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What type of bones cells make new bone?
osteoblasts
What type of bone cells lie in a lacunae waiting for signals from either osteoblasts or osteoclasts?
osteocytes
What type of bone cells take over and remove old bone?
osteoclasts
Organic Matrix: _________ (unmineralized matrix)
• Collagen, type 1: tensile strength
• Proteoglycans: hyaluronic acid acts as “the cement” (vitreous humor, umbilical cord, synovial fluid)
• Cytokine and Growth factors
Osteoid
Elevation of what component of bone matrix should make us consider pathology?
alkaline phosphatase
What are the two major types of connective tissue matrices?
- interstitium
- basement membrane
What major type of connective tissue is made up of mesenchymal cells and forms the **stroma** of organs?
Interstitium
What major type of connective tissue is a thin sheet-like membrane comprised of endo-, epithelial cells?
Basement membrane
What are the 4 classes of extracellular macromolecules of connective tissue?
- Collagen (Stroma)
- Elastin (Scaffold)
- Glycoproteins (Adhesion Molecules)
- Proteoglycans (PTNs)
Type I collagen is what?
skin, tendon, bone
Type II collagen is what?
hyaline cartilage
Type III collagen is what?
blood vessels, parenchymal cells
Type IV collagen is what?
basement membrane
Type V collagen is what?
smooth muscle
Which of the 4 classes of Extracellular Macromolecules of Connective Tissue is an insoluble protein polymer comprised of tropoelastin, microfibrils (MAGP) and fibrillin.
Elastin (scaffold)
Which of the 4 classes of Extracellular Macromolecules of Connective Tissue is ***Structural?
– Major one is fibronectin; others are vitronectin, tenascin
• Also contains cartilaginous glycoproteins.
Glycoproteins (adhesion molecules)
Which of the 4 classes of Extracellular Macromolecules of Connective Tissue is comprised of proteins made up of several glycosaminoglycan side chains (N-acetylglucosamine & N-acetylgalactoseamine), hyaluronic acid, heparan sulfate, chondroitin sulfate?
Function as “multi-purpose glue” binding extracellular matrix components together, mediate cell binding to the matrix and restrain soluble molecules such as growth factors in the matrix and cell surfaces.
Proteoglycans
What are the 3 types of normal cartilage?
- Hyaline (joints)
- Fibrin (cartilage/fibrous, pubic symphesis; can self repair)
- Elastin (C-spine ONLY)
Cartilage types in various Joints- Classification
1. __________ (synarthrodial) no movement (fixed)
•No cartilage lining
•Joined by fibrous connective tissue
•Cranium & distal Tib-Fib
Fibrous
Cartilage types in various Joints- Classification
2. ______________ (amphiarthrodial) minimal movement
• Hyaline cartilage, ligaments, slight movement
• Costochondral joints, pubic symphysis, spine
Cartilaginous
Cartilage types in various Joints- Classification
3. .__________ (diarthrodial) freely mobile
• Joint capsule, hyaline artivular cartilage & synovial fluid
Synovial
The capsule about the joint that joins the ends of the 2 bones forms from the primitive mesenchymal cells in the surrounding soft tissues. What are the 3 layers of the capsule?
– Outer fibrous layer
– Intermediate layer
– Inner synovial membrane
Type A synoviocytes are what?
phagocytic
Type B synoviocytes do what?
provide hyaluronic acid, proteoglycans, and nutritional components
In Crystal Analysis, what kind of crystal presents as fine, needle-like negatively (yellow) birefringent?
- e.g. Gout
Monosodium urate
In Crystal Analysis, what kind of crystal presents as short, rhomboid positively (blue) birefringent?
- e.g. Pseudogout/CPPD
Calcium pyrphosphate
In Crystal Analysis, what kind of crystal presents as translucent and appears as stacked panes of glass?
e.g. Hyperlipidemic states
Cholesterol
In Crystal Analysis, what kind of crystal presents as bipyramidal (irregular) & positively birefringent?
- e.g. HPTH, myositis ossificans
Calcium oxalate
In Crystal Analysis, what kind of crystal cannot be seen w/o EM or Alizarin red stain?
- E.g. Milwaukee shoulder
Hydroxyapatite
What procedure do you perform to send joint fluid for the following:
•3 C’s:
- Cell count (with diff)
- Crystal analysis
- Culture & sensitivities
Remember the 3 C’s!
NOTE: Drain joint fluid completely!
Arthrocentesis
What test looks for clumping of RBCs?
Hemagglutination
What test looks at staining patterns of ANA autoantibodies under a Fluorescent light?
