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Section I GENERAL PATHOLOGY

CHAPTER 1
1 Introduction to Pathology

Introduction to Pathology
STUDY OF PATHOLOGY
The word ‘Pathology’ is derived from two Greek words—pathos
(meaning suffering) and logos (meaning study). Pathology is,
thus, scientific study of changes in the structure and function
of the body in disease. In other words, pathology consists of the
abnormalities in normal anatomy (including histology) and
normal physiology owing to disease. Another commonly used
term with reference to study of diseases is ‘pathophysiology’
(patho=suffering, physiology=study of normal function).
Pathophysiology, thus, includes study of disordered function
(i.e. physiological changes) and breakdown of homeostasis in
diseases (i.e. biochemical changes). Pathologists contribute in
patient management by providing final diagnosis of disease.
Therefore, knowledge and understanding of pathology is
essential for all would-be doctors, as well as general medical
practitioners and specialists because unless they have
knowledge and understanding of the language in the form
of pathology laboratory reports, they would not be able to
institute appropriate treatment or suggest preventive measures
to the patient.
For the student of any system of medicine, the discipline of
pathology forms a vital bridge between initial learning phase
of preclinical sciences and the final phase of clinical subjects.
The role and significance of learning of pathology in clinical Figure 1.1  Sir William Osler (1849–1919). Canadian physician and one
medicine is quite well summed up by Sir William Osler (1849- of the four founding Professors of Johns Hopkins Hospital, Baltimore,
1919), acclaimed physician and teacher in medicine considered US, is regarded as ‘Father of Modern Medicine’, Sir Osler had keen interest
in pathology, was an acclaimed teacher and is also remembered for his
as ‘Father of Modern Medicine’ by his famous quote “your
famous quotations.
practice of medicine will be as good as is your understanding
of pathology” (Fig. 1.1).

HEALTH AND DISEASE healthy state. The term syndrome (meaning running together)
is used for a combi­nation of several clinical features caused by
Before there were humans on earth, there was disease, albeit in altered physiologic processes.
early animals. Since pathology is the study of disease, then what
is disease? In simple language, disease is opposite of health
i.e. what is not healthy is disease. Health may be defined as a
COMMON TERMS IN PATHOLOGY
condition when the individual is in complete accord with the It is important for a beginner in pathology to be familiar with
surroundings, while disease is loss of ease (or comfort) to the the language used in pathology (Fig.1.2):
body (i.e. dis+ease). However, it must be borne in mind that in ”” Patient is the person affected by disease.
health there is a wide range of ‘normality’ e.g. in height, weight, ”” Lesions are the characteristic changes in tissues and cells
blood and tissue chemical composition etc. It also needs to be produced by disease in an individual or experimental animal.
appreciated that at cellular level, the cells display wide range ”” Pathologic changes or morphology consist of exami­nation
of activities within the broad area of health similar to what is of diseased tissues. These can be recognised with the naked
seen in diseased cells. Thus, a disease or an illness means a eye (gross or macroscopic changes) or studied by microscopic
condition marked by pronounced deviation from the normal examination of tissues.
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SECTION I
General Pathology

Figure 1.2  Diagrammatic depiction of disease and various terms used in pathology.

