Pathology is the scientific study of disease. It involves examining tissues and cells to understand changes caused by disease and injury. Key techniques used in pathology include autopsy, biopsy, histopathology, immunohistochemistry, molecular biology techniques, and newer digital methods. Pathology provides critical information to diagnose diseases, determine causes of death, and guide treatment. It is a foundation of clinical practice and research into the mechanisms of disease.

1. Pathology
---Introduction
Xi’an Jiaotong University
2017.1.2017.1.

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Pathology is the scientific study of
disease
Literally: Path (pathos, suffering ) ology (logos, study)
Pathology is a bridge between basic
science and clinical practice.
The road taking the medicine from art to science (witch doctor,
conjure man)
Pathology provides the scientific
foundation for the practice of medicine
Disease may be defined as an abnormal alteration of structure or
function in any part of the body. Pathology is the study of structural and
functional abnormalities that manifest as diseases of organs and
systems.
Seeing is believing

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What is scientific methods
---A process for experimentation that is used to
explore observations and answer questions. Scientists use
the scientific method to search for cause and effect
relationships in nature. In other words, they design an
experiment so that changes to one item cause something
else to vary in a predictable way.

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Pathology is the scientific study of
disease
Literally: Path (pathos, suffering ) ology (logos, study)
Pathology is a bridge between basic
science and clinical practice.
The road taking the medicine from art to science (witch doctor,
conjure man)
Pathology provides the scientific
foundation for the practice of medicine
Disease may be defined as an abnormal alteration of structure or
function in any part of the body. Pathology is the study of structural and
functional abnormalities that manifest as diseases of organs and
systems.
Seeing is believing

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The Core of Pathology
Etiology or cause.
Genetic (e.g., inherited mutations and disease- associated
gene variants or polymorphisms)
Acquired (e.g., infectious, nutritional, chemical, physical)
Pathogenesis
The sequence of cellular, biochemical, and molecular events
that follow the exposure of cells or tissues to an injurious
agent.

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Morphologic changes
The structural alterations in cells or tissues that are either
characteristic of a disease or diagnostic of an etiologic process.
Morphology remains at the heart of diagnostic pathology
Functional derangements and clinical
manifestations
The end results of genetic, biochemical, and structural
changes in cells and tissues are functional abnormalities, which
lead to the clinical manifestations(symptoms and signs) of
disease, as well as its progress(clinical course and outcome)

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The pathologist is interested not only in recognition
of structural alteration, but also in their significance, i.e.,
the effects of these changes on cellular and tissue
function and ultimately the effect of these changes on
the patient. it is not a discipline isolated from the living
patient, but rather a basic approach to a better
understanding of disease and therefore a foundation of
sound clinical medicine.
(1957) stanley robbines

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To render diagnoses and guide therapy in
clinical practice
Basic activities of anatomic pathology:
1). establishing the diagnosis
2). providing prognostic information,
3). most importantly for our clinicians, offering predictive
information about therapeutic modalities

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Pathologists often have been accused, and
sometimes justly, of stressing the morphologic
changes in disease to the neglect of functional effects.
nevertheless, pathologic anatomy and histology
remain as an essential foundation of knowledge about
disease, without which basis, the concepts of many
disease are easily distorted.
1948 W.A.D. Anderson

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History and development of pathology
Hippocrates of Kos.
460 – c. 370 BC
The first person to believe that diseases
were caused naturally, not because of
superstition and gods. He separated the
discipline of medicine from religion,
believing and arguing that disease was
not a punishment inflicted by the gods but
rather the product of environmental
factors, diet, and living habits.
However, Hippocrates did work with
many convictions that were based on what
is now known to be incorrect anatomy and
physiology, such as Humorism

