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A Band I Band I Band Myosin – Myosin – Myosin - - Myosin – Myosin – Myosin - Actin - Actin - Actin - Actin Actin - Actin - Actin – Actin - Myosin – Myosin – Myosin - - Myosin – Myosin – Myosin Z line - Z line - Z line - Z line - Z line - Z line M line - M line - M line - M line - M line - M line Z line - Z line - Z line - Z line - Z line - Z line - Actin - Actin - Actin - Actin Actin - Actin - Actin – Actin - Myosin – Myosin – Myosin - - Myosin – Myosin – Myosin - Actin - Actin - Actin - Actin Actin - Actin - Actin – Actin - Myosin – Myosin – Myosin - - Myosin – Myosin – Myosin H Band
Not the Norm • What is the overall process that generally effects this norm? • Myasthenic Syndrome • Curare • Clostridium botulinum • Clostridium tetani • Myasthenia Gravis
Myasthenic Syndrome Myasthenia Gravis Myasthenia Gravis vs Myasthenic syndrome (Lambert-Eaton)
Cholinergic Neurotransmitter:Acetylcholine • Released from parasympathetic system and from motor neurons • Attaches to cholinergic receptors • Nicotinic receptors: excite skeletal muscle cells • Muscarinic receptors: slow heart, stimulate GI tract, vasodilate • Neurotransmitter is removed from synapse by acetylcholinesterase
What is the clinical presentation? What muscles are most commonly affected? eye and periorbital muscles ptosis due to eyelid weakness diplopia due to extraoccular muscle weakness • Dysphagia and possible pulmonary aspiration • Limb weakness usually more pronounced in proximal than distal parts of extremity • Speech impairment • Weakness less pronounced in the morning and worsens throughout the day What muscles are most commonly affected? • Progresses to generalized weakness, including respiratory muscles
What are the basics of muscle innervation? • What is information is this picture giving us?
Bone tissue T/F Spongy bone makes up the majority of the skeleton. FALSE….spongy 15%, compact 85% Basic structural system in compact bone is the haversian system. TRUE All bones are covered with a double layered connective tissue called the endosteum. False…..periosteum
Osteo What??? • Osteoblast • Osteocytes • Osteoclasts
CASE STUDY • You are a nurse practitioner working in a busy primary care practice. Your first patient of the day is a 25 year old gentleman who was seen in the ED last week after injuring his RIGHT WRIST in a flag football game. He was diagnosed as having a R ulnar fracture and was splinted. He presents to your office today for placement of a cast. • He is anxious to return to his team and asks you how long it is going to take for his fracture to heal.
CASE STUDY • Outline the process of BONE REPAIR. • How does this differ from the process of BONE REMODELING?
Remodeling vs Repair REMODELING Large injuries heal in similar manner as soft tissue injuries, however, new bone is made rather than scar tissue. Occurs in 4 phases and varies in duration depending on extent of injury and physiologic resources of patient, but can take as long as 4 years. REPAIR • Maintains internal structure of the bone and repairs microscopic bone injuries • Carried out by clusters of bone precursor cells that differentiate into osteoclasts and osteoblasts • Occurs in 3 phases and takes about 4 months.
