Cellular
On this page 43 sections
REACTION TO INJURY
Overview
Cells respond to stress and injury through adaptation, reversible injury or irreversible injury leading to cell death.
| Response | Meaning | Example |
|---|---|---|
| Adaptation | Cellular changes that permit survival under stress | Hypertrophy, hyperplasia, atrophy, metaplasia |
| Reversible injury | Cellular dysfunction that can recover when the stimulus is removed | Cellular swelling, fatty change |
| Irreversible injury | Severe damage beyond the point of recovery | Necrosis |
| Programmed cell death | Regulated removal of cells | Apoptosis |
Cellular Adaptations
A. Hypertrophy
Definition: Increase in cell size, producing enlargement of an organ or tissue.
Mechanism:
- Increased synthesis of proteins and intracellular organelles.
- Occurs especially in tissues with limited ability to divide.
- May be physiological or pathological.
| Type | Example |
|---|---|
| Physiological | Skeletal muscle enlargement with exercise |
| Physiological | Uterine smooth muscle enlargement during pregnancy |
| Pathological | Left ventricular hypertrophy due to hypertension |
MCQ tip: Hypertrophy = increase in cell size, not cell number.
B. Hyperplasia
Definition: Increase in the number of cells due to increased cellular proliferation.
| Type | Example |
|---|---|
| Physiological hormonal | Breast glandular proliferation during pregnancy |
| Physiological compensatory | Liver regeneration following partial hepatectomy |
| Pathological | Endometrial hyperplasia from excessive estrogen stimulation |
| Pathological | Benign prostatic hyperplasia |
Remember: Hyperplasia occurs in tissues capable of cell division.
C. Atrophy
Definition: Reduction in cell size and often cell number, leading to reduced tissue or organ size.
Causes include:
- Disuse.
- Denervation.
- Reduced blood supply.
- Malnutrition.
- Loss of hormonal stimulation.
- Aging.
- Pressure.
Mechanisms include decreased protein synthesis, increased protein degradation and autophagy.
Dental relevance: Alveolar ridge resorption after tooth loss is an example of tissue atrophy/remodeling associated with reduced functional stimulation.
D. Metaplasia
Definition: Reversible replacement of one differentiated cell type by another that is better adapted to a persistent stress.
| Example | Cellular change |
|---|---|
| Cigarette smoking | Respiratory ciliated columnar epithelium → stratified squamous epithelium |
| Barrett esophagus | Esophageal squamous epithelium → intestinal-type columnar epithelium |
| Chronic irritation | May cause adaptive epithelial replacement |
Metaplasia results from altered differentiation of tissue stem cells rather than direct transformation of one mature cell into another.
Exam tip: Persistent metaplastic changes can increase the risk of dysplasia and malignancy, depending on the tissue and cause.
E. Dysplasia
Dysplasia refers to disordered cellular growth and maturation with cytologic and architectural atypia.
Typical features:
- Cellular pleomorphism.
- Nuclear hyperchromasia.
- Increased nuclear-to-cytoplasmic ratio.
- Loss of normal cellular orientation.
- Increased or abnormal mitotic activity.
Dysplasia is not simply another adaptive response. It is an abnormal proliferative change that may precede malignancy.
Dental relevance: Oral epithelial dysplasia is an important histopathological finding in potentially malignant oral disorders.
Comparison of cellular adaptations
| Feature | Hypertrophy | Hyperplasia | Atrophy | Metaplasia |
|---|---|---|---|---|
| Cell size | Increased | Usually unchanged | Decreased | Variable |
| Cell number | Usually unchanged | Increased | May decrease | Usually maintained |
| Main process | Protein synthesis | Proliferation | Reduced synthesis/increased degradation | Altered differentiation |
| Reversible | Often | Often | Often | Often |
| Example | LV hypertrophy | BPH | Disuse muscle atrophy | Barrett esophagus |
Hypoxic Cell Injury
Causes of hypoxia
| Cause | Mechanism |
|---|---|
| Ischemia | Reduced blood supply |
| Anemia | Reduced oxygen-carrying capacity |
| Carbon monoxide poisoning | Impaired hemoglobin-mediated oxygen transport |
| Respiratory failure | Reduced blood oxygenation |
| Cyanide poisoning | Inhibition of cellular oxygen utilization |
Mechanism of hypoxic injury
Reduced oxygen delivery leads to impaired mitochondrial oxidative phosphorylation and ATP depletion.
