12 MSK

HIGH-YIELD SYSTEMS
Musculoskeletal, Skin,
and Connective Tissue
“Rigid, the skeleton of habit alone upholds the human frame.” ``Anatomy and
—Virginia Woolf Physiology 434
“Beauty may be skin deep, but ugly goes clear to the bone.” ``Pathology 448
—Redd Foxx
``Dermatology 461
“The function of muscle is to pull and not to push, except in the case of
the genitals and the tongue.” ``Pharmacology 470
—Leonardo da Vinci
“To thrive in life you need three bones. A wishbone. A backbone. And a
funny bone.”
—Reba McEntire
This chapter provides information you will need to understand certain

anatomical dysfunctions, rheumatic diseases, and dermatologic
conditions. Be able to interpret 3D anatomy in the context of radiologic
imaging. For the rheumatic diseases, create instructional cases or
personas that includes the most likely presentation and symptoms:
risk factors, gender, important markers (eg, autoantibodies), and other
epidemiologic factors. Doing so will allow you to answer the higher
order questions that are likely to be asked on the exam.
433
FAS1_2018_11-Musculo_indexed_435-474.indd 433 10/11/17 12:51 PM

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434 SECTION III Musculoskeletal, Skin, and Connec tive Tissue 

anatomy and physiology
MUSCULOSKELETAL, SKIN, AND CONNECTIVE TISSUE—ANATOMY AND PHYSIOLOGY

``
Arm abduction
DEGREE MUSCLE NERVE
0°–15° Supraspinatus Suprascapular
15°–100° Deltoid Axillary
> 90° Trapezius Accessory
> 100° Serratus Anterior Long Thoracic (SALT)
Rotator cuff muscles Shoulder muscles that form the rotator cuff: SItS (small t is for teres minor).
A
Supraspinatus (suprascapular nerve)—
Clavicle
abducts arm initially (before the action Supraspinatus
of the deltoid); most common rotator

Humerus Acromion
Glenoid cuff injury (trauma or degeneration and

impingement tendinopathy or tear [arrow Coracoid
in A ]), assessed by “empty/full can” test.

Greater
Infraspinatus (suprascapular nerve)— tubercle
Infraspinatus
externally rotates arm; pitching injury.
teres minor (axillary nerve)—adducts and Subscapularis
externally rotates arm. Humerus
Teres minor
Subscapularis (upper and lower subscapular Biceps tendon
nerves)—internally rotates and adducts arm.
Innervated primarily by C5-C6.
Overuse injuries of the elbow

Medial epicondylitis Repetitive flexion (forehand shots) or idiopathic pain near medial epicondyle.
(golfer’s elbow)
Lateral epicondylitis Repetitive extension (backhand shots) or idiopathic pain near lateral epicondyle.
(tennis elbow)

Musculoskeletal, Skin, and Connec tive Tissue 
anatomy and physiology SECTION III 435
Wrist region Scaphoid, Lunate, Triquetrum, A

B
Pisiform, Hamate, Capitate, Trapezoid,
Trapezium A . (So Long To Pinky, Here 1st MC
Comes The Thumb).
Scaphoid (palpable in anatomic snuff box B )
is the most commonly fractured carpal bone,
typically due to a fall on an outstretched hand.
Complications of proximal scaphoid fractures
include avascular necrosis and nonunion due
Radius Ulna
to retrograde blood supply. Fracture not always
seen on initial x-ray.
Dislocation of lunate may cause acute carpal
tunnel syndrome.
Metacarpal neck Also called boxer’s fracture. Common fracture
fracture caused by direct blow with a closed fist (eg,
from punching a wall or individual). Most
commonly seen in 4th and 5th metacarpals.
Carpal tunnel Entrapment of median nerve in carpal tunnel Suggested by ⊕ Tinel sign (percussion of wrist
syndrome (between transverse carpal ligament and carpal causes tingling) and Phalen maneuver (90°
C
bones); nerve compression paresthesia, pain, flexion of wrist causes tingling).
and numbness in distribution of median nerve. Associated with pregnancy (due to edema),
Thenar eminence atrophies C but sensation rheumatoid arthritis, hypothyroidism, diabetes,
spared, because palmar cutaneous branch acromegaly, dialysis-related amyloidosis; may
enters hand external to carpal tunnel. be associated with repetitive use.
Guyon canal Compression of ulnar nerve at wrist. Classically

syndrome seen in cyclists due to pressure from
handlebars.
Flexor retinaculum (transverse carpal ligament)
Ulnar artery Flexor digitorum
Ulnar nerve superficialis tendons
Palmar surface
Guyon canal Median nerve
Flexor carpi
radialis tendon
Hypothenar
eminence Thenar
eminence
Pisiform
Triquetrum Scaphoid
Capitate
Hamate
Plane of
section
Flexor pollicis
Flexor digitorum
longus tendon
profundus tendons
Carpal tunnel (with contents)

Normal
Common pediatric fractures
Greenstick fracture Incomplete fracture extending partway through A B
width of bone A following bending stress;
bone fails on tension side; compression side
Normal Greenstick fracture
intact (compare to torus fracture). Bone is bent
like a green twig.
Torus (buckle) fracture Axial force applied to immature bone cortex
buckles on compression side and fractures B .
Greenstick fracture
Tension side (other side Normal
of cortex) remains Torus fracture
intact.
Normal Greenstick fracture Torus fracture Complete fracture
Greenstick fracture Complete fracture

Torus fracture
Hand muscles Thenar (median)—Opponens pollicis, Abductor Both groups perform the same functions:
pollicis brevis, Flexor pollicis brevis, superficial Oppose, Abduct, and Flex (OAF).
Thenar Hypothenar head (deep head by ulnar nerve).
eminence eminence Hypothenar
Torus fracture (ulnar)—Opponens digiti minimi,
Complete fracture
Abductor digiti minimi, Flexor digiti minimi
brevis.
Dorsal interossei (ulnar)—abduct the fingers. DAB = Dorsals ABduct.
Palmarfracture
Complete interossei (ulnar)—adduct the fingers. PAD = Palmars ADduct.
Lumbricals (1st/2nd, median; 3rd/4th, ulnar)—
flex at the MCP joint, extend PIP and DIP
joints.

Upper extremity nerves

NERVE CAUSES OF INJURY PRESENTATION
Axillary (C5-C6) Fractured surgical neck of humerus Flattened deltoid
Anterior dislocation of humerus Loss of arm abduction at shoulder (> 15°)
Loss of sensation over deltoid muscle and lateral
arm
Musculocutaneous Upper trunk compression Loss of forearm flexion and supination
(C5-C7) Loss of sensation over lateral forearm
Radial (C5-T1) Compression of axilla, eg, due to crutches or Wrist drop: loss of elbow, wrist, and finger
sleeping with arm over chair (“Saturday night extension
palsy”) grip strength (wrist extension necessary for
Midshaft fracture of humerus maximal action of flexors)
Repetitive pronation/supination of forearm, eg, Loss of sensation over posterior arm/forearm and
due to screwdriver use (“finger drop”) dorsal hand
Median (C5-T1) Supracondylar fracture of humerus (proximal “Ape hand” and “Pope’s blessing”
lesion) Loss of wrist flexion, flexion of lateral fingers,
Carpal tunnel syndrome and wrist laceration thumb opposition, lumbricals of 2nd and 3rd
(distal lesion) digits
Loss of sensation over thenar eminence and
dorsal and palmar aspects of lateral 31⁄2 fingers
with proximal lesion
Ulnar (C8-T1) Fracture of medial epicondyle of humerus “Ulnar claw” on digit extension
“funny bone” (proximal lesion) Radial deviation of wrist upon flexion (proximal
Fractured hook of hamate (distal lesion) from lesion)
fall on outstretched hand Loss of wrist flexion, flexion of medial fingers,
abduction and adduction of fingers (interossei),
actions of medial 2 lumbrical muscles
Loss of sensation over medial 11/2 fingers
including hypothenar eminence
Recurrent branch of Superficial laceration of palm “Ape hand”
median nerve (C5-T1) Loss of thenar muscle group: opposition,
abduction, and flexion of thumb
No loss of sensation
Humerus fractures, proximally to distally, follow the ARM (Axillary Radial Median)
C5
Axillary nerve C6
C7
C8
T1
Median nerve
Axillary nerve
Musculocutaneous nerve Ulnar nerve
Intercostobrachial
Radial nerve nerve
Radial nerve Radial nerve
Medial brachial
cutaneous nerve Palm of hand
Median nerve Ulnar nerve

Musculocutaneous nerve Medial antebrachial
cutaneous nerve Median nerve
Radial nerve
Ulnar nerve
Recurrent branch Radial nerve
of median nerve Radial nerve
Dorsum of hand

