Pathology of Sudden Natural Death

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Determination of cause of death in natural deaths, particularly when the death occurred suddenly, unexpectedly, or in the young, is an important part of forensic autopsy practice, for reasons including the following:

Performance of a complete and thorough autopsy on apparent natural deaths can provide invaluable information in the interest of public health by identifying public health risks and monitoring disease trends

Identification of disease processes and patterns provides epidemiologic data that can be used to control disease outbreaks, identify emerging infectious disease or changes in disease patterns, or to identify reportable diseases, such as meningococcal meningitis, so that close contacts can receive prophylactic treatment

The timely and accurate diagnosis of medically important diseases can have a significant impact on the relatives of the deceased by allowing them the opportunity to seek treatment for certain hereditary diseases in which the presenting symptom may in fact be sudden death

Finally, performance of an autopsy when there is no readily obvious cause of death can provide the deceased’s family and friends with answers, thereby helping with the grieving process

Accidental or intentional injuries comprise the leading cause of death in individuals from ages 1 to 44 years; still, at least half of the deaths coming to the attention of the medical examiner will be due to natural causes. ^{[1, 2]} Most natural deaths are due to cardiac-related disorders, malignancy or infection. In rare cases, a definitive cause of death may not be identified following a complete and thorough autopsy. Although this quite unsatisfying for the pathologist and the family, a “negative” autopsy can still prove to be of vital importance. The lack of a definitive cause may prompt further investigations; rare hereditary diseases, hazardous environmental conditions, unusual toxic exposures, or unsafe consumer products may only be suspected or identified after a complete, detailed and through autopsy rules out more likely causes. ^[3]

Even when a death is unequivocally due to a natural disease process, careful attention should be paid to an individual’s risk factors for that particular disease. A number of common natural diseases can occur spontaneously or can be secondary to a non-natural, injurious event. The inciting event may be recent, but it does not have to be to be; care should be taken when reviewing the decedent’s history. Identification of a non-natural proximate cause can significantly change the manner of death, as illustrated in the example provided below:

A quadriplegic man who had been living in an assisted living facility dies of aspiration pneumonia, which is both natural and is a known complication of quadriplegia. However, the manner of death in this case should be based not on the pneumonia (the immediate cause of death) but on the event that caused the man to become quadriplegic in the first place. If he was quadriplegic due to a non-traumatic myelopathy, the manner remains natural. However, if he was quadriplegic from a gunshot wound to the neck, the manner of death becomes a homicide, because the gunshot wound set in motion the chain of events that ultimately lead to the man getting the pneumonia.

The following image is from the autopsy of a young boy who suddenly collapsed and died during a walk with his family.

See also Autopsy Request Process, The Autopsy Report, Adjuncts to the Forensic Autopsy, Religions and the Autopsy, Autopsy of the Transplant Recipient, Autopsy Rate and Physician Attitudes Toward Autopsy, Universal Precautions and High-Risk Autopsies, Autopsy Quality Control Metrics, and Medicolegal Issues and the Autopsy.

The definitions of “sudden” and “unexpected” are relative. The World Health Organization (WHO) defines sudden death as a death occurring within 24 hours of the onset of symptoms when the death is not instantaneous and not due to sudden cardiac death or sudden infant death syndrome (SIDS) (International Statistical Classification of Diseases, 10^th revision, [ICD-10] code R96.1). ^[4] The definition of sudden cardiac death is most commonly taken to mean death within 1 hour of the onset of symptoms (ICD-10 code I46.1). ^[4] Still other authors may take “sudden” death to be synonymous with “instantaneous” death and, in fact, an ICD-10 code for instantaneous death exists (ICD-10 code R96.0). ^[4]

From the medical examiner’s or death investigator’s prospective, sudden (natural) death is generally viewed in a much broader sense and includes all deaths in which an adequate diagnosis of a lethal medical disease has not been reached before death, regardless of the duration of the illness. ^[3] The definition of “unexpected” is somewhat more straightforward and is based more on the probability that a decedent would have died at that particular time given the individual’s medical history, or lack thereof. Unexpected deaths may occur in previously healthy individuals and in those with known natural disease when the severity of the person’s condition does not explain death. Frequently, the latter situation occurs when the primary physician does not feel the decedent’s medical problems would have likely resulted in death.

A number of terms, acronyms, and abbreviations are used to refer to specific types of untimely death. Commonly used terms include the following:

Sudden cardiac death (SCD): Unexpected loss of heart function within seconds/minutes of onset of symptoms

Sudden unexplained death syndrome (SUDS): Sudden death in an otherwise healthy individual with no cause identified following a complete and detailed autopsy and death investigation; also known as “sudden adult death syndrome” or “sudden arrhythmogenic death syndrome” (SADS).

Sudden unexplained death in children (SUDC): The sudden and unexpected death of a child older than age 12 months, which remains unexplained after a thorough case investigation is conducted

Sudden unexplained nocturnal death syndrome (SUNDS): Sudden death during sleep in a young, previously healthy male, typically of Southeast Asian descent

Sudden unexpected death in epilepsy (SUDEP): The sudden, unexpected, and nontraumatic death of persons with epilepsy in whom the postmortem examination fails to reveal a structural or toxicologic cause of death; the event may be witnessed or unwitnessed and can occur with or without evidence of a seizure (excluding documented status epilepticus

Sudden infant death syndrome (SIDS): The sudden death of an infant younger than 1 year that cannot be explained after a thorough investigation is conducted, including a complete autopsy, examination of the death scene, and review of the clinical history ^[5]

Sudden unexpected infant death (SUID): Infant deaths that occur suddenly and unexpectedly, and whose manner and cause of death are not immediately obvious before investigation ^[5]

The medical examiner is charged with investigating all sudden or unexpected deaths; the determination of what qualifies as either sudden or unexpected is somewhat subjective. ^{[3, 6, 7]} In most cases, the younger the individual or the more sudden the death, the more likely it is to fall under medical examiner jurisdiction, and, likewise to receive an autopsy as opposed to an external examination. Depending on the history and circumstances, the death may be certified by the medical examiner with only an external examination and review of the decedent’s medical history. See the following example:

Two men are found dead in their respective apartments. Both apartments are locked and secured, and there are no signs of foul play. One decedent is 20 years old and was previously healthy. The other decedent is 80 years old and had a history of coronary artery disease with multiple cardiac bypass grafts. The death of the 20-year-old man is significantly more suspicious and more likely to receive a complete autopsy than the older man with a history of heart disease.

Another circumstance in which medical examiners routinely assume jurisdiction over a probable natural death is when there is no other physician available or willing to certify the death.

Sudden natural death in all age groups can result from diseases or conditions arising in any organ system, although conditions affecting the heart, lungs, and brain are the most likely to result in truly sudden death. Before performing the autopsy, all attempts should be made to obtain and review a decedent’s past medical history in addition to any findings/information gathered by the death investigation team. The decedent’s past medical history and symptomatology before death may prove invaluable in interpreting the autopsy findings and in identifying a cause of death.

A complete and thorough autopsy, including external and internal examinations, should be performed by, or under the direct supervision of, a forensic pathologist. ^{[3, 6]} Ancillary tests for microbiology and toxicology can be collected and sent immediately or stored for future use. Depending on the age and demographics, appropriate samples should be obtained at the time of autopsy in anticipation of future studies (eg, saving material for molecular genetic testing). Consultation with specialists in forensic neuropathology and cardiovascular pathology may be necessary in certain cases.

