CV Pathology

What is myocardial hibernation

state of chronic myocardial ischemia = both myocardial metabolism and function = reduced to match a reduction in coronary blood flow

A 21-year-old Caucasian male presents to the emergency department following an episode of syncope. The syncopal episode was not provoked by any activity or circumstance, nor was it preceded by lightheadedness. The patient has no significant past medical history and he is not taking any medications. An ECG obtained in the ER reveals QT-interval prolongation but is otherwise unremarkable. Assuming this is an inherited condition, the relevant mutation most likely affects which of the following structures?

Membrane K+ channel protein This patient's sudden-onset syncopal episode suggests a sudden cardiac arrhythmia. QT prolongation in an otherwise healthy young individual is usually congenital. The QT-interval reflects the cardiac myocyte action potential duration, which is determined in part by K+ currents through channel proteins. There are two important congenital syndromes that cause QT prolongation: Jervell and Lange-Nielsen syndrome (autosomal recessive, with neurosensory deafness) and the more common Romano-Ward syndrome (autosomal dominant, no deafness). Both may predispose to torsades de pointes (a ventricular tachyarrhythmia) at a young age, causing syncopal episodes and possible sudden cardiac death.

A 22-year-old Caucasian male presents to the emergency room complaining of severe headaches and vomiting. Soon after, he slips into a coma and dies. Autopsy shows a ruptured cerebral aneurysm with extensive intracranial hemorrhage. This patient's condition is most likely associated with:

Since there is no history of head trauma, this patient most likely suffered a spontaneous intracranial hemorrhage (SICH). The most common causes of SICH in young adults are arteriovenous malformations, ruptured cerebral aneurysms, or abuse of sympathomimetic drugs such as cocaine. We are told that this patient had a ruptured cerebral aneurysm, and are asked to identify an associated congenital cardiac anomaly. Although coarctation of the aorta may occur as a solitary defect, it may also be associated with other congenital cardiac anomalies or with berry aneurysms of the Circle of Willis. Berry aneurysms are particularly prone to rupture when associated with coarctation, because of hypertension in branches of the aortic arch proximal to the coarct. Subarachnoid hemorrhage is the result.

A 53-year-old woman comes to the office due to aching pain in her legs. She is a hair stylist and has cut down on her work hours due to the discomfort. The patient has a history of migraine and untreated chronic hepatitis C. She smokes a pack of cigarettes daily but does not use alcohol or illicit drugs. She has varicose veins. An abnormality in what structure most likely causes this?

Venous blood normally flows from superficial veins through perforating veins into the deep veins of the extremities. Blood from the deep veins then travels upward and eventually drains into the inferior vena cava. Valves located in the superficial, perforating, and deep veins prevent backward flow from deep to superficial veins. Chronically elevated intraluminal pressure can lead to dilation of the veins (varicose veins) and incompetence of the valves. This allows retrograde flow into superficial veins and results in a further increase in venous pressure. The resulting tissue ischemia causes venous stasis dermatitis and is associated with poor wound healing. Extravasation of red blood cells into the tissues leads to iron deposition and the characteristic brawny discoloration. This patient has dilated superficial veins (red arrows) and associated skin changes consistent with stasis dermatitis (black arrows). Common risk factors for varicose veins and stasis dermatitis include obstruction of venous return (eg, obesity, pregnancy) and conditions that damage the venous valves (eg, deep venous thrombosis). Prolonged standing and sedentary lifestyles are also associated with varicose veins.

A 38yro woman w/ worsening SOB. She has ankle puffiness. She delivered a healthy child 2 months ago without complications. Blood pressure is 96/60 mm Hg and pulse is 92/min and regular. The apical impulse is palpated along the anterior axillary line, and S3 is heard at the apex. There are no heart murmurs. Which of the following best describes the left ventricular changes in this patient? Inc/Dec EF? Inc/Dec Compliance?

**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.

A 68-year-old man comes to the office due to exertional shortness of breath and fatigue. The patient has a history of HTN. He is a lifetime nonsmoker. His father died of a "heart attack" at age 70. Blood pressure is 144/74 mm Hg, and pulse is 72/min and regular. Cardiac auscultation reveals a 3/6 ejection-type, late-peaking systolic murmur and a barely audible S2. The murmur diminishes in intensity during the straining phase of the Valsalva maneuver. Which of the following processes underlies this patient's current condition?

**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.

The autopsy of a 78-year-old Caucasian male who died of esophageal cancer reveals a small heart without significant coronary artery atherosclerosis. Myocardial cells show prominent intracytoplasmic granules that are tinged yellowish-brown. Which of the following most likely accounts for the observed microscopic changes?

**Lipid Peroxidation** An insoluble pigment composed of lipid polymers and protein-complexed phospholipids, lipofuscin is considered a sign of "wear and tear" or aging. This yellow-brown, finely granular perinuclear pigment is the product of free radical injury and lipid peroxidation. It is commonly seen in the heart and liver of aging or cachectic, malnourished patients.

A 44yro man w/ occasional chest discomfort that is not consistently related to exertion. PMH for HTN and hyperlipidemia. His grandfather experienced a myocardial infarction at age 50. Coronary CT angiography reveals several nonobstructive atherosclerotic plaques in the coronary arteries. One plaque in the proximal left anterior descending artery appears extensive, has a large hypodense core, and occupies 40% of the lumen. One year later, the patient comes to the ED with acute severe chest pain and is found to have thrombotic occlusion of the proximal LAD. High intraplaque activity of which of the following enzymes most likely resulted in this patient's myocardial infarction?

**Metalloproteinases Patients with coronary atherosclerosis can be asymptomatic but typically develop symptoms of stable angina (exertional chest pain relieved with rest/nitroglycerin) if progressive enlargement of the atherosclerotic plaque causes >70% luminal stenosis. Acute coronary syndrome usually occurs due to plaque rupture, which leads to superimposed thrombosis and vessel occlusion. The likelihood of plaque rupture is typically related to plaque stability rather than plaque size or degree of luminal narrowing. Plaque stability largely depends on the mechanical strength of the fibrous cap: Thin-cap fibroatheromas are generally unstable and more vulnerable to rupture. During the chronic inflammatory progression of an atheroma, the fibrous cap is continually being remodeled. The balance of collagen synthesis and degradation determines the mechanical strength of the cap. Thin-cap fibroatheromas are characterized by a large necrotic core covered by a thin fibrous cap. Activated macrophages infiltrating the atheroma contribute to the breakdown of extracellular matrix proteins (eg, collagen) by secreting metalloproteinases. Ongoing intimal inflammation can destabilize the mechanical integrity of the plaque through release of these metalloproteinases, resulting in plaque rupture and consequent acute coronary syndrome.

