Cellular InjuryIntracellular degeneration

ByDr. Hemn Hassan Othman

PhD, Pathology2019-2020

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Types of cell injury Cell injury is divided into: 1. Reversible cell injury 2. Irreversible cell injury

Reversible cell injury It is a type of cell injury in which the pathological changes will regress and disappear when the injurious agent is removed and the cells will return to normal morphological and functional status.

Irreversible cell injury It is a type of cell injury which occurs when the injurious agent persists or when it is severe from the beginning. At first the injury is reversible, but later it reaches the point of no return, where it becomes irreversible.

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Point of no return

It is the precise moment of transition from reversible to irreversible cell injury.

At this point, no adaptation can save the cell and the progression to cell death is inevitable (unavoidable).

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For example, If the blood supply to a portion of the heart

musculature is cut off for few minutes and then restored; the

affected myocardial cells will sustain reversible injury, i.e., after

restoration of the blood it will recover and function normally

(as in mild cases of angina pectoris).

But if the cessation of blood supply continues from 30 to 60

minutes and then restored, the affected myocardial cells will

suffer from irreversible injury (Cell Death).

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Cell death

Two phenomena characterize irreversibility

1. Inability to reverse mitochondrialdysfunction

2. Development of profound disturbancesin membrane function

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Classification of cell death

1) Necrosis

Result of catastrophic injury to the

mechanisms that maintain cell

integrity

2) Apoptosis

Result of genetically determined

cell-death (programmed cell death).

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Reversible Cell Injury (Degeneration):

Degenerations

Definition: When cellular injury is sub lethal andsustained, cells and tissues tend to accumulatesubstances in abnormal quantities. Thesematerials may be endogenous or exogenous.

Location: Intracellular and/or Extracellular

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( 1 ) Intracellular edema (Cellularswelling , cloudy swelling, hydropicdegeneration)

Definition: Accumulation of watery fluid incells.

Morphologic change:

• Gross features: Swelling and paleness tothe organ.

• Light microscopic features( LM):

Parenchymal cells swollen.10/9/2019 10

• Early stages:

Granularity degeneration——a fine granularity like ground-glass in the cytoplasm.

• Later stages:

Hydropic degeneration——clear vacuoles in the cytoplasm Progressive dilatation of the swollen cell.

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Left Granularity change in kidney Right Hydropic change

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Leukoedema (Geographical Tongue)Migratory Glossitis

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Mechanism hydropic degeneration:

Lack of oxygen (Hypoxia).

Toxic materials.

Osmotic effect.

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Pathogenesis of cellualr swelling:

Damage to mitochondria or itsenzymatic pathways.

The diminished formation of ATPaffects all the energy requiring reactionin the cell but in particular leads tofailure of the sodium pump.

Sodium ions enter the cell inexchange for potassium and as theformer have a larger hydration shell,there is a net influx of water.

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Liver

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Kidney/ Cortex10/9/2019 22

Kidney / Tubular epithelium10/9/2019 23

(2) Fatty change

(Fatty Degeneration):

Definition: There is an accumulation ofneutral fat (triglycerides) in the parenchyma ofnon-fatty cells e.g. Liver, Heart, Kidneys.

Gross features: The organ enlarges andbecomes yellow, soft, and greasy to touch.

LM: Fatty change appears as clear vacuoleswithin parenchymal cells pushing the nucleusto periphery of the cell.

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• Liver: Since this organ plays a central rolein fat metabolism, the accumulation of fatin toxic conditions can be veryconsiderable, fatty distribution varieswith the cause, e. g. :

Toxins, alcohol, infections, etc.

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Fatty change of liver

Left: Gross photograph Center: HE Stain Right: Oil Red-O Stain

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Gross & microscopic appearance of fatty changes

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Fatty liver change 10/9/2019 30

Heart: It occurs in two patterns, in one, prolonged

moderate hypoxia, such as that produced byprofound anemia, causes intracellular depositsof fat, which create grossly apparent bands ofyellowed myocardium alterations with bands ofdarker, red-brown, uninvolved myocardium(tigered effect).

In the other pattern of fatty change producedby more profound hypoxia or myocarditis, themyocardial cells are uniformly affected.

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Fatty Degeneration in the heart

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• Kidney:

In most cases fatty change is confinedto the epithelium of the renaltubules, but in severe intoxication itmay affect all structures includingthe glomerular.

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Glomeruli

Renal tubules

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Causes:

Poisons. e. g. carbon tetrachloride, phosphorus(liver)

Chronic alcoholism (liver)

Infections

Congestive cardiac failure

Severe anemia

Ischemia

Diabetes mellitus

Malnutrition and wasting disease.10/9/2019 36

Mechanism:

• Impaired metabolism of fat.

• Impaired secretion of fat.

• Excessive triglyceride into the cell.

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Fatty Infiltration:

Fatty infiltration, in contrast to fatty change,describes infiltration by normal-appearinglipocytes into the interstitial connectivetissues of organs that do not normally containappreciable quantities of adipose tissue.

It occurs commonly in the heart and pancreasand is often found along with obesity.

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Fatty infiltration of heart10/9/2019 40

Fatty infiltration of heart10/9/2019 41

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Fatty infiltration in heart

Fatty infiltration of pancrease

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3. Glycogen Deposition :Excessive accumulations of glycogen may occurpathologically in the cytoplasm of epithelialcells of the liver and kidneys.

Causes :1) Hyperglycemia, as occurs in diabetes

mellitus.

2) Steroid-induced hepatopathy.

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Glycogen Deposition

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(4) Intracellular Hyaline change:

Definition:

It’s The accumulation of protein in thecytoplasm of cells, usually in the form ofisolated eosinophilic droplets, is termedhyaline droplet formation.

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Pathogenesis:

It is seen most often in the cytoplasm ofepithelial cells of the renal tubules.

Plasma proteins leak from abnormalglomerular capillaries and are resorbed fromthe lumens of the tubules.

If protein leakage exceeds the absorptivecapacity of these cells, eosinophilicalbuminous or hyaline casts are present in thetubular lumens.10/9/2019 48

Types of Intracellular hyaline:

• Restorative droplets:

The cytoplasm of renal tubules filled withplasma protein during proteinuria.

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Protein reabsorption droplets in the renal tubular epithelium

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• Mallory alcoholic bodies:

liver cytoplasmic aggregates of fragmentedfine filaments and tubules, derived fromhepatocytes cytoskeleton.

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