Most common cause of unexpected natural death in the Western world

Signs and symptoms include chest pain, left arm and jaw pain, nausea and vomiting, EKG changes, and elevated cardiac enzymes (e.g., troponin I)

Marked narrowing of coronary arteries, typically >75% of lumen, in which a thrombus may or may not be present

Recent or remote myocardial infarct may be present

May see perivascular and interstitial fibrosis only, and, in some cases, no significant microscopic findings are present

Contraction band necrosis may be present in cases of ischemia but may also be an artifact of resuscitation

Pump failure or sudden arrhythmia

May or may not have a history of hypertension

No other symptoms, other than sudden cardiac arrest, may exist

Concentric left ventricular hypertrophy

Granular kidneys (i.e., arteriolar nephrosclerosis)

Myocardial fiber hypertrophy

Sclerosis of mural cardiac arteries

Hyaline arteriolosclerosis (hyperplastic arteriolosclerosis in malignant hypertension)

Sudden arrhythmia due to the increased oxygen demand of hypertrophied muscle mass

Hypertensive cardiovascular disease may coexist with atherosclerotic heart disease and lead to the acceleration of coronary atherogenesis

Bicuspid aortic valve (males, 50–70-year-old age group)

Rheumatic valvular disease (women, 35–55 years old; mitral involvement also common)

Degenerative valvular changes involving all three cusps (>60 years of age)

Calcification and obstruction of aortic valve

Left ventricular hypertrophy

Calcification of valve

Myocardial fiber hypertrophy

Sudden arrhythmia due to instability from obstructive blood flow to coronary arteries

Affects approximately 1 in 3,000–5,000 individuals

Individuals with QT interval prolongation greater than 500 ms are highly likely to have LQTS, but in males, greater than 450 ms is significant, and in females, greater than 460 ms is significant

Autosomal dominant and autosomal recessive inheritance patterns are identified, and, in about 15% of cases, the mutation is sporadic

Sixty percent of affected individuals present with syncope, seizures, or sudden death

Forty percent of affected individuals are asymptomatic throughout life

May be the etiology of some cases of sudden infant death syndrome (SIDS)

May suffer drowning or near drowning (in LQT1 most commonly)

Thirteen variants LQT₁–LQT₁₃:

In addition to hereditary forms of LQTS, the condition can also be drug induced, with some commonly prescribed responsible medications including verapamil, erythromycin, fluoroquinolones, haloperidol, thiazides, and methadone

Rule out cardiomyopathy

Must do molecular workup to confirm a channelopathy

Cardiac ion channelopathy leading to lethal dysrhythmia

Most common cause of sudden death in athletes <35 years of age

Male: female ratio = 2:1

May be symmetrical or asymmetrical thickening of interventricular septum at distal outflow tract, but there is a wide range of phenotypes

Fibrosis of aortic outflow tract corresponding to the anterior leaflet of the mitral valve

Myofiber disarray most prominent in interventricular septum

Plexiform interstitial fibrosis

Thickened intramural coronary arteries

Arrhythmia or cardiac failure

Autosomal dominant with variable penetrance, affecting 1 in every 500 people

Mutations in genes that encode sarcomere proteins

Mutation in cardiac myosin-binding protein C gene may result in late onset (middle age and favorable prognosis)

May be associated with progressive congestive heart failure and early death or with sudden death

May develop secondarily in viral myocarditis, chronic alcoholism, the peri- or postpartum period, hemochromatosis, or with Duchenne’s or myotonic dystrophy

Enlarged flabby heart with all four chambers dilated

Frequent endocardial thickening; may have mural thrombi

Interstitial fibrosis and hypertrophied and attenuated myocytes

Associated with systemic diseases such as amyloidosis, hemochromatosis, and glycogen storage diseases

Lower incidence than hypertrophic and dilated cardiomyopathy

Decreased diastolic relaxation and elevated ventricular filling pressure

Myocardium is stiff due to infiltration from a benign or malignant process, scarring, or intracellular accumulations

Dependent on etiology of cardiomyopathy

May be associated with sudden death or progressive heart failure

Most commonly associated with viruses but also bacteria, fungus, protozoa, or autoimmune reactions

May have history of recent viral-like symptoms

Heart may be slightly dilated and flabby

May have focal areas of mottling or may be grossly normal

Diffuse or patchy cellular infiltration, mainly lymphocytes

In some cases, accompanied by marked myocardial fiber necrosis

Ectopic cardiac irritability leading to ventricular dysrhythmias

Associated clinical condition is mitral valve prolapse, which occurs in ~5–10% of the general population

Primary form has autosomal dominant pattern of inheritance

Midsystolic click heard on auscultation

Most common presenting symptom is palpitations due to premature ventricular contractions (PVCs)

