Cardiovascular System and Lymphatic Vessels

Blood Vessels: The aorta originates from the left ventricle and provides oxygenated blood to the entire body via arteries. In a treelike manner, arteries branch and become smaller arterioles as they approach capillary beds (see Web Fig. 10-1; also see Chapter 2). These beds and postcapillary venules provide the site for exchange of oxygen, carbon dioxide, nutrients, and waste. Small venules return the exchanged fluid and blood to larger veins and eventually the postcava and precava drain into the right atrium. The poorly oxygenated blood enters the pulmonary artery from the right ventricle. Oxygen exchange occurs in the capillaries of the lung, and oxygenated blood is returned to the heart via the pulmonary veins into the left atrium.

Lymphatic Vessels: Lymphatic vessels are thin walled, endothelial-lined channels that originate near the capillary beds and serve as a drainage system for returning interstitial tissue fluid and inflammatory cells to the blood. Afferent lymphatic vessels drain lymph into regional lymph nodes, which then filter and provide immunologic surveillance of the lymph, its cells, and the foreign matter it contains. The filtered lymph continues into larger efferent lymphatic vessels, which eventually drain into the caval blood via the thoracic duct. Both lymphatic vessels and veins have valves to prevent backflow of fluid. A more complete description can be found in Chapter 2.

Sinoatrial Node: The SAN is positioned adjacent to the epicardial adipose tissue and is often centered around a branch of the right coronary artery (Fig. 10-5, A). Several large autonomic nervous system ganglions can occasionally be seen clustering in the epicardium adjacent to the node. The SAN lacks discrete structure, and its ill-defined borders merge with the adjacent atrial wall. It structurally consists of a collection of haphazardly oriented myofibers that appear as a pseudosyncytium and are embedded within abundant loose collagenous and elastic connective tissue, with rare cores of epicardially oriented dense collagen fibers (Fig. 10-5, A1). The nodal myofibers have discrete cell borders, a moderate amount of wavy sarcoplasm with sparse myofibrils, and an elongated nucleus that contains clumps of coarse chromatin (Fig. 10-5, A2).

Atrioventricular Node, Atrioventricular Bundle, and Bundle Branches: The AVN lies within the right atrial subendocardium and consists of a discrete, compact to loose mass of interconnecting myofibers that are often embedded within adipose tissue. A small nodal artery, parasympathetic ganglia, and large myelinated autonomic nerves are often present adjacent to the AVN. The nodal myofibers that have characteristic pale eosinophilic and thin sarcoplasm generally run parallel to each other but occasionally have an interweaving pattern with intervening loose collagen fibers. These myofibers contain a moderate amount of sarcoplasm with abundance of distinct striations and a short oval to elongated nucleus with dispersed chromatin.

The AV bundle (Fig. 10-5, B) emerges from the cranial pole of the AVN (Fig. 10-5, B1) and pierces through the CFB, approximately at the level of the annuli of the aortic and mitral valves (Fig. 10-5, B2), to become the left and right bundle branches. The size of an AV bundle myofiber progressively enlarges and its cytomorphology transitions from a pale eosinophilic, small and thin (AVN-like morphology) myofiber to a pale eosinophilic, foamy to waxy, large, and somewhat rectangular myofiber that lacks cross striations (a Purkinje-like cellular morphology) (Fig. 10-5, C).

Autonomic Nervous System: The nerve supply to the heart is autonomic and includes sympathetic, parasympathetic, and nonadrenergic noncholinergic innervation. Histologically, large nerves can be seen in the epicardium and adjacent to the coronary blood vessels, whereas special staining techniques are required for demonstration of neural tissue elsewhere. Electron microscopy and immunohistochemistry allow differentiation between sympathetic and parasympathetic nerves that are otherwise indistinguishable with H&E stain. Preganglionic parasympathetic fibers pass to the heart through the cardiac branch of the vagal nerve and synapse with parasympathetic ganglionic neurons. Postganglionic neurons are distributed to the SAN and AVN, as well as to atrial and, to a much lesser extent, ventricular myocardium (however, the ventricular conduction system is well supplied by cholinergic innervation). Postganglionic sympathetic fibers arising from the cervicothoracic and middle cervical ganglia intensely innervate the SAN and AVN and to lesser extent the AV bundle. The atrial endocardium, myocardium, and epicardium are evenly innervated, whereas the ventricles are considerably less innervated with epicardium more densely populated by neural tissue than the endocardium.