”” Causal factors responsible for the lesions are included in PREHISTORIC TIMES TO MEDIEVAL PERIOD
etiology of disease (i.e. ‘why’ of disease).
”” Mechanism by which the lesions are produced is termed Present-day knowledge of primitive culture which was
pathogenesis of disease (i.e. ‘how’ of disease). prevalent in the world in prehistoric times reveals that religion,
”” Functional implications of the lesion felt by the patient magic and medical treatment were quite linked to each other
are symptoms and those discovered by the clinician are the in those times. The earliest concept of disease understood by
physical signs. the patient and the healer was the religious belief that disease
”” Clinical significance of the morphologic and functional was the outcome of ‘curse from God’ or the belief in magic that
changes together with results of other investigations help to the affliction had supernatural origin from ‘evil eye of spirits.’
arrive at an answer to what is wrong (diagnosis), what is going To ward them off, priests through prayers and sacrifices, and
to happen (prognosis), what can be done about it (treatment), magicians by magic power used to act as faith-healers and
and finally what should be done to avoid complications and invoke supernatural powers and please the gods. Remnants
spread (prevention) (i.e. ‘what’ of disease). of ancient superstitions still exist in some parts of the world.
The link between medicine and religion became so firmly
established throughout the world that different societies had
EVOLUTION OF PATHOLOGY their gods and goddesses of healing; for example: mythological
Pathology as the scientific study of disease processes has its Greeks had Aesculapius and Apollo as the principal gods of
deep roots in medical history. Since the beginning of mankind, healing, Dhanvantri as the deity of medicine in India, and
there has been desire as well as need to know more about orthodox Indians’ belief in Mata Sheetala Devi as the pox
the causes, mechanisms and nature of diseases. The answers goddess.
to these questions have evolved over the centuries—from The insignia of healing, the Caduceus, having snake and
supernatural beliefs to the present state of our knowledge staff, is believed to represent the god Hermes or Mercury,
of modern pathology. However, pathology is not separable which according to Greek mythology has power of healing
from other multiple disciplines of medicine and owes its since snake has regenerative powers expressed by its periodic
development to interaction and inter­dependence on advances sloughing of its skin. God of Greek medicine, Aesculapius,
in diverse neighbouring branches of science, in addition to performed his functions with a staff having a single serpent
the strides made in medical technology. As we shall see in the wound around it. Later (around AD1800), however, the
pages that follow, pathology has evolved over the years as a Caduceus got replaced with twin-serpents wound around
distinct discipline from anatomy, medicine and surgery, in that a staff topped by a round knob and flanked by two wings
sequence. and now represents the symbol of medicine instead of cross
The following brief review of fascinating history of pathology (Fig. 1.3).
and its many magnificent personalities with their outstanding The period of ancient religious and magical beliefs was
contribution in the form of a disease or a process known by followed by the philosophical and rational approach to disease
their names, is meant to stimulate and generate interest in by the methods of observations. This happened at the time
the inquisitive beginner in pathology as to how this colourful when great Greek philosophers—Socrates, Plato and Aristotle,
specialty has emerged. introduced philosophical conc
 But the real practice of medicine began with Hippocrates 3
(460–370 BC), the great Greek clinical genius of all times and
regarded as ‘the father of medicine’ (Fig. 1.4). Hippocrates
dissociated medicine from religion and magic. Instead, he

CHAPTER 1
firmly believed in study of patient’s symptoms and described
methods of diagnosis. He recorded his observations on cases
in the form of collections of writings called Hippocratic Corpus
which remained the mainstay of learning of medicine for
nearly two thousand years. However, the prevailing concept at
that time on mechanism of disease based on disequili­brium of
four basic humors (water, air, fire, and earth) was propagated
by Hippocates too but this concept was later abandoned.
Hippocrates followed rational and ethical attitudes in
practice and teaching of medicine and is revered by the medical

Introduction to Pathology
profession by taking ‘Hippocratic oath’ at the time of entry into
practice of medicine.
After Hippocrates, Greek medicine reached Rome (now
Italy) which controlled Greek world after 146 BC and, therefore,
it dominated the field of development of medicine in ancient
Europe then. In fact, since old times, many tongue-twisting
terminologies in medicine have their origin from Latin
language which was the official language of countries included
in ancient Roman empire (Spanish, Portuguese, Italian, French
and Greek languages have their origin from Latin).
In Rome, Hippocratic teaching was propagated by Roman
physicians, notably by Cornelius Celsus (53 BC-7 AD) and
Figure 1.4  Hippocrates (460–370 BC). The great Greek clinical genius
Claudius Galen (130–200 AD). Celsus first described four
and regarded as ‘the Father of Medicine’. He introduced ethical aspects
cardinal signs of inflammation—rubor (redness), tumor to medicine.
(swelling), calor (heat), and dolor (pain). Galen postulated
humoral theory, later called Galenic theory. This theory
suggested that the illness resulted from imbalance between book of surgical sciences by Sushruta, and includes about 700
four humors (or body fluids): blood, lymph, black bile (believed plant-derived medicines.
at that time to be from the spleen), and biliary secretion from The end of Medieval period was marked by back­ ward
the liver. steps in medicine. There were widespread and devastating
The hypothesis of disequilibrium of four elements consti­ epidemics which reversed the process of rational thinking
tuting the body (Dhatus) similar to Hippocratic doctrine finds again to supernatural concepts and divine punishment for
mention in ancient Indian medicine books compiled about ‘sins.’ The dominant belief during this period was that life was
200 AD—Charaka Samhita, a finest document by Charaka on due to influence of vital substance under the control of soul
medicine listing 500 remedies, and Sushruta Samhita, similar (theory of vitalism). Thus, dissection of human body was strictly
forbidden at that time as that would mean hurting the ‘soul.’