Myxomatous mitral valves are associated with Marfan syndrome, Ehlers-Danlos syndrome, pseudoxanthoma elasticum, osteogenesis imperfecta, straight thoracic spine syndrome, and pectus excavatum

Predisposed to infectious endocarditis and mitral regurgitation

Redundancy of leaflets with prolapse into left atrium (Fig. 7.3), with secondary fibrosis of leaflets eventually occurring

Elongation of chordae tendineae

Ventricular friction lesion

Myxomatous degeneration with acid mucopolysaccharides and thickening and mucinous infiltration of zona fibrosa of mitral valve

Frequent PVCs from impact of anterior mitral leaflet on ventricular septum

Rarely, a lethal dysrhythmia develops (Fig. 7.4)

Risk factors include hypertension (coexists in 70–90% of patients) and weakness of the aortic wall (e.g., Marfan syndrome)

Male predominant (3:1)

Increased incidence in pregnancy

Dissection usually heralded by onset of severe sharp chest pain or back pain

Initiating event is a tear in the aortic intima after which blood dissects into the media

Dissection can propagate distally and/or proximally

Most common cause of death is rupture of aortic dissection into either the pericardial space or the left chest cavity

Varies from cystic medial degeneration to no specific pathologic changes

Exsanguination

Predisposing factors:

Hereditary predispositions:

Prevalence of venous thromboembolism in antithrombin III, protein C, or protein S deficiency is >50%

Clinical symptoms: sudden death, chest pain, or shortness of breath

Coiled thrombi that do not conform to the shape of the pulmonary arterial tree in which they are found at autopsy, such as postmortem clots would

Less than 95% arise in the large deep veins of lower legs, including popliteal, femoral, and iliac vein

Occasionally, thrombi are also recovered in pelvic veins, especially during pregnancy, or in the periprostatic veins

Rarely, thromboemboli may cross through an interatrial or interventricular defect to the systemic circulation (i.e., paradoxical embolus)

Platelet-fibrin-red blood cell mass with lines of Zahn

Veins may demonstrate organization

May see organizational changes in pulmonary arterial wall if there is survival for several days postembolic event

Occlusion of pulmonary trunk and right ventricle

Minimal flow to left ventricle, leading to sudden death or cardiovascular collapse

Occlusion of smaller arteries may lead to sudden death by vasospasm, sudden increase in blood pressure and right heart failure, or bradycardia due to vasovagal reflex

Associated with hypertension

Most common in middle-aged and elderly

May present with headaches and seizures

Common sites of hemorrhage: external capsule and basal ganglia, cerebellum, thalamus, and pons

Sharp demarcation of hematoma from surrounding brain with death of neurons and glia in adjacent tissue

If survival is >24 h, cerebral edema is present with early organizational changes consisting of monocytes and macrophages invading into edges of hematoma

If preexisting hemorrhage has occurred, hemosiderin may be present, and if small hematoma occurs with survival after several years, residual cysts with brown-orange discolored walls may be present with hemosiderin and gliosis (so-called apoplectic cyst)

Accounts for 4–5% of sudden, rapid natural deaths

Median age of patient at the time of rupture is 50 years

Berry aneurysms exist in 1–2% of population

Increased incidence of saccular aneurysms in certain disorders:

Large saccular aneurysms at branch points may be easily identified (Fig. 7.5A–C); however, in other cases, aneurysms may be small, extensively damaged when they rupture, and difficult to detect at autopsy

Aneurysms occur at bifurcations of intracranial arteries, with 40% related to intracranial portion of internal carotid artery, usually at juncture of internal carotid and posterior communicating artery, 30% at the anterior communicating artery, 20% at the middle cerebral artery, and 5–10% associated with posterior cerebral arteries and basilar and vertebral artery

Aneurysms may rupture into and dissect into brain parenchyma

When subarachnoid hemorrhage is identified at autopsy, a search for a ruptured berry aneurysm should be performed prior to fixation

Typically thin-walled pouch in which endothelium may be incomplete and with adjacent blood clot

Muscle coat and elastic lamina typically stop abruptly at the neck of aneurysm and wall of aneurysm is fibrotic

Cerebral ischemia with cerebral infarction

In binge drinkers, alcohol can be a cardiac irritant and lead to sudden arrhythmia

Long-term alcohol abuse with well-known complications

Alcohol withdrawal with delirium tremens and Wernicke disease

May include a variety of findings:

Specific to particular disease processes

Alcohol may function as a cardiac irritant or may cause electrolyte abnormalities (e.g., magnesium deficiency)

