Neo Blood Vessels- Phase 3 Flashcards
ReKap
The azygos vein is located on the right anterolateral aspect of the spine and is the major venous pathway for drainage of the chest wall as well as the thoracic esophagus.
Congestion of the esophageal venous plexus may result from portal hypertension. This leads to the formation of torturous veins known as varices.
Patients with portal hypertension are at high risk for esophageal variceal rupture, which carries a very high risk of recurrence and mortality.
Analysis
The correct answer is E. This patient has end-stage liver disease. The clinical clues in the question stem that suggest cirrhosis are scleral icterus, telangiectasias, gynecomastia, tremor, and blood on the stool. Severe cirrhosis can cause portal hypertension. The azygos vein (choice E) Label E is a major accessory pathway for venous return in patients with end-stage liver disease and critical portal hypertension. The pathway starts at the left gastric vein, which drains into the portal vein. With portal hypertension, flow through the left gastric vein reverses and blood flows into the esophageal venous plexus. The azygos vein is the major outlet for the esophageal venous plexus and is somewhat helpful in relieving some of the pressure of the esophageal vein. However, it is the esophageal vein that bears the burden in the setting of esophageal varices.
When the esophageal varices become engorged, variceal rupture, perhaps the most dreaded complication of portal hypertension, can occur. These varices have a high incidence of rupture and each episode carries a 50% chance of death; nearly half of survivors have recurrent episodes.
Transverse CT scan of the upper 1/3rd of the chest with major vascular structures labeled. A. Internal thoracic artery, B. Common pulmonary artery, C. Ascending aorta, D. Superior vena cava, E. Azygous vein, F. Descending aorta.
Choice A shows the internal thoracic vessels, also known as the internal mammary vessels. The internal thoracic vessels supply the anterior chest wall and give rise to the anterior intercostal vessels. The left internal thoracic artery is frequently used in coronary artery bypass.
Choice B is the pulmonary trunk, which is not related to portal blood flow because the pulmonary circulation is entirely separate from the systemic circulation.
Choices C and F are the ascending aorta and descending aorta, respectively, which are unrelated to venous drainage.
Choice D is the superior vena cava (SVC), which is the final destination of the azygos vein but is not related to variceal bleeds and is not a direct portal venous circulation accessory pathway.
ReKap
Spironolactone is a potassium-sparing diuretic that blocks aldosterone receptors in the distal nephron.
It also has antiandrogenic effects that can lead to increased male breast tissue, known as gynecomastia.
Analysis
The correct answer is A. This male patient has increased breast tissue, known as gynecomastia, which is relatively common in men as they age and may be related to the extra-glandular conversion of androgens to estrogen. A variety of pathologic and drug-related etiologies can also lead to this condition. Causes of gynecomastia include:
Deficient production/action of testosterone
Renal failure
Increased estrogen production (as a result of various tumors)
Liver disease
Drugs
Medications associated with gynecomastia development:
Spironolactone
Digoxin
Cimetidine
Alcohol
Ketoconazole
Estrogens
Omeprazole
Calcium channel blockers
Each of the answer choices in this question represents the mechanisms of action for five different classes of medications used to treat hypertension and/or congestive heart failure. Spironolactone is a potassium-sparing diuretic that acts as a competitive inhibitor of aldosterone receptors in the distal segments (distal convoluted tubule, connecting tubule, and collecting tubule/duct); it is used to treat edema, hypertension, primary hyperaldosteronism, diuretic-induced hypokalemia, and NYHA Class III/IV heart failure. Other less common indications include idiopathic hirsutism and acne vulgaris.
Spironolactone may cause gynecomastia by displacing androgen from the androgen receptor and sexual-hormone-binding globulin, increasing metabolic clearance of testosterone, and increasing bodily estradiol production. Spironolactone can also cause hyperkalemia and metabolic acidosis.
Hydrochlorothiazide and indapamide are thiazide diuretics that inhibit the reabsorption of sodium and chloride ions in the distal renal tubules (choice B). Thiazides can cause hypokalemia, metabolic alkalosis, and hypercalcemia.
The loop diuretics act by inhibiting the reabsorption of sodium, potassium, and chloride ions in the loop of Henle (choice C). Furosemide, for example, can cause electrolyte changes such as hypokalemia (with alkalosis), hypocalcemia, and hypomagnesemia. It is ototoxic and can be associated with allergies.
The angiotensin-converting enzyme (ACE) inhibitors inhibit the conversion of angiotensin I to angiotensin II (choice D), thereby decreasing the plasma angiotensin II concentration, and resulting in decreased aldosterone secretion. ACE inhibitors such as captopril, enalapril, and ramipril can be associated with cough, hyperkalemia, hypovolemia, angioedema (rare), and are teratogenic.
Metoprolol and atenolol are beta-1 adrenergic receptor antagonists (choice E). Beta-1 receptors are in cardiac muscle and beta-2 receptors are in bronchi. The beta-1 selectivity of the drug makes it less likely to aggravate bronchospasm in an asthmatic patient. These agents also cause bradycardia, sexual dysfunction, and lipid abnormalities.
ReKap
Niacin (vitamin B3) decreases VLDL, LDL, and triglyceride levels. It increases HDL levels.
Facial flushing is the most common side effect associated with niacin and occurs in ~90% of patients. This symptom is the primary reason for patient noncompliance.
Aspirin can be used to alleviate the severity and duration of the flushing associated with niacin therapy.
Analysis
The correct answer is A. This patient has hypertriglyceridemia as evidenced by his skin lesions (eruptive xanthomas; caused by accumulations of chylomicrons in macrophages when triglycerides > 1000 mg/dL) and very high triglyceride levels. Pancreatitis is a risk with triglycerides > 1000 mg/dL and therapy should be directed to lower these levels. Three classes of medications are used to manage major elevations in triglycerides: fibric acid derivatives, niacin, and omega-3 fatty acids. Statins are often given concomitantly, although they are not as effective in lowering triglycerides.
