Please enable JavaScript.

Coggle requires JavaScript to display documents.

NEUROMUSCULAR DISEASES (= peripheral nervous system) (Rare Neuromuscular…

- - - - General Pathology
        
        no dystrophin protein made at all
        --> due to nonsense or frameshift mutation
        
        dystrophin gene is on the x chromosome
        --> gene has huge number of base pairs so is prone to mutation
        --> largest gene found in humans
        
        Both DMD and BMD are x-linked recessive
        --> more common in males
        
        dystrophin is used to anchor actin filaments to the intramembrane proteins that link the cell to extracellular proteins
        --> when you lose dystrophyn you lose this structure and anchor to the extracellular matrix
        --> get perforation, loss of Creatine Kinase and Calcium gets into the cell
        --> inflammation and cell death
        
        muscle groups die off and are replace with fat and fibrosis
        --> myofibroblasts make (hardening collagen)
        
        recall that X-linked recessive diseases where mother is carrier
        --> 50% of sons get it (they have 50/50 of getting the mutant X)
        --> 50% of daughters are carriers (same 50/50)
        
        die before 25 usually
      - Clinical Presentation
        
        since no dystrophin proteins made for muscles present within first 5 years of life
        
        general muscle atrophy and weakness
        
        muscle weakness proximal more than distal
        --> reason why you get Gower's sign (GO WUP)
        
        kids not walking until later in life
        
        present with waddling gait when they finally start to walk late
        
        Calf PSEUDOHYPERTROPHY = appear to have thick calves
        --> not due to hypertrophy of the calves
        --> actually the opposite, atrophy leads to fat deposit and fibrosis of the calf muscles to make them appear larger
        
        Gower's Sign = leg muscles too weak to stand up
        --> need to use arms to "climb" up their legs
        
        have high amount of blood creatine kinase
        --> this escapes from the muscle cells when they are damaged by the lack of dystrophin
        
        Gower's Sign
        
        leg muscles too weak to stand up
        
        need to use arms to "climb" up their legs
        
        Late Presentations and Complications
        
        poor prognosis and survival
        
        heart arrhythmas
        
        cardiomyopathy
        
        wheelchair bound --> weak legs
        
        respiratory problems and infections
    - - General Pathology
        
        note that Beckers Muscle Dystrophy is the same as Duchenes but less severe symptoms since all cells have 50/50 chance of the good X gene being silenced during lionization
      - Clinical Presentation**
        
        since milder form of DMD doesn't present until about** ages 10-20
        
        improperly folded dystrophin protein made
        --> due to missense (small) mutation
        
        dystrophin gene is on the x chromosome
        --> gene has huge number of base pairs so is prone to mutation
        
        Both DMD and BMD are x-linked recessive
        --> more common in males
    - - General Pathology and Key Signs
        
        key sign is heart failure very young aged 10-20
        
        rare but a MUST NOT MISS DISEASE
- - - - Treatment
        
        ACh-Esterase Inhibitors
        --> rivastigmine, neostigmine, etc.
        
        steroids
        --> suppress the immune system
        
        surgical removal of the thymus
        --> recall the thymus makes T cells
        --> the Helper T Cells help promote the B cells to make antibodies
      - Clinical Presentation
        
        young women, old men, weak extraoccular muscles
        
        weak muscles after repetitive use or as the day goes on
        
        weakness of eye muscles
        --> ptosis = eyelid drooping (need toe- truck to TOW them back up)
        --> diplopia = double vision
        
        Myasthenic crisis
        --> in a small number of people the autoantibodies can attack Acetyl chol nicotinic receptors of the diaphragm
        --> can lead to death by asphyxia
        
        in women they may have Thymic Hyperplasia
        --> thymus makes T cells and can up B cell antibody production
      - General Pathology
        
        autoimmune disease that attacks the acetylcholine nicotinic receptors on muscles
        --> recall muscarinic 1-5 are for ANS system and nicotinic are for the somatic skeletal system
        
        the autoantibodies don't just block the nicotinic receptors
        --> they also activate the compliment system and cause muscle destruction
        
        bimodal distribution of onset for men and women
        
        women aged 20-30
        
        men aged 60-70
        
        Some have anti-MuSK (muscle specific Tyrosine Kinase)
        --> these antibodies go into the post nerve cell and cause even more destruction
    - - Case
        
        Notes:
        
        the thymus is actually the source of autoantibodies in MG
        
        the thymus contains muscle cells with ACh receptors that APC's mistaken as antigens and activate helper T cells and B cells to create immunoglobulins = antibodies
        
        thymectomy is indicated for most MG, even if they don't have a thymoma or thymus hyperplasia
        
        Clinical Case:
    - - Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
- - - - Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that