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INRODUCTION  Cell death is a state of irreversible injury  May occur as  Local/Focal change  Apoptosis & Necrosis

 Changes that follow  Gangrene & Pathologic calcification

normal cell mild damaging stimulus Removal of cause of damage

Sublethal cell injury continued damage

cell death

Irreversible cell injury



APOPTOSIS  Falling off  Physiological cell death  Generally, affects single cell or cluster of cells

APOPTOSIS  Appearance  Shrunken cell  Closely packed, intact cytoplasmic organelles  Nuclei show condensed chromatin

APOPTOSIS  Apoptotic bodies  Cell breaks down into membrane bound structures  Phagocytosed by neighboring phagocytes

APOPTOSIS  Not associated with inflammatory reaction or fibrosis  Examples  Normal hormone dependent endometrial shedding during menstruation  Pink shrunken Councilman bodies in viral hepatitis  Cell damage by radiation and UV light

From The biology of cancer, Weinberg


Morphological changes Affected cells Cell volume Chromatin Lysosomes Mitochondria Inflammatory response Cell fate

Molecular changes Gene activity Chromosomal DNA Ca2+ intracellular Ion pumps


Programmed tissues Programmed remodelling Genomic damage Hypoxia Hypoxia

Metabolic stresses Metabolic Changes in pH, temperature Changes Hypoxia, anoxia Injuries Injuries

Individual cells Decreased Condensed Unaffected Normal initially None Apoptotic bodies are phagocytated

Group of cells Increased Fragmented Abnormal Aberrant morphologically Marked Lysis

Required Not needed Cleaved at specific sites Random cleavage Increased Unaffected Functioning Lost


Wilde, 1999


NECROSIS  Definition  Necrosis is defined as focal death and autolysis of a tissue

 Invariably accompanied by inflammatory reaction

NECROSIS  Causes  Hypoxia  Chemical and physical agents  Microbial agents  Immunological injury

NECROSIS  Essential changes  Cell digestion by lytic enzymes  Denaturation of proteins

NECROSIS  Morphologically – characteristic cytoplasmic and nuclear changes  Cytoplasm – homogenous and intensely eosinophilic  Nuclear Changes  Pyknosis- condensation of nuclear chromatin  Karyolysis – dissolution of nucleus  Karyorrhexis - fragmentation into many granular clumps






Types of NECROSIS  Coagulative necrosis  Liquefaction necrosis –Colliquative necrosis  Caesous necrosis  Fat necrosis  Fibrinoid necrosis

COAGULATIVE NECROSIS  Most common type of necrosis  irreversible focal injury  Causes  Sudden cessation of blood flow (ischemia)  Bacterial & chemical agents

 Commonly affected heart, kidney and spleen

COAGULATIVE NECROSIS  Grossly,  Early stage – pale, firm & slightly swollen  Progression – more yellowish, softer & shrunken

Coagulative necrosis of the left ventricular wall


Hard Palate Necrosis after Bilateral Internal Maxillary Artery Embolization for Epistaxis

Splenic Infarction - Coagulative necrosis

Renal Infarction - Coagulative

COAGULATIVE NECROSIS  Microscopically,  Tombstones – hallmark feature  Outlines of the cells are retained – cell type can recognized  Cytoplasmic and nuclear details are lost

 Necrosed cells – swollen & more eosinophilic

COAGULATIVE NECROSIS  Probable cause for the microscopic change  Denaturation of structural and enzymatic proteins

 No cell digestion and liquefaction  Necrotic focus is infiltrated by inflammatory cells and the dead cells are phagocytosed leaving granular debris and fragments of cells

Renal Infarction - Coagulative necrosis

Myocardial Infarction- Necrosis

LIQUEFACTION NECROSIS  Colliquative necrosis  Commonly causes  Ischeamic injury  Bacterial infection

 Due to degeneration of tissue by the action of powerful hydrolytic enzymes  Examples – Infarct brain & abscess cavity

