Cell injury-3

Morphology of irreversible cell injury

* Light microscopy of irreversible cell injury

• Pyknosis = Shrinkage and darkening of the

nucleus.

• Karyorrhexis = fragmentation and breakdown

of the nucleus, (into "nuclear dust").

• Karyolysis = dissolution of the nucleus.

Nuclear pyknosis Karyorrhexis

Karyolysis

* Types of cell death:

• Necrosis: local death of a group of cells within

the living body.

• Apoptosis: genetically controlled programmed

single cell death.

* Types of necrosis:

1. Coagulation necrosis.

2. Liquefactive necrosis.

3. Caseation necrosis.

4. Fat necrosis.

5. Fibrinoid necrosis.

Coagulative necrosis* Mechanism:

– Denaturation and coagulation of structural and

enzymatic proteins due to intracellular acidosis.

– Denaturation of lysosomal enzymes by intracellular

acidosis prevents autolysis.

– Preserving cell outlines and tissue architecture.

– Acute ischemia is the most common cause.

Liquefactive necrosis

* Definition: necrosis with complete loss of cell and

tissue structure due to liquefaction by hydrolytic

enzymes.

* Mechanism:

– Enzymes derived from either cell’s own lysosomes

(autolysis) or from Neutrophils and macrophages

(heterolysis).

Coagulative vs. Liquefactive necrosis

Coagulative necrosis Focus of liquefactive necrosis

Lung AbscessesNecrotic material

with loss of cellular architecture

Necrotic tissue

Neutrophils

Caseation necrosis

• It is a combination of coagulative and

liquefaction necrosis. The tissue is firm (grossly)

and without cellular details or tissue outline

(microscopically).

• Most commonly associated with tuberculosis

Caseous necrosis

Lung: tuberculosis

Caseous necrosis

Fat necrosis

1. Traumatic fat necrosis Secondary to trauma to fatty tissue.Trauma to fatty tissue acute inflammatory

reaction (neutrophils) healing by fibrous tissue and dystrophic calcification.

Commonly seen in women with pendulous breasts.

Clinical significance:– Scar tissue feels firm, retracts the overlying skin and

shows calcifications on mammography.– “These findings also seen in breast cancer”.

2. Enzymatic fat necrosis

• Focal areas of fat destruction due to the action

of pancreatic enzyme on fatty tissue located

around pancreas.

• Occurs as a complication of Acute pancreatitis.

Apoptosis

• Genetically, programmed single cell death.* Morphologically: • The cell membrane does not rupture. • The cell contents are not released into the

extracellular space, and inflammation does not occur.

• May be physiological or pathological.

* Morphologic appearance of apoptotic cells:

1. Cell shrinkage.

2. The cytoplasm becomes deeply esinophilic.

3. The nucleus becomes pyknotic then fragments.

4. Formation of cytoplasmic buds.

5. Each nuclear fragment of go with a cytoplasmic bud and

breaking off to form apoptotic bodies.

6. Phagocytosis of apoptotic bodies by adjacent cells or

macrophages.

7. A lack of inflammatory response.

* Physiologic examples of apoptosis:

1. Embryogenesis.

• Development of lumen within hollow organs (e.g

bowel and heart).

2. Hormone-dependent involution in adults.

– Post-lactational atrophy of breast.

– Prostate atrophy following castration.

3. Involution of Thymus in the adult.

* Pathologic examples of apoptosis:

1. Councilman bodies = dead hepatocytes in viral hepatitis.

2. Psammoma bodies: apoptosis of neoplastic cell with

subsequent calcification.

3. Tumor cell death by cytotoxic T cells.

4. Neurons that are lost in Alzheimer's disease.

5. HIV-positive T-lymphocytes die by apoptosis.

Apoptosis of epidermal cells

Apoptotic cell in liver

Apoptosis vs. Necrosis

Intact, may be released in apoptotic bodies.

Enzymatic digestion; may leak out of cell

Cellular contents

Fragmentation

Pyknosis karyorrhexis karyolysis

Nucleus

Reduced (shrinkage)

Enlarged (swelling)

Cell size

Apoptosis Necrosis Feature

Often physiologic, may be pathologic

Always pathologic

Physiologic or pathologic role

NoFrequent Adjacent inflammation

Apoptosis Necrosis Feature

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