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CONTENTS
 Introduction to Pathology: Divisions & subdivisions in pathology, Disease
and types of disease, Cellular responses, Hypertrophy, Hyperplasia,
Atrophy, Metaplasia
 Cell injury & Cell death: Causes of cell injury, Mechanisms of cell injury ATP
depletion, Mechanisms of cell injury Damage to Mitochondria, Mechanisms
of cell injury Disturbances in calcium homeostasis, Disturb cell membrane
function, Mechanisms of cell injury Production of Oxygen free radicals,
Damage to DNA & Proteins, Cell Death Necrosis & Apoptosis.
 Mechanism of necrosis: Necrosis Different Types of necrosis, Apoptosis
Mechanism of Apoptosis,Differences b/w Necrosis & Apoptosis.
 Inflammation: Types of inflammation Acute and chronic inflammation,
Immunity & its types, immune system, cells of immune system, Advantages
& disadvantages of inflammation, Exudates & transudate, Leukocyte
cellular events, types of inflammatory cells & sequence of cellular events,
Clinical signs of acute inflammation & outcome of acute
inflammation,Chronic Inflammation
 Cell Repair & wound healing: Cell repair, control of cell growth, cell cycle,
Repair by connective tissue (scar formation), steps of repair, Healing
Primary and secondary healing, mechanism of wound healing, Bone repair,
steps of repair of fractured bone, Complications of wound healing, factors
affecting the healing process.
DEFINITION OF PATHOLOGY
“the scientific study
It is the “Scientific of the molecular,
study of the causes cellular, tissue, or
and effects of organ system
disease or injury". Or response to injurious
agents."

Pathology serves as a "bridge" or "link" between

the preclinical sciences (anatomy, physiology,
biochemistry, etc.) and the courses in clinical
medicine (Cardiology, surgery, diabetology,
etc.).
WHAT IS THE DISEASE?
 The disease may be defined as an abnormal

alteration of structure or function in any part of

the body that is harmful to the organism.

 It is “the state in which an individual exhibits a
biochemical, anatomical, or physiological
deviation from the normal”.
 Occurs when the cellular environment changes
to such a degree that cells and tissues are no longer
able to perform their function optimally.
Developmental – genetic,
congenital.
CLASSIFICATION OF DISEASES:
Acquired:

• * Inflammatory – Trauma, infections,

immune, etc.
• * Neoplastic – tumors cancers
• * Degenerative – ageing
• * Metabolic- type 2 diabetes
• * Iatrogenic: alteration during diagnosis/
treatment/surgery
BASİC TERMINOLOGY OF
Pathology is the study of suffering (Greek
PATHOLOGY
word)
• – Pathos= suffering
• – Logos = study

Etiology = Cause

Pathogenesis = sequence of events

Morphology = structural alterations in cells and

tissues
• Gross = Changes in the tissue or organ
• Microscopy = Changes noted under a light
microscope
BRANCHES OF PATHOLOGY:
I. General Pathology
II. Systemic Pathology
III. Histopathology
IV. Cytopathology
V. Hematology
VI. Forensic Pathology
VII. Immunology
VIII. Chemical Pathology
IX. Genetics
X. Toxicology
XI. Microbiology
GENERAL PATHOLOGY
 General Pathology

 Deals with general principles of disease

 Common changes in all tissues. e.g., inflammation,
cancer, aging, edema, hemorrhage ….etc.

Systemic Pathology:
 that includes study of disease pertaining to the
specific organ and body systems.
WHAT SHOULD WE KNOW ABOUT A
DISEASE?
STUDY OF DISEASE: (PATHOLOGY)
 Epidemiology –Incidence, distribution
 Etiology - Causes
g y
 Pathogenesis - Evolution
o lo
 Morphology - Structural Changes
at h
P
 Clinical Significance – Functional Changes

