Arthritis

1. ARTHRITIS Lec 7

2. SYNOVIAL JOINTS

3. Arthritis
• Arthritis = inflammation of the joints. Term also
used by lay people to describe pain in soft tissues.
• Over 200 forms of arthritis.
• About 30% of adults have arthritis.
• Major symptom = in or around jointsPAIN

4. ARTHRITIS
–DEGENERATIVE (OSTEOARTHRITIS)
–RHEUMATOID
–NON-INFECTIOUS: Ankylosing Spondylitis .
–INFECTIOUS: Suppurative .
–GOUT (URATE)

6. Osteoarthritis
Breakdown in cartilage and new bone
formation
Increased risk with older age, obesity, overuse
or previous injury to joints

7. “DEGENERATIVE” ARTHRITIS
aka, “OSTEO”ARTHRITIS
• Etiology/Risk Factors: Age, Trauma, Genes
• Pathogenesis: Progressive EROSION of articular
cartilage
• Morphology: X-Ray, “eburnation”, “joint mice”,
osteophytes
• Clinical Expression: PAIN, Limitation of motion

8. 8PROF SDS

9. Progressive erosion of articular cartilage, eburnated articular
surface , subchondral cyst and residual articular cartilage
(Osteoarthritis)
Ms-Sk - 7

10. Mushroom-shaped osteophytes (bony outgrowths ) develop at the
margins of the articular surface and are capped by fibrocartilage
and hyaline cartilage that gradually ossify . (Osteoarthritis)
Ms-Sk - 8

12. RHEUMATOID ARTHRITIS
Rheumatoid arthritis (RA) is a chronic systemic
inflammatory disorder that may affect many
tissues and organs—skin, blood vessels, heart,
lungs, and muscles—but principally attacks the
joints, producing a nonsuppurative proliferative
and inflammatory synovitis that often progresses
to destruction of the articular cartilage and
ankylosis of the joints.

13. RHEUMATOID ARTHRITIS
• Etiology/Risk Factors: Autoimmune
• Mean age 45 YRS (1% of population F>>M)
• Pathogenesis: Progressive SYNOVITIS
• Morphology: Synovial lymphocytes,
macrophages, plasma cells, neutrophils,
osteoclasts, “pannus”, hyperemia, rheumatoid
“nodules”, vasculitis
• Clinical Expression: PAIN, Limitation of motion,
malaise, fatigue, rheumatoid factor IgM-IgGFc,

14. DIAGNOSIS
• By clinical features and presence of 4 of the
following criteria :
– MORNING STIFFNESS
– ARTHRITIS in 3 or more JOINT AREAS
– “TYPICAL” hand findings, MP ULNAR deviation
– SYMMETRIC ARTHRITIS
– RHEUMATOID NODULES
– SERUM RHEUMATOID FACTOR
– “TYPICAL” X-RAY findings

16. Rheumatoid Arthritis
Pathology
Synovitis
chronic inflamation, synovial hypertrophy,
effusion
Destruction
proteolytic enzymes, pannus
Deformity
articular destruction, capsular stretching,
tendon rupture

17. Rheumatoid arthritis
affecting the head of
the femur.
The synovium
becomes edematous,
thickened and
hyperplastic and
transforming its
smooth contour to one
covered by delicate
and bulbous fronds .
Ms-Sk - 9

18. Hyperplastic synovial lining with villous like projections , underlying
dense lymphocytic infiltration and vascular congestion
Ms-Sk - 10

19. Section shows a pannus consisting of fibrinous inflammatory
exudates with underlying markedly inflamed synovium . Later on,
the pannus may fill the joint space and undergo fibrosis ,
calcification and causes permanent ankylosis adhesions
Ms-Sk -12

20. Differentiating Features
• Rheumatoid Arthritis
• Young age
• Female more
• Morning stiffness>1 h.
• Symmetrical
• Small joints
• Autoimmune
• Synovial inflammation
• Synovium- Cartilage
• Rh. Factor positive
• Osteoarthritis
• Old age
• Both sexes equal
• Pain through the day
• Asymmetrical
• Large joints
• Degenerative
• Catilage degeneration
• Cartilage-synovium
• Rh.Factor negative

