The word "pathology" is derived from the Greek word pathos (which means suffering) and logos (which means word, study, or reasoning). Thus, "pathology" literally means the study of pain and suffering. It is the medical science that deals with all aspects of disease, with special reference to the causes and mechanisms of disease.

Our first topic is Cell Injury. For over 100 years, physicians and scientists have understood that disease represents injury to the smallest living unit of the body, namely the cell. Throughout life, cells of the body experience changes in their microenvironment (for example, changes in the delivery of oxygen, nutrients, and trophic factors). When these environmental changes are mild, cells are able to adapt. Examples of chronic adaptation include atrophy, hypertrophy and hyperplasia. When environmental changes are prolonged or severe, cells undergo coagulative necrosis. Various types of coagulative necrosis are recognized morphologically. These types include liquifactive, fat, and caseous necrosis.

Sources of Persistent Stress

• Functional demand (work load)
• Oxygen supply (blood supply)
• Nutrient supply (blood supply)
• Trophic signals (hormones, growth factors)
• Persistent cell injury (chronic inflammation)
• Aging

Morphological Reactions to Persistent Stress

• Atrophy (decrease in cell size or function)
• Hypertrophy (increase in cell size or function)
• Hyperplasia (increase in cell number)
• Metaplasia (trans-differentiation, one to another)
• Dysplasia (alterations in the uniformity of histogenesis)
• Neoplasia (new uncontrolled cell proliferation)
• Intracellular storage (exaggeration of a normal function)

Cellular Changes due to Reversible Cell Injury

• Hydropic (cloudy) swelling
• Distention of endoplasmic reticulum cisternae
• Mitochondrial swelling
• Plasma membrane blebs
• Nucleolar fibrillar/granular changes

Note: These cellular and ultrastructural changes are mediated by a decrease in intracellular ATP levels or impairment of membrane-associated Na/K ATPase.

Intracellular Storage Disorders
Storage Material	Example
Fat	Alcoholic fatty liver
Glycogen	Uncontrolled diabetes
Complex carbohydrates	Tay-Sachs disease
Metals (Cu, Fe)	Hereditary hemochromatosis
Lipofuscin	Wear and tear pigment (aging)
Melanin	UV light (tanning)
Exogenous pigments	Anthracosis (coal-miners' lung)

Cellular Changes due to Irreversible Cell Injury

Membrane/Cytoplasm
• Plasma membrane blebs
• Increased intracellular volume
• Swelling and calcification of mitochondria
• Aggregation of cytoskeletal elements
• Disaggregation of ribosomes
• Dilation of endoplasmic reticulum cisternae

Nucleus
• Shriveled nuclear membrane
• Chromatin condensation (pyknosis)
• Progressive fragmentation of chromatin (karyorrhexis and karyolysis)

Pathogenesis of Coagulative Necrosis

• Irreversible injury and cell death
• Loss of plasma membrane integrity
• Influx of sodium, calcium, and water
• Appearance of coagulative necrosis

Note: Loss of plasma membrane integrity may precede irreversible cell injury.

Morphology of Necrosis

• Coagulative (hallmark)
• Liquifactive (abscess, brain)
• Fat (pancreas, fat tissue)
• Caseous (tuberculosis)
• Fibrinoid (blood vessels)
• Apoptosis (programed cell death, viral hepatitis)

Deposition of Calcium Salts

Dystrophic Calcification
• Necrosis and release of intracellular lipases
• Liberation of organic phosphates and precipitation of calcium phosphates

Metastatic Calcification (hypercalcemia)
• Increased calcium absorption (vitamin D intoxication)
• Increased mobilization of calcium from bone (hyperparathyroidism)

Here are the Key Points:

1. Pathology is the study of structural and functional abnormalities of cells, tissues and organ systems. Cells in stress may either undergo i) acute reversible changes, ii) chronic adaptation, or iii) coagulative necrosis.

2. Reversible cell injury is often associated with hydropic swelling.

3. Morphological adaptations to chronic injury include: atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia and intracellular storage disorders.

4. Necrosis may be described morphologically as either: coagulative, caseous, fat, fibrinous or liquefactive, depending on the tissue and type of injury.

The following images illustrate Key Morphological Concepts:

1. This is an example of ATROPHY. Note the thinned gyri and widened sulci on the external surface of the brain. Brain atrophy occurs in Alzheimer disease and aging.

2. This is an example of concentric, left ventricular HYPERTROPHY. This occurs in patients with long-standing systemic hypertension.

3. This is an example of SQUAMOUS METAPLASIA. Normal columnar epithelium (on the right) is replaced by squamous epithelium (on the left). This process of adaptation to chronic injury commonly occurs in the lungs of smokers and in the uterine cervix.

4. This is an example of fatty liver, an INTRACELLULAR STORAGE DISORDER commonly seen in chronic alcoholics. Note the yellow discoloration of the liver. Under the microscope, liver cells are seen to contain numerous lipid droplets.

5. This is an example of COAGULATIVE NECROSIS affecting the entire lower leg. This massive necrosis is also referred to as gangrene. Under the microscope, necrotic cells show fragmentation and loss of chromatin, owing to the reflux of DNAs and RNAs into the nucleus.

6. This is an example of LIQUIFACTIVE NECROSIS affecting the brain. Rapid liquefaction of the necrotic tissue leads to the formation of a permanent brain cyst. Liquifactive necrosis also occurs in an abscess.