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143 Cards in this Set
- Front
- Back
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What are 2 things that cause muscles to ATROPHY?
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-Denervation
-Disuse |
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What types of muscle fibers can be involved in denervation atrophy?
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Both RED - type I, and WHITE - type II
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What can be seen histologically on cross section of a muscle that has undergone denervation atrophy?
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TARGET FIBERS
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What are Target fibers?
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Fibers with a central dark area like a bulls eye seen on cross section
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What happens when a denervated muscle becomes RE-innervated?
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Fiber-Type Grouping
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What is Fiber-Type grouping?
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One group of all one type of fiber, next to another group of all one type
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What do muscle fiber groups normally contain?
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MIXTURES of both type I and type II fibers
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What is Disuse atrophy associated with?
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Prolonged immobilization
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What is the primary finding in disuse atrophy histologically?
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Angular atrophy of type II fibers - not so much type I
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What is a group of genetic, progressive disorders with skeletal muscle degeneration and profound wasting and weakness?
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MUSCULAR DYSTROPHY
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What are 3 ways to distinguish between muscular dystrophies?
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-Age
-Muscle groups affected -Mode of inheritance |
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What is a characteristic lab finding in muscular dystrophies?
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Increased serum CK from muscle degeneration
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What is the most COMMON and most SEVERE of the muscular dystrophies?
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Duchenne muscular dystrophy
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In what sex is Duchenne muscular dystrophy predominant and at what age does it begin?
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-MALES
-Begins at 1 yr old |
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What are the first/progressive signs of Duchenne's MD?
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Progressive weakness ending in immobilization, wasting, muscle contracture, and death in teens
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What is the cause of Duchenne's MD?
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Lack of the protein DYSTROPHIN
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What is the Dystrophin gene inherited on?
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The X chromosome
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What do mutations of the Dystrophin gene lead to?
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DNA coding frameshifts that form STOP codons and Dystrophin synthesis failure.
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What are the major histologic findings in Duchenne's MD?
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-Random variation in muscle fiber size
-Necrosis of individual fibers -Necrotic fibers replaced by Fibrofatty tissue |
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What is the major lab finding in Duchenne MD?
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Increased serum CK
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What muscles are initially affected in Duchenne MD? How do they respond?
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Proximal - compensatory hypertrophy
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What does the hypertrophy transition into as muscles are replaced by fibrofatty tissue?
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Pseudohypertrophy
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What variant of MD is similar but less severe than Duchenne?
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Becker
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How is Becker MD different from Duchenne?
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Not a complete failure of dystrophin synthesis; just less functional
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Why is the Dystrophin protein just less functional?
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No coding frameshift within the gene; just segmental deletions
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What are 2 autosomal DOMINANT forms of MD?
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-Fascioscapulohumeral
-Myotonic |
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What are the main things to know about Fascioscapulohumeral musc dystrophy?
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-Auto dom
-Not disabling -Slowly progresses -Expect a normal lifespan |
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What is Myotonic dystrophy characterized by?
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Inability to RELAX the muscles causing muscle weakness
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What are 3 additional findings in men with Myotonic dystrophy?
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-Cataracts
-Testicular atrophy -Balding |
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What makes Myotonic dystrophy unique?
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It is a Trinucleotide Repeat disorder!!!
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What is the repeat that expands in Myotonic dystrophy?
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CTG
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What makes myotonic dystrophy distinguishable from CONGENITAL myopathies?
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Congenital myopathies show distinct morphologic changes and NO increase in serum CK
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How do babies with congenital myopathy tend to present at birth?
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Floppy infant syndrome - marked hypotonia
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What are the 3 congenital myopathies?
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-Central core disease
-Nemalin myopathy -Mitochondrial myopathies |
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What fibers are affected in Central core disease? How?
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Type I fibers - Loss of mitochondria and other organelles in the CENTRAL portion of the fibers
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How does Central core disease typically progress?
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Infants born floppy, but eventually become ambulatory
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What fibers are affected in Nemalin myopathy? How?
