INTRACELLULAR ACCUMULATIONS AND PATHOLOGIC CALCIFICATION Flashcards
Cells can accumulate abnormal amounts of various substances. These may be:
•A. Normal endogenous substances which are produced at normal or increased rate, with the metabolic rate inadequate for their removal (e.g., fat accumulation in liver cells)
•B. Abnormal endogenous substances (product of a mutated gene)- may accumulate because of defective folding or transport and inadequate degradation (e.g., α1-antitrypsin disease)
C. A normal substance can accumulate due to genetic or acquired defects in its metabolism (e.g., lysosomal storage disease)
•D. Abnormal exogenous substances may accumulate in normal cells because they lack the machinery to degrade such substances (e.g., macrophages laden with environmental carbon).
Common intracellular accumulations include
•Lipids
•Proteins
•Hyaline changes
•Glycogen
•Pigments
Discuss Steatosis (fatty changes)
accumulation of TGs within parenchymal cells either due to excessive entry or defective metabolism and export.
•It can occur in the heart, muscle, kidney and especially the liver causing fatty liver.
•Causes of fatty liver include alcohol abuse, protein malnutrition, DM, obesity, toxins and anoxia.
Accumulation of Cholesterol and cholesterol esters
•Accumulation of cholesterol seen as intracellular cytoplasmic vacuoles can be seen in the following conditions –
•Atherosclerosis
•Xanthomas
•Cholesterolosis
•Niemann-Pick disease, type C
Accumulation of PROTEINS
*Intracellular protein accumulation may be due to excessive synthesis, absorption, or defects in cellular transport.
*Microscopically, visible accumulation appear as rounded, eosinophilic cytoplasmic droplets.
*In some disorders, abnormal proteins deposit primarily in the extracellular space (e.g., amyloidosis)
Example of intracellular protein accumulation are
- Reabsorption droplets of proteins accumulate in proximal renal tubules in response to chronic proteinuria.
- Immunoglobulin (improperly folded or degraded) in plasma cells, when produced in excessive amounts, producing Russell bodies .
- Defective intracellular transport and secretion (e.g. α1-antitrypsin deficiency, where partially folded intermediates or mutated proteins accumulate in hepatocytes ER)
- Accumulated cytoskeletal proteins: e.g. keratin in alcoholic hyaline, neurofibrillary tangles containing neurofilaments in Alzheimer disease.
- Aggregates of abnormally folded proteins (e.g in genetic mutations, aging) can accumulate in either intracellular and/or extracellular space and cause pathologic change (e.g. amyloid)
Accumulation of HYALINE CHANGE (intracellular and extra cellular)
*Hyaline change refers to any deposit that imparts a homogenous, glassy pink appearance in H&E-stained histologic sections.
Examples:
*Intracellular hyaline change – . Intracellular accumulations of protein, described earlier (reabsorption droplets, Russell bodies, alcoholic hyaline), are examples of intracellular hyaline deposits.
*Extracellular hyaline change- occurs in damaged arterioles (e.g. due to chronic hypertension), presumably due to extravasated proteins.
Hyaline degeneration in Leiomyomas (fibroids). Microscopy shows whorls of smooth muscle cells which are spindle-shaped, having abundant
Accumulation of GLYCOGEN
*Glycogen is commonly stored within the cells as a ready energy source
*Excessive intracellular deposits (seen as clear vacuoles) are seen with abnormalities of: -
➢ Glycogen storage – glycogenoses (GSD), or In macrophages of patients with defects in lysosomal enzymes that break down glycogen (glycogen storage diseases), and
➢ Glucose metabolism – diabetes mellitus
Accumulation of PIGMENTS
(Types and examples)
*Pigments are coloured substances that can be exogenous or endogenous.
*Exogenous pigments: e.g., carbon or coal dust (anthracosis aka black lung disease), tattoo pigments
*Endogenous pigments: e.g.,
- Lipofuscin (yellow-brown intracytoplasmic granules)
-Melanin (brown-black pigment in melanocytes)
-Homogentistic acid (black pigment in patients with alkaptonuria (black urine disease) causing ochronosis)
- Hemosiderin (golden-brown granular intracellular pigment composed of aggregated ferritin)
PATHOLOGIC CALCIFICATION
•Pathologic calcification is an abnormal tissue deposition of calcium salts in tissues other than osteoid or enamel.
•It is also associated with deposition of small amounts of iron, magnesium, and other minerals.
Two types of calcification
Dystrophic and Metastatic
Discuss DYSTROPHIC CALCIFICATION
•Dystrophic calcification arises in non-viable tissues in the presence of normal calcium serum levels
•It can be a marker of prior cellular injury
•It can also be a source of significant pathology (e.g. psammoma bodies)
•Can be intracellular or extracellular
•Deposition ultimately involves precipitation of a crystalline calcium phosphate similar to bone hydroxyapatite.
Example of dystrophic calcification include
ABCDE:
•-Atherosclerosis
•-Psammoma Bodies
•-Caseous necrosis
•-Damaged heart valves, Dead eggs/parasites
•-Enzymatic fat necrosis
•Others: Mockenberg’s medial calcific sclerosis
MECHANISM of DYSTROPHIC CALCIFICATION phases
initiation and propagation phases.
INITIATION (NUCLEATION) PHASE:
•Occurs extracellularly or intracellularly
•Extracellular initiation occurs on membrane-bound vesicles form dead or dying cells that concentrate calcium due to their content of charged phospholipids.
