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NECROSISGANGRENEAPOPTOSIS
PATHOLOGIC CALCIFICATIONS
DR. AKSHAY AGARWAL
DEGENERATION
Definition : It is defined as a retrogressive change in the cell following a cell injury , more so in the cytoplasm than the nucleus, caused by a factor which is not stong enough to cause cell death.
It is a reversible cell injury.
FOUR TYPES :
1. Cellular swelling
2. Fatty change
3. Hyaline change
4. Mucoid change
CELLULAR SWELLING It is the most common and earliest form of cell injury .
Results from impaired regulation of cellular volume
GROSS: The affected organ is enlarged , pale , the cut surface bulges out .
MICROSCOPY :The cells are swollen with cytoplasmic granularity and they compress the surrounding microvasculature.
HYDROPIC CHANGE : Small clear vacuoles are seen in the cells
Organs affected:
Kidney (Large white kidney ) , islets of Langerhans in DM
FATTY CHANGE Occurs due to intracellular accumulation of neutral
fats.
CAUSES:
Excess alcohol consumption,obesity malnutrition ,starvation ,diabetes mellitus, chronic ilnesses , late pregnancy, hypoxia , hepatotoxins [ carbontetra chloride , chloroform , ether,aflatoxins ] certain drugslike estrogen steroids tetracycline etc.
Liver is the most common organ affected . Other organs affected are heart, kidney and skeletal muscle.
FATTY LIVER
Gross :The organ is enlarged yellow tense glistening capsule and rounded margins. C/S – bulges and pale yellow and greasy to touch.
MICROSCOPY
Fat in the cytoplasm of the hepatocytes is seen as clear area which may vary from minute droplets in the cytoplasm of a few hepatocytes [microvesicular] to distension of the entire cytoplasm of most cells by coaslesced droplets [macrovesicular] pushing the nucleus to the periphery of the cell.
Occ. the adjacent cell containing fat, rupture producing fatty cysts
Special stains such Sudan III & IV,Sudan black Oil red O can be employed to demonstrate fat in the tissue
HYALINE CHANGE
Hyaline is a glassy homogenous material that stains pink in H&E sections.
Two types :
1. Intra cellular (epithelial )
2. Extra cellular (connective tissue)
Intra cellular (epithelial ) hyaline :
1. Zenkers degeneration in typhoid.
2. Mallory’s hyaline in ALD
3. Russel bodies in plasma cells
Extra cellular (connective tissue) hyaline
1. Hyaline degeneration of splenic capsule , leiomyomas of uterus.
2. Hyaline arterisclerosis in HT and DM.
3. Copora amylacea in prostate.
MUCOID CHANGE
Epithelial mucin:
Catarrhal infection, cystic fibrosis, mucin secreting tumors.
Connective tissue mucin:
Myxiod degeneration in tumors , dissecting aneurysm of aorta
DEF OF NECROSIS
Focal death along with degradation of tissue by hydrolytic enzymes liberated by cells. accompanied by inflammatory reaction.
NECROSIS
DEF.-It refers to spectrum of morphological changes that follows cell death in living tissue largely resulting from progressive degradative action of enzymes on lethally injured cell.
Irreversible cell injury.
Nucleus – pyknosis, karyolysis, karyorrhexis.
Cytoplasm – homogenous ,intensely eosinphilic.
TYPES
Coagulative Necrosis
Liquefactive Necrosis
Caseous Necrosis
Fat Necrosis
Fibrinoid Necrosis
COAGULATIVE NECROSIS
Mc , caused by sudden cessatiion of blood flow.
Organs commonly affected are kidney , heart , spleen.
Gross :they are pale or anemic & wedge shaped with the base resting under the capsule & apex pointing towards the medulla.
Microscopy: the hallmark of coagulative necrosis is that architectural outlines of cells may be preserved although the cellular details are lost.
LIQUEFACTIVE NECROSIS
Occurs commonly due to ischemic injury and bacterial and fungal infections.
Due to degradation of tissue by the action of powerful hydrolytic enzymes.
Eg : infarct brain , abcess cavity
well defined,soft with liquified centre containing necrotic debris later a cyst wall is formed
-The cystic space contains necrotic cell debris & macrophages containing phagocytosed material.The cyst wall is formed by proliferating capillaries ,inflammatory cells and proliferating glials cells.
CASEOUS NECROSIS
It is found in the centre of tuberculous foci
It combines features of both coagulative ana liquefactive necrosis.
GROSS :The necrotic areas appear dry, cheesy, soft and yellowish
Microscopy :The necrosed foci are structureless ,granular eosinophilicThe surrounding tissue shows chacteristic granulomatous reaction
CAUSES hypoxia,chemical and physical agents.
Microbial agents and immunologic injury.
Changes---cell digestion by lytic enzymes.& denaturation of proteins. manifested morphologically by changes in nucleus &cytoplasm.
CYTOPLASM ---EOSINOPHILIC/WITH VACUOLATION OR DYSTROPHIC CALCIFICATION.
