Thoracic aortic aneurysm (TAA) can involve the ascending or descending aorta above the diaphragm. This patient likely experienced progressive TAA expansion with symptomatic compression of surrounding structures, followed by acute rupture that led to shock and cardiac arrest.
TAA usually results from age-related degenerative changes in the medial layer of the aorta; these changes are likely accelerated by risk factors, including dyslipidemia, hypertension, tobacco use, and family history. Connective tissue diseases such as Marfan or Ehlers-Danlos syndrome also increase the risk.
The most common symptomatic presentation of TAA is pain, which is typically localized to the chest and back. If the TAA impinges upon the esophagus, it can also cause dysphagia. Similarly, compression of the left recurrent laryngeal nerve or left vagus nerve results in hoarseness, whereas compression of the phrenic nerve can cause hemidiaphragmatic paralysis. Respiratory manifestations, including wheeze, cough, hemoptysis, and dyspnea may occur due to tracheobronchial obstruction. Other complications include heart failure due to aortic valve regurgitation and superior vena cava syndrome from venous compression and occlusion.
The autopsy findings - endocardial thickening and fibrosis of tricuspid and pulmonary valves - are characteristic of carcinoid heart disease. Carcinoids are well-differentiated neuroendocrine tumors found most commonly in the distal small intestine and proximal colon, with a strong propensity for metastasis to the liver. These tumors secrete several products (including histamine, serotonin, and vasoactive intestinal peptide) that are metabolized in the liver. In patients with liver metastasis, these hormones are released directly into the systemic circulation, leading to carcinoid syndrome.
Carcinoid heart disease is caused by excessive secretion of serotonin, which stimulates fibroblast growth and fibrogenesis. Pathognomonic plaque-like deposits of fibrous tissue occur most commonly on the endocardium, leading to tricuspid regurgitation, pulmonic valvulopathy, and right-sided heart failure (eg, ascites, peripheral edema). Endocardial fibrosis and thickening are generally limited to the right heart as vasoactive products are inactivated distally by pulmonary vascular endothelial monoamine oxidase.
5-hydroxyindoleacetic acid (5-HIAA) is an end product of serotonin metabolism, and elevated 24-hour urinary 5-HIAA levels are helpful in diagnosing suspected carcinoid syndrome.
This patient's muscle pain, which occurs with exercise and remits with rest, is consistent with intermittent claudication; smoking is an important risk factor. Claudication is usually due to atherosclerosis of the large arteries, specifically resulting from fixed stenoses caused by lipid-filled intimal plaques that bulge into the arterial lumen (atheromas). These stenoses prevent a sufficient increase in blood flow to muscles during exercise, leading to ischemic muscle pain. The pain is rapidly relieved by rest, as residual blood flow is adequate to meet the metabolic demands of resting, but not exercising, muscle.
Thigh claudication is suggestive of occlusive disease of the ipsilateral external iliac artery or its more distal branches (ie, common femoral, superficial femoral, profunda femoris arteries). Accompanying impotence and/or gluteal claudication suggests more proximal aortoiliac occlusion (so-called Leriche syndrome), which, in addition to affecting the external iliac artery, also diminishes blood flow to the internal pudendal and gluteal branches of the internal iliac artery.
This young patient likely had Marfan syndrome complicated by aortic root disease, leading to aortic dissection with acute aortic regurgitation and heart failure. Aortic dissection typically presents with sudden-onset, severe chest or back pain. In Marfan syndrome, the dissection almost always affects the ascending aorta; it can propagate proximally to impair aortic valve closure, causing acute aortic regurgitation (evidenced by a decrescendo diastolic murmur) and heart failure (evidenced by pulmonary edema).
Marfan syndrome results from a mutation that disrupts the synthesis, secretion, and incorporation into the extracellular matrix of fibrillin, a protein that provides the glycoprotein scaffolding for elastin structure. The most common histologic findings in aortic root disease include fragmentation and loss of the elastic lamellae with fibrosis and cystic medial degeneration (replacement of collagen, elastin, and smooth muscle by a basophilic mucoid extracellular matrix with irregular fiber cross-linkages and cystic collections of mucopolysaccharide). Cystic medial degeneration also occurs with normal aging, but is accelerated in Marfan syndrome.