Congestive Heart Failure: Congestive heart failure usually develops slowly from gradual loss of cardiac pumping efficiency coupled with either pressure or volume overload or myocardial damage (Figs. 10-7 and 10-8; also see Figs. 8-29, 8-30, and 9-39). Pathophysiologically, congestive heart failure is initiated by development of cardiac disease (e.g., myocardial, valvular, congenital) or increased workload associated with pulmonary, renal, or vascular disease leading to loss of cardiac reserve and development of decreased blood flow to peripheral tissue (forward failure) and accumulation of blood behind the failing chamber (backward failure). Reduced renal blood flow creates hypoxia in the kidneys and increases renin release from the juxtaglomerular apparatus, resulting in stimulation of aldosterone release from the zona glomerulosa of the adrenal cortex. Sodium and water retention are the results of the action of aldosterone on the renal tubules; increased plasma volume follows, as does accumulation of edema fluid (mainly in body cavities). Hypoxia also stimulates increased erythropoiesis in bone marrow and extramedullary organs, such as the spleen, causing polycythemia and thus increased viscosity of the blood. The hypervolemia from aldosterone-induced water retention increases the workload on the already failing heart. Thus a vicious cycle of cardiac decompensation is initiated that eventually leads to death from cardiac failure unless therapeutic intervention occurs. Cardiac dilation, hypertrophy, and increased heart rate can provide some compensation for the increased workload.

Acute and Chronic Left-Sided Heart Failure: Acute left-sided heart failure is manifested by pulmonary congestion and edema, whereas chronic left-sided heart failure is manifested by chronic passive pulmonary congestion, chronic pulmonary edema, hemosiderosis (“heart failure cells”; see Fig. 9-39), and fibrosis. The most common causes are (1) myocardial contractility loss associated with myocarditis, myocardial necrosis, or cardiomyopathy; (2) dysfunction of the mitral or aortic valves; and (3) several congenital heart diseases.

Acute and Chronic Right-Sided Heart Failure: Acute right-sided heart failure results in acute passive congestion (see Fig. 2-35) leading to hepatomegaly and splenomegaly (see Figs. 2-35 and 13-50, A), whereas chronic right-sided heart failure (see Fig. 2-36) results in hepatic congestion (nutmeg liver) (see Fig. 8-30) and more severe sodium and water retention than in left-sided heart failure. Edema is evident predominantly as ventral subcutaneous edema in horses and ruminants (see Fig. 10-8), ascites in dogs, and hydrothorax in cats. Causes of right-sided failure include (1) pulmonary hypertension, (2) cardiomyopathy, and (3) disease of the tricuspid and pulmonary valves. (See Chapters 8 and 9 for further details on hepatic and pulmonary lesions, respectively, associated with congestive heart failure.)

Clinical Diagnostic Procedures:

Information on this topic including Web Appendix 10-3 is available at evolve.elsevier.com/Zachary/McGavin/.

Hemorrhage: Hemorrhage involving the pericardium and epicardium (Fig. 10-9; Web Fig. 10-7) results from stretching, tearing, lacerating, or crushing blood vessels in these structures and may be caused by penetrating wounds (foreign objects, bullets, or knives), lacerations from fractured bone, shear forces that stretch and ultimately tear vessels in tissues (blunt force trauma), and tears and rupture of tissue resulting from loss of structural integrity attributable to invasive and destructive properties of neoplasms such as hemangiosarcomas (see Chapter 2).

Effusions: See the discussions on the mechanisms of edema formation and Fig. 2-6 in Chapter 2 and on the formation of transudates and exudates and Figure 3-3 in Chapter 3.

Serous Atrophy: Serous atrophy of fat is readily identified by the gray gelatinous appearance of epicardial fat deposits (Fig. 10-13). Healthy animals normally have abundant white or yellow epicardial fat deposits, especially along the AV junction. Microscopically, lipocytes are atrophic and edema is present in the interstitial tissue. Serous atrophy of epicardial fat occurs rapidly during anorexia, starvation, or cachexia because fat is catabolized to maintain energy balance.

Pericardial Dilatation: The pericardium responds to excess fluid in the pericardial space by dilation. However, this outcome requires adequate time to allow adjustments in size. In hemopericardium, blood rapidly fills the pericardial cavity and death often occurs unexpectedly from cardiac tamponade, a condition with compression of the heart caused by blood accumulation leading to reduced cardiac output. Hydropericardium is the accumulation of clear, light yellow, watery, serous fluid (i.e., transudate) in the pericardial sac (see Fig. 10-12; see Web Fig. 10-8). In cases associated with vascular injury, a few fibrin strands are present, and the fluid could clot after exposure to air.

