MSK Flashcards

1
Q

what nerve root is the biceps reflex?

A

C5-C6

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2
Q

what nerve root is the triceps reflex?

A

C7-C8

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3
Q

what nerve root is the knee reflex?

A

L3-L4

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4
Q

what nerve root is the ankle reflex?

A

S1-S2

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5
Q

what nerve is the deltoid muscle innervated by?

A

C5

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6
Q

what nerve is the triceps muscle innervated by?

A

C7

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7
Q

what nerve is the quadriceps muscle innervated by?

A

L3

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8
Q

what nerve are the long flexors innervated by?

A

L8

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9
Q

what nerve is the gastrocnemius innervated by?

A

S1

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10
Q

Lateral epicondylitis:

  • AKA
  • what illicits pain?
  • how long do episodes last for?
A

tennis elbow
• Pain and tenderness localized to the lateral epicondyle
• Pain worse on resisted wrist extension with the elbow extended or supination of the forearm with the elbow extended also there is pain on middle finger extension
• Episodes typically last between 6 months and 2 years. Patients tend to have acute pain for 6-12 weeks

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11
Q

Medial epicondylitis:

  • AKA
  • what illicits pain
  • where can numbness/tingling be felt?
A

Golfers elbow
Features
• Pain and tenderness localized to the medial epicondyle
• Pain is aggravated by wrist flexion and pronation
• Symptoms may be accompanied by numbness / tingling in the 4th and
5th finger due to ulnar nerve involvement

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12
Q

Radial tunnel syndrome

  • what is this most commonly due to?
  • where is the pain
  • what movements worsen pain?
A

Most commonly due to compression of the posterior interosseous branch of the radial nerve. It is thought to be a result of overuse.
Features
• Symptoms are similar to lateral epicondylitis making it difficult to diagnose
• However, the pain tends to be around 4-5 cm distal to the lateral epicondyle
• Symptoms may be worsened by extending the elbow and pronating the forearm, not like tennis elbow where supinating is the problem

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13
Q

what is cubital tunnel syndrome?

  • where is tingling felt
  • what may worsen symptoms
A

Due to the compression of the ulnar nerve.
Features
• Initially intermittent tingling in the 4th and 5th finger
• May be worse when the elbow is resting on a firm surface or flexed for extended periods
• Later numbness in the 4th and 5th finger with associated weakness

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14
Q

what is olecranon bursitis?

A

Swelling over the posterior aspect of the elbow. There may be associated pain, warmth and erythema. It typically affects middle-aged male patients.

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15
Q

what is de-quervains tenosynovitis?

-who does this typically affect?

A

De Quervain’s Tenosynovitis is a common condition in which the sheath containing the extensor pollicis brevis and abductor pollicis longus tendons is inflamed. It typically affects females aged 30 - 50 years old

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16
Q

what are the features of de-quervains tenosynovitis?

  • where is pain? where is tender?
  • what movement is particularly painful?
  • what is finkelstein’s test?
A

Features
• Pain on the radial side of the wrist
• Tenderness over the radial styloid process
• Abduction of the thumb against resistance is painful
• Finkelstein’s test: with the thumb is flexed across the palm of the hand, pain is reproduced by
movement of the wrist into flexion and ulnar deviation

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17
Q

what is the management of de-quervains tenosynovitis?

A

Management
• Analgesia
• Steroid injection
• Immobilization with a thumb splint (SPICA) may be effective
• Surgical treatment is sometimes required

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18
Q

lateral epicondylitis: what activities typically cause this? who does it most commonly affect? which arm?

A

Lateral Epicondylitis typically follows unaccustomed activity such as house painting or playing tennis (‘tennis elbow’). It is most common in people aged 45-55 years and typically affects the dominant arm.

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19
Q

what is the management of lateral epicondylitis?

A
Management options
• Advice on avoiding muscle overload
• Simple analgesia
• Steroid injection
• Physiotherapy
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20
Q

what is carpal tunnel syndrome caused by?

A

Carpal Tunnel Syndrome is caused by compression of MEDIAN NERVE in the carpal tunnel

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21
Q

what is the typical history of carpal tunnel syndrome?

A

History
• Pain/pins and needles in thumb, index, middle finger e.g. At night
• Patient flicks hand to obtain relief

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22
Q

what is found on examination in carpal tunnel syndrome?

