THE CLINICAL CHEMISTRY SECTION

Clinical Chemistry
- Branch of medical science that involves the analysis of chemical components of body fluids to provide diagnostic
information on the state of the human body

I. HISTORY OF CLINICAL CHEMISTRY

Early beginnings: Attribution of Diseases to Imbalances of Bodily Humors vs. Anatomic Approach
a. Hippocrates (Already discussed in Topic 1)
- Father of Medicine
- Started the belief that diseases are caused by imbalances of humors in the body.
- Sparked an interest among early physicians to observe bodily fluids

b. Giovanni Morgagni
- Introduced the anatomic approach of disease process
- Explained diseases in terms of localized pathologic anatomy, rather than as attributable to an imbalance of the
humors diffused throughout the system

c. Antoine Laurent Lavoisier

- Father of Modern Chemistry
- Recognized and named oxygen and hydrogen
- Discovered the role of oxygen in the process of combustion and that respiration is a slow combustion process.
- Started the belief that chemical analysis is a refined type of dissection
- Sparked a renewal of interest in the examination of body fluids

Vitalists & Mechanists: Opposing figures

Vitalists
- The very essence of life is due to a ‘vital force’ present in living organisms
- Fundamentals of the vitalism theory:
o Processes within living organisms were unique and could not be duplicated in the laboratory.
o Only living organisms can produce organic compounds and in vitro synthesis of ‘organic’ compounds is
impossible
o Only plants can synthesize complex compounds. Animals acquire such compounds via consumption of
plants
o Chemistry has no role in physiology
- Was the popular belief among leading physiologists and physicians including Marie Francois Xavier Bichat,
Johannes Muller, and Justus Baron von Leibig

Mechanists
- Life could be explained fully by chemical and physical principles and properties alone.
- Man is not unique as proven by the continuity between man and the animals (evolution theory) in Charles
Darwin’s publication ‘Origin of Species’

Animal Chemistry and How It Slowly Toppled Vitalism

a. Antoine Francois de Fourcroy

- Isolated urea from urine samples
- Believed that chemical laboratories should be located near the wards, where chemical analysis of urine and other
excretions of the sick could be carried out.

b. Friedrich Wohler
- Synthesized urea in vitro by evaporating an isomeric solution of ammonium cyanate
o ‘Organic’ substance could be synthesized in vitro without any ‘vital force’ in a living organism
o Bridge between the ‘organic’ and ‘inorganic’ worlds

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 c. Marcellin Berthelot
- Was able to synthesize organic compounds such as ethanol, formic acid, and benzene in vitro via chemical
treatments of inorganic compounds

d. Claude Bernard
- Discovered that glycogen was formed by the liver which contradicted the vitalism belief that only plants can
produce complex compounds.

e. John Bostock
- Was the first to observe that urea and albumin concentration in plasma decreases as their concentration
increases in the urine of the patient

Chemistry in Medical Education

a. William Prout
- Credited as the first to make the true connection between chemistry and medical practice
- Was a vitalist but advocated the benefits to be derived from the application of chemistry to physiology in the
treatment of disease
- Favored the study of physics and chemistry by medical students

b. Henry Bence Jones

- Stressed the practical diagnostic value of chemistry
- Urged the medical school curriculum to include a first-rate instruction in English; “Medical men would be much
better served if they spent some time in acquiring knowledge about chemistry and physics instead of learning
some Latin and Greek.”

c. Thomas Hodgkin
- “Chemical studies are relevant to clinical medicine”
- Continuous exchange between the solid parts & blood, “It is in the blood that we must look for many important
modifications in connection with disease”

During the 19th century, the average medical student or average practitioner had barely a nodding acquaintance with
chemistry and could not use a microscope.

d. Massachusetts General Hospital

- 1847: Recognizing the powerful aid that the science of medicine “has received from the study of organic
chemistry and the knowledge and use of the microscope”, authorized the purchase of a microscope at a cost n
- 1851: Established the position of “Chemist-Microscopist”

To cope with the growing number of chemical tests, the physician would usually enlist the help of chemists or physicians
skilled in chemistry
e. Otto Knut Folin
- Proposed that American hospitals employ clinical chemists to advance their ability to differentiate between the
physiologic and the pathologic

Clinical Chemistry Takes the Center Stage

a. Otto Knut Folin & Donald Dexter Van Slyke

- Determined reference intervals
- Correlated variations with pathologic conditions
- Elucidated metabolic pathways in health and disease

b. Donald Dexter Van Slyke

- Invented a volumetric gas-measuring apparatus for the determination of carbon dioxide concentration

c. Otto Knut Folin

- Together with Hsien Wu: Made a method for production of a protein-free filtrate that can be used for determining
blood sugar
- Developed the Duboscq type colorimeter for the measurement of creatinine in urine

