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Medical Laboratory Technology: Volume 3
Figure 29.5 Haemoglobin degradation and bilirubin metabolism
deoxyribonucleic acid (DNA). In higher animals, DNA is the carrier of genetic information
from the parent to ospring. The nitrogenous bases found in various nucleic acids include
purines and pyrimidines. Pyrimidines are aromatic heterocyclic, while purines are a
pyrimidine ring fused to an imidazole ring. Adenine and guanine are purines, whereas
uracil, cytosine and thymine are pyrimidines. Nucleotides are composed of phosphoric acid,
a sugar and a nitrogenous base (purine or pyrimidine). These come together to form nucleic
acids. Adenosine is the most important nucleotide and is composed of an adenine base and a
ribose—a pentose sugar molecule. Adenosine diphosphate (ADP) and adenosine triphosphate
(ATP) are examples of nucleotides involved in energy transfer throughout the body (Figure
29.6). The formation, of ATP is mediated by the breakdown of various organic compounds.
Bond energy within carbon-carbon
bonds are utilized to bind phosphates
to adenosine, thus creating ATP. ATP is
utilized as mobile energy units and is
actively transported throughout the body
based on energy demand. The release of
energy when the 3’ phosphate is cleaved
from ATP is signicant and it is used to
Figure 29.6 Process of energy transfer in the body
drive millions of reactions every second. The resultant product ADP, is then recycled into ATP
by binding an extra inorganic phosphate via catabolism.
Lipids make up the fourth most important group of organic compounds aer carbohydrates,
proteins and non-protein nitrogenous compounds. They are insoluble in water but soluble in
organic solvents such as chloroform, ether and alcohol. In chemical terms, lipids are esters of
Biochemical Processes of the Body Under Normal and Pathogenic Conditions
907
fay acids with the basic elemental composition of C, H and O. Although the same elements
form the basic structure of carbohydrates as well, lipids are in a more reduced state. Simply
put, they have more hydrogen and thus can store more energy (calories) within a smaller
unit area. Complex lipids may include phosphorus and nitrogen to form phospholipids
and lipoproteins. Esters are formed by the chemical reaction of fay acids with an alcohol
(contains OH group). This is similar to the formation of salt by the reaction of an acid with a
base or alkali (this also contains an OH group).
HC1 + NaOH = NaCl + H2O
Fay acid + Glycerol = Ester + H2O
Triglyceride is a simple lipid that is formed by the union of glycerol and three fay acids—
stearic, oleic and palmitic (Figure 29.7). Complex lipids are also esters but they include
other chemical groups (phosphate to form phospholipids, protein to form lipoproteins and
glucose to form glycolipids). In sphingolipids, glycerol is replaced by an amino alcohol called
sphingosine. Vitamins A, D, E and K are fat soluble and bilirubin of bile, waxes, carotene
and fay acids are soluble in organic solvents; hence, they are also classied as lipids. Most
dietary fats are rst digested by the fat-digestive enzyme lipase, which hydrolyses the fat
into fay acids and glycerol. These enzyme products are water-soluble and absorbed directly
into the body from the digestive tract, whereas fay acids, which are not soluble in water, are
absorbed by the body from micelles (colloidal suspension) produced in the digestive tract
with the help of bile salts (sodium glycocholate and sodium taurocholate). Glycerol, other
than from the dietary origin, is also a metabolic product of glucose breakdown. Thus the
body can re-synthesize its own fat from the basic ingredients—fay acids and glycerol. The
liver plays an important role in the synthesis of body fats. Fat is transported in the body by
the lipoproteins, which are synthesized in the liver and small intestine. In the body, the lipids
can serve as structural and functional elements (e.g., plasma membrane), as precursors of
many essential substances as a secondary energy source and as an insulator.
