Chapter One Introduction to Pathology

1
Chapter OneIntroduction to Pathology
Section A
DEFINITION OF PATHOLOGY
2
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.

3
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.

4

• 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?

5

• One etiologic agentone disease.
• Several etiologic agentsone disease.
• One etiologic agentseveral diseases.

6
Causes of cell injury and disease

• Oxygen deprivation ( hypoxia, ischemia)
• Nutritional imbalances
• Physical agents
• Chemical agents and drugs
• Infectious agents
• Immunologic reactions
• Genetic derangements

7
HYPOXIA

• Ischemia ( loss of blood supply ).
• Inadequate oxygenation
• ( cardiorespiratory failure ).
• Loss of oxygen-carrying capacity of the blood (
  anemia or CO poisoning ).

8
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.

9
Four biochemical themes

• Oxygen-derived free radicals.
• Loss of calcium homeostasis and increased
  intracellular calcium.
• ATP depletion.
• Defects in membrane permeability.

10
PHYSICAL AGENTS

• Trauma
• Heat
• Cold
• Radiation
• Electric shock

11
CHEMICAL AGENTS AND DRUGS

• Endogenous products urea
• Exogenous agents
• Therapeutic drugs hormones
• Nontherapeutic agents
• lead or alcohol

12
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.

13
MECHANISMS OF CHEMICAL INJURY

• 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.

14

• 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.

15
FREE RADICAL INITIATION

• Absorption of energy (UV light and x-rays)
• Oxidative metabolic reactions
• Enzymatic conversion of exogenous chemicals or
  drugs (CCl4gtCCl3.)
• Oxygen-derived radicals
• Superoxide

16
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.

17
INFECTIOUS AGENTS

• Viruses
• Rickettsiae
• Bacteria
• Fungi
• Parasites

18

• 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.

19

• 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.

20
CELLS REACT TO ADVERSE INFLUENCES

• ADAPTING
• SUSTAINING REVERSIBLE INJURY
• SUFFERING IRREVERSIBLE INJURY AND DYING

21
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.

22
The core of the science of pathology the study
the pathogenesis of the disease.
23
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.

24
Pathogenesis
Immunologic, cytogenetic and molecular analyses
of tissues and cells are increasingly becoming
guides to render diagnoses, to assess prognosis,
and to suggest therapy.
25
MORPHOLOGY
Morphology remains at the heart of diagnostic
pathology.

• Morphologic change
• Characteristic of the disease
• Diagnostic of the etiologic proceess
• Functional derangements
• Clinical significance

26

Section B

• Development of Pathology

• Organ pathology
• Cell pathology
• Molecular pathology