Neo Blood Vessels- Phase 2 Flashcards
ReKap
ACE inhibitors, such as enalapril, are useful to control hypertension in patients with diabetic nephropathy, heart failure, and hyperuricemia.
ACE inhibitors are the preferred antihypertensive in diabetic patients because they slow the progression of renal disease.
Analysis
The correct answer is B. The question is essentially asking, “Which of the following agents would be recommended in a woman with diabetic nephropathy, heart failure, and hyperuricemia?” The angiotensin-converting enzyme (ACE) inhibitors, such as enalapril, lisinopril, and captopril, are recommended for the treatment of hypertension in diabetic and/or heart failure patients, especially those with renal complications, since these agents have been shown to delay the progression of renal disease.
Atenolol (choice A) is a beta-1 adrenergic antagonist that is generally not recommended for diabetic patients since it can “block” the appearance of the normal signs and symptoms of hypoglycemia.
The thiazide diuretics, such as hydrochlorothiazide (choice C) and indapamide, are commonly associated with hyperuricemia. Furthermore, they can precipitate an acute gout attack in patients with hyperuricemia. Thiazides also cause hyperglycemia and hyperlipidemia, which would aggravate similar findings from the patient’s disease.
The loop diuretics, such as furosemide, bumetanide, and torsemide (choice D) are associated with both hyperuricemia and hyperglycemia. These agents would not be recommended for use in this patient.
Verapamil (choice E) is a non-dihydropyridine calcium channel blocker used in the treatment of hypertension, angina, paroxysmal supraventricular tachycardia conversion and treatment, and atrial fibrillation. Verapamil is contraindicated for use in patients with heart failure since it decreases both heart rate and contractility, resulting in decreased cardiac output.
ReKap
Fetal circulation: the ductus arteriosus shunts blood from the left pulmonary artery into the aorta.
After birth, the pressure gradient reverses, and the flow is reversed from the aorta to the left pulmonary artery.
If the ductus arteriosus remains patent, pulmonary hypertension can ensue.
Analysis
The correct answer is A. The ductus arteriosus connects the left pulmonary artery to the aortic arch. It is derived from the left sixth aortic arch.
During prenatal life, the pressure gradient causes blood to flow from the left pulmonary artery to the aorta. However, after birth, the pressure gradient reverses, and if the ductus arteriosus remains patent, the flow is from the aorta to the left pulmonary artery (see image below). Normally, the ductus arteriosus closes shortly after birth under the influence of increased oxygen tension, the release of bradykinin, and the decrease of circulating prostaglandin levels.
The characteristic continuous murmur of patent ductus arteriosus (PDA) is also called a “machinery” murmur, which is heard best at the upper left sternal border. If flow through a PDA is sufficiently great, pulmonary hypertension can result.
The ductus arteriosus does not connect to the pulmonary vein (choice B).
Flow from the aorta to the left ventricle (choice C) would result from an incompetent aortic valve and cause a diastolic murmur that is heard best near the apex of the heart in the left sternal border or over the right second intercostal space.
Blood flow is from the left pulmonary artery to the aorta (choice D) through the ductus arteriosus in the prenatal fetus because of the right-to-left pressure gradient. Postnatally, however, because the pressure gradient has reversed, the direction of blood flow has reversed.
Flow from the left pulmonary artery (or more precisely, from the pulmonary trunk) to the right ventricle (choice E) would result from an incompetent pulmonic valve and would cause a diastolic murmur heard best at the left sternal border in the second or third intercostal spaces.
ReKap
The spontaneous rupture of an abdominal aortic aneurysm commonly causes severe abdominal pain that radiates to the back.
Physical findings can include a pulsatile abdominal mass, an abdominal bruit, and hemodynamic instability (due to hemorrhagic shock).
Analysis
The correct answer is A. This patient is suffering from a ruptured abdominal aortic aneurysm (AAA). It is important to realize that the aorta is retroperitoneal and lies anterior to the vertebral bodies and is generally located slightly to the left of midline. Therefore, aortic pathology is usually associated with back pain. Thus, patients with AAA typically have abdominal pain that radiates to the back, and AAA should be considered in the differential diagnosis of the acute abdomen. This patient’s history of diabetes, hypertension, and hypercholesterolemia gives him an increased risk for this condition. Rupture of the aneurysm is indicated by this patient’s hemodynamic instability (tachycardia and hypotension). This is a surgical emergency with poor prognosis if not diagnosed quickly.
Neither the descending colon (choice B) nor the duodenum (choice C) would be expected to cause sudden and severe pain associated with hypotension.
Severe damage to the inferior vena cava (choice D) might produce hemodynamic instability, but generally only occurs in the setting of severe abdominal trauma.
Stones in the kidney (choice E) or ureter (choice F) might produce severe pain, but the pain would typically be in the flank. In addition, renal calculi do not cause the hemodynamic instability seen here.
ReKap
Some antihypertensive medications, such as metoprolol and thiazides, can cause lipid abnormalities.
β-blockers interfere with lipid metabolism and are associated with elevation of serum triglyceride levels and decreases in HDL concentrations. The effect varies based on the receptor selectivity and pharmacologic profile of each individual β-blocker.
