Embolic obstruction of medium-sized arteries and sub- sequent rupture of downstream capillaries rendered anoxic can cause pulmonary hemorrhage. Such emboli do not usually cause pulmonary infarction because the area also receives blood through an intact bronchial cir- culation (dual circulation). However, a similar embolus in the setting of left-sided cardiac failure (and dimin- ished bronchial artery perfusion) can lead to a pulmo- nary infarct. #301 | | |
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Embolism to small end-arteriolar pulmonary branches usually causes infarction. #303 | | |
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Multiple emboli occurring through time can cause pul- monary hypertension and right ventricular failure (cor pulmonale). #305 | | |
Fig. 4.15 Embolus derived from a lower-extremity deep venous thrombus lodged in a pulmonary artery branch. #306 | | |
Systemic Thromboembolism #307 | | |
Most systemic emboli (80%) arise from intracardiac mural thrombi; two-thirds of these are associated with left ven- tricular infarcts and another 25% with dilated left atria (e.g., secondary to mitral valve disease). The remainder originate from aortic aneurysms, thrombi overlying ulcerated ath- erosclerotic plaques, fragmented valvular vegetations (Chapter 11), or the venous system (paradoxical emboli); 10% to 15% of systemic emboli are of unknown origin. #308 | | |
By contrast with venous emboli, which lodge primarily in the lung, arterial emboli can travel virtually anywhere; their final resting place understandably depends on their point of origin and the relative flow rates of blood to the downstream tissues. Common arteriolar embolization sites include the lower extremities (75%) and central nervous system (10%); intestines, kidneys, and spleen are less common targets. The consequences of embolization depend on the caliber of the occluded vessel, the collateral supply, and the affected tissue’s vulnerability to anoxia; arterial emboli often lodge in end arteries and cause infarction. #309 | | |
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Soft tissue crush injury or rupture of marrow vascular sinusoids (eg, due to a long bone fracture) release micro- scopic fat globules into the circulation. Fat and marrow emboli are common incidental findings after vigorous car- diopulmonary resuscitation but probably are of little clini- cal significance. Similarly, although fat and marrow embolism occurs in some 90% of individuals with severe skeletal injuries (Fig. 4.16A), less than 10% show any clini- cal findings. However, a minority of patients develop a symptomatic fat embolism syndrome characterized by pul- monary insufficiency, neurologic symptoms, anemia, thrombocytopenia, and a diffuse petechial rash that is fatal in 10% of cases. Clinical signs and symptoms appear 1 to 3 days after injury as the sudden onset of tachypnea, dyspnea, tachycardia, irritability, and restlessness, which can progress rapidly to delirium or coma. Thrombocytope- nia is attributed to platelet adhesion to fat globules and subsequent aggregation or splenic sequestration; anemia can result from similar red cell aggregation and/or hemo- lysis. A diffuse petechial rash (seen in 20%–50% of cases) is related to rapid onset of thrombocytopenia and can be a useful diagnostic feature. #311 | | |
The pathogenesis of fat emboli syndrome involves both mechanical obstruction and biochemical injury. Fat micro- emboli occlude pulmonary and cerebral microvasculature, both directly and by triggering platelet aggregation. This deleterious effect is exacerbated by fatty acid release from lipid globules, which causes local toxic endothelial injury. Platelet activation and granulocyte recruitment (with free radical, protease, and eicosanoid release) (Chapter 3) com- plete the vascular assault. Because lipids are dissolved by the solvents used during tissue processing, microscopic demonstration of fat microglobules (i.e., in the absence of #312 | | |
accompanying marrow elements) requires specialized techniques (frozen sections and fat stains). #313 | | |
Fig. 4.16 Unusual types of emboli. (A) Bone marrow embolus. The embolus is composed of hematopoietic marrow and marrow fat cells (clear spaces) attached to a thrombus. (B) Amniotic fluid emboli. Two small pulmonary arterioles are packed with laminated swirls of fetal squamous cells. The sur- rounding lung is edematous and congested. (Courtesy of Dr. Beth Schwartz, Baltimore, MD.) #314 | | |
Amniotic Fluid Embolism #315 | | |
Amniotic fluid embolism is an uncommon, grave compli- cation of labor and the immediate postpartum period occurring in 1 in 40,000 deliveries. The mortality rate approaches 80%, making it the most common cause of maternal death in the developed world and the fifth most common cause of maternal death in the United States, accounting for 10% of maternal deaths in this country; 85% of survivors suffer some form of permanent neurologic deficit. Onset is characterized by sudden severe dyspnea, cyanosis, and hypotensive shock, followed by seizures and coma. If the patient survives the initial crisis, pulmonary edema typically develops, along with (in about half the patients) disseminated intravascular coagulation second- ary to release of thrombogenic substances from amniotic fluid. Indeed it is thought that morbidity and mortality in such cases results not from mechanical obstruction of pul- monary vessels but from biochemical activation of the coagulation system and the innate immune system caused by substances in the amniotic fluid. #316 | | |
