Tissue Types in the Human

Tissue Types in the Human • Epithelial • Primarily used for protection • Very little extracellular material between cells • Endothelium: specialized epithelial cells in blood vessels • Connective • Primarily used for support • Nerve • Primarily used for control • Muscle • Primarily used for movement • • Epithelial Tissue Cells are polyhedral (many sided) Cover outermost layer of tissue (skin) • • • • • • • Skin Lungs, GI tract, Urinary tracts, Reproductive tracts, Covers innermost and layer of most organs and cavities One side always exposed to: • • • • • • Body exterior Organ tract or cavity READING FOR EPITHLEIUM Makes up the exocrine and endocrine glands Exocrine (“excreting”): sweat glands, digestive glands, mammary glands Endocrine (“hormones”): thyroid, pancreas, adrenal cortex Rely on perfusion for O2 supply Cells have high regeneration potential but are avascular Some epithelial cells rest on a “Basement Membrane” Basement Membrane = Basal Laminae + Reticular Laminae Basal Laminae: flat “sheet” of nonliving adhesive-like collagen and glycoprotein • • Reticular Laminae: “foundation” for the Basil Laminae • secreted by epithelial cells • • • • • • • Adjectives Describing Epithelial Tissue Squamous (meaning “scale”) - flat cells Cuboidal - cells as tall as they are wide Columnar - tall and column shaped Simple - having a single layer of cells Stratified - having multiple / stacked layers Transitional - dome shaped surface cells capable of stretching (bladder) Ciliated –cilia on the exposed surface • Examples you should remember: • • • SIMPLE SQUAMOUS EPITHELIUM Permeable cell structure - used for filtration and exchange Examples: capillaries, alveoli, kidney glomeruli STRATIFIED SQUAMOUS EPITHELIUM Used for “protection” • • • • • • Examples: skin, inside of mouth, vagina CILIATED COLUMNAR EPITHELIUM • basil cells (cells next to basement membrane) may be cuboidal Used to move substances along a particular direction using the cilia Examples: upper respiratory tract, fallopian tubes Examples of Epithelial Tissue Simple Squamous Epithelium Kidney Glomerulous (arrow: cell nucleus) Stratified Squamous Epithelium Human Skin • Matrix - “non-living” component of connective tissue • Ground Substance • Proteoglycan aggregates (PGA) - pine tree shaped molecules • Glycosaminoglycans - neg charged binds Na+ & K+ attract H20 • Hyaluronic Acid - negative charged slippery polysaccharride • Condroitin sulfate • Fluid - H2O, gasses, nutrients for cells (H2O facilitates “plasticity”) • Minerals - Calcium salts Connective Tissue • Adhesive molecules – hold PGA’s together & to membranes • Fibers • • • • • Chondronectin (cartilage), osteonectin (bone), fibronectin (fibrous tissue) • Cells - “living” component of connective tissue “Blast” Cells, “Cyte” Cells, “Clast” Cells Macrophages and white blood cells READING ON CONNECTIVE TISSUE Mast cells containing Heparin & Histamine Adipose tissue • Collagen, Elastin, and Reticular Fibers Proteoglycans Micrograph of actual Proteoglycan Aggregate Types of Fibers Collagen • • • • • • • Fibrous protein in connective tissue structure Derived from Greek word meaning “to glue together” Constitutes about 50% of the proteins in man Present to some degree in all human organs Collagen has a finite life span after which it is degraded to the constituent amino acids and replaced by new fibers. Has high tensile strength: 4.5 pound load needed to break collagen fiber 1 mm thick Maximal strength of “scar” collagen is about 75% of the original tissue • Collagen Fibers Collagen Fiber (Fibril) each collagen molecule (also called a tropocollagen) is connected to the other via hydroxypyridinium bonds Microfibril Collagen Structure A Collagen Molecule (Tropocollagen) each chain connected to the other two with hydrogen bonds Alpha Helix Chains Within Each Collagen Molecule Individual Amino Acid Bonds Are Reinforced With Hydrogen Bonds • Overproduction of Collagen Fibers Diseases that Affect Collagen • Lung Fibrosis (Cystic Fibrosis) – excess glandular secretions (mucous) • Liver Cirrhosis – irreversible scarring (fiber deposition) in the liver • Obstructions and fluid in lungs r breathing disorders and infections • Obstructions in pancreas r d digestive enzymes r d nutrient absorption • Malnutrition r d growth • Insufficient Collagen • Atherosclerotic heart disease • Common causes: Hepatitis-C Hepatitis-B, alcoholism • Alcohol blocks normal metabolism of protein, fats, and carbs r injury • Cirrhosis r ascites, u infection risk, jaundice, bruising & bleeding • Cirrhosis will elevate liver Aminotransferase enzymes • ALT, AST, GGT (aka SGOT-often associated with alcoholism) • Ehlers-Danlos syndrome - rubber man - contortionist disease • Osteogenesis Imperfecta - brittle bones • Scurvey -Vitmain C deficiency • Too few hydrogen bonds in the formation of the collagen molecule • Inferior tissue formation in bones, blood vessels, skin, and teeth Diseases that Affect Collagen Autoimmune Disorders that Damage Collagen • Lupus Erythematosus • Collagen damage and inflammation - can occur anywhere in the body • Most Common areas affected: skin, articular tissue, • Some have inner organ problems (heart, lungs, kidneys, blood vessels, brain) • Cystic Fibrosis Therapy for Common Collagen Diseases • Clearance techniques for excess lung secretions • Pancreatic enzyme replacement for pancreatic duct obstruction • Healthy diet and exercise • Drugs: • Lupus • Ibuprofin – slows rate of decline of pulmonary function • Corticosteroids – d inflammation in lungs, joints, and vasculature • Antibiotics – to treat and reduce the incidence of lung infections • Rotation of drugs to prevent development of resistance • NSAID’s, corticosteroids and other immunosuppresants • Hydroxychloroquine (antimalarial) • Experimental drugs • Drugs: • Stem cell infusion very promising • Healthy diet and exercise OtherTypes of Fibers • Reticular Fibers: • Actually very fine collagen fibers • Usually form a network • Fill “space” between other tissues & organs • Contained in the reticular laminae • Elastic Fibers: • Contain protein called ELASTIN • Elastin molecules look like “coiled springs” • Return to original shape after distortion Elastin Fibers (a) Stretched or taught (b) Relaxed Types of Connective Tissue • Fibroconnective Tissue • Cartilage • Bone Types of Connective Tissue • Fibro connective Tissue - matrix composed mostly fibers • Areolar -”Loose connective tissue” • Adipose - highly vascular insulator, shock absorber & energy store • Reticular - fibers forming a soft internal skeleton for other tissues • Dense regular - contains closely packed parallel collagen fibers • Dense irregular - closely packed non-directional collagen • Elastic - composed of mostly elastin fibers • Examples: • Found where tension is exerted in a particular direction • Examples: tendons, ligaments • Forms “sheets” where tension is exerted in many directions • Examples: dermis of skin, muscle fascia, organ & nerve coverings vocal cords, ligamenta flava (vertebral connective tissue) • Component of some basal membranes (attaches underlying structures) • Separates muscles - allows for muscles to slide over each other • Composed of collagen & elastin serves as “packing material” • Cells account for 90% of tissue mass (little matrix present) • Composed of collagen & elastin Areolar Tissue Elastic Fiber Fibrocyte Nucleus Collagen Fiber Adipose Tissue X 200 ( bv = blood vessel ) ( arrow: adipocyte nucleus ) bv Reticular Tissue Dense Regular Tissue (Tendons & Ligaments) Horse Tendon x100 arrow: orientation of collagen fibers Dense Irregular Tissue (Dermis of Skin & Muscle Fascia) • Cartilage - matrix mostly fibers & ground substance • Avascular (slow to heal) and not innervated • Cartilage matrix: • Ground substance: chondroitin sulfate & hyaluronic acid • Collagen (main fiber) & sometimes elastin Types of Connective Tissue • Perichondrium – surrounding tissue from which nutrients diffuse • Types of