Chapter 1

Introduction to Pathology

Zhao Guoqiang
Introduction to Pathology
• Definition of Pathology

• Evolution of Pathology

• Subdivision of Pathology

• Methods for the study of pathology

 Definition of Pathology

The word “Pathology” is derived from two

Greek word ----
pathos meaning suffering
logos meaning study
 Definition of Pathology

Pathology is scientific study of structure and

function of the body in disease.

It deals with causes, effects, mechanisms and

nature of disease.
The knowledge and understanding of
pathology is essential for all would-be
doctors as well as general practitioners and
specialists since unless they know the causes
and mechanisms of disease and understand
the language spoken by the pathologist in
the form of laboratory reports, they would not
be able to institute appropriate treatment or
suggest preventive measures to the patient.
For the medical student, the discipline
of pathology forms a vital bridge
between initial learning phase of
preclinical science and the final phase
of clinical subjects.
 Evolution of Pathology
• From religious beliefs to rational approach
(Antiquity to AD 1500)
• Era of gross pathology (AD 1500 to 1800)
• Era of technology development and cellular
pathology (AD 1800 to 1950s)
• Modern pathology (1950s to dawn of 21st
century)
From religious beliefs to rational approach
(Antiquity to AD 1500)
• Hippocrates (Greece) 460-377 BC
Permanently dissociated medicine from religious
mysticism.
Started study of patient’s symptoms as method of
diagnosis.
• Cornelius Celsus (Rome) 53 BC-7 AD
Described 4 cardinal signs of inflammation (redness, heat,
swelling, pain)
Hippocrates (Greece) 460-377 BC
Era of gross pathology (AD 1500 to 1800)
• Giovanni B Morgagni (Italy) 1682-1771
Introduced clinicopathologic correlation (CPC) in the
study of disease
• John Hunter (Scotland) 1728-1793
Introduced pathology museum in the study of disease.
• R.T.H. Laennec (France) 1781-1826
Described several lung diseases such as various
tuberculous lesions of lungs, bronchiectasis.
Described cirrhosis of liver (later called Laennec’s
cirrhosis).
Invented stethoscope.
John Hunter (Scotland) 1728-1793
R.T.H. Laennec (France) 1781-1826
Era of technology development and cellular
pathology (AD 1800 to 1950s)
• Rudolf Virchow (Germany) 1821-1905
Father of cellular pathology
Introduced histopathology as a diagnostic branch by his
cellular theory
• George N. Papanicolaou (USA) 1883-1962
Father of exfoliative cytology
Developed Pap smear for detection of cervical cancer in
1930s
Rudolf Virchow (Germany) 1821-1905
George N. Papanicolaou (USA) 1883-1962
Modern pathology (1950s to dawn of 21st
century)
• Watson and Crick 1953
Described the structure of DNA
• Nowell and Hagerford 1960
Philadelphia chromosome in CML i.e. t(9;22)
• Gall and Pardue 1969
In Situ Hybridization
• Kary Mullis 1983
Introduced polymerase chain reaction (PCR)
Prof. Liang Boqiang 1899-1968
Prof. Qin Guangyu 1902-1969
 Subdivision of Pathology
• General Pathology --- dealing with general
principles of disease
• Systemic Pathology --- includes study of
diseases pertaining to the specific organs
and body systems
 Subdivision of Pathology
• Histo-Pathology
• Experimental Pathology
• Molecular Pathology
• Chemical Pathology
• Geographic Pathology
• Immunology
• Haematology
• Medical Genetics
Methods for the study of Pathology

• Autopsy

• Biopsy

• Cytology
What is Autoposy?
Autopsy means "see for yourself". It is a
special surgical operation, performed by
specially-trained physicians, on a dead
body. Its purpose is to learn the truth about
the person's health during life, and how the
person really died.
What is Bioposy?
A biopsy is the removal of a sample of tissue
from the body for examination. The tissue
will be examined under a microscope to
assist in diagnosis. Therefore, only very small

samples are needed.

