Page 12 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

1 Fundamentals S. Silbernagl and F. Lang

Cell Growth and Cell Adaptation
It is more than a hundred years ago that Rudolf some division and migration to the poles) fol-
Virchow first conceived of his idea of cellular lowed by the telophase (formation of nuclear
pathology, i.e., that disease is a disorder of the envelope). Cytokinesis begins in the late stage
physiological life of the cell. The cell is the of the anaphase with developmentof the cleav-
smallest unit of the living organism (Wilhelm age furrow in the cell membrane. After this a
Roux), i.e., the cell (and not any smaller entity) new G 1 phase begins.
is in a position to fulfill the basic functions of Cells with a short life-span, so-called labile
the organism, namely metabolism, movement, cells, continually go through this cell cycle,
reproduction and inheritance. The three latter thus replacing destroyed cells and keeping the
processes are made possible only through cell total number of cells constant. Tissues with la-
division, although cells that can no longer di- bile cells include surface epithelia such as
vide can be metabolically active and are in those of the skin, oral mucosa, vagina and cer-
part mobile. vix, epithelium of the salivary glands, gastroin-
With the exception of the germ cells, whose testinal tract, biliary tract, uterus and lower
chromosome set is halved during meiotic divi- urinary tract as well as the cells in bone mar-
sion (meiosis), most cells divide after the chro- row. The new cells in most of these tissues
mosome set has first been replicated, i.e., after originate from division of poorly differentiated
mitosis (so-called indirect division of the nu- stem cells (→ p. 28ff.). One daughter cell (stem
cleus) followedby division of the cell (cytokine- cell) usually remains undifferentiated, while
sis). In this process every cell capable of mito- the other becomes differentiated into a cell
sis undergoes a cell or generation cycle (→ A) which is no longer capable of dividing, for ex-
in which one mitosis (lasting ca. 0.5–2 h) is al- ample, an erythrocyte or granulocyte (→ A).
ways separated from the next one by an inter- Spermatogenesis, for example, is also charac-
phase (lasting 6–36 h, depending on the fre- terized by such differentiated cell division.
quency of division). Most importantly, the cell The cells of some organs and tissues do not
cycle is governedbycertain cycle phase–specif- normally proliferate (see below). Such stable
ic proteins, the cyclines. They form a complex or resting cells enter a resting phase, the G 0
with a protein kinase, called cdc2 or p34 cdc2 , phase, after mitosis. Examples of such cells
which is expressed during all phases. When are the parenchymal cells of the liver, kidneys,
cytokinesis is completed (= end of telophase; and pancreas as well as connective tissue and
→ A), cells that continually divide (so-called mesenchymal cells (fibroblasts, endothelial
labile cells; see below) enter the G 1 phase (gap cells, chondrocytes and osteocytes, and
phase 1), during which they grow to full size, smooth muscle cells). Special stimuli, trig-
redifferentiate and fulfill their tissue-specific gered by functional demand or the loss of tis-
tasks (high ribonucleic acid [RNA] synthesis, sue (e.g., unilateral nephrectomy or tubular
then high protein synthesis). This is followed necrosis; removal or death of portions of the
by the S phase, which lasts about eight hours. liver) or tissue trauma (e.g., injury to the
During this phase the chromosome set is dou- skin), must occur before these cells re-enter
bled (high DNA synthesis). After the subse- the G 1 phase (→ A,B). Normally less than 1%
quent G 2 phase, which lasts about one to two of liver cells divide; the number rises to more
hours (high protein and RNA synthesis; energy than 10% after partial hepatectomy.
storage for subsequent mitosis; centriole divi- The conversion from the G 0 phase to the G 1
sion with formation of the spindle), the next phase and, more generally, the trigger for cell
mitosis begins. The prophase (dedifferentia- proliferation requires the binding of growth
tion of the cell, e.g., loss of microvilli and Golgi factors (GFs) and growth-promoting hor-
apparatus; chromosomal spiraling) is followed mones (e.g. insulin) to specific receptors that
by the metaphase (nuclear envelope disap- are usually located at the cell surface. How-
2 pears, chromosomes are in the equatorial ever, in the case of steroid receptors these are
plane). Then comes the anaphase (chromo- in the cytoplasm or in the cell nucleus (→ C).
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Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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