Brachial plexus lesions

Erb palsy (“waiter’s tip”) C5 Upper Lateral Randy
Klumpke palsy (claw hand) Musculocutaneous Travis
Wrist drop C6 Drinks
Axillary
Winged scapula
Middle Posterior Cold
Deltoid paralysis C7 (Extensors) Median (flexors) Beer
“Saturday night palsy” (wrist drop)
Difficulty flexing elbow, variable Radial
C8 Lower Medial
sensory loss
Decreased thumb function, Ulnar
“Pope’s blessing” T1
Trunks Divisions Cords Branches
Intrinsic muscles of hand,
claw hand
Long thoracic
Roots
Erb-Duchenne palsy
CONDITION INJURY CAUSES MUSCLE DEFICIT FUNCTIONAL DEFICIT PRESENTATION
(”waiter’s tip”)
Erb palsy (“waiter’s Traction or Infants—lateral Deltoid, Abduction (arm
tip”) tear of upper traction on neck supraspinatus hangs by side)
(“Erb-er”) trunk: during delivery Infraspinatus Lateral rotation (arm
C5-C6 roots Adults—trauma medially rotated)
Biceps brachii Flexion, supination
(arm extended and
pronated)
Klumpke palsy Traction or tear Infants—upward Intrinsic hand Total claw hand:
of lower trunk: force on arm muscles: lumbricals normally
C8-T1 root during delivery lumbricals, flex MCP joints and
Adults—trauma interossei, extend DIP and PIP
(eg, grabbing a thenar, joints
tree branch to hypothenar
break a fall)
Thoracic outlet Compression Cervical rib Same as Klumpke Atrophy of intrinsic A
syndrome of lower trunk (arrows in A ), palsy hand muscles; C5
and subclavian Pancoast tumor ischemia, pain, C6

C7
vessels and edema T1
due to vascular
compression
Winged scapula Lesion of long Axillary node Serratus anterior Inability to anchor B
thoracic nerve, dissection after scapula to thoracic
roots C5-C7 mastectomy, cage cannot
(“wings of stab wounds abduct arm
heaven”) above horizontal
position B

Distortions of the hand At rest, a balance exists between the extrinsic flexors and extensors of the hand, as well as the
intrinsic muscles of the hand—particularly the lumbrical muscles (flexion of MCP, extension of
DIP and PIP joints).
“Clawing”—seen best with distal lesions of median or ulnar nerves. Remaining extrinsic flexors
of the digits exaggerate the loss of the lumbricals fingers extend at MCP, flex at DIP and PIP
joints.
Deficits less pronounced in proximal lesions; deficits present during voluntary flexion of the digits.
PRESENTATION
CONTEXT Extending fingers/at Making a fist Extending fingers/at Making a fist

rest rest
LOCATION OF LESION Distal ulnar nerve Proximal median Distal median nerve Proximal ulnar nerve
nerve
SIGN “Ulnar claw” “Pope’s blessing” “Median claw” “OK gesture”
Note: Atrophy of the thenar eminence (unopposable thumb “ape hand”) can be seen in median nerve lesions, while
atrophy of the hypothenar eminence can be seen in ulnar nerve lesions.

Knee exam Lateral femoral condyle to anterior tibia: ACL. Femur
Medial femoral condyle to posterior tibia: PCL.

LAMP. Lateral
condyle
Medial
condyle
ACL PCL
LCL MCL
Lateral Medial
meniscus meniscus
Fibula Tibia
TEST PROCEDURE
Anterior drawer sign Bending knee at 90° angle, anterior gliding

of tibia (relative to femur) due to ACL injury. ACL tear
Lachman test also tests ACL, but is more Anterior drawer sign
sensitive ( anterior gliding of tibia [relative to
femur] with knee bent at 30° angle).
Posterior drawer sign Bending knee at 90° angle, posterior gliding of
tibia due to PCL injury.
PCL tear
Posterior drawer sign
Abnormal passive Knee either extended or at ∼ 30° angle, lateral

Abduction
abduction (valgus) force medial space widening of (valgus)
MCL tear
tibia MCL injury. force
Abnormal passive Knee either extended or at ~ 30° angle, medial

Adduction
adduction (varus) force lateral space widening of tibia (varus) LCL tear
LCL injury. force
McMurray test During flexion and extension of knee with

rotation of tibia/foot: External Medial tear
Pain, “popping” on external rotation rotation
medial meniscal tear (external rotation

Lateral tear
stresses medial meniscus) Internal
Pain, “popping” on internal rotation rotation
lateral meniscal tear (internal rotation

stresses lateral meniscus)

Common hip and knee conditions

Trochanteric bursitis Inflammation of the gluteal tendon and bursa lateral to greater trochanter of femur. Treat pain with
NSAIDs, heat, stretching.
“Unhappy triad” Common injury in contact sports due to lateral force applied to a planted leg. Classically, consists
of damage to the ACL A , MCL, and medial meniscus (attached to MCL); however, lateral
meniscus injury is more common. Presents with acute knee pain and signs of joint injury/
Lateral instability.
force ACL
LCL
MCL
PCL
Medial
meniscus
Right knee
Prepatellar bursitis Inflammation of the prepatellar bursa in front of the kneecap (red arrow in B ). Can be caused by
repeated trauma or pressure from excessive kneeling (also called “housemaid’s knee”).
Baker cyst Popliteal fluid collection (red arrow in C ) in gastrocnemius-semimembranosus bursa commonly
communicating with synovial space and related to chronic joint disease (eg, osteoarthritis,
rheumatoid arthritis).
A B C
Fem
Pat Fem Fem Fem
(lat cond) (med cond)
L Tib
AC Ant meniscus
Post meniscus
Tib Pop a
Ankle sprains Anterior TaloFibular ligament—most common ankle sprain overall, classified as a low ankle sprain.
Due to overinversion/supination of foot. Always Tears First.
Anterior inferior tibiofibular ligament—most common high ankle sprain.
Fibula Anterior inferior

tibiofibular ligament
Tibia
Posterior inferior Anterior talofibular
tibiofibular ligament ligament
Navicular
Posterior talofibular Cuneiform bones
ligament
Talus
Calcaneus Cuboid
Calcanofibular
ligament
Tarsals Metatarsals Phalanges

Lower extremity nerves

NERVE INNERVATION CAUSE OF INJURY PRESENTATION/COMMENTS
Iliohypogastric Sensory—suprapubic region Abdominal surgery Burning or tingling pain in
(T12-L1) Motor—transversus abdominis surgical incision site radiating
and internal oblique to inguinal and suprapubic
region
Genitofemoral nerve Sensory—scrotum/labia Laparoscopic surgery anterior thigh sensation
(L1-L2) majora, medial thigh beneath inguinal ligament;
Motor—cremaster absent cremasteric reflex
Lateral femoral Sensory—anterior and lateral Tight clothing, obesity, thigh sensation (anterior and
cutaneous (L2-L3) thigh pregnancy, pelvic procedures lateral)
Obturator (L2-L4) Sensory—medial thigh Pelvic surgery thigh sensation (medial) and
Motor—obturator externus, adduction
adductor longus, adductor
brevis, gracilis, pectineus,
adductor magnus
Femoral (L2-L4) Sensory—anterior thigh, Pelvic fracture thigh flexion and leg
medial leg extension
Motor—quadriceps, iliacus,
pectineus, sartorius
Sciatic (L4-S3) Motor—semitendinosus, Herniated disc, posterior hip Splits into common peroneal
semimembranosus, biceps dislocation and tibial nerves
femoris, adductor magnus
Common peroneal Superficial peroneal nerve: Trauma or compression of PED = Peroneal Everts and
(L4-S2) Sensory—dorsum of foot lateral aspect of leg, fibular Dorsiflexes; if injured, foot
(except webspace between neck fracture dropPED
hallux and 2nd digit) Loss of sensation on dorsum
Motor—peroneus longus of foot
and brevis Foot drop—inverted and
Deep peroneal nerve: plantarflexed at rest, loss of
Sensory—webspace eversion and dorsiflexion;
between hallux and 2nd “steppage gait”
digit
Motor—tibialis anterior
Tibial (L4-S3) Sensory—sole of foot Knee trauma, Baker cyst TIP = Tibial Inverts and
Motor—biceps femoris (long (proximal lesion); tarsal Plantarflexes; if injured, can’t
head), triceps surae, plantaris, tunnel syndrome (distal stand on TIPtoes
popliteus, flexor muscles of lesion) Inability to curl toes and loss of
foot sensation on sole; in proximal
lesions, foot everted at rest
with loss of inversion and
plantarflexion

Lower extremity nerves (continued)

NERVE INNERVATION CAUSE OF INJURY PRESENTATION/COMMENTS
Superior gluteal Motor—gluteus medius, gluteus Iatrogenic injury during Trendelenburg sign/gait—
(L4‑S1) minimus, tensor fascia latae intramuscular injection pelvis tilts because weight-
Trendelenburg
to superomedial gluteal bearing leg cannot maintain
Normal sign region (prevent by choosing alignment of pelvis through
superolateral quadrant, hip abduction
preferably anterolateral Lesion is contralateral to the
region) side of the hip that drops,
ipsilateral to extremity on
which the patient stands
Inferior gluteal (L5-S2) Motor—gluteus maximus Posterior hip dislocation Difficulty climbing stairs, rising
from seated position; loss of
hip extension
Pudendal (S2-S4) Sensory—perineum Stretch injury during childbirth sensation in perineum and
Motor—external urethral and genital area; can cause fecal
anal sphincters or urinary incontinence
Can be blocked with local
anesthetic during childbirth
using ischial spine as a
landmark for injection
Actions of hip muscles

ACTION MUSCLES
Abductors Gluteus medius, gluteus minimus
Adductors Adductor magnus, adductor longus, adductor brevis
Extensors Gluteus maximus, semitendinosus, semimembranosus
Flexors Iliopsoas, rectus femoris, tensor fascia lata, pectineus, sartorius
Internal rotation Gluteus medius, gluteus minimus, tensor fascia latae
External rotation Iliopsoas, gluteus maximus, piriformis, obturator

