MSK Histology/Path

Question 1

what is this a cross-section of? (in Green)

Answer 1

area of myofibrils (each green dot is a cross section of one myofibril)

Question 2

True/false:

A myofibril is composed of many mucle cells

Answer 2

FALSE!

Muscle cells (myocyte) are made up of multiple myofibrils

Question 3

what level of skeletal muscle organization is shown in green

Answer 3

Muscle bundle (aka fascicle)

a fascicle is a bundle of myocytes/muscle cells and their associated endomysium

Question 4

Each skeletal muscle cell is
surrounded by reticular connective
tissue called _______, contains type ___
collagen fibers)

Answer 4

endomysium

type III collagen

Question 5

what connective tissue ensheaths each fascicle

Answer 5

perimysium

Question 6

what connective tissue ensheaths the whole muscle

Answer 6

epimysium

(e.g. the biceps is covered by an epimysium)

Question 7

Each cell contains myofibrils; each myofibril is
made up of __________

Answer 7

myofilaments (thin actin
filaments and thick myosin filaments)

Question 8

what are myofibers

Answer 8

another name for myocytes and muscle cell

Question 9

what delineates a sarcomere?

Answer 9

Z line to Z line of a myofibril and is the basic contractile unit of a muscle cell

Question 10

sarcolemma vs sarcoplasmic reticulum

Answer 10

Question 11

True/False

skeletal muscle cells are held together by cell junctions

Answer 11

FALSE

instead, their membranse are fused into a multinucleated
syncytium

Question 12

muscle cells have limited regenerative capacity, but ___________ cells can act as a stem cell and differenciate into a muscle cell

Answer 12

satellite –> myoblast –> myofiber

Question 13

T/F: mitochondria and nuclei are located just beneath the cell membrane

Answer 13

True

Question 14

where in a muscle cell does the sarcolemma invaginate into a T tubule

Answer 14

on either side of the A bands (strip of myosin)

Question 15

what are type 1 muscle fibers

Answer 15

Type I muscle fibers= slow oxidative fibers à slow-twitch

1. specialized for aerobic activity.
2. contain a high amount of myoglobin (carries oxygen), capillaries, and mitochondria
3. low glycolysis activity à less ATPase à don’t stain brown
   
   1. àlow lactic acid production
4. more NADH à stain blue
5. appear red in fresh tissue.
6. Low power but fatigue-resistant motor units.

e.g. Muscles of the deep back responsible for maintaining posture are mostly made up of Type I slow oxidative fibers.

Question 16

T/F: all muscles of the same type are group together in normal physiological muscle

Answer 16

FALSE

No single muscle fiber is entirely surrounded by muscle
fibers of its own type. When groups occur and are welldeveloped, the question of denervation-reinnervation
must be raised.

Question 17

compare the muscle fiber types

Answer 17

Question 18

myasthenia gravis vs lambert eaton myasthenic syndrome

Answer 18

Question 19

an action potential starts in the dorsal or ventral horn of the spinal cord

Answer 19

ventral (ie anterior)

Question 20

How is acetylcholine made?

Answer 20

Acetyl CoA comes from mitochondria (end product of glycolysis) and choline comes from re-uptake from synaptic cleft. (also diet?)

–> choline acetyltransferase converts these^ to acetylcholine

Question 21

what is the FIRST thing to happen when acetylcholine (2molecules per receptor) binds to nicotinic receptors on post-synaptic neurons

Answer 21

Na+ influx causes a small change in membrane potential = miniature end-plate potential (mEPP) in the myofiber membrane (<1mV/vesible)

IS NOT the same as the action potential

Question 22

how is an AP generated in a muscle cell

Answer 22

the endplate potential (EPP) must be above threshold. if it is, then voltage gated sodium channels open succession, causing AP run along sarcolemma. Once it hits the T tubules of sarcolemma, causes Ca2+ release from SR –> muscle contraction

Question 23

Where does all the calcium come from during a musclar excitation?

Answer 23

NO calcium comes from extracellular space (it’s only involved in pre-synaptic mechanism of Ach release). Instead, it comes from the sarcoplasmic reticulum, which stores TONS of calcium. It is gated by a Ryanodine Receptor (RyR).

Question 24

what opens the Ryanodine Receptor on the sarcoplasmic reticulum?