Epicardial Calcification: Epicardial calcification is a feature in hereditary calcinosis in mice and cardiomyopathy in hamsters (Web Fig. 10-9). Myocardial mineralization (discussed later) may be visible on the epicardial surface in vitamin E–selenium deficiency in sheep and cattle, vitamin D toxicity in several species, calcinogenic plant toxicosis in cattle (“Manchester wasting disease”), and spontaneous myocardial calcification in aged rats and guinea pigs.

Gout: Visceral gout has not been reported in domestic animals but does occur in birds and reptiles (Web Fig. 10-10; see Chapter 1).

Pericarditis: Inflammation of the pericardium is frequently seen with bacterial septicemias and typically results in fibrinous pericarditis. Grossly, both the visceral and parietal pericardial surfaces are covered by variable amounts of yellow fibrin deposits, which can result in adherence between the parietal and visceral layers. When the pericardial sac is opened the attachments are torn away (so-called bread-and-butter heart) (Fig. 10-14). Microscopically, an eosinophilic layer of fibrin with admixed neutrophils lies over a congested epicardium (Fig. 10-15).

The outcome of fibrinous pericarditis varies. Early death is frequent because many of these lesions result from infection by highly virulent bacteria and concurrent septicemia. When survival is prolonged, adhesions form between the pericardial surfaces after fibrous organization of the exudate.

Suppurative pericarditis is seen mainly in cattle as a complication of traumatic reticuloperitonitis (“hardware disease”). Foreign bodies, such as nails or pieces of wire that accumulate in the reticulum, occasionally penetrate the reticular wall and diaphragm, enter the adjacent pericardial sac, and introduce infection. Some affected cattle survive for weeks to months until death ensues from congestive heart failure or septicemia. Grossly, the pericardial surfaces are notably thickened by white, often rough, shaggy-appearing masses of fibrous connective tissue that enclose an accumulation of white to gray, thick, foul-smelling, purulent exudate (Fig. 10-16).

Constrictive pericarditis is a chronic inflammatory lesion of the pericardium accompanied by extensive fibrous proliferation and eventual formation of fibrous adhesions between the surfaces of the visceral and parietal pericardium. The condition is seen in some cases of suppurative pericarditis in cattle and pigs with chronic fibrinous pericarditis. Severe lesions obliterate the pericardial sac and constrict the heart with fibrous tissue and can interfere with cardiac filling and thus cardiac output. Compensatory myocardial hypertrophy can result in diminished ventricular chamber volumes and contribute to the eventual development of heart failure.

Hemorrhage: Trauma (Physical Injury): See the discussion on hemorrhage in the section on Pericardium and Epicardium, Disturbances of Circulation, and the discussion on hemorrhage in Chapter 2.

Hypertrophy: Hypertrophy of the myocardium represents an increase in muscle mass, which is the result of an increase in the size of cardiac muscle cells (Fig. 10-18; see Fig. 10-6, B). Hypertrophy is generally secondary and is the result of a compensatory response to increased workload; it is usually reversible on removal of the cause. However, primary hypertrophy also occurs, as in cats and dogs with idiopathic hypertrophic cardiomyopathy (see later discussion), and is not reversible. Two anatomic forms of hypertrophy are recognized. Eccentric hypertrophy results in a heart with enlarged ventricular chambers and walls of normal to somewhat decreased thickness; it is produced by lesions that increase blood volume load such as valvular insufficiencies and septal defects. In concentric hypertrophy the heart is characterized by small ventricular chambers and thick walls; it results from lesions that increase pressure load such as valvular stenosis, systemic hypertension, and pulmonary disease. Some cats with hyperthyroidism have a cardiac hypertrophy that is mediated by enhanced production of myocardial contractile proteins under the influence of increased concentration of circulating thyroid hormones (Fig. 10-19). The hypertrophy is reversible on return to euthyroidism.

Physiologic Atrophy: Physiologic atrophy of heart muscle may occur in confined animals and also occurs as a result of decompensation of cardiac myocytes in chronic congestive heart failure (see Fig. 10-6, A). Initially, these myocytes respond through hypertrophy with increased contractile force according to the Frank-Starling phenomenon. However, stretching beyond certain limits decreases contractile strength and eventually leads to loss of contractile proteins within these cells or loss of these cells resulting in atrophy of the affected myocardium (see Fig. 10-18).