The decedent must have an antemortem diagnosis of epilepsy to certify it as a cause of death

An agonal convulsive episode is not adequate for the diagnosis of epilepsy

May have anatomically normal brain (i.e., no seizure focus is identified)

May have mesiotemporal sclerosis within Sommer sector of hippocampus

May find contusion of tongue or pulmonary edema, which are both nonspecific

When present, cell loss may be seen in CA1 and CA4 sectors of hippocampus

May have prolonged tonic-clonic seizures with cardiac and respiratory exhaustion

May have nonvisible seizure with paroxysmal autonomic dysfunction

History of asthmatic bronchitis; death typically occurs during acute asthmatic paroxysm

Death may not correlate with the severity of the autopsy findings

Death more common at night or in early morning

Higher incidence of death in African-Americans than Caucasians (rule out concomitant sickle cell disease trait)

Mucoid plugging of bronchi and edema of mucosa

Voluminous hyperexpanded lungs with indentation by ribs

Prominent mucus in the bronchus, with goblet cells and eosinophils in mucus

Charcot–Leyden crystals, which are derived from major basic protein

Hyaline thickening of basement membrane in bronchial mucosa

Bronchiolar and bronchial smooth muscle and goblet cell hyperplasia

Peribronchial neutrophilic, lymphocytic, and eosinophilic inflammation

Decreased oxygenation and elevated carbon dioxide retention

Increased pulmonary vascular resistance, metabolic acidosis

Eventual exhaustion and death

Headache and neck stiffness

Purulent meninges (Fig. 7.7A-D)

Extensive neutrophilic infiltrate underneath the arachnoid

Local effects of the inflammatory process and the presence of the bacterial organism

Bilateral adrenal hemorrhage

Skin changes ranging from petechiae to purpura

Cerebral hemispheres may or may not be visibly suppurative

Adrenal glands with varying degrees of hemorrhage

Affected skin and adrenal glands may show acute neutrophilic infiltrate

Bacterial toxemia and adrenal insufficiency leading to catastrophic rapid onset of shock

Sudden episodes of headache associated with position of the head

Appearance in adult life

Sudden acute hydrocephalus due to obstruction of foramen of Monroe

1–4 cm gelatinous and hyaline cyst in the anterior region of the third ventricle

Cerebral edema

Epithelial layer of collagenous capsule

Mucus goblet cells present

Stains for mucin with mucicarmine and PAS are positive

Acute hydrocephalus with herniation and compression of brainstem

History of diabetes mellitus in most cases; however, onset may precede formal diagnosis of disease

May be unremarkable

Large amounts of glucose and acetone, often detected in vitreous humor

Blood may contain acetone

Subnuclear vacuolation in renal proximal convoluted tubule epithelial cells (i.e., Armanni–Ebstein lesion)

Other findings associated with diabetes mellitus are Kimmelstiel–Wilson glomerulopathy and pancreatic islet amyloidosis

Metabolic acidosis, dehydration, and rarely cerebral edema

Sudden onset of shortness of breath and edema of face, hives, and vascular collapse

May develop from insect bites, medication, or food

Edema of epiglottis and airway obstruction

Edema and eosinophilic infiltration in airways occasionally

Hypereosinophilia within vasculature of liver and heart

Cardiovascular collapse with sudden onset of shock from systemic vasodilatation that includes pulmonary edema and obstructive angioedema of upper airway

Elevated total tryptase level with beta-tryptase level >1 ng/mL, indicating mast cell degranulation

Manner of death may be determined to be either natural or accident, depending upon the preference of the forensic pathologist certifying the death

Description: Sudden death of infant <1 year of age, which remains unexplained after performance of a complete postmortem investigation, including review of the case history, examination of the scene of death, and complete autopsy with toxicologic studies and metabolic screening

Based upon the degree of postmortem investigation (e.g., whether or not toxicologic analysis and/or blood cultures are performed), SIDS may be classified into one of three categories, each indicating the extensiveness of investigation prior to the determination of SIDS

In the past, and most likely currently, the diagnosis of SIDS has been used in a wastebasket fashion, with many infants being improperly diagnosed as having died from SIDS, when a subsequent autopsy revealed a definitive cause of death, sometimes even inflicted injury

Some forensic pathologists have recently began to advocate for discontinuing the use of the term “sudden infant death syndrome” and favor certifying all infant deaths without an identifiable cause as undetermined cause and undetermined manner of death

SIDS/infant deaths with no identifiable cause of death represent 10–12% of deaths in the first year of life