A 54-year-old man comes to the office due to 2 days of redness and pain in his right arm. He was recently diagnosed with superficial thrombophlebitis involving the left lower and upper extremities. His symptoms then subsided within days of nonsteroidal anti-inflammatory drug therapy only. The patient has no other past medical history. He has some abdominal discomfort that he attributes to gastroesophageal reflux disease. On examination, there is erythema and tenderness extending linearly from the right forearm to just anterior to the right antecubital fossa. No fluid collection is palpable. Complete blood count shows mild leukocytosis. The patient's symptoms may indicate the presence of which of the following?

**Visceral adenocarcinoma Migratory thrombophlebitis should raise suspicion for cancer. Hypercoagulability is a very common paraneoplastic syndrome seen most frequently in visceral adenocarcinomas of the pancreas, colon, and lung. Hypercoagulability develops because adenocarcinomas produce a thromboplastin-like substance capable of causing chronic intravascular coagulations that can disseminate and tend to migrate. Migratory superficial thrombophlebitis, known as Trousseau syndrome, is named after Armand Trousseau, a well-respected French physician who first described the association with cancer. Trousseau later diagnosed his own visceral cancer after developing the syndrome. Trousseau also described the Trousseau sign (hand/forearm muscle spasms on sphygmomanometric measurement) associated with hypocalcemia.

A 64-year-old man dies suddenly while playing tennis. In the preceding months, the patient experienced fatigue and some exertional dyspnea. Autopsy reveals rupture of an unsuspected ascending aortic aneurysm. Heart examination shows a septal thickness of 1.2 cm (normal: <1.1), a posterior wall thickness of 1.2 cm (normal: <1.1), and an internal left ventricular diameter of 6.8 cm (normal: 3.5-5.9). No focal myocardial scarring is seen. Which of the following is the most likely cause of the cardiac findings seen in this individual?

*Aortic Regurgitation* This individual's autopsy reveals a dilated left ventricular (LV) cavity with relatively thin ventricular walls, a finding consistent with eccentric hypertrophy. Eccentric hypertrophy results from the addition of myocardial contractile fibers in series in response to chronic volume overload. The adaptation allows the left ventricle to increase stroke volume and maintain cardiac output; however, LV wall stress increases, resulting in eventual decompensation and the development of heart failure. Common causes of eccentric hypertrophy include cardiomyopathy, ischemic heart disease, and chronic aortic or mitral valve regurgitation. In developed countries, aortic root dilation is one of the most common causes of chronic aortic regurgitation. This individual with an ascending aortic aneurysm likely had aortic root dilation with consequent chronic aortic regurgitation, leading to LV volume overload and eccentric hypertrophy.

18yro woman w/ midsystolic click followed by a short late-systolic murmur at the cardiac apex. The murmur disappears with squatting. This patient's condition is most likely related to an abnormality involving which of the following tissues?

*Connective tissue* The presence of a midsystolic click followed by a systolic murmur at the cardiac apex that disappears with squatting is most consistent with mitral valve prolapse (MVP). The click is caused by sudden tensing of the chordae tendineae as they are pulled taut by the ballooning valve leaflets, and the murmur results from regurgitation of blood due to malalignment of the valve margins with prolapse. During systole, there is a critical left ventricular (LV) size at which prolapse occurs; therefore, maneuvers that change LV end-diastolic volume affect the timing of the click and murmur. Squatting increases venous return and LV volume, increasing the tension and decreasing the slack in the mitral valve apparatus. Because the ventricular walls have farther to travel to reach the critical LV size at which prolapse occurs, prolapse occurs later in systole or not at all. Primary MVP is most commonly a sporadic disorder and is characterized by myxomatous degeneration (ie, pathologic deterioration of the connective tissue) affecting the mitral valve leaflets and chordae tendineae. Secondary MVP is associated with inherited connective tissue disorders, including Marfan or Ehlers-Danlos syndrome and osteogenesis imperfecta.

A 56-year-old man comes to the clinic for a routine checkup. Medical history includes hypertension, type 2 diabetes mellitus, hyperlipidemia, and mild intermittent asthma. Blood pressure is 152/101 mm Hg and pulse is 87/min. Waist circumference is 110 cm (43 in). Which of the following vascular beds is most likely to carry the highest atherosclerotic burden in this patient?

*Coronary* This patient has multiple risk factors (eg, hypertension, diabetes mellitus, hyperlipidemia) that contribute to atherosclerosis. Atherosclerosis is focal intimal thickening due to accumulation of lipid-laden macrophages and extracellular matrix ("fatty streaks"). With advancing age, fatty streaks transition into atherosclerotic plaques, such as fibrous cap atheromas and fibrous plaques. More advanced lesions develop a lipid-rich necrotic core and areas of calcification. Atherosclerosis is a chronic disease of the arterial walls and involves all major vascular beds. The most susceptible vascular regions involve bends and branch points that encourage turbulent blood flow, which disrupts vascular wall integrity and leads to endothelial cell dysfunction. Turbulent blood flow also leads to decreased shear stress on the vascular walls and prolonged endothelial contact with cholesterol particles. The hemodynamics of the lower abdominal aorta and the coronary arteries make these vascular beds the most susceptible to atherosclerosis of all the major vascular beds in the body. In fact, atherosclerotic lesions (eg, intimal thickening, fatty streaks) occur in these vessels as early as the second decade of life.

Forest ranger with complete AV block is most likley due to?

*DISSEMINATED SPIROCHETE AKA LYME* This patient most likely has early disseminated Lyme disease. Lyme disease is caused by the bacterial spirochete Borrelia burgdorferi, which is transmitted by the Ixodes tick that is endemic to the northeastern and parts of the midwestern United States. Most cases initially present with a non-itchy, bull's-eye-shaped rash, known as erythema migrans, at the site of infection. Left untreated for several weeks or more, a small percentage of those infected will develop cardiac involvement (Lyme carditis). Lyme carditis most commonly manifests with varying degrees of atrioventricular (AV) conduction block. Many patients remain asymptomatic; however, patients who develop complete AV block are likely to have symptoms of dyspnea, lightheadedness, or syncope. Treatment for symptomatic AV block due to Lyme carditis typically requires hospitalization with temporary pacing and the administration of intravenous antibiotics (ceftriaxone is the drug of choice).

In experiments, transient myocardial ischemia causes myocardial cells to increase in size. This effect is due in part to which of the following?

*Intracellular Ca2+ accumulation** When blood flow cannot meet myocardial demands, cardiac myocytes transition from aerobic to anaerobic metabolism. However, anaerobic metabolism cannot maintain proper intracellular ATP levels, and ADP, AMP and adenosine accumulate. Without ATP, the membrane Na+/K+-ATPases and the sarcoplasmic reticulum Ca2+-ATPases fail, leading to increased intracellular Na+ and Ca2+ and increased intramitochondrial Ca2+ concentrations. These increased concentrations attract free water, causing cellular and mitochondrial swelling. Failure of the sarcoplasmic reticulum to resequester Ca2+ leads to cessation of contraction within ischemic zones of myocardium.

