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Musculoskeletal System
Table of Contents

Chapter 1: Embryology of Musculoskeletal System...............................................................................................................................5

Chapter 2: Anatomy of Upper Limb Muscles.........................................................................................................................................7

Rotator Cuff Muscles (SITS)...................................................................................................................................................................7
Neck Region............................................................................................................................................................................................8
Wrist Region...........................................................................................................................................................................................9
Hand Muscles.........................................................................................................................................................................................9
Bony Landmarks related to Nerves......................................................................................................................................................10

Chapter 3: Anatomy of Upper Limb Nerves.........................................................................................................................................11

Brachial Plexus Lesions.......................................................................................................................................................................11
Neurovascular Pairing.........................................................................................................................................................................14

Chapter 4: Anatomy of Lower Limb Muscles and Nerves..................................................................................................................14

Divides at popliteal fossa (upper border) into common peroneal nerve (lateral branch) & tibial nerve.........................................14
Signs of Lumbosacral Radiculopathy (Lumbosacral Plexus)..............................................................................................................17
Back Pain..............................................................................................................................................................................................17
Common Musculoskeletal Conditions FA 470.....................................................................................................................................18

Chapter 5: Anatomy of Knee and Ankle...............................................................................................................................................19

Knee Ligaments....................................................................................................................................................................................19
Ankle Sprains........................................................................................................................................................................................21

Chapter 6: Physiology of Muscles..........................................................................................................................................................22

Muscle Structure...................................................................................................................................................................................22
Motoneuron Action Potential to Skeletal Muscle Contraction.............................................................................................................23
Vascular Smooth Muscle Contraction and Relaxation........................................................................................................................24

Chapter 7: Physiology of Bones..............................................................................................................................................................25

Bone Formation....................................................................................................................................................................................25
Cell Biology of Bones...........................................................................................................................................................................25

Chapter 8: Pathology of Bones...............................................................................................................................................................26

Common Pediatric Fractures...............................................................................................................................................................26
Pathology of Skeletal Bone...................................................................................................................................................................26
Iliopsoas Abscess FA 468................................................................................................................................................................26
Avascular Necrosis of Femoral Head FA 473.................................................................................................................................26
Achondroplasia................................................................................................................................................................................27
Osteogenesis Imperfecta..................................................................................................................................................................27
Osteopetrosis....................................................................................................................................................................................27
Osteoporosis (porous bones)............................................................................................................................................................28
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Osteomalacia / Rickets (weak bones)..............................................................................................................................................28

Paget disease of Bone (Osteitis Deformans)....................................................................................................................................29
Osteomyelitis...................................................................................................................................................................................29
Bone Tumors.........................................................................................................................................................................................30
Polyarthritis (> 5 joints pathology).....................................................................................................................................................32
Monoarthritis........................................................................................................................................................................................33
Gout..................................................................................................................................................................................................33
Pseudogout (Calcium Pyrophosphate Deposition Disease).............................................................................................................33
Septic Arthritis.................................................................................................................................................................................34
Seronegative Spondyloarthropathies (PAIR).......................................................................................................................................34
Autoimmune Connective Tissue Disease..............................................................................................................................................35
Systemic Juvenile Idiopathic Arthritis.............................................................................................................................................35
Sjogren Syndrome............................................................................................................................................................................35
Systemic Lupus Erythematosus (SLE)............................................................................................................................................35
Mixed Connective Tissue Disease...................................................................................................................................................36
Anti-phospholipid Syndrome...........................................................................................................................................................36
Scleroderma (Systemic Sclerosis) FA 485.......................................................................................................................................36
Raynaud Phenomenon......................................................................................................................................................................36

Chapter 9: Pathology of Skeletal Muscles.............................................................................................................................................37

Chapter 10: Pathology of Blood Vessels (Vasculitis)............................................................................................................................38

Chapter 11: Pathology of Neuromuscular Junction.............................................................................................................................40

Chapter 12: Soft Tissue Tumors............................................................................................................................................................41

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Chapter 1: Embryology of Musculoskeletal System

Osteogenesis Imperfecta
 Defective synthesis in type I collagen by osteoblast
 Blue sclera caused by thin scleral collagen allows underlying darker choroid vasculature to be seen
 Small malformed teeth
Congenital Torticollis (CoTo)
 It typically develops by 2 to 4 weeks of age.
 Cause:
o Birth trauma (breech delivery)
o Malposition of head in utero due to fetal macrosomia or oligohydramnios
 Associated abnormalities:
o talipes equinovarus (clubfoot) or adduction of the forefoot
o hip dysplasia
o plagiocephaly
o facial asymmetry
 Diagnosis is made clinically:
o Both birth trauma or malposition results in SCM injury and fibrosis.
o Head is tilted toward affected side with chin pointed away from contracture.
 Treatment: most cases resolve with conservative therapy & stretching exercises.
Pierre-robin Sequence
 Triad of micrognathia causes gaossoptosis (posterior displacement of tongue)
 It prevents fusion of 2o palate (U shaped palate)
Cleft Lip Development
 Lips and 1o palate formed during 5 – 6th week of development through a series of fusions.
 Fusion of 2 medial nasal prominence forms inter-maxillary segment (midline nose)
 2 maxillary prominences (1st pharyngeal arch) fuse with midline intermaxillary segment to form:
o philtrum of upper lip, 4 medial maxillary teeth,
o 1o palate
 Failure of medial nasal prominence development leads to midline facial defects in holoprosencephaly.
 Failure of fusion between maxillary prominences & intermaxillary segments forms cleft lip.
Cleft Palate Development
 Palate is formed during 7 – 8th weeks during development
 1o palate ➝ formed by fusion between medial nasal prominence and maxillary prominence.
 2o palate
o formed from palatine shelves (arised from maxillary prominence)
o which fuse in midline, posterior to incisive foramen.
 Primary & secondary palates fuse at incisive foramen to form the definitive hard palate (Y-shape).
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Chapter 2: Anatomy of Upper Limb Muscles

