This result 
i.s an impossibility as a funct.ion only of the concentra­
tion forces of blood corPuscles. These forces, which 
were distributed unevenly to ooe side of the "tumour", 
should instead create their o"'n concentration centres 
outside the "tumour". The only known force that can 
possibly produce radiating structures of t.he observed 
extensions and locations in the lung is a closed circuit Fig. X/:8. After desanguinauon of the dog, the lung and ad­
jacont chost wall were removed en bloc. The radiograph 
shows the specimen after stipt inflation of the lung. No 
structure:s are evident corresp:mding to ''A'' and ••a•• zones 
obKrved in vivo. Some irregular infiltrations around the 
"tumour'' represent local blood. This experiment illusuares 
som<: of the critical discrepancies between an examination in 
. ;,-o and at necropsy . In lhc l•ftl! the distens;oa of the pattn­
chyma in vivo by subatmospheric intrapleural pressures and 
by vascular perfusion pressures are of particular importance 
in structural analyses. Artificial tumour in doc lunc I 09 Fig. Xl:9. Postmortem radiograph of slightly inflated lung 
with multjple metastases from carcinoma of colon. Note 
faint radiolucent areas("A" zone) around several tumours. electric field. Neverthe less, we have already :argued 
that the "tumour" itself, by virtue of its insulating 
shellac layer, is excluded from any closed circuit tissue 
channels. The only remaining possibility to explain the 
development of the radiating structures must be the 
creation of tissue injury during the implantation of the 
tumour. Tissue, inclurling blood, adjacent to the im· 
planted tumour should then have polarized electro­
chemically against surrounrling noninjured tissue. In 
order to resolve our dilemma we are now forced logi­
cally to postulate that a closed electric circuit must 
exist between surrounding normal tissues and degrad· 
ing blood and cell material adjacent to the "tumour". The corona structures observed radiologically 
around the artificial "tumour" were disarranged or 
not evident after removal of the lung. This finding is 
not surprising. As soon as the chest is opened in any 
animal, the mechanical factors in the lung parenchyma 
are changed. The effects of subatmospheric pleural 
pressures, interstitial and intravascular fluid pressures , 
etc., are changed rarlically compared to the situation in 
vivo. These differences appear to explain why radiolo­
gic observations in vivo of structures in the lung (pro­
duced by fluid and movable cellular elements) are not 
readily recognized on histologic or radiographic exami­
nations of removed lungs. This situation shourd hold 
at least when the pathologi c condition has been present 
for only a relatively short period of biologic time, e.g., 
2 weeks. Permanent fiXations of the structural arrange­
ment are, however, possible. Thus, faint rarliolucent 
"A" zones are seen in Fig. XI: 9, which is a postmor­
tem radiograph of a slightly inflated lung, containing 
many small metastases from a carcinoma of the colon 
(radiograph kindly submitted to the author by Dr. L. 
Kreel, Northwick Park Hospital, Harrow, Middlesex , 
England). Similar fmdings can also be seen in vivo in 
processes of long duration, e.g., a granuloma (Fig. IV: I) even after a pneumothorax has been produced . Factors contributing to the development of corona 
structures are reviewed in Fig. XI: 10. The tumour in 
110 Artificial tumour in dog lung Fig. XI: 10. Factors producing corona structures around a 
tumour during an electropositive phase. Surrounding tissue 
is electronegative. Transport of material takes place over a 
postulated biologically closed electric circuit (BCEC). The 
tumour blocks the local flow of pleural fluid toward the JU. lum. Electroosmosis acts to prevent this fluid from moving 
near the surface of the tumour, giving rise to a perifocal halo, 
the u A" zone (hydropcnic zone). The displaced tissue water 
produces increased opacity, a "B" zone (hydropic zone). At 
rhe interface between these zones hydrostatic turgor pressure 
and electroosmo tic pressure balance each other. Small arches 
develop at the interface of the "A" and "B" zones. Electric 
edge enhancement at small protrusions of the tumour surface 
causes dipole indu ction in dielectric movable materials, 
which form radiating structures. Their hygroscopi c material 
contracts i.n the hydropenic zone, contributing to the shape 
of the arches and to the production of retraction packets in 
the pleura. this figure is represented as polarized elecrropositively 
in relation to surrounding lung tissue. The existence of 
a biologically closed electric circuit across polarizing 
regions of tissue is postulated in Fig. XI: 10. Note that 
protrusions on the surface of the tumour locally en· 
hance the electric field. Under the combined influence 
of the forces within an activated closed circuit and of 
the physicochemical forces of ionic and nonionic mov­
able materials in the tissue matrix, different structures 
will beeome produced or modified. One of the most 
characteristic modifications in the circuit is transport 
of water. Water moving in a closed electric circuit 
through a matrix of cotton wool or lung tissue was 
demonstrated in Chapter IX. Cotton wool and lung 
each carry a surplus of fiXed electronegative charges, 
so water moves from anode to cathode. Such move-ment will produce a hydropenic (radiolucent) "A" 
zone around an anodic tumour. Movement of water 
will also produce a hydropic (radiopaque ) "B" zone 
outside the "A" zone when water moves against a 
hydrostatic pressure. Equilibrium is then created be· 
tween the two opposing force$, giving rise to an inter­
face, seen as a row of arches forming an arcade. The 
actual structural changes seen in radiographs are, how­
ever, created not only by water but also by movement 
and reorientation of charged or dielectric corpuscular 
elements, i.e., cells, cellular debris, macromolecules 
and electrolytes. Concentration forces also connibute 
to the development of radiating structures and arches 
(as well as nonhydropenic and nonhydropic "A" and 
"B" zones, respectively ), as shown in vivo in this 
chapter. The radiating structures around tumours con· 
sist mainly of fibrous, partly hygroscopic, partly non­
hygroscopic material. Within the hydropenic zone a 
local scar-shrinking effect may occur. Such a shrinking 
of a well-developed radiating structure extending to 
nearby pleura should then be able to produce a retrac­
tion pocket (see also Chapters III and XVI). At this juncture it must be evident to the reader that for all component s of corona structures to develop, 
particularly over distances of several centimetres , elec­
tric forces acting over closed circuits are a prerequisite. We have now arrived at a point central to the study of 
tissue transformation by local electrochemical polariza­
tions between tissues. The introduction of this concept 
will make it easier to understand not only the corona 
structures but also phenomena connected with tissue 
healing and tissue development. In the next two chap· 
ters a mechanism will be described which permits 
extensive transformations of tis.~ue over long periods of 
time at low voltage gradients. This mechanism will 
now be described as the biologically closed electric 
circuit (BCEC). Reference s 
1. Arnulf, G., and Chacoma c, R.: L'antriographk me{hodque des 
artCres o>ronaires grice i l'utili7.ation de: l'acCtylcholint; donnees 
cxpC_rimtnta l~s ct cliniqu~. Lyon Chir. 54:2121, 1958. 2. TOmcll, G., and Nordcn.strOm, 8.: Unpublished data, 1962. Artificial tumour in dog lung Ill XII. Biologically closed 
electric circuits (BCEC) 
When an electrolyte is brought in contact with a metal, 
an electric double layer will develop at their inter­
face (26, 27). This interaction can be regarded as a 
structuring process, usually in a zone no thicker than a 
few A. This restricted spatial extension of the electric 
double layer and of its surrounding diffuse layer, 
indicates that further explanation is required for the 
uneven distribution of material sometimes seen radio­
graphically (Fig. XII: 1) within one to two millimetres 
adjacent to metallic fiXAtion devices in tissue. Corro­
sion is one factor to consider. Associated events are 
always connected with electric transports over closed 
circuits between relAtively anodic and cathodic sites. In tissue, such mechanisms should involve electric 
transports over the metal and conducting tissue chan­
nels and also include at least one anodic and one 
cathodic site of reaction. Multiple reaction sites of 
different kinds and their corresponding conducting 
channels will be seen shordy in a variety of combina­
tions. Corrosion of metallic devices in vivo will be de­
scribed in this chapter as a radiographically detectable 
expression of closed electric circuits. A preliminary 
description will be offered of a dynamic interaction 
