Skip to main content
UploadLanguage (EN)Support
BusinessMobileSocial MediaMarketingTechnologyArt & PhotosCareerDesignEducationPresentations & Public SpeakingGovernment & NonprofitHealthcareInternetLawLeadership & ManagementAutomotiveEngineeringSoftwareRecruiting & HRRetailSalesServicesScienceSmall Business & EntrepreneurshipFoodEnvironmentEconomy & FinanceData & AnalyticsInvestor RelationsSportsSpiritualNews & PoliticsTravelSelf ImprovementReal EstateEntertainment & HumorHealth & MedicineDevices & HardwareLifestyle
Uploaded byAhteshamSami1
PPTX, PDF17 views

1. CELL DEATH 17-5-2023 oral pathology.pptx

Oral pathology

Science◦
Download to read offline
CELL DEATH UNDER THE GUIDANCE OF: DR. PROF. MEGHANAND T. NAYAK HEAD OF DEPARTMENT DR. SHILPA DUTTA MALIK (GUIDE) Presented by; Dr. Mohammad Ahtesham Khan PG 1st year
• CELL DEATH IS THE EVENT OF BIOLOGICAL CELL CEASING TO CARRY OUT ITS FUNCTIONS. THIS MAY BE THE RESULT OF THE NATURAL PROCESS OF OLD CELLS DYING AND BEING REPLACED BY NEW ONES, AS IN PROGRAMMED CELL DEATH, OR MAY RESULT FROM FACTORS SUCH AS DISEASES, LOCALIZED INJURY, OR THE DEATH OF THE ORGANISM OF WHICH THE CELLS ARE PART. • THE BODY IS VERY GOOD AT MAINTAINING A CONSTANT NUMBER OF CELLS. SO THERE HAS TO EXIST MECHANISMS FOR ENSURING OTHER CELLS IN THE BODY ARE REMOVED, WHEN APPROPRIATE. CELL DEATH
 DEATH OF CELLS OCCURS IN TWO WAYS 1. APOPTOSIS – (PROGRAMMED CELL DEATH) VITAL PROCESS THAT HELPS ELIMINATE UNWANTED CELLS—AN INTERNALLY PROGRAMMED SERIES OF EVENTS EFFECTED BY DEDICATED GENE PRODUCTS IN MULTICELLULAR ORGANISMS 2. NECROSIS – (IRREVERSIBLE INJURY) PREMATURE DEATH OF CELLS IN LIVING TISSUE CAUSED BY FACTORS EXTERNAL TO THE CELL OR TISSUE—CHANGES PRODUCED BY ENZYMATIC DIGESTION OF DEAD CELLULAR ELEMENTS
MECHANISMS OF CELL DEATH MECHANISMS OF CELL DEATH CAUSED BY DIFFERENT AGENTS. HOWEVER, CERTAIN BIOCHEMICAL EVENTS ARE SEEN IN THE PROCESS OF CELL NECROSIS:  ATP DEPLETION  LOSS OF CALCIUM HEMOSTASIS AND FREE CYTOSOLIC CALCIUM  FREE RADICALS: SUPEROXIDE ANIONS, HYDROXIDE RADICALS, HYDROGEN PEROXIDE  DEFECTIVE MEMBRANE PERMEABILITY  MITOCHONDRIAL DAMAGE  CYTOSKELETAL DAMAGE
APOPTOSIS  THIS PROCESS HELPS TO ELIMINATE UNWANTED CELLS BY AN INTERNALLY PROGRAM SERIES OF EVENTS EFFECTED BY DEDICATED GENE PRODUCTS. WHICH SERVES SEVERAL VIRAL FUNCTIONS AND SEEN UNDER VARIOUS SETTINGS.  DURING DEVELOPMENTAL, FOR REMOVAL OF EXCESS CELLS DURING EMBRYOGENESIS  TO MAINTAIN CELL POPULATION IN TISSUES WITH HIGH TURNOVER OF CELLS, SUCH AS SKIN.  TO ELIMINATE IMMUNE CELLS AFTER CYTOKINES DEPLETION, AND AUTOREACTIVE T-CELLS IN DEVELOPING THYMUS  TO REMOVE DAMAGED CELLS BY VIRUS  TO REMOVES CELLS WITH DNA DAMAGE BY RADIATION, CYTOTOXIC AGENTS ETC.  HORMONE-DEPENDENT INVOLUTION – ENDOMETRIUM, OVARY, BREASTS ETC  CELL DEATH IN TUMORS