The underlying cause is the entry of amniotic fluid (and its contents) into the maternal circulation via tears in the placental membranes and/or uterine vein rupture. Histo- logic analysis shows squamous cells shed from fetal skin, lanugo hair, fat from vernix caseosa, and mucin derived from the fetal respiratory or gastrointestinal tracts in the maternal pulmonary microcirculation (Fig. 4.16B). Other findings include marked pulmonary edema, diffuse alveo- lar damage (Chapter 13), and systemic fibrin thrombi gen- erated by disseminated intravascular coagulation. #317 | | |
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Gas bubbles within the circulation can coalesce and obstruct vascular flow and cause distal ischemic injury. Thus, a small volume of air trapped in a coronary artery during bypass surgery or introduced into the cerebral arte- rial circulation by neurosurgery performed in an upright “sitting position” can occlude flow, with dire consequences. Small venous gas emboli generally have no deleterious effects, but sufficient air can enter the pulmonary circula- tion inadvertently during obstetric or laproscopic proce- dures or as a consequence of a chest wall injury to cause hypoxia, and very large venous emboli may arrest in the heart and cause death. #319 | | |
A particular form of gas embolism called decompression sickness is caused by sudden changes in atmospheric pres- sure. Scuba divers, underwater construction workers, and persons in unpressurized aircraft who undergo rapid ascent are at risk. When air is breathed at high pressure (e.g., during a deep sea dive), increased amounts of gas (particu- larly nitrogen) become dissolved in the blood and tissues. If the diver then ascends (depressurizes) too rapidly, the nitrogen expands in the tissues and bubbles out of solution in the blood to form gas emboli, which cause tissue ische- mia. Rapid formation of gas bubbles within skeletal muscles and supporting tissues in and about joints is responsible for the painful condition called the bends (so named in the #320 | | |
1880s because the afflicted person arches the back in a manner reminiscent of a then-popular women’s fashion pose called the Grecian bend). Gas bubbles in the pulmo- nary vasculature cause edema, hemorrhages, and focal atel- ectasis or emphysema, leading to respiratory distress, the so-called “chokes”. Bubbles in the central nervous system can cause mental impairment and even sudden onset of coma. A more chronic form of decompression sickness is called caisson disease (named for pressurized underwater vessels used during bridge construction), in which recur- rent or persistent gas emboli in the bones lead to multifocal ischemic necrosis; the heads of the femurs, tibiae, and humeri are most commonly affected. #321 | | |
Placing affected persons in a high-pressure chamber, to force the gas back into solution, treats acute decompression sickness. Subsequent slow decompression permits gradual gas resorption and exhalation so that obstructive bubbles do not re-form. #322 | | |
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An embolus is a solid, liquid, or gaseous mass carried by the blood to a site distant from its origin; most are dislodged thrombi. #326 | | |
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Pulmonary emboli derive primarily from lower-extremity deep vein thrombi. Their effects depend mainly on the size of the embolus and the location in which it lodges. Consequences may include right-sided heart failure, pulmonary hemorrhage, pulmonary infarction, or sudden death. #328 | | |
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Systemic emboli derive primarily from cardiac mural or valvu- lar thrombi, aortic aneurysms, or atherosclerotic plaques; whether an embolus causes tissue infarction depends on the site of embolization and the presence or absence of collateral circulation. #330 | | |
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Fat embolism can occur after crushing injuries to the bones; symptoms include pulmonary insufficiency and neurological damage. Amniotic fluid embolism may follow childbirth and can give rise to fatal pulmonary and cerebral manifestations. Air embolism can occur upon rapid decompression, most commonly in divers; it results from sudden bubbling of nitrogen dissolved in blood at higher pressures. #332 | | |
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An infarct is an area of ischemic necrosis caused by occlu- sion of the vascular supply to the affected tissue. Infarc- tion primarily affecting the heart and the brain is a common and extremely important cause of clinical illness. Roughly 40% of all deaths in the United States are a consequence of cardiovascular disease, with most of these deaths stem- ming from myocardial or cerebral infarction. Pulmonary infarction is a common clinical complication, bowel infarc- tion often is fatal, and ischemic necrosis of distal extremi- ties (gangrene) causes substantial morbidity in the diabetic population. #334 | | |
