Evaluation of histopathological changes in fatal aluminum phosphide poisoning
Author(s): Omid Mehrpour, Mandana Dolati, Kambiz Soltaninejad, Shahin Shadnia, Bashir Nazparvar
Vol. 2, No. 2 (2008-07 - 2008-12)
Omid Mehrpour1, Mandana Dolati2, Kambiz Soltaninejad3, Shahin Shadnia4, Bashir Nazparvar5
1 Department of Forensic Medicine, Faculty of Medicine, Medical Sciences/University of Tehran, Iran,
2 Department of Forensic Pathology, Scientific and Educational Research Center of Legal Medicine Organization of Iran, Tehran, Iran,
3 Department of Forensic Toxicology, Scientific and Educational Research Center of Legal Medicine Organization of Iran, Tehran, Iran,
4 Loghman Hakim Poison Center, Faculty of Medicine, Medical Sciences/University of Shaheed Beheshti, Tehran, Iran,
5 Autopsy Service, Scientific and Educational Research Center of Legal Medicine Organization of Iran, Tehran, Iran
Abstract
This study examines histopathological changes of human
organs in cases with aluminum phosphide fatal poisoning.
The cases with aluminum phosphide fatal poisoning in Tehran
Legal Medicine Center over 12 month period starting in March
2006, were studied. Necropsy was performed for all cases
and liver, lung, brain, kidney and spleen were collected from
all cases and fixed in formaldehyde solution (37%
formalin). Tissue specimens were taken from organs and
processed by routine histological method. Then any
histhopathological changes were recorded by pathologist. In
gross examination, almost all the vital organs were found to
be congested. In microscopic study, the most frequent
histopathological findings in liver were central venous
congestion, degeneration of hepatocytes and mononuclear
infiltration. In lung, alveolar thickening, and dilated capillaries
were detected. Findings in the brain tissue revealed
degenerated Nissel granule in the cytoplasm and deeply
stained degenerated eccentric nucleus in brain cortex.
Changes in the kidney included glomerulus’s and
intraparanchymal congestion. These findings indicated that
histopathological changes are common in aluminum
phosphide fatal poisoning.
Key words: Aluminum phosphide, histopathology, fatal poisoning
Introduction
Aluminum phosphide (ALP) is a highly toxic, low cost,
and easily practicable pesticide. It is widely used in Iran as a
fumigant for pests control in grain storage facilities1. It is
marketed in Iran as round tablets under several trade names
as Phostoxin®, Celphos® and Quickphos®; each tablet
weighed 3 g and contained 56% ALP and 44% ammonium
carbonate. It is easily accessible for public. From this view,
aluminum phosphide poisoning is common in Iran1-3. Previous
study demonstrated that ALP was the common type of
pesticide in Iran for suicide attempts4.
ALP ingestion is highly toxic, with a high mortality5-7.
ALP poisoning is rarely accidental and intentional ingestion
of ALP for suicidal purpose is common in the countries in
which this pesticide is sold without restriction5,8,9. Its toxicity
is due to release of the phosphine gas when it comes in
contact with moisture7. The toxicity mechanism of phosphine
is still not clear and suggested many mechanisms involved in
phosphine toxicity. Phosphine is a mitochondrial poison that
interferes with enzymes and protein synthesis5,10. In addition
experimental studies show that it inhibit cytochrom-c oxidase
which may lead to multi-organ dysfunction11. Some studies
have shown free radical production induced toxicity during
ALP poisoning in human and experimental animals12.
In aluminum phosphide poisoning, histopathological
examination of tissue reveals pronounced degenerative
changes in liver, heart, and kidney of ALP intoxicated animals
and humans13-15. However, there are few studies about
aluminum phosphide induced histopathological changes in
cases with fatal poisoning. In medico-legal investigations,
histopathological findings are very important factors for
diagnosis of cause of death, especially in suspected cases
with fatal poisoning. Therefore, in this study we evaluate
histopathological changes of human organs in cases with ALP
fatal poisoning.
