Cellular Injury PDF

CELLULAR INJURY DR. MUHAMMAD ALI SOOMRO  INTRODUCTION: It is a variety of changes of stress that a cell suffers due to external as well as internal environmental changes. Cells can alter their function in response to stress to maintain steady state. More severe physiological s...

CELLULAR INJURY DR. MUHAMMAD ALI SOOMRO  INTRODUCTION: It is a variety of changes of stress that a cell suffers due to external as well as internal environmental changes. Cells can alter their function in response to stress to maintain steady state. More severe physiological stress or advert pathological stimuli insult induce either (1) adaptation, (2) reversible or (3) irreversible injury.  CAUSES: Oxygen deprivation. Physical agents i.e. trauma, heat, cold etc. Chemical agents esp. drugs. Infectious agents. Impaired nutrient supply. Genetic derangements. Immunologic disorders. Iatrogenic. CAUSES:  TARGETS: The most notable components of the cell that are targets of cell damage are the DNA and the cell membrane. DNA damage: In human cells, both normal metabolic activities and environmental factors such as ultraviolet light and other radiations can cause DNA damage, resulting in as many as one million individual molecular lesions per cell per day. Membrane damage: damage to the cell membrane disturbs the state of cell electrolytes, e.g. calcium, which when constantly increased, induces apoptosis(cell death).  BIOCHEMISTRY: ATP (adenosine triphosphate) depletion is a common biological alteration that occurs with cellular injury. A reduction in intracellular ATP can have a number of functional and morphologic consequences during cell injury. These effects include: – Failure of the ATP dependent pumps (Na+/K+ pump and Ca2+ pump), resulting in a net influx of Na+ and Ca2+ ions and osmotic swelling. – ATP-depleted cells begin to undertake anaerobic metabolism to derive energy from glycogen which is known as glycogenolysis. – A consequent decrease in the intracellular pH of the cell arises, which mediates harmful enzymatic processes. – Early clumping of nuclear chromatin then occurs, known as 'pyknosis', and leads to eventual cell death.  TYPES OF DAMAGE: Sub-lethal (reversible): Cellular swelling: – Cellular swelling may occur due to cellular hypoxia, which damages the sodium-potassium membrane pump; it is reversible when the cause is eliminated. – When it affects many cells in an organ, it causes some pallor, increased turgor, and increase in weight of the organ. – On microscopic examination, small clear vacuoles may be seen within the cytoplasm; these represent distended and pinched-off segments of the endoplasmic reticulum. – This pattern of non-lethal injury is sometimes called hydropic change or vacuolar degeneration TYPES OF DAMAGE: – Hydropic degeneration is a severe form of cloudy swelling. It occurs with hypo-kalemia due to vomiting or diarrhea. – The ultra-structural changes of reversible cell injury include: » Blebbing. » Blunting. » Distortion of micro-villi. » Loosening of intercellular attachments. » Mitochondrial changes. » Dilation of the endoplasmic reticulum. TYPES OF DAMAGE: Fatty change: – The cell has been damaged and is unable to adequately metabolize fat, hence small vacuoles of fat accumulate and become dispersed within cytoplasm. – In the liver, the enlargement of hepatocytes due to fatty change may compress adjacent bile canaliculi, leading to cholestasis. – Fatty change is generally reversible.  TYPES OF DAMAGE: Lethal (ir-reversible): – Necrosis: Necrosis is characterised by cytoplasmic swelling, irreversible damage to the plasma membrane, and organelle breakdown leading to cell death. The stages of cellular necrosis include: 1. Pyknosis (clumping of chromosomes and shrinking of the nucleus of the cell). 2. Karyorrhexis (fragmentation of the nucleus and break up of the chromatin into unstructured granules). 3. Karyolysis (dissolution of the cell nucleus). Cytosolic components that leak through the damaged plasma membrane into the extracellular space can incur an inflammatory response.  TYPES OF DAMAGE: – Apoptosis: Apoptosis is the programmed cell death of excessive or potentially harmful cells in the body. It is an energy dependent process mediated by proteolytic enzymes called caspases, which trigger cell death through the cleaving of specific proteins in the cytoplasm and nucleus. The dying cells shrink and condense into small bodies. Unlike necrotic cell death, neighbouring cells are not damaged by apoptosis as cytosolic products are safely isolated by membranes. Inhibition of apoptosis can result in a number of cancers, autoimmune diseases, inflammatory diseases, and viral infections.  REPAIR AND REGENERATION: When a cell is damaged the body will try to repair or replace the cell to continue normal functions. If a cell dies the body will remove it and replace it with another functioning cell, or fill the gap with connective tissue to provide structural support for the remaining cells. The motto of the repair process is to fill a gap caused by the damaged cells to regain structural continuity. Normal cells try to regenerate the damaged cells but this cannot always happen. Asexual reproduction is what repairs cells.  REPAIR AND REGENERATION: Regeneration: – Regeneration of parenchyma cells, or the functional cells, of an organism. – The body can make more cells to replace the damaged cells keeping the organ or tissue intact and fully functional. Replacement: – When a cell cannot be regenerated, the body will replace it with stromal connective tissue to maintain tissue/organ function. – Stromal cells are the cells that support the parenchymal cells in any organ. Fibroblasts, immune cells, pericytes, and inflammatory cells are the most common types of stromal cells THANKS THE END!