Pathology lecture for 3 rd stage
Introduction
The term “pathology” is derived from the Greek words pathos which means disease
and logos which means study, thus pathology is a branch of biological sciences that
deals with the study of all structural and functional abnormalities (at the level of cells,
tissues, organs and body fluids) that take place as a result of a disease.
Pathology is considered a vital link between basic sciences (anatomy, physiology,
biochemistry…….etc) and clinical sciences (internal medicine, a
Disease and Disease Circumstances
Disease
The disease is a condition in which an individual (human or animal) shows an
anatomical, chemical and/or physiological deviation from the normal and exhibits a
discomfort with its (his) environment or surroundings. It is caused by defects,
excesses, deficiencies, and injuries that take place at the level of cell and tissue and
leads to clinically apparent symptoms and/or signs.
Etiology
The term etiology refers to the science that deals with the causes or origin of the
disease or the factors that produce or predispose toward a certain disease or disorder.
Lesions
The term “lesions” refers to abnormal (pathological) structural and functional
changes that occur in animal or human body during a particular disease.
Pathogenesis
Pathogenesis is the sequence of events in the response of cells and tissues to an
injurious agent (pathogen) starting from the initial stimulation to the ultimate
expression of the disease. It is also defined as the step by step developmental process
from the beginning of the disease to its termination, or the mechanism by which the
disease is developed.
Pathogenicity
The term pathogenicity refers to the ability of the pathogen (usually microbial
pathogens) to cause disease
Symptom
The term symptom refers to any evidence of a disease as told by the patient (in case
of human being) or the owner (in case of animals).
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Pathology lecture for 3 rd stage
Sign
The term sign refers to any evidence of a disease detectable to a clinician (can be
observed by the clinician).
Diagnosis
The term diagnosis refers to the art or act of identifying a particular disease from its
signs and symptoms.
Prognosis
It is the prediction of the probable outcome of a disease. There are four possible
outcomes:
1. Healing and recovery: The damaged cells and tissues are regenerated or repaired
and the functions are restored.
2. Functional deficit (Functional shortage): In some cases, full restoration in structure
and function are not possible, and thus the disease leaves impairment in either
structure or function, or both.
3. Death
4. Impasse: An impasse is that steady (stable) state where the pathological agent
cannot induce sufficient damage to cause functional impairment or death, and the
human or animal body cannot eliminate that pathological agent.
An example of impasse is the carrier states in human and animals where a disease is
present in a subclinical manner (i.e., no observable signs and symptoms of the disease
are present) such as the carrier states of coccidiosis in poultry and salmonellosis in
human & pigs.
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Pathology lecture for 3 rd stage
Adaptation
In normal conditions, the cells of the body are in equilibrium with their external
environment. They maintain their internal machinery in a dynamically stable and
steady state called homeostasis.
When this homeostasis is disrupted by an external disturbance (e.g., stress or
pathogen), some changes occur within the cells to counteract the external disturbance.
These changes are referred to as adaptations.
The aim of the adaptations is to prevent cell injury i.e., preserve viability of cells and
tissues during their exposure to a certain stress or injurious agents.
Types of cellular adaptation
The types of cellular adaptation include hypertrophy, atrophy, hyperplasia, &
metaplasia.
A. Hypertrophy
Hypertrophy is increase in the size of cells. Increased workload leads to increased
protein synthesis & increased size & number of intracellular organelles which, in turn,
leads to increased cell size. The increased cell size leads to increased size of the organ.
Examples: the enlargement of the left ventricle in hypertensive heart disease & the
increase in skeletal muscle during strenuous exercise.
B. Atrophy
Atrophy is a decrease in the size of a cell. This can lead to decreased size of the organ.
The atrophic cell shows autophagic vacuoles which contain cellular debris from
degraded organelles
Atrophy can be caused by:
1. Disuse
2. Undernutrition
3. Decreased endocrine stimulation
4. Denervation
5. Old age
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Pathology lecture for 3 rd stage
C. Hyperplasia
Hyperplasia is an increase in the number of cells. It can lead to an increase in the size
of the organ. It is usually caused by hormonal stimulation. It can be physiological as
in enlargement of the breast during pregnancy or it can pathological as in endometrial
hyperplasia.
