gout, muscular dystrophy, bone cancer Flashcards
what is gout
• Crystal induced joint disease
o Uric acid deposits in joints–As a result of this the joint isn’t able to fx properly and it causes inflm
what categories is gout divided into
primary and secondary
primary gout
who does this occur in?
Primary
- 90%
- It is a metb disorder
- Mostly in men—95%
secondary gout
Secondary
- Cell destruction—especially from rapidly proliferating cells/cells with rapid turnover like in leukemia. when the cell dies it prduces uric acid
- Renal—impaired renal fx–>retaining uric acid instead of excreting it
- Other—alcohol particularly beer, chemo (cell destr)
name the 5 nitrogenous bases
how are they divided what are we concerned with
adenine, guanine, thymine, cytosine, uracil. They can be divided into pyrimidines and purines
adenine, guanine are purines. the metb of these is alt with gout
patho of gout
- alt purine metb->asympt hyperuricemia—the more purines you break down the higher your uric acid
- later: crystals deposit in synovial joints—initially it wasn’t causing problem but now it is.
- WBC influx and complement activation–d/t the foreign deposits
- WBC phagocytosse crystals–>WBC necrosis–>lysosomal E release—>inflm joint damage
- Recurrent acute attacks–>tophi
what is a tophus and what can it be compared to
tophus is singular. In osteoarthritis we had osteophytes. In RA there was pannus. In gout we have tophi.
Tophi are hard accum of uric acid in the joint
how many stages are there to gout?
what is onset like?
does it happen again?
5
acute onset
yes, recurrent attacks
stages of gout
- Asympt hyperuricemia
- Acute inflm (overnight, 1 joint?)
Food, drugs, alcohol, excess exercise?? - Subsides in 1wk approx
- Asympt (months to years)
- Frequent recurrent attackspermanent damage
stage 2 of gout. where is the acute inflm?
why is it occuring overnight?
why in the joint?
then one night the indiv will wake up with unusually only one v painful swollen joint most often lg toe joint, can be ankle or knee. Sometimes more than 1 joint.
o Uric acid is more soluble in blood than it is in synovial fluid (when it gets into the joint it crystallizes THIS DOESNT HAPPEN IN BLOOD). The temp in lg toe is much lower in lg toe than rest of body. You want something soluble you heat it. When sleeping your HR is dec and there is venous stasis??easier to accum
dx of gout
- Serum and urine uric acid–Youd expect to meas hyperuricemia but there are many people who don’t have gout but have hyperuricemia. You still start with this.
- Uric acid in joints—this is more specific
tx of gout
meds for acute attack?
to prevent further attacks?
• Acute attack (pain and inflm) NSAIDS Or Colchicine Steroids—anti inflm • To dec hyperuricemia -increasing uric acid excretion.— inc fluid intake helps • Elim alcohol • Dec the protein in your diet—as protein generates purines (adenine and guanine)
colchicine as tx of gout
Colchicine—one of the properties being targeted is leukocytes in joint. Theyll be coming in via chemotaxis. It inhibits chemotaxis
what is muscular dystrophy
what is most common type?
how many per live births?
• Sk muscle degen. It is progressive–The body attempts to replace the muscle tissue with adipose
o d/t atrophy, necrosis and pseudohypertrophy—this is false hypertrophy
• diff types
Duchenne MD is most common
1 in 3500 live births in males
factors regarding how to classify muscular dystrophy types
- this is genetic problem so we can differentiate by looking at mode of inheritance 2. Look at which muscle groups are affected. 3. Look at rate of which the deter happens. 4. Age of onset
et of muscular dystrophy
recessive, X linked trait o Mother (carrier) to son
not positive if this is accurate?
the mother has two X chromosomes, if one is defective and the male inherits it he will inherit the condition because he only has 1 x chr. If passed to female she has two xes and the other x overrides the def one
o –we need 2 defective alleles for recessive to present. But here we have sex chr. This defective gene is on short arm of chr. Monogenic.
what is the membrane of a muscle fiber called
sarcolemma
patho of musc dystrophy
• Gene on short arm of X chr o Codes dystrophin (membr protein) -Attachment of contractile filaments • Mutation-->alt protein-->poor contractile proteins attachment-->fibre necrosis with use-->poor repair and regen-->more necrosis-->Ca influx and E release eg CK • Fibrofatty CT replaces muscle
what is dystrophin and where is it? fx?