Common musculoskeletal conditions

Iliotibial band Overuse injury of lateral knee that occurs primarily in runners. Pain develops 2° to friction of
syndrome iliotibial band against lateral femoral epicondyle.
Medial tibial stress Also called shin splints. Common cause of shin pain and diffuse tenderness in runners and military
syndrome recruits. Caused by bone resorption that outpaces bone formation in tibial cortex.
Limb compartment pressure within a fascial compartment of a limb (defined by compartment pressure to diastolic
syndrome blood pressure gradient of < 30 mm Hg) venous outflow obstruction and arteriolar collapse
anoxia and necrosis. Causes include significant long bone fractures, reperfusion injury, animal
venoms. Presents with severe pain and tense, swollen compartments with limb flexion. Motor
deficits are late sign of irreversible muscle and nerve damage.
Plantar fasciitis Inflammation of plantar aponeurosis characterized by heel pain (worse with first steps in the
morning or after period of inactivity) and tenderness.
De Quervain Noninflammatory thickening of abductor pollicis longus and extensor pollicis brevis tendons
tenosynovitis characterized by pain or tenderness at radial styloid. ⊕ Finkelstein test (pain at radial styloid with
active or passive stretch of thumb tendons).
Ganglion cyst Fluid-filled swelling overlying joint or tendon sheath, most commonly at dorsal side of wrist. Arises
from herniation of dense connective tissue.
Childhood musculoskeletal conditions

Developmental Abnormal acetabulum development in newborns. Results in hip instability/dislocation. Commonly
dysplasia of the hip tested with Ortolani and Barlow maneuvers (manipulation of newborn hip reveals a “clunk”).
Confirmed via ultrasound (x-ray not used until ~4–6 months because cartilage is not ossified).
Treatment: splint/harness.
Legg-Calvé-Perthes Idiopathic avascular necrosis of femoral head. Commonly presents between 5–7 years with
disease insidious onset of hip pain that may cause child to limp. More common in males (4:1 ratio). Initial
x-ray often normal.
Slipped capital Classically presents in an obese ~12-year-old child with hip/knee pain and altered gait. Increased
femoral epiphysis axial force on femoral head epiphysis displaces relative to femoral neck (like a scoop of ice
cream slipping off a cone). Diagnosed via x-ray. Treatment: surgery.
Osgood-Schlatter Overuse injury caused by repetitive strain and chronic avulsion of the secondary ossification center
disease (traction of proximal tibial tubercle. Occurs in adolescents after growth spurt. Common in running and
apophysitis) jumping athletes. Presents with progressive anterior knee pain.
Radial head Common elbow injury in children < 5 years. Caused by a sudden pull on the arm immature
subluxation annular ligament slips over head of radius. Injured arm held in flexed and pronated position.
(nursemaid’s elbow)

Signs of lumbosacral Paresthesia and weakness related to specific Intervertebral discs generally herniate
radiculopathy lumbosacral spinal nerves. Usually, the posterolaterally, due to the thin posterior
intervertebral disc herniates into central canal, longitudinal ligament and thicker anterior
affecting the inferior nerves (eg, herniation of longitudinal ligament along the midline of the
L3/4 disc affects L4 spinal nerve, but not L3). vertebral bodies.
SPINAL LEVEL FINDINGS
L3–L4 Weakness of knee extension, patellar reflex
L4–L5 Weakness of dorsiflexion, difficulty in heel-
walking
L5-S1 Weakness of plantar flexion, difficulty in toe-
walking, Achilles reflex
Neurovascular pairing Nerves and arteries are frequently named together by the bones/regions with which they are
associated. The following are exceptions to this naming convention.
LOCATION NERVE ARTERY
Axilla/lateral thorax Long thoracic Lateral thoracic
Surgical neck of humerus Axillary Posterior circumflex
Midshaft of humerus Radial Deep brachial
Distal humerus/ cubital fossa Median Brachial
Popliteal fossa Tibial Popliteal
Posterior to medial malleolus Tibial Posterior tibial

Motoneuron action T-tubules are extensions of plasma membrane in contact with the sarcoplasmic reticulum, allowing
potential to muscle for coordinated contraction of striated muscles.
contraction
ction potential opens presynaptic voltage-
A
Myelin sheath
gated Ca2+ channels, inducing acetylcholine
(ACh) release.
Action potential
Postsynaptic ACh binding leads to muscle
Q Axon
Ca2+ cell depolarization at the motor end plate.
ACh vesicle
Depolarization travels over the entire
Action potential muscle cell and deep into the muscle via the
R ACh S T-tubules.
AChR Membrane depolarization induces
Motor end plate conformational changes in the voltage-
DHPR
sensitive dihydropyridine receptor (DHPR)
T
Sarcoplasmic
and its mechanically coupled ryanodine
Ca2+ Ca2+
reticulum receptor (RR) Ca2+ release from the
RR
sarcoplasmic reticulum into the cytoplasm.
T-tubule Tropomyosin is blocking myosin-binding
sites on the actin filament. Released
Ca2+ binds to troponin C (TnC), shifting
U Ca
2+
TnC tropomyosin to expose the myosin-binding
Actin Tropomyosin
sites.
The myosin head binds strongly to actin,
Ca2+ Y ADP P i
forming a crossbridge. Pi is then released,
initiating the power stroke.
Myosin
Cocked
During the power stroke, force is produced
Myosin-binding site as myosin pulls on the thin filament. Muscle
shortening occurs, with shortening of H
ATP
X V
ADP Pi
and I bands and between Z lines (HIZ
W
shrinkage). The A band remains the same
Detached Crossbridge length (A band is Always the same length).
ADP ADP is released at the end of the power
ATP Pi
stroke.
ADP
Power stroke Binding of new ATP molecule causes
detachment of myosin head from actin
filament. Ca2+ is resequestered.
ATP hydrolysis into ADP and Pi results
in myosin head returning to high-energy
position (cocked). The myosin head can bind
to a new site on actin to form a crossbridge if
Ca2+ remains available.

Types of muscle fibers

Type 1 muscle Slow twitch; red fibers resulting from Think “1 slow red ox.”
mitochondria and myoglobin concentration
( oxidative phosphorylation) sustained
contraction. Proportion after endurance
training.
Type 2 muscle Fast twitch; white fibers resulting from
mitochondria and myoglobin concentration
( anaerobic glycolysis). Proportion after
weight/resistance training, sprinting.
Smooth muscle contraction and relaxation
Agonist Acetylcholine,
bradykinin, etc
Endothelial cells
Receptor
Ca2+
Ca2+
NO synthase
L-arginine NO
L-type voltage Ca
2+
Smooth muscle cell NO diffusion
gated Ca 2+
channel
Action
potential – ↑ Ca2+
NO
–
–
ne n ↑ Ca2+–calmodulin GTP cGMP
bra atio
em lariz complex
Myosin
o
de M
+ actin
p
Myosin–light-chain Myosin–light-chain
kinase phosphatase
(MLCK) Myosin-P (MLCP)
+ actin
CONTRACTION RELAXATION
↑ Ca2+ CONTRACTION Nitric oXide RELAXATION
Bone formation
Endochondral Bones of axial skeleton, appendicular skeleton, and base of skull. Cartilaginous model of bone is
ossification first made by chondrocytes. Osteoclasts and osteoblasts later replace with woven bone and then
remodel to lamellar bone. In adults, woven bone occurs after fractures and in Paget disease.
Defective in achondroplasia.
Membranous Bones of calvarium, facial bones, and clavicle. Woven bone formed directly without cartilage. Later
ossification remodeled to lamellar bone.

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Pathology
Cell biology of bone

Osteoblast Builds bone by secreting collagen and catalyzing mineralization in alkaline environment via ALP.
Differentiates from mesenchymal stem cells in periosteum. Osteoblastic activity measured by
bone ALP, osteocalcin, propeptides of type I procollagen.
Osteoclast Dissolves (“crushes”) bone by secreting H+ and collagenases. Differentiates from a fusion of
monocyte/macrophage lineage precursors. RANK receptors on osteoclasts are stimulated
by RANKL (RANK ligand, secreted by osteoblasts). RANK receptors blocked by OPG
(osteoprotegerin, a RANKL decoy receptor) osteoclast activity.
Parathyroid hormone At low, intermittent levels, exerts anabolic effects (building bone) on osteoblasts and osteoclasts
(indirect). Chronically PTH levels (1° hyperparathyroidism) cause catabolic effects (osteitis
fibrosa cystica).
Estrogen Inhibits apoptosis in bone-forming osteoblasts and induces apoptosis in bone-resorbing
osteoclasts. Causes closure of epiphyseal plate during puberty. Estrogen deficiency (surgical or
postmenopausal) cycles of remodeling and bone resorption risk of osteoporosis.
MUSCULOSKELETAL, SKIN, AND CONNECTIVE TISSUE—PATHOLOGY

``
Achondroplasia Failure of longitudinal bone growth (endochondral ossification) short limbs. Membranous
ossification is affected large head relative to limbs. Constitutive activation of fibroblast growth
factor receptor (FGFR3) actually inhibits chondrocyte proliferation. > 85% of mutations occur
sporadically; autosomal dominant with full penetrance (homozygosity is lethal). Associated with
paternal age. Most common cause of dwarfism.