D. Metaplasia
Metaplasia is the replacement of one differentiated tissue by another differentiated
tissue. There are different types of metaplasia. Examples include:
Cell injury
The term cell injury is used to indicate a state in which the capacity for
physiological adaptation is exceeded. This may occur when the stimulus is
excessive or when the cell is no longer capable to adapt without suffering some
form of damage. The capacity for adaptation and the sensitivity to different types
of injury varies according to cell type (i.e. myocardial cells and neurons are
highly sensitive to ischemic injury; hepatocytes are more sensitive to chemical
than ischemic injury). Cell injury may be reversible (non-lethal damage which
generally can be corrected by removal of the stimulus) or irreversible (lethal
damage). The transition between reversible and irreversible damage, commonly
referred to as the "point of no return" is of major importance. Recognition of the
point of no return is a key element for devising therapeutic strategies to prevent
cell death after injury.
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Pathology lecture for 3 rd stage
Mechanisms of cell injury
Injurious agents induce cell injury by affecting on one or more of the following
cellular targets:
1. The cell membranes
2. Aerobic respiration that is responsible for ATP production
3. Synthesis of enzymes and structural proteins
4. The genetic apparatus.
Factors influencing the severity of cell injury
1. Type, duration and severity of the injurious agent.
2. Type of the affected cells:
a. The neurons are highly susceptible to ischemic damage. They undergo irreversible
damage when deprived of oxygen (by ischemia) for 3-5 minutes.
b. Myocardial cells and hepatocytes are of intermediate susceptibility to ischemic
damage (30-60 minutes).
c. Skeletal muscles, epidermis of the skin and fibroblasts are of low susceptibility to
ischemia (many hours).
Types of cell injury
Cell injury is divided into:
1. Reversible cell injury
2. Irreversible cell injury
Reversible cell injury
It is a type of cell injury in which the pathological changes will regress and disappear
when the injurious agent is removed and the cells will return to normal morphological
and functional state.
Irreversible cell injury
It is a type of cell injury which occurs when the injurious agent persists or when it is
severe from the beginning. At first the injury is reversible, but later it reaches the
point of no return, where it becomes irreversible.
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Pathology lecture for 3 rd stage
Point of no return
It is the precise moment of transition from reversible to irreversible cell injury. At
this point, no adaptation can save the cell and the progression to cell death is
inevitable (unavoidable).
Cell and tissue degeneration
If the injury is not severe enough to kill the cell, the cell exhibit various morphological
changes. These changes are considered reversible and are classically called
degenerative changes. The term degeneration means deterioration, i.e., change of tissue
from a higher to a lower or less functionally active form.
Patterns of cell and tissue degenerations
The patterns of cell and tissue degenerations include:
A. Intracellular and extracellular accumulation
B. Intracellular and extracellular pigmentation
A. Intracellular and extracellular accumulation (Reversible cellular changes &
accumulations).
The intracellular and extracellular accumulation includes:
1. Water (Cellular swelling)
2. Triglycerides (Fatty change)
3. Protein (Hyaline change and amyloidosis)
4. Glycogen (Glycogen degeneration)
5. Mucopolysaccharide (Mucoid Degeneration).
1. Cellular swelling (Cloudy swelling)
It is an early pathological change characterized by accumulation of water within the
cytoplasm of the affected cells. It can be seen in many examples of reversible cell
injury. The extra-fluid may be seen by light microscopy as an increase in the size of
the cell with pallor of the cytoplasm (cloudy swelling).
Hydropic degeneration
This term is used to describe a more severe condition of cellular swelling characterized
by formation of clear vacuoles within the cytoplasm of the affected cells due to
continuous accumulation of water. In general, hydropic degeneration is reversible,
provided that the injurious agent is eliminated prior to cell death.
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Pathology lecture for 3 rd stage
2. Fatty change (Fatty degeneration)
This term refers to abnormal accumulation of fat within the cytoplasm of parenchymal
cells such as those of the liver, kidney and heart. It is an example of reversible (nonlethal) cell injury and is often seen in the liver because of the central role of this organ
in fat metabolism.This is accumulation of triglycerides inside parenchymal cells. It is
caused by an imbalance between the uptake, utilization, & secretion of fat. Fatty
change is usually seen in the liver, heart, or kidney. Fatty liver may be caused by
alcohol, diabetes mellitus, malnutrition, obesity, & poisonings. These etiologies cause
accumulation of fat in the hepatocytes by the following mechanisms:
a. Increased uptake of triglycerides into the parenchymal cells.
b. Decreased use of fat by cells.
c. Overproduction of fat in cells.
d. Decreased secretion of fat from the cells.