A

Examination
• Weakness of thumb abduction
• Wasting of thenar eminence (NOT
HYPOTHENAR)
• Tinel’s sign: tapping causes paraesthesia
• Phalen’s sign: flexion of wrist causes symptoms

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23
Q

what are the causes of carpal tunnel syndrome?

A

Causes: pregnancy, premenstrual, edema (CCF), lunate fracture, RA

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24
Q

what is seen on electrophysiology studies in carpal tunnel syndrome?

A

Electrophysiology

• Motor + sensory: prolongation of the action potential

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25
Q

what is the treatment of carpal tunnel syndrome?

A

Treatment
• Carpal injection
• Wrist splints at night
• Surgical decompression (flexor retinaculum division)

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26
Q

what is the role of the median nerve in the upper arm?

A

Arm: The median nerve has no voluntary motor or cutaneous function in the (upper) arm. It gives vascular branches to the wall of the brachial artery. These vascular branches carry sympathetic fibers.

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27
Q

what is the role of the median nerve in the forearm?

A

Forearm: It innervates all of the flexors in the forearm except flexor carpi ulnaris and that part of flexor digitorum profundus that supplies the medial two digits. The latter two muscles are supplied by the ulnar nerve (specifically the Muscular branches of ulnar nerve).

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28
Q

what does the main portion of the median nerve supply in the forearm?

A
The main portion of the median nerve supplies the following muscles:
Superficial group:
o Pronator teres
o Flexor carpi radialis 
o Palmaris longus
Intermediate group:
o Flexor digitorum superficialis muscle
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29
Q

what does the interosseus branch of the median nerve supply?

A

The anterior interosseus branch of the median nerve supplies the following muscles: Deep group:
o Flexor digitorum profundus (only the lateral half)
o Flexor pollicis longus
o Pronator quadratus

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30
Q

what is the motor supply of the median nerve in the hand?

A

The muscles of the hand supplied by the median nerve can be remembered using the mnemonic, “LOAF” for Lumbricals 1 & 2, Opponens pollicis, Abductor pollicis brevis and Flexor pollicis brevis.

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31
Q

what is the sensory innervation of the median nerve in the hand?

A

The median nerve innervates the skin of the palmar side of the thumb, the index and middle finger, half the ring finger, and the nail bed of these fingers.
The lateral part of the palm is supplied by the palmar cutaneous branch of the median nerve, which leaves the nerve proximal to the wrist creases. This palmar cutaneous branch travels in a separate fascial groove adjacent to the flexor carpi radialis and then superficial to the flexor retinaculum. It is therefore spared in carpal tunnel syndrome.

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32
Q

what does median nerve injury at a level above the elbow cause?

A

• Injury of this nerve at a level above the elbow results in loss of pronation and a reduction in flexion of the hand at the wrist.

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33
Q

what syndrome could cause entrapment of the median nerve at the level of the elbow or proximal forearm?

A

Entrapment at the level of the elbow or the proximal forearm could be due to the pronator teres
syndrome.

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34
Q

what causes anterior interosseous syndrome?

A

Injury to the anterior interosseous branch in the forearm causes the anterior interosseous
syndrome.

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35
Q

what does severing the median nerve cause?

A

• Severing the median nerve causes median claw hand
In the hand, thenar muscles are paralyzed and will atrophy over time. Opposition and flexion of
the thumb are lost. The thumb and index finger are arrested in adduction and hyperextension. This appearance of the hand is collectively referred as ‘ape hand deformity’..

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36
Q

anterior interosseous nerve:

  • what is this?
  • where does this arise?
A

Anterior Interosseous Nerve: is the largest branch of the median nerve arising distal to the lateral epicondyl. It is a favorite nerve in MRCP-I. It accounts for < 1% of all compression palsies in the upper limb.

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37
Q

what does anterior interosseous nerve supply?

A

It supplies:
• Flexor pollicis longus
• Felxer digtorium profundus to the index and sometimes middle finger
• Pronator quadrates

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38
Q

what are the symptoms of anterior interosseous nerve damage?

A

The typical symptoms:
• Inability to oppose the thumb and index finger
• Inability to flex the thumb IP joint
• Inability to flex the distal IP joint of the index
• Pronator quadrates paralyzed

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39
Q

where does the radial nerve arise from?

