Phẫu Thuật Bỏng: Tiếp Cận Và Phương Pháp Điều Trị Từ Trung Quốc (Chinese Burn Surgery)

443
14 and 21, the plasma endotoxin levels in the control group
still had no downward trend (Table 16.136 ).
In our laboratory, the plasma endotoxin level ≥40 ng/L
had been considered abnormal. As shown in Table 16.137 ,
during the entire 21-day observation period, the abnormal
rate of plasma endotoxin levels in the control group was sig-
nifi cantly higher than that in the treatment group ( p < 0.05).
The proportions of the TBSABin the two groups were
greater than 30 %. However both extreme TBSA in two
groups of this study, because of their large, different stress
response, caused the serum IL-1, IL-6, and CRP to undergo
wide fl uctuations. Because the deep second-degree and
third-degree burns are mostly the impact factors of stress and
the prognosis of the burn, we used the coeffi cient unit of
burned surface (UBS) as an index to evaluate the severity of
burns patients; namely, UBS is equal to the percentage of the
burn area plus three times both the percentage of deep
second- degree burn and the percentage of third-degree burn.
UBS scores between 80 and 280 as a selected standard; 10
cases in the treatment group and 11 cases in the control group
were divided again to compare the two new groups of
patients. It was found that these serum levels of the IL-1,
IL-6 and prognostic infl ammatory nutritional index (PINI);
namely, α1-acid glycoprotein * C-reactive protein/prealbu-
min* albumin) increased gradually with the course of the
disease, stabilized or declined on the PBD 21. On the PBDs
10, 14, and and 21, the serum levels of IL-1, IL-6, and PINI
were higher in the control group than those in the treatment
group. There were signifi cant differences in IL-6 levels on
PBDs 10 and 14 and the PINI on day 10 between the two
groups (Table 16.138 ).
Positive blood culture was regarded as a diagnostic crite-
rion for sepsis, and then the sepsis incidences were 15 %
(three cases) in the treatment group and 25 % (fi ve cases) in
the control group. The total infection complication (includ-
ing pneumonia, urinary tract infection, and catheter-related
infection) incidences were 40 % (eight cases) in the treat-
ment group and 55 % (11 cases) in the control group, of
which four were venous catheter bacterial culture-positive
(one case with plural bacteria) in the treatment group and
seven (three cases with plural bacteria) in the control group.
There were two deaths (one case in an older patient with
existing coronary heart disease, died of heart failure) in the
treatment group and one in the control group. No statistically
signifi cant differences were found between the two groups,
although the infection incidence was lower in the treatment
group than in the control group.
With the expansion of drug-resistant bacteria, it is pre-
dicted that a post-antibiotic era is coming. Thus, in 1994, the
micro-organism therapeutic intervention was put forward
again by the World Health Organization. Infection after
severe burns was related to intestinal bacteria overgrowth,
translocation, and excessive infl ammatory response. The lac-
tic acid bacteria in animal experiments and controlled clini-
cal studies have been proven to be effective in reducing
severe acute pancreatitis, abdominal surgery, and infection
rate after liver transplantation.
This study showed that the endotoxin levels in the blood
increased signifi cantly after burn. While using early EN con-
taining synbiotics, the severity of endotoxemia in those
severe burn patients had been improved. Overseas studies
suggest that the treatment dosage of probiotics (CFU) is at
least 108–109 CUF/g.d. In this study synbiotics Cocktail
2000 has lactic acid bacteria of more than 109 CFU/g, which
are derived from the habitual resident bacteria in the body,
and can be tolerated at gastric acid and bile and adhesion to
colonization on the mucosal cells of the human digestive
tract, thus with biological activities such as effective preven-
tion of bacteria and endotoxin translocation.
Prebiotics can also play its role alone. In this study, some
of the observed parameters showed no signifi cant differences
between the two groups. Visceral protein and acute phase
proteins could be refl ected in the ratio of infl ammation and
nutritional status of the body to guide the clinical distinction
between malnutrition, or excessive infl ammatory response,
and transjugular intrahepatic portosystemic shunting (TIPS)
prognosis. Manelli considered a PINI of more than 170 to be
a poor prognosis. In this study, on the PBD 10 the PINI in the
control group was up to 174.2, while that in the treatment
group was signifi cantly lower, suggesting that lactic acid
bacteria synbiotics might play a benefi cial role. Infection
incidences between the two groups were similar, maybe
because of the small samples enrolled in this study and inad-
equate dosage of the synbiotics. In addition, because at
Table 16.136 Plasma endotoxin levels (ng/L) in two groups of patients at different time points post-burn
Groups
PBD 1
PBD 3
PBD 7
PBD 10
PBD 14
PBD 21
Treatment
51.65 ± 10.30
39.39 ± 7.71
50.21 ± 9.64
37.95 ± 5.36*
47.50 ± 7.53
37.3 ± 6.45
Control
53.75 ± 8.50
45.79 ± 7.72
48.75 ± 7.49
59.05 ± 7.96
55.7 ± 9.29
52.5 ± 7.89
Compared with the control group * p < 0.05
Table 16.137 Abnormal rate of plasma endotoxin levels in two groups
of patients over the course of 21 days
Groups
Samples
Sample number of
≥40 ng/L
Abnormal rate (%)
Treatment
120
44
36.7*
Control
120
59
49.2
Compared with the control group * p < 0.05
16.6 Eco-immune Nutrition

444
present we could not culture and identify these four types of
probiotics in the stool of those patients, and did not analyze
the intestinal fl ora, it is diffi cult to determine whether the
lactic acid bacteria colonize in the colon or not.
Synbiotics application is aimed at the prevention and
treatment of endogenous infections, especially in the treat-
ment of diarrhea [ 127 ]. There was a marked effect of synbi-
otics in the treatment of acute pancreatitis and liver transplant
patients in some studies. No research in severe burn patients
has been reported, however. Our preliminary research sug-
gests that synbiotics with early EN in severely burned
patients can improve the infl ammatory stress response and
endotoxemia, which may be benefi cial to the prevention of
endogenous infection.
Why is TPN mentioned less nowadays? Because before
we did not recognize the importance of the gastrointestinal
immune function, the mucosal barrier integrity, the micro-
bial enzymes of the lower digestive tract releasing anti-
oxidants and other nutrients for human health, and did not
recognize the importance of the 10 L of digestive fl uids
secreted per day to local immunization and infection control.
In today’s clinical practice, the most critically ill patients
(such as those staying in the ICU) only are given the worst
food, usually some sort of semi-synthetic nutrient powder.
This should be immediately changed, so that these patients
can eat fresh fruit and vegetables, in addition to lactic acid
bacteria. Thus, a new treatment strategy is needed. The expe-
rience of synbiotics for the treatment of critical illness is still
limited, but the current results are encouraging.
16.7
Trace Elements in Burns
Zhenrong Guo , Ligen Li , and Feng Li
Previous studies on trace elements were mainly related to
nutritional defi ciency or endemic diseases such as iodine
defi ciency goiter, Keshan disease caused by selenium (Se)
defi ciency, etc., until the 1990s, when Zhenrong Guo et al.
recognized the changes in the trace element content in burns
patients, especially those with severe burns [ 128 , 129 ].
Among these trace elements, zinc has a substantial effect on
the vital movements and is defi cient in patients with severe
burns. Since then, less attention has been paid to trace
elements and more attention has been focused on macro-
nutrition such as sugar, lipid, protein, etc. However, it is
these trace elements that may have a great effect on the
whole situation.
16.7.1
Regular Changes in Trace Elements
After Burns
16.7.1.1 The Changes in Zinc, Copper, and Iron
in the Serum, Urine, and Blister Fluid
of Burns Patients
Since the 1990s, researchers have recognized the changes in
trace elements after a burn. Guo et al. performed a dynamic
observation at the levels of zinc (Zn), copper (Cu), and iron
(Fe) in the serum, urine, and blister fl uid of the 103 patients
with different burn surface areas, and primarily revealed the
law of the changes of trace elements. The range of trace ele-
ment changes is closely related to the extent of the burn and
the time period after the burn [ 128 , 130 – 132 ] (Tables 16.139 ,
16.140 , 16.141 , and 16.142 ).
The Changes in Zinc
The serum Zn in the L group (with large-area burns)
decreased signifi cantly 1~3 days after the burn, and was
lower than that in the S group (with small-area burns;
p < 0.01). On the second day it was lowest, at a concentration
of 0.4 μg/ml. Its level began to increase after PBD 3 and
reached 0.73 μg/ml on PBD 7; however, it was still lower
than that in the S group ( p < 0.05). The serum Zn in the S
group was always within the normal range, although it also
decreased a certain degree within 7 days after the burn.
Table 16.138 Comparison of the stress parameters and prognostic infl ammatory nutritional index (PINI) on different days after burn injury in the
two groups of burns patients with 80–280 units of burned surface (UBS) score
Group
No.
UBS
IL-1 (ng/ml)
IL-6 (ng/ml)
PINI
D10
D14
D21
D10
D14
D21
D10
D14
D21
Treatment 10
163.6 14.2 ± 2.3
14.8 ± 2.1 16.7 ± 2.4
42.6* ± 5.4 30.0* ± 3.6
30.9 ± 4.6
144.4* ± 9.4 98.9 ± 7.5
34.1 ± 5.5
Control
11
170.7 17.7 ± 2.1
18.4 ± 1.9 19.9 ± 2.3
60.7 ± 6.1
54.0 ± 4.6
39.4 ± 4.2
174.2 ± 9.9
102.6 ± 6.9
50.0 ± 5.3
Compared with the control group * p < 0.05
Group
No. of case
TBSA (%)
Third-degree (%)
PBD of collecting sample
(serum and urine)
L
49
63.2 ± 20.1
38.9 ± 21.9
1, 2, 3, 7, 14, 21, 28
S
57
23.5 ± 11.4
5.3 ± 3.2
1, 2, 3, 7, 14, 21, 28
Note: L large burn area group, S small burn area group, PBD post-burn day
Table 16.139 Grouping of
burns patients and the time points
of sampling
16 Nutrition in Burns

445
The urinary Zn in the L group increased signifi cantly on the
fi rst day after burn and reached a peak on the 14th day, which
was three to seven times the normal value. It had recovered to
the normal level by 42 days after the burn. It also showed a
tendency to increase in the S group, but to a lesser extent than
that in the L group, and the urinary Zn in the S group recov-
ered to the normal level 28 days after the burn. The difference
between these two groups was extremely signifi cant.
The content of Zn in blister fl uid was higher than that in
the plasma at the same time point, which was close to the
upper limit of the normal range and reached its peak on the
second day after the burn.
The Changes in Copper
The changes in serum Cu were similar to those of Zn. The
serum Cu in the L group decreased signifi cantly 1–3 days
after the burn, and was lowest on the second day with a con-
centration of 0.5 μg/ml (normal range 0.7–1.4 μg/ml). Its
level reached the lower limit of the normal level 1 week after
the burn and had recovered to the normal level by 2 weeks
after the burn. The changes in serum Cu in the S group were
consistent with those in the L group, but the extent of
decrease had a deviation of about 0.2 μg/ml.
The urine Cu in the L group also presented a tendency to
increase and reached the peak 14 days after the burn with a
value 3.6–36 times the normal level. It had recovered to the
upper limit of the normal values by 42 days after the burn.
The increasing extent in the S group was lower than that in
the L group, and it had recovered to the normal level by
2 weeks after the burn. The content of Cu in blister fl uid was
lower than that in serum of the burns patients at the same
time point.
Changes in Fe
The serum Fe in the L group increased drastically on the fi rst
day after the burn, and then decreased to a large extent. The
level in the L group was lower than that in the S group after
PBD 7; however, the serum Fe in the S group remained
Table 16.140 Changes in serum Zn, Cu, and Fe in burns patients (μg/ml, x
s
±
)
Elements and
normal values
Group
PBD
1
2
3
7
14
21
28
Zn (0.5–1.5)
L
0.44* ± 0.15
0.40* ± 0.12
0.51* ± 0.25
0.73* ± 0.24
0.85* ± 0.26
0.96* ± 0.27
1.01 ± 0.29
S
0.98 ± 0.23
0.91 ± 0.11
0.95 ± 0.16
0.96 ± 0.38
1.10 ± 0.32
1.14 ± 0.20
1.14 ± 0.23
Cu (0.7–1.4)
L
0.49* ± 0.19
0.46* ± 0.18
0.59* ± 0.17
0.72* ± 0.25
0.98 ± 0.27
0.96* ± 0.27
0.98 ± 0.17
S
0.68 ± 0.20
0.67 ± 0.13
0.76 ± 0.20
0.99 ± 0.24
1.12 ± 0.25
1.14 ± 0.24
1.18 ± 0.16
Fe (0.6–1.9)
L
2.40** ± 0.57
1.42* ± 0.49
1.27 ± 0.32
1.08 ± 0.30
1.07 ± 0.40
1.07* ± 0.36
1.04 ± 0.29 *
S
1.59 ± 0.34
1.15 ± 0.23
1.10 ± 0.30
1.15 ± 0.18
1.18 ± 0.35
1.28 ± 0.24
1.14 ± 0.17
Note: L large area group, S small area group
vs S:* p < 0.05, ** p < 0.01
Table 16.141 Changes in urinary Zn, Cu, and Fe in burns patients (mg/day, x
s
±
)
Elements
(normal value)
Group
PBD
1
2
3
7
14
21
28
Zn (0.3–0.6)
L
0.44** ± 0.15
0.40** ± 0.12
0.51** ± 0.25
0.73* ± 0.24
0.85* ± 0.26
0.96* ± 0.27
1.01 ± 0.29
S
1.39 ± 0.49
0.71 ± 0.27
0.82 ± 0.25
0.81 ± 0.25
0.93 ± 0.27
1.27 ± 0.34
0.66 ± 0.01
Cu
(0.005–0.05)
L
0.27* ± 0.02
0.16 ± 0.10
0.17 ± 0.01
0.22 ± 0.02
0.23** ± 0.03
0.14** ± 0.09
0.15** ± 0.01
S
0.10 ± 0.01
0.16 ± 0.02
0.12 ± 0.01
0.11 ± 0.06
0.03 ± 0.01
0.043 ± 0.01
0.041 ± 0.01
Fe (0.2–0.3)
L
0.54* ± 0.04
0.90 ± 0.04
0.89 ± 0.06
0.73 ± 0.05
0.61 ± 0.03
0.66* ± 0.05
0.33 ± 0.02
S
1.11 ± 0.34
1.58 ± 0.31
0.43 ± 0.14
0.47 ± 0.17
0.39 ± 0.10
0.21 ± 0.02
0.12 ± 0.01
Note: L = large area group; S = small area group
vs S:* p < 0.05, ** p < 0.01
Table 16.142 Changes in Zn, Cu, and Fe in blister fl uid of burn patients (μg/ml x
s
±
)
Element
PBD
1 ( n = 19)
2 ( n = 21)
3 ( n = 16)
4 ( n = 11)
Zn
1.20 ± 0.26
1.37 ± 0.37
1.13 ± 0.22
1.10 ± 0.17
Cu
0.48 ± 0.15
0.42 ± 0.14
0.45 ± 0.12
0.33 ± 0.09
Fe
0.70 ± 0.27
0.68 ± 0.13
0.43 ± 0.11
0.58 ± 0.13
16.7 Trace Elements in Burns

