STUDY OF DISEASES (p. 1)
The word ‘Pathology’ is derived from two Greek words—pathos meaning suffering, and logos meaning study. Pathology is, thus, scientific study of structure and function of the body in disease; or in other words, pathology consists of the abnormalities that occur in normal anatomy (including histology) and physiology owing to disease. Knowledge and understanding of pathology is essential for all would-be doctors, general medical practitioners and specialists. Remember the prophetic words of one of the eminent founders of modern medicine in late 19th and early 20th century, Sir William Osler, “Your practice of medicine will be as good as your understanding of pathology.”
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 condition when the individual is in complete accord with the surroundings, while disease is loss of ease (or comfort) to the body (i.e. dis-ease).
It is important for a beginner in pathology to be familiar with the language used in pathology:
- ♦ Patient is the person affected by disease.
- ♦ Lesions are the characteristic changes in tissues and cells produced by disease in an individual or experimental animal.
- ♦ Pathologic changes or morphology consist of examination of diseased tissues.
- ♦ Pathologic changes can be recognised with the naked eye (gross or macroscopic changes) or studied by microscopic examination of tissues.
- ♦ Causal factors responsible for the lesions are included in etiology of disease (i.e. ‘why’ of disease).
- ♦ Mechanism by which the lesions are produced is termed pathogenesis of disease (i.e. ‘how’ of disease).
- ♦ Functional implications of the lesion felt by the patient are symptoms and those discovered by the clinician are the physical signs.
EVOLUTION OF PATHOLOGY (p. 1)
Pathology as the scientific study of disease processes has its deep roots in medical history. Since the beginning of mankind, there has been desire as well as need to know more about the causes, mechanisms and nature of diseases. The answers to these questions have evolved over the centuries—from supernatural beliefs to the present state of our knowledge of modern pathology.
FROM RELIGIOUS BELIEFS AND MAGIC TO RATIONAL APPROACH (PREHISTORIC TIME TO ad 1500) (p. 2)
Present-day knowledge of primitive culture prevalent in the world in prehistoric times reveals that religion, magic and medical treatment were quite linked to each other in those times. The earliest concept of disease understood by the patient and the healer was the religious belief that disease was the outcome of ‘curse from God’ or the belief in magic that the affliction had supernatural origin from ‘evil eye of spirits.’ To ward them off, priests through prayers and sacrifices, and magicians by magic power used to act as faith-healers and invoke supernatural powers and please the gods. Remnants of ancient superstitions still exist in some parts of the world.2
But the real practice of medicine began with Hippocrates (460–370 BC), the great Greek clinical genius of all times and regarded as ‘the father of medicine’(Web Image 1.1). Hippocrates followed rational and ethical attitudes in practice and teaching of medicine as expressed in the collection of writings of that era. He firmly believed in study of patient's symptoms and described methods of diagnosis.
Hippocrates introduced ethical concepts in the practice of medicine and is revered by the medical profession by taking ‘Hippocratic oath’ at the time of entry into practice of medicine.
Hippocratic teaching was propagated in Rome by Roman physicians, notably by Cornelius Celsus (53 BC-7 AD) and Cladius Galen (130–200 AD). Celsus first described four cardinal signs of inflammation—rubor (redness), tumor (swelling), calor (heat), and dolor (pain). Galen postulated humoral theory, later called Galenic theory.
The hypothesis of disequilibrium of four elements constituting the body (Dhatus) similar to Hippocratic doctrine finds mention in ancient Indian medicine books compiled about 200 AD—Charaka Samhita and Sushruta Samhita.
FROM HUMAN ANATOMY TO ERA OF GROSS PATHOLOGY (AD 1500 to 1800) (p. 3)
The backwardness of Medieval period was followed by the Renaissance period i.e. revival of leaning. Dissection of human body was started by Vesalius (1514–1564) on 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 human anatomic dissection for which special postmortem amphitheatres came in to existence in various parts of ancient Europe (Web Image 1.2).
Antony van Leeuwenhoek (1632–1723), a cloth merchant by profession in Holland, during his spare time invented the first ever microscope.
The credit for beginning of the study of morbid anatomy (pathologic anatomy), however, goes to Italian anatomist-pathologist, Giovanni B. Morgagni (1682–1771). He laid the foundations of clinicopathologic methodology in the study of disease and introduced the concept of clinicopathologic correlation (CPC), establishing a coherent sequence of cause, lesions, symptoms, and outcome of disease (Web Image 1.3).