A

Radial Nerve: arises from the posterior cord of the brachial plexus (C5-8)

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40
Q

what is the motor innervation of the radial nerve?

A

Motor to

• Extensor muscles (forearm, wrist, fingers, thumb)

41
Q

what is the sensory innervation of the radial nerve?

A

Sensory to
• Dorsal aspect of lateral 3 1/2 fingers
• However, only small area between the dorsal aspect of the 1st and 2nd metacarpals is
exclusively by the radial nerve

42
Q

what is seen in radial nerve damage?

-what if there is axillary damage?

A

Patterns of damage
• Wrist drop
• Sensory loss to small area between the dorsal aspect of the 1st and 2nd metacarpals

Axillary damage
• As above
• Paralysis of triceps

43
Q

what does the ulnar nerve arise from?

A

Ulnar Nerve: arises from medial cord of brachial plexus (C8, T1)

44
Q

what is the motor innervations of the ulnar nerve?

A
Motor to
• Medial two lumbricals
• ADductor pollicis
• Interossei
• Hypothenar muscles: ABductor digiti minimi, flexor digiti minimi • Flexor carpi ulnaris
45
Q

what is the sensory innervation of the ulnar nerve?

A

Sensory to

• Medial 1 1/2 fingers (palmar and dorsal aspects)

46
Q

what is seen on radial nerve damage at the wrist?

-what if the damage is at the elbow?

A

Damage at wrist
• ‘Claw hand’
• Wasting and paralysis of intrinsic hand muscles (except lateral two lumbricals)
• Wasting and paralysis of hypothenar muscles
• Sensory loss to the medial 1 1/2 fingers (palmar and dorsal aspects)

Damage at elbow
• As above
• Radial deviation of
wrist

47
Q

Adhesive capsulitis:

  • what condition is this assoc with?
  • what are the phases of illness?
  • how long does the episode last for?
A

Adhesive Capsulitis (frozen shoulder) has a known association with diabetes. Patients typically
have a painful freezing phase, an adhesive phase and a recovery phase. The episode typically lasts 2-3
years.

48
Q

what is diabetic amyotrophy?

  • what happens?
  • where is affected?
  • who does this occur in?
A

Diabetic Amyotrophy: or proximal diabetic neuropathy or lumbosacral radiculoplexus
neuropathy, is a diabetic neuropathy characterized by painful muscle wasting and weakness. It affects
the lower limbs and is typically asymmetric. Proximal diabetic neuropathy typically occurs in aged
type 2 diabetic males, though it may occur in younger diabetic patients and females.

49
Q

what are red flags for back pain?

A
Red flags for lower back pain
• Age<20yearsor>50years
• History of previous malignancy
• Night pain
• History of trauma
• Systemically unwell e.g. Weight loss, fever
50
Q

Describe low back pain of facet joints?

A

May be acute or chronic
Pain worse in the morning and on standing
On examination there may be pain over the facets. The pain is typically worse on extension of the back

51
Q

describe what is seen in spinal stenosis:

  • what is the onset?
  • where is the pain?
  • what relieves the pain?
  • what is seen on examination
  • what is required for diagnosis?
A

Usually gradual onset
Unilateral or bilateral leg pain (with or without back pain), numbness, and weakness which is worse on walking. Resolves when sits down. Pain may be described as ‘aching’, ‘crawling’.
Relieved by sitting down, leaning forwards and crouching down
Clinical examination is often normal
Requires MRI to confirm diagnosis

52
Q

ankylosing spondylitis:

  • who does this most typically affect??
  • describe the symptoms?
A

Typically a young man who presents with lower back pain and stiffness Stiffness is usually worse in morning and improves with activity Peripheral arthritis (25%, more common if ♀)

53
Q

Describe the pain in peripheral artery disease?

  • what may be seen on examination?
  • what may be in the past medical history?
A

Pain on walking, relieved by rest

Absent or weak foot pulses and other signs of limb ischemia Past history may include smoking and other vascular diseases

54
Q

In lumbar disc prolapse:

  • what does this normally produce?
  • what pain is found?
  • when is the pain worse?
A

Prolapsed lumbar disc usually produces clear dermatomal leg pain associated with neurological deficits.
Features
• Leg pain usually worse than back
• Pain often worse when sitting

55
Q

Spinal cord compression:

-who is this more common in?

