2.  Define calcification  Types of calcification  Causes, feature and effect of dystrophic calcification  Causes, feature and effect of metastatic calcification

3.  is a common process in a wide variety of disease states  it implies the abnormal deposition of calcium salts with smaller amounts of iron, magnesium, and other minerals.

4.  Dystrophic calcification:  When the deposition occurs in dead or dying tissues  it occurs with normal serum levels of calcium  Metastatic calcification:  The deposition of calcium salts in normal tissues  It almost always reflects some derangement in calcium metabolism (hypercalcemia)

6.  Dystrophic calcification is encountered in areas of necrosis of any type.  It is certain in the atheromas of advanced atherosclerosis, associated with intimal injury in the aorta and large arteries

7.  Although dystrophic calcification may be an incidental finding indicating insignificant past cell injury, it may also be a cause of organ dysfunction.  For example,  Dystrophic calcification of the aortic valves is an important cause of aortic stenosis in the elderly

8. Dystrophic calcification of the aortic valves

9.  calcium salts are grossly seen as fine white granules or clumps, often felt as gritty deposits.  Sometimes a tuberculous lymph node is essentially converted to radio-opaque stone.  Histologically, calcification appears as intracellular and/or extracellular basophilic deposits.  In time, heterotopic bone may be formed in the focus of calcification.

10. Dystrophic calcification in the wall of the stomach

11.  Initiation (or nucleation)  Propagation (intracellular or extracellular) The ultimate end product is the formation of crystalline calcium phosphate

12.  Initiation in extracellular sites occurs in membrane- bound vesicles about 200 nm in diameter in degenerating cells.  Phosphates accumulate as a result of the action of membrane-bound phosphatases  Initiation of intracellular calcification occurs in the mitochondria of dead or dying cells that have lost their ability to regulate intracellular calcium.

13.  After initiation in either location, propagation of crystal formation occurs.  This is dependent on: 1. the concentration of Ca2+ and PO4- in the extracellular spaces 2. the presence of mineral inhibitors 3. the degree of collagenization, which enhances the rate of crystal growth

15.  Metastatic calcification can occur in normal tissues whenever there is hypercalcemia.

16. 1.increased secretion of parathyroid hormone 2.destruction of bone due to the effects of accelerated turnover (e.g., Paget disease), immobilization, or tumors (multiple myeloma, leukemia, or diffuse skeletal metastases) 3.vitamin D-related disorders including vitamin D intoxication and sarcoidosis 4.renal failure, in which phosphate retention leads to secondary hyperparathyroidism.

17.  Metastatic calcification can occur widely throughout the body but principally affects the interstitial tissues of the vasculature, kidneys, lungs, and gastric mucosa.  The calcium deposits morphologically resemble those described in dystrophic calcification.

18.  Extensive calcifications in the lungs may produce remarkable radiographs and respiratory deficits  Massive deposits in the kidney (nephrocalcinosis) can cause renal damage.

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21.  Depositions of lipids:  Fatty change: accumulation of free triglycerides in cells, resulting from excessive intake or defective transport (often because of defects in synthesis of transport proteins); manifestation of reversible cell injury

22.  Cholesterol deposition: result of defective catabolism and excessive intake; in macrophages and smooth muscle cells of vessel walls in atherosclerosis

23.  Deposition of proteins: reabsorbed proteins in kidney tubules; immunoglobulins in plasma cells  Deposition of glycogen: in macrophages of patients with defects in lysosomal enzymes that break down glycogen (glycogen storage diseases)

24.  Deposition of pigments: typically indigestible pigments, such as  carbon,  lipofuscin (breakdown product of lipid peroxidation),  iron (usually due to overload, as in hemosiderosis)

25.  Dystrophic calcification: deposition of calcium at sites of cell injury and necrosis  Metastatic calcification: deposition of calcium in normal tissues, caused by hypercalcemia (usually a consequence of parathyroid hormone excess)