Emergent coronary angiography is performed, which demonstrates significant atherosclerotic involvement of the left anterior descending and circumflex arteries. Development of these vascular lesions most likely involved growth factors released from which of the following sources?

*Platelets* 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.

long with a lipid core, these atheromas have a fibrous cap formed from dense deposition of collagen. Which of the following cells are directly responsible for synthesizing this fibrous cap?

*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.

A 32-year-old man dies suddenly. An autopsy shows a left ventricle with a large area of apical thinning composed of fibrotic scar tissue. The mid and basal left ventricular segments show normal myocardial thickness. The coronary arteries show no evidence of obstructive atherosclerosis. The right ventricle appears normal in size. No apparent valve damage is present. Dilation and wall-thickening of the esophagus is also noted. Which of the following factors in this patient's medical history would be most helpful in determining the cause of death?

*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.

WHat is myocardial preconditioning?

1. Short term ischemia preconditions myocardium. Results in delay of myocardial necrosis during following period of ischemia

A 35yro w/ fatige and SOB, bilateral leg swelling and abdominal distension despite overall weight loss. Patient dies. Autopsy reveals significant endocardial thickening with dense fibrous deposits around the tricuspid and pulmonary valves as well as moderate pulmonary valve stenosis. The left-sided cardiac chambers and valves are normal. Measuring the levels of which of the following substances would have helped in diagnosing this patient?

5 HIAA 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.

What channels are affected in Brugada syndrome?

Brugada syndrome is an autosomal dominant condition that can be associated with mutations in cardiac sodium or L-type calcium channels, leading to characteristic ECG changes (eg, pseudo right bundle branch block, ST-segment elevation in leads V1-V3) and an increased risk of ventricular tachyarrhythmias and sudden cardiac death.

Histopath of cardiac amyloidosis

Cardiac amyloidosis involves deposition of abnormal proteins in myocardial tissue and typically manifests as restrictive cardiomyopathy initially. SCD can occur, but histopathology demonstrates pink amorphous material (amyloid) surrounding normal-appearing cardiomyocytes.

A 37-year-old man is found unresponsive under a tree during a thunderstorm. He is not breathing when paramedics arrive on the scene. On examination, his pupils are fixed and dilated. Several cutaneous erythematous marks in a fern-leaf pattern are seen on his lower extremities. Second-degree burns are present on both arms. Cardiopulmonary resuscitation is started; however, the patient does not respond and is pronounced dead on arrival at the hospital. Which of the following is most likely to be the primary cause of his death?

Cardiac arrythmia The finding of an unconscious person on wet ground or under trees during a thunderstorm suggests a lightning injury. This patient's Lichtenberg figures (erythematous cutaneous marks in a fern-leaf pattern) and second-degree burns confirm the suspicion. Although lightning injuries are rare, they are associated with a 25% fatality rate, and more than 70% of survivors have long-lasting complications. Two-thirds of lightning-related deaths occur within the first hour following injury; the most common causes are fatal arrhythmias and respiratory failure. A comprehensive and thorough physical examination should always be performed on lightning strike victims as injury patterns are widely variable and skin findings can significantly underestimate the extent of internal injury.

Differentiate Churgg Strauss vs. Granulomatosis w/ polyangitis vs. Thrombangitis Obliterans

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.

The patient has no ear pain, discharge, or upper respiratory symptoms. Initial testing suggests that he has bilateral sensorineural hearing loss. His paternal uncle died suddenly at age 12. Examination of the ears, nose, and throat is normal. ECG shows normal sinus rhythm with a prolonged QT interval (520 msec). A genetic defect affecting which of the following is most likely present in this patient?

K+ channels This patient's clinical presentation is suggestive of Jervell and Lange-Nielsen syndrome, an autosomal recessive disorder characterized by profound bilateral sensorineural hearing loss and congenital long QT syndrome, which predisposes individuals to syncope and sudden cardiac death. This syndrome occurs secondary to mutations in genes (eg, KCNQ1, KCNE1) that encode the alpha and beta subunits of voltage-gated potassium channels. These subunits contribute to the slow-acting component of the outward-rectifying potassium current, which is responsible for ventricular repolarization during phase 3 of the cardiac action potential. Mutations in the potassium channel lead to a decrease in potassium current with prolongation of action potential duration and the QT interval. QT interval prolongation predisposes to the development of life-threatening ventricular arrhythmias, such as torsades de pointes and ventricular fibrillation.

What is Monckeberg Medial Calcific Sclerosis? What does it ususally cause?

Monckeberg sclerosis (medial calcific sclerosis) is a form of arteriosclerosis characterized by calcific deposits in the medial layer of muscular arteries. These lesions generally occur in patients age >50 and are thought to cause isolated systolic hypertension due to arterial hardening. Although visible radiologically and often palpable on physical examination, these calcifications are clinically asymptomatic because they do not narrow the vessel lumen.

A 34yro woman w/ chest and left shoulder pain. The patient describes the pain as constant and worse in certain positions. A month ago, she was treated for a skin rash and joint pain. Her father has hypertension and had a stroke at age 64. A triphasic, scratchy sound is heard over the left sternal border with the patient sitting up. The lungs are clear on auscultation. ECG shows sinus rhythm with ST-segment elevation in all leads except avR and V1. Which of the following is the most likely diagnosis?

Fibrinous pericarditis 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.

Newborn with strawberry hemangioma. You inform the parents that the lesion is benign and will most likely...

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.

Aortic dissection involves a tear in what layer?

It is initiated by a tear in the aortic intima that typically extends for about 1-5 cm in a transverse or oblique direction. Dissections involving any portion of the ascending aorta are classified as type A; those confined to the descending aorta are classified as type B. As the dissecting intramural hematoma spreads along the aortic wall, it can compress major arterial branches. This patient's brachial blood pressure discrepancy suggests compromise of the brachiocephalic trunk servicing his right arm. Hypertension is the primary risk factor for aortic dissection. In many patients with longstanding hypertension, there is medial hypertrophy of the aortic vasa vasorum and, consequently, reduced blood flow to the aortic media. This can cause medial degeneration with a loss of smooth muscle cells, leading to aortic enlargement and increased wall stiffness. Both of these changes exacerbate aortic wall stress, which is already increased due to the hypertension itself. This synergistic increase in aortic wall stress greatly increases the risk of intimal tearing and subsequent development of aortic dissection.

A 4yro boy is brought in by his parents for evaluation of a fever that has persisted for the past 5 days. He has also been more irritable than usual and had 2 or 3 episodes of vomiting. He has received all recommended vaccinations. He traveled to China last year to visit his grandparents and cousins but has not traveled outside of the country this year. Physical examination shows bilateral conjunctival injection with no exudates. His tongue is bright red and lips are cracked. Nonpitting edema is present on his hands and feet. Which of the following complications is this patient at greatest risk for developing?

