Chapter One
Introduction to Pathology
DEFINITION OF PATHOLOGY
Definition of pathology
? Pathology is to study diseases by
scientific methods.
? Disease may be defined as an
abnormal alteration of structure
or function in any part of the
body.
Pathology focuses on 4 aspects of disease
? ETIOLOGY,Cause of disease.
? PATHOGENESIS:
Mechanisms of development of disease.
? MORPHOLOGY,The structural alterations induced in cell
and tissues.
? FUNCTIONAL CONSEQUENCES:
Functional consequences of the morphologic changes,as
observed clinically.
Knowledge of etiology remains the backbone:
Disease diagnoses
Understanding the nature of diseases
Treatment of diseases.
While much still needs to be
uncovered to link abnormal genes
and the expression of disease,gone
are the time when the mechanisms
of most diseases were unknown?
or obscure? or mysterious?
One etiologic agent—one disease.
Several etiologic agents—one disease.
One etiologic agent—several diseases.
Causes of cell injury and disease
? Oxygen deprivation ( hypoxia,ischemia)
? Nutritional imbalances
? Physical agents
? Chemical agents and drugs
? Infectious agents
? Immunologic reactions
? Genetic derangements
HYPOXIA
Ischemia ( loss of blood supply ).
Inadequate oxygenation
( cardiorespiratory failure ).
Loss of oxygen-carrying capacity of the
blood ( anemia or CO poisoning ).
HYPOXIC INJURY
? Loss of oxidative phosphorylation and ATP
generation by mitochondria.
? Decreased ATP (with increase in AMP),
stimulating fructokinase and phosphorylation,
resulting in aerobic glycolysis.
? Depleted glycogen.
? Reduced intracellular pH,Lactic acid and
inorganic phosphate.
? Clumping of nuclear chromatin.
Four biochemical themes
? Oxygen-derived free radicals.
? Loss of calcium homeostasis and
increased intracellular calcium.
? ATP depletion.
? Defects in membrane permeability.
PHYSICAL AGENTS
? Trauma
? Heat
? Cold
? Radiation
? Electric shock
CHEMICAL AGENTS AND DRUGS
?Endogenous products,urea
?Exogenous agents:
Therapeutic drugs,hormones
Nontherapeutic agents,
lead or alcohol
MECHANISMS OF CHEMICAL INJURY
? Directly,Mercury of mercuric
chloride binds to SH groups of cell
membrane proteins,causing
increased permeability and
inhibition of ATPase-dependent
transport.
? By conversion to reactive toxic
metabolites which in turn cause cell
injury either by direct covalent binding
to membrane protein and lipid,or
more commonly by the formation of
free radicals.
MECHANISMS OF CHEMICAL INJURY
CCl4 in SER of liver cell (P-450) – CCl3,– lipid
peroxidation and autocatalytic reactions – swelling
and breakdown of ER,dissociation of ribosome,
and decreased hepatic protein synthesis ( loss of
lipid acceptor protein – fatty change of liver cell) –
progressive cellular swelling,plasma membrane
damage,and cell death.
FREE RADICAL INITIATION
? Absorption of energy (UV light and x-rays)
? Oxidative metabolic reactions
? Enzymatic conversion of exogenous chemicals
or drugs (CCl4>CCl3.)
? Oxygen-derived radicals
? Superoxide
Cell injury caused by free radicals through
? Peroxidation of lipids.
? Cross linking proteins by the formation of
disulfide bonds.
? Induction of DNA damage that has been
implicated both in cell killing and malignant
transformation.
INFECTIOUS AGENTS
? Viruses
? Rickettsiae
? Bacteria
? Fungi
? Parasites
Marfan syndrome
Fibrillin,a scaffolding on which tropoelastin
is deposited to form elastic fibers.
FBN1,15q21,mutations in Marfan syndrome.
FBN2,5q3,mutations in congenital
contractual arachnodactyly,
Adenomatous polyposis coli
APC loci,5q21
Adenomatous polyposis in colons (in teens).
100% malignant transformation ( ? 40ys ).
APC protein in the cytoplasm.
Several partners,including ?-catenin.
?-catenin ?entering the nucleus?activating
transcription of growth-promoting genes.
Causing degradation of ?-catenin?maintaining
low level of ?-catenin in the cytoplasm.
CELLS REACT TO ADVERSE
INFLUENCES
? ADAPTING
? SUSTAINING REVERSIBLE INJURY
? SUFFERING IRREVERSIBLE INJURY
AND DYING
CELL INJURY AND NECROSIS
General mechanisms:
? Maintenance of the integrity of cell membranes,
? Aerobic respiration and production of ATP,
? Synthesis of enzymes and structure proteins,
? Preservation of the integrity of the genetic
apparatus.
The core of the science of
pathology — the study the
pathogenesis of the disease.
Pathogenesis
The sequence events in the response
of the cells or tissues to the etiologic
agent,from the initial stimulus to the
ultimate expression of the disease.
Pathogenesis
Immunologic,cytogenetic and
molecular analyses of tissues and cells
are increasingly becoming guides to
render diagnoses,to assess prognosis,
and to suggest therapy.
? Morphologic change
Characteristic of the disease
Diagnostic of the etiologic proceess
? Functional derangements
? Clinical significance
MORPHOLOGY
Morphology remains at the heart of
diagnostic pathology.
