Veterinary General Pathology

For 3rd year DVM students

SCHOOL OF VETERINARY MEDICINE

WOLLO UNIVERSITY
 Introduction to General Pathology

Learning Objectives
1. Define pathology
2. Discuss the purposes and branches of
Pathology
3. Discuss the core aspects of disease in
pathology
4. Know the various categories of the causes of
diseases
 Introduction to General Pathology

Definition of pathology
Literal translation
 Pathology is derived from two Greek words:
-Pathos (suffering) & logia (study)
 Therefore, the word pathology literally translates
to the study (logos) of disease/suffering (pathos).
 Specific/technical definition
• Pathology is the scientific study of the functional,
biochemical and morphological alterations in cells,
tissues and organs as a result of disease.
 Two categories of pathology for pedagogical reasons

General Pathology: the study of the

mechanism and basic reactions of cells and
tissues to abnormal stimuli and to inherited
defects, that underlie all diseases.
Systemic Pathology: the study of the specific
responses of specialized organs and tissues
to more or less well defined stimuli.
It deals with the changes in specific
diseases/responses of specialized organs and
tissues.
 Why is Veterinary Pathology important?
 Accurate disease diagnosis: Pathological examination helps
differentiate between different animal diseases with similar
clinical signs, leading to precise treatment.
 Prognosis: Understanding the disease process allows for
predicting its course and potential outcomes.
 Disease prevention and control: by identifying risk factors and
underlying mechanisms of diseases
 One Health Concept: assess the risk of animal diseases to
human populations
 Drug Development: Pathology provides the scientific foundation
for drug development by investigating
the causes and mechanisms of diseases at all levels.
 Animal welfare: Pathology plays a crucial role in ensuring animal
welfare by contributing to the understanding and management
of diseases that impact animal health and well-being.
 Scope of pathology
Pathology is the “scientific Study of Disease”
 Disease is a condition in which an individual shows an
anatomical, chemical or physiological deviation from
the normal (Health).
 Health is a state of an individual living in complete
harmony, with his environment; surroundings.
 Pathology gives explanations of a disease by studying
the following four core aspects of the disease process:
1. Etiology
2. Pathogenesis
3. Morphologic changes
4. Functional derangements and Clinical significance
+ Molecular Pathology
1. Etiology – the cause of disease
 The causative factors of a disease can be divided
into two major categories:
A. Genetic (Intrinsic): mutations
B. Environmental (Acquired)
- Infectious, Chemical, Nutritional, Physical, etc
2. Pathogenesis - the mechanism by which the
causative factor/s produces structural and functional
abnormalities.
 It deals with sequence of events that occur in the
cells or tissues from initiation of cell or tissue injury
to disease development of any disease process.
 It starts with the entry of cause in body and ends
either with recovery or death.
 Usually, etiological agents takes some time to
manifest the disease. Few causative agents produce
signs and symptoms of the disease immediately
after exposure. == It varies depending on the
disease
 Incubation period: In disorders caused by infectious
(due to bacteria, viruses, etc.) agents, the period
between exposure and the development of disease
is called the incubation period.
 It usually ranges from days to weeks. Most of the
infectious agent have characteristic incubation
period
3. Morphologic Changes - the structural alterations
in cells, tissues or organs affected by disease.
• Two types of morphologic changes:
- Gross morphologic changes - naked eye
- Microscopic changes - microscope
• Gross morphologic changes : many diseases have
characteristic gross pathology and a fairly
confident diagnosis can be given before light
microscopy.
• Microscopic changes
• Microscopy/Light microscopy: abnormalities in
tissue architecture and morphological changes in
cells can be studied by light microscopy (paraffin
technique or frozen section)
4. Functional derangements /Clinical significance:
 The effects of genetic, biochemical, & structural
changes in cells and tissues are functional
abnormalities
 For example excessive secretion of a cell product (e.g.
nasal mucus in the common cold); insufficient secretion
of a cell product (e.g. insulin lack in diabetes mellitus).
 Clinical manifestations:
 The functional derangements produce to clinical
manifestations of disease (symptoms and signs).
The nature of the morphologic changes and their
distribution in organs / tissues influence normal
function and determine the clinical signs, course and
prognosis of the disease.
 Terminologies
• Lesion - any structural (or functional) abnormality in
an organ, tissue or cell.
 Pathognomonic abnormalities (lesion or sign): If the
structural changes are specifically
distinctive/characteristic of a single disease or
pathological condition, it is called as pathognomonic.
 Pathognomonic feature a lesion or sign that is
absolutely unique to a specific disease, or disease
category.
e.g.
‘Diamond skin disease’-
Erysipelothrix rhusiopathiae
• Rabies: The presence of Negri bodies (cytoplasmic
inclusions) in the brain tissue of infected animals
is pathognomonic for rabies.
Additional
signs/lesions.
 Symptoms: any subjective evidence of disease of
animal characterized by an indication of altered
bodily or mental state as told by owner (Complaints
of the patients).
 Signs: indication of the existence of something, any
objective evidence of disease, perceptible to
veterinarian (Observations of the clinicians).
 Biopsy - the removal and examination of tissue
from the living body to establish a precise diagnosis
• Diagnosis (Dx) = a concise statement or
conclusion concerning the nature, cause or
name of a disease process.
- It is an art of precisely knowing the cause
of a particular disease
- Differential Dx - a list of disease Dx that
could account for the clinical signs or
lesions in a case
- Clinical Dx - a Dx based on the data
obtained from the case history, clinical
• Morphologic Dx - a Dx based on the
predominant lesion(s) in the tissues
• Etiologic Dx - a Dx that names the cause
of the disease
• Disease (Definitive) Dx - a specific Dx
that states the “name of the disease”
• Prognosis - the probably outcome of a
disease in a living individual.
 EXAMPLE:

• A 4 yr-old dairy cow with a history of

chronic diarrhea and emaciation

1. Clinical Diagnosis
- Chronic diarrhea/emaciation
 Normal control

Note expansion of lamina propria with

inflammatory cells

Morphologic Dx .... Severe, chronic,

segmental, granulomatous enteritis
Etiologic Diagnosis
- Mycobacterial enteritis
Disease Diagnosis
- Johne’s Disease (Paratuberculosis)
• Necropsy/Autopsy - postmortem
examination of an animal after death.
- To determine the nature of pathological
processes that contributed to death or
disease.
- Autopsy - examination of a human body
 Descriptions in Gross Pathology
 Description should be concise, anatomically
precise and correct
 Components of a description
• Tissue - Identify the organ or structure
• Number - How many lesions are present?
• Shape - Spherical, rectangular, symmetrical, etc
• Colour
• Distribution
•Size - metric , length, vol., Weight
•Pattern - zonal, reticulated, mottled
•Consistency- soft, firm, hard, fluctuant
•Special features - papillated,pedunculated
etc
•Other like odor, surface appearance, etc
• Severity - mild, moderate, severe
• Duration - acute, subacute, chronic
• Nature of the lesion:
- if inflammatory – type of exudate
- if degeneration – type of degeneration
- if neoplastic – type of neoplasia
• Organ (prefix) + type of disease (suffix)
- Organ + itis (inflammation)
(greek root) eg, Hepatitis
+ osis (degeneration /
necrosis)
eg, Hepatosis,
+ pathy (non- inflammatory;

etiology unknown)
eg, Hepatopathy
 Branches of Pathology
• Post-mortem Pathology: Necropsy or Autopsy.
• Microscopic Pathology: deals with examination of cells/
tissues/ organs using microscope.
- It is also known as histopathology / cellular pathology.
• Clinical Pathology - includes certain laboratory methods
which helps in making the diagnosis using animal excretions/
secretions/ blood/ skin scrapings/ biopsy etc. e.g. Urine
examination, Blood examination.
• Experimental Pathology - concerns with the production of
lesion through experimental methods.
• Comparative Pathology: is the study of diseases of animals
with a comparative study in human beings and other animals.
e.g. Zoonotic diseases such as Tuberculosis.
• Cytopathology
• Nutritional Pathology…………………
 CELLULAR PATHOLOGY
CELL ADAPATION, INJURY & DEATH
Chapter 2: Cell pathology
• Cell adaptation
• Cell injury
• Cell death
• All organ injuries start with structural or
molecular alterations in cells” - (Virchow in
1800's )