IN THE HUMAN BODY ~ 1 MILLION CELLS ARE PRODUCED EVERY SECOND BY MITOSIS AND A SIMILAR NUMBER DIE BY APOPTOSIS DEVELOPMENT AND MORPHOGENESIS o DURING LIMB FORMATION, SEPARATE DIGITS EVOLVE o ABLATION OF CELLS NO LONGER NEEDED (TADPOLE) HOMEOSTASIS o IMMUNE SYSTEM o > 95% T AND B CELLS DIE DURING MATURATION (NEGATIVE SELECTION) DELETION OF DAMAGED/DANGEROUS CELLS
MECHANISMS OF APOPTOSIS APOPTOSIS CAN BE INDUCED BY VARIOUS FACTORS UNDER BOTH PHYSIOLOGICAL AND PATHOLOGICAL CONDITIONS. IT IS AN ENERGY-DEPENDENT CASCADE OF MOLECULAR EVENTS WHICH INCLUDE PROTEIN CLEAVAGE BY A GROUP OF ENZYMES (CASPASES), PROTEIN CROSS-LINKING, DNA BREAKDOWN. APOPTOSIS IS REGULATED BY A LARGE FAMILY OF GENES SOME OF WHICH ARE INHIBITORY (BCL-2) AND SOME ARE STIMULATORY (BAX).
THERE ARE A NUMBER OF MECHANISMS THROUGH WHICH APOPTOSIS CAN BE INDUCED IN CELLS THE SENSITIVITY OF CELLS TO ANY OF THESE STIMULI CAN VARY DEPENDING ON THE NUMBER OF FACTORS SUCH AS: o THE EXPRESSION OF PRO- AND ANTI-APOPTOTIC PROTEINS (EG. THE BCL-2 PROTEINS OR THE INHIBITOR OF APOPTOSIS PROTEINS). o THE SEVERITY OF THE STIMULUS o THE STAGE OF THE CELL CYCLE.
ROLE OF MITOCHONDRIA IN APOPTOSIS • THE PRO-APOPTOTIC BCL-2 PROTEINS ARE OFTEN FOUND IN THE CYTOSOL WHERE THEY ACT AS SENSORS OF CELLULAR DAMAGE OR STRESS. • FOLLOWING CELLULAR STRESS THEY RELOCATE TO THE SURFACE OF THE MITOCHONDRIA WHERE ANTI-APOPTOTIC PROTEINS ARE LOCATED. • THIS INTERACTION BETWEEN PRO- AND ANTI-APOPTOTIC PROTEINS DISRUPTS THE NORMAL FUNCTION OF THE ANTI-APOPTOTIC BCL-2 PROTEINS AND CAN LEAD TO THE FORMATION OF THE PORES IN MITOCHONDRIA AND THE RELEASE OF CYTOCHROME C AND OTHER PRO-APOPTOTIC MOLECULES FROM THE INTER-MEMBRANE SPACE. • THIS IN TURN LEADS TO THE FORMATION OF THE APOPTOSOME AND THE ACTIVATION OF THE CASPASE CASCADE • THE RELEASE OF CYTOCHROME C FROM THE MITOCHONDRIA IS A PARTICULARLY IMPORTANT EVENT IN THE INDUCTION OF APOPTOSIS. • ONCE CYTOCHROME C HAS BEEN RELEASED INTO THE CYTOSOL IT IS ABLE TO INTERACT WITH THE PROTEINS CALLED APAF-1. THIS LEADS TO THE RECRUITMENT OF PRO-CASPASE 9 INTO A MULTI-PROTEIN COMPLEX WITH CYTOCHROME C AND APAF-1.
CASPASES AND APOPTOSIS • ONE OF THE HALLMARKS OF THE APOPTOSIS IS THE CLEAVAGE OF CHROMOSOMAL DNA INTO NUCLEOSOMAL UNITS. • THE CASPASES PLAY AN IMPORTANT ROLE IN THIS PROCESS BY ACTIVATING DNASES, INHIBITING DNA REPAIR ENZYMES AND BREAKING DOWN STRUCTURAL PROTEINS IN THE NUCLEUS.