446
within the normal range, except for the slight increase on the
fi rst day after the burn.
The urine Fe also increased; however, the differences
were that the urine Fe in the S group was higher than that in
L group during the fi rst 2 days after the burn, and the urine
Fe in the L group was higher than that in the S group in the
time after that.
Han et al. observed the dynamic changes of seven trace
elements in the serum and 24-h urine of eight patients with
severe burns and found that Zn, Fe, and Se in serum decreased
signifi cantly; the change in Cu was not clear, and the amounts
of the seven urinary trace elements such as Zn, Cu, Fe, Se,
etc. were signifi cantly higher than the reported normal
values.
16.7.1.2
Mechanism and Effect of Trace Element
Changes on the Burn Organism
The changes in serum Zn after a burn are related to the size
of the burn surface area and the time period after the burn.
The curves of serum Zn changes in patients with different
burn surface areas were similar, but the decrease in serum Zn
in patients with a burn covering a large area was signifi cantly
greater than that in the patients with a burn covering a small
area. The causes of the decrease in serum Zn include:
1. The wound surface causes a great loss of Zn: this is the
main reason for the decrease in serum Zn.
2. The excretion of urinary Zn increases: the normal urinary
Zn is 0.3–0.6 mg/day, and the daily amount of urinary Zn
may reach 4 mg/day in patients with extensive burns. The
daily intake of Zn is about 10–15 mg in healthy people,
and the intake of Zn cannot supplement the excretion as
the patients’ ingestion decreases after a burn.
3. Redistribution of Zn: under the state of stress, the distri-
bution of Zn in the body changes, the serum Zn transfers
into the cells. In particular, the content of Zn in hepatic
cells increases signifi cantly owing to the increase in the
synthesis of liver metallothionein (MT) induced by IL-1.
One MT molecule can bind with seven Zn atoms, which
results in the accumulation of a large amount of Zn in the
liver and a decrease in the serum Zn. The results of ani-
mal experiments also confi rmed this conclusion. The con-
tent of Zn in liver increases at 1 and 3 days after the burn
when the serum Zn decreases may be one of the regula-
tory mechanisms of the body.
4. Large amounts of glucose solution and physiological
saline are infused in the process of resuscitation, but Zn is
not supplemented promptly enough, which is also one of
the reasons why the serum Zn is decreased after a burn.
The decrease in serum Zn induces many adverse effects
on the patients. Zn is the component of over 300 types of
in vivo enzymes, and the decrease in serum Zn affects their
functions of catalysis, structure, and regulation. SOD is a
metalloenzyme containing Zn, and its activity and anti-
oxidant capability are both decreased after a burn. It also
affects the functions of the metabolic enzymes of sugar, fat,
and protein. Zn is extensively involved in the metabolism of
nucleic acid and protein; thus, the decrease in Zn affects the
essential vital processes, such as cell differentiation, espe-
cially cell replication. The decrease in serum Zn results in
the reduction of Zn on the wound surface, which affects the
healing of the wound surface. Zn is the co-factor for the bio-
synthesis of collagen; therefore, maintaining appropriate
serum Zn is necessary to promote wound healing and tissue
repair. There have been many reports on the decreased serum
Zn and increased urinary Zn after a burn; however, the rea-
sons for the increased urinary Zn have not been very clear.
Davies suggested that the catabolism of muscle after a burn
might be the main reason for increased urinary Zn. He
observed the parallel changes in creatine and Zn in urine.
Hedelin thought that urinary Zn might be related to tissue
damage, and he found that urinary Zn increased immediately
after operation. Toxins can lead to tissue damage, and Zn
released from the damaged tissue is excreted from urine; for
example, the urinary Zn increases signifi cantly in patients
with septicemia. Meanwhile, some people considered that
the increased urinary Zn after a burn might result from the
increases in amino acids and the other small molecular sub-
stances in plasma, which combine with Zn as well as com-
bining loosely with albumin and pass through the renal
glomerulus. Second, severe hemo-catheresis after burn
releases carbonic anhydrase containing a large quantity of
Zn, which can be fi ltrated through the renal glomerulus and
result in increased urinary Zn. Hemo-catheresis can release a
large quantity of Zn. The content of Zn in urine is related to
the burn surface area and a larger burn surface area leads to
higher and longer lasting urinary Zn. High urinary Zn may
refl ect hypermetabolism, which results in a great loss of Zn.
Ninety to ninety-three percent of plasma Cu combines
with copper protein. The main reason for decreased serum
Cu after a burn is the loss of copper protein through exuda-
tion, and a larger burn surface area leads to a larger and
longer- lasting decrease. Experiments on the application of
silver sulphadiazine (AgSD) to the wound surface confi rmed
that high serum silver can decrease the level of copper pro-
tein to reduce serum Cu. Haddon considered that low serum
Cu and decreased serum Fe might be related to the shorten-
ing of the life span of red blood cells. People have already
observed that for anemic patients after a burn, simple supple-
mentation of Fe cannot correct the anemia before the Cu
defi ciency is corrected. The decreased serum Cu results in
the reduction of the activity of SOD and its anti-oxidant
capability. Increased urine Cu is related to the increase in
plasma cortical hormones after a burn and the cortical hor-
mones promote the excretion of Cu through urine [ 133 , 134 ].
The serum Fe increased drastically on the fi rst day after a
burn, and the extent in patients with a large burn surface area
was greater than that in patients with a small burn surface
area, which was mainly related to the hemolysis after the
16 Nutrition in Burns

447
burn. The urinary Fe also increased signifi cantly on the fi rst
and second days after the burn, but the extent in patients with
a small burn surface area was greater than that in patients with
a large burn surface area. The mechanism is still unknown
and it is postulated that it might be related to inhibition from
the large amount of excretion of Zn and Cu through urine.
The blister fl uid Zn is at the upper limit of the normal
range in serum, which is related to the exudation of a large
quantity of albumin. Eighty percent of Zn combines with
albumin in plasma, and the exudation of a large quantity of
albumin results in higher blister fl uid Zn; however, the con-
tent of Cu in blister fl uid is lower than that in serum, which
may be related to the combination of Cu in blood. Ninety
percent of Cu combines with copper protein and the exuda-
tion of this protein is less than that of albumin. The concen-
tration of Fe in blister fl uid is close to its normal concentration
in serum, but signifi cantly lower than that in the serum on the
same PBD. These results indicate that the Fe in exudates
does not contain the Fe carried by the hemoglobin after
erythrolysis caused by burns.
16.7.2
Clinical Application of Trace
Elements
Trace elements have multiple effects on the human body. The
researchers have carried out many experiments and clinical
studies and have achieved fi ne results. Since the 1980s,
enlightened by the effectiveness of the application of different
dosage forms of AgSD in Pseudomonas aeruginosa infection
after a burn in 50 rats, based on the AgSD cream + Azone
(penetration enhancer), Guo et al. formulated the externally
applied agent supplementing Zn through the wound surface
by adding zinc sulphadiazine (ZnSD)—silver sulfadiazine
and zinc sulfadiazine cream. To verify the biological func-
tions of Zn, the experiment had been done twice, one after the
other. Forty-eight rat models of Pseudomonas aeruginosa
infection were used in every experiment and were smeared
with AgSD, ZnSD, AgSD+ZnSD, AgSD+ZnSD+Azone, a
ground substance of cream, and a ground substance of
cream+Azone, in addition to a control burn group without
application of any agent. Both experiments indicated that:
1. The concentrations of Zn in the blood and liver increased
signifi cantly in the animals smeared with the externally
applied agents containing Zn, which illustrated that the
wound surface is an important route in supplementing Zn.
2. The bacterial content under the crust was lower in the
animals treated with the agents containing Zn and/or
silver, and the effect of silver sulfadiazine and zinc sulfa-
diazine cream was the best among these agents.
3. In the silver sulfadiazine + zinc sulfadiazine cream group,
the bacterial detection rates of the lung and kidney were
lower, the amount of bacteria was less, and the histopath-
ological changes were mild.
4. Silver sulfadiazine and zinc sulfadiazine cream promoted
the healing of the wound surface and the average duration
of deep second-degree wound healing was 12.3 days;
however, there was only 66.7 % wound healing on PBD
22 in the control group. The sample collected at 3 weeks
showed complete cover of the squamous epithelium and
the initial growth of dermal attachments. The results of
screening proved that the curative effect of silver sulfadi-
azine + zinc sulfadiazine cream is the best among these
agents [ 135 ].
In the studies on the wound surface of the sarcolemma in
mini-pigs, it was discovered that, compared with the physi-
ological saline group and the dressing group, in the silver
sulfadiazine + zinc sulfadiazine cream group, there were
fewer bacteria in the granulation tissue, the granulation tis-
sue grew faster with a higher fi lling-in rate, and the wound
surface shrank rapidly with greater anti-tensile strength,
which suggested that silver sulfadiazine + zinc sulfadiazine
cream promoted the growth of granulation and epithelial
cells with a fi ne quality of repair.
Silver sulfadiazine + zinc sulfadiazine cream have been
applied clinically since 1991, and the results showed that it
not only has an anti-infection function, but also promotes
healing of the wound surface. In 1996, the curative effects of
48 patients with extensive burns (total area of 55.3 ± 19.9 %
of the TBSA, third-degree 23.6 ± 9.8 % of the TBSA) treated
by silver sulfadiazine + zinc sulfadiazine cream and 35 burns
patients with the same class treated with iodophors were
compared and the results were summarized in Table 16.143 ,
the calipers (calibrator) was utilized to continuously monitor
the process of the growth of 100 skin paddles, and it was
found that the spreading speed of skin paddles was faster
(0.42 ± 0.08 mm/day [normal speed: 0.27 mm/day]) after the
application of silver sulfadiazine + zinc sulfadiazine cream.
The results indicated that the application of silver sulfadia-
zine + zinc sulfadiazine cream alleviated the infection of the
wound, shortened the time of the systematic application of
antibiotics, accelerated the healing of the burn wound,
Table 16.143 Comparison of curative effects among silver sulfadiazine, zinc sulfadiazine cream, and iodophors
Negative conversion rate of
wound surface bacterial
culture (%)
Duration of systematic
application of antibiotics
(days)
Times of skin grafting
Time of basic wound
healing (days)
Silver sulfadiazine and zinc
sulfadiazine cream group
41.4
8.1 ± 3.3
3.5 ± 1.4
31.4 ± 3.3
Iodophors group
24
13.3 ± 3.3
4.8 ± 1.0
37.5 ± 2.7
16.7 Trace Elements in Burns

448
decreased the duration of the operation, and shortened the
duration of healing [ 136 ].
In the last several years, the clinical application of exter-
nally applied agents containing Zn has been one of the
important achievements of the studies on trace elements.
Researchers are still exploring the effects of the other trace
elements on the metabolism and healing of the wound sur-
face in burns patients.
16.7.3
Some Experimental Studies
on the Zn Supplement After a Burn
Zinc is the main focus because of its closest relationship with
wound healing, although there are 14 kinds of essential trace
elements, and in the burn wound fi eld, there are many more
studies on Zn than on the other trace elements. Like those
mentioned above, the patients with extensive burns have a
severe Zn defi ciency for a considerably long time after the
burn, and the clinical treatment does not usually include a
special measure to supplement Zn; thus, Zn supplementation
is usually neglected. Under most conditions, the curative
effects of an externally applied compound cream containing
SD-Ag + SD-Zn are recognized through the fi ndings that its
application signifi cantly accelerates the healing of the wound
surface.
Guo et al. found this result earlier and conducted a pri-
mary and helpful exploration of Zn supplementation via oral
administration and the wound surface route in animal experi-
ments. The results are summarized below:
1. The animal model of Zn defi ciency was established. The
1-month-old rats were fed with low-Zn forage (Zn con-
tent: 1.6 μg/g) for 1 week, and the animal model of Zn
defi ciency was successfully established. The earliest and
most obvious symptoms of Zn defi ciency are anorexia
and decreased food consumption in addition to growth
retardation resulting from the former two symptoms.
After 4 days of feeding with low-Zn forage, the rats pre-
sented the typical symptoms such as anorexia, growth
retardation, etc., followed by dispiritedness, limb stiff-
ness, cyanosis, and coolness of the limbs and tails, loss of
hair, relaxation of the skin, extreme dilation of the intesti-
nal tracts, parorexia, etc., which are all symptoms of Zn
defi ciency. Observation with light microscopy showed
atrophy of the intestinal mucosa, thinness of the skin, and
reduction of the collagen fi bers and hair follicles. Serum
Zn and bone Zn decreased signifi cantly and the activity of
alkaline phosphatase (AKP) was considerably reduced
[ 137 , 138 ]. With the same food consumption, a simple
increase in the content of Zn in each group could not
improve the nitrogen equilibrium and decrease the loss of
body weight in rats, which suggested that simple Zn sup-
plementation without an increase in the intake of energy
and nitrogen is insuffi cient to affect the nutritional state of
the body from the integrated level. These results further
hinted to us that the critical effects of Zn supplementation
should be established on the basis of an adequate intake
of energy and nitrogen.
2. In the animal experiments, the researchers mainly
observed the effects of Zn defi ciency and the burn on the
contents of Zn in serum and tissue, and on the hormones,
proteins, and enzymes containing Zn.
The contents of Zn in serum, liver, bone, skin, and the
levels of serum alkaline phosphatase (ALP), GH, and
liver MT in the rats with Zn defi ciency before a burn are
lower than those in the normal rats; skin and bone are the
most sensitive tissues to Zn defi ciency; thus, the content
of Zn in these tissues decreases rapidly to a large extent
when Zn is defi cient. In normal rats after a burn, the
contents of Zn in serum and bone, in addition to ALP,
decrease, the levels of GH, liver MT, and Zn of the liver
and burnt skin present a tendency to increase, The levels
of ALP, GH, MT, and Zn of serum and tissue increased
signifi cantly after Zn supplementation; however, the
extent of the changes in the rats with regard to Zn defi -
ciency is smaller than that in the normal rats [ 139 , 140 ].
Zinc defi ciency and burns have effects on the fragility
of erythrocytes. Zn defi ciency and burns increase the fra-
gility of the erythrocytes, and the increased fragility of
erythrocytes decreases after Zn supplementation and the
serum Fe also decreases, which may be related to the
function of Zn, to maintain the stability of the erythrocyte
membrane [ 141 ].
Zinc supplementation can increase the content of
hydroxyproline (HYP) in burnt skin, which may be one of
the mechanisms of Zn that promotes the healing of the
wound surface [ 142 ].
3. Effects of Zn supplementation via different routes. Both
oral administration and the wound surface route for Zn
supplementation mainly increases the content of Zn in
serum and tissues. The oral administration mainly
increased the content of Zn in serum and the liver in addi-
tion to the levels of liver MT and GH, and decreased the
fragility of the erythrocyte; however, the wound surface
route mainly increased the content of Zn and HYP in skin
and decreased the content of calcium in the tissue of the
wound surface. Han et al. observed the changes in Zn and
Cu in 46 patients with severe burns and the effect of
double- blind oral administration of zinc sulfate (660 mg/
day), for patients with a severe burn with the coeffi cient
of the burn surface area of over 180, the healing of the
wound surface in the treatment group was 8 days earlier
than in the control group and the serum Zn in the treat-
ment group was higher than that in the normal control
group at the time of healing, which suggested that the
administration of Zn in patients with a severe burn might
16 Nutrition in Burns

449
have some curative effect, but that the course of treatment
should not be too long [ 143 ].
4. Simple Zn supplement is also benefi cial to the body. The
benefi t is mainly presented in some of the organs that are
most sensitive to the nutritional state of Zn, which can be
called target organs. The animal experiments indicated
that the nutritional state of Zn almost has no effect on the
content of protein in tissues; however, the factor critically
affected by the nutritional state of Zn is the content of
DNA, which is very signifi cant in some organs such as the
jejunal mucous membrane, kidney, testis, spleen, etc. Zn
affects the synthesis of DNA in two ways: the fi rst was to
reduce the amount of DNA precursor (nucleotides) to
decrease the rate of nucleotide (e.g., thymine) integrating
into DNA; the second way was to decrease the activity of
DNA synthetase [ 144 ].
Substantially, the content of DNA in tissue refl ects the
number of cells and the rapidity of cell renewing. This
effect of Zn can be refl ected accurately from the histomor-
phological point of view through the counting of the num-
ber of cells in the mitosis metaphase (these cells have a
distinct karyokinesis phase under the microscope).
Compared with the morphological changes, the functional
changes present earlier (e.g., intestinal mucosa). The
intestinal mucosal barrier is a very sensitive system, and
the increased intestinal mucosa permeability and bacterial
translocation after severe burns are considered to be the
initiating factors, resulting in SIRS and MODS. Satisfactory
resuscitation during the shock phase and the increase in
the intestinal mucosal blood fl ow are the main measures to
protect the intestinal mucosal barrier. Meanwhile, early
feeding and an appropriate change of diet formulation also
have the function of protecting the intestinal mucosal bar-
rier. Some experiments showed that 24 h of fasting in rats
resulted in a signifi cant increase in intestinal mucosa per-
meability; malnutrition also increased intestinal mucosa
permeability; the addition of nutritional ingredients such
as glutamine, arginine, cellulose, unsaturated fatty acid,
etc., in the food protected the integrity of the structure of
the intestinal mucosa and alleviated the bacterial translo-
cation. The experiment conducted by 304 Hospital indi-
cated that intestinal mucosal permeability increased in rats
with Zn defi ciency before the burn, and the burn further
aggravated Zn defi ciency and the intestinal mucosal per-
meability; however, enhanced Zn supplement within just
1 day and a half can decrease the permeability [ 145 ].
Testis is another main target organ of Zn. The main
functions of the testis are spermatogenesis and endocrino-
logical. In the clinical treatment of patients with severe
burns, the male hormone is usually applied to promote
wound healing. However, it is hardly to investigate
whether Zn can stimulate the production of endogenous
testosterone and avoid the adverse effects of testosterone.
The experiments showed that, in the animal model of Zn
defi ciency with burns, 1 week of Zn supplementation sig-
nifi cantly increased the level of endogenous testosterone;
thus, at least it has the function of promoting the repair of
the wound in theory [ 146 , 147 ].
5. Effects of Zn supplementation on the cytokines and prog-
nosis for patients with severe burns patients. Qiu et al.
treated the patients with severe burns with oral adminis-
tration of 10 ml of zinc gluconate solution, twice per day
for 28 days, and monitored its effects on the levels of
cytokines of these patients. They found that the levels of
endotoxin, TNF-α, and IL-6 at 14 and 28 days after the
burn were all signifi cantly lower than those in the control
group; after Zn supplementation, the systematic infec-
tion, MODS, and mortality were all lower than those in
the control group [ 148 ].
6. The safety of Zn supplementation after a burn. Treatment
with a large dose of Zn is still doubtful, although it is
generally considered that Zn is a type of nontoxic metal,
i.e., whether Zn supplementation, especially large doses
of Zn supplementation, affect the absorption and metabo-
lism of the other mineral substances and trace elements.
“The elements with similar physical and chemical proper-
ties show biological antagonism to each other.” This
viewpoint is considered to be the basic law of the interac-
tion between Zn and the other bivalence trace elements
and mineral substances. The inter-antagonistic elements
of Zn include Cu, Fe, Mg, Ca, etc. The experiment con-
ducted by 304 Hospital confi rmed that, after a severe
burn, large doses of Zn supplement in a short time within
the special period of Zn defi ciency is benefi cial and
innocuous and does not affect the absorption of the other
mineral substances or trace elements. The experiment
investigated the contents of Cu, Fe, Mg, and Ca in addi-
tion to Zn in liver, spleen, kidney, testis, and serum in the
burns patients after 1 week of feeding with a zinc-rich
diet, in which the content of Zn is ten times that in the
common diet, and no defi ciency of any related element or
excessive accumulation of Zn in any organ was found.
The results indicated that the in vivo poikilocytosis regu-
lation of Zn is very effective, i.e., the absorptivity of Zn
decreases when the content of Zn in food exceeds the
requirement of the body and the excess Zn is eliminated
with excrement and urine, without absorption; thus, the
absorption of Zn will not increase uncontrollably because
of excessive Zn supplementation. A large dose of Zn sup-
plementation to treat Zn defi ciency does not reduce the
absorption of related elements, and we considered that
the main reason lay in the intestinal tract. Like those men-
tioned above, the intestinal tract is the most sensitive
organ to the nutritional state of Zn. Zn defi ciency changes
the intestinal mucosal structure and reduce its absorptive
function, which can be recovered by Zn supplementation.
16.7 Trace Elements in Burns

