PATHOLOGY

Rudolf Ludwig Carl Virchow (1821-1902)

father of modern pathology
was a German doctor, anthropologist, pathologist, prehistorian, biologist,
writer, editor, and politician, known for his advancement of public health.
 PATHOLOGY
Is the study (logos) of suffering (pathos)

PATHOLOGY
Is a bridging discipline involving:
basic science
clinical practice

PATHOLOGY
Is devoted to the study of the structural and
functional changes in cells, tissues and organs
that underline disease.
 PATHOLOGY
Pathomorphology
&
Pathophysiology

GENERAL SPECIAL
PATHOLOGY (SYSTEMIC)
PATHOLOGY
 GENERAL PATHOLOGY

Is concerned with the basic reactions of cells

and tissues to abnormal stimuli that underline
all diseases.

SPECIAL (SYSTEMIC) PATHOLOGY

examines the specific responses of specialized
organs and tissues to more or less well-defined
stimuli.
 ETIOLOGY (CAUSE)

INTRINSIC (GENETIC)

ACQUIRED e.g. infectious, nutritional, chemical, physical

Knowledge or discovery of the primary cause

remains the backbone on which:
a diagnosis can be made
a disease understood
a treatment developed
 PATHOGENESIS

Refers to the sequence of events in the

response of cells or tissues to the etiologic
agent:

from the initial stimulus

to the ultimate expression of the
disease
 MORPHOLOGIC CHANGES

Morphologic changes refer to the

structural alterations in cells or
tissues that are either characteristic
of the disease or diagnostic of the
etiologic process.
All forms of organ injury start
with molecular or structural
alterations in cells
 FUNCTIONAL DERANGEMENTS

Morphological changes influence normal

function and determine:
the clinical features (symptoms)
course of the disease
prognosis of the disease
 FUNCTIONAL DEARANGEMENTS

Different cells in tissues constantly interact

with each other, and an elaborate system
of extracellular matrix is necessary for the
integrity of organs.

CELL – CELL and CELL - MATRIX

interactions contribute to the response to injury,
leading collectively to tissue and organ injury.
 CELLULAR RESPONSES TO STRESS
AND NOXIOUS STIMULI

Normal cell is able to handle normal

physiologic demands, maintaining a steady
state called

HOMEOSTASIS
 CELLULAR RESPONSES TO STRESS
AND NOXIOUS STIMULI

More severe physiologic stresses and some

pathologic stimuli may cause a number
of physiologic and morphologic

CELLULAR ADAPTATIONS

during which
a new but altered steady states
are achieved
 ADAPTIVE RESPONSES:

HYPERPLASIA:
- an increase in the number of cells

HYPERTROPHY:
- an increase in the size of individual cell

ATROPHY:
- an adaptive response in which there is
a decrease in the size and function of cells
 HYPERPLASIA
Hyperplasia is an increase in the number of cells
in a tissue or organ, usually resulting in increased
volume of the tissue or organ.
Hyperplasia takes place if the cellular population
is capable of syntesizing DNA, thus permitting
mitotic division.
 Mechanism of Hyperplasia

- An increase of local production of GROWTH FACTORS.

- An increase of density of growth factor receptors on the
responding cells.
- Activation of particular intracellular signalling pathways.
- All these changes lead to production of transcription factors that
turn on many cellular genes, including genes encoding growth
factors and cell cycle regulators – result in cellular proliferation.
- In hormonal hyperplasia hormones may act as growth factors.
- The increase in tissue mass may be achieved by the remaining
cells but also by the development of new cells from
STEM CELLS
 Physiologic hyperplasia
Physiologic hyperplasia can be divided into:
Hormonal hyperplasia - which increases the functional
capacity of a tissue when needed e.g. physiologic
hyperplasia that occurs in the female breast at puberty and
in the pregnant uterus.

