Cell injury bkg.pptx Bulet kumar gupta Pathophysiology

Cell injury Homeostasis acidosis

1. PATHOPHYSIOLOGY b.Pharma 3 rd semester unit-1 st CELL INJURY & ADAPTATION Mr. Bulet Kumar Gupta Assistant Professor Sai College of Pharmacy, Mau

2. Homeostasis Homeostasis is the state of steady internal chemical and physical conditions maintained by living systems. When the body monitors a parameter and elicits change to return a parameter to normal, the resulting state is termed homeostasis. A homeostasis example is internal body temperature. If the internal body temp. climbs too high, the body will respond by sweating to cool it off. Once the body has cooled down, homeostasis has been achieved. The goal of homeostasis is to maintain a steady internal environment. 

3. Negative Feedback Mechanism

4. Positive Feedback Mechanism

5. CELL INJURY Cell injury is defined as a variety of stresses a cell encounters as a result of changes in its internal and external environment. Changes in biochemical functioning resulting from the some stress. Various forms of cellular responses to cell injury may be as follows-- CELLULAR ADAPTATIONS- When there is increased functional demand, the cell may adapt to the changes which are expressed morphologically and then revert back to normal after the stress is removed. REVERSIBLE CELL INJURY- When the stress is mild to moderate, the injured cell may recover. IRREVERSIBLE CELL INJURY- While when the injury is persistent cell death may occur. INTRACELLULAR ACCUMULATIONS- Metabolites may accumulate within the cell.

6. (Etiology) The cells may be broadly injured by two major ways: By acquired causes By genetic causes

7. B) By genetic causes— Development disease—Thalidomide Malformation. Cytogenic defect - Change in no. of chromosomes Single gene defect – DNA get permanently damage.

8. PATHOGENESIS OF CELL INJURY Ischemia and Hypoxia results in irreversible changes in structure and function of the cell. i.e. cell death. The pathogenesis of cell injury involves certain events like damage of cell membrane, mitochondrial damage, ribosomal damage, nuclear damage. Activated phospholipases: ( Membrane damage)- Following step involve in pathogenesis of cell membrane damage— Decrease synthesis of Phospholipids Increase degradation of Phospholipids Cytoskeleton damage Increased calcium activates endogenous phospholipases. These in turn degrade membrane phospholipids progressively which are the main constituent of the lipid bilayer membrane.

9. 2) Calcium influx: (Mitochondrial damage)- As a result of continued hypoxia, a large cytosolic influx of calcium ions occurs, especially after reperfusion of irreversibly injured cell. Excess intracellular calcium collects in the mitochondria disabling its function. Morphologically, mitochondrial changes are vacuoles in the mitochondria and deposits of amorphous calcium salts in the mitochondrial matrix. 3) Activated endonucleases: (Nuclear damage)- The nucleoproteins are damaged by the activated lysosomal enzymes such as proteases and endonucleases. Irreversible damage to the nucleus can be in three forms: Pyknosis: Nucleus Shrinks. Karyorrhexis: Nucleus rupture. Karyolysis: Nucleus piece broken down further to their basic building blocks.

10. 4) Ribosome  damage: Damage to ribosomal and cellular proteins such as  protein misfolding , leading to apoptotic enzyme activation.

11. Morphology of cell injury-Adaptive changes

12. Atrophy- It  is a decrease in cell/organ size and functional ability. Causes of atrophy include decreased workload/disuse (immobilization); ischemia (atherosclerosis); lack of hormonal or neural stimulation, malnutrition, and aging. Light microscopic examination shows small shrunken cells with lipofuscin granules. Electron microscopy shows decreased intracellular components and autophagosomes. 2) Hypertrophy-  is an increase in cell size and functional ability due to increased synthesis of intracellular components. Causes of hypertrophy include: Increased mechanical demand can be physiologic (striated muscle of weight lifters) or pathologic (cardiac muscle in hypertension). Hypertrophy is mediated by growth factors, cytokines, and other trophic stimuli and leads to increased expression of genes and increased protein synthesis.

13. 3) Hyperplasia- It  is an increase in the number of cells in a tissue or organ. Some cell types are unable to exhibit hyperplasia (e.g., nerve, cardiac, skeletal muscle cells). Physiologic causes of hyperplasia include compensatory mechanisms (e.g., after partial hepatectomy), hormonal stimulation (e.g., breast development at puberty), and antigenic stimulation (e.g., lymphoid hyperplasia). Pathologic causes of hyperplasia include endometrial hyperplasia and prostatic hyperplasia of aging. Hyperplasia is mediated by growth factors, cytokines, and other trophic stimuli; increased expression of growth-promoting genes (proto-oncogenes); and increased DNA synthesis and cell division.

14. 4) Metaplasia- It is a reversible change of one fully differentiated cell type to another, usually in response to irritation. It has been suggested that the replacement cell is better able to tolerate the environmental stresses. For example, bronchial epithelium undergoes squamous metaplasia in response to the chronic irritation of tobacco smoke. 5) Dysplasia- It refers to the abnormal development of cells within tissues or organs. It can lead to various conditions that involve enlarged tissue, such as hip dysplasia. It can also lead to the formation of precancerous cells. Dysplasia does not always become cancer, but it might. Depending on the type of dysplasia, the risk of Developing cancer varies. Developmental dysplasia is common in children and can affect many parts of the body, including the skeleton. Each type of dysplasia has different risk factors. It is not possible to prevent all types of dysplasia.

15. CELL SWELLING Cell swelling is refers to excessive water accumulation in the cytoplasm of cells, its called Hydropic changes. Organ- Kidney & Liver. MECHANISM Causes- Ischemia, Hypoxia Effects of Poisons.

16. Calcification Calcification is  a process in which calcium builds up in body tissue, causing the tissue to harden . This can be a normal or abnormal process

17. ENZYME LEAKAGE Enzyme leakage refers to the unintentional release of enzymes from cells or organelles into the extracellular space. This can occur as a result of cellular damage, including cell injury or disease, or due to a failure in the normal regulation of enzyme secretion. PATHOGENESIS: The development of Enzyme leakage typically involves the following- 1). Initial injury: Enzyme leakage is triggered by an injury to the cell. such as physical damage, exposure to toxins, or the lack of oxygen & nutrients. 2). Loss of membrane integrity: The injury leads to the loss of integrity of the cell membrane, allowing substances that are normally contained within the cell to leak out into the surrounding tissue.

18. 3). Swelling and lysis: The damaged cell swells and eventually bursts, releasing its contents into the surrounding tissue. This can lead to further damage to nearby cells and tissues, and can also cause the release of harmful substances such as enzymes and free radicals. This process is known as Enzyme leakage. 4. Phagocytosis: Immune cells, such as phagocytes, then move in to engulf and remove the dead cells and cellular debris, helping to prevent inflammation and further tissue damage.