Kawasaki disease is a vasculitis of medium-sized arteries that affects young children (usually age <5 years). It occurs most commonly in patients of Asian ethnicity. The diagnosis of Kawasaki disease is based on a fever for >5 days plus 4 of the following findings: 1. Bilateral non-exudative conjunctival injection (erythema) 2. Cervical lymphadenopathy 3. Mucositis: Erythema of the palatine mucosa, fissured erythematous lips, "strawberry" tongue 4. Extremity changes: Edema of hands and feet, erythema of palms and soles, desquamation of the fingertips (periungual) Rash: Polymorphous (usually urticarial) erythematous rash on the extremities that spreads centripetally to the trunk A serious complication of Kawasaki disease is coronary artery inflammation leading to the development of coronary artery aneurysms.

In a patient with amyloid cardiomyopathy, what would be found on echo? Left atrial cavity: Dilated/Not dilated Left ventricular cavity: Dilated/Not dilated LV Wall thickness: Increased/Normal LV relaxation: Normal/Impaired

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).

What are examples of reversible myocyte injury

Myofibril relaxation is an early sign of reversible injury in cardiac myocytes, which occurs within the first 30 minutes of severe ischemia. Myofibril relaxation corresponds with intracellular ATP depletion and lactate accumulation due to anaerobic glycolysis during this period. Disaggregation of polysomes denotes the dissociation of rRNA from mRNA in reversible ischemic/hypoxic injury. Depletion of intracellular ATP is thought to promote the dissolution of polysomes into monosomes as well as the detachment of ribosomes from the rough endoplasmic reticulum. Disaggregation of polysomes results in impaired protein synthesis. Disaggregation of granular and fibrillar elements of the nucleus is associated with reversible cell injury. Another common nuclear change associated with reversible cell injury is clumping of nuclear chromatin, perhaps secondary to a decrease in intracellular pH. Triglyceride droplet accumulation is characteristic of reversible cell injury, especially in hepatocytes, and also in striated muscle cells and renal cells. This fatty change may result from the decreased synthesis of intracellular proteins that occurs with cell injury. In the hepatocyte, decreased production of lipid acceptor proteins prevents the normal incorporation of triglycerides into lipoproteins. Since triglycerides cannot be rapidly exported from the cell in the form of lipoproteins, they accumulate intracellularly. Glycogen loss is another early and reversible cellular response to injury. As a result of lowered mitochondrial ATP production, ATP must be supplied to the cell via anaerobic glycolysis of glucose derived from the cell's glycogen stores. Myocardial glycogen stores may be completely depleted within 30 minutes of the onset of severe ischemia.

A 34-year-old Asian female is hospitalized with progressive exertional dyspnea, lower extremity edema and cough. She also describes frequent nocturnal episodes of breathlessness and recent hoarseness. She does not use tobacco, alcohol or drugs. Auscultation reveals loud first and second heart sounds and a mid-diastolic rumble best heard at the cardiac apex. This patient's hoarseness is most likely caused by:

Nerve impingement In rare instances, the left recurrent laryngeal nerve may be compressed to the point of neurapraxia (failure of nerve conduction due to blunt injury) by enlargement of the left atrium and/or other structures in the vicinity of its course as it loops behind the ligamentum arteriosum, underneath and around the aortic arch, and back up alongside the trachea to the larynx. Mitral stenosis can cause left atrial dilatation sufficient to impinge on the left recurrent laryngeal nerve (Ortner syndrome). The recurrent laryngeal nerves innervate all of the intrinsic muscles of the larynx except the cricothyroid muscle. Paresis of vocal cord muscles innervated by left recurrent laryngeal nerve can cause hoarseness.

A 45-year-old man comes to the emergency department because of severe chest pain, diaphoresis, and palpitations. The patient dies two hours after the onset of his symptoms. Autopsy reveals 100% occlusion of the left anterior descending artery. At the time of the patient's death, light microscopy of the affected myocardium would most likely demonstrate which of the following?

Normal myocardium The cause of death was most likely an acute myocardial infarction. In myocardial infarction, changes on light microscopy are usually not apparent until 4 hours after the onset of severe ischemia. Although a variable waviness of myofibrils at the border of the infarct (due to myofibril relaxation) might be observed before this, more definite signs of early coagulative necrosis, such as cytoplasmic eosinophilia and nuclear pyknosis, take at least 4 hours to develop.

What is hyperplastic arteriosclerosis?

Onion-like concentric thickening of arteriolar walls due to layers of smooth muscle cells and reduplicated basement membrane is seen in hyperplastic arteriolosclerosis, which can occur in severe chronic hypertension (eg, blood pressure >180/120 mm Hg). Although arterioles in all tissues may be affected, those in the kidneys, retinas, and intestines are most common; skeletal muscle is less likely to be symptomatically involved.

A 38-yro dies Postmortem reveals an occluding thrombus overlying a ruptured atherosclerotic plaque on the left anterior descending artery. The patient is also found to have thickened mitral valve leaflets with multiple small vegetations on both valvular surfaces and fibrinoid necrosis of arterioles. Other findings include glomerular capillary basement membrane thickening with wire-loop changes. This patient was most likely suffering from which of the following conditions?

SLE Cardiovascular manifestations of SLE include accelerated atherosclerosis with increased risk of myocardial infarction. Small arteries and arterioles can also show evidence of vasculitis with fibrinoid necrosis in any tissue. Other cardiac features include pericarditis and less commonly verrucous (Libman-Sacks) endocarditis, characterized by thickened valve leaflets (typically mitral [red arrows] and/or aortic [black arrows]) with multiple small vegetations on both surfaces. The vegetations are composed of sterile platelet thrombi intertwined with strands of fibrin, immune complexes, and mononuclear cells. These vegetations are easily dislodged and can result in systemic embolization. Renal involvement in SLE most often manifests as diffuse proliferative glomerulonephritis, which is characterized by proliferative and necrotizing lesions with crescent formation during active disease. Light microscopy also classically shows diffuse thickening of the glomerular capillary walls with "wire-loop" structures due to subendothelial immune complex deposition.

A 62-year-old man dies suddenly in his sleep. The patient had a history of type 2 diabetes mellitus and hypertension, and he smoked a pack of cigarettes daily for 25 years. His adherence to medical care was poor. Autopsy is performed, and a histologic section of his left ventricular myocardium is shown below. What directly promotes formation of fibrosis?

TGF-B Inflammation: Hours to days post-MI, neutrophils and macrophages remove necrotic tissue and release cytokines and growth factors that initiate tissue proliferation. Proliferation: Days to weeks post-MI, transforming growth factor-beta (TGF-β) and other anti-inflammatory cytokines downregulate the inflammatory response and stimulate fibroblast migration and proliferation, causing extensive type I and III collagen deposition. Remodeling: Weeks to months post-MI, TGF-β also stimulates production of matrix metalloproteinases (MMPs) that facilitate collagen remodeling (ie, fiber rearrangement) and crosslinking to form dense scar tissue.