22. ANKYLOSING SPONDYLITIS
0.2% of population0.2% of population
Mainly affects spine and Sacroiliac jointsMainly affects spine and Sacroiliac joints
• [HLA-B27] positive
(M>>F)
• Strongly familial
• More than 25% have iritis
Third and fourth decadeThird and fourth decade

23. Ankylosing Spondylitis
flexion deformities
arthritis with large osteophytes
ankylosis

24. Ankylosing Spondylitis

26. INFECTIOUS ARTHRITIS
• From OSTEOMYELITIS
• USUALLY SUPPURATIVE
• Gonococcal(GC), staph, strep, H. flu, E. coli,
(Salmonella in sicklers)
• 3 cardinal signs, fever, leukocytosis, increased
ESR

27. Frequency
• 2-10 cases per 100,000 in the general
population
• 30-70 cases per 100,000 in patients with
immunological disorders or deficiencies, and
joint replacements
• Gonococcal: women 3x > men

28. Infection Sources
• Trauma: direct
• Hematogenous: IV drug injection
• Osteomyelitis adjacent to joint capsule
• Soft tissue infections: cellulitis, abscess,
bursitis, tenosynovitis

30. GOUT
• Endpoint of HYPERURICEMIA from ANY
cause resulting in JOINT deposition of
monosodium urate crystals (TOPHI)
–ACUTE
–CHRONIC
• 10% of population has hyperuricemia (>7
mg/dl), but only 1/20 of these has gout

31. 31PROF SDS
CRYSTAL DEPOSITION DISEASE
( CDD )
GOUT
Disorder of purine metabolism characterized by hyperuricaemia
& recurrent attacks of acute synovitis
M:F = 20:1
2 Types:
Primary (95%): inherited disorder with overproduction or
under excretion of uric acid
Secondary (5%): myeloproliferative disorders, renal disease
Only a small number of people with hyperuricaemia develop
gout.

32. 32PROF SDS
CDD - GOUT
Clinical:
The joints most commonly affected by gout are:
Forefoot
podagara: - classic presentation of acute attack of first MTP
joint, Elbows and hands
unlike RA hand and wrist joints will have preserved joint
spaces and normal mineralization
The large joints (hips, knees, ankles and shoulders) are
infrequently involved
Spine very rarely affected.
Nephrolithiasis is major extraarticular manifestation; - only
small % of pts w/ gout get tophi, but many get renal stones; -
pure uric acid stones are found in 80%, & uric acid is probably
nidus for Ca-Phos & oxalate calculi in remainder; - in 1/2, sx from
renal stones actually precede arthritis

33. Acute gouty arthritis on the big toe of an
elderly man.
Ms-Sk -13

34. Gouty arthritis of the knee joint

36. Assessment
• The most common type of arthritis in old age
is :
• A. Gouty arthritis
• B. Rheumatoid arthritis
• C. Osteoarthritis
• D. Tuberculous arthritis
• E. Septic arthritis

37. • The main pathology of osteoarthritis is:
• A. Autoimmune destruction of the
synovial membrane.
• B. Degeneration of the articular cartilage
• C. Osteoporosis
• D. Vitamin D deficiency
• E. Tophi formation

39. MYOPATHY Lec 8

40. Muscle Anatomy: gross and microscopic

41. INTRODUCTION
• Muscle development and normal activity are
dependent on and closely integrated with the
central and peripheral nervous system.
• Together they contribute to the motor unit.
• A motor unit is composed of;
– Motor neuron in the brain or spinal cord
– Peripheral axon
– Neuromuscular junction
– Skeletal muscle fiber

42. Type 1 and 2 muscle fibers
• Type 1
slow twitch, oxidative
• Type 2
fast twitch, mainly glycolytic
• Normal human muscle
mosaic pattern (checkerboard) of both fiber
types

43. ATPase histochemical
staining, at pH 9.4,
of normal muscle
showing
checkerboard
distribution of
intermingled type 1
(light) and type 2
(dark) fibers.
NORMAL MUSCLE FIBERS

44. Muscle pathology
• Two major types of pathology
• Neurogenic
• - loss of nerve stimulation
• Myopathic
• - intrinsic abnormality of muscle

45. Neurogenic atrophy
• It is a special form of progressive atrophy seen when the
nerve is damaged with deprivation of normal muscle
innervation.
• Causes ;
– Complete resection of a peripheral nerve
– Hereditary diseases characterized by loss of
spinal motor neurons as spinal muscular
atrophy (Werdnig Hoffman disease ).

