Cells DeathCells Death

Lecture on pathological anatomy for Lecture on pathological anatomy for the 3-rd year students the 3-rd year students

T.FilonenkoT.Filonenko

Cells DeathCells DeathIt is the premature death and destruction of It is the premature death and destruction of cell in the living organism under action of cell in the living organism under action of factors of critical damage factors of critical damage

Classification of Cells Death, based on the Classification of Cells Death, based on the mechanism of development:mechanism of development:

necrosisnecrosis

pathogenic inducted apoptosispathogenic inducted apoptosis

immunological elimination of cells.immunological elimination of cells.

karyolysiskaryolysis

karyorrhexiskaryorrhexis

karyopicnosiskaryopicnosis

According to the cause of According to the cause of necrosis there are the following necrosis there are the following

types of necrosis:types of necrosis:

traumatic necrosis;traumatic necrosis;

toxic necrosis;toxic necrosis;

trophoneurotic necrosis;trophoneurotic necrosis;

allergic necrosis;allergic necrosis;

vascular or ischemic necrosis.vascular or ischemic necrosis.

Two essential changes bring about irreversible cell injury in necrosis - cell Two essential changes bring about irreversible cell injury in necrosis - cell digestion by denaturation of proteins and lytic enzymes.digestion by denaturation of proteins and lytic enzymes.

coagulative necrosis coagulative necrosis develops (during denaturation of proteins ).develops (during denaturation of proteins ).

Liquefactive necrosis Liquefactive necrosis is a progressive catalysis of cell structures (during enzymic is a progressive catalysis of cell structures (during enzymic digestion)digestion). . Liquefactive necrosis is typical of organs in which the tissues have a lot of lipid (such as brain) or when there is an abscess with lots of acute inflammatory cells whose release of proteolytic

Both of these processes require hours to developBoth of these processes require hours to develop

Main types of necrosisMain types of necrosis

Zenker degeneration (waxy degeneration): This refers to necrosis of skeletal muscle in infectious diseases with high fevers (such as typhoid

fever). The musculature becomes opaque and waxy, tears easily, and loses its cross-striation.

The liver shows a small abscess here filled with many neutrophils. This abscess is an example of localized liquefactive necrosis.

The two lung abscesses seen here are examples of liquefactive necrosis in which there is a liquid center in an area of tissue injury. Liquefactive necrosis is typical of organs in which the tissues have a lot of lipid (such as brain) or when there is an abscess with lots of acute inflammatory cells whose release of proteolytic enzymes destroys the surrounding tissues.

Clinic-morphological forms of Clinic-morphological forms of necrosis necrosis

1) 1) Gangrene Gangrene – total necrosis of the organ, reported with the – total necrosis of the organ, reported with the external environment:external environment:dry dry – at the thrombosis of arteries, an organ acquires the black coloring– at the thrombosis of arteries, an organ acquires the black coloringmoist (wet) –moist (wet) – at the thrombosis of arteries and veins + influencing of putrid at the thrombosis of arteries and veins + influencing of putrid bacteria.bacteria.gas gangrenegas gangrene bedsorebedsore is a type of gangrene, death of the tissue under the influence of is a type of gangrene, death of the tissue under the influence of pressure (sacral area, buttocks, great trochanter). It is trophoneurotic pressure (sacral area, buttocks, great trochanter). It is trophoneurotic necrosis of the bed- patientsnecrosis of the bed- patientsnomanoma – widespread necrosis of soft tissue of person. – widespread necrosis of soft tissue of person.

2) 2) SequesterSequester – fragment of dead tissue, which can’t be autolysed, – fragment of dead tissue, which can’t be autolysed, replaced by connective tissue and which is localized among replaced by connective tissue and which is localized among alive tissuealive tissue

3) 3) InfarctionInfarction – vascular or ischemic necrosis; – vascular or ischemic necrosis;4) 4) Fat necrosisFat necrosis5) 5) Caseous necrosisCaseous necrosis6) 6) Fibrinoid necrosisFibrinoid necrosis. .

This is gangrene. In this case, the toes were involved in a frostbite injury. This is an example of "dry" gangrene in which there is mainly coagulative necrosis from the anoxic injury.

This is gangrene of the lower extremity. In this case the term "wet" gangrene is more applicable because of the liquefactive component from superimposed infection in addition to the coagulative necrosis from loss of blood supply. This patient had diabetes mellitus.

Gangrene

nomanoma – – Moist

gangrene of the soft

tissue of the face in

measels

SequesterSequester in bone – fragment of dead tissue, which can’t be in bone – fragment of dead tissue, which can’t be autolysed, replaced by connective tissue and which is localized autolysed, replaced by connective tissue and which is localized

among alive tissueamong alive tissue

This is fat necrosis of the pancreas. Cellular injury to the pancreatic acini leads to release of powerful enzymes which damage fat by the production of soaps, and these appear grossly as the soft, chalky white areas seen here on the cut surfaces.

Microscopically, fat necrosis is seen here. Though the cellular outlines vaguely remain, the fat cells have lost their peripheral nuclei and their cytoplasm has become a pink amorphous mass of necrotic material.