450
Thus, the absorption of various nutrient substances,
including trace elements and mineral substances, is
enhanced [ 144 ].
The other routes for Zn supplementation, including
intravenous nutrition and wound surface absorption, in
addition to a course of Zn supplementation and the speci-
fi ed dose, still need further study.
7. Effects of Zn supplementation after a burn on Ca 2+ in
serum and tissue.
In the animal experiments, it was found that the contents
of Ca 2+ in serum, liver, bone, and skin increased signifi -
cantly after a burn; in particular, in the burnt skin, the con-
tent of Ca 2+ was almost doubled. The results of these
experiments indicated that oral administration of Zn sup-
plementation signifi cantly decreased the content of Ca 2+ in
liver; Zn supplementation through the wound surface sig-
nifi cantly decreased the content of Ca 2+ in the burnt skin
and it also inhibited the decrease in Ca 2+ in bone. One
important physiological function of Zn is antioxidation. It
can also be combined with the hydrosulfi de groups on the
cell membrane to prevent the formation of a disulfi de bond
by oxidation and to maintain the integrity and permeability
of the cell membrane to reduce Ca 2+ infl ow, decrease intra-
cellular Ca 2+ overload, and alleviate the lipid peroxidation
lesion. It can also increase the activity of Ca 2+ -ATPase in
promoting the pumping out of intracellular Ca 2+ , reducing
calcium overload, and inhibiting the abnormal distribution
of Ca 2+ in the body to alleviate tissue damage. One of the
mechanisms of Zn that promotes healing of the wound sur-
face may be related to its function of inhibiting calcium
overload in the cells of burnt skin and alleviating tissue
damage to shorten the healing time [ 149 , 150 ].
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References

455
Z. Yang, Chinese Burn Surgery, DOI 10.1007/978-94-017-8575-4_17,
© Springer Science+Business Media Dordrecht and People’s Medical Publishing House 2015
Severe thermal burn injury is a complex disease process; it
not only destroys the cutaneous barrier protecting the patient
from a hostile environment, but it also causes pathophysio-
logical changes in every other organ system. The extent and
duration of organ function alterations are directly related to
the extent of thermal injury. These identical changes occur to
some degree in all injured patients. The purpose of this chap-
ter is to review the pathological changes of visceral organs
and endocrine glands.
Partial lesions in this system are related to sepsis. The
extreme stress, fl uid imbalance, changes in metabolism, and
hormonal fl uctuations that occur in burn patients have led us
observer to scrutinize the endocrine glands for morphologi-
cal evidence of degenerative or hyperplastic changes.
This chapter consists of seven parts and mainly concerns
the pathological changes in the heart, blood vessels, respira-
tory tract and lungs, kidneys, gastrointestinal tract, liver,
brain, and endocrine glands after burns. In accordance with
contents, there are gross, light, and electron microscopic pic-
tures to be selected. With a few exceptions, most of them
from author’s own work, some have been published formerly
in various medical journals.
17.1
Pathological Changes in the Heart
and Blood Vessels After Burns
Firstly, we will review the cardiovascular complications of
burn injury. Most of the lesions in this part are related to can-
nula trauma and sepsis.
In some patients and experimental animal materials, mini-
mal focal myocarditis or abscess, intracytoplasmic transverse
band (Fig. 17.1 ), focal intracytoplasmic degeneration (FCD)
(Fig. 17.2 ), intramyocardial mitochondria showing crepe
paperlike structure (Fig. 17.3 ), myocardial mitochondrial
matrix having large amount of calcium saltlike granule deposit
(Fig. 17.4 ), interstitial edema (Fig. 17.5 ), and minimal numbers
of neutrophils were present in the foci. The extent of severity
of these myocardial changes was no greater than pneumonia or
other septic processes. In 10 % of cases (Teplitz, who showed
these myocardial changes), death was due to sepsis.
Current studies have shown that the vascular endothelial
cell damage presents the pathological basis of increased
Pathological Changes of Visceral
Organs and Endocrine Glands
After Burns
Yisheng Chen and Jingquan Shi
17
Fig. 17.1 Intracytoplasmic transverse band of the myocardium (TEM
×20,000)
Fig. 17.2 Focal intracytoplasmic degeneration ( FCD ) of the
myocardium (TEM ×20,000)

456
capillary permeability in burn shock, which in turn causes
hypovolemia, hypoxia, and tissue ischemia. Therefore, the
studies of the mechanism and protection from the hypoxic
and ischemic damages occurring in early period of burn
injury are demanded.
The myocardial apoptosis might be induced by delayed
fl uid resuscitation in burned rat model. The decreased NO
and the production of oxygen-derived free radicals are also
observed in this process.
17.1.1 The Relationship Between Myocardial
Injury and the Changes of [Ca 2+ ]i,
Proto-Oncogene, and Myosin Isoforms
During the Early Stage After Burn
Many investigations revealed that external signals were trans-
mitted to nuclei of cardiac myocytes through complicated
pathways under many pathological conditions, inducing the
expressions of early reactive proto-oncogenes c - fos and c -
myc , which initiated the expressions of late reactive genes
β-myosin heavy chain and α-actin. Then new proteins were
synthesized which resulted in the remodeling of the myocar-
dium and its functional changes. Some researchers suggested
that the expressions of c - fos and c - myc were closely related to
calcium ions. Now it has been known that the myocardial
contractility is usually reduced and accompanied by calcium
overload with pathological changes of the myocardium after
burn. However, there are fewer investigations about the
expressions and effects of proto-oncogenes c - fos and c - myc
and β-myosin heavy chain of the myocardium post burn.
We reproduced a rat model of 30 % TBSA III degree
burn. The present study was divided into four parts: (a) The
histological and ultrastructural changes of the myocardium
after burn were observed by light microscopy and electron
microscopy. (b) The concentration of free calcium in the
cytoplasm of cardiac myocytes was detected by Fura-2/Am.
(c) The expressions of c - fos and c - myc protein and mRNA
were determined by IHC (immunohistochemistry) and ISH
(in situ hybridization), respectively. (d) The transformation
of myosin was observed by SDS-PAGE. The aim of this
study was designed (a) to explore the changing rules of myo-
cardial damage, [Ca 2+ ]i, expression of proto-oncogene, and
transformation of myosin isoforms; (b) to observe effects of
different factors (burn, resuscitation, and calcium inhibitor)
on different indices; and (c) to study the possible effect of
calcium on myocardial damage and gene expressions and
investigate the possible protective effects of different factors
on the myocardium and the molecular mechanism of myo-
cardial dysfunction.
The main fi ndings were as follows: (a) Rat cardiac myo-
cytes revealed various histological and ultrastructural
changes after burn. The degree was gradually decreased in
Fig. 17.3 Intramyocardial mitochondria ( M ) showing crepe paperlike
structure (TEM ×15,000)
Fig. 17.4 Myocardial mitochondrial matrix having large amount of
calcium saltlike granule (→) deposit (TEM ×25,000)
Fig. 17.5 Interstitial edema of the ventricular myocardium (TEM
×20,000). E edematous fl uid, V vacuole



17 Pathological Changes of Visceral Organs and Endocrine Glands After Burns

457
simple burn group, resuscitation group, and verapamil group.
(b) Intracellular concentration of calcium increased signifi -
cantly both in burn and resuscitation groups ( p < 0.01), while
it increased slightly in calcium inhibitory group ( p > 0.05).
(c) The expressions of c - fos and c - myc mRNA could be
observed 30 min after burn and obviously decreased at 72 h
post burn which had no signifi cant difference from control
group ( p > 0.05). The expression was gradually decreased in
burn group, resuscitation group, and verapamil group. (d)
Myosin in each group began to transform to V 3 from the 12th
hour after burn, and the percentage of V 3 reduced gradually
in burn, resuscitation, and calcium inhibitory group. (e) The
expression of c - myc mRNA was not related to the concentra-
tion of calcium inhibitory group ( p > 0.05), while both c - myc
and c - fos mRNA and protein were related to calcium in any
other groups.
Our fi ndings indicated that (a) histological and ultrastruc-
tural changes of the myocardium which resulted from burn
were the morphological basis of myocardial dysfunction after
burn. Verapamil, the inhibitor of calcium, obviously decreased
the degree of pathological changes which showed some pro-
tective effect on the myocardium, while resuscitation only
had slight protective effect. (b) [Ca 2+ ]i increased evidently
after burn leading to calcium overload. Verapamil could obvi-
ously reduce calcium overload post burn, while resuscitation
could not effectively inhibit calcium overload. The changes
of [Ca 2+
]i possessed phasic character. The concentration
reached its climax at the 3rd hour after burn, while that at
30 min and 72 h post burn in experimental groups were
clearly lower than that in control group. There was no such
report in the myocardium post burn. The exact mechanism
and signifi cance needed further study. (c) We fi rstly reported
the expressional characteristics of early reactive proto-onco-
genes c - fos and c - myc in the myocardium after burn. The
expression of c - fos and c - myc mRNA could be observed at
30 min post burn and obviously decreased at 72 h post burn
which had no signifi cant difference from control group
( p > 0.05). Their expression level could be decreased obvi-
ously by verapamil, while resuscitation after burn could not
effectively inhibit their expressions. It was thought that c - fos
and c - myc might play a role in myocardial hypertrophy post
burn, which was the molecular basis of myocardial remodel-
ing. (d) Myocardial contractile protein- myosin isoform V 1
transformed to V 3 post burn which reduced the activity of
ATP (adenosine triphosphate) and myocardial contraction.
Verapamil could evidently reduce the myosin transformation
from V 1 to V 3 , while resuscitation after burn could not. (e)
Changes of [Ca 2+ ]i post burn were related to the expression
levels of c - fos and c - myc mRNA and protein. Myocardial
dysfunction was related to calcium overload. And myocardial
remodeling with the increase of expression levels of c - fos and
c - myc and myosin isoform V 3 was possibly the molecular
basis of myocardial dysfunction.
17.2
Early Histopathological
and Ultrastructural Changes
of the Myocardium in Dogs
with Smoke Inhalation Injury
Light and electron microscopic changes of the myocardium
of dogs after smoke inhalation injury were described in detail
with the purpose of demonstrating the effects of smoke inha-
lation on the myocardium. Temperature of inhaled smoke
was about 37 °C.
The results of the present study were identical with steam
inhalation injury. The most prominent changes were intersti-
tial edema of the myocardium, myofi brinolysis, slight thick-
ening of Z bands, mitochondrial swelling and vacuolation,
and dilatation of sarcoplasm. Their causes were in relation to
carbon monoxide poisoning and anoxia.
17.3
The Effects of Postburn Fluid
Resuscitation on the Pathohistological
and Ultrastructural Changes
of Multiple Organ with Dysfunction
in Severely Burned Dogs
This experiment is to investigate the postburn fl uid resuscita-
tion on the pathological and ultrastructural changes of mul-
tiple organs with dysfunction in severely burned dogs.
Forty-four mongrel dogs were randomly divided into four
groups: (a) immediate infusion, (b) delayed infusion, (c)
non-infusion, and (d) normal control. The dogs were infl icted
with 50 % third-degree fl ame burn produced by napalm in a
concentration of 30 g/L burning for 30 s on the back. Small
pieces of tissue samples of the heart, lungs, liver, kidneys,
and gastrointestinal tract were taken from injured dogs at
72 h post burn or moribund stage for the examination with
light microscope and transmission electron microscope.
Results exhibited different degrees of blood circulation dis-
turbance and degenerative changes were found in all the
above internal organs. These changes were more evident in
delayed infusion group than in delayed infusion group and
no infusion group. Therefore, delayed postburn fl uid resusci-
tation could induce multiple organ dysfunction in early post-
burn stage.
17.3.1 An Experimental Study of the Systemic
Effects of Phosphorus Burn in Rats
This experiment was designed to investigate the systemic
effects of phosphorus burn in rats by means of radioactive
phosphorus tracing, biochemical study of blood and urine,
determination of LD 50 DSA (burn surface area), as well as
histological and ultrastructural observations of the vital
17.3 The Effects of Postburn Fluid Resuscitation on the Pathohistological and Ultrastructural Changes

458
internal organs at various time intervals up to the 30th day
post burn. The pathological changes of the myocardium
were as follows:
The damage of the myocardium appeared early. The pathologi-
cal fi ndings were intracellular edema, interstitial edema, and
diapedesis of red blood cells. It was formerly suggested that
abnormalities found in electrocardiogram were simply due
to the disturbances of serum electrolytes. The present study
suggests that morphological changes found in the myocar-
dium might account for the ECG abnormalities.
17.4
Pathological Changes
in the Respiratory Tract and Lungs
After Burns
Pathological changes in the respiratory tract and lungs after
burns are common in which pulmonary lesions may usually
be the important cause of death in severely burned patients.
The causes of respiratory tract and lung lesions in burned
patients may be either primary or secondary. The primary
factors consist of inhaling hot air, fl ame, fumes, smoke, and
irritant gases. The secondary factors may be systemic effects
affecting the lungs, such as general circulatory disturbances
leading to pulmonary edema or bronchopneumonia.
17.4.1 Lesions in the Respiratory Tract
1. The Larynx
Among 61 necropsy cases from fatally burned patients,
there were 18 cases (29.5 %) showing lesions in the lar-
ynx. These included: congestion and edema in the mucous
membrane, sometimes the mucous membrane showing
patchy hemorrhage, erosions, ulceration, fi brinous infl am-
mation, and hyperkeratosis. Clinically there were two
cases presenting respiratory suffocation: one of them was
due to marked congestion and edema in the glottis and
another case due to deposition of keratin materials in the
glottis leading to respiratory obstruction.
2. The Trachea and Bronchi
Among 61 necropsy cases from fatally burned patients,
there were 52 cases (85.2 %) showing a variety of lesions
in the trachea and bronchi. About half of 52 cases exhib-
ited varying degrees of congestion and edema in the
mucosa; the other half of 52 cases showed tracheitis and
bronchitis, including pseudomembranous infl ammation
as well as hemorrhagic necrotic infl ammation.
Occasionally, erosions and acute ulceration in the
mucous membrane may be seen. In some cases, bronchi-
oles were plugged with sticky mucinous substance, which
may lead to atelectasis in their distal part of the lung tis-
sue when completely obstructed.
17.4.2 Pulmonary Lesions
Among 61 necropsy cases from fatally burned patients, there
were 56 cases (91.8 %) showing a variety of pulmonary
lesions.
1. Pulmonary edema
Pulmonary edema may be mild, moderate, and severe
in degree. In mild type, 12 out of 52 cases, no obvious
changes in lung weight, microscopic examination exhib-
ited partial alveolar spaces fi lled with fi ne pinkish protei-
nous granules. In moderate type, 15 out of 52 cases, slight
increase in lung weight (about 1,000 g), microscopically,
most alveolar spaces fi lled with fi ne pinkish proteinous
granules may be found. In the remaining cases belonging
to severe type, marked increase in lung weight (1,140–
1,750 g), microscopically, majority of alveolar spaces
fi lled with fi ne pinkish proteinous granules may be seen.
In some cases intra-alveolar spaces were lined by hyaline
membrane (especially in those cases with massive plasma
transfusion).
As to the pathogenesis of pulmonary edema, combined
with our clinical data, during shock phase, pulmonary
edema may be related to respiratory burn and rapid and
over-venous transfusion. After shock phase it might be
related to sepsis.
2. Pulmonary hemorrhage
Among 56 necropsy cases from fatally burned patients,
there were 25 cases (44.6 %) showing varying degrees of
pulmonary hemorrhage. The pattern of hemorrhage may
be petechial, focal, or diffuse parenchymal. Among these,
the focal hemorrhages were most frequent. Diverse etiol-
ogies may be associated with these fi ndings. Two of the
more common causes are (a) inhalation injury, such as
inhaling irritant gases, and (b) an outstanding feature of
sepsis.
3. Atelectasis (collapse of the lung)
According to the literature, the frequency of atelectasis
may be as high up to 30–50 %. In our necropsy materials,
there were only fi ve cases (8.9 %) showing atelectasis,
manifested as segmental or lobar pattern. Grossly, the
lesion presented as circumscribed solid patch or area,
accompanied by vascular congestion, deep red in color,
referred to as congestive atelectasis. Microscopically, the
affected area exhibited vascular congestion and collapse
of alveolar spaces. In the vicinity of lesions, bronchioles
plugged with mucopurulent exudate may be found.
4. Lobular pneumonia (bronchopneumonia)
Clinically lobular pneumonia is a common type of
complication in burned patients. In our 56 necropsy mate-
rials, there were 17 cases (33 %) suffering from lobular
pneumonia. About one-third of cases presented hemor-
rhagic necrotizing type of pneumonia, in which the
majority of cases that coexisted with sepsis are caused by
17 Pathological Changes of Visceral Organs and Endocrine Glands After Burns

