Pathology of Muscle Pain

Question 1

• What kind of disorder is dermatomyositis?
  
  • What is the etiology/ association?

Answer 1

• Inflammatory disorder of the skin and skeletal muscle
  
  • unknown etiology
  • associated with carcinoma (gastric)

Question 2

• What are the 3 clinical features of Dermatomyositis?
• What are the 3 lab findings?
  
  • What is seen on biopsy?

Answer 2

Inflammatory disorder of skin and skeletal muscle

• Clinical features
  
  1. bilateral, proximal muscle weakness (can’t comb hair or climb stairs)
  2. Rash of the upper eyelides (helitrope rash), malar rash
  3. red papules on elbow, knuckles and knees (Gottron papules)
• Lab findings
  
  • Increase creatine kinase (from muscle breakdown)
  • Positive ANA and anit-Jo-1 antibody
  • Perimysial inflammation (CD4+ T cells) with perifasicular atrophy on biopsy (i.e. closer to skin)

Question 3

• What kind of disorder is polymyositis?
  
  • How does it differ from dermatomyositis?
    
    • What is seen on biopsy?

Answer 3

• Inflammatory disorder of skeletal muscle
  
  • resembles dermatomyositis clinically, but skin is not involved (i.e. no malar rash)
• Endomysial inflammation (CD8+ t cells) with necrotic muscle fiber see on biopsy

Question 4

• McArdle Disease is what kind of disorder?
  
  • due to deficiency in which enzyme?
  • results in?
  • are blood glucose levels affected?

Answer 4

Glycogen storage disease:

• Due to:
  
  • deficiency is skeletal muscle glycogen phosphorylase
• Results in:
  
  • increase glycogen in muscle but can’t break it down
    
    • painful muscle cramps and myoglobinuria with strenuous exercise
• Blood gluocse is not affected

Question 5

Terminology:

• Pyomyositis
• Psoas abscess
• Acute bacterial myositis

Which bacteria is seen with each?

Answer 5

• Pyomyositis:
  
  • acute intramuscular infection that is secondary to hematogenous spread of microorganism in the body of skeletal muscle
  • S. aureus
• Psoas abscess:
  
  • hematogenous bacterial spread
  • S. aureaus
  • Triad of fever, pain and limp
• Acute bacterial myositis:
  
  • diffuse muscle infection without an intramuscular abscess
  • mostly gram (+) organism like MRSA

Question 6

Streptococcus pyogenes toxins:

• Streptolysin O
• Exotoxin A
  
  • MOA
  • Cause/manifestation

Answer 6

• Streptolysin O
  
  • protein that degrades cell membranes
  • lyses RBC; contributes to beta hemolysis
• Exotoxin A:
  
  • Binds to MHC II and TCR outside of antigen binding site to cause overwhelming release of IL-1, IL-2, IFN alpha and TNF alpha
  • Cause toxic shock syndrome
    
    • fever, rash, shock

Question 7

• What type of bacterai is Clostridium perfringens and where is it found?
• What toxin does Clostridium perfringens contain?
  
  • MOA?
  • Causes?
  • Who is at risk?

Answer 7

• Clostridium perfringens:
  
  • Gram (+) found in soil, GI tract
• Toxin:
  
  • Alpha toxin
• MOA:
  
  • Phospholipase that degrades tissue and cell membranes
• Manifestation:
  
  • degredation of phospholipids causes myonecrosis “gas gangrene” and hemolysis
    
    • elderly people and diabetics more at risk

Question 8

• Necrotizing fasciitis is caused by which bacteria?
• What does it result in?
• Causes?

Answer 8

• Deeper tissue injury
  
  • usually from anaerobic bacteria or Strep. pyogenes
• Results in:
  
  • ​creptius (grating sound of bone on bone) from methane and CO2 production
  • “flesh eating bacteria”
• Causes:
  
  • ​bullae and a purple color to skin

Question 9

• Clostridium tetani contains which toxin?
  
  • MOA?
  • Causes?

Answer 9

• Toxin:
  
  • Tetanospasmin
• MOA:
  
  • protease that cleave SNARE a set of proteins required for neurotransmitter release via vesicular fusion
• Cause:
  
  • spastic paralysis, risus sardonicus, “lockjaw”
    
    • prevent release of inhibitory neurotransmitter (GABA and glycine) from Renshaw cells in spinal cord

Gram (+), spore forming bacteria

Question 10

Where (in what layer) do each of the folowing infections occur and what is each infection caused by?

