Cellular Injury II PDF - Wasit University 2024

Ministry of Higher Education and Stage: 2nd Scientific Research Module: mechanism of Wasit University disease College of medicine...

Ministry of Higher Education and Stage: 2nd Scientific Research Module: mechanism of Wasit University disease College of medicine Cellular Injury II Dr. Zainab abbas alquraishy M.B.Ch.B C.A.B.H.S, DipRCPath Department of pathology and forensic medicine  :Cell necrosis Morphological changes that follow cell death in a living tissue or.organ Death of groups of contiguous cells in tissue or organ Resulting from degrading action of enzymes on irreversibly.damaged cells with denaturation of cellular proteins Morphological changes cytoplasmic - nuclear - Cytoplasmic changes in necrosis More eosinophilia - Loss of cytoplasmic RNA - Increased binding of eosin to the denatured proteins. More homogeneous appearance - loss of glycogen particles The cytoplasm becomes vacuolated when enzymes have digested the cytoplasmic organelles, Nuclear changes in necrosis chromatin clumping Pyknosis karyorrhexis karyolysis Nuclear changes show one of three patterns, all due to nonspecific breakdown of DNA karyolysis : basophilia of the chromatin may fade -1 Pyknosis, (also seen in apoptotic cell death) is characterized by nuclear -2 shrinkage and increased basophilia. Here the DNA apparently condenses.into a solid, shrunken basophilic mass.Karyorrhexis: fragmentation of the nucleus -3 With the passage of time (a day or two), the nucleus in the necrotic cell totally disappears Liver cell necrosis: Nuclear changes normal pyknosis karyorrhexis karyolysis Morphology of necrosis By electron microscopy, necrotic cells are characterized by : overt discontinuities in plasma membrane, marked dilation of mitochondria with the appearance of large amorphous densities, intracytoplasmic myelin figures, amorphous osmiophilic debris, and aggregates of fluffy material probably representing denatured protein :Types of necrosis 1. Coagulative necrosis. 2. Liquefactive necrosis. 3. Fat necrosis 4. Caseation (caseous) necrosis 5. Gangrenous necrosis  Necrosis is a dynamic process H&E stained section is just a snapshot in time: what one sees depends on the following factors Degree of enzyme release: (more favours liquefactive– (necrosis From lysosomes in dying cells (autolysis) and/or Infiltrating inflammatory cells (heterolysis) Versus Degree of protein denaturation (more favours– (coagulative necrosis Versus Extent to which necrotic debris have been cleared away– enzymatic digestion (autolysis and heterolysis), fragmentation and phagocytosis Coagulative necrosis Outlines of cells are still discernible, but Fine structural details lost. The nuclei are lost. The cytoplasm stains homogeneous deeply eosinophilic Sudden severe ischemia in organs cause denaturation not only of structural proteins but also of enzymes, which blocks proteolysis of the dead cells  Coagulative necrosis Alive Coagulative < Protein denaturation necrosis enzymatic digetsion Cells dead but basic shape and architecture of tissue endures Most common manifestation.of necrosis in tissues Affected tissue maintains.solid consistency  Coagulative necrosis-kidney Normal Infarct The renal cortex has undergone anoxic injury at the left so that the cells appear pale and ghost-like. There is a hemorrhagic zone in the middle where the cells are dying or have not quite died, and then normal renal parenchyma at the far right. This is an example of coagulative necrosis Within the area of necrosis (Lt) the outlines of tubules and glomeruli are still preserved but fine structural details are lost (inset)  Coagulative necrosis Kidney Microscopic view of the edge of the infarct, with normal kidney (N) and necrotic cells in the infarct (I). The necrotic cells show preserved outlines with loss of nuclei, and an inflammatory infiltrate is present  Coagulative necrosis myocardium The necrotic myocytes are intensely eosinophilic with loss of both cross striations & nuclei. The outlines of individual fibres are still maintained. There are inflammatory cells infiltration & RBCs in-between the necrotic fibers. Liquefaction (liquefactive) necrosis Is characteristic of focal bacterial or, occasionally, fungal infections. It is also seen in hypoxic death of cells within the central nervous system. Liquefaction completely digests the dead cells. 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 Lung abscess This is an example of liquefactive necrosis. There is confluent broncho- pneumonia (scattered pale areas) complicated by abscess formation, which is seen here as a cystic cavity (arrow). The contained pus poured off during the sectioning of the lung tissue. Brain infarction: This is an example of liquefactive necrosis; the affected area is wedge-shaped, pale, soft & cystic. Gangrene Gangrenous necrosis :A term used in surgical practice lower limb, intestine = Gangrene coagulative necrosis (ischemia) + liquefactive necrosis (bacterial infection) Two subtypes Dry gangrene 2- Wet gangrene -1  Ganagrene of lower limb Dry gangrene Wet gangrene Caseous necrosis Is a type of coagulative necrosis, seen in tuberculous infection. The term caseous is derived from the cheesy white gross appearance of the area of necrosis. On microscopic examination, the necrotic area appears as amorphous pink granular debris surrounded by granuloma.  