Cell injury

Causes of cell injury Oxygen deprivation Genetic defects Chemical agents Nutritional imbalances Infectious agents Physical agents Immunologic reactions Aging

Types of cell injury 1- Reversible cell injury 2- Irreversible cell injury

The ultrastructural changes of reversible cell injury include: 1- Plasma membrane alteration: Blebbing, blunting of microvilli and loosening of intracellular attachments. 2- Mitochondrial changes: Swelling and appearance of small phospholipid-rich amorphous densities. 3- Dilatation of the ER with detachment of ribosomes. 4-Clumping of nuclear chromatin.

Two patterns of morphologic change of Reversible injury 1- Cellular swelling (Hydropic change) 2-Fatty change

Cellular swelling (Hydropic swelling or change): The first manifestation of all forms of cell injury. It is a reversible increase in cell volume. It reflects an increased water content . Difficult to be recognised by LM and may be more apparent at the level of the whole organ.

Gross appearance: Pallor and increased weight of the organ Gross appearance: Pallor and increased weight of the organ. Microscopically : Large , pale cytoplasm and a normally located nucleus.

The ultrastructural changes of irreversible cell injury include: Cell membrane defects. The accumulation of Ca+2-rich densities in the mitochondrial matrix. Continued loss of proteins and leaking of vital metabolites. Leaked enzymes can also “mark” the cell type damaged as reflected by the elevated serum level of the somewhat cell-specific isoenzymes: - Liver function tests: Alkaline phosphatase - Cardiac muscles: Creatine kinase

5- Lysosomal rupture: leakage of hydrolytic enzymes. 6- Nuclear changes include: Pyknosis: Nuclear shrinkage & increased basophilia . Karyorrhexis: Fragmentation of pyknotic nucleus. Karyolysis: The basophilia of chromatin fades.

7- After cell death, cellular constituents are digested by lysosomal hydrolase. 8- Dead cells may be replaced by large, whorled phospholipid masses: Myelin figures Myelin figures are then phagocytosed by other cells or degraded into fatty acids. Calcification of fatty acid residues.

Irreversible cell injury Necrosis Is the death of group of cells in living tissue. The morphologic changes of necrosis are the result of : 1- Enzymatic digestion 2- Protein denaturation

Types of necrosis Coagulative necrosis Liquefactive necrosis Caseous necrosis Fibrinoid necrosis Fat necrosis Gangrenous necrosis

1- Coagulative necrosis Common form in hypoxic injury of cells in all tissues except the brain. Myocardial infarction is a prime example of coagulative necrosis. Protein denaturation is dominant. Preservation of the basic structural outline of the affected cells.

Morphology of coagulative necrosis Renal infarction

2-Liquefactive necrosis Mainly caused by bacterial or fungal infections. Enzymatic digestion is dominant. e.g. 1)infarction of brain and spinal cord (softening and liquefaction are due to the high lipid and fluid content of the nervous tissue and lack of extracellular proteins) 2)amebic abscess >>> liquefaction is due to the action of liquefactive enzymes produced by the parasite.

3)pyogenic abscess where the central necrotic core is liquefied by proteolytic enzymes released from pus cells.

3-Caseous necrosis common in tuberculous infection. is a combination of coagulative and liquefactive necrosis. The term “caseous” is derived from the cheesy white gross appearance of the central necrotic area. The tissue architecture is completely obliterated.

Microscopically, the necrotic focus is composed of structureless, amorphous granular debris enclosed within a granulomatous inflammation.

4-Fibrinoid (Fibrin-like) necrosis refers to immunologic injuries to arteries and arterioles. characterized by the accumulation of fibrin, immunoglobulins and other plasma proteins within walls of affected vessels.

+ 5-Fat necrosis Enzymatic fat necrosis Traumatic fat necrosis e.g., trauma of subcutaneous tissue of female breast e.g., acute pancreatitis Pancreatic enzymes (Lipases) Breast lump Fat Free fatty acids + Calcium White-yellow chalky material = calcium soaps

White-yellow chalky deposits (Ca+2–soap formation) Fat necrosis White-yellow chalky deposits (Ca+2–soap formation)

6-Gangrenous necrosis Gangrene is defined as massive necrosis with superadded putrefaction. There is initial hypoxic coagulative necrosis, later modified by liquifactive action of enzymes derived from bacteria and leucocytes.

Thank you Dr/Mona Kamal