PBL 17: Connective tissue disease Flashcards
Discuss the basic epidemiology, pathophysiology, presentation, investigation, management and prognosis of polymyalgia rheumatica
What is Polymyalgia Rheumatica:
Inflammatory Condition That Causes Pain and Stiffness in Proximal Muscles of Neck, Shoulders and Pelvic Girdle (in the Absence of Objective Weakness)
Associated With Giant Cell Arteritis: If Patients Untreated for PMR, Can Develop GCA
Epidemiology:
Must Be ≥ 50 years old - Average Age 70
More Common in Caucasians and Women (3:1)
Prevalence ≈ 20 per 100,000 in People Over 50
Pathophysiology:
Unclear
Immune Imbalance - PMR Patients Have Decline of Immunosuppressive T-Regulatory Lymphocytes and Increase in Pro-Inflammatory T-Helper Cells
Inflammatory Role of IL-6, IL-1: Clinical Expressions (Morning Stiffness, Fatigue, Pain) Believed To Be Mediated By Inflammatory Cytokines
Associated with HLA-DR4
Presentation:
Symmetrical Pain and Stiffness in Shoulder and Pelvic Girdle For ≥ 2 Weeks
Bilateral Hip Pain + Limited Range of Motion
Disturbs Sleep
Morning Stiffness > 45 Minutes
Systemic Symptoms: Weight Loss, Fatigue, Low-Grade Fever, Low Mood, Night Sweats
Often Without Synovitis - Associated With Redness, Warmth, Swelling and Pain On Movement
No Loss of Function, Weakness or Wasting - Problems with Movement are because of Pain and not Functional Issues (Guarding Instead of Neuromuscular Dysfunction, Which Can Be Proven By Neurological Exam)
Acronym to Describe Clinical Features of PMR: SECRET
Stiffness or Pain
Elderly Patients
Constitutional Symptoms
Rheumatism
ESR Elevated
Temporal Arteritis
Investigation:
Blood Tests
ESR - High (can present with normal ESR but rare)
FBC - Normocytic, Normochromic Anaemia
CRP - Elevated
Creatine Kinase - Normal
Anti-CCP - To Rule Out Rheumatoid Arthritis
ANA - To Rule Out SLE
Imaging
Ultrasound of Temporal Arteries - To Exclude Giant Cell Arteritis
PET Scan - Glucose Accumulates Around Shoulders, Sternoclavicular and Hip Joints
Biopsy
Temporal Artery Biopsy - To Exclude Giant Cell Arteritis
Management:
Glucocorticoids e.g. Prednisolone (10-15 mg)
Bone-Protective Drugs e.g. Bisphosphonates & Vit D
Individualised Exercise Programs For Muscle Mass and Function Maintenance, and to Reduce Fall Risk (especially frail older patients on long-term steroids)
Regular Monitoring - Dose of medication should be progressively reduced, according to symptoms and ESR
For Recurrent Flares - Methotrexate or Azathioprine.
Prognosis:
Overall Prognosis for PMR is Good
Relapses or Symptom Exacerbations are Common
Most patients should no longer be receiving treatment after 2 years
Discuss the basic epidemiology, pathophysiology, presentation, investigation, management and prognosis of systemic lupus erythematosus
Definition
SLE is a chronic multisystem disorder that most commonly affects women during their reproductive years. It is characterised by the presence of antinuclear antibodies. In addition to constitutional symptoms, it most frequently involves the skin and joints, although serositis, nephritis, haematological cytopenias, and neurological manifestations may occur during the course of the disease.
Epidemiology
Affects African American Women the most. Affects White American Men the least.
Pathophysiology
The heritability of SLE has been estimated to be 43.9%
Immune function in SLE is abnormal, with T- and B-cell dysfunction causing B-cell hyperactivity and impaired immune complex clearance from tissues. Dysfunction of the complement system and aberrant programmed cell death means that intracellular material is not disposed of correctly, allowing autoantibody production to develop against nuclear material. A wide variety of autoantibodies have been described, some of which are directly pathogenic (anti- double-stranded DNA, anti-Ro). The coagulation system may be abnormal and vasculopathy is common, resulting from clotting cascade antibodies (anti-C).