Rotator Cuff Muscles (SITS)
Innervated primarily by C5-C6.
Supraspinatus
 Action: Abducts arm initially (before the action of deltoid)
 Nerve Supply: Suprascapular nerve assessed by "empty/full can" test.
 Rotator cuff syndrome
o A tendon of supraspinatus muscle is MC affected in rotator cuff syndrome.
o Due to its superior location, this tendon is vulnerable to chronic repeated trauma or
degeneration and impingement between head of humerus and acromioclavicular joint.
o This leads to rotator cuff tendinopathy or tear.
Infraspinatus
 Action: Externally rotates arm and supplied by suprascapular nerve.
 Clinical: Pitching injury can involve tendons of this muscle.
Teres minor - adducts and externally rotates arm; supplied by axillary nerve.
Subscapularis - internally rotates and adducts arm; supplied by upper and lower subscapular nerves.
Anterior Shoulder Dislocation
 Caused by a blow to externally rotated & abducted arm.
 Clinical Features:
o Flattening of shoulder (flat deltoid)
o Fullness at anterior axilla
o Prominence of acromion bone
o Damage of the axillary nerve
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Neck Region
Latissimus Dorsi
Originate from iliac crest & lumbar fascia to spinous processes T7-12 & lower ribs.
Inserts at the bicipital groove of the humerus & innervated by thoracodorsal nerve (C6-8).
Actions: include extension, adduction, and internal rotation of humerus.
Clinical:
 Vulnerable to external trauma and sports injury (forceful downward movement of humerus) such as
throwing, climbing, or swinging a tennis racket overhead.
 Cardiomyoplasty Procedure
o Wrap latissimus dorsi around heart & electro-stimulate dorsi in synchrony w ventricular systole.
o Supports failing heart pt. with low CO + NOT a cardiac transplant candidate
Serratus Anterior
 Originates from side of chest along 1st to 8th ribs and inserts at medial border of scapula.
 Winging of scapula (see nerve lesions)
 Chest tube insertion pass through it at 4th or 5th intercostal space along mid or anterior axillary line.
Clavicle Fracture
Cause: fall on outstretched hand or by direct trauma to shoulder in children & as birth trauma.
CF:
 Fractures at middle third segment because weakest point is at junction of middle & lateral thirds.
 Shoulder drop, Shortened clavicle
 depressed lateral fragment due to arm weight & medially rotated by arm adductors [pectoralis major].
Scalene Triangle
 Formed by anterior & middle scalene muscles & first rib.
 Brachial plexus & subclavian artery pass between 2 scalene muscles.
 Subclavian vein runs anteromedial to scalene triangle.
Thoracic Outlet Syndrome (TOS) FA 456
Injury: Compression of lower trunk of plexus & subclavian vessels, most commonly within scalene triangle.
Causes: Anomalous cervical rib (extra rib from C7), scalene muscular hypertrophy/anomaly; Pancoast’s tumor.
CF:
 Lower trunk compression as it passes thoracic outlet ➝ UL numbness, weakness (Same as Klumpke’s)
 Compression of subclavian vein ➝ upper extremity swelling.
 Compression of the subclavian artery ➝ exertional arm pain.
Interscalene Nerve Block
Aim: Local anesthesia of brachial plexus ➝ paralysis of all UL muscles except trapezius & SCM.
Site: Anesthetic is given in scalene triangle (b/w anterior & middle scalene)
Associated with ipsilateral diaphragmatic paralysis (phrenic nerve paralysis) thus avoided in chronic lung
disease or pt. with contralateral phrenic nerve dysfunction.
Overuse injuries of Elbow
Medial epicondylitis (Golfer’s Elbow): repetitive flexion or idiopathic ➝ pain near medial epicondyle.
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Lateral epicondylitis (tennis elbow): repetitive extension (backhand shots)/idiopathic ➝ pain near lateral.
Radial head subluxation (nursemaid’s elbow) FA 471
 MC elbow injury in children < 5 years because the annular ligament become strong at age of 5.
 Caused by a sudden pull on the arm ➝ immature annular ligament slips over head of radius.
 Injured arm is held in slightly flexed and pronated position.

Wrist Region
Bones
 Scaphoid, Lunate, Triquetrum, Pisiform (proximal).
 Trapezium, Trapezoid, Capitate, Hamate (distal).
Anatomical Snuffbox
Boundaries:
 Medially by extensor pollicis longus tendon
 Laterally by abductor pollicis longus & extensor pollicis brevis tendons
 Floor is formed by scaphoid (palpable in anatomic snuff) & trapezium
Fall on outstretched hand ➝ scaphoid fracture, lunate dislocation (exist together), distal radius fracture.
Hamate Hook Fracture - can cause ulnar syndrome.
Lunate Dislocation - impinges median nerve and causes carpal tunnel syndrome.
Scaphoid Fracture
 CF: Persistent pain & tenderness in anatomical snuff box.
 Nerve supply: supplied by dorsal scaphoid branch of radial artery.
 Complication: avascular necrosis & non-union d/t retrograde blood supply from branch of radial artery.
Carpal Tunnel
Boundaries: Anterior is flexor retinaculum (transverse carpal ligament*) while posterior is lunate bone.
Contents:
 Tendons: flexor digitorum (superficialis, profundus), flexor pollicis longus, transverse carpal ligament
 Median nerve
Carpal Tunnel Syndrome:
 Median N trapped between transverse carpal ligament & carpal bones ➝ Nerve compression in tunnel
 Associated with
o pregnancy due to edema, dialysis-related amyloidosis, rheumatoid arthritis,
o hypothyroidism, diabetes, acromegaly; may be associated with repetitive use.
 CF:
o paresthesia, pain, numbness in distribution of median nerve (lateral 3 ½ digits)
o Thenar eminence atrophies
o Sensation spared because palmar cutaneous branch enters hand external to carpal tunnel
 Diagnosis:
o Tinel sign ⊕ - percussion of wrist causes tingling
o Phalen maneuver - 90° flexion of wrist causes tingling.
 Surgery: longitudinal incision through transverse carpal ligament relieves pressure on nerve.
Guyon Canal
Definition: fibro-osseous tunnel formed by hook of hamate and pisiform bone.
Guyon Canal Syndrome:
 Compression of ulnar nerve at wrist, seen in cyclists due to pressure from handlebars.
 Also be seen with fracture/dislocation of the hook of hamate.
 CF: Paresthesia and anesthesia over hypothenar eminence. and medial 1 1/2 fingers.
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Metacarpal Neck Fracture (Boxer’s Fracture)

 Caused by direct blow with a closed fist (punching a wall); MC seen in 5th metacarpal bone.
Hand Muscles
Both groups (thenar & hypothenar) ➝ perform the same functions i.e., Oppose, Abduct, and Flex (OAF).
Thenar (median nerve)
 Opponens pollicis, Abductor pollicis brevis, Flexor pollicis brevis, superficial head (deep head by ulnar).
Hypothenar (ulnar nerve)
 Opponens digiti minimi, Abductor digiti minimi, Flexor digiti minimi brevis.
Other Muscles
 Dorsal interossei (ulnar) abduct the fingers. (DAB = Dorsal Abduct)
 Palmar interossei (ulnar)—adduct the fingers. (PAD = Palmar Adduct)
 Lumbricals (1st/2nd, median; 3rd/4th, ulnar)—flex at the MCP joint, extend PIP and DIP joints.
Hand Distortions
At rest:
 balance exists between extrinsic flexors & extensors, as well as 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 digit’s extrinsic flexors exaggerate lumbrical loss ➝ fingers extend at MCP, flex at DIP & PIP.
Deficits are less pronounced in proximal lesions; deficits are present during voluntary flexion of digits.
Note:
 Thenar eminence atrophy (unopposable thumb ➝ "ape hand") is seen in median nerve lesions,
 Hypothenar eminence atrophy seen in ulnar nerve lesions.

