LECTURE 1 - Cellular Responses to Stress and Toxic Insults

Homeostasis

Cells normally maintain a stable internal environment

Type and severity of stress

Duration of the insult

Type and metabolic state of the cell

Ability of the cell to adapt

cellular responses depend in

Hypertrophy

An increase in the size of individual cells, resulting in enlargement of an organ.

• Skeletal muscle enlargement with exercise

• Cardiac hypertrophy due to hypertension

• Uterine smooth-muscle hypertrophy during pregnancy

Hyperplasia

An increase in the number of cells in a tissue or organ

Physiologic Hyperplasia

Hormonal and Compensatory

Hormonal Physiologic Hyperplasia

breast glandular proliferation during pregnancy

Compensatory Physiologic Hyperplasia

liver regeneration after partial hepatectomy

Pathologic Hyperplasia

Endometrial hyperplasia from excessive hormonal stimulation

Benign prostatic hyperplasia

Atrophy

A reduction in the size of cells, often resulting in decreased organ size

Causes of Atrophy

-Decreased workload

-Loss of innervation

-Diminished blood supply

-Inadequate nutrition

-Loss of endocrine stimulation

-Aging Pressure

Metaplasia

A reversible change in which one differentiated adult cell type is replaced by another differentiated cell type.

usually an adaptive response to chronic irritation.

In smokers: Normal bronchial columnar epithelium → stratified squamous epithelium

Oxygen Deprivation

hypoxia, ischemia

Physical Agents

Trauma; Radiation; Temperature extremes

Causes of cell injury

•Oxygen deprivation

•Physical agent

•Chemical agents and drugs

•Infectious agents

•Immunologic reactions

•Genetic abnormalities

•Nutritional imbalances

•Aging

Reversible Cell Injury

Early or mild injury can be reversed if the damaging stimulus is removed

Irreversible Cell Injury

when the cell cannot recover despite removal of the original insult.

Necrosis, Apoptosis

two major patterns of cell death

Necrosis

associated with severe cellular injury

• Cell swelling

• Membrane rupture

• Enzyme leakage

• Often provokes inflammation

Apoptosis

Regulated form of cell death

• Cell shrinkage

• Nuclear fragmentation

• Formation of apoptotic bodies

• Usually little or no inflammation

Cellular Aging

results from accumulated cellular damage over time

Important mechanisms of cellular aging

• DNA damage

• Decreased cellular replication

• Telomere shortening

• Defective protein homeostasis

• Reduced mitochondrial function

• Accumulation of metabolic damage

Coagulative necrosis

The most common type caused by ischemia (loss of blood flow) in solid organs like the heart, kidneys, and spleen, where the cell architecture and firm shape remain preserved for a few days.

Liquefactive necrosis

Dead cells are completely digested by enzymes into a viscous liquid mass, commonly seen in brain infarctions (strokes) and bacterial abscesses containing pus.

Caseous necrosis

A "cheese-like" whitish, crumbly dead tissue pattern typically associated with tuberculosis infections enclosed in a granuloma

Fat necrosis

Enzymatic destruction of fat cells (such as during acute pancreatitis) where released fatty acids combine with calcium to form chalky white deposits (saponification).

Fibrinoid necrosis

Damage to blood vessel walls causes immune complexes and leaked pink fibrin protein to deposit in the vessel lining, often seen in severe hypertension or vasculitis

Gangrenous necrosis

A clinical term for ischemic death of a large tissue area, usually involving a limb