Presentation
Key diagnostic factors
Butterfly Rash - 35%
Photosensitive Rash
Discoid rash
Constitutional Symptoms → Fever, Fatigue, Weight Loss.
Risk Factors
More common in Women (10:1) ratio
More common in 30 years olds +
African Descent in US and Europe
Drug Use such as Hydralazine and Procainamide
Other Manifestations
Renal Disease (Indicator of Severe Disease) (Constant care required)
Cardiac Disease (Pericarditis, myocarditis and Libman–Sacks endocarditis) (Atherosclerosis)
Lung Disease (Pleuritic pain (serositis) or pleural effusion) (Increased DVT with Antiphospholipid Antibodies present)
Neurological Disease (Headache and poor concentration)
Gastrointestinal Involvement (Mouth Ulcers)
Haematological Disease (Lymphopenia → Indicator of Disease)
Investigation
Full blood count and differential → Anaemia, leukopenia, thrombocytopenia
Urea and electrolytes → elevated urea and creatinine
Erythrocyte sedimentation rate and C-reactive protein → elevated (non-specific)
Antinuclear antibodies, double-stranded (ds)DNA, Smith antigen → Positive
Urinalysis → Haematuria, casts (red cell, granular, tubular, or mixed) or proteinuria
Management
Joint symptoms and serositis
1st Line: Hydroxychloroquine: 200-400 mg/day orally given in 1-2 divided doses, maximum 5 mg/kg/day (base)
Add on:
Belimumab (monoclonal antibody targets the β-cell growth factor BLyS.
Prognosis
The outlook for patients with SLE is improving. Ten-year survival is over 90%. It is widely recognized that patients have a higher cardiovascular mortality and risks are managed aggressively. Malignancy and infection rates are higher.
Discuss the basic epidemiology, pathophysiology, presentation, investigation, management and prognosis of the common vasculitidies
Vasculitis is the inflammation of blood vessels
Primary vasculitis is an uncommon disease where vasculitis is the predominant feature
Secondary vasculitis is where vasculitis arises due to another disease (CTD, infection or medication)
Pathology:
idiopathic autoimmune-driven inflammation
due to inflammatory cell infiltration of blood vessel wall => fibrinois necrosis (necrotizing vasculitis)
antineutrophil cytoplasmic antibodies (ANCA) - specific and aid diagnosis and classification
Classification of primary vasculitides:
large-vessel vasculitis:
giant cell (temporal) arteritis and polymyalgia rheumatica
takayasu arteritis
medium-vessel vasculitis:
polyarteritis nodosa
kawasaki disease
small-vessel vasculitis:
Wegner syndrome (ANCA)
Churg-strauss syndrome (ANCA)
microscopic polyangitis (ANCA)
Henoch-Schonlein purpura
essential crypglobulinaemic vasculitis
giant cell (temporal) arteritis and polymyalgia rheumatica
What is giant cell arteritis and polymyalgia rheumatic?
inflammation of carotid arteries and their branches
epidemiology of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR)
usually coexist
PMR is not vasculitis
1-5 in 10 000
>60
2x more likely in women
presentation of giant cell arteritis (GCA)
insidious and abrupt onset of symptoms
unilateral headache with scalp tenderness - skin ishaemia
pain chewing - jaw claudication
thickening of temporal artey - beaded on palpation, pulseless
visual change - optical artery ischaemia, blindness can occur
Presentation of polymyalgia rheumatic
symmetrical pain and stiffness in shoulder and pelvic girdle
investigations into GCA?
temporal artery biopsy
blood test - ESR/CRP
investigations into PMR?