between tissue and metal during corrosion in vivo. A 
description will then follow of a mechanism in tissue 
112 Biologicall y closed electric circuits which appears to be of importance for understanding 
the development of normal and pathologic structures 
in tissue. The mechanism takes plAce over what will be 
called biologically closed electric circuits (BCEC). A. Corrosion in vivo 
Corrosion is often encountered in vivo around metallic 
surgical implants. Often misinterpreted radiologicall y, 
the process is called "bone resorption" because the 
implant appears as if it were resting in a bony cavity 
containing a narrow (1-3 mm) space between the·im· 
plAnt and a radiopaque line seemingly defming a cavi­
tary wall (Fig. Xll: 1). The differential diagnosis between a real cavity in 
bone surrounding a loose implant and corrosion 
around a well-fiXed implant is a very important clinical 
problem which has been largely ignored. A discussion 
of some of these problems at current levels of under­
standing has been presented by Frank and Ziner (18). The electrochemical stability of a metal is given by 
its normal potential, related to the standard normal 
hydrogen electrode (NHE). The normal potentials of Table XII: I. Nomo4/ potrnliols of nuta/J and nutal-blood 
pountia/s in rtlariOII tc tlbmtalloydrogm <ltctrod• (NHE) 
MtuYMflal ion RaU,. po<mtial 
srandud electrode ........ ).blood 
potmtial iotufKC 
M<ul (V, NRE) (V, NHE) 
Mg -2.315 -1.3«) 
AI -1.670 -0.750 
Cd -o.402 -0.050 
Cu +0.346 +0.025 
Ni -0.230 +0.029 
Au + 1.410 +0.120 
PI + l.blO +0.125 
some metal-metal ion combinations and some metal­
blood potentials ar< shown in Table XII: I (68). Corrosion of a metal implant means that an electro­
chemical interaction with electrolyu:s in 1hc surround­
ing tissue partially destroys the meta.l. Redox reactions 
take place, in which oxidation means delivery of elec­
trons to the met:al and reduction mean~ acceptance of 
dect.rons by the ti.ssue (rom the metal. The process of 
corrosion requires an anode, a cathode, an electrolyte 
and at least one closed circuit between anode and 
cathode. Different "inert" metallic prostheses contain local 
differences in quality of the metal. Such local changes 
in metal, for instance, can be created by a hammer­
stroke during surgery, producing a local "injury po­
tential" in the metal. The varying potentials of the 
connected internal regions of a metallic prosthesis con­
stitute its relativel! anodic and cathodic pans. Sur­
rounding electrolytes complete the electric circuit. Current will Oow dtrough such a galvanic "battery". The anodic (negative) or "active" part of the metal is 
tlac dvuul' u( ~h:t.:trun:i' am.l lx:\:vmc~ ~. :urnx.lcd (oxi­
dized). The cathodic (positive) or "passive" (noble) 
parts of the metal forrn the electron acceptor and is 
the site of reduction. The cathodes do not corrode. Chemical analyses of bone tissue close to metal im­
plants have been performed by Ferguson, Laing and 
Hodge (16), who found metal in the tissue in concen­
trations significantly higher than expected, despite the 
supposed ly "noncorrosive" character of the metallic 
implant. The dissolution of metal takes place at the anode: 
e.g., Metal;::tMeUI12++2e-. Metal ions will then either diffuse in the solution or 
combine with hydroxyl ions as a precipitate : 
Metal1• +20H-~Metal(OH)z. The solubility of hydroxides of different metals var­
ies with ionic concentrations and values of pH in the 
tissue Ouid (Fig. XII: 2) (65). Fig. XII: I. "Uncomplicated corrosion" betw~n mewl and 
bone, radiograprucally seen at the lateral aspeCt of a metal 
l'fOStbetic implant in the rup. A radiopaque mttal deposit 
lies panlleland 1-2 mm Ia toni to the $haft of the prosthesis 
(:>lack arrows). The deposit appcan farthest from the bone 
q>posite a sliahtly irregular dent (whitt &JTOW1). The dis· 
tan<l< between th< surface of the mtllll and tht motallic de­
posit in the bone is greatest in this region. Note that no 
"Une" is present opposite the distal part of the prosthesis. Corrosion requires a complete electric circuit. The cor· 
roded part of tho metal (under the metal dtposit) constitutes 
tbe anode, the noncorroded part the cathodt. Tissue electro­
lytes repre#nt the uextemal'' ionic part of aheeltctri c cir· 
cuit, lht mtlJil between the anode and cathode tht tlecrronic 
·~ntunal" port of tbt circuit. Wbcn rnistivicy of the "exteroal"" condutti•g medium is 
bagb, CO<roS>OO will usually be c:nhaDO<d close to the tnnsJ· 
llOn zon< between the anodic and c:athodic por:s of the met· 
al. So-called general corrosion takes pla<l< 01 multiple micro· 
s.""Opic anodic and cathodic sitos, which oven change thtir po­
larity in time. This effect will abo lead to oorrosion over a 
macroscopic surface. Biologically closed electric circuits 113 .... 
~~~ 
Hydroxide 
Pf'tCipitates 
0 I 2 3 4 5 6 7 8 9 ~ 11 12 13 M 
pH---
Fig. XII: 2. Solubilities of some metal hydroxides at differ­
ent vaJues of pH and ionic concentrations. Tissue pH does vary to some extent, within physio­
logical limits. For instance, arterial plasma is slightly 
more alkaline than arterial whole blood during phys­
ical exercise. When acid-base equilibrium is acutely 
disturbed, pH may fluctuate, during short periods, 
between 6.8 and 7.8 (18). Corrosion-dissolved metal in 
tissue is partly engulfed by histiocytes, macrophages 
and leukocytes and is eventually transported away or 
encapsulated in fibrous tissue. Metal ions may also be 
resorbed and produce general or local toxic effects. Local accumulation of metal precipitates is also con­
sidered to lead to aseptic necrosis (18). Oxygen around the cathode is reduced, as follows: 
'h02+H20+2e-~20H-. The above explanation for in vivo corrosion is gener­
ally accepted, but in the author's opinion, incomplete 
in rwo respects: the sites of the driving force of the 
reaction and the transport channels. It is likely that corrosion often originates from the 
differences berween relatively anodic and cathodic 
parts of an implant, an internal phenomenon usually 
found in such devices. This process will here be called 
"uncomplicated" corrosion. Regardless of local differences in quality of the im­
planted metal, local metabolic changes in the tissue in 
the vicinity of the implant also are a source of local 
electrochem ical differences. Even an inserted nail 
should locally stress bone and theoretically produce 
local polarization as a piezoelectric effect. Pathologi c 
changes such as local bleeding, aseptic necrosis or 
infection may create considerable differences of elec­
trochemical potential berween local regions in tissue 
and the metal. Such "polarizing" foci are of consider­
able clinical importance. They lead to what is here 
114 Biologicall y closed electric circuits called "complicated corrosion", indicating the pres­
ence of a complicating reaction in the tissue. Another source of energy can be found in the meta­
bolic fluctuations of the physicochemical potential of 
the surrounding normal tissue. This source will influ­
ence both complicated as well as uncomplicated corro­
sion. I. Ordinary "uncomplicated corrosion" 
This type of corrosion is synonymous with the classical 
concept of corrosion , based on a closed circuit reaction 
berween relatively anodic and cathodic parts of a metal 
in contact with an electrolyte. A radiograph of a stainless steel prosthesis in the 
right femur 12 months after surgery is shown in Fig. Xll: I. The metal of this prosthesis is made of a 
material "as inert as possible", as are other similar 
fiXation devices of metal. The prosthesis consists of 
iron combined with chromium, nickel and molybde­
num (Table XII: 2 shows the complex composition of 
rwo types of common metal implants used in bone 
surgery). The prosthesis was inserted into the femur without 
the use of any cement. A thin, slightly irregular 
"line", half a mm thick and about 10 em long, is seen 
along the upper straight lateral part of the implant. The distal part of the line gradually disappears, so that 
no line is seen at the lower lateral part of the metal. The greatest width berween the line and the implant 
Table XII: 2. Ctnnposili<m of maruials 
S14inlm Srul Typ~ 316 S/2 
Carbon 0.03% Maximum 
Silicon 0.20 10 1.00% 
Mlllli••= 0.50 10 2.00% 
Nickel 11.00 10 14.00% 
Otromium 16.S.O to IS. SO% 
Molybdenum 2.25 10 3.00% 
SuJphur 0.03% Maximum 
Phosphorus 0.04% Maximum 
Iron Balance 
Cobalt Chromt tlllqy 
Chromium 
Nickel 
Molybdenum 
Carbon 
Iron 
Silicon 
Manganese 
Cobah Z7 .00 10 30.00% 
2.50% Maximum 
5.00 10 7.00% 
0.20 10 0.35% 
0.75% Maximum 
1.00% Mnimum 
1.00% Maximum 
Balance 
The: tabJc: shown above: is from British Standard 3531: 1968, "Metal 
Implants and Tools used in Bone Surgery ... corresponds to a shallow dent in the metal over a 
distance of about 2 em. A radiolucent zone around prosthetic metal in the 
skeleton often indicates that the metal is movable and 
