REVERSIBLE CELL INJURY

II B.Pharm 2006-2007

Outline
Introduction Severity of injury - mild (reversible) - moderate (reversible) Severe (irreversible) STRUCTURAL CHANGES of reversible injury - Cell swelling - Cloudy degeneration - Hydropic degeneration - Fatty degeration - Cell accumulation BIOCHEMICAL CHANGES - Energy; Protein; Fat metabolism

Introduction

Degree of damage (severity) depends on - nature of injurious agent - duration of injury - nature of tissue affected

Severity of cell injury

Based on degree of damage
Mild damage:

Moderate damage Severe damage Cell exposure injury >>>>> mild damage>>>> moderate damage>>> >>>severe damage>> cell death

 Mild damage- Recoverable (Reversible) Moderate - Recoverable unless of long duration (Reversible) Severe Irrecoverable (Irreversible)

Mild damage (reversible)

Cell metabolism disturbed Anabolism arrested Catabolism excessive Structural change no change (minimal disturbance of cell volume) Cell function disturbed Recovery- reversible

Moderate damage (partly reversible)

Cell metabolism Disturbed Anabolism Arrested Catabolism Excessive Structural change structural change in cytoplasm swelling >>>degeneration>>>Accumulation Cell function disturbed Recoveryreversible unless of long duration

Severe damage (irreversible)

Cell metabolism Disorganized Anabolism enzyme system wrecked Catabolism cell death (necrosis) Structural change structural change in cytoplasm & Nucleus - calcification

Cell function permanent loss of cell function Recovery- irrecoverable (necrosis)

Manifestations of reversible Injury

Structural changes: Light microscope observation Biochemical observation Energy metabolism
Protein metabolism Fat metabolism

Structural changes during reversible injury

Mild damage no change; minimal disturbance of cell volume Moderate damage- structural change in cytoplasm; - Cloudy degeneration - Hydropic degeneration - Fatty change - Intracellular accumulations

INJURY ( Toxic chemical or Ischemia)

Mitochondrion

ATP

Na Pump Influx of Ca++; H2O & Na Efflux of K+

Other Effects

Anaerobic glycolysis

Detachment of ribosomes

Glycogen

PH

Protein synthesis ER swelling; Cell swelling ; loss of microvilli; Blebs Lipid deposition Clumping of Nuclear Chromatin

Structural changes (reversible injury)

Cell swelling due to decreased function of sodium pump Injurious agent >>>> mitochondria >>>> oxidative phosphorylation >>>> ATP generation >>>> reduced activity of plasma membrane energy-dependent sodium pump >>>> Na+ accumulation and K+ diffusion out of the cell>>>> isosmotic gain of water >>>> cell swelling & dilation of endoplasmic reticulum

Ultra structural changes

Plasma membrane alterations: blebbing, blunting, distortion of microvilli, creation of myelin figures & loosening of intracellular attachments Mitochondrial changes: swelling, rarefaction, appearance of small phospholipid rich amorphous densities Dilation of endoplasmic reticulum: Ribosomes detatched polysomes Nuclear alterations: disaggregation of granular and fibrillar elements

Energy metabolism Cellular energy metabolism altered Oxidative phosphorylation ceases and cells rely on glycolysis for energy production ATP >>> AMP >>> anaerobic metabolism >>> glycolytic enzymes >>>> phospho fructokinase and phosphorylase activity >>> glycogen stores >>> Lactic acid accumul >>> PH >>>> activity of cellular enzymes

Protein metabolism
Intracellular Na+ accumulation >>>> Osmotic pressure >>>> water intracellular flow >>>> swelling & dilation of Endoplasmic reticulum >>>> Ribosome detatchment >>>> Protein synthesis

Lipid metabolism
Ribosome detatchment >>>> Apoprotein synthesis >>> Fat release from cell as lipoprotein

Manifestations of moderate injury (reversible injury)

Cloudy degeneration >>>>Hydrophic degeneration >>>>Fatty change >>>>
Intracellular accumulations

Cloudy degeneration (cellular edema)

Minor degree of cell damage Change is of short duration (affected cells come back to normal) Result of sub-lethal or reversible injury Most common in parenchyma cells (liver cells, renal tubules, muscle fibers) Swollen lining of cells

Hydropic degeneration
Swollen lining of cells Water logging Blunting of edges, cell borders frayed Cellular blebbing Cytoplasm full of eosinophilic granules (protein) Nuclei normal Tubular lamina narrow/ granular

Fatty degeneration (Fatty change) (Fatty metamorphosis)

Accumulation of neutral fats within cells Apoprotein synthesis >>>>> Fat release from cell as lipoprotein >>>>> lipid accumulation >>>>> Fatty change

Microscopical fat globules in cytoplasm

Intracellular accumulations
TYPE Lipids Protein DISORDER Fatty change Hyaline droplets TISSUE INVOLVED Liver; Heart Proximal renal tubule Plasma cells

Immunoglobulin Russel bodies

Glycogen

Glycogen storage disease; Diabetes mellitus

Connective tissue disorder

Liver Muscle Islet of langerhans

Liver, Glomerulous; Epithelial Tissue; Connective Tissue

Hyaline