no specific tests - need to exclude mimics such as malignancy
CRP/ESR
Management of GCA and PMR?
corticosteroids (prednisolone)
high dose -> lower dose
patients should no longer be receiving treatment after 2 years
Takayasu arteritis
what is Takayasu ateritis? (+epidemiology)
a type of large-vesse vasculitis that affects the aorta and it’s major branches
mainly women age 25-30
most common in Asia
pathology of Takayasu arteritis
granulomatous inflammation of the vessel wall, leading to occlusion or weakening of the vessel wall.
presentation of Takayasu arteritis
claudication (myalgia due to ischaemia triggered by activity and relieved by rest)
visual disturbance
dizziness
stroke
clinical examination - subclavian bruits, difference in BP between limbs, loss of pulses
investigations into Takayasu arteritis
CT
MRI
PET
blood test - anaemia
angiography - coarctation, occlusion and aneurysmal dilatation
management for Takayasu arteritis?
high dose steroids
surgery (such as vascular bypass surgery)
polyarteritis nodosa
what is polyarteritis nodosa? (+epidemiology)
Medium vessel vasculitis
necrotising arteritis that leads to aneurysm formation
2x more likely to affect men, age 40-50
risk factor of polyarteritis nodosa?
hepatitis B
presentation of polyarteritis nodosa?
skin ulceration
rashes (livedo reticularis)
peripheral neuropathy
what is granulomatosis with polyangitis ? + epidemiology
small-vessel vasculitis causing inflammation of blood vessels in nose, sinus, throat, lungs and kidneys
40-65 years of age
presentation of granulomatosis with polyangitis?
fever
fatigue
haematuria
skin lesions/rashes
vision problems
coughing
shortness of breath
complications of granulomatosis with polyangitis?
lung failure
kidney failure
saddle nose
DVT
what is eosinophilic granulomatosis with polyangitis? (EPGA - Churg-strauss syndrome)
small vessel vasulitis that occurs in people with asthma/allergies
three stages of eosinophilic granulomatosis with polyangina?
- atopic stage
atopy
allergic rhinitis
adult onset asthma - eosinophilic stage
eosinophilia in blood samples
weight loss
night sweats
cough
diarrhoea
wheezing - vasculitis stage
rashes
mononeuritis multiplex
renal failure
abdominal pains
investigations into granulomatosis with polyangitis [2]/ eosinophilic granulomatosis with polyangitis
blood test - ESR/CRP, PR3 ANCA
biopsy of affected bloof vessels
management of granulomatosis with polyangitis?/ EPGA
cyclophosphamide in conjunction with corticosteroids
rituximab (B-cell depletion)
limited, non-life threatening - lowdose glucocorticoids and immunosuppressants such as azathioprine/methotrexate
Henoch–Schönlein purpura
what is Henoch–Schönlein purpura? (+epidemiology)
small vessel vasculitis
blood vessels in skin, joints, intestines and kidneys become inflammed and bleed
usually in children and adolescents
pathology of Henoch–Schönlein purpura?
immune complex vasculitis in blood vessels of skin, joints, intestines and kidneys after an infectious trigger
presentation of Henoch–Schönlein purpura
palpable purpuric rash on legs and buttocks
abdominal pain
GI bleeding
arthralgia
nephritis
investigations into Henoch–Schönlein purpura?
biopsy of affected tissue shows a vasculitis with IgA deposits in the vessel wall.
management of Henoch–Schönlein purpura?
usually only supportive treatment
glucocorticoids and immunosuppressants - severe disease
prognosis of Henoch–Schönlein purpura?
usually self-limiting disease that settles without specific treatment
Behçet’s disease
what is Behçet’s disease? (+epidemiology)
inflammation of small arteries and venules
rare in uk
more common in men 20s-30s
more common in people from countries in the Middle East and East Asia, including Turkey, Iran, Japan and China
aetiology of Behçet’s disease?
unknown
autoimmune
presentation of Behçet’s disease?