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The history of Chinese Medicine
Huang Di Nei Jing Su Wen
五脏 : 肝、心、脾、肺、肾
六腑 : 胆、胃、大肠、小肠、膀胱和
三焦
六淫： 风，寒，暑，湿，燥，火
七情： 喜，怒，忧，思，悲，恐， 惊Wind, cold, heat(hot weather), damp, dryness,fire,
Happy, angry, worry, think(anxiety), sorrow(sad, grief), fear, be
frightened(shock)

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An Italian anatomist ， the father
of modern anatomical pathology
He brought out the great work which,
once for all, made pathological
anatomy a science, and diverted the
course of medicine into new channels
of exactness or precision
In his five books, treating of the
morbid conditions of the body a capite
ad calcem, and together containing the
records of some 646 dissections
The Founder Of Organ Pathology
Giovanni Battista Morgagni
Italian,1682-1771 DC

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A German pathologist ,the
father of modern pathology
His scientific writings alone crossed
2,000 in number, “Cellular Pathology ”
published in 1858 is regarded as the
root of modern pathology. This work
also popularised the third dictum in
cell theory “All cells arise only from
pre-existing cells”
Rudolf Ludwig Carl Virchow
(1882-1902 AD)

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Autopsy— postmortem examination (necropsy)
A highly specialized surgical
procedure that consists of a
thorough examination of a corpse
to determine the cause and
manner of death and to evaluate
any disease or injury that may be
present. It is usually performed by
a specialized medical doctor
called a pathologist.
Classic TechniquesClassic Techniques
Of PathologyOf Pathology

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Autopsies are useful for :
1. Determining the cause of death
2. Audit of the accuracy of clinical diagnosis
3. Research into the causes and mechanisms of
disease
4. Gathering accurate data and information about
disease incidence and endemic
5. Education of medical students and professionals

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Biopsy --- An examination of pathologic samples from
living body to set up diagnosis
The intervention of the microscope is not at all necessary to
decide whether such and such a tumor, which has been removed, is
or is not of cancerous nature.-- Dr. Velpeau, famous professor of clinical
surgery at the Univ.of Paris in 1853
In the 1870s, Carl Ruge of the
Univ. of Berlin, introduced the
surgical biopsy as an essential
diagnostic tool.

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Histopathology and Cytopathology
The investigation and diagnosis of disease come from the
examination of tissues or isolated cell. ( tissue or cell
biopsies )

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Observation and new technique of
morphology
size,
shape
weight
color
consistency
surface
edge, section

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Microscopic observation (HE)
Most common and basic formalin fixed → HE
(hematoxylin and eosin) stained sections

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Electron microscopy—Ultrastructural pathology
Electron microscopy has extended the range of pathology to the
study of disorders at an organelle level, and to the demonstration of
viruses in tissue samples from some diseases.
Early (stage 1)
membranous
glomerulonephritis.
Two small
subepithelial kappa
light-chain deposits
are evident
(arrows). The
capillary lumen is
at the top.
(Mag×46,200.)
coronavirus
Embryonal
rhabdomyosarcoma
in the deltoid muscle.
Rigid myosin-
ribosome complexes
are randomly
distributed throughout
the cytoplasm. The Z-
disc substance is
indicated by an
arrow. (Magnification
×24,000).

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Immunohistochemistry
Tumor infiltrating lymphocytes

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S-100–positive melanoma.
Note the nuclear reactivity,
characteristic of melanoma
Keratin positivity in breast
cancer , which is typically seen
in carcinomas

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Candida. This example from the
esophagus shows magenta
pseudohyphae and yeasts
(arrows, periodic-acid Schiff
stain).
Cryptococcus. The organisms
are significantly larger and show a
range of sizes and shapes on
Gomori’s methenamine silver stain.
Microbiology---tissue section based

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Mycobacteria on acid-fast
bacteria stain. In this
example, tiny wine-red
rods are visible
within the tissue (arrows).
Helicobacter pylori. The
bacilli are sometimes visible
on hematoxylin and eosin
stain, as seen here (arrows),
in the pits of the gastric
mucosa Barry J.Marshall the University
of Western Australia 2005 nobel prize