When interpreting pathologic findings and assessing their significance, it is important to keep in mind that people may die with a disease and not from the disease. The likelihood of finding atherosclerotic vessels increases with age and will be present many more times than not, especially in older individuals. One should be careful not to automatically assume that the atherosclerotic disease is the cause of death, and a diligent search for other causes should always be performed.

Both natural and non-natural causes of death may have very subtle or very few findings which can be easily overlooked in the presence of other natural disease processes. ^{[3, 7]} Special attention should be paid to the neck for subtle signs of trauma such as in manual strangulation or smothering. Evidence of low-voltage electrocution may be difficult to identify. Poisoning, accidental or intentional, may require a high index of suspicion in order to collect and process the appropriate toxicology specimens, particularly if a volatile substance is suspected. Some poisonous agents, such as cyanide, can only be smelled by genetically-able individuals (the classic burnt almond smell) and thus may go unnoticed.

Conversely, the pathologist should not overinterpret injuries related to resuscitation or medical intervention. These injuries can occasionally be profound, particularly if they occur perimortem. Misinterpretation or oversight is not limited to gross findings but also to the histologic slides. Entities, such as myocarditis, are patchy and require adequate sampling for diagnosis. Other findings may be easily overlooked, such as calcium oxalate crystals in the kidney in cases of ethylene glycol poisoning. ^[7]

It is also important to remember that an apparently negative autopsy is not synonymous with “no anatomic cause of death.” ^{[3, 6]} Additional historical and investigative information should be sought, potentially including revisiting the death scene. Some diagnoses may eventually need to be made on the basis of exclusion, particularly when due to a functional disorder such as cardiac arrhythmia.

Common misconceptions include the following:

Routine performance of an autopsy in natural deaths is unnecessary

The presence of coronary atherosclerosis does not a heart attack make

Herbal remedies and over-the-counter (OTC) supplements are safe and are not important

Natural deaths occurring outside of a hospital or other care facility may fall under the jurisdiction of the medical examiner. In cases that appear legitimately nonsuspicious and natural in nature, the indications can be thought of in 2 respects, as follows:

Indications to perform a medicolegal death investigation and

Indications to perform an autopsy in an apparent natural death

The exact determinants in either situation may be somewhat dependent on the jurisdiction and/or medical examiner; however certain standards have been set. ^[6]

The forensic pathologist or death investigator is “charged by statute to investigate deaths deemed to be in the public interest—serving both the criminal justice and public health systems.” ^[6] In addition to the investigation of non-natural, suspicious or violent deaths, an autopsy or an investigation by a medical examiner may be indicated in certain natural deaths. Standards set forth by the National Association of Medical Examiners (NAME) require medicolegal investigation of the following potentially natural deaths ^[6] :

Unexpected or unexplained deaths in infants and children

Unexpected or unexplained deaths when an individual was in apparent good health

Deaths known or suspected to be caused by disease constituting a threat to public health

Deaths of persons not under the care of a physician

See also The Medical Examiner and Coroner Systems.

Sudden, unexpected deaths can occur in all age groups; however etiologies vary by age and, in some cases, by ethnicity. The individual’s age, personal medical history, and family history can provide valuable information in developing a differential diagnosis and in directing ancillary studies at autopsy.

Across all age groups, cardiac-related diseases play a significant role in both sudden and unexpected death. Although the type and etiology varies, heart diseases as a collective account for a considerable number of deaths in the United States in all age groups, ranking 6^th in children 10-14 years old, 5^th in adolescents and young adults aged 15-34 years, 3^rd in adults 35-44 year, and 2^nd in adults aged 45-74 years. ^{[1, 2, 8]} Heart disease is the leading cause of death in adults older than 75 years. ^[2] Malignancy is also common in all age groups, but, likewise, increases with age. ^[2]

In most cases, deaths in infants and children are, by nature, both sudden and unexpected. Although many different types of hereditary and acquired diseases cause deaths in adults, natural deaths in children and young adults are more likely to be the result of congenital disorders, infections or malignancies. ^{[2, 5]} Cardiovascular causes of death in infants and young children are typically due to myocarditis (usually viral), various congenital diseases or syndromes with either primary or secondary involvement of the heart, or congenital heart defects. Gross autopsy findings may be subtle (endocardial fibroelastosis, myocarditis) and may first be suspected on review of the histologic slides.

Adolescents and young adults dying suddenly and unexpectedly from natural processes typically have some form of heart disease, of which hypertrophic cardiomyopathy is the most common. ^[9] Many cases of congenital disease are diagnosed in utero or shortly after birth and usually do not fall under the medical examiner’s jurisdiction, however a number of congenital and hereditary conditions may remain asymptomatic, are minimally symptomatic, or are rapidly fatal and thus are thus brought to the attention of the medical examiner. Fortunately, the overall incidence of these diseases is low; therefore, they constitute a smaller number of cases requiring medicolegal investigation.

In this section, causes of instantaneous or sudden death, causes of unexpected death, and autopsy-negative causes of death are reviewed primarily by organ system.

Instantaneous or sudden death may result from dysfunction/abnormalities of the heart and its vessels, noncardiac vessels, pulmonary system, and central nervous system (CNS).

Heart and coronary arteries

Ventricular fibrillation may present in the following ways and cause instantaneous/sudden death:

Coronary arteries: Occlusion (atherosclerosis, thrombosis, embolus), structural abnormalities of the epicardial arteries, coronary artery dissection or aneurysm

Hypertensive heart disease: Fibrosis

Cardiomyopathies: Hypertrophic cardiomyopathy, dilated cardiomyopathy (genetic, myocarditis, toxic, peripartum, idiopathic), restrictive cardiomyopathy (idiopathic, amyloidosis, sarcoidosis, radiation fibrosis, metastasis, deposition disease/inborn errors of metabolism)

Other cardiomyopathies: Arrhythmogenic right ventricular dysplasia, arrhythmogenic left ventricular dysplasia, left ventricular non-compaction, restrictive conditions (endomyocardial fibrosis, Loeffler endomyocarditis, endocardial fibroelastosis)

Inflammatory: Myocarditis, pericarditis (bacterial, viral, Dressler syndrome)

Valvular: Congenital abnormalities (bicuspid valve), rheumatic heart disease

Functional abnormalities: Long QT syndrome (LQTS), short QT syndrome (SQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), Brugada syndrome, Asian sudden unexplained nocturnal death syndrome (SUNDS)

Acute myocardial infarction, cardiac tamponade, cardiac outflow obstruction (aortic stenosis, valvular prosthesis thrombosis, atrial myxoma), and congenital heart disease are also heart conditions that can lead to instantaneous/sudden death.