The autopsy finding of thick, fibrous tissue in the pericardial space is consistent with constrictive pericarditis, a potential complication of chest radiation therapy for non-Hodgkin lymphoma. This dense, rigid pericardial tissue encases the heart and restricts ventricular filling, causing low cardiac output (manifesting with fatigue and dyspnea on exertion) and progressive right-sided heart failure (manifesting with hepatomegaly and peripheral edema).
Physical examination in constrictive pericarditis typically shows elevated jugular venous pressure (JVP) with prominent x and y descents and a pericardial knock (early diastolic sound that occurs before S3) and may also demonstrate pulsus paradoxus (>10 mm Hg drop in systolic blood pressure during inspiration). In addition, Kussmaul sign may be present. Under normal circumstances, the decrease in intrathoracic pressure during inspiration increases venous return to the right side of the heart and lowers JVP. However, in constrictive pericarditis, the rigid pericardium prevents the right side of the heart from accommodating increased venous return, which leads to a paradoxical rise in JVP during inspiration, referred to as Kussmaul sign.
This patient likely died from acute myocarditis, a condition most often caused by viral infection. Numerous viruses, including coxsackievirus, adenovirus, influenza, and HIV have been implicated. Histopathology typically shows myofibrillary necrosis accompanied by inflammatory mononuclear cell infiltrate consisting of lymphocytes and some macrophages. Other less common etiologies of acute myocarditis, including bacterial, parasitic, and rheumatologic, often have similar histologic appearance but may demonstrate additional findings (eg, granulomas in mycobacterial disease, visible organisms in parasitic disease).
The clinical presentation of acute myocarditis can vary significantly; many patients remain asymptomatic with subclinical infection, but some experience severe complications including decompensated heart failure (eg, dyspnea, fatigue, peripheral edema) due to dilated cardiomyopathy. Ventricular arrhythmias leading to sudden cardiac death (SCD) can also occur.
*Dec in EF, Inc in Compliance*
This patient with progressive dyspnea and peripheral edema, as well as a laterally displaced PMI and S3 on physical examination, likely has heart failure due to peripartum cardiomyopathy. Peripartum cardiomyopathy is relatively uncommon and manifests as a dilated cardiomyopathy that occurs during the last month of pregnancy or within 5 months after delivery. The pathogenesis of the condition is poorly understood, but it may be related to impaired function of angiogenic growth factors (eg, vascular endothelial growth factor) during the peripartum period. In addition, certain individuals may have genetic mutations affecting cardiac structural proteins that predispose to the development of peripartum cardiomyopathy.
In dilated cardiomyopathy, myocardial dysfunction causes an increase in left ventricular EDV, which is compensated for by eccentric hypertrophy to maintain cardiac output. The dilation of the left ventricle allows for increased compliance to accommodate the increase in end-diastolic volume. Eventually, however, overwhelming wall stress leads to left ventricular failure with reduced ejection fraction and symptomatic heart failure.
Left atrial cavity: Dilated
Left ventricular cavity: Not dilated
LV Wall thickness: Increased
LV relaxation: Impaired
This patient with decompensated heart failure has copious pink, amorphous material (hyaline) on cardiac biopsy, which is characteristic of amyloid cardiomyopathy. Amyloidosis is a systemic disorder caused by the extracellular deposition of fibrils of misfolded amyloid protein in various tissues (eg, liver, kidney, blood vessels), resulting in organ enlargement and dysfunction (hepatomegaly, nephrotic syndrome, easy bruising).
Cardiac amyloid deposition typically causes a restrictive cardiomyopathy with uniformly thickened ventricular walls (normal thickness is seen with other noninfiltrative etiologies) that are stiff with impaired diastolic relaxation. Left ventricular (LV) cavity size is normal or decreased, and the impaired diastolic relaxation both increases LV filling pressure and reduces cardiac output (leading to dyspnea). The elevated LV pressure is transmitted backward, leading to left atrial dilation, increased pulmonary arterial pressure, and progressive right-sided heart failure (eg, jugular venous distension, peripheral edema).