Sir Percival Pott (1714–1788), famous surgeon in England, identified the first ever occupational cancer in the chimney sweeps in 1775 and discovered chimney soot as the first carcinogenic agent. However, the study of anatomy in England during the latter part of 18th Century was dominated by the two Hunter brothers:John Hunter (1728–1793), a student of Sir Percival Pott, rose to become greatest surgeon-anatomist of all times and he, together with his elder brother William Hunter (1718–1788) who was a reputed anatomist-obstetrician (or man-midwife), started the first ever museum of pathologic anatomy (Web Image 1.4).
R.T.H. Laennec (1781–1826), a French physician, dominated the early part of 19th century by his numerous discoveries. He described several lung diseases (tubercles, caseous lesions, miliary lesions, pleural effusion, bronchiectasis), chronic sclerotic liver disease (later called Laennec's cirrhosis) and invented stethoscope.
Morbid anatomy attained its zenith with appearance of Carl F. von Rokitansky (1804–1878), self-taught German pathologist who performed nearly 30,000 autopsies himself.
ERA OF TECHNOLOGY DEVELOPMENT AND CELLULAR PATHOLOGY (AD 1800 TO 1950 s) (p. 4)
Pathology started developing as a diagnostic discipline in later half of the 19th century with the evolution of cellular pathology which was closely linked to 3technology advancements in machinery manufacture for cutting thin sections of tissue, improvement in microscope, and development of chemical industry and dyes for staining.
The discovery of existence of disease-causing micro-organisms was made by French chemist Louis Pasteur (1822–1895). Subsequently, G.H.A. Hansen (1841–1912) in Germany identified Hansen's bacillus as causative agent for leprosy (Hansen's disease) in 1873.
Developments in chemical industry helped in switch over from earlier dyes of plant and animal origin to synthetic dyes. The impetus for the flourishing and successful dye industry came from the works of numerous pioneers as under:
- ♦ Paul Ehrlich (1854–1915), described Ehrlich's test for urobilinogen using Ehrlich's aldehyde reagent, staining techniques of cells and bacteria, and laid the foundations of clinical pathology (Web Image 1.5).
- ♦ Christian Gram, who developed bacteriologic staining by crystal violet.
- ♦ D.L. Romanowsky, Russian physician, who developed stain for peripheral blood film using eosin and methylene blue derivatives.
- ♦ Robert Koch, German bacteriologist who, besides Koch's postulate and Koch's phenomena, developed techniques of fixation and staining for identification of bacteria, discovered tubercle bacilli in 1882 and cholera vibrio organism in 1883.
- ♦ May-Grunwald and Giemsa developed blood stains.
- ♦ Sir William Leishman described Leishman's stain for blood films.
- ♦ Robert Feulgen described Feulgen reaction for DNA staining.
Until the end of the 19th century, the study of morbid anatomy had remained largely autopsy-based and thus had remained a retrospective science. Rudolf Virchow (1821–1905) in Germany is credited with the beginning of microscopic examination of diseased tissue at cellular level and thus began histopathology as a method of investigation. Virchow gave two major hypotheses:
- ♦ All cells come from other cells.
- ♦ Disease is an alteration of normal structure and function of these cells.
Virchow came to be referred as Pope in pathology in Europe and is aptly known as the ‘father of cellular pathology’(Web Image 1.6).
The concept of frozen section examination when the patient was still on the operation table was introduced by Virchow's student, Julius Cohnheim (1839–1884).
The concept of surgeon and physician doubling up in the role of pathologist which started in the 19th century continued as late as the middle of the 20th century in most clinical departments. Assigning biopsy pathology work to some faculty member in the clinical department was common practice; that is why some of the notable pathologists of the first half of 20th century had background of clinical training.
A few other landmarks in further evolution of modern pathology in this era are as follows:
- ♦ Karl Landsteiner(1863–1943) described the existence of major human blood groups in 1900 and was awarded Nobel prize in 1930 and is considered father of blood transfusion (Web Image 1.7).
- ♦ Ruska and Lorries in 1933 developed electron microscope which aided the pathologist to view ultrastructure of cell and its organelles.
- ♦ The development of exfoliative cytology for early detection of cervical cancer began with George N. Papanicolaou(1883–1962), in 1930s who is known as ‘father of exfoliative cytology’(Web Image 1.8).
