Download - INTRACELLULAR ACCUMULATIONS A SHORT REVIEW
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INTRACELLULAR ACCUMULATIONS
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• Accumulation of abnormal amounts of various substances due to manifestations of metabolic derangements of the cell
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INTRACELLULAR ACCUMULATIONS
NORMAL CELLULAR COMPONENTS
lipid, carbohydrates
ABNORMAL SUBSTANCES
Endogenous and Exogenous
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SITES• Cytoplasm (phagolysosomes)• Nucleus
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MECHANISM OF ACCUMULATIONS
• Due to overproduction
• Due to inadequate metabolism
• Lack of enzyme machinery to remove
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Normal substance produced at normal or increase rate
Metabolism is inadequate to remove it
Accumulation
Fatty change in liver
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Mutated gene
Abnormal protein folding
Inability to degrade abnormal protein
AccumulationAlpha 1 antitrypsin
def.
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Normal endogenous substance
Enzyme Deficiency
Metabolite Accumulation
Storage disorders
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Exogenous substance
No enzymatic machinery for its degradation or transport
AccumulationAccumulation of carbon in lungs
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ACCUMULATION OF LIPIDS
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Normal lipid metabolism Free fatty acids from adipose tissue or ingested food
Transported to hepatocytes
Esterified Converted to Oxidized to
Triglycerides Cholesterol or phospholipids Ketone bodies
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STEATOSIS OR FATTY CHANGE• Abnormal accumulation of triglycerides in liver
parenchyma
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Alcohol Toxin and Malnutrition Hypoxia Starvation
Mitochondria Apoproteins Inhibit oxidation Mobilization
Accumulation of lipids
Fatty change or steatosis
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FATTY CHANGE - LIVERGrossly • Liver enlarges, become increasingly yellow, soft and greasy.
Microscopically • Small vacuoles in cytoplasm around the nucleus• Vacuoles coalesce displacing the nucleus to periphery• Occasionally fatty cysts are formed
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FATTY CHANGE - HEART• Occurs due to prolonged moderate hypoxia as in
anemia• In case of infectious myocarditis like of diphtheria.
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Grossly• Bands of yellow myocardium alternating with bands of
darker red brown uninvolved myocardium• Tigered effect
Microscopically • Intracellular deposits of fat
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CHOLESTEROL AND CHOLESTEROL ESTERS
• Atheromatous plaque
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• Cholesterolosis
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Xanthomas
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PROTEINIntracellular accumulation of protein usually appear as • Round eosinophilic droplets,• Vacuoles or• Aggregatesin cytoplasm
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Alhpa 1 antitrypsin def
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GLYCOGEN• It’s a readily available energy source in cytoplasm of
cells• Excessive intracellular accumulation occurs in
abnormal glucose or glycogen metabolism• DM (renal tubular epithelial cells, liver, beta cells,
heart muscles)• Glycogen storage disorders
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Angiokeratoma corporis diffusum (Fabry's disease)
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EWINGS SARCOMA
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PIGMENT
• Exogenous• Endogenous
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Exogenous• Most common is carbon (coal dust).• Common air pollutant.• Inhaled by macrophages within alveoli • Leads to Anthracosis (blackening of lungs)• Severe accumulation like in coal miners leads to coal
worker’s pneumoconiosis
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Pneumoconiosis• Silicosis – Silica dust, stone and sandblasters• Asbestosis – Asbestos dust in shipbuilding workers• Byssinosis – Cotton dust
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EndogenousLipofuscin
• Lipochrome or wear and tear pigment
• Derived through lipid peroxidation of polyunsaturated lipids of
membranes
• Telltale sign of lipid peroxidation and free radical injury
• In sections appears as yellow brown, finely granular, cytoplasmic,
often perinuclear pigment
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• Seen in cells undergoing slow regressive changes as in liver and heart of aging patients or patient with severe malnutrition or cachexia.
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Other pigmentsMelaninHemosiderinBilirubin
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