The above autopsy image shows cystic medial degeneration (necrosis), the classic histologic finding in aortic dissection from Marfans. The tunica media is the largest and strongest of the 3 portions of the aortic wall. With aging, collagen, elastin, and smooth muscle in the aortic media are broken down and replaced by a mucoid extracellular matrix. There is elastic tissue fragmentation in a "basket weave" pattern with development of many cystic collections of mucopolysaccharide. These changes result in progressive loss of integrity, reducing the vessel's ability to handle wall stress from conditions such as systemic hypertension.
Once cystic medial degeneration develops, a small intimal tear can readily extend into and throughout the media, creating a lengthy dissection plane that propagates proximally or distally. As blood enters the dissection plane a false aortic lumen is created and aortic branches (eg, left subclavian artery, renal arteries) may become obstructed. The enlarging hematoma in the false lumen can eventually penetrate the adventitia, resulting in full-thickness rupture.
This patient has pulsus paradoxus (a fall in systolic blood pressure > 10 mm Hg on inspiration), jugular venous distention, and tachycardia. Based on his history and physical examination findings, cardiac tamponade is the most likely diagnosis. Cardiac tamponade should be suspected in any patient who has the characteristic triad of muffled heart sounds, jugular venous distention, and hypotension.
During inspiration, the pressure in the pleural space and lung interstitium decreases, increasing pulmonary vascular capacitance. This causes a fall in venous inflow to the left heart, resulting in decreased left ventricular stroke volume and a drop in systolic blood pressure (normally < 10 mm Hg). The inspiratory drop in systolic blood pressure is exacerbated in cardiac tamponade due to extrinsic compression of the ventricles. This external compression acts to equalize left and right ventricular diastolic pressures, allowing the intraventricular septum to bulge into the left ventricle as a result of the inspiratory increase in right ventricular filling. This further reduces left ventricular stroke volume, leading to a drop in systolic blood pressure > 10 mm Hg.
Pulsus paradoxus can also occur in other conditions, including constrictive pericarditis, chronic obstructive pulmonary disease, asthma, and pulmonary embolism.
Increase in size and then regress
This child has a cutaneous, strawberry-type capillary hemangioma (juvenile hemangioma). These lesions consist of unencapsulated aggregates of closely packed, thin-walled capillaries. Strawberry hemangiomas are benign and quite common, occurring in 1/200 births. They may be multiple, and can be found in the skin, subcutaneous tissues, oral mucous membranes, or lips. Capillary hemangiomas may also occur in the liver, spleen, and kidneys. Like most hemangiomas, these are present at birth, and initially grow in proportion to the child. These lesions regress spontaneously at or before puberty. Typically, capillary hemangiomas begin to fade between the ages of 1 to 3 years. In 75-95% of cases, these hemangiomas will have regressed completely by age 7.
This patient presents with skin and mucosal telangiectasias as well as recurrent severe nosebleeds. The most likely diagnosis is Osler-Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia), a condition characterized by the autosomal dominant inheritance of congenital telangiectasias to the skin and mucous membranes. The mucosal involvement may affect the lips, oronasopharynx, respiratory tract, gastrointestinal tract, or urinary tract. In rare instances, the telangiectasias of Osler-Weber-Rendu syndrome may occur in the brain, liver, and spleen as well. Rupture of these telangiectasias may cause epistaxis, gastrointestinal bleeding, and hematuria. This patient with chronic swelling and thickened skin of the right leg most likely has chronic lymphedema. Lymphedema can be congenital, but it most commonly results from an acquired disruption of lymphatic drainage that allows for accumulation of lymphatic fluid in the interstitial tissue. Malignancy and its treatment (eg, radiation, lymphadenectomy) are frequent underlying causes; other causes include chronic inflammation (eg, recurrent cellulitis, connective tissue disease) and parasitic infection (ie, filariasis due to Wuchereria bancrofti). Obesity is often a strong contributing factor.
