Intracellular accumulations

Intracellular accumulations

Intracellular accumulations

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Intracellular Accumulations - The Cellular Hoarders

  • Four main pathways: Inadequate removal, excessive production, deposition of an abnormal exogenous substance, or inherited metabolic defects.
  • Key Examples:
    • Lipids: Steatosis (liver), cholesterol (atherosclerosis).
    • Proteins: Mallory bodies (liver), Russell bodies (plasma cells).
    • Pigments: Lipofuscin (wear-and-tear), hemosiderin (iron), carbon (anthracosis).

⭐ Hemosiderin is an iron-storage complex; its accumulation (hemosiderosis) is visualized with a Prussian blue stain, which turns the iron bright blue.

Lipid Accumulation - Greasy & Grimy

  • Steatosis: Abnormal accumulation of triglycerides within parenchymal cells, most commonly the liver. Also seen in heart, muscle, and kidney.
  • Causes: Alcoholism, obesity, diabetes mellitus, toxins (e.g., CCl₄), and protein malnutrition.
  • Pathogenesis: Imbalance between fatty acid delivery/synthesis and their subsequent metabolism/export.
  • Morphology:
    • Gross: Enlarged, heavy, yellow, and greasy organ.
    • Microscopy: Clear, sharply demarcated cytoplasmic vacuoles that displace the nucleus. Requires frozen sections with Oil Red O or Sudan Black B for positive staining.

Hepatic Steatosis with Macrovesicular Fat

⭐ In alcoholic fatty liver, the metabolism of ethanol by alcohol dehydrogenase and aldehyde dehydrogenase leads to a massive increase in the intracellular ratio of NADH to NAD+. This ↑ NADH/NAD+ ratio promotes lipid synthesis.

Protein Accumulation - Misfolded Mayhem

  • Results from defects in protein folding, transport, or degradation, leading to toxic aggregates.
  • Chaperones attempt refolding; the ubiquitin-proteasome system attempts degradation.
  • Key Examples:
    • Alpha-1-antitrypsin (AAT) deficiency: Misfolded AAT accumulates in liver ER.
    • Mallory bodies: Damaged cytokeratin filaments in hepatocytes (alcoholic liver disease).
    • Neurofibrillary tangles (NFTs): Hyperphosphorylated tau in Alzheimer's.
    • Russell bodies: Immunoglobulin buildup in plasma cells.

Mallory bodies in hepatocyte histology

⭐ AAT deficiency causes both loss-of-function (emphysema from low circulating AAT) and toxic gain-of-function (liver damage from protein aggregates).

Pigment Accumulation - Colorful Clues

  • Lipofuscin: "Wear-and-tear" pigment.
    • Yellow-brown granules from lipid peroxidation.
    • Indicates past free radical injury; seen in aging heart, liver, and brain.
  • Hemosiderin: Iron-storage complex.
    • Golden-yellow-brown granules from hemoglobin breakdown.
    • Identified by Prussian blue stain.
    • Marks prior hemorrhage (bruise) or systemic iron overload (hemosiderosis). Hemosiderin in alveolar macrophages (Prussian blue stain)

Anthracosis (coal worker's pneumoconiosis) is the most common exogenous pigmentation, caused by inhaled carbon particles engulfed by alveolar macrophages, blackening lung tissue.

Pathologic Calcification - Rock-Solid Evidence

  • Dystrophic Calcification

    • Occurs in damaged, necrotic tissues despite normal serum Ca²⁺ & phosphate levels.
    • Seen in atherosclerosis, damaged heart valves, and areas of caseous necrosis.
    • Pathogenesis involves initiation via damaged membranes and propagation of crystal formation.
  • Metastatic Calcification

    • Results from hypercalcemia; deposits in otherwise normal tissue.
    • Causes: ↑PTH, bone destruction, vitamin D-related disorders, renal failure.
    • Affects tissues that lose acid, creating an alkaline environment (e.g., stomach, kidneys, lungs).

Psammoma bodies: background, histology, and locations

⭐ Psammoma bodies are distinctive, laminated calcific spherules seen in specific neoplasms. 📌 Papillary thyroid carcinoma, Serous cystadenocarcinoma of ovary, Meningioma, Mesothelioma.

High‑Yield Points - ⚡ Biggest Takeaways

  • Steatosis (fatty change), most common in the liver, is often linked to alcohol abuse and is reversible.
  • Atherosclerosis is characterized by foam cells, which are macrophages laden with cholesterol.
  • Mallory bodies are damaged cytokeratin filaments in hepatocytes, classic for alcoholic hepatitis.
  • Russell bodies are immunoglobulin inclusions found in plasma cells.
  • Lipofuscin is the yellow-brown "wear-and-tear" pigment, a marker of free radical injury.
  • Hemosiderin accumulation indicates iron overload (hemosiderosis).
  • Anthracosis is the accumulation of carbon pigment in alveolar macrophages.

Practice Questions: Intracellular accumulations

Test your understanding with these related questions

A 45-year-old man comes to the physician for a routine health maintenance examination. He feels well. He has type 2 diabetes mellitus. There is no family history of serious illness. He works as an engineer at a local company. He does not smoke. He drinks one glass of red wine every other day. He does not use illicit drugs. His only medication is metformin. He is 180 cm (5 ft 11 in) tall and weighs 100 kg (220 lb); BMI is 31 kg/m2. His vital signs are within normal limits. Examination shows a soft, nontender abdomen. The liver is palpated 2 to 3 cm below the right costal margin. Laboratory studies show an aspartate aminotransferase concentration of 100 U/L and an alanine aminotransferase concentration of 130 U/L. Liver biopsy shows hepatocyte ballooning degeneration, as well as inflammatory infiltrates with scattered lymphocytes, neutrophils, and Kupffer cells. Which of the following is the most likely diagnosis?

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Flashcards: Intracellular accumulations

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Nonalcoholic fatty liver disease is characterized by fatty infiltration of hepatocytes with cellular "_____" and eventual necrosis

TAP TO REVEAL ANSWER

Nonalcoholic fatty liver disease is characterized by fatty infiltration of hepatocytes with cellular "_____" and eventual necrosis

ballooning

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