46. Neurogenic atrophy
• Clinical features;
• Muscle weakness, which may be mild and
localized or severe and generalized with
respiratory compromise.

47. Neurogenic atrophy
• Morphology;
• The denervated atrophic muscles are sharply small
and angulated.
• They are distributed among adjacent normally
innervated fibers.
• After the injured axon regenerates, its sprouts
(newly formed buds) tend to innervate adjacent
myofiber, resulting in aggregation of muscle fibers of
the same type
• With loss of random distribution (fiber type grouping
– Grouped atrophy – type 2 muscle fiber atrophy)

48. Spinal muscular atrophy with groups of atrophic muscle
fibers resulting from denervation atrophy of muscle with
adjacent groups of normal fibers.
Neurogenic atrophy, Morphology:

49. Myopathy
• Def. : disorders with structural changes or functional
impairment of a muscle; unrelated to any disorder of
innervation or NMJ.
• Classification :
1. Acquired
2. Hereditary/ genetic : mutations or deletions of genes
coding for parts of a muscle ( filament proteins,
mitochondrial enzymes, sarcoplasmic reticulum, specialized
channels for entry of ca+2
, Na+2
, Cl-
, K+1
transverse tubules,
sarcolemma )

50. CAUSES OF MYOPATHY
INHERITED
MUSCULAR DYSTROPHIES CONGENITAL MYOPATHIES
MITOCHONDRIAL MYOPATHY SYNDROMES CHANELLOPATHIES
INHERITED DISORDERS OF METABOLISM
ACQUIRED
INFLAMMATORY
PM, DM, IBM
ENDOCRINE ^METABOLIC
HYPOTHYRIODISM
HYERTHYRIODISM
ACROMEGALLY
CUSHING’S SYNDROME
(INCLUDING IATROGENIC)
ADDISONS DISEASE
CONN’S DISEASE
OSTEOMALACIA
HYPERCALCEMIA
HYPOKALEMIA
TOXIC
ALCOHOL (CHRONIC,
ACUTE SYNDROME)
VIT. E
ORGANOPHOSPHATS
SNAKE VENOMES
INFECTIONS
Trichinosis
Cysticercosis
Toxoplasmosis
HIV
Coxackie - A& B
Influenza
Lyme disease
Staph. aureus
/pyomyositis/
DRUGS
STEROIDS
STATINS
B-BLOCKERS
ZIDOVUDINE
AMIODARONE
CHLOROQUINE
CLOFIBRATE
VINCRISTINE
CYCLOSPORINE
OPIATES
E-AMINOCPROIC ACIDS
COLCHICINE
D-PENICILLAMINE

51. Clinical presentation
• Muscle weakness
• Fatigue
• Muscle pain( myalgia), cramps and stiffness
• Muscle contracture
• myoglobinuria
• Myotonia
• Muscle enlargement and atrophy
• Manifestations of specific illnesses

52. Epidemiology
• Worldwide incidence of all inheritable myopathies is
about 14%
• Overall incidence of muscular dystrophy is about 63
per 1 million.
• Worldwide incidence of inflammatory myopathies is
about 5–10 per 100,000 people. More common in
women
• Corticosteroid myopathy is the most common
endocrine myopathy and endocrine disorders are
more common in women
• Overall incidence of metabolic myopathies is
unknown.

53. Muscular dystrophy
• Muscular dystrophy is a heterogeneous group
of hereditary noninflammatory but
progressive muscle disorders without a
central or peripheral nerve abnormality.
• It’s clinically characterized by progressive
muscle weakness and wasting.

55. • DMD is the most severe and common type of
muscular dystrophy.
• DMD is characterized by the wasting away of
muscles.
• DMD affects males at a rate of 1 in 10000
births
• Diagnosis in boys usually occurs between 16
months and 8 years.

