细胞的适应变性与死亡课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,精品课件,病理学,-,适应、变性和死亡,细胞的适应、损伤与死亡,Cellular adaptation,cell injury, and cell death,病理系 刘从容,Congrong Liu Department of Pathology,congrong_liu,精品课件,Adaptation,Cell injury,Altered physiologic stimuli,Injurious stimuli,Metabolic stimuli,Degeneration,Cellular Responses,confined to a very,narrow range,of function and structure,handle normal physiologic demands, maintaining a,steady state,- “homeostasis”,Normal Cell,Stimuli,Cell death,Too much overloaded,Tissue,renewal and r,epair,Inability to adapt,2,精品课件,Cellular A,daptation,Definition,Physiologic stresses or pathologic stimuli,A new, but altered state preserving the viability of the cell, decreased, increased, increased,By, transformation,Size,Number,Type,Atrophy,Hypertrophy,Hyperplasia,Metaplasia,3,精品课件,ATROPHY,Shrinkage in the size of the cell by loss of cell substance,Adaptation,Cell atrophy, tissue atrophy organ atrophy,Physiologic vs. Pathologic,Diminished function, but achieve a new equilibrium - protein synthesis vs. degradation,Common causes,Decreased workload,Loss of innervation,Diminished blood supply,Inadequate nutrition,Aging,（,senile atrophy,）,Loss of endocrine stimulation,Pressure,4,精品课件,Fig 2-5,Normal Thymus,Atrophic Thymus,Physiologic,Atrophy,5,精品课件,Normal,Striated,Muscle,Atrophic Striated,Muscle,Atrophic Skeletal Muscle,Atrophy of Disuse or Innervation Atrophy,Thinner striated muscle fibers by losing sarcoplasm,Looser arrangement, replaced with adipose tissue,6,精品课件,Smooth and convex outer surface, fine granularity,Symmetrically reduced in size and decreased in weight,Alternating areas of atrophy and hypertrophy,Hypertensive heart disease,and,late stage of chronic glomerulonephretis,Granular,Atrophy,of kidney,7,精品课件,Aging (Senile) Atrophy or Ischemic Atrophy,Brown atrophy,Decreased size and thinner walls,Prominent tortuous coronary arteries on the percardial surface,Normal Heart,Brown,Atrophy,of,Heart,Normal Heart,Brown,Atrophy,of Heart,8,精品课件,Pressure Atrophy,of,Brain,Pressure,Atrophy,of,kidney,- Hydronephrosis,Compressed atrophy of kidney,Atrophy,can be manifested as an,increased organ size,Dilated renal pelvis, compressed atrophy of renal,parenchyma,9,精品课件,Morphology of Atrophy,Brown atrophy,residual bodies present in sufficient amounts,a brown discoloration to the tissue,Lipofuscin granules,Some cell debris within the,autophagic vacuole,may resist digestion,Persist as membrane-bound,residual bodies,Remain as a sarcophagus in the cytoplasm,Decreased number of cell,organelles,Increased,autophagic vacuoles,membrane-bound vacuoles,contain fragments of cell components,hydrolytic contents discharged by lysosomes,destined for destruction,Lipofuscin,Granules,Brown,Atrophy,of Heart,10,精品课件,ATROPHY,Adaptation,HYPERTROPHY,Increased cell size by synthesizing more components,Cell hypertrophy, organ hypertrophy,Physiologic vs. pathologic,Specific hormonal stimulation,Increased functional demands,11,Occur,concomitantly with hyperplasia or not,?,Cells,capable of division hypertrophy + hyperplasia,Nondividing cells, hypertrophy only,精品课件,Normal uterus,Hyertrophic Uterus,Normal Uterus,Hyertrophic,Uterus,Normal,Heart,Hyertrophic,Heart,Normal heart,Hyertrophic heart,12,精品课件,ATROPHY,Adaptation,HYPERTROPHY,HYPERPLASIA,Increased number of cells in an organ or tissue,Physiologic,Hormonal hyperplasia & Compensatory hyperplasia ( the myth of Prometheus ),Pathologic,Excessive hormone & locally produced GFs,Abnormal but remains controlled, will regress after stimulation is,eliminated,However, a fertile soil for cancerous proliferation,13,精品课件,Prostate Hyperplasia,14,Prostate Hyperplasia,精品课件,ATROPHY, HYPERTROPHY,&,HYPERPLASIA,Adaptation,METAPLASIA,One,adult,cell,type