Forensic Science International 144 (2004) 221–231

Vitality and time course of wounds

M. Oehmichen*
Department of Legal Medicine, Institute of Forensic Medicine, University Hospital Schleswig-Holstein,
Campus Kiel, Arnold-Heller-Str. 12, D-24105 Kiel, Germany

Available online 19 June 2004

Abstract

The term ‘‘wound’’ describes the morphologic-functional disruption of the continuity of a tissue structure. A wound can be
inflicted during life—when the cardiovascular and respiratory system is still intact—or after death, i.e. after cardiac and
respiratory arrest. Traumatization during life triggers vital reactions that do not occur in postmortem wounds. Three types of
vital reactions in wound healing can be distinguished:
1. Reactions of the scavenger type, which are almost exclusively mediated by blood cells.
2. Reactions by complex signal transduction pathways, which involves cascade-like release of chemokines, cytokines and
adhesion molecules and may influence type 1 and type 3 reactions.
3. Reactions of the scarring type, which involve the final repair of the damaged tissue and are carried out primarily by cells
residing at the wound edges, i.e. partly concerning mesenchymal cells and partly tissue-specific cells dependent on the
involved organ system.
The three different types of reaction follow roughly parallel temporal courses that include cascade-like interactions among
themselves. Whereas demonstration of a vital reaction suffices to differentiate an intravital wound from a postmortem wound,
the vital reactions themselves follow strictly temporal courses. The regular time-dependent occurrence of each phenomenon
allows—in limits—a reliable temporal classification of wound healing.
A review will be given especially demonstrating the actual German scientific research in vitality and in skin wound timing as
well as in timing of mechanical injury of the brain.
# 2004 Elsevier Ireland Ltd. All rights reserved.

Keywords: Vitality; Wound age; Skin wound; Mechanical brain injury

1. Introduction cutaneous wounds as well as of mechanically caused brain

The problems considering vital reactions and wound age
are specific in the field of forensic medicine. To address these
questions conceptual approaches must be applied which are
often banal and easy to understand; often the essential
subject of the forensic pathologist may be ‘‘plausibly’’
answered. However, not all problems are easy and not all
the difficulties can be stressed within 10 pages. This paper
will give a short review on the terminology, the history of
research and the state-of-the-art of vitality and timing of
*
Tel.: þ49-431-597-3600; fax: þ49-431-590-3612.
E-mail address: oehmich@rechtsmedizin.uni-kiel.de
(M. Oehmichen).
injury.
2. Terminology
Vital reaction presupposes a still autonomous function of
one—or more—organ systems (Table 1). The functional
activity of the circulatory system, for example, is necessary
for exsanguination, petechial hemorrhages, or embolies.
Aspiration or inhalation of gases such as carbon monoxide
or the occurrence of skin emphysema (pneumoderma)
require an intact respiratory system. It can be assumed that
the gastrointestinal system was largely functional if swal-
lowing, peristaltic transport of gastric contents or absorption
can be demonstrated, etc.

0379-0738/$ – see front matter # 2004 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.forsciint.2004.04.057
222 M. Oehmichen / Forensic Science International 144 (2004) 221–231

