Musculoskeletal disorders Muscle diseases.pptx

Muscle disorder

1. Muscle Pathology

2. Skeletal muscle Smooth muscle Cardiac muscle Voluntary muscles Consciously choose to contract the muscle Skeletal muscles Involuntary muscles Under control of subconscious brain Smooth muscles and cardiac muscle Types of Muscles

3. Medical Terminology: A Living Language , Fourth Edition Bonnie F. Fremgen and Suzanne S. Frucht Copyright ©2009 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Figure 4.21 – The three types of muscles: skeletal, smooth, and cardiac.

4. Medical Terminology: A Living Language , Fourth Edition Bonnie F. Fremgen and Suzanne S. Frucht Copyright ©2009 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Figure 4.22 – Characteristics of the three types of muscles.

5. Attached to bones Produce voluntary movement of skeleton Also referred to as striated muscle Looks striped under microscope Muscle is wrapped in layers of connective tissue Called fascia Tapers at the end to form tendon Inserts into periosteum to attach muscle to bone Are stimulated by motor neurons Point of contact with muscle fiber is called myoneural junction Skeletal Muscles

6. Muscle fibers bundled into fascicles - Modified Gomori trichrome stai n

7. Striated appearance of skeletal muscle High magnification, H&E stain

8. Electron micrograph of normal skeletal muscle

9. Type 1 and 2 muscle fibers Type 1 - slow twitch, oxidative Type 2 - fast twitch, mainly glycolytic Normal human muscle - mosaic pattern (checkerboard) of both fiber types Muscle fiber types

10. ATPase (pH 9.4, pH 4.6, pH 4.2) - differentiates type 1 and type 2 myofibers Modified Gomori's trichrome - collagen - mitochondria and other organelles - inclusions NADH-TR oxidative stain H&E demonstrates myofiber degeneration and regeneration Special stains

11. Normal muscle - H&E stain

12. Myosin ATPase stain of normal skeletal muscle

13. Modified Gomori's trichrome stain on normal skeletal muscle - Sarcoplasmic dots' - mitochondria

14. NADH-TR ( nicotinamide adenine dinucleotide - tetrazolium reductase ) Normal skeletal muscle

15. Associated with internal organs Also called visceral muscle Stomach Respiratory airways Blood vessels Called smooth because it has no microscopic stripes Produces involuntary movement of these organs Smooth muscles

16. Also called myocardium Makes up walls of heart Involuntary contraction of heart to pump blood Cardiac muscle

17. Atrophy Dystrophy Myopathy Neuromuscular junction diseases Skeletal muscle tumors Skeletal muscle pathology outline

18. Two major types of pathology Neurogenic - loss of nerve stimulation Myopathic - intrinsic abnormality of muscle Muscle pathology

19. Amyotrophic lateral sclerosis Spinal muscular atrophy (SMA) Hereditary neuropathies Trauma Vascular diseases Infections Neurogenic diseases

20. Grouped atrophy Small angulated fibers Both fiber types are atrophic Fiber type grouping = reinnervation Nuclear clumps Target fibers Neurogenic pathology

21. Chronic neurogenic disorder 1 . Normal 2 . Early denervation 3. Reinnervation 4. Continued - fiber type grouping denervation –group atrophy

22. Non-specific response to a variety of muscle disorders Type of fibers affected, their distribution and their specific morphology aid in identifying aetiology Causes: neurogenic, disuse, steriods (endogenous or exogenous), myopathy Muscle atrophy

23. Neurogenic atrophy - grouped' atrophy

24. Neurogenic versus myopathic

25. Large fiber type groups indicative of chronic neurogenic disease - ATPase stain .

26. Marked atrophy of clusters of myofibers

27. Dystrophic muscle diseases Inflammatory myopathies Myasthenia gravis Congenital myopathies Metabolic myopathies Myopathic diseases

28. Wide variation in fiber size Degeneration and regeneration Inflammation Central nuclei Fibrosis Architectural changes Myopathic pathology

29. Heterogenous group of inherited disorders characterized by progressive degeneration of muscle fibers leading to muscle weakness and wasting Muscular dystrophy

30. Duchene muscular dystrophy X-linked Pelvic and shoulder girdles Deletion of gene that encodes dystrophin Degeneration of muscles, impaired repair, fibrosis, fibrofatty deposits Elevated serum creatinine kinase Death form respiratory insufficiency, cardiac arrhythmia, 10-15 years of age wheel chair-bound

31. Pathology Variation in fiber size with large rounded fibers Marked endomysial fibrosis Some regeneration Eventually muscle replaced by fat and fibrous tissue Duchene Muscular Dystrophy