Methods
All of the cases with ALP fatal poisoning in Tehran Legal
Medicine Center (TLMC) over 12 month period starting in
March 2006, were studied. The clinical manifestations, scene
investigations, autopsy and toxicological findings supported
the diagnosis of only ALP fatal poisoning as well as cause of
death and the postmortem interval of all of cases less than
24 hours.
A questionnaire form was designed and demographic
data from all cases were obtained.
Necropsy was performed for all cases. All cases were
necropsy by experience prosecutors supervised by a forensic
medicine specialist and descriptions of all macroscopic
abnormalities (e.g. congestion, edema and hemorrhage) were
recorded. Liver, lung, brain, kidney and spleen were collected
from all cases and fixed in formaldehyde solution (37%
formalin).Then organs transported to forensic pathology
laboratory.
Tissue specimens were taken from organs and processed
by routine paraffin embedding method. Tissues cut at a
thickness 3-4 micrometers and stained with haematoxylin and
eosin (H&E) stain. Slides of the all processed samples were
examines by a pathologist. The Statistical Package for Social
Sciences (SPSS) version 11.5 was used for data analysis.
Results
In this period, 45 cases were related with ALP fatal
poisoning. 26(57.78 ) of cases were male and 19(42.22)
were female. Male to female ratio was 1.37:1. The age of
cases was 29.53 ± 13.7(mean ± SD) years old. The victim’s
age range from 13-66 years (table-1).The highest frequency
of poisoning (37.78%) was found in age group 20-29 years
old. The route of exposure to the ALP was deliberate ingestion
in all cases. Average amount of ALP tablets ingested was
1.56±0.90 tablets. The number of tablets consumed by cases
varied from 1 to 4.
Table 1: Age groups distribution of cases
Age(years)
No. of Cases
Percent
0-9
0
0
10-19
14
31.11
20-29
17
37.78
30-39
7
15.55
40-49
4
8.88
50-59
2
4.45
60-69
1
2.23
TOTAL
45
100
Table 2: Histopathological findings of liver in cases with fatal aluminum phosphide poisoning
Microscopic features
No. of cases
Percent
Congestion
31
68.9
Microvacoualization
26
57.8
Hydropic degeneration of
hepatocytes
22
48.9
Mononuclear infiltration
24
53.3
Microvesicular steatosis
22
48.9
Macrovesicular steatosis
14
31.1
Bile pigment in the cytoplasm
of the hepatocytes
12
26.7
Central venous congestion
9
20
Sinusoidal dilation
5
11.1
Centrilobular necrosis
8
17.8
Portal congestion
9
20
Hemorrhage
10
22.2
Patchy necrosis
7
15.6
Sinusoidal clusters of
polymorphonuclear leukocytes
6
13.3
Table 3: Histopathological findings of lung in cases with fatal aluminum phosphide poisoning
Microscopic features
No. of cases
Percent
Congestion
33
73.3
Edema
31
68.9
Hemorrhage
31
68.9
Collapse of Alveoli
22
48.9
Alveolar thickening
16
35.6
Alveolar wall disturbance
6
13.3
Dilated capillaries
8
17.8
Table 4: Histopathological findings of brain in cases with fatal aluminum phosphide poisoning
Microscopic features
No. of cases
Percent
Mild capillary dilation
and congestion of
cortex
26
57.8
Cerebral oedema
27
60
Cerebellar edema
24
53.3
Subaracnoid hemorrhage
2
4.4
Intraparenchyma hemorrhage
3
6.7
Degenerated Nissel granule
in the cytoplasm and deeply
stained degenerated eccentric nucleus
in brain cortex
28
62.2
Degenerated neuron and infiltration
of round cell in to the
molecular layer in cerebella
27
60
Table 5: Histopathological findings of kidney in cases with fatal aluminum phosphide poisoning
Microscopic features
;No. of cases
Percent
Glomerulus congestion
37
82.2
Intraparenchymal congestion
32
71.1
Tubular degeneration
16
35.6
In gross (macroscopic) examination, almost all the vital
organs were found to be congested. The lungs were heavy,
edematous and congested.