Aorta and noncardiac vessels

The following conditions affecting the aorta and noncardiac vessels can cause instantaneous/sudden death:

Aneurysmal rupture (atherosclerotic, mycotic, traumatic aneurysm): Cardiac tamponade, intrapleural or retroperitoneal hemorrhage

Aortic dissection: Coronary ostia occlusion due to retrograde dissection, infarction of abdominothoracic organs

Mesenteric artery thrombosis: Bowel infarction and septic shock

Miscellaneous: Ruptured ectopic pregnancy, arterial fistula (aortoenteric fistula)

Pulmonary system

Pulmonary conditions that can result in instantaneous/sudden death include the following:

Asphyxia: Mechanical airway obstruction (café coronary); laryngeal edema from infection (epiglottitis), anaphylaxis, neoplasm, and trauma; sleep apnea (Ondine’s curse, Pickwickian syndrome)

Pneumothorax

Bronchial asthma

Pulmonary embolism: Embolization from pelvic or deep veins of the lower extremities, fat/bone marrow emboli, amniotic fluid embolus, air embolus

Massive acute hemorrhage: Neoplasms, pulmonary tuberculosis (Rasmussen aneurysm), lung abscess

Central nervous system

Conditions affecting the CNS that can lead to instantaneous/sudden death include the following:

Acute hemorrhage: Atherosclerosis, hypertension, spontaneous rupture of aneurysm (eg, berry aneurysm), rupture of vascular malformation, thrombosis, sagittal sinus thrombosis, cerebral amyloid angiopathy

Infection: Leptomeningitis, encephalitis, abscess

Cerebral edema

Gastrointestinal system

The following are conditions affecting the gastrointestinal (GI) system that can cause instantaneous/sudden death ^[10] :

Massive gastrointestinal hemorrhage: Duodenal or gastric ulcers, esophageal varices, acute hemorrhagic gastritis, Mallory-Weiss tears, Boerhaave syndrome, vascular malformation, angiodysplasia

Esophageal polyps

Acute hemorrhagic pancreatitis

Cardiovascular causes of unexpected death include the following:

Congestive heart failure: Ischemic heart disease, hypertensive heart disease

Valvular heart disease: Rheumatic, congenital

Alcoholic cardiomyopathy ^[11]

Bacterial endocarditis: HACEK organisms (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella species [spp]), Staphylococcus spp, Streptococcus spp

Previously repaired congenital heart disease

Drug induced cardiac toxicity: Iatrogenic and illicit (anthracycline, cocaine) ^[12]

Pulmonary causes of unexpected death include the following:

Infection, such as from bronchopneumonia, lobar pneumonia, aspiration pneumonia; these may include:

community acquired organisms (eg, S pneumoniae, community-acquired methicillin-resistant S aureus [CA-MRSA] , Klebsiella pneumoniae);

mycobacterial infections (disseminated [miliary] tuberculosis [TB], secondary [reactivation] TB, Rasmussen aneurysm;

other non-TB mycobacterial infection (eg, M kansasii, M avium complex [MAC]); and

opportunistic infections (eg, Pneumocystis carinii pneumonia , Aspergillosis, mucormycosis)

Chronic lung disease: Chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, bronchitis

CNS causes of unexpected death include the following:

Vascular: Cerebral vascular accident, aneurysm

Encephalopathy: Acute ethanol-induced (Wernicke) encephalopathy, acute hemorrhagic leukoencephalopathy, transmissible spongiform encephalopathy (TSE)

Neoplasms: Primary or metastatic

Other: Multiple sclerosis, Chiari malformation

GI causes of unexpected death include the following:

Neoplasms: Benign, malignant, primary, or metastatic

Acute peritonitis: Perforated gastric or duodenal ulcer, perforated appendix, pelvic inflammatory disease (PID)

Intestinal obstruction: Neoplasm, incarcerated hernia, volvulus, adhesions

Genitourinary (GU) tract causes of unexpected death include the following:

Acute pyelonephritis with sepsis

End-stage renal disease (ESRD) with uremia

Chronic pyelonephritis

Glomerulonephritis

Acute renal failure (ARF)

Rupture of ectopic pregnancy

PID

Acute endometritis

Eclampsia

Hematopoietic system causes of unexpected death include the following:

Acute leukemia, aplastic anemia/bone marrow crisis, hemophagocytic syndrome (following viral illness)

Acute hemolytic crisis: Sickle cell crisis, malaria, microangiopathic hemolytic anemia, thrombotic thrombocytopenic purpura (TTP)

Infectious causes of unexpected death include the following:

Bacterial: Meningococcal meningitis, CA-MRSA (Panton Valentine leukocidin),

Rickettsial: Rocky Mountain spotted fever

Viral: Influenza, viral hemorrhagic fever, rabies

Other: Naegleria

Miscellaneous causes of unexpected death include the following:

Neoplasms: Lung, breast, GI tract (especially the colon), pancreas, ovary/uterus, testis, melanoma, lymphoma

Hypophysitis and other pituitary lesions

Pheochromocytoma

Death from the following conditions may cause negative autopsies:

Endocrinopathies: Diabetes mellitus (diabetic ketoacidosis, hypoglycemia); thyroid storm and thyrotoxicosis; adrenocortical insufficiency and hyperaldosteronism

Electrolyte abnormalities: Dehydration, diarrhea, vomiting, endocrine dysfunction (Addison disease, Schmidt syndrome), uremia, water intoxication, hypokalemia

Cardiac dysrhythmia: Channelopathies, drug induced, electrolyte imbalance

Other: Seizure disorder, anaphylaxis, neuroleptic malignant syndrome, serotonin syndrome

The scene of a natural death can provide valuable information, and it is imperative that the medical examiner be notified of any findings before the start of autopsy. Not only can the scene findings be used to arouse or refute suspicions of foul play, useful clues pertaining to natural disease processes can be obtained.

It is also important to remember that, on occasion, evidence from the scene may have been moved, removed, or “cleaned up” by family members and friends. Paramedics may have moved the body or removed clothing or evidence (ie, ligatures around the neck) in an attempt to resuscitate the individual, and police officers or other emergency personnel may have altered the scene in some way for safety or access purposes.

If not directly examined at the scene, any prescription bottles (and their contents) should be sent with the body, including over-the-counter (OTC) medications. Proscription medications can give important information as to the person’s medical history, provide contact information for healthcare providers, and help direct toxicology testing. Furthermore, many medications are associated with known lethal side effects, including direct toxicity, interaction with other medications and/or exacerbation of certain underling conditions (ie, potentiation of arrhythmias in persons with long QT syndrome [LQTS] or Wolff-Parkinson-White Syndrome [WPW]).

Over-the-counter medications, herbal remedies and supplements should not be overlooked or disregarded as “safe.” Alone, or in combination with standard prescription medications, a number of herbal remedies and over-the-counter supplements have been shown to cause adverse events, including death. Oversight and monitoring of the quality and content of many of these products is lacking, and cases of contamination with other toxic substances have been reported. ^[5] In this capacity, the medical examiner’s office may play an important role in identifying trends associated with certain products which may pose a public health risk.

The following are other issues to consider at the scene:

As with any scene, it should be noted whether the premises is locked and secured

Is the scene in appropriate order, or does there appear to have been a struggle, effort to clean up, etc?

When, and in what condition, was the decedent last seen? By whom?

What condition is the body in (rigor mortis, livor mortis, decomposition, etc)?

Where and how was the body found? How were they dressed? (This may require interviewing emergency medical personnel or other first responders.)

What do they appear to have been doing at the time of death (ie, sleeping, vomiting, exercising)?

