1.7 - Intracellular Accumulations

Cells can accumulate abnormal amounts of substances when they make too much, cannot metabolize them, cannot transport/package them, lack an enzyme needed to degrade them, or encounter something they have no machinery to remove.

intracellular accumulations

abnormal amounts of various substances within cells, originating in the cell itself (endogenous) or produced elsewhere (exogenous)

• accumulations often found in lysosomes

• mechanisms —

  • metabolic rate inadequate to remove substance

  • genetic defect in packaging/transporting/folding

  • inherited enzyme deficiency preventing degradation

  • cell lacks machinery to handle the material

    • example — silica and carbon

fatty change

abnormal triglyceride accumulation within parenchymal cells

• parenchymal cells carry out function, while stromal cells provide structure

• examples —

  • liver fatty change in hepatocytes:

    • cause → alcoholism, diabetes associated with obesity

    • most cases are reversible

    • severe accumulation precedes cell death

  • cardiac fatty change in myocytes:

    • cause → hypoxia

    • patterns → alternating bands, uniform movement

cholesterol and cholesteryl ester accumulation

normally tightly regulated to maintain cell membrane integrity

• mechanism —

  1. macrophages accumulate when cleaning up necrotic cells by ingesting cholesterol-rich membrane debris

     • called foam cells or xanthoma cells

  2. macrophages become filled with lipid

• classic setting — atherosclerosis, other pathologic processes

protein accumulation

less common than lipid accumulation

• kidney:

  • in glomerular disorders, protein can leak into urine/filtrate and proximal tubular cells may reabsorb excess protein

  • results in albumin accumulation in proximal convoluted tubular cells

• plasma cells:

  • normally synthesize immunoglobulins

  • large accumulations may form spherical cytoplasmic structures called Russell bodies

• cell injury:

  • Mallory bodies seen in alcoholic liver disease

  • Alzheimer disease associated with protein accumulation and neuronal structural abnormalities

glycogen accumulation

occurs when glucose/glycogen metabolism is abnormal

• examples —

  • poorly controlled diabetics → accumulation in several cell types

  • glycogen storage diseases → stockpiling results in cell injury and death

pigment accumulation

pigments are colored substances that may be endogenous or exogenous

• examples —

  • carbon → inhaled pollutant

    • cells cannot effectively degrade it

  • lipofuscin → wear-and-tear pigment

    • marker of long-term free radical injury

    • lipid-protein complexes that have undergone oxidative or peroxidative damage

  • melanin → endogenous pigment that provides UV protection

    • produced by melanocytes

    • accumulates in tissue, dermal macrophages, mucosal macrophages

iron accumulation

iron is stored in tissue partially as hemosiderin

• accumulates in areas of local and systemic excess

  • example — heart failure cell = hemosiderin-laden macrophage

• bruising → hemoglobin breakdown after trauma accounts for array of colors in bruising

• hemosiderosis → deposition of iron in tissue due to systemic overload

  • may produce bronze hue

  • usually no organ damage despite accumulation

• hereditary hemochromatosis → excessive iron deposition with tissue injury

pathologic calcification

abnormal deposition of calcium salts, often calcium phosphate, in tissues

• dystrophic calcification → occurs in dead or dying tissues despite normal systemic calcium metabolism

  • dead tissue + normal serum calcium = dystrophic

  • damaged mitochondria lose ability to regulate calcium, and calcium phosphate deposition begins in injured/dead tissue

  • hypercalcemia may worsen it, but is not required for initiation

  • examples — atherosclerosis, aortic stenosis of elderly, lymph node tuberculosis

• metastatic calcification → occurs in normal tissue due to abnormal systemic calcium metabolism

  • high calcium = calcium deposits in normal tissue

  • deranged calcium metabolism → hypercalcemia is prerequisite

    • increased secretion of parathyroid hormone

    • breakdown of bone (tumors, bone turnover disease)

    • vitamin D-related disorders

    • renal failure

  • mainly deposited in vasculature, kidneys, lungs, and gastric mucosa