is replaced by another,adult,cell type,Genetic reprogramming of stem cells induced by cytokines, GFs and extracellular matrix components,An adaptive substitution: sensitive to stress,（,eg. fragile,columnar,better,able to withstand the adverse environment (rugged squamous),Two-edged sword, malignant transformation,Epithelial vs. mesenchymal metaplasia,15,精品课件,Squamous M,etaplasia,of B,ronchial Epithelia,AB/PAS S,taining Shows,G,oblet,C,ells,Intestinal,M,etaplasia,of,Gastric,M,ucosa,Sqamous Metaplasia of Cervical,M,ucosa,精品课件,17,精品课件,Degeneration,Definition,Metabolic derangement,Accumulation,of abnormal amounts of various,substances,Features,Transiently or permanently,Harmless or severely toxic,Located in cytoplasm or nucleus,，,intracelluar or extracelluar,Produced by itself or merely stores products coming from elsewhere,18,精品课件,Causes,A normal endogenous substance is,produced,at a normal or increased rate,but,the rate of metabolism is inadequate,to,remove,it.,Fatty degeneration,in hepatocytes,Hyaline degeneration,in renal tubular cells,A normal or abnormal endogenous,substance,accumulates, because,of,genetic,or acquired,defects,in the,metabolism,packaging, transport, or,secretion,of the substance.,Storage disease,An abnormal exogenous substance is,deposited,and accumulates.,Carbon or tattooing,19,精品课件,water,Degeneration,Normal,cellular constituent,Abnormal substance,Pigments,lipids,proteins,carbohydrate,Cellular swelling,Fatty change,Cholesteral and cholesteral esters,Hyaline change,Amyloidosis,exogenous,endogenous,Carbon & tattooing,lipofuscin,Melanin,Hemosiderin,Bilirubin,Categorized by,stockpiled substance,20,精品课件,Cellular,Swelling,（,Hydropic,C,hange,）,Loss of function of,plasma,membrane,energy-dependent,ion pumps,Incapable of maintaining,ionic and fluid homeostasis,First manifestation,of cell injury,21,精品课件,Morphology,Whole organ: pallor, turgor and increased weight,Enlarged, round and swollen cells. Pale and clear cytoplasm. clear vacuoles.,Swelling and rarefaction of Mt,Pinched,off segments of ER,Hydropic degeneration in hepatocyte,22,精品课件,Fatty,Change (Steatosis),Abnormal accumulation of,triglycerids,within,parenchymal,cells,Causes,Toxins (eg. alcohol abuse), protein malnutrition, diabetes mellitus, obesity and anoxia,Often in,liver,(major organ involved in fat metabolism), also occurs in heart, muscle and kidney,23,精品课件,Significance,More,severe may impair cellular function,A,harbinger of cell death,Nonalcoholic,steatohepatitis may lead to,cirrhosis,and even hepatocellular cancer,When,mild have no effect on cellular function,Morphology,Intracellular clear vacuoles,: Sudan III / Oil red,O staining,24,精品课件,Bright,Yellow,Soft,and,Greasy,Fatty,Change,in,Hepatocyte,Small vacuoles around nucleus,Cleared space displace the nucleus to the periphery of the cell,Fatty cysts,25,精品课件,Cholesterol and cholesterol esters accumulation,Several,pathologic processes,Atherosclerosis,Foam,C,ells,Sudan III,Staining,cholesterol laden atheromas,Normally, in most cells for synthesis of cell membrane,26,精品课件,Xanthomas,Tumourous masses produced by cholesterol laden Macropahges cluster in skin and tendons,Acquired and hereditary hyperlipidemic states,Inflammation and necrosis,Cholesterolosis in gallbladder,Niemann-Pick disease,Lysosomal storage disease,Enzyme involved in cholesterol trafficking is mutated,Cholesterol accumulates in multiple organs,27,精品课件,Proteins,Accumulation,Pathogenesis,Excess in amount,Absorption droplets in proximal renal tubules,Russell bodies in plasma cells,28,精品课件,Causes,A normal endogenous substance is,produced,at a normal or increased rate,but,the rate of metabolism is inadequate,to,remove,it.,Fatty degeneration,in hepatocytes,Hyaline degeneration,in renal