Cell Injury PDF

Cell injury
presented by:
Wesal Ahmed
Faculty of Medicine –University of Gazera
DEFINITION OF PATHOLOGY  Study of suffering  Patho means suffering  Logos means study  It is adiscpling that bridge clinical practice and basic science and it is involve the inv...

Cell injury
presented by:
Wesal Ahmed
Faculty of Medicine –University of Gazera
DEFINITION OF PATHOLOGY  Study of suffering  Patho means suffering  Logos means study  It is adiscpling that bridge clinical practice and basic science and it is involve the investigation of etiology of the disease and the under line pathogenesis. WHAT IS ADISEASE  An abnormal condition that is negatively affect the structure and function of different organ of living organism  Pathology is divided in to two general and systemic Cellular response to stress and injurious stimulus

Cell injury Cell injury result when cells are stressed or severly that no longer able to adapt  Causes cell injury physical agent mechanical trauma, extremes of temperature (burns and deep cold), sudden changes in atmospheric pressure, radiation, electric shock Chemical Agents and Drugs Simple chemicals such as glucose or salt in hypertonic concentrations. Even oxygen, in high concentrations, is severely toxic. poisons, such as arsenic, cyanide, or mercuric alcohol. Chemical Agents and Drugs environmental and air pollutants, insecticides, and herbicides; industrial and occupational hazards, such as carbon monoxide and asbestos; social stimuli, such as alcohol and narcotic drugs; variety of therapeutic drugs. Infectious Agents. viruses bacteria, fungi, Immunologic Reactions. The anaphylactic reaction to a foreign protein or a drug is a prime example, autoimmune disease Oxygen Deprivation. Hypoxia is a deficiency of oxygen, which causes cell injury by reducing aerobic oxidative respiration. Hypoxia is an extremely important and common cause of cell injury and cell death. causes of hypoxia Loss of the oxygen-carrying capacity of the blood, as in anemia. Hypoxemia: reduced amount of oxygen in the blood ischemia loss of blood supply from impeded arterial flow or reduced venous drainage in a tissue. Ischemia compromises the supply not only of oxygen, but also of metabolic substrates, including glucose (normally provided by flowing blood). ischemic tissues are injured more rapidly and severely than are hypoxic tissues. Genetic Derangements. genetic injury may result in a defect as severe as the congenital malformations associated with Down syndrome, caused by a chromosomal abnormality, sickle cell anemia. Nutritional Imbalances. mal nutrition or over nutrition Mechanism of cell injury ATP DEPLETION MITOCONDRIAL DAMEGE INCREASE CYTOSOLIC CALCUM REACTIVE OXYGEN SPEcies Membrane damage Reversible injury generalized swelling of the cell and its organelles; blebbing of the plasma membrane; detachment of ribosomes from the endoplasmic reticulum; and clumping of nuclear chromatin. Laminated structures (myelin figures) derived from damaged membranes of the cell and the plasma membrane and made up of phosphp lipids and calcium. Thank You ….. Irreversible cell injury Necrosis Series of morphological changes resulting from degradating action of enzymes on lethaly injured cells causes 1/intracellular structural and functional proteins denaturations (destroy). 2/Enzymatic digestion. 3/loss of cell membrane integrity Type of Necrosis coagulative necrosis When denaturation is the primary pattern liquefactive necrosis dominant enzyme digestion, caseous necrosis fat necrosis Fibroids Necrosis Coagulative necrosis is most common type of necrosis *it is caused commonly by ischemia in all solid organs except the brain. * preservation of the basic outline of the coagulated cell for a span of at least some days Pathogenesis : Denaturation of enzymes and structural proteins Liquefactive necrosis Is characteristic of focal bacterial or, occasionally, fungal infections, because microbes stimulate the accumulation of inflammatory cells For obscure reasons, hypoxic death of cells within the central nervous system often evokes liquefactive necrosis. The end result is transformation of the tissue into a liquid viscous mass. If the process was initiated by acute inflammation the material is frequently creamy yellow because of the presence of dead white cells and is called pus. Morphology: complete loss of cellular details, the out line also destroy. gangrenous necrosis It is usually applied to a limb, generally the lower leg, that has lost its blood supply and has undergone coagulative necrosis. wet gangrene). When bacterial infection is superimposed, coagulative necrosis is modified by the liquefactive action of the bacteria and the