In microscopic examination, histopathological changes
observed in the all of organs (Tables 2 to 5).
On microscopic study, the liver showed central venous
congestion, microvacuolizition, degeneration of hepatocytes
and mononuclear infiltration were the most frequent
histopathological findings. (Table- 2).
Microscopy of the lungs revealed congestion, edema,
and hemorrhage, collapse of alveoli, alveolar thickening,
alveolar thickening, alveolar wall disturbance and dilated
capillaries and round cell infiltration around bronchioles
(Table-3). Microscopic investigation of the brain tissue showed
distinct changes due to the effect of aluminum phosphide.
Findings in the brain tissue revealed degenerated Nissel
granule in the cytoplasm and deeply stained degenerated
eccentric nucleus in brain cortex. Degenerated neuron and
infiltration of round cell in to the molecular layer in cerebellar
tissue and cerebral oedema were the most frequent findings
in microscopic features of brain tissue (Table- 4).
Changes in the kidney included glomerulus’s and
intraparanchymal congestion (Table- 5). In microscopic feature
of spleen, congestion was only histopathological finding in
this study that observed in 75.6% of cases.
Discussion
Acute pesticide poisoning is an important cause of
morbidity and mortality in Iran and worldwide. ALP is the
most common type of pesticide causes death in Iran4.
ALP is used for suicidal purpose, and use of it is increasing
rapidly, because it is cheap, easily available and highly lethal.
Acute exposure to ALP is highly toxic with high mortality rate.
In present study we found many histopathological
changes in victims of ALP fatal poisoning. These results are
similar to findings which obtained by other researchers.
In previous studies, a significant feature visualized during
autopsy by naked eye was that all the major vital organs were
found to be congested12,15,16. It is accordance with our finding.
Phosphine is rapidly absorbed throughout the gastrointestinal
tract after ingestion and it is partly carried to the liver by the
portal vein17. Congestion of the liver and other vital organs,
in gross and microscopic pathology examination were
observed in almost of our cases. This finding suggested the
cellular hypoxia during ALP poisoning. Previous studies
suggested that phosphine is a mitochondrion poison and has
cytochrom oxidase inhibitor11. Similar observation has been
reported by previous studies13,15. In our study, the most
common microscopic finding in the liver was sinusoidal
congestion that it was accordance with other authors13,15-19.
Microvacuolizition was another finding that was seen in many
of our cases. It was accordance with previous study, which
has reported fine isomorphic cytoplasmic vacuoles in liver
histopathology of ALP induced poisoning17.
Microvesicular and macrovesicular steatosis were the
other histopathological findings observed in our liver’s cases.
This is similar to finding of previous study17. They have
reported macrovesicular steatosis in 13.2% of cases. Fatty
changes have reported by some other authors13,15,19. Hydropic
degeneration of hepatocytes was seen in our cases. It was
accordance with previous report14. In this study, hemorrhages
was observed in 22.2% of cases. Us Sinha et al was reported
hemorrhage in 56.6% of cases. They also have reported
sinusoidal dilation (54.72%), centrilobular necrosis (43.3%),
bile stasis (49.06%), mononuclear infiltration and fatty
changes (20.75%) that were accordance with our study with different percent. However, they had not reported
microvacuolizition, patchy necrosis, portal congestion, that
were seen in our study. Saleki et al were found central vein
congestion in 60.5% of cases that was 20% in our study;
they also have reported sinusoidal congestion, sinusoidal
clusters of polymorphonuclear leukocytes (31.6%),
Microvacuolizition (94.7%), macrovesicular steatosis (13.2%)
and hepatocyte nuclear fragmentation (15.8%) in cases. These
findings supported by previous studies18,20.
