Muscle And Integument: Muscle Pathology

Front 1

What is this disease?

- muscle weakness begins at age 5, in pelvic girdle muscle, extends to shoulder girdle muscles
- delayed walking, clumsieness, wheelchaired by age 10.

Back 1

Duchenne muscular dystrophy: x-linked deletion of dystrophin gene.

Front 2

What is the normal function of dystrphin?

Back 2

- links cell membrane (bata subunit of sarcoglycan)to actin.
- concentrated underneath sarcolemma over Z band.

Front 3

Pathogenesis of Duchenne muscular dystrophy.

Back 3

deletion of dystrophin -> physical trauma to myocyte -> myocyte necrosis -> compensatory hypertrophy (pseudohypertrophy), fat and fibrocyte infiltrate

Front 4

What is this disease?

muscle biopsy:
- variation of fiber size
- some internalized nuclei
- increased endomysial connective tissue
- blue regenerating fibers.
- both typeI and typeII fibers affected

Back 4

Duchenne muscular dystrophy

Front 5

What characteristics do carriers for Duchenne muscular dystrophy have?

Back 5

- female
- elevated CPK
- risk for dilated cardiomyopathy

Front 6

What complications might Duchenne muscular dystrophy patients die of?

Back 6

- repiratory insufficiency
- pulmonary infection
- cardiac decompensation,heart failure

Front 7

What is this disease?

- X-linked
- mutations in dystrophin gene

Back 7

Becker muscular dystrophy

Front 8

What is this disease?

- AD
- mutations in sarcoglycan complex

Back 8

Type I Limb Girdle muscular dystrophy.

Front 9

What is this disease?

- AR
- mutations in sarcoglycan complex

Back 9

Type II Limb Girdle muscular dystrophy.

Front 10

What is this disease?

- age onset: 15
- heart disease
- low progression in muscle weakness in proximal musculature and trunk.
- X-linked

Back 10

Becker muscular dystrophy

Front 11

What is this disease?

- muscle weakness in proximal musculature and trunk.
- AD or AR

Back 11

Limb Girdle muscular dystrophy

Front 12

What is this disease?

- AD
- CTG repeats on CH19 during meiosis I

Back 12

Myotonic dystrophy

Front 13

Pathogenesis of myotonic dystrophy.

Back 13

CTG repeats on CH19 during meiosis -> DMPK mRNA defective -> may affect other RNAs (ie Cl channel)

Front 14

What is this disease?

- stiffness
- difficulty relaxing muscle after it's contracted
- cataracts
- atrophy of facial muscles, ptosis

Back 14

myotonic dystrophy

Front 15

What is this disease?

- variation in muscle fiber size
- large number of internalized nuclei
- ring fiber
- increased connective tissue

Back 15

myotonic dystrophy

Front 16

What is this and which disease do you see these in?

- sub-plasmalemmal band of myofibrils arranged in rings around normal longitundinal myofibrils.

Back 16

ring fibers in myotonic dystrophy

Front 17

What is this genetic phenomenon called?

- triplet repeat
- earlier age onset and more severity in each subsequent generations.

Back 17

anticipation

Front 18

What is this congenital muscle disease?

- abnormal glucose tolerance test
- decreased plasma IgG
- frontal balding, gonadal atrophy, cardiomyopathy, smooth muscle involvement
- cataracts
- relative Type I fiber atrophy early in the course

Back 18

myotonic dystrophy

Front 19

What is this congenital muscle disease?

- start in late childhood: abnormal gait
- progress to weakness in hand intrinsic muscles and wrist extensors.
- muscle stiffness, difficulty relaxing muscles

Back 19

myotonic dystrophy

Front 20

What is the genetic inheritance of mitochondrial myopathies?

Back 20

- maternal
- variable expressivity

Front 21

What is this disease?

Micro:
- ragged red fibers

EM:
- parking lot inclusions

Back 21

mitochondrial myopathies

- ragged red fibers: aggregates of mitochondria
- parking lot inclusions: altered mitochondrial cisternae structure.