Gross features of fatty degeneration
In the liver, mild fatty change shows no gross changes, but with progressive
accumulation, the organ enlarges and become increasingly yellow, soft and greasy to
touch. Fatty degeneration should not be confused with fatty infiltration which
describes infiltration of normal fat cells (lipocytes) into the interstitial connective
tissue spaces of organs that, normally, do not contains appreciable quantities of fat
tissue such as myocardial and skeletal muscles Fatty infiltration is not degeneration
and is often found along with obesity..
3. Hyaline change (hyalinosis)
The term “hyaline change” usually refers to an intracellular or extracellular alteration
which gives a homogeneous, glassy, pink appearance in routine stained histological
sections. The term “routine-stained histological sections” means hematoxylin and
eosin stained histological sections (H and E stained histological sections). Hyaline
change is almost always associated with the accumulation of a protein in the tissue
either intracellularly (intracellular hyaline) or exracellularly (extracellular hyaline).
Examples of intracellular hyaline
a. Re-absorption protein droplets (tubular epithelial hyaline droplets) seen within the
cytoplasm of the lining epithelial cells of the renal tubules in cases of protein losing
nephropathies such as the nephrotic syndrome. In such conditions, the lining
epithelial cells of the renal tubules try to re-absorb the excessive quantities of the
proteins that had leaked through the glomerular filtrate.
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Pathology lecture for 3 rd stage
b. Mallory body (Alcoholic hyaline or Mallory's hyaline) The term “Mallory body”
refers to a homogenous, eosinophilic inclusion with a characteristic twisted-rope
appearance found in the cytoplasm of liver cells. The Mallory bodies are classically
found in liver cells of people suffering from alcoholic liver disease and they were
thought to be specific for this disease, however, they are also recognized in other
pathological conditions such as primary biliary cirrhosis, morbid (pathologic) obesity
and hepatocellular carcinoma.
Examples of extracellular hyaline
a. The collagenous fibrous connective tissue in old scars may appear hyalinized (i.e.,
gives a homogeneous, glassy, pink appearance in H and E stained histological
sections),
b. In long-standing hypertension and diabetes mellitus, the walls of arterioles,
especially in the kidney, become hyalinized, due to deposition of extravasated plasma
protein.
4. Amyloidosis
Amyloidosis is an inherited or acquired pathological lesion and it refers to a variety
of conditions in which amyloid proteins are extracellularly accumulated in organs
and/or tissues.
In routine H and E stained-stained histological sections, the amyloid proteins appear
as amorphous, homogenous, eosinophilic, material aggregated extracellularly in the
affected tissue or organ.
Classification of amyloidosis
a. According to distribution:
i. Systemic amyloidosis which affects more than one body organ or system.
ii. Localized amyloidosis which affects only one body organ or tissue type.
b. According to etiology:
i. Primary amyloidosis which arises from diseases associated with disordered immune
cell function such as:
plasma cells.
ə]) which refers to
immunocyte abnormalities.
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Pathology lecture for 3 rd stage
ii. Secondary amyloidosis (Reactive systemic amyloidosis) which occurs as a
complication of some chronic inflammatory or tissue destructive disease such as
rheumatoid arthritis or tuberculosis.
5. Glycogen accumulation
It is an accumulation of glycogen (which appears as clear vacuoles) within the
cytoplasm of affected cells particularly the parenchymal cells of the liver and kidney,
the leukocytes, and the myocardial and skeletal muscle fibers. It occurs in:
a. Prolonged hyperglycemia, particularly in diabetes mellitus which causes glycogen
accumulation within the cells of the liver and heart, the epithelial cells of distal renal
tubules and cells of the Langerhans islet within the pancreas.
b. Glycogen storage disease: A genetically determined disease associated with
absence of an enzyme required to metabolize the carbohydrates.
c. Steroid induced hepatopathy.
6. Mucoid Degeneration (Mucopolysaccharidosis)
Mucoid degeneration is the degeneration of connective tissue into a gelatinous or
mucoid-like substance due to extracellular accumulation of mucopolysaccharide. It
is seen in some specific conditions such as:
a. Endocardiosis, a degenerative, sometimes senile condition of the heart valves.
b. It is also seen in the dermis of the skin in cases of hypothyroidism
B. Intracellular and extracellular pigmentation
Pigments can be exogenous or endogenous.
