NATURAL DISEASE
 
CARDIOVASCULAR DISEASE
Coronary Atherosclerosis:
Left coronary artery shows a higher incidence of thrombosis compared to right.
Few (13%) show gross thrombosis.
Bridging: LAD dips into myocardium.
Coronary spasm possible mechanism if stenosis <75%.
Myocardial rupture of infarct: usu ventricular free wall, 3 - 7 days after MI.
Dissecting Coronary Aneurysm:
Spontaneous (80% peripartum) or traumatic (angiography).
Sudden Death During Exercise:
Older (>35yo) = coronary atherosclerosis.
Younger = hypertrophic cardiomyopathy or congenital anomalies of coronary arteries (anomalous origin of LCA from sinus of Valsalva).
Hypertensive Cardiovascular Disease:
mechanism - arrhythmia (v. fib)
Cardiomyopathy
Dilated/Congestive Chronic ETOH, peripartum, myocarditis, idiopathic, cobalt, adriamycin,
Hypertrophic IHSAS, AD, familial, in 0.2% population, myofiber disarray
Restrictive/Obliterative Amyloid, hemochromatosis, sarcoid, glycogen storage, hypereosinophilic syndrome
Valvular Disease
Mitral valve prolapse: diagnosis of exclusion, usually female.
Aortic stenosis: congenital/rheumatic (fused comissures)/secondary calcification of a bicuspid (0.4% pop)/normal valve.
Acute bacterial endocarditis (tricuspid valve, IVDA)
Coronary Artery Anomalies: Sudden death in children.
Myocarditis
Infectious (bacterial, rickettsial, viral, protozoal, fungal) patchy or diffuse areas of necrosis with interstitial inflammation (neuts, lymphs, plasma cells, eos)
Connective Tissue Disease (rheumatic fever, rheumatoid arthritis)  
Physical Agents (poisons or drugs)  

Adenovirus - infants; Coxsackieviruses A & B - adults
PCR useful in diagnostics
Controversy: intragenomic viral DNA diagnostic; not always associated with lymphocytes on histology!
Giant cell myocarditis: uncertain cause and poor prognosis; multinucleate giant cells (derived from muscle) and a mixed inflammatory infiltrate; focal but frequently extensive necrosis.
Aortic Dissection
Hypertension, heredity, inflammation.
Marfan's Syndrome: fibrillin, cystic medial necrosis
Ehler's Danlos Syndrome; Osteogenesis imperfecta.
Weight lifting, cocaine,
Physiological Basis for Sudden Death: Long QT interval
Wolf-Parkinson White Syndrome
Congenital hereditary: Jervell & Lange-Nielsen Syndrome and Romero-Ward Syndrome
Acquired: drugs, electrolyte abnl, hypothermia, anorexia-nervosa, liquid dieting
Long QT syndrome may be idiopathic or acquired
QT> 0.44 sec, may be triggered by bradycardia or sympathetic stimulation.
Origin of blood supply to SA node: bronchial arteries via ramus ostii cavae superioris (55% RCA, 45% LCA)n& atrial branches; also supplied by Kugel artery from the LCA.
AV node: 90% from RCA reinforced by LAD.
Right Ventricular Dysplasia (Uhl's Disease)
Young adults with slightly dilated right ventricles and microscopic increase in interstitial fibrosis and fatty infiltration into right ventricle. Occasionally lymphoid infiltrates.
Usually sudden death following recreational exercise.
Kawasaki's Arteritis
Coronary arteritis; usually in children (80%< 4 years); Associated with mucocutaneous LN syndrome. Aorta and veins may be involved.
Clinical: fever, conjunctival and oral erythema and erosion, edema of hands and feet, erythema of palms and soles, skin rash with desquamation, enlarged cervical LN. Usually self-limited but 20% have cardiovascular sequelae. Acute fatalities in 1% due to coronary arteritis with superimposed thrombosis or ruptured coronary artery aneurysm.
Micro: range of lesion from intimal infiltration with abseny fibrinoid necrosis to trans-mural involvement with a dense inflammatory infiltrate.
Endocardial Fibroeleastosis
Focal or diffuse fibroelastic thickening of the mural left ventricular endocardium.
Most present in first 2 years of life and have a congenital anomaly as well: e.g. Aortic valve obstruction (1/3)
Many present with congestive heart failure
 
INTRACRANIAL LESIONS
Epilepsy
3-4% of all natural deaths; 2-17% epileptics die a sudden, unexplained death
Sleep: predisposes to attacks and affects cardiac vulnerability
In vast majority, no lesion to explain sz found: sclerosis, AVMs, adhesions bet cx and dura
Sclerosis of hippo is probably secondary related to cerebral edema during an epileptic attack.
Mechanism: arrhythmia

Non-traumatic Subarachnoid Hemorrhage
Berry aneurysms: HTN and smoing predisposing factors, 90% at ACA/MCA/ICA bifurcation, multiple 20 - 30%, familial 12 - 15%
Death is due to generalized vasospasm and ischemia.
Intracerebral hemorrhages: more common in males, blacks.
HTN hemorrhages: basal ganglia, pons and cerebellum
AVM: majority parietal
Sturge-Weber Syndrome: vasular nevi of face, epilepsy, multiple AVMs
Uncommon: blood dyscrasias, endocarditis with emboli, anticoagulant toxicity, tumors and sickle cell (diffuse SAH over convexities).

