A renal cell carcinoma (chromophobe type) viewed on a hematoxylin & eosin stained slide
Pathology is the study and diagnosis of disease through examination of
organs, tissues, cells and bodily fluids. The term encompasses both the
medical specialty which uses tissues and body fluids to obtain clinically useful
information, as well as the related scientific study of disease processes.
History
The histories of both experimental and medical pathology can be traced to the earliest application of the scientific method to the field of medicine, a development which
occurred in the Middle East during the Islamic Golden
Age[1] and in Western Europe during the Italian Renaissance.[2] Most early pathologists were also practicing
physicians or surgeons. Like other medical fields, pathology
has become more specialized with time, and most pathologists today do not practice in other areas of medicine.
Origins of pathology
The concept of studying disease through the methodical dissection and examination of diseased bodies, organs, and tissues may
seem obvious today, but there are few if any recorded examples of true autopsies performed prior
to the second millennium. Though the pathology of contagion was understood by Muslim physicians since the
time of Avicenna (980-1037),[3] the first physician known to have made postmortem dissections was the Arabian physician Avenzoar (1091–1161) who proved that the skin disease scabies was caused by a
parasite, followed by Ibn al-Nafis (b. 1213) who used
dissection to discover pulmonary circulation in 1242.[4] In the 15th century, anatomic dissection was repeatedly used by the Italian
physician Antonio Benivieni (1443-1502) to determine cause of death.[2] Perhaps the most famous early gross pathologist
was Giovanni Morgagni (1682-1771). His magnum
opus, De Sedibus et Causis Morborum per Anatomem Indagatis, published in 1761, describes the findings of over 600
partial and complete autopsies, organised anatomically and methodically correlated with the symptoms exhibited by the patients
prior to their demise. Although the study of normal anatomy was already well advanced at this date, De Sedibus was one of
the first treatises specifically devoted to the corrolation of diseased anatomy with clinical illness.[5][6] By the
late 1800s, an exhaustive body of literature had been produced on the gross anatomical findings characteristic of known diseases.
The extent of gross pathology research in this period can be epitomized by the work of the Viennese pathologist (originally from
Hradec Kralove in the Czech Rep.) Carl Rokitansky (1804-1878), who is said
to have performed 20,000 autopsies, and supervised an additional 60,000, in his lifetime .[2][7]
Origins of microscopic pathology
Rudolf Virchow (1821-1902) is generally recognized to be the father of microscopic
pathology. While the compound microscope had been invented approximately 150 years prior,
Virchow was one of the first prominent physicians to emphasize the study of manifestations of disease which were visible only at
the cellular level.[2][8] A student of Virchow's, Julius
Cohnheim (1839-1884) combined histology techniques with experimental manipulations to
study inflammation, making him one of the earliest experimental pathologists.[2] Cohnheim also pioneered the use of the frozen section; a version of this technique is widely
employed by modern pathologists to render diagnoses and provide other clinical information intraoperatively.[9]
Modern experimental pathology
As new research techniques, such as electron microscopy, immunohistochemistry, and molecular biology have
expanded the means by which biomedical scientists can study disease, the definition and boundaries of investigative pathology
have become less distinct. In the broadest sense, nearly all research which links manifestations of disease to identifiable
processes in cells, tissues, or organs can be considered experimental
pathology.[10]
Pathology as a science
Pathology is a broad and complex scientific field which seeks to understand the mechanisms of
injury to cells and tissues, as well as the
body's means of responding to and repairing injury. Disease processes may be incited or exacerbated by a variety of external and
internal influences, including trauma, infection,
poisoning, loss of blood flow,
autoimmunity, inherited or acquired genetic
damage, or errors of development. One common theme in pathology is the way
in which the body's responses to injury, while evolved to protect health, can also contribute in some ways to disease
processes.[11] Elucidation of general
principles underlying pathologic processes, such as cellular adaptation to injury, cell death, inflammation, tissue repair, and
neoplasia, creates a conceptual framework with which to analyze and understand specific human diseases.
Adaptation to injury
Cells and tissues may respond to injury and stress by specific mechanisms, which may vary according to the cell types and
nature of the injury. In the short term, cells may activate specific genetic programs to protect their vital proteins and organelles from heat shock
or hypoxia, and may activate DNA repair pathways
to repair damage to chromosomes from radiation or chemicals. Hyperplasia is a long-term
adaptive response of cell division and multiplication, which can increase the ability of a
tissue to compensate for an injury. For example, repeated irritation to the skin can cause a protective thickening due to hyperplasia of the epidermis.