Fx of dystrophin=normally helps in attachment of contractile filaments eg actin and myosin.
it is membrane protein on inner side of sarcolemma
Sliding filament theory (contraction and relaxation) in order to do this they must be properly attached (to memb, matrix, each other) dystrophin facilitates this attachment.
why is there Ca influx in muscular dystrophy
o Considering that this is a defective membr protein the properties of the membr are altered. Perm will change and Ca moves into muscle fiber (this isn’t site for Ca storage…bone is..not this). When cells die they release their content, this is a protein rich cell.
what is CK
o CK=creatine kinase (this is specific to sk muscle. This is released d/t necrosis of sk muscle. It is therefore a serum marker.
why is fibrofatty lesion deposited in muscle in muscular dystrophy
o if you have injury/atrophy/necrosis the body will attempt to adapt to change and limit the change. If youre losing muscle mass the obvious response is to inc muscle mass. Instead of depositing muscle components in the muscle fiber it deposits connective tissue (mostly adipose tissue as well as fibrous CT)
gen lifespan of MD pt
why do they die
20-25
cardiomyopathy and dec CO and resp issues
mnfts of duchennes MD
- Asympt until age 2-3–after this time use of the muscle inc. Baby is born with issue but injury sets in with use of the muscle and the muscle needs to be used for several yrs before injury is inflicted. From the time of injury, damage is cumulative and progresses quickly
- Prog muscle weakness—weak and atrophied.
- Resp and cardiac muscle affected– Although it is sk muscle thats affected it eventually will affect both resp and cardiac fx. Diff breathing and CO impacted (perfusion affected). Cardiomyopathy!
- Usually death from resp and cardiac complications—short lifespan (20-25) the CO and cardiomyopathy with breathing issuesdeath
dx of duchennes MD
• Hx
• Voluntary movement— cant just say Duchenne…it could be neuromuscular eg myasthenia gravis
• Serum creatine kinase.
• Biopsy— (they are looking for adipose tissue/fibrofatty tissue). You could see dystrophin… (with special microscope)…the next two are less imp Pseudohypertrophy. Ca.
–Additionally you can look at the mother CARRIER SCREENING. This is most useful because you know before conception that this is present and they can make informed decision about their pregnancy. (the mother gives to son)
o –PRENATAL…testing not sure (12 wk gestation onward)
how do you get definitve dx of Duchenne
to get definitive Dx you take muscle biopsy
tx of duchenne
- No cure—its genetic problem. You cant reverse necrosis
- Supportive and symptomatic
- Inc comfort and fx—breathing exercises are indicated but there is catch 22. You use these musclesdamage but if you don’t train them then you cant breathe. Using aids for walking eg braces are useful
is primary or secondary bone Ca more prevalent
- Primary is uncommon
* Secondary is common
what are the parts of the bone (outer) where does ossification occur. what does bone grow from
• –he sketches long bone which has diff parts (the top part is they epiphysis..it is what we called the head) The diaphysis is the space between the epiphysis. The metaphysis is where we would expect the epiphyseal plate. Bone formation is ossification which occurs in metaphysis. The bone forms from cartilage
examples of primary bone CA
which one did we study more
osteosarcoma
o –A cartilage forming tumour would be chondrosarcoma (in bone)
o –also in bone is fibrosarcoma
o –others. 1: Ewing. 2: osteoclastoma
osteosarcoma
how does it compare to other primmary malignancies what does it form where is it generally spread timing
- Bone forming tumor—WHY? This is bone forming instead of cartilage forming. In the metaphysis there is ossification. When you form bone you could have cartilage forming bone (not articulating cartilage between the bone).
- Most common –(form of PRIMARY malignancy in bone)
- Usually in vicinity of knee
- Aggressive (mets to lung)
- Approx 75% before age 20—
why does most primary bone CA occur before age 20
when else might it occur
most longitudinal bone growth occurs before age 20. During this period of more division there is inc probability of mutation. The remaining 30% occurs in elderly, this is usually in those who have underlying bone pathology particularly those with Paget’s (one of the problems is excess resortopion and remodelling…the excess changeinc chances to have mutation
secondary bone CA
common
where does it spread from
what is unique about this CA
mnfts
• Bone is common secondary site
o ~50% of all CA spreads to bone
o >85% from breast, lung, prostate
• Lytic or blastic lesions—any malignancy anywhere on body, when tumour grows it is space occupying, in orer to do this it breaks down normal tissue (lysis) in the bone it breaks down matrix. The blastic means that it is proliferating. IT doesn’t do both at same time
• Pain, swelling, fractures—fx is serious potential complication as healing etc is impaired
dx of bone CA
which of these is more likley to be done if secondary
- Xray, CT, MRI—you need substantial necrosis before it is visible by xray, a hot spot could be seen. CT and MRI are much more reliable
- Biopsy—they can identify the type (primary or secondary). IF secondary you already know where the primary tumour is and what the tissue of origin will be
- Bone scans—may or may not require it. This is more likely if theres mets as it could go to many places
tx of bone CA
- Chemo, radiation and sx—removing the tuour from bone is called bloc excision. You cant go in and remove the bone and leave a vacuum so they add restorative grafting (graft normal bone)
- Pain
- Prevent fracture!!—the issue is healing