Niacin decreases hepatic VLDL and LDL production, inhibits adipose tissue lipolysis, increases lipoprotein lipase activity, and prevents (to some degree) hepatic triglyceride esterification. High-dose niacin can decrease triglyceride levels by at least 40% and can raise HDL-c levels by 40% or more. It can also significantly lower LDL-c levels.
The most common adverse effect of niacin is a harmless but uncomfortable flushing with a sensation of warmth, especially in the face and neck. This reaction may be so severe in many patients that they discontinue therapy. Aspirin can be helpful in alleviating the severity and duration of the flushing because this reaction is partially mediated through prostaglandin synthesis. Niacin’s most serious adverse effect is chemical hepatitis.
Note: Niacin should be used cautiously in patients with type 2 diabetes since it can worsen blood glucose control.
Gastrointestinal distress (choice B) is a frequent adverse effect with bile acid sequestrants such as cholestyramine and colestipol. Additionally, these medications can increase triglyceride levels and would not be an appropriate choice for this patient.
Niacin can cause hyperglycemia (choice C) and hyperuricemia, but not hypoglycemia.
Rhabdomyolysis (choice D) is a rare, but potentially life-threatening, side effect of statins. Statins act by inhibiting HMG-CoA reductase; examples include simvastatin, pravastatin, lovastatin, and atorvastatin. Other adverse effects of statins include myopathy and hepatotoxicity.
Right upper quadrant abdominal pain (choice E) is a sign of gallstones, which can be caused by fibrates (e.g., gemfibrozil, fenofibrate, clofibrate). Fibrates can also cause myopathy and can increase the risk of rhabdomyolysis when used in combination with statins. Fibrates decrease VLDL production but they do not decrease lipolysis, which is why this answer choice is incorrect.
ReKap
Coarctation of the aorta decreases renal perfusion pressure and activates the RAAS, which increases circulating levels of angiotensin II.
Angiotensin II promotes salt and water retention, which increases cardiac preload and output. This causes a rise in systolic blood pressure proximal to the coarctation (thoracic aorta).
Analysis
The correct answer is B. The pressure tracings from the thoracic and abdominal aorta are characteristic of coarctation of the aorta. Pressure proximal to the coarctation, in the thoracic aorta, is increased through activation of the renin–angiotensin–aldosterone system (RAAS) and increased angiotensin II activity.
Coarctation (constriction) of the aorta:
Reduces aortic blood flow by introducing a vascular resistance.
>95% occur just distal to the left subclavian artery and ductus arteriosus (postductal; see panel B in the figure below).
Collateral vessels facilitate flow to the lower body (see panel C in the figure) but pressures here are lower than normal.
Low renal perfusion pressure triggers renin release from juxtaglomerular cells in the glomerular afferent arteriole, thereby stimulating the RAAS.
Angiotensin II promotes salt and water retention to increase left ventricular preload and thereby increase pressure proximal to the constriction (thoracic aorta).
Renal arterial pressure becomes almost normal as hypertension develops in the upper body.
Typical symptoms of coarctation include tachycardia, tachypnea, irritability, sleepiness, poor responsiveness, and difficulty eating.
Coarctation of the aorta
Location of aortic narrowing in A. pre-ductal (infant) coarctation of the aorta and B. post-ductal (adult) coarctation of the aorta. C. Pathway of collateral flow in coarctation of the aorta.
Parasympathetic activity (choice A) would be increased, not decreased, as a result of hypertension in the thoracic aorta. The aortic arch and carotid sinus contain baroreceptors that sense the elevated arterial pressure and promote increased parasympathetic tone (and decreased sympathetic tone) via medullary cardiovascular control centers.
Increased antidiuretic hormone (ADH) (choice C) release from the posterior pituitary does indeed contribute to hypertension proximal to coarctation of the aorta but is a less significant contributing factor compared to increased levels of angiotensin II. ADH promotes water retention. ADH is released as a result of angiotensin II stimulating the hypothalamus directly, as well as angiotensin II/aldosterone-mediated salt retention, and both pathways are required for volume expansion.
The extracellular volume expansion that is induced by coarctation of the aorta increases atrial filling volume and stretches the myocytes, causing them to secrete atrial natriuretic peptide (ANP; choice D). ANP antagonizes the actions of angiotensin II and ADH, however, and thereby opposes the development of elevated blood pressure.
Sympathetic activity would be decreased, not increased (choice E), as a result of the elevated arterial pressure proximal to the coarctation of the aorta. As discussed above, decreased sympathetic tone is mediated by the baroreceptor reflex.
ReKap
Vasospastic angina is caused by coronary artery spasm and usually occurs at rest in younger patients without significant comorbidities.
An ECG typically shows transient ST-segment elevation in leads corresponding to the affected vessel during vasospasm.
Analysis
The correct answer is E. The pattern of angina described is vasospastic angina (previously known as Prinzmetal or variant angina) and is due to coronary artery vasospasm occurring during rest. Up to 75% of patients with this disorder can have a fixed obstruction within 1 cm of the site of arterial spasm. Patients with vasospastic angina are often younger than patients with unstable angina secondary to coronary atherosclerosis. An ECG will show ST-segment elevation (transmural ischemia) in the leads corresponding to the affected vessel. The diagnosis may be confirmed by observing a spontaneous coronary artery spasm, provoking one by administering ergonovine or acetylcholine, or instructing the patient to hyperventilate during angiography.
Acute pericarditis (choice A) has many causes, most commonly a viral illness. The presentation generally includes positional chest pain that improves when the patient leans forward. An ECG would show diffuse ST-elevation in all leads.
Coronary artery aneurysms (choice B) are dilatations of the coronary arteries associated with vasculitis and are typically asymptomatic. Kawasaki disease is a pediatric febrile illness of unknown etiology associated with coronary artery vasculitis and subsequent aneurysm formation.
Coronary artery atherosclerosis (choice C) is characterized by intimal thickening of the coronary arterial wall and lipid deposition, resulting in atheromatous plaque formation and narrowing of the coronary vessels. Risk factors include hyperlipidemia, hypertension, smoking, and diabetes. Symptoms generally include chest pain that worsens with exertion and improves with rest. An ECG will show ST-segment depressions in the leads corresponding to the affected vessel.