Fat necrosis

This is more extensive caseous necrosis, with confluent cheesy tan granulomas in the upper portion of this lung in a patient with tuberculosis. The tissue destruction is so extensive that there are areas of cavitation (cystic spaces) being formed as the necrotic (mainly liquefied) debris drains out via the bronchi.

Microscopically, caseous necrosis is characterized by acellular pink areas of necrosis, as seen here at the upper right, surrounded by a granulomatous inflammatory process.

Caseous necrosis

Sometimes the small arteries and arterioles can be damaged so severely in malignant hypertension that they demonstrate necrosis with a pink fibrin-like quality that gives this process its name - fibrinoid necrosis.

Fibrinoid necrosis

INFARCTionINFARCTionDefinition:Definition: A localized area of A localized area of ischemic necrosis usually caused ischemic necrosis usually caused by vascular blockage. by vascular blockage.

Types of infarcts: wedge-shaped or irregular shape.According to the propagation: 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: white, white with hemorrhagic halo and red. The causes of infarction: prolonged spasm, thrombosis, embolism.

Morphology of infarcts, Morphology of infarcts, differs with different differs with different

tissuestissuesThe color of infarct depends on the features of The color of infarct depends on the features of

the blood supply of the organ. the blood supply of the organ.

White:White: pale, often roughly wedge-shaped, in solid pale, often roughly wedge-shaped, in solid organs with single blood supply (ex: kidneys ,spleen)organs with single blood supply (ex: kidneys ,spleen)

Red:Red: hemorrhagic, in organs which are soft and have hemorrhagic, in organs which are soft and have dual blood supply or collaterals (ex: lungs ,bowels, dual blood supply or collaterals (ex: lungs ,bowels, liver)liver)

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

Here are splenic infarcts in a patient with infective endocarditis. Portions of the vegetations have embolized to the spleen. These infarcts are typical of ischemic infarcts: they are based on the capsule, pale, and wedge-shaped.

This is an acute renal infarction. Note the wedge shape of this zone of coagulative necrosis resulting from loss of blood supply with resultant tissue ischemia that produces the pale infarct.

White (pale, ischemic)infarction

Microscopically, the renal cortex has undergone anoxic injury at the left so that the cells appear pale and ghost-like. There is a hemorrhagic zone in the middle where the cells are dying or have not quite died, and then normal renal parenchyma at the far right. This is an example of coagulative necrosis.

The contrast between normal adrenal cortex and the small pale infarct is good. The area just under the capsule is spared because of blood supply from capsular arterial branches. This is an odd place for an infarct, but it illustrates the shape and appearance of an ischemic (pale) infarct well.

White infarctionWhite infarctionwith hemorrhagic halowith hemorrhagic halo

The interventricular The interventricular septum of the heart septum of the heart has been sectioned has been sectioned to reveal an to reveal an extensive extensive acute acute myocardial myocardial infarctioninfarction. The dead . The dead muscle is tan-yellow muscle is tan-yellow with a surrounding with a surrounding hyperemic border.hyperemic border.

Red Red ((hemorrhagic) hemorrhagic)

infarctioninfarction in lung in lung Occlusion of a medium-

sized branch of pulmonary artery can lead to a pulmonary infarction in a person with compromised cardiac or respiratory status.

A pulmonary infarct is hemorrhagic because of the dual blood supply from the non-occluded bronchial arteries which continue to supply blood, but do not prevent the infarction.

hemorrhagic hemorrhagic infarctioninfarction inin BowelBowelThe small intestine is

infarcted. The dark red to grey infarcted bowel contrasts with the pale pink normal bowel at the bottom. Some organs such as bowel with anastomosing blood supplies, or liver with a dual blood supply, are hard to infarct. This bowel was caught in a hernia and the mesenteric blood supply was constricted by the small opening to the hernia sac.

This infarct in the brain is organizing and being resolved, the liquefactive necrosis leads to resolution with cystic spaces. The microscopic appearance of this acute cerebral infarction reveals marked edema (the pale areas).

Infarction in brain

At high magnification, liquefactive necrosis of the brain demonstrates many

macrophages at the right which are cleaning up the necrotic cellular debris.

Clinical Significance of Clinical Significance of infarcts:infarcts:

usually causeusually cause pain; pain;

may cause may cause loss of functionloss of function (example: myocardial infarct may (example: myocardial infarct may cause heart failure); cause heart failure);

may cause may cause hemorrhage or sepsishemorrhage or sepsis (examples: lung infarct causes (examples: lung infarct causes hemoptysis, bowel infarct causes hemoptysis, bowel infarct causes GI bleeding or peritonitis). GI bleeding or peritonitis).

Regeneration of tissues – replacement of the dead tissue with a new one;Incapsulation – formation of the connective tissue capsula around necrotic area;Organization – replacement of the dead tissue with connective tissue;Petrification – replacement of the dead tissue with calcium salts;Incrustation – replacement of the dead tissue with any other salts exept calcium;Ossification – the formation of the bone tissue in the necrotic area;Hyaline change – the appearance of the hyaline-like substance in the necrotic area;Sequestration – formation of sequester;Mutilation – spontaneous tearing away of the dead tissue;Cystic formation.Suppuration fusion of necrotic tissues

The outcomes of necrosis