HUMAN ANATOMY AND ERA

OF GROSS PATHOLOGY
The backwardness of Medieval period was followed by the
Renaissance period i.e. revival of learning. The Renaissance
began from Italy in late 15th century and spread to whole of
Europe. During this period, there was quest for advances in
art and science. Since there was freedom of thought, there was
emphasis on philosophical and rational attitudes again.
The beginning of the development of human anatomy
took place during this period with the art works and drawings
of human muscles and embryos by famous Italian painter
Leonardo da Vinci (1452–1519). Dissection of human body
was started by Vesalius (1514–1564) on freshly executed
criminals. His pupils, Gabriel Fallopius (1523–1562) who
described human oviducts (Fallopian tubes) and Fabricius
who discovered lymphoid tissue around the intestine of
birds (bursa of Fabricius) further popularised the practice of
Figure 1.3 The Caduceus, representing symbol of medicine, is the human anatomic dissection for which special postmortem
traditional symbol of god Hermes or Mercury. It features twin serpents amphitheatres came in to existence in various parts of ancient
winding around a winged staff. Europe.
4 Antony van Leeuwenhoek (1632–1723), a cloth merchant French physician, dominated the early part of 19th century by
by profession in Holland, during his spare time invented the his nume­rous discoveries. He described several lung diseases
first ever microscope by grinding the lenses himself through (tubercles, caseous lesions, miliary lesions, pleural effusion,
which he recognised male spermatozoa as tiny preformed men and bronchiectasis), chronic sclerotic liver disease (later called
(or “homunculi”) and other single-celled organisms which he Laennec’s cirrhosis) and invented stethoscope.
SECTION I

called animalcules. He also introduced histological staining in Morbid anatomy attained its zenith with appearance of Carl
1714 using saffron to examine muscle fibres. F. von Rokitansky (1804–1878), self-taught German pathologist
Marcello Malpighi (1624–1694) used microscope exten­ who performed nearly 30,000 autopsies himself. He described
sively and observed the presence of capillaries and described acute yellow atrophy of the liver, wrote an outstanding
the malpighian layer of the skin, and lymphoid tissue in the monograph on diseases of arteries and congenital heart
spleen (malpighian corpuscles). Malpighi is known as ‘the defects. Unlike most other surgeons of that time, Rokitansky did
father of histology.’ not do clinical practice of surgery but instead introduced the
The credit for beginning of the study of morbid anatomy concept that pathologists should confine themselves to making
(pathologic anatomy), however, goes to Italian anatomist- diagnosis which became the accepted role of pathologist later.
General Pathology

