PATHOLOGY
Dr. Özlem Özer Yücel, Assaociate Professor
PhD in Periodontics
PhD in Oral Pathology
References:
Kumar V., Abbas A.K., Fausto N: Pathologic Basis of Disease, seventh edition, Philadelphia: W.
B. Saunders Co., 2004
Editör: Robbins, Çeviri editörü: Prof. Dr. Uğur Çevikbaş. Robbins Temel Patoloji (Basic Pathology,
sekizinci basım, Nobel Tıp Kitabevi, 2007
PATHOLOGY
PATHOLOGY
Patos Log
os Suffering (disease) Study
Introduction to Pathology
1- Etiology: refers to the underlying causes and modifying
factors that are responsible for the initiation and
progression of diseases.
2- Pathogenesis: refers to the mechanisms of
development and progression of disease.
3- Morphology: refers to structural changes in gross or
microscopic appearance of disease.
4- Clinical manifestations: refers to clinical outcomes and
progression of disease.
Overview of Basic Cellular Responses
1. Cellular adaptations
2. Cell Injury and Cell Death
3. Acute and chronic inflammation
4. Tissue repair
5. Hemodynamic Disorders, Thromboembolism, and
Shock
6. Diseases of the Immune System
7. Neoplasia
Abnormalities that give rise to diseases originites
from cell
Virchow was the first scientist who asserted
that disease originates at the cellular level.
The cell as a unit of health and disease
Cellular functions;
1-Energy generation: ATP
2-Synthesis of proteins and macromolecules
3-Transportation
4-Digestion and detoxification
5-Storage
6-Mobility
7-Recognising and signalling
8-Reproduction
Cellular responses to stress
Cells actively interact with their environment, constantly adjusting
their structure and function to accommodate changing demands and
extracellular stresses. They remain fairly constant, a state referred to as
homeostasis.
ADAPTATION ?
Under physiologic stresses or potentially
injurious conditions, cells can achieve a
new steady state and preserving viability
and function which is called adaptation
Cellular responses to stress
➢ Adaptations are reversible changes in the number, size, phenotype, metabolic
activity, or functions of cells in response to changes in their environment.
➢ If the adaptive capacity is exceeded or the external stress is excessive, cell
injury develops. Within certain limits injury is reversible, however if the stress is
persisent or severe it results in cell death.
CELLULAR ADAPTATIONS
Pyhsiologic Pathologic
Causes of cellular adaptations?
1- Physiologic adaptations usually represent responses of cells to normal stimulation by
hormones or endogenous chemical mediators or to the demands of mechanical stress.
2- Pathologic adaptations are responses to stress that allow cells to modulate their structure
and function and thus escape injury, but at the expense of normal function. (hypoxia,
chemical changes, hormonal imbalance, immunologic reactions)
How do cells undergo adaptation?
The mechanisms driving cellular adaptation in response to phsyologic or
pathologic stimulus involve a series of functions in protein metabolism:
➢ Intracellular signal transduction
➢ Copying of target genes (transcription)
➢ Increased or decreased protein synthesis
Changes in cells that undergo adaptation
Increased metabolic activity
Reduced metabolic
activity
Changes in cells that undergo adaptation
Morpholocical changes
Forms of adaptation
Hyperplasia
Hypertrophy
Atrophy
Metaplasia
Hyperplasia
❑ Hyperplasia is an increase in the number of cells in an
organ that stems from increased proliferation.
❑ Hyperplasia takes place if the tissue contains cell
populations capable of replication.
❑ It may occur concurrently with hypertrophy and often in
response to the same stimuli.(ex. growth hormones)
Hyperplasia
Physiologic hyperplasia Pathological hyperplasia
1. Hormonal 1. Pathologic hyperplasia are
hyperplasia ( ex. proliferation of the caused by excessive hormonal or
glandular epithelium of the female breast
at puberty and during pregnancy) growth factor stimulation (ex.
increased estrogenic stimulation
2. Compensatory hyperplasia, in causes endometrial hyperplasia
which residual tissue grows after removal or
loss of part of an organ. (when part of a liver is
2. Stimulation by growth factors also is involved
in the hyperplasia that is associated with certain
resected)
viral infections (ex. HPV)
Hyperplasia
Physiologic hyperplasia and
hypertrophy of the uterus
during pregnancy. (A)
Gross appearance of a
normal uterus (right) and a
gravid uterus (left) that was
removed for postpartum
bleeding.
Hyperplasia
Increased estrogenic stimulation causes endometrial hyperplasia
a- Inactive endometrium b- Proliferative endometrium
Hyperplasia
Normal prostatic gland
Benign
prostatic
hyperplasia
Hyperplasia
Fibrotic gingival hyperplasia
Phenitoin induced gingival
hyperplasia
Hyperplasia
▪Cellular proliferation is stimulated by growth factors that
are produced by a variety of cell types.
The stimuli for hyperplasia triggers intracellular signalling p
athways for essential for DNA synthesis.
▪The hyperplastic process remains controlled; if the signals
that initiate it abate, the hyperplasia disappears.
Forms of adaptation
Hyperplasia
Hypertrophy
Atrophy
Metaplasia
Hypertrophy
❑ Hypertrophy is an increase in the size of cells resulting in an
increase in the size of the organ.