cartilage: • Limits cartilage thickness - nutrients must diffuse entire tissue thickness • Gives rise to chondrocytes • Hyaline - tough & flexible - much matrix / few cells - shock absorber • Covers ends of long bones (articular cartilage – eroded in OA) • Forms “skeleton” of trachea and bronchi • Fibrocartilage - less firm than hyaline - more cells and fibers • Similar in structure to dense regular tissue (tendon) • Transitional tissue between tendon and articular hyaline cartilage • Forms intervertebral disks and spongy knee menisci • Elastic - contains more elastin fibers • forms ear pinna & epiglottis Hyaline Cartilage X 250 arrows: Perichondrial borders Hyaline Cartilage Perichondrium on the left Chondrocytes form in the perichondrium and move out into the tissue Fibrocartilage Elastic Cartilage (note numerous chondrocytes and elastic fibers) Types of Connective Tissue • Bone - matrix mostly calcium and phosphate • 65% of bone weight • • • is calcium hydroxyapatite Calcium phosphate, calcium hydroxide, calcium carbonate Tropocollagen subunits giving bone elasticity and fracture resistance Bone collagen d with age r u fracture risk • Highly vascular and well innervated • Contains lymph channels • Functions in mineral storage and blood cell production • Bone remodeling - deposition and resorption - negative feedback • d blood Ca r u Parathormone (PTH) r u osteoclast activity • u blood Ca r u Calcitonin r u osteoblast activity • Red marrow: contains hematopoietic tissue - produces blood cells ++ ++ • Influences on Bone Growth: • Levels of Ca ++, Phosphorous, Vitamin D, HGH, estrogen, testosterone Epiphyseal Plates Review of Bone Histology Haversian System (osteon) Compact (Cortical) Bone Haversian Canal (contain blood vessels) Marrow Endosteum Lamellae (concentric rings of hard bone) Osteocytes in Lacunae Volkmans Canal Periosteum Canaliculi (connecting tunnels) Trabecular (Cancellous) Bone Cross Section of Cortical Bone Osteons Growth Plates (epiphyseal plates) in Long Bone Hematopoietic Tissue Growth Plate (epiphyseal plate) in Long Bone zone of resting hyaline cartilage zone of proliferation zone of hypertrophy zone of calcification ossified bone Epiphysis (bone end) Length Increase (Growth) Occurs Toward Diaphysis Diaphysis (bone shaft) Chondrocytes Chondrocytes divide and stack on top of Red Bone Marrow one another Chondrocytes die upon calcification - blood vessels from diaphysis grow into the area • Osteoporosis - d bone density r injury predisposition • • • • • • • u bone resorption in the presence of normal bone metabolism d both cortical (thick) and trabecular (porous) bone density Women start losing bone density about age 40, men at age 60 Over 28 million people in the U.S. have osteoporosis Bone Diseases & Treatments • 80% of this 28 million are women • 1 in 2 women and 1 in 4 men over age 50 will have an osteoporosis related fracture in their lifetime. May have 20% d in bone mass by 5 to 7 years after menopause Causes: Aging Prolonged treatment with corticosteroids Anorexia nervosa Inadequate diet, especially during pregnancy and breast feeding Treatment: Calcium supplementation Vitamin D supplementation • • • • • • • • • Estrogen replacement (for postmenopausal women)?? Bisphosphonate drugs (also called diphosphonates) Fosamax, Actonel, Boniva - drugs that inhibits osteoclasts Also used to treat bone cancer & other bone weakening diseases Calcitonin (u osteoblast activity), Teriparatide (PTH analog) • • Bone Diseases & Treatments • Osteomyelitis - bone inflammation & destruction • Caused by bacteria and fungi spreading from other infection sites • Symptoms: fever, localized warmth & swelling, localized pain • Treated with antibiotics • Osteoarthritis - Degenerative changes in cartilage & bone Bone Diseases & Treatments • • • • Cause • • Loss of articular cartilage (proteoglycan loss r water loss r d compliance) Roughening, pitting, & destruction in hyaline cartilage r u “stiffness” Most common in hands, hips, and