Musculoskeletal Pathology

Mind Map by , created almost 6 years ago

Doctorate Pathology (Systems Pathology) Mind Map on Musculoskeletal Pathology, created by melian.yates on 27/11/2013.

Created by melian.yates almost 6 years ago
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Musculoskeletal Pathology
1 Skeletal Muscle
1.1 Muscles of posture, movement & respiration
1.2 Response of Muscle to Injury
1.2.1 Degeneration/ Necrosis Tends to be segmental (Necrosis of entire myofibre is uncommon => crush injury or widespread ischaemia resulting from pressure on a large artery) Lots of causes Common triggering factor is increase in Ca2+ w/in the cell Allows muscle contraction Ca-dependent enzymes & lysosomal enzymes increase => myofibre destruction Muscle cell contents may leak into blood if the cell membrane is damaged Creatine kinase (CK) is an enzyme which leaks following injury & is commonly used to measure the extent of muscle damage
1.2.2 Regeneration Requirements: Intact basal lamina (Sarcolemmal tube) Blood supply => macrophages to clear up debris Viable satellite cells (act as progenitor cells for new sarcoplasm production) If not met, fibrosis will occur Skeletal muscle myofibres have substantial regenerative ability
1.2.3 Atrophy Entire muscle or individual myofibres within are reduced in diameter Causes: Disuse (Ex. fracture, failure to use limb, recumbancy) Cachexia, old age, malnutrition Denervation (nerve provides trophic factors: any interference or damage => muscle atrophy) Endocrine disease Ex. Equine "roarers" - Laryngeal hemiplegia (Damage to left recurrent laryngeal nerve) Can be rapid - over 50% of muscle mass lost in a few weeks
1.2.4 Hypertrophy Entire muscle or individual myofibre diameter increases in size Causes: Increased work load Compensatory Ex. COPD heaves lines Physiological
1.2.5 Innumerable factors can induce these changes (Trauma, toxins, infectious agents, nutritional deficiencies, Ischaemia, Hereditary disease) => Specific Dx is NOT POSSSIBLE based on morphological or histological features alone
1.3 Muscle Diseases
1.3.1 Inflammation: Myositis Infectious Bacteria Gain entry via direct penetration, haematogenously or extension (Ex. from an infected joint) Disease or manifestation Abscesses Arcanobacterium pyogenes (Bovine, Pigs) Streptococcus equi (Equine) Corynebacterium pseudotuberculosis (Sheep, Goats, Equine) Black leg Clostridium chauvoei ( Bovine, Sheep) Activation of latent spores Gas gangrene Clostridium septicum & C. novyi (Sheep, Bovine, Equine), C. perfringens & C. sordelli (Pigs) Penetrating wounds Wooden tongue Actinobacillus lignieresii (Bovine) Viruses (Rare) Parasites Nematodes Trichinella, Ancylostoma & Ascarid larvae Cestodes Taenia solium (cysticercosis in swine & humans). T.ovis (cystercercosis in sheep) Protozoa Toxoplasma gondii, Neospora caninum, Sarcocystis Immune mediated Canine Masticatory Muscle Myositis (MMM) Autoantibodies SELECTIVELY attack muscle of mastication (Type IIM fibres) Manifests in the masseter & temporalis muscles (Bilateral) Acute stage: Eosinophillic myositis Chronic stage: Atrophic myositis Extraocular myositis Autoantibodies selectively target only the muscles around the eye in the Dog Canine Polymyositis Can affect masticatory muscles but Dogs DO NOT have antibodies to type IIM fibres Generalized inflammatory myopathy Muscle necrosis, regeneration & fibrosis Muscle enzymes may be increased Fever, pain, weakness, resp. distress T Lymphocytes, plasma cells, granulocytes Single biopsy may not be enough to make the Dx (it tends to be multifocal & disseminated) DDx = Toxoplasma gondii, MMM Other Paraneoplastic, drug-induced, idiopathic