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Type I fibers - show small rod-shaped granules in tangles
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What is the characteristic finding in Mitochondrial myopathies?
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Maternal inheritence of defective mitochondrial enzymes
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What is a common histologic appearance of muscle fibers in Mitochondrial myopathies?
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Ragged red fibers
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What is the autoimmune disorder where auto-Ab develops against the ACh receptor?
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Myasthenia gravis
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When are patients better/worse in M. gravis?
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Better in the morning and with rest
Worse after exercise |
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In what sex is M. gravis 3x more common?
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Females
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What paraneoplastic syndrome has symptoms similar to M. gravis?
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Lambert-Eaton syndrome
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What type of cancer tends to cause Lambert-Eaton syndrome?
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Small cell carcinoma of the lung
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When are patients with Lambert-Eaton syndrome best?
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After exercise - the abnormally high released ACh gets degraded then!
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What is Metabolic bone disease usually characterized by?
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Osteopenia
Altered serum Ca/Phosphorus, or ALP |
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Osteopenia:
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Diffuse radiolucency of bone
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What is the main feature seen in Osteoporosis?
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Decreased BONE MASS
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What are 2 things that can cause bone mass to be decreased?
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-Decreased bone synthesis
-Increased bone resorption |
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What is the result of decreased bone mass?
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Inadequete weight bearing - frequent fractures lead to spinal deformity and shortness.
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What spinal deformity does osteoporosis usually lead to?
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kyphosis
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What causes osteoporosis?
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-Estrogen defic in menopause
-Inactivity -Hypercortisol -Hyperparathyroid -Calcium deficiency |
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What is von Recklinghausen disease of bone synonymous with?
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Osteitis fibrosa cystica
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Is Von recklinghausen's disease of bone related to Von recklinghausen's neurofibromatosis?
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NO
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What is Von recklinghausen's disease of bone caused by?
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Primary or Secondary hyperparathyroidism
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What are the common findings in Von recklinghausen's disease of bone?
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-Osteolytic lesions
-Brown tumors! |
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What are Brown tumors?
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Bone cysts lined by multinucleated OSTEOCLASTS and filled with high vascularity - hemorrhage gives brown color
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How can Von recklinghausen's disease of bone mimic osteoporosis?
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Both cause diffuse radiolucency of bone
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What are the lab findings in Von recklinghausen's disease of bone
-Calcium -Phosphorus -ALP |
Ca = high
Phosphorus = low ALP = high remember its due to Hyper PTH! |
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In contrast what are the labs in Osteoporosis?
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Ca = Normal
P = Normal ALP = Normal or low |
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What causes Osteomalacia?
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Deficiency of Vit D in adults
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What does Osteomalacia result in?
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Defective calcification of bone osteoid matrix - diffuse radiolucency of bone
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What is it called when Vit D is deficient due to renal disease?
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Renal osteodystrophy
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Why do we differentiate between Vit D deficiency in ADULTS vs CHILDREN?
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Because they cause completely different pictures of pathology!
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So lack of Vit D in ADULTS leads to:
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Deficient calcification of Osteoid
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Lack of Vit D in CHILDREN leads to:
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EXCESS accumulation of osteoid and INCREASED THICKNESS OF EPIPHYSEAL GROWTH PLATES
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What does the excess thickness of epiphyseal growth plates lead to?
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Skeletal deformities!
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What are 2 head findings in Rickets?
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-Craniotabes - thinning and softening of the occipital and parietal bones
-Late closure of the fontanelles |
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What is Rachitic Rosary?
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Costochondral thickening in Ricket's - leads to the ribs looking like string of beads
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What is Harrison Groove?
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A depression along the line of insertion of the diaphragm into the ribcage.
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What is Pigeon breasting?
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Protrusion of the Ribcage in rickets
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What does spinal deformity in Rickets cause?
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Decreased height
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What is Osteitis deformans aka and at what age is it mostly seen?