lying more or less free in a cavity or bony canal. The 
implant shown in Fig. XII: I, however, is not mov­
able. The line which gives the impression of a radiolu­
cent zone close to the metal is only a local change next 
to the superolateral rwo-thirds of the implant. The 
local deposition of metal corresponds only to a certain 
region of the metal without other signs of local changes 
in the bone. The metal may have its most intense 
anodic focus in the shallow dent in the metal, corre­
sponding to the place where the radiopaque line in the 
bone is thickest and most distant from the metal sur­
face. The mechanism for this process of "uncomplicated 
corrosion" is suggested in Fig. XII: 3. The metal has 
in this instance one anodic and one cathodic part and is 
surrounded by the tissue and its electrolytes. The 
anodic part is electronegative due to accumulation of 
electrons in the metal from dissolving iron. Secondar­
ily, electrons flow in the metal to the cathode. In the 
meantime, anions such as (OH)-in the electrolyte 
migrate to the anodic part of the metal. The ionized iron then combines with hydroxyl ions 
to produce Fe(OH)z (and later on, probably 
Fe,03 • nH20), which forrns the radiographic line 
close to the metal: 
Fe->Fe+++2e-, 
Fe+•+2H20 -.Fe(OH)2+2H+. At the cathode, oxygen will be reduced and hy­
droxyl ions liberated: 
02+2H20+4e---> 4(0H)-. The hydroxyl ions will then move in the tissue fluid 
toward the anode. They will, however, never reach the 
anode, as instead they combine with H+ ions, which 
are moving toward the cathode, to become water. 2. Corrosion influenced by BCEC: 
"complicated corrosion" 
The terrn "complicated corrosion " is introduced to 
indicate that the driving force of the corrosive process 
originates in pathologic tissue locally polarizing adja­
cent to a metal implant. Polarizing sites in the metal 
itself may then be absent or minimal. Fig. XII: 4 illustrates a fixation of a hip fracture, in 
which corrosion probably originates from local electro­
chemical differences in different parts of bone sur­
rounding the metal. Fig. XII: 4a shows rwo scrows 
(von Bahr) after surgical repair of a fracturo of the 
medial aspect of the femoral neck. The screws are ELECTROLYTE 
4H20----.._ I ---40H~-~ 
4H+ Anodic 
\ T 
40H----- ~o 
a( Cathodic 
4e 
Fig. X ll: 3. Schematic •explanation of "uncomplicated corro­
sion". The driving foroe is found between relatively anodic 
and cathodic regions in the metal. The dissolved iron in the 
anodic region recombine s with hydroxyl ions to form 
Fe(0H)2 as a "line" (*) adjacent to the metal. No corrosion 
takes place in the cathodic, electron-donating metal. correctly aligned. Th.e round margin of the bead of the 
femur shows a smooth cortical contour. Trabeculae 
appear norrnal. Two years later, two different views 
(Fig. XII: 4 b, c) exposed during the same examination 
show a radiopaque line in bone around the more crani­
al screw in portions distal to the head. No correspond ­
ing radiopaque iine is seen in bone along the other 
screws. Fig. XII: 4b and c also show that the cranial 
screw is situated close to a fracture line (arrow) divid· 
ing the femoral head into rwo parts. The cranial frag­
ment (left) shows an irregular bone-cartilage contour 
and irregularly calcified and decalcified regions, as in 
developing necrosis. The inferior part (right) of the 
femoral head shows norrnal bone, including the bone­
cartilage contour. This patient complained of some 
pain in the hip, but no clinical signs of local infection 
were present. The presence of a radiopaque line in 
bone along only one of the two hip screws and outside 
BiologicaUy closed electric circuits liS Fig. Xl/:4. "Complicated corrosion" . Radiographic appear· 
anceof a human hip after surgery. (a) Two screws in position 
after operation for fracture of the femoral neck. Note normal 
bony trabeculae and the cortical margin of the femoral head. (band c) Two projections of the hiprwo years after operation. The femoral head is split in two(cortical fracrure, arrow). The cranial (left) part is necrotic. The bone-cartil'lge inter · 
face is irregular and bony structures are blurred and irregu· 
lar. A meta) deposit distal to the region of necrosis surrounds 
lhc cranial screw. No metal deposit is seen around the pan of 
the screw which is in necrodc bone. No metallic Hne is pre-
the necrouzmg fragment in the femoral head here 
suggests the development of "complicated corrosion". Fig. XII: 5 tentatively describes this corrosion process. The fundamental characteristic of "complicated cor· 
rosion" is that the driving potential emerges between, 
e.g., a metal and a dynamically changing local process 
in tissue, from which catabolic energy is liberated. Such a process here localized to the lateral side of the 
femoral bead (Tissue I) may be a result of hypoxic 
degradation of various components of injured bone 
tissue and accumulated blood. An adjacent prosthesis 
which consists of different metals may further influ. ence the catabolic reactions by the various catalytic 
properties of the metals. The multitude of reactions 
involved in these processes are difficult to define for 
various reasons. Reactants and reaction products can, 
e.g., be anticipated to be exposed to modulations by 
selective transports within closed electric circuits. Some of the possible events in complicated corrosion 
will ncverthelcs ,s be briefly discussed. During an early phase of hypoxic degradation the 
116 Biologically closed electric circuits sent adjacent to the other screw. Evidence in the text suggests that i_njured tissue in the ne~ 
erotic part of the femoral head creates an electrochemical po­
larization ("injury pOtential") in relation 10 the metal and the 
normal tissue in the trOChanter and neck. The screw consti· 
tutes one branch and the intercellular tissue fluid the other 
branch of an electrically closed circuit. Another closed elec· 
trie circuit, coupled in parallel, is created by a vascular-inter· 
stitial connection between the injured and normal tissue {see 
also Fig. Xfl: 8). tissue will become acid, mainly as a result of hypoxic 
degradation of glucose into lactic acid (38). Anaerobic 
glycolysis will further increase the amount of A TP 
which, by hypOxic hydrolysis, contribute s to tissue 
acidity: 
ATP+H20-+ADP+H + +energy+phosphate . In previously reported experiments on spontaneous 
degradation of blood, an initial decrease of pH was 
observed (page 70). It has further been suggested that 
the frrst biochemical manifestation of tissue injury is a 
loss of ATP (37). Irrespective of its mode of develop· 
ment the initial acidity may explain the common radio· 
logic observation of calciolytic areas in recently injured 
bone. It should be noted, however, that hydrolysis of 
A TP is used in Fig. XU: 5 only as one example of 
possible reactions which may contribute to make Tis· 
sue I initially acid and as one reaction capable to 
deliver phosphate ions, a necessary component for the 
eventual precipitation of apatite. Other sources for Anoxic Tissue I -Calciolytic phase 
Lagging alkalinity 
in tissuell 
Fig. XII: S. "Complicated corrosion", schematic illustra· 
tion. No initially anodic and cathodic regions of metal are 
n«essary in this type of corrosion. In time, the chemica) ac­
tivity of tissue fluids and tissue currents DUly secondarily po­
larize the metal. lnju.ry to tissue, e.g., local necrosis or infec­
tion, releases electrochemical energy, which supplies the 
driving force. Acidity, produced in the "calciolytic phase" 
by the degrading Tissue I, dissolves calcium and iron ions, 
production of phosphate ions as phospbocreatin, phos­
phoarginine and polymetaphosphate are even more 
likely to supply the tissue with substantial amounts of 
phosphate for a. subsequent precipitation of apatite. The initial acidic (calciolytic ) phase of complicated 
corrosion can not lead to the development of a precipi­
tation "line" as in uncomplicated corrosion because of 
extensive acidity in Tissue I. The decalcified areas 
further make the entire matrix irregular which should 
counteract the development of a regular "line" of 
precipitated Fe(0H)2 and later FezOJ. As long as the 
tissue is acid, calcium ions and dissolved ions from the 
implant and protons will spread by diffusion (and 
migration in the closed circuit) in the injured tissue: 
e.g., Ca(Anion)2+2H+-. 2H(Anion)+Ca2+ 
Fe-.Fe2++2e-. Because circulation is impaired to the damaged tissue 
(which in itself is likely to induce an hypoxic injury 
reaction), the surrounding tissue fluid is restricted in Anoxic Tissue I -Mineralization phase 
precipitati Substrates locally 
produced or available 
by diffusion or by 
BCE C transports 
Diffusion barriers by Red.subst r. + OH-_ 
polarization products -Oxid.COl-substr . +H• +2e-
Fe<OH '' '' '' 
'' '' '' 
which then precipitate in the alkaline "mine,ralization phase .. 