Neoplastic Transformation: Rhabdomyomas and rhabdomyosarcomas are primary tumors that originate from the myocardium in domestic animals (see Chapter 6). Fibrosarcomas also occur rarely. Numerous types of secondary tumors, such as lymphosarcomas, metastasize to the myocardium and are discussed in this chapter and other chapters of this book. Hemangiosarcomas are tumors of blood vessels of the myocardium of the right atrium and are discussed later.

Oncotic Necrosis: Necrosis of cardiac muscle cells is generally followed by leukocytic invasion and phagocytosis of sarcoplasmic debris (Fig. 10-24; see Figs. 15-15 and 15-16). The end result is persistence of collapsed sarcolemmal “tubes” of basal lamina surrounded by condensed interstitial stroma and vessels. Lesions with severe disruption of the myocardium have residual changes of fibroblastic proliferation and collagen deposition to form scar tissue. Regeneration of cardiac muscle cells generally does not occur, except in less evolved animals, such as amphibians and fish, and in certain inbred mouse strains. The continual contraction of intact cardiac muscle cells impairs the mechanisms for regeneration. Also, in hearts of neonatal animals and more often in avian hearts, a limited amount of myocyte regeneration has been reported. Recent studies indicate that stem cells exist in adult animal and human hearts, and with myocardial injury, these cells may differentiate into cardiac muscle cells. However, the extent of myocyte regeneration is probably minimal. Hyperplasia of myocytes is a normal component of cardiac growth in the first several months of life. Then proliferation ceases. Normal growth then is the result of hypertrophy of myocytes until cell sizes normal for the species are reached.

Apoptosis: Apoptosis (programmed cell death of cardiac myocytes) is increasingly recognized for its role in the development of various myocardial lesions and cardiac diseases (see Chapter 1). These conditions include cardiac development, ischemic injury, several types of experimentally induced heart failure (ischemia-reperfusion, hypoxia, pressure-overload hypertrophy), and cardiotoxicity. In some cell systems, apoptosis can be triggered by the presence of excessive amounts of oxygen free radicals. Cells dying by apoptosis shrink and form apoptotic bodies. In contrast to cell death by necrosis, apoptosis is not accompanied by an inflammatory reaction and fibrosis.

Fatty Infiltration: Fatty infiltration is the presence of increased numbers of lipocytes interposed between myocardial fibers. The lesion is associated with obesity and age and appears as abundant epicardial and myocardial deposits of adipose tissue. Grossly, the myocardium has irregular layers of adipose tissue infiltrating normal myocardium. The atria and right ventricle are most often affected.

Fatty Degeneration: Fatty degeneration (fatty change) is the accumulation of abundant lipid droplets in the sarcoplasm of myocytes. Microscopically, affected myocytes have numerous variably sized spherical droplets that appear as empty vacuoles in paraffin sections but stain positively for lipids with lipid-soluble stains in frozen sections. This lesion occurs with systemic disorders, such as severe anemia, toxemia, and copper deficiency, but is seen much less often in the heart than in the liver and kidneys (also see Chapter 1).

Hydropic Degeneration: Hydropic degeneration, a distinctive microscopic alteration in cardiac muscle cells, is associated with chronic administration of anthracyclines, a group of antineoplastic drugs. Chronic passive congestion with ascites and cardiac dilation may result (Web Figs. 10-11 and 10-12; see Figs. 10-6, A and 10-7). Affected fibers have extensive vacuolization of sarcoplasm that is initiated by distention of elements of sarcoplasmic reticulum and eventually ends in lysis of contractile material (Web Figs. 10-13 and 10-14).

Hydropic degeneration of cardiac muscle cells may also result from drug-induced injury to mitochondria. Antiretroviral drugs, such as nucleoside reverse transcriptase inhibitors (zidovudine or AZT), are linked to this distinctive lesion. Scattered cardiac muscle cells appear swollen with pale sarcoplasm by light microscopy. Electron microscopy reveals extensive mitochondrial swelling and disruption of cristae with subsequent formation of myelin figures from the membrane debris of damaged mitochondria.

Myofibrillar Degeneration: Myofibrillar degeneration (myocytolysis) represents a distinctive sublethal injury of cardiac muscle cells. Affected fibers have pale eosinophilic sarcoplasm and lack cross-striations. Ultrastructurally, myofibrils have a variable extent of dissolution (myofibrillar lysis). This lesion has been described in furazolidone cardiotoxicity in birds (Fig. 10-25; Web Fig. 10-15) and potassium deficiency in rats.

Lipofuscinosis: Lipofuscinosis (brown atrophy) of the myocardium occurs in aged animals and in animals with severe cachexia, but it also has been described as a hereditary lesion in healthy Ayrshire cattle. Severely affected hearts appear brown and microscopically have clusters of yellow-brown granules at the nuclear poles of myocytes. These granules represent intralysosomal accumulation of membranous and amorphous debris (residual bodies).

