What is Pathology?

•“Scientific study of disease" or the alterations that occur when abnormal influences (bacteria, viruses, etc.) affect cells, tissues, or body systems. More specifically, pathology may be defined as the "scientific study of the molecular, cellular, tissue, or organ system response to injurious agents or

adverse influences".

Pathology Deals with…

• The causes of disease (etiology)

• Mechanisms of disease (pathogenesis)

• Structural alterations of cells and tissues

• Functional alteration and consequences of disease

Function of Pathology

Pathology serves as a "bridge" or "link" between the preclinical subjects (anatomy, physiology, etc.) and the courses in clinical medicine. Actually, pathology provides a logical means of relating the knowledge of normal structure and function (anatomy and physiology) to abnormal structure and function as encountered in a diseased animal.

General Pathology

•It explores and explains the development of basic pathologic mechanisms:

•Introduction to pathology•Inflammation, repair and regeneration ,

•Cell injury, degenerations and infiltrations •Haemodynamic (circulatory) disorders .

•Granulomatous inflammations .•Growth disorders and neoplasia.

Cell Injury and Necrosis

Causes of Cell Injury

•Oxygen Deprivation

•Physical Agents

•Chemical Agents and Drugs

•Infectious Agents

•Immunologic Reactions

•Genetic Derangements

•Nutritional Imbalances

Oxygen Deprivation

•Hypoxia – deficiency of oxygen

•Ischemia – loss of blood supply (arterial flow or reduced venous drainage)

Causes of Cell InjuryCauses of Cell Injury

Physical Agents

•Mechanical trauma

•Extremes of temperature – burns, deep cold

•Radiation

•Electric shock

Causes of Cell InjuryCauses of Cell Injury

Chemical Agents and Drugs

•Hypertonic concentration of salt – deranging electrolyte homeostasis

•Poisons – arsenic, cyanide, or mercuric salts

•Insecticides and Herbicides

•Air pollutant – carbon monoxide

•Occupational hazard – asbestos

•Alcohol and Narcotic drugs

Causes of Cell InjuryCauses of Cell Injury

Infectious Agents

•Parasites

•Fungi

•Bacteria

•Rickettsiae

•Viruses

Causes of Cell InjuryCauses of Cell Injury

Immunologic Reactions

•Anaphylactic reaction to foreign protein or drug

•Reactions to endogenous self-antigens – autoimmune diseases

Causes of Cell InjuryCauses of Cell Injury

Genetics Derangements

•Congenital malformation – Down syndrome

•Decreased life of red blood cell – Thalassemia, Sickle cell anemia

•Inborn errors of metabolism

Causes of Cell InjuryCauses of Cell Injury

Nutritional Imbalances

•Protein-calorie deficiencies

•Vitamin deficiencies

•Anorexia nervosa

•Excesses of lipids – Obesity, Atherosclerosis

•Metabolic diseases – Diabetes

Causes of Cell InjuryCauses of Cell Injury

Mechanisms of Cell Injury

•Depletion of ATP•Mitochondrial Damage

•Influx of Intracellular Calcium and Loss of Calcium Homeostasis

•Accumulation of Oxygen-Derived free radical (Oxidative stress)

•Defects in Membrane Permeability

Na+

K+

Ca2+

Mechanisms of Cell InjuryMechanisms of Cell Injury

Depletion of ATP

Mitochondrial DamageMechanisms of Cell InjuryMechanisms of Cell Injury

CausesCauses

Hypoxia, Toxins

Cytosolic Ca2+

Oxidative stress

Lipid breakdown product

Mitochondrial DamageMechanisms of Cell InjuryMechanisms of Cell Injury

• Mitochondrial permeability transition of inner membrane (formation of high-conductance high-conductance channelchannel)