Another pioneering contribution in pathology in the 20th century was by an eminent teacher-author, William Boyd(1885–1979), dominated and inspired the students of pathology all over the world due to his flowery language and lucid style for about 50 years till 1970s (Web Image 1.9).4
MODERN PATHOLOGY (1950 s TO PRESENT TIMES) (p. 6)
The strides made in the latter half of 20th century until the beginning of 21st century have made it possible to study diseases at molecular level, and provide an evidence-based and objective diagnosis and enable the physician to institute appropriate therapy. Some of the revolutionary discoveries during this time are as under (Web Image 1.10):
- ♦ Description of the structure of DNA of the cell by Watson and Crick in 1953.
- ♦ Identification of chromosomes and their correct number in humans (46) by Tijo and Levan in 1956.
- ♦ Identification of Philadelphia chromosome t(9;22) in chronic myeloid leukaemia by Nowell and Hagerford in 1960 as the first chromosomal abnormality in any cancer.
- ♦ Flexibility and dynamism of DNA invented by Barbara McClintock for which she was awarded Nobel prize in 1983.
- ♦ In 1998, researchers in US found a way of harvesting stem cells, a type of primitive cells, from embryos and maintaining their growth in the laboratory, and thus started the era of stem cell research. Stem cells are seen by many researchers as having virtually unlimited application in the treatment of many human diseases such as Alzheimer's disease, diabetes, cancer, strokes, etc.
- ♦ In April 2003, Human Genome Project (HGP) consisting of a consortium of countries, was completed which coincided with 50 years of description of DNA double helix by Watson and Crick in April 1953. The sequencing of human genome reveals that human genome contains approximately 3 billion of the base pairs, which reside in the 23 pairs of chromosomes within the nucleus of all human cells. Each chromosome contains an estimated 30,000 genes in the human genome.
These inventions have set in an era of human molecular biology which is no longer confined to research laboratories but is ready for application as a modern diagnostic and therapeutic tool.
SUBDIVISIONS OF PATHOLOGY (p. 7)
Human pathology is the largest branch of pathology. It is conventionally divided into General Pathology dealing with general principles of disease, and Systemic Pathology that includes study of diseases pertaining to the specific organs and body systems.
- HISTOPATHOLOGY. Histopathology, used synonymously with anatomic pathology, pathologic anatomy, or morbid anatomy, is the classic method of study and still the most useful one which has stood the test of time. It includes the following 3 main subdivisions:
- Surgical pathology deals with the study of tissues removed from the living body.
- Forensic pathology and autopsy work includes the study of organs and tissues removed at postmortem for medicolegal work and for determining the underlying sequence and cause of death.
- Cytopathology includes study of cells shed off from the lesions (exfoliative cytology) and fine-needle aspiration cytology (FNAC) of superficial and deep-seated lesions for diagnosis.
- HAEMATOLOGY deals with the diseases of blood.
- CHEMICAL PATHOLOGY includes analysis of biochemical constituents of blood, urine, semen, CSF and other body fluids.
- The concept of clinicopathologic correlation (CPC) by study of morbid anatomy was introduced by:
- Hippocrates
- Virchow
- John Hunter
- Morgagni
- The first ever museum of pathologic anatomy was developed by:
- John Hunter
- Rokitansky
- Rudolf Virchow
- Morgagni
- ABO human blood group system was first described by:
- Edward Jenner
- Karl Landsteiner
- Hippocrates
- Laennec
- Frozen section was first introduced by:
- Cohnheim
- Ackerman
- Virchow
- Feulgen
- Electron microscope was first developed by:
- Barbara McClintock
- Watson and Crick
- Tijo and Levan
- Ruska and Lorries
- Structure of DNA of the cell was described by:
- Watson and Crick
- Tijo and Levan
- Ruska and Lorries
- Barbara McClintock
- Flexibilty and dynamism of DNA was invented by:
- Watson and Crick
- Tijo and Levan
- Ruska and Lorries
- Barbara McClintock
- Father of cellular pathology is:
- Carl Rokitansky
- Rudolf Virchow
- G. Morgagni
- FT Schwann
- Humans genome consists of following number of genes:
- 20,000
- 30,000
- 50,000
- 100,000
- Stem cell research consists of:
- Human cells grown in vitro
- Plant cells grown in vitro
- Cadaver cells grown in vitro
- Synonymous with PCR
- PCR technique was introduced by:
- Ian Wilmut
- Watson
- Nowell Hagerford
- Kary Mullis
- Human genome project was completed in:
- 2001
- 2002
- 2003
- 2004
KEY |
1 = D | 2 = A | 3 = B | 4 = A |
5 = D | 6 = A | 7 = D | 8 = B |
9 = B | 10 = A | 11 = D | 12 = C |