Tishk International UniversityScience FacultyMedical Analysis Department

Pathology

Fourth Grade- Spring Semester 2020-2021

Cell injury 2- Reversible & Irreversible cell injury

Dr. Jalal A. JalalAssistant Professor of Pathology

Objectives

1. Types of reversible cell injury

• Fatty change and hydropic swelling.

2. Types of irreversible cell injury

• Necrosis and apoptosis.

3. Patterns of tissue necrosis.

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OVERVIEW OF CELL INJURY AND CELL DEATH

• Reversible cell injury.

• In early stages or mild forms of injury thefunctional and morphologic changes arereversible if the damaging stimulus is removed.

• At this stage, although there may be significantstructural and functional abnormalities, theinjury has typically not progressed to severemembrane damage and nuclear dissolution.

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Cell death

• With continuing damage, the injury becomesirreversible, at which time the cell cannot recoverand it dies.

• There are two types of cell death-necrosis andapoptosis-which differ in their morphology,mechanisms, and roles in disease and physiology.

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Necrosis

• When damage to membranes is severe, enzymesleak out of lysosomes, enter the cytoplasm, anddigest the cell, resulting in necrosis.

• Cellular contents also leak out through thedamaged plasma membrane and elicit a hostreaction (inflammation).

• Necrosis is the major pathway of cell death inmany commonly encountered injuries, such asthose resulting from ischemia, exposure to toxins,various infections, and trauma.

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Apoptosis

•When a cell is deprived of growth factors or thecell's DNA or proteins are damaged beyond repair,the cell kills itself by another type of death, calledapoptosis which is characterized by nucleardissolution without complete loss of membraneintegrity.

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• Apoptosis is an active, energy-dependent,tightly regulated type of cell death that isseen in some specific situations.

•Whereas necrosis is always a pathologicprocess, apoptosis serves many normalfunctions and is not necessarily associatedwith pathologic cell injury.

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Agents of cell injury

1. Oxygen deprivation: mainly due to lack of blood supply

2. Physical agents (trauma, temp, pressure, electric shock)

3. Chemical agents (CN-, Hg, CO, drugs, ROS)

4. Infectious agents (viruses, bacteria, fungi)

5. Immunologic reactions (anaphylaxis, autoimmune diseases)

6. Genetic defects (Thalassemia, Down syndrome)

7. Dietary (vitamins def/x’s, malnutrition, x’s calories)

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THE MORPHOLOGY OF REVERSIBLE CELL INJURY

• Reversible Injury

• two main morphologic patterns of reversible cellinjury are cellular swelling and fatty change.

• Fatty change (Steatosis)

• Is abnormal accumulation of lipid in parenchymalcells of an organ.

• occurs in hypoxic injury and various forms of toxicor metabolic injury.

• It occurs mainly in cells involved in and dependenton fat metabolism, such as hepatocytes andmyocardial cells.

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Morphology OF Fatty change

• Grossly: liver is enlarged and yellow in color and shiny orgreasy in appearance because it contains excess fat.

• Microscopically: is manifested by the appearance of small orlarge lipid vacuoles in the cytoplasm of hepatocytes.

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Irreversible cell injury-Necrosis

• Refers to a series of changes that accompanycell death, largely resulting from thedegradative action of enzymes on lethallyinjured cells.

• Necrotic cells are unable to maintainmembrane integrity, and their contents oftenleak out.

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• The enzymes responsible for digestion of thecell are derived either from the lysosomes ofthe dying cells themselves or from thelysosomes of leukocytes that are recruited aspart of the inflammatory reaction to thedead cells.

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Morphology

• The necrotic cells show increased eosinophilia(i.e., pink staining from the eosin dye, the "E" in"H&E").

• This is attributable in part to increased binding ofeosin to denatured cytoplasmic proteins and inpart to loss of the basophilia that is normallyimparted by the ribonucleic acid (RNA) in thecytoplasm (basophilia is the blue staining fromthe hematoxylin dye, the "H" in "H&E").

