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
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
11.
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
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
21.
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
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
29.
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
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
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 )
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.
54.
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
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
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
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
Editor's Notes
This is a massively good diagram because it beautifully outlines most joints of the body, which are “synovial” joints.
Even the “degenerative” diseases of joints are called “arthritis”.
eburnation (e″bәr-na´shәn) conversion of bone into a hard, ivory-like mass
The rheumatoid “factor” is an antibody AGAINST the FC portion of IgG, often present in the serum of patients with RA and other autoimmune diseases.
The MAIN HISTOPATHOLOGY of rheumatoid arthritis is a WHOPPING SYNOVITIS!
ULNAR DEVIATION of MP joints is MOST consistent reliable finding.
Bouchard:Rheumatoid (PIP)::Heberden:Degenerative (DIP)
Section shows hyperplastic synovial lining with villous like projections , underlying dense lymphocytic infiltration and vascular congestion .
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 ) .
A TOPHUS is a GRANULOMATOUS response to monosodium urate crystals.
No skin changes, only in adults, no big association with cancer, and the inflammation is ENDOMYSEAL rather than PERIVASCULAR.
15% of dermatomyositis patients also have cancer, many are young adults and therefore there is a juvenile variant. Note the eyelid appearance and eyelid edema.