Coronary artery thrombosis (choice D) results from the rupture of an atherosclerotic plaque. Complete occlusion of the coronary artery can result in transmural cardiac ischemia and the ECG would show ST-elevations in the leads corresponding to the affected vessel.
ReKap
Thiazide diuretics, such as hydrochlorothiazide, can cause drug-induced gout due to a decreased renal elimination of uric acid.
Gout is characterized by hyperuricemia with pain and inflammation of joint spaces, most commonly in the first metatarsophalangeal joint.
Factors that lead to gout include acute alcohol intoxication, overindulgence of foods high in purines, rapid weight loss, dehydration, trauma, and medications (e.g., thiazide or loop diuretics, allopurinol, uricosuric agents, low-dose aspirin).
Analysis
The correct answer is D. The patient is presenting with a gout flare, most likely triggered by an acute increase in serum uric acid levels. Thiazides such as hydrochlorothiazide can increase serum urate concentrations by as much as 35% by decreasing its renal clearance.
Acute gouty arthritis (AGA) is characterized by the rapid onset of pain, swelling, and inflammation. The attack is often monoarticular at first, affecting the first metatarsophalangeal (MTP) joint. Eventually, it may also involve the insteps, ankles, heels, knees, wrists, fingers, and elbows. Over 90% of all gout patients experience attacks in the great toe. Uric acid levels are generally >7.5 mg/dL when an attack occurs.
Acute gouty arthritis occurs in urate crystal deposition disease (gout), which results from uric acid or urate accumulating in blood or tissues. When the tissues become supersaturated, urate salts precipitate and form crystals. Crystals are more likely to form in cool, peripheral joints. Phagocytosis of the urate crystals by leukocytes causes their rapid lysis, which subsequently leads to an inflammatory reaction that causes intense joint pain, erythema, warmth, and swelling.
Gout flares can result from acute alcohol intoxication, overindulgence of foods high in purines, rapid weight loss, dehydration, and trauma. Medications (e.g., thiazide or loop diuretics, allopurinol, uricosuric agents, low-dose aspirin) can also precipitate gout.
None of the other drugs affect uric acid elimination and are not associated with the development of AGA.
Aripiprazole (choice A) is an atypical antipsychotic used for the treatment of schizophrenia, bipolar disorder, and adjunct treatment of major depression. It is not associated with AGA but can cause weight gain, extrapyramidal side effects (though less than the typical antipsychotics), and insomnia.
Enalapril (choice B) is an angiotensin-converting enzyme (ACE) inhibitor that is associated with anaphylactoid reactions, angioedema, hypotension, hyperkalemia, and a dry cough. The ACE inhibitors may also cause an increase in uric acid levels. However, this patient has an elevated calcium level (seen with thiazides) and borderline low potassium level.
Felodipine (choice C) is a calcium-channel blocking agent associated with hypotension, reflex tachycardia, peripheral edema, and dizziness.
Pravastatin (choice E) is a HMG-CoA reductase inhibitor indicated for the treatment of hyperlipidemia. This drug is most commonly associated with the development of myopathy, myalgia, rhabdomyolysis (rare), and hepatic enzyme elevation.
ReKap
Takayasu arteritis is a granulomatous large-vessel vasculitis mainly involving aortic arch vessels.
It commonly affects Asian-American women between 20 - 45 years of age.
Absence of peripheral pulses in the upper extremities should point to the diagnosis of Takayasu arteritis (pulseless disease).
Analysis
The correct answer is E. Takayasu arteritis is an uncommon large vessel vasculitis that is most prevalent in young Asian women. In Takayasu arteritis, an inflammatory process produces fibrous thickening of the aortic arch, causing narrowing or near obliteration of the origins of arteries that branch from the aortic arch. Pathologic examination will typically reveal a granulomatous inflammation of the vessel wall.
Reduced blood pressure (BP) in one or both arms is common; a pressure differential of 10 mm Hg between the arms is typically present. The classic sign leading to the diagnosis is the weak or absence of pulses in the upper extremities (pulseless disease) if the area proximal to the innominate artery is stenotic. Arterial pulses in the legs can also be diminished. In our patient, stenosis is most likely located in the aortic arch between the innominate artery and the left subclavian artery, resulting in BP differences between the arms (increased BP in the right arm, decreased BP in the left).
Other vessels may also be involved. Abdominal pain, diarrhea, and gastrointestinal hemorrhage may result from mesenteric artery ischemia. Vascular bruits occur more commonly in carotid and abdominal arteries but can also occur in subclavian and femoral arteries. Ocular (visual loss, retinal hemorrhages) and neurologic abnormalities (dizziness, syncope) may also be present. Erythrocyte sedimentation rate (ESR) and C-reactive protein are elevated. Treatment is with corticosteroids.
Buerger disease (also known as thromboangiitis obliterans) (choice A) is a disease of young to middle-aged adult males with a history of heavy cigarette smoking. It is characterized by segmental thrombosis of arteries and veins, involving the extremities. Clinical presentation is significant for severe pain (claudication), digital thrombophlebitis associated with microabscesses, ulceration, and gangrene. Although there is a heavy tobacco smoking history in this patient, the presentation does not fit with Buerger’s disease.
Fibromuscular dysplasia (choice B) is a congenital, non-inflammatory, non-atherosclerotic disorder that leads to arterial stenosis, usually of the renal and internal carotid arteries. Patients present with hypertension, transient ischemic attack, and stroke; however, it is not associated with the systemic symptoms of Takayasu arteritis. This type of stenosis produces smooth muscle thickening of the arterial walls and is found in younger patients.
Giant cell arteritis (choice C), whose best-known form is temporal arteritis, causes inflammation with giant cell formation that tends to affect medium-sized arteries of the head, such as the temporal and ophthalmic arteries. This type of arteritis is found typically in older female patients and is readily treatable with prednisone. It is also associated with polymyalgia rheumatica and elevated erythrocyte sedimentation rate and C-reactive protein.