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Molecular Biology…….
In situ hybridization
HPV DNA &RNA in situ hybridization in
squamous cell carcinoma

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Polymerase chain reaction amplification
of DNA extracted from microdissected
paraffin-embedded tissue with human
papillomavirus (HPV)-16 E7-type primers,
processed by Southern blotting, and
hybridized to HPV-16 E7 DNA. Lanes 1–5
show the following: (1) no primers, no
DNA; (2) primers only; (3) DNA only; (4)
microdissected stromal tissue; (5)
microdissected tumor tissue

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Cytogenetics and Fluorescence in Situ
Hybridization FISH
(Left) Achromosome spread from a human body cell midway through
mitosis, when the chromosomes are fully condensed. This preparation
was treated with fluorescent-labeled staining reagents that allow each of
the 22 pairs and the X and Y
(Right) Chromosomes from the preparation on the left arranged in pairs
in descending order of size, an array called a karyotype. The presence of
X and Y chromosomes identifies the sex of the individual as male
Chromosome Painting---multiplex fluorescence
in situ hybridization (M-FISH)
Her2 amplification in
breast cancer (FISH
and IHC)

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Types of primers that can be used to
initiate reverse transcription and
synthesis of complementary DNA
(cDNA) for reverse transcriptase
polymerase chain reaction (RT-PCR).
Verification of the specificity
of the polymerase chain
reaction (PCR) product

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Microsatellites are DNA
sequences that are
repeated a variable
number of times in the
genome and inherited in a
mendelian fashion. The
microsatellite region is
amplified by polymerase
chain reaction (PCR); the
products are separated by
gel electrophoresis,
processed by Southern
blotting, and hybridized to
a sequence-specific probe.
Microsatellite instability in colon cancer

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Animal experimentation
Transplant tumor model
in nude mice

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Tissue and cell culture

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Flow cytometry
Image analysis
Image digitizing technology
……….
The study of the nature of disease , which
constitutes pathology in the broad sense, has
many facets. Any science or technique which
contributes to our knowledge of the nature and
constitution of disease belongs in the realm of
pathology.

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The Branch of Pathology
Modern Pathology (1920S-)
Ultrastructural Pathology
Molecular Pathology
Immunopathology
Genetic Pathology
Remember: start from cellular pathology and
return to cellular pathology ultimately The cell is the basic
unit of structure and organization in organisms

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Pathology is best taught and learnt in two stages:
General pathology: A discussion of disease
fundamentals oriented horizontally (nature of
process). i.e. injury, repair, inflammation, neoplasia.
Systemic pathology: A more detailed discussion of
diseases oriented vertically. i.e. cardiovascular
diseases, respiratory diseases, alimentary diseases,
endocrine diseases, renal diseases, infectious
diseases.

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LEARNING OF PATHOLOGY
There are two apparent difficulties that face the new
student of pathology: language and process.
(1) Language——Vocabulary of special terms: These need
to be learnt and understood not just because they are
the language of pathology; they are also a major part of
the language of clinical medicine.
Concepts to master: lots of concept is basic processes of
studying pathology.
Cause(why) + Location (where) +Change(what)

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LEARNING OF PATHOLOGY
(2) The process —— a logical and orderly way of
thinking about disease.
Incidence
Aetiology
Pathogenesis
Pathological and clinical feature
Complications and sequel
Prognosis
Treatment

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LEARNING OF PATHOLOGY
(3) Pathology is learnt through a variety of media.
Textbook
Lecture
Practical classes (the gross and microscopic
observation)
Postmortem teaching (autopsy)

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LEARNING OF PATHOLOGY
(4) The problem-oriented and disease-oriented
approach.
In learning pathology, the disease-oriented approach
is more relevant because medical practitioners require
knowledge of disease (e.g. pneumonia, cancer, ischemic
heart disease) so that correct diagnoses can be made and
the most appropriate treatment given.