Some forms of necrosis

Coagiilativc necrosis.This is the most common type of necrosis which is caused by ischaemia, and

less often by bacterial and chemical agents. The organs commonly affected are the heart, kidney and spleen. Macroscopically the foci of coagulative necrosis in the early stage are pale, firm and slightly swollen. With progression, they become more yellowish, softer and shrunken. The hallmark of coagulative necrosis is the conversion of normal cells into their «tombstones» i.e., the outlines of the cells are retained so that the cell type can still be recognized but their cytoplasmic and nuclear details are lost. The narcotized cells are swollen and appear more eosinophilic than the normal, along with nuclear changes. This pattern of microscopic change probably results from denaturation of structural and enzymatic proteins but cell digestion and liquefaction fail to occur. Eventually, the narcotized focus is infiltrated by inflammatory cells and the dead cells are phagocytosed leaving granuar debris and fragments of cells.

Colliquative necrosisoccurs due to ischaemic injury and bacterial infections, because of hydration and colliquation of tissue by the action of powerful hydrolytic enzymes. The common examples are brain infarct and abscess cavity.

Macroscopically, the affected area is soft and swollen. Late a cyst wall is formed. Microscopically, the cystic space contains necrotic cell debris and macrophages filled with phagocytosed material. The cyst wall is formed by proliferating capillaries, inflammatory cells, and gliosis (proliferating glial

cells) in the case of brain, and proliferating fibroblasts in the case of abscess cavity.

Gangreneis a form of necrosis of tissue with superadded putrefaction. The type of necrosis is usually coagulative due to ischemia. In either case, the coagulative necrosis undergoes liquefaction by the action of putrefactive bacteria.

There are 3 main forms of gangrene dry, wet and gas gangrene.

Dry gangrene begins in the distal part of a limb due to ischaemia. The typical example is the dry gangrene in the toes and feet of an old patient due to arteriosclerosis. The gangrene spreads slowly upwards until it reaches a point where the blood supply is adequate to keep the tissue viable. A line of separation is formed at this point between the gangrenous part and the viable part.

Macroscopically, the affected part is dry, shrunken and dark black, resembling the foot of a mummy. It is black due to liberation of hemoglobin from hemolysed red blood cells which is acted upon by the hydrogendisulfide (HG) produced by the bacteria resulting in formation of black iron sulfide. The line of separation usually brings about complete separation with eventual falling off of the gangrenous tissue if it is not removed surgically. Microscopically, there is necrosis with smudging of the tissue. The line of separation consists of inflammatory granulation tissue.

Wet gangrene occurs in naturally moist tissues and organs such as the mouth, bowel, lung, cervix, vulva, etc. Diabetic foot is another example of wet gangrene due to high sugar content in the necrosed tissue which favors growth of bacteria. Bedsores occurring in a bed-ridden patient due to pressure on sites like the sacrum, buttocks and heels are the other important clinical conditions included in wet gangrene. In wet gangrene, the tissue is effected by saprogenic microorganisms (Bac. perfringes, fusiformis, putri-ficans, etc.), becomes swollen and emits fetid smell. It develops in the tissues rich in water: lungs, intestine, noma (water cancer) gangrene of cheek in children at measles. Wet gangrene usually develops rapidly due to blockage of venous and/or arterial blood flow. The affected part is stuffed with blood which favours the rapid growth of putrefactive bacteria. The toxic products formed by bacteria are absorbed causing systemic manifestations of septicemia, and finally death. The spreading wet gangrene lacks clear cut line of separation and may spread to peritoneal cavity causing peritonitis. Macroscopically, the affected part is soft, swollen edematous, putrid, rotten and dark. The part is stained dark due to the same mechanism as in dry gangrene. Microscopically, there is coagulative necrosis with stuffing of affected part with blood. There is ulceration of the mucosa and intensive inflammatory infiltration. The lumen of the bowel contains mucus and blood. The line of separation

between gangrenous segment and viable intestine is generally not clear cut.

Gas gangreneis a special form of wet gangrene caused by gas-forming Clostridia (gram-positive anaerobic bacteria) which gain entry into the tissues through open contaminated wounds, especially in the muscles, or as a complication of operation on the colon which normally contains Clostridia. Clostridia produce various toxins which cause necrosis and edema locally and are also absorbed producing profound systemic manifestations. Macroscopically, the affected area is swollen, edematous, painful and crepitant due to accumulation of gas bubbles within the tissues. Subsequently, the affected tissue becomes dark black and foul-smelling. Microscopically, the muscle fibers undergo coagulative necrosis with liquefaction. Large number of gram-positive bacilli can be identified. At the periphery, a zone of leucocytic infiltration, edema and congestion are found. Capillary and venous thrombi are common.

Bedsoreis a kind of gangrene, death of the tissue under the influence of pressure (sacral area, spinous processes, great trochanter). It is trophoneurotic necrosis in severity ill patients.