Development of Pathology
? Organ pathology
? Cell pathology
? Molecular pathology
Introduction to Pathology
DEFINITION OF PATHOLOGY
Definition of pathology
? Pathology is to study diseases by
scientific methods.
? Disease may be defined as an
abnormal alteration of structure
or function in any part of the
body.
Pathology focuses on 4 aspects of disease
? ETIOLOGY,Cause of disease.
? PATHOGENESIS:
Mechanisms of development of disease.
? MORPHOLOGY,The structural alterations induced in cell
and tissues.
? FUNCTIONAL CONSEQUENCES:
Functional consequences of the morphologic changes,as
observed clinically.
Knowledge of etiology remains the backbone:
Disease diagnoses
Understanding the nature of diseases
Treatment of diseases.
While much still needs to be
uncovered to link abnormal genes
and the expression of disease,gone
are the time when the mechanisms
of most diseases were unknown?
or obscure? or mysterious?
One etiologic agent—one disease.
Several etiologic agents—one disease.
One etiologic agent—several diseases.
Causes of cell injury and disease
? Oxygen deprivation ( hypoxia,ischemia)
? Nutritional imbalances
? Physical agents
? Chemical agents and drugs
? Infectious agents
? Immunologic reactions
? Genetic derangements
HYPOXIA
Ischemia ( loss of blood supply ).
Inadequate oxygenation
( cardiorespiratory failure ).
Loss of oxygen-carrying capacity of the
blood ( anemia or CO poisoning ).
HYPOXIC INJURY
? Loss of oxidative phosphorylation and ATP
generation by mitochondria.
? Decreased ATP (with increase in AMP),
stimulating fructokinase and phosphorylation,
resulting in aerobic glycolysis.
? Depleted glycogen.
? Reduced intracellular pH,Lactic acid and
inorganic phosphate.
? Clumping of nuclear chromatin.
Four biochemical themes
? Oxygen-derived free radicals.
? Loss of calcium homeostasis and
increased intracellular calcium.
? ATP depletion.
? Defects in membrane permeability.
PHYSICAL AGENTS
? Trauma
? Heat
? Cold
? Radiation
? Electric shock
CHEMICAL AGENTS AND DRUGS
?Endogenous products,urea
?Exogenous agents:
Therapeutic drugs,hormones
Nontherapeutic agents,
lead or alcohol
MECHANISMS OF CHEMICAL INJURY
? Directly,Mercury of mercuric
chloride binds to SH groups of cell
membrane proteins,causing
increased permeability and
inhibition of ATPase-dependent
transport.
? By conversion to reactive toxic
metabolites which in turn cause cell
injury either by direct covalent binding
to membrane protein and lipid,or
more commonly by the formation of
free radicals.
MECHANISMS OF CHEMICAL INJURY
CCl4 in SER of liver cell (P-450) – CCl3,– lipid
peroxidation and autocatalytic reactions – swelling
and breakdown of ER,dissociation of ribosome,
and decreased hepatic protein synthesis ( loss of
lipid acceptor protein – fatty change of liver cell) –
progressive cellular swelling,plasma membrane
damage,and cell death.
FREE RADICAL INITIATION
? Absorption of energy (UV light and x-rays)
? Oxidative metabolic reactions
? Enzymatic conversion of exogenous chemicals
or drugs (CCl4>CCl3.)
? Oxygen-derived radicals
? Superoxide
Cell injury caused by free radicals through
? Peroxidation of lipids.
? Cross linking proteins by the formation of
disulfide bonds.
? Induction of DNA damage that has been
implicated both in cell killing and malignant
transformation.
INFECTIOUS AGENTS
? Viruses
? Rickettsiae
? Bacteria
? Fungi
? Parasites
Marfan syndrome
Fibrillin,a scaffolding on which tropoelastin
is deposited to form elastic fibers.
FBN1,15q21,mutations in Marfan syndrome.
FBN2,5q3,mutations in congenital
contractual arachnodactyly,
Adenomatous polyposis coli
APC loci,5q21
Adenomatous polyposis in colons (in teens).
100% malignant transformation ( ? 40ys ).
APC protein in the cytoplasm.
Several partners,including ?-catenin.
?-catenin ?entering the nucleus?activating
transcription of growth-promoting genes.
Causing degradation of ?-catenin?maintaining
low level of ?-catenin in the cytoplasm.
CELLS REACT TO ADVERSE
INFLUENCES
? ADAPTING
? SUSTAINING REVERSIBLE INJURY
? SUFFERING IRREVERSIBLE INJURY
AND DYING
CELL INJURY AND NECROSIS
General mechanisms:
? Maintenance of the integrity of cell membranes,
? Aerobic respiration and production of ATP,
? Synthesis of enzymes and structure proteins,
? Preservation of the integrity of the genetic
apparatus.
The core of the science of
pathology — the study the
pathogenesis of the disease.
Pathogenesis
The sequence events in the response
of the cells or tissues to the etiologic
agent,from the initial stimulus to the
ultimate expression of the disease.
Pathogenesis
Immunologic,cytogenetic and
molecular analyses of tissues and cells
are increasingly becoming guides to
render diagnoses,to assess prognosis,
and to suggest therapy.
? Morphologic change
Characteristic of the disease
Diagnostic of the etiologic proceess
? Functional derangements
? Clinical significance
MORPHOLOGY
Morphology remains at the heart of
diagnostic pathology.
Development of Pathology
? Organ pathology
? Cell pathology
? Molecular pathology