Pathology SECTION III 449
Osteoporosis Trabecular (spongy) and cortical bone lose mass Can lead to vertebral compression
expansion Restricted Normal Normal and interconnections despite normal bone fractures A —acute back pain, loss of height,
ertebral intervertebral
foramen
intervertebral
disc
intervertebral
foramen
mineralization and lab values (serum Ca2+ and kyphosis. Also can present with fractures of
PO43−). femoral neck, distal radius (Colles fracture).
Most commonly due to bone resorption related A
to estrogen levels and old age. Can be 2° to
drugs (eg, steroids, alcohol, anticonvulsants,
d compression fracture Normal vertebrae anticoagulants, thyroid replacement
therapy) or other medical conditions (eg,
Central expansion Restricted Normal Normal
of intervertebral intervertebral hyperparathyroidism,
intervertebral hyperthyroidism,
intervertebral
disc foramen disc foramen
multiple myeloma, malabsorption syndromes).
Diagnosed by bone mineral density
measurement by DEXA (dual-energy X-ray
absorptiometry) at the lumbar spine, total hip,
Mild compression fracture and femoral neck, with a T-score of ≤ −2.5 or
Normal vertebrae
by a fragility fracture (eg, fall from standing
height, minimal trauma) at hip or vertebra.
One time screening recommended in women
≥ 65 years old.
Prophylaxis: regular weight-bearing exercise
and adequate Ca2+ and vitamin D intake
throughout adulthood.
Treatment: bisphosphonates, teriparatide,
SERMs, rarely calcitonin; denosumab
(monoclonal antibody against RANKL).
Osteopetrosis Failure of normal bone resorption due to defective osteoclasts thickened, dense bones that are
A prone to fracture. Mutations (eg, carbonic anhydrase II) impair ability of osteoclast to generate
acidic environment necessary for bone resorption. Overgrowth of cortical bone fills marrow space
pancytopenia, extramedulla ry hematopoiesis. Can result in cranial nerve impingement and
palsies due to narrowed foramina.
X-rays show diffuse symmetric sclerosis (bone-in-bone, “stone bone” A ). Bone marrow transplant is
potentially curative as osteoclasts are derived from monocytes.

Pathology
Osteomalacia/rickets Defective mineralization of osteoid B

A (osteomalacia) or cartilaginous growth plates
(rickets, only in children). Most commonly due
to vitamin D deficiency.
X-rays show osteopenia and “Looser zones”
(pseudofractures) in osteomalacia, epiphyseal
widening and metaphyseal cupping/fraying in
rickets. Children with rickets have pathologic
bow legs (genu varum A ), bead-like
costochondral junctions (rachitic rosary B ),
craniotabes (soft skull).
vitamin D serum Ca2+ PTH
secretion serum PO43−.
Hyperactivity of osteoblasts ALP.
Paget disease of bone Common, localized disorder of bone Hat size can be increased due to skull
(osteitis deformans) remodeling caused by osteoclastic activity thickening A ; hearing loss is common due to
A
followed by osteoblastic activity that forms auditory foramen narrowing.
poor-quality bone. Serum Ca2+, phosphorus, Stages of Paget disease:
and PTH levels are normal. ALP. Mosaic Lytic—osteoclasts
pattern of woven and lamellar bone (osteocytes Mixed—osteoclasts + osteoblasts
within lacunae in chaotic juxtapositions); long Sclerotic—osteoblasts
bone chalk-stick fractures. blood flow from Quiescent—minimal osteoclast/osteoblast
arteriovenous shunts may cause high-output activity
heart failure. risk of osteogenic sarcoma. Treatment: bisphosphonates.
Osteonecrosis Infarction of bone and marrow, usually very Branch of

Watershed
zone (infarcted)
(avascular necrosis) painful. Most common site is femoral obturator artery
A
head (watershed zone) A (due to insufficiency
of medial circumflex femoral artery). Causes
Medial femoral
include Corticosteroids, Alcoholism, Sickle circumflex
cell disease, Trauma, “the Bends” (caisson/ artery (posterior)
decompression disease), LEgg-Calvé-Perthes Lateral femoral
disease (idiopathic), Gaucher disease, Slipped circumflex
artery (anterior)
capital femoral epiphysis—CAST Bent LEGS.

Lab values in bone disorders

DISORDER SERUM Ca2+ PO 43− ALP PTH COMMENTS
Osteoporosis — — — — bone mass
Osteopetrosis —/ — — — Dense, brittle bones. Ca2+ in severe,
malignant disease
Paget disease of bone — — — Abnormal “mosaic” bone architecture
Osteitis fibrosa cystica “Brown tumors” due to fibrous replacement of
bone, subperiosteal thinning
Primary Idiopathic or parathyroid hyperplasia, adenoma,
hyperparathyroidism carcinoma
Secondary Often as compensation for CKD ( PO43−
hyperparathyroidism excretion and production of activated
vitamin D)
Osteomalacia/rickets Soft bones; vitamin D deficiency also causes 2°
hyperparathyroidism
Hypervitaminosis D — Caused by oversupplementation or
granulomatous disease (eg, sarcoidosis)
= 1° change.

Pathology
Primary bone tumors Metastatic disease is more common than 1° bone tumors.
TUMOR TYPE EPIDEMIOLOGY LOCATION CHARACTERISTICS
Benign tumors
Osteochondroma Most common benign Metaphysis of long bones. Lateral bony projection of growth
bone tumor. plate (continuous with marrow space)
Males < 25 years old. covered by cartilaginous cap A .
Rarely transforms to chondrosarcoma.
Osteoma Middle age. Surface of facial bones. Associated with Gardner syndrome.
Osteoid osteoma Adults < 25 years old. Cortex of long bones. Presents as bone pain (worse at night)
Males > females. that is relieved by NSAIDs.
Bony mass (< 2 cm) with radiolucent
osteoid core.
Osteoblastoma Vertebrae. Similar histology to osteoid osteoma.

Larger size (> 2 cm), pain unresponsive
to NSAIDs.
Chondroma Medulla of small bones of Benign tumor of cartilage.
hand and feet.
Giant cell tumor 20–40 years old. Epiphysis of long bones Locally aggressive benign tumor.
(often in knee region). Neoplastic mononuclear cells that
express RANKL and reactive
multinucleated giant (osteoclast-like)
cells. “Osteoclastoma.”
“Soap bubble” appearance on x-ray B .
Malignant tumors
Osteosarcoma Accounts for 20% of 1° Metaphysis of long bones Pleomorphic osteoid-producing cells
(osteogenic sarcoma) bone cancers. (often in knee region) C . (malignant osteoblasts).
Peak incidence of 1° Presents as painful enlarging mass or
tumor in males < 20 pathologic fractures.
years. Codman triangle (from elevation of
Less common in periosteum) or sunburst pattern on
elderly; usually 2° to x-ray. Think of an osteocod (bone
predisposing factors, fish) swimming in the sun.
such as Paget disease Aggressive. 1° usually responsive to
of bone, bone infarcts, treatment (surgery, chemotherapy),
radiation, familial poor prognosis for 2°.
retinoblastoma,
Li-Fraumeni syndrome.
Chondrosarcoma Medulla of pelvis and central Tumor of malignant chondrocytes.
skeleton.

Primary bone tumors (continued)

TUMOR TYPE EPIDEMIOLOGY LOCATION CHARACTERISTICS
Ewing sarcoma Most common in Diaphysis of long bones Anaplastic small blue cells of
Caucasians. Generally (especially femur), pelvic neuroectodermal origin (resemble
boys < 15 years old. flat bones. lymphocytes) D .
Differentiate from conditions with
similar morphology (eg, lymphoma,
chronic osteomyelitis) by testing for
t(11;22) (fusion protein EWS-FLI1).
“Onion skin” periosteal reaction in
bone.
Aggressive with early metastases, but
responsive to chemotherapy.
11 + 22 = 33 (Patrick Ewing’s jersey
number).
A B
Round cell lesions

Ewing sarcoma
Diaphysis
Myeloma
Fibrous dysplasia
Osteoid osteoma
C D
Simple bone cyst
Epiphysis Metaphysis
Osteosarcoma
Osteochondroma
Physis
Giant cell tumor


Pathology
Osteoarthritis and rheumatoid arthritis

Osteoarthritis Rheumatoid arthritis
PATHOGENESIS Mechanical—wear and tear destroys articular Autoimmune—inflammation induces formation
cartilage (degenerative joint disorder) of pannus (proliferative granulation tissue A ),
inflammation with inadequate repair. which erodes articular cartilage and bone.
Chondrocytes mediate degradation and
inadequate repair.
PREDISPOSING FACTORS Age, female, obesity, joint trauma. Female, HLA-DR4 (4-walled “rheum”),
smoking. ⊕ rheumatoid factor (IgM antibody
that targets IgG Fc region; in 80%), anti-cyclic
citrullinated peptide antibody (more specific).
PRESENTATION Pain in weight-bearing joints after use (eg, Pain, swelling, and morning stiffness lasting
at the end of the day), improving with rest. > 1 hour, improving with use. Symmetric
Asymmetric joint involvement. Knee cartilage joint involvement. Systemic symptoms
loss begins medially (“bowlegged”). No (fever, fatigue, weight loss). Extraarticular
systemic symptoms. manifestations common.*
JOINT FINDINGS Osteophytes (bone spurs), joint space narrowing, Erosions, juxta-articular osteopenia, soft tissue
subchondral sclerosis and cysts. Synovial swelling, subchondral cysts, joint space
fluid noninflammatory (WBC < 2000/mm3). narrowing. Deformities: cervical subluxation,
Involves DIP (Heberden nodes B ) and PIP ulnar finger deviation, swan neck D ,
(Bouchard nodes C ), and 1st CMC; not MCP. boutonniere E . Involves MCP, PIP, wrist; not
DIP or 1st CMC. Synovial fluid inflammatory.
TREATMENT Acetaminophen, NSAIDs, intra-articular NSAIDs, glucocorticoids, disease-modifying
glucocorticoids. agents (methotrexate, sulfasalazine,
hydroxychloroquine, leflunomide), biologic
agents (eg, TNF-α inhibitors).
*Extraarticular manifestations include rheumatoid nodules (fibrinoid necrosis with palisading histiocytes) in subcutaneous
tissue and lung (+ pneumoconiosis Caplan syndrome), interstitial lung disease, pleuritis, pericarditis, anemia of chronic
disease, neutropenia + splenomegaly (Felty syndrome), AA amyloidosis, Sjögren syndrome, scleritis, carpal tunnel syndrome.
Normal Osteoarthritis Normal Rheumatoid
arthritis
Thickened
capsule Bone and
cartilage
Slight synovial
Joint capsule Joint capsule erosion
hypertrophy
and synovial and synovial
lining Osteophyte lining
Increased
Synovial Ulcerated Synovial synovial fluid
cavity cartilage cavity Pannus
Sclerotic bone Cartilage formation
Cartilage
Joint space
narrowing
Subchondral
bone cyst
A B C D E