Cystic medial degeneration is consistent with what?

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.

A 54-year-old Caucasian male comes to the emergency room with retrosternal chest pain of 30 minutes duration. The patient also complains of sweating and mild dyspnea. A single tablet of nitroglycerin is delivered sublingually, and the patient's pain decreases significantly. The patient has experienced several similar episodes of pain over the last 12 hours, all of which resolved spontaneously. Which of the following ultrastructural changes would most likely indicate irreversible myocardial cell injury in this patient?

The appearance of vacuoles and phospholipid-containing amorphous densities within mitochondria generally signifies irreversible injury, and implies a permanent inability to generate further ATP via oxidative phosphorylation. When the mitochondria are injured irreversibly, the cell cannot recover. Simple mitochondrial swelling may be associated with reversible cellular injury, however.

A 54 yro w/ severe fatigue and dyspnea. PMH of heart failure that has been resistant to treatment. He was treated with chest radiation 10 years ago for non-Hodgkin lymphoma and has been in remission. He dies. Gross inspection of the heart shows dense, thick, fibrous tissue in the pericardial space between the visceral and parietal pericardium. Which of the following signs would most likely have been detected during a physical examination of this patient just prior to his death?

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.

Autopsy of a 56 yro man shows the following heart findings: Left atrium: enlarged Left ventricular myocardial mass: increased Left ventricular wall thickness: increased The structural changes observed in this patient's heart are most likely associated with which of the following conditions?

The autopsy findings of this patient's left ventricle (LV) are consistent with concentric hypertrophy most likely due to chronic hypertension. LV hypertrophy is generally defined as an increase in the left ventricular mass due to increased wall thickness (concentric) or cavity size (eccentric). Concentric hypertrophy is characterized by uniform thickening of the ventricular wall with the outer dimensions of the ventricle remaining almost unchanged, resulting in a narrowed ventricular cavity size. It is due to chronic elevation of ventricular pressures during systole, which is usually caused by long-standing hypertension or aortic stenosis (increased LV afterload). Patients may develop diastolic dysfunction with left atrial enlargement and congestive heart failure due to impaired ventricular compliance and filling.

Student dies suddenly. Histologic examination of this patient's myocardium shows cardiomyocyte hypertrophy with haphazard cellular arrangement and prominent interstitial spacing with fibrosis. His condition is caused by a mutation to what structural protein?

These findings are consistent with hypertrophic cardiomyopathy (HCM). HCM is caused by genetic mutations affecting structural proteins of the cardiac sarcomere, most commonly beta-myosin heavy chain and myosin-binding protein C. Autosomal dominant. HCM is one of the most common causes of sudden cardiac death (SCD) in young adults. Although SCD due to HCM often occurs with exertion, it can occur at rest. It is believed that cardiomyocyte disarray and fibrosis alters the spatial relationship of intercalated discs (the primary mediators of organized cardiac conduction), increasing susceptibility to ventricular arrhythmia (eg, ventricular tachycardia, ventricular fibrillation). Chronic myocardial ischemia, which can occur due to insufficient blood supply to hypertrophied myocardium, also contributes to interstitial fibrosis and the risk of arrhythmia.

A 54-year-old man comes to the emergency department due to worsening shortness of breath for the last 3 days. His symptoms initially occurred with exertion but are now present at rest. The patient could not sleep last night because of a suffocating cough each time he tried to lie down. He considers himself generally healthy and states, "I've never had to see a doctor for any problems." Family history is remarkable for asthma and hypertension. Blood pressure is 162/86 mm Hg, pulse is 92/min, and respirations are 26/min. An x-ray of the chest is shown in the exhibit. Which of the following is the most likely diagnosis?

This patient has progressive dyspnea and orthopnea (cough when lying down), along with chest x-ray findings of prominent pulmonary vessels, patchy bilateral airspace opacities (red arrows), blunting of the costophrenic angles (pleural effusions [yellow arrows]), and a fissure sign (created by fluid trapped between the right upper and middle lobe [blue arrow]). These findings are consistent with acute decompensated heart failure (ADHF) due to left ventricular systolic or diastolic dysfunction. In ADHF, increased atrial and ventricular filling pressures are transmitted to the pulmonary vasculature, causing fluid transudation into pulmonary interstitial and alveolar spaces (cardiogenic pulmonary edema). The chest x-ray may also show Kerley B lines—short, horizontal lines perpendicular to the pleural surface that represent edema of the interlobular septa. Cardiomegaly (cardiac-to-thoracic width ratio >50%) is also common in heart failure, but it is difficult to assess on anteroposterior view due to magnification of the heart.

A 35-year-old previously healthy man is brought to the emergency department after being involved in a motor vehicle accident. He has significant blunt chest and head trauma. Shortly after he arrives, his blood pressure drops suddenly and he begins experiencing respiratory distress. On physical examination, the patient is tachycardic and tachypneic. His lungs are clear to auscultation with vesicular breath sounds heard bilaterally. He has jugular venous distention, and his systolic blood pressure falls 15 mm Hg with inspiration. Which of the following is the most likely cause of this patient's deterioration?

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.

A 78-year-old female is brought to the ER because of altered mental status of recent onset and difficulty walking. She has a history of Parkinsonism and has had difficulty walking lately. She lives alone and has had a few falls recently. Her BP is 180/100 mm Hg and pulse is 68/min. Her head CT scan shows a crescent-shaped mass. What is the most likely cause of symptoms?

This patient has suffered a subdural hematoma, an accumulation of blood between the dura mater and arachnoid. The blood comes from the bridging cortical veins which carry blood from the cortex to the venous sinuses. They can rupture as a result of acceleration-deceleration injury. As the hematoma expands, it raises the intracranial pressure and compresses the brain. Venous bleeding is relatively slow, which explains the gradual onset of symptoms in subdural hematoma. Patients complain of gradually worsening headache and display a slow decline in mental function. On CT scan, subdural hematoma is seen as a crescent-shaped mass. Subdural hematoma often occurs in elderly individuals after a minor trauma. This increased incidence is explained by age-related brain atrophy. As the distance from the skull to the brain surface increases, cortical bridging veins are under more tension and rupture more easily. In elderly patients, subdural bleeding is called a "great imitator" due to its subtle and variable presentation. It may present as gait abnormalities, seizures, somnolence, confusion and memory loss. These patients may go undiagnosed for weeks.

Differentiate arterial from venous insufficiency

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.

A 38-year-old man dies suddenly. He had experienced chest discomfort, SOB, and fatigue in the week preceding the event. The man was overweight but otherwise had no significant medical history. Both parents are alive and healthy; a maternal uncle reportedly died of a heart attack at age 50. Autopsy was performed and myocardial findings show inflammatory infiltrate. What was the likely cause?

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.