tubular cells,A normal or abnormal endogenous,substance,accumulates, because,of,genetic,or acquired,defects,in the,metabolism,packaging, transport, or,secretion,of the substance.,Storage disease,An abnormal exogenous substance is,deposited,and accumulates.,Carbon or tattooing,29,精品课件,Defective intracellular,transport and,secretion,ER stress induced by,unfolded and misfolded,proteins,Aggregation of abnormal,proteins,Defects in,Structure,-,Protein,F,olding,D,efects,Nascent,Polypeptide,Chains,Protein in,Proper,C,onfiguration,Partially folded intermediates,stabilized,by molecular chaperones,30,Familial Hypercholesterolemia,Parkinsons Disease,Certain forms of Amyloidosis,精品课件,Definition,An alteration,within cells,or in,extracellular,space, which gives a,homogenous, glassy, pink appearance,in routine histologic sections stained with H&E.,Hyaline,changes/degeneration,A,descriptive,histologic term,Produced by a variety of alterations, not represent a specific,pattern,of accumulation,31,精品课件,Intra,cellular hyaline changes,Reabsorption droplets; Russell bodies; Mallory,alcoholi,hyalin;,Viral inclusions,Reabsorption droplets in renal tubular cells,Numerous coarse red granules,within,the cytoplasm,Frequently in,glomerulonephritis,32,精品课件,Russell bodies in plasma cells,Round hyaline inclusions,within,cytoplasm,Immunoglobulins,Hugely distend ER,Large homogenous inclusions,33,精品课件,Extra,cellular hyalin,Hyaline degeneration of arterioles in long-standing,hypertension, due to extravasated plasma protein and deposition of basement material,Hyaline degeneration of connective tissue (in old scar),Amorphous pink staining,material,on the wall,Hardening of the wall and,narrowing,of the lumen,Hyaline degeneration of small arteries in spleen,34,精品课件,Amyloidosis,Definition:,A,heterogeneous,group of pathogenic,fibrillar proteins,accumulating in,extracelluar,space.,EM: nonbranching,fibrils,of indefinite,length,and diameter,H&E: an amorphous,eosinophilic, hyaline,extracellular,substance,Not a single disease, only in,common,the deposition of,similar-appearing,proteins,Three major and several,minor,biochemical forms,Other,Features,Likely related to abnormal protein folding,A systemic disease that may involve components of immune system,With progressive accumulation, encroaches on and produces pressure atrophy of adjacent cells,35,精品课件,Chemical,Nature,of,Amyloid Fibrils,Three,major forms,AL,(,a,myloid,l,ight chain protein): derived from plasma cells and contains immunoglobulin monoclonal B cell proliferation,AA,(,a,myloid-,a,ssociated protein): synthesized in liver and elevated in inflammatory states,A,amyloid, mainly in Alzheimer disease,Minor forms of amyloid fibrils,Beta-2-microglobulin,(the component of class I MHC molecules):,in,long-term hemodialysis,36,精品课件,Clinical,Forms,of Systemic,Amyloidosis,Primary amyloidosis (B-cell dyscrasia, AL),Bence Jones protein,(monoclonal light chain secreted in serum by neoplastic B cells and will be excreted in urine),Secondary or reactive amyloidosis (AA),Chronic inflammatory conditions: bronchiectasis, chronic osteomyelitis, rheumatoid arthritis,Hemodialysis-related,Beta-2-microglobulin deposition,Hereditary (AA),37,精品课件,Nodular (tumor-forming deposits, B-cell,dyscrasia),Endocrine amyloidosis (procalcitonin),Amyloidosis of aging: Heart, lung, pancreas,spleen,brain,Localized A,myloidosis,38,精品课件,Amyloidosis in the,liver,Amorphous, eosinophilic, hyaline, extracellular substance,39,精品课件,Exogenous,Carbon: coal dust,(urban life, in,alveoli and regional lymph,nodes);,anthracosis,; emphysema,Tattooing: reside,for the remainder of the life,Endogenous,Lipofuscin:,wear-and-tear or aging pigment, not injurious,Melanin: melanocytes,Bilirubin,：,normal pigment in