Arterial thrombosis or arterial embolism underlies the vast majority of infarctions. Less common causes of arterial obstruction include vasospasm, expansion of an atheroma secondary to intraplaque hemorrhage, and extrinsic com- pression of a vessel, such as by tumor, a dissecting aortic aneurysm, or edema within a confined space (e.g., in ante- rior tibial compartment syndrome). Other uncommon causes of tissue infarction include vessel twisting (e.g., in testicular torsion or bowel volvulus), traumatic vascular rupture, and entrapment in a hernia sac. Although venous thrombosis can cause infarction, the more common outcome is simply congestion; typically, bypass channels rapidly open to provide sufficient outflow to restore the arterial inflow. Infarcts caused by venous thrombosis thus usually occur only in organs with a single efferent vein (e.g., testis or ovary). #335 | | |
MORPHOLOGY Infarcts are classified based on their color (reflecting the amount #336 | | |
of hemorrhage) and the presence or absence of microbial infec- tion. Thus, infarcts may be either red (hemorrhagic) or white (anemic) and may be either septic or bland. #337 | | |
Red infarcts (Fig. 4.17A) occur (1) as a result of venous occlu- sions (such as in ovarian torsion); (2) in loose tissues (e.g., lung) where blood can collect in infarcted zones; (3) in tissues with dual circulations such as lung and small intestine, where partial, albeit inadequate perfusion by collateral arterial supplies is typical; (4) in previously congested tissues (as a consequence of sluggish venous outflow); and (5) when flow is reestablished after infarction has occurred (e.g., after angioplasty of an arterial obstruction). #338 | | |
White infarcts occur with arterial occlusions in solid organs with end-arterial circulations (e.g., heart, spleen, and kidney), and where tissue density limits the seepage of blood from adjoining patent vascular beds (Fig. 4.17B). Infarcts tend to be wedge- shaped, with the occluded vessel at the apex and the organ periphery forming the base (Fig. 4.17); when the base is a serosal surface, there is often an overlying fibrinous exudate. Lateral margins may be irregular, reflecting flow from adjacent vessels. The margins of acute infarcts typically are indistinct and slightly hemorrhagic; with time, the edges become better defined by a narrow rim of hyperemia attributable to inflammation. #339 | | |
Infarcts resulting from arterial occlusions in organs without a dual circulation typically become progressively paler and more sharply defined with time (Fig. 4.17B). By comparison, hemor- rhagic infarcts are the rule in the lung and other spongy organs (Fig. 4.17A). Extravasated red cells in hemorrhagic infarcts are phagocytosed by macrophages, and the heme iron is converted to intracellular hemosiderin. Small amounts do not impart any appreciable color to the tissue, but extensive hemorrhages leave a firm, brown residue. #340 | | |
In most tissues, the main histologic finding associated with infarcts is ischemic coagulative necrosis (Chapter 2). An inflammatory response begins to develop along the margins of infarcts within a few hours and usually is well defined within 1 to 2 days. Eventually, inflammation is followed by repair, beginning in the preserved margins (Chapter 3). In some tissues, parenchy- mal regeneration can occur at the periphery of the infarct, where the underlying stromal architecture has been spared. Most infarcts, however, are ultimately replaced by scar (Fig. 4.18). The brain is an exception to these generalizations; ischemic tissue injury in the central nervous system results in liquefactive necrosis (Chapter 2). #341 | | |
Septic infarctis occur when infected cardiac valve vegeta- tions embolize, or when microbes seed necrotic tissue. In these cases the infarct is converted into an abscess, with a correspond- ingly greater inflammatory response and healing by organization and fibrosis (Chapter 3). #342 | | |
Fig. 4.17 Red and white infarcts. (A) Hemorrhagic, roughly wedge-shaped pulmonary infarct (red infarct). (B) Sharply demarcated pale infarct in the spleen (white infarct). #343 | | |
Fig. 4.18 Remote kidney infarct, now replaced by a large fibrotic scar. #344 | | |
Factors That Influence Infarct Development #345 | | |
The effects of vascular occlusion range from inconse- quential to tissue necrosis leading to organ dysfunction and sometimes death. The range of outcomes is influenced by the following three variables: #346 | | |
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Anatomy of the vascular supply. The presence or absence of an alternative blood supply is the most important factor in determining whether occlusion of an individ- ual vessel causes damage. The dual supply of the lung by the pulmonary and bronchial arteries means that obstruction of the pulmonary arterioles does not cause lung infarction unless the bronchial circulation also is compromised. Similarly, the liver, which receives blood from the hepatic artery and the portal vein, and the hand and forearm, with its parallel radial and ulnar arterial supply, are resistant to infarction. By contrast, the kidney and the spleen both have end-arterial circula- tions, and arterial obstruction generally leads to infarc- tion in these tissues. #348 | | |
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Rate of occlusion. Slowly developing occlusions are less likely to cause infarction because they allow time for the development of collateral blood supplies. For example, small interarteriolar anastomoses, which normally carry minimal blood flow, interconnect the three major coro- nary arteries. If one coronary artery is slowly occluded (e.g., by encroaching atherosclerotic plaque), flow in this collateral circulation may increase sufficiently to prevent infarction—even if the original artery becomes com- pletely occluded. #350 | | |