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Paget disease of bone - most common in elderly
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What causes Paget disease of bone?
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We don't know - maybe a slow virus like Paramyxovirus
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What is the hallmark of Paget disease of bone?
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Abnormal bone ARCHITECTURE due to increases in BOTH osteoBLASTIC and osteoCLASTIC activity
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What bones are most commonly affected in Paget disease?
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-Skull calvaria
-Spine -Pelvis -Femur -Tibia |
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What are the lab findings in Paget disease of bone?
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-Normal Ca/P
-MARKEDLY increased ALP |
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What causes the huge increase in ALP in Paget's?
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The increased OSTEOBLAST activity
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What is Monostotic vs Polyostotic?
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Monostotic = only one bone
Polyostotic = multiple bones involved |
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What are the 3 morphologic phases characteristically seen in Paget?
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1. Osteolytic phsae
2. Mixed osteoblastic/lytic phase 3. Late phase |
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What predominates on the Osteolytic phase?
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Bone resorption
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What does the new bone formation by osteoblasts in the MIXED phase lead to?
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MOSAIC pattern of bone
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What does the Late phase consist of?
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Increased bone density with THICK trabeculae and PROMINENT mosaic pattern
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What are 4 complications of Paget disease of bone in older people?
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-Bone pain from fractures
-High output cardiac failure -Hearing loss -Osteosarcoma |
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Why would fractures occur if there is increased osteoblast activity?
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The new bone is WEAK
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What causes hi-output cardiac failure?
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Early lesions are highly vascularized and form AV malformations
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What causes the hearing loss?
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Narrowing of the auditory canal and damage to the ossicles
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What is unique about Osteosarcoma in Paget disease?
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This is the only time it would be seen in OLDER patients - normally Osteosarcoma is seen in YOUNG.
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What vitamin deficiency leads to impaired Osteoid matrix formation? Why?
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Vitamin C/Scurvy - impairs collagen formation - lack of Lys/Pro hydroxylation.
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What bone changes are seen as a result of Scurvy?
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-Subperiosteal hemorrhage
-Osteoporosis -No replacement of epiphyseal cartilage with osteoid! |
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What inherited bone defect leads to DWARFISM?
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Achondroplasia
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What is Achondroplasia associated with?
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Advanced paternal age
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What is the inheritance of Achondroplasia?
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Autosomal dominant
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What gene mutation/chromosome is associated with Achondroplasia?
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FGF receptor on 4p16.3
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What are the skeletal changes seen in Achondroplasia?
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-Short limbs
-Normal sized head/trunk |
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What is Fibrous dysplasia?
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Replacement of bone with fibrous tissue
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What are 3 forms of Fibrous dysplasia?
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-Monostotic - asymptomatic or pain from fractures
-Polyostotic - deformity -McCune Albright Syndrome |
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What are the 4 components of McCune Albright syndrome and in what patients does this occur?
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-Very young girls
-Precocious puberty -Polyostotic fibrous dysplasia -Irregular Cafe au Lait spots -Short stature |
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What is the Gene defect in McCune Albright syndrome?
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Postzygotic somatic mutation in GNAS1
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What can infarction due to disruption of blood supply to bone lead to?
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Aseptic necrosis!
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What can Aseptic necrosis lead to in growing children?
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Specific bone deformity diseases
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What is affected in Legg Calve Perthes disease?
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The head of the FEMUR
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What is affected in Osgood Schlatter disease?
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the Tibial Tubercle
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What is affected in Kohler bone disease?
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The navicular bone!
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What disorder is characterized by multiple FRACTURES but minimal bone trauma?
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Osteogenesis imperfecta
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What is OI also known as?
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Brittle bone disease
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What is Osteogenesis Imperfecta caused by?
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Defect in collagen synthesis
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Hallmark finding in OI:
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Blue sclera
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What is the inheritance pattern of the most common type of OI?
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Auto dominant
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What is osteopetrosis?
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THICKENING of the skeleton from failure of OSTEOCLASTS
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What are the symptoms of Osteopetrosis?