Tertiary syphilis (choice D) can cause aortic root dilation, and sometimes secondarily involves the vessels originating in the aortic arch. The dilation is due to inflammation, damage, and obliteration of the vasa vasorum supplying the aortic vessel wall. Recall that the vasa vasorum supplies oxygen and nutrients to the outer layer of the aortic wall. Ischemia of the outer media and adventitial layers occur, which leads to aortic wall weakening and dilation. The dilation can compromise the aortic valve, causing insufficiency. Furthermore, the regurgitated blood increases cardiac preload and peak systolic pressure, which is represented by bounding pulses in the extremities. Tertiary syphilis is now very rarely diagnosed in the United States, probably because most people have had several courses of antibiotics of some sort during their lifetimes, so people with undiagnosed syphilis are treated.
ReKap
Criteria for distinguishing different forms of angina from myocardial infarction:
Infarctions produce enzyme elevations, whereas angina does not because of absent or minimal myocyte necrosis.
Both infarctions and angina can produce ECG changes.
Stable or typical angina occurs with exertion, improves with rest and/or nitroglycerin, and the episodes do not rapidly increase in severity or frequency.
Prinzmetal variant angina and unstable angina occur at rest.
Analysis
The correct answer is D. This patient has angina. Myocardial infarction is excluded by the failure of serum cardiac enzymes to rise, as well as by a normal electrocardiogram (ECG). Thus, this patient has angina rather than infarction. This patient’s chest pain is recurrent, triggered by exertion, and relieved by rest or nitroglycerin. All these factors suggest a diagnosis of stable (typical) angina. New-onset angina is, by definition, unstable and should be monitored closely. It is typical to admit patients with chest pain and multiple risk factors for myocardial infarction to the hospital for a 24–48 hour period to repeat cardiac enzyme testing, follow-up ECGs, and stress testing.
Gastroesophageal reflux disease (GERD) (choice A) can cause heartburn, dysphagia, regurgitation, and substernal chest pain that may radiate to the back, neck, jaw, and arms. GERD symptoms typically coincide with the postprandial period. Unlike angina, GERD symptoms would not be expected to worsen with exertion or be alleviated by nitroglycerin.
Pericarditis (choice B) causes anterior chest pain that may radiate to the shoulders, which may make it difficult to distinguish from the pain associated with myocardial ischemia. Auscultation often reveals a pericardial friction rub, which is a finding specific to pericarditis. Pericarditis would not be expected to respond to sublingual nitroglycerin.
Prinzmetal variant angina (choice C) is less likely as this is a rare diagnosis, more common in women, and is not reliably relieved with rest or nitroglycerin. This variant of angina is due to coronary vasospasm that causes transient coronary obstruction and ischemia.
Unstable angina (choice E) is a more severe form of angina that occurs with progressively milder triggers. It may cause small elevations of cardiac enzymes (up to twice the upper limit of normal), possibly because of the death of a few myocardial cells. Often, ECG changes are seen, such as ST-segment depression.
ReKap
Arteries: Thick-walled, low-capacity vessels, 14% of total blood volume.
Veins: Thin-walled, high-capacity vessels, 60–70% of total blood volume.
Analysis
The correct answer is G. Blood volume distribution within the circulation is directly related to the compliance and capacitance of the individual components. Systemic veins distend easily (thin walls and therefore high compliance) and are wide-bored vessels (high-capacitance). Under normal, resting conditions the systemic venules and veins contain about 46% of the total blood volume, or about 2,300 mL in this patient.
Blood distribution can be altered by posture or exercise, for example, to a limited extent. The supine posture at rest is typically used as the basal state for comparisons, which reduces gravitational effects of distribution and avoids the activation of the baroreflex, which alters vascular smooth muscle tone and capacitance.
The aorta and large arteries (choice A) together contain about 300 mL (6% of total). They are high-pressure, low-compliance conduits for blood flow.
Small arteries and arterioles (choice B) contain about 400 mL (8% of total). They are high-pressure, small-bored vessels whose internal diameter is varied as a way of modulating blood flow to the capillary beds.
Capillaries (choice C) contain about 300 mL (6% of total). They have internal diameters of ~8 μm and they are ~1 mm long, which means that their total capacity is limited, despite their huge numbers (~1010 total). Their function is to facilitate the exchange of materials between blood and tissues, assisted by their large collective surface area and thin walls.
The heart chambers (choice D) together contain about 360 mL (7.2% of total) at the end of diastole.
The pulmonary vasculature (choice E) contains about 440 mL (8.8% of total). Pulmonary vessels are all low-pressure, high-compliance vessels, meaning that significant shifts in blood volume can occur between the systemic and pulmonary circulations.
The large veins and venae cavae (choice F) are low-pressure conduits for blood flow back to the heart. They together contain about 900 mL (18% of total), which represents a significant reservoir that supports cardiac output when intrathoracic pressure increases (during a Valsalva maneuver, for example) or during gravity-induced shifts in vascular contents (standing causes ~400 mL of blood to shift from the upper body regions into the lower extremities and compensation takes a few heartbeats).
The table below reviews different parts of the circulatory system and their respective characteristics and contribution to total blood volume.
ReKap
Adult-onset coarctation of the aorta can present with headaches, hypertension of the upper extremities, weak lower extremity pulses, and claudication of the lower extremities.
Rib notching, which is appreciated as irregularities and scalloping on the undersurface of the ribs, is due to the formation of collateral circulation associated with adult-onset (post-ductal) coarctation of the aorta.
Analysis
The correct answer is A. Coarctation of the aorta occurs in two patterns. In the infantile type, the stenosis is proximal to the insertion of the ductus arteriosus (preductal; see Panel A in the figure); this pattern is associated with Turner syndrome.
Location of stenosis in pre-ductal (infantile) versus post-ductal (adult) coarctation of aorta. Collateral circulation is established through the intercostal arteries.