Table 1 Systematic investigations to determine vitality and esti-

Vital reactions of the different organ systems mate wound age must in all cases apply a protocol involving
Circulatory system at least three important points [2]:
Exsanguination  Morphological and/or biochemical phenomena must be
Petechial bleeding investigated in relation to the survival time.
Embolism
 The evidence must be evaluated in light of the postmortem
Air
Fat interval, taking into account differences in temperature
Tissue during the interval.
Bone marrow  Both agonal and supravital changes must be distinguished
Foreign bodies from vital reactions.
Respiratory system Moreover, independent of the organ system which is
Aspiration involved in the wounding process we have to distinguish
Alveolo-capillar diffusion (of gases) three types of reactions:
Pneumoderma
Type 1: Scavenger cell reaction (i.e. blood cell reaction)
Gastrointestinal tract
marked by an emigration of neutrophilic leukocytes,
Swallowing
Peristaltic transport of gastric contents monocytes and lymphocytes;
Absorption Type 2: Molecular mediated reaction by chemokines,
especially cytokines as well as adhesion molecules, etc.;
Endocrine glands Type 3: Focal tissue reaction by collagen-releasing
Agonochemical stress reaction
fibroblasts, endothelial cells and activation and/or
Nervous system proliferation of tissue/organ-specific cell types.
‘‘Crownfoot-like’’ pattern
Secretion of saliva and mucus Though we have to suggest a distinct regularity of the
Parasympathic nervous system process of (sterile) wound healing [3] we have also to accept
a wide variability of the time-depending phenomenology,
which is caused by various factors like age, sex, localization
of the wound, involved organ systems, extension of the
The forensic expert must be able to distinguish vital wound, circulatory, respiratory and immunological capacity,
reactions from agonal and from supravital reactions, time between wounding and death, as well as duration of
and—finally—from postmortem changes (for review, see formalin fixation, etc.
Ref. [1]). While agonal changes can arise during a state of
vita minima, changes are considered to represent a supravital
reaction if they are expressed after circulatory arrest and may 3. History of forensic wound age estimation
have the appearance of a vital reaction.
Moreover, the forensic literature discusses not only ‘‘vital The problem of ‘‘vitality’’, i.e. whether a traumatization
reactions’’ but also ‘‘vital processes’’, which represent the occurred on a living or dead victim, was first discussed by
reaction of the whole organism to damage and require the Walcher [4] and Orsos [5]. While these authors reviewed the
continued autonomous function of various organs. The term results of the literature and summed up their own experi-
‘‘vital signs’’, by contrast, describes only changes indicative ences, Raekallio was the first who approached the problem
of a functional organ activity. by scientific experimental investigations in 1965, especially

Table 2
Markers of post-traumatic survival time caused by mechanically induced hemorrhage of skin wounds [31]

Wound age Paraffin section Frozen section (hematoidin)

Erythrophages Siderin Hematoidin

1h    
1 day þ   
3 days þþ (þ)  (þ)
4 days þþþ þ  þþ
7 days (þ) þþ  þþ
10 days  þþþ  þþ
11 days  þþþ þ þþþ
 M. Oehmichen / Forensic Science International 144 (2004) 221–231 223

Table 3
Biochemical-mediated early wound alterations according to the most recent references

Post-traumatic interval Epitope Species N Reference

<30 min Fibronectin Human 53 [10]

Human 46 [11]
Cathepsin D Human 53 [18]
D-Dimer Human 67 [20]
TNF-a Mouse [24]
IL-1b Mouse [24]
Leukotriene B4 Human 7 [32]
P-selectin Human 197 [14]
>1 h E-selection Human 197 [14]
>1.5 h ICAM-1 (CD54) Human 157 [13]
>3 h VCAM-1 (DD106) Human 197 [15]
>4 h IL-1a Mouse [25]
>6 h IL-6 Mouse [24]
200 h IL-2 Human 19 [16]
IL-6

Fig. 1. Demonstration of vital reactions at the wound edges by immunoelectrofocusing technique: serotonin release (a) and increase of
histamine (b) with a peak of 10–20 min after traumatic insult [21,22].
224 M. Oehmichen / Forensic Science International 144 (2004) 221–231

regarding skin wounds. Raekallio [6] introduced the appli-
cation of a new method, the technique of enzyme histo-
chemistry, and he was able to present a couple of new data
for estimating the wound age.
An important new issue was addressed some years later
by Berg et al. [7,8] who introduced biochemical methods,
especially the demonstration of serotonin and histamine at
the wound edges, which gave evidence of vital phenomena.
During the next 10 years there was a fulminant development
in the immunologic scientific research and immunohisto-
chemistry. The application of the immunohistochemical
technique opened a new field of wound age investigation
by forensic pathologists, beginning with Eisenmenger et al.
[9] and Oehmichen [3]. During the next 10 years the knowl-
edge of basal immunologic principles and the application of
immunocytochemical methods characterized the scientific
development especially in Germany [10–17], in Spain
[18–23], and in Japan [24,25]. A comprehensive review
of the state of art was given on occasion of the Fifth Lübeck
Workshop (1994), which was published in ‘‘Research in
Legal Medicine’’, vol. 13, 1996 [26].
All these findings were concentrated on skin wounds only. A
second field of research has been the timing of brain wounds,
i.e. mechanically caused cortical hemorrhages of the brain.
These investigations were done by Eisenmenger et al. [27] as
well as by Oehmichen and Raff [28,29] and Hausmann [30].
4. Open skin wounds
4.1. Blood cell reaction
A stabbing, cut or blow to the skin can lead to tissue
destruction, tearing or rupture of blood vessels, and results in

