Adult Medical Autopsy and Natural Death

What is sudden natural death?

An unexpected death due to intrinsic (non-traumatic, non-toxic) disease, typically occurring within minutes to hours of symptom onset

• Often unwitnessed or collapse with little to no warning

What is the most common cause of sudden natural death in adults?

Cardiovascular disease

• Coronary artery disease (CAD)

What coronary artery stenosis is generally considered severe?

Greater than 75% luminal narrowing

What must be excluded to attribute a death to natural disease?

Trauma

Toxic exposure

Unnatural causes

What is the avg. weight of a MALE heart?

300-350 g

What is the avg. weight of a FEMALE heart?

250-350 g

What is the average LEFT ventricular wall thickness?

1.3-1.5 cm

What is the average RIGHT ventricular wall thickness?

0.3-0.5 cm

What is the basis approach for general investigations?

Review scene

Obtain medical hx

Perform a complete ex/internal examination

Retain tissue/samples for histology/toxicology

Correlate all findings before final cause

Can severe CAD cause sudden death WITHOUT an acute myocardial infarction?

Yes — Severe stenosis may trigger fatal arrhythmias without histologic evidence of a fresh MI

What findings suggest a prior myocardial infarction?

Fibrous myocardial scarring (healed infarct)

What cardiac conditions besides CAD can cause sudden natural death?

Hypertensive heart disease

Cardiomyopathies

Valvular disease

Infective endocarditis

Myocarditis

Conduction system abnormalities

Congenital coronary anomalies

What gross finding is characteristic of hypertensive heart disease?

Left ventricular hypertrophy (LVH) with increased heart weight

Which cardiomyopathies are commonly associated with sudden death?

Dilated cardiomyopathy

Hypertrophic cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC)

What gross finding is characteristic of valvular disease?

Aortic stenosis

Mitral valve prolapse

Infective endocarditis with embolic phenomena

What might also be needed for conduction system abnormalities?

May require specialized histologic sectioning to identify

How is myocarditis confirmed?

Often subtle or absent grossly

Confirmed only on microscopic examination

What conditions predispose to aortic dissection?

Chronic hypertension

Connective tissue disorders (especially Marfan syndrome)

What are the hallmark findings of aortic dissection?

Intimal tear

False lumen

What are the hallmark findings of a ruptured abdominal aortic aneurysm?

Retroperitoneal hemorrhage

Often seen in older adults with atherosclerosis

What is produced with a ruptured intracranial (berry) anerysum?

Produces subarachnoid hemorrhage

What are the hallmark findings of a pulmonary thromboembolism?

Examine deep veins of the legs and pelvis for the embolic source

• Asses for saddle embolus

What is a saddle pulmonary embolus?

An embolus lodged at the bifurcation of the main pulmonary artery

During evaluation of pulmonary embolism, where should the embolic source be sought?

Deep veins of the legs and pelvis

What gross findings are associated with fatal asthma?

Hyperinflated lungs

Mucus plugging

Bronchial wall eosinophilia

What are some examples of pulmonary causes of natural death?

Massive pulmonary thromboembolism

Severe asthma

Pneumonia and COPD exacerbation

What are major CNS causes of sudden natural death?

Hypertensive intracerebral hemorrhage

Subarachnoid hemorrhage

SUDEP (Sudden Unexpected Death in Epilepsy)

What is SUDEP?

Sudden Unexpected Death in Epilepsy

Generally, a diagnosis of exclusion without an identifiable anatomic cause

What GI conditions may cause sudden natural death?

Peptic ulcer hemorrhage

Esophageal variceal hemorrhage

Mallory-Weiss tear

Mesenteric ischemia

Acute pancreatitis

Bowel rupture

Diabetic ketoacidosis/Severe hypoglycemia

Adrenal hemorrhage/Acute adrenal insufficiency — Uncommon but important to consider

Which postmortem specimen is useful for diagnosing diabetic ketoacidosis?

Vitreous humor for glucose and ketone analysis

What are the "big four" categories of sudden natural death?

Cardiac

Vascular

Pulmonary

CNS

Which cause of sudden natural death is most commonly associated with a completely normal gross examination?

Fatal arrhythmia

What is sepsis?

SIRS occurring in the setting of documented or suspected infection

What is septic shock?

Sepsis with hypotension refractory in fluid resuscitation

What is SIRS?

Systemic inflammatory response syndrome

Clinical criteria based on:

• Temp

• Heart rate

• Rspiratory rate

• WBC count

What is severe shock?

Sepsis accompanied by evidence of organ dysfunction or hypoperfusion

What is MODS?

Multi-organ dysfunction syndrome

Progressive dysfunction of two or more organ systems

May progress even after infection is resolved

Which cytokines drive sepsis?

TNF-α

IL-1

IL-6

What major vascular process contributes to sepsis/MODS?

Endothelial injury leading to increased permeability and microvascular thrombosis (DIC)

What gross spleen finding is characteristic of sepsis?

Enlarged, soft, hyperemic "septic spleen"

What gross lung findings may be seen in sepsis?

Consolidation

Abscesses

Diffuse alveolar damage consistent with ARDS

What pulmonary findings are common sources of infection?

Bronchopneumonia

Lobar pneumonia

Aspiration pneumonia

What genitourinary findings are common sources of infection?

Pyelonephritis

Urosepsis

What abdominal findings are common sources of infection?

Peritonitis

Cholangitis

Intra-abdominal abscess

Bowel perforation

What skin/soft tissue findings are common sources of infection?

Cellulitis

Necrotizing fasciitis

Decubitus (pressure) ulcers

What indwelling devices are common sources of infection?

Vascular catheters

Surgical lines

Prosthetic material

What infective endocarditis findings are common sources of infection?

