Sudden Natural Death


In addition to performing a postmortem examination on the body of an individual who dies as a result of trauma, forensic pathologists may also examine the body of individuals who have died as a consequence of natural disease processes.
Sudden natural death as investigated by a coroner or medical examiner may have significant medico-legal ramifications in addition to providing valuable information to the deceased’s immediate family and the community as a whole.


The definition of sudden natural death varies between organizations and jurisdictions. Although the World Health Organization defines sudden death as occurring within 24 h of the onset of symptoms, many forensic pathologists would only include cases where the death has occurred within hours of signs and symptoms or where the immediate clinical history is unknown.

Common Causes of Sudden Natural Death

Cardiovascular disease and, in particular, coronary artery atherosclerosis, is the most common cause of death in Western societies.
The resultant myocardium ischemia caused by coronary artery atherosclerosis may lead to a lethal cardiac arrhythmia and be the first sign of occult disease.
Hypertensive heart disease in the presence of normal coronary arteries can lead to sudden death as a consequence of a cardiac arrhythmia. Hypertension can contribute to sudden death by precipitating rupture of an abdominal aortic aneurysm or dissection of the thoracic aorta, or in causing an intracerebral hemorrhage.
Pulmonary thromboembolism is a relatively common cause of sudden death with most cases associated with the predisposing factors of trauma and immobility.
The following discussion examines the varied causes of sudden natural death with respect to the
individual organ systems. The order of the systems examined and the description of each disease process within a particular system, is a reflection of the relative incidences of that disease.