oral ulcers
genital ulcers
skin sores
uveitis
arthralgia
GI symptoms - abdominal pain, diarrhoea, bleeding
redness, swelling/ pains in arms and legs
aneurysms (inflammation of large arteries)
recurrent thromboses may occur
complications of Behçet’s disease?
decreased vision/blindness
investigations into Behçet’s disease?
no difinitive diagnosis - made on clinical grounds
tests to rule out other conditions:
pathergy test - pricking your skin with a needle to see if a particular red spot appears within the next day or two; people with Behçet’s disease often have particularly sensitive skin
Current guidelines state a diagnosis of Behçet’s disease can usually be confidently made if you’ve experienced at least 3 episodes of mouth ulcers over the past 12 months and you have at least 2 of the following symptoms:
genital ulcers
uveitis
skin lesions
pathergy
management of Behçet’s disease?
treat inflammation:
glucorticoids
immunosuppressants
Discuss the basic epidemiology, pathophysiology, presentation, investigation, management and prognosis of main connective tissue diseases (autoimmune and inherited)
Autoimmune:
Four main types:
Polymyositis and Dermatomyositis
Rheumatoid Arthritis
Systemic Sclerosis
Sjorgens syndrome
Polymyositis and Dermatomyositis
Polymyositis —> chronic inflammation of muscles
Dermatomyositis —> chronic inflammation of skin and muscles
Epidemiology
Both can develop at any age
More women than men
Pathophysiology
Autoimmune
Both can be caused by an underlying malignancy (lung, breast, ovarian, gastric)
Presentation
Skin involvement (Dermatomyositis only)
Gottron lesions (knuckles, elbows, knees)
Photosensitive erthyemataous rash
Purple rash on face and eyelids (heliotrope)
Periorbtial oedema
Subcutaneous calcinosis
Muscle fatigue and weakness
Insidious (3-6 month) onset
Usually painless
Proximal muscle weakness
Dysphonia and swallowing affected (other striated muscle damage)
Investigation
Elevated creatine kinase
Clinical presentation
Electromyography (EMG)
Muscle biopsy
Positive antibodies (myositis line blot)
Anti-Jo-1 ( Polymyositis and Dermatomyositis)
Anti-Mi-2 (Dermatomyositis)
Anti-nuclear (Dermatomyositis)
Management
Corticosteroids, prednisone, as first line for both conditions
Other options:
Immunosuppressants (azathioprine)
IV immunoglobulins
Biologics (infliximab and etanercept)
Prognosis
Continual management; could have flare ups. Maintain muscle strength as much as possible.
Systemic Sclerosis (Scleroderma)
Systemic sclerosis → autoimmune inflammatory and fibrotic connective tissue disease. Affects skin and internal organs
Scleroderma → hardening of the skin
Most patients with systemic sclerosis have scleroderma - there is also a localized version of scleroderma that only affects the skin
There are two types:
Limited cutaneous systemic sclerosis (lcSScl)
Diffuse cutaneous systemic sclerosis (dcSScl)
Epidemiology
Female, 40-50 years
Pathophysiology
Autoimmune - cause unclear
Presentation
Limited cutaneous systemic sclerosis
C - Calcinosis
R - Raynaud’s
E - oEsophageal dysmotility
S - Sclerodacyly
T - Telangiectasia
Diffuse cutaneous systemic sclerosis
CREST plus affecting internal organs
Cardiovascular (hypertension, CAD)
Lung (pulmonary hypertension and pulmonary fibrosis)
Kidney (glomerulonephritis and scleroderma renal crisis)
Investigation
Positive antinuclear antibodies (ANA) - not systemic sclerosis specific
Positive Anti-centromere antibodies - most associated with lcSScl
Positive Anti-Scl-70 antibodies - most associated with dcSSc
Nailfold Capillaroscopy - abnormal capillaries present in SS
Diagnosed with EULAR criteria
Management
Steroids and immunosuppressants (no current standard treatment for SS)
Medical
Nifedipine for Raynuad’s symptoms
PPIs for GI symptoms
Analgesia for joint pain
Abx for skin infections
Antihypertensives for HTN
Non medical
Stop smoking
Gentle skin stretching to maintain range of motion
Avoiding cold to not trigger Raynauds
Physio for healthy joints
Occupational health for help with ADLs
Prognosis
Continual management with MDT team
Sjorgens syndrome
Affects the exocrine glands, leads to dry mucous membranes
Primary Sjorgens → occurs in isolation
Secondary Sjorgens → occurs related to SLE or Rheumatoid Arthritis.