PATHWAYS OF APOPTOSIS  The two main pathways of apoptosis are extrinsic and intrinsic. Each requires specific triggering signals to begin an energy- dependent cascade of molecular events.  Each pathway activates its own initiator caspase (8, 9, 10) which in turn will activate the executioner caspase 3.  The extrinsic pathway of apoptosis begins outside a cell when conditions in the extracellular environment determine that a cell must die.  The intrinsic pathway of apoptosis begins when an injury occurs within the cell, and the resulting stress activates the apoptotic pathway
MORPHOLOGY OF APOPTOSIS  SHRINKAGE OF CELLS  CONDENSATION OF NUCLEAR CHROMATIN PERIPHERALLY UNDER NUCLEAR MEMBRANE.  FORMATION OF APOPTOTIC BODIES BY FRAGMENTATION OF THE CELLS AND NUCLEI. THE FRAGMENTS REMAIN MEMBRANE-BOUND AND CONTAIN CELL ORGANELLES WITH OR WITHOUT NUCLEAR FRAGMENTS.  PHAGOCYTOSIS OF APOPTOTIC BODIES BY ADJACENT HEALTHY CELLS OR PHAGOCYTES.  UNLIKE NECROSIS, APOPTOSIS IS NOT ACCOMPANIED BY INFLAMMATORY REACTION.
• IN THIS FETAL THYMUS, THERE IS INVOLUTION OF THYMIC LYMPHOCYTES BY THE MECHANISM OF APOPTOSIS • IN THIS CASE, IT IS AN ORDERLY PROCESS AND A PART OF NORMAL IMMUNE SYSTEM MATURATION. • INDIVIDUAL CELLS FRAGMENT ARE CONSUMED BY PHAGOCYTES TO GIVE THE APPEARANCE OF CLEAR SPACES FILLED WITH CELLULAR DEBRIS. • GENES SUCH AS BCL-2 ARE TURNED OFF AND BAX GENES ARE TURNED ON. • INTRACELLULAR PROTEOLYTIC ENZYMES CALLED CASPASES PRODUCE MUCH CELLULAR BREAKDOWN.
• APOPTOSIS IS A MORE ORDERLY PROCESS OF CELL DEATH IN WHICH THERE IS INDIVIDUAL CELL NECROSIS, NOT NECROSIS OF LARGE NUMBER OF CELLS. • IN THIS EXAMPLE, LIVER CELLS ARE DYING INDIVIDUALLY (ARROWS) FROM INJURY BY VIRAL HEPATITIS. A LARGE PINK CELL UNDERGOING “BALLOONING DEGENERATION” CAN BE SEEN UNDER RIGHT ARROW. • THE CELLS ARE PINK, AND WITHOUT NUCLEI.
NECROSIS • NECROSIS IS THE FORM OF CELL INJURY WHICH RESULTS IN THE PREMATURE DEATH OF CELLS IN LIVING TISSUE BY AUTOLYSIS. • NECROSIS IS THE SUM TOTAL OF MORPHOLOGIC CHANGES THAT FOLLOW CELL DEATH IN A LIVING TISSUE OR ORGAN
• CELLULAR DEATH DUE TO NECROSIS DOES NOT FOLLOW THE APOPTOTIC SIGNAL TRANSDUCTION PATHWAY, BUT RATHER VARIOUS RECEPTORS ARE ACTIVATED AND RESULT IN THE LOSS OF CELL MEMBRANE INTEGRITY AND AN UNCONTROLLED RELEASE OF PRODUCTS OF CELL DEATH INTO THE EXTRACELLULAR SPACE. • THIS INITIATES IN THE SURROUNDING TISSUE AN INFLAMMATORY RESPONSE, WHICH ATTRACTS LEUKOCYTES AND NEARBY PHAGOCYTES, WHICH ELIMINATE THE DEAD CELLS BY PHAGOCYTOSIS. • HOWEVER, MICROBIAL DAMAGING SUBSTANCES RELEASED BY LEUKOCYTES WOULD CREATE COLLATERAL DAMAGE TO SURROUNDING TISSUES • THIS EXCESS COLLATERAL DAMAGE INHIBITS THE HEALING PROCESS. THUS, UNTREATED, NECROSIS RESULT IN THE BUILDUP OF DECOMPOSING DEAD TISSUE AND CELL DEBRIS AT OR NEAR THE SITE OF THE CELL DEATH.
