and increased for MI
various forms of liver disease, most notably alcoholic cirrhosis
HDL Cholesterol
HDL decreases the atherosclerotic process decreased risk of CAD
increased risk of coronary artery disease
LDL Cholesterol
LDL is directly associated with atherosclerosis and CAD
Triglyceride Test
in Type I, IIb, IV, and V hyperlipoproteinemias, pancreatitis alcoholism, obesity, hypothyroidism, nephrotic syndrome,
and storage diseases (Gaucher, Niemann-Pick)

ENZYMES AND CARDIAC ASSESSMENT

ENZYMES
Proteins that function as biological catalyst
Neither consumed nor permanently altered during a chemical reaction
Appear in the serum in increased amounts after cellular injury or tissue damage
Based on the px sxs, several enzymes may be chosen for analysis to determine if a pattern develops that aids in
identifying the tissue source source of the enzyme elevation
1. Lactate dehydrogenase (LD)
Tissue location
1. Highest concentrations: liver, heart, skeletal muscle, kidney, erythrocytes
2. LD isoenzymes
a. Each LD isoenzymes is a tetramer with five isoenzymes types:
LD-1 & LD-2 asso. with AMI and RBC destruction
LD-3- asso. with pulmonary disorders, pancreatitis and lymphocytosis
LD-4 & LD-5 asso. With liver & skeletal muscle d/o

Clinical significance:
1. cardiac disorders (AMI)
Hepatic diseases (viral hepatitis, cirrhosis, infectious mononucleosis), skeletal muscle dses
Haemolytic and hematologic d/o, pernicious anemia, neoplastic d/o (ALL)
2. In AMI, LD levels rises within 8-12 hours, peak at 24-48 hours, and returns to normal in 7-10 d.

2. Creatinine kinase (CK) and CK isoenzymes
Tissue location
1. Highest concentrations: Skeletal muscle, heart muscle, brain tissue
2. CK isoenzymes
a.Two subunits: M for muscle and B for brain
b. CK-MM (CK-3), CK-MB (CK-2), and CK-BB (CK-1)
c. CK-MB indicative of AMI when used in conjunction with other markers, such as troponin
DDx: skeletal muscle damage
CK-MM assoc. with skeletal muscle and heart muscle d/o
CK-BB in CNS d/o & tumor of various organs, e.g. prostate

Clinical Significance
1. total CK asso. with cardiac d/o, such as AMI, skeletal m. d/o, e.g. muscular dystrophy
Occasionally, d/o of the CNS, incl. seizures and CVA
2. CK-MB >6% of total CK: suggestive of AMI
When AMI suspected, troponin is assayed in conjunction with CK-MB, and sometimes myoglobin too.
Following AMI, CK-MB levels rise within 4-6 hrs, peak at 12-24 hrs, and return to normal within 2-3d.

3. Aspartate aminotransferase (AST)
Highest in heart, liver, and skeletal m.

Clinical Significance
1. AST is used to evaluate hepatocellular disorders (up to 100x upper reference limit in viral hepatitis,
hepatitis, up to 20x in infectious mononucleosis, and up to 4x in cirrhosis)
Skeletal m. d/o (up to 8x)
Pulmonary emboli (up to 3x)
Acute pancreatitis
2. In AMI, AST rises within 6-8 hours, peaks at 18-24 hrs, & returns to normal within 4-5 d.

4. Alanine aminotransferase (ALT)
Highest in liver, with lesser amounts in other tissues, including kidneys and erythrocytes

Clinical Significance:
Hepatocellular d/o (hepatitis, cirrhosis) exhibit higher ALT. ALT is more specific for liver disease than AST.
Elevated ALT & AST = to assess liver involvement in an AMI

5. Alkaline phosphatase (ALP)
Highest in liver, bone, intestine, spleen, kidney, placenta

Clinical Significance:
in hepatobiliary and bone d/o (with osteoblastic involvement)
In obstructive hepatobiliary d/o ALP levels are increased more significantly than ALT and AST
a. In biliary tract obstruction, synthesis of ALP is induced by cholestasis, which cause ALP levels to rise 3-10x
b. In hepatitis and cirrhosis, (hepatocellular conditions) ALP rise up to 3x
c. Highest elevations of ALP seen in Paget disease
6. Acid phosphatase (ACP)
Highest in prostate gland, with lesser amount in bone (osteoclasts), liver spleen, erythrocytes, platelets

Clinical Significance
1. Increased in prostate cancer, BPH, bone disease, Paget disease, breast cancer with bone metastases, Gaucher
disease, platelet damage, idiopathic thrombocytopenic purpura
2. Use of ACP in forensic cases involving rape vaginal washings containing seminal fluid would exhibit
ACP activity

7. Gamma-glutamyltransferase (GGT)
Found in liver (canaliculi of hepatic cells and epithelial cells lining biliary ductules), kidneys, pancreas,
intestine, etc.

