Cell Injury & Adaptation

• Cell adaptation is the temporary change in structure and function as a result of injury.
• Cell injury results from various internal and external environmental changes.
• Disruption of cellular components causes cell injury.
• Cell injury is common to all pathologic processes.

Causes of Cell Injury

• Hypoxia/ischemia
• Chemical exposure
• Physical trauma
• Infection
• Inflammation
• Genetic defects
• Nutritional imbalances

Effects of Cell Injury

• Mild injury/stress leads to reversible changes like atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia.
• Severe injury/stress results in cell death via apoptosis or necrosis.

Hypoxic Injury

• Hypoxic injury is common and potentially deadly.
• Reduced oxygen in the air, such as from bronchial obstruction, can cause hypoxic injury.
• Loss of hemoglobin function, like in carbon monoxide poisoning, causes hypoxic injury.
• Decreased red blood cells, such as from bleeding, can cause hypoxic injury.
• Cardiovascular and respiratory diseases, such as heart failure, cause hypoxic injury.
• Loss of cytochromes (mitochondrial proteins), such as from cyanide poisoning, causes hypoxic injury.

Chemical Injury

• Chemical agents can cause cellular injury.
• Poisons like pesticides can block acetylcholinesterase, disrupting nerve transmission.
• Lead exposure can cause brain injury and neurological dysfunction.
• Carbon monoxide binds to hemoglobin, preventing oxygen delivery and potentially causing death.
• High doses of ethanol can cause severe CNS depression, hypoventilation, and cardiovascular collapse.
• Pharmacologic agents can produce toxic products when metabolized, especially in overdose situations, like acetaminophen causing liver toxicity.

Other Injurious Factors

• Chromosomal abnormalities like Down Syndrome can cause cell injury.
• Gene mutations can cause cell injury.
• Hereditary factors can cause cell injury.
• Nutritional imbalances (malnutrition, vitamin excess/deficiency) alter physical & mental growth.
• Physical agents like heat, cold, and radiation can cause cell injury.

Adaptations to Stress

• Adaptation is the process of changing structure and function temporarily as a result of injury.
• Types of adaptation include:
  • Hypertrophy
  • Hyperplasia
  • Atrophy
  • Metaplasia

Atrophy

• Atrophy is a decrease in the size of a body part (cells, tissues).
• It involves a reduction in the number or size of cells, or both, due to decreased workload, inadequate nutrition, or loss of innervation.

Types of Atrophy

• Physiological atrophy includes atrophy of the thymus.
• Pathological atrophy includes:
  • General atrophy due to malnutrition, starvation, or senility
  • Localized atrophy due to disuse, pressure, vascular issues, neuropathic conditions, or endocrine factors

Hypertrophy

• Hypertrophy is an increase in cell size, leading to increased tissue size.
• It happens when non-dividing cells like myocardium and skeletal muscles are exposed to stress.
• Physiological causes include increased functional demand (e.g., striated muscle cells) and hormonal stimulation (e.g., uterus enlargement during pregnancy).
• Pathological causes include left ventricle hypertrophy due to hypertension or aortic valve disease.
• Adaptive hypertrophy is exemplified by left ventricular hypertrophy in aortic valvular stenosis.

Hyperplasia

• Hyperplasia is an increase in the number of cells, resulting in increased organ size, usually due to hormonal stimulation.
• Physiological hyperplasia:
  • Hormonal, such as enlargement of female breasts at puberty
  • Mammary gland in lactating mothers
• Pathological hyperplasia:
  • Endometrial hyperplasia
  • Wound healing

Metaplasia

• Metaplasia is the change of one fully differentiated cell type into another.
• Types:
  • Epithelial metaplasia (squamous metaplasia)
  • Connective tissue metaplasia (osseous metaplasia)

Epithelial Metaplasia

• Epithelial metaplasia is the metaplasia of columnar or cuboidal epithelium into stratified squamous epithelium.
• Locations include the bronchi, bronchiole, gall bladder, and urinary bladder.
• Causes include chronic irritation and avitaminosis A (Vitamin A deficiency).

Morphology of Cell Injury - Reversible

• Cellular Swelling (hydropic change) refers to accumulation of water in the cell.
• Fatty Change refers to accumulation of lipid in the cell, manifested by lipid vacuoles in the cytoplasm.
• Fatty change commonly affects the liver.
• Causes of fatty change include hypoxic injury, toxins (alcohol), metabolic issues (diabetes mellitus), and malnutrition.

Morphology of Cell Injury - Irreversible (Cell Death)

• Irreversible cell injury leads to cell death.
• Cell death occurs in two ways: necrosis and apoptosis.
• Necrosis involves changes produced by enzymatic digestion of dead cellular elements.
• Apoptosis is a vital process that eliminates unwanted cells via internally programmed events.

Necrosis

• Necrosis is the local death of cells inside the living body.
• The morphologic appearance is due to enzymatic digestion of the cell (e.g., lipase in the pancreas) and denaturation of proteins.

Microscopic Appearance of Necrotic Dead Cells

• Nuclear changes occur due to breakdown of DNA
  • Pyknosis is the condensation of nuclear chromatin (smaller than normal nucleus).
  • Karyorrhexis is the splitting of the nucleus into numerous pieces.
  • Karyolysis is the dissolution of nuclear chromatin.

Apoptosis

• Apoptosis is a regulated mechanism of cell death that eliminates unwanted or damaged cells.
• Affects single cells scattered in a population of healthy cells.
• Cells are shed in many organs as they reach the end of their lifespan via apoptosis.
• Physiological apoptosis includes normal tissue turnover, hormone-induced atrophy (e.g., endometrium in menstrual cycle), and processes during embryogenesis.
• Pathological apoptosis includes processes during viral infections and tumor regression induced by chemotherapy.

Gangrene

• Gangrene is necrosis of a large tissue area with putrefaction, creating a black, foul-smelling appearance.
• The necrosed tissue is infected with putrefactive organisms.
• Hemoglobin (from red blood cells) + hydrogen sulfide (H2S) (produced by bacteria) yields iron sulfide (black in color).

Types of Gangrene

• Dry gangrene
• Wet gangrene
• Gas gangrene

Dry Gangrene

• Dry gangrene only occurs on the skin surface (limbs, especially toes).
• It's caused by arterial obstruction.
• Common in people with impaired peripheral blood flow, such as diabetics.
• Grossly, it appears dry, shrunken, and dark reddish-black, resembling mummified flesh.

Wet Gangrene

• Wet gangrene affects the small intestine, appendix, lung, and uterus.
• It's caused by both arterial and venous obstruction.
• Grossly, it appears wet, swollen, foul-smelling, black, or green.
• Systemic manifestation includes absorption of toxic bacterial products, causing septicemia and potentially death.

Gas Gangrene

• Gas gangrene affects deep contaminated wounds with muscle damage, such as war wounds.
• Gross lesions are obviously swollen with gas bubble formation.