Cardiovascular system

Coronary artery atherosclerosis Coronary artery atherosclerosis is the most common cause of sudden death in Western societies. The stenosis or occlusion of a particular coronary artery results in ischemia of the supplied region of myocardium which may result in acute myocardial infarction and/or a lethal cardiac arrhythmia. Risk factors for coronary artery atherosclerosis include smoking, hypertension, diabetes mellitus, hyperlipidemias, obesity and familial factors.
Coronary artery atherosclerosis tends to occur in the proximal aspects of the left main coronary artery, right main coronary artery, at branching points and the proximal aspects of the left anterior artery and left circumflex arteries. Acute critical occlusion of a vessel may result in the sudden onset of symptoms. The acute change may result from complications within an atheromatous plaque including plaque rupture with subsequent thrombosis of the vessel and sudden hemorrhage into a plaque resulting in loss of luminal area and subsequent myocardial ischemia.
As most forensic cases of sudden natural death due to coronary artery atherosclerosis occur within hours of the onset of symptoms, the pathologist does not usually find acute myocardial infarction upon macroscopic and microscopic examination of the heart. The earliest features of acute myocardial infarction include interfiber edema and contraction band necrosis, findings which typically require hours of survival postinfarction but which can be seen as an artifact of resuscitation.
It is generally accepted that at least 12-24 h of survival postinfarction must occur for the earliest recognizable histological changes to evolve in the heart. One may see eosinophilia of myocardial fibers with loss of nuclear detail followed by neutrophil infiltration, often peaking at about 24-36 h survival postinfarction. Enzyme histochemistry and immuno-peroxidase stains have been used in an attempt to reveal earlier stages of infarction, however, it would appear that these special stains are best demonstrated when infarction is easily seen on routine hematoxylin and eosin-stained sections.
Organization or repair of an acute myocardial infarct is characterized by macrophages removing  necrotic tissue and new blood vessel formation followed by collagen deposition by fibroblasts. Important early complications of acute myocardial infarction include cardiac arrhythmias and congestive cardiac failure. Later complications include ventricular wall rupture, mural thrombosis with embolization, aneurysm formation and cardiac failure.
Hypertensive heart disease Hypertensive heart disease may be reliably diagnosed from the pathological features of an enlarged heart showing concentric left ventricular hypertrophy in the absence of valve disease or cardiomyopathy. Objective evidence for cardiomegaly may be obtained from referring to published studies of heart weight with respect to sex, height, weight and body size. Characteristic hypertensive changes may be observed in the kidney and in older individuals, the lenticulostriate vessels within the basal ganglia of the brain.
Pulmonary thromboembolism Pulmonary thromb o-embolism is a common cause of sudden death especially in individuals with a recent history of trauma and/or immobility. Peripheral venous thrombosis occurs as a result of (1) status of blood flow, (2) damage to the endothelial lining of the blood vessel and (3) abnormalities in blood coagulation. Recent studies have indicated that abnormalities in coagulation factors may have a familial basis with obvious ramifications for immediate family members.
Aortic aneurysm Rupture of an abdominal aortic aneurysm results in sudden collapse from massive exsanguination. Typically an elderly individual, often with the typical risk factors for coronary artery atherosclerosis, complains of severe abdominal pain culminating in collapse from catastrophic hemorrhage. Dissection of the thoracic aorta may cause death as a consequence of rupture into the pericardial sac with subsequent pericardial tamponade, rupture into the pleural cavity resulting in exsanguination or from dissection of major arteries such as the coronary and carotid arteries with associated organ infarction. Aortic dissection may occur in individuals with hypertension and in individuals with genetic disorders of collagen formation such as Marfan’s and Ehlers-Danlos syndrome.
Valve disease Valve disease is a not uncommon cause of sudden death in elderly individuals. The relative decline in the incidence of rheumatic heart disease has resulted in relatively more cases of congenital and degenerative valve disease with dystrophic calcification. Stenotic or incompetent valves lead to compensatory physiologic hypertrophy or dilatation of the heart muscle in order to maintain cardiac output which, however, will eventually result in heart failure and the possibility of lethal cardiac arrhythmias.
The following entities may also occur in older persons, but their relationship to sudden death in young fit individuals belies the rarity of the conditions.
Myocarditis refers to inflammation within the myocardium associated with fibre necrosis. The myocardial inflammation may be a direct result of a viral infection or from the effects of stimulation of the immune system. Depending on the degree of muscle involvement, an individual may suffer with symptoms of cardiac failure or may die as a consequence of a lethal cardiac arrhythmia.
A cardiomyopathy refers to a disorder of heart muscle. A classification of the cardiomyopathies according to the World Health Organization includes (1) dilated cardiomyopathy, (2) hypertrophic cardiomyopathy, (3) restrictive cardiomyopathy and (4) arrythmogenic right ventricular dysplasia. It is believed that some cases of dilated cardiomyopathy may occur as a consequence of the effects of a remote viral myocarditis whereas other etiological factors include exposure to toxins or familial disorders. Hypertroph-ic cardiomyopathy is a genetic disorder characterized by disarray of myocardial fibers on microscopic examination of heart muscle and may be associated with sudden death. Arrythmogenic right ventricular dysplasia shows inflammatory and fibrofatty infiltration of the right ventricle associated with ventricular tachyarrhythmias and is believed to be a cause of sudden death.
In rare cases no morphological abnormality or uncertain anatomical abnormalities are identified at postmortem in individuals thought to have died of a sudden cardiac event. In some of these cases conduction abnormalities such as the long QT syndrome may be responsible for the death. Such cardiac arrhythmias may occur as a consequence of a functional abnormality or may be due to the effects of drugs. Obviously as no definite morphological abnormality can be demonstrated the pathologist is heavily dependent on supportive clinical information in formulating a diagnosis.

