Embed Size (px)
Citation preview
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
*