Analysis
The correct answer is D. The question states that the patient began antihypertensive therapy and now has elevated total cholesterol and triglyceride levels, as well as a low HDL level. Therefore, there is a strong possibility that the antihypertensive medication caused dyslipidemia. Metoprolol is a β-adrenergic antagonist that is known to cause dyslipidemias in patients. Although thiazides also cause this, none of the other medications given as choices are associated with the development of dyslipidemias. Metoprolol is commonly used in the treatment of hypertension and cardiac arrhythmias. This agent is also associated with the development of bradycardia, dizziness, sexual dysfunction, and potentially, heart failure and bronchospasm.
The angiotensin-converting enzyme inhibitor benazepril (choice A) is commonly used in the treatment of hypertension, heart failure, and diabetic nephropathy. Common adverse effects include chronic cough, hyperkalemia, and angioedema.
Clonidine (choice B), a centrally acting α2-receptor agonist, is generally used in patients unresponsive to other antihypertensive therapies. It has been shown to be effective at ameliorating symptoms of alcohol, tobacco, opiate, and benzodiazepine withdrawal. Clonidine is also used in the treatment of attention deficit hyperactivity disorder. Clonidine causes severe hypotension, depression, and syncope.
The calcium channel blocker diltiazem (choice C) is used to treat essential hypertension and cardiac arrhythmias. This agent is associated with the development of bradycardia, atrioventricular (AV) nodal block, orthostatic hypotension, and sexual dysfunction. It is not associated with the development of dyslipidemias.
Prazosin (choice E), a selective α1 blocker, represents another class of antihypertensive agents that has a favorable effect on plasma lipids by lowering total cholesterol, reducing triglyceride levels, and mildly raising HDL. Prazosin is associated with the development of a characteristic “first-dose effect,” which is a profound onset of orthostatic hypotension. Therefore, it is recommended that this agent be taken at bedtime.
ReKap
Atherosclerosis is thought to begin with endothelial dysfunction, which may be related to injury to the intimal (endothelial) lining of blood vessels.
Arterial hypertension, diabetes mellitus, and hyperlipidemia are risk factors for endothelial cell injury.
Analysis
The correct answer is B. The photomicrograph shows the features of advanced atherosclerotic disease displaying marked narrowing of the arterial lumen. In particular, the intima is markedly thickened and disrupted, and there is fragmentation and partial duplication of the internal elastic lamina.
Pathogenesis of atherosclerosis:
The initial event is endothelial cell dysfunction or injury. This is coupled with the oxidation of low-density lipoprotein (LDL) particles in the circulation.
High blood pressure, nicotine, diabetes mellitus, immune mechanisms, and hyperlipidemia are important factors implicated in endothelial injury.
Plasma-derived lipids and proteins accumulate within the intima with subsequent formation of an atheroma (atherosclerotic plaque).
Underproduction of nitric oxide by the endothelium also can lead to atherosclerosis.
Pathology slide demonstrating atherosclerosis of the coronary artery with narrowed lumen and fragmentation and partial duplication of the internal elastic lamina.
Collagen and elastin production (choice A), as well as proteoglycan synthesis, are fundamental in the development of atheromatous lesions. This intercellular matrix often undergoes secondary calcification. Modified smooth muscle cells and fibroblasts produce these components. The image displayed above primarily shows narrowing as a result of intimal damage.
Monocyte immigration (choice C) is another important step in the pathogenesis of atherosclerosis. Monocytes immigrating into the intima become macrophages and take up cholesterol bound to LDLs. Thus, cholesterol-laden monocytes with characteristic vacuolated cytoplasm accumulate in the center of the atheroma as “foam cells.” They secrete several cytokines (interleukin [IL]-1 and tumor necrosis factor [TNF]-α) that stimulate fibroblasts and smooth muscle cells to proliferate and produce collagen, elastin, and proteoglycans. Endothelial dysfunction may act as a precursor to enhance leukocyte adhesion and pave the way for monocyte immigration.
Platelet adhesion (choice D) is a consequence of endothelial injury. Microthrombi develop on the endothelial surface, acting as a source of platelet-derived growth factor (PDGF). PDGF attracts monocytes and stimulates smooth muscle cell proliferation.
Smooth muscle cell proliferation (choice E) is a response to various types of injury. In atherosclerosis, smooth muscle cells migrate from the media to the intima and transform into secretory cells that produce collagen, elastin, and proteoglycans. PDGF, interleukin-1, and tumor necrosis factor-α are important mediators of this process.
ReKap
Penile erection is mediated by nitric oxide NO, which stimulates guanylate cyclase and increases cGMP synthesis.
cGMP relaxes vascular smooth muscle, resulting in vasodilation and increased blood flow into the penile corpus cavernosum.
PDE-5 inhibitors such as sildenafil prevent the breakdown of cGMP and are indicated for the treatment of erectile dysfunction.
Analysis
The correct answer is D. Penile erection is under parasympathetic control. Parasympathetic activation increases penile nitric oxide (NO) levels and NO activates guanylate cyclase (GC).
Events leading to a penile erection:
Achieving an erection involves engorgement of the corpus cavernosum.
Parasympathetic nerve terminals release NO and acetylcholine (ACh) onto vascular smooth muscle within the corpus cavernosum.
ACh activates endothelial NO synthase (via ↑ [Ca2+]i) → ↑ NO.
NO activates GC, which raises cyclic guanosine monophosphate (cGMP) levels.
cGMP causes vascular smooth muscle relaxation and vasodilation, allowing the corpus cavernosum to fill with blood.
Increasing intrapenile pressure compresses penile veins, collapsing them and preventing outflow to achieve and sustain the rigidity.