 Management

 Complications

 Prevention
 STEPS IN THE EVOLUTION OF
DISEASE
 ETIOLOGY: Cause of disease. Anemia
Goiter
 PATHOGENESIS:
Mechanisms of development
and progression of disease.
 MORPHOLOGY: The
structural alterations induced
in cells and tissues.
 Molecular and FUNCTIONAL
CONSEQUENCES:
Molecular and Functional
results of the morphologic
changes, as observed
 Etiology
Disease diagnosis

“Study of the cause of a disease"

Knowledge of etiology remains the backbone of:

Understanding the
nature of diseases

Treatment of
diseases.
 ETIOLOGY:
WHAT IS THE CAUSE?
 Environmental agents:
• Physical
• Chemical
• Nutritional Multifactorial:
As Diabetes,
• Infections
Hypertension
• Immunological Cancer
• Psychological
 Genetic Factors:
• Age
• Genes
 ETIOLOGY

Disease Disease
Disease
Disease
Disease

•One etiologic
One etiologic • Several etiologic
agent
agent agents one
several
- disease, as diabetes.
diseases, as
one disease, as
smoking.
Malaria.
Cancer, heart
disease, stroke, lung
disease, diabetes,
PATHOGENESIS
The sequence of events in the response of the
cells or tissues to the etiologic agent, from the
initial stimulus to the ultimate expression of the
disease, from the time it is initiated to its final
conclusion in recovery or death.

The core of the science of

pathology — the study of the
pathogenesis of the disease.
MORPHOLOGY: STRUCTURAL
CHANGES

 Structural changes in disease.

 Tumor in cancer.
 Ulcer in an infection.
 Atrophy in dementia.

Gross & Microscopic.

Ulcer is the breach of the continuity of skin, epithelium or mucous

membrane caused by sloughing out of inflamed necrotic tissue
TECHNIQUES IN PATHOLOGY:
 Gross Pathology:
 Light Microscopy:
Histopathology, Cytology, Autopsy
 Histochemistry, Biochemical techniques

Immunohistochemistry. Immunochemistry
 Electron Microscopy for ultra-structural changes
(nm)
 Cell Cultures
 Molecular Pathology: PCR and other molecular

biology techniques.
TECHNIQUE OF MORPHOLOGY

Gross appearance:
size
shape
weight
color
consistency
surface
edge
section
HISTOLOGIC AND CYTOLOGIC
OBSERVATION:
most common and basic formalin fixed
→ HE (hematoxylin and eosin) stained
IMMUNOHISTOCHEMISTRY
1. Ag-Ab specific reaction
2. Applications
(1) Location analysis
cytoskeleton, cell membrane, etc.
(2) Clinical diagnosis and distinguishing
diagnosis of tumor histogenesis
IHC/IF

DAB (3,3′-Diaminobenzidine) is a derivative of benzene. It is most often used in

immunohistochemical (IHC) staining as a chromogen. It is also used in in situ hybridization (ISH) and sometimes
in dot blots and in western blotting.
LEIOMYOSARCOMA Actin (+)

Leiomyosarcoma: malignant cancer

cell of smooth muscle
Wahab et al., 2021
 SEM stands for
scanning electron
microscope while
ULTRASTRUCTURAL OBSERVATION
TEM stands for the
TEM (transmitting electron
transmission
The key difference electron
between microscope)
microscope.
SEM and TEM is that SEM
creates an image by
detecting reflected
electrons, whereas TEM
creates an image by
detecting transmitted
electrons. SEM analyzes the
surface of a sample while TEM
analyses the internal structure.
SEM (SCANNING ELECTRON
MICROSCOPE)
Podocyte

Podocyte are epithelial cells that cover the outer

surfaces of glomerular capillaris
FLOW CYTOMETRY (FCM)
1. One kind of cells→quantitative
2. Selection of collection of cells
 MOLECULAR BIOLOGY
TECHNIQUE
1. Polymerase chain reaction (PCR)
2. DNA sequencing
3. qPCR
4. Biochip technique
(1) Gene chip (DNA chip)
(2) Protein chip (protein microarray)
(3) Tissue chip (tissue microarray)