LIQUEFACTION NECROSIS  Grossly,  Area is soft with liquefied centre containing necrotic debris  Later, cyst wall is formed

Liquefactive Necrosis

Stroke- Liquifactive necrosis

Lung abscess: Liquifactive necrosis

LIQUEFACTION NECROSIS  Microscopically,  Cystic space contains  Necrotic cell debris  Macrophages filled with phagocytosed material

 Cyst wall formed by  Proliferating capillaries  Inflammatory cells  Gliosis (proliferating glial cells) – Brain  Proliferating fibroblasts - Abscess cavity

Liver abscess: Liquifactive necrosis

CASEOUS NECROSIS  Found in the centre of tuberculous infections  Combines the features of coagulative and liquefactive necrosis

CASEOUS NECROSIS  Grossly,  Foci of caseous necrosis  Resemble dry cheese and are soft, granular and yellowish  Partly attributed to histotoxic effects of lipopolysaccarides present in the capsule of the tubercle bacilli, Mycobacterium tuberculosis

A tuberculous lung with a large area of caseous necrosis ROBBINS BASIC PATHOLOGY , 2003 )

Caseous necrosis Tuberculosis hilar lymphnode

Extensive Caseous necrosis Tuberculosis

CASEOUS NECROSIS  Necrosed foci  Structure less, eosinophilic and contain granular debris

 Surrounding tissue  Granulomatous inflammatory reaction  Epitheloid cells  Interspersed Langhans’ or foreign body type giant cell  Peripheral mantle of Lymphocytes


Langhans Giant cell

Foreign body type Giant cell


Caseous necrosis - Tuberculosis

FAT NECROSIS  Special form of cell death  Acute pancreatic necrosis  Traumatic fat necrosis commonly in breasts

FAT NECROSIS  In pancreas  Liberation of pancreatic lipase from injured or inflammed tissue  Results in necrosis of pancreas as well as of the fat depots throughout the peritoneal cavity  Sometimes, even affecting the extra-abdominal adipose tissue

FAT NECROSIS  Damaged adipose cells - cloudy appearance  Only free fatty acids remains after glycerol leaks out  Free fatty acid – complex with calcium to form calcium soaps (saponification)

FAT NECROSIS  Grossly,  Yellowish white and firm deposits  Formation of calcium soaps imparts the necrosed foci firmer and chalky white appearance

FAT NECROSIS  Microscopically,  Fat cells have cloudy appearance  Surrounded by an inflammatory reaction  Calcium soaps – amorphous, granular and basophilic material

Fat Necrosis - Peritoneum.

Fat Necrosis

FIBRINOID NECROSIS  Characterized by deposition of fibrin like material  Immunologic tissue injury   

Immune complex vasculitis Autoimmune diseases Arthus reaction

 Arterioles in hypertension  Peptic ulcer

FIBRINOID NECROSIS  Histologically  Brightly eosiniophilic, hyaline like deposition in the vessel wall or on the luminal surface of a peptic ulcer  Local haemmorages may occur due to rupture of these blood vessels

Fibrinoid change in blood vessel


GANGRENE  It is a form of necrosis of tissue with superadded putrefaction  Necrosis is usually coagulative  Due to ischemia  Gangrene of bowel, gangrene of limbs

 Due to infection  Acute appendicitis

Coagualtive necrosis undergoes liquefaction by the action of putrefying bacteria

DRY GANGRENE  Caused by a reduction of blood flow through the arteries.  It appears gradually and progresses slowly  In most people, the affected part does not become infected.  In this type of gangrene, the tissue becomes cold and black, begins to dry, and eventually sloughs off.