A

Spinal Cord Compression is an oncological emergency and affects up to 5% of cancer patients. It is more common in patients with lung, breast and prostate cancer

56
Q

what are the features of spinal cord compression

  • describe the back pain
  • describe the neurological signs seen
A

Features
• Back pain: may be worse on lying down and coughing
• Neurological signs depend on the level of the lesion. Tendon reflexes tend to be increased
below the level of the lesion and absent at the level of the lesion

57
Q

Describe the symptoms from an L3 nerve root compression?

A

Sensory loss from anterior thigh to medial aspect of lower leg
Weak quadriceps
↓ knee reflex
Positive femoral stretch test

58
Q

Describe the symptoms from an L4 nerve root compression?

A

Sensory loss anterior aspect of knee
Weak quadriceps
↓ knee reflex
Positive femoral stretch test

59
Q

Describe the symptoms from an L5 nerve root compression?

A

Sensory loss dorsum of foot
Weakness in foot and big toe dorsiflexion
Reflexes intact
Positive sciatic nerve stretch test

60
Q

Describe the symptoms from an S1 nerve root compression?

A

Sensory loss posterolateral aspect of leg and lateral aspect of foot
Weakness in plantar flexion of foot
↓ ankle reflex
Positive sciatic nerve stretch test

61
Q

what is the management of nerve root compression?

A

Management
• Similar to that of other musculoskeletal lower back pain: analgesia, physiotherapy, exercises
• If symptoms persist then referral for consideration of MRI is appropriate

62
Q

what is a bakers cyst?

  • what is the lining of this?
  • what is the investigation of choice?
  • what is the most common complication of a bakers cyst?
A

Baker Cyst (Popliteal Cyst)
• Most common mass in the popliteal fossa
• Since the cyst is an extension from the knee joint, it is lined by synovium.
• Ultrasound is the investigation of choice in the evaluation of a popliteal mass.
• Complication: most common is rupture or dissection of fluid into the adjacent proximal
gastrocnemius muscle belly which results in a syndrome mimicking the symptoms of a deep vein thrombosis. Doppler ultrasound will, however, show the vascular lumen to be compressible (the lumen is not compressible in DVT due to the presence of the thrombus).

63
Q

what are the ottowa rules for ankle injury?

A

Ankle x-ray is required only if there is any pain in the malleolar zone and + 1 of the following findings:
• Bony tenderness at the lateral malleolar zone (from the tip of the lateral malleolus to include the
lower 6 cm of posterior border of the fibular)
• Bony tenderness at the medial malleolar zone (from the tip of the medial malleolus to the lower
6 cm of the posterior border of the tibia)
• Inability to walk four weight bearing steps immediately after the injury and in the emergency
department

64
Q

The low calcium and phosphate combined with the raised alkaline phosphatase point towards what?

A

osteomalacia

65
Q

what i osteomalacia?

A

Basics
• Normal bony tissue but ↓ mineral content
• Rickets if when growing
• Osteomalacia if after epiphysis fusion

66
Q

what are the different types of osteomalacia?

A
Types
• Vitamin D deficiency e.g. Malabsorption, lack of sunlight, diet
• Renal failure
• Drug induced e.g. Anticonvulsants
• Vitamin D resistant; inherited
• Liver disease, e.g. Cirrhosis
67
Q

what are the features of osteomalacia/rickets?

A

Features
• Rickets: knock-knee, bow leg, features of hypocalcemia
• Osteomalacia: bone pain, fractures, muscle tenderness, proximal myopathy

68
Q

what are the investigations for osteomalacia?

A
Investigation
• Low Ca2, PO34-, 25(OH) vitamin D
• Raised ALP
• X-ray: children - cupped, ragged metaphyseal surfaces; adults - translucent bands (Looser’s
zones or pseudofractures)
69
Q

what is the treatment of osteomalacia?

A

Treatment

• Calcium with vitamin D tablets

70
Q

♂ with osteoporosis without significant Hx → check ?

A

testosterone

71
Q

what is the treatment of osteoporosis?

-when is this indicated?

