Drug	Class	Mechanism of Action
Aspirin	Nonselective cyclooxygenase inhibitor	Irreversibly inhibits COX-1, decreasing platelet production of thromboxane A₂, a vasoconstrictor and promoter of platelet aggregation
Clopidogrel	P2Y₁₂ antagonist	Irreversibly inhibits P2Y₁₂, a platelet ADP receptor necessary for activation of the glycoprotein IIb/IIIa pathway of platelet aggregation
Statins (e.g., atorvastatin, rosuvastatin, fluvastatin, lovastatin, pravastatin, simvastatin)	HMG-CoA reductase inhibitors	Inhibit HMG-CoA reductase, the rate-limiting step in endogenous production of cholesterol, to reduce the buildup of cholesterol in atherosclerotic plaques
Cilostazol	Phosphodiesterase III inhibitor	Inhibits cAMP phosphodiesterase III to reduce cAMP degradation, vasodilating peripheral arteries and inhibiting platelet aggregation
Pentoxifylline	Phosphodiesterase inhibitor	Inhibits cAMP phosphodiesterase; increases platelet flexibility and decreases blood viscosity

ADP, adenosine diphosphate; cAMP, cyclic adenosine monophosphate; CoA, coenzyme A; COX-1, cyclooxygenase-1; HMG, hydroxymethylglutarate.

Summary Box: Peripheral Vascular Disease

Peripheral vascular disease (PVD) is caused by atherosclerotic narrowing of peripheral arteries, usually of the lower extremities (LEs).

Atherosclerotic lesions form preferentially at branch points and sites of tethering, as a result of turbulent blood flow and endothelial shear stress.

Blood flow to the LE: aorta → common iliac → external iliac → common femoral → profunda femoris (ends in thigh) and superficial femoral → popliteal → anterior tibial (supplies anterior compartment and ends as dorsalis pedis in the dorsum of the foot) and tibiofibular trunk → fibular (supplies lateral compartment) and posterior tibial (supplies posterior compartment) → lateral and medial plantar arteries.

From lateral to medial, the femoral triangle contains the femoral Nerve, Artery, Vein, canal (Empty space), and the Lacunar ligament. Remember the acronym NAVEL.

Case 26-2, Part A

Oscar, a 22-year-old college student, presents to the emergency department (ED) after rear-ending a car while driving his new motorcycle. He claims that the major site of impact was his left shoulder, but his head and neck were wrenched to the right as well. He is clearly intoxicated and has managed to sit up, though his left upper extremity (UE) hangs by his side in medial rotation. His forearm is extended and pronated and his wrist is frozen in flexion. The intern on call claims to be able to diagnose Oscar’s injury from across the room.

1 What structure has Oscar injured, and how has it led to his upper extremity position?

Oscar has torn nerve roots C5 and C6 (or the upper trunk) of the brachial plexus, resulting in a condition known as Erb-Duchenne palsy. His left UE hangs by his side in medial rotation because the C5 component of the axillary nerve is necessary for shoulder flexion and abduction (via the deltoid) and lateral rotation (via the teres minor). His forearm is extended and pronated because C5 and C6 are the main components of the musculocutaneous nerve, which supplies the two major forearm flexors (brachialis and biceps) and the major forearm supinator (biceps). His wrist is flexed because the C6 component of the radial nerve is necessary for wrist extension (via the extensor muscles of the posterior compartment of the forearm).

2 If Oscar had forced his upper extremity above his head by grabbing the handlebars of the motorcycle to prevent his fall, he may have presented with a loss of sensation and impaired flexion in digits 4 and 5, impaired wrist flexion, hyperextension of the metacarpophalangeal joints, and an inability to abduct and adduct digits 2 to 5. What would be the diagnosis in this situation?

This pattern of injury is characteristic of a tear of nerve roots C8 and T1 (or a lower trunk tear) of the brachial plexus, a condition known as Klumpke’s paralysis. The ulnar nerve is exclusively supplied by C8 and T1 and is responsible for sensory innervation to the fifth digit, the medial half of the fourth digit, and the corresponding palmar surface of the hand. It controls the majority of medial digit flexion (via the medial heads of the flexor digitorum profundus and the flexor digiti minimi muscles) as well as abduction (via the dorsal interossei) and adduction (via the palmar interossei) of digits 2 to 5. It is partially responsible for metacarpophalangeal joint flexion (via the lumbricals of digits 4 and 5) and wrist flexion (via the flexor carpi ulnaris) (Fig. 26-3).

Figure 26-3 Roots, trunks, divisions, cords, and branches of the brachial plexus.

(From Miller RD: Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005.)

Case 26-2, Part A continued:

One year later, Oscar’s wild ways have continued, and he admits to twisting his ankle during an episode of extreme intoxication last weekend. He did not go to the doctor then, as he was a bit embarrassed, and his ankle feels much better. He presents today with an inability to extend his right elbow and right wrist drop since he started using crutches a friend let him borrow.