Answer 24

Dihydrophyridineb Receptor*. It’s technically a voltage gated channel that causes shape change. Mechanically connected to RyR. AP causes DHP to change it’s shape a bit pulling open the RyR receptors and releasing calcium. (Presence of calcium prompts RyR to stay open a bit longer because the calcium binds to it). Calcium pumps eventually puts calcium back in storage stopping the muscle contraction.

*Not a true receptor in the case of skeletal muscle because it was named for its response to dihydrophyridine which is not present. but we keep the name

Question 25

what are the anti-cholinesterase agents? (3)

Answer 25

1. physostigmine, 2. neostigmine 3. pyridostigmine

Question 26

what is edrophonium

Answer 26

a medication that temprarily relieves the sx of Myasthenia gravis --\> used for diagnosis

Question 27

T/F: there is usually only one NMJ /motor end plate per muscle fiber

Answer 27

TRUE

Question 28

approx how many vessicles are leased into the synaptic cleft of NMJ per action potential running down the pre-synaptic neuron

Answer 28

~125 vessicles

Question 29

what is the specific function of the postjuncrtional folds in a NMJ

Answer 29

increase surface area for endplate potentials

Question 30

how long does ACh remain in the synaptic space

Answer 30

a few milliseconds

Question 31

T/F: ALL the ACh in the synaptic cleft is destroyed by Acetylcholinesterase

Answer 31

FALSE : some diffuses out of the space and is no longer available

Question 32

a-actin versus F-actin

Answer 32

Question 33

what comprises a complete thin filament

Answer 33

Question 34

sarcomere histo

Answer 34

Question 35

T/F: during muscle contraction, the A band gets shorter

Answer 35

FALSE, the A band is the myosin which doesn't change size.. the other bands change size as the actin slides along the unmoving myosin

Question 36

latent phase of muscle contraction

Answer 36

calcium has bound to troponin, exposing the active site and ATP has been hydrolyzed into ADP and Pi on the myosin head, triggering the myosin to cock back and bind to the actin--\> crossbridge formation --\> ready for contraction but hasn't contracted yet

Question 37

what chemical shifts allows the relaxation phase to occur after muscle contraction

Answer 37

K+ ions leaving the cell Ca2+ being taken back up by the sarcoplasmic reticulum

Question 38

DHP versus ryanodine receptors

Answer 38

Question 39

What is Gower's Sign

Answer 39

a classic physical exam finding in people with MD... patient has to push on knees to get up due to prosimal hip/leg muscle weakness

Question 40

diff between becker and duchenne on a molecular genetic level - in terms of the different mutations

Answer 40

Question 41

where is dystrophin located *specifically*

Answer 41

Question 42

a patient with the following physical exam findings presents to your office with a history of **symmetrical** muscle weakness and tenderness that has been slowly progressing over the past 3-6 months. lab values show **elevated serum creatine kinase.** what is the most likely dx?

Answer 42

dermatomyositis follow up studies are likely to reveal: abnormal EMG/NCS and abnormal muscle biopsy

Question 43

pathophysiology of dermatomyositis

Answer 43

1. autoimmune 2. characterized by perimysial inflammation and atrophy due to vasculitis of associated vessels d/t complement deposition on the vessels 1. perimysium is closer to the skin and therefore has cutaneous manifestations – “dermato” 3. Inflammatory cells are mostly CD 4+ T-cells, B cells + complement proteins 4. muscle damage from: inflammation --\> ischemia --\> necrosis

Question 44

pathophysiology of polymyositis

Answer 44

1. think of it as dermatomyositis but without the rash 2. differences: immune cells= Cytotoxic (CD8) T cells inflammation of endomysium (not perimesium) myophagocytosis instead of necrosis

Question 45

inclusion body myositis

Answer 45

1. insideous onset, of uncertain etiology (inflammation vs degenerative) that is comonest myopathy of older (\>65 yo) populations. 2. characterized by ASYMMETRIC distal weakness and slow progression + can include dysphagia 3. inflammation is similar to polymyositis with cytotoxic CD8 lymphocytes destroying myofibers, but the affected myofibers have cytoplasmic rimmed vacuoles with basophilic granules 4. namesake inclusion bodies (not the same thing as the vacuoles)

Question 46

what are the possible causes of Rhabdomyolysis

Answer 46

Influenza infections, strenuous exercise, heat stroke, halothane, Alcohol

Question 47

why would you be concerned about acute renal failure in a patient with rhabdomyolysis?