as complex calcium phosphate (apatite) and as Fe,(PO,),. Local sites of decalcification and calcium deposition are pro­
duced in Tissue I in this way. The precipitation uline" is 
produced as Fe(OH}z (and later, as Fc203 · nH20) when 
there is a net dissolution of metallic iron in Tissue II. BCEC 
= biologically closed electric circuits. its ability to buffer the local reactions. Protons wiU, 
however, diffuse and migrate more rapidly than phos­
phate ions and eventually combine with hydroxyl ions, 
diffusing from Tissue II, to form water. Such con­
sumption of protons may lead to an increasing accu­
mulation of phosphate ions. During these events, elec­
trons are produced in the metal adjacent to Tissue I, 
i.e., this part of the screw becomes electronegative. Electrons flow then to the relatively electropositive 
metal next to Tissue ll. The me~ then delivers elec­
trons to the tissue oxygen. Tissue II is not hypoxic, so 
oxygen is available: 
Because the circulation of blood is relatively intact in 
Tissue II, the alkaline reaction there will, however, be 
counteracted to some extent by the buffering and cir­
culation of tissue fluids. During a late stage of the 
development of complicated corrosion, the morpho­
logic appearance of the tissues (Fig_ XII: 4 b, c) gives a 
Biologically closed electric circuits 117 Malate Oxalacetate 
c, 
Ferricytochrome c 
hint to a drastic change of the tissue reactions: The 
anoxic Tissue I enters a phase of mineralization with 
irregular calcifications and the well oxygenized Tissue 
D shows a "line" of precipitation adjacent to the 
metal. These changes indicate that a reversal of flow of 
current must have taken place in the closed circuit. The biochemical reactions leading to these changes 
seem to be at least as complicated as those of the 
calciolytic phase. Associated events will only be pre­
liminary discussed as follows: 
The increasing accumulation of phosphate ions in 
Tissue I drives it toward the mineralization phase (Fig. XII: 5, right side). The question now arises whether 
this suggested relative accumulation of phosphate ions 
in Tissue I is sufficient to reverse the overall electric 
polarity of the system. This question is critical: a 
change of polarity of the injured tissue must be a 
prerequisite for an inflow of cations such as calcium 
and magnesium. It is, however, from an energetic 
point of view unlikely that proton loss and phosphate 
accumulation alone should be sufficient to reverse the 
polarity of the injured tissue. This preliminary expla­
nation of "complicated corrosion" does, on the other 
hand, not exclude the contribution of other biochemical 
reactions to such events. By diffusion or by closed 
circuit transports between Tissues I and II, oxidizing 
substances may accumulate in Tissue I. Similarly, 
reducing substances may accumulate in Tissue II. It is 
funhermore possible that these substances are also to 
some degree produced locally in Tissues I and II. Such 
118 Biologically closed electric circuits Fig. Xl/:6. Sequenc:<: of reaction steps inter­
minal oxidation of c:<:llular respiration (from 
Jordan). events should also be included in a discussion of rever­
sal of polarity between Tissues I and II. Several possibilities exist to support biochemical re­
versal of the driving potential in the reactions. Electric 
potential fluctuating between an injured tissue and a 
noninjured tissue over a closed circuit will now be 
presented as a prelintinary hypothesis. These consider­
ations are based mainly on information on degradation 
of tissue collected by Lehninger (38), Wilson, Dutton 
and Wagner (81) and Jordan (30). A large number of enzymes and substrates partici­
pating in degrading processes react with groups capa­
ble of acting as general acids or general bases, e.g., 
amino, carboxyl, sulfhydryl, phenolic hydroxyl and 
imidazole groups. However, an anodic phase of de­
grading tissue should not be able to enter a catho­
dic phase as a result of a single reaction. An alter­
native possibility might be that different reactions 
are superimposed on preceding phases of enzyme­
catalyzed reactions, as the maximum velocity for each 
reaction takes place at diflerent pH. In this way, 
sequences of electron-donat ing and electron-ac ­
cepting enzyme reacticns may produce fluctuations of 
the electric potential of the degrading tissue as the 
whole process drives toward equilibrium. Examples of 
such sequences are known, as in the electron transfer 
reactions of haemoproteins. Thus, Jordan (30) has 
described a redox potential cascade for the terminal 
oxidation chain of cellular respiration of the overall 
reaction: coo­
l 
CH2+!02-+ 
I 
HCOH 
I coo-coo­
l 
CH2+H20 
I co 
I coo-
as shown in Fig. XU: 6. Malate is not directly oxygenized in the presence of 
oxygen. The oxidation to oxalacetate occurs, however, 
rapidly via the intermediate steps shown in Fig. Xll: 6. This leads to a potential difference of more 
than I V, even though the potential differences for 
successive steps are small. It is also known that exer­
gonic reactions (with a negative standard-free-energy ) 
may change, e.g., the oxidation of glucose to water and 
carbon dioxide {ll.G0' = -686 kcal mol-1) into an en­
dergonic esterification of glucose and phosphate to 
glucose G-phosphate and water, which presents a posi­
tive standard-free-energy change (6.G0'=3.3 kcal 
mol-1). Such reactions may be generally expressed as: 
Exergonic A+B-+ C+ D+energy (Jl.G•negative) 
Endergonic energy (Jl.G•positive )+E+ F-+ G+H. How sequences of oxidizing and reducing reactions 
may change the direction of electron flow, or to which 
individual step or steps of a sequence should be attrib­
uted such functions in necrotizing tissue, e.g., bone, is 
presently not predictable. These mechanisms appear 
also to depend to a large extent on the function of 
adjacent normal tissue. Polarization products will also form at the cathodic 
metal surface during the calciolytic phase. This devel­
opment should impair the diffusion of oxygen toward 
the cathode. It should also facilitate a reversal of the 
direction of electron flow. The proposal of fluctuating and attenuating driving 
forces between Tissues I and II is based partly on the 
studies on injury potentials in tumours and spontane­
ously degrading sterile blood (Chapter VII), and partly 
on the physical fact that aU known spontaneous reac­
tions proceed in a fluctuating, attenuating fashion to­
ward equilibrium. It is inconceivable, moreover, to 
assume that the induction of a degrading process in 
vivo should proceed under the influence of a unidirec­
tional gradient of potential between the injured and 
surrounding normal tissue, simply because new distor­
tions of the ionic compositions at the reaction sites 
would then be created. Acceptance of a fluctuating 
injury potential between Tissues I and II also makes it 
possible to understand many biologic transformations 
which otherwise are difficult to explain. The early acidic phase of Tissue I is proposed to 
dissolve calcium in the bone matrix, hence this is here 
called the "calciolytic phase". Local decalcifications in 
bone are commonly seen radiographicaUy after bone 
injury, e.g., trauma. Direct evidence of a change of Tissue I from an 
acidic, "calciolytic phase" into an alkaline "mineral­
ization phase" is encountered in the development of 
radiographically evident, irregular zones of calcifica­
tion, appearing in previously decalcified bon<. This 
mineralization may now be explained as a result of 
inflow of calcium and magnesium ions as a selective 
transport over the closed electric circuit under the 
influence of the now cathodic reaction of the tissue. Local phosphate ions, in the meantime, are lagging in 
the process of diffusion in the degrading tissue and are 
therefore available for recombination with calcium and 
magnesium ions into complex calcium-magnesium­
phosphate salts as apatite. The development of decalci­
fied and calcified regions, which are radiographically 
common in aseptic necrosis or other kinds of bone 
injury, now in principle can be explained. As will also 
be shown later (Chapter XVI), the same principle can 
be applied experimeotaUy to produce rnicrocalcifica ­
tions in breast fat tissue. How does iron now appear as a precipitation line in 
the normal Tissue II? First, we may anticipate that 
hydroxyl ions remain in Tissue II from the phase when 
this tissue was an electron acceptor. When the polarity 
changes so that Tissue I consumes electrons, Tissue II 