What medications are found at the scene? (Don’t forget to look for empty bottles in the trash.) Is the decedent’s name on the medications? Are pill counts correct? Who is the prescribing physician? Note the physician’s name (and number, if provided) to contact for additional medical history

Include herbal/traditional remedies and supplements in the list of medications

Look in trash cans, toilets, etc, for evidence of diseases (ie, bloody emesis, melena), drug use, etc

Is there a suicide note? The presence or absence of a note is not a substitute for a thorough investigation and autopsy; the note may have been removed from the scene before the arrival of investigators or, less commonly, the individual may die of a natural disease before carrying out their suicidal intentions

Review witness and family statements; it may be useful to speak with family members and witnesses yourself in order to better elicit a history of certain symptoms (eg, chest and arm pain) before death; a detailed medical history, however, is best obtained from the decedent’s physician rather than friends or relatives

See also Forensic Scene Investigation.

The old adage “an ounce of prevention is worth a pound of cure” governs the approach to trace evidence collection in apparent natural deaths. No specific trace evidence is associated with a natural death; however, if something questionable is identified, it is probably best to collect it so that it will be available at a later date if new information is obtained.

Any potential trace evidence should be collected and processed accordingly, as in suspicious cases. As in non-natural deaths, the body and clothing should be carefully examined in order to rule out subtle signs of accidental or intentional injury. Medications, drug paraphernalia including syringes (capped or placed in special transport containers), or illicit substances should accompany the body and must be appropriately documented (type, number, additional prescription information). Examination of these items should be used to direct toxicology testing, particularly if the substance in question is not picked up on a routine drug screen (some acidic drugs, prescription drugs) or if special testing methods are required for drug isolation and identification (steroids, volatiles).

See also Forensic Toxicology – Drugs and Chemicals.

This section is divided by discussion of the general features of the gross external and internal examination, as well as by internal examination of the body systems most often implicated in sudden death.

External examination should proceed in accordance with routine autopsy procedures. ^[13] Special attention should be paid to external signs of disease, not unlike physical diagnosis in a living patient. Signs of malnutrition or dehydration may give important clues and help direct additional testing (vitreous electrolytes). Supraclavicular congestion is often seen in cases of sudden cardiac death. Findings such as fingernail clubbing and splinter hemorrhages may be seen in chronic heart disease and bacterial endocarditis, respectively. Signs of trauma, such as manual strangulation or low-voltage electrocution, may be subtle, so a detailed and thorough external examination is warranted in all cases.

Organs should be examined in situ, particularly if the pathologist is not directly performing the evisceration. Any fluid present within the pleural, pericardial, and abdominal cavities should be measured and described. The position of the bowel should be examined by the pathologist before it is manipulated to determine the presence of malrotation, volvulus, or herniation.

Blood in the thoracic cavities secondary to runoff from a vessel damaged in the removal of the chest plate should not be confused with true hemothoraces. Runoff may also contaminate a serous effusion. The pulmonary artery should be opened and examined for pulmonary emboli. Other findings, such as hyperinflated lungs, can be readily apparent in situ but may be more difficult to identify following evisceration. Special techniques are needed to demonstrate a tension pneumothorax, which are done before the thoracic cavity has been entered (see Special Dissections).

The following is a summary of the above considerations:

Organs should be examined in situ before manipulation

Are all organs present in normal anatomic position?

Fluid within any body cavity should be measured (volume) and described (serous, serosanguineous, purulent, chylous, frank blood)

Is intestinal volvulus or herniation present?

The lungs should be examined for evidence of hyperinflation (asthma, emphysema aquosum)

Evisceration should be performed, or directly observed, by the pathologist

Evaluations for tension pneumothorax should be done before the thoracic cavity is entered

The cardiovascular, pulmonary, central nervous (CNS), and gastrointestinal (GI) systems are discussed separately below.

Cardiovascular system

The heart should be weighed and its size and shape characteristics recorded. Determination of myocardial hypertrophy can be made using standard tables of predicted values based on body weight. ^[13] If right ventricular hypertrophy is queried, the right ventricle should be removed and weighted separately; thickness of the right ventricular free wall is not an accurate representation of the degree of hypertrophy. An enlarged, globoid or flabby heart may indicate structural abnormalities such as hypertrophic or dilated cardiomyopathy, whereas a normally-sized but overly stiff heart is seen in restrictive cardiomyopathies.

The origin and distribution of the coronary arteries should be noted. Acute angle takeoff of a coronary artery or other abnormalities of the coronary ostia may be the only finding in a sudden death. Other nonatherosclerotic coronary artery abnormalities associated with sudden death include location of the left main coronary artery between the aortic and pulmonary artery roots, origin from the pulmonary trunk, and tunneled coronary arteries. Other gross abnormalities can be identified, such as coronary artery dissection and rupture.

The coronary arteries should then be sectioned at 2-3 mm intervals to identify any significant stenosis or thrombotic occlusion. Acute thrombotic occlusion of a coronary artery may be very focal or may not be identified, even in cases of instantaneous death. The degree of luminal stenosis, determined by the cross-sectional area, should be recorded for the major vessels. In general, stenosis greater than 75% is more likely to be significant; however, death can be attributed to coronary artery disease (CAD) with less stenosis if other signs of chronic myocardial ischemia are apparent (left ventricular hypertrophy [LVH], fibrosis, previous infarct). ^[7] Stenosis may also be secondary to other causes such as fibromuscular dysplasia, which can affect both the small and large coronary vessels. ^{[3, 14]}

Pathologic lesions of the epicardial vessels commonly implicated in sudden death include the following:

Coronary artery occlusion: Atherosclerotic plaque, thrombus, platelet aggregates, embolus

Coronary artery aneurysm/rupture: Associated with Kawasaki disease, vasculitis, connective tissue disease

Coronary artery dissection: Often young females, multifocal, and associated with increased eosinophils

Arteritis: Multiple vasculitides, rheumatic conditions, connective tissue disorders, and drugs (eg, cocaine)

Coronary artery spasm

Congenital anomalies of coronary vessels: Abnormal origin and course, osteal malformations, hypoplasia, coronary artery tunneling

The heart can be opened by a number of methods, ^[13] of which the most common is to serially section the heart from apex to approximately 2 cm from the valves. The color and consistency of the myocardium should be noted; areas of hyperemia and softening can be associated with recent infarcts, and firm, tan-white areas are associated with healed infarcts. The thickness of the right and left ventricles and interventricular septum should be measured at that level. Myocardial hypertrophy can arise from a number of causes, both congenital and acquired; the weight of the heart is a better predictor of hypertrophy than is ventricular thickness. ^[14] Causes most commonly include hypertension (increased filling pressure), aortic stenosis or other causes of outflow obstruction.

Left ventricular hypertrophy, in and of itself, is a risk factor for sudden cardiac death, regardless of etiology. The risk of death is increased with increasing degrees of myocardial fibrosis. Death most commonly results from disruption of electrophysiologic pathways; however, fibrosis is also associated with myocardial rupture, acquired ventriculoseptal defects, valvular dysfunction and pump failure. The pattern (symmetric, asymmetric) (see the following images) and location (septum, free wall) should be noted.

It should also be noted if the myocardial fibers appear disorganized; a “herringbone” pattern is frequently observed in hypertrophic cardiomyopathy (see the image below). Disorganization with deep fissuring of the endocardium of the left ventricular cavity is suggestive of left ventricular noncompaction (LVNC).

Right ventricular hypertrophy, as determined by the right ventricular weight, can develop secondary to pulmonary disorders (pulmonary hypertension, chronic obstructive pulmonary disease [COPD], interstitial fibrosis, bronchopulmonary shunts, chronic pulmonary emboli, bronchitis) or as a result of heart disease (left heart failure).