459
Pseudomonas aeruginosa , less caused by mycotic
infections. In the remaining cases, there appeared a com-
mon type of lobular pneumonia in which alveolar exudate
was characterized predominantly by mononuclear cells.
5. Pulmonary thrombosis and infarction
In our 56 necropsy cases, there were some cases show-
ing thrombosis in the venules and capillaries in both
lungs. In gross examination no thrombi can be seen.
Microscopically, thrombi were composed of platelets and
fi brin or lysed red blood cells. In our necropsy cases, only
one case of hemorrhagic infarct of the lung could be
found.
6. Pulmonary abscess
Pulmonary abscess may be solitary or multiple.
Multiple abscesses were more common, found in those
cases with pyemia. Solitary abscess usually coexisted
with lobular pneumonia, probably as its complication of
the latter.
In our necropsy cases from fatally burned patients,
there were 31 cases showing body surface burn combined
with respiratory burn. In order to explore the pathomor-
phological characteristics in the respiratory tract and lung
parenchyma for such combined burns, 31 cases may be
divided into several groups according to various time
intervals post burn. The results were as follows: after burn
injury compared with simple body surface burn, in such
combined burns various lesions in the respiratory tract
and lung parenchyma were gradually exacerbated until
the 4th day. On the 4th day post burn, the lesions arrived
at a peak. Thereafter, the lesions in the respiratory tract
and lung parenchyma were gradually alleviated. The
lesions in the upper respiratory tract were prominent,
including increased secretory activity of goblet cells and
mucous glands and degeneration and necrosis of the
mucous membrane. The infl ammatory cells were charac-
terized predominantly by mononuclear cells, while poly-
morphonuclear neutrophils less encountered. In about
67 % of cases, thrombosis in the pulmonary vessels may
be found. In some cases “pseudothrombus” may be seen.
Prior to the 7th day post injury, megakaryocytes within
pulmonary capillaries may be found. In about half of
cases, interstitial fi brosing alveolitis may be present after
the 7th day post injury. Hemorrhagic lesions were rather
more frequent in combined burns than in simple body sur-
face burn.
In an experimental study of surface body burn on rabbits
caused by napalm, the pathological changes in the respira-
tory tract and lung parenchyma were manifested as a
dynamic process. The lesions appeared 4 h post burn and
most marked on day 3 and alleviated on day 7 post burn.
The mucosa of the trachea and bronchial tree showed con-
gestion, edema, and polymorphonuclear neutrophil (PMN)
infi ltration. The cilia of ciliated cells were adherent, dis-
rupted, and detached. The goblet cells and Clara cells were
increased in number.
The lung parenchyma exhibited interstitial edema, but no
intra-alveolar edema, PMN infi ltration, and sequestration of
PMN within pulmonary capillaries. In type II epithelial cells
lamellar bodies were reduced in number and vacuolated. The
lamellar bodies may be phagocytosed by macrophages.
Pathological changes of the respiratory tract and lung
parenchyma in experimental inhalation injury are as
follows:
Inhalation injury may be caused by inhaling hot air, fl ame,
steam, smoke, fumes, and irritant gases. In the last two
decades of the twentieth century, we have employed a
series of collaborative studies on experimental inhalation
injury with the Burn Institute of PLA in the Third Military
Medical University. Experimental inhalation injury inves-
tigation mainly consisted of two parts, namely, steam
inhalation injury (also called steam respiratory burn) and
smoke inhalation injury.
17.4.3 Experimental Studies of Severe Steam
Respiratory Burns
1. The experimental animals (dogs) were divided into four
groups: (a) simple respiratory burn, (b) simple body sur-
face burn, (c) combined burn, and (d) normal control. The
animals were killed at time intervals of 2 h, 6 h, 12 h,
24 h, 48 h, 3 days, 7 days, and 14 days post burn for path-
ological examination.
2. Pathological changes in the trachea and bronchial tree:
Early stage (within 48 h postburn). Grossly and histologi-
cally, the mucosa of the trachea and main bronchi showed
varying degrees of hyperemia and edema, degeneration,
necrosis, erosions, ulcers, and pseudomembrane forma-
tion (Fig. 17.6 ). In the trachea and main bronchi, 3 types
of lesions could be identifi ed: (a) simple lesions, (b) mul-
tiple minute ulcers, and (c) massive necrosis with slough-
ing followed by pseudomembrane formation. In the
trachea and main bronchi, the goblet cells of the mucosa
were increased in number. The pattern of increase of gob-
let cells may be (a) multifocal, (b) multi-segmental, and
(c) diffuse.
3. The intrapulmonary bronchial tree: In the surroundings of
the intrapulmonary bronchial tree, congestive zone,
edematous zone (Fig. 17.7 ), hemorrhagic zone (Fig. 17.8 ),
and infl ammatory cell infi ltration zone may be seen.
Besides, perivascular edematous cuff, hemorrhagic cuff,
edematous hemorrhagic cuff, edematous infl ammatory
cellular cuff, etc., may be found.
Late stage (3–14 days post burn)
On day 3 post burn, the damaged mucosa of the main
bronchi may be found to have been repaired by granulation
17.4 Pathological Changes in the Respiratory Tract and Lungs After Burns

460
tissue. On days 7 and 14, a large amount of granulation
tissue formation may be seen. Ultrastructurally in the
intrapulmonary bronchial tree, cilia, microvilli, and the
cell body of ciliated epithelial cells were all involved and
damaged. The cilia are reduced in number or fused
together. In cilia there were mushroom-shaped blebs
(Fig. 17.9 ) which were also seen in the microvilli. In the
ciliated epithelial cells, vacuoles were found in the
mitochondria and endoplasmic reticulum as a result of
edema. The cytoplasm at the top of the cell body occa-
sionally protruded and formed branching or sickle-shaped
elevation. Giant myelin fi gures could be seen above or
below the nucleus. These phenomena were seen sepa-
rately or simultaneously 2–48 h post burn.
4. Pulmonary lesions: In the lung parenchyma, there were
congestion, intra-alveolar edema, hemorrhage, localized
atelectasis, compensatory emphysema, and bronchopneu-
monia. Pulmonary edema was an outstanding feature in
steam respiratory burn. It was rather mild 2 h post burn
and became aggravated gradually from 4 to 24 h and sub-
sided to a certain extent 48 h post burn. Bronchopneumonia
was more frequently encountered and most marked 3 days
post burn and less common in later stage.
Ultrastructural changes in the lung parenchyma were
as follows:
Fig. 17.6 Pseudomembrane formation in the trachea, after its detach-
ment the tracheal rings became denuded. Steam respiratory burn in dog
Fig. 17.7 Perivascular edematous cuff. Steam respiratory burn in dog,
HE, low-power magnifi cation
Fig. 17.8 Peribronchial and perivascular edematous, hemorrhagic
cuff. Steam respiratory burn in dog, HE, low-power magnifi cation
Fig. 17.9 Ciliated columnar epithelial cells in the tracheal mucosa
showing swelling of cilia with mushroom-like process formation
( arrow ). Steam respiratory burn in dog; TEM ×8,400




17 Pathological Changes of Visceral Organs and Endocrine Glands After Burns

461
(1) The interstitial tissue of the alveolar septa: In the early
stage, the thick portion of blood-air barrier was mark-
edly edematous. Large vacuoles fi lled with edema fl uid
appeared. The mitochondria of the fi broblasts were
swollen and vacuolated. Interstitial edema of the alveo-
lar septa was still found 3 days post burn.
(2) Pulmonary capillary endothelial cells: The endothelial
cells of pulmonary capillaries showed no structural
changes 2 and 6 h post burn. The mitochondria of endo-
thelial cells were swollen and vacuolated 12 h post burn.
The most marked changes were seen 24 and 48 h post
burn. The endothelial cells were markedly swollen and
contained vacuoles of various sizes. The basal part of
their cells became disrupted.
(3) The alveolar epithelial cells: Type I alveolar epithelial
cells were swollen in which cytoplasmic matrix showed
marked edema and vacuole formation 4 h post burn.
Changes in the type I epithelial cells were more marked
12 and 24 h post burn. Part of type I epithelial cells
showed edema as well as a large number of vacuoles
which often contained myelin fi gures. Some of the type
I epithelial cells were fragmented. Type II alveolar epi-
thelial cells showed vacuole formation involving the
mitochondria and endoplasmic reticulum 12 h post
burn. Type II epithelial cells were increased in number
24 h post burn. Some of type II epithelial cells showed
a honeycomb appearance due to numerous vacuoles in
the cytoplasm, while the others contained giant lamel-
lar bodies. By 48 h post burn, type II epithelial cells
contained many huge vacuoles formed by coalescence
of smaller ones. The tops of these cells protruded into
the alveolar space. The type II epithelial cells exhibited
slight proliferation on day 3 post burn, more prominent
(Fig. 17.10 ) on days 7 and 14, followed by alveolar sep-
tal fi brosis and atelectasis. These phenomena are
consistent with the evolution process of “diffuse alveo-
lar damage” (DAD).
The alveolar spaces contained a varying amount of edema
fl uid and pulmonary surfactant material. Occasionally
hyaline membrane (Fig. 17.11 ) comprising of plasma
proteins, surfactant material could be found to line the
surface of type I epithelial cells and underlying alveolar
septa showing interstitial edema.
As above-mentioned, pulmonary edema was an outstand-
ing feature in steam respiratory burn. Initially it was an
interstitial edema, developing into intra-alveolar edema.
Concerning its pathogenesis, it is related to damage to the
alveolar-capillary membrane on the one hand and also
related to the role of increased plasma histamine level on the
other hand. Damage to the alveolar-capillary membrane was
evidenced by ultrastructural changes in capillary endothelial
cells as well as type I alveolar epithelial cells. In the present
experiment, mast cells in the wall of the tracheobronchial
tree showed degranulation. Histamine content determina-
tion of the blood plasma and lung tissue showed that hista-
mine content of the lung tissue was reduced, while the
histamine level of blood plasma elevated, thus indicating
that increased histamine originated from degranulation of
mast cells [ 1 , 2 ].
17.4.4 Experimental Studies of Smoke
Inhalation Injury
Experimental animals (including dogs and sheep) were
divided into two groups: experimental group and control
group. The animals in experimental group (including dog
and sheep) were killed at time intervals of 2, 4, and 24 h after
smoke exposure for pathological examination.
Fig. 17.10 Type II alveolar epithelial cells ( PII ) showing proliferation,
grouping in cluster. Steam respiratory burn in dog, TEM ×8,000
Fig. 17.11 Pulmonary hyaline membrane ( HM ) lining the surface of
type I alveolar epithelial cell ( PI ), underlying alveolar septa showing
interstitial edema. Steam respiratory burn in dog, TEM ×10,000


17.4 Pathological Changes in the Respiratory Tract and Lungs After Burns

462
17.4.4.1 Pathological Changes in the Trachea
and Bronchial Tree
Grossly, in sheep, the mucosa of the trachea and bronchi was
covered by a thin layer of exudate as early as 2 h after smoke
exposure. By 6 h after smoke exposure, pseudomembrane
covering the mucosa of the trachea and bronchi became
obvious, among which in one case the pseudomembrane was
detached and became a cast obstructing the main bronchi. By
24 h after smoke exposure, in all killed animals, there were
extensive tracheobronchial casts so that main bronchi and
lobar bronchi may be completely obstructed.
Microscopically, the lesions in dogs and sheep were
consistent. As early as 2 h after smoke exposure, the respira-
tory epithelial cells revealed varying degrees of necrosis, but
basal cells remained intact. The lamina propria and submu-
cosa showed hyperemia, edema, and neutrophil infi ltration.
By 6 h after smoke exposure, the lesions became gradually
aggravated and more frequent. By 24 h after injury, the
lesions were more marked. Necrosis of the tracheal wall may
deepen up to submucosa.
By scanning microscopy, in normal sheep, the cilia in cili-
ated epithelial cells were orientated in a given direction,
rather dense and blanket shaped; no goblet cells may be seen.
By 2 h after smoke exposure, the cilia in ciliated epithelial
cells showed swelling and are adhering into mass (Fig. 17.12 ).
By 6 h after injury, loss of cilia may be found, leaving a num-
ber of swollen, necrotic, denuded epithelial cells. By 24 h
after injury, bronchial mucosal epithelial cells were sloughed,
leaving an ulcerated surface covered with a number of neu-
trophils as well as red blood cells.
By transmission electron microscopy, in dogs, ultrastruc-
tural changes at various time intervals in the trachea and
bronchi were essentially similar, collectively described as
follows: Epithelial cells revealed diffuse or focal intracellular
edema. Ciliated epithelial cells showed mitochondrial swell-
ing and dilatation of cisternae of the endoplasmic reticulum,
the latter condition when marked appearing with cribriform
structure.
Ciliated epithelial cells exhibited dilatation of perinuclear
space and occasional bleb formation in plasma membrane.
Goblet cells showed dilatation of the endoplasmic reticulum
and Golgi complex, ultimately resulting in various sizes of
vesicles. Sometimes in goblet cells focal intracytoplasmic
degeneration containing myelin fi gure may be found. In
some area epithelial cells showed chromatin clumping and
high amplitude of mitochondrial swelling indicating cell
necrosis.
17.4.4.2 Intrapulmonary Bronchial Tree
Goblet cells in the bronchial mucosa revealed the following
pathological changes:
By 2 h after smoke exposure, goblet cells were increased
in number, characterized mainly by those goblet cells con-
taining PAS-positive mucous substance with AB/PAS stain.
By 6 h after injury, the increase of goblet cells was more
marked, characterized predominantly by those goblet cells
containing AB-positive mucous substance.
17.4.4.3 Peribronchial and Perivascular Lesions
By 2 h after smoke exposure, there were occasional peri-
bronchial and perivascular edema and hemorrhage. By 6 h
after injury, peribronchial and perivascular edematous cuff
and edematous hemorrhagic cuff may be seen. By 24 h after
injury, in various cuff-like lesions, hemorrhagic cuff and
infl ammatory cell infi ltrate predominated. In addition, there
were bronchitis and bronchiolitis in which the lumina were
plugged with mucopurulent exudate, sometimes with pseu-
domembrane formation.
17.4.4.4 Pathological Changes in the Lung
Parenchyma
Microscopically, pulmonary edema and bronchopneumonia
may be seen.
Ultrastructural changes in dogs and sheep after smoke
exposure may be summarized as follows:
By 2 h after smoke exposure, there was interstitial edema in
the thick portion of alveolar septa, manifested as loosening
of
interstitial
space
with
electron-lucent
matrix
(Fig. 17.13 ). Fibroblasts showed dilatation of perinuclear
space and cisternae of the endoplasmic reticulum. There
was accumulation of neutrophils and platelets within cap-
illary lumina. In sheep, capillary endothelial cells showed
increased pinocytotic vesicles and cellular swelling. In
endothelial cells, both lips of intercellular junction were
separated (Fig. 17.14 ). Type I alveolar epithelial cells
revealed mild cellular swelling with surface microvilli
Fig. 17.12 Cilia ( Ci ) of ciliated columnar epithelial cells in the bron-
chial mucosa showing disarray, adhesion with each other. Smoke inha-
lation injury in sheep, SEM ×1,500

17 Pathological Changes of Visceral Organs and Endocrine Glands After Burns

463
formation. Type II epithelial cells showed dilatation of
perinuclear space and cisternae of the endoplasmic reticu-
lum. In type II epithelial cells, emptying of lamellar bod-
ies was frequent, and surface microvilli were degenerated
and reduced in number.
By 6 h after injury, the above-mentioned alterations became
aggravated. In sheep, endothelial intercellular junctions
were completely separated, resulting in gaps (Fig. 17.15 ).
In type II epithelial cells, emptying of lamellar bodies was
more frequently encountered. Type I epithelial cells were
markedly swollen and vacuolated, sometimes disrupted.
Within alveolar space surfactant material was present in
the form of tubular myelin or myelin fi gure.
By 24 h after injury, interstitial neutrophil infi ltration was
frequent. Capillary endothelial cells were swollen with
surface microvilli formation, sometimes disrupted.
Separation of intercellular junction between endothelial
cells still may be found. Type I epithelial cells were swol-
len, vacuolated, or even necrotic. Type II epithelial cells
exhibited dilatation of the endoplasmic reticulum, vacuo-
lation, and emptying of lamellar bodies. In some areas
proliferation of type II epithelial cells may be seen which
began to repair or replace the damaged type I epithelial
cells.
By freezing itching replica electron microscopy, in sheep,
the main alterations in intercellular junction apparatus
between pulmonary capillary endothelial cells after smoke
exposure were as follows: disruption of strands, loss of gran-
ules, and destruction of the whole junction apparatus so as to
direct communication of both sides. In addition, there were
irregular strands and appearance of free ends. In intercellular
junction apparatus between alveolar epithelial cells, there
may be disruption of strands, irregular strands, and appear-
ance of free ends.
17.5
Pathological Changes
in the Gastrointestinal Tract
After Burns
17.5.1 General Pathological Changes
of Gastroduodenal Mucosal Lesions
Congestion, fi ne linear hemorrhages, and swelling of the
gastrointestinal mucosa are common and superfi cial erosions
are not infrequent. The superfi cial gastric and duodenal
Fig. 17.13 The thick portion of the alveolar septa showing interstitial
edema ( IE ). Smoke inhalation injury in dog, TEM ×15,000
Fig. 17.14 Pulmonary capillary endothelial cells ( End ) showing sepa-
ration of both lips of intercellular junction (→). Smoke inhalation injury
in sheep, TEM ×41,880
Fig. 17.15 Pulmonary capillary endothelial cells ( End ) showing sepa-
ration of intercellular junction (→), with gap formation. Smoke inhala-
tion injury in sheep, TEM ×44,690



