1.
The development of atheromatous plaque formation with subsequent complications is observed in an experiment.
Atherosclerotic plaques are shown to change slowly but constantly in ways that can promote clinical events, including
acute coronary syndromes. In some cases, changes occurred that were not significantly associated with acute coronary
syndromes. Which of the following plaque alterations is most likely to have such an association?
Correct Answer
A. Thinning of the media
Explanation
Atheromatous plaques can be complicated by various pathologic alterations, including hemorrhage, ulceration,
thrombosis, and calcification. These processes can increase the size of the plaque and narrow the residual arterial lumen.
Although atherosclerosis is a disease of the intima, in advanced disease, the expanding plaque compresses the media.
This causes thinning of the media, which weakens the wall and predisposes it to aneurysm formation.
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2.
A 60-year-old woman has reported increasing fatigue over the past year. Laboratory studies show a serum creatinine
level of 4.7 mg/dL and urea nitrogen level of 44 mg/dL. An abdominal ultrasound scan shows that her kidneys are
symmetrically smaller than normal. The high-magnification microscopic appearance of the kidneys is shown in the figure.
These findings are most likely to indicate which of the following underlying conditions?
Correct Answer
B. Systemic hypertension
Explanation
The figure shows an arteriole with marked hyaline thickening of the wall, indicative of hyaline arteriolosclerosis.
Diabetes mellitus also can lead to this finding. Sepsis can produce disseminated intravascular coagulopathy with arteriolar
hyaline thrombi. The debilitation that accompanies cancer tends to diminish the vascular disease caused by atherosclerosis. Syphilis can cause a vasculitis involving the vasa vasorum of the aorta. Polyarteritis can involve large to
medium-sized arteries in many organs, including the kidneys; the affected vessels show fibrinoid necrosis and
inflammation of the wall (vasculitis).
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3.
A 55-year-old woman visits her physician for a routine health maintenance examination. On physical examination, her
temperature is 36.8°C, pulse is 70/min, respirations are 14/min, and blood pressure is 160/105 mm Hg. Her lungs are clear
on auscultation, and her heart rate is regular. She feels fine and has had no major medical illnesses or surgical
procedures during her lifetime. An abdominal ultrasound scan shows that the left kidney is smaller than the right kidney. A
renal angiogram shows a focal stenosis of the left renal artery. Which of the following laboratory findings is most likely to
be present in this patient?
Correct Answer
F. Plasma renin 15 mg/mL/hr
Explanation
This is a classic example of a secondary form of hypertension for which a cause can be determined. In this case, the
renal artery stenosis reduces glomerular blood flow and pressure in the afferent arteriole, resulting in renin release by
juxtaglomerular cells. The renin initiates angiotensin II–induced vasoconstriction, increased peripheral vascular resistance,
and increased aldosterone, which promotes sodium reabsorption in the kidney, resulting in increased blood volume. Anti–
double-stranded DNA is a specific marker for systemic lupus erythematosus. ANCAs are markers for some forms of
vasculitis, such as microscopic polyangiitis or Wegener granulomatosis. Some patients with hepatitis B or C infection can
develop a mixed cryoglobulinemia with a polyclonal increase in IgG. Renal involvement in such patients is common, and
cryoglobulinemic vasculitis then leads to skin hemorrhages and ulceration. Hyperglycemia is a marker for diabetes
mellitus, which accelerates the atherogenic process and can involve the kidneys, promoting the development of
hypertension. HIV infection is not related to hypertension. Tertiary syphilis can produce endaortitis and aortic root dilation,
but hypertension is not a likely sequela.
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4.
A 7-year-old child has had abdominal pain and dark urine for 10 days. Physical examination shows purpuric skin lesions
on the trunk and extremities. Urinalysis shows hematuria and proteinuria. Serologic test results are negative for P-ANCAs
and C-ANCAs. A skin biopsy specimen shows necrotizing vasculitis of small dermal vessels. A renal biopsy specimen
shows immune complex deposition in glomeruli, with some IgA-rich immune complexes. Which of the following is the most
likely diagnosis?
