Intracellular Accumulations and Pathological Calcification Quiz

Intracellular Accumulations

• Intracellular accumulations can be normal or abnormal, and may be harmless or associated with varying degrees of injury
• Three categories of intracellular accumulations:
  • Normal cellular constituents (e.g. lipid, proteins, carbohydrates)
  • Abnormal substances (e.g. exogenous/endogenous)
  • Pigments (e.g. exogenous/endogenous)

Pathways of Abnormal Intracellular Accumulations

• Abnormal metabolism (e.g. fatty change in liver)
• Alterations in protein folding and transport (e.g. α1-antitrypsin deficiency)
• Deficiency of critical enzymes (e.g. storage diseases)
• Inability to degrade phagocytosed particles (e.g. accumulation of carbon or silica particles)

Types of Intracellular Accumulations

• Hydropic change (water)
• Fatty change (e.g. steatosis, fatty liver)
• Proteins (e.g. abnormal protein accumulation)
• Glycogen (e.g. glycogen storage diseases)
• Complex carbohydrates (e.g. mucopolysaccharidoses)
• Minerals (e.g. iron, calcium)
• Pigments (e.g. exogenous/endogenous)
• Amyloid

Fatty Liver

• Abnormal accumulation of triglycerides within parenchymal cells
• Caused by an imbalance between the uptake, utilization, and secretion of fat
• Commonly seen in the liver, but can also occur in other organs
• May be mild and reversible or severe and produce irreversible cell injury and death
• Major causes of fatty liver:
  • Alcoholic liver disease
  • Protein malnutrition (starvation)
  • Diabetes Mellitus
  • Obesity
  • Hepatotoxins
  • Hypoxia (anemia, cardiac failure)
  • Drugs

Pigments

• Exogenous pigments: carbon, introduced into the body from outside by ingestion, inhalation, or inoculation
• Endogenous pigments: melanin, bilirubin, hemosiderin, lipofuscin
• Accumulation of pigments can occur inside cells in different situations

Hemosiderin

• Golden yellow-to-brown, granular pigment
• Hemoglobin-derived
• One of the major storage forms of iron
• Identified by its staining reaction (blue color) with the Prussian blue dye
• Accumulates in tissues when there is a local or systemic excess of iron
• Two types of excess accumulation:
  • Hemosiderosis: accumulation of hemosiderin within tissue macrophages, not associated with tissue damage
  • Hemochromatosis: more extensive accumulation of hemosiderin, often within parenchymal cells, leading to tissue damage, scarring, and organ dysfunction

Lipofuscin

• Brownish-yellow, granular intracellular material
• Consists of lipids and phospholipids in complex with protein
• Derived from the free radical-catalyzed peroxidation of polyunsaturated lipids of subcellular membranes
• Not injurious to the cell or its functions, but is important as a marker of past free-radical injury
• Seen in a variety of tissues (e.g. heart, liver, brain) as a function of age or atrophy

Pathologic Calcification

• Abnormal deposition of calcium salts, together with smaller amounts of iron, magnesium, and other minerals
• Two forms:
  • Dystrophic calcification: deposition of calcium salts in dead or degenerated tissues
  • Metastatic calcification: deposition of calcium salts in vital tissues with abnormal calcium metabolism
• Causes of metastatic calcification:
  • Increased secretion of parathyroid hormone
  • Destruction of bone tissue
  • Vitamin D-related disorders
  • Associated with renal failure

Test your knowledge on the substances that can accumulate within cells, the pathways of abnormal intracellular accumulations, causes and mechanisms of fatty liver, endogenous and exogenous pigments, as well as terms like hemosiderosis, jaundice, and pathological calcification.