Cardiomyopathies result in impaired contractility (systolic dysfunction) or compliance (diastolic dysfunction) and are categorized as follows:

Hypertrophic cardiomyopathy (HCM) is typically asymmetric with a greater degree of thickening of the interventricular septum than the left ventricular free wall; fiber disarray is characteristic but may be focal; hypertrophic cardiomyopathy can develop into an end-stage dilated cardiomyopathy

Dilated cardiomyopathy can be recognized by an enlarged, flabby heart with a dilated left ventricle; the degree of left ventricular dysfunction is the best predictor of mortality; ejection fractions less than 30% are associated with an increased risk of arrhythmia and sudden death ^[14]

Restrictive cardiomyopathy results from decreased myocardial compliance, typically secondary to fibrosis, but it can also be due to infiltrative processes such as amyloidosis or sarcoidosis, in addition to various deposition diseases; most causes of restrictive cardiomyopathy are secondary—however, rare cases of both familial and sporadic primary restrictive cardiomyopathy do occur; although the ventricular volume and ventricular wall thickness in restrictive cardiomyopathy is typically preserved or only slightly abnormal, the atria are frequently dilated; the diagnosis of a specific etiology is made by microscopic examination ^{[9, 14]}

Physiologic hypertrophy is typically seen in high level athletes and has not been associated with sudden death ^[14]

Cor pulmonale, or right ventricular hypertrophy secondary to pulmonary pathology, should have at least one lung inflated and fixed before sectioning; death likely results from arrhythmia which is exacerbated by hypoxia, explaining the risk of death during sleep in individuals with COPD

Other rare cardiomyopathies include left ventricular noncompaction and arrhythmogenic right ventricular dysplasia (ARVD)

The base of the heart can be opened along the inflow and outflow tracts. The right ventricle should be opened from the inferior vena cava to the tip of the atrial appendage to preserve the sinoatrial (SA) node. ^[15] Examine the valves for congenital or acquired abnormalities, stenosis, and vegetations. Approximately two thirds of valvular disease involves the mitral or aortic valves. ^[14] Vegetation on the valves should be cultured, even if contamination has occurred. Consider the following:

The most common causes of valvular dysfunction are the result of degenerative processes due to aging, hypertension, or structurally abnormal valves (bicuspid valves)

Postinflammatory scarring (rheumatic heart disease) occurs in both the mitral and aortic valves (see the following image), causing stenosis and valvular regurgitation; infective endocarditis is also associated with valvular dysfunction

Mitral valve prolapse and papillary muscle dysfunction are associated with sudden death; in cases of mitral valve prolapse, autopsy examination of the mitral valve should demonstrate ballooning of thick, redundant valve leaflets; the chordae tendineae are typically thinned or ruptured (see the image below)

Rheumatologic and connective tissue diseases with aortic involvement may secondarily affect the aortic valve; conditions such as Marfan syndrome generally demonstrate other characteristic findings such as body habitus (see the following image)

Endocarditis can be either septic or aseptic; large, friable and destructive vegetations involving previously normal valves are typically caused by virulent organisms such as Staphylococcus aureus and have a rapid progression; frequently, septic infarcts are identified in the spleen, kidney, and brain; subacute bacterial endocarditis is typically less destructive and show more fibrosis and granulation tissue—causative organisms include Viridans group streptococci, coagulase-negative staphylococci, and the HACEK (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella species [spp]) group of organisms

Pulmonary system

After their removal, the lungs should be weighed individually. Document any pleural abnormalities. The pulmonary vasculature should be opened and examined for emboli (see the image below).

In natural deaths, particularly if a pulmonary etiology is suspected, at least one lung should be inflated with formalin through the mainstem bronchus. The lung can be sectioned in coronal plane or serially sectioned in the horizontal plane. The cut surfaces should be examined for areas of consolidation, infarcts, parenchymal loss, and fibrosis, as well as for the presence of excessive fluid. Firm, clotted material protruding out above the cut surface of the small- to medium-sized vessels can be seen with small pulmonary emboli; however, histologic conformation is required. Also, consider the following:

In asthma-related deaths, the lungs may appear hyperinflated; rib notches may be seen indented into the pleural surfaces

Pulmonary edema or pulmonary hemorrhage may be suggested by the presence of excessive fluid or blood emanating from the cut surfaces of the lungs (see the image below); the lungs my feel boggy and heavy

Pulmonary infarcts, usually due to systemic emboli, are more commonly seen in the lower lobes and in older individuals (who have a greater incidence of heart and lung disease, which decreases their ability to compensate for the hypoperfusion); the infarcts are raised, hyperemic, wedge-shaped areas arising at the periphery of the lung.

Bronchopneumonia is characterized by patchy areas of consolidation; lobar pneumonia typically involves an entire lobe with variable gross appearance depending on the disease stage (congestion, red hepatization, gray hepatization, and resolution) with or without fibrinous pleural exudates; viral and atypical pneumonias have patchy areas of congestion with a variable distribution throughout one or all lobes; gross identification of consolidation and pneumonia be enhanced by formalin perfusion and fixation

Lung abscesses are seen in the setting of aspiration (right lower lobe, single), secondary to pneumonia or bronchiectasis (basal, scattered, multiple), and with septic emboli (any location, multiple)

Tuberculosis may have a variety of appearances depending on the immunocompetence of the host and stage of the disease; the Ghon lesion/complex is a solitary caseous lesion, usually in the upper lobe or upper part of the lower lobes; Ranke complexes develop when the lesions resolve and undergo progressive fibrosis and calcification

Secondary tuberculosis may have multiple caseous lesions, cavities, empyema, military dissemination, or bronchopneumonia; erosion into a vessel may cause massive hemorrhage with rapid exsanguination.

Firm, brown, indurated lungs are associated with heart failure and longstanding valvular disease

Central nervous system

A thorough examination of the CNS is very important to the investigation of sudden death. The scalp is reflected to expose the calvarium, which is then removed to expose the dura covering the brain. The scapular soft tissue and galea should be examined for hemorrhages and contusions. ^[16] The calvarium is removed and the dura is examined. In cases of subdural or subarachnoid hemorrhage, the dura may appear darkened and/or tense. Following careful removal of the dura, the leptomeningeal coverings are exposed. Purulent inflammation (see the following image) or frank pus should be cultured; a cisternal tap can also be used at this point to help decrease the risk of contamination. If subarachnoid hemorrhage is present, a diligent search for ruptured saccular (Berry) aneurysms or arteriovenous (AV) malformations should be undertaken.

Other forms of spontaneous intracranial hemorrhage, including subdural and intraparenchymal hemorrhage are most likely due to hypertension although other causes of sudden death, such as epilepsy/seizure disorders, multiple sclerosis, primary CNS tumors, or Chiari malformation, are occasionally seen. Sudden death can also be seen with neurodegenerative disorders. In order to best evaluate the brain for subtle lesions, fixation in formalin is recommended. Consultation with a neuropathologist is also recommended, if available.

