Ultrastructure of acute ammonia toxicity in the human lung

A tanker truck carrying anhydrous ammonia (NH3) fell off a freeway, releasing a dense cloud of NH3 gas, killing several people. The driver was dead upon impact. To our knowledge, pulmonary NH3 toxicity in humans has not been studied previously by electron microscopy (EM). Therefore, in two cases, the paraffin-embedded tissue blocks of lung were deparaffinized and reembedded in plastic for 1-mu sections and EM examination. The lung tissue of a third case, the truck driver, was similarly processed as a control. Light-microscopic pulmonary findings in the acute NH3 deaths included denudation of the tracheobronchial epithelium, edema of the lamina propria, and marked alveolar edema, congestion, and hemorrhage. In contrast, in the truck driver's lungs, the bronchial epithelium was intact, and there was no gross odor of NH3. Massive pulmonary hemorrhages in his lungs were attributed to trauma rather than NH3 inhalation. EM examination of the lungs of the truck driver showed no discernible toxic alterations in either the capillary endothelial cells or the Type I or II alveolar epithelial cells, and alveolar and capillary basement membranes were intact. In contrast, EM study of the lungs from two individuals dying acutely of NH3 inhalation showed marked swelling and imbitional edema of Type I alveolar epithelial cells; however, alveolar basement membranes and capillary endothelial cells appeared as usual. These electron-microscopic findings demonstrate the Type I epithelial cell to be the target cell of acute alveolar wall injury in NH3 inhalation.     

Ultrastructural pathology of the alveolar apparatus in experimental drowning

Investigations were carried out on anaesthetized rats which by a tracheotomy tube actively aspirated liquids of different osmolarities covering a range from tap water to 2.9% NaCl solution. In every range of osmolarity, the ultrastructural alterations show areolar limitations and different stages of development. In freshwater the influx of liquid causes a hypoxemic-dysoric alveolose with diffuse of pulvinate oedematous swellings of all compartments of the blood-gas-barrier, cytolysis, karyolysis, membrane desintegration, hydropic alterations of the (cell) organelles, dilatation of the drainage tracts of the alveolar interstitium. Vesicular transformation caused by a dilatation of the pinocytotic system ending in endothelial and epithelial vesiculation. Salt-water drowning leads to a hypoxemic alveolose with a marked compaction of the matrix. The epithelium shows many alterations of the surface, numerous protrusions, constrictions and expose of the basement membrane (villous transformation). Erythrocyte sludge and thorn-apple-shaped erythrocytes are found in the capillaries. Application of electron microscopy in the diagnosis of drowning allows a more reliable classification and, correspondingly, decisive improvements of the reliability of lightmicroscopical findings.     

Is the appearance of macrophages in pulmonary tissue related to time of asphyxia?

In order to connect the appearance of macrophages and giant cells in pulmonary tissue with the time of asphyxia the authors analyzed 50 asphyxiated human lungs paying their attention on the number of alveolar and interstitial macrophages and giant cells. They compared histological specimens of 25 asphixiated humans lungs following a slow asphyxia (30 min or more) with 25 histological specimens of asphyxiated human lungs following a rapid asphyxia (10-15 min). Alveolar and interstitial macrophages and giant cells per section, were considered and numbered. Controls were done on histological examination of traumatized lungs. In the pulmonary alveoli following on acute asphyxia there were 27.7+/-4.4 macrophages per section. Subjects dead after a slow asphyxiation showed 68.2+/-7.1 alveolar macrophages per section (p<0.001). Interstitial macrophages were also frequently present. No differences are detectable in the number of polynuclear giant cells between rapidly and slowly asphyxiated human lungs. The number of alveolar and interstitial macrophages per section can be considered as a further histological evidence of a slow asphyxia and can differentiate a slow asphyxia from an acute one.     

