NecrosisNecrosis

Dr. Sarvajeet SinghDr. Sarvajeet Singh

M.D. ( Pathology)M.D. ( Pathology)

Irreversible cell injury or cell death occurs as a focal Irreversible cell injury or cell death occurs as a focal change or generalised throughout the body (during change or generalised throughout the body (during end of life).end of life).

Focal cell death occurs as Focal cell death occurs as

1. Necrosis1. Necrosis

2. Apoptosis2. Apoptosis

NecrosisNecrosis Results from action of degenerative hydrolytic enzymes Results from action of degenerative hydrolytic enzymes

on lethally damaged cellson lethally damaged cells.. Enzymes released either from lysosomes of dying cells Enzymes released either from lysosomes of dying cells

(Autolysis)(Autolysis) or leucocytes that infiltrate during or leucocytes that infiltrate during

inflammatory reactioninflammatory reaction (Heterolysis).(Heterolysis).

Morphology-Morphology- Necrotic cells appear Necrotic cells appear

1. intense eosinophilic due to increased binding of 1. intense eosinophilic due to increased binding of eosin to denatured cytoplasmic proteins & loss of eosin to denatured cytoplasmic proteins & loss of basophilia normally imparted by RNP. basophilia normally imparted by RNP.

2. Cytoplasmic vacuolations due to digested 2. Cytoplasmic vacuolations due to digested organelles.organelles.

3. Dead cells might replace by myelin figures 3. Dead cells might replace by myelin figures (phospholipid masses). Either phagocytosed or (phospholipid masses). Either phagocytosed or degraded into fatty acids & undergo degraded into fatty acids & undergo saponification. saponification.

4.Nucleus undergoes one of three patterns -4.Nucleus undergoes one of three patterns -Karyolysis-Karyolysis-decreased basophilia due to effect of decreased basophilia due to effect of DNAse/ DNAse/ Karyorrhexis-Karyorrhexis-NuclearNuclear fragmentation/fragmentation/ PyknosisPyknosis-Increased basophilia-DNA condenses-Increased basophilia-DNA condenses

Patterns of Tissue NecrosisPatterns of Tissue Necrosis Morphological patterns of tissue necrosis give clue Morphological patterns of tissue necrosis give clue

about the underlying cause.about the underlying cause.

1. Coagulative necrosis1. Coagulative necrosis

commonest pattern.commonest pattern.

Cells dead but preserve cell outlines & tissue Cells dead but preserve cell outlines & tissue architecture for several days.architecture for several days.

Denaturation of structural proteins & enzymes as well Denaturation of structural proteins & enzymes as well so inhibits proteolysis of dead cells . Later cells so inhibits proteolysis of dead cells . Later cells phagocytosed by infiltrating leucocytes & digestion by phagocytosed by infiltrating leucocytes & digestion by their enzymes.their enzymes.

Found in ischemic necrosis of solid organs except the Found in ischemic necrosis of solid organs except the brain.brain.

Coagulative Necrosis in Coagulative Necrosis in Myocardial InfarctionMyocardial Infarction

2. Liquifactive / Colliquative Necrosis2. Liquifactive / Colliquative Necrosis

Complete digestion of dead cells by hydrolytic enzymes & Complete digestion of dead cells by hydrolytic enzymes & transforms tissue into a liquid viscous mass.transforms tissue into a liquid viscous mass.

e.g. Hypoxic death of cells of Brain & focal bacterial e.g. Hypoxic death of cells of Brain & focal bacterial ( abscess)( abscess) & fungal infections (stimulate accumulation of inflammatory & fungal infections (stimulate accumulation of inflammatory cells).cells).

3. Caseous Necrosis3. Caseous Necrosis Term Caseous (cheese like) derived from friable yellow white Term Caseous (cheese like) derived from friable yellow white

appearance of necrosis. appearance of necrosis. Type of Coagulative necrosis.Type of Coagulative necrosis. MicroscopicallyMicroscopically – Collection of lysed cells enclosed within an – Collection of lysed cells enclosed within an

inflammatory border. inflammatory border. ((granuloma) granuloma) Necrosed area appears as Necrosed area appears as eosinophilic, amorphous & granular materialeosinophilic, amorphous & granular material

e.g. Tuberculous granuloma .e.g. Tuberculous granuloma .

Caseous Necrosis-GrossCaseous Necrosis-Gross

Tubercular GranulomaTubercular Granuloma

4 4 . . Fat NecrosisFat Necrosis Focal area of fat destruction resulting from release of Focal area of fat destruction resulting from release of

activated pancreatic lipases into pancreatic activated pancreatic lipases into pancreatic parenchyma & peritoneal cavity.parenchyma & peritoneal cavity.