A DNA microarray (also commonly known as DNA chip or biochip) is a

collection of microscopic DNA spots attached to a solid surface.
Scientists use DNA microarrays to measure the expression levels of large numbers of
genes simultaneously or to genotype multiple regions of a genome. Each DNA spot
contains picomoles (10 moles) of a specific DNA sequence, known as probes (or reporters
Further reading

STRUCTURAL VS.
FUNCTIONAL DISEASE
STRUCTURAL DISEASES
 Also called organic disease
 Characterized by structural changes within

the body, called lesions

 Lesions can be visually identified

 With molecular medicine and technology,

they can also now be identified at the

molecular level of proteins and genes
 Three broad categories:
 Geneticdiseases
 Degenerative and Inflammatory diseases
 Hyperplastic and Neoplastic diseases
GENETIC DISEASES
 Caused by abnormalities in the genetic makeup
at the chromosomal or genetic (gene) level
 Developmental diseases develop during

embryonic or fetal development

 Range of abnormalities very broad
 Deformities can be preset at birth (congenital
abnormalities)
 Biochemical changes caused by genes but
influenced by the environment can appear later on
(i.e., diabetes)
DEGENERATIVE AND
INFLAMMATORY DISEASE
 Caused by forces or agents that destroy cells,
or intercellular substances, deposit abnormal
substances in tissues or cells, or cause the
body to injure itself by means of the
inflammatory process
 External agents of injury
 Chemical substances and microbes
 Internal mechanisms of injury
 Vascularinsufficiency, immunologic reactions,
metabolic disturbances
DIRECT EFFECTS OF INJURY
 Necrosis – if cells are killed in injured area

 Sublethal cell injury – if injured cells are

capable of recovery
GENERAL REACTIONS TO
INJURY
 Inflammation – a vascular and cellular
reaction
 Attempts to localize the injury, destroy the
offending agent, remove damaged cells and
other materials

 Repair- replacement of damaged tissue by

new tissue
 Greatly influenced by the type of tissue or organ
that has been injured
HYPERPLASTIC AND
NEOPLASTIC DISEASES
 Basic abnormality is an increase in cell
populations

 Hyperplasia – proliferation (division and

reproduction) of cells with exposure to a
prolonged stimulus. Regresses or stops when
stimulus is removed

 Neoplasia – results from genetic changes that

favor the growth of a single population of
cells
 Two groups – benign and malignant (ability to
localize or spread)
FUNCTIONAL DISEASES
 Diseases in which there are no visible
lesions, at least not at the onset of the
disease
 The basic change away from homeostasis is

a physiologic or functional one

 More common functional disorders:
 Tension headache
 Functional bowel syndrome
 Hypertension
 Mental illnesses
CAUSES OF DISEASE
EXOGENOUS – AGENTS CAUSING
INJURY ACTING FROM OUTSIDE THE
BODY
 Direct Physical injury is called TRAUMA
 Physical agents causing disease include:
 Heat and cold
 Electricity

 Atmospheric Pressure changes

 Radiation (electromagnetic and particulate)

CHEMICAL INJURIES
 Subdivided into the manner of injury

 Poisoning (accidental, homicidal, or suicidal)

 Drug Reactions
 Toxiceffects of prescription or proprietary drugs
taken to treat disease)
MICROBIOLOGIC INJURIES
 Usually classified by the type of offending
organism
 Bacteria
 Fungi
 Protozoa
 Viruses

 These are called infections and diseases caused

are infectious diseases
ENDOGENOUS DISEASES –
ACTING FROM WITHIN THE BODY
 Vascular Diseases
 Obstruction to blood supply to an organ or tissue
(myocardial ischemia caused by arteriosclerosis)
 Hemorrhage (ruptured abdominal aortic
aneurysm)
 Altered blood flow (microvascular changes in
diabetes or hypertension)
IMMUNOLOGIC DISEASES
 Caused by aberrations to the immune system
 Failure of the immune system to work =

immunodeficiency disease
 Overreaction of the immune system causes

allergic or hypersensitivity diseases

 Abnormal reaction of the immune system to

substances that the body produces =

autoimmune diseases
PROGNOSIS AND DIAGNOSIS
 Prognosis is the expected outcome of the
disease; it is the clinician’s estimate of the
severity and possible result of a disease.

