cell injury 2023.pdf

Cell injury and adaptation Objective 1. Cell injury and adaptation 2. Wear & tear cell injury ‫ زينب العلي‬.‫د‬  Cells of our body continuously adjust their structure and function to accommodate change in demand and external stress and this state of equilibrium is referred as homeostasi...

Cell injury and adaptation Objective 1. Cell injury and adaptation 2. Wear & tear cell injury ‫ زينب العلي‬.‫د‬  Cells of our body continuously adjust their structure and function to accommodate change in demand and external stress and this state of equilibrium is referred as homeostasis. When the cells encounter stress which can be Physiological pathological then the cells will undergo adaptation in order to preserve its’ viability and function and to achieve a new steady state of equilibrium. If the adaptive capacity of the cells has been exceeded or the injury was severe and prolonged then cell injury would result, the cell injury may be reversable with in a certain limit and the cell returns to its’ stable baseline state or it may be irreversible leading to death of the affected cells. Cell injury is divided into 1-reversible cell injury :- changes in the cell will disappear when the injurious agent is removed and the cell will return back to normal function and morphology. 2- irreversible cell injury :- when the injurious agent persist or if it is sudden and severe , here the changes will not return to normal and will progress to cell death.  H% j - Thymus gland Causes of cell injury ñ T-cell ↓ iundevgvatual hypoxia % ' % ' anaoxia ↳ hypoximia 1. Oxygen deprivation. → 2. Chemical agents :- as poisons, drugs , carbon monoxide , air pollution. 3. Infectious agents :- such as viruses and bacteria… aelaimnin 4. Immunological reactions :- like in anaphylaxis and autoimmune diseases. 5. Genetic defects as in Down syndrome, sickle cell anaemia. 6. Nutritional imbalance :- as in protein calorie malnutrition , specific vitamine deficiency ,  obesity. mechanism of cell injury 1. ATP depletion 2. Accumulation of Oxygen-derived free radicals (Oxidative stress) generation 3. Loss of Ca+2 homeostasis 4. Defects in plasma membrane permeability 5.Mitochondrial damage damage to the membrane permeability is a consistent feature of most forms of cell injury (except apoptosis) plasma membrane may be directly damaged by bacteria, toxins, viruses, complement components, and many other chemical or physical agents. Alterations of the plasma permeability may be secondary to ATP depletion or from phospholipase activation by the high intracellular Ca+2 concentration.  The major causes of ATP depletion are:- 1- Decrease oxygen supply and nutrients. 2- Mitochondrial damage. 3- Action of some toxins (e.g. Cyanide) Depletion of ATP < 5% to 10% of normal levels has wide rang effects including:- 1- Decrease in the activity of plasma membrane Na inflex and leak of K + out of the cell(cell swelling). 2- Increase anaerobic glycolysis leads to glycogen stores depletion, accumulation of lactic acids and decrease in the PH. The decrease in the PH and ATP cause ribosomal detachment from rough endoplasmic reticulum which results in decrease in protein synthesis. - mitochondrial integrity is critical for cell survival and mitochondria Accumulation of Oxygen-derived free radicals (Oxidative stress) a single electron in an outer orbital they are extremely unstable and readily react with inorganic and organic chemicals. Reactive oxygen species (ROS) :these are byproducts of mitochondrial respiration that are produced normally in the cells but they are degraded and removed by the defense mechanism, like superoxide radicals (O2.-), hydrogen peroxide (H2O2) and OH.-. when the production of (ROS) increases this leads to a condition called oxidative stress, many situations like ischemic-reperfusion injury, chemical injury, radiation injury, O2 toxicity, cellular aging, and tissue injury by inflammatory cells. All these cause damage to the cells by free radicals. Three reactions relevant to cell injury caused by free radicals:- Membrane lipid peroxidation. DNA fragmentation. Cross linking of proteins. Factors that affect the severity of cell injury 1- The type, duration, and the severity of the injurious agent. 