Figure 29.7 Formation of triglyceride from glycerol and fatty acids through dehydration synthesis (opposite
of hydrolysis)
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Medical Laboratory Technology: Volume 3
Sterols have fat like properties (insoluble in
water but soluble in organic solvents). Steroids
are chemically related to sterols (e.g., steroid
hormones, vitamin D and bile acids). Steroids
have a characteristic chemical structure (Figure
29.8) composed of four rings. Cholesterol is
one of the important sterols of the body and is
a precursor to a number of steroid hormones.
Body cholesterol is found as free cholesterol
or esterified cholesterol. Esterification of
cholesterol occurs in plasma with the aid of
lecithin-cholesterol acyltransferase (LCAT), an
enzyme produced in the liver. Cholesterol is
present in all lipoproteins and two-thirds of the
plasma total cholesterol is esteried with longchain fay acids. Linoleic acid, specically, is
the predominant fay acid in humans. The
cholesterol esters in the plasma are in a state
of constant turnover because of their continual
hydrolysis and re-synthesis. It is suggested
that esteried cholesterol is easy to transport
through the plasma, from the tissues to the
liver—the seat of body-cholesterol synthesis.
Ketone bodies include three organic compounds—acetone, acetoacetic acid and betahydroxybutyric acid. These are products of
fat degradation through incomplete oxidation.
Interestingly, these compounds are the only
products of fat that can pass the blood-brain
barrier and provide energy to the cerebrum.
iNterrelated metabolic Processes of the body
The body performs a number of anabolic and
catabolic processes that are closely interconnected. Anabolism, the synthesis of complex
organic compounds from simpler compounds,
requires energy. Important anabolic processes
include the storage of glucose as glycogen, creation of proteins from amino acids, creation of
complex fats from fay acids and glycerol, and
the production of urea from ammonia and carbon dioxide.
Catabolism is the opposite of anabolism and results in the release of energy. The degradation
processes yield simpler products from complex organic compounds. Digestion and oxidation
are the two most common degradation processes. Oen times, products of digestion are
oxidized to water and carbon dioxide. Energy released by the breakdown of chemical bonds
is available for the growth and development of the body. Mitochondria, which are specic
organelles present in cells, leverage the energy generated by catabolism to generate ATP.
The interrelated metabolic processes, involving carbohydrates, fats and proteins, are shown
in Figure 29.9. Dietary glucose is stored in the liver as polysaccharide glycogen (animal starch).
When energy is required, glycogen is rst converted to glucose, which is then anaerobically
Figure 29.8 Chemical structures of some of the
important organic compounds in the
body. The shared steroid structure (four
shades rings) is seen in cholesterol,
corticosterone and cholic acid (bile).
Biochemical Processes of the Body Under Normal and Pathogenic Conditions
909
Figure 29.9 Interconnected biochemical processes of the body leading to aerobic respiration
degraded to pyruvic acid (a three-carbon compound) via a process called glycolysis. Pyruvic
acid is the end-product of glycolysis that may either lead to the formation of lactic acid under
anaerobic conditions, or to the formation of acetate (a 2-C compound, acetylcoenzyme A,
acetyl-CoA) prior to entry into the Krebs cycle. Acetate also acts as a ‘junction box’ for the
metabolic products of carbohydrates, fats and proteins in order to supply energy for the
growth and development of the body. Simply put, the degradation of carbohydrates, fats,
and proteins, all lead to the formation of acetyl-coA, which in turn enters the Krebs cycle and
becomes fully oxidized.
fuNctioNs of Various orgaNs
The function of the human body is regulated by its various organs. These organs do not
function independently, and coordinated by a network of chemical communication. In the
following sections we will elaborate on some of the most important organs of the body, their
normal functions, and signs of abnormal functions.