Lymphedema usually presents with swelling, heaviness, and discomfort in one or more extremities. In early disease, the edema is pitting and the skin remains soft. However, over time there is progressive deposition of subcutaneous collagen and adipose tissue, which leads to firm, dry, and thickened skin and nonpitting edema. Treatment is difficult and typically involves conservative management to increase lymphatic drainage via compression bandages or physiotherapy (ie, manual lymphatic drainage).
*Differentiation of valve fibroblasts into osteoblast-like cells*
This patient's soft S2 and late-peaking systolic ejection murmur that decreases in intensity with maneuvers that decrease left ventricular blood volume (eg, abrupt standing, Valsalva straining phase) are consistent with aortic stenosis, which most commonly occurs due to age-related calcific aortic valve disease (CAVD).
The early pathogenesis of CAVD is analogous to that of arterial atherosclerosis. The endothelium lining the aortic side of the aortic valve cusps is exposed to the same high pressure and turbulent blood flow as the aortic vascular endothelium. As occurs with atheroma development in the vascular endothelium, these mechanical forces (along with smoking, hyperglycemia, and hyperlipidemia) over time cause damage to the aortic valve cusp endothelium, triggering endothelial dysfunction and the onset of a similar atherosclerotic process. There is subendothelial lipid deposition and infiltration of inflammatory cells (ie, macrophages, T lymphocytes) followed by the release of inflammatory mediators (eg, interleukin-1-beta, transforming growth factor beta-1).
Subsequently, there is increased production of proteins involved in tissue calcification (eg, osteopontin). Fibroblasts differentiate into osteoblast-like cells, leading to aberrant bone matrix deposition with progressive valvular calcification and stenosis.
This patient's left atrial mass on echocardiography is consistent with an atrial myxoma; this benign tumor is the most common primary cardiac neoplasm. Approximately 80% originate in the left atrium, and they can present with systemic embolization (eg, stroke) from tumor fragments passing into the systemic circulation. The tumors may also lead to constitutional symptoms (eg, fatigue, weight loss, low-grade fever) resulting from cytokine release, and they may cause transient mitral valve obstruction, leading to symptoms that can mimic mitral valve stenosis (eg, dyspnea, orthopnea, hemoptysis).
Physical examination often reveals an intermittent or positional mid-diastolic murmur ("tumor plop") that results from the motion of the tumor mass obstructing the mitral valve orifice. Histopathologic examination of a myxoma reveals *amorphous extracellular matrix*with scattered stellate or globular myxoma cells within abundant mucopolysaccharide (myxoid) ground substance containing chondroitin sulfate and hyaluronic acid. Because of their high vascularity, these tumors often demonstrate areas of hemorrhage accompanied by brown, hemosiderin-laden macrophages.
This patient's vomiting, right upper quadrant pain, and gallbladder inflammation with no evidence of gallstones indicates acute acalculous cholecystitis. Although a variety of conditions cause acute acalculous cholecystitis, the presence of long-standing, nonspecific symptoms (eg, fatigue, weight loss, arthralgias) and biopsy findings of fibrinoid necrosis in the submucosal arteries of the gallbladder raise strong suspicion for polyarteritis nodosa (PAN).
PAN is a systemic vasculitis of medium-sized muscular arteries; biopsy of affected areas generally reveals the following:
Segmental fibrinoid necrosis (amorphic, eosinophilic areas) in the vessel wall
Infiltration of the vessel wall with mononuclear cells and neutrophils
Internal and external elastic laminae damage, which may cause microaneurysms
In contrast to many other vasculitides (eg, granulomatosis with polyangiitis), there is no granulomatous inflammation in PAN.
