lec

Lecture # 3

* Intracellular accumulations

(degenerations). Protein

degenerations, fatty changes,

parenchymatous carbohydrate

degenerations.

*PLAN:

* Definition of intracellular

accumulations.

* Protein degenerations.

* Fatty changes.

* Carbohydrate degenerations.

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

*PROTEIN

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.

*Kinds of intracellular

disproteinosis:

* Granular degeneration.

* Hyaline droplets degeneration

* Vacuolar (hydropic, balloon)

degeneration

* Hyperkeratosis

*Granular degeneration

*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.

*

*Hyaline droplet

degeneration

*Affected organs: kidney, more seldom liver & heart

*Causes: different kidney’s 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.

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 aren’t changed

*Mechanisms: infiltration, decomposition, disorder of system of reabsorbing of sodium & water

*Outcome: developing of balloon degeneration, liquefactive necrosis

*Hyperkeratosis

*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

*INTRACELLULAR LIPID

ACCUMULATIONS

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

*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.

Morphology of Fatty Liver

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.

*Fatty change of liver

Fatty changes in heart

HYPOXIA

(anemia, chronic

cardio-vascular

insufficiency)

TOXINS

(diphtheria, alcohol,

poisoning

by phosphorus, arsenic)

*Mechanism of fatty change in

heart due to hypoxia

1) Lack of oxygen leads to decreasing

of oxidative phosphorylation in

cardiomyocites

2) Damages of mitohondrias

3) Disorder of β-oxidation of fat acids

4) Decreasing of synthesis of ATP

*Mechanism of fatty

change in heart due to

action of toxins

Decreasing of β-oxydation of lipids

due to destruction of mitohondrias

Morphology of Fatty

changes in heart

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.

*

Intracellular accumulation of

carbohydrates maybe caused by disorder

of metabolism of glycogen &

glycoproteids.

*Disorder of metabolism

of glycogen

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 glycoproteids

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

*

Cystic fibrosis of pancreas

а – growth of connective tissue; b – proliferation of excretory ducts

c – accumulation of colloid masses in dilated lumens of excretory ducts

a

b

c

*