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Where are the muscarinic Ach receptors and what makes them different from Nicotinic?
- Sympathethic post synaptic (post ganglia) of sweat glands and some blood vessels
- Parasympathetic post ganglion/synamptic Heart smooth muscle and glands
- Muscarinic are G-protein linked while nicotinic are ion channels
What are the ligands of nicotinic Ach receptors?
Usually quarternary ammonium compounds (CATIONS)
Describe the nicotinic receptor action of muscle.
- Heteropentameric ligand gated ion channel with 2 alpha subunits which both must be bound. All or none 70% must be blocked and 90% for full paralysis
- Most receptors in muscles of respiration then for coarse movement
- Least occurs in the facial expression and eyes
What are the problems with curare?
- Blocks ganglia (no BP control)
- Affects muscarinic ( no parasymp to heart-> tachycardia)
- Releases histamine (bronchoconstriction & hypotension)
- 30 minute long duration
What are the major features of nondepolarizing neuromuscular blockers?
- Competitive antagonist (70% for effect, 90% for full)
- Rocuronium- most popular
- Cistacurium- Hoffman elimination (good for medically compromised)
- Onium = aminosteriod
Explain how the depolarizing neuromuscular blocker works.
- Rapidly stimulates and leaves Na channel inactive to prevent repolarization and is not broken down by Achesterase (plasma cholinesterase must break down)
- Phase 1 block for short 5 minute duration (except with plasma cholinesterase defficincies)
- Could lead to bradycardia and Hyperkalemia and malignant hyperthermia
Why can succinylcholine lead to malignant hyperthermia?
Variation in RYANODINE receptor in the sarcoplasmic reticulum can result in uncontrolled Ca2+ rls and a hypermetabolic response when triggered by succinylcholine and some volatile inhaled anesthetics like sevofluorane
Therapeutic uses of NMBs?
Surgery, intubation, tetnus (non), join, bone maniupulation, electroconvulsant (dep) and laryngospasm (dep)
Describe other agents that affect NMJ.
- GABA (valium, lioresal)
- Alpha 2 agonist (zanaflex)
- Tricyclic (flexeril)
- Ach rls blocker (botox)
- Raised lesion > .5 cm wit water, no pus
- Sometimes autoimmune
- Plug of sebaceous and dead skin in opening of hair follicle
- Closed = whitehead
Inanimate disease carrying object
What is the most common skin cancer dentists observe?
Basal cell carcinoma
- Change in skin color
- Flat not palpated
Papule and nodule
- Elevated small, no depth
- Nodule= papule w depth/elevation
- Pustule = pus-filled papule
Fluid-filled lesions less than .5 cm (sun blisters)
- Blood plasma leaks
- Allergic degranulation of mast cells
- Wheals=circumscribed rounded, slightly elevated lesions of hives
What are the different types of muscle fibers?
- Type I: slow, mitochondria/lipid rich (acid)
- Type II: fast, glycogen (alkaline)
- What types of stains used to observe mitochondria in muscles?
- OXIDATIVE found in inner mitochondrial membrane
- 1. NADH (more mit, darker)
- 2. SDH (complex II)
- 3. COX2
- Gmori will have purple spots if ragged red
What types of stains are used to discover neuropathic muscle problems?
- 1. NSE non-specific esterase: shows NMJ, dark = not well innervated
- 2. Alkaline phosphatase: regenerated, dermatomyositis (dark perimyosium
- 3. Acid phosphatase: lysosomal activity: macrophages
What are the exceptions for not biopsying muscle tissue?
- Genetic tests available: dystrophinopathies,
- Myasthenia gravis:Abs blocking Ach receptors and NMJ
- Endocrine myopathies
When do you want to do a biopsy of muscle tissue?
- Neuromuscular disease: myopathy, neuropathic
- Ststemic disorders: dermatomyositis
- Repeat or treatment related
- Fiber size variation
- ANGULAR atrophy
- Nuclear clumps
- Loss of mosaic pattern
- Eg diabetes, ALS, spinal muscular atrophy
- Random myofiber size
- ROUND atrophy
- Nuclear/cytoplasmic changes: regeneration/degeneration (bluer and mononucleated)
- Inflammatory cells: myositis
- Eg. Dystrophy
What are the dental manifestations of muscular dystrophy?
- Facial, head, neck muscles
- Teeth don’t meet
- Problems with TMJ checwing, headaches tenderness
- OH problems
- Non-infective inflammatory myopathy CD4 & MAC expression
- Rash, periorbital edema, proximal muscle weakness
- High serum creatine kinase
- PERIFASICULAR ATROPHY: (black) regenerated myofibers along edge of fascicle
- Often seen w alkaline phosphatase rxn