• Erypsipelas
• Cellulitis
• Necrotizing fasciitis
• Myositis
• Osteomyelitis

Answer 10

• Erysipelas
  
  • Dermal papillae
    
    • S. pyogenes
• Cellulitis
  
  • upper dermis
    
    • S. pyogenes
• Necrotizing fasciitis
  
  • deep dermis (subcutaneous fat)
    
    • S. pyogenes
• Myositis
  
  • muscle
    
    • S. aureus
• Osteomyelitis
  
  • bone
    
    • S. aureus

Question 11

What are 3 antimicrobials that inhibit cell wall synthesis?

Answer 11

1. Penicillins
   
   • -cillin
2. Cephalosporins
3. Carbapenemas
   
   • -penem

Question 12

• MOA of Penicillin (G =IV, V=oral)?
  
  • mostly used for?

Answer 12

• MOA:
  
  • Bind penicillin binding proteins (transpeptidase), block transpeptidase cross linking of peptidoglycan in cells wall
• Used for:
  
  • mostly Gram (+)
    
    • S. pneumonia, S. pyogenes

Question 13

• MOA of Cephalosporins (generations I-V)
  
  • used for?

Answer 13

• MOA:
  
  • Beta-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
  • Bactericidal
• Used for:
  
  • “Organisms typically not covered by 1st-4th generation cephalosporins are LAME”
    
    • Listeria
    • Atypicals (Chlamydia, Mycoplasma)
    • MRSA
    • Enterococci

Question 14

• MOA of Carbapenems?
  
  • all end in?
• Always administer with?
• Used for?

Answer 14

• -penem (Imipenem, meropenem)
• MOA:
  
  • broad spectrum Beta-lactamase; inhibit cell wall synthesis
  • ALWAY administered with cilastin to decrease activation of drug in renal tubule
• Used for:
  
  • Gram + cocci (S. aureus, S. pyogenes)

Question 15

• MOA of Vancomycin?
• Used for?

Answer 15

• MOA:
  
  • inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors
  • bactericidal against most bacteria
  • not suceptible to B-lacatmases
• Used for:
  
  • Gram (+) bugs only!
  • serious, multidrug resistant organisms include MRSA and sensitive Enterococcus species

Question 16

Aminoglycosides and Tetracyclines are what kind of drugs?

Answer 16

Antimicrobials!

• Protein synthesis inhibitors

Question 17

• Aminoglycosides most end in?
• MOA?
• Used for?

Answer 17

• -mycin (Gentamicin, Neomycin, Aminkacin, Tobramycin, Steptomycin)
• MOA:
  
  • irreversible inhibition of protein synthesis by binding to 30S subunit
    
    • cause misreading of mRNA and translocation
• Used for:
  
  • severe gram (-) rod infections
    
    • requires O₂ for uptake so ineffective against anaerobes

Question 18

• Tetracyclines all end in?
• MOA?
• Clinical use?

Answer 18

• -cycline
• MOA:
  
  • bind to 30S and prevent attachment of animoacyl-tRNA
  • proteins synthesis inhibitors
• Used for:
  
  • Borrelia burgdorferi (Lyme Disease)
  • M pneumoniae
    
    • drug’s ability to accumulate intracellularly makes them very effective against Rickettsia and Chlamydia

Question 19

What kind of drugs are:

Macrolides (-mycins), Cholramphenicol and Linezolid?

• Common MOA?

Answer 19

Macrolides (-omycin), Choloramphenicol, Linezolid

• Antimicrobials that target the 50S subunit; inhibit translocation
• proteins synthesis inhibitors

Question 20

• MOA of Chloramphenicol?
  
  • Used for?

Answer 20

• MOA:
  
  • blocks peptidyltransferase at 50S ribosomal subunit
• Used for:
  
  • Meningitis (H. influenza, N. menigitidis, S. pneumoniae)
  • Rocky Mountain Spotted fever (Rickettsia rickettsii)

Question 21

• MOA for Linezolid?
• Used for?

Answer 21

• MOA:
  
  • inhibit protein synthesis by binding to 50S subunit and preventing formation of the initiation complex
• Used for:
  
  • Gram (+) species
    
    • including MRSA and VRE

Question 22

• Macrolides all end in?
  