PAN typically attacks arteries of the kidneys (eg, increased BUN/creatinine), skin, neurologic system, and gastrointestinal tract; most cases present due to symptoms of tissue ischemia from artery lumen narrowing/thrombosis or bleeding from microaneurysm rupture. In this case, damage to the submucosal gallbladder arteries likely caused gallbladder ischemia, which lead to acalculous cholecystitis. Other common gastrointestinal findings in PAN include bead-like microaneurysm formation in the mesenteric vessels, mesenteric ischemia, and bowel necrosis/rupture.
area of residence
This man with a large area of localized cardiac apical wall thinning likely died of chronic Chagas cardiomyopathy. Chagas disease is caused by infection with the protozoan Trypanosoma cruzi, which is transmitted by the triatomine "kissing" bug (Reduviid family) found throughout the Americas as far north as the southern United States. Infection is rare in developed regions, but the disease is endemic throughout Central and South America where widespread open-air and thatched-roof housing exposes individuals to routine contact with the triatomine vector.
Years following initial infection, some individuals develop serious end-organ damage affecting the cardiac, gastrointestinal, and/or central nervous systems. Cardiac disease results from a chronic parasite-induced and immune-mediated myocarditis that leads to dilated cardiomyopathy (DCM). Chronic Chagas cardiomyopathy is relatively unique among DCMs in that there is characteristically localized apical wall thinning with the development of a large apical aneurysm. In addition to impairing ventricular systolic function, the aneurysm can harbor mural thrombus that may systemically embolize and cause stroke. Damage to the cardiac conduction system can also trigger ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation) that can lead to sudden cardiac death (the likely cause of death in this man).
The gastrointestinal manifestations of Chagas disease involve destruction of the myenteric plexus, which can lead to progressive dilation and dysfunction of the esophagus and, less commonly, the colon.
The development of atherosclerotic plaque, or atheroma, involves a multistep process:
Initially, factors including hyperlipidemia, hypertension, hyperglycemia, and smoking trigger endothelial injury and/or dysfunction. This leads to increased vascular permeability, enhanced leukocyte adhesion, and a higher propensity for thrombosis.
Lipoproteins (ie, LDL and oxidized LDL) enter the arterial wall intima and begin to accumulate. Monocytes adhere to the endothelial wall and enter into the intima as well; these cells transform into macrophages and engulf lipid particles to become foam cells. Platelets adhere to the abnormal endothelium and become activated.
Growth factors, namely platelet-derived growth factor (PDGF), are released from platelets, activated macrophages, and endothelial cells. This triggers smooth muscle cell (SMC) recruitment from the media and proliferation in the intima.
Over time, progressive SMC proliferation and accumulation of necrotic debris (due to macrophage/foam cell and SMC death) lead to growth of the atheroma. SMCs encourage plaque stability by synthesizing collagen, whereas activated inflammatory cells break down collagen and contribute to plaque instability. HDL likely extracts lipids from the intima back into the bloodstream and helps slow atheroma development.
This patient's ECG demonstrates third-degree atrioventricular (AV) block. Third-degree (complete) AV block involves a total lack of communication between the atria and ventricles due to AV node dysfunction. It can result from ischemia, infiltrative disease (eg, sarcoidosis), infection (eg, Lyme disease), or age-related fibrosis with cellular degeneration. Because conduction signals from the atria cannot communicate with the ventricles, the intrinsic pacemaker of the His bundle or ventricles is triggered, resulting in a junctional or ventricular escape rhythm. On ECG, there is dissociation of P waves and QRS complexes, with P waves marching out at the intrinsic rate of the sinoatrial node (~75/min) and QRS complexes at the intrinsic rate of the His bundle or ventricles (~45/min). The QRS-complex escape rhythm in this patient is particularly slow (ie, <30/min).
The slow ventricular rate in third-degree AV block leads to reduced cardiac output, potentially causing dyspnea, fatigue, lightheadedness, or syncope. Definitive management requires placement of a permanent pacemaker.
This patient's pulsating, central abdominal mass most likely represents an abdominal aortic aneurysm (AAA), which is a focal dilation of the abdominal aorta that typically occurs below the renal arteries.