Gastrointestinal system

Many causes of sudden death due to GI pathology may be grossly visible at the time of autopsy. ^[17] The pathologist should examine the bowel for evidence of obstruction (volvulus, intussusception, etc) before the organs are manipulated or removed. Many conditions may be immediately suspected upon opening the thoracic and abdominal cavities by the presence of blood or GI contents within the thoracic or abdominal cavities. It is important to keep in mind that similar findings can be seen as complications of resuscitation (gastric and esophageal ruptures) as well as with decomposition. The gastric contents should be examined; the identification of pill fragments may help identify a toxic cause of death. In addition, consider the following:

Acute hemorrhage is seen in numerous conditions include bleeding from esophageal varices, Mallory-Weiss tears of the esophagus, peptic ulcers, arteriovenous malformations, aortoenteric fistulas, and ruptured aneurysms.

Mallory-Weiss tears are linear, longitudinally oriented, and may span the gastroesophageal junction

Perforation/rupture of hollow viscous organs is seen in Boerhaave syndrome, perforated ulcers, stomach or esophageal rupture, diverticular disease, and fistula formation

Acute pancreatitis may be grossly identified by hemorrhage and necrosis; however, some cases may only be apparent microscopically

Hepatic cirrhosis and steatosis are also recognized causes of sudden death; cirrhotic livers appear hard, shrunken, and nodular; fatty livers may have a tan-yellow, homogeneous appearance with a “slippery” texture.

In pregnancy, both eclampsia and acute fatty liver of pregnancy can cause sudden death; subcapsular hepatic hematomas can be seen in eclampsia, which may rupture

In this section, evisceration techniques, dissection of the cardiac conduction system, and dissection in cases of suspected pulmonary embolism (PE) and deep vein thrombosis (DVT), pneumothorax, and gastroesophageal varices are briefly reviewed.

Four main evisceration techniques are used during routine autopsy practice, depending on the goals of the autopsy and preferences of the prosector: Virchow, Rokitansky, en bloc, or en mass techniques. The technical aspects of these techniques have been published elsewhere and will not be discussed in this section. ^{[13, 15]} For cases of natural deaths in which specific organ relationships and/or preservation of vascular structures is warranted, use of the en bloc or en mass technique may be useful, particularly if an autopsy assistant is performing the evisceration. Of note, regardless of the method of evisceration used, the prosector responsible for the autopsy should pay particular attention to the position of the bowel in situ so as not to miss cases of volvulus or herniation/incarceration.

The cardiac conduction system can be dissected at the time of autopsy; however, examination in every case is unlikely to be fruitful. In cases of sudden death without explanatory autopsy findings, the base of the heart can be saved in formalin and the conduction system dissected at a later time if necessary. ^[15]

SA node (located lateral to the ostium of the SVC)

To preserve the sinoatrial (SA) node, the right atrium should be opened from the inferior vena cava (IVC) ostium to the tip of the atrial appendage, rather than connecting the IVC and superior vena cava (SVC) ostia. A 2-cm square of tissue should be cut out around the terminal crest, located lateral to the SVC at the junction of the pectinate muscles and the smooth posterior atrial wall. If the section is taken correctly, the upper half of the block should have rough, trabeculated muscle, and the lower half should have smooth muscle with a horizontal ridge (the terminal crest) separating the two. The square of tissue containing the SA node can be serially sectioned perpendicular terminal crest for embedding. ^{[13, 15]}

AV node (located within the triangle of Koch)

Following normal dissection along the inflow and outflow tracks, the right-sided chambers are opened so that the tricuspid valve is visible. A full-thickness square of tissue containing the tricuspid valve anulus is taken from between the coronary sinus ostium (posterior) and the membranous septum, at the insertion of the septal leaflet of the tricuspid valve (anterior). If the section is taken correctly, the upper half of the square should be the inferior portion of the atrial septum, and the lower half should be the superior portion of the interventricular septum, with a horizontal groove (the fibrous anulus) separating the two. The tricuspid and mitral valves should be attached to either side of the fibrous anulus, with the mitral valve located more superiorly than the tricuspid valve. The square is serially sectioned perpendicular to the fibrous anulus for embedding. ^{[13, 15]}

Miscellaneous

Other helpful information includes the following:

Nodal vascular supply: Regarding the atrioventricular (AV) nodal artery, the right coronary artery (RCA) supply is greater than that of the left circumflex artery (LCx); the SA nodal artery is supplied by the RCA

Helpful stains: Masson trichrome, Movat pentachrome, Verhoeff-van Gieson

In all cases of sudden death, the pulmonary arteries should be examined in situ for the presence of thromboemboli, because removal of the organs or organ block may dislodge the emboli or otherwise obscure its true significance. This can be accomplished by incising the pulmonary artery and gently inserting a finger to feel for obstruction at the bifurcation or on either side. Further dissection of the pulmonary arteries can be made down to the hilum if necessary. In cases where thromboemboli are present or suspected, the deep veins of the leg and pelvis should be examined. This is most easily accomplished following evisceration and examination of the abdominopelvic and thoracic cavities.

The body is moved to a prone position, and a longitudinal incision is made along the posterior aspect of the legs. The muscles of the upper leg are reflected from the middle of the inguinal ligament to the medial knee, and the femoral, deep, and popliteal veins are opened longitudinally. Thrombi may not be present if they have already embolized (to the lungs). The Achilles tendon is severed at its insertion, and the gastrocnemius muscle is reflected superiorly. The deep surface of the reflected muscle is then serially sectioned perpendicular to the long axis and examined for venous thrombi in the tibial vein. It is generally assumed that if thrombi are present in the distal veins, they were at one time present in the proximal vein. ^[18]

Pneumothoraces can be caused by a variety of conditions. Several methods can be used to document a tension pneumothorax at autopsy. Plain film chest X-rays are the most reliable method for demonstration, and they also create a permanent record. Other methods include puncturing the thorax with a needle attached to rubber tubing, with the opposite end placed in a container of water. Alternately, after the Y-incision is made, a subcutaneous pocket is created along the lateral thorax which is filled with water. A blade can be inserted into the intercostal space below the water level. For both methods, the presence of bubbles in the water is indicative of a tension pneumothorax is present. ^[13]

Identification of gastroesophageal varices at autopsy is difficult, and even the most severe esophageal varices may remain elusive. After the loss of blood pressure, the vessels tend to collapse and become difficult to see, even on cross-sectioning. A helpful method for identifying the varices is to turn the esophagus inside out by using a pair of long hemostats inserted through the lumen at the distal end and grabbing the proximal end to pull through. ^[13]

Special handling requirements for bodies and specimens from natural deaths are typically related to decreasing the transmission of infectious diseases. Prevention of infectious diseases is primarily aimed at reducing aerosolization and limiting contamination of reusable equipment. ^[19]

Appropriate personal protective equipment (PPE) should be worn in all cases, including gown, gloves (preferably with a cut-resistant underglove), mask, eye protection, and surgical cap. An N-95 or N-100 mask can be worn if tuberculosis is suspected.

Reducing the risk of aerosolization can be accomplished by using manual saws, opening the intestines under water and removing organs individually. ^[20] Tissues should be fixed in formalin prior to sectioning in cases of suspected tuberculosis. In cases of transmissible spongiform encephalopathy (prion disease), the head should be opened in a plastic bag using a manual saw, and tissues should be places in formic acid following formalin fixation to reduce infectivity. ^[20] Using disposable equipment for highly infectious autopsies may be preferable to sterilizing reusable equipment, particularly in cases of potential prion disease. ^[21]

See also Universal Precautions and High-Risk Autopsies.