NUCLEUS—PYKNOSIS/KARYOLYSIS/KARYORRHEXIS.
Types of necrosis 5 types.
1)Coagulative necrosis---common type. caused by ischaemia. less commonly by bacterial or chemical agents.
Organs—HEART,KIDNEY & SPLEEN.
GROSS: Focii of coagulative necrosis ;pale firm &slightly swollen. With progression, becomes yellowish softer & shrunken .
Microscopy — cells can be recognized as merely having ghost architecture. the nuclear and cytoplasmic characters are lost. Cells swollen &more eosinophilic along with nuclear changes described. It is infiltrated by inflammatory cells.
Dead cells are phagocytosed./granular debris/fragments of cells.
Heart, coagulative necrosis
(myocardial infarct) - Gross, cross section
Heart, acute myocardial infarct - High power
2)Liquifactive necrosis--- combination of ischemic injury and bacterial or fungal infection. action of strong powerful hydrolytic enzymes. eg; infarct brain, abscess.
Gross— soft with liquefied centre containing necrotic debris. Later cyst wall is formed.
Microscopy— necrotic cell debris/macrophages with phagocytosed material. Cyst wall—proliferating capillaries, inflammatory cells, and gliosis in case of brain. fibroblasts.
Brain, old (cystic) infarct - Gross, coronal cut surface
Brain, liquefactive necrosis, old cerebral infarct
3)caseous necrosis---tuberculous infection.
Gross—resembles cheese are soft granular &yellowish
Microscopy--
Focus is structureless eosinophilic, contains granular debris. granulomatus inflammatory reaction with epitheloid cells, langhans giant cells.or forein body giant cells. peripheral mantle of lymphocytes.
Caseous Necrosis
4)fat necrosis —acute pancreatic necrosis,traumatic fat necrosis.
Gross-yellowish white &firm deposits.micro—cloudy appearance with inflammatory cells.
5)Fibrinoid necrosis —fibrin like material.seen in examples of immunologic injury.
Micro—brighitly eosinophilic hyaline material in vessel walls etc.
P – 215/73. Mesenteric fat necrosis
Omentum, fat necrosis in a case of pancreatitis - Gross
PATHOLOGIC CALCIFICATION
When calcium getrs deposited at sites other than bone and enamel it is called as pathologic or heterotopic calcification.
Two types :
1. Dystrophic
2. Metastatic
DYSTROPHIC
Deposits of Ca salts in dead and degenerated tissue.
Ca metab . is normal
Sr Ca levels normal
Causes : necrosis,infarcts,
thrombi,atheromas , Monckebergs sclerosis etc
METASTATIC
Deposits of Ca salts in normal tissue
Deranged
Hypercalcemia
Hyperparthyroidism,bony destructive lesions ,prolonged immobilisation etc
APOPTOSIS. Programmed & co-ordinated cell death.
Physiologic & pathologic processes.
Morphology: 1.No inflammatory reaction.
2.Death of single cells.3.Cell shrinkage.4.Apoptotic bodies.5.Cytoplasmic blebs & chromatin condensation.
Molecular Changes: 1. Lysosomes & other organelles intact.
2.Genetic activation by protooncogenes; onco-suppressor genes& cytotoxic T-cell mediated target cell killing
“ A FORM OF CELL DEATH DESIGNED TO ELIMINATEA FORM OF CELL DEATH DESIGNED TO ELIMINATE
UNWANTED HOST CELLS THROUGH ACTIVATION OFUNWANTED HOST CELLS THROUGH ACTIVATION OF
COORDINATED , INTERNALLY PROGRAMMED SERIES COORDINATED , INTERNALLY PROGRAMMED SERIES
OF EVENTS REGULATED BY A SET OF GENE PRODUCTSOF EVENTS REGULATED BY A SET OF GENE PRODUCTS ”
DEFINITION
GENETICALLY DETERMINED
BIOLOGICALLY MEANINGFUL
ACTIVE , SELF , DESTRUCTIVE PROCESS
PRO-APOPTOTIC ANTI-APOPTOTIC
Bax , Bad , Bcl-XS , Bak Bcl-2 ,
Bcl-xl
EF , P53 , C-myc A-1 , MCL-
1
NUR-77 , Cyclin-A BAG , PRb
ICE , Ned-2
GENETIC BASIS OF APOPTOSIS
DURING DEVELOPMENT
HOMEOSTASIS OF CELL POPULATION
AS A DEFENCE MECHANISM IN
IMMUNE REACTIONS
CELL DEATH BY DISEASE or
NOXIOUS AGENTS
IN AGING
DURING EMBRIOGENESIS
Implantation
Organogenesis
Developmental involution
Metamorphosis
HORMONE – DEPENDENT INVOLUTION
Menstual loss
Ovarin foll icular atresia during Menopause
Regression of lactating breast after weaning