Remodeling: A 3 phase process • PHASE 1—ACTIVATION PHASE • Osteoclasts are responsible for bone breakdown • Mediated only by the multi-nucleated osteoclastic cells • Bone precursors in a localized area of bone are stimulated to form osteoclasts
Osteoclasts……. • Origin • from hematopoeitic tissue (monocyte/macrophage lineage) • Function • multinucleated giant shaped cells that reabsorb bone • possess a ruffled brush border that increase surface area and aids in reabsorption • Signaling • has receptor for RANK L (ligand on osteoblasts, and tumor cells) that stimulates bone reabsorption • stimulated directly by calcitonin and IL-1 • inhibited by • IL-10 • bisphosphonates
Remodeling: A 3 phase process • PHASE 2: The Resorption Phase • Osteoclasts form a cutting cone, resorb bone and leave behind an elongated cavity • COMPACT BONE: resorption cavity follows longitudinal axis of the haversian system • SPONGY BONE: resorption cavity parallels the surface of the trabeculae
Remodeling: A 3 phase process • PHASE 3: The Formation Phase • New bone is laid down by osteoblasts lining the walls of the resorption cavity. • Successive layers (laminae) of compact bone are laid down until the resorption cavity is reduced and a new haversian canal around a blood vessel is formed. • New trabeculae are formed in spongy bone
OSTEOBLASTS…… • Origin • derived from undifferentiated mesenchymal cells • Function • form bone by producing: • alkaline phosphatase • type I collagen • osteocalcin (stimulated by 1,25 dihydroxyvitamin D)
OSTEOCYTES…… • Origin • are former osteoblasts trapped in matrix • Function • maintain bone (housekeepers) • make up 90% of cells in mature skeleton • important in regulation of calcium and phosphorous • Signaling • stimulated by calcitonin • inhibited by PTH • communicate with adjacent osteocytes via gap junctions in canaliculi
Bone Repair: A 4 Phase Process • 1. Hematoma formation • Hematoma forms and provides source of hemopoieitic cells capable of secreting growth factors. • 2. Procallus/Soft callus formation • Fibroblasts, capillary buds and osteoblasts move into wound and produce granulation tissue called procallus • Cartilage is formed as a precursor to bone and types I, II and III collagen are formed. • 3. Hard Callus formation--Primary callus forms within two weeks • Osteoblasts in procallus form membranous or woven bone (callus). • Enzymes cause deposition of calcium and phosphorous which hardens the bone • Osteoblasts replace the callus with lamellar or trabecular bone
Bone Repair: A 4 Phase Process • 4. Remodeling-Begins in middle of repair phase and continues long after clinical union • Periosteal and endosteal surfaces of bone are remodeled to the size and shape of bone before injury. • Shaped through • Wolff's law: bone remodels in response to mechanical stress • Piezoelectic charges : bone remodels in response to electric charges
FYI--Variables that Influence Fracture Healing • Internal variables • blood supply (most important) • Stabilization of fracture • External variables • Nicotine • rate of fracture healing, strength of fracture callus, risk of nonunion • Diet • protein malnourishment fracture callus strength • Low intensity pulsed ultrasound (LIPUS) • accelerates fracture healing and increases mechanical strength of callus (including torque and stiffness) • Physical activity/bone stimulators • direct current bone stimulators decrease osteoclast activity and increase osteoblast activity by reducing oxygen concentration and increasing local tissue pH • COX-2 • promotes fracture healing by causing mesenchymal stem cells to differentiate into osteoblasts
What is Osteomyelitis? • What factors contribute to the difficulty in treating it? • What is sequestrum? • What is involcrum?
What is the relationship between osetoblasts, RANKL, RANK, osteoprotegerin (OPG) and osteoclasts? What disease states occur when this relationship is altered?
Osteoblasts RANKL Receptor activator of nuclear factor kβligand RANK receptor Activates osteoclast and prolongs survival Osteoporosis Age Related bone loss Glucocorticoid induced osteoporosis Paget’s disease Be sure you know patho behind these diseases OPG-blocks RANK receptor
OSTEOPOROSIS • In short—osteoporosis is the loss of both compact and spongy bone. • Osteoporosis is defined by the World Health Organization (WHO) as a bone mineral density that is 2.5 standard deviations or more below the mean peak bone mass (average of young, healthy adults) as measured by DXA. • the term "established osteoporosis" includes the presence of a fragility fracture.