accumulates dissolving iron ions from the adjacent 
metal, which delivers electrons: 
Fe_. Fe2+ +2e-. Fe2+ ions then diffuse and migrate away from the 
metal surface to a region in Tissue II where the pH is 
favourable for the combination of Fe2+ with remain­
ing hydroxyl ions, to form insoluble Fe(OHh (and 
later, Fe203 • nHzO). Local sites with increased x-ray attenuation in Tis­
sue I are generally regarded as caused by deposition of 
calcium. It should not be surprising , however, if fu­
ture analyses will show that these sites also include 
precipitated iron, dissolved during the acidic phase of 
Tissue I. This preliminary description of "complicated corro­
sion" is simplified and incomplete in many respects. It 
probably represents only one of several possible expla­
nations. MetaJ implants consist of different combi na~ 
lions of metals, two of which are presented in Table 
XII: I. Dissolving of iron in stainless steels in active 
states is accompanied by similar reactions of chromi­
um, nickel, molybdenum and manganese. Further­
more, one may expect that in the tissue fluid various 
compounds, not considered here, must also induce 
reactions with the implant. BiologicaUy closed electric circuits 119 a 
NEC Fig. XII: 7. (a) Precipitation 
Hline" produced adjacent to 
metal in the relatively nor· 
mal Tissue II during its 
mineralization phase. CLOSED CIRCUIT 
ElECTRIC FIELD 
FORCES (b) The necrotic Tissue I 
consumes electrons deliv­
ered from the metal adjacent 
to Tissue II as iron there dis­
solves. The Fe++ ions pro­
duced, then recombine with 
hydroxyl ions to form 
Fe(OH),. (c) In cross sec­
tion, the iron precipitate 
forms an equilibrium depos­
it as a ring around the metal 
by the action of closed cir­
cuit electric field forces and 
concentration forces ( = for­
mationof"A" and .. B" 
zones). See also Chapter X, 
Figs. I, 7. The characteristic appearance of metallic precipita­
tion as a line structure in radiographs will now be 
considered. 3. The precipitation line 
Dissolved metal has been chemically identified adja­
cent to metal in bony tissue by Ferguson, Laing and 
Hodge (16). Its constituent chemicals are most likely 
Fe(0H)2 and Fe20l · nH20. During the mineralization phase of anoxic necrosis, 
the necrotic Tissue I consumes electrons from the 
metal (Fig. XII: 7 a). The dissolving metal adjacent to 
Tissue II donates electrons to the implant (Fig. XII: 7 b). A cross section of the implant (Fig. XII: 7 c) 
shows the precipitation of Fe(OH)2 as a ring. Its 
development can most easily be explained like that of 
the "A" and "B, zones of semolina grains around a 
charged body (Fig. X: I a, 7 b). Closed circuit electric 
field forces compete with the radial, circular and longi­
tudinal vectors of concentration forces (Fig. X: 3). The 
precipitate appears in cross section as a "B" zone 
separated by an "A" zone from the metal. These zones also represem two different phases in 
which preferential adsorption and local concentration 
take place at their interface (the small arches and 
arcades previously described berween the "A" and 
"B" zones around a lung tumour are also sometimes 
seen radiographically as a thin adsorption line of high­
er attenuation of x-rays than the surroundings ). The 
120 Biologica lly closed electric circuits line of Fe(OH)2 or Fe201 · nH20 in bone adjacent to 
a metal does, of course, not appear as arches but rather 
as one complete arcade, which is a circular ring (pro­
vided the metallic surface is circular and smooth). Only when small edges protrude from the metal can 
th.e precipitation line of the iron compounds be pre­
dicted to appear in the cross section as a line of small 
arehes corresponding to the edges. Alternative explanation s also must be considered in 
th.e development of a precipitation line. Thus, metal in 
a passive state (e.g., stainless steel) is known to dis­
solve slowly in any oxygenized environment, leading 
to secondary diffusion and precipitation of metal hy­
droxide of low solubility. Such a mechanism is very 
likely to be involved in the events described, but only 
as a partially contributing mechanism. Other modifi­
cations of bone structures adjacent to the implant can 
also become induced as a result of toxic effects on cells 
by dissolved metals. Such injuries enhance conductiv­
ity of BCEC systems, leading to a gradual increase in 
in·tensity of all associated closed circuit reactions. 4. Dynamic factors in in vivo corrosion 
The uncompUcated and complicated types of in vivo 
corrosion have thus far for didactic purposes been 
described as instantaneous stationary situations. Bio­
logically, the actual condition must be different. It is 
even unrealisti c to assume that uncomplicated or com­
plicated corrosions exist as isolated phenomena. One Relative electron-equivalent charge transport 
in tissue-metal corrosion 
a 
+ 
Normal 
fluctuating 
metabolic b 
Catabolic ' ' ' ' ' ' c 
,. ' , ' 
I \ 
' I + 
... ''-' \ ' ' ,~ , , , , ' ' ' ' ' I 
' I ... ~' + 
Metallic 
corrosion Fig. XII: 8. Relatively alternating polari<y 
in corrosion. (a) Normal tissue, (b) in­
jured tissue or (c) metal in tissue may be 
relatively electropositive or electronega­
tive, dependjng on the: actual time:·related 
phases of fluctuating rissue potentials. Note the more rapid change of potential 
of normal tissue than of degrading tissue, 
which also presents larg<r amplitudes. Ar­
rows indicate directions of increasing elec­
troposith •e gradientS between sites of reac· 
tion. The tissue sites representing the ori­
gins of the driving forces of the system 
can be anticipated to vary spatially during 
different phases of the fluctuations of the 
injury potential. demand potential injury 
potential potential 
or the other type may more or Jess dominate. A third 
important factor will now ·be introduced: the modify­
ing influence of surrounding normal tissue. In the theoretical situation of "pure" uncomplicated 
corrosion, substances are produced at the sites of re­
dox reactions. These materials lead to a local decrease 
of em ropy, which in turn induce a new spontaneous 
drive toward an equilibrium. In the theoretical situation of "pure" complicated 
corrosion , polarization in tissue represents the driving 
force, character ized by a catabolic, fluciWlting injury 
potential. During the process of healing, however, the 
injured tissue will interact not only with the adjacent 
metal implant but also with the surrounding normal 
tissue, as in any other healing process. The modifying 
effects of the normal tissue are also characterized by its 
own normally fluctuating, metabolic demand poten­
tials. These three partial components may influence 
each other in varying ways in an overall physicochemi­
cal corrosion reaction driving toward equilibrium. The 
dynamic interaction of such a system is outlined in 
Fig. XII: 8 in terms of relative polarity and direction 
of charge transpons in tissue-metal corrosion. It may 
be seen that in cenain phases any of the reactants may 
be anodic or cathodic. Locally decalcified and calcified 
irregular regions in necrotizing bone are now nearly 
ready to be linked to the described dynamic correla­
tions between injured and surrounding noninjured tis­
sue. A practical message from this presentation is that a 
radiographic uline" adjacent to a metaHic implant in 
bone is not necessarily a sign of poor fixation of the 
implant. It may be caused by relatively harmless un­
complicated corrosion. On the other hand, corrosion 
of an implant is not always synonymous with the 
classical "uncomplicated" example of relatively anodic 
and cathodic pans in the metal. Corrosion in living tissue, in the author's opinion, is quite complex and 
depends to a large extent on the activities of both 
pathologic and normal tissue adjacent to the metal. In analyzing these events, the reader must recognize 
a recurrent issue: the radiographically visible, in vivo 
modifications of tissue structures are created by driv­
ing forces which are separated by long distances. Such 
conversions of energy over long distances can only take 
place in combination with electric transports over suit· 
able conducting channels, i.e., biologically closed elec· 
tric circuits. 5. Pathways for the electric CurTent 
To explain the morphologic background of biological­
ly closed circuits is not simple, even in uncomplicated 
corrosion. The surface of an iron nail immersed in 
salt water, for instance, is in contact with the 
conducting salt solution. The redox reactions neces­