Histomorphologic lung findings in long-term artificial respiration with special reference to extreme continuous artificial respiration using pure oxygen

The respirator lung is characterized histologically in the first exudative phase by capillary congestion, intra-alveolary edema, hyaline membranes and in most cases by concomitant inflammatory alterations. In the following irreversible phase, fibrous organization processes dominate and show a variable tendency towards pulmonary fibrosis. In 27 cases with long-term artificial respiration from 4 days to 12 weeks, mainly the proliferative alterations were investigated. In 18 cases, the histopathological findings indicated fibrosis of the alveolar septa with disseminated distribution. In 9 cases, focal fibrosis with obliterations of alveoli prevailed. The extent of pathological results in the lungs does not correlate with the duration of artificial respiration. In cases of artificial respiration with pure oxygen, there is a special toxic component, which is illustrated by a young woman with polytraumatism who was administered artificial respiration for 5 weeks with pure oxygen. She died from respiratory insufficiency with severe pulmonary fibrosis. As different pathogenetic factors may cause irreversible pulmonary fibrosis, histomorphological classification is difficult later and, moreover, forensic problems result.     

2009 H1N1 Fatalities: The New Mexico Experience

Abstract: Histopathologic features of New Mexico 2009 H1N1 fatalities have not been representative of those reported nationwide. We retrospectively reviewed medical records of all New Mexico 2009 pandemic influenza A (pH1N1) fatalities (n = 50). In cases in which autopsy was performed (n = 12), histologic sections and culture results were examined. In contrast to previously published studies, the majority of our fatalities did not have diffuse alveolar damage (DAD) (2/12; 16.7%). Common findings included pulmonary interstitial inflammation and edema, tracheobronchitis, and pneumonia. Two cases had significant extra‐pulmonary manifestations: myocarditis and cerebral edema with herniation. The majority had a rapid disease course: range from 1 to 12 days (median, 2 days), and Native Americans were disproportionately represented among fatalities. These findings suggest that New Mexico H1N1 fatalities generally did not survive long enough to develop the classic picture of DAD. Pathologists should be aware that H1N1 may cause extra‐pulmonary pathology and perform postmortem cultures and histologic sampling accordingly.     

人体颅脑贯通枪创后心肌和肺的超微结构观察

本文报告6例人体颅脑贯通枪创后2小时所取心肌和肺的超微结构变化。6例心肌及肺的超微结构基本相似。心肌最明显的变化是:Z 带排列不规则,灶性肌原迁维溶解,线粒体肿胀、基质电子密度降低和嵴消失,间质水肿。肺组织的明显变化是肺泡隔和肺间质增宽伴电子密度降低,肺泡隔毛细血管内中性粒细胞聚集,肺间质或肺泡腔内中性粒细胞浸润。本文对主要病理变化的意义和发生原理进行了讨论,认为肺间质水肿与神经源性肺水肿有关,由于伤后经过时间长短不同或有无颅内高压形成,而出现间质性水肿或肺泡内水肿。心肌的变化与缺氧有关。     

Pulmonary edema in fatal heroin overdose: immunohistological investigations with IgE, collagen IV and laminin - no increase of defects of alveolar-capillary membranes

Pulmonary edema complicating heroin overdosage is a well recognized entity and regarded as the major mechanism contributing to death in heroin addicts. It's pathogenesis is unknown, several mechanisms are discussed: hypoxia-induced increase of pulmonary capillary permeability, depressed myocardial contractility, centrally induced respiratory depression, primary toxic effects on the alveolar capillaries and acute anaphylactic shock. The present study included opiate-related deaths (n=23) and a control group of sudden cardiovascular deaths (n=12) to verify the hypothesis, that defects of the alveolar capillary membranes and/or an acute anaphylactic reaction leads to pulmonary congestion, edema and hemorrhages. Lung specimens were obtained from these 35 autopsies of persons autopsied in the Institute of Forensic Medicine, University of Bonn, in 1997 and 1998. All specimens were examined with hematoxylin-eosin, prussian blue and investigated with immunohistological methods using primary antibodies against collagen IV, laminin and IgE. Defects of the basal laminae of the alveoli were found, demonstrated by laminin and collagen IV, and the number of IgE-positive cells was counted in both groups. There was an increased but not significant number of IgE-positive cells in the heroin-group and defects of the epithelial and endothelial basal laminae were found in both groups without significant differences.     