2- The type of the cells affected, e.g. neurons are highly susceptible to damage (3-5 minutes are enough to cause injury) while skeletal muscles and fibroblasts are less affected (require hours of ischemia to develop the injury). Morphological changes of reversible cell injury 2 patterns of changes can be recognized by the light microscope : Cellular swelling ;- it is the first manifestation of almost all forms of injury. Grossly when all cells in an organ are affected there is pallor , increase turgor and increase in weight. Microscopically small clear vacuoles may be seen with in the cytoplasm they represent distended segments of endoplasmic reticulum, these changes are called hydropic changes or vacuolar degeneration. Fatty changes :- occur in hypoxic injury , toxins and metabolic injury seen as lipid vacuoles in the cytoplasm , mainly seen in hepatocytes and myocardial cells. Morphologic changes in reversible and irreversible cell injury (necrosis). (A) Normal kidney tubules with viable epithelial cells. (B) Early (reversible) ischemic injury showing surface blebs, increased eosinophilia of cytoplasm, and swelling of occasional cells. (C) Necrotic (irreversible) injury of epithelial cells, with loss of nuclei and fragmentation of cells and leakage of contents.  Cellular adaptation to injury Cells counteract changes in their external environment whether physiological or pathological by undergoing changes to modulate their environment and escape injury , these changes are collectively known as adaptive responses. The adaptive responses include the following :- 1- Atrophy. 2- Hypertrophy. 3- Hyperplasia. 4- Metaplasia.  Atrophy it is the shrinkage in cell size caused by loss of cell substance , when sufficient number of cells are involved the entire organ or tissue diminishes in size (remember that atrophied cells are not dead yet). Atrophy may be caused by :- 1- Decrease in workload (e.g. immobilization of the limb for any reason). 2- Loss of innervations. 3- Decrease in blood supply. 4- Inadequate nutrition. 5- Loss of endocrine stimulation. 6- Aging.  Lipofuscin granules in the myocytes finely granular yellow-brown pigment within the cytoplasms of the myocardial fibers lipofuscin granules representing the indigestible residues of autophagic vacuoles formed during aging and atrophy Brain atrophy due to aging and atherosclerosis compared to a normal brain loss of brain substance narrows the gyri and widens the sulci Hypertrophy it is the increase in cell size and consequently an increase in organ size , it is due to synthesis of more structural components within the cell. Hypertrophy can be physiological or pathological, examples :- The massive physiological hypertrophy of the uterus during pregnancy. Skeletal muscles hypertrophy in weight lifters. Cardiac muscle hypertrophy that occur with hypertension.  Hypertrophy of the ventricular wall as compared with a normal ventricle on the left a cross section of the heart clearly shows left ventricular hypertrophy. The wall of the left ventricle is much thicker than normal.  Hyperplasia it is the increase in the number of cells in an organ or tissue hypertrophy and hyperplasia are closely related and often occur at the same time in tissues so both contribute to the increase in organ size.Hyperplasia can be:- Physiological hyperplasia:-which is either ; 1- Hormonal hyperplasia (like glandular proliferation of female breast in pregnancy ). 2- Compensatory hyperplasia that occur when part of tissue is removed or diseased. Pathological hyperplasia :-which is either: 1- Excessive hormonal stimulation :-like endometrial hyperplasia.  2-Growth factor stimulation :- like skin wart caused by Hyp erpl asia of the cer vica l epit heli um The cells of the cervical epithelium are increased in number with normal morphology End ome trial hyp erpl asia Metaplasia it is a reversible change in which one cell type (epithelial or mesenchymal ) is replaced by another cell type. Squamous metaplasia of respiratory epithelium in cigarette smokers(the normal columnar ciliated epithelium of trachea and bronchi is replaced by stratified squamous epithelium ) Although the metaplastic squamous epithelium has survival advantages, important protective mechanisms are lost, such as mucus secretion and ciliary clearance of particulate matter, furthermore the influences that induce metaplastic transformation, if persistent, may predispose to malignant transformation of the  Irreversible cell injury With persistent injury the cell