Correct Answer
B. Henoch-Schönlein purpura
Explanation
In children, Henoch-Schönlein purpura is the multisystemic counterpart of the IgA nephropathy seen in adults. The
immune complexes formed with IgA produce the vasculitis that affects mainly arterioles, capillaries, and venules in skin,
gastrointestinal tract, and kidney. In older adults, giant-cell arteritis is seen in external carotid branches, principally the
temporal artery unilaterally. Polyarteritis nodosa is seen most often in small muscular arteries and sometimes veins, with
necrosis and microaneurysm formation followed by scarring and vascular occlusion. This occurs mainly in the kidney,
gastrointestinal tract, and skin of young to middle-aged adults. Takayasu arteritis is seen mainly in children and involves
the aorta (particularly the arch) and branches such as coronary and renal arteries, with granulomatous inflammation,
aneurysm formation, and dissection. Telangiectasias are small vascular arborizations seen on skin or mucosal surfaces.
Wegener granulomatosis, seen mainly in adults, involves small arteries, veins, and capillaries and causes mixed
inflammation and necrotizing and non-necrotizing granulomatous inflammation with geographic necrosis surrounded by
palisading epithelioid macrophages and giant cells.
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5.
A 30-year-old woman has had coldness and numbness in her arms and decreased vision in the right eye for the past 5
months. On physical examination, she is afebrile. Her blood pressure is 100/70 mm Hg. Radial pulses are not palpable, but
femoral pulses are strong. She has decreased sensation and cyanosis in her arms, but no warmth or swelling. A chest
radiograph shows a prominent border on the right side of the heart and prominence of the pulmonary arteries. Laboratory
studies show serum glucose, 74 mg/dL; creatinine, 1 mg/dL; total serum cholesterol, 165 mg/dL; and negative ANA test
result. Her condition remains stable for the next year. Which of the following is the most likely diagnosis?
Correct Answer
D. Takayasu arteritis
Explanation
Takayasu arteritis leads to “pulseless disease” because of involvement of the aorta (particularly the arch) and
branches such as coronary, carotid, and renal arteries, with granulomatous inflammation, aneurysm formation, and
dissection. Fibrosis is a late finding, and the pulmonary arteries also can be involved. Aortic dissection is an acute problem
that, in older adults, is driven by atherosclerosis and hypertension, although this patient is within the age range for
complications of Marfan syndrome, which causes cystic medial necrosis of the aorta. Kawasaki disease affects children
and is characterized by an acute febrile illness, coronary arteritis with aneurysm formation and thrombosis, skin rash, and
lymphadenopathy. Microscopic polyangiitis affects arterioles, capillaries, and venules with a leukocytoclastic vasculitis that
appears at a similar stage in multiple organ sites (in contrast to classic polyarteritis nodosa, which causes varying stages
of acute, chronic, and fibrosing lesions in small to medium-sized arteries). Tertiary syphilis produces an endaortitis with
proximal aortic dilation. Thromboangiitis obliterans (Buerger disease) affects small to medium-sized arteries of the
extremities and is strongly associated with smoking.
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6.
A 61-year-old man had a myocardial infarction 1 year ago, which was the first major illness in his life. He now wants to
prevent another myocardial infarction and is advised to begin a program of exercise and to change his diet. A reduction in
the level of which of the following serum laboratory findings 1 year later would best indicate the success of this diet and
exercise regimen?
Correct Answer
A. Cholesterol
Explanation
Reducing cholesterol, particularly LDL cholesterol, with the same or increased HDL cholesterol level, indicates a
reduced risk of atherosclerotic complications. Atherosclerosis is multifactorial, but modification of diet (i.e., reduction in
total dietary fat and cholesterol) with increased exercise is the best method of reducing risk for most individuals. Glucose is
a measure of control of diabetes mellitus. Potassium, calcium, and renin values can be altered with some forms of
hypertension, one of several risk factors for atherosclerosis.
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7.