(a) Labelling Index %)

40 Intravital Biopsy

30

20

10

0
0 20 40 60 80 100 120
Survival Time (hrs)

(b) Labelling Index (%)

40 Postmortal Biopsy

30

20

10

0
0 20 40 60 80 100 120
Survival Time (hrs)

Fig. 2. Experimental studies on dermal basal cell kinetics after traumatization using in vitro bromodeoxyuridine technique. At the wound
edges an increase of proliferating cells is to be seen in intravital (a) and postmortem (b) specimens in dependence of the post-traumatic
survival time [29].
 M. Oehmichen / Forensic Science International 144 (2004) 221–231 225

Table 4
The scarring process with time-dependent synthesis and release of different collagen types and late cellular reaction [10]

Subtype Observation period

First appearance Regular appearance Last appearance

Collagen III >2–3 days 6 days Months

Collagens V, VI >3 days 6–7 days Months
Collagen I (fibroblast-assoc.) >4 days 7 days Months
Collagen I (fibers assoc.) >5–6 days 7 days Months
Muscle actin expr. fibroblasts >5 days 7 days Months

bleeding. Red blood cells that leave the blood vessels
become partly or totally spherical and are located in an
acidic environment in the perivascular tissue.
The very early vital blood cell reaction will be the
granulocyte emigration which will be seen in single cases
within 10 min, in most cases within 1–2 h. The biological
meaning of this type of cell reaction is still unknown;
otherwise we have to suggest that neutrophils release free
radicals with the result of a secondary tissue damage.
The second type of blood cell reaction is characterized by
a monocytic emigration and transformation of monocytes to
macrophages. Macrophages undertake the scavenger func-
tion, i.e. phagocytize cell debris and break down products
and clean the wound. This cell type will be demonstrated

Table 5
Different histomorphological phenomena which will be expressed during the wound healing process at the wound margins in dependence of
the post-traumatic interval
226 M. Oehmichen / Forensic Science International 144 (2004) 221–231