passes to the point of no return and undergo cell death, although there are no definitive morphologic or biochemical correlates of irreversibility, it is consistently characterized by three phenomena: a. Inability to restore mitochondrial function. b. Loss of structure and function of cell membrane. c. Loss of DNA and chromatin structural integrity. Irreversible cell injury falls into 2 categories: - Necrosis. Apoptosis. Necrosis it is the sequence of morphological changes that follow cell death in a living tissue , necrosis results from the degrading action of enzymes and protein denaturation. Cytoplasmic changes include Increase eosinophilia (pink staining). glassy appearance.The cytoplasm become vacuolated (moth eaten).Dead cells calcification may be seen. Nuclear change Pyknosis which is nuclear shrinkage and increase in basophilia ,the DNA condense in a shrinked mass. Karyorrehexis , where the pyknotic nucleus  fragments. Types of necrosis :- Coagulative necrosis:- here the protein denaturation is the primary event , there is preservation of structural outlines of the cell ,the nucleus is lost.results from sudden severe ischemia in organs as heart , kidney.. the best example for this form of necrosis is myocardial infarction. Gangrenous necrosis:- it is not a distinctive form of cell death but the term is still used in surgical practice , it refers to coagulative necrosis of the limb with superimposed infection by bacteria. Liquifactive necrosis:- seen in 2 situations 1.Brain infarcts.2.Abscess. It is characterized by complete digestion of dead cells by enzymes and the necrotic area is liquefied at the end (i.e. converted into a cyst filled with debris and fluid). Coagulative necrosis. (A) A wedge-shaped kidney infarct (yellow) with preservation of the outlines. (B) Microscopic view of the edge of the infarct, with normal kidney (N) and necrotic cells in the infarct Fat necrosis :- is a specific pattern of necrosis seen in adipose tissues due to action of lipase most commonly seen in acute pancreatitis. Caseous necrosis:- this type of necrosis is mainly seen in the center of tuberculus infection and the term caseous is derived from the cheesy white gross appearance of the central necrotic area. microscopically the necrotic focus is composed of structureless amorphous pinkish debris enclosed in a ring of granulomatous inflammation.unlike coagulative necrosis the tissue architecture is completely obliterated Fibriniod necrosis is a special form of necrosis usually seen in immune reactions involving blood vessels Liquifactive necrosis of brain tissue  Fat necrosis The areas of white chalky deposits represent foci of fat necrosis with calcium soap formation (saponification) at sites of lipid breakdown in the mesentery. Caseous necrosis in the lymph node appear as cheasy white material  Fibrinoid necrosis an artery in a patient with polyarteritis nodosa. The wall of the artery shows a circumferential bright pink area of necrosis with protein deposition and inflammation Apoptosis is a distinctive mode of cell death , it can be regarded as a form of [cellular suicide] it is responsible for the programmed cell death in many important physiological as well as pathological processes including 1-During embryogenesis it is responsible for shaping various organs and structures. 2-Hormone dependent physiological involution (involution of the endometrium during the menstrual cycle. 3-Cell deletion in proliferating populations such as intestinal crypt epithelium 4-Deletion of autoreactive T cells in the thymus. 5-A variety of mild injurious stimuli (heat, radiation, drug…..) that cause irreparable DNA damage that will by itself trigger apoptosis. Morphology of apoptosis it usually involve single cells or clusters of cells that appear as round oval masses with intense eosinophilic cytoplasm , condensed nuclear chromatin that aggregate at the periphery under the nuclear membrane into masses with different sizes and shapes and finally nuclear karryorrhexis occurs. The cell then rapidly shrink and form cytoplasmic buds and fragments into apoptotic bodies ,the fragments are then quickly extruded to be phagocytosed or degraded. Morphologic appearance of apoptotic cells. Apoptotic cells (some indicated by arrows) Note the fragmented nuclei with condensed chromatin and the shrunken cell bodies, some with pieces falling off.