Source of embolic seeding to multiple organs

What kidney finding is associated with septic shock?

Pale swollen cortex consistent with acute tubular necrosis (ATN)

What gross liver findings occur in sepsis?

Centrilobular necrosis

Cholestasis ("sepsis liver")

What would the gross findings of petechial hemorrhage on skin and serosal surfaces indicate with sepsis?

Disseminated intravascular coagulation

What histologic findings characterize lungs with sepsis/mods?

Diffuse alveolar damage

Hyaline membrane

Neutrophilic infiltrates

What histologic finding characterizes ATN (kidney) in sepsis?

Acute tubular necrosis with tubular epithelial sloughing

What microscopic finding supports DIC (microvasculature)?

Fibrin (hyaline) microthrombi

What histologic findings characterize livers of sepsis/mods?

Centrilobular hepatocyte necrosis

Cholestasis

Kupffer cell hyperplasia

Which organ usually fails first in MODS?

Lungs (ARDS)

What are the major organ manifestations of MODS?

ARDS - Acute respiratory distress syndrome

ATN - Acute tubular necrosis

Shock liver

Myocardial depression

DIC

GI ischemia

What histologic findings characterize heart of sepsis/mods?

Contraction band necrosis

Microabscesses if an embolic source present

What should be collected to minimize postmortem contamination?

Collect blood and tissue cultures promptly

What are the most common sources of sepsis?

Lung

GU tract

Abdomen

Skin/soft tissue

Indwelling devices

What is the first step in evaluating a natural death?

Review scene findings and circumstances surrounding collapse

What historical information is particularly important?

Cardiac disease

Hypertension

Diabetes

Seizure disorders

Substance use

Recent illness

Why should pathologists avoid fixation on the first abnormal finding?

Multiple disease processes may coexist, and the first lesion identified may not be the cause of death

What ancillary studies should routinely be considered?

Histology

Toxicology

Special stains

Additional tissue sampling

What is the difference between cause of death and incidental disease?

Cause of death explains the fatal event

Incidental disease is present but unrelated

Why can a prior diagnosis of disease not solely confirm the cause of death?

Correlation with autopsy findings is REQUIRED

What should autopsy findings correlate with?

Antemortem clinical course

Cultures

Imagining

Treatment records

Why must postmortem cultures be interpreted cautiously?

Contamination and agonal bacterial translocation may occur

What is the underlying cause of death?

The disease or injury that initiated the chain of events leading to death

How should a cause-of-death statement be written?

As a sequential chain from immediate cause back to underlying cause

What is an example of a proper sepsis cause-of-death statement?

Septic shock → bronchopneumonia → chronic neurologic impairment with aspiration risk

What are some examples of contributing conditions that should be documented?

Diabetes mellitus

Malnutrition

Immunosuppression

Malignancy

What is the primary goal when evaluating natural disease at autopsy?

Determine whether the disease process is sufficient to explain the death

Why should all significant findings be documented even if they are not the cause of death?

Their severity and potential contribution must be evaluated and recorded

When should ancillary studies be pursued?

When findings are equivocal or insufficient to establish cause of death

What is the most important cardiovascular disease to evaluate during autopsy?

Coronary atherosclerosis

What should be documented when examining coronary arteries?

Degree of stenosis

What is cardiomegaly?

Enlargement of the heart beyond expected size for body habitus

What valvular abnormalities should be documented?

Calcification

Fibrosis

Degenerative changes

What are the most common causes of cirrhosis?

Alcohol

Chronic viral hepatitis

Non-alcoholic steatohepatitis (NASH)

What are major complications of cirrhosis?

Esophageal varices → Portal hypertension

Gastric varices

Ascites

Hepatic encephalopathy

Why is peptic ulcer disease important at autopsy?

It may cause hemorrhage or perforation

What are the two major forms of pancreatitis?

Acute hemorrhagic pancreatitis

Chronic pancreatitis

What gross appearance is typical of kidney with sepsis?

Pale

Swollen cortices consistent with acute tubular necrosis (ATN)

What additional renal findings should be documented?

Renal cysts

Pyelonephritis

Nephrolithiasis

What is ascites?

Excess fluid accumulation within the peritoneal cavity

Which form of pancreatitis is more commonly associated with sudden death?

Acute hemorrhagic pancreatitis

What gross findings suggest acute hemorrhagic pancreatitis?

Hemorrhage

Fat necrosis

Edema

Soft friable pancreas

What gross findings suggest chronic pancreatitis?

Fibrosis

Calcifications

Atrophic pancreatic tissue

What causes the chalky white appearance seen in fat necrosis?

Saponification of fat by pancreatic lipase

Which laboratory enzyme is classically elevated in pancreatitis?

Lipase (more specific than amylase)

Which organ systems are commonly affected by diabetes mellitus?

Heart

Kidneys

Eyes

Peripheral nerves

What postmortem findings support diabetic ketoacidosis (DKA)?

Elevated vitreous glucose and ketone levels

What thyroid abnormality may be identified at autopsy?

Goiter

What adrenal abnormalities may contribute to death?

Hemorrhage

Atrophy

Addisonian crisis

Why is obesity important during autopsy?

Contributes to cardiovascular and metabolic disease burden

What are the three classic findings of diabetic ketoacidosis?

Hyperglycemia

Ketosis

Metabolic acidosis

Which adrenal hormone deficiency causes Addisonian crisis?

Cortisol deficiency

What thyroid condition is associated with severe hypothyroidism and death?

Myxedema coma

How can natural disease interact with trauma?

Severe disease may make relatively minor trauma fatal

What should be done when findings remain ambiguous?

Obtain additional testing before finalizing conclusions