Bony Landmarks related to Nerves

 Neck of humerus ➝ Axillary (circumflex) nerve.
 Shaft of humerus ➝ Radial nerve.
 Supra condylar area of humerus ➝ median nerve.
 Medial epicondyle of humerus ➝ ulnar nerve.
 Hamate Bone ➝ ulnar nerve.
 Lunate Bone ➝ Median nerve.
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Chapter 3: Anatomy of Upper Limb Nerves

Brachial Plexus Lesions
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Median Nerve (C5 – T1)

Course:
 Courses with brachial artery in groove between biceps and brachialis.
 Enters forearm in medial aspect of antecubital fossa & courses between 2 heads of pronator teres.
 Innervates anterior compartment of forearm except FCU & ulnar ½ of flexor digitorum profundus
 It courses between FDS & FDP and enters wrist deep to flexor retinaculum.
 Innervates hand muscles and sensations
o Thenar: 2 Lumbricals, Opponens pollicis, Abductor pollicis brevis, Flexor pollicis brevis (LOAF)
o Sensation over thenar eminence and dorsal and palmar aspects of lateral 3 ½ fingers.
Cause of Injury:
 Proximal median nerve injury due to supracondylar fracture of humerus.
 Distal median nerve injury
o Carpal tunnel syndrome & wrist laceration from suicide
o Preserved flexion of 2nd & 3rd digits, normal sensation over thenar eminence.
Presentation:
 Ape hand: Thumb adducted (Cannot oppose or abduct thumb) with thenar atrophy.
 Distal median nerve lesion causes median claw (Loss of wrist flexion & function of lateral 2 Lumbricals)
 Proximal median nerve lesion
o Hand of Benediction: ask to make fist ➝ Thumb & lateral fingers can’t flex.
o Loss of sensation over thenar eminence and dorsal and palmar aspects of lateral 3 1/2 fingers.
Recurrent Branch of Median Nerve (C5 – T1)
Innervation: motor innervation to thenar BUT NO sensory innervation.
Cause of injury is superficial laceration of palm.
Presentation:
 “Ape hand”
 No loss of sensation
 Loss of thenar muscle group: opposition, abduction, and flexion of thumb
Ulnar Nerve (C8 – T1)
Course:
 passes behind medial epicondyle of humerus to enter the forearm.
 Innervates the flexor carpi ulnaris and flexor digitorum profundus (medial portion).
 In wrist, ulnar pass between hook of hamate & pisiform in Guyon’s canal & divides into 2 branches
 Deep motor branch ➝ supplies most of the intrinsic muscles of hand (DAB, PAD).
 Superficial branch
o sensation over medial 1 ½ digits
o hypothenar (Opponens digiti minimi, Abductor digiti minimi, Flexor digiti minimi brevis)
Cause of injury:
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 Fracture of medial epicondyle of humerus (proximal lesion)

 Fractured hook of hamate (distal lesion) from fall on outstretched hand
 Nerve compression against hamate as wrist rests on handlebar during cycling
Presentation:
 “Ulnar claw” on digit extension
 Radial deviation of wrist upon flexion (proximal lesion)
  flexion of ulnar fingers, abduction and adduction of fingers (interossei), thumb adduction, actions of
ulnar 2 lumbrical muscles
 Loss of sensation over ulnar 1 1/2 fingers including hypothenar eminence
Axillary Nerve (C5 – C6)
Innervation: deltoid (abduction > 15o), teres minor, sensation over deltoid and lateral arm.
Cause of injury: Fractured surgical neck of humerus and Anterior dislocation of humerus
Presentation:
 Flattened deltoid and loss of arm abduction at shoulder (> 15°)
 Loss of sensation over deltoid and lateral arm
Musculocutaneous Nerve (C5 – C7)
Course:
 Innervates anterior compartment of arm and continues as lateral cutaneous nerve of forearm
 Thus, provides sensory innervation to skin of lateral forearm.
Cause of injury: upper trunk compression
Presentation:
  biceps (C5-6) reflex
 Loss of forearm flexion and supination; Loss of sensation over radial and dorsal forearm
Radial Nerve (C5 – T1)
Course:
 Course medial to surgical neck of humerus, deep to teres major (axilla)
 Enters forearm anterior to lateral epicondyle (radial groove of humerus) & divides into 2 branches.
 Superficial branch ➝ provides somatic sensory innervation to radial half of dorsal hand.
 Deep branch
o innervates extensor compartment muscles in forearm.
o Passing through supinator canal & goes to wrist to become posterior interosseous nerve which
innervates muscles involved in finger and thumb extension.
Cause of injury:
 Compression of axilla due to crutches or sleeping with arm over chair ("Saturday night palsy")
 Midshaft fracture of humerus
 Repetitive pronation/supination of forearm due to screwdriver use ("finger drop")
Presentation:
 Fracture at axilla ➝  triceps reflex.
 Midshaft fracture ➝ Triceps function and posterior arm sensation spared (intact triceps reflex).
 Injuries below the elbow cause distal paresthesias without wrist drop.
 Injuries above elbow
o loss of sensation over posterior arm/forearm & dorsal hand,
o wrist drop (loss of elbow, wrist, and finger extension)
o  grip strength (wrist extension needed for max action of flexors)
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Neurovascular Pairing

Chapter 4: Anatomy of Lower Limb Muscles and Nerves

Actions of Hip Muscle

Ilio-hypogastric Nerve (T12 – L1)

Arise from lateral border of psoas major, behind kidney & in front of Quadraus lumborum.
Innervates the anterolateral abdominal wall muscles and divides into 2 branches.
 Lateral branch: descend over the iliac crest to innervate the gluteal region.
 Anterior branch:
o emerge above superficial inguinal ring to innervate the skin of suprapubic region
o May be injured during appendectomy (abdominal surgery)
Sciatic Nerve (L4 – S3)
Divides at popliteal fossa (upper border) into common peroneal nerve (lateral branch) & tibial nerve.
Common Peroneal Nerve (fibular) (L4 – S2)
 Traverses laterally to come in contact with fibular neck (MC site of injury) where it divides into:
 Superficial peroneal: Motor to eversion muscle & sensory supply of dorsum of foot & lateral of leg.
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 Deep peroneal nerve: supply anterior compartment of leg