In the adult form, the stenosis is distal to the ductus arteriosus (postductal, Panel B in the figure) and is associated with notching of the ribs, seen as irregularities and scalloping on the undersurface of the ribs. Notching occurs as a result of rib erosion by a developing collateral circulation through the intercostal arteries (Panel C in the figure).
The classic presentation of coarctation of the aorta is the presence of hypertension in the upper extremities and weak pulses in the lower extremities. Headache, cold lower extremities, and lower extremity claudication are typical if the patient is symptomatic (many adults with mild distal coarctation may remain asymptomatic for years). Upper extremity hypertension with weak pulses in the lower extremities, and a midsystolic (or continuous) murmur over the chest or back, may be the only clinical signs in some patients.
Eisenmenger syndrome (choice B) occurs when a left-to-right shunt via a ventricular septal defect, an atrial septal defect, or a patent ductus arteriosus causes pulmonary hypertension and develops a subsequent right-to-left shunt. Patients develop dyspnea and late-onset cyanosis.
Tetralogy of Fallot (choice C) causes a right-to-left shunting that presents as early-onset cyanosis. The four classic features of this congenital disease include:
Pulmonary artery stenosis
Right ventricular hypertrophy
A septal defect that allows for right-to-left shunting and preferential flow of O2-poor blood into the systemic vasculature
An aorta that has a rightward deviation
The most common form of transposition of great arteries (choice D) directs systemic venous blood back into the systemic circulation via the aorta and oxygenated blood from the pulmonary vein back to the lungs via the pulmonary artery. This causes early-onset cyanosis and requires immediate medical intervention.
Ventricular septal defect (choice E), if small, might remain undiagnosed until adulthood but would not cause notching of the ribs.
ReKap
VEGF is an important vascular endothelial cell growth factor.
Many tissues secrete VEGF in response to even mild hypoxia.
High levels can be measured within an hour after exercise.
Regular exercise can lead to significant endothelial proliferation and the growth of new capillaries in muscle.
Analysis
The correct answer is E. The decrease in tissue oxygenation that occurs within muscles during exercise is a potent stimulus for vascular endothelial growth factor A (VEGF-A) production and secretion by the myocytes. VEGF-A rises to high levels within an hour after exercising.
Vascular endothelial growth factor:
A heparin-binding glycoprotein that is largely responsible for the endothelial proliferation and growth of new capillaries that follow tissue hypoxia.
There are at least 6 members of the VEGF family: VEGF-A is the family member that stimulates angiogenesis in response to hypoxia.
Essential for vascular development during embryogenesis. Known mutations in the VEGF-A gene are lethal early in gestation.
Cellular effects are mediated by a receptor tyrosine kinase.
Previously known as vascular permeability factor, it massively increases the passage of materials between the blood and interstitium.
VEGF-A and its receptor are prime targets for current research into the development of anti-cancer drugs.
Tissue hypoxia leads to the accumulation of hypoxia-inducible factor (HIF), a transcription factor. HIF increases transcription of VEGF-A (and also erythropoiesis, among other functions). HIF is produced at a constant rate but when tissue oxygenation is adequate, it is rapidly degraded.
Adenosine levels (choice A) increase during exercise, causing arteriolar vasodilation and increased blood flow to the active muscles. However, adenosine has a very short half-life, so levels normalize within minutes following exercise termination.
Basic fibroblast growth factor (bFGF; choice B) is a potent growth factor for many different types of cells, including endothelial cells. bFGF is not elevated by regular exercise under normal conditions, but may be elevated in muscles exposed to very severe hypoxia or ischemia under non-physiologic conditions.
Growth hormone (GH; choice C) levels increase during exercise but, like other peptide hormones, it has a short plasma half-life. It returns to near basal levels within one hour after exercise ceases. The question specified what condition would be found in the muscle one hour after exercise; by this time, circulating and tissue GH levels would be restored to near basal levels. In contrast, VEGF-A changes are persistent and potently increase muscle vascularity during endurance conditioning.
Oxygen levels (choice D) decrease in exercising muscles and return to normal levels within an hour after exercise has been terminated.
ReKap
Postductal coarctation of the aorta produces collateral flow via the internal thoracic (mammary) arteries.
The internal thoracic arteries branch from the subclavian arteries to supply the anterior intercostal arteries, which anastomose with the posterior intercostal arteries to carry blood to the aorta distal to the coarctation.
Due to this condition, the flow of oxygenated blood will be altered. Blood will flow anterogradely through the internal thoracic and anterior intercostals, but retrogradely through the posterior intercostals.
An enlargement of the posterior intercostals causes bone resorption along the lower borders of the ribs, seen as “notching” on chest x-ray.
Analysis
The correct answer is B. The patient has coarctation of the aorta:
Physical examination: Large difference in blood pressure between the upper and lower limbs.
In younger individuals (such as this patient), postductal coarctation of the aorta is the most probable diagnosis (see figure below).
In older individuals, severe atherosclerosis of the abdominal aorta, iliac system, and/or femoral system is the most probable diagnosis.
Anterograde flow through the stenotic portion of the aorta is severely limited.
Collateral anterograde flow via the internal thoracic arteries and anterior intercostal arteries occurs.
Retrograde flow is via anastomosis with the posterior intercostal arteries.
Rib notching occurs when increased flow through the intercostal arteries slowly enlarges these arteries resulting in resorption of bone along the lower borders of the ribs.
The image above shows coarctation of the aorta: (A) Preductal; (B) Postductal; (C) Collateral circulation.
The axillary arteries (choice A) are continuations of the subclavian arteries. Although there is anterograde flow through these arteries, they supply the upper limbs and not the lower limbs.
The isthmus of the aorta (choice C) is the common site for postductal coarctation of the aorta. The isthmus is the region of the aorta between the ligamentum arteriosum and the descending aorta. Because of the narrowing of the aorta in this region, there is very limited blood flow through the aorta.