Breakdown of cGMP by cGMP-specific phosphodiesterase (PDE-5) can limit vasodilation and erection.
The most common treatment for erectile dysfunction is with PDE-5 inhibitors, such as sildenafil. PDE-5 inhibitors increase cGMP levels within the corpus cavernosum and increase blood inflow. PDE-5 inhibitors cause flushing, nasal congestion, priapism, and vision changes. These drugs are contraindicated for use with nitrates (nitroglycerine, isosorbide dinitrate, nitroprusside) since the combination of the two synergistically increase the risk of severe hypotension.
Choline acetyltransferase (choice A) converts choline to ACh, a neurotransmitter that mediates the synaptic connections of parasympathetic neurons and neuromuscular junctions.
Cyclooxygenases and lipoxygenases (choice B) are involved in the synthesis of prostaglandins, thromboxanes, and leukotrienes, which are involved in multiple processes including acute inflammation and blood clot formation.
Glutamate decarboxylase (choice C) converts the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter GABA. These neurotransmitters are not involved with smooth muscle relaxation.
5α-reductase (choice E) converts testosterone to its active form dihydrotestosterone. In patients with benign prostatic hyperplasia (BPH), dihydrotestosterone promotes prostate growth. Finasteride and dutasteride are 5α-reductase inhibitors indicated for the treatment of BPH. In lower doses, finasteride is also indicated for the treatment of alopecia.
Updated on 06/14/22
ReKap
There is an important association between colon cancer and endocarditis due to Streptococcus bovis.
S. bovis is a group D Streptococcus.
Analysis
The correct answer is B. Streptococcus bovis biotype I (S. gallolyticus) is a group D Streptococcus and classified as a gram-positive coccus.
There is a significant association between S. bovis bacteremia and endocarditis in patients with carcinoma of the colon and other colonic diseases. The association with colonic neoplasia is strongest for S. bovis biotype I infections and for cases of infective endocarditis. Thus, every patient with S. bovis bacteremia should undergo gastrointestinal and cardiac evaluation.
Colonoscopy should be performed in all patients with S. bovis bacteremia or endocarditis.
S. bovis bacteremia is also associated with endocarditis, especially in patients with preexisting valvular lesions.
The treatments of choice for systemic Streptococcus bovis biotype I (S. gallolyticus) include penicillin and ceftriaxone. Vancomycin is the preferred agent for patients with a beta-lactam allergy.
S. agalactiae (choice A) is a group B Streptococcus that is the number-one cause of neonatal meningitis and septicemia in the United States.
S. mutans and S. sanguinis (choices C and F) are viridans streptococci, which are normal flora of the oral mucosa. While they are associated with bacterial endocarditis, these organisms are usually associated with invasive dental work and preexisting heart valve defects.
S. pneumoniae (choice D), which is a non-groupable Streptococcus species (it does not have a C cell wall carbohydrate), is the most common cause of typical pneumonia in the United States. It is also the most common cause of adult meningitis as well as otitis media and sinusitis in children.
S. pyogenes (choice E) is a group A Streptococcus and is associated with pharyngitis, post-streptococcal glomerulonephritis, rheumatic fever, and scarlet fever.
Updated on 04/06/21
ReKap
An arteriovenous fistula allows arterial blood to enter the venous system directly, causing a rise in central venous pressure, right atrial pressure, and ventricular preloading.
The vascular function curve (VFC) shifts to the right and rotates upward with no change in the cardiac function curve (CFC).
Analysis
The correct answer is A. A penetrating wound of the aorta has resulted in the formation of a pseudoaneurysm. A true aneurysm is a dilation (bulging) of the vessel wall with an increased lumen diameter; a pseudoaneurysm is a leakage of blood into the intima-media. The pseudoaneurysm has eroded into the vena cava, creating a large arteriovenous fistula.
The graph in the question vignette includes a cardiac function curve (CFC) and two vascular function curves (VFCs).
A CFC (also known as a Frank-Starling curve) shows the effect of left ventricular (LV) preload on cardiac output (CO); its slope and maximal values reflect cardiac contractility.
A VFC (or vascular function curve) shows the effect of varying CO on right atrial pressure (RAP); it reflects blood volume and compliance of the vasculature.
The intersection of the VFC with the x-axis indicates mean systemic pressure (MSP), i.e., the pressure in the vasculature roughly 1 minute after the heart has arrested and pressure in all parts of the cardiovascular system has come into equilibrium.
The intersection of a CFC and VFC defines an equilibrium point. The equilibrium point shows the amount of CO that can be supported by any given RAP and vice versa.
CO cannot change without a corresponding shift in the equilibrium point, either through changes in cardiac contractility or MSP.
Cardiovascular function curve.
In the present case, the patient’s arterial blood pressure has decreased greatly as arterial blood gushes into the venous system through the fistula. The increased volume of blood entering the venous system raises central venous pressure and RAP. The VFC shifts to the right as a result of this inflow, causing CO to increase from a normal resting value of 6 L/min to 14 L/min. This is all due to increased LV preload; myocardial contractility and the CFC remain unchanged. MSP shifts right from a normal +7 mm Hg to +12 mm Hg, reflecting venous distension and wall stretching. RAP and MSP would be expected to increase further as renal retention of salt and water increases blood volume to support CO.
Effects of an AV fistula on the cardiovascular function curve.
Note that the VFC also rotates upward. This is caused by the decrease in resistance to flow (systemic vascular resistance; SVR) that occurs when blood bypasses arterial resistance vessels (small arteries and arterioles). The observation of increased CO and LV preload with decreased SVR is consistent with a fistula, as might be expected with this patient’s history.