A 23-year-old man experiences sudden onset of severe, sharp chest pain. On physical examination, his temperature is
36.9°C, and his lungs are clear on auscultation. A chest radiograph shows a widened mediastinum. Transesophageal
echocardiography shows a dilated aortic root and arch, with a tear in the aortic intima 2 cm distal to the great vessels. The
representative microscopic appearance of the aorta with elastic stain is shown in the figure. Which of the following is the
most likely cause of these findings?
Correct Answer
D. Marfan syndrome
Explanation
This is a description of cystic medial degeneration, which weakens the aortic media and predisposes to aortic
dissection. In a young patient such as this, a heritable disorder of connective tissues, such as Marfan syndrome, must be
strongly suspected. Scleroderma and Wegener granulomatosis do not typically involve the aorta. Atherosclerosis
associated with diabetes mellitus and hypertension are risk factors for aortic dissection, although these are seen at an
older age. Takayasu arteritis is seen mainly in children and involves the aorta (particularly the arch) and branches such as the coronary and renal arteries, causing granulomatous inflammation, aneurysm formation, and dissection.
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8.
A 40-year-old man with a history of diabetes mellitus has had worsening abdominal pain for the past week. On physical
examination, his vital signs are temperature, 36.9°C; pulse, 77/min; respirations, 16/min; and blood pressure,
140/90 mm Hg. An abdominal CT scan shows the findings in the figure. Laboratory studies show his hemoglobin A1C is
10.5%. Which of the following is the most likely underlying disease process in this patient?
Correct Answer
C. Diabetes mellitus
Explanation
This patient has an atherosclerotic abdominal aortic aneurysm. His abdominal CT scan shows a 6-cm fusiformshaped
enlargement of the abdominal aorta. Diabetes mellitus, an important risk factor for atherosclerosis, must be
suspected if a younger man or premenopausal woman has severe atherosclerosis. His hemoglobin A1C value is consistent
with poorly controlled diabetes mellitus. Polyarteritis nodosa does not typically involve the aorta. Obesity, a “soft” risk
factor for atherosclerosis, also contributes to diabetes mellitus type 2; however, the extent of atherosclerotic disease in this
patient suggests early-onset diabetes mellitus, which is more likely to be type 1. Systemic lupus erythematosus produces
small arteriolar vasculitis. Syphilitic aortitis, a feature of tertiary syphilis, most often involves the thoracic aorta, but it is
rare, and most thoracic aortic aneurysms nowadays are likely to be caused by atherosclerosis.
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9.
A 10-year-old boy is brought to the physician for a routine health maintenance examination. The physician notes a 2
spongy, dull red, circumscribed lesion on the upper outer left arm. The parents state that this lesion has been present
since infancy. The lesion is excised, and its microscopic appearance is shown in the figure. Which of the following is the
most likely diagnosis?
Correct Answer
E. Hemangioma
Explanation
The figure shows dilated, endothelium-lined spaces filled with RBCs. The circumscribed nature of this lesion and its
long, unchanged course suggest its benign nature. Kaposi sarcoma is uncommon in its endemic form in childhood, and it
is best known as a neoplastic complication associated with HIV infection. Angiosarcomas are large, rapidly growing
malignancies in adults. Lymphangiomas, seen most often in children, tend to be more diffuse and are not blood-filled. A
telangiectasia is a radial array of subcutaneous dilated arteries or arterioles surrounding a central core that can pulsate.
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10.
A pharmaceutical company is developing an antiatherosclerosis agent. An experiment investigates mechanisms of
action of several potential drugs to determine their efficacy in reducing atheroma formation. Which of the following
mechanisms of action is likely to have the most effective antiatherosclerotic effect?
Correct Answer
A. Inhibits PDGF/Inhibits macropHage-mediated lipoprotein oxidation
Explanation
Atherosclerosis is considered a complex reparative response that follows endothelial cell injury.