about 7 h after traumatization in single cases and will peak at biopsy from the wound margins was immediately incu-
1–2 days. bated with bromodeoxyuridine in vitro. A second biopsy
Corresponding to their phagocytosing function we addi- was taken 24 h postmortem and incubated with the
tionally have to classify these cell types according to the same substance. Quantification of the bromodeoxyuri-
incorporated debris: fat ! lipophage; erythrocyte ! erythro- dine-expressing epidermal basal cells in the first series
phage; siderin ! siderophage; leukocyte ! leukophage; revealed an increase in the number of proliferating cells—
myelin ! myelophage, etc. The incorporated cell debris in direct relation to the survival time, as it was also
will be intracellularily broken down and digested and, for demonstrated in biopsies taken postmortem. It is still
example, the intracellular digestion of red blood cells will unknown whether these kinetic data from animal experi-
lead to deposition of intracellular siderin. These processes ments are to be transferred to human wounds. The results
take time and the time-dependent break down will be of investigations using Ki67 antibodies did not support
documented as an additional phenomenon for estimating these results [10]. Though the phenomenon of apoptosis at
the survival time (post-traumatic interval) of an unknown the wound margins will be of importance in scientific
wound. The time-dependent intracellular break down of red research, it will give no significant information in forensic
blood cells is demonstrated in Table 2. praxis [30,34].
A further important step of investigation has been the
4.2. Biochemically mediated types of reaction classification of collagen types by different antibodies [10]
which was first described by Eisenmenger et al. [9]. Col-
Very early after wounding proteins may be visualized lagen will be intracellularly synthesized by fibroblasts, and
and/or biochemically quantified, which are to be classified the different collagen types are released at different intervals
as markers of vitality. Especially by immunologists a very after wounding (Table 4).
complex system of signaling molecules which influence All these findings—and some more—are summarized as
each inflammatory process on the cellular and on the follows (Table 5): a temporal pattern is evident in the
biochemical level is described. Obviously, several mole- occurrence of phenomena in skin wounds, for which a wide
cules participate in the process of non-immunological range of markers are now available. Demonstration of these
wound healing [16,24], which are released by inflamma- findings can confirm or exclude the vitality of an injury, and
tory cells such as leukocytes, fibroblasts, platelets, macro- numerous other phenomena allow a rough temporal classi-
phages and mast cells. Besides the biogenic amines fication of skin injuries based on micromorphological
histamine and serotonin, the cytokines, proteoglycanes, methods.
proteases and lipid mediators are to be mentioned. The
most important signaling cell and tissue factors as well as
molecules applied in forensic wound analysis are summed
Table 6
up in Table 3. A recent survey is given by Hernández- Expression of different phenomena of axonal injury depending on
Cueto et al. [19]. the survival time of the causing insult
Berg et al. [7,8] using biochemical and histochemical
methods succeeded to demonstrate serotonin released by Phenomenon/technique First expression Reference
thrombocytes and histamine released by mast cells at the of b-APP (interval
after trauma)
wound margins. Quantitative results are more recently pub-
lished by Vieira [21] and Lorente [22] using tissue electro- Axonal bulbs and fibers
focusing techniques (Fig. 1). Meanwhile, fibronectin [10] 68 kD 60 min [41]
and P-selectin [15] are among others two new candidates of b-APP 105 min [42]
vitality markers at the wound edges. These molecules are 120 min [43]
mediatory between cells and connective tissue. However, we 180 min [44,45]
Ubiquitin (in a cat model) <360 min [46]
have to be aware that especially fibronectin is not highly
specific and valid because false positive reactions are Axonal bulbs
observed [11,17,23]. Other types of biochemical reactions Silver impreg. Technique 15–18 h [47,48]
are described to be time-dependent and are summed up in H&E 24 h [44]
Table 3. Microglia clusters around 15 h [49]
axonal bulbs 24–48 h [50,51]
4.3. Focal tissue reaction
Myelin degeneration
Marchi method 30–60 days [52]
A prolonged survival time can always be assumed if an
increase in proliferating epidermis cells can be demon- Axonal bulbs
Maximal survival time 4 weeks [42]
strated [33]. Experimental studies in vivo have shown the
3 months [50]
proliferative course, as depicted in Fig. 2. The authors
17 months [45]
have carried out experiments on rats [33] in which a
 M. Oehmichen / Forensic Science International 144 (2004) 221–231 227

5. Mechanically induced brain injury
Sequelae of a mechanically caused brain hemorrhage will
be associated with (1) blood cell emigration, (2) biochemi-
cally mediated reactivity as well as (3) local tissue reactions.
While the first two types of reagibility in the brain wound are
nearly the same as in skin wounds, the local cell reaction will
be highly specific (for review, see Refs. [35,36]).
The reagibility of neurons is limited. This cell type may
be reversibly or irreversibly damaged. Using routine H&E
stain the irreversible damage is expressed by an eosinophilia
of the cytoplasm; this phenomenon is regularly visible 2–3
days after traumatization. But there are meanwhile various
functional neuronal markers which partly can be applied in
paraffin sections. Under normal conditions neurons express
neuron-specific enolase and a-tubulin [37], somatostatin
[38], or microtubili-associated protein 2 (MAP2; see Ref.
[39]). Animal experiments gave evidence of a loss of protein
expression soon, i.e. within 10 min after the ischemic insult.
The reduction of the number of neurons expressing these
antigens is to be interpreted as a functional (reversible?)
lesion of the CNS [39,40].
Moreover there are axonal lesions characterized by dif-
ferent methods as demonstrated in Table 6. These phenom-
ena are capable of estimating the survival time within
distinct limits. Especially the detection of axonal injury
by means of beta-amyloid precursor protein (b-APP) must
be regarded as a definite sign of vitality [45] (see also
Ref. [42]). b-APP arises after about 100 min at the earliest
and is never found following postmortem injury, since it

Fig. 3. Axonal injury (AI) in the pons of human victims after fatal closed brain injury: 80–100% (b) of the examined cases (a) demonstrated
AI as an indication of vitality after a survival time of >100 min [41].
 228
Table 7
Demonstration of micromorphological phenomena in cortical hemorrhages in dependence of the post-traumatic survival time: a statistical evaluation [32]