56. DMD
• X-linked (males affected, female carriers)
• Weakness Quadriceps and Gastrocnemius first
followed by all proximal muscles
• Often swollen gastrocnemius region early in
disease.
• If untreated (respiratory support), usual age of
death around 18 ys

57. Duchenne muscular dystrophy
– Dystrophin gene mutation (at Xp21)
– No abnormality is noted in the patient at birth
– The symptoms appear at the age of 2~6 yr, and
patients are usually wheelchair-bound by 10 yr.
– Rapidly progressive
– Not only skeletal muscle but also cardiac and
smooth muscle and some patients are mentally
retarded
– Death occurs late in the second decade from
respiratory complications in over 90% of cases

58. Dystrophin
• Muscle membrane protein
• Has integral role in sarcolemmal stability
• Muscle biopsy show absence of dystrophin
by western blot analysis in DMD
• Absence of the dystrophin protein  weakens
the connections between proteins in the
muscle fibers & the cell membrane. (?the cell
membrane becomes weaker & ruptures)

59. Duchenne Muscular Dystrophy
Pathology
• Variation in fiber size with large rounded
fibers
• Marked endomysial fibrosis
• Some regeneration
• Eventually muscle replaced by fat and fibrous
tissue

60. Duchenne muscular dystrophy showing variations in muscle
fiber size , increased endomysial connective tissue , and
regenerating fibers
(blue tint) / hypercontracted fibres (hyaline fibres).

62. Beckers MD
• Is milder form
• 5/100,000
• Age :5-15y
• Wheelchair at 30y
• Cardiac similar to duchenne
• Death by age 40
• Dx: DNA, muscle biopsy decrease in dystrophin
• CK:moderatly elevated

63. Inflammatory Myopathies
Non infectious (Autoimmune )
•Polymyositis
•Dermatomyositis
•Inclusion body myositis
Infectious
•Trichinosis
•Viral myositis

65. Polymyositis (PM)
It means "inflammation of many muscles"; it is a
type of chronic inflammation of the muscles
possibly due to autoimmune causes

66. • Clinical presentation:
– Adults
– Bilateral proximal muscle weakness
– Elevated creatine kinase
• Microscopic:
– Endomysial lymphocytic inflammation
– Skeletal muscle fiber degeneration and
regeneration

67. Polymyositis - endomysial, chronic inflammatory cell
infiltrates and chronic myopathic changes. H&E stain.

68. Dermatomyositis
• Dermatomyositis (DM) is a connective-tissue
disease related to polymyositis (PM) that is
characterized by inflammation of the muscles and
the skin.
• The disease may also affect the joints, the
esophagus, the lungs, and, less commonly, the
heart.

69. Dermatomyositis
• Clinical presentation:
1. Children and adults
2. Bilateral proximal muscle weakness
3. Skin rashes (upper eyelids)
4. Peri-orbital edema
• Microscopic:
1. Perimysial and vascular lymphocytic
inflammation
2. Skeletal muscle fiber degeneration and

70. Eruption is associated with peri-orbital edema and
telangiectasias of the both eyelids.

71. Dermatomyositis
• The histologic
appearance of
muscle shows
perifascicular
atrophy of muscle
fibers and
inflammation .

73. MYASTHENIA GRAVIS
DEFINITION: Disorder of the NMJ (postsynaptic membr)
Forms:
• Transient neonatal (~10% of neonate myasthenic mothers)
– Different prognosis, effective treatment
• Congenital myasthenia
• Common myasthenia gravis
– Any age: 2 pics: 20-30 (F > M) & 60-70 M = F)
– Usually progressing (remission are possible but:
relapse later)

74. Myasthenia Gravis
–Associated with thymic hyperplasia&
thymomas
–Thymectomies often useful Rx:
–AUTOIMMUNE DISEASE, CLEARLY
–Ab’s to Acetylcholine receptors
–YOUNG WOMEN WITH EYE MUSCLE:
• Ptosis 
• Diplopia
• General Weakness

75. MYASTHENIA GRAVIS
CLINICAL FEATURES
- Onset: insidious
- Fluctuating weakness: ↑ with exercise
- Fatigability (worsening with exercise & improvement in rest)
- Precipitating factors: Infection, Pregnancy, stress, hot
temperature, drugs: muscle relaxants, phenytoin
antibiotics (neomycin)
Clinical presentation:
- Ocular: – ptosis, diplopia opthalmoplegia
- Bulbar: dysphagia, dysphonia, +/-facial weakness
- Generalized: +/-respiratory muscles weakness  risk
of death

76. Assessment
– Myasthenia gravis:
• A. Is inherited as autosomal dominant manner in
males
• B. The affected females may suffer from drooping
eye lid (ptosis)
• C. It may show antibodies to dystrophin protein
• D. Is caused by destruction of the anterior horn cells
in the spinal cord