INTRODUCTION TO GENERAL

PATHOLOGY
Dr. KAGIRA JM, PhD
DEFINITIONS
• Pathology = study of disease (pathos = disease + logos = study)
• Pathology = study of structure & function of the body in disease
[Opposite of Anatomy]
• Deals with the structural & functional changes in cells, tissues, &
organs that underlie disease
• Bridges basic science [anatomy, physiology, biochemistry] &
clinical practice [medical, surgical, gynecological treatment]
• Pathology covers five aspects of a disease process:
(1) Cause (aetiology)
(2) Mechanisms of its development (pathogenesis)
(3) Structural changes produced in cells and organs
(morphological changes)
(4) Functional consequences of the morphological changes
(clinical significance)
(5) Result or termination eg., death or recovery
• Macroscopic or gross pathology - examination of tissue
without the help of a microscope, use naked eye
• Microscopic pathology or histopathology - examination of
tissue with the help of a microscope, and involves the use of
stained tissue sections
– Study of disease at microscopic level
– Involves examination of the changes caused by or causing a
disease at the cellular level
• General Pathology [sem 1]- concerns with basic alterations of
tissues as a result of disease. e.g. fatty changes, thrombosis,
embolism, necrosis
• Systemic Pathology [sem 2]- deals with alterations in
tissues/organs of a particular system. e.g. respiratory system,
genital system etc.
• Clinical Pathology [3.1]- includes certain laboratory methods
which help in making the diagnosis using animal excretions/
secretions/blood/urine etc.
• Nutritional Pathology - study of diseases due to deficiency or
excess of nutrients e.g. rickets due to calcium deficiency
• Comparative Pathology - study of diseases of domestic
animals with a comparative study in human beings and other
animals. e.g. zoonotic diseases such as tuberculosis
• Oncology - study of cancer/tumor/neoplasms
• Immunopathology - study of diseases mediated by immune reactions -
includes Immunodeficiency diseases, hypersensitivity reactions
• Cytopathology - study of cells shed off from the lesions for diagnosis
• Postmortem examination - examination of an animal after death to
establish a disease, that is, cause of its death
• Necropsy - Postmortem examination of animals and birds
• Autopsy - postmortem examination of humans
• Biopsy - examination of tissue removed from the living animal to
determine the cause of disease eg., cancer
• Syndrome: group of symptoms that occur together & characterize a
particular abnormality, i.e: characteristic of a certain disease
• Health - condition in which the individual is in complete harmony with its
environment/ surroundings
• Disease -
– A condition in which an individual shows a structural, functional, or
chemical deviation from the normal
– Is a result of the interaction between a causative agent and the host
• Cause (aetiology): Are of two types:
i) Intrinsic (endogenous) causes of disease- predisposing factors, are those
characteristics (genus, breed, sex, age, etc.) over which an individual has
no control and which determine the type of disease present
Examples: Swine fever = disease of the pig; Canine distemper = dog
ii) Extrinsic (exogenous) causes of disease - those environmental factors
(physical, chemical, thermal, infectious, immunological, nutritional) that are
capable of producing disease in the individual
• Illness - a disease or period of sickness affecting the body
• Forensic Pathology - careful examination and recording of pathological
lesions in case of veterolegal cases
• Homeostasis - mechanism by which body keeps equilibrium between health
& disease. e.g. Adaptation to an altered environment.
• Diagnosis –
1. Art of precisely knowing the cause of a particular disease
2. Name given to a specific disease event such that diagnosis means the
same syndrome to all the veterinarians and animal health practitioners’
i.e. standard classifications scheme
3. Can refer to a specific aetiological agent (aetiological diagnosis) or
description of the morphological alterations evident (pathoanatomical
diagnosis) or a description of the clinical sign/s
• Symptoms: Any subjective evidence of disease of animal characterized by an
indication of altered bodily or mental state as told by owner
• Signs: Indication of the existence of something, any objective evidence of
disease, perceptible to veterinarian/AHP (observations of the clinicians/AHP)
• Syndrome: A combination of symptoms caused by altered physiological
process
• Lesion: Lesion is a pathological alteration in structure/ function that can be
detectable
• Incubation period: Incubation period is the time that elapses between the
action of a cause & manifestation of disease
• Pathogenesis/Course of disease: Course of disease is the duration for which
the disease process remains till fate either in the form of recovery or death
• Prognosis: estimate by a clinician of probable severity/outcome of disease
• Infection - invasion of the tissues of the body by pathogenic organisms resulting
in the development of a disease process.eg., Haemorrhagic lesion in heart
• Infestation - superficial attack of any parasite/organism on the surface of body
• Pathogenicity- capability of an organism for producing a disease
• Virulence - degree of invasiveness of pathogenic organism.
• Pathogens (agents of disease) are numerous but include four basic groups:
1. Physical agents eg., heat, cold , radiation, trauma
2. Genetic factors
3. Chemical agents eg., toxins, poisons, drugs, metabolites , free radicals
4. Infectious agents - bacteria, viruses, fungi, parasites, prions/infectious proteins
MANIFESTATIONS OF DISEASE (PATHOLOGY)
• Referred to as ‘pathological processes’ that occur in
tissues:
1. Inflammation & Repair (including Immunology)
2. Circulatory Disturbances
3. Disorders of Growth including Developmental
Disorders
4. Degeneration
5. Accumulation of Pigment and Tissue Deposits
CELL INJURY
Outcomes of lecture
1. Understand concepts of reversible cell injury & irreversible cell injury
leading to cell death.
2. Understand the central role of membrane function & dysfunction in cell
injury and the importance of free radicals in membrane damage.
3. Recognise the morphological characteristics of apoptosis & understand the
concepts of the pathogenesis of apoptosis
4. Recognise the morphological characteristics of necrosis & understand the
pathogenesis of necrosis.
5. Understand the fate of necrotic tissue & the linkage with the pathological
process of inflammation & repair
CELL INJURY
1. Any change in a cell which, if not reversed, could lead to the death of
that cell
2. A loss of ability to respond to functional demands
3. Any change that results in a loss of the ability to maintain the normal
or adapted homeostasis
• Morphological changes lag behind the biochemical events; & Cell may have
died before showing specific morphological changes
• Pathology/histopathology is a static examination of a dynamic process of
disease
• Cell injury is a continuation of the spectrum of adaptive change which is
continuous with the normal cell.
PATHOGENESIS OF CELL INJURY
• PATHOGENESIS: development of disease, including examination of the
relationship between the aetiological agent & lesion as well as the
relationship between the lesion & clinical signs