Epidemiology
Women, 40-50 years
Pathophysiology
Lymphocytic infiltration and fibrosis of salivary and lacrimal glands
Presentation
Dry eyes (conjunctivitis and blepharitis)
Dry mouth
Small joint pain
40 increased risk of lymphoma
Investigation
Schirmer Test - less than 10 mm of tears on paper strip tucked on lower eyelid after 5 mins
Management
Artificial tears
Artificial saliva
Vaginal lubricants
Hydroxychloroquine to slow progression of disease
Complications
Eye problems (conjunctivitis, corneal ulcers)
Oral problems (dental cavities, candida infections)
Vaginal problems (candidiasis and sexual dysfunction)
Lymphoma
Prognosis
Continual management of flare ups
Marfan syndrome
Affects connective tissue
Epidemiology
Rare, happening in about 1 in 5,000 people
Autosomal dominant
Equal in men and women
Pathophysiology
Mutation of FBN1
Presentation
Long bones
Spidery fingers
Aortic dissection
High arched palette
Lense dislocation
Myopia
Investigation
Genetic test
EKG
Eye exam
Management
No specific treatment
Mostly focuses on treating symptoms
Ehlers Danlos syndrome
Affects connective tissue Over 13 types of EDS
Epidemiology
1 in 5000
Presentation
joint hypermobility
hyperextensible skin
a varying degree of tissue fragility
Pathophysiology
Mutation of Collagen
Investigation
Genetic test
Management
Exercise to stabilise joints
Braces to prevent dislocation
Prognosis
Average life expectancy of 40 years
Osteogenesis imperfecta Type 1
Epidemiology
1 in 15,000 people
Presentation
Easily broken bones.
Bone deformities, such as bowing of the legs.
Discoloration of the white of the eye (sclera), which may be blue or grey in colour.
A curved spine.
Pathophysiology
Mutation of Collagen
Investigation
No specific test- diagnosed clinically
Management
No specific treatment just help with fractures
Prognosis
Normal lifespan
Osteogenesis imperfecta Type 2
Epidemiology
1 in 15,000 births
Presentation
Born with dwarfism
Blue sclerae
Short, bowed limbs
Pathophysiology
Mutation of Collagen
Investigation
Genetic testing
Management
Fractures but mist die within a few months after birth
Prognosis
Most die a few months after birth
Alport Syndrome
Epidemiology
1 in 7,500 births
Presentation
Hematuria
Proteinuria
Hypertension
Oedema
Pathophysiology
Mutation of Collagen
Investigation
Urine sample
BP
Kidney biopsy
Management
No specific treatment- treat symptoms
Prognosis
Lifespan up to 50’s
Epidermolysis bullosa (EB)
Rare skin disorder
Epidemiology
Very rare
Presentation
Blisters
Erosions
Nonhealing ulceration
Scars following minor trauma
Investigation
Skin biopsy
Management
No specific treatment
Supportive treatment
Wound care
Infectious control
Describe how tendons insert onto bone and briefly describe the presentations of the common clinical conditions which arise
Describe how tendons insert onto bone
Tendons →Attach muscle to bone
Anatomy
Composed of fascicles
separated by endotenon
surrounded by epitenon
The place where a tendon or ligament meets bone is called an enthesis.
