Under the Microscope: The Pathologhy of Sudden Death

 

Virtually all forensic pathologists deal not only with criminal,  suspicious, accidental and suicidal deaths, but with a wide range of deaths from natural causes. Many of these are sudden, unexpected, clinically unexplained or otherwise obscure,  even though there need be no unnatural element in their  causation.

It is good that such a large substrate of natural deaths is available to most forensic pathologists: the situation where they deal exclusively with trauma and crime is professionally unhealthy, as they become progressively more out of touch - - with morbid anatomy, and lose daily contact with disease processes and uninjured tissues and organs. Involvement with natural death means frequent professional intercourse with clinicians and non-forensic pathologists, with all the consequent benefits of cross-fertilization of knowledge and ideas. To work in a totally forensic vacuum is to lose touch with pathological and clinical reality, which is essential for a medico-legal expert to retain a sense of proportion and an awareness of contemporary medical advances.

Another indispensable benefit of sustained experience in natural disease is the fact that some of the most difficult problems in criminal and litigious cases arise not out of gross, rapidly fatal, trauma, but in deaths where concurrent natural disease or complications after trauma lead to a fatal outcome. The assaulted victim that dies later from a stroke or the negligent minor accident that has a fatal pulmonary embolism - these can pose far greater difficulties over causation than a gunshot wound or a stabbing. In this chapter no attempt is made to duplicate the detailed descriptions of disease processes provided in a score of illustrious textbooks of pathology, but a survey will be offered of the spectrum of causes of sudden or unexpected death as commonly encountered by forensic and 'coroner's' pathologists.

The definition of a sudden death varies according to authority and convention. The World Health Organization definition is of death within 24 hours from the onset of symptoms, but this is much too long for many clinicians and pathologists; some will only accept death within one hour from the onset of illness. We have to also bear in mind that a death may appear sudden and unexpected to an outsider but need not have been so from the point of the pathological disease process. The deceased may have been symptomless and utterly unaware of his chronic disease or he may have had symptoms but interpreted them as harmless. Also, fear, lack of human contact or his own disposition may have prevented him mentioning symptoms to anyone, including a doctor.

In many jurisdictions, deaths may only be certified by an attending physician if he has seen the patient recently and is satisfied that the death was caused by a potentially lethal disease from which he was aware the patient suffered. The fact that, without autopsy, this physician is wrong in his belief in between 25 and 50 per cent of cases cannot concern us at the moment, but the relevance is that, where a clinical doctor cannot so certify, the death is usually reported for medicolegal investigation. In many countries such notifications form by far the largest proportion of medico-legal autopsies, and in England and Wales they account for some 80 per cent of coroner's autopsies, the remainder being suicide, accident and homicide. The description 'sudden' or 'unexpected' is not always accurate, as 'unexplained' is an equally common reason for medico-legal investigation. Here the clinician is unable to offer a cause for the death, though the patient was under medical care. Even after autopsy, the cause of death may still not be revealed and this problem of the obscure autopsy is discussed elsewhere. In sudden death, the immediate cause is almost always to be found in the cardiovascular system, even though topographically the lesion is not in the heart or great vessels. Massive cerebral haemorrhage, subarachnoid bleeding, ruptured ectopic pregnancy, haemoptysis, haematemesis and pulmonary embolism, for example, join with heart disease and aortic aneurysms to contribute most of the vascular system reasons for sudden, unexpected death.

Complications in coronary atheromatous lesions

ULCERATED PLAQUES

The simple endothelial thickening develops to involve the media and usually becomes infiltrated with lipids. Whilst the covering endothelium remains intact, the danger to life is confined to the luminal reduction from the bulge of the enlarging plaque. When the fibro endothelial cap begins to break down under the pressure and erosion of the central necrosing process, the plaque may rupture into the lumen. This has several consequences, which may precipitate acute symptoms or even death.

Haemorrhage often occurs within an atheromatous plaque, usually into the softened, necrotic centre. This 'subintimal haemorrhage' may give rise to a sudden reduction in the blood-carrying capacity of a coronary artery and cause sudden death. The source of the bleeding is somewhat controversial, but the best explanation is that it comes from rupture  of small blood vessels  in the periphery of a plaque. A normal coronary artery does not have a blood supply to the intima - - but, in the disorganization frequently associated with the distorted microanatomy of a diseased coronary artery, such vessels may lie within the intima and be eroded by extension of the degenerative process.