Enzymes liquify the membranes of fat cells in the Enzymes liquify the membranes of fat cells in the peritoneum & lipases split triglyceride esters contained peritoneum & lipases split triglyceride esters contained in fat cells into fatty acids & glycerol. Fatty acids in fat cells into fatty acids & glycerol. Fatty acids combine with calcium to form grossly visible chalky combine with calcium to form grossly visible chalky white areas white areas (fat saponification).(fat saponification).

Microscopically-Microscopically-

shadowy outlines of necrotic fat cells with basophilic shadowy outlines of necrotic fat cells with basophilic calcium deposits surrounded by inflammatory cells.calcium deposits surrounded by inflammatory cells.

Fat Necrosis –Peritoneal Cavity

Fat NecrosisFat Necrosis

5. Fibrinoid Necrosis 5. Fibrinoid Necrosis

Occurs during immune reactions involving Occurs during immune reactions involving blood vessels.blood vessels.

Immune complexes of antigen & antibodies Immune complexes of antigen & antibodies deposit in the walls of arteries.deposit in the walls of arteries.

Immune complexes along with fibrin leaked out Immune complexes along with fibrin leaked out of the walls of vessels gives bright pink of the walls of vessels gives bright pink amorphous appearance.amorphous appearance.

e.g. Polyarteritis nodosa. Also seen in arterioles e.g. Polyarteritis nodosa. Also seen in arterioles in hypertension.in hypertension.

Fibrinoid NecrosisFibrinoid Necrosis

GangreneGangrene

Gangrenous necrosis-Gangrenous necrosis- Coagulative Coagulative necrosis superimposed with bacterial infection necrosis superimposed with bacterial infection that causes liquifaction & attract leucocytes.that causes liquifaction & attract leucocytes.

e.g. gangrene in limb / bowel.e.g. gangrene in limb / bowel.

Gangrenous inflammationGangrenous inflammation – Inflammation – Inflammation caused by virulent bacteria that cause massive caused by virulent bacteria that cause massive necrosis of tissues.necrosis of tissues.

e.g. Gangrenous appenicitis .e.g. Gangrenous appenicitis .

Types of Gangrene-Types of Gangrene- 1. Dry gangrene 2. Wet1. Dry gangrene 2. Wet Gangrene 3. Gas GangreneGangrene 3. Gas Gangrene

Dry GangreneDry Gangrene – Caused in the most distal parts – Caused in the most distal parts of the limbs e.g. of the limbs e.g. toes ,feettoes ,feet due to ischemia. due to ischemia.

Process initiates from where blood supply is very little Process initiates from where blood supply is very little and bacteria unable to grow rapidly.and bacteria unable to grow rapidly.

Gangrene spreads proximally in the limb until reaches Gangrene spreads proximally in the limb until reaches area with adequate blood supply.area with adequate blood supply.

There is a There is a line of separationline of separation (clear line) between (clear line) between gangrenous & viable part.gangrenous & viable part.

Grossly-Grossly- Gangrenous part looks dark black, dry & Gangrenous part looks dark black, dry & shrunken.shrunken.

Hydrogen sulphide from bacteria + hemoglobin from Hydrogen sulphide from bacteria + hemoglobin from broken RBCsbroken RBCs Iron sulphideIron sulphide (black). (black).

Line of demarcation composed of inflammatory Line of demarcation composed of inflammatory granulation tissue.granulation tissue.

Dry GangreneDry Gangrene

Dry GangreneDry Gangrene

Wet GangreneWet Gangrene – – found in moist tissues & found in moist tissues & organs e.g. mouth, bowel etc.organs e.g. mouth, bowel etc.

Caused due to rapid blockage of venous Caused due to rapid blockage of venous drainage drainage area gets stuffed with blood area gets stuffed with blood bacteria grow rapidly.bacteria grow rapidly.

Toxins from bacteria absorbed in blood & cause Toxins from bacteria absorbed in blood & cause septicemia & death.septicemia & death.

No line of demarcation.No line of demarcation.

Also found in Diabetes due to high sugar content Also found in Diabetes due to high sugar content in tissues.in tissues.

Microscopically –Microscopically – Coagulative necrosis with Coagulative necrosis with congestion of blood vessels, intense inflammation congestion of blood vessels, intense inflammation along with ulceration of mucosa.along with ulceration of mucosa.

Wet Gangrene-Small IntestineWet Gangrene-Small Intestine

Wet Gangrene - LungWet Gangrene - Lung

Wet Gangrene - FeetWet Gangrene - Feet

Gas Gangrene –Gas Gangrene –Form of wet gangreneForm of wet gangrene caused caused by gas forming clostridia.by gas forming clostridia.

e.g. opene.g. open contaminated wounds in muscles, as a contaminated wounds in muscles, as a complication of surgery on colon (normally contain complication of surgery on colon (normally contain Clostridia).Clostridia).

Clostidial toxins cause local necrosis , edema & Clostidial toxins cause local necrosis , edema & systemic manifestations .systemic manifestations .