17.5 Pathological Changes in the Gastrointestinal Tract After Burns

464
erosive lesions appear grossly as rounded or elongated
hemorrhagic foci of variable size. They are more commonly
seen in the gastric fundus or body than in the antrum. Deeper
mucosal lesions which extend to the muscularis mucosa are
termed ulcers. Microscopically, both the gastric and duode-
nal lesions are characterized by acute mucosal necrosis, usu-
ally with venular congestion and hemorrhage. Generally,
both the shallow erosive lesions and deeper ulcers of the
stomach and duodenum are free of signifi cant infl ammatory
infi ltrates. Most of the cases produce no symptoms, but
sometimes hemorrhage occurs. Numerous theories have
been advanced to explain the ulceration; these include the
secretion of histamine, gastric acidity, fat emboli, septic
emboli, infection, thrombosis, capillary stasis, dehydration,
hemoconcentration, shock, and nervous infl uences, but many
of these ideas are unsupported by facts and will be consid-
ered. Gastrointestinal hemorrhage and perforation are poten-
tially life-threatening complications in burn patients.
The mucous membrane of the intestine, particularly the
ileum, is commonly swollen and hyperemic. In some patients
there is also a diffuse submucosal and mucosal hemorrhage.
The lining of the bowel may have a dark red, chocolate-
colored, or blackish appearance.
17.5.2 Experimental Studies on Acute Gastric
Mucosal Lesions After Severe Burns
and the Signifi cance of Preventive
and Curative Effects of Early Enteral
Feeding
Acute gastric mucosal lesion, one of the most common vis-
ceral complications following severe thermal injury, is a
potential lethal threat against critically ill patients. Recent
studies have also demonstrated that early enteral feeding has
shown many benefi ts such as increasing gut blood fl ow,
decreasing the chance of gut-origin infection, reducing post-
burn hypermetabolism, and so on. They observe the dynamic
relationship between acute gastric mucosal lesions and
abdominal multivisceral ischemia and prophylactico-
therapeutic effects of early enteral feeding on postburn acute
gastric mucosal lesions and abdominal multivisceral
ischemia.
Severe burn could induce remarkable pathological and
pathophysiological changes in the gastric mucosa, which
mainly manifest as a compromise of barrier function, distur-
bance of energy metabolism, and degeneration and necrosis
of mucosal cells. Ischemia was the leading factor in the
pathogenesis of acute gastric mucosal lesions. Gastric
intramucosal pH could sensitively refl ect the abdominal mul-
tivisceral perfusion and their functional state after severe
thermal injury. Early enteral feeding is good not only at nota-
ble prophylactico-therapeutic effects on acute gastric
mucosal lesions but also in splanchnic resuscitation by
effectively increasing visceral blood fl ow, promoting recov-
ery of internal organ function.
17.5.3 Experimental Study on Pathological
Changes of the Intestinal Mucosa
in Burns
Two hundred two mice with 15 % TBSA third-degree burns
of the back were studied in order to determine the functional
and morphological changes of the intestinal mucosa after
burn injury. The animals were killed at various times from
the fi rst hour to 96th hour post burn, and specimens were
subjected to LM and EM examination, along with histo-
chemical tests. The fi ndings were as follows:
1. Severe circulatory disturbance of the intestinal wall.
Congestion of the venules and capillaries in all layers of
the intestinal wall, formation of microthrombi, dilatation
of lymphatic vessels, edema of the lamina propria, accu-
mulation of edema fl uid, and formation of subepithelial
gaps were observed.
2. Degeneration and necrosis of intestinal epithelial cells.
Epithelial absorptive cells showed cytoplasmic vesicle
formation, along with shrinkage of some nuclei. Both
mitochondria and endoplasmic reticulum were highly
swollen, and margination of chromatin and formation of
nuclear pseudoinclusion bodies were seen. There was
also a marked inhibition of epithelial alkaline phospha-
tase activity during the fi rst 72 h post burn.
3. Hyperactivity of secretory cells
Paneth’s cells and many mucous cells exhibited hyper-
secretory activity. At the 48th hour post burn, the number
of argentaffi n cells increased.
4. Normal synthesis of DNA in intestinal cells
No signifi cant changes were observed in postburn
mitotic activity. There was no shrinkage or shallowing of
crypts, and 3 H-TdR incorporation was only temporarily
affected.
In view of the similarity of the above-mentioned
pathological changes to those found in circulatory shock,
it is postulated that circulatory shock might be the pri-
mary cause of the observed changes in the intestinal
mucosa in burns.
17.5.4 Experimental Studies on a Study
of Early Intestinal Mucosal Injury
and Its Mechanism After Burn
Combined with Endotoxemia in Rats
Intestinal mucosal injury is one of the major initiating factors
that lead to multiple organ dysfunction syndrome (MODS)
17 Pathological Changes of Visceral Organs and Endocrine Glands After Burns

465
following serious burn injury, which has been confi rmed by
a lot of research works, but the characteristic of the early
intestinal mucosal injury and its mechanism after burn com-
bined with endotoxemia is obscure at present. In order to
study early intestinal mucosal injury and its mechanism after
burn combined with endotoxemia, an animal model in which
rats were subjected to 20 % TBSA III degree burn combined
with intraperitoneal injection of LPS (1 mg/kg B. M.) was
used for our department experiment. Simple burn, simple
endotoxin, and normal saline injection were used as control
groups, respectively. The histological and ultrastructural
changes of the intestine and phospholipase A 2 (PLA 2 ),
platelet- activating factor (PAF), xanthine oxidase (XO), per-
oxidase, malondialdehyde (MDA), tumor necrosis factor α
(TNFα), and interleukin-10 (IL-10) in the intestinal tissue
were investigated dynamically in 72 h after burn and/or
endotoxin injection. The main results were as follows:
1. Series of early morphological changes in the intestinal
mucosa were found after burn combined with endotox-
emia. These alterations were more evident and earlier and
persisted for a longer time than those of either simple
burn or simple endotoxin injection group. The main path-
ological changes are manifested as degeneration, necro-
sis, and denudation of intestinal epithelial cells and
epithelium at the top of intestinal villus, formation of sub-
mucosal space, exposure of the lamina propria, interstitial
edema, congestion, and infi ltration of neutrophil in the
lamina propria and submucosa. It was demonstrated that
burn combined with endotoxemia had a marked synergis-
tic effect on the early intestinal mucosal injury.
2. The mechanism of early intestinal mucosal injury after
burn combined with endotoxemia might be due to the
decrease of intestinal mucosal blood fl ow and release of
infl ammatory mediators, which induced activation of intes-
tinal epithelial cellular XO and intestinal macrophages,
production of free radicals, and increase of lipoperoxida-
tion. Then infi ltration of neutrophils synergistically pro-
moted the intestinal mucosal injury.
3. PAF is an early and major infl ammatory mediator that led
to intestinal mucosal injury, whose effect on the early
intestinal mucosal injury might be related to decrease of
intestinal mucosal blood fl ow, activation of XO and PLA 2 ,
chemotaxis, activation of neutrophils, and increase of
lipoperoxidation. Endotoxin induced production of TNFα
associated with PAF. It was demonstrated that the interac-
tion of PAF and TNF is an important factor which pro-
moted intestinal mucosal injury.
4. Epithelial cells and macrophages of the intestinal mucosa
are the major source of infl ammatory mediators, such as
PAF, TNF, free radicals, etc., which played a signifi cant
role in the local intestinal mucosal injury.
5. Translocation of enterogenous bacteria and endotoxin
promoted intestinal mucosal injury after burn combined
with endotoxemia, which formed vicious cycle and
caused death of animals. On the other hand, the transloca-
tion of moderate amount of bacteria and endotoxin might
decrease cellular function, resulting in induction of endo-
toxin tolerance in animals.
6. Interleukin-10 is an inhibitory cytokine, which might
play a certain role in intestinal mucosal repair after burn
and/or endotoxin injection.
17.6
Pathological Changes in the Liver
After Burns
The liver is unquestionably an extremely active organ in a
patient who suffers a serious burn. The pathologist and clini-
cian must be prepared to interpret and evaluate these multi-
ple adaptive, infl ammatory, and toxic hepatic changes that
may occur following thermal injury.
The most common pathological fi ndings were marked
sinusoid congestion and hepatic cell hyperplasia or regenera-
tion including the appearance of large nuclei, with prominent
nuclear membranes, large nucleoli, and binucleation of
hepatic cells. Hepatocellular fatty change was predominantly
centrilobular in distribution. This fi nding was a morphologi-
cal refl ection of metabolic dysfunction. Hepatic necrosis was
usually focal and nonspecifi c and most frequently seen in the
patients with sepsis and shock.
17.6.1 Histopathological and Ultrastructural
Changes in Hepatic Tissue from 59
Severely Burned Patients
During the past decades increasing attention has been paid to
the liver damage observed in burned patients who have not
been treated with tannic acid. Many reports have been con-
cerned with the morphological changes observed in the
hepatic tissue of burned animals. This study contains an
analysis of the changes in a large number of tissue samples
taken at autopsy from 59 severely burned patients with
particular reference to ultrastructural changes and the mono-
nuclear phagocyte system. The results using both light
microscopy and electron microscopy have been correlated
with various clinical data, and particular emphasis has been
laid on the relationship between the mononuclear phagocyte
system and the time of death and its cause.
In this study, 59 patients who died from burn injuries were
divided into two groups for study. The 44 cases of the fi rst
group had conventional autopsies performed, whereas the 15
cases of the second group had immediate autopsies per-
formed within 15 min of death. In addition, liver and spleen
specimens were taken from ten patients who died suddenly
of causes other than burns to serve as a control. Forty-nine of
17.6 Pathological Changes in the Liver After Burns

466
the burn cases have survived the shock phase. Liver function
tests had been performed in 19 cases, and no abnormalities
were found. LM and EM examination of specimens revealed
the following: patients who had died during the fi rst postburn
week showed the presence of Kupffer cells and necrotic cells
in hepatic sinusoids, whereas regeneration of hepatic cells
was seen in those who had died more than 10 days after
injury.
Histopathological studies were made on tissue samples
from the liver and spleen taken postmortem from 59 patients
with severe burns. Samples from eight patients were also
studied using the transmission electron microscope. The
main pathological fi ndings were as follows:
17.6.1.1 Hepatic Tissue Examined by Light
Microscopy
Most of the sections showed marked abnormalities, a normal
architecture of the hepatic lobules being a rare fi nding.
Abnormal fi ndings were not more common at the time of the
conventional autopsy than during immediate autopsy. The
most commonly observed abnormalities were fatty deposits
within hepatic cells and proliferation of Kupffer cells.
Necrosis of hepatic cells and the presence of necrotic cells
within hepatic sinusoids were more common in hepatic tis-
sue from patients who died within 10 days post burn, whereas
regeneration of hepatic cells became more prominent after
10 days post burn.
Degeneration and Necrosis of Hepatic Cells
Cloudy swelling and loose cytoplasm were observed in
hepatic cells taken from 35 patients. Varying amounts of fat
were present in hepatic cells taken from 54 of the 59 patients;
in two patients the fat content was very high, conforming to
the classical fatty liver. Most of the fatty changes were cen-
trilobular or perilobular and were scattered or diffuse in dis-
tribution. There was no obvious difference between the
degree of fatty degeneration in or surrounding necrotic or
nonnecrotic areas of tissue and in tissue from patients who
died early or late after burn injury.
The nuclei of hepatic cells were enlarged and many were
empty except for large nucleoli. Such fi ndings were common
in tissue taken from the 12 patients with burns covering over
80 % of the body surface area. It was most striking in the
patient with virtually 100 % burns.
Hepatic necrosis was moderate in 11 patients and more
severe in 3, the lesions being focal or massive (Fig. 17.16 )
and mostly situated in the central area or middle zone. In the
necrotic foci the nuclei of the hepatic cells had almost disap-
peared or showed pyknosis, karyorrhexis, and/or karyolysis.
The cytoplasm of the hepatic cells had become homogeneous
and was deeply pink stained. In some tissue samples the
cytoplasm contained small round vacuoles or pigmented
granules, and the reticular fi bers showed some evidence of
collapse. Proliferation of Kupffer cells was obvious in or
around some necrotic foci.
Bile Pigmentation of Hepatic Cells
This was observed in tissue samples from 50 patients and
consisted of granules or masses in small or large quantities.
Sometimes the cytoplasm of hepatic cells was so heavily pig-
mented that the nuclei were diffi cult to discern. Bile-stained
thrombi were seen in the small bile ducts of three patients
and in the bile canaliculi in fi ve patients.
Regeneration of Hepatic Cells and Proliferation
and Swelling of Kupffer Cells
In 20 patients there was evidence of regeneration of hepatic
cells. These new cells were either scattered or in clusters and
were recognized by hyperchromatic nuclei with large round
nucleoli or bi- or multinucleated cells. Mitotic fi gures were
only seen in three patients.
Proliferation of Kupffer cells (Fig. 17.17 ), which
appeared larger than their prototypes and are irregular in
outline and protruding into hepatic sinusoids, was seen in 42
patients. The nuclei within the Kupffer cells were oval or
spindle shaped and appeared hyperchromatic or vesicular.
Mitotic fi gures were seen in some of them. The volume of
cytoplasm was increased and acidophilic. Varying degrees
of phagocytosis were seen in the proliferating Kupffer cells
which contained mainly of pigment granules and erythro-
cytes and lesser amounts of nuclear debris and some lym-
phocytes (Fig. 17.18 ). In some patients the Kupffer cells
were very swollen with the cytoplasm full of pigment gran-
ules or up to eight erythrocytes; the nuclei were then diffi -
cult to observe.
Fig. 17.16 Centrilobular focal necrosis of hepatic cells (HE × low-
power magnifi cation)

17 Pathological Changes of Visceral Organs and Endocrine Glands After Burns

467
Necrotic Cells in the Hepatic Sinusoids
Varying numbers of necrotic cells were present in the hepatic
sinusoids in 30 patients. Normal cellular morphology could
hardly be recognized, since there was pyknosis or karyor-
rhexis of the nuclei and most cells showed a positive reaction
with the peroxidase stain. These necrotic cells may have
been neutrophilic granulocytes or monocytes.
Other Changes in Hepatic Tissue
Varying degrees of congestion were observed in 35 patients
and focal hemorrhages in 4. The Disse space showed varying
degrees of dilatation and contained edema fl uid in more than
half of the patients. In almost all patients most of the intrahe-
patic blood vessels including the central veins showed
degenerative changes with swollen endothelia and edema-
tous changes in the vessel walls. There was infi ltration of
lymphocytes, monocytes, neutrophilic granulocytes, or
eosinophils in the portal areas in 15 patients.
17.6.1.2 Hepatic Tissue Examined by Electron
Microscopy
In all eight patients electron microscopy of the tissue sam-
ples showed the same basic changes in the ultrastructural
morphology of the cells and interstitial components.
Hepatic Cells
Nucleolar condensation was apparent in a small number of
hepatic cells. Heterochromatins were observed as fl akes
along the inner surface of the nuclear membrane (chromatin
margination), and the normal amount of euchromatin was
much reduced. Most of the nuclear membranes appeared to
be intact, although there were some indentations giving rise
to pseudoinclusions in the nuclei in some cases. The perinu-
clear cisternae showed no evidence of dilatation.
Compared with the limited nuclear changes, the cyto-
plasm showed more marked changes with substantial num-
bers of lipid droplets and glycogen particles. Many
mitochondria had become swollen or vacuolated and their
cristae were reduced in number or had completely disap-
peared. The electron density of the mitochondrial matrices
was usually reduced even when there was vacuole formation.
Only in a small number of tissue samples was the density of
the mitochondrial matrix increased.
Some of the rough-surfaced endoplasmic reticulum
showed proliferation or dilatation, which appeared as fl at-
tened sacs or vesicles. These often aggregated to form clus-
ters showing a fi ngerprint pattern (Fig. 17.19 ) or surrounding
the decaying mitochondria. These decaying mitochondria
Fig. 17.17 Proliferation and swelling of hepatic Kupffer cells
(HE × low-power magnifi cation)
Fig. 17.18 Hepatic Kupffer cells containing lymphocytes and erythro-
cytes (HE × high-power magnifi cation)
Fig. 17.19 Proliferating rough-surfaced endoplasmic reticula ( RER )
aggregated to form fi ngerprint-like structures. N denotes nucleus
(TEM ×6,270)



17.6 Pathological Changes in the Liver After Burns

468
also showed a reduced number of organelles, swelling and
vacuole formation of the mitochondria and the endoplasmic
reticulum, and the formation of myelin-like fi gures. These
changes were most marked in the most severe burns where
there were additional alterations which have been termed
membrane-bound
focal
intracytoplasmic
degeneration
(FCD). This appeared as a network usually in the vicinity of
the hepatic cell nucleus (Fig. 17.20 ) and contained electron-
dense granular debris consisting of decaying mitochondria
and myelin-like fi gures.
Kupffer Cells and Disse Spaces
There were an increased number of Kupffer cells, the swol-
len state of which appeared irregular in outline and with
cellular processes protruding into the sinusoidal spaces.
The nuclei of the Kupffer cells were larger than normal
with an oval or spherical shape, a thickened nuclear mem-
brane, and chromatin margination. The cytoplasm con-
tained many normal organelles or decaying rough
endoplasmic reticula, mitochondria, and phagocytosed
erythrocytes (Fig. 17.21 ). The Disse spaces were enlarged
with swelling and detachment of the microvilli and con-
tained moderately electron- dense fl occulent substances and
a few Ito cells (fat-storing cells). Some collagen fi ber bun-
dles were beside the Ito cells.
17.6.1.3 Histopathological Changes
in the Spleen Tissue
As mentioned above, the Kupffer cells of the liver showed
proliferation and active phagocytosis. However, the spleen
specimens had fewer monocytes and reduced phagocytic
activity. It is postulated that the proliferation of Kupffer cells
with active phagocytosis might be a compensatory reaction
of the liver to the severe injury of the spleen. In the early
postburn stages, especially in those patients who died within
1–2 days of injury, the frequent occurrence of necrotic cells
in hepatic sinusoids might be due to the effects of burn tox-
ins. In the cases that died later on, this phenomenon was
rarely seen because the necrotic cells had been removed by
the phagocytes.
The most marked change in the spleen tissue from the
burned patients was considerable congestion. Cellular infi l-
tration was less marked than found in the tissue from septic
non-burned patients. Monocytes and evidence of their
phagocytic abilities were rarely seen.
Histopathological Changes in Hepatic and Spleen Tissue
Taken from Non-Burned Patients
None of the abovementioned pathological changes
observed by light or electron microscopy in the tissue from
burned patients were found in hepatic and spleen tissue from
the control non-burned patients who died from coronary
heart disease or primary cardiomyopathy.
Our study suggests:
1. Hepatic necrosis develops in the most severely burned
and that it may be the result of hepatic anoxia, so that
strenuous attempts to maintain hepatic blood fl ow by
appropriate and adequate fl uid therapy should be made as
soon as possible after extensive burn injury.
2. There is considerable regeneration of hepatic tissue from
the end of the fi rst week after post burn provided that the
patient survives long. Kupffer cells constitute much of the
new tissue and they may carry out some of the functions
normally associated with the spleen, i.e., removal of
necrotic tissue cells.
Fig. 17.20 Two foci of focal intracytoplasmic degeneration ( FCD ) of
hepatic cells containing electron-dense granular materials, degenerat-
ing mitochondria and myelin-like fi gures. Note major lipid droplets ( L )
in the cytoplasm of the hepatic cell. N denotes nucleus (TEM ×7,260)
Fig. 17.21 Proliferation of hepatic Kupffer cell ( KPC ) with swelling
and compression of the hepatic sinusoid. The Disse space ( DS ) is
enlarged with detachment of the microvilli (TEM ×1,980)


