NECROSIS “Necrosis is the morphological changes that follow cell death in a living tissue or organ, Resulting from the progressive degenerative action of enzymes on the lethally injured cell.” So, Necrosis begins with an impairment of the cell’s ability to maintain homeostasis, leading to an influx of water and extracellular ions

Apoptosis vs Necrosis The word apoptosis mean falling off. “Apoptosis is a process of programmed and targeted cause of cellular death” Necrosis is differ from apoptosis:

Apoptosis Necrosis Physiological or pathological Always pathological Cell shrinkage Cell swelling Apoptotic bodies form Do not form Dna cleavage No DNA cleavage Beneficial Detrimental Characteristic nuclear changes Nuclei lost No leak of lysosomal enzymes Leak of lysosomal enzymes

Causes of necrosis Anoxia Ischemia Physical agents Chemical agents Biological agents Immunological

Pathogenesis Necrotic changes in tissues are caused By Digestion of cell by enzymes Denaturation of proteins This digestion is of two types Autolysis: Digestion of cell by enzymes derived from their own lyosomes Heterolysis: Digestion of cell by enzymes derived from lysosmes of leukocytes.

By Denaturation of proteins Denaturation of proteins caused by intracellular acidosis and due to this result is that: Injury to the cell membrane Severe impairment of phosphorylation of cell Increase permeability of the cell Influx of Na+ and Ca+ in the cell Decreased intracellular activity of the cell

Changes in Necrosis Changes inside the cell Changes in mitochondria Changes in Nucleus Changes in cytoplasm

Changes inside the cell Endoplasmic reticulum is disorganized There is rupture of membrane Ribosomes are shed off Disorganization of polysomes & their structures Changes in mitochondria Mitochondria become swallon Loss of interamitochondrial granules Loss of cristae & change their shape Rupture of outer membrane of Mitochondria

Changes in Nucleus Pyknosis Karyorrhexis Karyolysis Nucleus becomes smaller Chromatin loses & become clumped Nucleus shows following changes Pyknosis Karyorrhexis Karyolysis

PYKNOSIS KARYORRHEXIS KARYOLYSIS “When the DNA is broken down by endonucleases fragments are formed & the nucleus becomes acid and stains basophillic” KARYORRHEXIS “The pyknotic nucleus may break up into fragments and disappear. This process is called karyorrhexis” KARYOLYSIS “The pyknotic nucleus may undergo lysis by the enzyme DNAse”

Changes in cytoplasm Cytoplasm becomes more eosinophilic: Due to loss of RNA & denaturation of cytoplasmic proteins Cytoplasm becomes opaque.

Basic types In special sites TYPES OF NECROSIS Coagulative necrosis Liquefactive necrosis Caseous necrosis In special sites Fat necrosis Fibrinoid necrosis Gangrenous necrosis

COAGULATIVE NECROSIS Examples “In this type of necrosis, the necrotic cell retains its cellular outline for several days” Coagulative necrosis typically occurs in solid organs such as kidney, heart and adrenal gland usually as a result of deficient blood supply and anoxia. Examples Myocardial infarction

Mechanism Denaturation of protein is the basic mechanism of coagulative necrosis The injury and the subsequent increasing acidosis denatures not only the structural proteins but also the enzymic proteins, thus blocking the cellular proteolysis. Morphology Preservation of basic structural outline of the coagulated cells Appears as a mass of coagulated, pink staining homogenous cytoplasm

LIQUEFACTIVE NECROSIS It is the type of necrosis that occurs due to autolytic and heterolytic actions of enzymes that convert the proteins of cells into liquid. It is characterized by softening and liquifaction of tissue. Examples Ischemic necrosis of brain Suppurative inflammation.

Mechanism Enzymatic degradation of proteins is the basic mechanism of liquefactive necrosis Morphology Complete loss of cellular detail Cellular outline is also destroyed

CASEOUS NECROSIS Morphology Combination of coagulative and liquefactive necrosis Characterized by the presence of soft, dry, cheesy homogenous necrotic material. It is not liquefied Examples Principaly in the center of tuberculous granuloma Morphology Microscopically the necrotic focus is composed of structureless amorphous granular debris enclosed within a ring of granulomatous inflammation.

Necrosis in special sites Fat necrosis It occurs in two forms: Enzymatic fat necrosis Traumatic fat necrosis

Enzymatic fat necrosis Most commenly seen in acute pancreatitis. “Refers to the necrosis in adipose tissue, induced by the action of pancreatic enzymes which are lead due to trauma to the pancreas” Morphology Chalky white opaque spots surrounded by inflammatory margins are seen Necrotic area shows acute inflammatory changes with dissolved fat cells

Traumatic fat necrosis It occur following severe injury to the tissues with high fat content such as the breast, subcutaneous tissue and abdomen. Morphology Foam cells and gaint cells are seen. necrotic foci contain a lot of phagocytes containing fat known as foam cells

FIBRINOID NECROSIS Type of connective tissue necrosis especially affecting arterial walls. Mostly seen in two conditions Auto immune diseases e.g Rheumatic fever SLE Malignant hypertension

GANGRENOUS 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. Gangree= Necrosis + infection + putrefaction

Causes of gangrene Arterial obstructon due to: Thrombosis of atherosclerotic artery Embolus Diabetes:- atherosclerotic artery , loss of sensation results reapeted trauma & increase chances of infection Infection Gas gangrene Gangrene of scrotum Trauma Crush injuries Physical agents Burns Chemicals

Types of gangrene Dry gangrene Wet gangrene Gas gangrene

Dry gangrene of foot

Wet gangrene of intestine Wet gangrene of appendix