attracted leukocytes Caseous necrosis this form is combination of coagulative necrosis and liquefactive necrosis caseous is derived from the cheesy white gross appearance of the area of necrosis Tissue architecture is completely obliterated. In center of tuberculosis granuloma. microscopic examination, the necrotic focus appears as amorphous granular material amorphous granular debris enclosed within a distinctive inflammatory border known as a granulomatous reaction Unlike coagulative necrosis, the tissue architecture is completely obliterated. Fat necrosis Refers to focal area of fat destruction resulting from release of activated pancreatic lipase into the substance of pancrease and peritoneal cavity. These enzymes leak out and liquefy the membrane of fat cells in the peritoneum and lipases split the triglycerideesters into glyceroland FFA which combind with ca to produced chalcky white area called sabonifications Fat necrosis/ On histologic examination, the necrosis takes the form of foci of shadowy outlines of necrotic fat cells, with basophilic calcium deposits, surrounded by an inflammatory reaction. Fibrinoid necrosis is a term used to describe the histological appearance of arteries in cases of vasculitis (primary inflammation of vessels) and hypertension, when fibrin is deposited in the damaged necrotic vessel wall Change occur in necrotic cell Nuclear change1/pyknosis 2/karyorrhexis 3/karyolysis *Cytoplasmic change : Increased eosinophilia. The cell have glassy homogenous appearance and the cytoplasm becomes vaculated. irreversible injury increasing swelling of the cell; disruption of cellular membranes; swelling and disruption of lysosomes; and profound nuclear changes. nuclear codensation (pyknosis), followed by fragmentation (karyorrhexis) and dissolution of the nucleus (karyolysis). Laminated structures (myelin figures) become more pronounced in irreversibly damaged cells.  APOPTOSIS Apoptosis is a form of ‘coordinated and internally Programmed cell death’ having significance in a variety ofphysiologic and pathologic conditions (apoptosis is a Greek word meaning ‘falling off’ or ‘dropping off’). Causes of apoptosis  physiologic and pathologic processes as under: Physiologic Processes:  Physiologic involution of cells in hormone-dependent tissuese.g. endometrial shedding, regression of lactating breast after withdrawal of breast-feeding.  Destruction of cells during empriogenesis Physiologic Processes:  Physiologic involution of cells in hormone-dependent tissues e.g. endometrial shedding, regression of lactating breast after withdrawal of breast-feeding. Pathologic Processes:  Cell death in tumours exposed to chemotherapeutic agents.  Cell death in viral infections  In degenerative diseases of CNS e.g. in Alzheimer’s disease, Parkinson’s disease, and chronic infective dementias. morphologic changes in apoptosis : 1. Involvement of single cells or small clusters of cells in the background of viable cells. 2. The apoptotic cells are round to oval shrunken masses of intensely eosinophilic cytoplasm (mummified cell) containing shrunken or almost-normal organelles. 3. The nuclear chromatin is condensed or fragmented (pyknosis or karyorrehexis). 4.There may be formation of membrane-bound nearspherical bodies on or around the cell called apoptotic bodies containing compacted organelles. 5. Characteristically, unlike necrosis, there is no acute inflammatory reaction around apoptosis. Cellular adaptation means ability of cellsto respondto various type of stimuli and adverse environmental change Mechanism of apoptosis Intrinsic pathway(mitochondria). Extrinsic pathway  ADAPTATIONS Adaptations – A new altered steady state with structural and functional changes in cell to handle the severe physiologic stress and some pathologic stimuli Cell adaptations are reversible and cell can revert back to normal when the stimuli is removed  CELL ADAPTATIONS HYPERPLASIA Increase in the number of cells in an organ or tissue resulting in increased volume of organ Hyperplasia takes place if the cells are capable of synthesizing DNA , thus permitting mitotic activity Hyperplasia can be a) Physiological b) Pathological  CELL ADAPTATIONS
HYPERPLASIA PHYSOLOGICAL HYPERPLASIA This can be divided into a) Hormonal hyperplasia – increase in functional capacity of a tissue when needed Eg – proliferation of glandular epithelium of female breast b) Compensatory hyperplasia – increase in tissue mass after damage or partial resection Eg – Liver after partial resection  PHYSIOLOGICAL HYPERPLASIA Action of hormones or growth factors Mammary gland hyperplasia in pregnancy and lactation Normal mammary tissue Mammary gland hyperplasia under the influence of estrogen and progesterone  CELL ADAPTATIONS