Answer 47

since myoglobin is released form muscles, you get Myoglobinuria: acute renal failure You also get dark urine d/t myoglobinuria

Question 48

pathology of rhabdomyolysis

Answer 48

notice: 1. foci of necrosis 2. clusters of macrophages 3. degeneration of muscle fibers

Question 49

Gottron’s papules pathognomonic of \_\_\_\_\_\_\_\_\_\_\_

Answer 49

dermatomyositis

Question 50

young versus old muscle pathological features

Answer 50

notice: shrinkage, (size and loss of fibers), groupingand loss of type II fibers (black)

Question 51

how to interpret this kind of stain

Answer 51

fibers have distinct myosin isoforms. Type 1 fibers are rich in oxidative enzymes, mitochondria, myoglobin (an oxygen carrier), and lipid --\> darker stain. Type 2 fibers are rich in glycogen and glycolytic enzymes. They are capable of fast, powerful, tonic contraction. By varying the pH of the ATPase preincubation, type 2 fibers can be further subdivided into 2a and 2b

Question 52

how do type 1 versus Type 2 muscle fibers change with age

Answer 52

Types IIA and IIB muscle fibers decrease with age in the area percentage, fiber number percentage, and mean fiber area, whereas Type I fibers increase in area and number but not in size. Morphologically, Type II fibers appeared smaller and flatter.

Question 53

what is the characteristic radiologic finding in benign bone tumors?

Answer 53

Question 54

what bone pathology is shown

Answer 54

osteochondroma (at metaphysis and appears to be a lateral bony projection of growth plate)

Question 55

typical radiographic features of osteosarcome (malignant)

Answer 55

Question 56

pathology of osteosarcoma

Answer 56

Question 57

is most metastatic spread FROM bone tumors lymphatic or hematogneous spread?

Answer 57

hemotogenous --\> lung most common site

Question 58

what is titin

Answer 58

Question 59

what causes rigor mortis

Answer 59

upon death, the clacium leaks our of SR and myosin heads bind to active site on actin. but ATP is degraded, so it is not available to detach the mysoin head again --\> muscles stay contracted

Question 60

isotonic versus isometric muscle contraction

Answer 60

Question 61

Which of the following histopathological features is consistent with a diagnosis of dermatomyositis? 1. endomysial inflamation 2. necrotic fibers 3. rimmed vacuoles 4. perifascicular atrophy

Answer 61

4: perifascicular atrophy hallmark feature of dermatomyositis

Question 62

rimmed vacuoles on microscopic appearance is characteristic of what muscle disease?

Answer 62

along with inclusion bodies, these vaculose are found in inclusion body myositis

Question 63

characteristic histology for the dystrophinopathies

Answer 63

Question 64

characteristic findings of McArdle Disease

Answer 64

mn: just get over the Mc"Hurdle"

Question 65

is there a greater risk of malignancy in dermatomyositis or polymyositis?

Answer 65

dermatomyositis

Question 66

dermatoyositis presents with weakness of which 2 classice areas

Answer 66

shoulder girdle (difficulty raising arms above head) and difficulty rising from a chair

Question 67

what is enchondromatosis

Answer 67

formation of bone tumors at the ends of long bones near growth plates complication is advancement of the cancer to a chondrosarcoma

Question 68

what are the digit disorders

Answer 68

Question 69

in Becker muscular dystrophy, patients can typically ambulate until ___ years

Answer 69

35-40

Question 70

A patient with frontal baldness struggles to release when shaking your hand. Of the following, which is the most likely diagnosis?

Answer 70

myotonic dystrophy type 1

Question 71

which myopathy is characterized by early contractures (joint deformities)

Answer 71

Emery-Dreifuss Muscular Dystrophy

Question 72

Which of the following is characteristically occasionally complicated by malignant hyperthermia (from anesthesias)? Emery-Dreifuss Muscular Dystrophy Pompe Disease (Acid Maltase Deficiency) Familial Periodic Paralysis Central Core Myopathy

Answer 72

Central Core Myopathy mn: central core in nuclear reactor gets really hot