1.3.2 Congenital Defects in muscular form Congenital diaphramatic defects Myofibrillar hypoplasia (Pigs - splayleg) Can spontaneously resolve, cause unknown, responsible for significant deaths Hyperplasia of muscle fibres (Calves, lambs) Double muscling due to increased number of myofibres in affected muscle (thighs, rump, loin) -> Predisposes to dystocia Muscular Dystrophies Inherited group (X-linked) of degenerative muscular diseases causing progressive muscle weakness & wasting Usually due to a genetic fault leading to a muscular protein deficiency Ex. Duchenne MD in humans due to dystrophin deficiency Dystrophin gene mutations reported in the Golden retriever, Rottweiler, Irish terrier, etc. Innervation is normal Muscle biopsy -> confirm lack of dystrophin with IHC
1.3.3 Toxic, Nutritional & Exertional Myopathies Toxic Plants Gossypol, Cassia (coffee senna) Drugs Monensin Coccidiostat Toxic to: Horses, Sheep, Cattle, Dogs, Birds Skeletal & myocardial necrosis Rapid onset recumbancy & potentially death Usually due to mixing errors in feed Ionophore Disturbs transport of Na & K across membrane Increases Ca2+ => Hypercontraction & Degeneration Chemicals Ex. Fe injections can cause local myonecrosis Mycotoxins Endocrine Hyperadrenocorticism & Hypothyroidism => Muscle atrophy Nutritional White Muscle Disease Economic importance in young Cattle, Sheep & Pigs (also foals) Se &/or Vit. E deficiency Grossly: Lesions are bilaterally symmetrical (hard working muscles) Pigs: lesions in heart & liver Pathogenesis: Oxygen free radicals (OFR) can damage cell membranes Vit. E involved in binding OFR & Glutathione peroxidase (includes Se) => Neutralizes effects of OFR If Vit. E & Se deficient: Balance shifts to membrane damage => Ca2+ entry & mitochondrial damage => cell swells & dies Exertional Caused by intensive & exhaustive activity of major muscle masses Classically occurs in the Horse after unaccustomed exercise Equine exertional rhabdomyolysis Dissolution of striped (skeletal) muscle Membrane damage & leakage of myoglobin Myoglobinura = rhabdomyolysis Azoturia Exercise following prolonged period of rest Unable to move, sweating, tremors Myoglobin leaks from muscle cells -> leaks into urine -> urine is dark red/brown (myoglobinuria) -> damages renal tubules Tying-up (similar to Azoturia, but milder) Linked to polysaccharide storage myopathy (many breeds) Ex. Equine polysaccharide storage myopathy (EPSM) Capture myopathy, Porcine stress syndrome
1.3.4 Neuromuscular Junction Myasthenia gravis (MG) 1) Acquired Autoimmune disease: Abs directed against acetyl choline receptors Associated w/ thymomas, megaoesophagus & hypothyroidism (Dogs) 2) Congenital Inherited deficiency in acetyl choline receptors (Rare) No Abs against acetyl choline receptors in serum Both forms manifest as weakness which worsens on exercise Botulism Due to ingestion of Clostridium botulinum toxin which inhibits acetyl choline release Dx: Demonstrate toxin in faeces, ingested material, serum
1.3.5 Neoplasia Rare in domestic animals Primary benign: Rhabdomyoma Primary malignant: Rhabdomyosarcoma Metastases can also occur to skeletal muscle (e.g. carcinoma, haemangiosarcoma)
1.4 Anatomy
1.4.1 Types of Myofibres
2 Bones function, structure & organization
2.1 Bone is a hard, highly specialized connective tissue, comprising interconnected cells embedded in a clacified, collagenous matrix
2.2 A living, dynamic, responsive tissue, growing & remodeling throughout life
2.3 Functions:
2.3.1 Supports movement Protects body Storage: Mineral bank Haematopoietic stem cells Fat
2.4 Structure:
2.4.1 Composed of cells & matrix
2.4.2 Cells: Osteoblasts Mesenchymal cells of bone marrow stromal origin Form the bone matrix (Osteoid) Osteoclasts Multinucleated cells derived from haematopoietic stem cells Responsible for bone resorption Osteocytes Osteoblasts that have become surrounded by mineralized bone matrix Occupy cavities called lacunae
2.4.3 Matrix: Composed of type I collagen & mineral Mineral - accounts for 65% of bone (includes: Ca, P, Mg, Mn, Zn, Cu & Na) Ground substance (water, proteoglycans, lipids) Strength
2.5 Bone Organization
2.5.1 Not all bones are organized in the same way Organization dictated by the pattern of collagen deposition