Sequence:
Hypoxia → decreased oxidative phosphorylation → ATP depletion → Na⁺/K⁺-ATPase failure → Na⁺ and water accumulation → cellular swelling.
Additional consequences:
- Increased anaerobic glycolysis causes lactate accumulation and intracellular acidosis.
- Ribosomal detachment reduces protein synthesis.
- Calcium homeostasis becomes impaired.
- Persistent mitochondrial and membrane injury leads to irreversible damage.
Reversible versus irreversible injury
| Reversible injury | Irreversible injury |
|---|---|
| Cellular swelling | Severe membrane disruption |
| Fatty change | Major mitochondrial dysfunction |
| Membrane blebbing | Lysosomal membrane damage |
| Ribosomal detachment | Nuclear breakdown |
| Can recover after stimulus removal | Leads to cell death |
Nuclear changes in necrosis
| Change | Meaning |
|---|---|
| Pyknosis | Nuclear shrinkage and chromatin condensation |
| Karyorrhexis | Nuclear fragmentation |
| Karyolysis | Dissolution/fading of the nucleus |
Memory aid: Pyknosis → Karyorrhexis → Karyolysis.
Free Radical Injury
Free radicals contain unpaired electrons and can damage cellular structures.
Sources of reactive oxygen species
- Mitochondrial electron transport.
- Inflammatory cell respiratory burst.
- Ionizing radiation.
- Chemical and drug metabolism.
- Reperfusion after ischemia.
Mechanisms of injury
| Target | Damage |
|---|---|
| Lipid membranes | Lipid peroxidation |
| Proteins | Oxidation and cross-linking |
| DNA | Strand breaks and base modifications |
| Mitochondria | Impaired energy production |
Antioxidant defense
| Antioxidant/enzyme | Action |
|---|---|
| Superoxide dismutase | Converts superoxide to hydrogen peroxide |
| Catalase | Converts hydrogen peroxide into water and oxygen |
| Glutathione peroxidase | Reduces hydrogen peroxide and lipid peroxides |
| Vitamins C and E | Antioxidant protection |
MCQ tip: Reperfusion injury may result from the sudden generation of reactive oxygen species when oxygen supply is restored.
Chemical Cell Injury
Chemical agents cause injury through direct toxicity or conversion into reactive metabolites.
Examples
| Agent | Mechanism |
|---|---|
| Cyanide | Inhibits cytochrome c oxidase, impairing oxidative phosphorylation |
| Carbon tetrachloride | Forms free radical metabolites, causing lipid peroxidation |
| Acetaminophen overdose | Produces toxic NAPQI metabolite, leading to hepatic injury |
Necrosis
Definition: Cell death associated with membrane disruption, enzymatic degradation and an inflammatory response in surrounding tissues.
Types of necrosis
| Type | Mechanism/appearance | Classic examples |
|---|---|---|
| Coagulative | Tissue architecture initially preserved; protein denaturation predominates | Ischemic infarction in most solid organs |
| Liquefactive | Enzymatic digestion produces liquid or soft tissue | Brain infarction, abscess |
| Caseous | Soft, cheese-like granular necrotic material | Tuberculosis |
| Fat | Lipase-mediated fat destruction or traumatic adipose injury | Acute pancreatitis, traumatic fat necrosis |
| Fibrinoid | Immune-mediated vascular wall injury with fibrin-like deposits | Vasculitis |
| Gangrenous | Clinical term for extensive tissue necrosis | Ischemic limb, bowel |
Coagulative necrosis
- Commonly caused by ischemia.
- Tissue outlines are initially preserved.
- Protein denaturation limits immediate enzymatic digestion.
- Seen in infarction of the heart, kidney and spleen.
Exception: Brain ischemia typically produces liquefactive necrosis.
Liquefactive necrosis
- Enzymatic digestion dominates.
- Tissue becomes soft or liquid.
- Characteristic of brain infarcts and pyogenic bacterial abscesses.
Caseous necrosis
- Grossly resembles cheese.
- Often associated with granulomatous inflammation.
- Classically seen in tuberculosis.
Fat necrosis
Enzymatic: Pancreatic lipases release fatty acids that combine with calcium, producing saponification.
Traumatic: Physical injury to adipose tissue may cause localized fat necrosis.
Gangrenous necrosis
| Type | Main feature |
|---|---|
| Dry gangrene | Ischemic coagulative necrosis |
| Wet gangrene | Ischemic tissue with superimposed infection and liquefaction |
| Gas gangrene | Clostridial infection causing tissue destruction and gas formation |
Dental relevance: Pulp necrosis can lead to periapical inflammation and abscess formation.