3 What structure has Oscar injured this time and how has it led to his upper extremity position?

A compression injury to the posterior cord of the brachial plexus can occur if underarm crutches are used incorrectly. The inability to extend his wrist is due to a lack of radial nerve (a branch of the posterior cord) input to the posterior compartment of the forearm. The radial nerve also innervates the triceps brachii and anconeus muscles, which are necessary for elbow extension. Pure radial nerve palsies (which often result from injury to the nerve at the spiral groove of the humerus) generally do not affect the triceps, because the branch of radial nerve to the triceps is very close to the origin at the posterior cord, proximal to the spiral groove.

Case 26-2, Part B

One month later, Oscar’s father, George (who happens to be a writer), presents to your clinic with paresthesias and pain involving his lateral palm, digits 1 to 3, and the lateral half of his fourth digit. He tells you that he has been typing long hours over the past few months and now has almost finished his latest masterpiece. On physical examination, you notice mild atrophy of the thenar eminence, a positive Tinel sign (tapping the middle of the wrist crease elicits paresthesias of the lateral hand), and a positive Phalen test (palmar flexion of the wrist for longer than 1 minute results in paresthesias of the lateral hand).

4 What structure has been injured and how has this happened?

Repetitive use of the hands—typing, in George’s case—can lead to inflammation, swelling, and subsequent compression of the structures within the carpal tunnel. This condition is known as carpal tunnel syndrome, and the pain, paresthesias, and muscle wasting are due to median nerve injury within the tunnel. George’s pain and paresthesias have arisen in the distribution of the sensory component of the median nerve, the lateral palm, and the lateral 3½ digits. Because the median nerve also innervates the intrinsic muscles of the thumb, early thenar wasting has occurred.

5 Outline the contents of the carpal tunnel

The carpal tunnel is formed by the eight wrist (carpal) bones and the transverse carpal ligament (flexor retinaculum), which spans from the tubercles of the scaphoid and trapezium to the pisiform and the hook of the hamate. The contents include the four flexor digitorum profundus tendons, the four flexor digitorum superficialis tendons, the flexor pollicis longus tendon, and the median nerve (Fig. 26-4).

Figure 26-4 Cross-sectional anatomy of wrist. Tendons and median nerve may be compressed by inflammation or infection because they are encompassed by synovial sheath and flexor retinaculum.

(From Noble J: Textbook of Primary Care Medicine, 3rd ed. St. Louis, Mosby, 2001.)

6 Name the muscles of the thenar and hypothenar eminences and describe their function

Thenar eminence (located proximal to the thumb): opponens pollicis, abductor pollicis brevis, and flexor pollicis brevis (all innervated by the median nerve after it passes through the carpal tunnel).

Hypothenar eminence (located proximal to the fifth digit): opponens digiti minimi, abductor digiti minimi, and flexor digiti minimi (all innervated by the ulnar nerve).

Function: These two groups have symmetrical function. As their names suggest, each group has a muscle that performs opposition, abduction, and flexion.

7 Describe the pattern of sensory innervation of the hand

Median nerve: lateral palm, thumb, digits 2 and 3, and lateral half of digit 4.

Ulnar nerve: medial palm, medial dorsal hand, digit 5, and medial half of digit 4.

Radial nerve: lateral dorsal hand, extending distally to the proximal interphalangeal (PIP) joint of digits 1 to 3 and the lateral half of digit 4 (Fig. 26-5).

Figure 26-5 Nerves of the hand. A, Volar aspect. B, Dorsal aspect. antebr. cut., antebrachial cutaneous; cut. br., cutaneous branch; dig. br., digital branch.

(From Noble J: Textbook of Primary Care Medicine, 3rd ed. St. Louis, Mosby, 2001.)

Case 26-2, Part B continued:

As George walks out of the office, he slips on icy steps and falls forward, breaking the fall with his right hand. He immediately feels severe pain in his wrist, and as his distal forearm is very obviously deformed, he carefully walks back into the clinic. You order an x-ray film, and the radiologist remarks that she sees the classic “dinner fork deformity” of a certain fracture commonly seen in patients over the age of 50.

8 What fracture has George suffered?

Colles’ fracture is a fracture of the distal radius in which the distal fragment is displaced posteriorly/dorsally. Radiographically, the angle of the radius and the fragment in combination with the angle of the fragment and the hand resembles the curvature of a fork. This fracture is common after the age of 50 and most often occurs when one breaks a fall with an outstretched hand.

Case 26-2, Part C

Two months later, you are working in the ED again, and you come across another member of the family, 20-year-old Jake. He is a former high school starting pitcher who was getting a lesson from Oscar on how to ride a motorcycle. Unfortunately, he too has taken a nasty fall. The attending at the ED says she is worried about a humerus fracture.