Liver
The liver plays a vital role in the metabolic processes of the body. These processes can be
broadly classied as synthesis, storage and excretion. The liver synthesizes a variety of
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Medical Laboratory Technology: Volume 3
organic compounds—albumin, brinogen, urea, uric acid, prothrombin, lipoprotein,
transferrin, glycoprotein, hippuric acid, cholesterol and other lipids. Glucose is stored in the
liver as glycogen and returned to blood circulation when body glucose levels decrease. Besides
glycogen, the liver stores fat-soluble vitamins (A, D, E and K) and vitamin B. The excretory
and detoxifying functions of the liver are evident in conversation of unconjugated bilirubin
to conjugated bilirubin. In the degradation of haemoglobin, the end-product (unconjugated
bilirubin) is delivered to the liver via binding to albumin. In the liver, bilirubin is conjugated
and later excreted as bile pigment into the intestine. Many other water insoluble, toxic
substances are similarly removed from blood circulation through the bile duct, as they cannot
be properly excreted through the kidneys.
Jaundice, hepatitis, cirrhosis (degeneration), fay liver, infection (abscess) and amyloids are
some of the many pathologic conditions of the liver. Diagnostic test results for the assessment
of liver function include increased serum transaminase activity, decreased blood urea nitrogen
(BUN), decreased serum albumin, increased prothrombin time (PT) in coagulation, increased
ammonia concentration in the blood, decreased levels of conjugated bilirubin, and esteried
cholesterol in serum (Table 29.1).
Table 29.1 Routine clinical chemistry proles
Ordering physician: Name of patient:
Date: Date of birth:
Outpatient Ward (Location)
Nurse
General Prole Glucose BUN Bilirubin Date of specimen collection:
Protein Albumin Calcium
Phosphorus Uric acid Alkaline
AST LDH Cholesterol
A/G ratio Globulin T4
Kidney (renal)
Prole
Liver (hepatic)
Prole
Cardiac Prole AST LDH CK (CPK)
Sodium Potassium CO
Chloride Glucose BUN
Creatinine
Bilirubin
total
Albumin Alk. Phos. AST
Serum LDH A/G ratio Globulin
ALT Gamma GT Liver LDH
CK isoenzymes: Only done if CK is elevated
Bilirubin
direct
Phos.
2
Protein
Time of specimen collection:
Technician collecting specimen:
Date of reporting result:
Time of reporting result:
Technician reporting:
Other comments:
Lipid Prole Cholesterol Triglyceride HDL
Thyroid Prole T3 T4 TSH Laboratory supervisor:
Iron Prole Total iron
Total iron binding capacity
Unsaturated iron binding capacity
A common test for liver disorders involves the injection of fructose and galactose into the
blood stream. Normally, these sugars are converted to glucose by the liver when present in
Biochemical Processes of the Body Under Normal and Pathogenic Conditions
serum. If these sugar levels are maintained over time, this is indicative of a liver disorder. The
detoxication action of the liver is assessed by administering bromosulphophthalein (BSP),
95% of which is removed from the blood within 15 min in normal liver function.
911
Kidney
The primary function of the kidney is to lter blood, however, it also reabsorbs essential
substances from the ltrate. Kidney function is also closely related to the homeostasis of the
body through the maintenance of the water-electrolyte balance and production of certain
hormones. The chemistry panel in a kidney function test is provided in Table 29.1. This
includes glucose, BUN, creatinine, uric acid and electrolytes. Renal failure is diagnosed by
the increased level of serum creatinine, and urea. The glomerular ltration rate (GMR) for
creatinine clearance is a reliable index to assess kidney diseases.
Heart
The heart is another important organ of the body and is the centre of the circulatory system.
Heart diseases are caused by a number of agents. The clinical laboratory assesses heart
condition through enzyme assays of creatine kinase (CK), AST and lactic dehydrogenase
isoenzymes (Table 29.1).
Pancreas
The pancreas externally secretes digestive enzymes (e.g., amylase, lipase) into the digestive
system. It also internally secretes insulin, an endocrine hormone, from the islets of Langerhans,
which are tiny isolated masses of ductless glands. Pancreatic pathology is diagnosed in the
laboratory by the assay of digestive enzymes in serum and in urine.