Sequestrationis an area of dead tissue which does not experience autolization, does not sclerotize and is freely located in the living tissue. It is characteristic for osteomyelitis (purulent inflammation of the bone).

Infarct(originates from Latin «stufF, fill») is vascular necrosis, the most frequent form of necrosis. It may be wedge-shaped or it may have an irregular shape.

According to the propagation it may be total (when the whole organ is affected), subtotal (when only a part of the organ is affected), microinfarct (when observed only microscopically).

According to the color it is divided into white, white with hemorrhagic rim and red. The color of infarct depends on the peculiarities of the blood supply of the organ. When an organ is supplied through the main vessel (spleen), infarct is white.

If under the background of the supply through the main vessel, microcirculatory system is well developed, infarct is white with hemorrhagic rim (kidney).

In the lungs, infarct is red as the lungs are supplied through the system of two arteries (pulmonary and bronchial).

The causes of infarction are prolonged stasis, thrombosis, embolism.

There are several special forms of necrosis. They are: caseous, fat and fibrinoid necrosis.

Caseous necrosislooks like cottage cheese (curd), the tissue is soft, granular and yellowish. As a rule it is observed in the center of tuberculous infection.

Fat necrosisis a special form of cell death occurring in two anatomically different locations but

morphologically similar lesions. They are acute pancreatic necrosis and traumatic fat necrosis commonly in breasts.

Macroscopically fat necrosis appears as yellowish-white and firm deposits. Calcium usually accumulates in these areas.

Fibrinoid necrosisdevelops due to fibrinoid swelling in mesenchymatous albumin degeneration.

The outcome of necrosis may be either favorable or unfavorable. Favorable outcomes: 1) organization, replacement by connective tissue with formation of a scar or a capsule; 2) petrifaction; 3) ossification, formation of bone; 4) aseptic autolysis. Unfavorable outcome- saprogenic fusion of necrosis focus followed by sepsis.

APOPTOSIS

This pattern of cell death has long been recognized by pathologists, but only recently it has been appreciated as a distinctive and important mode of cell injury, which should be differentiated from the common coagulative necrosis.

Apoptosis is an important means of reducing the number of cells in a tissue. It is a process which brings about death of established cells in an organ or tissue, causing a reduction in the number of functioning cells. There is activation of specific genes, which act to bring about cellular dissolution. One of the morphological

manifestations of this type of cell death is termed apoptosis.

Apoptosis of cells is a programmed and energy-dependent process designed specifically to switch cells off and eliminate them. This controlled pattern of cell death termed programmed cell death is very different from that which occurs as a direct result of a severe, damaging stimulus to cells.

Apoptosis is thought to be responsible for numerous physiologic and pathologic events including the following: the programmed destruction of cells during embryogenesis (including implantation, organogenesis, developmental involution) and metamorphosis, hormone-dependent involution in the adult, cell deletion in proliferating cell populations, such as intestinal crypt epithelia; cell death in tumors, most frequently during regression but also in tumors with active cell growth; death of immune cells; putliologic atrophy of hormone-dependent tissues and parenchymal organs after duct obstruction, cell injury in certain viral diseases; cell death produced by a variety of injurious stimuli.

The following morphologic features, best seen with the electron microscope, characterize cells undergoing apoptosis.

The cell shrinkage is observed. The cell is smaller in size: the cytoplasm is dense; and the organelles, although relatively normal, are more tightly packed.

The chromatin condensation develops. This is the most characteristic feature of apoptosis. The chromatin

aggregates peripherally, under the nuclear membrane, into well-delimited dense masses of various shapes and sizes. The nucleus itself may break up, producing two or more fragments.

Formation of cytoplasmic blebs and apoptotic bodies is observed. The apoptotic cell first shows extensive surface blebbing, then undergoes fragmentation into a number of membrane-bound apoptotic bodies composed of cytoplasm and tightly packed organelles, with or without a nuclear fragment.

Phagocytosis of apoptotic cells or bodies by adjacent healthy cells, either parenchymal cells or macrophages. The apoptotic bodies are rapidly degraded within lysosomes, and the adjacent cells migrate or proliferate to replace the space occupied by the now deleted apoptotic cell.

Microscopically, in tissues stained with hematoxylin and eosin, apoptosis involves single cells or small clusters of cells. The apoptotic cell appears as a round or oval mass of intensely eosinophilic cytoplasm with dense nuclear chromatin fragments. Because the cell shrinkage and formation of apoptotic bodies are rapid, and the fragments are quickly phagocytosed, degraded, or extruded into the lumen, considerable apoptosis may occur in tissues before it becomes apparent in histologic sections.

Thus, apoptosis is a distinctive form of cell death manifested by characteristic chromatin condensation and DNA fragmentation, whose function is the deletion

of cells in normal development, organogenesis, immune function, and tissue growth, but which can also be induced by pathologic stimuli.