Cellular Reactions to Injury PDF

CELLULAR REACTIONS TO INJURY By Dr: Thaera H. Fruka Cell injury is responsible about all diseases. So to understand diseases , has to start by knowing what cell injury is. When a cell is exposed to an injurious agent (i.e. the causes of disease) the possible outcomes are: 1. The cell ma...

CELLULAR REACTIONS TO INJURY By Dr: Thaera H. Fruka Cell injury is responsible about all diseases. So to understand diseases , has to start by knowing what cell injury is. When a cell is exposed to an injurious agent (i.e. the causes of disease) the possible outcomes are: 1. The cell may correct the situation or 2. The cell may get a reversible injury or 3. The cell may obtain an irreversible injury & may die. The cell may die via one of two ways: either by necrosis or by apoptosis. the result depends on the type, severity, & duration of the injury & on the type of the cell. Cellular adaptation refers to the ability of cells to adjust their structure and function in response to changes in their environment or stressors. These changes aim to enhance Types of cellular adaptation: Figure 1 A. Hypertrophy: Hypertrophy is increase in the size of cells. Increased workload leads to increased protein synthesis & increased size & number of intracellular organelles which, in turn, leads to increased cell size. The increased cell size leads to increased size of the organ. Examples: the enlargement of the left ventricle in hypertensive heart disease & the increase in skeletal muscle during over workload exercise. B. Hyperplasia: Hyperplasia is an increase in the number of cells. It can lead to an increase in the size of the organ. It is usually caused by hormonal stimulation. It can be physiological as in enlargement of the breast during pregnancy or it can pathological as in Benign Prostatic Hyperplasia- BPH). C. Atrophy: Atrophy is a decrease in the size of a cell. This can lead to decreased size of the organ. The atrophic cell shows autophagic vacuoles which contain cellular fragments from degraded organelles. Atrophy can be caused by: 1. Disuse 2. Malnutrition 3. Decreased endocrine stimulation 4. Denervation( lack of communication between the nerve and the muscle 5. Old age (Sarcopenia) D. Metaplasia: Metaplasia is the replacement of one differentiated tissue by another differentiated tissue. There are different types of metaplasia. Examples include: 1. Squamous metaplasia This is replacement of another type of epithelium by squamous epithelium. For example, the columnar epithelium of the bronchus can be replaced by squamous epithelium in cigarette smokers 2. Osseous metaplasia: This replacement of a connective tissue by bone, for example at sites of injury. Figure 1: Types of cellular adaptation Some of reversible cellular changes & accumulations 1. Fatty change This is accumulation of triglycerides inside parenchymal cells( Hepatocytes, Alveolar cell, Renal tubular cells, and Cardiomyocytes. Fatty change is usually seen in the liver, heart, or kidney. Fatty liver may be caused by alcohol, diabetes mellitus, malnutrition, obesity, & poisonings. These etiologies cause accumulation of fat in the hepatocytes by the following mechanisms: a. Increased uptake of triglycerides into the parenchymal cells. b. Decreased use of fat by cells. c. Overproduction of fat in cells. d. Decreased secretion of fat from the cells. 2. The accumulations of pigments Pigments can be exogenous or endogenous. Endogenous pigments include melanin, bilirubin, hemosiderin, & lipofuscin (inside lysosome). These pigments can accumulate inside cells in different situations. Exogenous pigments include carbon( coal dusts accumulate in lungs and lymphatic nodes- Anthracosis) or injected pigments like Tattoos. a. Melanin Melanin is a brownish-black pigment produced by the melanocytes found in the skin. Increased melanin pigmentation is caused by suntanning & certain diseases e.g. nevus, or malignant melanoma. Decreased melanin pigmentation is seen in albinism( reduced in melanin cells production) & vitiligo ( losing melanin due to melanocytes destruction). b. Bilirubin Bilirubin is a yellowish pigment, mainly produced during the degradation of hemoglobin. Excess accumulation of bilirubin causes yellowish discoloration of the sclerae, mucosae, & internal organs. Such a yellowish discoloration is called jaundice. C. Hemosiderin: Hemosiderin is an iron-containing pigment derived from ferritin. Hemosiderin exists normally in small amounts within tissue macrophages of the bone marrow, liver, & spleen as physiologic iron stores. It accumulates in tissues in excess amounts in certain diseases. Cell death Cells can die via one of the following two ways: 1. Necrosis 2. Apoptosis 1. Necrosis: In necrosis, excess fluid enters the cell, swells it, & ruptures its membrane which kills it. After the cell has died, intracellular degradative reactions occur within a living organism. Necrosis does not occur in dead organisms. In dead organisms, autolysis & heterolysis take place. Necrosis occurs by the following mechanisms: A. Hypoxia B. Free radical-induced cell injury C. Cell membrane damage D. Increased intracellular calcium level Types of necrosis: 1- Cogulative necrosis: most often results from sudden interruption of blood supply to an organ, characterized by general preservation of tissue structural design. It is marked by the following nuclear changes: **Pyknosis: (which is chromatin clumping & shrinking with increased basophilia) ** karyorrhexis: (fragmentation of chromatin), ** karyolysis: (fading of the chromatin material) 2. Liquefactive necrosis Liquefactive necrosis is characterized by digestion of tissue. It shows softening & liquefaction of tissue. It characteristically results from ischemic injury to the CNS. It also occurs in suppurative infections characterized by formation of pus. 3. Fat necrosis Fat necrosis can be caused by trauma to tissue with high fat content, such as the breast or it can also be caused by acute hemorrhagic pancreatitis in which pancreatic enzymes diffuse into the inflamed pancreatic tissue & digest it. 4. Caseous necrosis Caseous necrosis has a cheese-like (caseous, white) appearance to the naked eye. And it appears as an amorphous eosinophilic material on microscopic examination. Caseous necrosis is typical of tuberculosis. 5. Gangrenous necrosis This is due to vascular occlusion & most often affects the lower extremities & the bowel. It is called wet gangrene if it is complicated by bacterial infection which leads to superimposed liquefactive necrosis. Whereas it is called dry gangrene if there is only coagulative necrosis without liquefactive necrosis. Necrosis can be followed by release of intracellular enzymes into the blood, inflammation or dystrophic calcification. Table 1. Table 1: present the difference between Liquefactive Necrosis and Coagulative Necrosis Coagulative Necrosis Liquefactive Necrosis Coagulative Necrosis Feature Bacterial/Fungal infections Ischemia Cause or brain infraction Enzymatic digestion Protein coagulation delays tissues Mechanism rapidly dissolves tissue breakdown Tissue turns into liquid or Tissue architecture is preserved Structure pus.temporarily Soft, liquefied, and Well-founded, pale, and solid Appearance contains pus Brain, abscesses, areas of ,Heart, Spleen, Kidneys Common organs severe inflammation Apoptosis is the death of single cells within clusters of other cells. (Note that necrosis causes the death of clusters of cells.) In apoptosis, the cell shows shrinkage. This is followed by fragmentation of the cells. These fragments are called apoptotic bodies  Pathologic calcification is divided into: 1. Metastatic calcification This is caused by hypercalcemia, resulting from hyperparathyroidism, milk-alkali syndrome, sarcoidosis etc… 2. Dystrophic calcification This occurs in previously damaged tissue, such as areas of old trauma, tuberculous lesions, scarred heart valves, & atherosclerotic lesions. Unlike metastatic calcification, it is not caused by hypercalcemia. Normally, the serum calcium level is at level.