Causes of Cell Injury / Agent of Disease / Aetiological Agent

1. Hypoxia
Loss of oxygen supply is a common cause of cell injury and cell death
Affects cells aerobic oxidative respiration

i. Circulatory disturbances (ischaemia)

ii. Decrease in oxygen carrying capacity
iii. Interference with the respiratory chain

2. Physical agents
• Heat , cold, radiation, trauma
3. Genetic factors:
• Genetic injury may result in a defect as gross as congenital malformations
• Several inborn errors of metabolism due to congenital enzymatic
deficiencies - cell damage due to alterations at the level of DNA

4. Chemical agents:, toxins, poisons, drugs, metabolites, free radicals

• Any chemical substance or drug can cause cell injury
• Eg., glucose or salt in hypertonic concentrations may cause cell injury
directly, or by deranging their osmotic
• Poisons cause severe damage at the cellular level, and can result in the
death of the whole organism
• Chemicals or drugs cause changes by acting on some vital functions of the
cell, such as membrane permeability, osmotic homeostasis
• Others: air pollutants, herbicides, carbon monoxide, asbestos
• Even therapeutic drugs can cause cell or tissue injury
Inflammation
a) Infectious agents: bacteria, viruses , fungi , protozoa,
helminth, prions/infectious proteins
b) Immunological Responses: eg., anaphylactic reaction to a
foreign protein or a drug, & autoimmune diseases