Apoptosis
Apoptosis is regulated cell death that generally occurs without significant leakage of cellular contents or surrounding inflammation.
Apoptosis versus necrosis
| Feature | Apoptosis | Necrosis |
|---|---|---|
| Mechanism | Regulated, caspase-mediated | Severe cellular injury |
| Cell size | Shrinks | Swells |
| Cell membrane | Generally remains intact until removal | Disrupted |
| DNA | Controlled fragmentation | Irregular degradation |
| Inflammation | Usually absent or minimal | Usually present |
| Apoptotic bodies | Present | Absent |
| Typical role | Physiological and pathological | Primarily pathological |
Physiological apoptosis
- Embryological development.
- Removal of hormone-dependent cells after hormonal withdrawal.
- Elimination of self-reactive lymphocytes.
- Removal of excess or damaged cells.
Pathological apoptosis
- DNA damage.
- Viral infection.
- Accumulation of misfolded proteins.
- Certain chemotherapy-related effects.
Pathways
| Intrinsic pathway | Extrinsic pathway |
|---|---|
| Mitochondrial pathway | Death-receptor pathway |
| Regulated by BCL-2 family proteins | Fas and TNF-family receptor signaling |
| Cytochrome c release | Death-inducing signaling complexes |
| Caspase-9 activation | Caspase-8 activation |
| Executioner caspases | Executioner caspases |
MCQ tip: Caspases are central to apoptosis. Caspase-9 is associated with the intrinsic pathway, while caspase-8 is associated with the extrinsic pathway.
Reversible Cellular Changes and Accumulations
Cellular swelling
The earliest common manifestation of reversible cell injury.
- ATP depletion impairs ion pumps.
- Intracellular sodium increases.
- Water enters the cell.
- Organelles, especially the endoplasmic reticulum, may swell.
Fatty change
Abnormal triglyceride accumulation within cells.
Common sites include the liver and heart.
Causes:
- Alcohol exposure.
- Obesity and metabolic dysfunction.
- Diabetes mellitus.
- Toxins.
- Hypoxia and impaired lipid metabolism.
Hyaline change
A descriptive term for homogeneous, glassy, pink material seen on H&E staining.
Examples include hyaline arteriolosclerosis and certain intracellular protein accumulations.
Pathological Pigments
| Pigment | Source | Clinical association |
|---|---|---|
| Lipofuscin | Lipid peroxidation and cellular aging | Brown atrophy |
| Melanin | Melanocyte-derived pigment | Normal pigmentation and melanocytic lesions |
| Hemosiderin | Iron storage pigment | Hemorrhage and iron overload |
| Bilirubin | Heme breakdown | Jaundice |
| Carbon | Exogenous inhaled pigment | Anthracosis |
| Tattoo pigment | Exogenous material | Dermal pigment deposition |
Lipofuscin
- Yellow-brown intracellular pigment.
- Derived from oxidative damage to cellular membranes.
- Associated with aging and cellular atrophy.
- Sometimes called the wear-and-tear pigment.
Hemosiderin
- Golden-brown iron-containing pigment.
- May accumulate after local hemorrhage or systemic iron overload.
- Demonstrated with Prussian blue staining.
Bilirubin
- Yellow pigment derived from heme metabolism.
- Accumulation produces jaundice.
Pathological Calcification
| Feature | Dystrophic calcification | Metastatic calcification |
|---|---|---|
| Serum calcium | Usually normal | Often elevated |
| Tissue | Damaged or necrotic | Previously normal tissue |
| Main mechanism | Local deposition in injured tissue | Systemic disturbance of calcium/phosphate metabolism |
| Example | Calcified damaged heart valve | Hyperparathyroidism-related tissue calcification |
Dystrophic calcification
Occurs in dead or damaged tissues, even when serum calcium is normal.
Examples:
- Calcified atherosclerotic plaques.
- Damaged cardiac valves.
- Necrotic tissue.
Metastatic calcification
Occurs in otherwise normal tissues due to disturbed calcium-phosphate metabolism.
Causes include:
- Hyperparathyroidism.
- Malignancy-associated hypercalcemia.
- Vitamin D excess.
- Chronic renal disease with mineral metabolism disturbances.
Exam tip: Normal calcium + damaged tissue = dystrophic calcification.