17 Pathological Changes of Visceral Organs and Endocrine Glands After Burns

469
17.6.2 Pathological Changes of the Liver
in Rats with Phosphorus Burns
In this experimental study, 168 healthy male rats were
randomly divided into three groups: a phosphorous burn
group, a napalm burn control group, and an uninjured control
group. Using the appropriate agents, the rats of the fi rst two
groups were infl icted with 30 % TBSA full-thickness burns.
Blood and hepatic tissue specimens were taken at 2, 8, 24,
48, 72, 120, and 160 h after injury for quantitative analysis of
serum enzymes and histopathological liver examination.
The overall course of change observed in the liver speci-
mens was divided into three phases: the proliferation phase,
the degeneration and necrosis phase, and the regeneration
and repair phase. The proliferation phase was fi rst observed
at the second post-phosphorous burn hour and persisted
until 8 h.
The degeneration and necrosis phase was most devious
from 24 to 72 h after injury. The regeneration and repair
phase commenced at about the 120th hour and was promi-
nent until the 168th post-phosphorous burn hour. Liver
changes seen in the napalm burn group were the same as
those of the phosphorous burn group, indicating that these
three phases and their relative durations are common to both
sorts of burn injury. Not surprisingly, rats of the phosphorous
burn group showed elevated serum and liver phosphorous
levels.
Elevation of both SOCT (serum ornithine carbamoyl-
transferase) and SGPT was seen in varying degrees and was
found to be parallel with the degree of liver parenchymal
damage. Since SOCT is found predominately in the mito-
chondrial fraction of hepatic cells, the author suggests that
determination of its activity is of greater importance than
that of other serum enzymes.
17.6.3 Liver Mitochondrial Dysfunction in Rats
with Radiation Burn and Combined
Injuries
Experimental rats were injured and divided into three groups
on the basis of the type of injury given: Co gamma irradiated
group (IG), 5 KW bromine-tungsten burn group (BG), and
combined injury group (CIG).
State 3 and state 4 respiration rates (RR) and respiratory
control rates (RCR) of the liver mitochondria were deter-
mined in the control group (CG), sham-injury group (SIG),
and the three injury groups at various times. Likewise, liver
specimens were taken for ultrastructural study.
Liver mitochondrial RCR decreased after injury, becom-
ing more evident 5–9 days later. The amplitude of RCR
decrease was most noticeable in BG and CIG, amounting to
65–75 % of the control values. The difference between BG
and CIG was not signifi cant, but that between either of them
and IG was. This suggested that the burn injury was respon-
sible for the changes seen in CIG.
State 3 RR decreased somewhat after injury, while that of
state 4 tended to increase. However, there was no signifi cant
difference among the three injury groups. When state 4 to
state 3 RR ratios were compared, it was obvious that the
postinjury values were elevated. There was a defi nite differ-
ence between IG and BG or CIG, implying that the drop of
RCR was the result of both the lowering of state 3 and eleva-
tion of state 4 RRs.
Pathological changes in the liver mitochondria were
found in all groups. Supporting the polarographical evidence
of mitochondrial dysfunction, it was also found that the
ultrastructural damage was most severe in CIG, suggesting a
mutual additional effect of the two types of single injury.
17.6.4 An Experimental Study on Pathological
Changes of the Liver in Dogs
with Smoke Inhalation Injury
Light and electron microscopic fi ndings of the liver of dogs
after smoke inhalation injury are described in detail to dem-
onstrate the effects of smoke inhalation on the liver. The tem-
perature of the inhaled smoke is about 36–37 °C. The results
of this study are the same as the steam inhalation injury. The
main pathological fi ndings are degeneration and necrosis of
hepatic cells and proliferation of Kupffer cells showing
active phagocytosis. These lesions appear on the 2nd day and
progressively exaggerate on the 6th day after smoke inhala-
tion injury and then reduce gradually. These dynamic
changes are parallel to that of COHb. Thus, the authors con-
sider that the anoxia due to carbon monoxide poisoning may
be the main cause of the hepatic lesions.
17.6.5 Histopathological, Histochemical,
and Ultrastructural Changes
of the Liver in Dogs with Steam
Inhalation Burns
Twenty-fi ve dogs were divided into groups for study. The 15
dogs of the simple respiratory burn group (RBG) and burn
group (CBG) were killed and examined at various times dur-
ing the fi rst 2 weeks post injury. LM and EM examinations
along with histochemical tests were performed for this study.
The results were as follows:
Hepatic cell degeneration of various types was observed.
There was lytic necrosis and proliferation of some Kupffer
cells along with active phagocytosis followed by degeneration.
17.6 Pathological Changes in the Liver After Burns

470
Also seen were a decrease in alkaline phosphatase activity
and the presence of perivasculitis in the portal area.
Although similar, the perivasculitis in the portal area and
in the hepatic cells of the two groups was both more intense
and widespread in the CBG. In both groups, the changes
became more pronounced with the passage of time.
EM examination revealed that the disintegration of many
cytoplasmic apparatuses was responsible for the lytic necro-
sis of hepatic cells. The observed focal intracytoplasmic
degeneration was one of the apparatuses, which was respon-
sible for lytic necrosis of hepatic cells. The observed focal
intracytoplasmic degeneration was probably the initial pro-
cess of ensuing hepatic necrosis.
Some of the causes of hepatic cell necrosis were closely
related to the degeneration and diminished phagocytic activ-
ity of Kupffer cells, which could result in inadequate detoxi-
fi cation of wound infection-related substances. In light of the
liver’s vital detoxifi cation role, it is recommended that
appropriate attention should be paid to the liver’s state in the
management of burn patients.
17.7
Pathological Changes in the Kidneys
After Burns
After severe burn, stress reaction and shock may lead to renal
ischemia and intrarenal blood redistribution, resulting in
ischemic injury. Activation of infl ammatory cells, especially
neutrophils and macrophages, may release various infl am-
matory mediators and cytokines which affect the kidneys
and make injurious effects. In addition, fl uid imbalance is
also a factor affecting the renal function. Therefore, renal
dysfunction and morphological changes are rather common
and among the main causes of death in severely burned
patients. Pathological changes in the kidneys consist of (a)
glomerular lesions, such as endothelial hypertrophy and
hyperplasia, mesangial hyperplasia and hypertrophy, degen-
erative changes in podocytes, etc., and (b) tubular degenera-
tion and necrosis involving the proximal and distal tubules
with cast formation. According to author’s own work, the
materials for pathomorphological studies may be divided
into two parts: (a) autopsy materials from fatally burned
patients and (b) experimental studies of napalm burn as well
as phosphorus burn.
In the sixth decade of the twentieth century, Dr. Yan of
our department, via a pathological study on the kidneys from
24 fatally burned patients, found that in most cases the renal
glomeruli exhibited consistent morphological changes, char-
acterized by widening of the intercapillary space (mesangial
area) of tufts due to accumulation of eosinophilic material
and monocytic infi ltration resulting in glomerular ischemia.
He postulated that glomerular abnormalities might be the
main cause of renal dysfunction in severe burn patients.
Thereafter, by using light microscopy and electron
microscopy, we have employed an investigation on the kid-
neys from immediate autopsy of 17 fatally burned patients.
The purpose of this study is to investigate both histological
and ultrastructural features in the kidney, especially the
glomeruli, and explore the correlation between the morpho-
logical changes and functional derangement in severe burn
patients. The results were as follows [ 3 , 4 ]:
17.7.1 Histological Findings
Glomerular endothelial cells of glomerular capillary loops
appeared swollen, and capillary lumina were frequently
occupied by polymorphonuclear neutrophils and/or mono-
cytes. Mesangial areas became widened and usually fi lled
with increased PAS-positive eosinophilic materials. In some
cases glomerular cells increased in number so that the glom-
eruli became enlarged with narrowing of the capsular spaces.
The above changes led to the glomerular capillary loops
becoming ischemic in various degrees. The glomerular cap-
sular spaces as a rule contained many coarse or fi ne eosino-
philic granules. The parietal epithelial cells of Bowman’s
capsule became swollen and cuboidal, and occasionally they
appeared columnar, simulating epithelial cells of the proxi-
mal convoluted tubule. Glomerular capillary hyaline thrombi
were found only in one case.
In this context, swelling and/or hyperplasia of glomerular
cells (including capillary endothelial cells, mesangial cells,
and visceral epithelial cells of Bowman’s capsule) and wid-
ening of mesangial area as well as glomerular ischemia are
referred to as “acute glomerulopathy.”
Renal tubules: Cloudy swelling of the proximal convo-
luted tubules and dilatation of tubular lumen, especially the
distal tubules, were rather common. Hydropic change was
encountered in about half of the cases. Casts in the distal
convoluted tubules, Henle’s loops, and collecting tubules
were outstanding and often distended and/or blocked the
tubules. There were two types of casts: (a) pigmented cast,
brownish in color, coarsely or fi nely granular, and hemoglo-
bin stain positive, and (b) hyaline casts. Tubular necroses
occurring in both proximal and distal convoluted tubules
were mild in degree and focal in distribution in most cases,
but in a few cases they were rather severe and widespread.
Interstitium: Focal infi ltration with lymphocytes, plasma
cells, and mononuclear cells was found in about half of the
cases.
17.7.2 Ultrastructural Findings
Glomeruli: The glomerular fi ndings demonstrated by light
microscopy were confi rmed by electron microscopy.
17 Pathological Changes of Visceral Organs and Endocrine Glands After Burns

471
Enlarged capillary endothelial cells with increased amount
of cytoplasm were frequently found. The number of organ-
elles, especially the rough endoplasmic reticulum (RER),
was increased in the enlarged endothelial cells. RER was
arranged in whorled or fi ngerprint fashion around the
nucleus. In some cases free polyribosomes were increased.
Sometimes microvilli formed from plasma membrane of
endothelial cells were protruding into the capillary lumina
which were usually already occupied by neutrophils or
monocytes and thus made the capillary lumina narrowed or
obliterated. In some cases, endothelial cells revealed mito-
chondrial swelling and dilatation of RER (Fig. 17.22 ).
Occasionally, they became highly swollen with formation of
numerous vacuoles due to intracellular edema.
Mesangial areas were widened and associated with
increased number of mesangial cells (Fig. 17.23 ), which also
revealed hypertrophy with increased amount of cytoplasm
and well-developed RER. However, in some cases degenera-
tive changes in mesangial cells such as mitochondrial swell-
ing and dilatation of RER also occurred.
With the exception of two cases, the podocytes were
essentially normal in this group of patients. In one case they
showed high amplitude of swelling, manifesting mitochon-
drial swelling, dilatation of the endoplasmic reticulum, and
formation of numerous vacuoles. In another case they were
packed with numerous laminated membranous structures,
i.e., myelin fi gures.
The parietal epithelial cells of Bowman’s capsule revealed
mitochondrial swelling, vacuole formation, and distortion of
nuclei due to compression of vacuoles.
Renal tubules: The epithelial cells of the proximal convo-
luted tubules showed mitochondrial swelling and vacuola-
tion. In most cases, there were marked increases in lysosomes
located just beneath the microvilli. In some cases hypertro-
phy of RER was demonstrated in the proximal tubules. The
epithelial cells of the distal tubules also showed vacuolar
degeneration and in some cases revealed hypertrophy
of RER.
In order to explore the relationship between the patho-
morphological changes and renal dysfunction and the actual
role of acute glomerulopathy in the development of azote-
mia (manifesting as rise in the levels of blood urea nitrogen
and plasma creatinine), we have correlated acute glomeru-
lopathy and tubular necrosis with the occurrence of
azotemia.
There were ten cases presenting acute glomerulopathy
and tubular necrosis of various degrees simultaneously, and
all of them developed azotemia. There were four cases with
acute glomerulopathy of mild to moderate degree without
tubular necrosis, and three of them developed azotemia.
There were two cases with moderate tubular but mild glo-
merular lesions and one case with mild acute glomerulopa-
thy only, and none of them had azotemia. It seems probable
that acute glomerulopathy plays a more important role than
tubular necrosis in the development of azotemia or renal
insuffi ciency.
With the aid of rank correlation method, it was found that
a positive correlation exists between glomerulopathy and
blood urea or plasma creatinine level, that is to say, increase
in either blood urea or plasma creatinine level is parallel to
the degree of acute glomerulopathy. It was further clarifi ed
that the occurrence of azotemia is mainly caused by glo-
merulopathy resulting in a fall in the glomerular fi ltration
rate.
Fig. 17.22 Glomerular capillary endothelial cell ( End ) showing swell-
ing with vacuole ( V ) formation in the cytoplasm. Immediate autopsy
case from a fatally burned patient, TEM ×8,000
Fig. 17.23 Glomerular mesangial cells ( MESs ) showing proliferation.
Four mesangial cells in this picture may be seen. Immediate autopsy
case from a fatally burned patient, TEM ×5,000


17.7 Pathological Changes in the Kidneys After Burns

472
17.7.3 Pathological Changes in the Kidneys
in Experimental Body Surface Burn
Caused by Napalm
Within 30 days after napalm burn, experimental animals
(rabbits) appeared with obvious pathomorphological changes
and renal dysfunction, manifesting as glomerular capillary
loops initially hyperemic, followed by ischemia, glomerular
cells becoming hypertrophic and/or hyperplasic. The renal
tubules showed vacuolar degeneration and necrosis with cast
formation. Plasma urea and creatinine and serum potassium
rose markedly and gradually declined to normal level.
Glomerular lesions presented a dynamic process and may
be divided into three stages:
1. Early stage (2–24 h post burn)
Glomerular capillary tufts revealed hyperemia pre-
dominantly, and glomerular cells began to exhibit
swelling and hypertrophy.
2. Mid-stage (2–7 days post burn)
Glomerular capillary tufts were characterized by isch-
emia with widening of mesangial areas. Hypertrophy of
glomerular cells became more obvious, such as coarse
cytoplasmic process in endothelial cells (Fig. 17.24 ) and
abundant cytoplasm in mesangial cells with a large
amount of RER and free polyribosomes (Fig. 17.25 ). In
the meantime hyperplasia of endothelial and mesangial
cells may be found.
3. Later stage (14–30 days post burn)
The ultrastructural changes became gradually allevi-
ated and restored.
As to tubular necrosis, scattered single cell necrosis could
be found in the distal convoluted tubules, but no necrosis
may be seen in the proximal convoluted tubules [ 5 ].
17.7.4 Pathological Changes in the Kidneys
in Experimental Severe Steam
Respiratory Burn
Within 14 days after severe steam respiratory burn,
experimental animals (dogs) appeared with various patho-
logical changes in renal tissues. Histologically, widening of
the mesangial areas in some glomeruli and segmental isch-
emia in glomerular capillary tufts may be seen.
Ultrastructurally, glomerular cells exhibited hypertrophy,
hyperplasia, and swelling. Within capillary lumina neutro-
phils and/or monocytes may be seen. Mesangial cells showed
hyperplasia, accompanied by hypertrophy. Podocytes also
revealed hyperplasia and hypertrophy. These alterations
began to appear 3 days post burn and became more obvious
7 days post burn. However, podocytes may also appear with
degenerative changes, such as fusion of foot processes and
vacuolar changes of cell body. Parietal epithelial cells of
Bowman’s capsule showed mitochondrial swelling, dilata-
tion of perinuclear space, chromatin clumping, etc. The renal
tubules revealed vacuolar change and necrosis with cast for-
mation. Vacuolar degeneration and necrosis mainly affected
the proximal convoluted tubules, while cast formation more
frequently involved the distal tubules as well as the collect-
ing tubules [ 6 ].
17.7.5 Pathological Changes in the Kidneys
in Experimental Phosphorus Burn
17.7.5.1 Light Microscopic Findings
By 2 and 10 h after phosphorus burn, in experimental ani-
mals (rats) glomerular capillary tufts showed dilatation and
Fig. 17.24 Glomerular capillary endothelial cell ( End ) showing hyper-
trophy with irregular-shaped nucleus and course cytoplasmic process
(→) across the lumen. Napalm burn in rabbit, TEM ×10,000
Fig. 17.25 Glomerular mesangial cell ( MES ) showing hypertrophy
with abundant rough endoplasmic reticulum ( RER ) and ribosomes (→)
in the cytoplasm. Napalm burn in rabbit, TEM ×20,000