Exogenous pigmentation those from outside the body including:
a. Carbon (anathrocosis): means the carbon particles presents as black granules in the
organs such as lung and lymph node in the cytoplasm of the cell or between the cell,in
the lung it is present in the alveolar wall and in the interlobular septa ,within the
macrophage
b. Dust: means the minerals presents in the pulmonary tissue that called
penuomoconiosis.this include:
1-silicon (silicosis):when the silicon dioxide inhaled in the lung.
2- Asbestosis: mean inhalation of asbestos.
Microscopically: dust appears as crystal in the tissue which Indus collagenous fibrous
connective tissue proliferation to form sclerotic nodules.
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Pathology lecture for 3 rd stage
Endogenous pigments include melanin, bilirubin, hemosiderin, & lipofuscin.
Exogenous pigments include carbon. These pigments can accumulate inside cells in
different situations.
a. Melanin
Melanin is a brownish-black pigment produced by the melanocytes found in the skin.
Increased melanin pigmentation is caused by sun tanning & certain diseases e.g.
nevus, or malignant melanoma. Decreased melanin pigmentation is seen in albinism
& vitiligo.
Melanin which determines color of skin, hair and eyes. Melanin could appear in
increase or decrease in skin. There could be local or extensive process. There could
be congenital or acquired pathology.
Melanosis :means deposition of melamine in various organ manly in the lung and
aorta .
Hypomelanosis ( albinism ):
Extensive hypopigmentation or (albinism) appears as a result of hereditary
deficiency of tyrosinase Due to melanocyte unable to synthesis the tyrosinase enzyme
Local hypomelanosis
melanogenesis at
oidism,
b. Lipofuscin
Lipofuscin is is yellowish -brown granules in the cytoplasm of affected
parenchymalcells as insoluble pigment, also known as lipochrome and "wear-andtear" or aging pigment. Lipofuscin is composed of polymers of lipids and
phospholipids complexed with protein due to in ability in a complete metabolism of
the phospholipid of cell wall. Lipofuscin Accumulations in the liver , heart, brain of
aging patients or patients with severe malnutrition and cancer cachexia. It is usually
accompanied by organ shrinkage (brown atrophy) also in smooth muscles of the dog
due to vit E deficiency called brown dog gut
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Pathology lecture for 3 rd stage
Cloisonné kidneys: means dark red iron negative pigment occur in basement
membranes of proximal convoluted tube of kidney this conditions reported in goat
c. Bilirubin
Bilirubin is a yellowish pigment, mainly produced during the degradation of
hemoglobin. Excess accumulation of bilirubin causes yellowish discoloration of the
sclerae, mucosae, & internal organs. Such a yellowish discoloration is called
jaundice. Jaundice is most often caused by:
1. Hemolytic anemia
Hemolytic anemia is characterized by increased destruction of red blood cells.
2. Biliary obstruction
This is obstruction of intrahepatic or extrahepatic bile ducts. It can be caused by
gallstones.
3. Hepatocellular disease.
Type of Jaundice
Hemolytic jaundice: arises at infectious diseases, intoxications, isoimmune and
autoimmune conflicts, massive hemorrhage, as well as erythrocytopathy and
hemoglobinopathy.
Hepatocellular jaundice: arises at liver diseases of various a etiology, in case
defective hepatocytes are not able to capture bilirubin, its conjugation to glucuronic
acid and excretion are disturbed.
Obstructive (mechanical) jaundice: arises at retention of bile outflow from liver.
Clinical jaundice appears when bilirubin is elevated in blood and is deposited in tissues
This is associated with failure of conjugation of bilirubin.
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Pathology lecture for 3 rd stage
Causes:
1-blockedof bile cannuli duct.
2-obstraction due to liver flukes .
3-cholingitis .
4- Gall stone .
5- neoplastic cell.
d. Hemosiderin
Hemosiderin is an iron-containing pigment derived from ferritin. It appears in tissues
as golden brown amorphous aggregates & is identified by its staining reaction (blue
color) with the Prussian blue dye. Hemosiderin exists normally in small amounts
within tissue macrophages of the bone marrow, liver, & spleen as physiologic iron
stores. It accumulates in tissues in excess amounts in certain diseases.This excess
accumulation is divided into tow types:
1. Hemosiderosis: When accumulation of hemosiderin is primarily within tissue
macrophages & is not associated with tissue damage, it is called hemosiderosis.
2. Hemochromatosis: When there is more extensive accumulation of hemosiderin,
often within parenchymal cells, which leads to tissue damage, scarring & organ
dysfunction, it is called hemochromatosis.
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