Gout
FINDINGS Acute inflammatory monoarthritis caused by precipitation of monosodium urate crystals in
joints A . Risk factors: male sex, hypertension, obesity, diabetes, dyslipidemia. Strongest risk factor
is hyperuricemia, which can be caused by:
Underexcretion of uric acid (90% of patients)—largely idiopathic, potentiated by renal failure;
can be exacerbated by certain medications (eg, thiazide diuretics).
Overproduction of uric acid (10% of patients)—Lesch-Nyhan syndrome, PRPP excess, cell
turnover (eg, tumor lysis syndrome), von Gierke disease.
Crystals are needle shaped and ⊝ birefringent under polarized light (yellow under parallel light,
blue under perpendicular light B ).
SYMPTOMS Asymmetric joint distribution. Joint is swollen, red, and painful. Classic manifestation is painful
MTP joint of big toe (podagra). Tophus formation C (often on external ear, olecranon bursa,
or Achilles tendon). Acute attack tends to occur after a large meal with foods rich in purines
(eg, red meat, seafood), trauma, surgery, dehydration, diuresis, or alcohol consumption (alcohol
metabolites compete for same excretion sites in kidney as uric acid uric acid secretion and
subsequent buildup in blood).
TREATMENT Acute: NSAIDs (eg, indomethacin), glucocorticoids, colchicine.
Chronic (preventive): xanthine oxidase inhibitors (eg, allopurinol, febuxostat).
A B C
Calcium Previously called pseudogout. Deposition of The blue P’s—blue (when Parallel), Positive
pyrophosphate calcium pyrophosphate crystals within the birefringent, calcium Pyrophosphate, Pseudogout
deposition disease joint space. Occurs in patients > 50 years old;
both sexes affected equally. Usually idiopathic,
A
sometimes associated with hemochromatosis,
hyperparathyroidism, joint trauma.
Pain and swelling with acute inflammation
(pseudogout) and/or chronic degeneration
(pseudo-osteoarthritis). Knee most commonly
affected joint.
Chondrocalcinosis (cartilage calcification) on
x-ray.
Crystals are rhomboid and weakly ⊕
birefringent under polarized light (blue when
parallel to light) A .
Acute treatment: NSAIDs, colchicine,
glucocorticoids.
Prophylaxis: colchicine.

Pathology
Systemic juvenile Childhood arthritis seen in < 12 year olds. Usually presents with daily spiking fevers, salmon-pink
idiopathic arthritis macular rash, uveitis, and arthritis (commonly 2+ joints). Frequently presents with leukocytosis,
thrombocytosis, anemia, ESR, CRP. Treatment: NSAIDs, steroids, methotrexate, TNF
inhibitors.
Sjögren syndrome Autoimmune disorder characterized by A common 1° disorder or a 2° syndrome

A
destruction of exocrine glands (especially associated with other autoimmune disorders
lacrimal and salivary) by lymphocytic (eg, rheumatoid arthritis, SLE, systemic
infiltrates A . Predominantly affects women sclerosis).
40–60 years old. Complications: dental caries; mucosa-associated
Findings: lymphoid tissue (MALT) lymphoma (may
Inflammatory joint pain present as parotid enlargement).
Keratoconjunctivitis sicca ( tear production Focal lymphocytic sialadenitis on labial salivary
and subsequent corneal damage) gland biopsy can confirm diagnosis.
B Xerostomia ( saliva production B )
Presence of antinuclear antibodies,
rheumatoid factor (can be in the absence of
rheumatoid arthritis), antiribonucleoprotein
antibodies: SS-A (anti-Ro) and/or SS-B (anti-
La)
Bilateral parotid enlargement
Anti-SSA and anti-SSB may also be seen in
SLE. ⊕ Anti-SSA in pregnant women with
SLE risk of congenital heart block in the
newborn.
Septic arthritis S aureus, Streptococcus, and Neisseria gonorrhoeae are common causes. Affected joint is swollen A ,
A
red, and painful. Synovial fluid purulent (WBC > 50,000/mm3).
Gonococcal arthritis—STI that presents as either purulent arthritis (eg, knee) or triad of
polyarthralgia, tenosynovitis (eg, hand), dermatitis (eg, pustules).

Seronegative Arthritis without rheumatoid factor (no anti-IgG antibody). Strong association with HLA-B27
spondyloarthritis (MHC class I serotype). Subtypes (PAIR) share variable occurrence of inflammatory back
pain (associated with morning stiffness, improves with exercise), peripheral arthritis, enthesitis
(inflamed insertion sites of tendons, eg, Achilles), dactylitis (“sausage fingers”), uveitis.
Psoriatic arthritis Associated with skin psoriasis and nail lesions. Seen in fewer than 1 ⁄3 of patients with psoriasis.
Asymmetric and patchy involvement A .
Dactylitis and “pencil-in-cup” deformity of
DIP on x-ray B .
Ankylosing Symmetric involvement of spine and sacroiliac Bamboo spine (vertebral fusion) C . Can cause
spondylitis joints ankylosis (joint fusion), uveitis, aortic restrictive lung disease due to limited chest
regurgitation. wall expansion (costovertebral and costosternal
ankylosis).
More common in males.
Inflammatory bowel Crohn disease and ulcerative colitis are often
disease associated with spondyloarthritis.
Reactive arthritis Formerly known as Reiter syndrome. “Can’t see, can’t pee, can’t bend my knee.”
Classic triad: Shigella, Yersinia, Chlamydia, Campylobacter,
Conjunctivitis Salmonella (ShY ChiCS).
Urethritis
Arthritis
A B C

Pathology
Systemic lupus Systemic, remitting, and relapsing autoimmune disease. Organ damage primarily due to a type III
erythematosus hypersensitivity reaction and, to a lesser degree, a type II hypersensitivity reaction. Associated with
deficiency of early complement proteins (eg, C1q, C4, C2) clearance of of immune complexes.
Classic presentation: rash, joint pain, and fever in a female of reproductive age (especially of
African-American or Hispanic descent).
A Libman-Sacks Endocarditis—nonbacterial, RASH OR PAIN:
verrucous thrombi usually on mitral or aortic Rash (malar A or discoid B )
valve and can be present on either surface of Arthritis (nonerosive)
the valve (but usually on undersurface). LSE Serositis (eg, pleuritis, pericarditis)
in SLE. Hematologic disorders (eg, cytopenias)
Lupus nephritis (glomerular deposition of Oral/nasopharyngeal ulcers (usually painless)
DNA-anti-DNA immune complexes) can be Renal disease
nephritic or nephrotic (causing hematuria or Photosensitivity
B proteinuria). Most common and severe type is Antinuclear antibodies
diffuse proliferative. Immunologic disorder (anti-dsDNA, anti-Sm,
Common causes of death in SLE: Renal disease antiphospholipid)
(most common), Infections, Cardiovascular Neurologic disorders (eg, seizures, psychosis)
disease (accelerated CAD).
Lupus patients die with Redness In their
Cheeks.
Antiphospholipid 1° or 2° autoimmune disorder (most commonly Anticardiolipin antibodies can cause false-
syndrome in SLE). positive VDRL/RPR, and lupus anticoagulant
Diagnose based on clinical criteria including can cause prolonged PTT that is not corrected
history of thrombosis (arterial or venous) by the addition of normal platelet-free plasma.
or spontaneous abortion along with
laboratory findings of lupus anticoagulant,
anticardiolipin, anti-β2 glycoprotein antibodies.
Treat with systemic anticoagulation.
Mixed connective Features of SLE, systemic sclerosis, and/or polymyositis. Associated with anti-U1 RNP antibodies
tissue disease (speckled ANA).
Polymyalgia rheumatica
SYMPTOMS Pain and stiffness in proximal muscles (eg, shoulders, hips), often with fever, malaise, weight loss.
Does not cause muscular weakness. More common in women > 50 years old; associated with
giant cell (temporal) arteritis.
FINDINGS ESR, CRP, normal CK.
TREATMENT Rapid response to low-dose corticosteroids.
Fibromyalgia Most common in women 20–50 years old. Chronic, widespread musculoskeletal pain associated
with “tender points,” stiffness, paresthesias, poor sleep, fatigue, cognitive disturbance (“fibro
fog”). Treatment: regular exercise, antidepressants (TCAs, SNRIs), neuropathic pain agents (eg,
gabapentin).