• NORMAL CELLS
CELL ADAPATION, INJURY & DEATH
 Cellular response
 Homeostasis: Normal cells are capable of maintaining
their normal structure and function to handle normal
physiological demands and maintain a steady state called
homeostasis.
 Cellular Adaptation: When the cells are exposed to stress
or injurious stimuli, they may undergo adaptation
(functional or structural) to maintain their viability
 Cell Injury - if limits of the adaptive response are
exceeded or if adaptation is not possible, cell injury
occurs (may show features of injury)
 Cellular response to injurious stimuli depends on:
1. Type of injury 2. Duration of injury 3. Severity of injury

eg,- low doses or brief durations - reversible cell injury

- high doses or longer intervals - irreversible injury / cell death
 CELL INJURY
Causes of Cell Injury
1. Hypoxia: inadequate oxygenation of tissue.
 The most common causes of cell injury/death. Causes:
A) Deficient blood supply
 Ischemia: decreased blood supply from arterial flow
 Reduced venous drainage
B) Inadequate blood oxygenation (hypoxemia): due to
 Pulmonary disease
 Decreased perfusion of tissues: e.g. cardiac failure
 Reduced oxygen-carrying capacity of the blood
 Anemia and severe blood loss.
 Hb dysfunction: e.g. nitrate, nitrite & Co poisoning
c) Interference with oxidative phosphorylation
• eg, cyanide poisoning - inactivates cytochrome oxidase
 Cont..
2. Physical agents
- Direct mechanical trauma - Electric Shock
- Temperature extremes (heat or cold)
- Radiation (UV light, x-rays)
- Sudden changes in atmospheric pressure
3. Chemicals, Drugs & Toxins
• Poisons – Inorganic (lead, copper etc.) or Organic
(nitrate/nitrite, oxalate, hydrocyanic acid, etc.)
• Manufactured chemicals – drugs overdose, pesticides,
herbicides, rodenticides, etc
• Physiologic compounds - salt, glucose, oxygen, etc.
• Plant toxins (sweet clover, braken fern, etc.)
• Animal toxins (snake , spider, tick, etc.)
• Bacterial toxins/Mycotoxins: eg botulinum toxin,
aflatoxin, ergot, etc.
4. Infectious agents- Viruses, Bacteria, Fungi, parasites
5. Immunologic Reactions
• Immune/inflammatory response.
• Hypersensitivity (allergic) reactions
• Autoimmunity
6. Genetic Abnormalities - gene mutation, chromosomal
aberrations
 Deficiency of functional proteins
 Accumulation of damaged DNA or misfolded proteins
 Variations in the genetic makeup.
7. Nutritional Imbalances – deficiencies or over nutrition
8. Workload Imbalances – Overworked or underworked cells
9. Aging - cumulative effects of a life time of cell damage
10. Idiopathic: Cause is not known.
Targets and biochemical mechanism of cell injury
 Simplistically, cell injury disrupts cellular homeostasis.
 Cells are injured by numerous etiologic agents (intrinsic and
extrinsic sources); however, all of these causes activate one or
more of the following common targets and biochemical
mechanisms leading to cell injury.
 These principal targets and biochemical mechanisms of cell injury
are:
1. ATP depletion
2. Mitochondrial damage/dysfunction)
3. Permeabilization (damage) of cell membranes,
4. Disruption of biochemical pathways and
5. Damage to DNA and misfolding of proteins
6. Disturbance in calcium homeostasis.
7. Generation of reactive oxygen species (O2•, H2O2, OH•) and
TYPES OF CELLULAR RESPONSES TO INJURY