 Diagnosis is the the formal name(s) used to

describe a patient’s disease. It is the process
of identifying a disease based on the
patient’s symptoms, the doctor’s findings,
and the results of investigations and
laboratory tests.
TYPES OF PATHOLOGY

 There are three

main subtypes of
pathology:
 Anatomical
Pathology,
 Clinical Pathology
 Molecular
Pathology.
ANATOMICAL PATHOLOGY

 Anatomical pathology is the study

of anatomical features, such as
tissue removed from the body, or
even an entire body in the case of
an autopsy, to diagnose and
increase knowledge of disease.

 Anatomical pathology can include

looking at cells under a microscope,
but it also involves looking at
organs in general (e.g. a ruptured
spleen).
ANATOMICAL
PATHOLOGY TYPES
 Surgical pathology is the examination
of tissues removed during surgery. A
common example is the examination of a
small piece of tumor tissue to determine
whether the tumor is malignant
(cancerous) or benign and make a
diagnosis. This procedure is called a
biopsy.
 Histopathology is the examination of
cells under a microscope that have been
stained with dye to make them visible or
easier to see.
 Cytopathology is the study of small
groups of cells shed in bodily fluids or
obtained through scraping, such as those
taken during a cervical Pap smear.
CONT..

 Clinical Pathology

 Clinical pathology diagnoses disease through

laboratory analysis of bodily fluids and tissues.
 For example, the chemical components of
blood may be analyzed, along with analyzing
cells and identifying any microorganisms such
as bacteria that are present in a sample.
  Chemical pathology, or clinical chemistry, involves the
CHEMICA chemical analysis of bodily fluids, through testing and
microscopy.
L  Hematology is also related to the study of blood, but it has more
to do with identifying blood diseases specifically than chemical
PATHOLO pathology does.

GY-TYPES  Immunology, or immunopathology, is the study of immune

system disorders. It deals with immune responses to foreign
molecules, allergies, immunodeficiencies, and organ transplant
rejection.
MOLECULAR PATHOLOGY

 Molecular pathology is the study of abnormalities

of tissues and cells at the molecular level.
 It is a broad category that is used to refer to the
study of disease of any organ or tissue in the
body by examining what molecules are present in
cells.
 Some techniques that can be used in molecular
pathology include polymerase chain reaction
(PCR) to amplify DNA, fluorescence labeling and
karyotype imaging of chromosomes.
CELLULAR ADAPTATIONS

 Some diseases represent spontaneous

alterations in the ability of a cell to
proliferate and function normally,
 In such situations, cells must adapt to
the new environment.
 These adaptations
include hyperplasia, hypertrophy,
atrophy, and metaplasia, and can
be physiologic or pathologic,
depending upon whether the stimulus
is normal or abnormal
 Cell can adapt to a certain point, but
if the stimulus continues beyond that
point, failure of the cell, and hence
the organ, can result i
 CONT….
 Traditionally the study of
pathology is divided into general
pathology and systemic pathology.
General pathology is concerned
with the common reactions of cells
and tissues to injurious stimuli.
 Etiology or Cause. Contain into
two classes:
 genetic (e.g., inherited mutations
and disease-associated gene
variants, or polymorphisms) and
acquired (e.g., infectious,
nutritional, chemical, physical).
CELL INJURY

 If the limits of adaptive

responses are exceeded or
if cells are exposed to
injurious agents or stress,
deprived of essential
nutrients, or become
compromised by
mutations that affect
essential cellular
constituents, a sequence
of events follows that is
termed cell injury
CELLULAR
ADAPTATIONS TYPES

 Adaptations are
reversible changes in
the size, number,
phenotype, metabolic
activity, or functions
of cells in response to
changes in their
environment. Such
adaptations may take
several distinct forms.
HYPERTROPHY

 Hypertrophy refers to an increase in the size of cells, that results in an

increase in the size of the affected organ.
 The hypertrophied organ has no new cells, just larger cells.
 The increased size of the cells is due to the synthesis and assembly of
additional intracellular structural components.
 Hypertrophy can be physiologic or pathologic; the former is caused by
increased functional demand or by stimulation by hormones and
growth factors.
 For example, the bulging muscles of bodybuilders engaged in
“pumping iron” result from enlargement of individual muscle fibers in
response to increased demand.
CONT..