17 Pathological Changes of Visceral Organs and Endocrine Glands After Burns

473
hyperemia. By 24 h post burn, glomeruli appeared lobulated,
and capillary tufts collapsed. By 48 h post burn, glomerular
capillary tufts reopen containing red blood cells. By 72 h
post burn, glomerular capillary tufts became shrunken with
narrowing of lumina. By 168 h post burn, there were local
thickening of basement membrane and increased PAS-
positive material in the mesangial areas. Renal tubular epi-
thelial cells showed swelling and vacuolar change in the
early stage; by 48 h post burn the cytoplasm of epithelial
cells was detached into the lumina.
17.7.5.2 Electron Microscopic Findings
Within 48 h after phosphorus burn, glomerular capillary
endothelial cells and podocytes revealed marked hyperplasia
and hypertrophy. Endothelial cells exhibited increased cyto-
plasm containing abundant free polyribosomes and bi-nuclei.
Enlarged endothelial cells may occlude the capillary lumina.
Podocytes showed prominent nucleoli and well-developed
Golgi complex and dilatation of RER. By 72 h post burn,
glomerular endothelial cells may have coarse cytoplasmic
process formation, which may be adherent or fused with
opposite endothelial cell cytoplasm across the capillary
lumen. Sometimes endothelial cell body detached from
mesangial area may be found, hanging in the capillary lumen,
indicating that there was a lowering of adhesive capacity
between endothelial cell and its underlying mesangial tissue.
Mesangial cells showed marked hyperplasia and their cyto-
plasmic processes may extend beneath the endothelium or
protrude into the capillary lumen.
Stereological analysis indicated that along with volume
density of endothelial cells and mesangial areas increasing,
the volume density of capillary lumina appeared progres-
sively decreased. If the Chinese ink and gelatin were given
into rat’s artery, Chinese ink may be seen occluding the glo-
merular hila or only found at the periphery of capillary tufts.
Thus, narrowing or occlusion in glomerular capillary tufts
could be confi rmed. By 168 h post burn, there appeared deep
invaginations containing numerous vesicles in the nucleus of
endothelial cells, and there was increased basement
membrane- like material in the mesangial areas. Renal tubu-
lar epithelial cells revealed microvilli clumping, detachment,
and mitochondrial swelling. Within tubular lumina a large
amount of cellular debris may be frequently found [ 7 , 8 ].
17.7.6 Pathological Changes in Renal Tissues
in Experimental Multiple Organ
Dysfunction Syndrome After
Severe Burn
To explore the effects of resuscitation on pathological
changes of multiple organ dysfunction syndrome after severe
burn, experimental animals (dogs) were divided into three
groups: delayed transfusion group, non-transfusion group,
and immediate transfusion group.
17.7.6.1 Light Microscopic Findings
In delayed transfusion group, dog’s glomerular capillary
tufts appeared hyperemic and there were neutrophils within
the lumina. Mesangial cells showed mild to moderate hyper-
plasia with widening of mesangial areas. Renal tubular epi-
thelial cells revealed widespread and marked swelling and
vacuolar degeneration. Tubular necrosis was frequently
encountered.
In non-transfusion group, dog’s glomerular capillary tufts
were mostly collapsed, and tufts appeared lobulated.
Mesangial cells showed mild hyperplasia. Renal tubular epi-
thelial cells revealed luminal protein casts and cellular casts
could be found. There were vascular dilatation and conges-
tion in the interstitium with focal hemorrhage.
In immediate transfusion group, dog’s glomeruli had no
obvious changes except for mild mesangial hyperplasia.
However, the renal tubule still showed a certain degree of
degeneration and necrosis. There were congestion and mild
edema in the interstitium.
17.7.6.2 Electron Microscopic Findings
In delayed transfusion group, dog’s glomerular capillary
endothelial cells revealed hypertrophy with a large amount
of polyribosomes in the cytoplasm and their cell body may
protrude into or occlude capillary lumina. The nuclei of
endothelial cells were enlarged with irregular shape, some-
times appearing as bi-lobulated nuclei. Mesangial cells were
increased in number with abundant organelles and their cyto-
plasmic processes may interpose beneath the endothelium.
Podocytes exhibited mitochondrial swelling and dilatation of
the endoplasmic reticulum. There was sequestration of neu-
trophils within capillary lumina. Renal tubular epithelial
cells showed swelling of microvilli, increased lysosomes,
and occasional bleb formation. In tubular epithelial cells,
there was deposition of a large amount of calcium saltlike
dense granules within mitochondria. Epithelial cells were
frequently necrotic and detached with denudation of the
basement membrane. In the interstitium capillary endothelial
cells showed swelling with retention of neutrophils in the
lumina.
In non-transfusion group, dog’s glomerular capillary
endothelial cells showed degenerative changes with chroma-
tin margination and pyknosis. Within capillary lumina, neu-
trophils and platelets were frequently found. Podocytes
showed local fusion of their foot processes. The lesions in
tubular epithelial cells were essentially similar to those found
in delayed transfusion group, but there appeared a large
amount of myelin fi gures.
In immediate transfusion group, dog’s glomerular capil-
lary endothelial cells were rich in RER and Golgi complex
17.7 Pathological Changes in the Kidneys After Burns

474
was easily seen. There was sequestration of neutrophils
within capillary lumina. Tubular epithelial changes were
similar to those found in delayed transfusion group [ 9 ].
17.8
Pathological Changes
in the Endocrine Glands After Burns
After severe burn, the human body would be immediately
subjected to a stress state, leading to a series of neuroendo-
crine reactions as well as metabolic reaction. Neuroendocrine
reactions include: sympathetic adrenal medullary reaction,
adrenocortical hyperfunction, and functional alterations of
the adenohypophysis. Functional alterations are frequently
accompanied by morphological changes. So endocrine
glands may reveal various kinds of pathomorphological
changes in severely burned subjects as well as experimental
animals. This section will describe and discuss the morpho-
logical changes and their functional signifi cances in the ade-
nohypophysis, thyroid gland, adrenal gland, and pancreatic
islet beta cells after severe burn.
17.8.1 The Hypophysis (Pituitary Gland)
Among 61 necropsy cases from fatally burned patients, the
pathomorphological changes of the adenohypophysis (ante-
rior pituitary) in 12 cases have been thoroughly observed. In
all of the 12 cases, the adenohypophysis exhibited marked
vascular dilatation and congestion. In 10 of 12 cases, relative
number of three types of adenohypophyseal cells, i.e., acido-
phils, basophils, and chromophobes, were calculated. There
was a slight increase in value of eosinophils in nine cases.
The value of basophils was increased in three cases, while
the remaining seven cases being reduced. As to the value of
chromophobes, there was a reduction in all cases examined.
In addition, there was an anemic infarct of the anterior
pituitary in one case. Grossly, the infarct appeared yellowish
in color, surrounded by a gray-red zone. Microscopically, the
infarct area appeared with complete necrosis of tissues with-
out hemorrhage. The present case clinically was associated
with cerebellar contusion; the cause of pituitary infarct may
be probably due to disturbance of blood circulation in the
anterior pituitary.
An experimental study of ultrastructural changes of
growth hormone (GH)-producing cells in the adenohypoph-
ysis was carried out on severely burned rabbits within 1 week
by using electron microscopy [ 10 ]. The main pathological
alterations consisted of (a) hyperfunctional GH cells and (b)
an evidence of injury. Data from submicroscopic stereologi-
cal analysis demonstrated that ultrastructural changes in GH
cells post burn were manifested as a dynamic process and
might be divided into three phases:
1. Stress phase (3–12 h post burn)
In animals killed 3 h post burn, the GH cells exhibited
the following changes: nucleolar margination and slight
dilatation of perinuclear space with well-developed Golgi
complex and rough endoplasmic reticulum.
In animals killed 3 and 12 h post burn, besides the
above-mentioned alterations, there were increased nuclear
invaginations, the outer membrane of nuclear envelope
becoming thickened and undulating, and occasional intra-
nuclear pseudoinclusions. The Golgi complex may be
doubled or even tripled (Fig. 17.26 ). Occasionally, focal
vacuolation in the mitochondria may be found. These
ultrastructural changes indicate that GH cells post burn
have a hyperfunction on the one hand and a slight cellular
damage on the other hand.
2. Adjusting phase (24–72 h post burn)
In this phase, GH cells showed most marked dilatation
of perinuclear space, more nuclear membrane infolding,
well-developed Golgi complex with dilatation of its sac-
cules, more marked mitochondrial vacuolation, and sec-
ondary lysosomes containing degenerative mitochondria.
In animals killed 24 and 48 h post burn, multivesicular
bodies may be obviously increased in number in GH
cells.
3. Function-restoring phase (96–168 h post burn)
In this phase, GH cells appeared functionally active
and manifested morphologically as mitochondrial hyper-
plasia and have well-developed Golgi complex, usually
tripled, even quadrupled. Comparing with previous phase,
degeneration of organelles became less marked.
In various phases post burn, the alterations of secre-
tory granules in GH cells appeared essentially consistent.
Secretory granules were manifested as reduction in num-
ber, margination of secretory granules, and markedly
Fig. 17.26 Growth hormone-producing cell of the adenohypophysis
showing well-developed Golgi complex ( Go ). Napalm burn in rabbit,
TEM ×15,000

17 Pathological Changes of Visceral Organs and Endocrine Glands After Burns

475
increased
exocytosis.
Either
normal
exocytosis
(exocytosis adjacent to the sinusoids) or misplaced exo-
cytosis was frequently encountered. There were intact
granules within the sinusoids. These alterations may be
considered as the secretory activity strengthened and
became more rapid [ 10 ].
17.8.2 The Thyroid Gland
17.8.2.1 General Consideration
The extreme stress, fl uid imbalance, changes in metabolism,
and hormonal fl uctuations that occur in burn patients have
led us observers to scrutinize the thyroid for morphological
evidence of degenerative or hyperplastic changes.
Evidence of hypermetabolism state in thermally injured
patients naturally focuses on the thyroid gland. One such
case of burn patients with staphylococcal abscesses involv-
ing the thyroid had recurrent staphylococcal septicemia.
Perivascular and intravascular cocci within the thyroid repre-
sented the most likely source for septicemia in this patient.
17.8.2.2 A Study of Pathological Changes
in the Thyroid and Their Mechanisms
After Severe Burns in Rats
Responses of the severe burn injury form an important part
of the defensive mechanism of the human body. The thyroid
as an important endocrine gland participates in the process.
However, there have long been controversies among authors
on whether thyroid hormone contributes to the hypometabo-
lism after burns. The synthesis and release and the intermedi-
ate metabolism of thyroid hormone are very complex and
under the control of many factors. The changes of thyroid
function after severe burns have been investigated with the
determination of the serum level of thyroid hormone and
uptake test of radioiodine by the thyroid and the observation
of the pathological changes of the thyroid. The results
reported are discrepant.
In our unit, the pathological changes of the thyroid after
severe burns were observed under light and electron micros-
copy and with peroxidase histochemistry, and the mecha-
nisms of certain changes were tried to elucidate theoretical
basis for the treatment of burn injury.
The Results Were as Follows
The morphological changes of the thyroid after severe burns
were observed under light microscopy. It was found that the
follicles of the thyroid showed widespread dilatation in the
2nd, 12th, and 24th hour and on the 3rd day post burn and the
follicular lumen teemed with eosinophilic colloid. The epi-
thelial cells were obviously fl attened and became cuboidal or
squamous in shape. In the apical portion of the follicles,
there was scanty cytoplasm in the cells in which PAS-positive
granules decreased markedly in number and colloid droplets
almost entirely disappeared. In addition, many vesicles and
fi ssures appeared in the cytoplasm of follicular cells from the
12th hour to 3rd day post burn. Three days after injury, the
structure of the thyroid was gradually restored. In the cyto-
plasm of the follicular cells of the apical portion, many PAS-
positive colloid droplets were formed from the 10th to 15th
day post burn. The colloid in a part of follicular lumen was
nearly exhausted, which indicates the accelerated release of
the hormone.
The main ultrastructural changes of the thyroid in the 2nd,
12th, and 24th hour post burn were marked dilatation and
degranulation
of
the
rough
endoplasmic
reticulum
and reduced area of the Golgi complex with dilated cisternae
and decreased vacuoles (Fig. 17.27 ). The vacuoles and
microvilli of the apical portion of follicles were scant. No
colloid droplets or pseudopods could be seen. Lysosomes
were sparse. The mitochondria were also sparse and small
with focal vacuolation and pyknosis. The electric density of
the cytoplasm was increased and shape of the nucleus was
irregular with dilated perinuclear space and increased het-
erochromatin. Pseudoinclusions in the nuclei were often
seen in the 24th hour after injury and a large part of the cyto-
plasm was dissolved.
The follicular epithelial cells gradually returned to nor-
mal from the 3rd to 6th day post burn. The damages on the
organelles were alleviated markedly. The characteristic fea-
tures in this stage were the increase of lysosomes, multive-
sicular bodies, and autophagosomes in number, the formation
of many polyribosomes in the cytoplasm, and the increase of
euchromatin in the nuclei with large nucleoli (Fig. 17.28 ).
The follicular epithelial cells exhibited active functioning
from the 10th to 15th day post burn. The main morphological
changes were the formation of numerous pseudopods and
Fig. 17.27 Follicular epithelial cells of the thyroid showing high dila-
tation of the rough endoplasmic reticulum ( RER ), dilatation of perinu-
clear space (→), marked atrophy of the Golgi complex ( Go ). Two hour
post burn, TEM × 6,000. M denotes mitochondria

17.8 Pathological Changes in the Endocrine Glands After Burns

476
colloid droplets, well-developed microvilli, and large
amounts of lysosomes and mitochondria which accumulated
in the cytoplasm of follicular cells of the apical portion; dila-
tation of the rough endoplasmic reticulum; presence of well-
developed Golgi complex; abundant euchromatin with giant
nucleoli; digital intersections of the intercellular junctions;
and increase of fenestrations on the capillary endothelial
walls (Figs. 17.29 and 17.30 ).
The T 4 level in the 2nd and 12th hour post burn was sig-
nifi cantly lower in the burn group than in the control
( p < 0.05), and the difference in the 24th hour was not signifi -
cant statistically. The T 4 level returned nearly to the control
level on the 3rd to 6th day post burn and exceeded the control
level markedly on the 10th day ( p < 0.01).
T 3 level was signifi cantly lower in the burn group than in
the control at every time point, and the difference of T 3 level
among different time points was not signifi cant statistically.
Peroxidase was inhibited progressively in the 2nd, 12th,
and 24th hour post burn, and the number of peroxidase-
positive follicular lumen was signifi cantly lower in the burn
group than in the control. The activity of peroxidase began to
recover on the 3rd day post burn.
The above results indicated that the main pathological
changes of the thyroid after severe burns ran a dynamic
course and could be distinguished into three phases as
follows:
The fi rst phase was the phase of injury inhibition which
lasted from the 2nd to 24th hour post burn and was char-
acterized by the widespread dilatation of the thyroid fol-
licles. The follicular epithelial cells were fl attened and
became cuboidal or squamous in shape. The amount of
colloid was increased markedly and that of follicular epi-
thelial cells decreased signifi cantly. The ultrastructural
changes of the follicular cells were characterized by the
damage on the structures which synthesize thyroglobulin
(such as the rough endoplasmic reticulum, Golgi com-
plex, and cytoplasmic vesicles of the apical portion of the
follicles) and the underdevelopment of the hormone-
releasing
organelles
(such
as
pseudopodia
and
lysosomes).
The second phase was the phase of structural and functional
recovery which lasted from the 3rd to 6th day post burn.
The structure of the follicles was restored and various
organelles such as lysosomes, multivesicular bodies,
autophagosomes, giant nucleoli, and polyribosomes to
repair the functions of the thyroid were well developed.
The third phase was the phase of active functioning which
lasted from the 10th to 15th day post burn. The function
Fig. 17.29 Follicular epithelial cells of the thyroid showing slight dila-
tation of the rough endoplasmic reticulum ( RER ), well-developed Golgi
complex ( Go ), abundant mitochondria ( M ) and digital intersection of
intercellular junction. 144 h postburn, TEM ×10,000
Fig. 17.30 Follicular epithelial cells of the thyroid showing formation
of pseudopodia ( Pd ) and numerous lysosomes ( Ly ), mitochondria ( M ),
and colloid droplets ( CD ) in the apical cytoplasm. 240 h post burn, TE
×8,000
Fig. 17.28 Follicular epithelial cells of the thyroid showing increased
lysosomes ( Ly ), multivesicular bodies (↑), and polyribosomes (→).
Seventy-two hour post burn, TEM × 8,000