AAA is associated with several risk factors (eg, age >60, smoking, hypertension, male sex, family history) that lead to oxidative stress, vascular smooth muscle apoptosis, and chronic transmural inflammation of the aorta. Inflammatory cells (particularly macrophages) release matrix metalloproteinases and elastases that degrade extracellular matrix components (eg, elastin, collagen), leading to weakening and progressive expansion of the aortic wall. Furthermore, ischemia of the tunica media may play a role as the infrarenal abdominal aorta has a tenuous vasa vasorum, and atherosclerotic thickening of the intimal layer increases the diffusion distance for oxygen.
Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis) is a small-vessel necrotizing vasculitis characterized by allergic rhinitis, asthma, and peripheral eosinophilia. Although renal involvement is not typically prominent, patients can develop necrotizing crescentic glomerulonephritis.
Granulomatosis with polyangiitis (Wegener granulomatosis) is a small-vessel necrotizing vasculitis characterized by upper respiratory (eg, sinusitis, otitis media) and lower respiratory (eg, dyspnea, hemoptysis) symptoms as well as renal disease. Renal involvement typically manifests as focal necrotizing, crescentic glomerulonephritis.
Thromboangiitis obliterans (Buerger disease) is a small- to medium-vessel vasculitis that typically occurs with cigarette smoking and causes vascular insufficiency in the extremities (eg, gangrene, autoamputation of digits). It is characterized histologically by intraluminal thrombus and prominent inflammatory cell infiltrate with relative sparing of the vessel wall.
This patient's clinical presentation (eg, progressive exertional dyspnea, edema, ascites, elevated jugular venous pressure with rapid 'y' descent, prominent S4) and echocardiogram findings (eg, left atrial enlargement, left ventricular hypertrophy, normal ejection fraction) are consistent with diastolic heart failure due to restrictive cardiomyopathy.
Restrictive cardiomyopathy can be idiopathic or caused by infiltrative diseases (eg, amyloidosis, sarcoidosis, hemochromatosis), radiation fibrosis, or endomyocardial fibrosis. Although most cases are associated with normal ventricular wall thickness, infiltrative conditions such as cardiac amyloidosis may lead to significant ventricular hypertrophy. Infiltrative diseases can also cause conduction system abnormalities (eg, bradycardia) that may ultimately require pacemaker implantation.
Cardiac amyloidosis results from abnormal extracellular deposition of insoluble proteins such as monoclonal light chains (AL amyloidosis), mutated transthyretin (familial ATTR amyloidosis), or wild-type transthyretin (senile systemic amyloidosis) in myocardial tissue. Endomyocardial biopsy typically reveals cross-sections of normal myocardial cells (blue arrow) with other areas of myocardium infiltrated by an amorphous and acellular pink material (black arrow). Congo red stain classically shows apple-green birefringence under polarized light microscopy.
This patient with flank pain, hematuria, and a wedge-shaped kidney lesion on CT scan likely has a renal infarction, which results from interruption of the normal blood supply to the kidney. The lack of collaterals between segmental renal arteries ("end-organ" blood supply) means that any interruption of blood flow can lead to coagulative infarcts. Common laboratory findings include elevated lactate dehydrogenase (reflecting cell necrosis), mild leukocytosis, and hematuria. Serum creatinine is usually normal due to compensation by the unaffected kidney. Macroscopically, renal infarcts appear as pale wedges, with the base (widest part) at the renal cortex and the apex pointing to the medulla.
The most common cause of renal infarction is systemic thromboembolism from the left atrium or ventricle. Thromboembolism is a common complication of atrial fibrillation because the irregular contractions lead to sluggish, uneven flow in the left atrium and facilitate clot formation. Emboli from atrial fibrillation, which can be paroxysmal (thereby going undiagnosed), may have also caused this patient's recent stroke. The brain and kidneys are more likely than other organs to suffer embolic infarctions because they are perfused at a higher rate.
This patient's presentation is consistent with thromboangiitis obliterans (Buerger disease), a segmental, inflammatory vasculitis that affects the small- and medium-sized arteries and veins of the distal extremities. It typically affects young, heavy smokers (age <45) and is more common in men. It is also most prevalent in Asian populations. Toe and/or finger ischemia and ischemic ulcerations are the most common manifestation, and patients with involvement of proximal arteries can develop claudication affecting the lower legs, feet, or hands. Raynaud phenomenon and superficial thrombophlebitis (erythema, tenderness along veins) may also occur as early manifestations of the disease.