In the lung microscopy, congestion was the most
common finding in our study (73.3%), follow by oedema,
hemorrhage, collapses of alveoli, alveolar thickening, and
dilated capillaries. These data supported by Us Sinha et al,
although they differ in respect to percentage variation who
observed congestion (100%), alveolar thickening (98.11%),
edema (92.45%), dilated capillaries(81.31%) and hemorrhage
(58.49%). We also have found gray or red hepatization and
round cell infiltration around bronchioles in (17.8%) of cases,
this data obtain by other researchers12. For example, Siwach
et al observed congestion, thickening of alveoli by haemolysed
red cell, oedema, and dilated capillaries19. In our study
disturbance of alveolar wall was seen in 13.3%, that wasn’t
reported in other previous studies.
Histopathology of the kidney showed congestion of
parenchyma and tubular degeneration were the major
histopathological findings in present study. Similar findings
are described by Us Sinha et al, but they have observed
infiltration (62.2%) and lobular dilation (37.74%) that we have
not observed. Also Siwach et al and Chugh et al were reported
regeneration of tubular epithelium in their studies that we
did not observe.
Arora et al have seen dystrophic calcification of kidneys
in those cases that died after 72-96 hours of ingestion15, but
we could not found this change in kidney pathology. Chugh
et al have reported congestion, area of tubular degeneration
and regeneration and necrosis in their cases12.
In our study, histopathological examination of the brain
tissue showed mild capillary dilation and congestion of cortex,
cerebral oedema, and cerebellar oedema. Similar findings
observed by previous reports but with higher frequency13,15.
Also we observed degenerated Nissel granule in the
cytoplasm and deeply stained degenerated eccentric nucleus
in brain cortex and degenerated neuron and infiltration of
round cell in to the molecular layer in cerebella, it was
accordance with previous studies21. Subarachnoid
hemorrhage (SAH) was observed in few of our cases that never
have seen in other studies.
Morphological changes in various organs observed in
this study are similar to those produced by hypoxic injury
due to shock. These hypoxic changes in various organs in
ALP could be secondary to shock produced by phosphine
acting on circulating system or by direct effect of phosphine
itself13. Similar observation have reported by Arora et al and
Singh et al15,18. Shock produced by ALP poisoning is refractory
to usual treatment and irresponsibility to dopamine12. Arora
et al observed that in ALP intoxication cardio-respiratory
system affected and is the major cause of death20.
It should, however, be noted that our study was erformed
on the basis of multi-organ histopathology in fatal ALP
poisoning in forensic cases and post – mortem histological
changes was an important limitation in interpretation of our
findings in present study.
In conclusion, based on our finding the histopathological
changes in many of vital organs are the most important
findings in fatal ALP poisoning. These findings can used for
diagnosis of cause of death in ALP intoxicated suspected
forensic cases.
References
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retrospective study of poisoning in Tehran. J Toxicol Clin
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M. Pesticide poisoning during an 18-month period (1995-
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to strength; A drug and poison information centre. Essent
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2003-2004. J Forensic Leg Med, 2007; 14(6):352-54.
- Shadnia S, Rahimi M, Pajoumand A, Rasouli MH,
Abdollahi M. Successful treatment of acute aluminum
phosphide poisoning: possible benefit of coconut oil.
Hum Exp Toxicol 2005; 24: 215-18.
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following severe aluminum phosphide poisoning. J
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a review. J Toxicol Clin Toxicol, 1995; 33: 19-24.
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oxidase inhibition in ALP poisoned patients. Clin Toxicol
(phila) 2006; 44(2):155-58.
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Incidence and outcome of aluminum phosphide
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aluminum phosphide poisoning: An epidemiological
clinical and histopathological study. J Assoc Physicians
India, 1988;36:594-6.