Mineralization: Myocardial mineralization (calcium) is a prominent feature in several diseases, such as hereditary calcinosis in mice, cardiomyopathy in hamsters, vitamin E–selenium deficiency in sheep and cattle (Fig. 10-26; see Web Fig. 10-9), vitamin D toxicity in several species, calcinogenic plant toxicosis in cattle (“Manchester wasting disease”), and spontaneous myocardial calcification in aged rats and guinea pigs.

Myocardial Necrosis: Myocardial necrosis can result from a number of causes, including nutritional deficiencies, chemical and plant toxins, ischemia, metabolic disorders, heritable diseases, and physical injuries (see Box 10-5). Grossly, affected areas appear pale initially, and some progress to prominent yellow to white (see Fig. 10-69), dry areas made gritty by dystrophic mineralization. The lesions are focal, multifocal, or diffuse. The most frequent sites of focal lesions are the left ventricular papillary muscles and the subendocardial myocardium, especially when such lesions are related to transient reduction of vascular perfusion. These lesions can be overlooked at necropsy unless multiple incisions are made in the ventricular myocardium. In diseases with diffuse cardiac necrosis, such as white muscle disease of calves and lambs due to vitamin E–selenium deficiency, the discrete white lesions can be readily observed beneath the epicardial and endocardial surfaces (Fig. 10-27).

Microscopically, the appearance depends on the age of the lesions. Fibers in areas of recent necrosis often appear swollen and hypereosinophilic (hyaline necrosis). Striations are indistinct, and nuclei are pyknotic. Necrotic fibers often have scattered basophilic granules (Fig. 10-28) that represent calcified mitochondria and can be confirmed by electron microscopy (Web Fig. 10-16). In a second pattern of necrosis, affected myocytes have a “shredded” appearance because of hypercontraction and the formation of multiple transversely oriented bars of disrupted contractile material (often termed contraction band necrosis) (Web Fig. 10-17). A third pattern is seen in necrotic myocytes in large areas of ischemic necrosis (infarcts). These myocytes have features of coagulation necrosis and have relaxed rather than hypercontracted contractile elements.

Within 24 to 48 hours after injury, necrotic areas are infiltrated by inflammatory cells, mainly macrophages and a few neutrophils; these phagocytose and lyse the necrotic cellular debris (Web Fig. 10-18). In early stages of healing of necrosis, it is often difficult to distinguish the lesions from those found in some types of myocarditis (see later discussion). Later, when necrosis has progressed somewhat, lesions consist of persistent stromal tissue (interstitial fibroblasts, collagen, and capillaries) and empty “tubes” of basal laminae formally occupied by necrotic myocytes (see Chapter 15). The healing phase is characterized by proliferation of connective tissue cells (fibroblasts) (Fig. 10-29) and by deposition of connective tissue products (collagen and elastic tissue and acid mucopolysaccharides). Grossly, these areas with healing of myocardial necrosis appear as white, firm, contracted scars.

The outcome of myocardial necrosis varies, depending on the extent of the damage:

Hearts with minimal damage have only microscopically detectable myocardial fibrosis when death eventually occurs from other diseases.

Myocarditis: Myocarditis generally is the result of infections spread hematogenously to the myocardium and occurs in various systemic diseases. Infrequently, the heart is the primary location in affected animals and responsible for death. Types of inflammation provoked by infectious agents that produce myocarditis include suppurative, necrotizing, hemorrhagic, lymphocytic, and eosinophilic. Suppurative myocarditis results from localization of pyogenic bacteria in the myocardium (Fig. 10-30) that are trapped in thromboemboli originating from vegetative valvular endocarditis on the mitral and aortic valves. Septic infarcts with pale, disseminated lesions may be grossly evident in the myocardium. These foci consist of neutrophils and necrotic myocytes that form abscesses. The various infectious diseases that cause myocarditis in animals are summarized in Box 10-6.

The pathogenesis and expected outcome of cases of myocarditis remain an important area of research because of the severity of this lesion in cardiac failure in humans. The sequelae to myocarditis include (1) complete resolution of lesions, (2) scattered residual myocardial scars, or (3) progressive myocardial damage with acute or, in some cases, chronic cardiac failure as secondary dilated (congestive) cardiomyopathy. In experimental studies of myocarditis induced in mice by coxsackie B virus, the severity of myocarditis was influenced by the virulence of the virus and mouse strain and was enhanced by host factors such as young age, male sex, pregnancy, poor nutrition, whole-body ionizing radiation, cold environmental temperatures, alcohol ingestion, exercise, and cortisone administration. Much of the myocardial damage in coxsackie B virus infection is induced by immunologic reactions (with T lymphocyte involvement) rather than by direct viral injury.

