Cell injury

ByDr. Abdelaty Shawky Dr. Gehan Mohamed

Liquefaction necrosis * Definition: necrosis with complete loss of cell and tissue structure.* Mechanism: – Destruction of dead cells by hydrolytic enzymes.– Enzymes derived from either: • Cell’s own lysosomes (autolysis) or from• Neutrophils and macrophages (heterolysis).

* Seen in: – Suppurative bacterial infections: characterized by

formation of pus (liquefied tissue debris and neutrophils).

– In ischemic injury to brain tissue: Enzymatic destruction of brain tissue leaves behind a cystic cavity.

* Gross appearance:– Necrotic area: soft and filled with fluid.

* Microscopy:– Structureless tissue debris (no cellular outlines).– Neutrophils.

Lung AbscessesNecrotic material

with loss of cellular architecture

Necrotic tissue

Neutrophils

Coagulative vs. Liquefactive necrosis

Coagulative necrosis Focus of liquefactive necrosis

Caseation necrosis* Definition: a distinct form of necrosis without preservation of cellular outlines and tissue architecture, but firm in consistency.• It is a combination of Coagulative and liquefaction

necrosis.

* Most commonly associated with: – Granulomas like tuberculosis – Fungal infection like histoplasmosis.

* GROSS:– Yellowish white, “cheese-like” material.– Cheese-like appearance • Due to release of lipid from the cell walls of M.

tuberculosis and systemic fungi (histoplasma).• (Latin “caseous” – cheese)

* MICRO: – Eosinophilic material surrounded by activated

macrophages, multinucleated giant cells and helper T cells (= a granuloma).

Caseous necrosis

Lung: tuberculosis

Lymph node: histoplasmosis

B

Caseous necrosis

Langhan’s giant cells

Granuloma

Epithelioid cell

Langhan’s giant cell

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.• Acute pancreatitis: – Release of lipases and amylase from pancreas.– Lipases break triglycerides into fatty acids (FA).– FA combine with Ca2+ via the process of

saponification to form chalky white calcified deposits In the pancreas as well as in the omental fat.

White nodules on the surface of pancreas

Area of necrosis with blue discoloration

Fibrinoid necrosis• Is necrosis of immunologic injury.• Is marked by deposition of Pink staining, fibrin-like

proteinaceous material within tissue.• Examples:– Rheumatic heart disease vegetations on mitral valve.– Inflamed synovial tissue in rheumatoid arthritis.– Malignant hypertension within vessel walls.

• Microscopy: fibrinoid material has– Smudgy pink (Eosinophilic) appearance.

Fibrinoid Necrosis

Gangrenous necrosis- Most often occurs in lower limbs and bowel

secondary to loss of blood supply.- Two types:1. Dry gangrene: – Is a form of infarction that results from

ischemia.–Characterized primarily by coagulative

necrosis without liquefaction.–Dead tissue has mummified appearance.–Characteristic finding in diabetic foot.

Dry Gangrene

A

B

2. Wet gangrene:–Refers to necrosis with superimposed

bacterial infection.– Liquefactive necrosis is the primary type of

necrosis in wet gangrene.

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.

* Physiologic examples of apoptosis:

1. Embryogenesis.• Development of lumen within hollow organs (e.g

bowel and heart).2. Hormone-dependent involution in adults.– Endometrial breakdown in menstruation.– Post-lactational atrophy of breast.– Prostate atrophy following castration.

3. Involution of Thymus in the adult.4. Cells that are programmed to die; for

example, 1. The cells of the outer layers of epidermis, 2. Cells in the gut epithelium.

* 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.

* Morphologic appearance of apoptotic cells:

1. Have deeply pink staining cytoplasm.2. Have pyknotic nucleus which fragment.3. Are smaller in size.4. Formation of cytoplasmic buds.5. Breaking off cytoplasmic buds to form apoptotic

bodies.6. Phagocytosis of apoptotic bodies by adjacent cells or

macrophages.7. A lack of inflammatory response.

Apoptosis of epidermal cells

Apoptotic cell in liver

What if apoptosis is too little or too much!! = dysregulated apoptosis:

• Two groups of disorders:

1. Decreased apoptosis with increased cell survival can give rise to:• Cancers• Autoimmune disorders

2. Increased apoptosis with decreased cell survival:

– Neurodegenerative diseases (Alzheimer’s)– Death of virus infected cells: Lymphocyte depletion

as in AIDS

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

Good luck