The ductus arteriosus (choice D) is an embryonic structure that connects the pulmonary arterial system to the aortic arch. During fetal development, the ductus arteriosus provides a conduit through which the umbilical blood can bypass the pulmonary circulation and reach the systemic circulation. In adults, a patent ductus arteriosus would allow flow from the systemic circulation to the pulmonary circulation and would not account for the perfusion of the lower limbs. Additionally, in postductal coarctation of the aorta, the stenotic region is distal to the ductus arteriosus. Because the brachiocephalic trunk and the left subclavian artery both arise from the aortic arch proximal to the site of the aortic coarctation, the blood pressure in both upper limbs is elevated. In contrast, the common iliac arteries are distal to the aortic coarctation resulting in decreased blood pressure in the lower limbs.
The posterior intercostal arteries (choice E) arise from the descending aorta. Since flow distal to the aortic coarctation would be severely limited, anterograde flow into the posterior intercostal arteries would also be decreased. In order to perfuse the lower limbs, retrograde flow through the posterior intercostal arteries develops.
ReKap
Beta-blockers help to prevent angina by decreasing myocardial O2 demand through reduction of heart rate, myocardial contractility, and blood pressure.
Pindolol has intrinsic sympathomimetic activity (ISA) and thus acts as a partial beta-1 agonist.
Pindolol is contraindicated in angina because it does not reduce myocardial O2 demand.
Analysis
The correct answer is D. This patient meets the criteria for stable (exertional) angina: chest pain precipitated by stress or exertion and quickly relieved with rest and nitrates. The beta-adrenergic blockers prevent angina by decreasing myocardial O2 requirements through the reduction of heart rate, myocardial contractility, and blood pressure. Beta-blockers are considered to be first-line agents in the treatment of chronic angina. The beta-1 selective agents (such as atenolol and metoprolol) are most commonly used in the treatment of stable angina. However, beta-blockers with intrinsic sympathomimetic activity (ISA), e.g., acebutolol and pindolol, are not recommended for patients with angina because they may exacerbate the angina in some patients.
Pindolol, a nonselective beta antagonist with ISA, is contraindicated in angina because it does not reduce heart rate nor myocardial O2 consumption. Pindolol is indicated for the treatment of hypertension and ventricular arrhythmias. In addition to the beta blockers, exertional angina can be treated with dihydropyridine calcium channel blockers (amlodipine, felodipine, nifedipine) and/or isosorbide mononitrate or transdermal nitroglycerine. Adjunct treatment measures include the use of lipid-lowering agents (e.g., statins) and revascularization therapy.
Agents indicated for treatment of angina include the beta-1 antagonists atenolol (choice A) and metoprolol (choice B), and the nonspecific beta antagonists, nadolol (choice C) and propranolol (choice E).
Note: An easy way to remember beta-1 vs. nonspecific beta antagonists is that antagonists that start with A through M (A-M-olol) are beta-1 specific and those that start with N through Z (N-Z-olol) are nonspecific.
Updated on 06/22/22
ReKap
Coarctation of the aorta causes a large pressure gradient to develop between the upper and lower extremities.
Coarctation lowers pressure in the renal arteries, activating RAAS due to a decrease in afferent arteriolar (AA) pressure, decreased glomerular filtration pressure, and decreased NaCl presentation to the macula densa.
Activation of the RAAS causes hypertension in the arteries proximal to the coarctation.
Analysis
The correct answer is C. A pressure differential of >20 mm Hg between upper and lower extremities is diagnostic of coarctation of the aorta. Hypertension proximal to the coarctation (e.g., upper extremities and cerebral circulation) develops predominantly due to activation of the renin-angiotensin-aldosterone system (RAAS) following a decrease in renal perfusion.
Renin release from juxtaglomerular cells (JG, or granular cells) within the afferent arteriole (AA) is controlled through cAMP levels and cAMP-dependent protein kinase A (PKA). One of the major regulators of release is renal perfusion pressure.
Coarctation usually occurs in the postductal thoracic aorta just distal to the origin of the left subclavian artery (see Panel B in the figure). RAAS activates because the stricture limits flow and pressure development in the abdominal aorta and lower arteries, including the renal arteries, thereby reducing AA pressure and glomerular filtration.
Anatomy of preductal and postductal coarctation of the aorta. Coarctation typically occurs in the postductal thoracic aorta distal to the origin of the left subclavian artery.
Hypertension is limited to vessels that originate before the site of coarctation. Pressure below the coarctation may come back into the normal range with volume retention and development of collateral flow, but always remains below the pressure in the upper vessels.
Cerebral hypoxemia (choice A) promotes a sympathetic response that includes increases in heart rate, cardiac inotropy, venous tone, systemic vascular resistance, and catecholamine release from the adrenals, all of which raise arterial pressure. Sympathetic activation would be transient, however, and would not create a pressure difference between upper and lower extremities.
11-Deoxycorticosterone (11-DOC; choice B) is an intermediary in the pathway leading to corticosterone production by the adrenal cortex (see figure).
Pathways of corticosterone, cortisol, and adrenal androgen production in the zona fasciculata and zona reticularis.
Mutations in the 11-hydroxylase gene prevent the conversion of 11-DOC to corticosterone, which causes 11-DOC levels to rise. 11-DOC is a weak mineralocorticoid, so affected individuals present with hypernatremia, hypokalemia, and hypertension, along with congenital adrenal hyperplasia (CAH). This patient’s hypertension could be caused by CAH, but CAH does not explain the pressure differential between the upper and lower extremities.
Parasympathetic nervous system activity (choice D) is typically decreased because coarctation is associated with increased sympathetic activity, due to hypoperfusion.
Thyroid hormone levels (choice E) are elevated in patients with hyperthyroidism. Symptoms include systolic hypertension, chest pain, and sweating. Hypertension is a response to increased blood flow through the skin and other organs with raised metabolism and is not restricted to the upper extremities.
ReKap
Chronic hypertension in pregnancy:
Hypertension present before pregnancy, or before the 20th week of gestation, or that persists longer than the postpartum period (i.e., 12 weeks after delivery).
Untreated chronic hypertension increases the risk of preeclampsia or eclampsia.
Treatment: Labetalol, nifedipine, methyldopa, hydralazine.
Calcium channel blockers can cause peripheral edema, flushing, headaches, orthostatic hypotension, constipation, and dizziness.