sary for corrosion always require a closed circuit. It 
can be assumed that this circuit contains one branch 
within the metal, providing transport of electrons be­
tween the relatively anodic and cathodic sites. The 
electrolyte and water provide the other branch of the 
electric transpon units. The water molecules, by their 
dielectric propenies , then can be regarded as an insu­
lating and channelizing but movable matrix for the 
solute. In the case of complicated corrosion involving nor­
mal tissue, pathologic tissue and metal, as proposed in 
Fig. XII: 8, an explan:uion for closed circuit ionic 
exchange between normal and pathologic tissues has 
heretofore been lacking. One conducting branch is 
obviously formed by the electrically conducting inter­
stitial fluid in the interstitial tissue channels. To com­
plete the circuit, however, requires another branch. The following section deals with this problem. Biologically closed electric circuits 121 B. A biologicall y closed 
electric circuit over 
vascular-interstitial 
conducting channels 
This circuit will fim be doscribed on the basis of some 
preliminary observatio ns: 
Any vascu.lari:z.ed part of the body can in principle 
contain thU circuit. It contains five main compone.nts: 
I. insulating walls of blood vessels, 2. conducting 
intravascular plasma, 3. insulating tissue matrix (pos­
sibly including lymph vessels), 4. conducting intersti­
tial fluid, 5. electrical junctions for redox reactions. An entirely new function is now ascribed to the 
vascular system. As will be seen, the walls of large 
blood vessels insulate electrically (within certain lim-
Fig. X/1:9. Suagnted biologically dosed e.lcctric circuit in a 
lung with a necrotic tumour. One branch or the cir-
C.Ut is the plasma in blood ,·essds, the other is t.he interstitial 
fluid in the lung. The major driving force in the system is the 
Lung tissue 
Extra­
cellular 
space -I on Necrotic 
tumour 
centre its) the conducting medium of blood, i.e., plasma, 
.from extravascular interstitial fluid, which also is con· 
ducting. One essential junction exists between plasma 
and intentitial fluid: the capillary membranes, which 
allow an exchange of water and electrolytes between 
the two fluid branches. The normal physiologic activi­
ties of cells, of a region of tissue or of an entire organ 
will present gradients of electric potential compared to 
surrounding or distant cells, tissues or organs contain­
ing different metabolic, physicochemical potentials. Given the presence of a biologically closed electric 
circuit, energy exchange will take place between such 
sites. Structural modifications and functional effectS 
will follow. ln a conventional sense the movement of 
fluids mechanically transports ions and other neces­
sary materials to reaction sites in tissue. The existence 
of an additiona l pathway for energy exchange over a 
biologically closed electric circuit not only promotes 
localelect:rOChemical differcnce between surrounding tissue 
and degrading tissue, e.g., necrosis inside the tumour. For 
simpllcity, this example considers only the systemic circula­
tion. For funhtrdiscussion, sec text. Bronchial artery 
connections to 
Visceral leura 
Pulm. vessels 
nternal 
tumour veaael Aorta 
Bronchi ------!~:!!:.! !.~ -...J 
lymph nodes 
+ 
Potential difference 
122 BiologicaUy closed electric circuits Fig. XIJ: 10. Bronchial arteriogram , outlining the arteries 
supplying a bronchogenic carcinoma and other bronchial 
structures in the right upper lobe of a 52-year-old man. A 
catheter (arrow) has beeo placed in the aorta with its rip in a 
selective exchanges of ions but also permits reactions 
among distantly situated regions of tissue. In a closed 
circuit, energy exchange and reaction effects are possi­
ble at sites which are in the circuit but separated from 
the location of the driving forces of the system. Given this introduction, the structure of such a 
circuit will next be described. l. Structure of the vascular-interstitial 
closed circuit (VICC) 
The principle of electric communicat ions over bron­
chial arteries and interstitial fluid between a necrotiz­
ing lung tumour and adjacent lung is surveyed in Fig. XII: 9. It is understood that similar circuits also exist 
over bronchial veins, pulmonary arteries and veins and 
lymphatic vessels. The anticipated regions for ionic 
diffusion and redox transfer of electric charges are not 
indicated. The bronchial arteries are of particular interest in right bronchial artery. Radiographic contrast fills numerous 
pathological vessels in the tumour as well as vessels supply­
ing blood ro tissues surrounding the tumour. the lung because they are nutritional vessels in bron· 
chogenic carcinomas. The distribution of the bronchial arteries can be 
studied by techniques developed by the author for 
infusing the bronchial arteries in dogs (42, 43) and 
man (44). Fig. XII: 10 iUustrates a right bronchial 
arteriogram in a patient with a poorly differentiated 
squamous cell carcinoma of the right upper lobe. The 
right bronchial artery supplies numerous pathological 
vessels to the tumour. As the cancer grows, it may 
erode· or thrombose the bronchial arterial branches 
which supply it, thereby causing local haemorrhage or 
necl'O$iS. Usually the centre of a tumour is most sub· 
jeer to such dystrophic changes. Thoe living cells at the periphery of a tumour act as a 
"semipermr.able" sieve or barrier between the sur­
roundings and central necrosis in the mmour. This 
properry may at first inspection not be quite obvious. A prerequisite for continued life of any normal or 
path<>logical tissue is a functioning intercellular system 
of communicating channels for water, electrolytes , nu-
Biologically closed electric circuits 123 trients and wastes. The actual distance between cell 
surfaces in normal tissue bas been estimated between 
10 to 20 A (3) or 100 to 200 A, according to evidence 
from electron micrographs (15). The tissue matrix can 
therefore be considered as a kind of sieve. Many neoplasms make a tissue firmer and denser 
than surrounding normal tissue. The sieve function of 
the individual interstitial channels of such tumours 
will therefore be increased compared to the channels in 
the surrounding normal tissue. Hence, the network of 
interstitial channels in a tumour potentially constitutes 
a relative barrier to interstitial flow, i.e., a "tumour 
barrier". On both sides of a tumour barrier nonpermeab le 
bodies may be found, i.e., macromolecules, cellular 
debris and fragments, and whole cells such as individ· 
ual erythrocytes, leukocytes, thrombocytes , macro· 
phages and tumour cells. Such units usually carry net 
electric charges. Consequently they will be transported 
electrophoretically in a closed circuit. Many such bio· 
logical units may then be too large to pass through the 
intercellular spaces of an organized tissue. In this sense 
the intercellu lar sieve of a tumour acts as a barrier 
where material can be adsorbed or trapped by cJjffu· 
sion and closed electric transports . 2. Resistivity of tissue and body fluids 
The conductances of different tissues have been deter· 
mined by a number of investigators (19-21, 32, 55, 62, 
63). It has long been known that living cells become 
polarized by electric fields, as is the case with dielec· 
tric materials. This property gives cells low resistance 
for high frequency currents and increasing ly high re· 
sistance as frequency decreases. It also means in gener· 
al that cells possess high resistance for DC currents. The impedances of organ tissues have been deter· 
mined in vivo by Schwan and Kay (64) to be too small 
to influence significantly common ecg tracings. In 
studies of impedance of various human tissue exposed 
to low frequency alternating currents (Table XII: 3), 
they found the following values for specific resistance 
(=resistivity) in situ: 
Table XII: 3. Resistivity of cissues, according w Schwan and 
Kay 
Resistivity 
Qm IOcps IOOcps I 000 cps 10 000 Cp$ 
Lung tl.20 10.90 10.40 9.So 
Muscle 9.6S 8.80 8.30 7.60 
Liver 8.40 8.00 7.6S 6.8S 
Heart muscle 9.6S 9.2S 8.4S 
Fatty tissue IS.OO-SO.OO 
124 Biologically closed electric circuits Table XII: 4. Rerisriviry of rissue and body fluids, actO! 'ding ro 
Kaufman and Jolmrron (Qm) 
Resistivity Resistivity 
pre-bioi. post-bioi. Specimen caJjbr. caJjbr. Lung. inspir;ujon 7.66 7.44 
Lung, supcrinflation 13.67 
Lung, deOation 4.01 
Muscle 7.11 S.7S 
Liver 6.72 S.06 
Hcan 2.24 2.07 
Pericardium 4.34 4.0S 
