Cell Injury and Inflammation Lecture Quiz

Cell Injury, Inflammation, and Repair (3 lecture hours)

• Recommended Reading: Robbins Basic Pathology, 10th Edition (2018)

Cell Injury

• Learning Objectives:
  • Understand the underlying principles of cell injury.
  • Define and describe cell injury-related concepts: homeostasis, adaptation, hypertrophy, hyperplasia, atrophy, metaplasia.
  • Detail all possible mechanisms of cell injury.
  • Describe morphological changes associated with cell injury.

Homeostasis

• Definition: The stable internal environment of cells, tightly regulated to maintain a constant state.

• Intracellular Milieu:

  • Concentration of anions and cations
  • Concentration of enzymes
  • Enzymatic activity
  • Concentration of various proteins
  • pH of cytosol and cell organelles

Cellular Adaptation

• Purpose: Preserve cell viability and function when encountering stress (physiological or pathological).

• Stress Types: Physiological stress (increased workload) or pathological stress (nutrient deprivation, injuries).

• Cellular Injury: Occurs if the adaptive capacity is exceeded.

Cellular Injury Progression

• Normal Cell (Homeostasis) → Injurious Stimulus → Reversible Injury (mild) → Severe, Progressive Injury (Severe) →Irreversible Injury → Cell Death:
  • Irreversible injury leads to two paths: necrosis or apoptosis

Overview: Adaptive Responses

• Hypertrophy: Increase in cell size (e.g., striated muscle cells).
• Hyperplasia: Increase in cell number (e.g., glandular epithelium in the female breast).
• Atrophy: Decrease in cell size (e.g., due to loss of innervation, decreased workload, or reduced blood supply ).
• Metaplasia: Change in cell type (e.g., squamous epithelium in respiratory tract of smokers).

Hypertrophy

• Mechanism: Enlargement of existing cells by increasing structural proteins and organelles.
• Examples: Physiological (exercise, pregnancy), pathological (hypertension, myocardial infarction).

Hyperplasia

• Conditions where cells can replicate: Smooth muscle cells a. Physiologic: Stimulated by hormones (e.g., female breast during puberty/pregnancy), response to removal of tissue part. b. Pathologic: Caused by excess hormones or growth factors (e.g., endometrial hyperplasia).

Atrophy

• Causes
  • Pathologic: Loss of innervation, decreased workload, reduced blood supply, inadequate nutrition
  • Physiologic: Reduced endocrine stimulation (e.g., menopause) or aging (senile atrophy)

Metaplasia

• Definition: Reversible change where one cell type is replaced by another type, better suited to the adverse environment.
• Example: Replacement of columnar epithelium by squamous epithelium in the trachea/bronchi of smokers.
• Important protective mechanisms are lost (e.g., mucus secretion, cilia).

Cell Death

• Overview: Cells die via two major paths:
  • Necrosis
  • Apoptosis

Necrosis

• Characteristics:
  • Cellular swelling
  • Nuclear swelling & lysis
  • Death of many cells
  • Lysosome breakdown
  • Inflammation
  • Calcification
  • Cessation of protein synthesis
  • Energy-independent

Apoptosis

• Characteristics:
  • Cellular shrinkage
  • Chromatin condensation and fragmentation (apoptotic bodies)
  • Death of single cells
  • Lysosomes intact
  • No inflammation
  • No calcification
  • Requires protein synthesis
  • Energy-dependent
• Phagocytosis of apoptotic bodies which prevents inflammation.

Mechanisms of Cell Injury

• Oxygen Deprivation: Interruption of oxidative phosphorylation. Common cause is ischemia.
• Chemical Agents: Reactive oxygen species (ROS)
• Infectious Agents: Viruses, bacteria, fungi
• Immunologic Reactions: Autoimmune and allergic reactions
• Genetic Defects: Deficiency of functional proteins
• Physical Agents: Trauma, radiation, extreme temperatures

Reversible Cellular Injury Morphology

• Cellular Swelling: Failure of ATP-dependent ion pumps, loss of ionic and fluid homeostasis.
• Fatty Change (Steatosis): Appearance of lipid-filled vacuoles in cytoplasm. Impairment in lipid metabolism.

Necrosis Morphology

• Increased eosinophilia: Increased pink staining with H&E due to less RNA and increased protein denaturation
• Myelin Figures: Structural characteristics.
• Calcification: Mineral deposition in cells/tissues.
• Nuclear Changes: Karyolysis, pyknosis, karyorrhexis

Autophagy and Autophagy

• Definition: Lysosomal digestion of the cell's own components (i.e., cellular components). Can be considered a survival mechanism during nutrient deprivation.
• Residual Bodies:
  • contain undigested debris.
  • contain pigmentation (e.g ink)

Induction (Hypertrophy) of Smooth ER

• Mechanism: Related to drug metabolism by the P450 enzyme system in the liver.
• Consequence: Protracted drug use leads to smooth ER adaptation (increase in size), and the need to increase the dose of the drug.

Mitochondrial Alterations

• Changes in size, shape, and number
• Constant fusion and fission. Exercise, for instance, increases mitochondrial numbers.

Cytoskeletal Abnormalities

• Cytoskeleton: A protein fiber array that provides cell shape, structural support, facilitates separation of chromosomes, and plays an important role in maintaining cell integrity.
• Types:
  • Microtubules
  • Actin filaments
  • Intermediate filaments
• Cells constantly remodel their intracellular scaffolding in response to environmental stresses..
• Membrane stability depends on cytoskeleton. Drugs like anticancer drugs bind to microtubules and prevent proliferation.

Mechanism of Cell Injury Overview

• Injury stimulus → Damage to various cellular components (e.g., ATP depletion, membrane damage, cytoskeletal damage, DNA damage, protein misfolding). → Multiple downstream effects → Cell death (necrosis or apoptosis).

ATP Depletion

• Cause: Lack of oxygen/nutrients, direct mitochondrial damage, toxins (e.g. cyanide).
• Effects:
• • Decreased ionic pump activity in cell → osmotic gain of water → cellular swelling
• Consequences
• Increased intracellular calcium levels
• Mitochondrial damage (loss of ATP)
• Increased formation of ROS
• Protein misfolding/degradation

Increased Cytosolic Calcium

• Cause: Failure of ATP-dependent calcium transporters.
• Effects: Leads to enzyme activation, potentially damaging proteins and organelles.

Oxygen-Related Cell Injury (Oxidative Stress)

• ROS (Reactive Oxygen Species), generated during incomplete oxygen reduction.

• Sources of ROS:

• NO synthase, xanthine oxidase, NADPH oxidases, mitochondria

• Consequences: ROS damage organelles/structure, and cellular components (lipids, proteins, and DNA), leading to cellular injury & death.

• Removal of ROS: antioxidant mechanisms (SOD, catalase).

ROS Paradigm Shift

• ROS are not always harmful, but can be physiological 2nd messengers (example is hydrogen peroxide) for different biochemical pathways.
• Pathologic excess comes from unregulated ROS product over response to hypoxia/stress.

Test your knowledge on cell injury, inflammation, and repair as discussed in Robbins Basic Pathology. This quiz covers key concepts including homeostasis, cellular adaptation, and mechanisms of cell injury. Ensure you understand the principles and morphological changes associated with these conditions.