Haemorrhages, both fresh and old, can often be demonstrated in histological sections of atheromatous plaques. It is reasonable to presume that such a bleed may be precipitated by some sudden rise in blood pressure from exertion or emotion, though, if a vessel is sufficiently eroded by atheroma, such a precipitation is not strictly necessary for such an event to take place. The sudden release of blood into an atheromatous lesion can rapidly enlarge it and may raise the cap of the plaque towards the other side of the already stenosed lumen. It may even rupture the plaque: some subintimal haemorrhages may track circumferentially, causing a 'mini dissection'

Whatever the precise origin of the blood, it is clear that subintimal haemorrhage is a potent factor in rapidly reducing the available lumen of a coronary artery - and sometimes precipitating thrombosis by further stretching and damaging the overlying intimal cap.

CORONARY THROMBOSIS

The atheromatous plaque may not undergo these more dramatic changes, but progressive internal necrosis may erode the luminal surface and expose the fibrofatty contents. This loss of normal covering endothelium then forms a nidus for thrombus formation, which may gradually accrete in layers so further reducing the lumen or even occluding it, especially if a combination of lesions causes the plaque to expand at the same time as roughening the surface. Thus mural thrombus may completely block or severely narrow the residual lumen, with d the consequences of reduced blood flow to the distal myocardium.

A narrow lumen is by no means. Essential to the formation of thrombosis, as it may occur in the abnormally wide, virtually aneurysmal, coronary arteries sometimes seen in aged people. The lumen may be up to a centimetre wide yet be firmly thrombosed, presumably solely because of damage to the intima. Thrombosis often occurs in recanalized vessels, secondary thrombosis taking place after organization and re-establishment of a lumen through the previous block.

Multiple coronary thromboses are by no means unusual. Many are post-infarct, the original thrombus causing myocardial necrosis and the resulting stasis in circulation, together with the thrombogenic effect of tissue damage leading to sluggish flow of readily coagulable blood.

It has also been noted that coronary thrombosis may be accompanied by thrombotic lesions elsewhere in the body. For example, a coronary thrombosis may be followed by a pulmonary embolus from thrombosed leg vein - and the converse may also occur in non-fatal pulmonary embolism. The coagulability of the blood, together with circulatory stasis, aided by immobility in bed, are obvious factors.

The autopsy demonstration of an acute lesion in the heart, such as an early myocardial infarct, can have profound medico-legal implications. In a fatal traffic accident, or even rail or air crash, the proof of an acute disabling myocardial lesion in the driver may be vital in the investigation of the event and the apportionment of legal liability. In potentially criminal deaths, the presence of a recent infarct again may be relevant in causation or as a contribution to the death. It is thus important to make a full histological 'search for evidence of myocardial fibre damage, using all the methods available, including histochemical and fluorescent techniques. The macroscopic appearances of myocardial infarction are described with a considerable lack of uniformity in most  pathology texts, partly because of the varying ages of infarct that the authors depict. The age of an infarct is notoriously difficult to establish in the human, as the onset of clinical symptoms, however dramatically abrupt, are often much later than the onset of the pathological lesion precipitated by a coronary occlusion. In animal experiments, a coronary vessel can be ligated at zero time and serial sacrifices made at different intervals to gain an accurate estimate of the age of the infarct. In the human, the time of chest pain and shock cannot be used in a similar fashion. When a victim of coronary disease dies say, 8 hours after the onset of acute symptoms, though one might expect an early infarct to be visible histologically or histochemically, not infrequently a demarcated yellow or tigroid area of necrosis is present, which must be several days old.

The laminar infarct goes through the same cycle of changes, but this is often less intense. Eventual fibrosis may be widespread but remains thin, often subendocardial, especially on the left ventricular aspect of the interventricular septum where a wide glistening sheet may obscure the underlying muscle. The apex also may show widespread fibrosis and all muscle may be replaced in this region, sometimes leading to a cardiac aneurysm on the free wall. Infarcts may be transmural, extending from epicardium to endocardium, or they may be confined to the inner zone. It is almost impossible to have an infarcted area confined to the outer subepicardial zone because of the topography of the coronary supply.

