Degeneration &

Necrosis1

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

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DEGENERATIONLoss 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.

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• Most literatures define the process as:

• Degeneration: the accumulation of 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 overload2) metabolite overload3) 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.

Effects of defective energy production

• 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 the defective energy production are:i. Intracellular accumulation of water and

electrolysis

Earliest detachable biochemical evidence- diminished 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.

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Assessment

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NECROSIS

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

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Nuclear changes in cell death

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Causes of Necrosis1. Loss of blood supply -

2. Bacterial toxins –

3. Physical irritants –

4. Chemical irritants –

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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

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

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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)

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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.

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Coagulative necrosis – Renal infarction

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Coagulative necrosis – Spleenic infarction

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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.

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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.

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Liquefactive necrosis - Stroke

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Liquifactive necrosis – Liver abscess

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iii) Caseous necrosis

Found in the centre of foci of tuberculosis infections.

It combines features of both coagulative & liquefactive necrosis.

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Grossly: resemble dry cheese and are soft,

granular & yellowish.

Micro:

the necrosed foci are structureless, eosinophilic & contain granular debris.

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Caseous necrosis -Tuberculosis

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Caseous necrosis -Tuberculosis

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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.

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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.

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v) Fibrinoid necrosisCharacterized 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.

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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.

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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.

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Dry gangreneMacro: 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.

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vii) Wet gangreneMacro; 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.

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viii) Gas gangreneGrossly: 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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THANK YOU for UR ATTENTION

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