Hypertrophy is an increase in the size of cells in a tissue in response to
stress, an example being hypertrophy of muscle cells in the heart in response to increased resistance to blood flow as a result of narrowing of the heart's outflow valve. Metaplasia occurs when
repeated damage to the cellular lining of an organ triggers its replacement by a different cell type.[11]
Cell death
Necrosis is the irreversible destruction of cells as a result of severe injury in a setting
where the cell is unable to activate the needed metabolic pathways for survival or orderly degeneration. This is often due to
external pathologic factors, such as toxins or loss of oxygen supply. Milder stresses may lead to a process called reversible
cell injury, which mimics the cell swelling and vacuolization seen early in the necrotic process, but in which the cell is
able to adapt and survive. In necrosis, the components of degenerating cells leak out, potentially contributing to inflammation
and further damage. Apoptosis, in contrast, is a regulated, orderly degeneration of the cell
which occurs in the settings of both injury and normal physiological processes.[11]
Inflammation
A transmission electron microscope image of an immune cell crossing from the bone marrow into the circulation
Inflammation is a particularly important and complex reaction to tissue injury, and is
particularly important in fighting infection. Acute
inflammation is generally a non-specific response triggered by the injured tissue cells themselves, as well as specialized
cells of the innate immune system and previously developed adaptive immune mechanisms. A localized acute inflammatory response triggers vascular changes in
the injured area, recruits pathogen-fighting neutrophils, and begins the process of developing a new adaptive immune response.
Chronic inflammation occurs when the acute response fails to entirely clear the
inciting factor. While chronic inflammation can lay a positive role in containing a continuing infectious hazard, it can also
lead to progressive tissue damage, as well as predisposing (in some cases) to the development of cancer.[11]
Tissue repair
Tissue repair, as seen in wound healing, is triggered by inflammation. The process may
proceed even before the resolution of a precipitating insult, through the formation of granulation tissue. Healing involves the proliferation of connective tissue cells and blood vessel-forming cells as a
result of hormonal growth signals. While healing is a critical adaptive response, an aberrent healing response can lead to
progressive fibrosis, contractures, or other changes which can compromise function.[11]
Neoplasia
Neoplasia, or "new growth," is a proliferation of cells which is independent of any
physiological process. The most familiar examples of neoplasia are benign tumors and
cancers. Neoplasia results from genetic changes which cause cells to activate genetic programs
inappropriately. Dysplasia is an early sign of a neoplastic process in a tissue, and is marked
by persistence of immature, poorly differentiated cell forms. Interestingly, there are many similarities in the gene pathways
activated in cancer cells, and those activated in cells involved in wound healing and inflammation.[11]
Pathology as a medical specialty
Physicians who practice pathology diagnose and characterize disease in living patients by examining biopsies and other
specimens. For example, the vast majority of cancer diagnoses are made or confirmed by a pathologist. Pathologists may also
conduct autopsies to investigate causes of death. The medical practice of pathology grew out the tradition of investigative
pathology, and many of the academic leaders in pathology today are accomplished in both basic
science research and diagnostic practice. However, as with other specialties in medicine, most
modern physician-pathologists are employed in full-time practice, and do not perform original research.
Pathology is a unique medical specialty in that pathologists typically do not see patients
directly, but rather serve as consultants to other physicians (often referred to as "clinicians" within the pathology community).
However, in the United States and in many other countries, pathologists receive the same doctorate training, and undergo the same
medical licensure process as other physicians. Pathology is a diverse field, and the organization of subspecialties within
pathology vary between nations.
Anatomical Pathology
This mastectomy specimen contains an infiltrating ductal carcinoma of the breast. A pathologist will use immunohistochemistry and
fluorescent in-situ hybridization to detect markers which determine the optimal chemotherapy regimen for this patient.
-
Anatomical pathologists diagnose disease and gain other clinically significant
information through the examination of tissues and cells. This generally involves gross and microscopic visual examination of tissues, with
special stains and immunohistochemistry employed to visualize specific proteins and other substances in and around cells. More
recently, anatomical pathologists have begun to employ molecular biology techniques to gain additional clinical information from
these same specimens. Anatomic pathologists serve as the definitive diagnosticians for most cancers, as well as numerous other
diseases.