• DEAD CELLS USUALLY SHOW CHANGES IN BOTH THE CYTOPLASM AND IN THE NUCLEUS • CYTOPLASMIC CHANGES  INCREASED EOSINOPHILIA  GLASSY APPEARANCE  GRANULAR OR VACUOLATED CYTOPLASM  SWOLLEN MITOCHONDRIA  MAY ALSO SHOW CALCIFICATION • NUCLEAR CHANGES  KARYOLYSIS  PYKNOSIS  KARYORRHEXIS
CAUSES OF NECROSIS NECROSIS MAY OCCUR DUE TO EXTERNAL OR INTERNAL FACTORS: • EXTERNAL FACTORS MAY INVOLVE:  MECHANICAL TRAUMA (PHYSICAL DAMAGE TO THE BODY THAT CAUSES CELLULAR BREAKDOWN)  DAMAGE TO BLOOD VESSELS (WHICH MAY DISRUPT BLOOD SUPPLY TO ASSOCIATED TISSUE)  THERMAL EFFECTS (EXTREMELY HIGH OR LOW TEMPERATURE CAN RESULT IN NECROSIS DUE TO THE DISRUPTION OF CELLS)
• INTERNAL FACTORS CAUSING NECROSIS INCLUDES: TROPHONEUROTIC DISORDERS: INJURY AND PARALYSIS OF NERVE CELLS. PANCREATIC ENZYMES (LIPASES) ARE THE MAJOR CAUSES OF FAT NECROSIS. IMMUNOLOGICAL BARRIERS : NECROSIS PROGRAMS IN CELL WITH IMMUNOLOGICAL BARRIERS (INTESTINAL MUCOSA) MAY ALLEVIATE INVASION OF PATHOGENS THROUGH SURFACES AFFECTED BY INFLAMMATION. BACTERIAL TOXINS: ACTIVATED NATURAL KILLER CELLS; AND PERITONEAL MACROPHAGES. TOXINS AND PATHOGENS MAY CAUSE NECROSIS; TOXINS, SUCH AS SNAKE VENOM MAY INHIBIT ENZYMES AND CAUSE CELL DEATH.
MECHANISM OF NECROSIS • LOSS OF METABOLIC FUNCTIONS • LOSS OF THE INTEGRITY OF THE CELL MEMBRANE • CESSATION OF THE PRODUCTION OF PROTEINS AND ATP • CELL ORGANELLES SWELL AND BECOME NON-FUNCTIONAL • DEPLETION OF ATP LEADS TO BREAKDOWN OF THE CELL’S ION BALANCE • REDUCED OXYGEN LEVEL (HYPOXIA) • OXIDATIVE STRESS- THE PRESENCE OF EXCESS OXYGEN RADICALS
PATTERNS OF NECROSIS IN TISSUE OR ORGANS • AS A RESULT OF CELL DEATH THE TISSUES OR ORGANS DISPLAY CERTAIN MACROSCOPIC CHANGES: 1. COAGULATION NECROSIS 2. LIQUEFACTIVE NECROSIS 3. FAT NECROSIS 4. CASEOUS NECROSIS 5. GANGRENOUS NECROSIS 6. FIBRINOID NECROSIS
1.COAGULATION NECROSIS • IT IS CHARACTERIZED BY THE FORMATION OF GELATINOUS (GEL-LIKE)SUBSTANCE IN THE TISSUES IN WHICH THE ARCHITECTURE OF THE TISSUE IS MAINTAINED. • COAGULATION OCCURS AS A RESULT OF PROTEIN DENATURATION, CAUSING ALBUMIN TO TRANSFORM INTO THE FIRM AND OPAQUE STATE. • THIS PATTERN OF NECROSIS TYPICALLY SEEN IN HYPOXIC (LOW OXYGEN) ENVIRONMENTS SUCH AS INFARCTION. • IT OCCURS PRIMARILY IN TISSUE SUCH AS KIDNEY, HEART AND ADRENAL GLANDS. • SEVERE ISCHEMIA MOST COMMONLY CAUSES NECROSIS OF THIS FORM