Nervous system

Sudden and unexpected death attributable to the central nervous system most commonly occurs as a consequence of intracranial hemorrhage. Individuals with hypertension may succumb to hemorrhages within the basal ganglia, pons or cerebellum. The presence of the resultant hematoma can lead to death from a critical rise in intracranial pressure with obstruction to the flow of cerebrospinal fluid or, especially in the case of pontine hemorrhages, may result in lethal brainstem dysfunction.
Hemorrhage into the subarachnoid space most commonly occurs from rupture of an aneurysm within the circle of Willis at the base of the brain. Less commonly the hemorrhage can be due to rupture of arteriovenous or other vascular malformation. Death is believed to occur due to the volume of blood within the subarachnoid space in addition to autonomic instability.
Forensic pathologists and clinical neurologists are aware of deaths in individuals with epilepsy in the absence of morphological abnormalities. Sudden unexpected death in epilepsy (SUDEP) is not associated with status epilepticus and is believed to relate to cardiac arrhythmias which have been demonstrated to occur during epileptiform seizures.
Although most cases of central nervous system tumors will present with localizing or general symptoms and signs prior to death, in some instances acute hemorrhage into the tumor or other local complications may lead to sudden death with the diagnosis made at autopsy. A rare cause of sudden death due to central nervous system disease is the colloid cyst of the third ventricle. In this condition a thin-walled cyst within the third ventricle causes acute obstruction to cerebrospinal fluid flow with subsequent acute hydrocephalus and death.
Sporadic cases of meningoencephalitis are most commonly associated with Neisseria meningitidis with septicemia and adrenal hemorrhage.

Gastrointestinal system

Sudden death in disease processes occurring in the gastrointestinal system primarily involve massive gastrointestinal hemorrhage. The etiological factors are protean and include esophageal varices, peptic erosions and ulceration and tumors.
Individuals with cirrhosis of the liver from any cause may develop varices of submucosal esophageal veins which are prone to trauma and subsequent massive hemorrhage. The concomitant liver dysfunction results in coagulation abnormalities which exacerbates the hemorrhage.
Peptic ulceration is often associated with the bacterium Helicobacter pylori and may cause torrential hemorrhage if erosion of a submucosal artery occurs. Widespread gastric erosions are seen in severe ‘stress’ of any cause and is believed to relate to increased circulatory glucocorticoids. Uncommonly, benign and malignant upper gastrointestinal hemorrhages may cause fatal hemorrhage.
Acute and chronic pancreatitis is most commonly related to gallstones or excessive alcohol intake but is also seen in hypertriglyceridemia, the vasculitides and other inflammatory conditions. The severe end of the spectrum of inflammation seen within the pancreas, hemorrhagic pancreatitis, can lead to death due to multiple system failure induced by systemic inflammatory mediators in the systemic inflammatory response syndrome.
In cases where medical attention is not sought or in rare cases where the diagnosis is unrecognized, acute surgical emergencies such as acute appendicitis, perforated peptic ulcer, obstructed bowel, mesenteric thrombosis and peritonitis may present as a sudden unexpected death.

Respiratory system

Sudden death is described in individuals with asthma. Analogous to the syndrome of sudden death in epilepsy, individuals with asthma may suffer sudden and unexpected death and not necessarily with a clinical acute asthmatic attack. Although the mechanism is obscure, it is believed to relate to a lethal cardiac arrhythmia.
Acute epiglottitis is an acute infective condition of the epiglottis that is well-recognized in children but which may also occur in adults. The causative organism is usually Haemophilus influenzae. Death results from acute upper airway obstruction.
Pneumonia may lead to ‘sudden death’ in socially isolated individuals and in other cases where the gravity of the infection is not recognized. The common community-acquired causative organism is Streptococcus pneumoniae. Rare cases of Legionnaire’s disease may be seen.
Occult malignant tumors may erode major blood vessels resulting in torrential hemorrhage with exsan-guination and airway obstruction.

Endocrine system

Diabetes mellitus can lead to sudden unexpected death as a consequence of diabetic ketoacidosis. Often, in retrospect, a young individual may have had a history of polydipsia and polyuria and been vaguely unwell before death ensued. Postmortem toxicological examination can reveal a raised glucose concentration within the vitreous humor of the eye. Microscopic examination of the kidney may show vacuolization of the collecting ducts.

Genitourinary system

Sudden deaths in relation to the kidneys and urinary system are relatively rare. An individual may have underlying chronic renal impairment which may deteriorate rapidly from a further insult such as urinary tract infection, dehydration or administration of a nephrotoxic drug. The diagnosis requires collation of all clinical, pathological and toxicological data.
Sudden death may occur as a complication of pregnancy. An ectopic pregnancy usually occurring in the Fallopian tube may rupture causing death from exsanguination from massive intraperitoneal hemorrhage.

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