Iatrogenic histopathological findings. A systematic compilation

A series of drugs and diagnostic agents are deposited (mostly in a metabolized form) in various human organs or cause characteristic histological pictures there. These iatrogenic alterations can frequently be recognized even after a short time and can be demonstrated for varying lengths of time. They may become relevant in various respects in terms of forensic medicine: (1) as an aid to identification in unknown cadavers or cadaver parts, (2) in establishing iatrogenic damage, (3) as an evaluation of findings in sudden and unexpected death from natural causes, and (4) in problems of insurance law with regard to morphological demonstration of chronic drug abuse, especially abuse of analgesics. In a systematic review broken down according to organs, a series of these drugs or diagnostic agents are presented with the morphological alterations they caused, the methods of histological demonstration and the duration of identifiability.     

Diagnostic dilemma of sudden deaths due to acute hemorrhagic pancreatitis

Sudden death due to acute pancreatitis has been rarely determined. A review of 3305 autopsies performed between 1991 and 2001 at the Council of Forensic Medicine found 12 cases (0.36%) with sudden death due to acute hemorrhagic pancreatitis without symptoms. A history of chronic alcohol ingestion was obtained from family in four cases (33%), and no stones were found in the bile ducts or in the gall bladders. During the autopsies, hemorrhage and edema were localized on the head of the pancreas in three cases and the whole pancreas in nine cases. The most common extrapancreatic pathology was found in the lung including pulmonary edema, alveolar hemorrhage, pleural effusion, and pulmonary congestion. There was no correlation between pulmonary and pancreatic damage. It is suggested that the forensic pathologists who are dealing with sudden unexpected death must not ignore the examination of pancreatic and extrapancreatic regions to avoid missing acute pancreatitis.     

Exogenous Lipoid Pneumonia as a Contributory Factor in a Drug‐related Death

Postmortem investigation often reveals various conditions, which may or may not have played a part in the death of the individual. The case of a 32‐year‐old woman is reported, with a long history of drug addiction. She was found dead in her bed. The autopsy revealed diffuse pulmonary edema with congestion of the lungs, brain, liver, and spleen. Microscopic examination of the lungs showed multiple intra‐alveolar and interstitial foamy macrophages and extracellular fat droplets surrounded by polynuclear giant cells. Death was attributed to acute polydrug intoxication. As microscopic examination had revealed severe pulmonary lesions, lipoid pneumonia was considered as a contributing factor to death. Lipoid pneumonia is an uncommon entity with the characteristic radiograph features and histologic findings of alveoli filled with vacuolated, lipid‐laden histiocytes. It can be either exogenous or endogenous in cause, based on the source of the lipid. Exogenous lipoid pneumonia usually results from aspiration or inhalation of fat‐like material, such as mineral oil or petroleum‐based lubricants and decongestants, resulting in pulmonary inflammatory reactions.     

Brain changes in parathion poisoning: observations in 42 cases

A total of 42 cases were examined neuropathologically to determine possible toxic changes occurring in the brain after parathion intoxication. Sporadic anoxic alterations were observed in 7% of 41 cases in which the cause of death was acute intoxication. Nearly all cases (93%), however, showed marked hyperemia, often coupled with small reactionsless, periventricular hemorrhages which occurred in 40% of the cases. In one third of the cases (33%) there was moderate swelling of the oligodendroglia. Whereas histological evidence of edema was found in nearly one third of the cases (30%), comparison of the brain weights in these subjects with those of a large comparative collective showed definite pathologic brain weights in only five cases (12%) with 95% confidence limits. It is true that in 18 cases (42%) the brain weight was above the normal value if the confidence limit is ignored. Pronounced anoxic alterations were observed in only one case in which the individual survived the acute intoxication for 4 weeks after initial respiratory arrest. Predominantly toxic changes, however, could not be detected in any of the cases examined. This negative morphologic finding does not agree with the physiologic alterations reported by other investigators using animal models; they considered the cause of death in cases of parathion intoxication to be the result of toxic paralysis of the respiratory center. The literature was discussed.     

Peri-mortem skin lesions caused by regurgitation of gastric juice. 2 case reports and differential diagnostic considerations

Two cases of regurgitation of gastric juice peri mortem are reported which resulted in lesions of the thoracic skin and led to the suspicion of being caused by another possibly dangerous chemical agent. In both cases, however, other causes of death could be established. Neither could any foreign chemical substances be detected by extensive toxicological investigations nor were any alterations of esophagus and gastric mucosa revealed in the course of the autopsy. Histological investigations demonstrated a circumscribed recent necrosis of the epidermis and dermis. Therefore, regurgitation of the acidic gastric content as the agent impairing the skin was most likely. The impressive histological appearance of the peri mortem regurgitation skin lesions lesions may be due to the circulatory arrest as well as stagnation of vital cellular reactions and repair mechanisms, dehydration of the altered tissue and postmortem permanence of the impairing agent.     