What is Cytology?
Cytology can also refer to
cytopathology, which analyzes cell
structure to diagnose disease .
肖 萍 (Xiao Ping) 老师
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 Chapter 2
Cellular Adaptations and Cell Injury
Cellular Adaptations and Cell Injury
• Cellular Responses to Stress and Noxious Sti
• Cellular adaptations
• Causes of cell injury
• Mechanisms of cell injury
• Morphology of cell injury
Human body is quite complex and is
made of 70,000 billion cells.
In health, these cells remain in accord
with each other.
However, most forms of diseases begin
with cell injury and consequent loss of
cellular function .
Injury is defined as an alteration in cell
structure or function resulting from
some stress that exceeds the ability of
the cell to compensate through normal
physiologic adaptive mechanisms.
Cells typically respond to potentially injurious
stress in one of two ways:

Adaptation - Cells can alter their structure and/or

biochemical processes in order to achieve a new
"steady state" and maintain near-normal physiologic
functions (homeostasis).
Injury - If stressed cells cannot adequately adapt,
critical cell functions may be impaired, and the cell is
said to be injured.
Reversible and irreversible injury
If injured cells recover their normal functions
when the stress is removed, the injury is said
to be reversible.
If the injury is severe enough, however, a
“Point of no return” is reached and the cell
suffers irreversible injury and dies.
Cellular Responses to Stress and
Noxious Stimuli
Adaptation,

Reversible injury,

Irreversible injury (Cell death)

may be considered as different stages of a
progressive impairment of the cell’s normal
function and structure.
 Cellular adaptations
• Atrophy

• Hypertrophy

• Hyperplasia

• Metaplasia
 Atrophy
Reduction of the number and size of
parenchymal cells of an organ or its
parts which was once normal is called
atrophy.
It may occur from physiologic or
pathologic causes.
 Physiologic Atrophy
• Atrophy of thymus after puberty

• Atrophy of gonads after menopause

• Atrophy of brain with aging

 Pathologic Atrophy
• Malnutrition atrophy
• Denervation atrophy
• Disuse atrophy
• Pressure atrophy
• Endocrine atrophy
• Ischaemic atrophy
Atrophy of one kidney, gross
Atrophy, muscle fibers, microscopic
 Hypertrophy
Hypertrophy is an increase in the size of
parenchymal cells resulting in
enlargement of the organ or tissue,
without any change in the number of
cells.
It may be physiologic or pathologic.
Physiologic Hypertrophy
 Pathologic Hypertrophy

• Hypertrophy of cardiac muscle

• Hypertrophy of smooth muscle

• Hypertrophy of skeletal muscle

• Compensatory hypertrophy
. Hypertrophy, heart, gross
 Hyperplasia
Hyperplasia is an increase in the number
of parenchymal cells resulting in
enlargement of the organ or tissue.
Hyperplasia occurs due to increased
recruitment of cells from C0 (resting)
phase of the cell cycle to undergo
mitosis,when stimulated.
Hyperplasia, prostate, gross
 Metaplasia
Metaplasia is defined as a reversible
change of one type of epithelial or
mesenchymal adult cells to another type of
adult epithelial or mesenchymal cells,
usually in response to abnormal stimuli,
and often reverts back to normal on
removal of stimulus.
 Metaplasia
• Epithelial metaplasia
1. Squamous metaplasia
2. Columnar metaplasia
• Mesenchymal metaplasia
1. Osseous metaplasia
2. Cartilaginous metaplasia
Metaplasia, squamous, larynx, microscopic
 Metaplasia
, gastric columnar mucosa in esophagus, microsc
 Causes of cell injury
• Hypoxia and ischaemia
• Physical agents
• Chemical agents and drugs
• Infection agents
• Immunologic reactions
• Genetic derangements
• Nutritional imbalances
 Hypoxia and ischaemia
Hypoxia is the most common causes of cell
injury. The causes of hypoxia are as under:
• The most common mechanism of hypoxic cell
injury is by reduced supply of blood to cell i.e.
ischaemia.
• Oxygen deprivation of tissues may result from
other causes as well e.g. in anaemia, CO
poisoning, cardiorespiratory insufficiency, and
increased demand of tissues.
 Physical agents
Physical agents in causation of disease
are:
• Mechanical trauma (e.g. road accidents);
• Thermal trauma (e.g. by heat and cold);
• Electricity;
• Radiation (e.g. ultraviolet and ionising);
• Rapid changes in atmospheric pressure.
 Chemicals and Druges
Important example include:
• Chemical poisons such as cyanide, arsenic, mercury;
• Strong acids and alkalis;
• Environmental pollutants;
• Insecticides and pesticides;
• Oxygen at high concentration;
• Hypertonic glucose and salt;
• Social agents such as alcohol and narcotic drugs;
• Therapeutic administration of drugs.
 Infection agents
Injuries by microbes include infections
caused by :
• Bacteria;
• Rickettsiae;
• Viruses;
• Fungi;
• Protozoa;
• Metazoa;
• Other parasites.
 Immunologic reactions
Immunity is a “double-edged sword”
--- it protects the host against various
injurious agents but it may also turn lethal
and cause cell injury e.g.
• Hypersensitivity reactions;
• Anaphylactic reactions;
• Autoimmune reactions.
 Genetic derangements
Genetic defects as causes of cell injury are of major
interest to scientists and physicians today.
• The genetic injury may result in a defect caused by
a chromosomal abnormality (e.g. the congenital
malformations associated with Down syndrome).
• Variations in the genetic makeup can also influence
the susceptibility of cells to injury by chemicals and
other environmental insults.
 Nutritional imbalances
A deficiency or an excess of nutrients may result in
nutritional imbalances.
• Nutritional deficiency diseases may be due to overall
deficiency of nutrients (e.g. starvation), of protein
calorie (e.g. marasmus, kwashiorkor), of minerals
(e.g. anaemia), or of trace elements.
• Nutritional excess is a problem of affluent societies
resulting in obesity, atherosclerosis, heart disease and
hypertension.
Mechanisms of cell injury