Majority of deaths occur between 2 and 4 months of age

Incidence is 1–2 per 1,000 infants

Recurrence rate in a family is ~1–2%

Many infant deaths occur while the infant is bed sharing with an adult, sibling, or even possibly pets. In deaths of this manner, an accidental overlay is one consideration, especially when the adult is obese or intoxicated. As the circumstances indicate a possible nonnatural cause of death (i.e., smothering), the criteria for SIDS would not be fulfilled, and the determination of an undetermined cause and manner or other appropriate wording to indicate the possibility of an accidental overlay would be appropriate. Definitive diagnosis of an overlay by autopsy alone, without good corroborating scene investigation, is extremely difficult and most often cannot be made

Maternal risk factors associated with SIDS:

Infant risk factors associated with SIDS:

Theories proposed include:

The preventative measure suggested is putting an infant to sleep on its side or back instead of on its stomach

SIDS very likely represents a group of disorders that have not yet been delineated as causes of sudden death in infants, and metabolic disorders and unapparent viral syndromes may comprise a significant part of this group

A very small number of infant deaths diagnosed as due to SIDS are undoubtedly concealed homicides, particularly smotherings, therefore potentially one of the reasons behind certifying all such infant deaths (i.e., those with no identifiable cause) as undetermined cause and manner of death

Petechiae of the thymus, pleura, or epicardium

Gliosis of the brainstem and central nuclei

Pulmonary edema or intra-alveolar hemorrhage

Pulmonary hemosiderosis has been described

Histologic evidence of recent viral illness

Extramedullary hematopoiesis

Increased amounts of brown fat in periadrenal adipose tissues

SIDS is a death presumably due to natural causes

Disorders of β-oxidation of fatty acids

Glycogen storage disorders

Other disorders

Fatty acids are an important source of energy for neonates

Enzymes necessary to carry out β-oxidation can be developmentally immature and inadequate in the perinatal period

Infants usually present with sudden death or hypoketotic hypoglycemia

Collapse of metabolic pathways due to concurrent illness or physiologic stress can precipitate symptoms after depletion of hepatic glycogen stores

Myopathy, cardiomyopathy, and liver dysfunction result from the accumulation of fatty acids in the mitochondria and microsomes

Fatty changes of the liver are indistinguishable from Reye syndrome

Medium-chain acyl-CoA dehydrogenase deficiency (MCAD):

Long-chain acyl-CoA dehydrogenase deficiency (LCAD):

Short-chain acyl-CoA dehydrogenase deficiency (SCAD):

Multiple acyl-CoA dehydrogenase deficiency (MADD):

General features:

Diagnosis:

Therapy for carnitine-related disorders

Myophosphorylase deficiency (McArdle disease)

Glycogen storage disease 1a (glucose-6-phosphatase deficiency)

Glycogen storage disease 1b (transport protein T1 deficiency)

Glycogen storage disease 1c (transport protein T2 deficiency)

Lactic acidemias

Aminoacidopathies

Disorders of carbohydrate metabolism

Hyperglycinemia

Urea cycle defects

Wound-producing capacity of kinetic energy is determined by weight and velocity:

Kinetic energy of a moving object increases proportionally with weight, but exponentially with velocity (e.g., doubling the weight of a bullet doubles the kinetic energy, but doubling the velocity quadruples the kinetic energy)

Further energy may be present if a rotational component exists, again best demonstrated in bullets:

The shorter the duration of impact, the greater energy transfer and the greater the potential for injury

The larger the area through which force is transmitted, the less the intensity and potential for injury

Some tissues are more fragile than other tissues, and a fixed amount of force applied to one tissue may cause no injury versus the same force applied to another tissue

Hemorrhage

Aseptic inflammation: noninfected inflammatory response to injury

Local infection occurs when the protective layer of tissue is injured and an infectious agent is carried into the wound during the traumatic event or at a later time

Primary shock:

Secondary shock:

Shock injuries to organs:

Thromboembolism:

Fat embolism:

Fat embolism syndrome:

Air embolism:

A superficial scrape or scratch injuring the upper layers of skin:

An area of hemorrhage into the tissues caused by tearing of blood vessels during blunt trauma:

Dating of contusions:

A tear produced by a blunt instrument stretching the tissues beyond their elastic tensile strength or crushing and forcible separation of the tissues during compression between two hard surfaces, such as a weapon and the bone underlying the skin

The edges of the tear have abraded margins and ragged edges

There is tissue bridging of the defect by vessels, nerves, and connective tissue (Fig. 7.12A, B)

Broken bones due to blunt force injury (Fig. 7.13):

Motor vehicle accidents can cause massive blunt force injuries:

The tempered side window glass of an automobile produces a special type of injury known as a dicing abrasion:

Blunt force injuries of the head result in several interrelated traumatic lesions

Lacerations (Fig. 7.15A, B)