Polymyositis/ CK, ⊕ ANA (nonspecific), ⊕ anti-Jo-1 (histidyl-tRNA synthetase) (specific), ⊕ anti-SRP (specific),
dermatomyositis ⊕ anti-Mi-2 (specific) antibodies. Both disorders associated with interstitial lung disease.
Treatment: steroids followed by long-term immunosuppressant therapy (eg, methotrexate).
Polymyositis Progressive symmetric proximal muscle weakness, characterized by endomysial inflammation with
CD8+ T cells. Most often involves shoulders.
Dermatomyositis Clinically similar to polymyositis, but also involves malar rash (similar to that in SLE but involves
nasolabial folds), Gottron papules A , heliotrope (violaceous periorbital) rash B , “shawl and face”
rash C , darkening and thickening of fingertips and sides resulting in irregular, “dirty”-appearing
marks. risk of occult malignancy. Perimysial inflammation and atrophy with CD4+ T cells.
A B C
Neuromuscular junction diseases

Myasthenia gravis Lambert-Eaton myasthenic syndrome
FREQUENCY Most common NMJ disorder Uncommon
PATHOPHYSIOLOGY Autoantibodies to postsynaptic ACh receptor Autoantibodies to presynaptic Ca2+ channel
ACh release
CLINICAL Ptosis, diplopia, weakness (respiratory muscle Proximal muscle weakness, autonomic
involvement can lead to dyspnea) symptoms (dry mouth, impotence)
Worsens with muscle use Improves with muscle use
Improvement after edrophonium (tensilon) test
ASSOCIATED WITH Thymoma, thymic hyperplasia Small cell lung cancer
AChE INHIBITOR ADMINISTRATION Reverses symptoms (edrophonium to diagnose, Minimal effect
pyridostigmine to treat)
Raynaud phenomenon blood flow to skin due to arteriolar (small vessel) vasospasm in response to cold or stress:
A color change from white (ischemia) to blue (hypoxia) to red (reperfusion). Most often in the
fingers A and toes. Called Raynaud disease when 1° (idiopathic), Raynaud syndrome when 2°
to a disease process such as mixed connective tissue disease, SLE, or CREST syndrome (limited
form of systemic sclerosis). Digital ulceration (critical ischemia) seen in 2° Raynaud syndrome.
Treat with Ca2+ channel blockers.

Pathology
Scleroderma (systemic Triad of autoimmunity, noninflammatory vasculopathy, and collagen deposition with fibrosis.
sclerosis) Commonly sclerosis of skin, manifesting as puffy, taut skin A without wrinkles, fingertip pitting
B . Can involve other systems, eg, renal (scleroderma renal crisis; treat with ACE inhibitors),
pulmonary (interstitial fibrosis, pulmonary HTN), GI (esophageal dysmotility and reflux),
cardiovascular. 75% female. 2 major types:
Diffuse scleroderma—widespread skin involvement, rapid progression, early visceral
involvement. Associated with anti-Scl-70 antibody (anti-DNA topoisomerase I antibody).
Limited scleroderma—limited skin involvement confined to fingers and face. Also with
CREST syndrome: Calcinosis cutis C , anti-Centromere antibody, Raynaud phenomenon,
Esophageal dysmotility, Sclerodactyly, and Telangiectasia. More benign clinical course.
A B C

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Dermatology SECTION III 461
MUSCULOSKELETAL, SKIN, AND CONNECTIVE TISSUE—DERMATOLOGY

``
Skin layers Skin has 3 layers: epidermis, dermis, Californians Like Girls in String Bikinis.
subcutaneous fat (hypodermis, subcutis). A
Epidermis layers from surface to base A :
Stratum Corneum (keratin)
Stratum Lucidum (most prominent in palms
and soles)
Stratum Granulosum C
Stratum Spinosum (desmosomes)
Stratum Basale (stem cell site)
L
G
Epithelial cell junctions

A
Apical
Tight junction (zonula occludens)—prevents paracellular
E-cadherin movement of solutes; composed of claudins and occludins.
Actin Adherens junction (belt desmosome, zonula adherens)—below

filaments tight junction, forms “belt” connecting actin cytoskeletons of
adjacent cells with CADherins (Ca2+-dependent adhesion
proteins A ). Loss of E-cadherin promotes metastasis.
Cytokeratin
B Desmosome (spot desmosome, macula adherens)—structural
Desmoplakin support via intermediate filament interactions B .
Autoantibodies to desmoglein  pemphigus vulgaris.
Connexon Gap junction—channel proteins called connexons permit

with central electrical and chemical communication between cells.
channel
Cell membrane
Basolateral Basement membrane
Integrins—membrane proteins that maintain integrity Hemidesmosome—connects keratin in basal cells to
of basolateral membrane by binding to collagen, underlying basement membrane. Autoantibodies  bullous
laminin, and fibronectin in basement membrane. pemphigoid. (Hemidesmosomes are down “bullow”).

Dermatology
Dermatologic macroscopic terms

LESION CHARACTERISTICS EXAMPLES
Macule Flat lesion with well-circumscribed change in Freckle, labial macule A
skin color < 1 cm
Patch Macule > 1 cm Large birthmark (congenital nevus) B
Papule Elevated solid skin lesion < 1 cm Mole (nevus) C , acne
Plaque Papule > 1 cm Psoriasis D
Vesicle Small fluid-containing blister < 1 cm Chickenpox (varicella), shingles (zoster) E
Bulla Large fluid-containing blister > 1 cm Bullous pemphigoid F
Pustule Vesicle containing pus Pustular psoriasis G
Wheal Transient smooth papule or plaque Hives (urticaria) H
Scale Flaking off of stratum corneum Eczema, psoriasis, SCC I
Crust Dry exudate Impetigo J
A B C D E
F G H I J
Dermatologic microscopic terms

LESION CHARACTERISTICS EXAMPLES
Hyperkeratosis thickness of stratum corneum Psoriasis, calluses
Parakeratosis Retention of nuclei in stratum corneum Psoriasis
Hypergranulosis thickness of stratum granulosum Lichen planus
Spongiosis Epidermal accumulation of edematous fluid in Eczematous dermatitis
intercellular spaces
Acantholysis Separation of epidermal cells Pemphigus vulgaris
Acanthosis Epidermal hyperplasia ( spinosum) Acanthosis nigricans

Pigmented skin disorders

Albinism Normal melanocyte number with melanin production A due to tyrosinase activity or defective
tyrosine transport. risk of skin cancer.
Melasma (chloasma) Hyperpigmentation associated with pregnancy (“mask of pregnancy” B ) or OCP use.
Vitiligo Irregular patches of complete depigmentation C . Caused by autoimmune destruction of
melanocytes.
A B C
Seborrheic dermatitis Erythematous, well-demarcated plaques with greasy yellow scales in areas rich in sebaceous glands,
A
such as scalp, face, and periocular region. Common in both infants and adults, associated with
Parkinson disease. Sebaceous glands are not inflamed, but play a role in disease development.
Possibly associated with Malassezia spp. Treat with topical antifungals and corticosteroids.

Dermatology
Common skin disorders

Acne Multifactorial etiology— sebum/androgen production, abnormal keratinocyte desquamation,
Cutibacterium (formerly Propionibacterium) acnes colonization of the pilosebaceous unit
(comedones), and inflammation (papules/pustules A , nodules, cysts). Treatment includes retinoids,
benzoyl peroxide, and antibiotics.
Atopic dermatitis Pruritic eruption, commonly on skin flexures. Associated with other atopic diseases (asthma, allergic
(eczema) rhinitis, food allergies); serum IgE. Mutations in filaggrin gene predispose (via skin barrier dysfunc-
tion). Often appears on face in infancy B and then in antecubital fossa C in children and adults.
Allergic contact Type IV hypersensitivity reaction that follows exposure to allergen. Lesions occur at site of contact
dermatitis (eg, nickel D , poison ivy, neomycin E ).
Melanocytic nevus Common mole. Benign, but melanoma can arise in congenital or atypical moles. Intradermal nevi
are papular F . Junctional nevi are flat macules G .
Pseudofolliculitis Foreign body inflammatory facial skin disorder characterized by firm, hyperpigmented papules and
barbae pustules that are painful and pruritic. Located on cheeks, jawline, and neck. Commonly occurs as
a result of shaving (“razor bumps”), primarily affects African-American males.
Psoriasis Papules and plaques with silvery scaling H , especially on knees and elbows. Acanthosis with
parakeratotic scaling (nuclei still in stratum corneum), Munro microabscesses. stratum
spinosum, stratum granulosum. Auspitz sign ( I )—pinpoint bleeding spots from exposure of
dermal papillae when scales are scraped off. Associated with nail pitting and psoriatic arthritis.
Rosacea Inflammatory facial skin disorder characterized by erythematous papules and pustules J , but no
comedones. May be associated with facial flushing in response to external stimuli (eg, alcohol,
heat). Phymatous rosacea can cause rhinophyma (bulbous deformation of nose).
Seborrheic keratosis Flat, greasy, pigmented squamous epithelial proliferation with keratin-filled cysts (horn cysts) K .
Looks “stuck on.” Lesions occur on head, trunk, and extremities. Common benign neoplasm of
older persons.
Leser-Trélat sign L —sudden appearance of multiple seborrheic keratoses, indicating an underlying
malignancy (eg, GI, lymphoid).
Verrucae Warts; caused by low-risk HPV strains. Soft, tan-colored, cauliflower-like papules M . Epidermal
hyperplasia, hyperkeratosis, koilocytosis. Condyloma acuminatum on anus or genitals N .
Urticaria Hives. Pruritic wheals that form after mast cell degranulation O . Characterized by superficial
dermal edema and lymphatic channel dilation.
A B C D E
F G H I J
K L M N O

