Metabolic Derangements & Tissue Accumulations

• Tissue accumulations result from metabolic derangements in the cell.
• These derangements can cause disturbances in purine amino acids, glycoproteins and CHate, protein, calcium, and pigments.

Gout

• Gout is a disturbance in purine metabolism involving the deposition of sodium urate in tissues, increasing its levels in blood and urine.
• It particularly affects the skin, kidneys, and joints, notably the metatarsophalyngeal joint of the big toe.
• Primary causes: Familial, more common in males than females, due to increased purine breakdown or decreased clearance.
• Secondary causes: Increased cellular destruction, such as in Polycythaemia rubra vera.

Glycoproteins and CHate

• Glycogen accumulation occurs in glycogen storage diseases and is due to abnormal glycogen metabolism.
• Microscopically, cells appear swollen with clear cytoplasmic vacuoles.
• A special stain used is PAS (Periodic Acid Schiff stain) positive.

Mucin

• Examples include Catarrhal inflammation and Mucoid carcinoma.
• Microscopically, the cells are swollen with mucin (signet-ring cell).
• The cells may rupture with release of mucin, leading to mucin lacks.

Hyalinosis (Hyaline deposition)

• It is the presence of glassy, refractile, homogenous, structureless protein material that stains red with eosin.
• Examples: Russell's bodies in Rhinoscleroma and Corpora amylacia in prostatic hyperplasia.

Amyloidosis

• It is the extracellular deposition of abnormal fibrillary protein, appearing as homogenous eosinophilic material.
• Amyloidosis results in progressive organ dysfunction due to vascular compression and pressure atrophy.

Classification of Amyloidosis

• Localized: Nodular deposits affect the tongue, larynx, and lung.
• Senile amyloidosis affects the cardiac or cerebral regions (Alzheimer disease).
• Endocrine amyloidosis occurs in endocrine tumors.
• Systemic (generalized): Primary amyloidosis occurs in plasma cell tumors called multiple myeloma.
• Secondary amyloidosis (also called reactive amyloidosis) occurs in inflammatory diseases like tuberculosis (TB).
• Heredofamilial amyloidosis is also a type.

Diagnosis of Amyloidosis

• Tissue biopsy is used for diagnosis.
• Staining with Hx & E results in an esinophilic appearance.
• Congo red staining results in an orange-red color.
• Under polarized light, Congo red shows an apple-green color.

Pathological Calcification

• It involves the abnormal deposition of calcium salts in tissues other than bone and teeth.
• N/E (Naked eye exam): Appears chalky white and hard.
• M/E (Microscopic exam): Appears dark blue.

Types of Calcification

• Dystrophic calcification: Occurs in nonviable tissue with normal blood calcium levels, most common form
  • Examples include fat necrosis, walls of chronic abscesses, old scars, dead bilharzial ova, fibrosed valves, and atheroma of large vessels.
• Metastatic calcification: Occurs in viable tissue with hypercalcemia
  • Causes: Excess absorption of calcium from the intestine (e.g., hypervitaminosis D, milk-alkali syndrome).
  • Excess mobilization of calcium from bone (e.g., endocrinal disorders, prolonged immobilization, bone destruction by malignant tumors).
  • Sites: Kidney (in tubules), walls of arteries, mucosa of the stomach, and lung alveoli.
• Stone formation: Occurs in the ducts of the biliary tract, urinary tract, and salivary gland.

Pathological Pigmentation

• Pigments: Colored substances that stain the tissue and can be exogenous or endogenous.

Exogenous Pigments

• Enter the body via various routes.
• Inhalation leads to anthracosis (carbon particles).
• Ingestion leads to chronic lead poisoning (plumbism).
• Inoculation leads to tattooing.

Endogenous Pigments

Melanin Pigment

• Melanin hyperpigmentation:
  • Localized: Nevus and melanoma.
  • Generalized: Prolonged exposure to sunlight.
• Melanin hypopigmentation:
  • Localized: Vitiligo.
  • Generalized: Albinism.

Lipochrome (lipofuscin) Pigment

• It is yellowish-brown, fat-soluble, normally present in the heart, testis, seminal vesicles, corpus luteum, and adrenal cortex.
• This pigment increases due to tissue breakdown, leading to the release of phospholipids that are phagocytosed by healthy neighboring cells, resulting in intracellular accumulation.
• Causes: Old age (brown atrophy of the heart), wasting diseases, and cancer cachexia.

Hemosiderin Pigment (Hemosiderosis)

• It is the deposition of hemosiderin (iron-containing brown pigment), identifiable with a special stain (Prussian Blue).
• Types:
  • Localized hemosiderosis: Due to localized hemorrhage.
  • Generalized hemosiderosis: Can be primary (due to inborn error of metabolism) or secondary (due to repeated blood transfusions and hemolytic anemias).

Tissue accumulations can result from metabolic derangements, affecting purine amino acids, glycoproteins, and more. Gout, a purine metabolism disturbance, leads to sodium urate deposition in tissues, impacting the skin, kidneys, and joints. Glycogen accumulation occurs in glycogen storage diseases due to abnormal glycogen metabolism.