OSTEOPOROSIS • In osteoporosis the bone mineral density (BMD) is reduced, bone micro-architecture is deteriorating, and the amount and variety of proteins in bone are altered. Bone resorption EXCEEDS bone growth
Causes of Osteoporosis: Menopause Effects of Aging Replicative activity of osteoprogenitor cells Synthetic activity of osteoblasts Biological activity of matrix bound growth factors Physical activity • Estrogen • Osteoclastic activity
Risk Factors: Non-modifiable Excess ETOH Vitamin D deficiency Tobacco use Nutrition deficiency Underweight/inactive Excess physical exercise Heavy Metal exposure Certain medications Potentially Modifiable • Advanced age • Female gender • Estrogen deficiency • Decreased testosterone* • European or Asian ancestry • Family hx • Small stature
Name that bone disorder! • metabolic disease characterized by inadequate & delayed mineralization of osteoid; usually due to Vit D deficiency • Malignant tumor usually found in bone marrrow; moth eaten pattern of bone destruction • Rate of bone resorption greatly exceeds rate of bone formation • Excessive resorption of bone due to genetic manipulations involving RANK-NF-kβ signaling pathways • Osteomalacia • Osteosarcoma • Osteoporosis • Paget’s disease
Bobby is a 3 year old Caucasian boy who was brought to a pediatrician’s office where his mother states, “Bobby is clumsy, frequently falls, and has difficulty in climbing stairs.” On physical examination, Bobby tends to walk on his toes, exhibits a positive Gower sign, and appears to have hypertrophy of calf muscles.
What disease do you suspect? • What is this disease process? • X-linked disorder caused by deletion of a segment of DNA • Absence of dystrophin protein which causes loss of muscle bulk and fibers • In late stages: interstitial connective tissue and fat replace muscle fibers • Why would he present with these S&S? • Slow motor development • Problems with walking and coordination • Generalized weakness • Hypertrophy of calf muscles Duchenne muscular dystrophy
Differentiation: Rheumatoid & Osteoarthritis(Overview) Osteoarthritis Rheumatoid Arthritis Onset – 22-55 yrs Peak – 35-40 yrs Female > male Variable course Flares/remissions Slow/aggressive progression Symmetrical joint involvement • Onset - > 45 yrs • Equal prevalence male vs. female until after 55 yrs. in women • Gradual progressive course • Asymmetrical joint involvement
Rheumatoid vs. Osteoarthritis(Pathophysiology) Osteoarthritis Rheumatoid arthritis Inflammatory Autoimmune – synovium seen as “foreign”. IgG /anti-IgG triggers inflammatory response. Phagocytosis/lysozomal enzyme, IL-1, & TNF key in joint lining destruction and pannus formation. Pannus invades, erodes, cartilage and bone. Systemic involvement: IL-6 induction Fever, myalgia, wt loss, & acute phase protein induction • Degenerative • Progressive loss of articular cartilage with remodeling of subchondral bone. Total joint –bone, cartilage, tendon, & ligament attachment • Joint space narrowing • Osteophytes • Subchondral cysts • Subchondral sclerosis • Nonsystemic involvement
Comparison of the morphologic features of RA and osteoarthritis
Rheumatoid vs. Osteoarthritis(Signs and Symptoms) Osteoarthritis Rheumatoid arthritis Family history Slowly progressive symptoms with “explosive episodes” Pain improves with moderate activity Morning stiffness > 1 hr. Systemic systems • Bone/structural abnormalities • Hx. Joint trauma • Obesity • Occupational factor • Pain activity induced, with rest • Morning stiffness limited 20-30 min. • No systemic systems
Physical Findings Osteoarthritis Rheumatoid Arthritis Hand – bilateral Ulnar deviation –MCP jts Swan-neck deformity Boutonnière deformity UlnarStyloid erosion Rupture extensor tendons Carpel Tunnel Syndrome Spine- Cervical C1-C2subluxation Cord compression Knee Baker Cyst • Hand – dominate • DIP, PIP, & 1st MCP jts. • Nodes • Heberden’s – DIP • Bouchard’s – PIP • Spine: cervical & lumbar • Disc degeneration • Apophseal joint • Nerve root compression • Knee • Varus deformity • bowlegged • Valgus deformity • Knock-knee