Exercise (choice B) increases cardiac performance, causing the CFC to move upward and to the left. Exercise does not decrease blood pressure.
In heart failure due to impaired left ventricular contractility (choice C), the CFC is shifted down and to the right because of decreased myocardial contractility.
A narcotic overdose (choice D) is expected to depress the myocardium, causing the CFC to shift down and to the right.
Hemorrhage (choice E) reduces blood volume, which decreases MSP and shifts the VFC down and to the left. Hemorrhagic shock would eventually also decrease myocardial contractility, causing a rightward shift in the CFC.
ReKap
Systemic vascular resistance (SVR) represents the total resistance to blood flow from every part of the systemic vasculature, excluding the pulmonary vasculature.
SVR = (MAP - RAP)/CO.
Analysis
The correct answer is B. The patient has an SVR of 19 mm Hg·min·L-1.
SVR can be calculated using a hemodynamic application of the Ohm law (R= V/I) and the data included in the case history.
Thus,
SVR = ΔP/Q
where ΔP is the pressure gradient driving flow (Q) through the systemic vasculature.
Q = Cardiac output.
ΔP = Mean arterial pressure - right atrial pressure (MAP - RAP).
MAP = diastolic + 1/3 of pulse pressure (i.e., systolic-diastolic), so:
MAP = 85 + (127 - 85)/3 = 99 mm Hg
SVR = (99 - 4)/5 = 19 mm Hg·min·L-1
(Multiply by 80 to convert to dyn-s-cm-5 = 1,520)
The units mm Hg·min·L-1 are also known as Wood units or peripheral resistance units (PRUs).
Using the correct equation SVR = (MAP - RAP)/ CO, all other SVR values would be incorrect (choices A, C, D, and E).
ReKap
A pulsatile abdominal mass on physical examination suggests an abdominal aortic aneurysm (AAA).
One common etiology of AAA is atherosclerosis, risk factors for which include diabetes, hypertension, and hypercholesterolemia.
An abdominal ultrasound or CT scan will show dilation of the abdominal aorta.
Analysis
The correct answer is A. This patient has a typical presentation of an abdominal aortic aneurysm (AAA):
AAA can result from atherosclerosis, which weakens the vessel walls and can lead to gradual dilation secondary to maladaptive remodeling by aortic connective tissue and smooth muscle. Risk factors for AAA are similar to those of atherosclerosis. Diabetes, hyperlipidemia, and hypertension are the most common risk factors.
AAAs may rupture, leading to a triad of a pulsatile abdominal mass, pain, and hypotension. This triad will progress to hemorrhagic shock and death unless emergency surgery is performed to replace the dilated section of the aorta with a vascular graft. To lower the risk of a AAA progressing to emergency surgery, aneurysms that exceed 5.5 cm in size are typically repaired, regardless of a patient’s current symptoms.
The presence of a non-ruptured AAA is often difficult to detect on physical examination alone. Imaging with abdominal ultrasound or a CT scan of the abdomen is the gold standard method of definitive diagnosis.
Congenital weakness of vessels (choice B) can produce saccular aneurysms (berry aneurysms), particularly at branch points where cerebral vessels depart from the circle of Willis. Berry aneurysms are associated with adult-type autosomal dominant polycystic kidney disease and hereditary connective tissue disorders, such as Ehlers-Danlos syndrome. Thoracic aortic aneurysms may occur due to congenital weakness, but AAAs as a result of congenital abnormalities are uncommon.
Cystic medial necrosis (choice C) of vessels is characteristic of hereditary connective tissue disorders, such as Marfan syndrome or Ehlers-Danlos syndrome, where there is degeneration of collagen, elastin, or smooth muscle in the vessel wall. This disease should be suspected in cases of thoracic aortic aneurysms (not AAAs) or aortic dissection.
Syphilitic aneurysms (choice D) typically involve the aortic root. Disseminated spirochetes may induce thrombosis of the vasa vasorum, which supplies the outer wall layer of the thoracic aorta, resulting in weakening and aneurysm formation. This is rare, and only occurs in longstanding/chronic tertiary syphilis.
Vasculitis (choice E) can also produce arterial aneurysms, although, for the abdominal aorta, atherosclerosis is a much more common cause. Takayasu arteritis instead typically causes stenosis as a result of granulomatous inflammation of the vessel wall.
ReKap
Graft vascular disease (GVD) is a late and serious complication of heart transplantation and is a form of chronic transplant rejection.
GVD is characterized by intimal thickening of the coronary arteries, resulting in progressive stenosis of the lumen.
Patients are asymptomatic as the donor heart is denervated, resulting in sudden death.
Analysis
The correct answer is C. Patients receiving heart transplants are prone to develop a number of complications, the most serious of which is graft vascular disease (also known as graft arteriosclerosis), which is a result of chronic transplant rejection.
This complication develops years after transplantation and is due to intimal and medial thickening of coronary arteries without associated atheroma formation or significant inflammation. Thickening of the arterial wall is due to the proliferation of fibroblasts and myocytes and leads to progressive stenosis of the lumen. This form of hyperplasia is its own distinct condition and would not be classified as a hyperplastic arteriolosclerosis associated with hypertension. Since transplanted hearts are denervated, ischemic injury is not associated with chest pain.