Hemorrhage: Endocardial hemorrhages are commonly seen and may be the result of trauma or septicemias, especially those with endotoxins, or can occur agonally at death (Fig. 10-31). See the previous sections on the Pericardium and Epicardium and the Myocardium and also Chapter 2.

Valvular Anomalies and Dysplasia: See the discussion on valvular anomalies and dysplasia in the section on Endocardium and Heart Valves, Disturbances of Growth, Disorders of Domestic Animals.

Myxomatous Valvular Degeneration (Endocardiosis): See the discussion on myxomatous valvular degeneration (endocardiosis) (see Fig. 10-84) in the section on Disorders of Dogs.

Mineralization: Mineralization of the endocardium is seen with Vitamin D toxicity, calcinogenic plant toxicosis in cattle, and calcium phosphorus imbalance, as well as in Johne’s disease (Fig. 10-32; see Chapter 7). The endocardium and large elastic arteries are prone to mineralization because of their abundant elastic fibers.

Vegetative Valvular and Mural Endocarditis: Endocarditis is usually the result of bacterial infections, except for lesions produced by migrating Strongylus vulgaris larvae in horses and rarely in mycotic infections. The lesions are often very large by the time of death and are present on the valves (valvular endocarditis), although some lesions originate from the underlying myocardium or extend from the affected valve to the adjacent wall (mural endocarditis). Grossly, the affected valves have large, adhering, friable, yellow-to-gray masses of fibrin termed vegetations, which can occlude the valvular orifice (see Figs. 10-73, A, and 10-76). In chronic lesions, the fibrin deposits are organized by fibrous connective tissue to produce irregular nodular masses termed verrucae (wartlike lesions). Microscopically, the lesion consists of accumulated layers of fibrin and numerous embedded bacterial colonies underlain by a zone of infiltrated leukocytes and granulation tissue (see Fig. 10-73, B). Relative frequency of valvular involvement with endocarditis in animals is mitral > aortic > tricuspid > pulmonary.

The pathogenesis of endocarditis is complicated and incompletely understood, but the components of Virchow’s triad in thrombogenesis—endothelial injury, turbulence, and hypercoagulability—are involved. Affected animals often have preexisting extracardiac infections, such as gingivitis, mastitis, hepatic abscesses or dermatitis, that have resulted in one or more bouts of bacteremia. Turbulent intracardiac blood flow associated with congenital anomalies or the presence of intracardiac and vasculature devices, such as catheters, may contribute to initiation of the lesion. Focal trauma–induced endothelial disruption on the surface of the normally avascular valves allows bacteria to adhere, proliferate, and initiate an inflammatory reaction that results in subsequent deposition of masses of fibrin. Death is the result of cardiac failure from valvular dysfunction or the effects of bacteremia. In some animals, septic emboli lodge in organs such as the heart and kidneys, leading to infarction and localized inflammation or abscess formation. Also see the discussion of vegetative valvular and mural endocarditis in the section on Endocardium, Disorders of Domestic Animals.

Atrial Thrombosis: Atrial thrombi may occur with valvular or myocardial disease and are the result of hemostatic abnormalities resulting from stasis or turbulence.

Hemorrhage: Hemorrhage resulting from vascular injury is a frequent lesion of the epicardium, endocardium, and myocardium. Hemorrhages vary in size from petechiae (1- to 2-mm diameter), to ecchymoses (2- to 10-mm diameter), to suffusive (diffuse). Animals dying from septicemia, endotoxemia, anoxia, or electrocution often have prominent epicardial (see Fig. 10-9) and endocardial (see Fig. 10-31) hemorrhages. Horses dying of any cause usually have agonal hemorrhages on the epicardial and endocardial surfaces. A distinctive example of a specific disease with cardiac hemorrhage is mulberry heart disease, associated with vitamin E–selenium deficiency in growing pigs. In these pigs, hydropericardium accompanies severe myocardial hemorrhage that results in a red, mottled (mulberry-like) appearance of the heart. Also see the previous discussions on disturbances of circulation in the sections on the Pericardium and Epicardium and the Myocardium in the Responses to Injury section.

Effusions: See the previous discussion on disturbances of circulation in the section on the Pericardium and Epicardium.