2.5.2 1) Immature (Woven) Bone Collagen is arranged in a "random weave" This is only normal in the fetus In adults: Randomly woven bone => sign of pathological condition (e.g. fracture, inflammation, neoplasia)
2.5.3 2) Mature (Lamellar ) Bone The collagen is arranged in orderly layers which are much stronger than woven bone Two main types: Compact or cortical bone forms the diaphyses of long bones & the shell of all other bones (contains Osteons) Cancellous (spongy or trabecular) bone occurs in vertebrae, flat bones & epiphysyes of long bones (Contains NO Osteons)
2.6 Periosteum
2.6.1 A sheath of connective tissue covering the bone (except at the articular surfaces) The inner layer merges w/ the outer layer of bone & contains osteoblasts & stem cells The blood supply to the mature bone enters via the periosteum Damage to the periosteum triggers a hyperplastic rxn of the inner layer
2.7 Bone Development
2.7.1 2 Main Types: Intramembranous ossification Flat bones mainly (e.g. skull) Mesenchymal cells differentiate into osteoblasts There is NO cartilage precursor template Endochondral ossification Long bones mainly Cartilage model of the bone to be formed is vascularised & replaced by bone
2.8 Physis (Growth plate)
2.8.1 Esentially the remnant of the cartilage model located at the junction of Diaphysis & Epiphysis
2.8.2 Imp. site: Many congenital or nutritional bone diseases in the growing animal manifest here
2.8.3 In neonates & growing animals: Growth plate is "open", i.e. chrondrocyte proliferation balances cell maturation & death The growth plate "closes" & ossifies @ maturity
2.9 Bone Resorption
2.9.1 Mediated by PTH & Calcitonin
2.9.2 Parathyroid Hormone (PTH) Produced by chief cells in the parathyroid glands Increases serum Ca2+ levels (released in response to decreased serum Ca2+) STIMULATES Osteoclasts
2.9.3 Calcitonin Produced by C -cells in the thyroid glands Decreases serum Ca2+ levels ( released in response to Increased serum Ca2+) INHIBITS Osteoclasts
2.9.4 Low serum Ca2+ -> Induces PTH secretion -> Osteoclasts increase in # -> Attach to bone & resorb mineralized matrix => Serum Ca2+ INCREASES
2.10 Bone Dynamics
2.10.1 Bone growth & maintenance of normal structure are directly related to mechanical forces which generate bioelectrical potentials (piezoelectricity) These potentials strengthen bone while inactivity reduces them, leading to bone loss
2.10.2 Neonates: Bone growth predominates & modeling is Imp. Adults: Formation of bone is balanced by resorption (remodeling)
2.10.3 Bone resorption may exceed formation in pathological stages (Hormonal, trauma, nutritional) or in old age & disuse
3 Pathology of Bone
3.1 Fractures
3.1.1 Traumatic Normal bone broken by excessive force
3.1.2 Pathological Abnormal bone broken by minimal or no trauma
3.1.3 Fracture Repair
3.1.4 Callus Bridges the gap, Encircles fracture site, Stabilizes fracture
3.1.5 Factors which delay healing: Malnutrition Inadequate blood supply (leads to hypoxia) Leads to excess cartilage in Callus Healing can still occur since this can turn to bone Excess movement Leads to excess fibrous tissue in Callus This forms a false joint & can't heal properly Presence of Necrotic bone (may form a sequestrum) Bacterial Infection
3.2 Metabolic Bone Diseases
3.2.1 Manifestation of Systemic Disease in the skeleton (Endocrine, Nutritional or Toxic Origin)
3.2.2 Hyperparathyroidism (Fibrous Oesteodystrophy) Bone is resorbed & replaced by Fibrous, "rubbery" connective tissue Caused by: Persistently elevated PTH Causes of Increased PTH: Primary (Rare) Increased production of PTH NOT related to Ca2+ or P levels (i.e. autonomous) Due to parathyroid neoplasia or bilateral idiopathic parathyroid hyperplasia Results in => Hypercalcaemia Secondary (much more common) Renal Chronic renal failure (Reduced perfusion) => Retention of P ( & inadequate production of Vit. D by kidneys) Hyperphosphataemia & Hypocalcaemia (High P depresses Ca2+) Low Ca2+ => PTH production => Increased Ca2+ resorption from bone ("Rubber jaw") => Fibrous Osteodystrophy Nutritional (Poor diet) - "Rubber Jaw" Low Ca2+/ High P diets/ Vit. D deficiency Increased Osteoclastic resorption of bone & deposition of fibro-osteoid matrix that fails to mineralize Flat bones of the skull (Maxillary & Nasal bones) => Swell Long bones become soft w/ thin cortices (fracture easily) Ex: Horses - Grain/corn/bran Swine - Fed grain rations Dogs & Cats - Fed meat only diets More common in young, fast growing animals (w/ exception of horses) PTH secretion triggered by Decreased plasma Ca2+ Paraneoplastic Parathyroid hormone- related protein produced by certain neoplasms
