Cellular Pathology: Intracellular Accumulations

Intracellular Accumulations

• Cells accumulate abnormal amounts of substances, potentially harmless or harmful.
• Substances can be in the cytoplasm, organelles (like lysosomes), or the nucleus.
• Substances may be synthesized by the affected cells or produced elsewhere.
• Abnormal accumulation occurs due to inadequate removal/degradation, excessive production of endogenous substances, or deposition of exogenous materials.

Fatty Change (Steatosis)

• Accumulation of triglycerides within cells.
• Primarily seen in the liver (major fat metabolism organ), but can also affect heart, skeletal muscle, and kidneys.
• Common causes:
  • Increased TG synthesis or secretion into the blood.
  • Excessive alcohol consumption
  • Diabetes Mellitus
  • Obesity
  • Malnutrition
• Alcohol abuse and obesity-related diabetes are frequent causes of fatty liver.

Cholesterol and Cholesteryl Esters

• Macrophages become laden with lipids (triglycerides, cholesterol, and cholesteryl esters).
• Causes: Increased intake or decreased catabolism of lipids.
• Significantly related to atherosclerosis.
• Xanthelasma (yellow plaques on eyelids) is a visible sign of high cholesterol levels due to this accumulation.

Proteins

• Excess protein presentation to cells or excessive cell synthesis can cause protein accumulation.
• Nephrotic syndrome: Albumin, usually filtered and reabsorbed in the proximal convoluted tubule, leaks heavily, leading to accumulation.
• Russell bodies: Newly synthesized immunoglobulins accumulate within plasma cells.

Glycogen

• Abnormal glycogen or glucose metabolism causes glycogen accumulation.
• Glycogen storage diseases: Deficiency in glucose-6-phosphatase causes a rise in glucose-6-phosphate, leading to increased glycogen synthesis and excess in hepatocytes and renal tubular cells (hepatorenomegaly).
• Poorly controlled diabetes mellitus: Glycogen builds up in renal tubules, cardiac cells, and islet cells.

Pigments

• Pigments are colored substances, categorized as:
  • Exogenous: From outside the body (e.g., carbon).
  • Endogenous: Synthesized within the body (e.g., lipofuscin, melanin).
• Body's inability to degrade phagocytosed exogenous materials can cause pigment accumulation.

Carbon

• Common pollutant linked to urban life and coal working environments.
• Anthracosis: Carbon aggregates in lymph nodes and lungs, causing black pigment.

Lipofuscin

• "Wear-and-tear pigment." A brownish-yellow intracellular material accumulating with aging or atrophy.
• Common in heart, liver, and brain.

Melanin

• Endogenous brown-black pigment, synthesized by melanocytes in the skin.
• Protects against harmful UV radiation.
• Increased melanin is associated with sun tanning and freckles.
• Malignant melanoma is a concern with increased melanin pigmentation.

Hemosiderin

• Golden yellow to brown hemoglobin-derived pigment.
• Accumulation due to local or systemic iron excess.
• Small amounts in bone marrow, spleen, and liver (normal red blood cell breakdown).
• Hemosiderosis: Excessive hemosiderin deposition, potentially due to:
  • Hemorrhage
  • Multiple blood transfusions
  • Excessive dietary iron intake
• Hereditary hemochromatosis: A genetic disorder with increased iron absorption, leading to organ damage (liver, pancreas, myocardium, skin)

Bilirubin

• Catabolic product of heme in hemoglobin.
• Accumulation causes jaundice (yellowing of blood, sclerae, mucosae, and internal organs).
• Causes include:
  • Hemolytic anemia (increased red blood cell destruction).
  • Liver disease.
  • Biliary tract obstruction.

Calcification

• Abnormal deposition of calcium salts resulting in white granules (gross) and basophilic deposits (histological).

Dystrophic Calcification

• Calcium levels are normal but deposits build up in injured or dead tissue.
• Examples: Atherosclerosis, aging/damaged heart valves.

Metastatic Calcification

• Associated with hypercalcemia and occurs in normal tissues.
• Primarily in blood vessels, kidneys, lungs, and stomach.
• Causes of hypercalcemia:
  • Hyperparathyroidism
  • Bone destruction
  • Hypervitaminosis D
  • Chronic renal failure