Pt who had lymphadenectomy after cancer resection later has swelling of lower leg. What is the treatment?

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).

A 35-year-old primigravid woman comes to the clinic during the second trimester. The patient reports that she has had some tiredness, which she attributes to pregnancy. She takes 1 nap during the day. She has no chest pain, cough, or lower extremity swelling. As a child, the patient was told that she has a murmur but does not know any details and says that she has felt well until recently. On physical examination, a 3/6 midsystolic murmur is heard at the left upper sternal border and S2 is widely split. Which of the following is the most likely diagnosis?

This patient likely has pulmonic valve stenosis (PS), which most commonly occurs as an isolated congenital defect and rarely occurs as an acquired defect (eg, rheumatic fever, carcinoid syndrome). Severe PS is typically diagnosed early in life due to presentation with right-sided heart failure, but patients with relatively mild PS often remain asymptomatic throughout childhood and develop symptoms (eg, dyspnea, fatigue) in adulthood. The physiologic changes of pregnancy (eg, increased plasma volume) can unmask underlying PS. Cardiac auscultation in PS reveals a pulmonic ejection click followed by a harsh crescendo-decrescendo systolic murmur best heard at the left upper sternal border. The stenosis causes the pulmonic valve to close later than usual as it takes longer for the right ventricle to push blood through the narrowed valve. This results in widened splitting of the aortic and pulmonic components of S2. Inspiration draws additional blood into the right side of heart, which increases the intensity of the murmur and further widens the splitting of S2.

A 65yro man dies. Hx of HTN nd chronic kidney disease. The patient smoked a pack of cigarettes daily for 38 years and immigrated to the United States 20 years ago. Autopsy is performed, and microscopic examination of the lungs reveals alveolar macrophages containing aggregates of golden-brown cytoplasmic granules that turn dark blue with Prussian blue staining. Which of the following conditions is most likely associated with this patient's microscopic findings?

This patient most likely had heart failure due to left ventricular dysfunction. Impaired forward pumping by the left ventricle causes increased pulmonary capillary pressure that can lead to pulmonary edema and dyspnea. The rise in hydrostatic pressure also disrupts the integrity of the pulmonary capillaries, leading to extravasation of red blood cells and alveolar hemorrhage. The red blood cells are eventually phagocytosed by macrophages, and the iron from hemoglobin is converted to hemosiderin. Prussian blue stain detects intracellular iron. In the Prussian blue reaction, colorless potassium ferrocyanide is converted by iron to blue-black ferric ferrocyanide. Macrophages containing golden-brown cytoplasmic granules that turn blue with Prussian blue staining represent hemosiderin-laden macrophages (siderophages). These cells may be found in any tissue where macrophages encounter extravasated red blood cells; in the alveolar parenchyma, they are often called "heart failure cells."

A 39yro man w/ anterior chest pain. The patient says the pain is sharp and makes it difficult to take a deep breath. The patient's father died of a heart attack at age 52, and his mother suffers from rheumatoid arthritis. He does not use alcohol or tobacco. Temperature is 37.4 C (99.3 F), blood pressure is 112/65 mm Hg, and pulse is 103/min and regular. Bedside ultrasound examination demonstrates a moderate pericardial effusion. What is the most likely cause of this patient's current condition?

This patient most likely has acute viral pericarditis; viral infection is thought to be the most common cause of pericarditis and many viruses (eg, adenovirus, coxsackievirus, echovirus, influenza virus) have been implicated. Because the viral infection often cannot be confirmed, presumed viral pericarditis is sometimes referred to as idiopathic. Pericarditis typically presents with substernal pleuritic chest pain that may radiate to the bilateral scapulae posteriorly. The pain is typically worse when lying flat and improves with sitting up and leaning forward. Cardiac auscultation in acute viral pericarditis classically reveals a triphasic pericardial friction rub (occurring during atrial systole, ventricular systole, and early ventricular diastole); however, the rub may be absent, especially in the presence of significant pericardial effusion. Mild to moderate-sized pericardial effusion is common and can rarely lead to cardiac tamponade. ECG characteristically demonstrates diffuse ST elevation caused by inflammation of the ventricular myocardium.

A 33yro woman w/ sudden SOB and left-sided chest pain. The symptoms began an hour ago while she was doing yard work. BP is 84/58 mm Hg, pulse is 122/min, and respirations are 24/min. Pulse oximetry is 86% on room air. She has JVD. Lungs are clear to auscultation bilaterally with no crackles or wheezes. Arterial blood gas results are pH 7.52, PaCO2 28 mm Hg, and PaO2 54 mm Hg. Which of the following is most likely to be seen on bedside echocardiography?

This patient most likely has an acute pulmonary embolism (PE). The classic presentation is acute-onset chest pain and shortness of breath that may be accompanied by syncope or near-syncope. Patients usually have tachycardia, tachypnea, jugular venous distension, and clear lungs. Arterial blood gas results typically show hypoxemia and acute respiratory alkalosis due to hyperventilation. Massive PE can lead to hypotension and obstructive shock. There is a rapid increase in pulmonary arterial resistance that leads to an increase in pulmonary arterial and right ventricular (RV) pressure. The rapid pressure increase causes RV cavity enlargement due to increased RV wall tension and cardiac muscle stretching. RV myocardial oxygen demand increases and coronary artery perfusion decreases, leading to a supply/demand mismatch and RV ischemia. Consequent RV dysfunction then leads to an inability to pump blood through the pulmonary circulation, resulting in decreased left-sided preload and decreased cardiac output. Such RV failure caused by an increase in pulmonary vascular resistance is sometimes called cor pulmonale.

A 23-year-old Caucasian male who notes recurrent severe nosebleeds is found to have pink spider-like lesions on his oral and nasal mucosa, face, and arms. The patient most likely suffers from:

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.

A 64-year-old man comes to the emergency department due to flank discomfort and red urine. He has a history of hypertension and type 2 diabetes mellitus. Three months ago, the patient had an ischemic stroke and now has mild, residual, right-sided weakness. Serum creatinine is 0.9 mg/dL, and serum lactate dehydrogenase is elevated. Urine microscopy shows many red blood cells. The findings of a CT scan of the abdomen with contrast are shown in the image below

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.

A 25 yro woman w/ fatigue, myalgias, arthralgias, and a 5-kg (11-lb) weight loss. She has also recently experienced leg pain with activity, which resolves with rest. BP is 160/90 mm Hg in the right arm and 120/80 mm Hg in the left. A bruit is heard over the left subclavian artery. Left radial pulse and dorsalis pedis pulses in both legs are weak. The remainder of the examination shows no abnormalities. Laboratory results reveal a Hb level of 9.8 g/dL and an erythrocyte sedimentation rate of 110 mm/hr. Which of the following most likely underlies this patient's current condition?