Analysis
The correct answer is D. Chronic hypertension in pregnancy is defined as hypertension present before pregnancy, or before the 20th week of gestation, or that persists longer than the postpartum period (i.e., 12 weeks after delivery). A major risk with chronic hypertension is the development of preeclampsia or eclampsia later in pregnancy, which is seen in up to 30% of women.
Calcium channel blockers (CCBs), such as nifedipine and amlodipine, are commonly used for antihypertensive therapy during pregnancy. These two drugs are dihydropyridines and their adverse effects include peripheral edema, flushing, headaches, orthostatic hypotension, and dizziness.
The management of patients with chronic hypertension in pregnancy involves closely monitoring maternal blood pressure and watching for the superimposition of preeclampsia or eclampsia, as well as monitoring fetal growth and well-being. Antihypertensive medication in women with chronic hypertension is generally recommended when the systolic blood pressure is ≥ 160 mm Hg or diastolic blood pressure is ≥ 105 mm Hg.
Methyldopa is an alpha-2 agonist (choice A) that was the most commonly used antihypertensive medication in pregnancy for many decades. It may still be used, although it is less effective than labetalol or nifedipine. Its adverse effects are sedation, depression, drug-induced lupus, and direct Coombs-positive hemolytic anemia.
Angiotensin-converting enzyme inhibitors (ACEIs; choice B) can cause fetal malformation and they are not recommended in pregnancy. The risk of fetal malformation increases in each trimester, being minimal in the first trimester and significant in the third. Women seeking to become pregnant are often transitioned to another medication. Angiotensin receptor blockers act in a similar manner to ACEIs and are, therefore, presumed to have the same potential adverse fetal effects.
Labetalol is a combined alpha- and beta-blocker (choice C) that is considered first-line antihypertensive therapy in pregnancy. The side effects are dizziness, fatigue, orthostatic hypotension, and nausea. The use of beta-specific blockers is not recommended during pregnancy because they may cause fetal growth restriction and neonatal hypoglycemia so they are not used for the chronic control of hypertension in pregnancy. Risks and benefits of beta-specific blockers must be weighed if the mother has an indication for a beta-blocker due to a cardiac condition.
Hydralazine is a direct-acting vasodilator (choice E) that is commonly used for urgent control of severe acute hypertension in pregnancy or as an adjunct agent with labetalol or methyldopa. It causes compensatory tachycardia, fluid retention, headache, angina, and SLE-like syndrome. It needs to be dosed three to four times a day which reduces patient compliance and makes it a less-desirable first-line agent.
Diuretics (choice F) are not used for blood pressure control in pregnancy but may be continued in a patient who already has been on such therapy before becoming pregnant. All diuretics may interfere with breast milk production. Thiazide diuretics, when given near delivery, may cause fetal thrombocytopenia with associated bleeding and electrolyte disturbances.
ReKap
Key angiographic findings:
Medial calcific sclerosis (Mönckeberg arteriosclerosis) is a benign condition of older age in which the media of small-to-medium arteries calcifies.
Atherosclerosis affects all arteries, with luminal narrowing due to plaques.
Arteriolosclerosis affects small arteries/arterioles, causing luminal narrowing without calcifications.
Analysis
The correct answer is E. Medial calcific sclerosis, also called Mönckeberg arteriosclerosis, is a disease of older age (>60 years old) in which ring-like calcifications form in the media of medium-sized to small muscular arteries. It is usually an incidental radiographic finding. The arrows in the x-ray (left) and a negative image of the x-ray (right) point to common femoral artery calcification, extending into the superficial femoral artery and profunda femoris artery. Calcification does not cause symptoms because there is no change in the vessel lumen diameter. The patient’s hip pain is not related to this medial calcific sclerosis.
Atheromatous plaques (choice A) might be calcified, but would narrow the vessel lumen. This might produce claudication, which would be consistent with the patient’s pain, but the angiogram did not show any narrowing of the vessel lumen.
Hyaline arteriolosclerosis (choice B), which can occur with diabetes mellitus and benign hypertension, and hyperplastic arteriolosclerosis (choice C), which is associated with malignant hypertension, typically do not cause calcification. Furthermore, they involve small arteries and arterioles, not medium-sized arteries.
Hypersensitivity angiitis (choice D), generally manifesting as leukocytoclastic vasculitis, is a disease of small vessels and does not cause calcification. Histologically, there is extravasation of neutrophils, neutrophil debris, and fibrinoid necrosis of the vessel walls. The prognosis is generally good unless visceral involvement (e.g., of the kidneys) is present.
The table below summarizes key features of the different types of arteriosclerosis and related angiographic findings. Note that angiography typically cannot discern the decrease in lumen size that occurs as a result of wall thickening in arteriolosclerosis.
ReKap
Untreated hypertension leads to microvascular remodeling.
The wall-to-lumen ratio increases as the walls of the arteriolar blood vessels thicken, thereby decreasing lumen diameter and reducing flow.
Analysis
The correct answer is D. Untreated hypertension leads to microvascular remodeling. Typical changes include an increase in arteriolar wall thickness, presumably to help the vessels counter the chronically increased blood pressure. Wall hypertrophy occurs at the expense of the vessel lumen, which is reduced (choice C).
Additional changes include a decrease in the density of microvessels, including anastomoses (choice A), arterioles (choice B), and capillaries (choice E). These changes all increase the resistance of microvasculature and reduce flow, which may lead to ischemia and organ damage. Patients with poorly controlled hypertension typically have reduced cerebral blood flow as they age, an effect that is independent of atherosclerosis. Cerebrovascular complications of hypertension include ischemic or hemorrhagic stroke.
Known factors that cause remodeling of arteries and arterioles in hypertensive patients include the renin-angiotensin-aldosterone system and reactive oxygen species; other factors are also implicated. The vessel walls are subjected to extra amounts of stretch at the higher luminal pressures, which may stimulate smooth muscle cell growth; both hypertrophy and hyperplasia of vascular smooth muscle can occur. Thus, the thickened walls of cerebral arteries and arterioles in hypertensive patients are an adaptation to hypertension.
