Biomedical Engineering Reference
In-Depth Information
(a)
(b)
(c)
(d)
(e)
Cell and nuclear diamet
er vs. time
cell diameter
nuclear diameter
Cell volumes thr
oughout necrosis
calcification
cytoplasmic solids
cytoplasmic fluids
nuclear fluids
nuclear solids
30
250
25
200
20
150
15
100
10
50
5
0
0
0
2
4
6
8
10
12
0
10
20
30
40
50
60
time (hours)
time (days)
Fig. 3 Necrosis schematic. Top: a, b The necrotic cell swells until its membrane splits and leaks
its fluid content c. Its remaining nuclear solid content degrades d, and the remaining cytoplasm
degrades and is sometimes calcified e. Bottom: Preliminary simulation [
64
] of early necrotic cell
volume composition (left) and nuclear/total diameters (right). Figures courtesy of [
64
]
shrinkage (pyknosis). However, the DNA is not cleaved into regularly-sized
fragments, nor is it encapsulated into apoptotic bodies. Instead, it remains and
degrades over time, eventually rupturing and dissipating into the remaining
cytoplasm. See Fig.
3
(top: d and bottom: right). In many tumors, necrotic tissue is
removed by infiltrating macrophages; see the mathematical modeling of this
process (and corresponding references) in [
73
]. We note that this brief overview of
early-to-mid necrosis is a simplification, and the lines between apoptosis and
necrosis can be blurred. For example, apoptotic bodies that are not cleared can
become necrotic [
44
,
65
], and while necrosis is seemingly ''passive'', it involves
numerous significant biochemical processes [
7
,
46
]. Excellent reviews of necrosis
can be found in [
6
,
7
,
46
,
66
,
87
].
2.2.1 Dystrophic Calcification
In DCIS, the necrotic core is separated from immune cells (and the stroma) by an
intact basement membrane, preventing the removal of necrotic material. Instead, it
remains and continues to degrade. In this and other cancers where the necrotic
material is not cleared but rather persists for long periods of time, the necrotic core
can undergo dystrophic calcification [
40
,
47
]. In this process, calcium ions interact
with remaining phospholipids in the necrotic cell (the membrane, vesicles, etc.) to
Search WWH ::
Custom Search