This patient with lower extremity claudication (ie, exertional pain due to limited blood flow reserve) and constitutional symptoms has typical features of Takayasu arteritis (TA). TA is a chronic, large-artery vasculitis that primarily involves the aorta and its branches. TA predominantly affects women of reproductive age and is more common in Asians. Arterial narrowing in TA can manifest as audible bruits, blood pressure discrepancies, pulse deficits, and distal ulcerations. Characteristic findings on histopathology include mononuclear infiltrates and granulomatous inflammation of the vascular media, leading to arterial wall thickening and occlusion. The pathologic abnormalities in TA closely resemble giant cell (temporal) arteritis; however, TA primarily affects younger individuals, whereas giant cell arteritis occurs almost exclusively in patients age ≥50.

A 52-year-old man comes to the office due to periodic substernal chest heaviness. The pain is precipitated by fast walking, especially uphill and against the wind, and remits after 5 minutes of rest. The patient has a history of hypertension and smokes a pack of cigarettes a day. Blood pressure is 140/80 mm Hg and pulse is 80/min. The lungs are clear to auscultation, and no heart murmurs are heard. There is no peripheral edema. Which of the following pathologic states is most likely to be present in this patient?

This patient with multiple risk factors for coronary artery disease (eg, age, hypertension, smoking) has intermittent substernal chest heaviness consistent with stable angina pectoris. Stable angina is characterized by substernal or left-sided chest pressure, tightness, or pain that is reliably produced by exertion and relieved by rest. It occurs due to temporary myocardial ischemia resulting from demand-supply mismatch of oxygen-rich blood to the myocardium. Myocardial oxygen demand is determined by heart rate, blood pressure (afterload), left-ventricular end-diastolic volume (preload), and cardiac contractility, whereas myocardial oxygen supply is determined by coronary blood flow. The demand-supply mismatch of stable angina results from restricted coronary blood flow due to a fixed atherosclerotic lesion that obstructs >70% of the coronary artery lumen. These lesions allow sufficient blood flow to the myocardium during rest but insufficient blood flow to meet myocardial oxygen demands during exertion.

A 63yro man w/ chest pain and SOB. On cardiac auscultation, a systolic murmur is heard. Basilar crackles are present on both sides. After initial evaluation, the patient is taken to the cardiac catheterization laboratory and is found to have a coronary artery occlusion, which is successfully revascularized. The next morning, the patient appears comfortable and wants to go home. The lungs are clear on auscultation, and no heart murmur is present. The murmur heard during initial presentation is most likely explained by a pathologic process involving which of the following structures?

This patient with myocardial infarction developed a new systolic murmur that resolved following revascularization, which is consistent with mitral regurgitation (MR) due to papillary muscle dysfunction. Myocardial infarction can cause ischemia of the papillary muscle and the adjacent LV wall on which it is mounted. This results in hypokinesis and outward displacement of the papillary muscle, creating increased tension on the attached chordae tendineae and preventing complete closure of the corresponding mitral valve cusp. Timely restoration of adequate blood supply with coronary revascularization restores papillary muscle and LV wall motion, often leading to resolution of the MR. In contrast to papillary muscle dysfunction, papillary muscle rupture is a mechanical complication of MI that occurs acutely or within 3-5 days and leads to acute MR; it does not resolve with coronary revascularization and typically requires surgical repair.

Describe third degree AV block

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.

Autopsy reveals thrombotic occlusion of the left anterior descending artery. In addition, it shows 95% atherosclerotic narrowing of the proximal right renal artery but no significant stenosis of the left renal artery. Compared with the right kidney, this patient's left kidney is more likely to demonstrate which of the following findings?

This patient's autopsy findings are consistent with severe, unilateral renal artery stenosis (RAS), a condition that occurs most commonly in older individuals due to atherosclerosis. Hypoperfusion of the stenotic (right) kidney stimulates renin release by JG cells. Renin converts angiotensinogen to angiotensin I, which is then converted by ACE to angiotensin II, a potent vasoconstrictor that causes systemic hypertension. Narrowing of the renal artery in the stenotic (right) kidney leads to hypoperfusion and renal parenchymal ischemia, which manifests as diffuse cortical thinning, tubular atrophy, interstitial fibrosis, and small crowded glomeruli. Juxtaglomerular apparatus enlargement can also occur due to chronic stimulation and increased renin release. Nonstenotic (left) kidney is exposed to high blood pressure and shows signs of hypertensive nephrosclerosis, which is characterized by arteriolar wall thickening due to hyaline arteriolosclerosis (hyalinization of the arterioles due to extravasation of plasma proteins) and hyperplastic arteriolosclerosis (concentric smooth muscle cell proliferation in response to pressure ["onion-skinning"]).

Intravenous fluids and vasopressors are administered, but the patient remains hypotensive and dies 3 hours later. Autopsy examination is performed and reveals bilateral hippocampal necrosis. Which of the following areas of the colon would be most likely to also demonstrate necrosis?

This patient's bilateral hippocampal necrosis is characteristic of the effects of global cerebral ischemia due to systemic hypotension. The hippocampus is particularly vulnerable during shock because of the high metabolic demand of its CA1 pyramidal neurons. Watershed areas located between the distal terminal branches of 2 different vascular territories (border zones) are also susceptible to ischemia because they have a low baseline perfusion pressure and poorly tolerate sustained decreases in systemic blood pressure. Important watershed areas in the body include: Gastrointestinal (colon) Splenic flexure: the border zone supplied by branches of the superior mesenteric artery and inferior mesenteric artery Rectosigmoid junction: the border zone supplied by the sigmoid arteries and the superior rectal arteries Brain: the borders of the areas supplied by the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery

The single most important risk factor for aortic dissection is?

This patient's chest CT scan reveals a widened, ascending thoracic aorta with a nonenhancing septum dividing the lumen of the ascending and descending aorta. The "septum" is actually the tunica intima of the aorta, which has been torn from the remainder of the aortic wall. A tear in the tunica intima is thought to be the primary event in the process leading to aortic dissection. As more and more blood is forced through the tear, an intramural hematoma begins to develop between the intimal flap and medial wall, creating a false lumen. The dissection can extend both proximally toward the heart and distally, sometimes extending all the way to the iliac and femoral arteries. Hypertension is the single most important risk factor for the development of intimal tears leading to aortic dissection. Cystic medial degeneration, which may be seen in connective tissue diseases such as Marfan syndrome, also predisposes patients (especially younger ones) to aortic dissection.

A 34-year-old woman comes to the emergency department because of sharp chest pain that radiates to the left shoulder. The pain increases with inspiration and is partially relieved by sitting up and leaning forward. Review of her outpatient medical records shows that she was seen for a facial rash 6 months ago. She is also being evaluated for proteinuria that was identified during her last clinic appointment. Which of the following is the most likely cause of this patient's chest pain?