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histopathology of fatal phosphine poisoning. Forensic
Sci Int, 2007; 166(2-3):190-93.
- Singh S, Singh D, Wig N, Jit I, Sharma BK. Aluminum
phosphide ingestion—a clinico-pathologic study. J Toxicol
Clin Toxicol, 1996; 34(6):703-6.
- Siwach SB, Dua A, Sharma R, Sharma D, Mehla RK. Tissue
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Running Title
Histopathological Effects of Aluminum Phosphide
Corresponding address:
Dr. Kambiz Soltaninejad, Laboratory of Forensic Toxicology,
Scientific and Educational Center of Legal Medicine Organization of Iran, Tehran
Tel. +982155613731, Fax. +982155613731
Email : kamsoltani (at) yahoo.com
Omid Mehrpour1, Mandana Dolati2, Kambiz Soltaninejad3, Shahin Shadnia4, Bashir Nazparvar5
1 Department of Forensic Medicine, Faculty of Medicine, Medical Sciences/University of Tehran, Iran,
2 Department of Forensic Pathology, Scientific and Educational Research Center of Legal Medicine Organization of Iran, Tehran, Iran,
3 Department of Forensic Toxicology, Scientific and Educational Research Center of Legal Medicine Organization of Iran, Tehran, Iran,
4 Loghman Hakim Poison Center, Faculty of Medicine, Medical Sciences/University of Shaheed Beheshti, Tehran, Iran,
5 Autopsy Service, Scientific and Educational Research Center of Legal Medicine Organization of Iran, Tehran, Iran
Abstract
This study examines histopathological changes of human organs in cases with aluminum phosphide fatal poisoning. The cases with aluminum phosphide fatal poisoning in Tehran Legal Medicine Center over 12 month period starting in March 2006, were studied. Necropsy was performed for all cases and liver, lung, brain, kidney and spleen were collected from all cases and fixed in formaldehyde solution (37% formalin). Tissue specimens were taken from organs and processed by routine histological method. Then any histhopathological changes were recorded by pathologist. In gross examination, almost all the vital organs were found to be congested. In microscopic study, the most frequent histopathological findings in liver were central venous congestion, degeneration of hepatocytes and mononuclear infiltration. In lung, alveolar thickening, and dilated capillaries were detected. Findings in the brain tissue revealed degenerated Nissel granule in the cytoplasm and deeply stained degenerated eccentric nucleus in brain cortex. Changes in the kidney included glomerulus’s and intraparanchymal congestion. These findings indicated that histopathological changes are common in aluminum phosphide fatal poisoning.
Key words: Aluminum phosphide, histopathology, fatal poisoning
Introduction
Aluminum phosphide (ALP) is a highly toxic, low cost, and easily practicable pesticide. It is widely used in Iran as a fumigant for pests control in grain storage facilities1. It is marketed in Iran as round tablets under several trade names as Phostoxin®, Celphos® and Quickphos®; each tablet weighed 3 g and contained 56% ALP and 44% ammonium carbonate. It is easily accessible for public. From this view, aluminum phosphide poisoning is common in Iran1-3. Previous study demonstrated that ALP was the common type of pesticide in Iran for suicide attempts4.
ALP ingestion is highly toxic, with a high mortality5-7. ALP poisoning is rarely accidental and intentional ingestion of ALP for suicidal purpose is common in the countries in which this pesticide is sold without restriction5,8,9. Its toxicity is due to release of the phosphine gas when it comes in contact with moisture7. The toxicity mechanism of phosphine is still not clear and suggested many mechanisms involved in phosphine toxicity. Phosphine is a mitochondrial poison that interferes with enzymes and protein synthesis5,10. In addition experimental studies show that it inhibit cytochrom-c oxidase which may lead to multi-organ dysfunction11. Some studies have shown free radical production induced toxicity during ALP poisoning in human and experimental animals12.