Select histologic findings in common cardiovascular and pulmonary causes of sudden death are reviewed in this section.

Cardiomyopathies and myocardial infarction are common cardiovascular causes of sudden death.

Cardiomyopathies ^{[14, 22]}

Restrictive cardiomyopathy histologic features include the following:

Mostly nonspecific patchy fibrosis

Fibrosis of the endocardium as well as subendocardium and fibroelastic thickening of the endocardium are seen with endomyocardial fibrosis and endocardial fibroelastosis, respectively; trichrome and elastic stains may be helpful

Loeffler endomyocarditis is characterized by endocardial fibrosis with focal necrosis and eosinophilic infiltrates

A congo red stain can be used to demonstrate amyloid deposition in amyloidosis

Storage diseases may demonstrate infiltration by an abnormal population of cells

In dilated cardiomyopathy, there is nonspecific myocyte hypertrophy and interstitial fibrosis.

Myocardial infarction

Histologic changes and other considerations in myocardial infarction and sudden include the following ^[14] :

Sudden death from occlusive coronary artery disease (CAD) is unlikely to produce significant changes in the myocardium; coagulative necrosis is the first histologic change specific for infarction, but it is not detected by light microscopy until at least 4 hours after the ischemic event

Contraction bands and wavy fibers can be seen between 1 and 4 hours, but they are not specific for irreversible myocardial injury and are seen in a variety of other conditions (see the following images)

Progressive necrosis, edema, and hemorrhage are the primary findings up to 12 hours; between 12 and 24 hours, neutrophilic inflammation becomes detectable, myocytes become hypereosinophilic, the nuclei become pyknotic, and distinct contraction band necrosis become apparent

From 1 to 3 days, acute inflammation and coagulative necrosis are predominant (see the image below); myocyte nuclei and striations are absent

Disintegration of the dead cells and replacement of the neutrophilic inflammation by macrophages, particularly at the edge of the infarct occurs from 3 to 7 days, and becomes well-developed within 10 days

Granulation tissue with collagen deposition occurs at approximately 2 weeks, and by 2 months a scar is formed, with progressive loss of cellularity from there onward

Histologic changes and other considerations in pulmonary causes of sudden include the following ^{[14, 22]} :

The histologic appearance of pulmonary edema is characterized by accumulation of pink, granular, proteinaceous material, typically with alveolar capillary engorgement

Histologic features characteristic of status asthmaticus are acute airway edema and thick, cellular mucus plugs blocking small bronchi and bronchioles; the mucus contains eosinophils, Charcot-Leiden crystals, and sloughed epithelial cells; chronic changes in longstanding asthma include airway remodeling with fibrosis, muscular hypertrophy in the bronchial walls, and mucus gland hyperplasia

Acute pneumonias show varying degrees of acute inflammation, edema, fibrinosuppurative exudate and organization, depending on the stage; viral and atypical pneumonias may show more interstitial edema and mononuclear inflammation confined to the alveolar walls, which appear widened and hypercellular; proteinaceous exudates and hyaline membranes can also be seen

All types of lung abscesses demonstrate suppurative destruction of the lung parenchyma with cavitation

Pulmonary emboli should be distinguished from postmortem blood clots by histologic organization; true emboli antemortem emboli should have the characteristic lines of Zahn, caused by separation and layering of platelets, fibrin, and red cells in the clot

No specific photographs or documentation is necessary beyond those that are standard for routine autopsies, including an identification (ID) photograph, external body diagram, and autopsy report. Overall body photographs and photographs of pertinent positive and negative findings are not required; however, they may prove to be helpful, particularly if the diagnosis is challenged in the future. Although probably good practice in all cases, photographic documentation may be particularly relevant in cases of natural death in custody and in cases of sudden, unexplained deaths in infants and children.

Ancillary and adjunctive studies may include toxicology ^{[3, 6, 18]} and microbiology ^{[13, 23, 24, 25, 26]} specimen collection, cytogenetic and chromosome analysis, ^[13] and postmortem chemistry. ^[13]

Specimens are routinely collected for toxicology in all medical examiner cases. Routine specimens should include both central (aortic) and peripheral (femoral) blood samples, vitreous, brain, and liver. Blood should be collected in tubes with sodium fluoride; all specimens should be kept refrigerated until use; then, they can be frozen. In decomposed bodies, the decomposition fluid can be collected from the thoracic cavity.

In addition to the standard specimens, bile and gastric contents may be helpful. These nonroutine specimens can be collected and refrigerated or frozen until needed. If inhalation of volatile substances is a possibility, lung tissue can be collected in special bottles for head-space analysis.

The utility of postmortem microbiology has been debated, due to frequent contamination of postmortem cultures, use of antibiotics, and lack of agreement between antemortem and postmortem cultures. Even with a high rate of culture contamination and postmortem bacterial overgrowth, carefully selected specimens can provide important information, particularly if a known pathogenic organism is isolated in pure culture from a sterile site or from tissue that looks grossly infected.

A number of specimens can be sent for microbiologic analysis. Blood, cerebrospinal fluid (CSF), spleen, brain, pericardial fluid, and pleural effusions, as well as grossly infected tissue from any site are frequently examined for bacterial, fungal, and acid fast organisms. A Gram stain of touch preps or smears of the suspicious tissue or body fluid can help direct the best course of action. Isolation of viruses can be accomplished by several methods including direct detection (immunofluorescence [IF], enzyme immunoassay [EIA], or polymerase chain reaction [PCR]), viral culture, and serology.

Most postmortem viral cultures can be collected in viral transport media (VTM) and stored at 4-8° C. CSF and stool should not be put in VTM. If testing for cytomegalovirus (CMV) and respiratory syncytial virus (RSV) is necessary, samples should not be refrigerated.

As much as is possible, sterile techniques should be used to collect microbiologic specimens. Common methods include cleaning the skin with iodine before needle stick or searing the surface of an organ from where the sample will be taken. Sterile needles, blades, swabs, syringes, and containers should be used. Saving material to use for future studies can be done using touch preps and air-dried smears, use of special fixatives (glutaraldehyde) for electron microscopy, and flash freezing fresh tissue.

Body fluids

Body fluid specimen testing may include bacterial, fungal, acid-fast bacilli (AFB), and viral studies.

Specimen collection of body fluids for bacterial, fungal, and AFB studies is as follows:

Collect 2-3 cc in a sterile, capped needleless syringe

Swabs are suboptimal, but if necessary use a sterile, cotton-tipped swab, unless culture is specifically looking for Neisseria species; do not used calcium alginate swabs

Specimen collection of body fluids for viral studies is as follows:

Aspirated fluid or swabs can be transported in VTM

Spinal fluid should be sent in a sterile container; do not put in VTM

Samples for RSV and CMV testing should not be refrigerated and need to be transported to the laboratory immediately

Tissues

Tissue specimen testing may include may include bacterial, fungal, acid-fast bacilli (AFB), viral, and blood culture studies.

When collecting tissue for bacterial, fungal, and AFB studies, tissue samples measuring 1-2 cm³ should be sent in a sterile container without fixative. Specimens that are too small may dry out and may not be useful. Specimens that are too large are difficult for the microbiology laboratory to process. Tissue can be frozen for future use.

When collecting tissue for viral studies, the tissue sample should be at least 5 mm³ and is transported in VTM.

