Irreversible Cell injury (Cell Death)

CELLS REACT TO INJURIOUS STIMULI

ADAPTING SUSTAINING REVERSIBLE INJURY SUFFERING IRREVERSIBLE INJURY AND DYING

TYPES OF CELL DEATH

APOPTOSIS (normal death or physiologic death) NECROSIS (premature or untimely death due to causes(Pathologic death)

NECROSIS
It refers to a series of morphologic changes that follow cell death in living tissues OR is the gross and light-microscopic appearances that indicate cell death.

 The surrounding living tissue almost always show inflammatory reaction The necrotic cell undergo lysis Autolysis is the dead cell being selfdigested by its lysosomal enzymes, while heterolysis is the cell being digested by the body's living white cells.

Morphology of Necrotic Cells

Increased Eosinophilia of cytoplasm - loss of RNA (basophilia) - denatured cytoplasmic protein bind tightly to eosin Nuclear Changes - Pyknosis ( shrinkage & basophilia) - Karyorrhexis (Fragmentation of pyknotic nuclei) - Karyolysis (fading of chromatine DNAase effect Myelin figure (EM) large, whorled phospholipid mass (phospholipid precipitate)

HISTOLOGIC FEATURES OF COAGULATIVE NECROSIS

Normal cell

Reversible cell injury with cytoplasmic & organelle swelling, blebbing & ribosome detachment

Karyorrhexis

Irreversible cell injury with rupture of membrane & organelles, & nuclear pyknosis

Karyolysis

Myocardial infarction (coagulative necrosis) Cytoplasmic eosinophilia & nuclear karyolysis

Pathogenesis of necrosis 1. Denaturation of intracellular proteins ( structural & enzymatic) 2. Enzymetic digestion of the cell (Auto & Heterolysis)

Morphologic Pattern of Necrotic Cell mass TYPES OF NECROSIS

COAGULATIVE NECROSIS LIQUEFACTIVE NECROSIS CASEOUS NECROSIS FAT NECROSIS FIBRINOID NECROSIS GANGRENE

COAGULATIVE NECROSIS
Death of groups of cells with preservation of general tissue architecture-tombstone appearance for at least a few days. Affected tissue is firm due to denaturation of structural & enzymatic proteins(intracellular acidosis) Example . Ischemic injury of heart, kidney, ,spleen.

Coagulative necrosis

Preservation of structure Firm Protein denaturation Hypoxic tissue death (except brain)

Spleen; Coagulative necrosis

 The microscopy is distinctive. After loss of their nuclei, the cytoplasm of the cells remains intact for days. The "tombstones" reveal the structure of the living tissue. If the patient lives, the edges of the necrotic area become inflamed, and eventually the dead cells will be removed by white blood cells RULE: Unless otherwise specified in this section, the death of a group of cells will result in coagulation necrosis (Ischemic necrosis=Infarction)

Kidney infarct exhibiting coagulative necrosis, with loss of nuclei and clumping of cytoplasm but with preservation of basic outlines of glomerular and tubular architecture

DEATH: LIGHT MICROSCOPY

Morphologic pattern of Necrotic Cell mass

Liquefactive Necrosis - focal bacterial (or fungal) infections accumulation of inflammatory cells - hypoxic death of cells within CNS

LIQUEFACTIVE NECROSIS
(* "colliquative necrosis" in Europe): When the cells die, they are rapidly destroyed by lysosomal enzymes, either their own or those from neutrophilic leukocytes The tissue becomes liquid viscous mass Material is creamy yellow in color Seen in ischemia of brain, abscess

Normal brain

Liquefactive necrosis

CASEOUS NECROSIS
*Type of coagulative necrosis *Tissue is cheesy white in appearance *All the cells in the area die & surrounded by inflammatory cells (granulomatous inflammation). *The tissue architecture is completely distructed & turn into friable tissue. *Seen in tuberculous infections &certain fungal infections (as Histoplasmosis)

A tuberculous lung with a large area of caseous necrosis

Caseous necrosis of lymph nodes

Caseous necrosis with Giant cells

Fat necrosis

Not a specific pattern Focal areas of fat digestion Usually via release of lipases from pancreas Lipase releases free fatty acid (saponification) from the local lipids (membranes, depot triglyceride). FFA combine with Ca to produce salt soaps

Foci of Fat necrosis with saponification in the mesentry . The areas of white chalky deposits represent calcium soap formation at sites of lipid breakdown.

Microscopic appearance of fat necrosis

FIBRINOID NECROSIS
is a term for damage to the walls of arteries which allows plasma proteins to leak out, and precipitate in, the media

FIBRINOID NECROSIS

GANGRENE
("gangrenous necrosis") is not a separate kind of necrosis at all, but a term for necrosis that is advanced and visible grossly. The word gangrene comes from the Latin word gangraena, an eating sore. Gangrene is death and decay of a body part mostly ischemic necrosis of limbs

 Gangrene is defined as the gradual destruction of living tissue, due to an obstruction in the supply of blood and oxygen to an area of the body (Ischemia) Gangrene = ischemic necrosis

TYPES OF GANGRENE
.DRY GANGRENE .WET GANGRENE

 Dry gangrene This is mostly coagulative necrosis without infection (free of infection). It is usually brought on by frostbite, or poor circulation that cause the tissues to become dry & black.

DRY GANGRENE

dry gangrene (coagulative necrosis)

WET GANGRENE
there's mostly liquefactive necrosis (i.e., the typical foul-smelling, oozing foot infected with several different kinds of bacteria).

"wet

gangrene in patient with Diabetes millitus

Ischemic necrosis of the bowel (bowel infarction)