Path 2 Flashcards
dermatomyositis affects? classic vs revised model
skin & muscles. humoral attack on muscle capillaries and arterioles –> MAC deposits in perivascular sites –> capillaries destroyed and muscle fibers atrophy vs overprod of IFN-inducible proteins –> high type I IFN –> endothelial cells and muscle fibers injured –> perifascicular atrophy
skin vs muscle vs constitutional sxs of DM
gottron papules, Heliotrope eruption; facial erythema; poikiloderma at Shawl/V neck/Holster sign; nailfold abnlities vs slow progressive prox muscle weakness vs interstitial lung dz, dysphagia, heart, polyarthritis/joints
DM subtypes: Clinically amyopathic DM vs juvenile DM vs malig-assoc DM
no skin sxs vs <18yo vs adenocarcinoma to cvx, lung, ovaries, pancreas, bladder, stomach; Myositis-specific ag = highly expressed in ca tissue –> immune rxns against ca cross-react w/ skel muscle fibers –> myositis
DM ab: antiMi2 vs antiJo1 vs antip155/140
against DNA helicase; exclusive in DM vs against histidyl tRNA synthetase; more common in PM vs against transcpxn factor for cellular differentiation; more common in malig associated DM
PM affects? Perforin pathway. any perifascicular atrophy of infiltrates?
skin. Perforin and granzyme granules of CD8 cells = directed towards healthy muscle fibers w/ MHC I –> necrosis. no b/c not DM
PM muscle vs constitutional sxs
Symmetrical, proximal muscle weakness in UE and LE; Facial and ocular muscles not affected vs Lung, heart, oropharynx, joints
PM subtypes: juvenile PM vs malig assoc PM
<18yo vs Colorectal, lung, hepatic ca
PM labs: ANA vs Anti Jo1 ab vs Anti-signal recognition particle (SRP) ab
nonspecific for inflamm or autoimmune vs against histidyl tRNA synthetase vs targets cytosolic protein-RNA complex that couples synthesis of nascent proteins to their proper membrane localization
how to tx PM?
glucocorticoid
Inclusion body myositis affects? Hallmark?
muscles. rimmed autophagic vacuoles containing protein aggregates like in degen dzs –> degen theory of s-IBM
proteins found in IBM
intracellular amyloid that’s immunoreactive to β-amyloid protein; phosphorylated tau, α-synuclein, ubiquitin, presenilin
IBM sxs
Asymmetrical slow progressive weakness of distal and proximal muscles
* Weak quads, finger dexterity, and grip strength
* Atrophy of quads and forearm flexors
IBM labs: high CK vs Anti-cytosolic 5’-nucleotidase (cN1A) ab
blank vs colocalize w/ granular intravacuole deposits and vacuole rims
* Exclusive in inclusion-body myositis
how to tx IBM?
glucocorticoids, wheelchair by 10yo
IBM has autoimmune pathogenesis by?
CD8 cell, B cell, anti-cN1A ab
What is immune-mediated necrotizing myopathy? any CD8 cells (PM/IBM) or perifascicular atrophy (DM) involved?
muscle fiber degeneration, necrosis, regeneration. no
IMNM skin vs muscle vs constitutional sxs
gottron, heliotrope, V sign vs prox muscle weakness vs interstitial lung dz, unknown malig risk
how to dx IMNM?
muscle bx: more necrosis, less inflamm/phag but macs can be seen around necrotic fibers
IMNM labs: High CK; Nml or high ESR, CRP vs Anti-SRP ab vs Anti-HMGCR ab
self explanatory vs triggered by VZV, HPV; targets cytosolic protein-RNA complex that couples synthesis of nascent proteins to their proper membrane localization vs Triggered by statins
how to tx IMNM?
Corticosteroids w/ methotrexate; mortality rte 2-3x higher than gen pop
metabolic myopathies
auto rec d/o leading to insufficient energy prod d/t defect of glycogen, lipid, or mito metab
Disorders of glycogen metab
mutations in genes encoding proteins for glycogen synthesis or degradation –> glycogen can accumulate in tissue
GSD Type II/Pompe dz
Mutation in GAA gene encoding acid α-glycosidase (lysosome) deficiency –> glycogen accumulates in lysosomes of skel or cardiac muscle cells –> enlarged lysosomes –> compressed cell organelles –> injure and replace muscle fibers –> dec cardiac and muscle fxn
Pompe dz clinical pres: infant onset vs late onset
1-5% of residual α-glycosidase activity; cardiomegaly, resp distress, muscle weakness, failure to thrive vs 15-40% of residual α-glycosidase activity; no cardiomegaly, resp fail d/t diaphragm, muscle weakness in limb girdle distribution (prox muscle most affected)
pathology of Pompe dz: light vs e- microscopy
vacuolar myopathy that stain pos for glycogen w/ PAS stain vs see glycogen in enlarged lysosomes –> injured muscle fibers
how to dx vs tx Pompe dz?