In thromboangiitis obliterans, chronic exposure to tobacco products is thought to cause direct endothelial injury or trigger a delayed-type hypersensitivity reaction against the endothelium. Histopathology shows highly cellular, inflammatory intraluminal thrombi (ie, containing neutrophils, multinucleated giant cells) in the arteries and veins with sparing of the vessel wall and internal elastic lamina. This segmental, thrombosing vasculitis often extends into contiguous veins and nerves, a feature rarely seen in other types of vasculitis.
Smooth muscle Cells
Atherosclerosis is a chronic inflammatory and fibroproliferative disease. Endothelial cells, vascular smooth muscle cells (VSMCs), and leukocytes play an important role in the development and progression of this disease. The process is initiated by chronic hemodynamic stress and hyperlipidemia, which cause endothelial cell injury. This leads to increased expression of surface vascular cell-adhesion molecules (VCAMs) that allow adherence and migration of monocytes and T lymphocytes into the intima. The infiltrating leukocytes and dysfunctional endothelium release cytokines and growth factors (eg, platelet-derived growth factor, fibroblast growth factor, endothelin-1, interleukin-1) that promote migration and proliferation of VSMCs within the intima. VSMCs are also stimulated to synthesize extracellular matrix proteins (eg, collagen, elastin, proteoglycans) that form the fibrous cap typical of mature atheromas. Disruption of the fibrous cap with luminal thrombosis (atherosclerotic plaque rupture) has catastrophic clinical consequences and is responsible for the majority of acute coronary syndrome cases and sudden cardiac deaths.
This patient with pleuritic-type chest pain radiating to the shoulder and a recent history of skin rash and joint pain likely has acute fibrinous pericarditis due to systemic lupus erythematosus. Fibrinous pericarditis is the most common type of pericarditis and consists of pericardial inflammation with serous fluid and fibrin-containing exudate in the pericardial space.
Patients typically have pleuritic (sharp, worse with breathing or movement) anterior chest pain that can radiate to the left shoulder or posteriorly to the bilateral scapulae. Fibrin deposition causes roughening of the visceral and parietal pericardium, often heard as a triphasic friction rub (occurring during atrial systole, ventricular systole, and early ventricular diastole) on cardiac auscultation; however, the rub can be absent if significant pericardial effusion is present. ECG typically shows diffuse ST elevation due to inflammation of the ventricular myocardium.
Other causes of fibrinous pericarditis include viral infection, myocardial infarction, uremia, and other rheumatologic disease (eg, rheumatoid arthritis). If acute fibrinous pericarditis goes without treatment, chronic constrictive pericarditis can develop in some patients.
This patient has varicose veins - dilated, tortuous veins typically involving the superficial venous drainage of the leg. Increased intraluminal pressure or loss of vessel wall tensile strength can lead to venous dilation and failure of the venous valves. The resulting backflow of blood exacerbates the venous hypertension, precipitating a vicious cycle that leads to further valvular incompetence and venous congestion.
Varicose veins are most common in patients age >50, and the risk is increased by conditions that cause elevated venous pressure (eg, prolonged standing, pregnancy, obesity). There is also often a familial association, suggesting possible genetic factors involving the venous wall or valves. Common complications include chronic edema, stasis dermatitis, skin ulcerations, poor wound healing, and infection.
Intermittent claudication is achy or crampy pain in the legs caused by inadequate arterial blood flow, usually due to atherosclerosis in the branches of the femoral artery. In contrast to venous disease, in which the pain is worsened by prolonged standing or sitting with the legs dependent, claudication due to arterial disease is worse with exertion and relieved with rest. Because peripheral artery atherosclerosis is often associated with atherosclerotic disease elsewhere, patients with intermittent claudication have an increased risk for ischemic stroke and myocardial infarction.