• Depending on the nature of stimulus/injury,

cellular responses can be mainly divided into four
types:
1. Cellular adaptations
2. Cell injury
 Reversible cell injury
 Irreversible cell injury
3. Intracellular accumulations
4. Pathologic calcification.
 CELLULAR ADAPTATIONS OF GROWTH AND
DIFFERENTATION
Cellular Adaptations
 When the cell is exposed to stimuli, the cells can
achieve a new, steady altered state that allows them
to survive and continue to function in an abnormal
environment. These are reversible changes and
constitute cellular adaptations.
 Major adaptive responses that occur in cells
- Atrophy
- Hypertrophy
- Hyperplasia
1. Cellular atrophy - the decrease in size of a cell,
after normal growth has been attained, through
a loss of cell substance (organelles, etc.)
Causes
• decreased workload (disuse atrophy)
• loss of innervation (denervation atrophy)
• loss of hormonal (trophic) stimulation,
• aging (senile atrophy).
• reduced blood supply / hypoxia
• inadequate nutrition
• compression
• persistent cell injury
 Cont…
• Grosslly - decreased in size of tissue/organ
• Microscopic
- small sized cells
2. Cellular hypertrophy - an increase in cell size
- cells are enlarged because more organelles are
synthesize (larger and more numerous organells)
 Etiology
• Increased work load:
- physiological - eg, exercise
- pathological - eg, heart failure
• a response to trophic signals:
- physiologic hypertrophy eg: uterus and mammary
gland in pregnancy, lactation
- Pathological hypertrophy eg: myocardial hypertrophy
in hyperthyroid cats
• certain drugs or toxins: increased SER in liver
4. Cellular hyperplasia - an increase in the
number of cells and subsequently
• It is usually caused by increased functional
demand/hormonal stimulation
• hypertrophy and hyperplasia occur together in
many tissues which can undergo division
• skeletal muscle, cardiac muscle and nerve cells
have no capacity for hyperplastic growth.
Hyperplasia of the thyroid gland

Normal thyroid Hyperplastic thyroid

gland gland
4. Cellular metaplasia - one adult cell type is
replaced by another adult cell type
- substitution of cells more sensitive to stress by
other cells which are more resistant to stress.
- eg, in chronic smokers - squamous metaplasia of
trachea (ciliated columnar to stratified
squamous epithelium)
- less differentiated "reserve cells" are conditioned
to differentiate into another cell type
 Cell injuries

-Reversible Cell Injury - removal of stress/injury

complete restoration of str. & fun. integrity
 MORPHOLOGY OF CELL INJURY

• Ultrastructural changes in the sick/ill cell

- In the ill cell, prominent morphologic or
functional changes are usually associated
with the cell membrane, mitochondria,
endoplasmic reticulum and lysosomes;
nuclear changes are minimal.
 Light microscopic changes in the sick

• The alterations that develop within a sick

cell are found principally in the
cytoplasm. The nucleus is unaffected
I. REVERSIBLE CELL INJURY (CELL
DEGENERATION)
1) Cellular Swelling
2) Fatty Change
 I. REVERSIBLE CELL INJURY (CELL DEGENERATION)

1) Cellular Swelling - an increase in cell size

due to increased intracellular
accumulation of water
• early, universal manifestation of cell injury
a) Etiology / Pathogenesis
• disruption of controls for ionic and
osmotic homeostasis at the cell
membrane level, resulting in increased
Gross appearance of cellular swelling
• organ swollen with rounded edges
• cut surface: tissue bulges and wet /
heavy
• Histologic appearance of cellular swelling
- if mild, may have cloudy appearance; “cloudy
swelling”
- “ washed out” appearance of the cytoplasm..
• Hydropic Degeneration
- poorly delineated cytoplasmic vacuolation
• Ballooning degeneration – cells are
greatly enlarged and the cytoplasm is
basically a clear space
2. Fatty change - an abnormal accumulation of
fat within cells
- In those cells involved in, or dependent on,
fat metabolism (cells of the liver, heart and
kidneys
Causes
• Increased dietary fat
• Starvation – mobilized fat & ↓ protein
synthesis
• Hypoxia – ↓ oxidation & ↓ protein synthesis
• Toxins – ↓ protein synthesis
Histologic appearance
- well-delinated lipid
vacuoles (cyoplasmic
vacuolation)