For blood cultures, blood can be collected from the right atrium, inferior vena cava, or aorta using sterile technique after the chest plate is removed, before manipulation of the organs or removal of the bowel. Other options include blind sticks of the femoral artery or subclavian vein after sterilization of the skin. ^[26]

For bacterial blood cultures, aerobic and anaerobic blood culture bottles should be immediately inoculated with 5-10 mL of blood. For viral blood cultures, collect blood in a tube with an anticoagulant, and transport to the laboratory within 2 hours. Do not refrigerate if CMV is suspected.

Specimen storage

Specimen storage for bacterial and viral testing are as follows:

Bacterial: Refrigerated, frozen

Viral: 4-8° C or frozen at -70° C; do not refrigerate or freeze CMV or RSV

Molecular testing

Molecular testing may be preferred for the following:

Meningitis, encephalitis, or central nervous system (CNS) involvement by enteroviruses, herpes simplex virus (HSV), arboviruses, Epstein-Barr virus (EBV), CMV, and varicella zoster virus (VZV) (in immunocompromised patients), Toxoplasma gondii (in immunocompromised patients): CSF; PCR

Human immunodeficiency virus (HIV), hepatitis C virus (HCV): Plasma, PCR

Mycobacterium tuberculosis and Bordetella pertussis,Mycoplasma pneumonia, Legionella pneumophila, and respiratory viruses in immunocompromised patients: Respiratory specimen; PCR ± direct fluorescent antibody (DFA)

In certain cases, it may be necessary to collect material for cytogenetic analysis. Samples should be collected in sterile fashion and submitted to the laboratory within 1-2 days. Avoid exposure to extreme temperatures. Blood and bone marrow should be anticoagulated with sodium heparin. Fascia lata (for fibroblast culture) should be wrapped in sterile gauze moistened with Hanks balanced salt solution (HBSS). Solid tumors can be submitted in HBSS. If no fresh tissue is available, some cases may still be amenable to fluorescent in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue.

Many of the same biochemical tests that are performed on living individuals can also be performed postmortem; however, there is typically a lack of standardized reference values for postmortem samples, making interpretation of the results more difficult. Typically, reference ranges are calibrated based on blood, serum, or urine from living patients, and their applicability to postmortem samples may be limited. Another limiting factor is the postmortem stability of the analyte as well as the effects of hemoconcentration and postmortem redistribution.

Various types of body fluids may be used for postmortem biochemical testing (blood, urine, CSF, joint fluid, vitreous humor); however, vitreous humor is typically the most useful for routine analyses. Compared with blood and other body fluids, vitreous humor is relatively more stable, well-protected from contamination or passive diffusion, and is easily collected.

Reference values

A panel of biochemical tests, essentially equivalent to a basic metabolic panel in living patients, is routinely performed on postmortem vitreous samples. The panel includes vitreous sodium, potassium, chloride, urea nitrogen, creatinine, and glucose. Reference ranges have been established for these tests and quantitative results and overall patterns can be of diagnostic significance (see Table 1, below).

Table 1. Postmortem Vitreous Reference Ranges for Some Common Chemistries (Open Table in a new window)

Analysis

Reference Range

Sodium (Na⁺)

135-150 mmol/L

Chloride (Cl^–)

105-135 mmol/L

Potassium (K⁺)

< 15 mmol/L

Creatinine (Cr)

0.6-1.3 mg/dL

VUN

8-20 mg/dL

Glucose

< 200 mg/dL

Ketoacids

Negative

Alcohol

Negative

Source : Rose KL, Collins KA. Vitreous postmortem chemical analysis. NewsPath [serial online]. College of American Pathologists. December 1, 2008. ^[27]

VUN = urea nitrogen concentration in vitreous humor.

Common patterns

Common patterns are as follows in selected conditions ^[27] :

Hypertonic dehydration: ↑ Na⁺, ↑ Cl^–, ↑ Cr, ↑↑ VUN (>40 mg/dL)

Hypotonic dehydration: ↓ Na⁺, ↓ Cl^–, +/- ↑ Cr, ↑ VUN

Isotonic dehydration: Normal Na⁺, normal Cl^–, ↑ Cr, ↑ VUN

Renal failure (azotemia, uremia): Normal Na⁺, normal Cl^–, ↑ Cr, ↑↑↑ VUN (>150 mg/dL)

Decomposition: ↓ Na⁺, ↓ Cl^–, ↑ K⁺, positive alcohol

Vomiting: ↓ Cl^–

Low salt, water intoxication: ↓ Na⁺, ↓ Cl^–, ↓ K⁺

Differential diagnosis

The differential diagnosis of certain analytes are summarized below. ^[27]

Elevated glucose ↑↑ (>200 mg/dL) occurs in the following conditions:

Diabetes

Diabetic ketoacidosis: Ketoacids +

Hyperosmolar nonketotic acidosis: May have ↓ Na, ↑ Cr, ↑ VUN

Positivity for ketoacids can occur in the following conditions:

Diabetic ketoacidosis (glucose >200 mg/dL)

Alcoholic ketoacidosis (glucose < 200 mg/dL)

Malnutrition/starvation

Isopropanol ingestion

Positivity for alcohols can occur in the following situations:

Decomposition (↑ K)

Ethanol ingestion, acute ethanol toxicity (>350 mg/dL)

Isopropanol

See also Adjuncts to the Forensic Autopsy, Forensic Toxicology – Drugs and Chemicals, Postmortem Vitreous Analyses.

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Analysis

Reference Range

Sodium (Na⁺)

135-150 mmol/L

Chloride (Cl^–)

105-135 mmol/L

Potassium (K⁺)

< 15 mmol/L

Creatinine (Cr)

0.6-1.3 mg/dL

VUN

8-20 mg/dL

Glucose

< 200 mg/dL

Ketoacids

Negative

Alcohol

Negative

Source : Rose KL, Collins KA. Vitreous postmortem chemical analysis. NewsPath [serial online]. College of American Pathologists. December 1, 2008. ^[27]

VUN = urea nitrogen concentration in vitreous humor.

Candace H Schoppe, MD Resident Physician, Department of Anatomic and Clinical Pathology, Wake Forest University Baptist Medical Center; Medical Examiner, Forsyth County, North Carolina

Candace H Schoppe, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, National Association of Medical Examiners, United States and Canadian Academy of Pathology, American Academy of Forensic Sciences

Disclosure: Nothing to disclose.

Patrick E Lantz, MD Professor of Pathology, Wake Forest University School of Medicine; Associate in Surgical Sciences-Otolaryngology, Bowman Gray School of Medicine; Director of Autopsy Services, North Carolina Baptist Hospital; Forsyth County Medical Examiner; Regional Forensic Pathologist, North Carolina State Medical Examiner

Patrick E Lantz, MD is a member of the following medical societies: American Society for Clinical Pathology, College of American Pathologists, American Academy of Forensic Sciences

Disclosure: Nothing to disclose.

J Scott Denton, MD Clinical Assistant Professor of Pathology, University of Illinois College of Medicine at Peoria; Forensic Pathologist and Illinois Coroners’ Physician

J Scott Denton, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Illinois State Medical Society, National Association of Medical Examiners, American Academy of Forensic Sciences, Illinois Society of Pathology, Peoria Medical Society

Disclosure: Nothing to disclose.

Pathology of Sudden Natural Death

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