Hypercholesterolemia (high LDL cholesterol level) is believed to cause subtle endothelial injury. The oxidation of LDL by
macrophages or endothelial cells has many deleterious effects. Oxidized LDL is chemotactic for circulating monocytes,
causes monocytes to adhere to endothelium, stimulates release of growth factors and cytokines, and is cytotoxic to
smooth muscle cells and endothelium. Smooth muscle proliferation in response to injury, important in the development of
atheromas, is driven by growth factors, including platelet-derived growth factor. HDL is believed to mobilize cholesterol
from developing atheromas; high HDL levels are protective. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell
adhesion molecule-1 (VCAM-1) are adhesion molecules on endothelial cells that promote adhesion of monocytes to the
site of endothelial injury.
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11.
A 73-year-old man who has had progressive dementia for the past 6 years dies of bronchopneumonia. Autopsy shows
that the thoracic aorta has a dilated root and arch, giving the intimal surface a “tree-bark” appearance. Microscopic
examination of the aorta shows an obliterative endarteritis of the vasa vasorum. Which of the following laboratory findings
is most likely to be recorded in this patient's medical history?
Correct Answer
E. Antibodies against Treponema pallidum
Explanation
This description is most suggestive of syphilitic aortitis, a complication of tertiary syphilis, with characteristic
involvement of the thoracic aorta. Obliterative endarteritis is not a feature of other forms of vasculitis. High-titer doublestranded
DNA antibodies are diagnostic of systemic lupus erythematosus, and the test result for P-ANCA is positive in
various vasculitides, including microscopic polyangiitis. A high sedimentation rate is a nonspecific marker of inflammatory
diseases. Ketonuria can occur in individuals with diabetic ketoacidosis.
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12.
For the past 3 weeks, a 70-year-old woman has been bedridden while recuperating from a bout of viral pneumonia
complicated by bacterial pneumonia. Physical examination now shows some swelling and tenderness of the right leg,
which worsens when she raises or moves the leg. Which of the following terms best describes the condition involving the
patient's right leg?
Correct Answer
C. ThrombopHlebitis
Explanation
Thrombophlebitis is a common problem that results from venous stasis. There is little or no inflammation, but the
term is well established. Lymphedema takes longer than 3 weeks to develop and is not caused by bed rest alone.
Disseminated intravascular coagulopathy more often results in hemorrhage, and edema is not the most prominent
manifestation. Thromboangiitis obliterans is a rare form of arteritis that results in pain and ulceration of extremities.
Varicose veins are superficial and can thrombose, but they are not related to bed rest.
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13.
A 49-year-old man is feeling well when he visits his physician for a routine health maintenance examination for the first
time in 20 years. On physical examination, his vital signs are temperature, 37°C; pulse, 73/min; respirations, 14/min; and
blood pressure, 155/95 mm Hg. He has had no serious medical problems and takes no medications. Which of the following
is most likely to be the primary factor in this patient's hypertension?
Correct Answer
B. Renal retention of excess sodium
Explanation
This patient has essential hypertension (no obvious cause for his moderate hypertension). Renal retention of
excess sodium, which is thought to be important in initiating this form of hypertension, leads to increased intravascular fluid
volume, increase in cardiac output, and peripheral vasoconstriction. Increased catecholamine secretion (as can occur in
pheochromocytoma), gene defects in aldosterone metabolism, and renal artery stenosis all can cause secondary
hypertension. Hypertension secondary to all causes is much less common, however, than essential hypertension.
Increased production of atrial natriuretic factor reduces sodium retention and reduces blood volume.
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14.
A 50-year-old man has a 2-year history of angina pectoris that occurs during exercise. On physical examination, his
blood pressure is 135/75 mm Hg, and his heart rate is 79/min and slightly irregular. Coronary angiography shows a fixed
75% narrowing of the anterior descending branch of the left coronary artery. Which of the following types of cells is the
initial target in the pathogenesis of this arterial lesion?
Correct Answer
E. Endothelial cells
Explanation
Atherogenesis can be considered a chronic inflammatory response of the arterial wall to endothelial injury. The injury promotes participation by monocytes, macrophages, and T lymphocytes. Smooth muscle cells are stimulated to
proliferate. Platelets adhere to areas of endothelial injury. Neutrophils are not a part of atherogenesis, although they can
be seen in various forms of vasculitis. The process begins with endothelial cell alteration.
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15.
