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Intracellular accumulations (degenerations). Protein degenerations, fatty changes, parenchymatous carbohydrate degenerations.

Lecture # 3

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Definition of intracellular accumulations. Protein degenerations.

Fatty changes.
Carbohydrate degenerations.

*PLAN:

Intracellular accumulations are manifestation of metabolism disorder in high functionally specialized cells.

* The

processes that result in abnormal intracellular accumulation includes:

1) Abnormal metabolism In this condition a normal endogenous substance is produced at a normal or increased rate, but the rate of metabolism is inadequate to remove it. Example: Fatty change in the liver. 2) Lack of enzyme In this situation a normal or abnormal endogenous substance accumulates because it can not be metabolized due to genetically lack of an enzyme that is necessary for the metabolism. Example: Storage diseases e.g. glycogen storage disease.

PROTEIN DEGENERATIONS FATTY CHANGES

CARBOHYDRATE DEGENERATIONS

The essence of disproteinosis consist of changing of physical, chemical & morphological properties of cell proteins. They are denatured & coagulated or undergone a liquefaction with following hydropsy of cell cytoplasm.

DEGENERATIONS

*PROTEIN

*Kinds of intracellular
* * *
Granular degeneration.

disproteinosis:

Hyaline droplets degeneration

Vacuolar (hydropic, balloon) degeneration

Hyperkeratosis

*Affected organs: liver, kidney, heart *Causes: blood & lymph circulation disorder, infections,

toxins, etc. *Microscopical picture: swelling of cells, dull cytoplasm, swelling & vacuolization of mitochondria, extension of cisterns of ER. *Gross examination: organs are increased, flabby consistence, surface of the cut is dull, without glitter. *Mechanisms: decomposition, infiltration, transformation. *Outcome: it has reversible character in majority of cases.

*Granular degeneration

*Affected

heart *Causes: different kidneys diseases, hepatitis, alcohol cirrhosis *Microscopical picture: hyaline droplets in cell cytoplasm, destruction of mitohondria, ER. *Gross examination: changes of organs accordingly with basic disease *Mechanisms: infiltration, decomposition, unnatural synthesis. *Outcome: irreversible process, leading to coagulated necrosis.

organs: kidney, more seldom liver &

*Hyaline droplet

degeneration

Vacuolar (hydropic) degeneration

*Affected organs: epithelium of the skin, epithelium
of renal tubules, hepatocytes, myocytes, neurons, cells of the cortex of suprarenal glands *Causes: infections, toxins, hypoproteinemia, etc *Microscopical picture: vacuoles in cell cytoplasm, nucleus located at periphery of the cell *Gross examination: organs arent changed *Mechanisms: infiltration, decomposition, disorder of system of reabsorbing of sodium & water *Outcome: developing of balloon degeneration, liquefactive necrosis

*Localization:

excess production of keratin in stratified squamous keratinized epithelium, pathologic keratinization of mucous membrane, epithelial cancer. *Causes: skin malformations, chronic inflammation, viral infections, hypovitaminosis *Microscopical picture: revealing of keratohyalin in stratum lucidum of epidermis *Gross examination: hyperkeratosis of skin, unnatural keratinization of mucous membranes *Mechanisms: infiltration, transformation *Outcome: recovery of tissue or cell death

*Hyperkeratosis

Disorder of lipid metabolism is expressed in increasing of content of lipids:

*in cells, where they are present normally *in cells where they are not occurred
usually

*in

formation of lipids of unusual chemical structure

*INTRACELLULAR LIPID

ACCUMULATIONS

*Fatty change (steatosis)

Fatty change refers to any abnormal accumulation of triglycerides within parenchymal cells leading to an absolute increase in intracellular lipids. It is an example of accumulation of endogenous substances due to abnormal metabolism .

Common sites

1. Liver: most

commonly affected organ because it is the major organ involved in fat metabolism. 2. Heart. 3. Skeletal muscles. 4. Kidney. 5. Any other organ.

Causes of fatty liver 1. Alcohol abuse. 2. Diabetes mellitus. 3. Obesity. 4. Protein malnutrition (starvation). 5. Hepatotoxins. 6. Drugs. 7. Pregnancy.

Mechanism of fatty liver

Accumulation of triglycerides in the cytoplasm of liver cells occurs due to: 1) Increased mobilization of adipose tissue resulting in an excessive fatty acid entry into the liver cells e.g. in starvation and diabetes. 2) Rate of conversion of fatty acids to triglycerides in the liver cell is increased due to overactivity of the involved enzyme e.g. due to alcohol. 3) Decreased oxidation of triglycerides e.g. in anemia and hypoxia. 4) Decreased synthesis of lipid acceptor protein such as apoprotein due to protein malnutrition and carbon tetrachloride poisoning.

Gross Liver becomes enlarged, yellow, soft and greasy. Light Microscopic Fatty change is seen as small fat vacuoles in the cytoplasm around the nucleus. As the process progresses, the vacuoles fuse to form larger globules which displace the nucleus to the cell periphery. Significance of fatty change *Mild: no effect on cellular function. *Moderate: may impair cellular function. *Severe: Cellular damage.
Note: In most of the conditions fatty change is reversible if the cause is corrected.

Morphology of Fatty Liver

*Fatty change of liver

HYPOXIA (anemia, chronic cardio-vascular insufficiency)

TOXINS (diphtheria, alcohol, poisoning by phosphorus, arsenic)

Fatty changes in heart

*Mechanism of fatty change in

1) Lack of oxygen leads to decreasing of oxidative phosphorylation in cardiomyocites 2) Damages of mitohondrias

heart due to hypoxia

3) Disorder of -oxidation of fat acids

4) Decreasing of synthesis of ATP

Decreasing of -oxydation of lipids due to destruction of mitohondrias

change in heart due to action of toxins

*Mechanism of fatty

Gross Miocardium is flabby of pale yellow colour, chambers of heart are dilated. Apparent bands of yellowed myocardium alternated with bands of darker, red-brown, uninvolved myocardium (tigered effect). Light Microscopic Lipid are found in cardiac muscle in the form of small droplets. Changed myocardiocytes are located near venules. Significance of fatty change Contractile ability of heart is decreased.

Morphology of Fatty changes in heart

Intracellular accumulation of carbohydrates maybe caused by disorder of metabolism of glycogen & glycoproteids.

Causes: diabetis mellitus, glycogen storage diseases Mechanism of changes in kidneys: Decreasing of reserve of glycogen in tissues leads to glucosuria infiltration of epithelium of renal tubules Morphology Gross (diabetic) glomerulosclerosis Light Microscopic Glycogen is found in epithelial cells of the distal portions of the proximal convoluted tubules & sometimes in descending loop of Henle Significance Disorder of kidneys function

*Disorder of metabolism
of glycogen

Affected organs: mucous membranes of bronchi, thyroid gland, exocrine apparatus of GIT, urogenital system, etc
Causes: inflammation of mucous membranes, cystic fibrosis

Mechanism of development: Increasing of mucus production, changing of physical & chemical properties of mucus
Morphology Formation of cysts Significance It may lead to atrophy & sclerosis of mucous membranes

*Disorder of metabolism
of glycoproteids

b
c

Cystic fibrosis of pancreas growth of connective tissue; b proliferation of excretory ducts c accumulation of colloid masses in dilated lumens of excretory ducts