Primary Brain Tumors
<0.2% of sudden, unexpected death.
Meningitis
Assoc: infection of the ears and sinuses, alcoholism, splenectomy, pneumonia and septicemia
Organisms (Adults): S. pneumoniae (esp s/p trauma w/ dural disruption), N. meningitis, L. monocytogenes and H. influeneza
Neonates and infants < 2 mos: coliform bacteria (listeria, e coli, klebsiella) and Group B strep.
Reyes Syndrome
Multiple small fatty cytoplasmic vesicles in the liver, myocardial fibers and tubular cells of kidneys.
Can be confused w/inborn errors of metabolism so need to do EM for mitochondrial alterations.
Hydrocephalus
Psychiatric Patients
Phenothiazines in schizophrenics
Schizophrnia
Chronic Alcoholism: cerebellar atrophy with loss of granule cells and Bergmann gliosis.
Rabies: Negri bodies are eosinophilic, sharply defined, round or oval intracytoplasmic neuronal inclusions. Most common in Purkinje cells, pyramidal cells of hippocampus and in cerebral cortex.
 
RESPIRATORY SYSTEM
Asthma
Occupational asthma: exposure to irritant gases and fumes (chlorine, ammonia)
Epiglottitis: H. influenza
Pulmonary Thromboemboli:
Stasis, Vein Injury, Hypercoagulable state
Pneumonia: bronchopneumonia must be secondary to a chronic disease
Hemoptysis: tumor, TB
Spontaneous Pneumothorax of Newborns: 1-2% live births, CXR
Bronchiolitis: RSV in infants< 1 year can cause atelectasis or fatal bronchospasm
Hantavirus: Sin Nombre Virus (SNV). Diagnosis best with serum IgM and IgG. Pulmonary edema and mild interstitial thickening with only focal hyaline membranes. Immature leukocytes in capillaries. Pleural effusion on autopsy
 
GI TRACT: hematemesis secondary to varices from cirrhosis, perforated ulcers & peritonitis
Agonal postmortem esophagogastromalacia: autodigestion of the lower esophagus and stomach. Tissue grayish-white to black & friable. Micro: no inflamm.
SPLEEN: Rupture assoc with mononucleosis, malaria, leukemia.
Sickle cell crisis: spleen had congested red pulp and pale areas of fibrosis from ischemic damage. Under high power sinusoids are dilated with sickled cells. (Robbins p. 614)
PANCREAS: pancreatitis, diabetes mellitus (vitreous glucose >200mg/dL is diagnostic)
LIVER:
Fulminant hepatic necrosis - acetaminophen, Amanita phalloides (mushroom poisoning).
Cirrhosis with non-traumatic intra-abdominal hemorrhage.
Microvesicular fat: Reyes, tetracycline or valproate toxicity, fatty liver of pregnancy, unripe fruit of jamaican boa tree, (marasmus, glucocorticoids).
Alcoholic fatty liver (usually mixed macro and microvesicular): carbos replaced by ETOH, can cause sudden death, can be seen with alcoholic hepatitis, may have negative post-mortem ETOH, caused by triglyceride accumulation in the liver
OTHER: ruptured tubal pregnancy, adrenal pheochromocytoma, meningococcemia with Waterhouse-Friderichson Syndrome (bilateral adrenal hemorrhagic necrosis), idiopathic pulmonary hemosiderosis, central pontine myelinolysis, cystercercosis, undiagnosed malignant tumors.
 
Valsalva: Increased intrathoracic pressure, intrapulmonary pressure; decreased RV output, coronary artery flow, O2 diffusion by lung
GYNECOLOGIC/OBSTETRIC
Pre-eclampsia:
hyperuricemia, proteinuria, facial edema, HTN
Eclampsia (seizures): ppt by bromocriptine mesylate. Liver: irregular, focal subcapsular and intraparenchymal hemorrhages. Fibrin thrombi in portal capillaries with peripheral (periportal) hemorrhagic necrosis.
Sheehan's Syndrome: post-partum pituitary ibfarction usu a complication of obstetric hemorrhage or shock as a result of retained placental tissue; proportinal to amount of pituitary gland infarcted; CT may show an "empty sella."
Air embolism risk factors: abortion (dilation of os with tears of cervical veins), C-section, placenta previa, oral-genital intercourse with air blowing