Tibial Nerve (L4 – S3)
 It traverses the popliteal fossa, goes deep to soleus muscle then enters tarsal tunnel
 Proximal injury (knee trauma, baker’s cyst) ➝ causes dorsiflexion and eversion
 Distal injury (tarsal tunnel syndrome) ➝ ONLY sensory loss with intact muscle action
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Signs of Lumbosacral Radiculopathy (Lumbosacral Plexus)

Definition: pain syndrome caused by compression or irritation of nerve roots in the lower back.
Spine:
 Made up of vertebrae separated by intervertebral disks (act like cushions to absorb shock).
 intervertebral discs consist of thick, fibrous outer ring called annulus fibrosus surrounding a soft
gelatinous core called the nucleus pulposus.
Cause:
 Intervertebral disc (nucleus pulposus) herniates posterolat. through annulus fibrosus into spinal canal
 This is due to thin posterior & thicker anterior longitudinal ligament along midline of vertebral bodies.
 Nerve affected is usually below the level of herniation.
CF:
 Paresthesia and weakness related to specific lumbosacral spinal nerves.
 ⊕ straight leg raise, ⊕ contralateral straight leg raise, ⊕ reverse straight leg raise (femoral stretch).

Back Pain
Degenerative (osteoarthritis) Back pain is positional, relieved with rest
Vertebral Osteomyelitis ~ Back pain has focal tenderness
~ Fevers and night sweats
~ Recent infection, IV drug abuse, or immune compromise
Spondyloarthropathy ~ Young men with back pain, prolonged morning stiffness
~ Relieved with exercise (HLA-B27)
Lumbosacral Radiculopathy (disc herniation) ~ Back pain radiates to leg with straight leg raising test ⊕
~ Sensory and motor findings ⊕
Spinal stenosis ~ Back pain with standing (spinal extension)
~ relieved by spinal flexion
Spinal Metastasis ~ Constant back pain worse at night
~ NOT responsive to positional changes
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Common Musculoskeletal Conditions FA 470

Temporomandibular Disorder
Definition: Group of disorders that involve temporomandibular joint (TMJ) & muscles of mastication.
Associated with TMJ trauma, poor head & neck posture, abnormal trigeminal nerve pain processing.
CF:
 Constant unilateral, dull facial pain that worsens with jaw movement,
 otalgia, headache, TMJ dysfunction (limited range of motion)
Costochondritis
Definition: Inflammation of costochondral or costo-sternal junctions due to minor trauma.
CF:
 Pleuritic chest pain and focal tenderness to palpation in younger female patients.
 May mimic myocardial infarction, pleuritis, or pulmonary embolism.
Treatment: analgesics, stretching therapy.
De Quervain Tenosynovitis
Definition: Non-inflammatory thickening of abductor pollicis longus and extensor pollicis brevis tendons
Risk increases in new mothers (lifting baby), golfers, racquet sport players, “thumb” texters.
CF: ⊕ Finkelstein test (pain or tenderness at radial styloid with active or passive stretch of thumb tendons).
Ganglion Cyst
Definition: Fluid-filled swelling overlying joint or tendon sheath, most commonly at dorsal side of wrist.
Cause: Arises from herniation of dense connective tissue.
Treatment: Usually resolves spontaneously.
Dupuytren’s Contracture
Cause: unknown etiology; MC in males > 50 years old of Northern European descent.
CF: fibroblastic proliferation & thickening of superficial palmar fascia at base of ring & little fingers.
Iliotibial Band Syndrome
Cause: Overuse injury of lateral knee in runners.
CF: Pain develops 2° to friction of iliotibial band against lateral femoral epicondyle.
Medial Tibial Stress Syndrome (Shin Splints)
Caused by bone resorption that outpaces bone formation in tibial cortex.
CF: common cause of shin pain and diffuse tenderness in runners and military recruits.
Plantar Fasciitis
Inflammation of plantar aponeurosis associated with
 obesity,
 prolonged standing or jumping (dancers, runners),
 flat feet.
CF: tenderness and heel pain worse with 1st steps in morning or after inactivity. Heel spurs often coexist.
Limb Compartment Syndrome
Patho:  pressure w/in limb compartment ➝ venous outflow obstruction & arteriolar collapse ➝ anoxia,
necrosis, rhabdomyolysis ➝ acute tubular necrosis.
Cause:
 Trauma: long bone fracture (tibia), reperfusion injury (crush inj.), thermal injury (burn), animal venom
 Non-traumatic like bleeding
CF:
 Severe pain & tense, swollen compartments with passive stretch of muscles in affected compartment.
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 5P’s: Pain, Pallor, Paresthesia, Pulselessness, Paralysis

Investigations:  serum creatine kinase & motor deficits are late signs of irreversible muscle & nerve damage.
Management: Emergency fasciotomy (compartment pressure >30 mm Hg indicates significant CS)

Chapter 5: Anatomy of Knee and Ankle

Knee Ligaments
Lateral femoral condyle to anterior tibia is the Anterior Cruciate Ligament (ACL).
Medial femoral condyle to posterior tibia is the Posterior Cruciate Ligament (PCL).
PCL injury: Posterior Drawer Sign shows  posterior gliding of tibia when bending knee at 90o due to PCL injury
ACL injury
Lachman Test:  anterior tibial gliding with knee flexed at 30° and pulling leg anteriorly (more sensitive).
Anterior Drawer Sign
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 With the knee flexed at 90°, the leg can be pulled anteriorly like a drawer being opened
 i.e.,  anterior gliding of tibia relative to femur.