pathologist, Giovanni B. Morgagni (1682–1771). Morgagni

was an excellent teacher in anatomy, a prolific writer and ERA OF TECHNOLOGY DEVELOPMENT
a practicing clinician. By his work, Morgagni demolished
AND CELLULAR PATHOLOGY
the ancient humoral theory of disease and published his
life-time experiences based on 700 postmortems and their Up to middle of the 19th century, correlation of clinical
corresponding clinical findings. He, thus, laid the foundations manifestations of disease with gross pathological findings
of clinicopatho­logic methodology in the study of disease and at autopsy became the major method of study of disease.
introduced the concept of clinicopathologic correlation (CPC), Sophistication in surgery led to advancement in pathology. The
establishing a coherent sequence of cause, lesions, symptoms, anatomist-surgeons of earlier centuries got replaced largely
and outcome of disease (Fig. 1.5). with surgeon-pathologists in the 19th century.
Sir Percivall Pott (1714–1788), famous surgeon in England, Pathology started developing as a diagnostic discipline
described arthritic tuberculosis of the spine (Pott’s disease) in later half of the 19th century with the evolution of cellular
and identified the first ever occupational cancer (cancer of pathology which was closely linked to technology advance­
scrotal skin) in the chimney sweeps in 1775 and discovered ments in machinery manufacture for cutting thin sections
chimney soot as the first carcinogenic agent. The study of of tissue, improvement in microscope, and development of
anatomy in England during the latter part of 18th Century was chemical industry and dyes for staining.
dominated by the two Hunter brothers. These were John Hunter The discovery of existence of disease-causing micro-
(1728–1793), a student of Sir Percivall Pott, who rose to become organisms was made by French chemist Louis Pasteur (1822–
the greatest surgeon-anatomist of all times (Fig. 1.6) and his 1895), thus demolishing the prevailing theory of spontaneous
elder brother William Hunter (1718–1788) who was a reputed generation of disease and firmly established germ theory
anatomist-obstetrician. These brothers together started the of disease. Subsequently, G.H.A. Hansen (1841–1912) in
first ever museum by collection of surgical specimens from Germany identified Hansen’s bacillus in 1873 as the first
their flourishing practice, arranged them into separate organ microbe causative for leprosy (Hansen’s disease). While the
systems, made comparison of specimens from animals and study of infectious diseases was being made, the concept of
plants with humans, and included many clinical pathology immune tolerance and allergy emerged which formed the
specimens as well, and thus developed the first museum basis of immunisation initiated by Edward Jenner. Metchnikoff
of comparative anatomy and pathology in the world which (1845-1916), a Russian zoologist, introduced the existence of
became the Hunterian Museum, now housed in Royal College phenomenon of phagocytosis by human defense cells against
of Surgeons of London. Among many pupils of John Hunter invading microbes.
was Edward Jenner (1749–1823) whose work on inoculation in Developments in chemical industry helped in switch over
smallpox is well known. Another prominent English pathologist from earlier dyes of plant and animal origin to synthetic dyes;
was Matthew Baillie (1760–1823), nephew of Hunter brothers, aniline violet being the first such synthetic dye prepared by
who published first-ever systematic textbook of morbid Perkin in 1856. This led to emergence of a viable dye industry
anatomy in 1793. The era of gross pathology had three more for histological and bacteriological purposes. The impetus for
illustrious and brilliant physician-pathologists in England who the flourishing and successful dye industry came from the
were colleagues at Guy’s Hospital in London: works of numerous pioneers as under:
”” Richard Bright (1789–1858) who described non-suppurative ”” Paul Ehrlich (1854–1915), German physician, conferred
nephritis, later termed glomerulonephritis or Bright’s disease; Nobel prize in 1908 for his work in immunology, described
”” Thomas Addison (1793–1860) who gave an account of Ehrlich’s test for urobilinogen using Ehrlich’s aldehyde
chronic adrenocortical insufficiency termed Addison’s disease; reagent, staining techniques of cells and bacteria, and laid the
and foundations of clinical pathology (Fig. 1.7).
”” Thomas Hodgkin (1798–1866), who observed the complex of ”” Christian Gram (1853–1938), Danish physician, developed
chronic enlargement of lymph nodes, often with enlargement bacteriologic staining by crystal violet.
of the liver and spleen, later called Hodgkin’s disease. ”” D.L. Romanowsky (1861–1921), Russian physician,
Towards the end of 18th century, Xavier Bichat (1771–1802) developed stain for peripheral blood film using eosin and
in France described that organs were composed of tissue methylene blue derivatives.
and divided the study of morbid anatomy into General Pathology ”” Robert Koch (1843–1910), German bacteriologist, besides
and Systemic Pathology. R.T.H. Laennec (1781–1826), another Koch’s postulate and Koch’s phenomena, developed techniques
 FATHER OF CPCs FATHER OF MUSEUM IN PATHOLOGY FATHER OF CLINICAL PATHOLOGY
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CHAPTER 1
Introduction to Pathology
Figure 1.5 Giovanni B. Morgagni (1682– Figure 1.6  John Hunter (1728–1793). Figure 1.7  Paul Ehrlich (1854–1915). German
1771), an Italian physician-anatomist who Scottish surgeon, regarded as the greatest physician, conferred Nobel prize for his work
introduced clinicopathologic methodology surgeon-anatomist of all times who estab­ in immunology, described Ehrlich’s test for
in the study of disease by correlation of li­
shed first ever unique collection of urobilinogen, staining techniques of cells
clinical findings with findings at postmortem pathological specimens that later resulted in and bacteria, and laid the foundations of
examination. the Hunterian Museum of the Royal College haematology and clinical pathology.
of Surgeons, London.

