Metastaticcalcificationcanoccurwidelythroughoutthebodybutprincipallyaffectstheinterstitialtissuesofthevasculature,kidneys,lungs,andgastricmucosa.Thecalciumdepositsmorphologicallyresemblethosedescribedindystrophiccalcification.Althoughtheygenerallydonotcauseclinicaldysfunction,extensivecalcificationsinthelungsmaybeevidentonradiographsandmayproducerespiratorydeficits,andmassivedepositsinthekidney(nephrocalcinosis)canleadtorenaldamage.
Abnormaldepositsofmaterialsincellsandtissuesaretheresultofexcessiveintakeordefectivetransportorcatabolism.
Fattychange:accumulationoffreetriglyceridesincells,resultingfromexcessiveintakeordefectivetransport(oftenbecauseofdefectsinsynthesisoftransportproteins);manifestationofreversiblecellinjury
Cholesteroldeposition:resultofdefectivecatabolismandexcessiveintake;seeninmacrophagesandsmoothmusclecellsofvesselwallsinatherosclerosis
Depositionofproteins:reabsorbedproteinsinkidneytubules;immunoglobulinsinplasmacells
Depositionofglycogen:inmacrophagesofpatientswithdefectsinlysosomalenzymesthatbreakdownglycogen(glycogenstoragediseases)
Depositionofpigments:typicallyindigestiblepigments,suchascarbon,lipofuscin(breakdownproductoflipidper-oxidation),oriron(usuallyresultingfromoverload,asinhemosiderosis)
Dystrophiccalcification:depositionofcalciumatsitesofcellinjuryandnecrosis
Metastaticcalcification:depositionofcalciuminnormaltissues,causedbyhypercalcemia(usuallyaconsequenceofparathyroidhormoneexcess)
Individuals age because their cells age. Although public attention on the aging process has traditionally focused on its cosmetic manifestations, aging has important health consequences, because age is one of the strongest independent risk factors for many chronic diseases, such as cancer, Alzheimer disease, and ischemic heart disease. Perhaps one of the most striking discoveries about cellular aging is that it is not simply a consequence of cells’ “running out of steam,” but in fact is regulated by a limited number of genes and signaling pathways that are evolutionarily conserved from yeast to mammals.
Cellular aging is the result of a progressive decline in the life span and functional activity of cells. Several abnormalities contribute to the aging of cells (
Fig. 2.27 • Accumulation of mutations in DNA. A variety of metabolic insults over time may result in damage to nuclear and mitochondrial DNA. ROS induced by toxins and radiation exposure contribute to DNA damage associated with aging. Although most DNA damage is repaired by DNA repair enzymes, some persists and accumulates as cells age, especially if repair mechanisms become inefficient over time. Accumulation of mutations in nuclear and mitochondrial DNA ultimately compromise the functional activities and survival of cells.