D R S H O AI B R AZ A

VARIOUS FORMS OF CELL INJURY & NECROSIS

ISCHEMIC & HYPOXIC INJURY

• Most common type

• Ischemia tends to cause more rapid and severe cell

injury than does hypoxia in the absence of ischemia

• ↓ ATP, failure of sodium pump, loss of potassium,

water influx, and cellular swelling

• Progressive loss of glycogen and decreased protein

synthesis

CONTINUING HYPOXIC / ISCHEMIC INJURY

• Worsening ATP depletion

• Blebs formation, myelin figures, swollen

mitochondria, dilated ER; reversible alterations

• Severe swelling of mitochondria, extensive damage

to plasma membrane, lysosomal swelling and

release of lysozyme, opaque densities formed in

mitochondria; irreversible alterations usually leads to

necrosis

IRREVERSIBLE CELL INJURY (HYPOXIA)

• Massive Ca influx, and enzyme activation

• Entry of extracellular macromolecules into the dying

cells

• The dead cell may become replaced by large

masses composed of phospholipids in form of

myelin figures

• Calcification may occur

• Leakage of enzymes in plasma

ISCHEMIA/REPERFUSION INJURY

• Reoxygenation may induce synthesis of reactive

oxygen species

• Ischemic injury is associated with inflammation

• Activation of the complement system may

contribute to ischemia reperfusion injury

CHEMICAL (TOXIC) INJURY

• Chemicals induce cell injury by

• Some chemicals directly injure the cell e.g. mercuric

chloride poisoning

• Hg binds to cell membrane protein, inhibit ion transport.

Cyanide poisons mitochondria. Cytotoxic drugs, etc.

• Some chemicals are converted into free radicals, e.g.

• CCl4 is converted in CCl3. in the liver , resulting in carbon

tetrachloride poisoning

NECROSIS

Sum of all morphological changes that follow cell

death due to progressive degradative actions of the

enzymes.

Autolysis

Heterolysis

Leakage of cellular constituents in extracellular space

may elicit an inflammatory response

MORPHOLOGY

• Increased eosinophilia

• Myelin figures

• Nuclear changes:

• Pyknosis:

• Shrinkage and ↑ basophilia

• Karyolysis:

• Nonspecific breakdown of DNA followed by disappearance

• Karyorrhexis:

• Pyknotic nucleus undergoes fragmentation

PATTERNS OF TISSUE NECROSIS

• Several morphologically distinct patterns

• Coagulative necrosis

• Liquefactive necrosis

• Gangrene

• Caseous necrosis

• Fat necrosis

COAGULATIVE NECROSIS

• Architecture of the dead tissue is preserved for a

span of at least some days

• Hypoxia/ischemia is the leading cause

• ↓ pH inactivates the enzyme, preventing autolysis

• Necrotic cells are removed by phagocytic cells

• A localized area of coagulative necrosis is called as

INFARCT

• Brain infarct yields liquefactive necrosis

Normal cell

Reversible

cell injury

with

cytoplasmi

c &

organelle

swelling,

blebbing

&

ribosome

detachme

nt

Irreversible

cell injury

with

rupture of

membrane

&

organelles,

& nuclear pyknosis

Karyorrhexis

Karyolysis

Ischemic necrosis of the myocardium

A, Normal myocardium.

B, Myocardium with coagulation necrosis

LIQUEFACTIVE NECROSIS

• Characterized by digestion of the dead cells,

transforming the dead tissue into a liquid viscous

mass.

• Seen in bacterial, fungal or other infections, and in

brain infarction

• Accumulation of leukocytes

• PUS formation and pyogenic infections

GANGRENE

• Is a combination of both coagulative and

liquefactive necrosis

• Usually seen in injuries having dual cause e.g.

hypoxia and infection

• Is of three types

• Dry gangrene (e.g. lower limb)

• Wet gangrene (e.g. infarction of intestine)

• Gas gangrene (infection with clostridium)

CASEOUS NECROSIS

• Seen in tuberculosis

• Caseating granuloma are formed in TB

• Necrotic area appear as collection of fragmented

or lysed cells and amorphous granular debris

enclosed within a distinctive inflammatory border

• Usually surrounded by epitheloid cells (modified

macrophages) and lymphocytes

A tuberculous lung with a

large area of caseous necrosis

FAT NECROSIS

• Not a specific pattern of necrosis

• Necrosis of fat or adipocytes

• Traumatic fat necrosis

• Accident, trauma, etc.

• Enzymatic fat necrosis

• Acute pancreatitis

• Breast of lactating mother

• Foci of shadowy outlines of necrotic fat cells

Foci of fat necrosis with

saponification in the mesentery

FIBRINOID NECROSIS

• Seen in immune reactions involving blood vessels

• Antigen-antibody complexes deposit in the vessel

wall along with fibrin

• Bright pink and amorphous appearance

• Immunologically mediated vasculitis syndromes

FATE OF NECROSIS

• Most necrotic cells and their contents disappear by

phagocytosis of the debris and enzymes by the

immigrant leukocytes (PMN, Macrophage)

• If not removed, they tend to attract calcium

resulting in Dystrophic Calcification