Nutritional imbalances:
• Nutritional deficiencies eg., avitaminoses and others are
important causes of cell injury
• Excesses of nutrition - important causes of morbidity &
mortality
• Diets rich in animal fat, cause atherosclerosis and obesity
DEVELOPMENT OF CELL INJURY
• Requirements for normal cell function: intact membranes & energy supply
• Harmful agent interacts with a cell & cause:
1. Membrane damage (involving plasma and/or organelle membranes)
2. Energy (ATP) depletion (and so failure of energy-dependent processes)
• Leads to an increase in membrane permeability, which will cause loss of
concentration gradients and swelling or even lysis of the cell

MEMBRANE DAMAGE
• Cell membranes - lipid bi-layer + integrated functional proteins
• Energy-dependent enzymic ion pumps esp. Na-K-ATPase, which pumps Na+
out and K+ in
• Membranes act as selective barrier, controlling ion exchange to maintain
correct internal osmolarity
• Damaged membrane: leaky membrane, allow influx of Na+, Ca2+, water
into the cell & organelles
• Results: swelling of cell & substrates diffuse around the cell - inhibition of
cell function
• Most agents inflict membrane damage via free radicals
– Highly reactive small molecules, most often charged oxygen molecules
released when the agent interacts with cellular components
– Eg: produced by ionising radiation & many toxins
– Also released by normal biochemical reactions but are quickly mopped
up by the cell's own anti-oxidants (selenium, vitamin E & glutathione)
• Actual damage to membranes inflicted by free radicals involves the
peroxidation of membrane lipids
• Free radicals react with membrane lipids & form lipid peroxides, a chain
reaction of lipid peroxidation then follows & eventually significant
membrane damage occurs thus increasing permeability
DIRECT DAMAGE TO CELL MEMBRANES
• Agents including irradiation, toxins, complement, deficiency of Vitamin E
or selenium cause direct damage to cell membranes
• Membrane damage is caused by:
1. Direct interaction
2. Formation of free radicals commonly derived from cellular oxidation-
reduction reactions
• Important free radicals: superoxide anion & hydroxyl radical
• Free radicals are substances that have unpaired electrons & highly reactive
- exist only briefly & do not travel far
• Rapid bursts of superoxide production occur in activated neutrophils
during inflammation
• Once produced Superoxide can be inactivated either spontaneously or
more rapidly by the enzyme superoxide dismutase (SOD), forming H202
• Free radicals damage to membrane, DNA, enzymes & structural proteins
• Consequence: membrane dysfunction leading to:
1. Protein synthesis disruption due to ER damage
2. Membrane permeability disruption
3. Mitochondrial respiration disruption due to membrane damage &
influx of calcium
Normal Protection against oxidative injury
• Cells have built in systems designed to protect against damage by free
radicals by quenching them.
• Systems include:
1. Superoxide dismutases (catalyse conversion of superoxide anion to
hydrogen peroxide)
2. Catalases (break down hydrogen peroxide)
3. Endogenous anti-oxidants such as vitamin E (lipid soluble),
glutathione + selenium as a catalyst, and ascorbate (aqueous)
• Dietary lack of these antioxidants can lead to disease, esp. Se & Vit E
deficiencies
– Leads to necrosis of cell populations due to oxidative damage (i.e white
muscle disease)
ENERGY (ATP) DEPLETION START HERE
• Cells need energy for:
1. Driving ion pumps to maintain osmotic gradients,
2. Synthesis of structural molecules and enzymes,
3. Carrying out specialised functions (e.g. contraction, secretion), heat
production etc.
• Earliest manifestation of energy depletion: swelling of cell & organelles due
to:
1. Failure of the energy-dependent Na-K-ATPase ion pump
2. Na+ floods in taking water with it which causes swelling
3. K+ rushes out which may upset cardiac conduction
• Mitochondria & rER are most affected by the swelling :
– Leads to energy shortage & disruption of protein synthesis
What causes energy (ATP) depletion?
• ATP production

