PATHOLOGICAL CALCIFICATION It is abnormal tissue deposition of calcium salts , together with small amounts of Iron, Magnesium & other mineral salts. 2 Types Dystrophic calcification Metastatic calcification
It is local, deposition of calcium in dead & degenerating cells . calcium metabolism and serum calcium are normal. DYSTROPHIC CALCIFICATION
Calcification in Dead cells- 1. Necrosis- caseous , liquefactive and fat necrosis 2. Infarcts 3. Thrombi 4. Hematomas 5 dead parasites Calcification in degenerated tissue- Dense old scars Atheromas Stroma of tumors -Fibroid , Ca. breast , thyroid tumors Monckenberg’s Sclerosis Cyst walls Old age- cartilage Atherosclerotic plaques , Monckenberg , Sclerosis ,damaged heart valves
Pathogenesis a) Intiation phase b)Propagation phase
Initiation phase ( Enucleation phase) Intracellular Deposition first occurs in mitochondria of dying cells. Extracellular Deposition occurs in phospholipids of membrane bound vesicles. Calcium is concentrated in these vesicles by process of membrane facilitated calcification.
Steps of initiation phase- Calcium binds to the phospholipids present in the plasma membrane/ organellae membrane. Phosphatases which are present in membrane generate phosphate group to which calcium binds This cycle of calcium and phosphate binding is repeated , so calcium phosphate is deposited near membrane ( Micro crystal formation ).
Propagation Phase The same cycle repeats to form more crystals ,which can then propagate and perforate the membrane Propagation depends on- Concentration of Ca & Po4 Presence of inhibitors and other proteins in extra cellular space, such as connective tissue matrix proteins.
Calcification occurring in normal tissues. Serum calcium levels are raised . It occurs due to hypercalcemia secondary to disturbance in calcium metabolism. Metastatic calcification
Pathogenesis of metastatic calcification- Increased serum calcium excessive binding of inorganic phosphate precipitation of calcium phosphates.
Increased secretion of Parathyroid hormone increased bone resorption. Eg ..Parathyroid tumors and ectopic PTH secretion. Destruction of bone tissue multiple myeloma, diffuse skeletal metastasis, prolonged immobilization. Vitamin D related disorders Vitamin D intoxication, William syndrome. Chronic renal failure. Other Aluminum intoxication, Milk alkali syndrome, Excessive intake of antacids. Causes of Metastatic calcification
MORPHOLOGY OF CALCIFICATION (same for dystrophic and metastatic)
Morphology - same for dystrophic and metastatic Gross – Fine white granules or clumps, and often felt as gritty deposits.
Microscopy Basophilic amorphous granular appearance, sometimes clumped. It can be intracellular /extra cellular/ both. Sometimes a single necrotic cell constitute the seed of the crystal that may become encrusted by minerals in progressive layers or laminations called Psammoma bodies . Eg Meningioma , papillary carcinoma of thyroid and papillary serous cystadenoma of ovary.
Monckeberg’s Sclerosis Dystrophic calcification in the tunica media of large and medium sized muscular arteries Site: Extremeties & genital tract Commonly seen in elderly (degenerative process) Little or no significance
Morphology Gross: thickened vessel, palpated clinically, lumen patent Microscopy: - Deposition of basophilic calcium salts in form of granules - Smooth muscle replaced by acellular hyalinized fibrous tissue - Lumen normal, filled with red blood cells - Tunica intima and adventitia spared