Cell Injury, Adaptations, and Maladaptive Changes - Study Notes (Chap 2)

Etiology

• Etiology = original cause of cell alteration or disease

• Etiologic agents = causes of the cell alteration or disease (e.g., infection, trauma)

• Characteristic changes with specific etiologic agents

  • Examples: cold temperature causes frostbite; streptococcal bacteria causes sore throat

• In response to an etiologic agent, the cell may:

  • Develop adaptive, compensatory changes

  • Develop maladaptive changes

Basic Terminology

• Histology = microscopic study of tissue

• Biopsy = sample for histological analysis

• Autopsy = examination of tissue from deceased organisms

• Pathognomonic changes = unique, identifying disease presentations

  • Example: crater-like formation in stomach indicates ulcer

Basic Cellular Adaptations

• Atrophy = cells revert to smaller size due to reduction in metabolic demand

  • Example: paralysis causing shrinkage of skeletal muscle

• Hypertrophy = increase in individual cell size

• Types of hypertrophy

  • Physiological hypertrophy = cell enlargement with adequate supporting tissues

  • Example: enlargement of cardiac cells with exercise training

  • Pathological hypertrophy = increase in cell size without increased support structures

  • Example: enlargement of heart tissue due to hypertension

• Hyperplasia = increase in number of cells

  • Occurs only in cells capable of mitosis

  • Can result from hormonal stimulation

  • Example: estrogen stimulates growth of breast cells in pregnancy

  • May evolve into maladaptive compensation

  • Cell number increases too much

  • Example: keloid formation

• Metaplasia = replacement of one cell type with another

  • Genetic reprogramming to ensure cell survival

  • Example: GERD — lower esophageal cells transform from squamous epithelium to columnar stomach-like cells

• Dysplasia = deranged cellular growth

  • Often a result of chronic inflammation or a precancerous condition

  • Cells vary in size, shape, and organization compared with normal

  • Example: cervical dysplasia detected by Pap test

• Neoplasia = “new growth”

  • Disorganized, uncoordinated, uncontrolled cell growth; cancerous behavior

  • Neoplasm = often interchanged with the term “tumor”

  • Neoplasms may be benign or malignant (see next section)

• Benign vs Malignant neoplasms

  • Benign

  • Cells resemble normal cells

  • Well-differentiated cells

  • Do not metastasize

  • Well-defined borders

  • Malignant

  • Cells appear different from healthy cells

  • Poorly differentiated cells

  • Increased likelihood of metastasis

  • Poorly defined borders

Basic Concepts of Cell Injury

• Dysfunction of sodium-potassium pump

  • Loss of electrochemical gradient

  • $ext{Na}^+$ accumulates in cell, disrupting osmotic balance

  • Lack of ATP results in intracellular $ext{Ca}^{2+}$ accumulation

• Loss of plasma membrane integrity

  • Barrier disrupted → harmful substances can enter the cell; important substances lost from cell

• Defects in protein synthesis

  • Can lead to cell death

• Intracellular accumulations

  • Excessive deposits can disrupt cell function

  • Examples: fatty liver; xanthomas and xanthelasma

• Genetic damage

  • Injury to cell’s DNA may result in mutations

Intracellular Accumulations

• Intracellular accumulations can impair cell function when excessive

• Common examples referenced: fatty liver; cholesterol deposits such as xanthomas/xanthelasma

Causes of Cell Injury

• Hypoxia

  • Diminished oxygen to cells

  • Causes include ischemia (diminished circulation), problems with RBCs (anemia), pulmonary issues

  • Cells switch to anaerobic metabolism; lactic acid increases

• Free radical injury

  • Formed during aerobic metabolism; reactive oxygen species (ROS)

  • Contain unpaired electrons that interact with and disrupt plasma membranes

  • Protective mechanisms: enzymes (e.g., superoxide dismutases)

  • Oxidative stress: protective mechanisms overwhelmed

• Physical agents of injury

  • Examples: lacerations, falls, temperature extremes, burns, electrical shock

• Chemical injury

  • Endogenous: elevated ions; high blood glucose

  • Exogenous: drugs, pollutants, smoking

• Infectious agents of injury

  • Bacteria, fungi, parasites can cause cell damage

• Injurious immunological reactions

  • Autoimmune diseases

  • Chronic inflammation

• Nutritional imbalances

  • Deficiency or excess of macromolecules, vitamins, minerals

Endothelium and Vascular Injury

• Endothelium = cells lining interior of vessels

• Endothelium is active tissue: secretes

  • Vascular endothelial growth factor (VEGF)