Front 22

What is this material?

- circular DNA
- encode 20% of mitochondrial oxidative phosphorylation proteins.
- encode 22 mitochondrial specific tRNA, 2 rRNA species.
- high mutation
- maternal inheritance, variable expressivity

Back 22

mitochondrial DNA.

Front 23

What is this disease?

- proximal muscle weakness
- external ophthalmoplegia
- lactic acidosis
- cardiomyopathy

Back 23

mitochondrial myopathy

Front 24

What is genetic phenomenon called?

- variation in phenotypical effects among individuals with the same mutant genotype: ie severity of disease, age onset, organs affected.

Back 24

expressivity

Front 25

What is genetic phenomenon called?

- % of heterozygotes for a mutation who develop any features of the disease within a specified time period.

Back 25

penetrance

Front 26

What is the cause of this disease?

- myoclonic epilepsy with ragged red fibers

Back 26

point mutations in mitochondria DNA

Front 27

What is the cause of this disease?

- Leber hereditary optic neuropathy

Back 27

point mutations in mitochondria DNA

Front 28

What is the cause of this disease?

- mitochondrial encephalopathy

Back 28

point mutations in mitochondria DNA

Front 29

What is the cause of this disease?

- Leigh syndrome: subacute necrotizing encephalopathy

Back 29

mutation in nuclear DNA that encodes mitochondrial proteins

Front 30

What is the cause of this disease?

- Barth syndrome: infantile X-linked cardioskeletal myopathy

Back 30

mutation in nuclear DNA that encodes mitochondrial proteins

Front 31

What is the cause of this disease?

- ophthalmoplegia
- pigmented degeneration of retina
- complete heart block

Back 31

(Kearns-Sayre syndrome)
- deletion or duplication of mitochondrial DNA

Front 32

What disease can duplication or deletion of mtDNA cause?

Back 32

- chronic progressive external ophthalmoplegia
- Kearns-Syare syndrome:ophthalmoplegia, pigmented degeneration of retina, complete heart block.

Front 33

Point mutations in mitochondrial DNA may cause what diseases?

Back 33

- myoclonic epilepsy with ragged red fibers
- mitochondrial encephalopathy

Front 34

What is this disease?

- lipid vacuoles dispersed diffusely in type I fibers.
- abnormal carnitine transport

Back 34

lipid myopathy

Front 35

What is this disease?

- lipid vacuoles dispersed diffusely in type I fibers.
- abnormal mitochondrial dehydrogenase enzymes (acyl-coA dehydrogenase, CPT)

Back 35

lipid myopathy

Front 36

What type of SMA is this?

- onset: 4 month old
- floppy baby syndrome, hypotonia
- death in 3 yrs

Back 36

Type I: Werdnig-Hoffman disease
- panfascicular atrophy

Front 37

What type of SMA is this?

- onset: 3-15 month old
- some learn to walk
- suvival more than 4 yrs

Back 37

Type II

Front 38

What type of SMA is this?

- onset: after 2 yrs old
- can walk
- survival to adulthood

Back 38

Type III

Front 39

What is this disease?

Micro:
- atropic muslce fibers
- panfasicular pattern atropy

Back 39

SMA type I:
- AR
- deletion of SMN (contain Tudor homology region for RNA splicosome function) on CH5
- may also involve NAIP mutation

Front 40

Pathogenesis of SMA.

Back 40

- AR SMNI loss -> less survival of anterior horn motor neuron and cranial nerve motor neurons -> denervation muscle atrophy
- NAIP loss -> apoptosis of anterior horn motor neuron and cranial nerve motor neurons-> denervation muscle atrophy

Front 41

Loss of which gene confers worse prognsis in SMA?

Back 41

NAIP (neuronal apoptosis inhibitory protein) gene

Front 42

Which type of inheritance is this?

- in both males and females
- horizontal pattern
- skips generation

Back 42

AR

Front 43

Which type of inheritance is this?