• Leakage of Cytochrome cCytochrome c into cytosol

ATP productionATP production

Mitochondrial Oxidative Phosphorylation

Mechanisms of Cell InjuryMechanisms of Cell Injury

Mitochondrial Damage

Influx of Intracellular Calcium and Loss of Calcium

Homeostasis

Mechanisms of Cell InjuryMechanisms of Cell Injury

Mechanisms of Cell InjuryMechanisms of Cell Injury

Morphology of Cell Injury and Necrosis

•Cell Injury – Reversible

– Irreversible

•Cell Death – Necrosis

– Apoptosis

Morphology of Cell Injury

•Plasma membrane alteration

•Mitochondrial Changes

•Dilation of Endoplasmic reticulum

•Nuclear Alteration

Reversible InjuryReversible InjuryCellular swelling

Fatty change

Morphology of Necrotic Cells

•Increased Eosinophilia - loss of RNA (basophilia)

- denatured cytoplasmic protein•Nuclear Changes

- Pyknosis - Karyorrhexis

- Karyolysis• Myelin figure

– large, whorled phospholipid mass (phospholipid precipitate)

HISTOLOGIC FEATURES OF HISTOLOGIC FEATURES OF COAGULATIVE NECROSISCOAGULATIVE NECROSIS

Normal cellNormal cell

Reversible Reversible cell injurycell injury with with cytoplasmic & cytoplasmic & organelle organelle swelling, swelling, blebbing & blebbing & ribosome ribosome detachmentdetachment

Irreversible Irreversible cell injurycell injury with rupture of with rupture of membrane & membrane & organelles, & organelles, & nuclear nuclear

pyknosispyknosis

KaryorrhexisKaryorrhexis

KaryolysisKaryolysis

Morphologic pattern of Necrotic Cell mass

•Coagulative necrosis

•Liquefactive necrosis

•Caseous necrosis

•Fat necrosis

• Coagulative Necrosis

: intracellular acidosis

– protein denatured

– proteolysis inhibited

Morphologic pattern of Necrotic Cell mass

Ischemic necrosis of the myocardium

A, Normal myocardium.

B, Myocardium with coagulation necrosis

•Liquefactive Necrosis

: focal bacterial (or fungal) infections

– accumulation of inflammatory

cells

: hypoxic death of cells within CNS

Morphologic pattern of Necrotic Cell mass

Coagulative and liquefactive necrosisA, Kidney infarct exhibiting coagulative necrosis

B, A focus of liquefactive necrosis in the kidney

•Caseous necrosis

:gross appearance

: microscopic – granulomatous inflammation

Morphologic Pattern of Necrotic Cell Mass

A tuberculous lung with a large area of caseous necrosis

Foci of fat necrosisfat necrosis with saponification in the mesentery

Explain the difference(s) between reversiblereversible and irreversibleirreversible cell injury. 

REVERSIBLE  IRREVERSIBLE

Loss of ATP  Irreversible mitochondrial damage Phospholipid breakdown Massive peroxidation due to due to PLPase activation  uncontrolled chain reaction  Depolymerization of actin  Cleavage of CSK proteins by proteases 

Increase in ROS  Uncontrolled ROS; inflammation

Release of calcium from Uncontrolled calcium influxstorage site  

Altered metabolism  Loss of amino acids

Explain the difference(s) between reversiblereversible and irreversibleirreversible cell injury. 

REVERSIBLE  IRREVERSIBLE

Loss of ATP  Irreversible mitochondrial damage Phospholipid breakdown Massive peroxidation due to due to PLPase activation  uncontrolled chain reaction  Depolymerization of actin  Cleavage of CSK proteins by proteases 

Increase in ROS  Uncontrolled ROS; inflammation

Release of calcium from Uncontrolled calcium influxstorage site  

Altered metabolism  Loss of amino acids

Describe Patterns of Necrosis in Tissues or Organs

As a result of cell death the tissues or organs display certain macroscopic changes:

1. CoagulativeCoagulative necrosis

outline of the dead cells is maintained and the tissue is somewhat firm. Example: myocardial infarction 

3. CaseousCaseous necrosis

form of coagulative necrosis (cheese-like)

Example: tuberculosis lesions

4. FatFat necrosis

enzymatic digestion of fat

example: necrosis of fat by pancreatic enzymes.

5. GangrenousGangrenous necrosis

Necrosis (secondary to ischemia) usually with superimposed infection

example: necrosis of distal limbs, usually foot and toes in diabetes