• ATP production is mainly impaired by hypoxia (oxygen shortage) leading to

failure of aerobic respiration
• Without oxygen, electron transport cannot occur - production of ATP by
oxidative phosphorylation is inhibited [READ]
• This slows ATP production by the TCA cycle
HYPOXIA
• Develop with a lesion anywhere from nostrils down to the mitochondrial
enzymes and involve:
i. Oxygen not reaching the blood e.g. airway obstruction , lung
inflammation
ii. Oxygenated blood not reaching the tissues e.g. infarction, constant
pressure on a tissue from a tumour
iii. "Respiratory poisons" acting at specific sites in the respiratory
pathway. Eg., cyanide
• Susceptibility to hypoxia:
– Greatest in cells with a high metabolic rate (i.e. high energy demand)
such as neurons, myocardial fibres & renal epithelium
At what point does reversible cell damage become irreversible?
1. Inability to reverse mitochondrial dysfunction ⇒ ATP depletion
2. Profound disturbances in membrane function
• Severe mitochondrial change is best indicator of the onset of irreversible
cell damage
• Irreversible injury is associated morphologically with:
a) Severe swelling of mitochondria
b) Extensive damage to plasma membranes
c) Swelling of lysosomes
• Extracellular calcium enters into the cell: accumulate in the mitochondrial
matrix
• After this, there is continued loss of proteins, essential coenzymes, and
ribonucleic acids from the hyper-permeable plasma membrane
• Falling pH (due to accumulation of lactic acid and inorganic phosphates)
causes injury to the lysosomal membranes
• Followed by leakage of their lysosomal enzymes into the cytoplasm &
activation of acid hydrolases
• Activation of these enzymes leads to enzymatic digestion of cytoplasmic
& nuclear components
MORPHOLOGICAL CHANGES OF CELL INJURY
CELLULAR SWELLING - [cloudy swelling, oncosis]
• Most common manifestation of cell injury
• Cell becomes enlarged & visible changes evident in the cytoplasm of the
cell
• Cell becomes more granular than normal
• Caused by the mildest irritants & results from the shift of extracellular
water into the cell
• Cloudy swelling = gross appearance of the affected organ
• Aetiology (Causes):
(1) Bacterial toxins (the most common cause).
(2) Rise in body temperature (fever)
(3) Metabolic diseases (diabetes and acetonaemia)
(4) Organic or inorganic poisons (lead, arsenic, alcohol), and circulatory
disturbances (infarction, hyperaemia, haemorrhage) when insufficient
oxygen is brought to the cell
Macroscopically:
• Affected organ (liver, kidney) is slightly enlarged, the edges are slightly
rounded, and there is an increase in weight
• Changes are due to an increased amount of fluid in the affected cells
• Organ appears pale or anaemic, because the swollen cells compress the
capillaries reducing the amount of blood in the organ
• When incised, the cut surface bulges
• Cut surface is cloudy, slightly opaque, and appears
as if it had been slightly scalded or cooked
Microscopically:
• Cells become swollen, and their edges become rounded
• Staining characteristics changes, then formation of intracellular vacuoles
becomes apparent - vacuolar degeneration /hydropic degeneration
• Vacuoles - due to the influx of water into the cell & cytoplasmic organelles
• Cytoplasm of the cell is more granular than normal
• Significance and result:
– Is a reversible injury & indicates the cell has been exposed to a mild
irritant, or that hypoxia has been present
– When the cause is removed, the granules disappear, the fluid leaves
the cell, and the cell returns to normal.
FATTY CHANGE [fatty degeneration and fatty infiltration]
• Refers to any abnormal accumulation of neutral fat (triglycerides) within
parenchymal cells
• Appearance of fat vacuoles - absolute increase in intracellular fat
• Mostly seen in liver - involved in fat metabolism; also in others
Aetiology:
• Caused by a variety of irritants that are more severe than those which
produce acute cellular swelling
1. Inadequate amounts of oxygen:
• Occurs in anaemia, following haemorrhage/hemolysis in diseases eg.,
babesiosis - destruction of RBCs
2. Hepatotoxins:
• Both organic & inorganic chemical substances cause fatty change
• Includes: bacterial (salmonella) toxins, plants (Crotalaria); chemical
poisons eg., carbon tetrachloride, chloroform
• Humans - alcohol is a hepatotoxin
3. Metabolic diseases: eg., diabetes mellitus & ketosis
4. Miscellaneous: Protein malnutrition, deficiency in choline, corticosteroids,
starvation, obesity
Macroscopic appearance - Liver:
• Progressive accumulation of fat - organ becomes increasingly yellow
• Liver enlarges - borders become rounded
• Consistency – soft, greasy, less able to withstand mechanical forces
• Fingers are easily forced into the liver
• Cut surface – bulges, greasy appearance
• Droplets of fat are visible on the surface of the knife blade
Microscopically
• Small clear (fat) vacuoles of varying size in the cytoplasm around the
nucleus
• Vacuoles coalesce to create cleared spaces that displace the nucleus to
the periphery of the cell, until it is elongated and barely visible
HYDROPIC DEGENERATION
• Closely related to cellular swelling
• Cells take on clear fluid to such an extent that they swell & may burst
• Aetiology: Similar to those of cellular swelling but are more severe, and
include:
(1) Mechanical injuries of a rubbing nature. Eg: skin of the hands of men
exposed to the friction from a shovel; ill fitting shoes cause blister
(2) Thermal injuries, both heat and cold cause hydropic degeneration: hot
water, oil, metal or flame produce blisters in animals. Skin injured by freezing
temperatures also cause hydropic degeneration.
(3) Chemical injuries: treatment of lameness by croton oil, red iodide of
mercury, and oil of mustard - sharp blisters
(4) Infectious agents, eg., pox viruses, foot-and mouth
(5) Neoplasms - esp cervix
Macroscopically:
• Blister on the skin; upon incision, fluid escapes & blister collapses
• If pyogenic bacteria enter the injured epithelium, suppurative
inflammation may result eg., burns or pox virus