knees May result in the formation of osetophytes (bone spurs) or nodes 80 – 90 % of people over age 65 have some evidence of osteoarthritis • • Genetics (60%), infection, endocrine disorders, joint injury, overuse • Treatment • • • • • • • • • • Fracture or Ligament Injury r bad joint alignment + instability r u “wear and tear” Exercise - helps maintain ROM, healthy cartilage, strength and reduces pain Rogind et.al. 1998; Gur et.al. 2002 Immobilization can worsen the course of the disease Weight loss for OA in weight bearing joints NSAIDS and COX2 inhibitors for pain (COX 2 inhibitors ???) Injections of HYALURONIN (hyaluronic acid) or new artificial injectible materials Corticosteroid injections may be useful when inflammation is present Joint replacement (when conservative therapy fails)(unilateral or bilateral) “Tissue engineering” to regenerate cartilage has had some success Glucosamine & Chondroitin Supplements…..jury still out….majority say no benefit 1500mg of daily Glucosamine has shown benefit for knee OA pain (Herrero-Beumont et al 2007) • Osteoarthritis of the Knee Bone on bone in this resected tibial plateau Knee Arthroplasty Bouchard’s nodes Osteophytes • Bone Diseases & Treatments Rheumatoid Arthritis (RA) – Autoimmune inflammatory disease • May be related to genetic factors • Usually occurs between ages 25 & 55 and affects mostly young and • • middle age females - may fluctuate substantially in severity Rheumatoid factor (autoantibody) + globulins r immune complexes • Immune complexes activate the compliment system r inflammation Involves synovial membranes of joints (most common manifestation) • • • Inflammation leads to swelling & thickening of synovial membrane (u ESR) Joints most often affected: wrists, fingers, knees, feet, and ankles May possibly affect: Heart – endocarditis, pericarditis, CHF, valvular fibrosis, MI - RA and other autoimmune disease patients have an u risk for CHD Lungs – fibrosis and plerual effusion Kidneys – amyloidosis (deposition of insoluble proteins in organ tissue) GI tract – anemia resulting from chronic disease and constant NSAID use - most RA patients are anemic • • • • • Fibrin deposition (fibrosis) and necrosis are also present • 60% of RA patients are unable to work 10 years after disease onset • Most research says that life span is reduced 5 – 10 years • Bone Diseases & Treatments Treatments for Rheumatoid Arthritis • NSAID’s • COX2 inhibitors • Corticosteroids • Disease-Modifying Anti-Rheumatic Drugs (DMARD’s) • Methotrexate • d TNF, neutrophils, histamine, lymphocyte number & function • d growth of certain cells in blood, skin, GI tract, & immune system • Cytotoxic + inhibits metabolism rd immune function • Developed in 1940s’ as chemotherapy for Leukemia • Sulfasalazine (d immune function) • Hydroxychloroquine – an antimalarial drug • Gold salt injections • Exercise to maintain joint mobility • Surgery: synovectomy or joint replacement (unilateral or bilateral) • Gene therapy: inection of genes that produce desired protein via a vector (various type of viruses) • Physiotherapy, physical therapy, water exercise New Anti-Arthritic Drugs – “Biological Agents” Tumor Necrosis Factor (TNF) blockers: • Must be given by subcutaneous injection or IV HUMIRA adalimumab REMICADE infliximab ENBREL etanercept Mechanism (Effects): Indications: • Rheumatoid Arthritis • Effective in 70% of patients who have not responded to Methotrexate Adverse effects: • Ankylosing Spondylitis • Immunosuppression !! • Psoriatic Arthritis • u risk of infection !! • Psoriasis • Tuberculosis common • Chron’s Disease • Allergic reactions • • • • Binds to TNF • Prevents attachment to its receptor • Inhibits inflammatory mediators • d inflammation in joint r d pain KINERET Anakinra Mechanism: Injectable man-made protein that blocks interleukin-1 (IL-1) IL-1 r cartilage degradation, u bone resorption Adverse Reactions: Injection site reactions, systemic infections (d immunity) malignancies, neutropenia Bone Diseases & Treatments Rheumatoid Arthritis • • • Blood & Body Fluids 62.5% of total body fluid is intracellular (ICF) 37.5% is extracellular (ECF) (blood & interstitial fluid) Average blood volume: 5 L (3 L plasma - 2 L RBC’s) • Hematocrit (Hct): packed RBC volume .45-men .40 female • Anemia: Hct < .40 men Hct < .35 women (Hb < 14 g/dL • • • • • < 12 g/dL) Anemia can easily lead to fatigue & weakness and may be caused by: Colon cancer, IBS, Bleeding Ulcer , Chron’s, other internal bleeding Cancer r u cytokines (TNF, IL-1, Interferon-g) r d RBC production Chemotherapy & Radiation (RBC destruction + d RBC production) Kidney disease (d erythropoetin, uremia r d RBC’s & d platelet function) Iron and vitamin deficiencies (B12, Folic Acid) • • Blood functions related to injury / healing • Hemostasis, Inflammation & Immune function, Transport (nutrients, waste, metabolites) Blood components • Formed elements • Plasma • Red blood cells, White blood cells, Platelets • Serum = fluid remaining after coagulation occurs - Blood Plasma = Serum + clotting proteins (fibrinogen) • Red blood cells (Erythrocytes) - formed in bone marrow • Production and homeostasis regulated by tissue oxygenation • d tissue O2 r u erythropoietin from kidneys & liver r u RBC’s Blood & Body Fluids • White blood cells (Leukocytes) • • • • • • Primary effector against infection & tissue damage • WBC’s engulf foreign substances & lysozomal enzymes digest them • Inadequate circulatory or lymphatic function r abscess • GRANULOCYTES (Polymorphonuclear cells) - granulated WBC’s • AGRANULOCYTES – phagocytotic non-granulated WBC’S • • • Neutrophils - 62% of WBC’s - 1st to travel & arrive at injury – “kamikazi” phagocytotic Eosinophils - 2% of WBC’s - destroy parasites - involved in allergies Basophils - < 1% of WBC - release histamine & heparin Monocytes - 5.3% of WBC’s - become lysosome filled macrophages Play important role in remove dust and necrotic tissue in lungs Macrophages - monocytes that have left the circulation – long lived Macrophages release cytokines and compliment proteins (inflam. mediators) Lymphocytes - Tcells & Bcells - 30% of WBC’s Function in acquired immunity (antigen r B cells r antibody production) • Macrophage: (in the box) Arrow: Pedicle for locomotion: Monocytes large arrow: Basophil small arrow: Neutrophil Arrow: Eisonophil Blood & Body Fluids • Platelets - Thrombocytes • Plasma • Sticky cells that function in all aspects of hemostasis • Water (90% of plasma volume) • Metabolic by products: lactic acid, urea, creatinine, etc. • Nutrients: glucose, FFA’s, lipids, cholesterol, vitamins • Electrolytes: sodium, potassium, magnesium, bicarbonate, etc. • Gasses: oxygen, nitrogen, carbon dioxide, etc. • Fibrinogen & other clotting proteins • Plasma (continued) Blood & Body Fluids • Proteins: Total Blood Protein = Albumin + Globulin • Albumin - (60%) manufactured by the liver • Maintains oncotic pressure • Transports FFA’s, thyroid & other hormones, bilirubin (heme catabolite) • Functions as a free radical scavenger (antioxidant) • Globulins (36%) • Alpha – transport biliruben & steroids • Beta – transport copper and iron, form lipoproteins (mostly LDL) • Gamma (or immunoglobulin) – “Ig” – contains antibodies • • • • • - Produced by immune system in response to infection, allergic reaction - Provide short term disease protection (GG injections are possible) NOTE: d hepatic function r d Albumin / Globulin ratio Fibrinogen - (4%) functions in hemostasis (the clotting process) Enzymes – catalyzes physiological reactions (PFK, citrate synthase….) Antibacterial Proteins – CAP18, LL37 Protein Hormones – Insulin, HGH, LH, FSH, ADH(vasopresin), Nerve Tissue Skeletal Muscle or Motor Unit Action Potential + + Excitatory postsynaptic potentials + + + + Nerve Tissue X 200 Large arrow: Soma (cell body) Small arrow: axon body Box: Axon Hillock Propagation of a Neural Impulse 1. Acetylcholine released from pre-synaptic neuron causes receptor operated (acetylcholine gated) channels