• An embolus = a detached solid, liquid, or gas inside blood vessels that travels from its origin to a distant site.
• It eventually lodges in a vessel too small to pass through → partial or complete vascular obstruction.
• This may cause tissue dysfunction or infarction.
• Most emboli come from dislodged thrombi → called thromboembolism.
• Less common emboli may consist of:
  • fat droplets
  • air or nitrogen bubbles
  • atherosclerotic/cholesterol debris
  • tumor fragments
  • bone marrow
  • amniotic fluid
• The final location of an embolus depends on its site of origin and direction of blood flow.
• Systemic embolism → blocks arterial blood supply → ischemia → infarction.
• Pulmonary embolism more commonly causes hypoxia, hypotension, and right-sided heart failure.

Pulmonary Thromboembolism

• Pulmonary emboli usually originate from deep venous thrombosis (DVT).
• More than 95% of venous emboli arise from deep leg veins proximal to the popliteal fossa.
• Therefore, risk factors for pulmonary embolism (PE) are essentially the same as those for DVT.
• A fragment from a DVT travels:
  deep leg veins → larger veins → right side of heart → pulmonary arteries.
• Depending on size, the embolus may:
  • block the main pulmonary artery
  • lodge at the bifurcation of right and left pulmonary arteries → saddle embolus
  • travel into smaller pulmonary arteries/arterioles (Fig. 3.15)
• Pulmonary emboli may occur:
  • one after another, or
  • as multiple small emboli released from one large thrombus.
• A patient who has had one PE has an increased risk of another PE.
• Rarely, a venous embolus crosses an atrial or ventricular defect and enters systemic circulation → paradoxical embolism.
• Most pulmonary emboli (60%–80%) are small and clinically silent.
• Over time, they may organize and become incorporated into the vessel wall.
• Organization may sometimes leave fibrous webs within pulmonary vessels.
• A large embolus obstructing a major pulmonary artery → may cause sudden death.
• A medium-sized pulmonary artery embolus usually does not cause infarction because the lung has a dual blood supply, including bronchial arteries.
• However, with left-sided heart failure, reduced bronchial arterial perfusion may allow the same embolus to cause a pulmonary infarct.
• Emboli in small end-arteriolar branches usually cause infarction.
• Capillary rupture in the poorly oxygenated area may also produce hemorrhage.
• Repeated pulmonary emboli over time → pulmonary hypertension → right ventricular failure (cor pulmonale).

KEY CONCEPT

• Embolus = material traveling through blood that blocks a distant vessel.
• Most emboli are thromboemboli.
• DVT → right heart → pulmonary arteries = pulmonary embolism.
• Large PE → sudden death.
• Small peripheral PE → pulmonary infarction.
• Repeated PE → pulmonary hypertension → cor pulmonale.
• Paradoxical embolism = venous embolus enters systemic circulation through a cardiac defect.

CONCEPTUAL EXAMPLES

• Leg DVT breaks off → travels through right heart → blocks pulmonary artery → PE.
• Large embolus lodges at pulmonary artery bifurcation → saddle embolus.
• Small embolus blocks a terminal pulmonary branch → lung infarction.
• Repeated small emboli → progressively ↑ pulmonary pressure → right-sided heart failure.

Systemic Thromboembolism

• About 80% of systemic emboli arise from intracardiac mural thrombi.
• Of these:
  • about 2/3 are associated with left ventricular infarction
  • about 25% arise from a dilated left atrium, such as with mitral valve disease
• Other sources include:
  • aortic aneurysms
  • thrombi over ulcerated atherosclerotic plaques
  • fragmented valvular vegetations
  • venous thrombi entering systemic circulation → paradoxical emboli
• About 10%–15% have no identified source.
• Unlike venous emboli, which mainly travel to the lungs, systemic arterial emboli can travel almost anywhere.
• Their final site depends on:
  • point of origin
  • amount of blood flowing to downstream organs
• Common sites:
  • Lower extremities → ~75%
  • Central nervous system → ~10%
  • Less commonly → intestines, kidneys, spleen
• The effect depends on:
  • size of the blocked vessel
  • presence of collateral circulation
  • tissue sensitivity to lack of oxygen
• Infarction is common because arterial emboli often lodge in end arteries.

Fat Embolism

• Crush injury to soft tissue or rupture of bone-marrow vessels, especially after a long-bone fracture, can release:
  • microscopic fat droplets
  • marrow elements
    into the circulation (Fig. 3.16A).
• Fat emboli may occur after vigorous cardiopulmonary resuscitation and are often clinically insignificant.
• A small number of patients with severe skeletal injury develop fat embolism syndrome.
• Major features:
  • pulmonary insufficiency
  • neurologic symptoms
  • anemia
  • thrombocytopenia
  • diffuse petechial rash
• Symptoms usually appear 1–3 days after injury:
  • rapid breathing
  • dyspnea
  • tachycardia
  • irritability
  • restlessness
• Severe cases may progress to delirium or coma.
• Death occurs in about 10% of cases.
• Thrombocytopenia occurs because platelets adhere to fat droplets → aggregate or become sequestered in the spleen.
• Anemia may result from red-cell aggregation and/or hemolysis.
• Petechial rash occurs in about 20%–50% of cases and is related to thrombocytopenia.
• Fat embolism syndrome develops through two main mechanisms:
  • Mechanical obstruction → fat microemboli block pulmonary and cerebral microvessels and promote platelet aggregation.
  • Biochemical injury → fatty acids released from fat droplets damage endothelium.
• Platelet activation and granulocyte recruitment further damage vessels through release of:
  • free radicals
  • proteases
  • eicosanoids
• Routine tissue processing dissolves fat, so demonstrating isolated fat droplets microscopically requires special fat stains on frozen sections.