Microscopically:
• Increase in the size of the cells due to accumulation of fluid
• Small clear vacuoles - cytoplasm
• Change is also sometimes called vacuolar degeneration
• Fluid is taken into the cells, they enlarge, the droplets coalesce &
finally the cells become so distended that they burst
• Stratified squamous epithelium - blister or vesicle formation
MUCINOUS OR MUCOUS DEGENERATION
• Excessive accumulation of mucin in degenerating epithelial cells
• Mucin - glassy, viscid, stringy, slimy glycoprotein, is normally produced by
columnar & cuboidal epithelial cells
• Goblet cells - mucous membrane of the large intestine – produce mucin
• Mucus - mucin is mixed with water or tissue fluid
Aetiology:
• Occurs whenever a mild irritant is applied to a mucous membrane
• Causes include mild mechanical injury to a mucous membrane; mild
chemicals eg., disinfectants; infectious agents, eg., viral diarrhea of cattle
Macroscopically:
• Mucous membrane is covered with a clear, white transparent material,
which is stringy and slimy in consistency Eg: common cold mucus
• MM - hyperaemic
• Layer of mucus often encloses the faecal excrement of animals when they
are constipated
• Large amounts of mucus are produced by the genital tract during oestrus -
physiological mucus
• Microscopically:
– Mucin first appears in the cytoplasm of the cell as a small droplet
– Droplets coalesce forming larger droplets
– Displaces the nucleus to one side, which eventually gets compressed
against the cell wall.
– Cell enlarges & ultimately ruptures
– Ruptured cell dies & desquamated
• Significance and results:
– Remove causative agent - overproduction of mucin stops & lost
epithelium is repaired by regeneration of the surviving cells