3.2.3 Osteoporosis a LESION, not a distinct disease entity Reduction in bone quantity, not quality Bone resorption exceeds formation -> Pathological loss of bone The bone that remains is normally mineralized (Just not enough of it) => Prone to fractures due to reduced strength Causes: Starvation, nutritional deficiency (Ca2+) Senility Physical inactivity (Disuse) Farm animals (Most common cause) Calves on indigestible milk replacer Cattle on low quality hay in cold climates Localized or general Bone atrophy or osteopaenia
3.2.4 Rickets Disease of the young, fast growing skeleton Pathogenesis: Failure of mineralization of Physeal & Epiphyeal cartilage during endochrondral ossification & of newly formed osteoid Due to diets low in Vit. D (or P - less common) Vit. D. maintains normal plasma levels of Ca2+ & P (acts on intestines, bones, kidneys) Calcitriol enhances GI absorption of Ca & P w/o Vit. D, only 10-15% of dietary Ca2+ is absorbed Growth plates are thickened As the zone of proliferation does not mineralize & mature => blood vessels & chondroclasts cannot invade so the cartilage is not removed Metaphyses are flared Because bone & cartilage cannot be removed (Osteoclasts cannot bind to poorly mineralized bone -> further accentuated by weight bearing) Enlarged costochondral junctions
3.2.5 Osteomalacia Similar to Rickets, except disease of adult skeleton Failure of newly formed osteoid to mineralize
3.2.6 Others Hormone -related (Hormones which directly affect bone growth & resorption - other than PTH & Calcitonin) Insulin, Growth hormone (Somatotrophin), Glucocorticoids, Oestrogens, Androgens & Thyroid Hormones Vitamin -Related Conditions Vitamin A Hypervitaminosis A Cats fed liver for prolonged periods Vertebrae fuse (Vertebral ankylosis) with each other due to bone proliferation (esp. in neck) Pathogenesis not clear Can also be teratogenic -> Cleft palate Hypovitaminosis A Due to dietary deficiency in Dam: Can be teratogenic in Pigs & large Cats More commonly, due to dietary deficiency in Neonates (Puppies, Kittens, Calves, Piglets) Deficiency => Failure of osteoclastic remodeling => Bone overgrowth & nerve compression (esp. optic nerves) Essential for normal bone growth in foetuses & neonates Stimulates osteoclasts Hypervitaminosis D Dietary or iatrogenic origin Usually chronic Hypercalcaemia: Metastatic calcification of soft tissues Vitamin C (Ascorbic Acid) Scurvy in Pigs, NHPs Imp. for collagen formation Haemorrhage Fractures
3.3 Inflammation
3.3.1 Causes Bacteria (Most common) Viral, Fungal, Protozoal (Less common) Staphy, Strep, A. pyogenes, Gram -ve
3.3.2 Routes of Infection Direct Inoculation At time of fracture Direct Extension From other infected sites (sinuses, middle ear, joints) Arthritis, synovitis, otitis media, rhinitis, sinusitis, meningitis or tooth root abscess Haematogenous Mostly young farm animals
3.3.3 Gross lesions Suppurative exudate (in bacterial infection), Necrosis, Bone proliferation, Pathological fractures Dead bone portions may be separated from blood supply => forming bone sequestra
3.3.4 Consequences Extension to adjacent bone Haematogenous spread to other bones & soft tissue Possible consequence of sepsis in young animals Salmonella dublin, A. pyogenes, Strep Animal often dies of sepsis prior to bone lesions appearing Pathologic features Draining fistulas, necrosis & loss of bone, new bone Sinus tracts to exterior
