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Indian Journal of Forensic Medicine & Toxicology

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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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

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