Cellular Accumulations and Metabolic Disturbances

• Tissue accumulations in cells occur due to metabolic derangements.

Disturbances & Resulting Conditions:

• Purine amino acid metabolism disturbance results in Gout.
• Glycoprotein and CHate metabolism disturbance results in Glycogen storage and mucin disturbances.
• Protein metabolism disturbance results in Hyalinosis and Amyloidosis.
• Calcium metabolism disturbance results in Pathological calcification.
• Pigment disturbance results in Pathological pigmentation.

Gout

• Defined as a disturbance in purine metabolism.
• This disturbance leads to the deposition of sodium urate in tissues.
• Which increases the sodium urate level in blood and urine.
• Primarily affects the skin, kidneys, and joints, notably the metatarsophalyngeal joint of the big toe.

Gout Causes:

• Primary: Familial, more common in males than females, due to increased purine breakdown or decreased clearance.
• Secondary: Due to increased cellular destruction, such as in Polycythaemia rubra vera.

Glycoproteins and CHate Disturbances:

• Can manifest as Glycogen or Mucin disturbances.

Glycogen:

• Occurs in Glycogen storage diseases, etiology is due to abnormal glycogen metabolism.
• Microscopically, cells appear swollen with clear cytoplasmic vacuoles.
• Special stain used is PAS (Periodic Acid Schiff stain) positive.

Mucin:

• Examples include Catarrhal inflammation and Mucoid carcinoma.
• Microscopically, cells appear swollen with mucin, described as signet-ring cells.
• Cells may rupture and release mucin.

Hyalinosis (Hyaline Deposition):

• Defined as the presence of glassy, refractile, homogenous, structureless protein material.
• Stains red with eosin.
• Examples: Russell's bodies in Rhinoscleroma, Corpora amylacia in prostatic hyperplasia.

Amyloidosis:

• Defined as the extracellular deposition of abnormal fibrillary protein.
• Appears as homogenous eosinophilic material.
• Leads to progressive organ dysfunction due to vascular compression and pressure atrophy.

Classification of Amyloidosis:

• Localized: Nodular deposits affect the tongue, larynx, and lung.
• Systemic (generalized): 1ry amyloidosis is found in plasma cell tumors or multiple myeloma.
• 2ry amyloidosis (reactive amyloidosis) occurs in inflammatory diseases like tuberculosis (TB).
• Endocrine amyloidosis occurs in endocrine tumors.
• Heredofamilial amyloidosis is also a classification.

Diagnosis of Amyloidosis:

• Achieved through tissue biopsy.
• Hx & E stain appears as an esinophilic.
• Congo red stains show orange red.
• Congo red under polarized light appears apple green.

Pathological Calcification:

• Defined as the abnormal deposition of calcium salts in tissue other than bone & teeth.
• Gross examination: Chalky white and hard (N/E).
• Microscopic examination: Dark blue (M/E).

Types of Pathological Calcification:

• Dystrophic Calcification: Occurs in nonviable tissue with normal blood calcium level, is the most common form.
• Examples: fat necrosis, wall of chronic abscess, old scar, dead bilharzial ova, fibrosed valve, and atheroma of large vessels.
• Metastatic Calcification: Occurs in viable tissue with hypercalcemia.
• Causes of hypercalcemia: Excess absorption of calcium from the intestine (hypervitaminosis D, milk-alkali syndrome).
• Excess mobilization of calcium from bone (endocrinal disorders, prolonged immobilization in bed, bone destruction by malignant tumors).
• Sites: Kidney (in tubules), wall of arteries, mucosa of the stomach, lung alveoli.
• Stone Formation : Occurs in ducts of the biliary tract, urinary tract and salivary gland.

Pathological Pigmentation:

• Pigments are colored substances that stain the tissue.
• Can be exogenous (from external sources) or endogenous (produced within the body).

Exogenous Pigments:

• Enter the body through various routes: Inhalation, ingestion, and inoculation.
• Inhalation: Anthracosis (carbon particles).
• Ingestion: Chronic lead poisoning (plumbism).
• Inoculation: Tattooing.

Endogenous Pigments:

• Melanin, Lipochrome (lipofuscin), and Hemosiderin.

Melanin Pigment:

• Melanin hyperpigmentation: Localized (nevus, melanoma), Generalized (prolonged exposure to sunlight).
• Melanin hypopigmentation: Localized (vitiligo), generalized (albinism).

Lipochrome (lipofuscin) Pigment:

• Yellowish-brown, fat-soluble pigment normally present in the heart, testis, seminal vesicles, corpus luteum, and adrenal cortex.
• Increases due to tissue breakdown, released phospholipids are phagocytosed by neighboring cells leading to intracellular accumulation.
• Causes: Old age (brown atrophy of the heart), wasting diseases, and cancer cachexia.

Hemosiderin Pigment:

• Deposition of hemosiderin (iron-containing brown pigment).
• Special stain: Prussian blue (stains the pigment blue).
• Types: Localized hemosiderosis (due to localized haemorrhage), generalized hemosiderosis.
• Primary hemosiderosis is due to inborn error metabolism.
• Secondary hemosiderosis is due to repeated blood transfusions or hemolytic anemias.

This lesson covers tissue accumulations in cells due to metabolic derangements. It discusses disturbances in purine, glycoprotein, protein, calcium, and pigment metabolism. Specific conditions like gout, glycogen storage disorders, hyalinosis, amyloidosis, pathological calcification, and pigmentation are explained.