Amphetamines in washed hair of demonstrated users and workplace subjects

Cardiovascular complications of cocaine abuse include myocardial ischemia and infarction, dysrhythmias, cardiomyopathies and aortic dissection. The case in point pertains to a 26-year-old, Caucasian male, substance abuser who suffered a thoracic aortic dissection following the use of crack cocaine. The autopsy and histological findings showed a connective tissue abnormality including a focal microcystic medial necrosis and a fragmentation of the elastic fibers in the arterial walls. Blood concentrations of cocaine and benzoylecgonine, taken individually, were considered to be within a potentially toxic range. Blood concentrations of methadone also indicated use of this drug at the same time. The small amounts of morphine found in the blood and urine were compatible with heroine or morphine use more than 24 h before death.     

Reconstruction of root morphology in skeletonized remains with postmortem dental loss.

A reversible technique is presented in which the root morphology of missing teeth in skeletonized human remains can be reconstructed for the purpose of radiographic comparison and postmortem identification. In this technique, which is based upon pilot studies with skeletonized mandibles of archival remains, the alveolar socket walls are sealed with a coat of cyanoacrylate cement and injected with a mixture of vinyl polysiloxane and barium sulfate. Radiographs are produced with the radiopaque mixture in place, which highlights the antemortem morphology of the roots. Subsequently, the impression material is removed, resulting in no gross alteration of the evidence. The radiographs made with this technique, as well as the impressions, can be stored for later use at a trial or pending the discovery of antemortem dental evidence.     

Postmortem Diagnosis of Fatal Hypothermia by Fourier Transform Infrared Spectroscopic Analysis of Edema Fluid in Formalin-Fixed,Paraffin-Embedded Lung Tissues

The goal of this study was to investigate whether pulmonary edema could become a specific diagnostic marker for fatal hypothermia using Fourier transform infrared (FTIR) spectroscopy in combination with chemometrics. The spectral profile analysis indicated that hypothermia fatalities associated with pulmonary edema fluid contained more β-sheet protein conformational structures than the control causes of death, which included sudden cardiac death, brain injury, cerebrovascular disease, mechanical asphyxiation, intoxication, and drowning. Subsequently, the results of principal component analysis (PCA) further revealed that the content of β-sheet protein conformational structures in the pulmonary edema fluid was the main discriminatory marker between fatal hypothermia and the other causes of death. Ultimately, a robust postmortem diagnostic model for fatal hypothermia using a partial least-squares discriminant analysis (PLS-DA) algorithm was constructed. Pulmonary edema fluid spectra collected from eight new forensic autopsy cases that did not participate in the construction of the diagnostic model were predicted using the model. The results showed the causes of death of all these eight cases were correctly classified. In conclusion, this preliminary study demonstrates that FTIR spectroscopy in combination with chemometrics could be a promising approach for the postmortem diagnosis of fatal hypothermia.     

Problems associated with the diagnosis of vitality in burned bodies

The most important signs of vitality in burned bodies are soot deposits in the respiratory tract, the esophagus and the stomach as well as elevated CO-Hb values in the blood. But these findings show only that a person was exposed to fire fumes while alive; they are no indicator for vital heat exposure. As the external findings in burned bodies are often not very conclusive due to postmortem consumption by the fire, the internal findings are all the more important. Macroscopic signs that hot fumes were inhaled may be edematous swelling and vesicular detachment of the mucosa in the pharynx, the larynx and/or the upper section of the esophagus. As histological changes in the respiratory tract soot deposits, vesicular detachment of the epithelium, hyperemia and edema of the tracheal and bronchial mucosa as well as increased secretion of mucus have been described. These findings may partly be absent although the victim was alive during the fire, which can make diagnosis more difficult. Especially in peracute deaths vitality findings are usually sparse. The significance of the macroscopic and histological parameters of vitality was systematically investigated on the basis of our own autopsy material from the years 1996-2002 (88 cases) and compared with the statements found in the literature. In our study material, the vitality parameters were incomplete in 23% of the burned corpses. In 3% of the cases the question whether there was an antemortem heat exposure could not be answered.     