3.3.5 Metaphyseal Osteopathy Idiopathic/ unknown cause (Infectious aetiology ?) Young, fast growing Dogs (Large or giant breeds) Distal radius & ulna most severely affected: bilaterally symmetrical Swelling in metaphyses of long bones (Neutrophilic infiltrate) Fever, lameness, suppurative inflammation & necrosis of metaphyses Most resolve spontaneously, but can progress to periosteal bone proliferation May wax & wane
3.4 Neoplastic Bone Diseases
3.4.1 Bone tissue: Osteoma Uncommon Horses & Cattle Flat bones (skull & scapula) Disfigurement: Obstruct nasal passages Recur if not completely removed Osteosarcoma (OSA) Any neoplasm of mesenchymal origin in which the cells produce Osteoid Dogs & Cats (Otherwise uncommon) Dogs: OSA(80%) > Chrondrosarcoma (10%) > Fibrosarcoma/haemangiosarcoma (7%) > Lymphoid & myeloid tumors of marrow Giant breeds of Dog are at massively increased risk Strong site preference (Dogs): Appendicular skeleton 3-4x more frequently involved than axial Proximal humerus, distal radius, proximal tibia & distal femur "Away from the elbow - towards the knee" Survival time is slightly better for axial than appendicular OSA (Dogs) Prognosis is poor due to early metastasis Pulmonary metastases Bone metastases
3.4.2 Cartilage: Chondroma Benign neoplasm of cartilage Rare Slow growing, Expansile w/ smooth border Chrondrosarcoma Any malignant neoplasm in which mesenchymal cells produce chondroid matrix Dogs (most common), Sheep Flat bones Slower growth rate, longer clinical course & later to metastasize than OSA Metastatic rate: 20%
3.5 Hyperostotic Bone Diseases
3.5.1 Hypertrophic Pulmonary Osteopathy (HPO) Periosteal proliferation of bone on diaphyses & metaphyses of distal limbs Progressive & bilateral Most cases: Have intrathoracic neoplasm or chronic inflammatory focus Has also been associated w/ intra-abdominal lesions - Ex. Botryoid rhabdomyosarcoma in the canine urinary bladder & ovarian tumors in Horses
3.5.2 Craniomandibular Osteopathy West Highland terriers & Scottish terriers Puppies: Arises @ 4 -7 months Bilaterally symmetrical periosteal proliferation of new bone Irregular thickening of rami of mandibles & skull bones (tympanic bullae)
3.6 Developmental Bone Diseases
3.6.1 Primary abnormalities of Bone, Cartilage or Mesenchyme
3.6.2 Hereditary or Environmental
3.6.3 Localized or Generalized Generalized Proportionate Dwarfism Minature breeds: Due to growth factor deficit Chondrodysplasia Abnormal cartilage formation Cattle, Dogs, Sheep, Pigs & Cats Affects bones which form from a cartilage model (endochondral ossification) - long bones are shorter than normal Leads to Disproportionate Dwarfism Localized forms occur in some Dogs as a breed associated characteristic (e.g. affecting skulls of Pekingnese & Bulldogs or the limbs of Dachshunds & Basset hounds) Osteopetrosis (Marble bone disease) Hyperactive osteoblasts/ Failure of resorption by osteoclasts => Failure of remodeling of cancellous bone Bones become thickened & dense, but brittle Associated w/ viral infections (e.g. FeLV, BVD) Localized Cervical Vertebral Stenotic Myelopathy (Wobblers) Equine disease Narrowing of the vertebral canal due to vertebral malalignment or maldevelopment Fast growing males ranging from 8 months to 4 yrs Hind limb ataxia: Due to cord compression Dogs: Great dane, Doberman Static: C5-C7 (1-4yrs) Dynamic: C3 -C5 (1 yr) Angular Limb Deformity Lateral deviation of distal portion of limb (usually) Most common in foals: Congenital or Acquired Causes: Malpositioning (in utero), excessive joint laxity, hypothyroidism, trauma, overnutrition, defective endochrondral ossification
3.7 Miscellaneous Bone Lesions
3.7.1 Ossifying Pachymeningitis Plaques of bone form in the Dura of the spinal cord (especially in older dogs) No clinical significance
3.7.2 Heterotopic Bone Spicules of bone form in the lungs of older dogs No clinical significance
3.7.3 Ossifying Epulides Neoplasms of peridontal fibroblast origin Occur in oral cavity (esp. Boxers) Benign -> Complete removal -> Good prognosis