objective• Understand the process of regeneration and degeneration occurs• Able to differentiate between regeneration and degeneration biochemical process.
REGENERATIONMaintain proper structure of tissueThe replacement of cell can happen in two ways:by regeneration: the necrotic cells are replaced by the same tissue as was originally there.by repair: injured tissue is replaced with scar tissue.Most organs will heal using a mixture of both mechanism.
• In order for an injury to be healed by regeneration, the cell type that was destroyed must be able to replicate.• Most cells have this ability, although it is believed that cardiac muscle cells and neurons are two important exceptions.• Cells also need a collagen framework along which to grow.
• Alongside, most cells there is either a basement membrane or a collagenous network made by fibroblasts that will guide the cells growth.• Proliferation of original cell occur from the margin of injury.• Since ischaemia and most toxins do not destroy collagen, it will continue to exist even when the cells around it are dead.
• Local factors that interfere with the healing process such as:• 1. Presence of inert foreign bodies in the wound• 2. Occlusion of blood vessels• 3. Malnutrition
DEGENERATIONLoss of function of the cell, tissue or organ.Degeneration and infiltration are retrogressive changes in cells and tissues characterized by abnormal structural changes and decreased functions.They are nonspecific responses of cells and tissues following a variety of injuries.Some of these processes may be reversible if the injury is mild. If the injury is severe and persistent, it may progress to the point where the involved cell dies.
• The distinction between the point where the cells would recover and the point where the process is irreversible and leads to cell death is arbitrary.• In theory, the difference between the two processes is vague.• Most literatures however define these two processes as:• Degeneration: the accumulation of metabolites or other substances in a cell damaged by preceding injury.
• Infiltration: the overloading of previously normal cells by materials which are abnormal in either type of quantity.• Following these definitions, the changes in the cells in both degeneration and infiltration may appear similar, and many consider the two processes as identical.
• The patterns of cellular degeneration and infiltration used by pathologist are grouped according to the dominant expression of injury as: 1) water overload 2) metabolite overload 3) Storage overload
• 1. Water overload – cellular swelling.• 2. Metabolite overload which involves excessive accumulation of normal metabolic products such as fat, glycogen, or protein (hyaline or proteinaseous).• 3. Storage loading which involves overloading by non-degradable products such as pigments, minerals, and exogenous substances.
• The causes of impaired energy production in the mechanism of cellular degeneration are:• 1. Hypoglycemia – glucose is the main substrate for energy production in most tissue and sole energy source in brain cells. – low glucose level = deficient ATP production.• 2. Hypoxia – oxygen carried by blood. Lack of oxygen in the cells may cause = ischemia, anemia, respiratory obstruction, alteration of hemoglobin.
• 3. Enzyme inhibition- chemical interfering with a vital enzyme. Ex= cyanide inhibit cytochrome oxidase final enzyme in the respiratory chain causing acute ATP deficiency in all cells and cause rapid death.• 4. Uncoupling of oxidative phosphorylation - occur either through chemical reactions or through physical detachment of enzyme from mitochondrial membrane. Ex= mitochondrial swelling is common changes associated with injury.
Effects of defective energy production• Failure of energy production will first affect those cells with the highest demand for O2 – high basal metabolic rate.• The earliest clinical sign of hypoxia and hypoglycemia are disturbance of the normal consciousness such as :• A) intracellular accumulation of water and electrolysis• B)changes in organelles• C) switch to anaerobic metabolism.
Effects of the defective energy production are:i. Intracellular accumulation of water and electrolysisEarliest detachable biochemical evidence- diminished availability of ATP is dysfunction of sodium pump on plasma membraneInflux of water and sodium into cellSwollen and cloudy cellMay lead to enzyme inhibition.Early and reversible effects of cell injury
• ii. Changes in organelles• Endoplasmic reticulum distend• Ribosomes detached• Interfere protein synthesis• Mitochondrial swelling
• iii. Switch to anaerobic metabolism• Production of lactic acid, low the intracellular pH• Chromatin to clump in nucleus• Lysosomal membrane disrupt leading to release of enzymes into cytoplasm, damage the vital intracellular molecules.• Cellular degeneration becomes irreversible – result in necrosis.