Production of carbon monoxide in cadavers

Carbon monoxide (CO), total hemoglobin (Hb) and carboxyhemoglobin (HbCO) in the blood and reddish discolored body cavity fluids of cadavers which had not been exposed to fire and CO were analyzed. In 13 cadavers found on land, the maximum saturation of HbCO in the blood was 3.6%, and was 10.1% in the body cavity fluids. There was only one case in which the HbCO saturations in the body cavity fluids were more than 10%. In seven drowned bodies found in fresh water, the highest HbCO saturation in the blood was 6.1%, and was 44.1% in the body cavity fluids. There were three cases in which the HbCO saturations in the body cavity fluids were more than 10%. In 12 drowned bodies found in sea water, the HbCO saturations in the blood were not more than 6.2%, and the maximum saturation of HbCO in the body cavity fluids was 83.7%. There were eight cases in which the HbCO saturations in the body cavity fluids were more than 10%. The results seem to indicate that the interpretation of HbCO saturation in the blood would not be affected significantly by the postmortem formation of CO, and that body cavity fluids should not be used for CO determination.     

Injuries of the large arteries of the brain and vital reactions. An electron microscopy study

In 90 forensic autopsies (Craniocerebral injury, gunshot, stabbing, blow, strangulation, etc.), semithin sections of great arteries were prepared from around 770 Epon blocks and checked for vital reactions at the mural and intimal ruptures. In 21 cases in which death had occurred immediately or soon after the trauma, with three exceptions, there was a subsequent electron microscopic investigation. In all six mural ruptures and in five of ten intimal ruptures, thrombocyte aggregates were found at the rupture margins. In five intimal ruptures, the possibility of the occurrence of preparations injuries had to be considered. In five cases, the results of the histological study were negative. The success rate is limited in principle in such a screening test since there are technical difficulties in preparing serial sections on long vessels. Death was rapid and the thrombocytes were observed to adhere to the injured wall sites immediately after the trauma. The "thrombocyte sign" is thus of substantial importance as the earliest local vital reaction. In two control cases (strangulation), thrombocyte aggregates were found at intimal ruptures of the basilar artery, which were regarded as the results of stretching via the vertebral arteries during attacks to the neck. The healing processes of intimal ruptures and traumatic medial necrosis in incomplete ruptures occurring later in life are discussed. Even if a cadaver is a few days old, the histological findings at the level of the thrombocytes can be evaluated.     

Usefulness of combining clinical and radiological dental findings for a more accurate noninvasive age estimation

The aim of this study was to establish correlations of clinical and radiological dental findings, alone or in combination, with chronological age in adults. Dental findings and orthopantomograms of 984 patients (aged 20-60 years; 524 females/460 males) were analyzed. DMF-T index and distance (alveolar bone level, ABL) between cemento-enamel junction and alveolar bone margin were recorded. Additionally, clinical and radiological findings at each tooth crown and root were collected according to the actual status of destruction and restoration, and a total score for each dentition (TSD) was calculated. After univariate correlation analysis, correlation coefficients for ABL and TSD were improved by using square root (sqrt). However, the determination accuracy was still not satisfactory; 90% of the residuals were in the range of about +/-10. The present study showed that clinical and radiological dental findings could not be used, not even in combination, for accurate age estimation as a single method, but that they could support other methods.     

Histological assessment of gestational age in human embryos and fetuses

A light microscopic study performed on 760 human fetuses allows us to define several stages in their visceral development and to relate these to gestational age. The histological examination of most viscera, such as the central nervous system, is useless when the tissue preservation is poor. Nevertheless, three organs may still be studied in macerated fetuses: the lungs (where different glandular, canalar, and alveolar stages of development are evident), the kidneys (where the respective numbers of rows of primitive glomeruli and of generations of mature glomeruli vary after week 22), and the adrenal glands (where neuroblastic nests are normally found between weeks 7 and 26 of gestation). It is important to compare the degree of histological maturation with the clinical, macroscopic, and radiologic data in order to define the profile of maturation proper to each human fetus.