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• Nuclear changes assume one of three patterns, all dueto breakdown of DNA and chromatin.

1. pyknosis, characterized by nuclear shrinkage andincreased basophilia; the DNA condenses into a solidshrunken mass.

2. second pattern is, karyorrhexis, the pyknotic nucleusundergoes fragmentation.

3. In the third pattern basophilia of the chromatin mayfade (karyolysis),In 1 to 2 days, the nucleus in a deadcell completely disappears.

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Patterns of Tissue Necrosis1. Coagulative necrosis

• is a form of tissue necrosis in which the componentcells are dead but the basic tissue architecture ispreserved for at least several days.

• The affected tissues take on a firm texture.Presumably the injury denatures not only structuralproteins but also enzymes and so blocks theproteolysis of the dead cells; as a result,eosinophilic, anucleate cells may persist for days orweeks.

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• Ultimately, the necrotic cells are removed byphagocytosis of the cellular debris byinfiltrating leukocytes and by digestion of thedead cells by the action of lysosomalenzymes of the leukocytes.

• Coagulative necrosis is characteristic ofinfarcts (areas of ischemic necrosis) in allsolid organs except the brain.

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Coagulative necrosisKidney

Preservation of structure

Firm

Protein denaturation

Hypoxic tissue death (except brain)

Coagulative necrosis

Preservation of structure

Firm

Protein denaturation

Hypoxic tissue death (except brain)

2. Liquefactive necrosis

• Is seen in focal bacterial or, occasionally, fungalinfections, because microbes stimulate theaccumulation of inflammatory cells and the enzymesof leukocytes digest ("liquefy") the tissue.

• For obscure reasons, hypoxic death of cells withinthe central nervous system often evokes liquefactivenecrosis.

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• Whatever the pathogenesis, liquefactioncompletely digests the dead cells, resulting intransformation of the tissue into a liquid viscousmass.

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3. Gangrenous necrosis

• It is usually applied to a limb, generally the lowerleg, that has lost its blood supply and hasundergone coagulative necrosis involvingmultiple tissue layers.

• When bacterial infection is superimposed,coagulative necrosis is modified by theliquefactive action of the bacteria and theattracted leukocytes (so-called wet gangrene).

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4. Caseous necrosis

• Is encountered most often in foci of tuberculousinfection.

• The term "caseous" (cheese-like) is derived from thefriable yellow-white appearance of the area ofnecrosis.

• On microscopic examination, the necrotic focusappears as a collection of fragmented or lysed cellswith an amorphous granular appearance.

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• Unlike coagulative necrosis, the tissuearchitecture is completely obliterated andcellular outlines cannot be discerned.

• Caseous necrosis is often enclosed within adistinctive inflammatory border; thisappearance is characteristic of a focus ofinflammation known as a granuloma

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A tuberculous lung with a large area of

caseous necrosis

Tuberculosis : caseous necrosis at the right and granuloma at left.

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5. Fat necrosis

• Refers to focal areas of fat destruction, typicallyresulting from release of activated pancreatic lipasesinto the substance of the pancreas and theperitoneal cavity.

• This occurs in acute pancreatitis.

• In this disorder, pancreatic enzymes that have leakedout of acinar cells and ducts liquefy the membranesof fat cells in the peritoneum, and lipases split thetriglyceride esters contained within fat cells.

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• The released fatty acids combine withcalcium to produce grossly visible chalkywhite areas (fat saponification).

• On histologic examination, the foci ofnecrosis contain shadowy outlines ofnecrotic fat cells with basophilic calciumdeposits, surrounded by an inflammatoryreaction.

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Summary

• Examples of Reversible Cellular changes are

• Fatty change and hydropic swelling

• Cellular changes which are irreversible include

• Necrosis and apoptosis

• Types of necrosis include:

• Coagulative, liquefactive, gangrenous, caseous, andfat necrosis.

• Necrosis is always a pathologic process.

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