9 What are the three most common sites of humerus fracture, and which nerve and artery are at risk at each of these sites?

See Table 26-2.

Table 26-2 Three Most Common Sites of Humerus Fracture

Humerus Fracture Site	Nerve	Artery
Surgical neck	Axillary	Anterior and posterior circumflex humeral (branches of the axillary artery)
Midshaft	Radial	Profunda brachii (branch of the brachial artery)
Supracondylar	Median	Brachial

10 On reviewing Jake’s past medical history, you note that his baseball career was marred by a partially torn rotator cuff. Describe why the rotator cuff makes the glenohumeral joint different from other joints, and name its four components

Most joints are stabilized primarily by a ligamentous capsule, but the glenohumeral joint is stabilized primarily by the rotator cuff, which consists of the tendons of four muscles—supraspinatus, infraspinatus, teres minor, and subscapularis (Fig. 26-6). This design allows the glenohumeral joint to have the widest range of motion of all joints in the body, at the expense of stability and resistance to injury. The rotator cuff stabilizes the glenohumeral joint by pulling the head of the humerus toward the glenoid fossa of the scapula as other muscles flex, extend, abduct, or adduct the arm. Rapid, forceful, or repetitive movements (such as repeatedly throwing a baseball) can tear the tendons of the rotator cuff, leading to a lack of joint stability, restricted movement, and pain.

Figure 26-6 Cross-sectional view of the shoulder with humeral head stabilized in shallow scapular glenoid by rotator cuff and capsule.

(From Noble J: Textbook of Primary Care Medicine, 3rd ed. St. Louis, Mosby, 2001.)

Step 1 Secret

Upper extremity injuries, particularly those that involve the brachial plexus, are popular subjects for Step 1 anatomy questions. You should learn all of the brachial plexus components and the muscles that they innervate. Remember, boards questions usually have a clinical focus! When you study the brachial plexus, spend most of your time reasoning through the various injuries that result from lesions to the different nerves, branches, trunks, divisions, and so on. You are expected to know the most common ways in which these injuries can occur, because it is likely that you will have to deduce this from the stem of the question (e.g., associate frequent computer use with median nerve damage). Lower extremity nerve injuries are also tested on boards but not quite as commonly as upper extremity injuries.

Summary Box: Upper Extremity Injuries

From proximal to distal, the brachial plexus consists of:

Five roots: C5 through T1

Three trunks: superior, middle, and inferior

Six divisions: three anterior and three posterior

Three cords: lateral, posterior, and medial

Five major branches: musculocutaneous, axillary, radial, median, and ulnar

The musculocutaneous nerve innervates the flexors of the elbow.

The axillary nerve innervates the deltoid and teres minor muscles as well as the long head of the triceps brachii.

The radial nerve innervates the extensors in the arm and forearm.

The ulnar nerve innervates the medial heads of the flexor digitorum profundus, the flexor carpi ulnaris, medial lumbricals, interossei, and hypothenar muscles.

The median nerve innervates the anterior forearm muscles not innervated by the ulnar nerve, the lateral lumbricals, and the thenar muscles.

The blood supply to the upper extremity (UE) is from the brachial artery, the continuation of the axillary artery after it crosses the teres major.

The carpal tunnel consists of the eight carpal bones and the transverse carpal ligament. It contains the median nerve and the tendons of the long flexors of the digits.

The rotator cuff consists of the tendons of four muscles: supraspinatus, infraspinatus, teres minor, and subscapularis.

Case 26-3, Part A

You are working in an outpatient pediatrics clinic, and your next patient is a 14-day-old infant who was born 2 weeks prematurely. The mother has no complaints, and you proceed to examine the child. The infant is mildly diaphoretic, and you notice a continuous (both systolic and diastolic) “machinery murmur,” auscultated best at the second left intercostal space.

1 What is the most likely diagnosis?

Patent ductus arteriosus (PDA) is likely.

2 What is the utility of the ductus arteriosus?

In utero, this connection between the aorta and the pulmonary artery acts as a right-to-left shunt. It allows the majority of oxygenated blood (which has entered the right side of the heart through the route of placenta → umbilical vein → ductus venosus → inferior vena cava) to bypass the developing (nonfunctioning) lungs and enter the systemic circulation. Just after birth, the ductus arteriosus normally closes and undergoes fibrotic degeneration to become the ligamentum arteriosum (Fig. 26-7).

Figure 26-7 Course of fetal circulation in late gestation. Note the selective blood flow patterns across the foramen ovale and the ductus arteriosus.

(From Miller RD: Miller’s Anesthesia, 6th ed. Philadelphia, Churchill Livingstone, 2005.)