A

• Treatment is indicated following osteoporotic fragility fractures in postmenopausal women who are confirmed to have osteoporosis (a T-score of – 2.5 SD or below). In women aged 75 years or older, a DEXA scan may not be required ‘if the responsible clinician considers it to be clinically inappropriate or unfeasible’
• Vitamin D and calcium supplementation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D replete
• Alendronate is first-line
• Around 25% of patients cannot tolerate
alendronate, usually due to upper gastrointestinal problems. These patients should be offered risedronate or etidronate.
• Strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates . Raloxifene may actually decrease the risk of breast cancer.

72
Q

bisphosphonates:

  • name 4
  • what fractures do these prevent?
A

Bisphosphonates
• Alendronate, risedronate and etidronate are all licensed for the prevention and treatment of post- menopausal and glucocorticoid-induced osteoporosis
• All three have been shown to ↓ the risk of both vertebral and non-vertebral fractures although alendronate, risedronate may be superior to etidronate in preventing hip fractures
• Ibandronate is a once-monthly oral bisphosphonate

73
Q

does vitamin D and calcium therapy decrease fracture rates?

A

Vitamin D and calcium
• Poor evidence base to suggest ↓ fracture rates in the general population at risk of osteoporotic fractures - may ↓ rates in frail, housebound patients

74
Q

what is raloxifene?

  • what fractures does this prevent?
  • what does this increase the risk of?
A

Raloxifene - selective estrogen receptor modulator (SERM)
• Has been shown to prevent bone loss and to ↓ the risk of vertebral fractures, but has not yet
been shown to ↓ the risk of non-vertebral fractures
• Has been shown to ↑ bone density in the spine and proximal femur
• May worsen menopausal symptoms
• ↑ risk of thromboembolic events
• May ↓ risk of breast cancer

75
Q

what is strontium ranelate?

  • how does this work?
  • what does this increase the risk of?
A

Strontium ranelate
• ‘Dual action bone agent’ - ↑ deposition of new bone by osteoblasts and ↓ the resorption of bone by osteoclasts
• Strong evidence base, may be second-line treatment in near future
• increased risk of cardiovascular events: any history of cardiovascular disease or significant risk of cardiovascular disease is a contraindication
• increased risk of thromboembolic events: a Drug Safety Update in 2012 recommended it is not used in patients with a history of venous thromboembolism
• may cause serious skin reactions such as Stevens Johnson syndrome

76
Q

what is teriparatide?

A

T eriparatide
• Recombinant form of parathyroid hormone
• Very effective at increasing bone mineral density but role in the management of osteoporosis
yet to be clearly defined

77
Q

HRT:

  • what does this decrease the risk of?
  • when should this be used?
A

Hormone replacement therapy
• Has been shown to ↓ the incidence of vertebral fracture and non-vertebral fractures
• Due to concerns about ↑ rates of cardiovascular disease and breast cancer it is no longer recommended for primary or secondary prevention of osteoporosis unless the woman is
suffering from vasomotor symptoms

78
Q

Hip protectors:

-who is this used in?

A

Hip protectors
• Evidence to suggest significantly ↓ hip fractures in nursing home patients
• Compliance is a problem

79
Q

patients who take which drug should be assessed for osteoporosis prophylaxis?
-what does this assessment involve?

A

Patients who take the equivalent of prednisolone 7.5 mg or more each day for 3 months or longer
should be assessed and where necessary given osteoporosis prophylactic treatment

Assessment for treatment - patients taking the equivalent of prednisolone 7.5 mg or more each day for 3 months, and one of the following
• Are over the age of 65 years
• Have a history of a fragility fracture
• Have a T-score less than - 1.5 SD

80
Q

what is the treatment given to patients who need osteoporosis prophylaxis due to prednisolone use?

A

Treatment
• First-line: oral bisphosphonate
• Second-line: alfacalcidol or calcitriol

81
Q

what is pagets disease?

A

Paget’s Disease is a disease of ↑ but uncontrolled bone turnover. It is thought to be primarily a disorder of osteoclasts, with excessive osteoclastic resorption followed by ↑ osteoblastic activity. Paget’s disease is common (UK prevalence 5%) and symptomatic in only 5%.

82
Q

what are the predisposing factors to pagets disease?

A
Predisposing factors
• Increasing age
• ♂sex
• Northern latitude
• Family history
83
Q

what are the clinical features of pagets disease?

