HypoxiaandischemialeadtoATPdepletionandfailureofmanyenergy-dependentfunctions,resultingfirstinreversibleinjuryand,ifnotcorrected,innecrosis.
Inischemia-reperfusioninjury,restorationofbloodflowtoanischemictissueexacerbatesdamagebyincreasingproductionofROSandbyinflammation.
OxidativestressreferstoaccumulationofROS,whichcandamagecellularlipids,proteins,andDNA,andisassociatedwithnumerousinitiatingcauses.
Proteinmisfoldingdepletesessentialproteinsand,ifthemis-foldedproteinsaccumulatewithincells,resultsinapoptosis.
DNAdamage(e.g.,byradiation)alsocaninduceapoptosisifitisnotrepaired.
Inflammationisassociatedwithcellinjurybecauseofthedamagingactionsoftheproductsofinflammatoryleukocytes.
We have now concluded the discussion of cell injury and cell death. As we have seen, these processes are the root cause of many common diseases. We end this chapter with brief considerations of three other processes: cellular adaptations to stresses; intracellular accumulations of various substances and extracellular deposition of calcium, both of which are often associated with cell injury; and aging.
Adaptations are reversible changes in the number, size, phenotype, metabolic activity, or functions of cells in response to changes in their environment. Physiologic adaptations usually represent responses of cells to normal stimulation by hormones or endogenous chemical mediators (e.g., the hormone-induced enlargement of the breast and uterus during pregnancy), or to the demands of mechanical stress (in the case of bones and muscles). Pathologic adaptations are responses to stress that allow cells to modulate their structure and function and thus escape injury, but at the expense of normal function, such as squamous metaplasia of bronchial epithelium in smokers. Physiologic and pathologic adaptations can take several distinct forms, as described in the following text.
Hypertrophy is an increase in the size of cells resulting in an increase in the size of the organ. In contrast, hyperplasia (discussed next) is an increase in cell number. Stated another way, in pure hypertrophy there are no new cells, just bigger cells containing increased amounts of structural proteins and organelles. Hyperplasia is an adaptive response in cells capable of replication, whereas hypertrophy occurs when cells have a limited capacity to divide. Hypertrophy and hyperplasia also can occur together, and obviously both result in an enlarged organ.
Hypertrophy can be physiologic or pathologic and is caused either by increased functional demand or by growth factor or hormonal stimulation.
The massive physiologic enlargement of the uterus during pregnancy occurs as a consequence of estrogen-stimulated smooth muscle hypertrophy and smooth muscle hyperplasia (
Fig. 2.20 ). In contrast, in response to increased workload the striated muscle cells in both the skeletal muscle and the heart undergo only hypertrophy because adult muscle cells have a limited capacity to divide. Therefore, the chiseled physique of the avid weightlifter stems solely from the hypertrophy of individual skeletal muscles.
An example of pathologic hypertrophy is the cardiac enlargement that occurs with hypertension or aortic valve disease (
Fig. 2.21 ). The differences between normal, adapted, and irreversibly injured cells are illustrated by the responses of the heart to different types of
Fig. 2.20 Physiologichypertrophyoftheuterusduringpregnancy.(A)Grossappearanceofanormaluterus(right) andagraviduterus(left) thatwasremovedforpostpartumbleeding.(B)Smallspindle-shapeduterinesmoothmusclecellsfromanormaluterus.(C)Large,plumphypertrophiedsmoothmusclecellsfromagraviduterus;comparewithB.(B andC, Samemagnification.) http://ebooksmedicine.net