Unhappy Triad
Cause: contact sport injury occurs due to lateral force impacting the knee when foot is planted on ground.
CF:
 Consists of damage to ACL (A), MCL, and medial meniscus attached to MCL.
 However, lateral meniscus is MC involved than medial meniscus in conjunction with ACL & MCL injury.
 Presents with acute pain and signs of joint instability.
Pre-patallar Bursitis (Housemaid’s Knee)
Definition: Inflammation of pre-patellar bursa in front of the kneecap (red arrow in B).
Cause: repeated trauma or pressure from excessive kneeling.
Popliteal Cyst (Baker’s Cyst)
Definition: Popliteal fluid collection in gastrocneImius-semi-membranosus bursa (red arrow in C) which
commonly communicates with synovial space & is related to chronic joint disease (Femur osteoarthritis, RA).
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Patellar Fracture
 Acutely swelling with focal tenderness
 Inability to extend the knee against gravity
 Palpable gap in the extensor mechanism
Pyriformis Syndrome
 Structures above piriformis include superior gluteal vessels and superior gluteal nerve.
 Structures below piriformis include inferior gluteal vessels, internal pudendal vessels, and sciatic nerve.
CF:
 Muscle injury/hypertrophy can compress sciatic N. to cause sciatica-like finding (piriformis syndrome)
 sciatica-like findings include pain, tingling, and numbness in buttocks and along the nerve distribution
Ankle Sprains
Anterior inferior tibiofibular ligament: most common high ankle sprain.
Anterior talofibular ligament (ATL)
 Classified as low ankle sprain MC ankle sprain d/t overinversion or supination of foot. Always tears first
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Chapter 6: Physiology of Muscles

Muscle Structure
Myofibrils:
 Thick myosin filaments: Found in A band & contains heads which bind to and pull-on the actin.
 Thin actin, tropomyosin, and troponin filaments:
o Found in I band & attached to Z lines (representing end of sarcomere).
o Troponin protein is formed of
 Troponin T binds to Tropomyosin,
 Troponin I Inhibits actin-myosin Interaction,
 troponin C binds to Ca++ to initiate contraction.
T-tubule:
 extensions of plasma membrane (sarcolemma) into the sarcomere; they are in contact with SR.
 It allows coordinated contraction of striated muscles by depolarizing dihydropyridine protein receptor.
Sarcoplasmic reticulum (SR):
 Definition: Tubular structure w terminal cisternae that is in contact to T-tubules, & contains stored Ca.
 Functions:
o Has Ca++ pump to store Ca++ from sarcoplasm & has calsequestrin to bind Ca++ inside it.
o Has ryanodine receptor channels which are Ca++ release channel.
Types of Skeletal Muscle Fibres
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Adaptation of Skeletal Muscle Fibres

Muscle Proprioceptors: Specialized sensory receptors that relay information about muscle dynamics.

Motoneuron Action Potential to Skeletal Muscle Contraction

Action Potential
 Action potential opens pre-synaptic voltage-gated Ca2+ channels, inducing acetylcholine (ACh) release.
 Post-synaptic ACh binding leads to muscle cell depolarization at the motor end plate.
 Membrane depolarization travels over the entire muscle cell and deep into the muscle via T-tubules.
 Depolarization induces conformational change in voltage-sensitive dihydropyridine R’ (DHPR) and its
mechanically coupled ryanodine receptor (RR)
 Ca2+ release from the sarcoplasmic reticulum (buffered by calsequestrin) into the cytoplasm.
Excitation Contraction Coupling
 Tropomyosin is blocking myosin-binding sites on the actin filament.
 Released Ca2+ binds to troponin C (TnC), shifting tropomyosin to expose the myosin-binding sites.
 Myosin head binds strongly to actin (crossbridge). Pi released, initiating power stroke.
 During the power stroke, force is produced as myosin pulls on the thin filament (actin).
 Muscle shortening occurs, with shortening of H & I bands and between Z lines (HI, I’m wearing shortZ).
 A band remains the same length (A band is Always the same length).
 ADP is released at the end of the power stroke.
Muscle Relaxation
 Binding of new ATP molecule causes detachment of myosin head from actin filament.
25

 Ca2+ is re-sequestered.
 ATP hydrolysis into ADP and Pi results in myosin head returning to high-energy position (cocked).
 Myosin head can bind to a new site on actin to form a crossbridge if Ca2+ remains available.
 Reuptake of calcium by sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) ➝ muscle relaxation.

Vascular Smooth Muscle Contraction and Relaxation

Smooth Muscle Contraction
 Thin & thick filaments are present but NOT arranged in sarcoplasm & NO troponin nor tropomyosin.
 Depolarization of smooth muscle membrane opens voltage-gated Ca++ channels, while hormones can
open ligand-gated Ca2+ channels.
 Ca2+ enters inside smooth muscle triggering Ca2+ release from SR i.e., Ca2+ induced Ca2+ release (CICR).
  Ca2+ in sarcoplasm stimulates myosin light chain kinase enzyme (MLCK).
 MLCK phosphorylates myosin head activating it. Thus, pulling on actin.
Smooth Muscle Relaxation
  Ca2+ in sarcoplasm or  cGMP can stimulate myosin light chain phosphatase (MLCP)
 MLCP dephosphorylates & deactivates myosin thus relaxation occurs.
26

Chapter 7: Physiology of Bones

Bone Formation
Endochondral Ossification
 Endochondral bone formation is characterized by formation of a cartilage matrix, which is then
 replaced by bone; it is the mechanism by which long bones grow.
 Occurs in bones of axial skeleton, appendicular skeleton, and base of skull.
 Cartilaginous model of bone is first made by chondrocytes.
 Osteoclasts and osteoblasts later are replaced with woven bone and then remodel to lamellar bone.
 In adults, woven bone occurs after fractures and in Paget disease.
 Defective in achondroplasia.
Membranous Ossification
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 Intra-membranous bone formation is characterized by formation of bone without a pre-existing

cartilage matrix; it is the mechanism by which flat bones (skull and rib cage) develop.
 Occurs in bones of calvarium, facial bones, and clavicle.
 Woven bone formed directly without cartilage ➝ they are later remodeled to lamellar bone.
Cell Biology of Bones
Osteoblast
 Osteoblasts produce osteoid which is then mineralized with calcium and phosphate to form bone.
 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, pro-peptides 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, expressed on osteoblasts).
 OPG (osteoprotegerin, a RANKL decoy R’) binds RANKL to prevent RANK-RANKL interaction.
 Thus, there is  osteoclast activity.
Parathyroid Hormone
 At low, intermittent lvls, PTH exerts indirect anabolic effect (building bone) on osteoblast & osteoclast.
 Chronically  PTH levels (1° hyperparathyroidism) cause catabolic effects (osteitis fibrosa cystica).
Estrogen
 It inhibits apoptosis in bone-forming osteoblasts & induces apoptosis in bone-resorbing osteoclasts.
 Causes closure of epiphyseal plate during puberty.
 Estrogen deficiency (surgical or postmenopausal)
o  cycles of remodeling and bone resorption thus  risk of osteoporosis.