to allow Na+ and K+ to pass through. This creates an Excitatory Post Synaptic Potential (EPSP) ie. a transient depolarization Receptor Operated Na+ / K+ channels 2. Axon Hillock has most voltage gated Na+ channels and fires an AP when enough EPSP's depolarize it to threshold. The greater the voltage reaching the axon hillock the greater the # of AP's fired. Membrane yet to Repolarization Depolarization be depolarized EPSP’s K+ Na+ Na+ K+ Voltage ++ Gated Ca Channels Soma Volatage Gated Na+ Channels Dendrites Axon Hillock 3. Action Potential(s) travel to terminal bouton and activate voltage gated Ca++ channels in direct proportion to AP frequency. Ca++ flows in and triggers the release of acetylcholine causing further propagation of the impulse or muscle fiber activation. Inhibition of Neural Transmission via GABA – the inhibitory neurotransmitter GABA - gamma aminobutyric acid Inhibitory GABA receptors exist on the post synaptic structure of the dendrite. Activation of these receptors permits Chloride ions to enter the dendrite and nullifies axon of inhibitory EPSP's. This takes the neuron further from depolarization neuron axon collateral GABA released Chlorine channels open in response to GABA release and chloride ions enter the neural cell. Excitatory axon Chloride ion hyperpolarizes the cell ( less depolarization) so AP's traveling down the axon are inhibited. This causes less Calcium to enter the terminal bouton, resulting in less acetylcholine release (neuronal transmission is retarded). Tranquilizing drugs of the benzodiazapine family (Valium, Ativan) bind to receptors in the brain and enhance the affinity of GABA for its receptor. This further promotes the inward chloride current, which reduces anxiety and promotes a calming effect Sensory - Motor Structure & Signal transmission Higher Neural Processing Centers Sensory Neuron Motor Neuron Axon Hillock Afferent Signal Efferent Signal Effector Muscle Free Nerve Endings (type of receptor) Regeneration of Nervous Tissue schwann cell columns axonal “sprouts” • Nerve Diseases & Associated Therapy Multiple Sclerosis - demyelination of nerve tissues – several types of MS exist • • Causes: autoimmune factors (exact antigen not identified), virus triggers (not proven), possible genetic predisposition, trauma. Symptoms: weakness, numbness (“pins & needles”), loss of balance, loss of coordination, bowel & bladder dysfunction, muscle spasticity, optic nerve neuritis • • symptoms are “epidsodic” Therapies • • • • Immunomodulator drugs: d inflammatory effects of lymphocytes inhibit cytokines r d inflammation, also d number of episodes Interferon b (1a & 1b) - AVONEX BETASERON REBIF (1st line drugs) Glatiramer Acetate - COPAXONE (2nd line drug) Immunosuppressants: dd inflammatory effects of lymphocytes, d inflammation (3rd line drug) Mitoxantrone, Cyclophosphamide, Methylprednisolone, ACTH • • • • • • • • Danger of infection from compromised immune system Weakness therapies: dopaminergic drugs – similar to drugs for Parkinson’s patients, exercise (water exercise & swimmingmost beneficial) Spacticity therapies: reflex inhibitors, ex: a 2 agonists (inhibit spinal motor neurons), muscle relaxer drugs Incontinence therapies: muscarinic achetylcholine receptors antagonists (relaxes bladder dutrussor muscle), antidiuretic hormone analogs Tremmor therapies: anticonvulsant drugs Visual problem therapies: corticosteroids to reduce ocular inflammation MRI of the brain showing a plaque associated with Multiple Sclerosis • Nerve Diseases & Associated Therapy Parkinson’s - loss of production of the neurotransmitter dopamine in the basal ganglia (loss of 80% of dopamine producing cells) r disruption of balance between dopamine and Ach r d voluntary movement control • Causes: free radical damage theory, toxin theory, age related d in dopamine producing neurons, genetic predisposition, repeated head trauma (boxing), illegal drug use, hydrocephalus (CSF accumulation in ventricle of the brain), encephalitis-most