- in both males and females
- verticle pattern
- does not skip generation

Back 43

AD

Front 44

What is the morphoplogic difference in SMA type I and denavation atrophy in adults?

Back 44

SMA type I: panfascicular pattern atrophy

denervation in adults: group atrophy

Front 45

Which disease is this?

- replapsing periods of hypotonic paralysis
- triggered by rigorous exercise, cold, or high-carbohydrate meal

Back 45

Hyperkalemic periodic paralysis:
- mutation in Na channel gene SCN4A

Front 46

Which disease is this?

- tachycardia, tachypnea, muscle spasms
- triggered by anesthesia with halogenated inhalational agents or succinylcholine.

Back 46

malignant hyperpyrexia:
- mutation in Ca channel, ryanodine receptor

Front 47

What is the cause of hypokalemic periodic paralysis?

Back 47

mutation in ca channel

Front 48

What is this disease?

- severe joint contractures in extremeties due to static mucle contractions
- hypotonia (floppy baby)

Back 48

nemaline myopathy:
- arthrogryposis
- occur in type I muscle

Front 49

What is this disease?

- rod shaped cytoplasmic inclusions in muscle fibers

Back 49

nemaline myopathy:
- nelamine rods: aggregates of material derived from alpha-actinin (Z band material)
- occur in type I muscle

Front 50

Pathogenesis of McArdle disease.

Back 50

Type V glycogenosis:
- mutation in phosphorylase

Front 51

Pathogenesis of Type VII glycogenosis.

Back 51

- mutation in phosphofructokinase

Front 52

What is this disease?

- painful cramps upon rigorous exercise
- exercise fail to raise lactic acid level

Back 52

glycongenosis

Front 53

What is this disease?

Micro:
- subsarcolemmal vacuoles and blebs

Lab:
- excercise fail to raise lactic acid level

Back 53

glycogenosis

Front 54

What is this disease?

- muscle weakness in the evening
- thymic hyperplasia
- intact sensory and autonomic function

Back 54

Myasthenia gravis
- type II hypersensitivity
- IgG Ab against Ach receptor

Front 55

What is this disease?

- proximal muscle weakness
- autonomic dysfunction

Back 55

Lambert-Eaton myasthenic syndrome:
- Ab against Ag of tumor cell cross react with presynaptic ca channel
- often associated with small cell carcinoma of lung

Front 56

Which test can differentiate Myasthenia Gravis from Lambert-Eaton myasthenic syndrome?

Back 56

Tensilon test: give AchE inhibitor (Edrophonium).
- if improve in 2-3 min -> myasthenia gravis
- if not, Lambert-Eaton myasthenic syndrome

Front 57

How to treat myasthenia gravis?

Back 57

- AchE inhibitors
- prednisone
- plasmapheresis
- thymectomy

Front 58

Which inflammatory myopathy is this?

- CD8 infiltration in endomysium
- mainly in adults

Back 58

polymyisitis

Front 59

Which inflammatory myopathy is this?

- CD4 and B cell infiltration in endomysium
- mainly in children and adolescents

Back 59

dermatomyositis

Front 60

Polymyositis or dermatomyositis?

- increased HLAI and II on sarcolemma

Back 60

polymyositis

Front 61

What type of antibody might you see in polymyositis?

Back 61

- anti-Jo1: acute onset, interstitial lung disease, fever, arthritis, Raynauds, mechanic hands.
- anti-SRP (poor prognosis): acute onset, severe weakness, cardiomyopathy

Front 62

What type of antibody might you see in dermatomyositis?

Back 62

- anti-Jo1: acute onset, interstitial lung disease, fever, arthritis, Raynauds, mechanic hands.
- anti-Mi-2 with Shawl sign and V sign: good prognosis

Front 63

What is this disease?

- painless muscle weakness
- elevated CPK, ESR
- no cutaneous findings

Back 63

polymyositis

Front 64

What is this disease?