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 d. Max Jaffe
- Developed the alkaline picrate method for determination of creatinine concentration

Early Instrumentation in Clinical Chemistry

a. Colorimetry
- Observation of the intensity of colored product after chemical reactions
- Pioneered by Folin after development of the duboscq-type visual colorimeter

b. Spectrophotometry
- Measurement of light intensity at selected wavelengths
- Initiated by the development of the Beckman DU Spectrophotometer by Cary and Beckman

c. AutoAnalyzer
- Continuous-flow instrument that reacted specimen and reagents to produce a measureable color density

d. Centrifugal analyzer
- Introduced by Norman Anderson
- Second attempt towards automation; First clinical analyser to incorporate a computer

e. Sequential Multiple Analyzer with Computer (SMAC)

- Capable of performing multiple tests analysed one after another on a given clinical specimen

f. Beckman Astra
- Introduced the perfected technology of automated pipetting which is the approach of choice for automation in
clinical chemistry laboratories even up to these days.

II. ROUTINE TESTS IN CLINICAL CHEMISTRY

1. Blood Glucose
- Detection of hyperglycemic and hypoglycemic states
- Determinations:
a. RBS: Random Blood Sugar
b. FBS: Fasting Blood Sugar
c. OGTT: Oral Glucose Tolerance Test (Often requested for pregnant population to rule out gestational
diabetes mellitus)

2. Blood Lipid Profile

- Important indicators of the patient’s pre-disposition to cardiovascular diseases and various metabolic disorders
- Lipids:
a. Fatty acids
 Simplest form of lipids; Not usually measured in the clinical laboratory
b. Triglycerides
 Storage form of fat
c. Cholesterol
 Steroid alcohol
 Precursor of hormones, Vitamin D, and bile salts
d. Lipoproteins
 Carriers of cholesterol and triglycerides
i. High density lipoproteins (HDL)
 “Good cholesterol” ; Transports cholesterol from peripheral tissues back to liver for
metabolism
ii. Low density lipoproteins
 “Bad cholesterol”; Transports cholesterol from liver to peripheral tissues

iii. Very low density lipoproteins

 Transports endogenous triglycerides to the muscles and adipocytes
iv. Chylomicrons
 Transports exogenous triglycerides to the muscle and adipocytes

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3. Renal Function Tests
- Diagnosis of renal diseases
- Tests:
a. Creatinine
 Waste product of muscle metabolism
 Blood levels are elevated in impaired renal function
b. Blood Urea Nitrogen (BUN)
 Waste product of protein catabolism
 Elevated concentration in kidney diseases
 Azotemia: Elevation of BUN
 Uremia: Elevated BUN levels accompanied by renal failure
c. Uric Acid
 Product of catabolism of purine nucleic acids
 Measured to detect kidney dysfunction, assist in the diagnosis of renal stones (renal calculi), and
to diagnose and monitor the treatment of gout.

4. Liver Function Tests

- Tests:
a. Bilirubin
 Brownish yellow pigment; Product of hemoglobin (heme) breakdown after red blood cell
destruction
 Two forms:
 Unconjugated Bilirubin (B1)/ Indirect Bilirubin
 Conjugated bilirubin (B2)/ Direct bilirubin
b. Liver enzyme tests
i. Aspartate aminotransferase (AST)
 Formerly called serum glutamic oxaloacetic transaminase (SGOT)
ii. Alanine aminotransferase (ALT)
 Formerly called serum glutamic pyruvic transaminase (SGPT)
* If ALT and AST are found together in elevated amounts in the blood, liver damage is most likely present
iii. Gamma-glutamyl transferase (GGT)
 Useful in the diagnosis of chronic alcoholism resulting in liver damage

5. Cardiac Function Tests

- Tests:
a. Troponin Test
 Troponins are regulatory proteins in the cardiac muscles
 Considered the most specific test for myocardial damage
 Isoforms: Troponin I and Troponin T (Both are specific to the myocardium)
b. Myoglobin
 Oxygen carrier in muscle tissue
 Not as specific as troponin for cardiac tissue
c. Cardiac enzymes
i. Creatine Kinase-MB (CK-MB)
ii. Aspartate aminotransferase (AST)
iii. Lactate Dehydrogenase (LDH)
** AST and LDH are not specific for myocardial damage

6. HbA1c
- “Hemoglobin A1c” , Glycated hemoglobin, Glycosylated hemoglobin
- Reflects the average blood glucose levels of the patient over a three-month period

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