Compensatory hyperplasia –
which increases tissue mass after
damage, or partial resection-
myth of Prometheus whose
liver regenerated every night.
 Pathologic Hyperplasia
- Most forms of pathologic hyperplasia are caused by EXCESSIVE
hormonal stimulation or growth factors acting on target cells.
Endometrial hyperplasia resulted from disturbed balance
between estrogens and progesterone.
Benign prostatic hyperplasia induced by androgens.
- Pathologic hyperplasia regresses if the hormonal stimulation
is eliminated.
- Stimulation of growth factors is also involved in the hyperplasia tha
is associated with certain viral infections such as papilloma viruses
which cause skin warts.
Pathologic hyperplasia constitutes a fertile soil in which
cancerous proliferation may eventually arise.
 Thyroid gland, diffuse hyperplasia of Graves disease - Gross

The gland is uniformly but not markedly enlarged. In contrast to

compensatory hyperplasia, this is an example of pathologic
hyperplasia.
 Slkk
l

HYPERTROPHY
ii
-HYPERTROPHY can be PHYSIOLOGIC
or PATHOLOGIC and it caused by increased functional
demand or by specific hormonal stimulation
-Hypertrophy occurs in nondividing cells (e.g. myocardium).
-Hypertrophy refers to an increase in the size of cells,
resulting in an increase in the size of the organ.
-The most common stimulus for hypertrophy of muscle is
increased workload. The enlarged muscle cell achieves a new
equilibrium, permitting it to function at a higher level of activity.
In the heart, the stimulus for hypertrophy is usually chronic
hemodynamic overload, resulting from either hypertension,
or faulty valves.
HIPERTROPHY
-PHYSIOLOGICAL
-PATHOLOGICAL
 Slkk
l
Mechanisms of HYPERTROPHY
Growth
Endothelin
factors
ANG II IGF-1 ii
α- adrenergic Mechanical
hormones stretch
Mechanisms of HYPERTROPHY

TRANSCRIPTON INIDUCTION OF INIDUCTION OF

CONTRACTLE EMBRYONIC GENS
FACTORS
PROEIN GENS

C-Jun Β-myosin haevy chain - ATP

Myosin light chain
c-Fos Skeletal α-actin
Cardiac α-actin
Erg-1
TGF-β ANF
IGF-1 Decresed
Increased workload
muscle
activity
 HYPERPLASIA & HYPRTROPHY
Although hyperplasia and hypertrophy are two
distinct processes, frequently both:
occur together
may be triggered by the same external stimulus
Hormone-induced enlargement of the uterus
involves both increased number of smooth muscle

and epithelial cells (hyperplasia) and also the

enlargements of these cells (hypetrophy).

 ATROPHY

Shrinkage in the size of the cell by loss of cell

substance is known as ATROPHY

Atrophy represents a form of adaptive response

and may culminate in CELL DEATH
ATROPHY:
Physiologic
Pathologic
 CAUSES OF ATROPHY

• Decreased workload
• Loss of innervations
• Diminished blood supply
• Inadequate nutrition
• Loss of endocrine stimulation
• Aging (senile atrophy)
• Pressure (an enlarging benign tumor can cause
atrophy)
 MECHANISM OF ATROPHY
Biochemical mechanisms responsible for atrophy are
likely to affect the balance between

PROTEIN SYNTHESIS PROTEIN DEGRADATION

For the degradation of many cytosolic and nuclear
protein is responsible ubiquitin-proteasome pathway.
Proteins to be degradated by this process are first
conjugated to ubiquitin and then degraded within
a large cytoplasmic proteolytic organelle called
proteasome.
Atrophy is often also accompanied by marked
increases in the number of autophagic
vacuoles.
Kidneys, normal (left) and ischemic atrophy (right) - Gross, cut surfaces

These kidneys are from a patient who had atherosclerotic stenosis

of one renal artery, leading to decrease in size (atrophy) of one
kidney. The atrophy primarily involves the cortex, which contains
the most metabolically active cells.
 AUTOPHAGOSOM

Section of a pancreatic acinar cell showing autophagosomes. Upper right:

Two portions of the rough endoplasmic reticulum segregated by a membrane.
Center: An autophagosome containing mitochondria plus rough
endoplasmic reticulum. Left: A residual body (R), with indigestible material.
 METAPLASIA
Metaplasia is a reversible change in which one adult cell type
(epithelial or mesenchymal) is replaced by another adult cell
type.
Metaplasia may represent an adaptive substitution of cells that
are sensitive to stress by cell types better able to withstand the
adverse environment:
The most common epithelial metaplasia is columnar to
squamous – in respiratory tract in response to chronic irritation.
Metaplasia from squamous to columnar epithelium may
occur in Barret oesophagus, in which the oesophageal
squamous epithelium is replaced by intestinal –like columnar
cells under the influence of gastric reflux.
 The most common epithelial metaplasia is columnar to
squamous – in respiratory tract in response to chronic irritation.

METAPLASIA
NEOPLASIA
Metaplasia from squamous to columnar epithelium may also occur in Barret
oesophagus, in which the oesophageal squamous epithelium is replaced by
intestinal–like columnar cells under the influence of gastric reflux.

Esophagus, adenocarcinoma in Barrett esophagus

 MECHANISMS OF METAPLASIA
METAPLASIA is the result of a reprogramming of stem
cells that are known to exist in normal tissue,
or of undifferentiated mesenchymal cells present in
connective tissue.
The differentiation of stem cells is stimulated by signals
generated by: cytokines
growth factors
extracellular matrix components.
For example: Members of TGF-B superfamily induce
chondrogenic or osteogenic expression in stem cells, while
supress differentiation into muscle or fat cells.
 CELL DEATH

Cell death is one of the most crucial events in the

evolution of the disease of any tissue or organ.
It results from diverse causes, including ischemia (lack
of blood flow), infection, toxins, and immune reactions.
Cell death is a normal and essential part:
of embryogenesis
development of organs
maintenance of tissur homeostasis
Cell death is also the aim if cancer therapy.
 CELL DEATH

TWO PRINCIPAL PATTTERNS OF CELL DEATH

NECROSIS – occurs after such abnormal stresses as ischemia

and chemical injury, and it is always pathologic
APOPTOSIS – occurs when a cell dies through activation
of an internally controlled suicide program.
It is designed to eliminate unwanted cells during embryogenesis
and in various physiologic processes, such as involution of
hormone-responsive tissues up on withdrawal of the hormone
It also occurs in pathologic conditions, when cells are damaged
beyond repair, and especially if the damage affects the cell’s
nuclear DNA.
 APOPTOSIS NECROSIS
• T

The word APOPTOSIS comes from the Greek meaning

„a falling off”
 APOPTOSIS

• T

The word APOPTOSIS comes from the Greek meaning

„a falling off”
 Why me?

NECROSIS APOPTOSIS
is a messy busines is an ordered event

W.B. Saunders Company items

and derived items Copyright (c)
Slide 1.1
Heart, coagulative necrosis (myocardial infarct) - Gross, cross section
A pale infarct is surrounded by a zone of hyperemia (vascular
dilatation).
 Stages in the cellular response to stress
and injurious stimuli

NORMAL CELL
homeostasis
Stress
incrased Injurous
demand stimulus

ADAPTATION CELL INJURY

CELL DEATH

ADAPTATION, REVERSIBLE INJURY and CELL DEATH can be

considered stages of progressive impairment of the cell’s normal
function and structure.
 ADAPTATION NORMAL CELLS CELL INJURY
homeostasis CELL DEATH

Hearts, hypertrophied, normal (middle), and dilated

- gross, cross sections
The heart on the left has undergone hypertrophy (increase in cell size
resulting in thickened myocardium) due to increased workload (adaptation).
In the heart on the right, the adaptation was insufficient, and the heart has
decompensated (note dilated chambers).
 ADAPTATION NORMAL CELLS CELL INJURY
homeostasis CELL DEATH

Hearts, hypertrophied, normal (middle), and dilated

- gross, cross sections
Cell injury is reversible up to a certain point, but if the stimulus persists or is
severe enough from the beginning, the cells reach a „point of no return” and
reversible cell injury changes into irreversible cell injury and ultimately
CELL DEATH