Njds Pathology - Cellular Pathology Iv: Intracellular Accumulations And Pathologic Calcifications

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Intracellular accumulations

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1. May be exogenous or endogenous

2. May accumulate in nucleus, cytoplasm, or organelle

3. May be harmless or cause cell injury

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Mechanisms of intracellular accumulation.

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1. Disruption in normal metabolic pathway ⇒ causing endogenous accumulation

2. Genetic defect - abnormal or deficiency of enzyme ⇒ causing accumulation of endogenous substance

3. Exogenous substance is nondegradable by normal cellular machinery

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Example of intracellular lipid accumulation

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Liver:

1. Metabolic block in lipoprotein production causes lipid accumulation in hepatocytes

2. FATTY CHANGE - the similar resemblence of heptacytes to adipocytes with clear round vacuoles are present w/in hepatocyte cytoplasm

3. Grossly, a FATTY LIVER appears enlarged and yellow (due to presence of kerotinoids) and greasy to the touch

4. Is an example of reversible cell injury

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Intracellular sphingolipid accumulation

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1. Genetic disease causing absence of lysosomal enzyme to degrade lipid

2. Microscopically, cells appear clear and vacuolated or granular-appearing cytoplasm due to distended lysosomes

3. Accumulation in either parenchmal cell or macrophages

4. Represents Tay Sach's or Gauchers Disease.

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Intracellular sphingolipid accumulation

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1. Genetic disease causing absence of lysosomal enzyme HEXOSAMINIDASE A ⇒ causing ↑ in gnagliosides

2. Microscopically, cells appear clear and vacuolated or granular-appearing cytoplasm due to distended lysosomes

3. Accumulation in either parenchmal cell or macrophages

4. Represents Tay Sach's or Gauchers Disease.

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Macrophage accumulation of phagocytosed lipids

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1. Lipids in the form of cholesterol, cholesterol esters, and modified lipoproteins

2. Affected cells have clear, swollen vacuoles, or "foamy" cytoplasm ⇒ FOAM CELLS

3. Macrophage may burst releasing lipids which cystallize into clear, needle structure called CHOLESTEROL CRYSTALS

4. Examples are inflammation and atherosclerosis

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Lipofuscin

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1. (aka Lipochrome) "brown lipid"

2. Represents lipid-protein complexes (non-digestable) accumulated in autophagic bodies

3. Found in atrophic cells of long lasting cells like cardiac myocytes and CNS neurons ⇒ thus given name WEAR-AND-TEAR PIGEMENT or AGING PIGMENT

4. Microscopically appears are yellow-brown granules

5. Grossly, appears to have brown discoloration

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T/F: melanosis coli is due to the accumulation of melanin.

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FALSE: Despite the name of the disease, melanosis coli involves accumulation of lipofuscin

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Protein accumulation

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1. HYALINE - the homogenous, pink, "glassy" look of protein accumulations

2. RUSSELL BODY - eosinophilic inclusion present in synthesizing plasma cells that have become engorged with Ig's

3. ALCHOLIC HYALIN - eosinophilic aggregates made of intermediate filaments in the cytoskeleton of hepatocytes in an alcoholic liver (mallor body)

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Melanosis coli

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1. dark discoloration of L. intestines due to long-term anthranoid laxative use

2. Anthrocene causes widespread apoptosis causing macrophages to phagocytose lipid complexes which become residual bodies

3. Due to lipofuscin accumulation

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Melanin

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1. Synthesized by melanocytes in metabolism of tyrosine to dihydroxyphenylalanine by tyrosinase

2. Microscopically appears as brown-black granules with melanocytes and macrophages (melanophages)

3. Clinically, appears as brown, grey, black, or blue depending on depth of melanin

4. melanin accumulates in Addison's disease, neurofibromatosis, and melanoma

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Hemosiderin

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1. derived from breakdown of red cell-derived hemoglobin and represents aggregates of ferrtin micelles

2. No physiological mechanism for iron removal (only through skin shedding), thus accumulates in iron-storing cells (e.g. macrophages) as hemosiderin

3. Microscopically appears as yellow-brown granules

4. Grossly, appears brownish discoloration

5. Distinguished from lipofuscin and melanin through PRUSSIAN BLUE STAIN

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Hemosiderosis

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1. localized or systemic body iron stores

2. Ecchymosis (bruise) is an example of localized hemosiderosis

3. Can be involved with systemic iron overload

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Endogenous pigments

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1. Bile pigments (bilirubin, biliverdin)

2. Hyperbilirubinemia ⇒ jaundice (aka icterus) w/ symptoms of yellow sclera of eye signaling disease of liver

3. ALKAPTINES - derived from homogentitstic acid from tyrosine metabolism causing black skin (ochronisis) and black urine (alkaptonuria)

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Exogenous pigments

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1. Carbon/coal dust (aka anthracotic pigment)

2. Insoluble drug complexes (e.g. antimalarial drugs like chloroquine and cardiovascular drugs like amiadarone which cause black skin like in ear)

3. Heavy metals (e.g. mercury, silver, bismuth, lead);

4. Cosmetic dye pigments

5. Hypercarotenemia - orange skin from eating carots (beta-carotene)

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Dystrophic and metastatic calcifications

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Dystrophic

1. Serum calcium level normal
2. Localized to necrotic tissue
3. Can lead to organ dysfunction
4. Sever depostion may be seen on radiographs
5. Examples: inflammation, atheroclerosis, and calcific aoritic stenosis

Metastatic

1. Serum calcium levels above normal (hypercalcemia)
2. Found in living tissue but can be accentuated with dystropic calcifications
3. Massive involvement in organ dysfunction
4. Sever deposition seen on radiographs
5. Examples: hyperparathyroidism, bone destruction in leukemia, vit-D disorders

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4 major reasons for hypercalcemia

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1. PTH disorder
2. Osseous destruction
3. Vit-D related disorders
4. Renal failure leading to phophate retention and secondary hypersecretion of PTH