A

Clinical features - only 5% of patients are symptomatic
Normal calcium and phosphate combined with a raised alkaline phosphate
• Bone pain (e.g. Pelvis, lumbar spine, femur)
• Classical, untreated features: bowing of tibia, bossing of skull
• Raised alkaline phosphatase (ALP) - calcium and phosphate are typically normal
(calcium can be raised)
• Skull x-ray: thickened vault, osteoporosis circumscripta

84
Q

what are the indications for treatment of pagets disease?

-what is used?

A

Indications for treatment include bone pain, skull or long bone deformity, fracture, periarticular Paget’s
• Bisphosphonate (either oral risedronate or IV zoledronate)
• Calcitonin is less commonly used now

85
Q

what are the complications of pagets disease?

A
Complications
• Deafness (cranial nerve entrapment)
• Bone sarcoma (1% if affected for > 10 years)
• Fractures
• Skull thickening
• High-output cardiac failure
86
Q

what is osteopetriosis?

-what can be used for treatment?

A
• AKA marble bone disease
• Rare disorder of defective osteoclast
function resulting in failure of normal
bone resorption
• Stem cell transplant and interferon-gamma
have been used for treatment
87
Q

what is osteogenesis imperfecta?

-what is the most common form?

A

Osteogenesis Imperfecta (more commonly known as brittle bone disease) is a group of disorders of collagen metabolism resulting in bone fragility and fractures. The most common, and milder, form of osteogenesis imperfecta is type 1

88
Q

how is osteogenesis imperfecta inherited?

-what is the pathogenesis?

A

Overview
• Autosomal dominant
• Abnormality in type 1 collagen due to ↓ synthesis of pro-α 1 or pro-α 2 collagen polypeptides

89
Q

what are the features of osteogenesis imperfecta?

A
Features
• Presents in childhood
• Fractures
• Blue sclera
• Deafness secondary to otosclerosis
90
Q

what are the features of rhabdomyolysis?

A
  • Acute renal failure with disproportionately raised creatinine
  • Elevated CK
  • Myoglobinuria
  • Hypocalcemia (myoglobin binds calcium)
  • Elevated phosphate (released from myocytes)
91
Q

what are causes of rhabdomyolysis?

A
  • Seizure
  • Collapse/coma (e.g. Elderly patients collapses at home, found 8 hours later)
  • Ecstasy
  • Crush injury
  • Mcardle’s syndrome
  • Drugs: statins
92
Q

what is the management of rhabdomyolysis?

A

Management
• IV fluids to maintain good urine output
• Urinary alkalinization is sometimes used

93
Q

why is there hypercalcaemia in myeloma?

A

Hypercalcemia in myeloma
• Due primarily to ↑ osteoclastic bone resorption caused by local cytokines released by the myeloma cells
• Other contributing factors include impaired renal function, ↑ renal tubular calcium reabsorption and elevated PTH-rP levels

94
Q

what is the diagnosis of myeloma?

A

• Monoclonal proteins in the serum and urine (Bence Jones proteins)
• ↑ plasma cells in the bone marrow
• Bone lesions on the skeletal survey
• Other findings on investigations:
o Rouleaux formation of RBCs on blood film

95
Q

what is a useful marker of prognosis in myeloma?

A

B2-microglobulin is a useful marker of prognosis - raised levels imply poor prognosis. Low levels of albumin are also associated with a poor prognosis

StageCriteriaMedian survival (months)
I B2 microglobulin < 3.5 mg/l Albumin > 35 g/l 62
II Not I or III 45
III B2 microglobulin > 5.5 mg/l 29

96
Q

what is ewings sarcoma?

  • who is this commonly found in?
  • male or female preponderance?
A

Ewing’s Sarcoma is the most lethal malignant primary bone tumor derived from the red bone marrow. It is most common in children and adolescents and rare after the age of 30 years. It has a ♂:♀= 3:2.

97
Q

what is the presentation of ewings sarcoma?

A

Presentation: earliest symptom is pain, which is usually intermittent but becomes increasingly intense. Delay in the diagnosis can occur due to the fact that the clinical picture may be similar to that of acute or chronic osteomyelitis. However, eventually most patients have a large palpable rapidly growing mass, which is tense and tender.

98
Q

what are poor prognostic features of ewings sarcoma?

A
  • Age > 12 years
  • ↑LDH
  • Anemia
  • Poor response to chemotherapy.