Acute allograft rejection (choice A) is certainly a major postoperative problem and occurs within weeks to months post-transplantation. However, thanks to early diagnosis based on periodic endomyocardial biopsy and the availability of immunosuppressant therapy, this complication can be prevented or successfully treated.
Cyclosporine (choice B) can cause headache, nausea, vomiting, diarrhea, gastrointestinal distress, acne, cramps, increased hair growth on the face/body, tremor, swollen/red/painful gums, dizziness, flushing, high blood pressure, and rarely, seizures. A drug reaction would most likely have occurred much earlier during the initial five years of immunosuppressant therapy. Cyclosporine toxicity can affect renal transplant function.
Hyaline arteriolosclerosis (choice D) and hyperplastic arteriolosclerosis (choice E) are pathologic changes that result from chronic damage to arteriolar walls due to hypertension. Hyaline arteriolosclerosis is associated with hypertension and diabetes. It consists of thickening of the media caused by the deposition of altered proteins. This change is actually not benign, as it leads to chronic ischemic injury to important organs such as the brain and kidneys (e.g., nephrosclerosis in the kidney and white matter damage in the brain).
Hyperplastic arteriolosclerosis follows untreated malignant hypertension. It leads to the thickening of arteriolar wall media from hyperplasia of vascular myocytes arranged in concentric layers (onion-skinning). Hyperplastic arteriolosclerosis leads to more severe and more rapid ischemic damage to the kidneys, heart, and brain. Neither type of arteriolosclerosis is observed in transplanted hearts.
ReKap
The velocity of blood within the vessels is inversely proportional to the cross-sectional area of those vessels.
This velocity is not dependent upon the diameter of a single vessel but rather the combined cross-sectional area of all vessels of that type (e.g. large arteries, arterioles, capillaries, venules, and veins).
Since the capillaries have the largest total combined cross-sectional area, the velocity at the capillary level is the slowest.
Analysis
The correct answer is C. The same volume of blood flows through each of the different types of blood vessels each minute. Individual capillaries have a tiny cross-sectional area, but because they are in parallel to each other, the total of their cross-sectional areas determines the velocity of flow, as described by the equation of continuity:
V = Q ÷ a
where V = velocity, Q = flow, and a = cross-sectional area.
Since cardiac output is distributed to all tissues, flow through the capillaries as a combined group is approximately equal to the cardiac output. Because the capillaries have the largest total cross-sectional area (averaging 2,500–5,000 cm2), and because the velocity of blood flow is inversely related to cross-sectional area, it is clear that the mean linear velocity of a red blood cell is lowest in the capillaries. Under resting conditions, the mean linear velocity of a red blood cell in the capillaries is 0.3–0.6 mm/sec, whereas the velocity in the aorta (choice A) is about 200 mm/sec. The low velocity of red blood cells in the capillary network allows plenty of time for oxygen to diffuse to the tissues.
Illustration of the gradual increase in cross-sectional area that occurs as blood vessels decrease in size but increase in number.
The velocity of blood flow is conventionally ranked from highest to lowest as follows: aorta and large vessels (choice A) > vena cavae (choice E) > large veins (choice E) > small arteries (choice D) > arterioles (choice B) > small veins (choice F) > venules (choice F) > capillaries. The intermediate vessels in the sequence can have very similar velocities of blood flow, and may, in fact, overlap over the range of vessels. This ranking assumes the vena cavae have a larger cross-sectional area than the aorta; however, when the vena cavae are partially collapsed (which occurs often), they have a lower cross-sectional area and a higher velocity of blood flow compared to the aorta.
ReKap
Decreased blood pressure and flow to the kidney (renal artery stenosis) causes:
Decreased glomerular filtration rate (GFR).
Increased renin secretion from granular cells.
Reflexive glomerular afferent arteriolar dilation.
Analysis
The correct answer is E. This patient has renal artery stenosis (RAS), which has reduced glomerular perfusion pressure and increased renin secretion from granular cells in the glomerular afferent arteriole (AA). Renin release initiates the renin–angiotensin–aldosterone system (RAAS), which promotes salt and water retention to raise mean arterial pressure (MAP). A rise in MAP increases renal blood flow and helps return glomerular perfusion pressure toward normal.
The RAAS is one of the pathways involved in the autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR; see figure). Autoregulation ensures that RBF and GFR remain stable despite wide variations in MAP and involves:
Myogenic responses. Reflex constriction and dilation of the glomerular arterioles following increases and decreases in perfusion pressure, respectively.
Tubuloglomerular feedback (TGF). Modulation of both AA and efferent arteriolar (EA) diameter in response to changes in the rate of NaCl delivery to the macula densa.
When renal perfusion pressure drops below ~100 mm Hg, RBF can no longer be maintained at a level that supports an optimal GFR. Significant functional impairment of autoregulation occurs once arterial luminal narrowing exceeds ~50% (note that this patient has an 80% stenosis). In older patients, the most common cause of RAS is atherosclerosis. Given that our patient has a history of diabetes mellitus, hypertension, and angina, atherosclerosis is the likely cause of her cardiac symptoms and RAS.
AA resistance (choice A) would decrease, not increase, in response to decreased glomerular perfusion pressure. This would involve both reflexive vasodilation (via the myogenic mechanism) and tubuloglomerular feedback.
RAS decreases GFR (choice B) because it decreases glomerular perfusion pressure.
RAS reduces rather than increases glomerular perfusion pressure (choice C). Glomerular perfusion pressure is the primary force driving GFR and is the reason GFR falls with RAS.