Chapter 8: Pathology of Bones

Common Pediatric Fractures
Greenstick Fracture
Definition: Incomplete fracture extending partway through width of bone following bending stress (A).
CF:
 Bone is bent like a green twig.
 bone fails on tension side.
 bone intact on compression side (compare to torus fracture).
Torus Fracture (Buckle Fracture)
Definition: Axial force applied to immature bone causes buckling of bone.
CF:
 Bone cortex buckles on compression (concave) side and fractures (B).
28

 Tension (convex) side remains solid (intact). (torus)

Pathology of Skeletal Bone

Iliopsoas Abscess FA 468
It’s a collection of pus in iliopsoas compartment which spreads from
 blood (hematogenous) or
 adjacent structure (vertebral osteomyelitis, tuberculous spondylitis AKA Pott disease, pyelonephritis)
Associated with Crohn disease, diabetes, and immunocompromised states.
Findings: flank bulge & pain, fever, inguinal mass, ⊕ psoas sign (hip extension exacerbates lower abdo. pain).
Labs:
 Leukocytosis; S. aureus MC isolated but may also occur 2° to tuberculosis.
 CT/MRI will show focal hypodense lesion within the muscle plane.
Treatment: antibiotics based on culture, CT-guided percutaneous drainage (PCD), or surgical drainage.

Avascular Necrosis of Femoral Head FA 473

Site: femoral head is a watershed zone thus insufficiency of medial circumflex femoral artery causes necrosis.
Causes: Casts Bend Legs
 Corticosteroids (glucocorticoids), Alcohol (chronic overuse), Sickle cell disease, Trauma, SLE,
 “Bends” (caisson/decompression disease),
 Legg-Calvé-Perthes disease (idiopathic), Gaucher disease, Slipped capital femoral epiphysis
Investigations: Microscopic analysis shows fat necrosis and dead bone i.e., clear empty lacunae.
Complications: Osteoarthritis and fractures
29

Achondroplasia
Etiology:
 Autosomal dominant with full penetrance (homozygosity is lethal). Associated with  paternal age.
 Due to activating mutation of fibroblast growth factor receptor 3 (FGFR3).
 Constitutive activation of fibroblast growth factor receptor (FGFR3) inhibits chondrocyte proliferation.
MC cause of dwarfism:
 Failure of longitudinal bone growth (endochondral ossification) ➝ short limbs.
 Membranous ossification is NOT affected ➝ large head relative to limbs (normal head size).
 Mental function, life span, and fertility are NOT affected.
Osteogenesis Imperfecta
Definition: autosomal dominant defect in collagen type I synthesis causes  bone formation.
CF:
 Structurally weak bone thus multiple fractures (can mimic child abuse but NO bruising).
 Blue sclera - Thinning of scleral collagen reveals underlying choroidal veins.
 Hearing loss - Bones of the middle ear easily fracture.
Osteopetrosis
Inherited failure of normal bone resorption d/t defective osteoclasts ➝ thick, dense bones that fracture easily.
Mutation (carbonic anhydrase II) impairs osteoclast ability to generate acidic environment for bone resorption
CF:
 Pancytopenia & extramedullary hematopoiesis because cortical bone overgrowth fills marrow space.
 Vision and hearing impairment due to cranial nerve impingement.
 Hydrocephalus due to narrowed foramen magnum.
 Renal tubular acidosis seen with carbonic anhydrase II mutation
o NO carbonic anhydrase ➝  tubular reabsorption of HCO3- ➝ leads to metabolic acidosis.
Labs: X-rays show diffuse symmetric sclerosis (bone-in-bone, “stone bone” A).
Treatment: bone marrow transplant is potentially curative as osteoclasts are derived from monocytes.
30

Osteoporosis (porous bones)

Cause:
  bone resorption ( osteoclast number and activity) related to  estrogen & old age.
 2° to drugs – steroids, alcohol, anticonvulsants, anticoagulants, thyroid replacement.
 Conditions – hyperparathyroidism, hyperthyroidism, multiple myeloma, malabsorption.
CF:
  trabecular (spongy) & cortical bone mass despite normal mineralization & lab values (Ca 2+, PO43−).
 Results in porous bone with  risk of fracture esp. in senile and post-menopausal women.
 vertebral compression fractures (weight-bearing areas) — acute back pain, loss of height, kyphosis.
 Also, it can present with fractures of femoral neck, distal radius (Colles’s fracture).
Diagnosis:
 Lab values are normal; One-time screening recommended in females ≥ 65 years old.
 bone mineral density measurement by
o by DEXA (dual-energy x-ray absorptiometry) at lumbar, hip, femoral neck with T-score ≤ −2.5 or
o by fragility fracture (fall from standing height, minimal trauma) at hip or vertebra.
Prophylaxis: weight-bearing exercise, adequate Ca2+ & vitamin D intake throughout adulthood.
Treatment:
 Bisphosphonates (induces apoptosis of osteoclasts), teriparatide, SERMs, calcitonin.
 Denosumab (monoclonal antibody against RANKL).
 Glucocorticoids are contraindicated (worsen osteoporosis).
Osteomalacia / Rickets (weak bones)
Vitamin D:
 Vitamin D is normally derived from skin upon exposure to sunlight (85%) and from diet (15%).
 Activation requires 25-hydroxylation by liver followed by 1-alpha- hydroxylation by proximal tubule
cells of kidney.
 Active vitamin D raises serum calcium and phosphate by acting on
o Intestine - increases absorption of calcium and phosphate
o Kidney - increases reabsorption of calcium and phosphate
o Bone - increases resorption of calcium and phosphate
Definition: Defective mineralization of osteoid (osteomalacia) or cartilaginous growth plate (rickets in child).
Vitamin D deficiency:
 Seen with  sun exposure (northern latitudes), poor diet, malabsorption, liver failure, renal failure.
 low vitamin D results in  serum Ca2+ ➝  PTH secretion ➝  serum PO43−.
 Hyperactivity of osteoblasts ➝  ALP.
CF:
 Osteomalacia d/t  vitamin D in adults ➝ Inadequate mineralization ➝ weak bone with  fracture risk.
 rickets is due to low vitamin D in children (<1 year)
o Pigeon-breast deformity – inward bending of ribs with sternal protrusion.
o Pathologic bow legs seen in ambulating children (genu varum A)
o rachitic rosary due to osteoid deposition at bead-like costochondral jxns (B)
o craniotabes (soft skull) & frontal bossing (due to osteoid deposition on skull)
Investigations:
 Lab findings include  serum calcium,  serum phosphate, PTH,  ALP.
 X-rays shows
o epiphyseal widening and metaphyseal cupping/fraying in rickets.
31

o osteopenia & pseudofractures in osteomalacia.