Measuring GAA enzyme activity in cultured skin fibroblasts or peripheral blood lymphocytes, high CK vs enzyme replacement therapy
GSD Type V/McArdle dz
Mutation in PYGM gene encoding myophosphorylase –> deficiency –> subsarcolemmal deposits of excess glycogen in periphery of fibers –> dec ATP b/c no glycogenolysis –> inc inorganic phosphate Pi in skel muscle –> inhibit ion pumps –> dec cellular integrity, muscle fiber dmg, rhabdomyolysis
McArdle dz clinical pres
- Exer intolerance in 1st decade of life
- Fatigue, severe muscle cramps relieved by rest
- Muscle contracture –> rhabdomyolysis
- Myoglobinuria –> acute renal failure requiring dialysis
- Second wind phenomenon = sxs subside d/t switch to alternative extramuscular fuel substrates for muscle metab
how to dx McArdle dz?
genetic test of PGYM gene; o Biochemical assay of myophosphorylase activity if genetic test unclear; Forearm exer test (flat lactate curve); high CK, myoglobinuria
how to tx McArdle dz?
no specific tx –> aerobic conditioning, high carb diet
disorders of lipid metabl
Carnitine palmitoyltransferase II deficiency: auto rec mutation of CPT2 gene –> deficiency –> dec mito beta-oxidation of long chain FA –> dec acetyl CoA synthesis –> insufficient energy output in liver, skel muscle, heart –> steatosis in liver, skel muscle, heart, renal tube epithelium; lipid accumulation in skel muscle; life-threatening cardiac arrhythmia
d/o of lipid metab clinical pres: myopathic vs severe infantile vs neonatal
most common and benign; 6-20yo, myoglobinuria by prolonged exer, High CK, No acute muscle or liver dysfunction vs 6mo-2yo; Liver failure w/ hypoketotic hypoglycemia, Cardiomyopathy and peripheral myopathy vs * Days after birth; Liver failure w/ hypoketotic hypoglycemia, Cardiomyopathy, Sz, Congenital anomalies
mito myopathies
muscle weakness and fatigue d/t defect in mito or in resp chain
what does resp chain consist of?
o 5 multimeric complexes in inner mito membrane
o 2 small e- carriers (CoQ10, cytochrome c)
describe mtDNA
small circular 2x stranded molec encoding 13 proteins of resp chain and RNA machinery for translation; High rate of spont mutations, Lack NER mechanism to repair mutations, maternal inheritance
Chronic progressive external ophthalmoplegia
slow progressive paralysis of extraocular and eyelid muscles
which 3 mutations are found in external ophthalmoplegia?
o Auto dom mutation in TWNK and SLC25A4 genes
o Auto dom or rec mutation in POLG and RRM2B genes
o Mito point mutation in MTTL1 gene
external ophthalmoplegia clinical pres
bil ptosis, limited eye movements, face/neck flexors, sometimes limb and bulbar muscle movement, sensorineural hearing loss
how to dx external ophthalmoplegia (3)?
DNA analysis of gene mutations in mtDNA (large deletion) and nDNA; High CK, blood lactate, alanine, Abnl urine organic acid; US/CT/MRI shows thin extraocular muscles
Kearns-Sayre syndrome
multisystem d/o of progressive external ophthalmoplegia, cardiac conduction block and retinitis pigmentosa; more severe than CPEO
what is cardiac conduction block vs retinitis pigmentosa of Kearns-Sayre syndrome?
d/t distal His bundle and bundle branches losing myofibrils and excess mito –> cardiac death vs Retinitis pigmentosa = progressive degen of rod photoreceptor cells in retina –> severe vision impairment
Infectious arthritis/septic arthritis/suppurative arthritis/purulent arthritis
synovial inflammation d/t invasion of joint space by microorganisms
gram pos vs neg pathogens causing nongono arthritis
Staph aureus and Streptococcus (pyogenes > pneumoniae) vs H. influenzae, E. coli, Pseudomonas aeruginosa (IVDU), Salmonella (sickle cell)
risk factors of nongono arthritis
o Large > small joints, males > females, children > adults
causes of nongono arthritis (4)
- Hematogenous spread into synovial capillaries
- Spread from contiguous infected foci like epiphyseal osteomyelitis
- Spread from neighboring soft-tissue infxn
- Direction inoculation of bacteria thru arthrocentesis, corticosteroid injection, arthroscopy