Enthesitis → inflamed enthesis
Insertion
Tendons are inelastic and transmit the power from muscle contraction to bone. There isn’t a clear boundary between tendon and bone; instead there are 4 transitional tissues:
Tendon → fibrocartilage → mineralised fibrocartilage (Sharpey’s fibres) → bone
Describe presentations of common clinical conditions which arise
Enthesopathy is an umbrella term for conditions that affect these connection points
Enthesitis → when they get inflamed and painful because of injury, overuse or disease
Jumpers knees
Pain over the inferior pole of the patella, from overuse.
Can also occur at insertion of quadraceps
Treatment
gelatinous material scooped out
surgery for exceptional cases
Tennis Elbow
Enthesitis in common extensor origin, at the lateral epicondyle
Pain is exacerbated by resisted wrist extension
Treatment
Pain killers
RICE
Physio
Surgery (rare) remove scar tissue
Golfers Elbow
Enthesitis of the wrist flexor to the medial epicondyle
Pain is exacerbated on resisted wrist flexion.
Treatment
Pain killers
RICE, Physio
Surgery (rare) remove scar tissue
Achilles tendonitis
pain over insertion of tendon onto Os-Calcis
Worse in morning- improves during day
Treatment
RICE
Analgesics e.g. NSAIDS
Physio
Surgery (last resort) → excision of fibrous adhesions
Tendon rupture
biceps = pop eye sign
Speed of injury can differ what happens
fast- tendon rupture
slow- bon avulsion
Treatment
Surgery to repair the tendon RARE
support braces
Physio
NSAIDS
Describe the main muscle groups that provide movement within the upper limb and demonstrate their location on the living patient
Movements in the arm:
Shoulder: (glenohumeral. Shoulder girdle was covered last week)
Flexion/Extension
Abduction/Adduction
Internal/External Rotation
Circumduction (all of the movements combined to form a cone shape)
Elbow:
Flexion/ extension
Pronation/Supination at the radioulnar joint
Wrist:
Flexion/Extension
Abduction/Adduction
Hand:
Flexion/Extension of fingers
Flexion/Extension of thumb
Abduction/Adduction of fingers
Abduction/Adduction of thumb
Opposition of thumb
Nerve Innovation at a glance:
extensors: Radial Nerve
Anterior Forearm: Median Nerve
Hand: ulna nerve
Exceptions to the rule:
Anterior forearm: Ulna side of flexor digitorum profundus and flexor carpi ulnaris are both innovated by ulna nerve
Hand: LOAF muscles innovated by median nerve.
LOAF: Lateral 2 Lumbricals, Opponens pollicis, Abductor pollicis, flexors pollicis
Shoulder:
Rotation: Rotator Cuff
Supraspinatus, Infraspinatus, Teres minor: External rotation
Subscapularis: Internal rotation
Flexion: Anterior Deltoid, Pectoralis major, Coracobrachialis
Extension: Posterior deltoid, teres minor and major, latissimus dorsi
Abduction: Supraspinatus (First part of action until deltoid has leverage) Medial deltoid,trapezius, serratus anterior
Elbow:
Flexion: Bicep Brachii, Brachialis, Brachioradialis
Extension: Tricep Brachii, acnoneus
Pronation: Pronator Teres, pronator quadratus, Flexor carpi radialis (aids)
Supination: Bicep Brachii, brachioradialis, supinator
Wrist:
Flexion: Flexor carpi radialis, flexor carpi ulnaris
Extension: Extensor carpi radialis brevis and longus, extensor carpi ulnaris
Adduction: Flexor carpi ulnaris + Extor carpi ulnaris
Abduction: Flexor carpi radialis + Extensor carpi radialis brevis and longus
Hand:
Fingers:
Flexion
DIP: Flexor digitorum profundus
PIP: Flexor digitorum superficialis
Extension:
Extensor digitorum longus
5th finger: Extensor digiti minimi
Index finger: Extensor indices
Abduction
Dorsal interosseous muscles
Adduction
Palmar interossei muscles
Lumbrical muscles:
Unique as they don’t insert onto bone, but tendons.