17 Pathological Changes of Visceral Organs and Endocrine Glands After Burns

477
of the thyroid was quite active and the hormone- synthesizing
and hormone-releasing organelles of the follicular epithe-
lial cells were well developed.
There was no sharp demarcation between nearby phases.
The changes of serum T 4 level in each phase were parallel to
the severity of the pathological changes.
Serum T 3 level was markedly suppressed in the fi rst
15 days after burn injury, which is consistent to the reports of
other authors. The changes of serum T 4 level were quite
complicated and parallel to the severity of the pathological
changes and peroxidase activity. The difference of the
changes of T 3 and T 4 results from the difference of their
sources and of the changes of hormone metabolism during
burn stress. T 4 is totally secreted by the thyroid, while a large
part of T 3 is derived from the deiodination of T 4 in the periph-
eral circulation and a small part is secreted by the thyroid
directly. After burn injury, the causes of low serum level of
T 3 were multiple. In the phase of injury inhibition, low T 3
level results from inadequate deiodination metabolism
because of low T 4 level, inhibition of 5-deiodinase, and
impairment of T 4 –T 3 conversion by large amounts of gluco-
corticoid released during burn stress and decline of T 3 secre-
tion by the thyroid. In the latter two phases, low T 3 level
results mainly from the inhibition of 5′-deiodinase and
impairment of T 4 -T 3 conversion by glucocorticoid.
The changes of T 4 level in this study were different from
those observed in patients with burn injury. In human being,
inhibition on T 4 can only be seen in patients with severe burn
injury or with burn complications. This difference of T 4
changes between human beings and rats can only be
explained by the difference of species. Shirani et al. reported
that T 4 level was inhibited in the fi rst 14 days after 60 %
TBSA full-thickness burns was infl icted to rats, which is not
consistent with our result. It is considered that the more
severe the burn injury, the more intense the inhibition on T 4 .
Since the burn area is smaller in our study, the duration of the
inhibition on T 4 is shorter. In the last phase of burn injury,
markedly elevated T 4 level may be related to the disturbance
of T 4 deiodination and the compensatory elevation of T 4 for
the low T 3 level. So it is suggested that T 3 be administered in
the late stage of burn injury.
Peroxidase is an important enzyme for the synthesis of
thyroid hormone and catalyzes the oxidation of iodides,
iodination of tyrosine, and coupling of iodotyrosines. Strum
et al. demonstrated that peroxidase is chiefl y located on the
nuclear membrane, rough endoplasmic reticulum, Golgi
complex, subapical vesicles, and the external surface of
microvilli. Many authors believed that only the peroxidase
located on the surface of microvilli has the catalyzing activ-
ity. In the phase of injury inhibition of this study, peroxidase
activity was progressively inhibited and the number of
peroxidase- positive
follicular
lumen
was
markedly
decreased. Under electron microscopy, it was found that the
organelles responsible for peroxidase synthesis were
damaged. Thyroid-stimulating hormone (TSH) exerts infl u-
ence on peroxidase activity. TSH can increase the amount of
peroxidase and accelerates the transportation of the enzyme
to the apical plasma membrane of the follicular epithelium.
Therefore, it is believed that the major causes of peroxidase
inhibition in the phase of injury inhibition are the inhibition
of TSH secretion by burn injury and the damage of the
organelles related to peroxidase synthesis such as degranula-
tion and dilatation of the rough endoplasmic reticulum and
vacuolation and pyknosis of the mitochondria by burn shock
or burn toxin. Inhibition of peroxidase activity and decrease
of the number of peroxidase-positive follicular lumen can
result in a disturbance of the synthesis of thyroid hormone,
which may be an important factor of the functional inhibition
of the thyroid after burn injury [ 11 – 16 ].
17.8.3 The Adrenal Glands
Among 61 necropsy cases from fatally burned patients,
grossly in majority of cases, the adrenal glands were con-
gested and swollen and the cortices being thickened and
hypertrophied. Sometimes the adrenal glands showed
marked congestion and hemorrhage in which some cases
were associated with cystic degeneration. Histopathological
appearances of the adrenal glands were as follows:
1. Cortical lipoid depletion
The normal resting adrenal cortex contains abundant
sudanophil lipoid, especially in the zona glomerulosa and
zona fasciculata. In routine HE staining sections, the
cytoplasm of cortical cells is foamy and translucent,
referred to as “clear cells.” After loss of lipoid, the cyto-
plasm of cortical cells becomes more dense and red in
color, referred to as “compact cells.”
In necropsy materials from fatally burned patients,
owing to cortical lipoid depletion, the clear cells in the
adrenal cortex were transformed into compact cells, par-
ticularly in the zona fasciculata. This may be considered
as morphological basis of hyperactivity and hypersecre-
tion of the adrenal cortex.
2. Hemorrhage
Within the fi rst 24 h after burn, marked congestion of
the adrenals may be frequently found, especially in the
boundary between the adrenal cortex and medulla, fol-
lowed by development of microscopic hemorrhage in the
cortex.
Among our 61 necropsy cases from fatally burned
patients, there were 15 cases demonstrating adrenal hem-
orrhage. Adrenal hemorrhage may involve the cortex and
medulla, much more in the former; the hemorrhage may
be focal or diffuse in distribution. Sometimes diffuse
hemorrhage may be complicated by septicemia, some
17.8 Pathological Changes in the Endocrine Glands After Burns

478
associated with disseminated intravascular coagulation
(DIC). In hemorrhagic areas the adrenal parenchyma may
be necrotic, even entirely destroyed.
3. Degenerative changes in the adrenal cortex
These included foci of necrosis of adrenal cortical cells
without hemorrhage, areas or groups of cortical cells show-
ing hydropic changes and ballooning degeneration to the
point of disruption, and irregular rupture of cells, thus the
solid columns of the zona fasciculata being transformed
into acinous or tubular-like structures by lysis of the central
cells, this picture being referred to as pseudo- acinous or
pseudo-tubular formation. In our 61 necropsy cases, there
were seven cases presenting pseudo-tubular formation.
Sometimes the cortical cell cytoplasm appeared vacu-
olar, the nucleus being located at the periphery of the
cells, highly resembling the fat cells, being referred to as
fat cell metaplasia. There were fi ve cases showing this
morphological change in our 61 necropsy cases.
4. Thrombosis
There were hyaline thrombi inside small veins in the
adrenal medulla in one case among our 61 necropsy
cases. This case was associated with fi ndings of hyaline
thrombi inside renal glomeruli. Thus, it may be consid-
ered that venous thrombosis in the adrenal medulla might
be a part of disseminated intravascular coagulation.
In an experimental study of phosphorus burn on rats,
microscopically,
adrenal
cortical
lipoid
depletion
occurred frequently, particularly in the zona fasciculata in
the early stage (0.5–12 h post burn); in 24–48 h post burn,
adrenal cortical cells showed swelling, disarray, pykno-
sis, or karyolysis and occasionally focal hemorrhage in
the zona reticularis. At this period, lipoid may reappear in
the cortical cells. In 96–144 h post burn, adrenal cortical
cells exhibited marked increase in lipoid content, espe-
cially in the zona fasciculata; in the meanwhile cortical
cell degeneration and necrosis were alleviated. 240–360 h
post burn, the morphology of the adrenal cortex essen-
tially returned to the normal condition.
By using an electron microscope, the ultrastructural
changes in adrenal cortical cells after phosphorus burn were
manifested as a dynamic process and may be divided into 3
phases:
1. Stress phase (0.5–12 h post burn)
The mitochondria and smooth endoplasmic reticulum
(SER) in cortical cells showed hypertrophy and hyperpla-
sia (Fig. 17.31 ), and the content of liposomes was reduced,
indicating an increased capacity of steroid hormone syn-
thesis. In cortical cells, the Golgi complex was well
developed, with an increased amount of coated vesicles
as well as dense bodies and an increased number of fi lo-
podia on the cell surface, protruding into the sinusoids
underlying the endothelial cells. In more severe cases cell
surface fi lopodia appeared with caulifl ower-like structures
protruding into the sinusoids. These alterations indicated
hypersecretion of adrenal cortical cells.
2. Injured (or damaged) phase (24–72 h post burn)
In this phase, cortical cell injury was more prominent
and manifested as pyknosis, karyolysis, mitochondrial
swelling and vacuolation, and focal intracytoplasmic
degeneration (FCD). Disarrayed wrinkled paperlike
membranous structures as well as lipid myeloid bodies
were obviously increased and also autophagic vacuoles
and secondary lysosomes. Enhanced activities of lyso-
somes might be related to degeneration, elimination, and
autophagy of organelles.
3. Proliferative and repair phase
In cortical cells, the Golgi complex and dense bodies
were increased in number again, cell surface fi lopodia
and cytoplasmic processes increased prominently, mito-
chondria and SER showing marked hyperplasia, and lipo-
somes also reappeared. These alterations identifi ed that
cortical cell structure and function are restored and syn-
thetic hyperfunction appeared more prominent than pre-
vious phase [ 17 ].
17.8.4 The Endocrine Pancreas
The endocrine tissue of the pancreas is scattered throughout
the gland in ovoid clusters of cells called the islets of
Langerhans (pancreatic islets). Each pancreatic islet is com-
posed of a few to several hundred hormone-producing cells.
There are three major cell types of pancreatic islets, namely,
A (alpha), B (beta), and D (delta) cells. The B cells are the
most numerous of the islet cells and they usually constitute
about 70 % of the total endocrine tissue.
Fig. 17.31 Adrenal cortical cell exhibiting marked hyperplasia of the
mitochondria ( M ) and smooth endoplasmic reticulum ( SER ) during
stress. TEM ×10,000

17 Pathological Changes of Visceral Organs and Endocrine Glands After Burns

479
The ultrastructural investigation on B cells of pancreatic
islets post burn has been less documented in the literature. In
an experimental study on ultrastructural changes of islet B
cells in rats after phosphorus burn, the following fi ndings
were achieved [ 18 ]:
1. The secretory granules in islet B cells were increased in
number, the size of secretory granules being essentially
consistent, more regular in shape 8 h post burn. In 24–48 h
post burn the size of secretory granules becomes variable
with defect and lysis of their limiting membranes. Finally
many secretory granules were coalesced and the endo-
plasmic reticulum merged together and vacuolated.
2. In islet B cells, the rough endoplasmic reticulum (RER)
exhibited hyperplasia and hypertrophy with dilatation of
cisternae in which were fi lled with electron-lucent materi-
als 4–8 h post burn. Occasionally, the mitochondria may
be surrounded by hyperplastic RER. The Golgi complex
also demonstrated hyperplasia and hypertrophy with dila-
tation of saccules. Hyperplastic Golgi complex was fre-
quently arranged in circular form. The Golgi complex as a
center, mitochondria, ER, as well as secretory granules
were located around them, this picture being referred to as
“horseshoe garland-shaped Golgi complex” (Fig. 17.32 ).
Twenty-four to forty-eight hours post burn, in islet B-cells,
various organelles were degenerated, manifesting as dila-
tation of ER and mitochondrial swelling with disruption of
cristae. Thus, according to developing process, ultrastruc-
tural changes in islet B-cells may be divided into two
phases: (a) hyperplasia and hypertrophy of organelles with
hyperfunction of cell synthetic activity and (b) degenera-
tive phase of organelles. Dr. Lei shi-ze considered that
hyperfunction of synthetic activity is related to increased
synthesis of secretory granules, while in degenerative
phase it is ascribed to inhibition of secretory activity.
17.9
Pathological Changes in the Brain
After Burns
Concerning the pathological studies on the central nervous
system after burns, as early as the third to fourth decade of the
nineteenth century, they have been described in the literature,
but thorough and scrutinized investigations have been less
documented. According to our own work, including autopsy
materials from fatally burned patients as well as experimental
animal materials, pathomorphological changes after burns
mainly consisted of (a) vascular changes in the brain; (b)
brain edema and brain swelling; (c) neuronal degeneration
and necrosis, (d) neuroglial cell reaction, especially prolifera-
tion; and (e) alterations in synaptic structures.
Necropsy fi ndings from 61 cases of fatally burned patients
in the brain may be summarized as follows:
17.9.1 Cerebral Congestion and Edema
All of the necropsy cases exhibited cerebral congestion, usu-
ally manifested as slight congestion in the pia-arachnoid and
brain parenchyma, some showing severe congestion.
Approximately half of the cases of this series showed brain
edema, manifested as widening of perivascular space fi lled
with pinkish proteinous materials, as well as with loosening
of brain tissue. Nine cases of this series showed striking
brain edema in which at necropsy there was a pressure con-
ing of the cerebellar tonsils around the medulla oblongata
and a coning of the uncus at the free margin of the tentorium
cerebelli, that is, brain herniation. Two of nine cases suffer-
ing from brain herniation demonstrated marked dyspnea
clinically due to pressure on the respiratory center in the
medulla oblongata.
17.9.2 Cerebral Hemorrhage
In 61 necropsy cases from fatally burned patients, there were
seven cases showing cerebral hemorrhage, mainly manifested
as ring hemorrhage around small blood vessels in subarachnoid
space and brain substance. The ring hemorrhages were scat-
tered in various regions of the cerebrum and also found in the
thalamus, pons, medulla oblongata, as well as cerebellum.
17.9.3 Neuronal Degeneration and Necrosis
In about one-third of necropsy of this series, neuronal degen-
eration manifested as chromatolysis (loss of Nissl’s bodies),
cellular swelling, and pyknosis, scattered in various areas of
the cerebrum, especially in the thalamus, may be found.
Occasionally, there were necrotic foci in the cervical region
Fig. 17.32 B cell of pancreatic islet showing horseshoe garland-
shaped Golgi complex structure. Go Golgi complex, M mitochondria,
RER rough endoplasmic reticulum, light granule ( arrow ) phosphorus
burn in rat, TEM ×14,000

17.9 Pathological Changes in the Brain After Burns

480
of the spinal cord. Dr. Li Yuangping in our department
reported a special case of fatally burned child, who had mul-
tiple epilepsy attacks (or episodes) antemortem. At necropsy
a widespread loss of Purkinje cells in the cerebellar cortex
may be found, the remaining Purkinje cells showed various
degrees of degeneration.
17.9.4 Neuroglial Proliferation
and Neuronophagia
In the above-mentioned cervical region of the spinal cord,
the necrotic foci were surrounded by proliferative neuroglial
cells, mainly astrocytes and less microglia. In another case,
neuronophagia in neuronal degenerative areas in the cerebral
cortex may be found.
17.9.5 Meningitis and Encephalitis
There were three cases presenting meningitis and encephali-
tis in these necropsy materials. Meningitis and encephalitis
were manifested as perivascular infl ammatory cell infi ltra-
tion in the pia-arachnoid and brain parenchyma, respectively.
The infl ammatory cells were characterized predominantly by
monocytes and lymphocytes.
17.9.6 Xanthydrol-Urea Crystal Reaction
in the Brain Tissue
When the brain tissues take from necropsy materials were
processed by xanth containing fi xative, there may be domon-
strated a lot of rosset like crystals demonstrated a lot of ros-
set like crystals for positive xanthyol-used reaction in
histological section of brain tissues.
17.9.7 Intravascular Hyaline Thrombi
There was one case of hyaline thrombi found in small blood
vessels in the brain tissue, in which case was accompanied by
systemic mycotic infection. There were two cases of hyaline
thrombi found in small blood vessels within the pia- arachnoid
in which one case was complicated with cerebellar contusion
and another case complicated by multiple infarcts in the spleen.
In the above-mentioned lesions, cerebral edema, cerebral
hemorrhage, neuronal degeneration, and necrosis may be
related to anoxia and toxic effects from burning; in addition
they are also related to acute renal failure and uremia.
In an experimental study on body surface burn caused by
napalm in rats, the histopathological and ultrastructural fi nd-
ings in the brain tissue were as follows [ 19 ]:
The pathological changes in the brain tissue became obvi-
ous 6 h post burn, most striking 3 days post burn, and gradu-
ally restored 30 days post burn. The neurons and neuroglial
cells exhibited various degenerations, such as swelling and
even necrosis so as to reduction in their number, particularly
the Purkinje cells in the cerebellum. Ultrastructurally, the
neurons showed mitochondrial swelling with reduction in
the number of cristae, the endoplasmic reticulum and Golgi
complex dilated and vacuolated (Fig. 17.33 ), ribosomes and
glycogen particles decreased in number, and microtubules
and neurofi laments disrupted. The neuropil became loose
and swollen. There were neuronophagia and neuronophagia-
like phenomena. The latter condition was manifested as
degenerative and necrotic neurons surrounded by oligoden-
droglia with fusion and loss of plasma membrane in both
cells (Fig. 17.34 ); fi nally the cytoplasm in both cells fused
together, resembling that of neuronophagia, referred to as
neuronophagia-like phenomena.
The presynaptic element and postsynaptic element exhib-
ited swelling with lysis and disruption of their synaptic
membranes.
The astrocytes showed swelling of their cytoplasmic pro-
cesses with reduction in number of organelles; footplates of
astrocytes attached to the capillary wall showed marked
swelling, eventually being vacuolated.
The capillary endothelial cells were swollen and pinocy-
totic vesicles increased in number with separation of tight
junction. The capillaries were surrounded by a few neuro-
glial cells and leukocytes. These morphological changes
indicate that the blood-brain barrier was impaired and vascu-
lar permeability increased, leading to brain edema.
Fig. 17.33 In the brain, capillary basement membrane ( BM ) became
swollen and adjacent neuron ( N ) exhibited pyknosis, dilatation of peri-
nuclear space ( arrow ), mitochondrial ( M ) swelling, vacuolation, and
dilatation of the endoplasmic reticulum ( ER ). Napalm burn in rat, TEM
×15,000

17 Pathological Changes of Visceral Organs and Endocrine Glands After Burns

481
The above-mentioned lesions may be considered as
pathomorphological basis of clinical manifestations of
encephalopathy in burned patients. Among these, swelling of
presynaptic and postsynaptic elements, disruption of synap-
tic membrane, as well as decreased in number of synaptic
vesicles may impair the conduction of nerve impulses,
leading to derangement of synaptic uptake and release and
inactivation of neurotransmitters. In addition, neuronal
degeneration and necrosis may also have their injurious
effects. These may explain why the central nervous system
might be situated in an inhibition state and there is even
occurrence of psychological effects (symptoms) in some
burned patients.
17.9.8 Mechanism of Cerebral Edema
As one of the visceral complications in severe burn, cerebral
edema occupies an important place in the prevention and
treatment of the visceral damage of the brain. According to
experimental studies, infl ammatory cytokines, lipopolysac-
charide, and free radicals account for the formation of the
early stage brain edema in severe burn. In addition, the
hypoxic and ischemic environment accelerated the edema
formation. The decrease of expression in VE (vascular
endothelial)-cadherin and CD31 might serve as some rea-
sons for the increase of blood-brain barrier permeability and
the edema formation.
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Fig. 17.34 In the brain, neuron ( N ) showing degenerative changes and
in close contact with it being an oligodendrocyte ( OL ). Napalm burn in
rat, TEM ×7,000

References