2. LIQUEFACTIVE NECROSIS • IT IS CHARACTERIZED BY THE DIGESTION OF DEAD CELLS TO FORM A VISCOUS LIQUID MASS. • THIS IS TYPICAL OF BACTERIAL, OR SOMETIMES FUNGAL INFECTIONS, BECAUSE OF THEIR ABILITY TO STIMULATE AN INFLAMMATORY RESPONSE. • THE NECROTIC LIQUID MASS IS FREQUENTLY CREAMY YELLOW DUE TO THE PRESENCE OF DEAD LEUKOCYTES AND IS COMMONLY KNOWN AS PUS. • HYPOXIC INFARCTS IN THE BRAIN PRESENTS AS THIS TYPE OF NECROSIS, BECAUSE THE BRAIN CONTAINS LITTLE CONNECTIVE TISSUE, BUT HIGH AMOUNT OF DIGESTIVE ENZYMES AND LIPIDS. • LOTS OF NEUTROPHILS AND CELL DEBRIS CAN BE SEEN.
3. FAT NECROSIS • IT IS A SPECIALIZED NECROSIS OF FAT TISSUE, RESULTING FROM THE ACTION OF ACTIVATED LIPASES ON FATTY TISSUES, SUCH AS THE PANCREAS. • IN FAT NECROSIS, NEUTRAL FATS IN ADIPOSE TISSUE ARE SPLIT INTO FATTY ACIDS AND GLYCEROL, USUALLY AFFECTING THE PANCREAS. • IN THE PANCREAS, IT LEADS TO ACUTE PANCREATITIS, A CONDITION WHERE THE PANCREATIC ENZYMES LEAK OUT INTO THE PERITONEAL CAVITY AND LIQUEFY THE MEMBRANE. • CALCIUM, MAGNESIUM, OR SODIUM, MAY BIND TO THESE LESIONS TO PRODUCE A CHALKY-WHITE SUBSTANCE
4. CASEOUS NECROSIS • CAN BE CONSIDERED A COMBINATION OF COAGULATIVE AND LIQUEFACTIVE NECROSIS, TYPICALLY CAUSED BY MYCOBACTERIA(EG. TUBERCULOSIS), FUNGI AND SOME FOREIGN SUBSTANCES. • THE NECROTIC TISSUE APPEARS AS WHITE AND FRIABLE, LIKE CLUMPED CHEESE. • DEAD CELLS DISINTEGRATE BUT ARE NOT COMPLETELY DIGESTED, LEAVING GRANULAR PARTICLES. • MICROSCOPIC EXAMINATION SHOWS AMORPHOUS GRANULAR DEBRIS ENCLOSED WITHIN A DISTINCTIVE INFLAMMATORY BORDER
5. GANGRENOUS NECROSIS. • IT CAN BE CONSIDERED A TYPE OF COAGULATIVE NECROSIS THAT RESEMBLES MUMMIFIED TISSUE. • IT IS CHARACTERISTIC OF ISCHEMIA(LOSS OF BLOOD SUPPLY) OF LOWER LIMB AND THE GASTROINTESTINAL TRACTS. • SKIN LOOKS BLACK AND DEAD; UNDERLYING TISSUE IS IN VARYING STAGE OF DECOMPOSITION. • INITIALLY, THERE IS COAGULATIVE NECROSIS FROM THE LOSS OF BLOOD SUPPLY (DRY GANGRENE), IF SUPERIMPOSED INFECTION OF DEAD TISSUE OCCURS, THEN THERE IS LIQUEFACTIVE NECROSIS (WET GANGRENE).
6. FIBRINOID NECROSIS • IT IS A SPECIAL FORM OF NECROSIS USUALLY CAUSED BY IMMUNE-MEDIATED VASCULAR DAMAGE. • IT IS MARKED BY COMPLEXES OF ANTIGEN AND ANTIBODIES, REFERRED TO AS IMMUNE COMPLEXES DEPOSITED WITHIN ARTERIAL WALLS TOGETHER WITH FIBRIN. • VESSEL WALLS ARE THICKENED AND PINKISH-RED CALLED “FIBRINOID”.