Paget disease of Bone (Osteitis Deformans)
Definition:
 localized bone remodeling disorder caused by  osteoclastic activity followed by  osteoblastic activity.
 This forms poor-quality bone (thick, sclerotic bone that fracture easily).
Stages of Paget disease:
 Early destructive (lytic): osteoclasts
 Intermediate (mixed): osteoclasts + osteoblasts
 Late (sclerotic/blastic): osteoblasts
 May enter quiescent phase
CF:
 Long bone chalk-stick fractures (microfractures causes bone pain).
  hat size due to skull thickening.
 Lion-like facies due to involvement of craniofacial bones.
 Hearing loss due to skull deformity (impingement on cranial nerve).
Investigations:
 Labs shows isolated  ALP in > 40-year-old. Serum Ca2+, phosphorus, and PTH levels are normal.
 Biopsy shows mosaic pattern of woven & lamellar bone (osteocytes in lacunae in chaotic juxtaposition)
Treatment: Calcitonin (inhibits osteoclast function) & Bisphosphonates (induces apoptosis of osteoclasts)
Complications:  osteosarcoma risk; formation of AV shunts causes  blood flow ➝ high-output heart failure.
Osteomyelitis
Definition: infection of marrow and bone in children.
Cause:
 MC bacterial; arises via hematogenous spread
o Transient bacteremia (children) seeds metaphysis.
o Open-wound bacteremia (adults) seeds epiphysis.
 Includes
o Staphylococcus aureus - most common cause (90% of cases)
o N gonorrhoeae - sexually active young adults
o Salmonella - sickle cell disease
o Pseudomonas - diabetics or IV drug abusers
o Pasteurella - associated with cat or dog bite/scratches
o Mycobacterium tuberculosis - usually involves vertebrae (Pott disease)
CF: Bone pain with systemic signs of infection (e.g., fever and leukocytosis)
Investigations:
 Diagnosis is made by blood culture.
 X-ray shows
o Lytic focus (abscess) surrounded by sclerosis of bone.
o Lytic focus is called sequestrum, and sclerosis is called involucrum.
32

Bone Tumors
33
34

Ewing Sarcoma
 Malignant proliferation of poorly-differentiated cells derived from neuroectoderm.
 Arises in diaphysis of long bones in male children (< 15 years of age).
 X-ray shows 'Onion-skin' appearance.
 Biopsy reveals small, round blue cells that resemble lymphocytes (Fig. 18.5).
o Can be confused with lymphoma or chronic osteomyelitis.
o t (11;22) translocation is characteristic.
 Often presents with metastasis; responsive to chemotherapy.
Metastatic Tumors
 More common than primary tumors result in osteolytic (punched-out) lesions.
 Prostatic carcinoma classically produces osteoblastic lesions.

Polyarthritis (> 5 joints pathology)

Rheumatoid Arthritis & Osteoarthritis (Degenerative Joint Disease)
35

Monoarthritis
Gout
Definition: Acute inflammatory monoarthritis caused by precipitation of monosodium urate crystal in joint (A)
36

Risk factors:
 Male sex, hypertension, obesity, diabetes, dyslipidemia, alcohol use.
 Strongest is hyperuricemia, which is caused by: (derived from purine pathway & excreted by kidney)
o Underexcretion of uric acid (90%)
 Largely idiopathic, potentiated by renal failure (renal insufficiency).
 Exacerbated by alcohol and certain medications (thiazide diuretics).
o Overproduction of uric acid (10%)
 Lesch-Nyhan syndrome, von Gierke disease.
 PRPP excess,  cell turnover (tumor lysis syndrome, Leukemia, myeloproliferative ds).
Acute Gout:
 Painful arthritis of MTP joint of big toe (podagra).
 Asymmetric joint distribution where joint is swollen, red, and painful.
 Acute attack occurs after
o large meal with foods rich in purines (red meat, seafood),
o trauma, surgery, dehydration, diuresis, or
o alcohol (beer > spirits) metabolites compete for same excretion sites in kidney as uric acid
 Thus,  uric acid secretion & subsequent buildup in blood.
Chronic Gout:
 Renal failure – urate crystals may deposit in kidney tubules (urate nephropathy).
 Tophus on external ear, olecranon bursa, or Achilles tendon.
o white, chalky aggregates of uric acid crystals with fibrosis & giant cell rxn in soft tissue & joints.
Investigations:
 Serum uric acid levels may be normal during an acute attack (hyperuricemia may also occur).
 Polarized light microscopy
o Crystals are needle shaped with
o ⊝ birefringent under polarized light (yellow under parallel light, blue under perpendicular light)
Treatment:
 Acute: NSAIDs (indomethacin), glucocorticoids, colchicine.
 Chronic (preventive): xanthine oxidase inhibitors (allopurinol, febuxostat).
Pseudogout (Calcium Pyrophosphate Deposition Disease)
Definition: Deposition of calcium pyrophosphate crystals within joint space in patients > 50 years old.
Cause: idiopathic but sometimes associated with hemochromatosis, hyperparathyroidism, joint trauma.
CF: Knee pain & swelling with acute inflam. (pseudogout) &/or chronic degeneration (pseudo-osteoarthritis).
Investigations:
 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.

Septic Arthritis
Definition: Unilateral arthritis (single joint, usually knee) where affected joint is swollen (A), red, and painful.
37

Cause:
 Streptococcus, S aureus (2nd MC; older children & adults), Neisseria gonorrhoeae (MC; young adults).
 Disseminated gonococcal infection
o STI that presents as either purulent arthritis (knee) or triad of polyarthralgia, tenosynovitis
(hand), dermatitis (pustules).
Diagnosis:
 Presents as a warm joint with limited range of motion & fever
 Synovial fluid is purulent (WBC > 50,000/mm3 i.e.,  WBC and  ESR).
Treatment: antibiotics, aspiration, & drainage (+/– debridement) to prevent irreversible joint damage.
Seronegative Spondyloarthropathies (PAIR)
It’s a Group of joint disorders characterized by
1. Arthritis without rheumatoid factor (NO anti-IgG antibody)
2. HLA-B27 association (MHC class I serotype)
3. Axial skeleton involvement
a. Subtypes (PAIR) share variable occurrence of
i. inflammatory back pain (associated with morning stiffness, improves with exercise),
ii. peripheral arthritis,
iii. enthesitis (inflamed insertion sites of tendons e.g., Achilles),
iv. dactylitis (sausage fingers), uveitis.
38

