How Cells Grow - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 574

So far we have been focused on the cell's endogenous needs with single-cell organisms.
For multicellular organisms, the endogenous organism needs also include the replacement
of dead cells. To certain degree, the cell death and division in multicellular organisms help
us understand cell endogenous metabolism needs.
Apoptosis is the process of programmed cell death (PCD) that may occur in multicellular
organisms. PCD involves a series of biochemical events that lead to a variety of morpholog-
ical changes, including blebbing changes to the cell membrane such as loss of membrane
asymmetry and attachment, cell shrinkage, nuclear fragmentation, chromatin condensation,
and chromosomal DNA fragmentation. Processes of disposal of cellular debris whose results
do not damage the organism differentiate apoptosis from necrosis.
In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular
injury, apoptosis, in general, confers advantages during an organism's life cycle. For example,
the differentiation of fingers and toes in a developing human embryo occurs because cells
between the fingers apoptose; the result is that the digits are separate. Between 50 and 70 billion
cells die each day due to apoptosis in the average human adult. For an average child between
the ages of 8 and 14 years, approximately 20 e 30 billion cells die a day. In a year, this amounts to
the proliferation and subsequent destruction of a mass of cells equal to one's body weight.
Research on apoptosis has increased substantially since the early 1990s. In addition to its
importance as a biological phenomenon, defective apoptotic processes have been implicated
in an extensive variety of diseases. Excessive apoptosis causes hypotrophy, such as in
ischemic damage, whereas an insufficient amount results in uncontrolled cell proliferation,
such as cancer.
Apoptosis occurs when a cell is damaged beyond repair, infected with a virus, or under-
going stressful conditions such as starvation. Damage to DNA from ionizing radiation or
toxic chemicals can also induce apoptosis via the actions of the tumor-suppressing gene.
The “decision” for apoptosis can come from the cell itself, from the surrounding tissue, or
from a cell that is part of the immune system. In these cases, apoptosis functions to remove
the damaged cell, preventing it from sapping further nutrients from the organism or halting
further spread of viral infection.
Apoptosis also plays a role in preventing cancer. If a cell is unable to undergo apoptosis
because of mutation or biochemical inhibition, it continues to divide and develop into
a tumor. For example, infection by papillomaviruses causes a viral gene to interfere with
the cell's protein, an important member of the apoptotic pathway. This interference in the
apoptotic capability of the cell plays a role in the development of cervical cancer.
In an adult multicellular organism, the number of cells is kept relatively constant through
cell death and division. Cells must be replaced when they malfunction or become diseased,
but proliferation must be offset by cell death. This control mechanism is part of the homeo-
stasis required by living organisms to maintain their internal states within certain limits. The
related term allostasis reflects a balance of a more complex nature by the body.
Homeostasis is achieved when the rate of mitosis (cell division resulting in cell multipli-
cation) in the tissue is balanced by the rate of cell death. If this equilibrium is disturbed, one
of two potentially fatal disorders occurs:
￿ the cells divide faster than they die, resulting in the development of a tumor.
￿ the cells divide slower than they die, causing cell loss.