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-Bone fractures
-Deafness -Blindness -CN impairment -Anemia |
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Why are these symptoms seen in spite of better skeletal density?
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The thick bone narrows foramina for the nerves to go through! And bone is weak and fractures easily
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Why the Anemia in Osteopetrosis?
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The BM space is too small for enough blood cells to be made
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What is the most common cause of pyogenic osteomyelitis in CHILDREN and how does it occur?
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Staph aureus - by bloodborne dissemination from an infection elsewhere
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What 2 bacteria are more frequently causes of Pyogenic osteomyelitis in NEONATES?
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-Group B streps - agalactiae
-E. coli |
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What bacteria is frequently associated with osteomyelitis in patients with Sickle Cell?
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Salmonella!
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What is the cause of pyogenic osteomyelitis in ADULTS?
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Compound fracture or surgery
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What organism causes Pyogenic osteomyelitis in IV Drug users?
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Pseudomonas
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What IS pyogenic osteomyelitis?
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Acute pyogenic infection of bone
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What part of the bone is involved in osteomyelitis? What are the 3 most common bones?
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The METAPHYSIS
-Distal Femur -Proximal tibia -Proximal humerus |
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How can Pyogenic osteomyelitis be treated in the ACUTE stage?
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With antibiotic and recovery
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What does Pyogenic osteomyelitis have the ability to do?
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Compress the vasculature and cause necrosis of bone/marrow
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What is necrotic bone?
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Sequestrum
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Why is Sequestrum bad?
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It's a foreign body and calls for PERSISTENT infection
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What is it called when a sleeve of new bone forms around Sequestrum?
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Involucrum
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What is it called when granulation tissue walls off the Involucrum?
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Brodie's tumor
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What complication can arise from chronic pygoenic osteomyelitis?
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Secondary - REACTIVE amyloidosis!
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What other bacterium can cause infection of bone?
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TUBERCULOSIS
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What is Tuberculous osteomyelitis of the vertebrae called? What does it have the ability to do?
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POTT disease - collapse causes spinal deformity
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What is the group of disorders that have proliferation of cells resembling Langerhans cells of the epidermis again?
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HISTIOCYTOSIS X SYNDROME!
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What are the cells in Histiocytosis X? Morphologic hallmark?
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Histiocytes - Birbeck granules with tennis racquet shape!
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Where have we seen Histiocytosis X cause disease before?
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In the lung - pulmonary fibrosis due to Eosinophilic granuloma
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What are the 3 disease entities encompassed in Histiocytosis S?
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-Letterer-Siwe disease
-Hand-Schuller-Christian disease -Eosinophilic granuloma |
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And what is the main problem in these Histiocytosis X syndromes?
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Histiocytes overproliferate, infiltrate tissues and cause damage!
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Which syndrome has the worst prognosis? Why?
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Letterer-Siwe disease - causes EARLY death in infants/children
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What are the main clinical manifestations of Letterer-Siwe disease?
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-Hepatosplenomegaly
-Lymphadenopathy -Pancytopenia -Recurrent infections/Lung problems |
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Which Histiocytosis X syndrome has a bit better prognosis than Letterer-Siwe?
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Hand-Schuller-Christian disease
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Why does Hand-Schuller-Christian disease have better prognosis?
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The inflammatory infiltrate is more mixed - less pancytopenia
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When does Hand-Schuller-Christian disease usually present?
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Before 5 yrs old
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What are the main findings in Hand-Schuller-Christian disease?
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-Infiltration of the Skull, Liver, and Spleen - main effects are on the skull
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So what is the classic triad of clinical symptoms in Hand-Schuller-Christian disease?
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-Skull lesions
-Diabetes insipidus -Exophthalmosis! |
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Which Histiocytosis X has the BEST prognosis?
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Eosinophilic Granuloma!
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What gives Eosinophilic granuloma the best prognosis?
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-It is RARELY fatal
-Lesions can heal w/ txmt |