Vascular tumors of skin

Angiosarcoma Rare blood vessel malignancy typically occurring in the head, neck, and breast areas. Usually in
elderly, on sun-exposed areas. Associated with radiation therapy and chronic postmastectomy
lymphedema. Hepatic angiosarcoma associated with vinyl chloride and arsenic exposures. Very
aggressive and difficult to resect due to delay in diagnosis.
Bacillary angiomatosis Benign capillary skin papules A found in AIDS patients. Caused by Bartonella infections.
Frequently mistaken for Kaposi sarcoma, but has neutrophilic infiltrate.
Cherry hemangioma Benign capillary hemangioma of the elderly B . Does not regress. Frequency with age.
Cystic hygroma Cavernous lymphangioma of the neck C . Associated with Turner syndrome.
Glomus tumor Benign, painful, red-blue tumor, commonly under fingernails D . Arises from modified smooth
muscle cells of the thermoregulatory glomus body.
Kaposi sarcoma Endothelial malignancy most commonly of the skin, but also mouth, GI tract, and respiratory tract.
Associated with HHV-8 and HIV. Rarely mistaken for bacillary angiomatosis, but has lymphocytic
infiltrate.
Pyogenic granuloma Polypoid lobulated capillary hemangioma E that can ulcerate and bleed. Associated with trauma
and pregnancy.
Strawberry Benign capillary hemangioma of infancy F . Appears in first few weeks of life (1/200 births); grows
hemangioma rapidly and regresses spontaneously by 5–8 years old.
A B C
D E F

Dermatology
Skin infections
Bacterial infections
Impetigo Very superficial skin infection. Usually from S aureus or S pyogenes. Highly contagious. Honey-
colored crusting A .
Bullous impetigo B has bullae and is usually caused by S aureus.
Erysipelas Infection involving upper dermis and superficial lymphatics, usually from S pyogenes. Presents with
well-defined, raised demarcation between infected and normal skin C .
Cellulitis Acute, painful, spreading infection of deeper dermis and subcutaneous tissues. Usually from
S pyogenes or S aureus. Often starts with a break in skin from trauma or another infection D .
Abscess Collection of pus from a walled-off infection within deeper layers of skin E . Offending organism is
almost always S aureus.
Necrotizing fasciitis Deeper tissue injury, usually from anaerobic bacteria or S pyogenes. Pain may be out of proportion
to exam findings. Results in crepitus from methane and CO2 production. “Flesh-eating bacteria.”
Causes bullae and a purple color to the skin F . Surgical emergency.
Staphylococcal scalded Exotoxin destroys keratinocyte attachments in stratum granulosum only (vs toxic epidermal
skin syndrome necrolysis, which destroys epidermal-dermal junction). Characterized by fever and generalized
erythematous rash with sloughing of the upper layers of the epidermis G that heals completely.
⊕ Nikolsky sign (separation of epidermis upon manual stroking of skin). Seen in newborns and
children, adults with renal insufficiency.
Viral infections
Herpes Herpes virus infections (HSV1 and HSV2) of skin can occur anywhere from mucosal surfaces to
normal skin. These include herpes labialis, herpes genitalis, herpetic whitlow H (finger).
Molluscum Umbilicated papules I caused by a poxvirus. While frequently seen in children, it may be sexually
contagiosum transmitted in adults.
Varicella zoster virus Causes varicella (chickenpox) and zoster (shingles). Varicella presents with multiple crops of
lesions in various stages from vesicles to crusts. Zoster is a reactivation of the virus in dermatomal
distribution (unless it is disseminated).
Hairy leukoplakia Irregular, white, painless plaques on lateral tongue that cannot be scraped off J . EBV mediated.
Occurs in HIV-positive patients, organ transplant recipients. Contrast with thrush (scrapable) and
leukoplakia (precancerous).
A B C D E
F G H I J

Blistering skin disorders

Pemphigus vulgaris Potentially fatal autoimmune skin disorder with IgG antibody against desmoglein (component of
desmosomes, which connect keratinocytes in the stratum spinosum).
Flaccid intraepidermal bullae A caused by acantholysis (separation of keratinocytes, resembling a
“row of tombstones”); oral mucosa is also involved. Type II hypersensitivity reaction.
Immunofluorescence reveals antibodies around epidermal cells in a reticular (net-like) pattern B .
Nikolsky sign ⊕.
Bullous pemphigoid Less severe than pemphigus vulgaris. Type II hypersensitivity reaction: involves IgG antibody
against hemidesmosomes (epidermal basement membrane; antibodies are “bullow” the
epidermis).
Tense blisters C containing eosinophils affect skin but spare oral mucosa.
Immunofluorescence reveals linear pattern at epidermal-dermal junction D .
Nikolsky sign ⊝.
Dermatitis Pruritic papules, vesicles, and bullae (often found on elbows) E . Deposits of IgA at tips of dermal
herpetiformis papillae. Associated with celiac disease. Treatment: dapsone, gluten-free diet.
Erythema multiforme Associated with infections (eg, Mycoplasma pneumoniae, HSV), drugs (eg, sulfa drugs, β-lactams,
phenytoin), cancers, autoimmune disease. Presents with multiple types of lesions—macules,
papules, vesicles, target lesions (look like targets with multiple rings and dusky center showing
epithelial disruption) F .
Stevens-Johnson Characterized by fever, bullae formation and necrosis, sloughing of skin at dermal-epidermal
syndrome junction, high mortality rate. Typically 2 mucous membranes are involved G H , and targetoid
skin lesions may appear, as seen in erythema multiforme. Usually associated with adverse drug
reaction. A more severe form of Stevens-Johnson syndrome (SJS) with > 30% of the body surface
area involved is toxic epidermal necrolysis I J (TEN). 10–30% involvement denotes SJS-TEN.
A B C D E
F G H I J

Dermatology
Miscellaneous skin disorders

Acanthosis nigricans Epidermal hyperplasia causing symmetric, hyperpigmented thickening of skin, especially in axilla
or on neck A B . Associated with insulin resistance (eg, diabetes, obesity, Cushing syndrome),
visceral malignancy (eg, gastric adenocarcinoma).
Actinic keratosis Premalignant lesions caused by sun exposure. Small, rough, erythematous or brownish papules or
plaques C D . Risk of squamous cell carcinoma is proportional to degree of epithelial dysplasia.
Erythema nodosum Painful, raised inflammatory lesions of subcutaneous fat (panniculitis), usually on anterior shins.
Often idiopathic, but can be associated with sarcoidosis, coccidioidomycosis, histoplasmosis, TB,
streptococcal infections E , leprosy F , inflammatory bowel disease.
Lichen Planus Pruritic, Purple, Polygonal Planar Papules and Plaques are the 6 P’s of lichen Planus G H .
Mucosal involvement manifests as Wickham striae (reticular white lines) and hypergranulosis.
Sawtooth infiltrate of lymphocytes at dermal-epidermal junction. Associated with hepatitis C.
Pityriasis rosea “Herald patch” I followed days later by other scaly erythematous plaques, often in a “Christmas
tree” distribution on trunk J . Multiple pink plaques with collarette scale. Self-resolving in 6–8
weeks.
Sunburn Acute cutaneous inflammatory reaction due to excessive UV irradiation. Causes DNA mutations,
inducing apoptosis of keratinocytes. UVB is dominant in sunBurn, UVA in tAnning and
photoAging. Exposure to UVA and UVB risk of skin cancer. Can also lead to impetigo.
A B C D E
F G H I J
Burn classifications
First-degree burn Superficial, through epidermis (eg, common Painful, erythematous, blanching
sunburn).
Second-degree burn Partial-thickness burn through epidermis and Painful, erythematous, blanching
dermis.
Skin is blistered and usually heals without
scarring.
Third-degree burn Full-thickness burn through epidermis, dermis, Painless, waxy or leathery appearance,
and hypodermis. nonblanching
Skin scars with wound healing.

Skin cancer
Basal cell carcinoma Most common skin cancer. Found in sun-exposed areas of body (eg, face). Locally invasive, but
rarely metastasizes. Waxy, pink, pearly nodules, commonly with telangiectasias, rolled borders,
central crusting or ulceration A . BCCs also appear as nonhealing ulcers with infiltrating growth
B or as a scaling plaque (superficial BCC) C . Basal cell tumors have “palisading” nuclei D .
A B C D
Squamous cell Second most common skin cancer. Associated with excessive exposure to sunlight,
carcinoma immunosuppression, chronically draining sinuses, and occasionally arsenic exposure. Commonly
appears on face E , lower lip F , ears, hands. Locally invasive, may spread to lymph nodes,
and will rarely metastasize. Ulcerative red lesions with frequent scale. Histopathology: keratin
“pearls” G .
Actinic keratosis, a scaly plaque, is a precursor to squamous cell carcinoma.
Keratoacanthoma is a variant that grows rapidly (4–6 weeks) and may regress spontaneously over
months H .
E F G H
Melanoma Common tumor with significant risk of metastasis. S-100 tumor marker. Associated with sunlight
exposure and dysplastic nevi; fair-skinned persons are at risk. Depth of tumor (Breslow
thickness) correlates with risk of metastasis. Look for the ABCDEs: Asymmetry, Border
irregularity, Color variation, Diameter > 6 mm, and Evolution over time. At least 4 different
types of melanoma, including superficial spreading I , nodular J , lentigo maligna K , and acral
lentiginous (highest prevalence in African-Americans and Asians) L . Often driven by activating
mutation in BRAF kinase. Primary treatment is excision with appropriately wide margins.
Metastatic or unresectable melanoma in patients with BRAF V600E mutation may benefit from
vemurafenib, a BRAF kinase inhibitor.
I J K L

Don’t delete
pharmacology
MUSCULOSKELETAL, SKIN, AND CONNECTIVE TISSUE—PHARMACOLOGY

``
Arachidonic acid pathway

MEMBRANE
PHOSPHOLIPIDS
ANTI-INFLAMMATORY AGENTS
Phospholipase A2 Glucocorticoids (corticosteroids)
LEUKOTRIENE
SYNTHESIS
(5-lipoxygenase) ENDOPEROXIDE SYNTHESIS
NF-κB IκB (cyclooxygenase)
Arachidonic acid
Zileuton COX-2 ONLY COX-1, COX-2
COX-2 Celecoxib Aspirin (irreversible)

Other NSAIDs (reversible)
LEUKOTRIENE 5-Lipoxygenase Ketorolac
RECEPTOR Diclofenac Ketorolac
ANTAGONISTS COX-1 Ibuprofen Naproxen
Naproxen
Indomethacin
Montelukast
5-HPETE Cyclic endoperoxides
Zafirlukast
Leukotrienes Prostacyclin Prostaglandins Thromboxane
LTC4 LTD4 LTE4 LTB4 PGI2 PGE1 PGE2 PGF2α TXA2

bronchial tone neutrophil platelet vascular uterine uterine platelet
chemotaxis aggregation tone tone tone aggregation
vascular tone vascular tone
Epoprostenol Alprostadil Dinoprostone Carboprost
LTB4 is a neutrophil chemotactic agent. Neutrophils arrive “B4” others.