3 What causes the ductus arteriosus to close after birth?

During life as a fetus, circulating prostaglandins and a low blood PO₂ keep the ductus arteriosus open. Blood PO₂ rises when breathing is initiated, signaling the newborn’s ability to obtain oxygenated blood from the lungs rather than from the umbilical vein. Along with rising PO₂, falling levels of prostaglandins act to close the ductus arteriosus. In the event that the ductus arteriosus remains patent after birth, it can often be closed by administering a drug that blocks the production of prostaglandin E₂, such as the COX inhibitor indomethacin. Alternatively, in the event that a baby is born with a congenital defect such as transposition of the great vessels, it is necessary to keep the ductus arteriosus open until the transposition can be surgically fixed. This can be achieved by administering alprostadil, a prostaglandin E₁ analog.

Case 26-3, Part B

It is a slow morning on your cardiology rotation when Rick, a 32-year-old man with a history of factor V Leiden and deep venous thrombosis (DVT), is brought by ambulance to the ED apparently suffering from a stroke. He has no history of atrial fibrillation, valvular disease, or MI. On cardiac auscultation, you hear a mild systolic ejection murmur and wide, fixed splitting of S₂. Neurology confirms that Rick has had an ischemic stroke, and a transesophageal echocardiogram (TEE) reveals interatrial blood flow.

4 What is the most likely diagnosis?

Atrial septal defect (ASD) is most likely. A thromboembolic stroke is relatively rare in patients without atrial fibrillation, valvular disease, or a past MI. Although factor V Leiden produces a hypercoagulable state, it is much more likely to cause DVT than a left-sided heart or arterial thrombus. The physical examination and TEE study findings strongly support ASD, so Rick’s stroke was most likely caused by a paradoxical embolus (in which an embolus of venous origin that traveled through the ASD and then to the cerebral vasculature).

5 Is atrial septal defect the most common congenital heart defect?

No. Ventricular septal defect (VSD) is the most common. ASD is the second most common congenital heart defect, and PDA is the third.

6 What are the three most common types of atrial septal defect?

1. Ostium secundum defect

Ostium secundum defect is the most common type of ASD. The atrial septum is formed by the septum primum and the septum secundum. In ostium secundum defect, there is usually excessive absorption of the septum primum, inadequate growth of the septum secundum, or enlargement of the foramen ovale (the opening at the inferior margin of the septum secundum). A subtype of ostium secundum defect is patent foramen ovale, in which the septum primum and septum secundum fail to fuse. This common defect may allow interatrial blood flow (note that this is physiologic in fetal life).

2. Ostium primum defect

In ostium primum defect, the septum primum fails to fuse with the endocardial (atrioventricular [AV]) cushion. This is often due to an endocardial cushion defect, commonly associated with Down syndrome. Note that the endocardial cushion is the point of fusion for the atrial septum, ventricular septum, mitral valve, and tricuspid valve, and the magnitude of the defect determines the pathology. For instance, partial ostium primum defect causes an interatrial connection, but complete ostium primum defect causes an AV connection.

3. Sinus venosus defect

Normally, the atrial septum develops completely to the left of the sinus venosus, the structure that is to become the superior and inferior venae cavae and part of the right atrium. In this rare defect, the septum develops anterior to the sinus venosus, allowing interatrial flow via the sinus venosus (Fig. 26-8).

Figure 26-8 Development of atrial septum. A, The septum primum (SP) grows down from the roof of the primitive common atrium to meet the atrioventricular cushions (AVCs) and divides the primitive common atrium into right atrium (RA) and left atrium (LA). The defect below the growing free lower edge of SP is called ostium primum (OP)—shown here as a dotted oval. The septum primum has reached the AVCs, which have developed into tricuspid (TV) and mitral (MV) valves. The drawing shows that the upper part of the SP has (normally) degenerated to leave the large ostium secundum (OS) or fossa ovale defect. B, A second interatrial septum—septum secundum (SS)—grows to the right of the SP. The upper portions of the two septa fuse and a portion of the upper part degenerates to form the OS. The lower edge of the SS grows downward to partially cover the OS but does not reach the AVCs. A valve-like opening—foramen ovale (FO)—is there by established, permitting a shunt from RA to LA but not in the reverse direction. The FO persists during fetal life (during which it transmits an essential right-to-left shunt), but after birth it usually seals off by fusion of the lower part of SP with SS. Note that the interventricular septum separates right ventricle (RV) from left ventricle (LV). The interventricular septum meets AVCs to the right of the atrial septum, so that one portion of the AVC separates RA from LV. This portion later forms the upper part of the interventricular septum, and it is through this portion that the Gerbode defect occurs.

(From Grainger RG, Allison D, Adams A: Grainger & Allison’s Diagnostic Radiology: A Textbook of Medical Imaging, 4th ed. Philadelphia, Churchill Livingstone, 2001.)