CASEOUS NECROSIS B A A- A tuberculous lung with a large area of caseous necrosis containing yellow-white and cheesy debris. B- Caseous necrosis in a hilar lymph node infected with tuberculosis. The node has a cheesy yellow to white appearance. Caseating TB granuloma Caseous necrosis is characterized by amorphous (acellular), granular pink areas of necrosis, surrounded by a granulomatous inflammatory process.  Fat necrosis Involves adipose tissue- Mediated through lipases- Seen in acute pancreatitis.1 breast trauma (traumatic fat necrosis).2 Grossly : chalky white- :Microscopically shadowy outlines of necrotic cells - surrounding inflammatory cells - calcium soaps: bluish deposits - Acute pancreatitis A, The microscopic field shows a region of fat necrosis (right), and focal pancreatic parenchymal.necrosis (center) B, The pancreas has been sectioned longitudinally to reveal dark areas of hemorrhage in the pancreatic substance and a focal area of pale fat necrosis in the peripancreatic fat.(arrow)  Fat necrosis in acute pancreatitis. The areas of white chalky deposits represent foci of fat necrosis with calcium soap formation (saponification) at sites of lipid breakdown in the mesentery.  Acute pancreatitis The fat necrosis consists of fat cells that have lost their nuclei and whose cytoplasm has a granular pink appearance. Some hemorrhage is seen at the left in this case..Fibrinoid necrosis of an artery in polyarteritis nodosa The wall of the artery shows a circumferential bright pink area of necrosis with protein deposition and inflammation (dark nuclei of  Infarction Like gangrene, also not a specific pattern of necrosis Term refers to the CAUSE: when necrosis is due ischaemia i.e. infarct = ischaemic necrosis  Infarction Infarction (ischaemic necrosis) can be coagulative e.g. myocardial infarct– liquefactive e.g. brain infarct– Two further ways of describing infarcts White ;Occlusion of end artery –the usual arrangement– in an organ and therefore commonest pattern Red/haemorrhagic: may occur in the following situations– ;Venous occlusion; Dual blood supply; Loose tissues Previously congested tissues White infarct Red infarct  :Apoptosis This form of cell death is a regulated suicide program in which the relevant cells activate enzymes (CASPASES) capable of degrading the cells' own nuclear DNA and.other nuclear and cytoplasmic proteins Apoptotic cells may appear as round or oval masses with intensely eosinophilic cytoplasm. Nuclei show chromatin condensation and aggregation and, ultimately fragmentation (karyorrhexis). The cells rapidly shrink, form cytoplasmic buds, and fragment into apoptotic bodies composed of membrane-bound vesicles of cytoplasm and organelles. Fragments of the apoptotic cells then break off.(apoptosis = "falling off") These fragments are quickly extruded and phagocytosed without eliciting an.inflammatory response Even substantial apoptosis may be histologically undetectable.Apoptosis is programmed cell death It is a pathway of cell death that is induced by a tightly regulated- intracellular program in which cells destined to die activate their own enzymes to degrade their own nuclear DNA, nuclear proteins.and cytoplasmic proteins The cell's plasma membrane remains intact, but its structure is- altered in such a way that the apoptotic cell sends signal to.macrophages to phagocytose it The dead cell is rapidly phagocytosed and cleared, before its contents have leaked out, and therefore cell death by this pathway does not elicit an.inflammatory reaction in the host Thus, apoptosis is fundamentally different from necrosis, which is characterized by loss of membrane integrity, enzymatic digestion of cells,.and frequently a host reaction.Apoptosis and necrosis sometimes coexist CAUSES OF APOPTOSIS ".Apoptosis means "falling off- It occurs normally in many situations, and serves to eliminate- unwanted or potentially harmful cells and cells that have outlived.their usefulness It is also a pathologic event when cells are damaged beyond- repair, especially when the damage affects the cell's DNA; in these.situations, the irreparably damaged cell is eliminated.Apoptosis can be physiologic, adaptive, and pathologic-  Apoptosis in Physiologic Situations.The programmed destruction of cells during embryogenesis- Hormone-dependent involution in the adult, such as endometrial cell- breakdown during the menstrual cycle, the regression of the lactating breast.after weaning, and prostatic atrophy after castration.Cell deletion in proliferating cell populations,eg. intestinal epithelia- Apoptosis in Physiologic Situations Death of host cells that have served their useful purpose, such as- neutrophils in an acute inflammatory response, and lymphocytes at the end.of an immune response..Elimination of potentially harmful