ImmunoFluorescence
What test assesses immune antiBodies via DNA/genetic typing?
ImmunoBlotting
What test looks at patterns in Petri *Dishes?
e.g. Ouchterlony Analysis
ImmunoDiffusion
What test separates particles according to electrical charges?
e.g. IPEP, SPEP
counter electrophoresis
What test measures the antibody rxn to a particular organism?
e.g. Lyme, HIV
ELISA (Enzyme Linked ImmunoAbsorbant)
What is a useful formula to calculate ESR?
Age in years divided by two (add 10 for females)
What are the two M/C lab tests to assess inflammation in the body?
- Erythrocyte Sedimentation Rate (ESR)
- C-reactive protein (CRP)
What enzyme catalyzes the conversion of Angiotensin I to Angiotensin II (potent vasoconstrictor), is synthesized by endo- epithelial cells and activated macrophages (rich in lung tissue)?
• E.g. Elevated = sarcoidosis, interstitial lung diseases, leprosy
• Low in scleroderma (endothelial injury)
Angiotensin-Converting Enzyme (ACE)
What is the preferred predictor (and TEST OF CHOICE) for Rheumatoid Arthritis (RA)?
(NOTE: may develop years before joint symptoms appear.)
Anti-CCP
(Anti-Cyclic Citrullinated Peptide Antibody)
What are antibodies that bind to enzymes present in the cytoplasm of neutrophils known as?
ANCAs
(Anti-Neutrophilic Cytoplasmic Antibodies)
Perinuclear/Anti-myeloperoxidase (P–ANCA) & cytoplasmic or anti-proteinase 3 (C-ANCA)
What are autoantibodies that react with various components of a cell's nucleus known as?
(NOTE: Results are reported in titers and patterns of immunofluorescence.)
ANA
(Anti-Nuclear Antibody)
ANA Titers __________ are significant.
> 1:320
(NOTE: Sensitive, but NOT SPECIFIC!)
What are antibodies that bind to negatively charged phospholipids, including cardiolipin? They correlates with fetal wastage, A/V thrombosis, and thrombocytopenia.
Antiphospholipid antibodies (APL)/Lupus Anticoagulant (LAC)
(NOTE: APL IGG = most pathogenic/disease.)
What assists immunoglobulins in attacking pathogens?
complements
(low levels seen in states where it is used up, such as infections or autoimmune conditions)
What might be released into circulation with the destruction of certain tissues such as muscle, heart, and brain?
CPK/CK and aldolase
(NOTE - Elevated in: myositis, MI, rhabdomyalysis, hepatitis, subdurals, trauma)
Elevated in those with purpura, what are known as immunoglobulins that reversibly precipitate in the COLD?
Cryoglobulins
What is a genetic marker for diseases associated with spondyloarthropathies like Ankylosing Spondylitis, Reiter’s, psoriatic and enteropathic arthritis?
HLA-B27
Serum antibodies produced by plasma cells to aid in humoral immune response.
• ____ can be elevated in secondary responses and confers long-term immunity or be deficient as in immunodeficiencies.
• ______ usually on mucosal surfaces. Often low in nephropathies and immunodeficiency syndromes.
• _____ rises in acute infections @ 3 to 6 weeks; can also become monoclonal & proliferative as in myeloma.
• _____ elevated in allergic rhinitis
"GAMED"
IgG
IgA
IgM
IgE
Antibodies directed against intracellular cytoplasmic ribonucleoproteins are also referred to as anti-synthetases.
• Often associated with myopathies, e.g. Polymyositis (PM), dermatomyositis (DM), statins, ICBM
• Anti Jo -1 (histidyl-tRNA most commom and correlates with interstitial lung disease, PM, machinist’s hands)
• Anti SRP (signal recognition particle poor prognosis and no rash seen)
• Anti Mi 2 (classic DM rash)
• Anti-HMG CoA reductase- statin induced.
• Anti-cytoplasmic 5'-nucleotidase (cN1A; NT5C1A)- inclusion body myositis(ICBM)
Myositis Specific antibodies (MSA)
What condition, seen more commonly in Women (early/middle adulthood), is defined by chronic widespread pain in all four quadrants of the body for more than three months?
(NOTE: Often associated with central sensitization syndromes such as IBS, vulvodynia, CFS, TMJ , HA, etc.
(NOTE 2: Abnormal levels of Neurotransmitters: Substance P & Glutamate are present in their spinal fluid!)
Fibromyalgia
What medications do you use to treat Fibromyalgia?