Clinical Significance
1. Increased levels in all hepatobiliary disease:
2-5x viral hepatitis, alcoholic cirrhosis
Very sensitive indicator for these conditions
2. Higher levels (5030x) observed in intra- and posthepatic biliary tract obstruction, increases before and
remains elevated longer than ALP, AST, ALT
3. GGT activity induced by drugs (e.g., phenobarbital and phenytoin) and by alcohol consumption

8. Amylase
Found in pancreas, salivary glands, SI, FT, and other tissues

Clinical Significance
1. Acute pancreatitis: increased levels in 2-12 hrs after the onset of pain, peak hrs, return to normal in 3-4 d.
2. Increased: Mumps, perforated peptic ulcer, intestinal obstruction, cholecystitis, ruptured ectopic pregnancy,
mesenteric infarction, acute appendicitis

9. Lipase (LPS)
Tissue location
Found in pancreas, with lesser amounts in gastric mucosa, intestinal mucosa, adipose tissue

Clinical significance
1. Acute pancreatitis increased levels in 4-8 hours after the onset of pain, peak in 24 hrs, return to normal in
8-14 d.
2. Increased: Perforated peptic ulcer, duodenal ulcers, intestinal obstruction, cholecystitis

10. Glucose-6-phosphate dehydrogenase (G6PD)
Found in RBCs, adrenal glands, thymus, lymph nodes, spleen

Clinical significance
1. Decreased: Primary importance of G6PD is in cases of deficiency, inherited as a sex-linked trait (x-
chromosome)
In G6PD deficiency a hemolysis occurs with administration of antimalarial drugs or primaquine, infections
and after ingestion of fava beans.
2. Increased: Megaloblastic anemias and AMI













CARDIAC PROFILE
Upon arrival to the ER, a cardiac profile would be ordered to establish baseline values. Then the cardiac profile would be
ordered for several sampling in 3- to 8hr intervals over a 12-24 hr pd. Frequently blood is drawn every 3 hrs for
analysis during the 1
st
12 hrs.
Laboratory tests to assess AMI include cardiac troponin T or I, CK-MB, and sometimes myoglobin. In many institutions,
sampling and testing is halted since it is considered diagnostic for AMI.

1. TROPONIN
Troponins T, I, and C form a complex of 3 proteins that bind to filaments of skeletal muscle and cardiac muscle
to regulate muscle contraction.

Clinical Significance
1. cTnT or cTnI (cardiac troponin T or cardiac troponin I) is used as an AMI indicator because of specificity
and early rise of serum concentration following AMI.
2. In cases of AMI cTnT increases in 3-4 hrs, peaks in 10-24 hrs and returns to normal in 10-14 d. whereas,
cTnI increases in 3-6 hrs, peaks in 14-20 hrs, and returns to normal in 5-10 d.

2. MYOGLOBIN
Found in skeletal and cardiac muscles

Clinical significance
1. Increased in skeletal muscle injuries, muscular injuries, muscular dystrophy and AMI
2. Released early in cases of AMI, rising in 1-3 hrs, peaks in 5-12 hrs, and returns to normal in 18-30 hrs.
However, it is not tissue specific.
It is better used as a negative predictor in the first 2-4 hrs following chest pain.

NATRIURETIC PEPTIDES: POLYPEPTIDE HORMONES
a. Three forms: ANP, CNP, BNP
b. Effects are minimal;
Function promote excretion of Na and H2O by increasing the GFR and decreasing the renal tubular reabsorption of
Na.
c. B-type (brain) natriuretic peptide (BNP) is synthesized in and secreted from myocardial ventricles in response to
ventricular volume expansion and pressure overload.
BNP causes vasodilation and promotes Na and H2O loss, thus reducing fluid load in the heart to improve cardiac
function.
d. Clinical significance: BNP increased in CHF


High Sensitivity CRP (hs-CRP)
1. C-reactive protein (CRP): -globulin that is an acute-phase reactant
2. Refers to the sensitivity of the assay to determine low level in serum.
3. Clinical significance: Used as a predictor for cardiovascular risk; increased levels seen in inflammation, infection, stress,
trauma, and AMI