In aluminum phosphide poisoning, histopathological examination of tissue reveals pronounced degenerative changes in liver, heart, and kidney of ALP intoxicated animals and humans13-15. However, there are few studies about aluminum phosphide induced histopathological changes in cases with fatal poisoning. In medico-legal investigations, histopathological findings are very important factors for diagnosis of cause of death, especially in suspected cases with fatal poisoning. Therefore, in this study we evaluate histopathological changes of human organs in cases with ALP fatal poisoning.
Methods
All of the cases with ALP fatal poisoning in Tehran Legal Medicine Center (TLMC) over 12 month period starting in March 2006, were studied. The clinical manifestations, scene investigations, autopsy and toxicological findings supported the diagnosis of only ALP fatal poisoning as well as cause of death and the postmortem interval of all of cases less than 24 hours.
A questionnaire form was designed and demographic data from all cases were obtained.
Necropsy was performed for all cases. All cases were necropsy by experience prosecutors supervised by a forensic medicine specialist and descriptions of all macroscopic abnormalities (e.g. congestion, edema and hemorrhage) were recorded. Liver, lung, brain, kidney and spleen were collected from all cases and fixed in formaldehyde solution (37% formalin).Then organs transported to forensic pathology laboratory.
Tissue specimens were taken from organs and processed by routine paraffin embedding method. Tissues cut at a thickness 3-4 micrometers and stained with haematoxylin and eosin (H&E) stain. Slides of the all processed samples were examines by a pathologist. The Statistical Package for Social Sciences (SPSS) version 11.5 was used for data analysis.
Results
In this period, 45 cases were related with ALP fatal poisoning. 26(57.78 ) of cases were male and 19(42.22) were female. Male to female ratio was 1.37:1. The age of cases was 29.53 ± 13.7(mean ± SD) years old. The victim’s age range from 13-66 years (table-1).The highest frequency of poisoning (37.78%) was found in age group 20-29 years old. The route of exposure to the ALP was deliberate ingestion in all cases. Average amount of ALP tablets ingested was 1.56±0.90 tablets. The number of tablets consumed by cases varied from 1 to 4.
Table 1: Age groups distribution of cases
Age(years) | No. of Cases | Percent |
---|---|---|
0-9 | 0 | 0 |
10-19 | 14 | 31.11 |
20-29 | 17 | 37.78 |
30-39 | 7 | 15.55 |
40-49 | 4 | 8.88 |
50-59 | 2 | 4.45 |
60-69 | 1 | 2.23 |
TOTAL | 45 | 100 |
Table 2: Histopathological findings of liver in cases with fatal aluminum phosphide poisoning
Microscopic features | No. of cases | Percent |
---|---|---|
Congestion | 31 | 68.9 |
Microvacoualization | 26 | 57.8 |
Hydropic degeneration of hepatocytes |
22 | 48.9 |
Mononuclear infiltration | 24 | 53.3 |
Microvesicular steatosis | 22 | 48.9 |
Macrovesicular steatosis | 14 | 31.1 |
Bile pigment in the cytoplasm of the hepatocytes |
12 | 26.7 |
Central venous congestion | 9 | 20 |
Sinusoidal dilation | 5 | 11.1 |
Centrilobular necrosis | 8 | 17.8 |
Portal congestion | 9 | 20 |
Hemorrhage | 10 | 22.2 |
Patchy necrosis | 7 | 15.6 |
Sinusoidal clusters of polymorphonuclear leukocytes |
6 | 13.3 |
Table 3: Histopathological findings of lung in cases with fatal aluminum phosphide poisoning
Microscopic features | No. of cases | Percent |
---|---|---|
Congestion | 33 | 73.3 |
Edema | 31 | 68.9 |
Hemorrhage | 31 | 68.9 |
Collapse of Alveoli | 22 | 48.9 |
Alveolar thickening | 16 | 35.6 |
Alveolar wall disturbance | 6 | 13.3 |
Dilated capillaries | 8 | 17.8 |
Table 4: Histopathological findings of brain in cases with fatal aluminum phosphide poisoning