Autoimmune Connective Tissue Disease

Systemic Juvenile Idiopathic Arthritis
Definition: Systemic arthritis seen in < 16-year-old which is associated with anterior uveitis.
CF: it presents with daily spiking fevers, salmon-pink macular rash, arthritis (2+ joints).
Investigation: leukocytosis, thrombocytosis, anemia,  ESR,  CRP.
Treatment: NSAIDs, steroids, methotrexate, TNF inhibitors.
Sjogren Syndrome
Autoimmune ds characterized by exocrine gland destruction esp. lacrimal & salivary by lymphocytic infiltrates.
Predominantly affects females 40–60 years old.
Cause: 1° disorder or 2° syndrome associated with other autoimmune disorders (RA, SLE, systemic sclerosis).
CF:
 Inflammatory joint pain
 Bilateral parotid enlargement
 Xerostomia ( saliva production) ➝ mucosal atrophy, fissuring of tongue (B).
 Keratoconjunctivitis sicca ( tear production thus corneal damage) ➝ gritty or sandy feeling in eyes.
Investigations:
 labial salivary gland biopsy shows focal lymphocytic sialadenitis (confirms diagnosis).
 Presence of antinuclear antibodies (ANA).
 Rheumatoid factor positive in absence of rheumatoid arthritis (RA).
 Anti-ribonucleoprotein antibodies: SS-A (anti- Ro) and/or SS-B (anti-La).
 Anti-SSA and anti-SSB may also be seen in SLE.
Complications:
 dental caries;
 MALT lymphoma (may present as parotid enlargement).
  risk of giving birth to baby with neonatal lupus.
Systemic Lupus Erythematosus (SLE)
Definition:
 Systemic, remitting, and relapsing autoimmune disease associated with deficiency of early complement
proteins (C1q, C4, C2) ➝  immune complexes clearance.
Cause: organ damage due to type III hypersensitivity reaction (primary) or type II hypersensitivity reaction.
CF: rash, joint pain, and fever in a female of reproductive age ( in Black, Caribbean, Asian, Hispanics in US).
 RASH OR PAIN:
 Rash (malar A or discoid B)
 Arthritis (nonerosive)
 Serositis (pleuritis, pericarditis)
 Hematologic disorders (cytopenia)
 Oral/nasopharyngeal ulcers (usually painless)
 Renal disease
 Photosensitivity
 Antinuclear antibodies
 Immunologic disorder (anti-dsDNA, anti-Sm, antiphospholipid)
 Neurologic disorders (seizures, psychosis)
Complications:
 Libman-Sacks Endocarditis (LSE in SLE).
 In anti-SSA ⊕ pregnant patient,  risk of newborn developing neonatal lupus which leads to
39

o congenital heart block, periorbital/diffuse rash, transaminitis, and cytopenia at birth.

 Lupus nephritis
o glomerular deposition of DNA-anti-DNA immune complexes can be nephritic or nephrotic
(causing hematuria or proteinuria).
o Most common and severe type is diffuse proliferative.
Common causes of death in SLE:
 renal disease (most common), infections, cardiovascular disease (accelerated CAD).
 Lupus patients die with redness in their cheeks.
Mixed Connective Tissue Disease
It has features of SLE, systemic sclerosis, &/or polymyositis; associated with anti-U1 RNP Ab (speckled ANA).
Anti-phospholipid Syndrome
Definition: 1° or 2° autoimmune disorder (most commonly in SLE)
Diagnosis based on:
 clinical criteria including history of thrombosis (arterial or venous) or spontaneous abortion along with
 laboratory findings of lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein I antibodies.
 Anticardiolipin antibodies ➝ causes false-positive VDRL/RPR.
 Lupus anticoagulant ➝ causes prolonged PTT that is NOT corrected by adding N platelet-free plasma.
Treatment: Systemic anti-coagulation.
Scleroderma (Systemic Sclerosis) FA 485
CF:
 Female (75%) with auto-immunity, non-inflammatory vasculopathy, collagen deposition with fibrosis.
 Commonly skin sclerosis manifests as puffy, taut skin (A) without wrinkles & pitting of fingertip (B).
 Other systems
o Cardiovascular,
o pulmonary (interstitial fibrosis, pulmonary HTN),
o GI ( peristalsis and LES tone ➝ dysphagia, heartburn)
o renal (scleroderma renal crisis; treat with ACE inhibitors)
Diffuse scleroderma
 widespread skin involvement, rapid progression, early visceral involvement.
 Associated with anti-Scl-70 antibody (anti-DNA topoisomerase-I antibody) and anti-RNA polymerase III.
Limited scleroderma
 More benign clinical course thus limited skin involvement confined to fingers and face.
 Also with CREST syndrome:
o Calcinosis cutis (C), anti-Centromere Ab
o Raynaud phenomenon,
o Esophageal dysmotility,
o Sclerodactyly,
o Telangiectasia.
Raynaud Phenomenon
Pathology:
  blood flow to skin due to arteriolar (small vessel) vasospasm in response to cold or stress:
 color change from white (ischemia) to blue (hypoxia) to red (reperfusion) in fingers (A) and toes
Raynaud disease when 1° (idiopathic)
Raynaud syndrome
 when 2° to a disease process such as mixed connective tissue disease, SLE, or CREST.
40

 Digital ulceration (critical ischemia) seen in 2° Raynaud syndrome.

Treatment: calcium channel blockers.

Chapter 9: Pathology of Skeletal Muscles

X-Linked Muscular Dystrophy

Degenerative disorder characterized by muscle wasting & replacement of skeletal muscle by adipose tissue.
Cause: defects of dystrophin gene
 Dystrophin is important for anchoring the muscle cytoskeleton to the extracellular matrix.
 Mutations are often spontaneous; large gene size predisposes to high rate of mutation.
Becker muscular dystrophy is due to mutated dystrophin; clinically results in milder disease.
Duchenne muscular dystrophy is due to deletion of dystrophin.
 CF:
41

o Proximal muscle weakness at 1 year of age which progresses to involve distal muscles.
o Calf pseudohypertrophy is a characteristic finding.
o Death results from cardiac or respiratory failure; myocardium is commonly involved.
 Investigations:  serum creatine kinase.
42

Chapter 10: Pathology of Blood Vessels (Vasculitis)

43
44

Chapter 11: Pathology of Neuromuscular Junction

45

Chapter 12: Soft Tissue Tumors

Lipoma
 Benign tumor of adipose tissue
 Most common benign soft tissue tumor in adults
Liposarcoma
 Malignant tumor of adipose tissue
 Most common malignant soft tissue tumor in adults C. Lipoblast is the characteristic cell.
Rhabdomyoma
 Benign tumor of skeletal muscle
 Cardiac rhabdomyoma is associated with tuberous sclerosis.
Rhabdomyosarcoma
 Malignant tumor of skeletal muscle
 Most common malignant soft tissue tumor in children
 Rhabdomyoblast is the characteristic cell; desmin positive
 Most common site is the head and neck; vagina is the classic site in young girls.