CELL INJURY AND

CELL DEATH
PRESENTED BY-
DR. SAURAV NATH
CELL INJURY
• Cell injury is defined as the effect of variety of
stresses due to etiological agents a cell encounters
resulting in changes in its internal and external
environment.

• The affected cell may recover from the injury

(reversible) or may die (irreversible).
ETIOLOGY OF CELL INJURY
• Hypoxia and ischemia
• Physical agents
• Chemical agents and drugs
• Microbial agents
• Immunologic agents
• Nutritional derangement
• Ageing
• Psychogenic diseases
• Iatrogenic diseases
• Idiopathic Diseases
 MORPHOLOGY OF CELL INJURY
Reversible:
• If ischaemia or hypoxia is of short duration the
effects may be reversible restoration of circulation.

• The sequential and biochemical changes in reversible

cell injury are:
• 1) Decreased generation of cellular ATP
• 2) Nuclear clumping
• 3) Hydropic swelling and other membrane changes
• 4) Reduced protein synthesis.
• Common examples of morphologic forms of reversible
cell injury are:
• 1) Hydropic changes
• 2) Hyaline change
• 3) Mucoid change
• 4) Fatty change
• Grossly, the affected organs such as kidney,
liver, pancrease or heart muscle is enlarged
due to swelling.

• The cut surface bulges outwards and is slightly

opaque.
• Microscopically, the features of hydropic swelling of
kidney are:
• 1) The tubular epithelial cells are swollen and their
cytoplasm contains small clear vacuoles and hence
called vacuolar degeneration. These vacuoles
represent distended cisternae of the ER.
• 2) Small cytoplasmic blebs may be seen
• 3) The nucleus may appear pale
• 4) The microvasculature of the interstitium is
compressed due to swollen tubular cells.
HYDROPIC
CHANGE IN
KIDNEY

THE TUBULAR EPITHELIAL CELLS ARE DISTENDED WITH CYTOPLASMIC

VACOULES WHILE THE INTERSTITIAL VASCULATURE IS COMPRESSED.
THE NUCLEI ARE PALE.
IRREVERSIBLE CELL INJURY
• Persistence of ischaemia or hypoxia results in irreversible
damage to the structure and function of the cell ( cell
death).

• The stage at which this irreversibility is reached from

reversible injury is unclear but the sequence of events is a
continuation of reversibly injured cell.

• In addition, there is further reduction in ATP, continued

depletion of proteins, reduced intracellular pH and
leakage of lysosomal enzymes into plasma.
EFFEC TS ON ULTRASTRUCTURAL
COMPONENT OF THE CELL ARE:
• MEMBRANE DAMAGE
• MITOCHONDRIAL DAMAGE
• Excess intracellular calcium collects leading to
vacuoles formation and deposits of amorphous
calcium salts in the matrix

• CYTOSKELETAL DAMAGE
• Normal cytoskeleton of cell is damaged due to
degradation by activated intracellular proteases.
• NUCLEAR DAMAGE
• Irreversible damage to nucleus can be in three
forms:

• 1) Pyknosis- condensation and clumping of nucleus

• 2) Karyorrhexis- nuclear fragmentation

• 3) Karyolysis- dissolution of nucleus.

LYSOSOMAL DAMAGE, CELL DEATH AND
PHAGOCYTOSIS

• The lysosomal membranes are damaged and results

in escape of lysosomal hydrolytic enzymes.
• These enzymes are activated due to lack of Oxygen
in the cell and acidic pH and on activation bring
about enzymatic digestion of cell components and
hence cell death.
• The dead cell is replaced by masses of
phospholipids called myelin figures which are
phagocytosed by macrophages.
NECROSIS
• It is a type of irreversible cell injury.

• It is defined as a localised area of death of tissue

followed later by degeneration by hydrolytic
enzymes liberated from dead cells.

• It is invariably accompanied by inflammatory

reaction.
• There are 5 types of necrosis based on etiology and
morphplogy:

• 1) COAGULATIVE
• 2) LIQUIFACTIVE
• 3) CASEOUS
• 4) FAT
• 5) FIBRINOID
COAGULATIVE NECROSIS
• This is the most common type caused by irreversible focal
injury, mostly from sudden cessation of blood flow and less
often from bacterial and chemical agents.

• The organs most effected are heart, kidney, spleen.

• Grossly, the necrotic foci is pale, firm and slightly swollen and
is called infarct.

• Microscopically, the hallmark is conversion of normal cells

into their “tombsones” i.e the cell outlines are retained but
their cytoplasmic and nuclear details are lost.
Coagulaitve necrosis in infarct
kidney
LIQUIFACTIVE NECROSIS
• It also occurs commonly due to ischaemic injury and bacterial or
fungal infections but the hydrolytic enzymes in tissue
degradation have a dominant role in causing semi fluid material.

• Common examples are infarct brain and abscess cavity.

• Grossly, the affected area is soft with liquefied centre having

necrotic debris. Later a cyst wall is formed.

• Microscopically, the cystic spaces contain necrotic debris and

macrophages filled with phagocytosed material.
LIQUEFACTIVE NECROSIS
BRAIN
CASEOUS NECROSIS
• It is found in the centre of foci of tuberculous infections. It
combines features of both coagulative and liquefactive necrosis.

• Grossly, the foci resemble dry cheese and are soft, granular and
yellowish.

• Microscopically, centre of the necrotic foci contain structureless,

eosinophilic material having scattered granular debris of
disintegrated nuclei. The surrounding tissue shows
characteristic granulomatous inflamatory reaction consisting of
epitheloid cells, interspersed giant cells of Langhan’s and foreign
body type and peripheral mantle of lymphocytes.
CASEOUS NECROSIS IN
LYMPH NODE
GANGRENE
• Gangrene is necrosis of tissue associated with
superadded putrefaction, most often following
coagulative necrosis due to ischaemia.

• There are 2 main types of gangrene

• 1) Dry gangrene
• 2) Wet gangrene
• In all types of gangrene, necrosis undergoes
liquefaction by the action of putrefactive bacteria.
CONTRASTING FEATURES OF
DRY AND WET GANGRENE
• DRY GANGRENE
•Commonly in limbs
•Acts by arterial occlusion.
•Macroscopically, the organ becomes
dry, shrunken and black.
•Putrefaction is limited due to very
little blood supply
•Line of demarcation is present at the
junction between healthy and
gangrenous part
•Bacteria fail to survive
•Prognosis is generally better
.
• WET GANGRENE
• Most common in bowel
• There is blockage of both
venous drainage and arterial
obstruction
• The organ is part moist, soft,
swollen, rotten and dark
• Marked putrefaction due to
stuffing of organ with blood
• No clear line of demarcation.
• Numerous bacteria present
• Generally poor prognosis
THANK YOU