❑ It occurs when cells have a limited capacity to divide.
❑ Cells containing increased amounts of structural proteins and
organelles.
❑ Can be physiologic or pathologic and is caused
either by increased functional demand or by growth factor or
hormonal stimulation.
Hypertrophy
A- Physiologic hypertrophy of the B- Small spindle-shaped uterine smooth
uterus during pregnancy. muscle cells from a normal uterus.
C- Large, plump hypertrophied smooth muscle
cells
Hypertrophy
Hypertrophy of
skeletal muscle in
response to
increased workload
Hypertrophy
Myocardial hypertrophy
a- Gross appearance of normal and hypertrophic ventriculs
b- Normal myocard cells
c- Hypertrophic myocardial cells.
Forms of adaptation
Hyperplasia
Hypertrophy
Atrophy
Metaplasia
Atrophy
❑Atrophy is shrinkage in the size of cells by the loss of cell [Link], the
entire tissue or organ is reduced in size.
❑Cellular atrophy results from a combination of decreased protein synthesis and
increased protein degradation.
❑Protein synthesis decreases because of reduced metabolic activity.
❑Although atrophic cells may have diminished function, they are not dead.
❑Causes of atrophy include a decreased workload (e.g., immobilization of a limb to
permit healing of a fracture), loss of innervation, diminished blood supply,
inadequate nutrition, loss of endocrine stimulation, and aging (senile atrophy).
Atrophy
➢ Physiologic : The loss of hormone stimulation in
menopause, atrophy of timus at
puberty, post menoposal atrophy of endometrium.
➢ Pathologic: Loss of innervation, diminished blood supply
in atherosclerosis ...
Atrophy A B
A- Atrophy of the brain in an 82-year-old man. Atrophy of the brain is caused by
aging and reduced blood supply.
B- Normal brain of a young adult.
Atrophy
Atrophy of skeletal muscle in
response to innervation loss
a- Normal skelatal muscle
cells
b- Atrophic cells due to loss
of innervation
Atrophy
➢Atrophy also is associated with autophagy. Autophagy is the process in
which the starved cell eats its own organelles in an attempt to survive.
➢During cell membrane degradation in atrophy, a form of non-soluble lipid
molecule called lipofuscin is stored in the cytoplasm . This brown colored
pigment present in large amounts, imparts an appearance to the tissue
that is called brown atrophy.
➢Cell loss is mediated by apoptosis .
Atrophy
Lipofuscin in
myocardial cells
which implicates
atrophy
Forms of adaptation
Hyperplasia
Hypertrophy
Atrophy
Metaplasia
Metaplasia
Metaplasia is a
change in which
one adult cell type
(epithelial or
mesenchymal) is
replaced by
another adult cell
type.
Metaplasia
➢ A cell type sensitive to a particular stress is replaced by another cell type
better able to withstand the adverse environment.
➢ Metaplasia is thought to arise by the reprogramming of stem cells.
➢ The influences that induce metaplastic change in an epithelium, if persistent,
may predispose to malignant transformation.
Metaplasia
➢ Epithelial metaplasia is exemplified by
the change that occurs in the
respiratory epithelium of habitual
cigarette smokers, in whom the normal
ciliated columnar epithelial cells of the
trachea and bronchi often are replaced
by stratified squamous epithelial cell.
(squamous metaplasia)
➢ Osseus metaplasia: Bone is
occasionally formed in soft tissues,
particularly in foci of injury.
Metaplasia:
In chronic gastric reflux, the normal stratified squamous epithelium of the lower
esophagus may undergo metaplastic transformation to gastric or intestinal-type
columnar epithelium. (Barret Esophagus)
Metaplasia
Metaplasia of normal
columnar (left) to squamous
epithelium
Metaplasia of the normal
stratified squamous epithelium of
the lower esophagus intestinal-
type columnar epithelium. (Barret
Esophagus)
Metaplasia
Original tissue Stimulus Metaplastic
tissue
Intestinal type smoking Squamous epithelium
columnar epithelium
Transitional calculus in bladder Squamous epithelium
epithelium of urinary
bladder
Connective tissue injury Bone
Squamous epithelium Gastric acid Intestinal type
of the lower columnar epithelium
esophagus
Non-keratinised Vitamin A deficiency Keratinised skuamous
skuamous epithelium epithelium
of cornea
❖Hypertrophy: increased cell and organ size, often in
response to increased workload; induced by growth factors
produced in response to mechanical stress or other stimuli;
occurs in tissues incapable of cell division
❖ Hyperplasia: increased cell numbers in response to
hormones and other growth factors; occurs in tissues whose
cells are able to divide or contain abundant tissue stem cells.
Lessons to take ❖ Atrophy: decreased cell and organ size, as a result of
home decreased nutrient supply or disuse; associated with
decreased synthesis of cellular building blocks and increased
breakdown of cellular organelles and autophagy
❖Metaplasia: change in phenotype of differentiated cells,
often in response to chronic irritation, that makes cells
better able to withstand the stress; usually induced by
altered differentiation pathway of tissue stem cells; may
result in reduced functions or increased propensity for
malignant transformation.