DRY GANGRENE  Dry gangrene is commonly seen in people  with blockage of arteries (arteriosclerosis) resulting from increased cholesterol levels,  Buerger’s disease –thromboangiitis obliterans  Raynaud’s disease  trauma  Ergot poisoning

DRY GANGRENE  Line of separation – gangrenous part and viable part  Initiated in one of the of the toes - farthest from blood supply that even bacteria find it difficult to grow in the necrosed tissue.  Slowly spreads upwards until a point is reached where blood supply is adequate to keep the tissue viable

DRY GANGRENE  Macroscopically,  Affected part is dry, shrunken and dark black, resembling the foot of a mummy  Black colour – iron sulphide - action of hydrogen sulphide (bacteria) on the haemoglobin (haemolysed red blood cell)  Line of separation –complete separation – eventual falling off of the gangrenous tissue

Dry gangrene

Gangrene - Diabetic foot

DRY GANGRENE  Microscopically,  Necrosis with smudging of the tissue  Line of separation – inflammatory granualtion tissue

Gangrene - Amputated Diabetic foot

WET GANGRENE  Wet or moist gangrene develops as a complication of an untreated infected wound.  Swelling resulting from the bacterial infection causes a sudden stoppage of blood flow.

WET GANGRENE  Occurs in naturally moist tissues and organs       

Mouth- Cancrum oris Bowel Lung Cervix Vulva Diabetic foot – high sugar Bed sores – pressure on sites –buttocks, sacrum and heels

WET GANGRENE  Cessation of blood flow facilitates invasion of the muscles by the bacteria and multiplication of the bacteria because white blood cells cannot reach the affected part.

WET GANGRENE - clinically  The affected area becomes swollen and decays.  It is extremely painful.  Local oozing occurs.  It produces a foul-smelling odor.  It becomes black.  The affected person develops a fever.

WET GANGRENE  Macroscopically,     

Soft Swollen Putrid Rotten Dark

Gangrene Intestine - Thrombosis.

Moist gangrenehernia, volvulus or intussusception

WET GANGRENE  Histologically,  Coagulative necrosis with stuffing of blood  Ulceration of mucosa  Intense inflammatory infiltrations  Lumen of bowel contains mucus and blood

 No line of demarcation

GAS GANGRENE  Special form of wet gangrene  Clostridial spores are widely distributed in the environment  May enter traumatic or surgical wounds  Contamination may also occur from patients own faecal flora

GAS GANGRENE  Gas gangrene results from the following clostridial species:  Clostridium welchii  Clostridium oedmatiens  Clostridium septicum

GAS GANGRENE-clinically  Patients are generally toxic and unwell  Often have features of shock, jaundice, haemolysis or acute renal failure  Local signs of gas gangrene include:  Myositis or myonecrosis  Gas formation with palpable crepitus  Mottled discolouration of the overlying skin  Plain X-ray often shows gas in the subcutaneous tissue and fascial plains

Spreading clostridial myonecrosis, or "gas gangrene," developed on the left lateral flank and left lower abdominal quadrant


GAS GANGRENE  Grossly,  Affected area is swollen, edematous & painful  Crepitates – accumulation of gas bubbles  Subsequently, tissue becomes dark black and foul smelling

GAS GANGRENE  Microscopically,  Coagulative necrosis with liquefaction  Gram positive bacilli  Periphery – a zone of leucocytic infiltration, oedema and congestion  Capillary and venous thrombi is common

GAS GANGRENE  Microscopy of wound exudate shows gram-positive bacilli  Rectangular shape without spore formation  Anaerobic culture on blood agar show haemolytic colonies (Clostridium welchii)  'Stormy' clot reaction with litmus milk  Clostridium welchii also shows positive Nagler reaction  Due to lecithinase reaction of alpha exotoxin

GAS GANGRENE  Treatment   

Failure of recognition often results in rapid deterioration Patients require adequate resuscitation Debridement or amputation should be considered to remove affected tissue or limb  Organisms are usually sensitive to penicillin  Hyperbaric oxygen may be helpful

 Prevention  Benzylpenicillin antibiotic prophylaxis in those with  Contaminated wounds  Diabetic undergoing elective peripheral vascular surgery

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