of fixation and staining for identification of bacteria, discovered microscopy had been laid which was followed and promoted
tubercle bacilli in 1882 and cholera vibrio organism in 1883. by numerous brilliant successive workers. This gave birth to
”” May-Grünwald in 1902 and Giemsa in 1914 developed biopsy pathology and thus emerged the discipline of surgical
blood stains and applied them for classification of blood cells pathology. Virchow also described etiology of embolism
and bone marrow cells. (Virchow’s triad—slowing of blood-stream, changes in the
”” Sir William Leishman (1865–1926) described Leishman’s vessel wall, changes in the blood itself), metastatic spread
stain for blood films in 1914 and observed Leishman-Donovan of tumours (Virchow’s lymph node), and components and
bodies (LD bodies) in leishmaniasis. diseases of blood (fibrinogen, leukocytosis, leukaemia).
”” Robert Feulgen (1884–1955) described Feulgen reaction for The concept of frozen section examination while the patient
DNA staining and laid the foundations of cytochemistry and was still on the operation table was introduced by Virchow’s
histochemistry. student, Julius Cohnheim (1839–1884). In fact, during the
Simultaneous technological advances in machinery initial period of development of surgical pathology around the
manufacture led to development and upgrading of micro­tomes
turn of the 19th century, frozen section was considered more
for obtaining thin sections of organs and tissues for staining by
acceptable by the surgeons.
dyes for enhancing detailed study of sections.
The concept of surgeon and physician doubling up in
Though the presence of cells in thin sections of non-living
the role of pathologist which started in the 19th century
object cork had been first demonstrated much earlier by
continued as late as the middle of the 20th century in most
Robert Hooke in 1667, it was revived as a unit of living matter
in the 19th century by F.T. Schwann (1810–1882), the first clinical departments. Assigning biopsy pathology work to
neuro­histologist, and Claude Bernarde (1813–1878), pioneer in some faculty member in the clinical department was common
pathophysiology. practice; that is why some of the notable pathologists of the
Until the end of the 19th century, the study of morbid first half of 20th century had background of clinical training
anatomy had remained largely autopsy-based and thus had e.g. James Ewing (1866–1943), A.P. Stout (1885–1967)
remained a retrospective science. Rudolf Virchow (1821–1905) and Lauren Ackerman (1905–1993) in US, Pierre Masson
in Germany is credited with the beginning of microscopic (1880–1958) in France, and R.A. Willis in Australia.
examination of diseased tissue at cellular level and thus A few other landmarks in further evolution of modern
began histopathology as a method of investigation. Virchow pathology in this era are as follows:
hypothesised cellular theory having following two components: ”” Karl Landsteiner (1863–1943) described the existence of
”” All cells come from other cells. major human blood groups in 1900 and is considered “father
”” Disease is an alteration of normal structure and function of of blood transfusion”; he was awarded Nobel prize in 1930
these cells. (Fig. 1.9).
Virchow was revered as Pope in pathology in Europe and ”” Ruska and Lorries in 1933 developed electron microscope
is aptly known as the ‘father of cellular pathology’ (Fig. 1.8). which aided the pathologist to view ultrastructure of cell and
Thus, sound foundation of diagnostic pathology based on its organelles.
6 FATHER OF CELLULAR PATHOLOGY FATHER OF BLOOD TRANSFUSION FATHER OF EXFOLIATIVE CYTOLOGY
SECTION I
General Pathology

Figure 1.8 Rudolf Virchow (1821–1905). Figure 1.9  Karl Landsteiner (1863–1943). An Figure 1.10  George N Papanicolaou (1883–
German pathologist who proposed cellular Austrian pathologist who first discovered the 1962). An American pathologist, who deve­
theory of disease and initiated biopsy existence of major human blood groups in loped Pap test for diagnosis of cancer of
pathology for diagnosis of diseases. 1900 and was recipient of Nobel prize in 1930. uterine cervix.

”” The development of exfoliative cytology for early detection MODERN PATHOLOGY

of cervical cancer began with George N. Papanicolaou
The strides made in the latter half of 20th century until recent
(1883–1962), a Greek-born, American pathologist, in 1930s and times in 21st century have made it possible to study diseases
is known as ‘father of exfoliative cytology’ (Fig. 1.10). at genetic and molecular level, and provide an evidence-
Another pioneering contribution in pathology in the based and objective diagnosis that may enable the physician
20th century was by an eminent teacher-author, William to institute targeted therapy. The major impact of advances in
Boyd (1885–1979), psychiatrist-turned pathologist, whose molecular biology are in the field of diagnosis and treatment
textbooks—‘Pathology for Surgeons’ (first edition 1925) and of genetic disorders, immunology and in cancer. Some of
‘Textbook of Pathology’ (first edition 1932), dominated and the revolutionary discoveries during this time are as under
inspired the students of pathology all over the world due to (Fig. 1.11):
his flowery language and lucid style for a few generations. ”” Description of the structure of DNA of the cell by Watson
M.M. Wintrobe (1901–1986), a pupil of Boyd who discovered and Crick in 1953.
haematocrit technique, regarded him as a very stimulating
”” Identification of chromosomes and their correct number in
teacher.
humans (46) by Tijo and Levan in 1956.

Figure 1.11  Molecular structure of human chromosome.