RAS decreases blood pressure in all renal arterial vessels, including the interlobar arteries (choice D). Increased interlobar arterial pressure might be seen in patients with hypertension, for example.
ReKap
The supracondylar aspect of the femur forms the floor of the popliteal fossa located on the posterior surface of the knee.
This fossa contains the popliteal artery.
A supracondylar fracture of the femur can cause compression or injury of the popliteal artery.
Analysis
The correct answer is C. The patient has suffered a supracondylar fracture of the femur.
The supracondylar aspect of the femur forms the floor of the popliteal fossa, which contains the popliteal artery in close proximity to the femur.
Because of its proximity, the popliteal artery is subject to injury from a supracondylar fracture of the femur or posterior dislocation of the knee.
Proximally, the vessel is called the superficial femoral artery; the name changes to popliteal when the artery passes through the adductor hiatus, an opening in the tendon of the adductor magnus.
After crossing the knee, the artery divides into the anterior and posterior tibial arteries, which supply the leg and foot.
The anterior tibial artery (choice A) is a branch of the popliteal artery that arises distal to the knee and would therefore not be directly injured by a femoral fracture. The anterior tibial artery supplies the anterior compartment of the leg and is renamed the dorsalis pedis artery after it crosses the ankle (thus this patient’s lack of a dorsalis pedis pulse).
The femoral artery (choice B) is in the anterior compartment of the thigh. It is the distal continuation of the external iliac artery. The name changes to femoral when the artery passes deep to the inguinal ligament. After passing through the adductor hiatus to reach the popliteal fossa, the femoral artery is renamed the popliteal artery.
The posterior tibial artery (choice D) is a branch of the popliteal artery that also arises distal to the knee and would therefore not be injured by a femoral fracture. The posterior tibial artery passes through and supplies the posterior compartment of the leg and, after passing behind the medial malleolus of the ankle (thus the lack of pulse posterior to the medial malleolus), divides into the medial and lateral plantar arteries to supply the plantar region of the foot.
The profunda femoris artery (choice E) arises from the femoral artery in the proximal thigh. It gives rise to branches that supply the posterior compartment of the thigh. This artery does not provide blood supply distal to the knee. The profunda femoris artery does not enter the popliteal fossa and would not be compressed by this fracture.
ReKap
Suspect a ruptured abdominal aortic aneurysm in a male with a smoking history who presents with back, abdominal, or flank pain.
Deterioration of elastin and collagen in the media causes weakening of the vessel wall and predisposes to the development of an aneurysm, which may eventually rupture.
Analysis
The correct answer is A. This is a typical presentation of an abdominal aortic aneurysm that may have ruptured posteriorly, and this patient may soon become hemodynamically unstable. This condition carries a high mortality rate. Aneurysms form as a result of deterioration of the abdominal aortic media tissue layer, which compromises the vessel’s ability to withstand high luminal pressures. Although the pathways involved have yet to be fully delineated, weakening occurs due to changes in the relative content and composition of collagen and elastin.
Abdominal Aortic Aneurysm (with rupture):
Presents as a pulsatile abdominal mass (seen in the media exhibit), typically located below the renal artery orifices.
When ruptured (usually in aneurysms > 6 cm), symptoms include back/flank and abdominal pain due to the aorta’s retroperitoneal location. Hypotension may rapidly ensue.
Classic risk factors include smoking cigarettes, male gender, age > 65 years, and hypertension.
A common finding is atherosclerosis within the vessel wall and destruction of the tunica media. This typically presents as a calcified fibrous plaque within the vessel wall and may present as dense spicules on CT scan.
Hemodynamically unstable patients with ruptured abdominal aortic aneurysm require urgent operative intervention.
Congenital weakness of vessels (choice B) affecting the aorta can be seen with Marfan syndrome and Ehlers-Danlos syndrome (type IV). Patients are usually young at presentation, and these aneurysms classically affect the thoracic aorta rather than the abdominal aorta. A more robust vasa vasorum makes thoracic aortic aneurysms rarer with atherosclerosis alone.
Another example of congenital vessel weakness is seen with saccular (berry) aneurysms in areas where the internal elastic lamina is weak and the media breaks down. Saccular aneurysms typically occur near branch points of the anterior and posterior cerebral arteries in the circle of Willis. A rupture can result in subarachnoid hemorrhage.
Cystic medial necrosis (choice C) is the histologic change associated with aortic dissection, as seen in Marfan syndrome. Aortic dissection typically occurs in the thoracic aorta and does not present as a pulsatile abdominal mass. Instead, a false lumen is created between layers of the vessel wall through which blood extravasates. Management is usually medical with aggressive hypertension management.
A syphilitic aneurysm (choice D) is a cardiovascular manifestation of tertiary syphilis and typically involves the aortic root as it leaves the heart. Typically, patients present with no history of previous treatment for syphilis. Syphilis aortitis is due to inflammation of the adventitia and the vasa vasorum with subsequent occlusion, essentially starving the outer aorta wall of blood supply. This results in dilation of the aortic root, proximal aortic aneurysm, and aortic regurgitation.
Vasculitis (choice E) can produce aneurysms in small arteries. For example, in Kawasaki disease, coronary artery aneurysms may develop.
ReKap
The right and left umbilical arteries arise from the internal iliac arteries. They carry fetal deoxygenated blood from the fetal circulation to the placenta.
After birth, these arteries obliterate and become the medial umbilical ligaments.