- painless muscle weakness
- elevated CPK, ESR
- Heliotrope rash, Grotton sign, shawl sign

Back 64

dermatomyositis

Front 65

What are some extramuscular findings in polymyositis and dermatomyositis?

Back 65

- interstitial lung disease
- vasculitis
- myocarditis
- esophageal muscle involvement
- risk for internal visceral cancers

Front 66

Polymyositis or dermatomyositis?

- variable autoantibodies against tRNA synthase

Back 66

polymyositis

Front 67

Polymyositis or dermatomyositis?

- perifascicular atrophy

Back 67

dermatomyositis

Front 68

Polymyositis or dermatomyositis?

- slow onset of muscle weakness: proximal muscle first, fine movement muscles only in late disease
- symmetric, some myalgia

Back 68

dermatomyositis

Front 69

How is inclusion body myositis different from polymyositis?

Back 69

- asymmetrical, distal muscles affected
- more in women over age 50
- mixed neuropathic/myopathic process
- insidious onset
- immunosuppressive therapy not useful
- intracellular deposits of beta-amyloid protein, tau protein
- rimmed valuoles, basophilic granules at periphery

Front 70

How to treat inflammatory myositis?

Back 70

- corticosteroids
- methotrexate
- IvIg
- Retuximab

Front 71

What are the hereditaty forms of IBM?

Back 71

AR: mutation in GNE gene
AD: mutation in genes coding myosin heavy chain IIa.

Front 72

What is this disease?

- wide spread painful joints
- chronic fatigue
- stiffness, no true muscle weakness
- normal ESR, CPK
- with mood disorder, IBD

Back 72

fibromyalgia syndrome:
- abnormal blood flow to brain pain centers.

Front 73

What is this disease?

- pain and stiffnes in proximal muscles, symmetrical
- no true muscle weakness
- normal CPK,ESR
- giant cell arteritis
- old age female

Back 73

polymyalgia rheumatica

Front 74

Which drug use cause this?

- muscle pain and some muscle weakness
- elevated CPK

Back 74

statins:
- HMG-CoA reductase inhibitors(those metabolized by CYP3A4)
- fibrates(gemfibrozil)

Front 75

Which drug use cause this?

- type II muscle atrophy
- normal CPK

Back 75

corticosteroids

Front 76

List some drugs that cause myopathies.

Back 76

- corticosteroids
- statins
- alcohol
- Zidovudin
- hydrochloroquine, colchicine,emetine, penicillamine

Front 77

What is the disease?

- high adrenal gland function
- muscle weakness

Back 77

Cushings

Front 78

What is the disease?

- low adrenal gland function
- muscle weakness

Back 78

Addison's

Front 79

What is the most common soft tissue sarcoma of childhood?

Back 79

- Rhabdosarcoma

Front 80

Pathogenesis of rhabdosarcoma.

Back 80

t(2,13): PAX and FKHR fusion -> dysregulation of muscle differentiation.

Front 81

What is this disease?

- eccentric eosinophilic cytoplasm rich in thick and thin filaments

Back 81

rhabdosarcoma

Front 82

What is this disease?

- cluster of grapes protruding into hollow structures
- allelic loss of 11q15.5
- in children under age 10

Back 82

embryonic variant of rhabdosarcoma: sarcoma botryoides

Front 83

What is this disease?

- network of fibrous septae dividing cells into clusters and aggregates
- t(2,13), t(1,13)
- mid adolescents

Back 83

alveolar variant of rhabdosarcoma

Front 84

What is this disease?

- large multinucleated bizzare eosinophilic cells
- in adults

Back 84

pleiomorphic variant of rhabdosarcoma

Front 85

Pathogenesis of Trichnosis.

Back 85

larvae in undercooked meat -> convert to adult worm in intestine, producing larvae -> gain access to blood -> encyst in muscle -> inflammation, fever, myalgia, eosinophilia.

Front 86

What type organism is trichinella spiralis?

Back 86

round worm (nematode)