The increase in blood pressure that occurs during normal exercise can cause the walls of arteries in all organs to thicken (thus the wall-to-lumen ratio increases). However, the normal resting blood pressure typically is not elevated in healthy individuals who exercise regularly (“wall-to-lumen ratio” refers to the ratio of wall thickness to lumen radius, or to the ratio of the two cross-sectional areas). Other vessels may dilate with reduced wall thickness, which increases risk of hemorrhagic stroke.
ReKap
Exercise-induced vasodilation increases blood flow to active muscles.
Increased flow is driven by increased capillary perfusion pressure, which shifts the balance of Starling forces in favor of fluid filtration.
Fluid filtering from capillaries is returned to the vasculature by the lymphatic system, so lymph flow from active muscles also increases.
Analysis
The correct answer is E. All forms of dynamic exercise cause reflex vasodilation within the active muscles, thereby increasing blood flow to supply the O2 and nutrients required for increased metabolic activity. Increased flow is driven by an increase in capillary perfusion pressure (capillary hydrostatic pressure, Pc), which concomitantly increases fluid filtration from the vasculature. A corresponding increase in lymph flow ensures that this fluid is returned to the circulation.
The exercise-induced increase in muscle blood flow occurs initially through autoregulation. Exercising muscles release various metabolites (e.g., K+, lactate, and adenosine), which promote reflexive vasodilation of surrounding resistance vessels (small arteries and arterioles). During intense exercise, the sympathetic nervous system responds to an increased need for flow by stimulating epinephrine release from the adrenal medulla. Epinephrine promotes vasodilation in the coronaries and skeletal vasculature through binding to β2-adrenergic receptors, which facilitates the increased flow.
At the level of the microcirculation, resistance vessel dilation increases capillary perfusion pressure. The increase is required to drive flow through the increased number of capillaries that are now supplying exercising muscle (capillary recruitment), but the increase impacts the balance of the Starling forces that govern the rate at which fluid filters across the capillary membrane:
The figure above explains the various forces involved in blood flow, fluid pressure, and direction. Starling’s law is a formula that explains the various important factors in fluid movement across a membrane.
Filtered fluid is returned to the vasculature by the lymphatic system, along with any proteins. Thus, lymph flow from active muscles increases substantially during exercise.
ReKap
Buerger disease is associated with smoking.
Features include peripheral ischemia (especially of the upper extremity), Raynaud phenomenon, paresthesias, claudication, ulceration/gangrene of fingers and toes.
Analysis
The correct answer is B. This is a typical presentation of Buerger disease.
Buerger disease:
Also known as thromboangiitis obliterans
Necrotizing vasculitis causes segmental thrombosis in arteries and veins of the extremities (especially in the digits)
Typically occurs in heavy smokers
May present with Raynaud phenomenon, paresthesias, claudication, ulceration/gangrene of fingers and toes
Main treatment is smoking cessation
Behçet syndrome (choice A) is a systemic vasculitis that classically presents with uveitis and recurrent aphthous ulcers on the genitalia or oral mucous membranes. The disease is likely immune-mediated and can involve different blood vessel types (veins and arteries) and sizes (small to large). The disease usually affects young adults 20–40 years of age. This patient’s presentation and smoking history makes Behçet syndrome unlikely.
Kawasaki disease (choice C) causes a vasculitis affecting medium-sized arteries in children. Coronary arteries can be involved, resulting in aneurysms and myocardial infarction in young individuals. Other characteristics of the disease include conjunctivitis, oropharyngeal erythema, rash, lymphadenopathy, and desquamation of tips of fingers (mucocutaneous lymph node syndrome). This is one of the few cases where children are given aspirin or intravenous gamma globulin (IVIG) to reduce inflammation.
Polyarteritis nodosa (choice D) is a recurrent, necrotizing vasculitis of medium and small muscular arteries. It is distinguished by its multiple-organ involvement and constitutional symptoms including fever, weight loss, myalgias, and arthralgias. There is sparing of the pulmonary vasculature. The histologic feature is fibrinoid necrosis.
Venous stasis ulcers (choice E) account for 70 to 80% of lower-limb ulcerations. Poorly-functioning valves cause blood to accumulate and dilate the veins, resulting in overlying skin ulcerations and extravasation of blood into the surrounding connective tissue. Disease of the upper extremities is unusual. In the lower extremity, the classic ulcer will occur immediately above the medial malleolus.
ReKap
More than 90% of pulmonary emboli begin in the deep veins of the lower limbs.
Venous thrombosis of the lower extremities commonly occurs in the popliteal veins and extends proximally.
The more proximal the clot, the more likely it is to embolize to the lungs.
Analysis
The correct answer is D. The patient most likely has a pulmonary embolism (PE). The large filling defects in the right pulmonary artery and the superior branch of the left pulmonary artery (see circles in the left image following this text) in the CT scan of the chest support the diagnosis. For comparison, a normal image through the same region is shown on the right.
The circles on the left image show the filling defects in the right pulmonary artery and the superior branch of the left pulmonary artery, suggesting a diagnosis of pulmonary embolus. Compare with the normal image on the right.
More than 90% of pulmonary emboli originate from the deep veins of the lower limbs. The only deep vein of the lower limb listed in the answer choices is the femoral vein. Venous thromboses can also form more distally in the popliteal vein. The risk of embolism increases as the clot extends proximally.
The basilic (choice A) and cephalic (choice C) veins are two superficial veins of the upper limbs and are the ones most frequently accessed with IV catheters. Virtually the only time you see major clots in the upper extremities is when they contain some sort of catheter.
The brachial vein (choice B) is the major deep vein of the upper extremities. Venous thromboses can form in the deep veins of the upper extremities but venous thromboembolism much more commonly arises from deep vein thromboses in the lower extremities.
The great saphenous (choice E) and lesser saphenous (choice F) veins are the superficial veins of the lower limbs and do not commonly result in pulmonary embolism. The great saphenous vein is commonly harvested for bypass procedures.