  • Nitric oxide (NO)

  • Endothelin

• Injury to the endothelium may lead to atherosclerosis

• Key risk factors/contributors: Hypertension, Hyperglycemia, Free radicals, Hyperlipidemia

Endothelial Injury and Atherosclerosis

• Hypertension

  • Increases shear force on endothelium

  • Can lead to aneurysm (weakened area of arterial wall that may rupture)

• Diabetic hyperglycemia

  • Glucose reacts with endothelium

  • Advanced glycation end products form (AGEs), causing further endothelial damage

  • Endothelin, a potent vasoconstrictor, is released

• Free radicals

  • Highly reactive oxidizing molecules that can injure endothelium

  • Cigarette smoking increases free radicals

• Persistent angiotensin II secretion

  • Potent vasoconstrictor; increases blood pressure burden on endothelium

  • Elevated in heart disease

• LDL cholesterol and atherogenesis

  • Initiated by endothelial injury

  • Injury sites attract LDL particles; LDL is taken up by macrophages to form foam cells

  • Foam cells contribute to plaque formation

  • Reduced endothelial NO (NO) exacerbates vessel blockage

Cell Degeneration: Apoptosis vs Necrosis

• Apoptosis

  • Programmed cell death

  • Organized process that does not cause inflammation or damage surrounding tissues

  • Some diseases involve apoptosis dysfunction

  • Prostate cancer: decreased apoptosis

  • Spinal muscular atrophy: increased apoptosis

• Necrosis

  • Cell death due to injury

  • Irreversible; membrane disintegrates, lysosomal activation, autolysis

  • Initiates inflammatory reaction

• Infarction

  • Ischemic necrosis; death of tissue due to prolonged ischemia

  • Example: myocardial infarction (cell contents released into circulation as proteins)

Morphologic/Pathophysiologic Differences: Apoptosis vs Necrosis

• Viable cell → Apoptosis

  • Cell shrinks, chromatin condenses, budding, apoptotic bodies form

  • Apoptotic bodies phagocytosed; no inflammation

• Viable cell → Necrosis

  • Cell swells, becomes leaky, blebbing

  • Cellular and nuclear lysis; inflammation

Cell Degeneration: Gangrene

• Gangrene = prolonged ischemia, infarction, and necrosis

• Clostridium perfringens can cause gas gangrene by emitting gas as it destroys tissues

Interventions to Prevent Permanent Cell Injury

• Transplantation of organ or healthy tissue

• Regenerative medicine using stem cells

• Therapeutic cloning

• Reproductive cloning

Connections to Foundational Principles and Real-World Relevance

• Cellular adaptation and injury reflect the balance between stress and cellular resilience

• Reversibility of injury depends on duration and severity of insult and the capacity of adaptive mechanisms

• Endothelial health is central to vascular diseases such as atherosclerosis; risk modification targets include blood pressure, glycemic control, lipid management, and smoking cessation

• Distinctions between apoptosis and necrosis inform disease mechanisms and therapeutic strategies (e.g., cancer therapies aim to modulate apoptosis)

• Understanding metaplasia, dysplasia, and neoplasia aids in recognizing precancerous changes and guiding screening (e.g., Pap tests for cervical dysplasia)

• Ethical and practical implications of regenerative and cloning technologies in transplantation and disease treatment

Key Terms to Remember (glossary-style)

• Etiology, etiologic agents

• Histology, biopsy, autopsy, pathognomonic changes

• Atrophy, hypertrophy (physiological vs pathological), hyperplasia, metaplasia, dysplasia, neoplasia

• Benign vs malignant neoplasms

• Endothelium, VEGF, NO, endothelin, AGE

• Atherogenesis, foam cells, LDL

• Hypoxia, ischemia, ROS, oxidative stress

• Apoptosis, necrosis, infarction, ischemic necrosis

• Gangrene, gas gangrene, Clostridium perfringens

• Transplantation, regenerative medicine, therapeutic cloning, reproductive cloning