Necrosis (1)

Necrosis (1)

1. NECROSIS Presented By: Maryam Manzoor Lecturer Pharmacology Rashid Latif College of Pharmacy

2. DEFINITION Necrosis is a form of cell death in which cellular membranes fall apart, and cellular enzymes leak out and ultimately digest the cell. Excessive inflammatory response. Enzymes secreted from lysozymes and leukocytes.

3. FOCAL AND DIFFUSED NECROSIS Focal/ Multifocal necrosis- terms used for one or more, small, clearly defined areas of necrosis. Diffuse necrosis- term used when necrosis affects a large area or the entire tissue or organ.

4. Apoptosis Necrosis ATP -dependent Cell membrane intact Organelles intact No inflammation (macrophages ingest apoptotic bodies) ATP not required Cell membrane rupture Organelles rupture Inflammation (neutrophils)

5. General causes of necrosis: Poisons and toxins: Chemical: Strong acids, alkalies , insecticides, mercury etc. Infectious agents: Bacteria ( Salmonella, Staphylococcus ), viruses, fungi, protozoa etc. Plant poisons- hepatotoxic alkaloids. Circulatory disturbance: Anemia, congestion and ischemia. Mechanical injuries: Cutting, crushing and rubbing types. Physical : Extreme temperature, electricity, free radical.

6. BIOCHEMICAL MECHANISMS Failure of energy generation in the form of ATP because of reduced oxygen supply or mitochondrial damage Damage to cellular membranes which results in leakage of cellular contents including enzymes I rreversible cell caused by reactive oxygen species (ROS )

7. Pathogenesis of Necrosis Denaturation of intracellular proteins Enzymatic digestion of cell . DIGESTION OF CELLS BY ENZYMES the digestion is of two types Autolysis : Digestion of cell by enzymes derived from their own lysosomes . Hetrolysis : Digestion of cell by enzymes derived from lysosmes of leukocytes.

8. Denaturation of proteins caused by intracellular acidosis which results in: injury to the cell membrane Severe impairment of phosphorylation of cell Decreased intracellular activity of the cell

9. TYPES OF NECROSIS Different types of necrosis are recognized according to the causes, pathogenesis and the tissue involved. Coagulative necrosis Liquefactive necrosis Caseous necrosis Fat necrosis Fibroid necrosis

10. Coagulative Necrosis Most common type of necrosis. Architectural outlines persist but cellular details are lost. Type of tissue can be recognized. Denaturation (coagulation) of structural and enzymatic proteins blocks proteolysis Myocardial infarction

11. Causes: Ischemia due to thrombosis/ embolism as in infarcts. Bacterial toxins Muscular dystrophy due to deficiency of selenium and vit . E. Necrosis of renal epithelium due to poisoning from mercuric salts.

12. Gross appearance: Necrotic area is firm, opaque with cooked meat appearance. It is sharply demarcated from the healthy areas. Microscopic appearance: Architectural outlines are present; cellular details are lacking. Result: Dead tissues remain in the body for a long period, ultimately removed by macrophages.

13. LIQUEFACTIVE NECROSIS There is digestion and liquefaction of necrotic tissue . Ischemic necrosis of brain. Causes: 1. Pyogenic (pus related) bacterial infections attract neutrophils. Bacterial and leukocytic enzymes liquefy dead cells and tissues. 2. Some chemicals like turpentine oil also attract neutrophils and cause pus formation and liquefactive necrosis .

14. LIQUEFACTIVE NECROSIS Gross appearance: The necrotic tissue is liquefied and filled with semisolid creamy liquid called pus. Pus: It is a thick, white or yellow, creamy liquid consisting of exudate of leukocytes, tissue debris and microorganisms. Proteolytic enzymes released from neutrophils cause liquefaction of dead cells. Abscess: It is a localized collection of pus, surrounded by fibrous capsule . Empyema: It is accumulation of pus in a body cavity.

15. LIQUEFACTIVE NECROSIS Microscopic appearance: No architectural or cellular details are visible in the area of necrosis. The entire necrotic mass is surrounded by a fibrous connective tissue capsule.

16. Caseous Necrosis Dead tissue is converted into a homogenous, granular mass resembling cottage cheese. Cause: Associated with lesions of Mycobacterium tuberculosis.

17. Gross appearance: The area of necrosis is amorphous, granular, white-gray resembling cottage cheese. The caseous mass is enclosed within a connective tissue capsule. Microscopic appearance: The necrotic tissue is amorphous, granular mass enclosed inside a zone of granulomatous inflammation, containing macrophages. Calcification commonly occurs in the necrotic areas.

18. Fat necrosis: Death of adipose tissue in a living animal. There are two types of fat necrosis: Pancreatic Traumatic

19. Pancreatic fat necrosis: Death of adipose tissue in and around pancreas. Causes: Pancreatitis and/or injury to pancreas and its ducts release lipases which attack adipose tissue in the peritoneum . Hydrolysis of triglycerides releases fatty acids which combine with calcium to produce chalky white areas (saponification ). Gross appearance : Necrotic fat appears as white or yellowish chalky masses. A zone of inflammation appears around the necrotic areas. Microscopic appearance: The necrotic tissue is solid and homogenous and there are numerous small needle-shaped clefts occupied by fatty acid crystals.

20. Traumatic fat necrosis: It occurs in subcutaneous adipose tissue caused by mechanical injury.

21. FIBRINOID NECROSIS It usually occurs in immune reactions in which complexes of antigens and antibodies are deposited in the walls of blood vessels. Deposited immune complexes and plasma proteins that leak into the wall of damaged vessels produce a compound called fibrinoid ( fibrin like ). e.g ., autoimmune disorder, SLE, Rheumatoid arthritis

22. GANGRENE NECROSIS Gangrene is the necrosis of tissue with superadded putrefaction (enzymatic decomposition ). It is the clinical condition in which extensive tissue necrosis is complicated to a variable degree by secondary bacterial infection. Gangrene = Necrosis + infection + putrefaction