Endocrine glands
Endocrine glands are ductless glands that produce internal secretion of hormones. The
brain, hypothalamus and pituitary act in concert to control the body functions through
the mediation of several target organs. Hormonal regulation is typically used to modulate
autonomic function that takes place over long periods of time (such as breathing and heart
rate).
Hormones are either steroids or proteins. They regulate the interdependent metabolic
processes of the body and its overall development. The laer involves the reproductive
system, formation of a personality, ability to combat stress, as well as pathogen resistance.
Insulin plays an important role in the carbohydrate metabolism and its deciency leads to
hyperglycaemia (increased glucose concentration of blood) and glucosuria (glucose excretion
in urine). Thyroid hormones—triiodothyronine or T3 and thyroxine or T4—are also intimately
connected with carbohydrate metabolism of the body and regulate several other metabolic
processes.
There are two components of the pituitary gland—anterior and posterior. The posterior
pituitary secretes only one hormone: vasopressin or anti-diuretic hormone (ADH). ADH
controls water absorption from the intestines and the kidneys. The anterior pituitary, on
the other hand, releases a number of hormones that trigger several target organs. The target
organs respond by releasing appropriate hormones to meet the physiological needs of the
body. Abnormal hormone levels may cause a number of pathophysiological problems which
will be discussed in detail in the subsequent pages.
The following are some examples of anterior pituitary-mediated hormones which are of
clinical signicance.
1. Thyroid-stimulating hormone (TSH): Controls the release of thyroid hormones T3 and
T4.
2. Adrenocorticotropic hormone (ACTH): Stimulates the adrenal gland cortex, which
secretes corticosteroids (e.g., aldosterone, 17-hydroxycorticosteroids and 17-ketosteroids) and androgens.
912
3. Gonadotropins: Stimulates the release of testosterone and 17-ketosteroids in the testes
(oestrogen and progesterone in the ovaries).
The following are the examples of pituitary-independent hormones:
• Adrenal medullary hormones: Epinephrine and norepinephrine (catecholamines);
hypersecretion of catecholamines is seen in pheochromocytoma, a vascular tumour of
chroman tissue of the adrenal medulla.
• Insulin (pancreatic secretion)
• Parathormone (parathyroid gland secretion)
• Serotonin (5-hydroxytryptamine): 5-hydroxyindoleacetic acid (5-HIAA) is produced
during serotonin metabolism. Increased discharge of 5-HIAA in urine is diagnostic of
certain intestinal tumours.
• Human chorionic gonadotrophin or HCG: Released from the placenta in pregnant women.
The chemistry panel for the thyroid function includes T3, T4 and TSH (Table 29.1).
Medical Laboratory Technology: Volume 3
Lungs
The lungs govern gas exchange in the body. Within alveoli, oxygen is provided to blood
within pulmonary capillaries and carbon dioxide is removed. Haemoglobin acts as a
carrier of these gases (CO2 and O2) between the lungs and the cells. The pathologic states of
respiratory acidosis and alkalosis originate from uctuations of the partial pressure of carbon
dioxide in blood. Metabolic acidosis and alkalosis, on the other hand, are governed by serum
bicarbonate level which is regulated by the kidney. Metabolic disorders like ketosis may also
lead to metabolic acidosis.
Brain
The brain is the primary centre for regulating and coordinating various neural activities of the
body. Pathologic states of the brain (infection, tumour, haemorrhage) can be assessed from
the laboratory study of cerebral spinal uid (CSF). CSF surrounds the brain and spinal cord;
physical and chemical changes of the spinal uid signal meningeal dysfunction.
biochemical chaNges iN the body uNder Pathologic coNditioNs
A delicate biochemical balance (homeostasis) is maintained by the body under normal
conditions. When this is disturbed, a pathologic state is suspected. As the chemical composition
of the body is greatly dependent on the functions of various organs and endocrine glands, a
study of the chemical changes can be helpful in speculating on the source of trouble.
