PATHOLOGIC CALCIFICATION

PATHOLOGIC CALCIFICATION

• Definition – Abnormal deposition of calcium salts in the tissue other than osteoid or enamel. Along with calcium salts, small amounts of Magnesium, iron and other mineral salts are also deposited

• Two types of pathologic calcifications are-

  • Dystrophic calcification

  • Metastatic calcification

• Dystrophic calcification

  • Calcification occurs in dead and degenerated tissues

  • Plasma calcium levels and Phosphate levels are normal

  • Pathogenesis

    • Deposition of calcium occurs in two phases

      1. Initiation phase

      2. Propagation phase

    • Initiation phase –

      • Initiation can occur intracellularly or extracellularly

      • Intracellular initiation phase

        • Damaged cell has increased inflow of calcium into cytoplasm

        • Calcium that has entered the cell has great affinity for mitochondria and gets deposited in mitochondria.

      • Extracellular initiation phase

        • Degenerated cells contain membrane bound vesicles which contain acidic phospholipids.

        • Calcium has increased affinity for acidic phospholipids and thus calcium deposits in vesicles

        • Cell membrane has membrane bound phosphatases which cause accumulation of phosphate

        • Once the calcium and phosphate accumulates in vesicles, it gets budded out of the cell and is released out.

    • Propagation phase

      • In the initiation phase tiny crystals of calcium are formed. Further Calcium deposition and propagation depends upon

        • Increased levels of calcium and phosphate in the extracellular space

        • Presence of collagen and other  proteins

        • Mineral inhibitors

      • These factors affect deposition of Calcium which binds to a calcium binding Phosphoprotein called Osteopontin

      • In normal condition Osteopontin causes mineralization of bone by calcium deposition. In dystrophic calcification Osteopontin is found in abundance resulting resulting in calcification of dead or degenerated tissue.

  • Types of dystrophic calcification

    • Calcification in coagulative, caseous or fat necrosis

    • Calcified dead parasites like cysticercosis

    • Calcifications in degenerated atheromatous plaques

    • Calcifications  in thickened myometrial vessels (Monckebergs sclerosis)

    • Calcifications in aging or damaged heart valves

    • Psammoma bodies in some tumors like papillary carcinoma thyroid/ Meningioma/ Papillary renal cell carcinoma/ Papillary serous cystadenoma. Psammoma bodies are formed by concentric deposition of calcium around necrotic cell which forms seed for calcium deposit. The term “psammoma” is derived from greek word “psammos” means sand grain

    • Gamma gandy bodies in congestive spleenomegaly

    • Asbestos bodies in Asbestosis of lung

  • Morphology

    • Grossly calcium deposition occurs as fine, white granules or clumps which are gritty

    • Microscopically, on Haematoxylin and Eosin stained sections, calcium appears as basophilic, amorphous granular or clumped

    • Heterotopic bone may be formed in the foci of calcifications

    • Special stain for calcium salts – VonKossa stain ( Calcium appears black in colour)

• Metastatic calcification

  • This type of calcification occurs in conditions where there is hypercalcemia

  • It is named as metastatic calcificaion as calcium from bone  is moved out and deposited in the distant tissues

  • Causes of metastatic calcification

    • Hyperparathyroidism – Increased secretion of parathyroid hormone leads to bone resorption. It occurs in conditions like

      • Parathyroid hyperplasia

      • Parathyroid tumors

      • Ectopic secretion of PTH- related protein by malignant tumors

    • Resorption of bone tissue – It occurs in 

      • Tumors of bone marrow (eg. Multiple myeloma, leukemia )

      • Diffuse skeletal metastasis (in breast cancer)

      • Accelerated bone turnover (pagets disease)

      • immobilization

    • Disorders of Vitamin D

      • Vitamin D intoxication (hypervitaminosis)

      • Sarcoidosis – in this condition macrophages activate Vit D precursors

      • Idiopathic hypercalcemia of infancy – sensitivity of Vitamin D is very high.

    • Renal failure- this leads to secondary hyperparathyroidism due to retention of phosphate

    • Miscellaneous causes –

      • Aluminium intoxication occurring in patients with chronic renal dialysis

      • Milk alkali syndrome due to excessive intake of milk

  • Sites of metastatic calcification– May occur through out the body but mainly affects the interstitial tissue of the organs which excrete acid and have internal alkaline compartment that predisposes to calcium deposition .  Most common organs are

    • Gastric mucosa

    • Kidneys

    • Lungs

    • Systemic arteries Pulmonary veins

  • Morphology – It is similar to that of dystrophic calcification

• Clinical features – Pathologic calcification dose not produce clinical dysfunction but massive depositions in organs can damage the organ (eg. Nephrocalcinosis producing renal damage)

References

1. Dr.A.K.Mandal, Dr. Sharmana Choudhury. Textbook of Pathology. Second edition. 2017

2. Kumar, Abbas, Aster. Robbins and Cotran. Pathologic Basis of Disease. 9th edition.2018