ORAL CAVITY AND NECROTIC LESIONS o TOOTH DISCOLORATION. o PERIAPICAL GRANULOMA o PERIAPICAL ABSCESS o OSTEORADIONECROSIS o OSTEOMYELITIS o NECROTIZING ULCERATIVE GINGIVITIS (VINCENT’S INFECTION) o ZYGOMYCOSIS o KAPOSI’S SARCOMA o TRAUMATIC ULCERATIONS • CHEMOTHERAPY-RELATED EPITHELIAL NECROSIS • WEGENER’S GRANULOMATOSIS • ORAL SQUAMOUS CELL CARCINOMA • SUBACUTE NECROTIZING SIALADENITIS • SIALADENOSIS (ISCHEMIC) • MUCOEPIDERMOID CARCINOMA • ADENOID CYSTIC CARCINOMA • ANGIOCENTRIC T-CELL LYMPHOMA • CEMENTO-OSSEOUS DYSPLASIA • SIMPLE BONE CYST (TRAUMATIC/HEMORRHAGIC) Based on etiology, pathogenesis of oral diseases, the following lesions are listed under necrotic lesions:
REFERENCES • CELL DEATH, THE ROLE OF PARP, CSABA SZABO. • KARAM J A. (2009). APOPTOSIS IN CARCINOGENESIS AND CHEMOTHERAPY. NETHERLANDS: SPRINGER. ISBN 978-1- 4020-9597-9 • CELL AND MOLECULAR BIOLOGY, NALINI CHANDER, SUSAN VISELLI. • ROCK, KENNETH (2008). “THE INFLAMMATORY RESPONSE TO CELL DEATH”. ANNUAL REVIEW OF PATHOLOGY. 3: 99- 126 • COTRAN RS, KUMAR C (1998). ROBBINS PATHOLOGIC BASIS OF DISEASES. PHILADELPHIA: W.B SAUNDERS COMPANY. ISBN 978-0-7216-7335-6. • FESIK SW, SHI Y (NOVEMBER 2001). "STRUCTURAL BIOLOGY. CONTROLLING THE CASPASES". SCIENCE. 294(5546): 1477–1478. • NIRMALA GJ, LOPUS M (2020). "CELL DEATH MECHANISMS IN EUKARYOTES". CELL BIOL TOXICOL. 36 (2): 145–164. • CRAFT J, GORDON C, TIZIANI A, HUETHER SE, MCCANCE KL, BRASHERS VL (2010). UNDERSTANDING PATHOPHYSIOLOGY (1ST ED.). CHATSWOOD, N.S.W.: ELSEVIER AUSTRALIA. ISBN 978-0729539517. • KUMAR V, ABBAS AK, ASTER JC, FAUSTO N (2010). ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE(8TH ED.). PHILADELPHIA, PA: SAUNDERS/ELSEVIER. PP. 12–41. ISBN 978-1416031215. • MCCONNELL TH (2007). THE NATURE OF DISEASE: PATHOLOGY FOR THE HEALTH PROFESSIONS. BALTIMORE, MAR.: LIPPINCOTT WILLIAMS & WILKINS. ISBN 978-0781753173. • SATTAR (2015). FUNDAMENTALS OF PATHOLOGY(2015TH ED.). CHICAGO, IL: PATHOMA LLC. P. 5. ISBN 978-0-9832246-2-4. • STEVENS A, LOWE JS, YOUNG B, DEAKIN PJ (2002). WHEATER'S BASIC HISTOPATHOLOGY: A COLOUR ATLAS AND TEXT(4TH ED.). EDINBURGH: CHURCHILL LIVINGSTONE. ISBN 978-0443070013. • KUMAR G A, DABBIRU C, NAVYA C. NECROTIC LESIONS OF THE ORAL CAVITY. INTERNATIONAL DENTAL JOURNAL OF STUDENT’S RESEARCH 2021;9(4):197-198.
1. CELL DEATH 17-5-2023 oral pathology.pptx