A study of atheroma formation leading to atherosclerotic complications evaluates potential risk factors for relevance in a
population. Three factors are found to play a significant role in the causation of atherosclerosis: smoking, hypertension,
and hypercholesterolemia. These factors are analyzed for their relationship to experimental models for atherogenesis.
Which of the following events is the most important direct biologic consequence of these factors?
Correct Answer
A. Endothelial injury and its sequelae
Explanation
Atherosclerosis is thought to result from a form of endothelial injury and the subsequent chronic inflammation and
repair of the intima. All risk factors, including smoking, hyperlipidemia, and hypertension, cause biochemical or mechanical
injury to the endothelium. Formation of foam cells occurs after the initial endothelial injury. Although lipoprotein receptor
alterations can occur in some inherited conditions, these account for only a fraction of cases of atherosclerosis, and other
lifestyle conditions do not affect their action. Inhibition of LDL oxidation should diminish atheroma formation. Vasomotor
tone does not play a major role in atherogenesis.
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16.
A 55-year-old woman has noted the increasing prominence of unsightly dilated superficial veins over both lower legs for
the past 5 years. Physical examination shows temperature of 37°C, pulse of 70/min, respirations of 14/min, and blood
pressure of 125/85 mm Hg. There is no pain, swelling, or tenderness in either lower leg. Which of the following
complications is most likely to occur as a consequence of this condition?
Correct Answer
A. Stasis dermatitis
Explanation
Venous stasis results in hemosiderin deposition and dermal fibrosis, with brownish discoloration and skin
roughening. Focal ulceration can occur over the varicosities, but extensive gangrene similar to that seen in arterial
atherosclerosis does not occur. The varicosities involve only the superficial set of veins, which can thrombose, but are not
the source of thromboemboli, as are the larger, deep leg veins. The thromboses in superficial leg veins do not lead to
disseminated intravascular coagulopathy. The varicosities do not affect muscle; however, lack of muscular support for
veins to “squeeze” blood out for venous return can predispose to formation of varicose veins.
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17.
A 35-year-old man is known to have been HIV-positive for the past 10 years. Physical examination shows several skin
lesions with the appearance shown in the figure. These lesions have been slowly increasing for the past year. Which of
the following infectious agents is most likely to play a role in the development of these skin lesions?
Correct Answer
A. Human herpesvirus-8
Explanation
Human herpesvirus-8 has been associated with Kaposi sarcoma and can be acquired as a sexually transmitted
disease. Kaposi sarcoma is a complication of AIDS. Individuals with HIV infection can be infected with various viruses,
including Epstein-Barr virus (EBV) and cytomegalovirus (CMV), but these have no etiologic association with Kaposi
sarcoma. EBV is a factor in the development of non-Hodgkin lymphoma, and CMV can cause colitis or retinitis or can be
disseminated. Hepatitis B virus can be seen in HIV-infected patients as well, particularly patients with a risk factor of
injection drug use. Adenovirus, which, although rare, can be seen in HIV-infected individuals, tends to be a respiratory or
gastrointestinal infection.
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18.
A 50-year-old man complains of a chronic cough that has persisted for the past 18 months. Physical examination shows
nasopharyngeal ulcers, and the lungs have diffuse crackles bilaterally on auscultation. Laboratory studies include a serum
urea nitrogen level of 75 mg/dL and a creatinine concentration of 6.7 mg/dL. Urinalysis shows 50 RBCs per high-power
field and RBC casts. His serologic titer for C-ANCA is elevated. A chest radiograph shows multiple, small, bilateral
pulmonary nodules. A nasal biopsy specimen shows mucosal and submucosal necrosis and necrotizing granulomatous
inflammation. A transbronchial lung biopsy specimen shows a vasculitis involving the small peripheral pulmonary arteries
and arterioles. Granulomatous inflammation is seen within and adjacent to small arterioles. Which of the following is the
most likely diagnosis?
