Pathophysiology Three Flashcards
what is cachexia?
- weight loss, wasting of muscle, loss of appetite, and general debility that can occur during a chronic disease
what are some diseases associated with cachexia
- cancer
- COPD
- DHF
- chronic kidney disease
- chronic inflammatory diseases (HIV/AIDs, rheumatoid arthritis, etc)
sarcopenia
age related loss of muscle mass, strength and function
can you have sarcopenia and cachexia at the same time
yes
cachexia reduces ______ and ______ of life
quality
length
T or F: cachexia increases chemo toxicity and decreases efficacy
T
t or f: cachexia increases post-surgical complications and increases medical costs
T
what is the #1, 2, and 3 causes of death in the US
1 - heart disease
2 - cancer
3 - COPD
COPD cachexia develops in ________% of patients
20-40
what is a major cause of cachexia
cytokine excess
______ energy expenditure and ________ energy intake are hallmarks of cachexia
increased
decreased
as a result of negative energy balance in cachexia, when you add inflammation you get ________ muscle protein synthesis and _____ muscle protein degradation
decreased
increased
can you come back from refractory cachexia?
no. you may be able to go from cachexia to precachexia though
what cancer has the highest frequency of weight loss?
pancreatic or gastric cancer
what is the key to prevent cachexia?
early detection
more weight lost in cachexia = more ________ lost
muscle
*not just losing fat!
T or F: administering exogenous IGF-1 prevented cachexia
F
IGF-1 decreased in those with cancer
what is PIF?
proteolysis inducing factor
why/what patients is PIF important for
- important in cancer, burns, and sepsis patients
what does PIF activate
increases calpain activity
- calpains chop up scaffolding for sarcomeres and allow proteins to be exposed for degradation
studies show increase in __________ activity in gastroc muscle from control mice to mice treated with PIF
proteasome
More PIF = ______ protein degradation
more
what is sepsis
a potentially life threatening condition that arises when the body’s response to infection causes injury to its own tissues and organs
what is septic cachexia
when an extreme response to infection destroys muscle tissue
who is at risk for septic cachexia
- very young or old
- immunocompromised (cancer, AIDS, severe burns/injury, pneumonia, meningitis, cellulitis, UTI, ruptured appendix)
what are primary causes of muscle weakness and cachexia with sepsis
- muscle function decreased
- decreased protein synthesis
- increased protein degradation
- sattelite cell activity blocked
increased TNF-a = _______ force production
decreased
T or F: sepsis affects all muscle fiber types the same
F
overall muscle protein synthesis is _______ in sepsis
decreased
calpains are _____ in sepsis
increased
T or F: calpains, myofilament release, ubiquitin and proteasome mRNA all increase in sepsis
T: calpains release myofilaments so proteasomes can go chop up the myofilaments.
T or F: a fast twitch muscle (like EDL) suffers more damage from sepsis than a slow twitch muscle (like soleus)
T, type 2 muscles undergo more damage from sepsis than type 1
if TNF-a is involved, muscle function and contractile force _______
decreases
if there is decreased protein synthesis, translation of RNA is _______ and type _____ muscles are effected more than type ______ muscles
decreased
2
1
increased protein degradation __________ calpain-proteasome system, caspases, and UPS
increases
what is a neuromusclar disease
any condition that affects the structure and/or function of any component of your neuromuscular system including peripheral nerves, NMJ, and muscle fibers
what is a mixed UMN/LMN disorder
ALS
what are some LMN diseases
peripheral nerve injury
Gullain-Barre syndrome
chronic inflammatory demyelinating polyneirapthy
SMA
poliomyelitis
charcot-marie-tooth disease
what are some diseases at the NMJ
- botulism
- lambert-eaton myasthenic syndrome (LEMS)
- nyasthenia gravis (MG)
ALS
- progressive neurodegenerative disease
- cause muscles to weaken, twitch, and waste
- normal cognition
- eventually lose voluntary movement
- fatal (from respiratory failure)
- no cure
SMA
- autosomal recessive disorder (mutations to survival motor neuron gene 1)
- skeletal muscle weakness caused often more severe in the trunk and upper leg/arm than in muscles of hands and feet
- ALSO: respiratory infections, scoliosis, and joint contractures (chronic shortening of muscles and tendons)
Poliomyelitis
- highly infectious viral disease
- mostly affects children
- preventable with vaccination
- in acute forms, causes inflammation of motor neurons oof the spinal cord and brain stem
- leads to paralysis, muscular atrophy, and often deformity
Gullain-Barre syndrome
- caused by immune system attacking PNS
- rapid onset muscle weakness
- typically both sides of body affected
- initial symptoms are changes in sensation or pain often in the back along with muscle weakness, beginning in feet/hands then spreading to arms and upper body
chronic inflammatory demyelinating polyneuropathy
- acquired autoimmune disease of PNS characterized by progressive weakness and impaired sensory function in arms and legs
- symmetric weakness in prox and distal muscles
- increased incidence with advancing age
Myasthenia Gravis
- women <40, men >60
- autoimmune disease
- antibodies block, alter, or destroy the ACh receptor/activity
what is the main symptom we need to know for MG?
drooping eyelid
burns induce skeletal muscle _________
proteolysis
(muscle wasting/cachexia)
burns cause hypermetabolic response which causes increases in…
body temp
glycolysis
proteolysis
lipolysis
futile substrate cycling
what are some treatments for burn-induced muscle wasting
- GH injections
- insulin
- catecholamine antagonists
- IGH1 and IGH binding
- anabolic steriods
Why is oxandrolone a good steroid to treat burns?
it doesnt harm the liver and doesnt cause androgen effects