Analysis
The correct answer is E. The medial umbilical fold is an elevation of the parietal peritoneum that covers the medial umbilical ligaments, the adult remnants of the umbilical arteries. The paired umbilical arteries arise from the internal iliac arteries. In the fetus, they convey fetal deoxygenated blood to the placenta (see below). After birth, the distal portion of the umbilical arteries obliterate and their vestigial remnants are known as the medial umbilical ligaments. The proximal portion of the umbilical artery remains patent and supplies the urinary bladder. Do not confuse the mediaL umbilical ligament with the mediaN umbilical ligament, which contains the urachus, a remnant of the allaNtois, a structure that connects the bladder to the umbilicus.
The image shows the fetal circulation. The right and left umbilical arteries carry deoxygenated blood from the fetal circulation to the placenta.
The abdominal aorta (choice A) gives rise to the common iliac arteries, which subsequently give rise to the external and internal iliac arteries.
The external iliac arteries (choice B) become the femoral arteries (choice C) when they pass deep to the inguinal ligaments.
Hepatic veins (choice D) receive blood from the liver sinusoids, which then drain to the inferior vena cava.
ReKap
Infants with tetralogy of Fallot and complete obstruction of the right ventricular outflow tract are dependent upon blood flow through the ductus arteriosus to maintain adequate systemic oxygenation.
Patency of the ductus arteriosus can be maintained by the administration of alprostadil, a synthetic prostaglandin E1 analog.
Analysis
The correct answer is A. The ductus arteriosus (DA) is a vessel connecting the pulmonary trunk with the aorta during intrauterine life. The fetal DA is kept patent by low arterial oxygen content and circulating prostaglandin E2 (PGE2), which is partially produced by the placenta. Closure of this embryonal vessel normally occurs in the first few days of life.
Tetralogy of Fallot (TOF) with pulmonary valve atresia (PA) and major aortopulmonary collateral arteries is the most severe, extreme variant of TOF, in which complete atresia of the pulmonary valve replaces pulmonary stenosis. TOF with PA occurs in about 2% of congenital heart disease cases. Clinical presentation in TOF with PA depends on the source and volume of pulmonary blood flow. The newborn infant, in whom the DA is the only source of pulmonary blood flow, is generally symptomatic within the first hours to days of life and becomes increasingly cyanotic as the DA closes. TOF with PA patients almost always benefit from the administration of prostaglandin E1 (PGE1) to maintain ductal patency until surgery can be performed. Hence, patency of the ductus can be maintained by PGE1 (alprostadil). The figure below depicts tetralogy of Fallot.
The pathologic changes in tetralogy of Fallot are depicted in the figure above.
Betamethasone (choice B), a glucocorticoid, can accelerate pulmonary maturation and stimulate the production of surfactant when given to the mother prior to delivery of premature infants. Betamethasone does not affect the DA.
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin (choice C), promote closure of the DA because they inhibit prostaglandin synthesis. They are used to treat cases of patent DA and would not be appropriate for this patient, since it is desired to keep the DA open until surgery.
Nitric oxide (choice D) is a pulmonary artery vasodilator that is used in infants with pulmonary hypertension. The medication would not be appropriate in an infant with TOF with PA because the blood is not being delivered to the pulmonary vascular bed due to the pulmonary atresia.
Oxytocin (choice E) is a hypothalamic hormone that stimulates the contraction of smooth muscle in the uterus and mammary glands. It has no effect on the DA.
ReKap
Fibrates (e.g., gemfibrozil, fenofibrate) lower triglycerides by approximately 35–50% and increase high-density lipoprotein (HDL)-c by 5–20%.
Fibrates activate peroxisome proliferator-activated receptor-α (PPARα) and increase the expression of lipoprotein lipases.
Adverse effects include gallstones and muscle toxicity.
Muscle toxicity is more pronounced in patients also treated with a statin.
Analysis
The correct answer is E. This patient has significant hypertriglyceridemia (>150 mg/dL is abnormal, >885 mg/dL is severe), which is independently associated with cardiovascular risk and acute pancreatitis, and thus warrants treatment. First-line therapy is weight loss and increased aerobic exercise, however, with very high levels, treatment with medications is initiated.
Fibrates such as gemfibrozil and fenofibrate activate peroxisome proliferator-activated receptor-α (PPARα) and increase the expression of lipoprotein lipases. PPARs are a group of nuclear receptor proteins that act as transcription factors. Fibric acid derivatives lower triglycerides by approximately 35–50% and increase HDL-c by 5–20%. Fibrates increase the cholesterol content of bile and therefore increase the risk of gallstones, which can lead to choledocholithiasis and right upper quadrant pain. Fibrates also cause muscle toxicity that can manifest as rhabdomyolysis, which is exacerbated when they are taken in combination with statins.
Eructation (choice A) is a frequent complaint with fish oil supplements containing omega-3 fatty acids and the halitosis associated with this is the most common reason for discontinuing fish oil. Fish oil is a treatment option for moderate to severe hypertriglyceridemia but is not a first-line agent for those at risk for triglyceride-induced pancreatitis.
Facial flushing (choice B) is an adverse effect of niacin. Niacin is an alternative therapy to fibrates for treating hypertriglyceridemia. However, it is associated with worsening glycemic control (choice C) and would not be appropriate for this diabetic patient. Niacin also causes hyperuricemia and transaminitis.