Grossly-Grossly- area swollen, painful & crepitant due to area swollen, painful & crepitant due to accumulation of gas bubbles in tissues. Later dark accumulation of gas bubbles in tissues. Later dark black in color with foul smelling.black in color with foul smelling.

Microscopically-Microscopically- coagulative necrosis with liquifaction coagulative necrosis with liquifaction and several clostridial bacteria. Surrounded by and several clostridial bacteria. Surrounded by leucocytic infiltration, edema & congestion of blood leucocytic infiltration, edema & congestion of blood vessels. vessels.

Gas Gangrene Gas Gangrene

Pathologic CalcificationPathologic Calcification Abnormal deposition of calcium salts along with small amounts Abnormal deposition of calcium salts along with small amounts

of iron ,magnesium & other salts,in the tissues.of iron ,magnesium & other salts,in the tissues.

Types-Types- A. Dystrophic CalcificationA. Dystrophic Calcification B. Metastatic CalcificationB. Metastatic Calcification Dystrophic calcificationDystrophic calcification Calcium deposition in dead & dying tissues.Calcium deposition in dead & dying tissues. CalciumCalcium metabolism normal & serum calcium levels normal. metabolism normal & serum calcium levels normal. PathogenesisPathogenesis-- involves involves a. Initiationa. Initiation ( Nucleation) ( Nucleation) b. Propagationb. Propagation Initiation Initiation -- extracellularly in membrane bound vesicles derived extracellularly in membrane bound vesicles derived

from degenerating cells. Calcium concentrates in vesicles due from degenerating cells. Calcium concentrates in vesicles due to affinity to membrane phospholipids . Phosphates accumulate to affinity to membrane phospholipids . Phosphates accumulate due to action of membrane bound phosphatases.due to action of membrane bound phosphatases.

Intracellularly occurs in mitochondria of dead & dying cells ( lost Intracellularly occurs in mitochondria of dead & dying cells ( lost capacity to regulate intracellular calcium ) . capacity to regulate intracellular calcium ) .

Propagation-Propagation- intracellular or extracellular propagation intracellular or extracellular propagation of crystal formation.of crystal formation.

Depends on concentration of extracellular calcium & Depends on concentration of extracellular calcium & phosphate ,presence of mineral inhibitors & enhanced phosphate ,presence of mineral inhibitors & enhanced by degree of collaginization .by degree of collaginization .

Examples-Examples- 1.Any type of necrosis1.Any type of necrosis 2.Atheromatous plaques in atheroscelerosis2.Atheromatous plaques in atheroscelerosis 3.Venous thrombi3.Venous thrombi( Phlebolith)( Phlebolith) 4.Hematoma around bones4.Hematoma around bones 5.Dead parasites (hydatid cyst)5.Dead parasites (hydatid cyst) 6.Calcified areas in few tumors.( Psammoma bodies in 6.Calcified areas in few tumors.( Psammoma bodies in

Papillary carcinoma thyroid & meningioma etc.)Papillary carcinoma thyroid & meningioma etc.)

Dystrophic CalcificationDystrophic Calcification

Calcified Hydatid CystCalcified Hydatid Cyst

Psammoma BodyPsammoma Body

Psammoma Bodies

Metastatic CalcificationMetastatic Calcification Occurs in normal tissues.Occurs in normal tissues. Calcium metabolism deranged & serum calcium Calcium metabolism deranged & serum calcium

levels high.( levels high.( Hypercalcemia).Hypercalcemia). Causes of Hypercalcemia-Causes of Hypercalcemia- 1. Increased secretion of parathyroid 1. Increased secretion of parathyroid

hormone-hormone- From parathyroid tumors or other malignant From parathyroid tumors or other malignant

tumorstumors 2. Destruction of bone-2. Destruction of bone- A Accelerated bone ccelerated bone

turnover e.g. prolonged immobilisation, Paget’s turnover e.g. prolonged immobilisation, Paget’s disease, some bone tumors.disease, some bone tumors.

3.Vitamin D related disorders-3.Vitamin D related disorders- Vitamin D intoxication Vitamin D intoxication & sarcoidosis& sarcoidosis4.Renal failure-4.Renal failure- phosphate retention causes phosphate retention causes secondary hyperparathyroidismsecondary hyperparathyroidismMorphologicallyMorphologically-- involves any organ principally involves any organ principally interstitial tissues of blood vessels, kidneys, lungs, & interstitial tissues of blood vessels, kidneys, lungs, & gastric mucosa.gastric mucosa.Appears in Hematoxylin & eosin stain as intra/ Appears in Hematoxylin & eosin stain as intra/ extracellular basophilic deposits. Heterotropic bone extracellular basophilic deposits. Heterotropic bone formation can occur. formation can occur. Special stains –Special stains –Von KossaVon Kossa -black color -black colorAlizarin Red SAlizarin Red S – Red color – Red color

Metastatic CalcificationMetastatic Calcification

Metastatic Calcification -LungMetastatic Calcification -Lung