A. Pain Meds
B. TCAs (Cyclobenzaprine/Amitriptyline)
C. SSRIs (Venlafaxine/Duloxetine/Tramadol)
D. Antiepileptics (Gabapentin/Pregabalin-FDA+)
B. TCAs (Cyclobenzaprine/Amitriptyline)
C. SSRIs (Venlafaxine/Duloxetine/Tramadol)
D. Antiepileptics (Gabapentin/PregabalinFDA+)
NO PAIN MEDS EVER!!!
What other (non-pharmacological) therapies can you use to treat Fibromyalgia?
A. Complementary and Alternative therapies (Melatonin)
B. Therapeutic Massage (myofascial release)
C. Meditation & Relaxation therapies
D. All of the Above
All of the Above
Chronic fatigue accompanied by cognitive difficulties for ≥ 6 months is known as what?
Chronic Fatigue Syndrome
What condition may be present if the below Sx are present?
- Crimson Crescents on both Peritonsillar Pillars (Absence of pharyngitis)
- Shotty pea-sized adenopathy (neck, axilla, inguinal)
Chronic Fatigue Syndrome
A 70 y/o Caucasian female patient presents with complaints of stiffness and achiness in her shoulders and hips (limb-girdle muscles) that is worse in the morning upon waking. Lab work shows significant elevation in her ESR and CRP. What is her suspected diagnosis, how would you treat her, and with what condition is this often associated?
Dx: Polymyalgia Rheumatica (2-3 years)
Rx: low-dose (10-15mg) prednisone (Dx response w/in 24-48 hours!)
Condition: Giant Cell Arteritis (Temporal Arteritis)
What syndrome is defined by loose, hypermobile joints that give rise to aches, pains, strains, and dislocations?
[NOTE: Commonly seen in Marfan's and Ehlers-Danlos Syndrome (EDS)]
Joint Hypermobility Syndrome ("Double Jointed")
Beighton criteria we need to know for Joint Hypermobility Syndrome (5)
• ***Score of ≥ 4/9 points*** (either currently or historically).
• Arthralgia lasting ≥ 3 months*** in ≥ 4 joints.
- Hyperextension of elbows ≥ 10º
- Hyperextension of the knees of ≥ 10º
- Touch floor with palms when bending over with knees extended
- Touch passively, the forearm with the thumb, while wrist is in flexion
- Passive extension of the 5th finger more than > 90º
Tx of _________________:
•Supportive
•ROM and strengthening of muscles
•Aqua therapy
•Neuro-massage
•Muscle relaxants
Joint Hypermobility Syndrome ("Double Jointed")
What form of tendonitis is often seen in tennis players?
Lateral epicondylitis
What form of bursitis is often seen in baseball pitchers?
Subacromial bursitis
What form of tendonitis is often seen in golfers?
Medial epicondylitis
What forms of bursitis is often seen in runners?
Trochanteric bursitis
What form of bursitis is often seen in housemaids/clergymen?
Infrapatellar bursitis
PE: palpable point tenderness along the involved tendon or its sheath (outer covering) or at one particular point within the tendon and pain when the muscle to which the tendon is attached is worked against resistance.
What is the Dx and Tx for this condition?
Dx: Tendinitis/Bursitis
Tx: R.I.C.E.
20 y/o Female presents with dull right-sided jaw pain that is worse after eating. Pt states her jaw "clicks and pops" when she chews.
What's your Dx? What imaging studies do you want to order to r/o Fx? Tx?
Dx: TMJ
Imaging Studies: Panorex
Tx: NSAIDs and benzodiazepines (Acute ER); TCAs, opioids, muscle relaxants, or steroid (intraarticular) therapy (protracted pain syndromes)
**Refer to ENT and/or Oral Surgeon
What syndrome, often manifesting as numbness in the fingers, is due to median nerve entrapment (edema) at the wrist? How do you treat it?
Dx: Carpal Tunnel Syndrome
Tx: Splinting the wrist (@ night), Cortisone injection, Surgical Release
Upper extremity Dxs
• CTS- median nerve
Tinel's Phalen's sign
Upper extremity Dxs
DeQuervain’s tenosynovitis
Finkelstein's test
Upper extremity Dxs
Trigger finger
"Catch" test on digital flexion
Upper extremity Dxs
Dupuytren’s contracture
Palpable fissure at 4-5th palmar fascia.