KEY CONCEPT

• Systemic embolus → usually from left-sided cardiac mural thrombus → travels to systemic arteries → commonly causes infarction.
• Fat embolism → usually follows severe skeletal injury or long-bone fracture.
• Fat embolism syndrome = respiratory distress + neurologic symptoms + anemia + thrombocytopenia + petechial rash.
• Mechanism = microvascular obstruction + fatty-acid–induced endothelial injury.

CONCEPTUAL EXAMPLES

• Left ventricular infarction → mural thrombus forms → fragment breaks off → travels to leg artery → systemic embolism and infarction.
• Long-bone fracture → marrow fat enters blood → reaches lung and brain microvessels → fat embolism syndrome.
• Fat droplets activate platelets → platelet count falls → thrombocytopenia + petechiae.

Amniotic Fluid Embolism

• Amniotic fluid embolism is a rare but very serious complication of labor or the immediate postpartum period.
• It occurs when amniotic fluid and fetal material enter the maternal circulation through tears in:
  • placental membranes
  • uterine veins
• It occurs in about 1 in 40,000 deliveries, but mortality approaches 80%.
• It causes about 5%–10% of maternal deaths in the United States.
• About 85% of survivors have some permanent neurologic deficit.
• Typical sudden presentation:
  severe dyspnea → cyanosis → shock → seizures → coma.
• If the patient survives the initial crisis:
  • pulmonary edema usually develops.
  • about half develop disseminated intravascular coagulation (DIC).
• DIC occurs because amniotic fluid contains thrombogenic substances that activate coagulation.
• The major injury is thought to result mainly from:
  • activation of the coagulation system
  • activation of the innate immune system
• Therefore, the severe effects are not mainly due to simple mechanical blockage of pulmonary vessels.
• In fatal cases, maternal pulmonary microcirculation may contain fetal material (Fig. 3.16B), including:
  • fetal squamous cells
  • lanugo hair
  • fat from vernix caseosa
  • fetal mucin
• Other pathologic findings include:
  • marked pulmonary edema
  • diffuse alveolar damage
  • widespread fibrin thrombi caused by DIC

KEY CONCEPT

• Labor/postpartum → amniotic fluid enters maternal blood → coagulation + innate immune activation → sudden respiratory failure, shock, neurologic symptoms, and often DIC.
• Classic sequence:
  sudden dyspnea + cyanosis + shock → seizures/coma → pulmonary edema ± DIC.

CONCEPTUAL EXAMPLES

• Tear in placental membranes → amniotic fluid enters maternal veins → sudden dyspnea and shock.
• Amniotic fluid activates coagulation → widespread fibrin formation → DIC.
• Fetal squamous cells, lanugo, fat, and mucin found in maternal lung vessels → supports amniotic fluid embolism.

Air Embolism

• Air/gas embolism occurs when gas bubbles enter the circulation, join together, and block blood flow → distal ischemia.
• Even a small amount of air can be dangerous if it enters:
  • a coronary artery during bypass surgery → severe cardiac ischemia
  • a cerebral artery during neurosurgery → severe brain ischemia
• Small venous gas emboli usually cause little harm.
• Larger amounts of venous air may enter during:
  • obstetric procedures
  • laparoscopic procedures
  • chest-wall injury
• This air can reach pulmonary vessels → hypoxia.
• A very large venous gas embolus may become trapped in the heart → death.
• Decompression sickness is a special form of gas embolism caused by a rapid fall in atmospheric pressure.
• It can occur in:
  • scuba divers
  • underwater construction workers
  • people in unpressurized aircraft after rapid ascent
• At high pressure, such as during deep diving:
  ↑ pressure → more nitrogen dissolves in blood and tissues.
• If pressure falls too quickly:
  dissolved nitrogen → expands → forms bubbles → gas emboli → tissue ischemia.
• Nitrogen bubbles in muscles and tissues around joints cause severe pain called “the bends.”
• Gas bubbles in pulmonary vessels → pulmonary edema + hemorrhage + focal atelectasis/emphysema → respiratory distress.
• Gas bubbles in the central nervous system may cause:
  • memory loss
  • ataxia
  • visual disturbances
  • sudden coma
• Caisson disease is the chronic form of decompression sickness.
• Recurrent or persistent gas emboli in bones → multiple areas of ischemic bone necrosis.
• Commonly affected sites include the heads of the:
  • femurs
  • tibiae
  • humeri
• Acute decompression sickness is treated by placing the patient in a high-pressure chamber → gas is forced back into solution.
• Then slow decompression allows gradual gas absorption and exhalation → prevents bubbles from forming again.

KEY CONCEPT

• Gas bubble → vessel obstruction → ischemia.
• Rapid decompression → dissolved nitrogen forms bubbles → decompression sickness.
• Muscle/joint bubbles → bends.
• Lung bubbles → respiratory distress.
• Brain bubbles → neurologic dysfunction/coma.
• Chronic bone involvement → caisson disease.
• Treatment → recompression followed by slow decompression.

CONCEPTUAL EXAMPLES

• Deep-sea diver ascends too quickly → nitrogen comes out of solution → gas emboli.
• Nitrogen bubbles around joints → severe pain → the bends.
• Gas bubbles enter pulmonary vessels → edema and hemorrhage → respiratory distress.
• Repeated decompression injury in bones → ischemic necrosis → caisson disease.