bile; derived from hemoglobin,but no,iron; normal formation and excretion is vital for,health; jaundice,Hemosiderin,Pigmentation,40,精品课件,Melanin,Bilirubin,41,精品课件,Hemosiderin,Hemoglobin-derived, golden yellow-to-brown, granular or crystalline pigment in which iron is stored in cells,iron,+,apoferritin,Ferritin micelles,Hemosiderin,aggregate,protein,The form iron is stored,Physiologic or pathologic,Local excess: gross hemorrhage,，,eg. common bruise,Systemic overload of iron,：,hemosiderosis,Bright red,(hemoglobin),Green,(biliverdin),Dark red,(bilirubin),Golden yellow,(hemosiderin),42,精品课件,Hemosiderin,coarse, gloden, granular pigment lying within cytoplasm,Prussian blue reaction,specific,for iron,43,精品课件,Pathologic calcification,Dystrophic Calcification,Metastatic Calcification,local,local or systemic,dying tissue (eg.,atheroma, damaged heart valves),normal tissue,normal serum level of calcium,hypercalcemia,Dystrophic calcification in damaged heart valve: fine, white granules or clumps, felt as gritty deposits,calcium,salt in H&E: basophilic, amorphous granular, sometimes clumped, appearance,44,精品课件,Causes,Increased secretion of parathyroid hormone (PTH), Destruction of bone tissue, Renal failure,Metastatic calcification,Affecting,Interstitial tissue of gastric mucosa, Kidneys, Lungs, Pulmonary veins, Systemic arteries,Psammoma Body,Single necrotic cells are encrusted by the calcium and progressively acquire outer layers creating lamellated,configuration,45,精品课件,Reversible cell injury vs. Cell death,No,precise cut-off point,Many ways, but not all fatal,Primary injury or ripple effects ?,“Point of no return” is still largely underdetermined,Two,phenomena characterize irreversibility,Inability to reverse mitochondrial dysfunction,Profound disturbances in membrane function,Leakage of intracelluar proteins provides a means of detecting tissue-specific cellular injury and death using blood serum samples,46,精品课件,Features of,Two Type,of,Cell Death,Necrosis,Apoptosis,Role,Invariable Pathologic,Often physiologic, May be pathologic,Mechanism,ATP depletion, Membrane,injury, Free radicals,Programmed Cell Death,Endonuclease, Gene activation,Nucleus,Pyknosis, karyorrhexis karyolysis,Fragmentation into,nucleosome size fragments,Cell size,Enlarged (swelling),Reduced (Shrinkage),Cellular,Contents,Enzymatic digestion;,May leak out of cell,Intact; May be released in apoptotic bodies,Number,Usu. Massive, occ. Single cell,Single cell or small cluster of cells,Adjacent inflammation,Frequent,No,47,精品课件,APOPTOSIS,(,Programmed cell death ),Literally, apoptosis in Greek,:,refer to eliminate unwanted or potentially harmful cells and cells that are,outlived,their usefulness; also a,when cells are damaged (esp. DNA) beyond repair,.,Pathologic event,“,falling,off ”,Numerous situations,Programmed destruction of cells during embryogenesis,Hormone dependent involution of tissues in the adult,Cell deletion in proliferating cell populations (intestinal crypt epithelia),and lymphoid organs,Cell death induced by cytotoxic T cells, a defense mechanism,48,精品课件,DNA breakdown,：,Endonucleases,multiples of 180-200bp nucleosome-size fragments,DNA ladders,Untrastructural,Features,of,Apoptosis,Protein cleavage by caspases,Nuclear scaffold,Cytoskeletal,protein,DNA ladders,Ch,aracteristic but not specific for apoptosis, also can be seen in necrosis,49,精品课件,Cell shrinkage,：,smaller size, denser cytoplasm, more tightly packed organelles,Formation of cytoplasmic blebs and apoptotic bodies,Lack of inflammation,：,phagocytosis of apoptotic bodies by adjacent healthy cells or macrophages,50,精品课件,Definition of Necrosis,Definition:,a spectrum of the morphologic changes that follow cell death in,living,tissue, resulting