Prostatic atrophy after castration
CELL DELETION IN INTESTINAL CRYPT EPITHELIA
CELL DEATH IN TUMORS
DEATH OF NEUTROPHILS IN ACUTE INFLAMMATION
DEATH OF IMMUNE CELLS
IN DUCT OBSTRUCTION
VIRAL HEPATITIS ( Councilman bodies )
CELL DEATH PRODUCED BY INJURIOUS STIMULI
( In low doses )
CELL SHRINKAGE
CHROMATIN CONDENSATION
FORMATION OF CYTOPLASMIC BLEBS
and APOPTOTIC BODIES
PHAGOCYTOSIS OF APOPTOTIC CELLS
MORPHOLOGIC EVENTS
PROTEIN CLEAVAGE
PROTEIN CROSS – LINKING
DNA BREAKDOWN
PHAGOCYTIC RECOGNITION
BIOCHEMICAL FEATURES
MECHANISM OF APOPTOSIS
SIGNALING PATHWAY
CONTROL and INTEGRATION STAGE
EXECUTION PHASE
REMOVAL OF DEAD CELLS
SIGNALING PATHWAYS
MORPHOGENS
GROWTH FACTORS
TNFR SUPERFAMILY
DIFFERENTIATION FACTORS
SIGNAL DETERMINANTS (+ or - )SURVIVAL APOPTOSIS
CONTROL AND INTEGRATION STAGE
FAS – FAS LIGAND MODEL
CYTOTOXIC T – LYMPHOCYTE
Bcl – 2 FAMILY PROTEINS
MITOCHONDRIAL MEMBRANE DAMAGE
FORMATION OF PORES
DECREASED MEMBRANE POTENTIAL
MITOCHONDRIAL SWELLING
INCREASED PERMIABILITY
CYTOCHROME – C RELEASE
BINDS - Apaf –1
TRIGGERS INITIATOR CASPASE
APOPTOSIS
EXECUTION PHASE
INITIATOR CASPASE EXECUTION CASPASE
CASPASE 9 ACTIVATE CASPASE 3
BINDS Apaf-1 ACTIVATE CASPASE 6
ACTIVATION OF CAS 8 NUCLEAR & CYTOPLASMIC
CHANGES
APOPTOSIS
APOPTOSIS NECROSIS Cell shrinkage Cell swelling
No inflammatory response Inflammatory response
Death of single cells Death of many contiguous cells
Cytoplasmic blebbing Plasma membrane disruption
Chromatin condensation Nuclear swelling & lysis
Intact lysosomes & other Lysosomal breakdown
organelles
Fragmentation of nucleus & Cell lysis & disentegration
cytoplasm
Phagocytosis by adj ‘ cells Phagocytosis by infl ‘ cells
Physiological & path ‘ stimuli Hypoxia , toxins mainly
Apoptotic bodies Damaged organelles
Programmed cell death Cell death by ATP depletion
Necrosis ApoptosisMorphological changes
Loss of membrane integrity
Begins with swelling of cytoplasm and mitochondria
Ends with total cell lysis
No vesicle formation, complete lysis
Disintegration (swelling) of organelles
Membrane blebbing, but no loss of integrity
Aggregation of chromatin at the nuclear membrane
Begins with shrinking of cytoplasm and condensation of nucleus
Ends with fragmentation of cell into smaller bodies
Formation of membrane bound vesicles (apoptotic bodies)
Mitochondria become leaky due to pore formation involving
proteins of the bcl-2 family.
Necrosis ApoptosisPhysiological significance
Affects groups of contiguous cells
Evoked by non-physiological disturbances (complement
attack, lytic viruses, hypothermia, hypoxia, ischemica,
metabolic poisons)
Phagocytosis by macrophages
Significant inflammatory response
Affects individual cells
Induced by physiological stimuli (lack of growth
factors, changes in hormonal environment)
Phagocytosis by adjacent cells or macrophages
No inflammatory response
GANGRENE necrosis of tissue with superadded putrifaction.usually coagulative.
3types.
DRY GANGREN—seen in distal part of limb due to ischemia. eg toes & FEET IN ATHEROSCLEROSIS
THROMBOANGITISOBLITERANCE.RAYNAUDS.
GROSS-DRY,SHRUNKEN,DARK BLACK.MICRO—SMUDGING OF TISSUE/INFL.GRANULATION TISSUE.
Foot, dry gangrene – Clinical presentation
Wet gangrene —moist tissues. Diabetic foot.high growth of bacteria.bed sores.venous blockage commonly than arterial.due to thrombosis,embolism.
Gross —soft swollen ,putrid rotten dark. eg-bowel gangrene.
Micro —coagulative necrosis with blood,. uleration, inflammatory infiltrate. No clear line of demarcation.
P – 779/83. Extensive Gangrene of small intestine.
Gas gangrene special form of wet gangrene—gas forming clostridia
infectswounds. ms., colonic operation.
GROSS—Swollen, oedematous, crepitant/ dark black, foul smelling.
Microscopy—ms. fibres show coagulative necrosis with liquefaction. gm +bacilli can be identified.
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