Histomorphologic criteria Observation period Total number Number of cases Relative frequency Estimated limits Distribution free

M. Oehmichen / Forensic Science International 144 (2004) 221–231

of examined with morphological of the observation of confidence tolerance intervals
First appearance Last appearance cases during alterations (n) (%) (Clopper and with 95% reliability
the observation Pearson, 1934) (%)
period (n) (%)

RBCs 1 min 5 months 305 237 77.70 72.6–82.3 98.0

Polymorphonuclear leukocytes (PMNs) 5 min 3 months 20 days 304 131 43.09 37.5–48.9 96.4
Macrophages 11 h 30 min 58 years 305 223 73.11 67.8–78.0 97.9
RBC-containing Ms 12 h 5 months 303 145 47.85 42.1–53.6 96.8
Hemosiderin 4 days 5 h 44 years 305 162 53.11 47.3–58.8 97.1
Hematoidin 12 days 1 year 304 36 11.84 08.4–16.0 87.5
Lipid-containing Ms 17 h 30 years 220 118 53.64 46.8–60.4 96.0
Fibroblasts 4 days 10 h 9 years 305 104 34.10 28.8–39.7 95.5
Endothelial cells 3 days 22 h 53 years 305 149 48.85 43.1–54.6 96.9
Collagenous fibers 5 days 58 years 305 118 38.69 33.2–44.4 96.0
Gemistocytic astrocytes 7h 35 years 305 139 45.57 39.9–51.3 96.6
Fibrillary gliosis 6 days 58 years 305 87 28.52 23.5–33.9 94.7
Siderin-containing astrocytes 5 days 53 years 305 101 33.11 27.9–38.7 95.4
Neuronal destruction 1 min 5 months 305 183 60.00 54.3–65.5 97.4
Neuronophagy 4 h 45 min 4 months 5 days 305 67 21.97 17.4–27.0 93.1
Axonal swelling 2 h 45 min 4 months 5 days 49 19 38.78 25.2–53.8 77.4
Axonal balls 15 h 44 years 282 143 50.71 44.7–56.7 96.7
Mineralization of neurons 6 days 44 years 303 36 11.88 8.5–16.1 87.5
 M. Oehmichen / Forensic Science International 144 (2004) 221–231
presupposes axonal transport of proteins and cellular orga-
nelles, which accumulate after traumatization in axonal
swellings or balls [49], obviously a reversible process
[53]. Axonal injury can be demonstrated in the pons in
almost all cases of fatal cerebral contusion after a post-
traumatic survival time of at least 180 min, even in the
absence of other types of primary or secondary injury in
the pons (Fig. 3).
Moreover, we have to evaluate the glial reactivity. While
the microglia reaction corresponds to the monocytic/macro-
phage reaction elsewhere in the body up to certain limits
according to different phenotypes [54–56], the astrocytic
reaction is brain-specific and characterized by an upregula-
tion of glial fibrillary acid protein (GFAP) and vimentin as
well as by a local proliferation. While the microglia reaction
gives evidence of a complex time-dependent pattern of
reactivity according to their different stages of function
and debri incorporation as well as digestion, an upregulation
of GFAP and vimentin in astrocytes is observed within a few
hours and an increase in the number of astrocytes will occur
at least on the second to sixth day after traumatic impact. A
survey on the known time-dependent alterations in cortical
hemorrhages after mechanically injured brain is given in
Table 7.
6. Conclusion
Meanwhile we have a couple of methods which may be
applied on forensic material and allow a rough estimation of
the survival time of a traumatic event—at least in wounds of
the skin and brain. However, we have always to be aware of
the variability of the phenomena and we have to be cautious
in interpreting the results as absolutely exact. Moreover, we
have to state that a statistical work up was carried out only in
a material of human mechanically caused brain injuries
(cortical hemorrhages) [36] but still not in a material of
skin wounds. We have to consider that all mentioned phe-
nomena are not expressed in every case at the same post-
traumatic interval, but only in a certain percentage of cases
of specific survival times. The forensic question according to
the degree of certainty will arise in court when the presence
or absence of one of the phenomena has to be interpreted.
This will be one of the most important problems in the
future.
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