  • MOA
  • Used for

Answer 22

• -omycin
  
  • Azithromycin, clarithromycin, erythromycin
• MOA:
  
  • inhibit protein synthesis by blocking translocation
  • binds to the 23S rRNA of the 50S ribosomal subunit
• Used for:
  
  • gram (+) cocci
    
    • strep. patients allergic to penicillin
  • STI (Chlamydia)
  • Atypical pneumonia (Mycoplasma)

Question 23

• Fluoroquinolones all end in?
• MOA?
• Used to treat?

Answer 23

• -oxacin
  
  • Ciprofloxacin, norfloxacin
• MOA:
  
  • inhibit prokaryotic enzymes topoisomerase II and topoisomerase IV (mictrobutules)
• Used for:
  
  • Gram (-) rods of urinary and GI tract
  • some gram (+)

Question 24

• What do sulfonamides and Trimethoprim both inhibit?
  
  • How do they work together?
  • Used for?

Answer 24

• MOA of Trimethorpim:
  
  • inhibits bacterial dihydrofolate reductase
• MOA of Sulfonamides
  
  • inhibit dihydropteroate syntheas, thus inhibiting folate synthesis
• Used together for:
  
  • Gram (+)
  • UTI
  • Nocardia, Chlamydia

Question 25

What is the treatment for TB? "**RESPI**"

Answer 25

* Rifampin * Ethambutol * **Streptomycin (Aminoglycoside)** * Pyrazinamide * Isoniazid

Question 26

* What infectious agent is Leprosy caused by? * involves what structures? * 1st line treatment?

Answer 26

* Infectious disease caused by ***Mycobacterium leprae*** * involves skin and peripheral nerves * _1st line treatment:_ * Dapsone, Rifampin, Clofazimine

Question 27

Treatment of Septic Arthritis? "Tri Fix the Fox"

Answer 27

* Aspiration and Effusion * Treatment: * Cef**tri**axone/ Ce**fix**ime/ Ce**fox**itin (Cephalosporin)+ Azithromycin (macrolide)

Question 28

What are treatments of choice for MRSA?

Answer 28

Vancomycin or Daptomycin

Question 29

What class of drugs is used to treat simple *Staphlococcus* skin infections?

Answer 29

Penicillins

Question 30

Strep. pyogenes causes which infections? ## Footnote **"LINES"**

Answer 30

* **L**ymphagiitis * **I**mpetigo * **N**ecrotizing fasciitis * **E**rysipelas * **S**carlet Fever

Question 31

* Chlamydiae are what kind of bacteria? * What does *Chlamydia trachomatis* cause? * Treatment?

Answer 31

* obligate intracellular organisms * can't make their own ATP * _*C. trachomatis* causes:_ * reactive arthritis (Reiter syndrome) * urethritis * follicular conjunctivitis * _Treatment_: * azithromycin (macrolides) or doxycycline (tetracyclines)

Question 32

* What kind of bacteria is N. gonorrhoeae? * MOA * What does it cause?

Answer 32

* **Gram (-) diplococci** * negative maltose utilization * Metabolize glucose and produce IgA protease (intracellular ) * _Causes_: * septic arthritis * gonorrhea * osteomyelitis (in sexually active individuals)

Question 33

What is characteristic of secondary tuberculosis?

Answer 33

* **caseating** granulomas with central area of necrosis and Langerhans **giant** cells (arrow)

Question 34

What type of bacterias is *Mycobacteria tuberculosis*?

Answer 34

**acid fast** organisms (pink rodes in picture)

Question 35

* Who does hematogenous osteomyelitis most commonly affect? * most frequent site?

Answer 35

* _commonly affects:_ * children and adolescents * _Frequent site:_ * **metaphysis** * actively growing site (increased blood flow) that favors bacterial growth and proliferation * lack of phagocytic properties

Question 36

* What are the 5 main causes of acute septic arthritis? * who does it affect?

Answer 36

1. S. aureus: most common 2. Neisseria gonorrhoeae * sexually active, STD 3. Borrelia borgdorferi * lyme disease 4. H. influenzae * eldery 5. Group B streptococcus * neonates

Question 37

* What fungi is responsible for chronic arthritis? * What site is most commonly affected? * associated with?

Answer 37

* _Caused by:_ * *Sporothrix schenckii* * _Common presentation_: * **knee**, wrist, elbow * joint is boggy with decrease ROM, usually not red or tender * _Associated with_ * **gardening**, outdoor activites