Hypertrophy: Arterial hypertrophy is a response to sustained increases in pressure or volume loads. Affected vessels are generally muscular arteries, and the increase in wall thickness is predominantly caused by hypertrophy (and to some degree, hyperplasia) of smooth muscle cells of the tunica media. Muscular pulmonary arteries of cats are frequently affected, and the lesion has been associated with infection by several parasites, including Aelurostrongylus abstrusus (the lungworm of cats), Toxocara sp., and Dirofilaria immitis (Fig. 10-36). However, the lesions often occur in the absence of parasitic infections (Fig. 10-37). Often, no clinical disease is associated with the lesion in cats, but asthmatic signs have been seen in cats with these parasitic infections. Similar hypertrophy of muscular pulmonary arteries occurs in cattle with hypoxia-induced pulmonary arterial vasoconstriction and subsequent pulmonary hypertension associated with right-sided heart failure from exposure to high altitudes (so-called high-altitude disease or “brisket disease”) (see the previous section on Stages of Myocardial Hypertrophy). Also, animals with cardiovascular anomalies that shunt blood left to right result in pulmonary hypertension and have hypertrophy of the muscular pulmonary arteries and can result in plexogenic pulmonary arteriopathy. Uterine arteries in pregnant animals also are hypertrophic.

Agenesis (Aplasia), Hypoplasia, and Dysplasia (Dysgenesis): See the discussion on Developmental Errors in the section on Endocardium and Heart Valves, Disorders of Domestic Animals.

Neoplastic Transformation: See Chapter 6; also see the section on Disorders of Dogs.

• Arteriosclerosis

• Atherosclerosis

• Arterial medial calcification

Arteriosclerosis: Arteriosclerosis is characterized by intimal fibrosis of large elastic arteries, atherosclerosis is characterized by intimal and medial lipid deposits in elastic and muscular arteries, and arterial medial calcification has characteristic mineralization of the walls of elastic and muscular arteries.

Arteriosclerosis is an age-related disease that occurs frequently in many animal species but rarely causes clinical signs. The disease develops as chronic degenerative and proliferative responses in the arterial wall and results in loss of elasticity (“hardening of the arteries”) and less often luminal narrowing. The abdominal aorta is most frequently affected, but other elastic arteries and peripheral large muscular vessels may be involved. Lesions are often localized around the orifices of arterial branches. Etiologic factors in the development of arteriosclerosis are not well defined, but the significant role of hemodynamic influences is suggested by the frequent involvement at arterial branching sites, in which blood flow is turbulent. Grossly, the lesions are seen as slightly raised, firm, white plaques. Microscopically, initially the intima is thickened by accumulation of mucopolysaccharides and later by the proliferation of smooth muscle cells in the tunica media and fibrous tissue infiltration into the intima. Splitting and fragmentation of the internal elastic lamina are common.

Atherosclerosis: Atherosclerosis, the vascular disease of greatest importance in humans, occurs only infrequently in animals and rarely leads to clinical disease such as infarction of the heart or brain. The principal alteration is accumulation of deposits (atheroma) of lipid, fibrous tissue, and calcium in vessel walls, which eventually results in luminal narrowing. Many studies have established that the pig, rabbit, and chicken are susceptible to the experimental disease produced by the feeding of a high-cholesterol diet; the dog, cat, cow, goat, and rat are resistant. Lesions of the naturally occurring disease have been detected in aged pigs and birds (especially parrots) and in dogs with hypothyroidism and diabetes mellitus that develop an accompanying hypercholesterolemia. Arteries of the heart, mesentery, and kidneys are prominently thickened, firm, and yellow-white (Fig. 10-38, A). Microscopically, lipid globules accumulate in the cytoplasm of smooth muscle cells and macrophages, often termed foam cells, in the media and intima (Fig. 10-38, B and C; also see Fig. 3-10). Necrosis and fibrosis develop in some arterial lesions.

Arterial Medial Calcification: Arterial medial calcification is a frequent lesion in animals that often have concurrent endocardial mineralization and involves both elastic and muscular arteries. The causes of arterial medial calcification include calcinogenic plant toxicosis, vitamin D toxicosis, renal insufficiency, and severe debilitation, as seen in cattle with Johne’s disease (Fig. 10-39). Medial calcification occurs spontaneously in horses, rabbits, aged guinea pigs, and in rats with chronic renal disease. Affected arteries, such as the aorta, have a unique gross appearance; they appear as solid, dense, pipelike structures with raised, white, solid intimal plaques (Fig. 10-40). Microscopically, in elastic arteries, prominent basophilic granular mineral deposits are present on elastic fibers of the media, but in muscular arteries, they can form a complete ring of mineralization in the tunica media (Fig. 10-41). Siderocalcinosis (so-called iron rings), the result of deposition of both iron and calcium salts, occurs in the cerebral arteries of aged horses. Lesions in the surrounding brain tissue are generally absent. Siderocalcinosis lesions are considered incidental.