Correct Answer
H. Wegener granulomatosis
Explanation
Wegener granulomatosis is a form of hypersensitivity reaction to an unknown antigen characterized by necrotizing
granulomatous inflammation that typically involves the respiratory tract, small to medium-sized vessels, and glomeruli,
although many organ sites may be affected; pulmonary and renal involvement can be life-threatening. C-ANCAs are found
in more than 90% of cases. Fibromuscular dysplasia is a hyperplastic medial disorder, usually involving renal and carotid
arteries; on angiography, it appears as a “string of beads” caused by thickened fibromuscular ridges adjacent to less
involved areas of the arterial wall. Glomus tumors are usually small peripheral masses. Granuloma pyogenicum is an
inflammatory response that can produce a nodular mass, often on the gingiva or the skin. Hemangiomas are typically
small, solitary, red nodules that can occur anywhere. Kaposi sarcoma can produce plaquelike to nodular masses that are
composed of irregular vascular spaces lined by atypical-appearing endothelial cells; skin involvement is most common, but
visceral organ involvement can occur. Polyarteritis nodosa most often involves small muscular arteries, and sometimes
veins; it causes necrosis and microaneurysm formation followed by scarring and vascular occlusion, mainly in the kidney,
gastrointestinal tract, and skin of young to middle-aged adults. Takayasu arteritis is seen mainly in children and involves
the aorta (particularly the arch) and branches such as the coronary and renal arteries, with granulomatous inflammation,
aneurysm formation, and dissection. Telangiectasias are small vascular arborizations seen on skin or mucosal surfaces.
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19.
While cleaning debris out of the gate in an irrigation canal, a 50-year-old man cuts his right index finger on a sharp
metal shard. The cut stops bleeding within 3 minutes, but 6 hours later he notes increasing pain in the right arm and goes
to his physician. On physical examination, his temperature is 38°C. Red streaks extend from the right hand to the upper
arm, and the arm is swollen and tender when palpated. Multiple tender lumps are noted in the right axilla. A blood culture
grows group A hemolytic streptococci. Which of the following terms best describes the process that is occurring in this
patient's right arm?
Correct Answer
B. LympHangitis
Explanation
The red streaks represent lymphatic channels through which an acute infection drains to axillary lymph nodes, and
these drain to the right lymphatic duct and into the right subclavian vein (lymphatics from the lower body and left upper
body drain to the thoracic duct). Capillaritis is most likely to be described in the lungs. Lymphedema occurs with blockage
of lymphatic drainage and develops over a longer period without significant acute inflammation. Phlebothrombosis and
thrombophlebitis describe thrombosis in veins with stasis and inflammation, typically in the pelvis and lower extremities.
Polyarteritis involves small to medium-sized muscular arteries, typically the renal and mesenteric branches. Varices are
veins dilated from blockage of venous drainage.
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20.
An experiment studies early atheromas. Lipid streaks on arterial walls are examined microscopically and biochemically
to determine their cellular and chemical constituents and the factors promoting their formation. Early lesions show
increased attachment of monocytes to endothelium. The monocytes migrate subendothelially and become macrophages;
these macrophages transform themselves into foam cells. Which of the following is most likely to produce these effects?
Correct Answer
D. Oxidized LDL
Explanation
Oxidized LDL can be taken up by a special “scavenger” pathway in macrophages; it also promotes monocyte
chemotaxis and adherence. Macrophages taking up the lipid become foam cells that begin to form the fatty streak.
Smoking, diabetes mellitus, and hypertension all promote free radical formation, and free radicals increase degradation of
LDL to its oxidized form. About one third of LDL is degraded to the oxidized form; a higher LDL level increases the amount
of oxidized LDL available for uptake into macrophages. C-reactive protein is a marker for inflammation, which can increase
with more active atheroma and thrombus formation and predicts a greater likelihood of acute coronary syndromes.
Increased homocysteine levels promote atherogenesis through endothelial dysfunction. Lp(a), an altered form of LDL that
contains the apo B-100 portion of LDL linked to apo A, promotes lipid accumulation and smooth muscle cell proliferation.
Platelet-derived growth factor promotes smooth muscle cell proliferation. VLDL is formed in the liver and transformed in
adipose tissue and muscle to LDL.
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