Lactic acidosis (choice D) is a potentially fatal adverse effect seen in patients taking metformin. Metformin is substantially excreted by the kidney and the risk of metformin accumulation and subsequent lactic acidosis increases in a patient with impaired renal function.
ReKap
A carotid bruit may be present in severe atherosclerosis.
Atherosclerotic disease of the carotid can cause microemboli or hypoperfusion of the ipsilateral eye (amaurosis fugax).
Aspirin should be initiated, and a carotid endarterectomy should be considered to reduce the risk of a cerebrovascular accident.
Analysis
The correct answer is E. The most common reason for painless transient monocular vision loss (also known as amaurosis fugax) is ischemia. The ischemic origins of amaurosis fugax can include atherosclerosis, embolus, vasculitis, hypercoagulability disorders, venous stasis, or systemic hypoperfusion. Atherosclerosis of the carotid artery is the most likely cause in a patient with a history of diabetes mellitus, hypertension, and smoking. Atherosclerosis may result in microembolic blockade or narrowing-induced hypoperfusion of the ophthalmic artery, leading to a transient or progressive dimming of the visual field, respectively.
The loss of vision typically lasts from seconds to minutes and is often described as unilateral blurring, fogging, dimming, or a window shade descending over the visual field. A carotid bruit on the ipsilateral side of the vision loss is likely to be present. This can be an important sign of an impending cerebrovascular accident (particularly if patient is over 45 years of age). Depending on the extent of carotid narrowing, treatments can include conservative therapy with aspirin or carotid endarterectomy.
A diastolic murmur at the right upper sternal border (choice A) is suggestive of aortic regurgitation. Symptoms include fatigue, weakness, dyspnea (especially on exertion), orthopnea, palpitations, angina, and ankle and foot edema.
Galactorrhea (inappropriate milk flow from the breast; choice B), is associated with hyperprolactinemia and/or increases in thyroid-stimulating hormone or thyrotropin-releasing hormone secretion. Most pituitary tumors are prolactin-secreting adenomas. When they become sufficiently large, deficits in peripheral visual fields can occur due to compression of the optic chiasm and cause progressive or complete vision loss. The visual loss produced by prolactinoma is classically a bitemporal hemianopia.
A holosystolic murmur (choice C) is suggestive of mitral or tricuspid regurgitation. Symptoms of mitral regurgitation can include fatigue, weakness, dyspnea (especially on exertion), lightheadedness, cough (especially when lying down), palpitations, edema of feet or ankles, and excessive urination. Tricuspid insufficiency can lead to symptoms of right-sided heart failure (e.g., ascites, hepatomegaly, edema, jugular venous distension).
Impairment of adduction on lateral gaze (choice D) describes internuclear ophthalmoplegia (INO), which is the result of demyelination of the medial longitudinal fasciculus. This is most commonly seen in multiple sclerosis. The ipsilateral eye cannot adduct with lateral gaze but is able to adduct on convergence.
ReKap
ACE inhibitors can cause a dry cough by blocking bradykinin metabolism.
Losartan, an angiotensin II receptor antagonist, has similar therapeutic effects to ACE inhibitors but has a much lower incidence of cough.
Switching from an ACE inhibitor to an angiotensin II receptor antagonist is generally effective in alleviating the chronic cough.
Analysis
The correct answer is E. The key to answering this question is identifying the current treatment associated with a chronic, nonproductive cough. Then you should determine which of the answer choices has a similar mechanism of action to the causative agent.
The lack of fever or sputum production suggests that the patient’s cough is not caused by a pathogen. However, coughing does occur in a small percentage of patients using an angiotensin-converting enzyme (ACE) inhibitor (e.g., enalapril, lisinopril). ACE converts angiotensin I to angiotensin II (ang-II), but it also inactivates bradykinin. ACE inhibitors are used in the treatment of hypertension because they block ang-II formation, but they also impair bradykinin metabolism. Bradykinin accumulation is suggested to cause dry cough.
The physician should replace the ACE inhibitor with an angiotensin II receptor blocker (ARB) such as losartan, which is an alternative therapy for hypertension. ARBs block the same pathway as ACE inhibitors (i.e., the renin-angiotensin-aldosterone system; RAAS) but have a lower incidence of chronic cough because they do not interfere with bradykinin metabolism. Losartan use is associated with hypotension, hyperkalemia, and angioedema.
Atenolol (choice A) is a beta-1 selective antagonist. Propranolol (choice F) is a nonselective beta antagonist that is associated with respiratory difficulties if administered to patients with asthma or chronic obstructive pulmonary disease (COPD). These agents are known to cause bradycardia, heart block, Raynaud phenomenon, and bronchospasm in asthmatic patients.
Diltiazem (choice B) is a calcium channel blocker used in the treatment of hypertension and cardiac dysrhythmias. Bradycardia and negative inotropic effects are commonly associated with the use of this agent. Therefore, this drug would not be recommended for use in a patient with heart failure.
Exenatide (choice C) is glucagon-like-peptide (GLP-1) receptor agonist indicated for the treatment of type 2 diabetes. It is most commonly associated with hypoglycemia, especially if administered with a sulfonylurea.
Glimepiride (choice D) is a sulfonylurea indicated for the treatment of type 2 diabetes and is commonly associated with hypoglycemia.
Sitagliptin (choice G) is an orally active inhibitor of dipeptidyl peptidase-4 (DPP4) and is indicated for the treatment of type 2 diabetes. It is most commonly associated with hypoglycemia, especially when administered with other oral hypoglycemic agents.