often viral-(inflammation of white and gray brain matter). • Symptoms: resting tremor - “pill rolling” motion (70%), bradykinesia (inability to generate movement), rigidity, postural instability, difficulty rising from sitting position, shuffling gait. • Therapy: • Levodopa: u dopamine levels in brain (current gold standard of treatment) • Stem cell infusion r u Dopamine neurons r likely 1 disease “cured” by SC • Catechol-O-methyltransferase inhibitors: (inhibits levodopa’s peripheral st • • • • metabolism r more available for transport across blood brain barrier) Dopamine agonists: stimulate post-synaptic dopamine receptors Monoamine Oxidase B inhibitors: slow dopamine neuron degeneration Embryonic tissue transplantation – not very successful so far DBS Surgery – brain “pacemaker” sends e- to parts of brain PET Scan showing reduced uptake of injected flurodopa (radioactive dopamine) in the dopamine producing neurons in the brain of a Parkinson’s Patient NM Juntion & Muscle Substructure (Skeletal Muscle) Presynaptic Synaptic Neuromuscular Terminal Bouton Vesicles Junction Acetylcholine Receptors Acetylcholine Synaptic cleft Mitochondria (ATP Producer) (Ca++ Reservoir) Acetylcholinesterase T-tubule Saroplasmic Reticulum (Site of Ca++ storage) Myosin Ca++ Actin Z disk A I H Motor End Plates (Skeletal Muscle) Neuromuscular Junction ( a Motor Neuron ) Action of Selected Toxins & Drugs Around the NM Junction Black Widow venom (Latrodectism) blocks AP transmission Local anesthetics Tetrodotoxin (puffer fish) Batrachotoxin (S.A. frog) 1 frog: toxin to kill 50 men u Ach release blocks Ach (B) or inhibitory neurotransmitter release (T) Botulinium toxin (B) Tetanus toxin (T) blocks Ach receptors Cobra / Mamba snake Curare Ach-ase inhibitors: nerve gas (Sarin, VX) Neostigmine–treat MG resp. muscles affected Dantroline: muscle relaxer used in MS treatment d CA++ release from SR Blocks AP transmission within muscle Quinine: (antimalarial drug): muscle relaxer Muscle Substructure (Molecular Level) A Brief Summary of Muscle Contraction Mechnisms Thoughts originate in higher centers or reflexes activated AP’s transported to motor neurons - travel down T-tubules Calcium Ions released from SR and bind to troponin Tropomyosin inhibition is negated - active sites revealed Actin-myosin crossbridges form – phosphate released (Calcium is pumped back into the SR if single twitch) Energy stored in myosin head slides actin filament ADP is released from myosin head Rigor complex exists ATP binds to myosin headpiece crossbridges uncouple unless cycle continues, series & elastic elements restore length Hydrolysis of ATP r ADP & P are formed Energy is stored in myosin headpiece If Ca++ is available, crossbridge cycling continues What are the differences between: 1. Physical Therapy 2. Occupational Therapy 3. Rehabilitation 4. Strength & Conditioning Development of Muscle Tension Muscle Fiber Types Type I Slow oxidative (SO) Many large mitochondria High aerobic capacity Fatigue resistant Type IIa Many mitochondria Medium aerobic capacity Fatigable Type IIb (IIx) Fast glycolytic(FG) Few mitochondria Low aerobic capacity Most fatigable Fast oxidative glycolytic (FOG) Low contractile speed Low ATP-ase activity High contractile speed High ATP-ase activity Highest contractile speed Highest ATP-ase activity • Per fiber, glycolytic fibers are larger & stronger - higher contractile velocities • Contain more myosin crossbridges per fiber area + u ATP-ase • Endurance Training: • Type IIa to Type I (fast to slow !) & Type IIb to Type IIa (fast to slow !) • Strength Training: • d %age of Type IIb fibers + u %age of Type IIa fibers (fast to slow !) • Hypertrophy of IIa and IIb fibers • Both endurance & strength training change characteristics of all fiber types from fast to slow, but this role is minimal compared to neural & hypertrophic changes Motor Unit Recruitment and Gradation of Muscle Contraction • Motor Unit - a motor neuron and the fibers that it innervates • Henneman's Size Principle • Number of fibers per motor unit ranges from 5 to 2000 • Single fiber rarely has polyneural innervation • Low force demand - low threshold Type I motor units recruited first • Small number of fibers per motor unit • High force demand - high threshold Type IIa & IIb units recruited next • Large number of fibers per motor unit • Firing frequency of motor units • Varying the recruitment of different number and types of motor units • Muscle fiber to motor neuron ratio of activated neurons • The Grading of Muscle Contractions is Influenced by: Postulated Muscle Fatigue Mechanisms • Power / Speed (< 10s, Type IIb fibers) • Short Term (10s - 3m, • Depletion of high energy phosphates (CP - ATP) • Fiber type distribution effects and recruitment capability • T-tubule AP transmission failure • Repolarization failure (extracellular Na+ , K+ accumulation) • u H+ inhibits Ca++ uptake and release by the SR • u H+ inhibits enzyme activity involved in ATP production Type IIb & IIa fibers) • Moderate Endurance (3m - 20m, Type I, Ila, Ilb fibers) • Long Term Endurance (20m - 4h, Type I, IIa fibers) • Depletion of glycogen stores • u body temperature • Body fluid depletion (dehydration) • Lactate tolerance and associated metabolic mechanisms Apparatus to Determine the Muscle Force (Tension) Generated at Different Muscle Lengths Length - Tension Relationships in Muscle Length - Tension Relationships in Muscle Optimal filament overlap resulting in maximal ACTVE TENSION Maximal TOTAL TENSION (ACTIVE TENSION + PASSIVE TENSION) Percent Maximal Tension TOTAL TENSION ACTIVE TENSION from muscle contraction PASSIVE TENSION from connective tissue 1/2 normal normal (optimal) 2X normal Muscle Length Force Velocity Relationships in Muscle u contractility Maximal Velocity (Vo) more optimal preload or strength training adaptation Velocity of Shortening (length / time) power (work / time) load X shortening velocity note that peak power is developed at 30% max force power plotted as a function of force Peak power = .3(Fo) Maximal Force (Fo) Fo exceeded during eccentric contraction Load Moved or Force Developed • Fibromyalgia- pain in muscles and connective tissues • Theoretical Causes: Thyroid problems, over growth of yeast bacteria, trauma, stress, neurotransmitter & hormone malfunction, infection, immune system dysfunction, autonomic nervous system malfunction Muscle Diseases & Associated Therapy • Symptoms: “Aching”, “un-refreshed by sleep”, GI problems, fatigue, • • anxiety & depression, “d energy”, presence of pain “trigger points” Symptoms may be chronic – better one day, worse the next Disease is often associated with other co-morbid conditions: Chronic Fatigue Syndrome Migraine Headache TMJ syndrome Irritable bowel syndrome Restless leg syndrome Depression • Therapy: symptom control, stress reduction, exercise, antidepressants, NSAID’s, growth hormone therapy, psychiatric help • Muscular Dystrophy - an inherited disorder characterized by progressive proximal muscle weakness with destruction of muscle fibers and replacement with connective tissue Muscle Diseases & Associated Therapy • Diagnosed between 2 & 5, wheelchair by 10 or 12, death in 20’s • Blood creatine kinase is elevated (indicator of muscle damage) • Some are mildly retarded • Causes: genetic absence of dystrophin, a muscle membrane protein • Initial Symptoms: “waddling” gait, falls, difficulty standing, difficulty climbing or descending stairs r muscle wasting, contractures, cardiac involvement, respiratory muscle weakness with complications (respiratory infections). • Therapy: daily steroids produce long term symptom improvement, exercise should be continued as long as possible, surgery may be done to release contractures, pneumonia vaccine (prophylactic), physical therapy to delay development of contractures. • Contractures – any condition that affects mobility or range of motion of a joint • Usually involves fiber deposition in skin, fascia, muscle or a joint capsule