self-reactive lymphocytes- Cell death induced by cytotoxic T cells, a defense mechanism against viruses- and tumors that serves to eliminate virus-infected and neoplastic cells  Apoptosis in Pathologic Conditions Cell death produced by a variety of injurious stimuli eg. radiation and-.cytotoxic anticancer drugs damage DNA.Cell injury in certain viral diseases, such as viral hepatitis- Pathologic atrophy in parenchymal organs after duct obstruction, such as-.occurs in the pancreas, parotid gland, and kidney.Cell death in tumors-  APOPTOSIS vsNECROSIS HISTOLOGICAL FEATURES Apoptosis Necrosis Patterns of death Single cells Groups cells ;Shrinkage Cell size Fragmentation Swelling Plasma membrane Preserved continuity Early lysis Increased membrane permeabilityCytochr Mitochondria ;omec release Swelling; Disordered structure ;Contracted Organelle shape "Apoptotic bodies" Swelling; Disruption Chromatin: Clumped ;Pyknosis; karryhexis Nuclei Fragmented & karyolysis Internucleosomal DNA degradation ;cleavage Diffuse & Random Phagocytosis; No Inflammation; Macrophage Cell degradation inflammation invasion  Apoptosis -triggers Intrinsic Withdrawal of growth stimuli, e.g. growth– factors DNA damage, e.g. p53-induced apoptosis– Extrinsic Death signals, e.g. TRAIL and Fas ligand– Apoptosis -mechanisms Intrinsic Extrinsic (Viral Hepatitis) The cell is reduced in size and contains brightly eosinophilic cytoplasm and a condensed nucleus. The cytoplasm is intensely eosinophilic (pinkish) and the nucleus condensed (pyknotic) Intracellular Accumulations.Intracellular accumulation of abnormal amounts of various substances a normal cellular constituent accumulated in excess, such as water, (1) lipids, proteins, and carbohydrates an abnormal substance, either exogenous, such as a mineral or products (2) of infectious agents, or endogenous, such as a product of abnormal synthesis or metabolism.a pigment (3).The substance may be either the cytoplasm or the nucleus- In some instances, the cell may be producing the abnormal substance, and In others it may be merely storing products of pathologic processes occurring elsewhere in the body  COMMON CAUSES OF INTRACELLULAR ACCUMULATION A normal endogenous substance is produced at a normal or increased rate, -1 but the rate of metabolism is inadequate to remove it. Eg.fatty change in.the liver A normal or abnormal endogenous substance accumulates because of -2 genetic or acquired defects in the metabolism, packaging, transport, or.secretion of these substances. Eg. lysosomal storage diseases An abnormal exogenous substance is deposited and accumulates -3 because the cell has neither the enzymatic machinery to degrade the substance nor the ability to transport it to other sites..Eg.accumulations of carbon particles  LIPID LAW ALL Lipids are YELLOW grossly and WASHED out (CLEAR) microscopically FATTY LIVER FATTY LIVER  PIGMENTS Pigments are colored substances, some of which are normal constituents of cells (e.g., melanin), whereas others are abnormal and collect in cells only.under special circumstances Pigments can be exogenous, coming from outside the body, or endogenous, synthesized within the body itself  Exogenous Pigments The most common exogenous pigment is carbon or coal dust, which is..an air pollutant When inhaled, it is picked up by macrophages within the alveoli and. is then transported through lymphatic channels to the regional.lymph nodes Accumulations of this pigment blacken the tissues of the lungs..(anthracosis) and the involved lymph nodes In coal miners, the aggregates of carbon dust may induce a. fibroblastic reaction or even emphysema and thus cause a serious. lung disease known as coal worker's pneumoconiosis ANTHRACOSIS Exogenous Pigments Tattooing is a form of localized, exogenous pigmentation of the skin..The pigments inoculated are phagocytosed by dermal macrophages  Endogenous Pigments they all look the same, (e.g., hemosiderin, melanin, lipofucsin, bile), in that hey are all golden yellowish brown on “routine” Hematoxylin & Eosin (H&E) stains.Lipofuscin is an insoluble pigment, also known as wear-and-tear or aging pigment-.Lipofuscin is not injurious to the cell or its functions Its importance lies in its being the telltale sign of free radical injury and lipid.peroxidation In tissue sections, it appears as a yellow-brown, finely granular intracytoplasmic, often perinuclear pigment It is prominent in the liver and heart of aging patients or patients.with severe malnutrition and cancer cachexia.Hemosiderin/Melanin/etc  Pathologic Calcification.Pathologic calcification is the abnormal tissue deposition of calcium salts There are two forms of pathologic calcification. When the deposition occurs locally in dying tissues, it is known as dystrophic calcification; it occurs despite normal serum levels of calcium and in the absence of.derangements in calcium metabolism In contrast, the deposition of calcium salts in otherwise normal tissues is known as metastatic calcification, and it almost always results from hypercalcemia secondary to some disturbance in.calcium metabolism THANK YOU