Foot 2l.OS 18.08 
Serum 1.78 0.98 
Blood 2.30 I. 7S 
The average resistivity of these tissues, about 10 
obm-m, may be compared with the resistivity of blood 
of only about one ohm-m, according to Schwan and 
Kay (64). Measurements of tissue resistivity have often yield· 
ed widely ranging results, which Kaufman and John· 
ston have ascribed to great technical difficulties en· 
countered in attempting to obtain such measuremen ts 
in living tissues (32). They obtained the following 
average values for resistivity of human tissues (Table 
XII: 4), using pulses of 500 to 10 000 Hz. Note that the 
values of resistivity decreased ("post-bioi. calibr. ") at 
the end of the experiments. Most determinations of resistivity in tissues have 
been made in vitro, a few in vivo. Galeotti noted 
difference s before and after death (21) and Crile, eta!., 
found that the resistivity of all measured tissues de­
creased with time after removal from the body (14). Resistivity of walls of blood vessel, in the experi· 
mcnts shortly to be described (see Section 3, page 
125), was shown to require in vivo conditions as well 
as great care to avoid damage to the vessel walls and to 
the vasa vasorum (otherwise, wall resistance rapidly 
decreased ). Geddes and Baker have reviewed the elec­
tric properties of tissues (22). From this report, certain 
figures of tissue resistivity will be cited. The resistivity of dog cardiac muscle has been found 
to differ by a ratio of 2.2 to I when measured parallel 
and transverse to the direction of the fibres (58). At 
average body temperature, low frequency resistivity 
for random orientation in canine cardiac muscle was 
estimated to be 7.5 obm-m. In studies of sk$letal mus· 
cles, the resistivities along and across the fibres also 
showed large differences. In the lung, determinations of resistivity have been 
made in vivo by many authors (14, 21, 32, 34, 58). During maximum inspiration and expiration, the re· 
sistivity of lung tissue in the dog varied between 21.70 
and 4.01 ohm-m (average mean, 12.75). The resistivity of human kidney is about I ohm·m 
and for other mammals about 3.7 ohm-m (21, 28, 34, 
45). The liver shows at "low frequencies" and at body 
temperature a variable range of resistivity (5.9-1 1.0 
ohm·m), average 8.2 ohm·m (28, 45, 58, 62). Nerve rissue fibres show notable differences between 
transverse and longitudinal resistivities in cow, pig and 
rabbit brain (51). Human adipcse cissue shows resistivity values of 27.3 
ohm-m at 200-900 MHz, and values of 28.80 ohm-m 
at low frequencies in canine fat (28, 58, 62). Bone shows high resistivity. Hemingway and 
McLendon found a resistivity of 18.0 ohm·m in hu· 
man bone (28) and Osswald average values between 
37.0 and 62.0 ohm·m in cow and pig (45). Differenc body fluids such as cerebrosp inal fluid, bile, 
amniotic fluid and urine all contain electrolytes and 
have therefore considerab ly lower resistivity than cel­
lular biological tissues. Cerebrospinal fluid has a resis· 
tivity of 0.64 ohm-m at I kHz, bile 0.59~. 76 ohm-m 
at SO kHz, and amniotic fluid 0.49~.65 ohm·m at 
I kHz. 0. 9% saline solution has a resistivity of 0. 7 ohm· 
m at 2o•c and 0.50 ohm·m at 37"C, both determined 
at I kHz (8, 22, 45, 62). Resistivity of bwod has been studied rather exten· 
sively (8, 14, 20, 21, 32, 34, 41, 45, 49, 56, 62, 67). The re~i~ tivity of human hlond varies with haematoc:r lt 
and temperature. Thus, 34.4% haematocri t gives a 
resistivity at 37"C of 1.38 ohm-m, and 1.80 ohm-mat a 
haematocrit of 56.4% (56). Kinnen, et al., found 1.55 
ohm·m in dog blood at41% haematOcrit; Rush, et al., 
1.60 ohm·m with 0.1 sec DC pulses (34, 58). It is known that turbulence of blood diminishes its 
resistance. Thus, a resistivity of 1.54 ohm-m was re­
ported ( 41) in flowing venous blood (at 120 kHz test 
current). For small densities of current, blood is 
equivalent electricall y to a resistor in series with a 
capacitor (19, 20, 74). The specific capacity of blood in 
man is due to the red corpuscles and amounts to a few 
hundred picofarads , while the specific resistance is 
about I .9 ohnt-m at low frequencies. Extrapolated. to 
infmitely high frequencies , the specific resistance of 
blood is 1.24 ohm-m (19). It has also been pointed out 
that the capacity of the blood corpuscles is indepen· 
dent of the frequency of the electric current, and that 
the capacity stays constant when the corpuscles are 
suspended in different media, as long as the shape of 
the corpuscles does not change (19). This indicates 
that the capacity represents a static property of a thin 
surface membrane of dielectric material. The high 
resistance of the blood cell is therefore due to its 
membrane, while the interior is highly conductive . The resistivity of human blood at 37•c is 1.60 ohm-m 
and that of plasma 0.70 ohm·m, according to other 
studies (8, 19, 62). This value of specific resistance for plasma does not differ very much from that of physio­
logical saline solution, which amounts to 0. 72 ohm-m 
at !SOC (8). According 10 Rosenthal and Tobias (56), 
human blood plasma shows an average of 0.61 to 0.67 
ohm·m at I kHz. Dog serum shows an average of 1.38 
ohm·m at I kHz, according to Kaufman and Burger, 
\O'ho also found a resistivity of 0.65 ohm·m in cow 
plasma (8, 32). Fricke found that calf serum had a 
resistivity of 0.894 ohm-m at 87 kHz (19), which is 
comparable to that of saline solution and interstitial 
fluid. There is no doubt that the cell membranes in orga· 
nized tissue are responsible for the high specific resis· 
ranees of different organs, including whole blood. The 
predominant conducting media in organs are found in 
their intercellular fluid, secretions and plasma. Plasma 
is in this respect almost comparable with physiologic 
saline solution. The ionic and nonionic concentrat ions of blood are 
not constant. They vary, for instance, as a result of 
food intake, starvation, dehydration , acid-base alter· 
ations and other metabolic changes which can be as· 
sumed to change the conductivity of blood plasma and 
interstitial fluid. Local variations of water content in 
the tissue should also produce changes in conductivity 
(the sudden change in ecg amplitudes as an electrode is 
moved through a hydropenic "A" zone into a hydropic 
''R" ?.nne in the lnng may he ex(llainerl hy variation ~ in 
water content; see also Figs. VI: 21, XVI: 16). Previous determinations of resistivity of tissues have 
often regarded tissues as homogeneous "bulk" matcri· 
als. Examples are the total effect of tissue impedance 
in electrocardiography or in electric accidents with 
large densities of current. The resistivity of one specif­
ic tissue now becomes important: the proposed hy· 
pothesis of vascular-interstitial conducting channels 
requires information concerning the resistivity of the 
walls of blood vessels. 3. Resistivity of the walls of blood vessels 
A hypothetica l picture of the physical and chemical 
properties of the arterial wall has been presented by 
Sawyers, et al. (60). The intimal surface of the vessel is 
composed partly of mucopolysaccharides containing 
sulfate and carboxylate groups. This chemical struc· 
ture gives the intima, compared to blood, a net poten· 
tial of -3 to -13 m V (59). This negative inner surface 
should therefore repel platelets, erythrocytes and other 
blood corpuscles, which also are negatively charged. Furthermore , the vessel wall should tend to adsorb 
positively charged ions. Any injury to the intima will 
locally make it positively charged and induce local 
thrombosis (59, 61). Thrombosis can also be produced 
by applying electrodes to the intima. Thrombi will be 
Biologically closed electric circuits 125 Fig. XII: 11. ln vivo determination of resistivity of a blood 
vessel of a dog. (a) A glass tube has been inserted through a 
branch of the femoral vein. Another glass tube was placed 
opposite the first tube against the external wall of the vein. The distance berwecn the tubes was determined by a spring· 
loaded measuring device, which also held the tubes. Separate 
produced only at the anode, while formation of clot is 
inhibited at the cathode (59, 61). The outer surface of 
vessel walls, meanwhile, is positively charged (60, 61). The resistive properties of vessel walls wi.ll now be 
studied cxpc.rimcntally. a) Alternati11g curretll 
Resistivity was determined for the femoral veins and 
arteries of 5 dogs. Anaesthesia (intravenous sodium pentobarbita l) was 
administered through a catheter placed in the vein of a 