Hyaline Degeneration, Fibrinoid Necrosis, and Amyloidosis: Hyaline degeneration, fibrinoid necrosis, and amyloidosis are vascular lesions of small muscular arteries and arterioles and occur in all animal species. These lesions are generally not detected grossly, but in some diseases with fibrinoid necrosis of vessels, hemorrhages and edema are seen in affected organs at necropsy. The microscopic feature shared by these lesions is the formation of a homogeneous eosinophilic zone in the vessel wall (Fig. 10-42; also see Fig. 10-79). Special stains allow differentiation into three types: (1) amyloid confirmed by Congo red and methyl violet; (2) fibrinoid deposits, positive by the periodic acid–Schiff technique; and (3) negative staining of hyaline deposits by these stains. Amyloidosis and hyaline degeneration are often observed in small muscular arteries of the myocardium, lungs, and spleen of old dogs. Lesions in the intramyocardial arteries can cause small foci of myocardial infarction.

Fibrinoid necrosis of arteries is associated with endothelial damage and is characterized by entry and accumulation of serum proteins followed by fibrin polymerization in the vessel wall. These materials form an intensely eosinophilic collar that obliterates cellular detail. This lesion is frequent in many acute degenerative and inflammatory diseases of small arteries and arterioles. Fibrinoid necrosis is seen frequently in dogs with uremia and in dogs with hypertension, although hypertension is an uncommon finding in animals.

Arteritis and Vasculitis: Arteritis occurs as a feature of many infectious and immune-mediated diseases (Box 10-7). Often, all types of vessels are affected rather than only arteries, and then vasculitis or angiitis (a term that includes blood and lymphatic vessels) is the term applied to the lesions. The vascular system serves as the major mechanisms for transport of organisms, e.g. Bacillus anthracis. In inflamed vessels, leukocytes are present within and surrounding the walls, and damage to the vessel wall is evident as fibrin deposits or necrotic endothelial and smooth muscle cells. As a result of endothelial damage, thrombosis, which can result in ischemic injury or infarction in the circulatory field, may be present. Arteritis and vasculitis can develop from endothelial injury caused by either infectious agents or immune-mediated mechanisms or may be caused by local extension of suppurative and necrotizing inflammatory processes in adjacent tissues. Arteritis is a prominent feature of several parasitic diseases.

Systemic infections with phlebitis as a lesion include salmonellosis in several species and feline infectious peritonitis. In pigs with various septicemias, such as salmonellosis and colibacillosis, the gastric fundic mucosa is often severely congested and hemorrhagic because of venous endothelial damage and thrombosis. In severe local infections, such as in metritis or hepatic abscesses, inflammation extends into the walls of adjacent veins and produces phlebitis, with or without thrombosis. Intravenous injections of irritant solutions, injecting solutions into the vascular wall, or intimal trauma produced by indwelling venous catheters result in vascular damage and create an opportunity for localization and proliferation of infectious agents and development of phlebitis and thrombosis (Fig. 10-43). Animals with phlebitis complicated by thrombosis have the additional risk of septic embolism, which can cause endocarditis and pulmonary abscesses or pulmonary infarcts.

Many reportable foreign animal diseases are viral diseases, which are endotheliotropic and result in vasculitis; examples include classic swine fever (hog cholera), African horse sickness, and African swine fever (see the sections on disorders of specific animal species).

Thrombosis and Embolism:

Effusions:

Agenesis (Aplasia), Hypoplasia, Dysplasia (Dysgenesis): See the discussion on Developmental Errors: Congenital Anomalies in the section on Disturbances of Growth, Lymphatic Vessels, Disorders of Domestic Animals.

Neoplastic Transformation: Tumors arising from lymphatic vessels are benign (lymphangioma) and malignant (lymphangiosarcoma). See Chapter 6 and also the section on Disorders of Dogs.

Effusions:

Developmental Errors: Congenital Anomalies:

Atrophy: See the previous discussion on serous atrophy of fat in the section on the Pericardium and Epicardium, in the Responses to Injury section.

Pericarditis: See the discussion on pericarditis in the section on the Pericardium and Epicardium, Responses to Injury.