This patient's chest pain is characteristic of acute pericarditis, which along with her facial rash and proteinuria is suggestive of underlying systemic lupus erythematosus (SLE). SLE is a chronic autoimmune disease predominantly affecting women age 20-40 that causes constitutional and multisystemic symptoms. Serosal inflammation is common in SLE and most often manifests as pleuritis or pericarditis. Pericarditis presents with severe and constant middle or left chest pain that may radiate to the neck and shoulders (particularly the trapezius ridge). The pain increases on inspiration (pleuritic) and is relieved by sitting up and leaning forward (postural). Auscultation of the chest reveals a scratchy sound called a pericardial friction rub that is best heard when the patient is leaning forward or lying prone. Additional cardiovascular manifestations in SLE include pericardial effusion, verrucous (Libman-Sacks) endocarditis, and increased risk of coronary artery disease.

A 42yro woman w/ chest pain. She was moving furniture in her summer house 2 days ago when she experienced sharp pain in the left side of the sternum that quickly subsided. Since then, the patient has had episodic pain with deep inspiration or trunk movement. She has localized tenderness to palpation at the left sternal border. The abdomen is soft and nontender. There is no peripheral edema. Which of the following is the most likely cause of this patient's symptoms?

This patient's chest pain is most likely due to costosternal syndrome (also known as costochondritis or anterior chest wall syndrome) involving the regional chest wall. It usually occurs after repetitive activity and involves the upper costal cartilage at the costochondral or costosternal junctions. The pain is typically reproduced with palpation and worsened with movement or changes in position (eg, horizontal arm flexion). Patients typically do not have palpable warmth, swelling, or erythema.

In a patient with CAD, what is most likely reason for sudden death?

This patient's clinical features are suggestive of coronary artery disease (chest pain and multiple risk factors) causing an acute myocardial infarction (MI). The diagnosis is confirmed by autopsy showing a large atheromatous plaque with superimposed thrombosis causing complete obstruction of the right coronary artery. Acute MI is a common cause of sudden cardiac death (SCD) (the abrupt cessation of organized cardiac activity leading to hemodynamic collapse and inadequate tissue perfusion). SCD due to acute MI usually results from a malignant ventricular arrhythmia (ie, *ventricular fibrillation* or ventricular tachycardia degenerating to ventricular fibrillation) that is triggered by electrical instability in the ischemic myocardium.

Describe cardiac amyloidosis

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.

A 5-week-old boy w/ hyperdynamic precordium, a mid-diastolic rumble at the left sternal border, and a 3/6 holosystolic murmur in the apex that radiates to the left axilla. An echocardiogram shows defects in the lower part of the interatrial septum and the interventricular septum. This patient's condition is most likely associated with which of the following genetic conditions?

This patient's echocardiogram suggests a complete atrioventricular (AV) canal defect, the most common type of cardiac defect in patients with Down syndrome, an autosomal trisomy. Failure of endocardial cushion fusion results in an ostium primum atrial septal defect; a ventricular septal defect; and a single AV valve. Significant left-to-right shunting and AV valve regurgitation lead to excessive pulmonary blood flow and symptoms of heart failure (eg, tachypnea, poor feeding). Auscultatory findings of AV valve regurgitation (holosystolic, best heard at apex) and increased pulmonary venous return (mid-diastolic rumble) are characteristic.

Patient with a cardiac tumor. What is the likely histopath?

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.

A 64yro man has had difficulty walking for 6 months, experiencing muscle cramps in his right thigh after walking a block on level ground. He has also had decreased sexual performance. PMH of hypercholesterolemia and MI. The patient smokes a pack of cigarettes daily but does not use alcohol or illicit drugs. He has no other problems. Which of the following is the most likely cause of this patient's symptoms?

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.

Cardiac catheterization shows 80% occlusion of the right coronary artery and 60% occlusion of the left coronary artery. The first step in the pathogenesis of this patient's coronary artery disease most likely involved which of the following cell types?

This patient's presentation is consistent with coronary artery atherosclerosis. The pathogenesis of atherosclerosis likely begins with 1) endothelial cell injury. Chronic endothelial cell injury may result from hypertension (and related hemodynamic factors), hyperlipidemia, smoking, and diabetes mellitus. Such injury leads to endothelial cell dysfunction and/or exposure of subendothelial collagen (endothelial cell denudation). Endothelial cell dysfunction results in monocyte and lymphocyte adhesion and migration into the intima while exposure of subendothelial collagen promotes platelet adhesion. Growth factors produced by monocytes and platelets stimulate medial smooth muscle cell (SMC) migration into the intima. At the same time, increased vascular permeability allows LDL cholesterol into the intima, where it is phagocytosed by the accumulating macrophages and SMCs to produce lipid-laden foam cells (fatty streak). The continued release of cytokines and growth factors results in a chronic inflammatory state within the underlying intima. This promotes further deposition of LDL cholesterol within the intima and stimulates SMC proliferation with increased production of collagen and proteoglycans. Necrosis of foam cells results in release of toxic oxidized LDL into the extracellular matrix, perpetuating a cycle of injury. The lesion eventually organizes into a core of lipid debris surrounded by monocytes and lymphocytes covered by a fibrous cap with intermixed SMCs (fibrofatty atheroma).

A 30-year-old Asian man comes to the clinic due to painful, ulcerated fingers. His symptoms began with pain and discoloration of the fingers several weeks ago, which progressed to ulceration at the fingertips. He also reports pain in the hands that occurs with activity and is relieved by rest. The patient has smoked 2 packs of cigarettes a day for the last 5 years. Radial pulses are diminished. There is erythema and tenderness along a superficial vein of the left forearm. Which of the following pathologic findings is most likely to be present in this patient?

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.

What is the underlying cause of abdominal aortic aneurysm?

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.

A 45yro w/ progressive pain in the RUQ, nausea, and vomiting. In the preceding year, the patient has had fatigue, weight loss, joint pain, and intermittent abdominal pain. Laboratory studies show increased blood urea nitrogen and serum creatinine. Right-upper quadrant ultrasound shows no evidence of gallstones, but an inflamed gallbladder is present. The patient undergoes cholecystectomy, and subsequent biopsy of the submucosal gallbladder vessels shows fibrinoid necrosis of the vessels. Which of the following is the most likely diagnosis?

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.

Cardiopulmonary examination reveals pectus excavatum, bilateral pulmonary crackles, and a decrescendo diastolic murmur at the right upper sternal border. The abdomen is soft and nontender. There is no peripheral edema. Subsequently, the patient develops cardiac arrest and dies. Which of the following histologic changes is most likely to be seen on autopsy?

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.

An 80-year-old man is brought to the hospital due to increasing chest pain. Over the past 6 wks, he has had dry cough, dysphagia, and a change in voice quality. The patient has a long history of hypertension. He is an ex-smoker with a 35-pack-year history. BP is 80/60 mm Hg, pulse is 120/min, and respirations are 20/min. He dies. Autopsy is most likely to show which of the following findings?

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.