HYPERPLASIA PATHOLOGICAL HYPERPLASIA It is caused by excessive hormonal stimulation or GF acting on target cells Eg – Endometrial hyperplasia because of estrogen - Benign prostatic hyperplasia because of growth factors Pathologic hyperplasia however constitutes a fertile soil in which cancerous proliferation may eventually arise  ENDOMETRIAL HYPERPLASIA Occurs due to prolonged stimulation by increased estrogen hormone Normal endometrium Endometrial hyperplasia Round tubular Estrogen glands with equal Crowded irregular gland to stromal glands with ratio atypia CAUSES OF HYPERESTROGENISM Granulosa cell tumor, Estrogen replacement therapy, Polycystic ovarian disease, anovulation and obesity  ENDOMETRIAL HYPERPLASIA Occurs due to prolonged stimulation by increased estrogen hormone Normal endometrium Endometrial hyperplasia Round tubular Estrogen glands with equal Crowded irregular gland to stromal glands with ratio atypia CAUSES OF HYPERESTROGENISM Granulosa cell tumor, Estrogen replacement therapy, Polycystic ovarian disease, anovulation and obesity  HYPERPLASIA NORMAL ENDOMETRIUM ENDOMETRIAL HYPERPLASIA  CELL ADAPTATIONS
HYPERTROPHY Hypertrophy refers to an increase in the size of cells , resulting in an increase in the size of the organ (no new cells but larger cells ) This is more common in non-dividing cells eg. Myocardial fibers It can be physiologic or pathologic & is caused by increased functional demand or by specific hormonal stimulation  CELL ADAPTATIONS
HYPERTROPHY Some of the examples of hypertrophy are a) Bulging of muscles in body builders b) Massive physiological growth of the uterus during pregnancy – hormone induced increase in size of an organ c) Hypertrophy of myocardium HYPERTROPHIED UTERUS HYPERTROPHY OF MYOMETRIUM IN UTERUS NORMAL MYOMETRIUM HYPERTROPHIED MYOMETRIUM MYOCARDIAL HYPERTROPHY ADAPTATION TO INCREASED WORK LOAD  MYOCARDIAL HYPERTROPHY NORMAL MYOCARDIUM HYPERTROPHIED MYOCARDIUM  CELL ADAPTATIONS
ATROPHY Reduction in the size of the organ or tissue resulting from decrease in cell size and number is called atrophy This is divided into - a) Physiologic b) Pathologic  CELL ADAPTATIONS
ATROPHY PHYSIOLOGIC ATROPHY Some embryologic structures like thyroglossal duct & Ductus arterioses Decrease in size of the uterus after parturition  CELL ADAPTATIONS
PATHOLOGIC ATROPHY ATROPHY This depends on the underlying cause – a) Decreased work load – immobilized broken limb in plaster cast b) Denervation atrophy c) Diminished blood supply – e.g. Brain in aged d) Inadequate nutrition – Marasmus and cachexia in cancer pts e) Loss of endocrine stimulation f) Ageing ( senile atrophy ) - in brain & heart g) Pressure – tissue compression for long time by enlarging benign tumor  CELL ADAPTATIONS
MECHANISM OF ATROPHY ATROPHY Results from decreased protein synthesis and increased protein degradation by ubiquitin proteosome pathway Nutrient deficiency and disuse may activate ubiquitin ligases which attach the small peptide ubiquitin to cellular proteins and target these proteins for degradation in proteosomes In some cases atrophy is due to autophagy of cells own organelles CELL ADAPTATIONS
ATROPHY NORMAL BRAIN SENILE ATROPHY  CELL ADAPTATIONS
METAPLASIA Metaplasia is a reversible change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type. E.g. a) Columnar to squamous – In habitual smokers , the normal ciliated columnar epithelial cells of trachea & bronchi are replaced by squamous epithelium b) Squamous to columnar – Barrett’s oesophagus  CELL ADAPTATIONS
METAPLASIA Connective tissue metaplasia is the formation of cartilage, bone or adipose tissue in tissues that normally do not contain these elements E.g. Myositis ossificans The influences that predispose to metaplasia if persistent , may induce malignant transformation in metaplastic epithelium METAPLASIA MECHANISM OF METAPLASIA Cytokines, growth factors and extracellular matrix components Signals are generated which stimulates expression of genes which drives towards different differentiation pathway Reprogramming of stem cells Metaplastic change SUMMARY ADAPTIVE CHANGES HYPERPLASIA METAPLASIA Increased in number of cells Change of one type of tissue into other type Physiological Barrett’s esophagus Mammary gland Myositis ossificans Liver HYPERTROPHY ATROPHY Decrease in number and size of Increase in size of the cell Pathological the cell Endometrial hyperplasia Physiological Physiological BPH Skeletal muscle after exercise Ductus arteriosus Pregnant uterus Thyroglossal duct Pathological Pathological Cardiomyopath y The real measure of your wealth is how much you would be worth if you lost all your money THANK YOU