The papillary muscles are usually involved,  being particularly vulnerable to ischaemia as they are at the end of the line of coronary supply. The central part of the muscle may necrose and even rupture. Infarction usually spares the immediate subendocardial zone, the three or four most superficial layers of fibres surviving, wen though they may show ischaemic damage. They presumably receive enough oxygen and nutrients from the ventricular blood to survive, though this does not seem to prevent deposition of mural thrombus over the infarcted area.

Fluorescent methods have been applied to demonstrate - - early myocardial infarctions and myocardial degeneration in animal experiments as well as in human heart either by using a fluorescent dye, e.g. acridin orange to stain unfixed cryostat sections or paraf5n sections or utilizing the fluorescent properties of eosin in the HE-stained myocardium. Intravenously or intraperitoneally injected tetracycline has also been used in experimental infarction for demonstration of the perfused region in myocardium. Acridin orange stained cryosections of intact myocardium show golden brown fluorescence which turns into greenish fluorescence with increasing ischaemia time whereas eosin fluorescence of normal myocardium in paraffin-embedded samples show olive-geen fluorescence which turns into yellow in injured tissue. Post-mortem autolysis does not seem to have any significant effect on the fluorescence but the high percentage of wrong positive samples indicates that at least eosin fluorescence is obviously too sensitive injury marker capable of demonstrating agonal ischaemic changes. A major handicap common to all classical histochemical staining methods is that the basis of these colour reactions is poorly understood. Considering the possible legal implications, it is not reasonable to use such diagnostic methods for medico-legal purposes, when their diagnostic significance, to say the least, is questionable and one does not know for sure what the methods are actually measuring.

Ruptured heart is the most common cause of a haemopericardium and cardiac tamponade, the rupture always occurring through an infarct. The softened, necrotic muscle gives way from the internal pressure of the ventricular blood during systole, there being no equalizing rise in external pressure. Hypertension will increase the risk, but a more potent factor is a senile, soft myocardium, so that the elderly woman is a common victim of a ruptured heart. This by no means excludes younger men if the infarct is extensive and transmural. The most common area for rupture is the more distal part of the free wall of the left ventricle. The septum occasionally ruptures and the consequent left-right shunt, whilst the patient survives, provides a classical diagnostic sign for the stethoscopes of clinicians. The rupture does not take. place in the early stages of a new infarct, but after a day or two when necrotic softening is well established. The blood usually tracks through tortuous channels between muscle bundles, rather than bursting a direct fistula from ventricle to pericardial sac. The infarcted area may not always be obvious, as the haemorrhagic patch may obscure it, but histologically the ragged tissues and the periphery may be seen to be necrosed.

Haemopericardium is the pathological condition found at autopsy and is not quite synonymous with 'cardiac tamponade', which is a clinical state caused by the progressive accumulation of blood within the closed pericardial sac. As the external pressure rises, the heart cannot fully expand in diastole to allow filling from the great veins. As input volume falls, so does stroke output. The venous drainage is dammed back so that congestion and cyanosis of the face and neck occur, until a fatal endpoint is reached.

Most sudden deaths from coronary insufficiency do not have myocardial infarction, even when the most sophisticated techniques are employed for its detection. Neither do the majority have a coronary thrombosis, though severe coronary stenosis is by definition present. The rare case of myocardial infarction with only moderate or even minimal coronary atheroma has to be relegated to the realms of mystery in the present state of knowledge, unless some embolism cause can be found. Some pathologists invoke 'spasm' of the coronary arteries when the vessels show minimal atheromatous stenosis, but this is a hazardous diagnosis for a pathologist to make. Though spasm is certainly seen by clinicians when performing cardiac catheterizations or cardiac operations, it can never be a morphological diagnosis at autopsy, for obvious reasons.

Fatal aneurysms of other vessels are rare, apart from the cerebral arteries. Atheromatous bulges can occur on the iliac and femoral vessels, and sometimes in the mesenteric arteries. Polyarteritis nodosa can produce mini-aneurysms from the inflammatory process eroding the wall, but death

is not caused by the direct effects of rupture, but by vascular problems in the coronary, renal and other arteries. Infective mycotic aneurysms are rare in civilian practice, as are traumatic arteriovenous fistulae, but are not uncommon.

 

Acknowledgements:

www.aived.nl    AIVD – @Erik Akerboom ©

www.politie.nl  Politiekorpschef  @Janny Knol©

www.politie.nl WEB Politie - @Henk van Essen©

 

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