- Surgical pathology is the most significant and time-consuming area of practice
for most anatomical pathologists. Surgical pathology involves the gross and microscopic examination of surgical specimens, as well as biopsies submitted by non-surgeons such as general internists, medical subspecialists, dermatologists, and interventional radiologists.
- Cytopathology is concerned with the microscopic examination of whole, individual cells
obtained from smears or fine needle aspirates.
- Molecular pathology refers to the use of nucleic acid-based techniques, such as
in-situ hybridization, reverse-transcriptase polymerase chain reaction, and nucleic acid microarrays for specialised diagnostic
studies of disease in tissues and cells.
- Autopsies are used to provide definitive evidence of the disease processes contributing to a
person's death.
- Forensic pathology receive specialized training in determining the cause of death
and other legally relevant information from the bodies of persons who died in a non-medical or potentially criminal circumstances.
Clinical pathology
-
Pathogenic organisms are grown from patient specimens in clinical microbiology labs, allowing selection of the correct
antibiotics
Clinical pathology, also known as laboratory
medicine, is the medical specialty concerned with diagnosing diseases based on the analysis of body fluids, such as
plasma, urine, stool, respiratory or mucosal secretions, inflammatory exudates, and pleural, pericardial, peritoneal, synovial, or cerebrospinal fluid. The practice of clinical pathology is centered around the clinical
laboratory. In modern clinical laboratories, many routine studies are largely automated. The clinical pathologist is responsible
for overseeing the work of laboratory technicians, performing quality assurance to assure the
validity of test results, performing interpretations of more complex studies, and serving as a consultant to clinicians so that
the most appropriate studies can be performed for the diagnosis or assessment of an individual patient's condition. In some
areas, non-pathologists, such as other physicians or Ph.D.'s may run clinical labs and perform functions within those specific
labs which are similar to the role of a board-certified clinical pathologist.
Sub-specialties within clinical pathology include the following:
Dental pathology
In the United States, subspecialty-trained doctors of dental surgery (D.D.S), rather than
medical doctors, can be certified by a professional board to practice dental
pathology.
Training of medical pathologists
Pathology in the United States
In the United States, pathologists are medical doctors (M.D.) or doctors of osteopathic medicine (D.O.), that have completed a four-year undergraduate
program, four years of medical school training, and three to four years of postgraduate training in the form of a pathology
residency. Training may be within two primary specialties, as recognized by the American Board of Pathology: Anatomic Pathology, and Clinical Pathology, each of
which requires separate board certification. Many pathologists seek a broad-based training and become certified in both fields.
These skills are complementary in many hospital-based private practice settings, since the day-to-day work of many clinical
laboratories only requires the intermittent attention of a physician. Thus, pathologists are able to spend much of their time
evaluating anatomic pathology cases, while remaining available to cover any special issues which might arise in the clinical
laboratories. Pathologists may pursue specialised fellowship training within one or more sub-specialties of either anatomic or
clinical pathology. Some of these sub-specialities permit additional board certification, while others do not.[12]
Pathology in the United Kingdom
In the UK pathologists are medical doctors registered with the UK General Medical Council. They will have completed an undergraduate medical education which in
most countries lasts 4-6 years. The training to become a pathologist is under the oversight of the Royal College of Pathologists. Typically a one year training attachment is followed by an
aptitude test. This is followed by further specialist training in surgical pathology, cytopathology, and post mortem pathology.
There are two examinations run by the Royal College of Pathologists termed
Part 1 and Part 2. The Part 2 examination is designed to test competence to work as an independent practitioner in pathology and
is typically taken after 5 years specialist training. All post-graduate medical training and education in the UK is overseen by
the Postgraduate Medical Education and Training Board. It is possible to take a specialist part 2 examination in paediatric
pathology or neuropathology. It is possible to take a special diploma in dermatopathology or cytopathology, recognising
additional specialist training and expertise.