Microscopic features | No. of cases | Percent |
---|---|---|
Mild capillary dilation and congestion of cortex |
26 | 57.8 |
Cerebral oedema | 27 | 60 |
Cerebellar edema | 24 | 53.3 |
Subaracnoid hemorrhage | 2 | 4.4 |
Intraparenchyma hemorrhage | 3 | 6.7 |
Degenerated Nissel granule in the cytoplasm and deeply stained degenerated eccentric nucleus in brain cortex |
28 | 62.2 |
Degenerated neuron and infiltration of round cell in to the molecular layer in cerebella |
27 | 60 |
Table 5: Histopathological findings of kidney in cases with fatal aluminum phosphide poisoning
Microscopic features | ;No. of cases | Percent |
---|---|---|
Glomerulus congestion | 37 | 82.2 |
Intraparenchymal congestion | 32 | 71.1 |
Tubular degeneration | 16 | 35.6 |
In gross (macroscopic) examination, almost all the vital organs were found to be congested. The lungs were heavy, edematous and congested.
In microscopic examination, histopathological changes observed in the all of organs (Tables 2 to 5).
On microscopic study, the liver showed central venous congestion, microvacuolizition, degeneration of hepatocytes and mononuclear infiltration were the most frequent histopathological findings. (Table- 2).
Microscopy of the lungs revealed congestion, edema, and hemorrhage, collapse of alveoli, alveolar thickening, alveolar thickening, alveolar wall disturbance and dilated capillaries and round cell infiltration around bronchioles (Table-3). Microscopic investigation of the brain tissue showed distinct changes due to the effect of aluminum phosphide. Findings in the brain tissue revealed degenerated Nissel granule in the cytoplasm and deeply stained degenerated eccentric nucleus in brain cortex. Degenerated neuron and infiltration of round cell in to the molecular layer in cerebellar tissue and cerebral oedema were the most frequent findings in microscopic features of brain tissue (Table- 4).
Changes in the kidney included glomerulus’s and intraparanchymal congestion (Table- 5). In microscopic feature of spleen, congestion was only histopathological finding in this study that observed in 75.6% of cases.
Discussion
Acute pesticide poisoning is an important cause of morbidity and mortality in Iran and worldwide. ALP is the most common type of pesticide causes death in Iran4.
ALP is used for suicidal purpose, and use of it is increasing rapidly, because it is cheap, easily available and highly lethal. Acute exposure to ALP is highly toxic with high mortality rate.
In present study we found many histopathological changes in victims of ALP fatal poisoning. These results are similar to findings which obtained by other researchers.
In previous studies, a significant feature visualized during autopsy by naked eye was that all the major vital organs were found to be congested12,15,16. It is accordance with our finding. Phosphine is rapidly absorbed throughout the gastrointestinal tract after ingestion and it is partly carried to the liver by the portal vein17. Congestion of the liver and other vital organs, in gross and microscopic pathology examination were observed in almost of our cases. This finding suggested the cellular hypoxia during ALP poisoning. Previous studies suggested that phosphine is a mitochondrion poison and has cytochrom oxidase inhibitor11. Similar observation has been reported by previous studies13,15. In our study, the most common microscopic finding in the liver was sinusoidal congestion that it was accordance with other authors13,15-19. Microvacuolizition was another finding that was seen in many of our cases. It was accordance with previous study, which has reported fine isomorphic cytoplasmic vacuoles in liver histopathology of ALP induced poisoning17.