 The massive physiologic

growth of the uterus
during pregnancy is a
good example of
hormone-induced
enlargement an organ
that results mainly from
hypertrophy of muscle
fibers.
 Uterine hypertrophy is
stimulated by estrogenic
hormones acting on
smooth muscles.
CONT..
 Hypertrophy is also
associated with a switch
of contractile proteins
from adult to fetal or
neonatal forms.
 For example, during
muscle hypertrophy, the
α isoform of myosin
heavy chain is replaced
by the β isoform, which
has a slower, more
energetically economical
contraction.
HYPERPLASIA

 Hyperplasia is defined as an increase in the number of cells in an

organ or tissue in response to a stimulus.
 Physiologic hyperplasia due to the action of hormones or growth
factors occurs in several circumstances
 when there is a need to increase functional capacity of hormone
sensitive organs; when there is need for compensatory increase
after damage.
 In individuals who donate one lobe of the liver for
transplantation, the remaining cells proliferate so that the organ
soon grows back to its original size.
 Labile Cell, Stable and Permanent cells
CONT..
 Pathologically, Hyperplasia is the result of
growth factor-driven proliferation of mature
cells and, in some cases, by increased output
of new cells from tissue stem cells.
 Hepatomegaly without any surgery.
 ATROPHY
 Atrophy is defined as a reduction in the
size of an organ or tissue due to a
decrease in cell size and number. Atrophy
can be physiologic or pathologic.

 Physiologic atrophy is common during

normal development.
 The decrease in the size of the uterus that
occurs shortly after parturition is another
form of physiologic atrophy.
CONT..
 Pathological Atrophy:
 Decreased workload (atrophy of disuse). When a
fractured bone is immobilized in a plaster cast or when a
patient is restricted to complete bed rest, skeletal muscle
atrophy rapidly ensues.
 Loss of innervation (denervation atrophy). The
normal metabolism and function of skeletal muscle are
dependent on its nerve supply. So, damage to this leads
this.
 Diminished blood supply. A gradual decrease in blood
supply (ischemia) to a tissue as a result of slowly
developing atrophy of organ.
 Inadequate nutrition. Profound protein-calorie
malnutrition (marasmus) is associated with the utilization
of skeletal muscle proteins lead to muscle wasting.
CONT..

 Loss of endocrine stimulation. The loss of estrogen

stimulation after menopause results in physiologic atrophy
of the endometrium, vaginal epithelium, and breast.

 Pressure. Tissue compression for any length of time can

cause atrophy. An enlarging benign tumor can cause
atrophy in the surrounding uninvolved tissues
METAPLASIA
 Metaplasia is a reversible change in which
one differentiated cell type (epithelial or
mesenchymal) is replaced by another cell
type.
 It often represents an adaptive response in

which one cell type that is sensitive to a

particular stress is replaced by another cell
type that is better able to withstand the
adverse environment.
ANATOMICAL
PATHOLOGY TYPES
 Surgical pathology is the examination
of tissues removed during surgery. A
common example is the examination of a
small piece of tumor tissue to determine
whether the tumor is malignant
(cancerous) or benign and make a
diagnosis. This procedure is called a
biopsy.
 Histopathology is the examination of
cells under a microscope that have been
stained with dye to make them visible or
easier to see.
 Cytopathology is the study of small
groups of cells shed in bodily fluids or
obtained through scraping, such as those
taken during a cervical Pap smear.