Flex the fingers at the metacarpophalangeal joint
Extend the fingers at the interphalangeal joints
Thumb:
Flexion: Flexor pollicis longus and brevis (Flexion at IP and MCP joints for longus and MCP Joint for brevis), [Abductor Pollicis brevis at IP joint]
Extension: Extensor pollicis pollicis longus and brevis (extension at IP and MCP joints for longus and MCP Joint for brevis) [Abductor pollicis longus at MCP joint]
Abduction: Abductor pollicis longus (MCP joint), abductor Pollicis brevis (Abduction of MCP joint )
Adduction: Adductor pollicis (adducts at carpometacarpal joint), opponens pollicis
Opposition: Opponens Pollicis, adductor pollicis, abductor pollicis brevis
Muscles origins and insertions:
Arm:
Bicep Brachii- Origin Long head: supraglenoid tubercle of the scapular. Origin Short Head: Coracoid process. Inserts on tuberosity of radius and fascia of forearm via bicipital aponeurosis
Tricep Brachii- Long head origin: Posterior surface of humerus, above radial groove. Medial head origin: Inferior ⅔ of humerus. Long head origin: infraglenoid tubercle of scapular. Inserts on posterior surface of olecranon process
Brachialis- anterior surface of distal half of humerus, just distal to deltoid insertion. Inserts on ulnar tuberosity and coranoid process of ulnar
Coracobrachialis- Coracoid process to anteromedial surface of the humerus
Forearm: Common flexor origin: medial epicondyle of humerus. Common Extensor origin: Lateral epicondyle of humerus
Brachioradialis- lateral supracondylar ridge of the humerus to base of radius styloid process
Flexor carpi ulnaris- Common flexor origin to carpal bones on ulna side
Flexor digitorum profundus- Common flexor origin to distal phalanges
Flexor digitorum superficialis- Common flexor origin to proximal phalanges
Flexor carpi radialis- Common flexor origin to carpal bones on radial side
Pronator teres- Common flexor origin to lateral surface of proximal radius
Pronator Quadratus- Distal ends of radius and ulna
Flexor pollicis longus-Common flexor origin to distal phalange of thumb
Palmaris longus-Common flexor origin to form palmar aponeurosis
Extensor carpi radialis Brevis- common extensor origin to base of 3rd metacarpal
Extensor carpi radialis longus- Common extensor origin to base of 2nd metacarpal
Extensor carpi ulnaris- Common extensor origin to base of 5th metacarpal
Extensor digitorum- Common extensor origin to splits to 4 tendons for each digit. Has attachments at proximal and distal phalanges
Extensor indicis- Common extensor origin to index finger
Extensor digiti minimi- Common extensor origin to 5th finger
Extensor pollicis longus- middle ⅓ of radius to distal phalanx of thumb
Extensor pollicis brevis- distal ⅓ of radius to proximal phalanx
Abductor pollicis longus- Distal ⅓ of radius to proximal phalanx of thumb
Supinator- passes between proximal ends of radius and ulna
Hand:
Lumbricals
Opponens pollicis-
Flexor pollicis brevis-
Abductor pollicis brevis
Abductor digiti minimi
Dorsal Interosseus
Flexor digiti minimi brevis
Palmar interosseus
Describe the structure and composition of connective tissue
Connective tissues
Highly specialised tissues
Provide mechanical support and assist in movement
Matrix around cells regulates their behavior
May contain blood vessels, nerves
Arena for fighting infection
Diverse structure and function, but composed of same building blocks
Connective tissue components
Cartilage, Bone, Tendon, Skin
Cells - dynamically synthesize and break down connective tissue
Extracellular matrix - structural components
Ground substance - where fibers sit - proteoglycans
Elastic fibers
Collagen fibers
Matricellular proteins - have regulatory, non structural roles
Proteoglycans
Consist of a protein core, decorated with sugar chains
Variable in size