32. Duchenne muscular dystrophy - H&E stain

33. Duchenne muscular dystrophy - modified Gomori's trichrome stain

34. Normal immunohistochemical sarcolemmal staining for dystrophin

35. Dystrophin staining in a patient with DMD

36. Autosomal muscular dystrophies Limb girdle dystrophies AD or AR Myotonic dystrophy (MD) Myotonia is a sustained involuntary contraction of a group of muscles AD Most common form of adult MD Progressive muscle weakness and wasting Atrophy of type I and hypertrophy of type II fibers Anticipation - Earlier age of onset and increased severity in successive generations Other dystrophies

37. Heterogenous group of disorders – morphologically and clinically Congenital and toxic ( aquired ) forms Congenital myopathy: ion channel, inborn errors of metabolism (glycogen and lipid) and mitochondrial abnormalities Toxic myopathies: intrinsic exposure eg thyroxine and extrinsic eg alcohol, therapeutic drugs ( eg chloroquine ) Myopathy

38. Polymyositis Dermatomyositis Inclusion body myositis Sarcoidosis Trichinosis Viral myositis Inflammatory Myopathies

39. Clinical Pain and aching in muscles Proximal weakness More common in females Elevated creatinine kinase Facial rash in dermatomyositis Respond to steroids Polymyositis andDermatomyositis

40. Pathology Chronic inflammatory infiltrate Degeneration and regeneration Variation in fiber size Moth-eaten fibers Perifascicular atrophy - dermatomyositis Polymyositis and Dermatomyositis

41. Inflammatory myopathy - chronic inflammatory cell infiltrate surrounding and infiltrating necrotic muscle fibers - H&E stain

42. Polymyositis - endomysial , chronic inflammatory cell infiltrate and chronic myopathic changes - H&E stain

43. Necrotic and regenerating myofibers - H&E stain

44. Moth-eaten' myofibers - NADH-TR stain

45. Dermatomyositis - perifasicular atrophy Modified Gomori's trichrome stain

46. Nematode Trichinella spp ( spiralis ) Clinical symptoms ~ 2 weeks after ingestion of contaminated food (pork) Vomiting and diarrhea (enteric phase) Periorbital and facial edema, fever, myalgia and proximal weakness (acute systemic phase) Larvae encyst in skeletal muscle Lymphocytic and eosinophilic response Eosinophilia Eventually calcify Trichinosis

47. Trichinella in host nurse cell.

48. Infantile-onset acid maltase deficiency Autosomal recessive Generalized progressive weakness, hypotonia , cardiomegaly and hepatomegaly Death usually from cardio-respiratory failure before age 2 Childhood-onset and adult-onset forms of acid maltase deficiency Less severe than infantile form Pompe's Disease

49. Pompe's disease - H&E stain

50. Pompe's disease - PAS stain

51. Myasthenia gravis Neuromuscular transmission disorder Fluctuating weakness, principally abnormal fatiguability after repeated activity Improvement after rest More common in females Circulating antibodies to acetylcholine receptors Leads to lysis of postsynaptic membranes Neuromuscular junction diseases

52. Autoimmune myopathies Dermatomyositis Complement mediated cytotoxic Abs against microvasculature of muscle Polymyositis Direct damage by cytotoxic T cells Myasthenia Gravis Muscular fatigability caused by circulating Abs to acetylcholine receptor at the myoneural junction Extraocular muscles, swelling muscles, extremities Pts can develop other autoimmune diseases 40% patients have thymoma 75% of remaining thymic hyperplasia Removal of thymus can be curative

53. Rhabdomyoma – very rare Rhabdomyosarcoma – Most common soft tissue sarcoma in children Common in head and neck and genitourinary tract Chromosomal translocations mostly t(2;13) Variable gross appearance – soft, gelatinous and grape-like (sarcoma botryoides) or poorly defined and infiltrating Histologically – embryonal, alveolar and pleomorphic Rhabdomyoblast – round or elongated (tadpole/strap cells) Skeletal muscle tumors

54. Rhabdomyosarcoma

55. Embryonal rhabdomyosarcoma

56. Embryonal rhabdomyosarcoma

57. Alveolar rhabdomyosarcoma

58. Alveolar rhabdomyosarcoma - The tumor cells may form solid nests and small alveolar collections (arrow) in desmoplastic stroma (big arrow) as seen in this case.

59. Alveolar rhabdomyosarcoma - The alveolar architecture is represented by round to oval collections of discohesive tumor cells.

60. Alveolar rhabdomyosarcoma – immunohistochemical stain for desmin is positive

61. Pleomorphic rhabdomyosarcoma

62. Pleomorphic rhabdomyosarcoma