Here, we will consider the abnormal carbohydrate metabolism of a patient with diabetes
mellitus, an insulin deciency, in order to illustrate the interrelated nature of biochemical
processes of the body (Figure 29.10).
Note Diabetes insipidus is caused by ADH deciency. Diabetes that develops over time is
referred to as type II diabetes or diabetes mellitus.
Four main abnormalities in diabetic patients are listed as follows:
1. Glucose is not readily removed from the circulation for storage in the liver as glycogen.
2. The Krebs cycle does not function eciently and thus glucose not adequately utilized in
generating energy.
3. Decreased availability of glucose, thus leading to a decreased ability match energy
demand. This results in anaerobic degradation of fats, as the Krebs cycle is inhibited by
lack of insulin.
Biochemical Processes of the Body Under Normal and Pathogenic Conditions
913
Figure 29.10 Metabolic disorder in diabetes mellitus
4. As a result, formation of ketone bodies (ketosis), metabolic acidosis and increased anion gap
accompany untreated diabetes.
The abnormal chemical composition of blood sera also reects organ or systemic dysfunction.
Biochemical test proles for various disorders of organs are presented in Chapter 34 of this
volume. Decreased protein concentration (particularly albumin), decreased PT, increased
bilirubin concentration and increased transaminase activity are some of many indications of
liver disorder. On the other hand, increased protein levels could be a sign of infection and/
or lymphoproliferative disorders. The increase in protein in the blood is inferred to result
from the increased synthesis and secretion of antibodies (globulin) from lymphocytes and
plasma cells. Similarly, elevated urea and creatinine in blood sera is indicative of kidney
abnormalities. The kidney typically clears waste materials, inorganic ions, and other
by-products of degradation from the blood; however, these substances will build up in the
blood during kidney dysfunction. Other laboratory information, such as the presence of
casts in urine (urine analysis) and decreased GFR (glomerular ltration rate) will support the
diagnosis of renal failure.
In recent years, accurate analysis of serum enzymes has greatly assisted in pinpointing
organs with abnormal function. Most organs of the body have the predominance of some
specic enzymes in their cells in order to carry out their biochemical functions. For example,
the liver contains a high concentration of transaminases to carry out transamination. If the
organ is in distress, its cellular enzymes are released into the blood stream. Thus, the elevation
of specic enzyme levels in blood may indicate a pathologic organ. Another example of this
is the increase in amylase and lipase activities in serum subsequent to pancreatic disorder.
These will be further discussed in the following sections.
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Medical Laboratory Technology: Volume 3
basic cliNical biochemistry
Chemistry Profiles
Blood chemistry tests are classied as ‘routine’ or ‘special’. Routine tests are those that
frequently ordered. Chemistry proles, or metabolic proles, are a group of tests performed
simultaneously on a patient specimen to provide a general assessment of the patient’s
condition. The physician can use the results of the chemistry prole, in conjunction with
a physical examination and patient history to assess the overall health of the patient (Table
29.1). Many automated chemistry analysers are capable of performing various chemistry
proles in a group.
Tests that are ordered less frequently, such as those that access hormone or certain drug
levels, may be performed occasionally and are sometimes referred to as ‘special’ tests. These
are typically carried out in special laboratories.
Types of Specimens for Chemical Analyses
Specimens arriving at the desk of a clinical laboratory commonly include blood, urine, etc.,
however, samples can also include CSF and synovial, pleural, or pericardial uid. Specimens
other than blood and urine are collected by the physician. Some collections of patient samples
require prior preparations on the patient’s side, such as samples for glucose. When measuring
fasting sugar levels, a patient should not have consumed food for a number of hours. The
technician collecting the specimen must also be aware of the specic contingencies involved
in various tests so as to ensure accurate collection and processing of the sample itself. Many
specimens (e.g., urine) change their chemical composition over time (compounds within the
sample degrade quickly), and such specimens should be handled quickly.