Hold water in tissues
Confer viscoelastic properties
Interact with cells, cytokines and collagen
Aggrecan
Forms huge multimetric aggregates in cartilage
Link protein stabilizes binding to hyaluronan backbone
Huge complexes of sulfated chondroitin & keratin sulfate are highly hydrophilic
Draws water into tissue so enables cartilage to resist compression
In osteoarthritis
Degradation of aggrecan and type II collagen impairs mechanical properties of cartilage
Altered joint mechanics causes breakdown of aggrecan and also collagen by proteolytic enzymes
This impairs cartilage functions, causing pain in affected joints
Elastic fibers
Consist of:
Elastin
Fibrillin -1, -2, -3
Fibulins esp 4 and 5
Matrix associated glycoproteins
Structured role:
Enable stretching of blood vessel walls, alveoli, bladder, tendons
Regulatory role
Regulate targeting and activation of growth factors (especially TGF beta)
Collagen fibers (Collagen fibrils - type I, II and III)
Collagen fibrils made up of 1-3 gene products make polypeptides that wrap round each other.
Collagen fibrils are made of many collagen molecules, with each molecule consisting of 3 “alpha” polypeptide chains arranged in a triple helix
Each chain is a single gene product
Either 3 identical alpha chains (homotrimer) e.g. type 2 collagen (cartilage)
Or two or more different alpha chains (heterotrimer) e.g. type I collagen (skin,bone)
Very stable and slowly turned over
Each molecule of fibrillar collagen is made up of 3 intertwined polypeptides
Unique amino acid composition
Tight packing of triple helix depends on glycine being every 3rd position
Proline and hydroxyproline provide rigidity and stability - unusual amino acid mostly found in collagen
Stabilised by hydrogen bonds between chains
Collagen fibril synthesis - polypeptides made on RER then hydroxylation occurs and glycosylation - 3 alpha chains then assemble and bonds form between them
Proline to proline hydroxylase needs vitamin C to produce Fe2+ for proline hydroxylase to work
Vitamin C deficiency causes reduced collagen hydroxylation and that causes scurvy
Weaker collagen fibrils leads to scurvy
Bleeding gums
Loss of teeth
Skin lesions, bruises
Poor wound healing
Joint pain and weakness
Connective tissue has different organisation of collagen composition
Skin - 60% type I, 30% type II - meshwork of fibres
Tendon / ligament - 90% type I, 5% type III - parallel fibres
In bone: Type I forms lamellae
Type I collagen is principle protein component
Type I collagen fibers are arranged into lamellae
Hydroxyapatite crystal deposits harden bone
In tendon: the insertion (enthesis) has a different matrix composition & organisation
Enthesis common site of tendon pathology
Is a region where mechanical stress is concentrated
Common site of microdamage and overuse injury
e.g. tennis elbow, golfers elbow
Changes associated with tendinopathy:
Loss of collagen fibril organisation and reduced fibril diameter
Changes in collagen content
Increased type III collagen
Increased turnover
Vascular nerve infiltration
Failure to repair
Skin and blood vessels
Rich in type III collagen
Forms mixed fibrils with type I
Deficiencies in type III lead to fragility of skin and blood vessels
Summary
To summarise, some examples of acquired connective tissue diseases are: Scurvy – a disease of impaired collagen synthesis Vitamin C deficiency causes poor proline hydroxylation
structure of fibril-forming collagens (types I, II and III) is weakened
Skin/bone/gums affected
Diseases of altered mechanics
Abnormal mechanics lead to altered connective tissue structure, which impairs the tissue function e. g. tendinopathy
Often affects the enthesis
Altered collagen content and organisation e. g. osteoarthritis increased breakdown of collagen (type II) and aggrecan in cartilage