Upper extremity Dxs
Rotator cuff dxs
Impingement, Neers, Empty can, Drop arm
Lower Extremity Dxs
• Chondromallacia Patella
Knee pop, Patella pain
Lower Extremity Dxs
• Anserine Bursits
Palpable pain at antero-medial region below the knee
Lower Extremity Dxs
• ACL injury
Drawer sign
Lower Extremity Dxs
• Baker’s/Popliteal cyst
Popliteal fullness-often assoc with OA
Compression of the neurovascular structures (extra rib/tumor/cyst/trauma) in the area just above the first rib and behind the clavicle. It represents a constellation of symptoms. 3 facets:
- Brachial plexus*** (95%)
- Subclavian vein (4%)
- Subclavian artery (1%)
What's the Dx? Imaging? Tx?
Dx: Thoracic Outlet Syndrome
Imaging: Radiography, CT Scan/MRI, Venography/Duplex Scan, EMG/Nerve Conduction
Tx: Surgery & PT
Chest wall inflammation & tenderness localized along the costochondral joints/ribs 2-5 that is accompanied by nonsuppurative redness and swelling is characteristic of what syndrome? How is it Tx?
Dx: Tietze syndrome
Tx: NSAIDs, Ice, Self-Limiting
Often following lower extremity trauma or surgery in women/girls, what condition is characterized by allodynia, edema, discoloration, and temperature change?
Reflex Sympathetic Dystrophy
(Complex Regional Pain Syndrome - CRPS)
Reflex Sympathetic Dystrophy (Complex Regional Pain Syndrome - CRPS) that involves an excessive sympathetic rxn of joints & tissue d/t trauma?
A. Type 1
B. Type 2
Type 1
Reflex Sympathetic Dystrophy (Complex Regional Pain Syndrome - CRPS) that involves an excessive sympathetic rxn of joints & tissue d/t trauma in which the etiology is a partial nerve injury?
A. Type 1
B. Type 2
Type 2
Meds as follows:
•Analgesics: codeine
•Antidepressants: amitriptyline
•Anticonvulsants phenytoin
•Anesthetics: lidocaine, tocainide
•Adrenergic compounds
–Phentolamine
–Phenoxybenzamine
–Clonidine
•Calcium channel blockers: nifedipine, amlodipine
•Corticosteroids: Prednisolone 60 mg rapidly tapered over 5-10 d
Reflex Sympathetic Dystrophy
(Complex Regional Pain Syndrome - CRPS)
What is essential to have in the body for muscle contraction, nerve function, and blood clotting?
Calcium
Calcium is stored in the bones in the form of what?
Hydroxyapatite
Calcium absorption is dependent on what two things?
PTH & vitamin D
What condition is defined as the softening of bone from little vitamin D or excessive loss or resorption of calcium?
Osteomalacia
What part of the body contains 99% of the calcium?
Bone
Daily calcium requirements vary with age & metabolic state:
1. Child _______________
2. Adolescent (growth) _______________
3. Adult _______________
4. Adult (peri & post menopausal)/Pregnancy/Patient with Fx(s) _______________
5. Breast feeding _______________
1. 800-1000 mg
2. 1,000-1,300 mg
3. 1,000 mg
4. 1,500 mg
5. 2,000 mg
What hormone in the body is important in the regulation of nucleic acids and phosphorylated lipids/proteins?
Phosphate
If a pt has high vitamin D and low calcium, what will phosphate be?
High
What hormone takes calcium and phosphate out of bones and moves it into the serum?
If overactive, (hyper-), can lead to INC Ca2+ --> Kidney stones!
Parathyroid Hormone (PTH)
What would cause parathyroid hormone to be secreted?
Low Serum Calcium
Hyperparathyroidism leads to increased serum calcium which can cause what two things?
- kidney stones
- abnormal bone formation
What hormone is synthesized in the liver and converted to its active form in the kidney?
Vitamin D
This anti-resorptive medication is prescribed for women who are at least 5 years post-menopause and are unable to tolerate or refuse other osteoporosis medications.
What hormone inhibits osteoclastic resorption of bone in order to prevent calcium from being removed from the bone and has been shown to DEC risk of vertebral fractures?
Calcitonin
What skeletal disorder is characterized by micro-architectural changes that result in compromised bone strength and INC propensity to fracture?
Osteoporosis
What is the M/C fracture in people with osteoporosis?
Vertebral fx
What is the most SERIOUS fracture in people with osteoporosis?
Hip Fx
What is gold standard in diagnosing osteoporosis?
bone mineral density/DEXA
Bone Mineral Density (BMD) (measured at the hip, spine or wrist):
Normal BMD = T-score better than _______
-1 SD