foreleg. The femoral artery and vein were surgically 
exposed. Two glass tubes (internal diameter 1.3 mm, 
external diameter 1.8 mm, surface area at the end of 
each tube 1.3267 mm2) were each provided with two 
platinum strings, one ending 1.2 em from the tip for 
measuring potential differences over the vessel wal.l 
and one 5.2 em from the tip to supply current. One 
tube was inserted through a perpendicular branch of 
the vessel, allowing the tip of the tube to be placed 
against the opposite internal vessel wall. The other 
glass rube was placed at the corresponding place 
against the external vessel wall. The tubes were cen­
tered against each other and held in place with two 
plastic holders connected to a spring-loaded precision 
instrument for determining distances (accuracy ±0.01 
mm at a constant total pressure of 30 g) (Fig. 126 Biologically closed electric circuits pWr5 of platinum electrodes positioned in the glass tubes 
supplied current and measured the voltage diffe-rence across 
the vessel wall. Conducting fluid in the glass tubes is 0.9% 
saline solution. (b) Even slight but continuous pressure by 
the glass tubes may produce ischaemie injury at the vascu.lar 
measuring sire, here seen as a white spot (arrow). XU: 11 a). Tbe frictional resistance of the spring-load­
ing branch was overcome by gently tapping on it with 
a pair of pliers. The tubes were filled with 0.9% NaCI 
solution. The femoral artery and vein had to be freely dissect­
ed to apply the electrode rubes. Some damage to the 
vessel walls and vasa vasorum could not be entirely 
avoided. The duration of spring-loaded pressure on 
the glass tubes was kept as short as possible (circa 10 
minutes) in order to minimize mechanical and circula­
tory injury to the vessel wall. Nevertheless, a small 
white spot, a sign of focal hypoxic injury, developed 
rather rapidly (after about 5 minutes) around the ex­
ternal glass rube (Fig. XII: II b). The resistivities were determined by an automatic 
recording system for measuring biological impedances, 
developed and described by T edner (73). The actual 
determinations of resistivity of the vessel walls and test 
liquids were carried out in cooperation with Mr B. T. 
Tedner (M.Sc.) and Mr H. Larsson (M.Sc.). In this 
system, a constant current of 10 ,uA is sent through the 
test object via the outer platinum electrodes in the 
glass tubes and an external reference resistor. The 
potentials developed between the measuring electrodes 
and over the reference resistor are then fed into two 
differentia l amplifiers via four high-impedance input 
amplifiers. The omputs from the differential amplifi­
ers are connected to a network analyser system wbicb Amplitude 
CdBlr--~~-~ 
25 
Fig. XII: JZ. Amplitudes of potential 
drop across walls of blood vessels (dog) 20 
by alternating current of different fre· 
quencies. A 10 microampe re constant 
current ranged in frequency from 100 
to 1 MHz over (a) 0.9% NaCl, (b) wall 
of femoral vein, (~) wall of femoral ar-
tery, (d) wall of femoral ar<ery after 15 
small local injury of the vessel. Each 
tracing consists of recordings from 160 
discrete, logarithmically spaced fre-
quencies. Sample$ for determinadon 
of resistivity were compared at tO 
kHz. From these recordings imped- 10 
ance values and then resistivities were 
calculated. 100 
measures ampliwde ratio and phase angle between the 
inputs at a given frequency. This system consists of a 
digital synthesizer and a network analyser controlled 
by a calculator. The ratio between the two potentials is 
recorded. Because amplitude readings are obtained in 
decibels, the impedance is calculated from 
Z=Rlo•o l2o 
where Z is the impedance, R the reference resistance 
and dB the amplitude value determined by the ana· 
lyser. The calculator is programmed 10 sweep auto· 
matically from one hundred Hz to one MHz at 160 
logarithmically- -spaced discrete frequencies.
631928626-Biologically-Closed-Electric-Ci-Bjorn-Nordenstrom-pdf.txt
Summarize the following text section accurately and concisely. Maintain specific details and numerical information, and use anti-repetition mechanisms:

        This result 
i. s an impossibility as a funct. ion only of the concentra­
tion forces of blood corPuscles. These forces, which 
were distributed unevenly to ooe side of the "tumour", 
should instead create their o"'n concentration centres 
outside the "tumour". The only known force that can 
possibly produce radiating structures of t. he observed 
extensions and locations in the lung is a closed circuit Fig. X/:8. After desanguinauon of the dog, the lung and ad­
jacont chost wall were removed en bloc. The radiograph 
shows the specimen after stipt inflation of the lung. No 
structure:s are evident corresp:mding to ''A'' and ••a•• zones 
obKrved in vivo. Some irregular infiltrations around the 
"tumour'' represent local blood. This experiment illusuares 
som<: of the critical discrepancies between an examination in. ;,-o and at necropsy. In lhc l•ftl. the distens;oa of the pattn­
chyma in vivo by subatmospheric intrapleural pressures and 
by vascular perfusion pressures are of particular importance 
in structural analyses. Artificial tumour in doc lunc I 09 Fig. Xl:9. Postmortem radiograph of slightly inflated lung 
with multjple metastases from carcinoma of colon. Note 
faint radiolucent areas("A" zone) around several tumours. electric field. Neverthe less, we have already :argued 
that the "tumour" itself, by virtue of its insulating 
shellac layer, is excluded from any closed circuit tissue 
channels. The only remaining possibility to explain the 
development of the radiating structures must be the 
creation of tissue injury during the implantation of the 
tumour. Tissue, inclurling blood, adjacent to the im· 
planted tumour should then have polarized electro­
chemically against surrounrling noninjured tissue. In 
order to resolve our dilemma we are now forced logi­
cally to postulate that a closed electric circuit must 
exist between surrounding normal tissues and degrad· 
ing blood and cell material adjacent to the "tumour". The corona structures observed radiologically 
around the artificial "tumour" were disarranged or 
not evident after removal of the lung. This finding is 
not surprising. As soon as the chest is opened in any 
animal, the mechanical factors in the lung parenchyma 
are changed. The effects of subatmospheric pleural 
pressures, interstitial and intravascular fluid pressures, 
etc. , are changed rarlically compared to the situation in 
vivo. These differences appear to explain why radiolo­
gic observations in vivo of structures in the lung (pro­
duced by fluid and movable cellular elements) are not 
readily recognized on histologic or radiographic exami­
nations of removed lungs. This situation shourd hold 
at least when the pathologi c condition has been present 
for only a relatively short period of biologic time, e. g. , 
2 weeks. Permanent fiXations of the structural arrange­
ment are, however, possible. Thus, faint rarliolucent 
"A" zones are seen in Fig. XI: 9, which is a postmor­
tem radiograph of a slightly inflated lung, containing 
many small metastases from a carcinoma of the colon 
(radiograph kindly submitted to the author by Dr. L. Kreel, Northwick Park Hospital, Harrow, Middlesex, 
England). Similar fmdings can also be seen in vivo in 
processes of long duration, e.
The radiograph shows that the "tumour" is not present in the lung, and some irregular infiltrations around the "tumour" may be seen.
What is the main difference between radiological observations in vivo and post-mortem examination?
The text does not explicitly state the primary force, but it discusses the possibility of a closed electric circuit as a potential explanation.
What is the primary force that can produce radiating structures of the observed extensions and locations in the lung?
The experiment is to show that the radiating structures are not visible in the post-mortem radiograph, and to demonstrate the importance of considering the tissue's electrical properties in understanding the development of the structures.
What is the purpose of the experiment with a dog?
The radiograph shows the presence of faint radiolucent areas ("A" zone) around the tumour.
What is the significance of the radiograph in Fig. X: 9?
The experiment is to determine the resistivity of the blood vessel walls, which is essential for understanding the development of the observed structures.
What is the purpose of the experiment in Fig. XII: 8?