Microvesicular and macrovesicular steatosis were the other histopathological findings observed in our liver’s cases. This is similar to finding of previous study17. They have reported macrovesicular steatosis in 13.2% of cases. Fatty changes have reported by some other authors13,15,19. Hydropic degeneration of hepatocytes was seen in our cases. It was accordance with previous report14. In this study, hemorrhages was observed in 22.2% of cases. Us Sinha et al was reported hemorrhage in 56.6% of cases. They also have reported sinusoidal dilation (54.72%), centrilobular necrosis (43.3%), bile stasis (49.06%), mononuclear infiltration and fatty changes (20.75%) that were accordance with our study with different percent. However, they had not reported microvacuolizition, patchy necrosis, portal congestion, that were seen in our study. Saleki et al were found central vein congestion in 60.5% of cases that was 20% in our study; they also have reported sinusoidal congestion, sinusoidal clusters of polymorphonuclear leukocytes (31.6%), Microvacuolizition (94.7%), macrovesicular steatosis (13.2%) and hepatocyte nuclear fragmentation (15.8%) in cases. These findings supported by previous studies18,20.
In the lung microscopy, congestion was the most common finding in our study (73.3%), follow by oedema, hemorrhage, collapses of alveoli, alveolar thickening, and dilated capillaries. These data supported by Us Sinha et al, although they differ in respect to percentage variation who observed congestion (100%), alveolar thickening (98.11%), edema (92.45%), dilated capillaries(81.31%) and hemorrhage (58.49%). We also have found gray or red hepatization and round cell infiltration around bronchioles in (17.8%) of cases, this data obtain by other researchers12. For example, Siwach et al observed congestion, thickening of alveoli by haemolysed red cell, oedema, and dilated capillaries19. In our study disturbance of alveolar wall was seen in 13.3%, that wasn’t reported in other previous studies.
Histopathology of the kidney showed congestion of parenchyma and tubular degeneration were the major histopathological findings in present study. Similar findings are described by Us Sinha et al, but they have observed infiltration (62.2%) and lobular dilation (37.74%) that we have not observed. Also Siwach et al and Chugh et al were reported regeneration of tubular epithelium in their studies that we did not observe.
Arora et al have seen dystrophic calcification of kidneys in those cases that died after 72-96 hours of ingestion15, but we could not found this change in kidney pathology. Chugh et al have reported congestion, area of tubular degeneration and regeneration and necrosis in their cases12.
In our study, histopathological examination of the brain tissue showed mild capillary dilation and congestion of cortex, cerebral oedema, and cerebellar oedema. Similar findings observed by previous reports but with higher frequency13,15.
Also we observed degenerated Nissel granule in the cytoplasm and deeply stained degenerated eccentric nucleus in brain cortex and degenerated neuron and infiltration of round cell in to the molecular layer in cerebella, it was accordance with previous studies21. Subarachnoid hemorrhage (SAH) was observed in few of our cases that never have seen in other studies.
Morphological changes in various organs observed in this study are similar to those produced by hypoxic injury due to shock. These hypoxic changes in various organs in ALP could be secondary to shock produced by phosphine acting on circulating system or by direct effect of phosphine itself13. Similar observation have reported by Arora et al and Singh et al15,18. Shock produced by ALP poisoning is refractory to usual treatment and irresponsibility to dopamine12. Arora et al observed that in ALP intoxication cardio-respiratory system affected and is the major cause of death20.
It should, however, be noted that our study was erformed on the basis of multi-organ histopathology in fatal ALP poisoning in forensic cases and post – mortem histological changes was an important limitation in interpretation of our findings in present study.
In conclusion, based on our finding the histopathological changes in many of vital organs are the most important findings in fatal ALP poisoning. These findings can used for diagnosis of cause of death in ALP intoxicated suspected forensic cases.
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Running Title
Histopathological Effects of Aluminum Phosphide
Corresponding address:
Dr. Kambiz Soltaninejad, Laboratory of Forensic Toxicology,
Scientific and Educational Center of Legal Medicine Organization of Iran, Tehran
Tel. +982155613731, Fax. +982155613731
Email : kamsoltani (at) yahoo.com