What is pathology
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What is Pathology?

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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


Causes of Cell Injury

Oxygen Deprivation

  • Hypoxia – deficiency of oxygen

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


Causes of Cell Injury

Physical Agents

  • Mechanical trauma

  • Extremes of temperature – burns, deep cold

  • Radiation

  • Electric shock


Causes 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 Injury

Infectious Agents

  • Parasites

  • Fungi

  • Bacteria

  • Rickettsiae

  • Viruses


Causes of Cell Injury

Immunologic Reactions

  • Anaphylactic reaction to foreign protein or drug

  • Reactions to endogenous self-antigens – autoimmune diseases


Causes 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 Injury

Nutritional Imbalances

  • Protein-calorie deficiencies

  • Vitamin deficiencies

  • Anorexia nervosa

  • Excesses of lipids – Obesity, Atherosclerosis

  • Metabolic diseases– Diabetes


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 Injury

Depletion of ATP


Mechanisms of Cell Injury

Mitochondrial Damage

Causes

Hypoxia, Toxins

Cytosolic Ca2+

Oxidative stress

Lipid breakdown product


Mechanisms of Cell Injury

Mitochondrial Damage

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

  • Leakage of Cytochrome c into cytosol

Mitochondrial Oxidative Phosphorylation

ATP production


Mechanisms of Cell Injury

Mitochondrial Damage


Mechanisms of Cell Injury

Influx of Intracellular Calcium and Loss of Calcium Homeostasis


Mechanisms of Cell Injury


Morphology of Cell Injury and Necrosis

  • Cell Injury – Reversible

    – Irreversible

  • Cell Death – Necrosis

    – Apoptosis


Morphology of Cell Injury

Reversible Injury

  • Plasma membrane alteration

  • Mitochondrial Changes

  • Dilation of Endoplasmic reticulum

  • Nuclear Alteration

Cellular 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 COAGULATIVE NECROSIS

Karyorrhexis

Normal cell

Reversible cell injury with cytoplasmic & organelle swelling, blebbing & ribosome detachment

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

Karyolysis


Morphologic pattern of Necrotic Cell mass

  • Coagulative necrosis

  • Liquefactive necrosis

  • Caseous necrosis

  • Fat necrosis


Morphologic pattern of Necrotic Cell mass

  • Coagulative Necrosis

    :intracellular acidosis

    – protein denatured

    – proteolysis inhibited


Ischemic necrosis of the myocardium

A, Normal myocardium.

B, Myocardium with coagulation necrosis


Morphologic pattern of Necrotic Cell mass

  • Liquefactive Necrosis

    :focal bacterial (or fungal) infections

    – accumulation of inflammatory

    cells

    :hypoxic death of cells within CNS


Coagulative and liquefactive necrosis

A, Kidney infarct exhibiting coagulative necrosis

B, A focus of liquefactive necrosis in the kidney


Morphologic Pattern of Necrotic Cell Mass

  • Caseous necrosis

    :gross appearance

    :microscopic – granulomatous inflammation


A tuberculous lung with a large area of caseous necrosis


Foci of fat necrosis with saponification in the mesentery


Explain the difference(s) between reversible and irreversible cell injury.

REVERSIBLE IRREVERSIBLE

Loss of ATP Irreversible mitochondrial damage

Phospholipid breakdown Massive peroxidation due todue to PLPase activation  uncontrolled chain reaction

Depolymerization of actin Cleavage of CSK proteins by proteases 

Increase in ROS Uncontrolled ROS; inflammation

Release of calcium fromUncontrolled calcium influx

storage site  

Altered metabolism Loss of amino acids


Describe Patterns of Necrosis in Tissues or OrgansAs a result of cell death the tissues or organs display certain macroscopic changes:1. Coagulative necrosis

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


3. Caseous necrosis

form of coagulative necrosis (cheese-like)

Example: tuberculosis lesions


4. Fat necrosis

enzymatic digestion of fat

example: necrosis of fat by pancreatic enzymes.


5. Gangrenous necrosis

Necrosis (secondary to ischemia) usually with superimposed infection

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


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