• Depletion of ATP
• Membrane damage
• Influx of intracellular calcium and loss
of calcium homeostasis
• Accumulation of oxygen-derived free
radicals (oxidative stress)
Cellular and biochemical sites of damage in
cell injury
Morphology of cell injury

• Degeneration/Intracellular
Accumulations

• Cell death
 Degeneration and Intracellular
Accumulations
• In conventional description of morphologic
change, the term degeneration has been used to
denote morphology of reversible cell injury.
• Currently, more acceptable terms of reversible
cell injury are applied to non-lethal cell injury.
• One of the manifestations of metabolic
derangements in cells is the intracellular
accumulation of abnormal amounts of
various substances.
The stockpiled substances fall into three categories:
1. A normal cellular constituent accumulated in
excess, such as water, lipids, proteins, and
carbohydrates;
2. An abnormal substance, either exogenous, such
as a mineral or products of infectious agents, or
endogenous, such as a product of abnormal
synthesis or metabolism;
3. A pigment.
Degeneration and Intracellular
Accumulations
• Cellular swelling
• Fatty change
• Hyaline change
• Amyloidosis
• Pigments
• Pathologic calcification
 Cellular Swelling
• Cellular swelling is the first manifestation of
almost all forms of injury to cells.
• Other synonyms of cellular swelling used in the
past are:
cloudy swelling (for gross appearance of the
affected organ)
hydropic change (accumulation of water within
the cell)
vacuolar degeneration (due to cytoplasmic
vacuolation)
 Cellular Swelling

• Grossly, the affected organ such as

kidney, liver or heart muscle is enlarged
due to swelling. The cut surface bulges
outwards and is slightly opaque.
 Cellular Swelling
• Microscopically, it is characterised by
the following features:
1. The cells are swollen and the
microvasculature compressed.
2. Small clear vacuoles are seen in the
cells and hence the term vacuolar
degeneration.
 Fatty change (Steatosis)
• The terms fatty change and steatosis describe
abnormal accumulations of triglycerides within
parenchymal cells.
• Fatty change is often seen in the liver because it
is the major organ involved in fat metabolism,
but it also occurs in heart, muscle, and kidney.
Fatty metamorphosis of liver, gross
. Fatty metamorphosis of liver, microscopic
Fatty change, liver, microscopic
 Hyaline Change
• The word “Hyaline” means glassy (hyalos =
glass).
• Hyaline is a descriptive histologic term for
glassy, homogeneous, eosinophilic appearance
of material in H.E stained sections and does not
refer to any specific substance.
• Hyaline change is associated with
heterogeneous pathologic conditions and may
be intracellular or extracellular.
 Intracellular Hyaline
• Intracellular hyaline is mainly seen in
epithelial cells. For example:
1. Hyaline droplets in the proximal tubular
epithelial cells in cases of excessive
reabsorption of plasma.
2. Mallory’s hyaline represents aggregates
of intermediate filaments in the hepatocytes
in alcoholic liver cell injury.
 Intracellular Hyaline

3. Nuclear or cytoplasmic hyaline

inclusions seen in some viral infections.
4. Russel’s bodies representing excessive
immunoglobulins in the RER of the plasma
cells.
Hyaline droplets in the renal tubular epithelium
Mallory's hyaline, liver, microscopic
 Extracellular Hyaline
• Extracellular hyaline is seen in connective tissues.
A few examples of extracellular hyaline change
are:
1. Hyaline degeneration in leiomyomas of the
uterus.
2. Hyalinised old scar of fibrocollagenous tissues.
3. Hyaline arteriosclerosis is renal vessels in
hypertension and diabetes mellitus.
4. Hyalinised glomeruli in chronic
glomerulonephritis.
Uterus, leiomyoma, microscopic
Renal hyaline arteriolosclerosis with diabetes melli