from,denaturation,of intracellular proteins and progressive,degradative action,of enzymes,How about cells placed immediately in fixative ?,They are dead but not necrotic,51,精品课件,Karyolysis,DNase Activity,Three,Pattern,of,Nuclear,C,hanges,in,Necrosis,-,chief,microscopic indicators of cellular injury,Karyorrhexis,Fragmentation,of,Pyknotic Nucleus,Pyknosis,DNA Condensation,52,精品课件,Morphologic Appearance of Necrosis,Increased eosinophilia,loss of,RNA,in the cytoplasm,Increased,binding of eosin to,denatured cytoplasmic,proteins,More glassy homogeneous appearance,loss,of glycogen particles,Vacuolated and moth-eaten cytoplasm,cytoplasmic organelles digested by enzymes,Calcification of necrotic cells,lower pH?,53,精品课件,Necrosis Classification,Coagulative necrosis,Denaturation Proteolysis,Liquefactive necrosis,Proteolysis Denaturation,Gangrene,Bacterial infection supervenes on necrotic tissue,Caseous necrosis,Complete dissolution of necrotic tissue,Fat necrosis,A well fixed term, not a specific pattern of necrosis,Fibrinoid necrosis,Mainly in allergic and hypersensitivity state,54,精品课件,Coagulative Necrosis of kidney,Coagulative Necrosis,Denaturation of both structural and enzymatic proteins by injury or the subsequent increasing intracellular,acidosis,Proteolysis,is blocked,Preservation of the basic outline of the coagulated cell for at least some days,Characteristic feature of hypoxic death,Grossly: firm,texture-dense,，,white,，,dry appearance,55,精品课件,Caseous Necrosis,A distinct form of coagulative necrosis,Tuberculosis,Grossly:,s,oft,c,heesy white appearance,Microscopically:,complete breakdown,of necrotic tissue into fine granular,material,completely obliterated,tissue architecture,Caseous Necrosis of TB,Lymph,N,ode,Caseous Necrosis,56,精品课件,Gangrene,A subtype of coagulation necrosis,Dry,Gangrene,of,E,xtremity,Wet,Gangrene,of S,mall Intestine,Gas,Gangrene,of,Deep,S,oft,P,art,57,精品课件,Liquefactive,Necrosis,Pathogenesis,Bacterial,or fungal infections,：,Microbes stimulate the accumulation of inflammatory,cells,abundant,enzymes,Necrotic cells are completely digested,Hypoxic,cell death in c,entral nervous system,Necrotic tissue is transformed into a liquid viscous mass,Loosely reticulated, pale-staining area,Liquefactive Necrosis of Brain,58,精品课件,A descriptive term, focal area of fat destruction, typically occurring as a result of release of activated pancreatic lipase into substance of the pancrease and the peritoneal cavity.,Acute pancreatitis calamitous abdominal enmergency,Escaped activated pancreatic enzymes, liquefy fat cell membrane,split,triglyceride esters,released fatty acids combined with calcium grossly visible chalky white area,Fat Saponification,Fat,Necrosis,59,精品课件,Deeply eosinophilic, amorphous pink material in strands and netlike formations which is similar in color and appearance to fibrin derived from blood,Allergic and hypersensitivity state,Collagen diseases,Necrotic vasculitis,Malignant hypertension,Fibrinoid Necrosis,60,精品课件,Absorption,Discharge,Erosion vs. Ulcer,Sinus vs. Fistula,Cavitation,Encapsulation,Organization,Calcification,Fates,of Necrosis,61,精品课件,Erosion of mucosa,Ulcer of skin,Fistula of intestine,Sinus of wrist skin,62,精品课件,TB cavity of lung,Tuberculoma of,Lung,Discharge,vs. Encapsulation,63,精品课件,Apoptosis,Necrosis,Coagulative,Liquefactive,Fat,Fibrinoid,Adaptation,Cell injury,Altered physiologic stimuli,Injurious stimuli,Metabolic stimuli,Degeneration,Cellular Responses,Cell death,Too much overloaded,Inability to adapt,64,Atrophy,Hypertrophy,Hyperplasia,Metaplasia,Hydropic,Fatty,Cholesteral,Hyaline,Amyloidosis,Lipofuscin,Hemosiderin,Caseous,Gangrene,Erosion,& Ulcer,Sinus Cavitation,Encapsulation,Calcification & Psammoma Body,精品课件,谢谢！,刘从容,congrong_liu,精品课件,