Professional Documents
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LECTURE
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Introduction
Pathology
is "Scientific study of disease"
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Morbid Anatomy: Autopsy or Post mortem study for legal
or educational purpose.
Aspects of disease
Disease (dis+ease)? "Discomfort due to Structural or
functional abnormality
Pathology of a disease is formally studied under four
subdivisions/aspects.
Etiology - Study of cause / causative agent of disease
Pathogenesis- Study of disease progression or evolution.
Morphology - Study of structural changes in disease (Gross &
microscopic)
Clinical Significance - Study of how clinical features are related
to changes.
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Factors causing disease
are mainly two types.
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Congenital disease Diseases which present since
birth .
Familial diseases Diseases which occur in families
1. Degenerative disorders
are due to lack of growth or ageing.
1. Neoplastic disorders
are due to excess cell division forming tumours.
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CELLULAR PATHOLOGY
individual organs,
requires knowledge of the function &
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Cellular Physiology is characterized by:
Close interdependence of the various cellular
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Plasma Membranes
Main function
maintain integrity of cell
Transport of substances
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Mitochondria
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Nucleus
The nucleus controls all cellular activities through
action of at least 50 000 genes,
Each of which encodes a protein with structural,
enzymatic or control functions.
Damage leads to
Development abnormalities
Hereditary disease
Susceptibility to diseases
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Lysosomes
Contain hydrolytic enzymes and responsible for
Digestion and disposal of complex substances.
disorders)
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Cell injury
The environment around cells is dynamic and
constantly changing.
In this fluid environment, cells are exposed to
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Injury is defined as
an alteration in cell structure or function
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2. Infections
Viruses,bacteria, parasites, and fungi (and
probably prions)
Mechanism of injury
Direct infection of cells
Production of toxins
Host inflammatory response
3. lnununologic reactions
Hypersensitivity reactions
Autoimmune diseases
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4. Congenital disorders
Inborn errors of metabolism (i.e., inherited
disorders )
i. Enzyme defects leading to the accumulation of toxic
products
ii. Enzyme defects leading to a deficiency of an important
product
iii. Genetic defects in structural proteins
iv. Cytogenetic disorders
v. Congenital malformations caused by abnormal
development
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5. Chemical injury
a. Drugs
c. Pollution
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6. Physical forms of injury
a. Trauma (blunt/penetrating/crush injuries,
c. Frostbite
d. Radiation
e. Pressure changes
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Mechanism of cell injury
Four intracellular vulnerable sites for action of the
stimuli (causes of cell injury)
Plasma membrane
protein synthesis
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The underlying mechanisms of cellular injury
usually fall into one of two categories:
hypoxic injury
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2.Impaired Na, K+ -ATPase pump, resulting in
diffusion of Na+ and H20 into cells and causing
cellular swelling
endoplasmic reticulum
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Enzyme activation
a. Activates phospholipase:
increases cell and organelle membrane permeability
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Free Radical Cell Injury
Free radicals are compounds with unpaired
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B. Drug and chemical free radicals:
conversion to free radicals occurs via the cytochrome P-
450 system in the liver.
glutathione peroxidase
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Free radicals are highly reactive and can injure
cells through:
Peroxidation of membrane lipids
Superoxide dismutase
Superoxide hydrogen peroxide
Glutathione peroxidase
Hydroxyl ions or hydrogen peroxide water
Catalase
Hydrogen peroxide oxygen and water
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Cellular Changes During Injury
1. General
a. Cellular responses to injury
i. Adaptation
(necrosis/apoptosis)
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b. Cellular response to injury depends on
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Eg:
Reversible damage:
Small dose of toxin
Brief period of ischemia
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On the other hand the effect of cellular injury on
tissue depends on the following four factors:
The duration of the injury;
the longer the duration of the injury the severe will be the
outcome.
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Reversible cell injury
Reversible cell injury is the mild form of cell injury which
can come to normal if the injurious agents are mild
enough and can be controlled by the cell.
Morphology
Cellular Swelling ( Hydropic degeneration)
Cytoplasm accumulates fluid and common in many of the cells
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Effects of reversible cell injury
a. Decreased synthesis of ATP by oxidative
phosphorylation
b. Decreased function of Na+K+ATPase
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c. Switch to glycolysis
may be seen
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Irreversible cell injury ( lethal cell injury )
If the injuries agent is so severe and persists
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Irreversible cell injury is associated with sub-
Apoptosis
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Necrosis
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Enzymatic digestion of the dead cell by enzymes
derived from two sources:
lysosamal enzymes of the dead cell in which
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Morphology of necrosis
Necrotic cells show the following morphologic changes at light
microscopic level.
Cytoplasm
Nucleus
Coagulative necrosis
which is the Comments type of necrosis
characterized by
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Liquefactive necrosis
This morphologic form of necrosis is characterized by
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Gangrenous necrosis (Gangrene)
It is a kind of necrosis characterized by
1.Dry gangrene
is a type of gangrene that occurs due to loss of blood supply
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2.Wet gangrene
is a type of gangrene that usually occurs following bacterial
Caseous necrosis
is a type of coagulative necrosis whereby the necrotic
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Gangrene - Amputated Diabetic foot
Gangrene Intestine - Thrombosis.
Fat necrosis
is a special type of necrosis that occurs in fat containing
tissues which are rich with fat enzymes like the lipases.
E.g. Pancreas, breast, liver
Fibriniod necrosis
is a special type of necrosis that occurs in smooth muscles
vessels.
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Apoptosis
Apoptosis is a from of cell death designed to eliminate
Immunologic tolerance.
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Morphology
The morphologic patterns seen in apoptosis
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The Difference between Necrosis and Apoptosis
Necrosis Apoptosis
1. Refers to a group of cell death 1. a Discrete morphological change on
single cell
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Cellular Adaptations
Cellular adaptations lies between reversible cell
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These adaptive response involves
changes in the number of cellular growth which is called
hyperplasia;
change in the size of the cell which could either be
in the form of increase in the size called hypertrophy or
decrease in the size called atrophy and
change in the cellular differentiation called metaplasia.
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Hyperplasia
is an increase in the number of cells in a tissue or organ
Endometrial hyperplasia
Prostatic hyperplasia of aging
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Hypertrophy
The increase in the size of the cell is not due to cellular swelling
but the synthesis of new structural proteins.
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Among the physiologic causes of hypertrophy are
The gravid uterus,
athlete’s muscle
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Atrophy / Hypoplasia
They are associated with a decrease in both the
number and size of the cells.
Hypoplasia refers when the process occurs before
the full development of the organ, which could be
either in the prenatal or postanatal period.
Atrophy is a condition of later life after full
maturation and development of the organ.
When a sufficient of cells are involved in the
process of atrophy or hypoplasia the entire tissue
or organ becomes atrophic or hypoplastic.
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Among the physiologic causes of atrophy are
Decreased Work load which is called disuse atrophy
Loss of endocrine stimulation as it occurs in the breast, uterus,
genitalias following menopause
Organ changes in aging called senile atrophy
Among the pathologic causes of atrophy are
Persistent Pressure following for example a tumor in the
adjacent organ is called pressure atrophy as in the case of
pituitary Adenoma.
Loss of innervations to a particular tissue which is called
denervation atrophy.
Inadequate nutrition as in the case of protein- energy
malnutrition.
Inadequate blood supply to a particular organ which is called
ischemic atrophy
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Metaplasia
Metaplasia is an adaptive response to injury in
transformation.
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Some of the examples of metaplasic transformation that
Dysplasia
an abnormal proliferation of cells that is characterized by
(preneoplastic lesion)
Example: cervical dysplasia
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