PGI2 inhibits platelet aggregation and promotes Platelet-Gathering Inhibitor.
vasodilation.
Acetaminophen
MECHANISM Reversibly inhibits cyclooxygenase, mostly in CNS. Inactivated peripherally.
CLINICAL USE Antipyretic, analgesic, but not anti-inflammatory. Used instead of aspirin to avoid Reye syndrome
in children with viral infection.
ADVERSE EFFECTS Overdose produces hepatic necrosis; acetaminophen metabolite (NAPQI) depletes glutathione and
forms toxic tissue byproducts in liver. N-acetylcysteine is antidote—regenerates glutathione.

pharmacology SECTION III 471
Aspirin
MECHANISM NSAID that irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) by covalent acetylation
synthesis of TXA2 and prostaglandins. bleeding time. No effect on PT, PTT. Effect lasts
until new platelets are produced.
CLINICAL USE Low dose (< 300 mg/day): platelet aggregation. Intermediate dose (300–2400 mg/day): antipyretic
and analgesic. High dose (2400–4000 mg/day): anti-inflammatory.
ADVERSE EFFECTS Gastric ulceration, tinnitus (CN VII), allergic reactions (especially in patients with asthma or nasal
polyps). Chronic use can lead to acute renal failure, interstitial nephritis, GI bleeding. Risk of
Reye syndrome in children treated with aspirin for viral infection. Toxic doses cause respiratory
alkalosis early, but transitions to mixed metabolic acidosis-respiratory alkalosis.
Celecoxib
MECHANISM Reversibly and selectively inhibits the cyclooxygenase (COX) isoform 2 (“Selecoxib”), which is
found in inflammatory cells and vascular endothelium and mediates inflammation and pain;
spares COX-1, which helps maintain gastric mucosa. Thus, does not have the corrosive effects
of other NSAIDs on the GI lining. Spares platelet function as TXA2 production is dependent on
COX-1.
CLINICAL USE Rheumatoid arthritis, osteoarthritis.
ADVERSE EFFECTS risk of thrombosis. Sulfa allergy.
Nonsteroidal Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac, meloxicam, piroxicam.

anti-inflammatory
drugs
MECHANISM Reversibly inhibit cyclooxygenase (both COX-1 and COX-2). Block prostaglandin synthesis.
CLINICAL USE Antipyretic, analgesic, anti-inflammatory. Indomethacin is used to close a PDA.
ADVERSE EFFECTS Interstitial nephritis, gastric ulcer (prostaglandins protect gastric mucosa), renal ischemia
(prostaglandins vasodilate afferent arteriole), aplastic anemia.
Leflunomide
MECHANISM Reversibly inhibits dihydroorotate dehydrogenase, preventing pyrimidine synthesis. Suppresses
T-cell proliferation.
CLINICAL USE Rheumatoid arthritis, psoriatic arthritis.
ADVERSE EFFECTS Diarrhea, hypertension, hepatotoxicity, teratogenicity.
Bisphosphonates Alendronate, ibandronate, risedronate, zoledronate.

MECHANISM Pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity.
CLINICAL USE Osteoporosis, hypercalcemia, Paget disease of bone, metastatic bone disease, osteogenesis
imperfecta.
ADVERSE EFFECTS Esophagitis (if taken orally, patients are advised to take with water and remain upright for 30
minutes), osteonecrosis of jaw, atypical femoral stress fractures.

pharmacology
Teriparatide
MECHANISM Recombinant PTH analog. osteoblastic activity when administered in pulsatile fashion.
CLINICAL USE Osteoporosis. Causes bone growth compared to antiresorptive therapies (eg, bisphosphonates).
ADVERSE EFFECTS risk of osteosarcoma (avoid use in patients with Paget disease of the bone or unexplained
elevation of alkaline phosphatase). Avoid in patients who have had prior cancers or radiation
therapy. Transient hypercalcemia.
Gout drugs
Chronic gout drugs (preventive)
Probenecid Inhibits reabsorption of uric acid in proximal Prevent A Painful Flare.
convoluted tubule (also inhibits secretion of Diet Purines Nucleic acids
penicillin). Can precipitate uric acid calculi.
Allopurinol Competitive inhibitor of xanthine oxidase
Hypoxanthine
conversion of hypoxanthine and xanthine
Xanthine
to urate. Also used in lymphoma and leukemia
oxidase
to prevent tumor lysis–associated urate Allopurinol,
Xanthine
nephropathy. concentrations of azathioprine febuxostat
Xanthine
and 6-MP (both normally metabolized by oxidase
xanthine oxidase). Plasma Urate crystals Gout
Pegloticase Recombinant uricase catalyzing uric acid to uric acid deposited
in joints
allantoin (a more water-soluble product).
Febuxostat Inhibits xanthine oxidase.
Tubular
Acute gout drugs reabsorption
NSAIDs Any NSAID. Use salicylates with caution (may Probenecid and
decrease uric acid excretion, particularly at high-dose salicylates
Tubular
low doses). secretion
Glucocorticoids Oral, intra-articular, or parenteral. Diuretics and

Urine low-dose salicylates
Colchicine Binds and stabilizes tubulin to inhibit
microtubule polymerization, impairing
neutrophil chemotaxis and degranulation.
Acute and prophylactic value. GI,
neuromyopathic side effects.
TNF-α inhibitors
DRUG MECHANISM CLINICAL USE ADVERSE EFFECTS
Etanercept Fusion protein (decoy receptor Rheumatoid arthritis, psoriasis,
for TNF-α + IgG1 Fc), ankylosing spondylitis Predisposition to infection,
produced by recombinant including reactivation of
DNA. latent TB, since TNF is
Etanercept intercepts TNF. important in granuloma
Infliximab, Anti-TNF-α monoclonal Inflammatory bowel disease, formation and stabilization.
adalimumab, antibody. rheumatoid arthritis, Can also lead to drug-induced
certolizumab, ankylosing spondylitis, lupus.
golimumab psoriasis

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HIGH-YIELD SYSTEMS

This chapter provides information you will need to understand certain

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434 SECTION III Musculoskeletal, Skin, and Connec tive Tissue 

MUSCULOSKELETAL, SKIN, AND CONNECTIVE TISSUE—ANATOMY AND PHYSIOLOGY

of the deltoid); most common rotator

Glenoid cuff injury (trauma or degeneration and

in A ]), assessed by “empty/full can” test.

Overuse injuries of the elbow

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Wrist region Scaphoid, Lunate, Triquetrum, A

Guyon canal Compression of ulnar nerve at wrist. Classically

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Normal Greenstick fracture Torus fracture Complete fracture

Greenstick fracture Complete fracture

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Upper extremity nerves

Median nerve Ulnar nerve

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Brachial plexus lesions

and subclavian Pancoast tumor ischemia, pain, C6

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CONTEXT Extending fingers/at Making a fist Extending fingers/at Making a fist

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Knee exam Lateral femoral condyle to anterior tibia: ACL. Femur

Medial femoral condyle to posterior tibia: PCL.

Anterior drawer sign Bending knee at 90° angle,  anterior gliding

Abnormal passive Knee either extended or at ∼ 30° angle, lateral

tibia  MCL injury. force

Abnormal passive Knee either extended or at ~ 30° angle, medial

McMurray test During flexion and extension of knee with

 medial meniscal tear (external rotation

 lateral meniscal tear (internal rotation

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Common hip and knee conditions

Fibula Anterior inferior

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Lower extremity nerves

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Lower extremity nerves (continued)

Actions of hip muscles

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Common musculoskeletal conditions

Childhood musculoskeletal conditions

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Types of muscle fibers

Smooth muscle contraction and relaxation

↑ Ca2+ CONTRACTION Nitric oXide RELAXATION

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Cell biology of bone

MUSCULOSKELETAL, SKIN, AND CONNECTIVE TISSUE—PATHOLOGY

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Osteomalacia/rickets Defective mineralization of osteoid B

Osteonecrosis Infarction of bone and marrow, usually very Branch of

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Lab values in bone disorders

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Osteoblastoma Vertebrae. Similar histology to osteoid osteoma.

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Primary bone tumors (continued)

Round cell lesions

Anterior drawer sign Bending knee at 90° angle, anterior gliding

tibia MCL injury. force

medial meniscal tear (external rotation

lateral meniscal tear (internal rotation