Units of Measure in Clinical Chemistry
Clinical chemistry test results are usually reported in metric units or SI units (Table 29.2).
Commonly used units are milligrams (mg) or micrograms (mg) per decilitre (dL), millimoles
per litre (mmol/L) or in the case of enzymes, enzyme activity units per litre (U/L). In developing
countries, however, older units may still be in use and, hence, a conversion factor has been
provided in Table 29.2 for reporting these results in modern units (SI).
Reference (Normal) Ranges
The reference (or normal) range of a substance is determined by measuring the level of the
substance in a portion of the general population and applying statistical methods to the data.
The reference range is not universal. Hence each hospital should maintain its own reference
range. The process of establishing reference ranges has been discussed in Chapter 7 of Vol. 1.
Table 29.2 gives the reference ranges of commonly tested analytes in a clinical laboratory. If a
patient’s results are beyond normal ranges, it must be highlighted or agged in order to draw
the aention of the physician. If the results are excessively high compared to the norm, the
physician should be informed immediately.
diagNostic biochemical Profiles
Biochemical proles are groups of tests performed in the biochemistry laboratories that are
used to assess the general function of the body or for the diagnosis of specic organ disorders
Biochemical Processes of the Body Under Normal and Pathogenic Conditions
Table 29.2 Clinical chemistry reference values in conventional and SI units
Test (Substances measured) Conventional Unit Conversion Factor SI Unit
Alanine aminotransferase (ALT) 3–30 U/L 1 3–30 U/L
Albumin 3.8–5.0 g/dL 10 38–50 g/L
Alkaline phosphatase (AP) 20–130 U/L 1 20–130 U/L
Aspartate aminotransferase (AST) 10–37 U/L 1 10–37 U/L
Bicarbonate (HCO
Bilirubin (Total) 0.1–1.2 mg/dL 17.1
–
) 22–28 mEq/L 1 mmol/L
3
2–21 mmol/L
915
Bilirubin (Direct) 0–0.3 mg/dL 17.1
BUN 8–18 mg/dL 0.357 2.9–6.4 mmol/L
Calcium 8.7–10.5 mg/dL 0.25 2.18–2.63 mmol/L
Chloride 98–108 mEq/L l 98–108 mmol/L
Cholesterol (Total) 140–250 mg/dL 0.026 3.6–6.5 mmol/L
Creatinine 0.7–1.4 U/L 88.5 62–125 umol/L
Creatinine kinase 30–170 U/L 1 30–170U/L
Gamma glutamyltransferase (GGT) 3–40U/L 1 3–40 U/L
Glucose 70–110 0.05 3.9–6.2 mmol/L
Iron 65–165 0.18
Lactate dehydrogenase (LD) 110–230 U/L 1 110–230U/L
Phosphorus 3.0–4.5 mg/dL 0.32 0.96–1.44 mmol/L
Potassium 3.5–5.4 mEq/L 1 3.5–5.4 mmol/L
Sodium 135–148 mEq/L 1 135–148 mmol/L
Thyroid stimulating hormone (TSH)
Total protein 6.0–8.0 g/dL 10 60–80 g/L
0.35–5.0 mIU/mL
1 0.35–5.0 mIU/L
0–6 mmol/L
11.6–29.5 mmol/L
Triglycerides 10–190 mg/dL 0.011 0.11–2.15 mmol/L
Uric acid 3.5–7.5 mg/dL 0.06 0.21–0.44 mmol/L
(Table 29.2). Measurements of the protein level of serum and electrolyte concentrations are
included in most routine chemistry proles, and hence are discussed separately.
Protein
Two major groups of serum proteins are albumins (60%) and globulins (40%). Albumin is
made in the liver while globulins, particularly immunoglobulin, are made by lymphocytes
and plasma cells.