Degenerati on & Necrosis


Learning Outcomes
• At the end of this lecture, student should be able to : • Define the basic concepts and principles of degeneration and necrosis. • Identify relation between degeneration and necrosis. • Differentiate between different types of necrosis


 Loss of function of the cell, tissue or organ.  Degeneration is a retrogressive changes in cells and tissues characterized by abnormal structural changes and decreased functions.  It is nonspecific responses of cells and tissues following a variety of injuries.

• Some of these processes may be reversible if the injury is mild. If the injury is severe and persistent, it may progress to the point where the involved cell dies  NECROSIS • The distinction between the point where the cells would recover and the point where the process is irreversible and leads to cell death is arbitrary.


• Most literatures define the process as: the accumulation of • Degeneration: metabolites or other substances in a cell damaged by preceding injury. Or • the overloading of previously normal cells by materials which are abnormal in either type of quantity.

• The patterns of cellular degeneration used by pathologist are grouped according to the dominant expression of injury as: 1) water overload 2) metabolite overload 3) Storage overload

• The causes of impaired energy production: • 1. Hypoglycemia – glucose is the main substrate for energy production in most tissue and sole energy source in brain cells. – low glucose level = deficient ATP production. • 2. Hypoxia – oxygen carried by blood. Lack of oxygen in the cells may cause = ischemia, anemia, respiratory obstruction, alteration of hemoglobin.

• 3. Enzyme inhibition- chemical interfering with a vital enzyme. Ex= cyanide inhibit cytochrome oxidase final enzyme in the respiratory chain causing acute ATP deficiency in all cells and cause rapid death. • 4. Uncoupling of oxidative phosphorylation - occur either through chemical reactions or through physical detachment of enzyme from mitochondrial membrane. Ex= mitochondrial swelling is common changes associated with injury.

• Failure of energy production will first affect those cells with the highest demand for O2 – high basal metabolic rate. • The earliest clinical sign of hypoxia and hypoglycemia are disturbance of the normal consciousness such as : • A) intracellular accumulation of water and electrolysis • B)changes in organelles • C) switch to anaerobic metabolism.

Effects of defective energy production

 Effects of the defective energy production are: i. Intracellular accumulation of water and electrolysis  Earliest detachable biochemical evidencediminished availability of ATP is dysfunction of sodium pump on plasma membrane  Influx of water and sodium into cell  Swollen and cloudy cell  May lead to enzyme inhibition.  Early and reversible effects of cell injury

ii. Changes in organelles • • • • Endoplasmic reticulum distend Ribosomes detached Interfere protein synthesis Mitochondrial swelling

iii. Switch to anaerobic metabolism • Production of lactic acid, low the intracellular pH • Chromatin to clump in nucleus • Lysosomal membrane disrupt leading to release of enzymes into cytoplasm, damage the vital intracellular molecules. • Cellular degeneration becomes irreversible – result in necrosis.

Assessme nt




Definition Of Necrosis
• Necrosis; defined as focal death along with degradation of tissue by hydrolytic enzymes liberated by cells. It’s invariably accompanied by inflammatory reaction. • Cell death due to lethal injury. • Microscopic changes in necrosis include pyknosis, karyorrhexis and karyolysis


Nuclear changes in cell death



Causes of Necrosis
1. Loss of blood supply 2. Bacterial toxins – 3. Physical irritants – 4. Chemical irritants –


Types Of Necrosis
• Morphologically, 5 types of necrosis are identified: i) Coagulative necrosis ii) Liquefaction (Colliquative) necrosis iii) Caseous necrosis iv) Fat necrosis v) Fibrinoid necrosis


• Gangrene is a form of necrosis of tissue with superadded putrefaction; gangrene necrosis


i) Coagulative necrosis
 Most common type of necrosis caused by irreversible focal injury (mostly because ischaemia).  Less often bacterial & chemical agents.  The organs commonly affected are HEART, KIDNEY & SPLEEN. (solid organ)


Grossly: • foci of coagulative necrosis in the early stage are PALE, FIRM & SLIGHTLY SWOLLEN. : with progression, they become more YELLOWISH, SOFTER & SHRUNKEN. Microscopic: • the pattern of microscopic change results from 2 processes which are DENATURATION OF PROTEINS & ENZYMATIC DIGESTION OF THE CELL.


Coagulative necrosis – Renal infarction


Coagulative necrosis – Spleenic infarction


ii) Liquefaction (Colliquative) Necrosis
Occurs commonly due to ischaemic injury & bacterial or fungal infections. Occurs due to degradation of tissue by the action of powerful hydrolytic enzymes. Examples are INFARCT BRAIN (stroke) & ABSCESS CAVITY.


Grossly: the affected area is soft with liquefied centre containing necrotic debris. : later, a cyst wall is formed. Microscopic: the cystic space contains necrotic cell debris & macrophages filled with phagocytosed material. : the cyst wall is formed by proliferating cappilaries, inflammatory cells & gliosis in the case of brain & proliferating fibroblasts in the case of abscess cavity.


Liquefactive necrosis - Stroke


Liquifactive necrosis – Liver abscess


iii) Caseous necrosis
Found in the centre of foci of tuberculosis infections. It combines features of both coagulative & liquefactive necrosis.


 Grossly:  resemble dry cheese and are soft, granular & yellowish. Micro: the necrosed foci are structureless, eosinophilic & contain granular debris.


Caseous necrosis -Tuberculosis


Caseous necrosis -Tuberculosis


iv) Fat Necrosis
 Special form of cell death peculiar to fatty tissue.  These are ACUTE PANCREATIC NECROSIS & TRAUMATIC FAT NECROSIS (breast).  In the case of pancreas, there is liberation of pancreatic lipase from injured or inflamed tissue that results in necrosis of the pancreas.  Fat necrosis in either of the two instances results in hydrolysis of neutral fat present in adipose cells into glycerol & free fatty acid.


Grossly: appears as yellowish-white & firm deposits. : formation of calcium soaps imparts the necrosed foci firmer & chalky white appearance. Micro: necrosed fat cells have cloudy appearance & are surrounded by an inflammatory reaction.


v) Fibrinoid necrosis
Characterized by deposition of fibrin-like material which has the staining properties of fibrin. It’s encountered in various examples of immunologic tissues injury, arterioles in hypertension, peptic ulcer etc. Does not have any distinctive gross appearance.


 Grossly:  is identified by brightly eosinophilic, hyaline-like deposition in the vessel wall or on the luminar surface of peptic ulcer. : local haemorrhages may occur due to rupture of these blood vessels.


vi) Gangrene necrosis
The type of necrosis is usually coagulative due to ischaemia. Is characterized by primarily inflammation provoked by virulent bacteria. 3 types; dry, wet & gas gangrene.


Dry gangrene  Macro:  the affected part is dry, shrunken & dark black, resembling the foot : it’s black due to liberation of haemoglobin from haemolysed red blood cells. Histo: the separation consists of inflammatory granulation tissue.



Wet gangrene

Macro; the affected part is soft, swollen, putrid, rotten & dark. : the example is gangrene of bowel. Histo: there is ulceration of the mucosa & intense inflammatory infiltration.


viii) Gas gangrene  Grossly: the affected area is swollen, edematous, painful & crepitant due to accumulation of gas bubbles within the tissues. : the affected tissue becomes dark black & foul smelling. Micro: at the periphery, a zone of leucocytic infiltration, edema & congestion are found.




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