Non-human pathology
Veterinary pathologists are veterinary practitioners who specialise in the
diagnosis and characterization of veterinary diseases through the examination of animal tissue and body fluids. Veterinary
pathologists are veterinarians with advanced training (board certification or Ph.D.) in either diagnostic pathology or research
into the biological processes underlying disease (pathobiology). Diagnostic veterinary pathologists are further subcategorized as
either anatomical pathologists or clinical pathologists. Clinical pathologists examine specimens such as blood, excretions or
biopsy material to diagnose disease in living animals. Anatomical pathologists utilize post mortem examinations of dead animals
to arrive at a diagnosis. Post mortem examinations entail a necropsy (an animal autopsy), histopathologic (microscopic) study of
tissue specimens collected at the necropsy and sometimes specialized studies (radiographic, toxicologic, etc.)[13]
Plant pathologists are specialized scientists who investigate the causes of diseases
in plants.
Notes
- ^ Toby E. Huff (2003), The Rise of Early Modern Science: Islam, China, and
the West, p. 54, 246-247, 216-218. Cambridge University Press, ISBN
0521529948.
- ^ a b c d e [1]
History of Pathology, at the USC School of Dentistry
- ^ Medicine And
Health, "Rise and Spread of Islam 622-1500: Science, Technology, Health", World Eras, Thomson Gale.
- ^ Islamic medicine, Hutchinson
Encyclopedia.
- ^ [2] A History of Medicine from the Biblioteca Centrale dell'Area Biomedica
- ^ [3] Founders of Modern Medicine: Giovanni Battista Morgagni. Medical Library and
Historical Journal. 1903 October; 1(4): 270–277.
- ^ [4] Karl von Rokitansky at Whonamedit.com
- ^ [5] Rudolf Virchow at Whonamedit.com
- ^ [6] Jewish Encyclopedia entry on Julius Cohnheim
- ^ [7] Mission of the American Society for Investigative Pathology
- ^ a b c d e f Ramzi Cotran, Vinay Kumar,
Tucker Collins (1999). Robbins Pathologic Basis of Disease, Sixth Edition. W.B. Saunders. ISBN
072167335X.
- ^ [8] Homepage of the American Board of Pathology
- ^ Veterinary Pathologist: Training - the Royal College of Pathologists.
See also
External links
|
Pathology: hematology
(primarily
C81-C96/200-208,
D45-D47, D50-D77/280-289) |
| WBCs |
hematological
malignancy (Lymphoma, leukemia)
-cytosis (Agranulocytosis, Leukocytosis,
Lymphocytosis, Monocytosis) • -penia
(Lymphopenia, Neutropenia) |
RBCs/anemia/
hemoglobinopathy |
nutritional anemia: Iron deficiency anemia, Plummer-Vinson syndrome,
Megaloblastic anemia (Pernicious
anemia)
hereditary hemolytic anemia: G6PD Deficiency, Thalassemia,
Sickle-cell disease/trait,
Hereditary spherocytosis, Hereditary elliptocytosis, Hereditary
stomatocytosis
acquired hemolytic anemia: Warm autoimmune hemolytic anemia,
HUS, MAHA,
PNH
aplastic anemia: Acquired
PRCA, Diamond-Blackfan anemia, Fanconi
anemia • Sideroblastic anemia • Hemochromatosis |
| Coagulation/platelets |
coagulopathy:
DIC • Hemophilia
(A, B, C,
XIII) • Von Willebrand
disease
Purpura: Henoch-Schönlein,
ITP, TTP
primary hypercoagulable state: Protein C deficiency - Protein S deficiency - Antithrombin III
deficiency
other hemorrhagic conditions: Bernard-Soulier syndrome -
Glanzmann's thrombasthenia - Grey
platelet syndrome |
| Histiocytosis |
WHO-I Langerhans cell histiocytosis - non-Langerhans-cell histiocytosis/WHO-II
(Juvenile xanthogranuloma, Hemophagocytic lymphohistiocytosis) - malignant histiocytic disorders/WHO-III
(Acute monocytic leukemia, Malignant
histiocytosis, Erdheim-Chester disease) |
| Other |
Asplenia/hyposplenism -
Methemoglobinemia |
|
Endocrine pathology:
endocrine diseases (E00-35, 240-259) |
| Thyroid |
Hypothyroidism
(Iodine deficiency, Cretinism, Congenital hypothyroidism, Goitre, Myxedema) - Hyperthyroidism (Graves
disease, Toxic multinodular goitre, Teratoma with thyroid tissue or Struma ovarii) - Thyroiditis (De Quervain's thyroiditis, Hashimoto's thyroiditis, Riedel's thyroiditis) -
Euthyroid sick syndrome |
| Pancreas |
Diabetes
mellitus (type 1, type
2, |