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23 Cards in this Set
- Front
- Back
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Cachexia
General Definition |
- progressive loss of body weight with significant morbidity and mortality
- arises from chronic disease ex. cancer (30% pts), aids/hiv ( ais wasting syndrom was intial aids diagnosis in up to 1/3 pts |
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Cachexia and Cancer
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- degree of cachexia is inversely correlated with survival time
- occurs before death --> poor prognosis - >20% of cancer deaths -- no treatment --> therapies admin to cancer causes anorexia and malnutrition - cure disease --> cure cachexia |
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Cachexia
Clinical Features |
1. unintentional weight loss
2. anorexia ( loss of appetite and early satiety) 3. malnutrition 4. asthenia (lack of muscle strength) |
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Cachexia
Hallmark Characteristic that distinguishes cachexia from other weight loss syndromes like starvation or hyperthroidism |
Hallmark
1. loss of skeletal muscle from the onset of weight loss 2. loss of adipose tissue may or may not accompany loss of muscle Distinguishes it - other syndromes loss of fat occurs before loss of muscle tissue |
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1. Advance cachexia
2. Early stages of cachexia |
1. - severe weight loss
- loss of skeletal and cardiac muscle - early satiety - weakness - anemia - edema 2. only subtle symptoms--> difficult to detect |
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Resting energy expenditure (REE)
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- may be inc in early cachexia
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Futile energy expenditures
Adipose tissue |
Adipose tissue:
- TG breakdown - re-esterification of free FA with glycerol-3P to Tg is inc several fold |
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Futile energy expenditures
Tumors |
Tumors:
- anaerobically consume large amts of glucose --> releasing it as lactate taken up by liver and converted back to glucose (energetically inefficient , inc 2-3 fold in cancer pts) |
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Futile energy expenditures
Muscle Cell |
Muscle:
- proton translocation across inner mito membrane is uncoumped from the phosphorylation of ADP (to ATP) via expression of uncopling proteins (UCP_ --> 1. heat production 2. increase in REE 3. Weight loss |
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Muscle catabolism
Whats in skeletal muscle What happens normally What happenns in cachexia |
- skeletal muscle --> contains majority of proteins subject to continuous turnover
-normal--> syn and degradation of muscle proteins is balanced to maintain its mass in adults/growth in children - Cachexia--> muscle protein syn is reduced and dgradation is inc--> accelerated muscle loss of muscle protein |
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Factors promoting Cachexia
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- arise from tumor or infectious agent
- from tissues responding to such factors - Cytokines from immune system play a prominent role -- "pathogen- associated molecular pattern" or "danger signals" trigger release of cytokines such as TNF-alpha which regulate the immune response- play a major role in inducing and maintaining cachexia - recent studies--> both tumors and host factors play impt role in tissue catabolism in cachexia--> leading to upregulation of degradative ptwys in skeletal muscle and adipose tissue |
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Cachectin
Tumor-necrosis factor alpha (TNF-alpha) |
- bacterial lipopolysaccharides --> cause release of cachectin
- cytokine factor that causes cachexia - identical to tumor- necrosis factor alpha(TNF-alpha) |
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Cachexia may arise form a deficiency of factors
Testosterone |
Testosterone
1. stimulates muscle protein synthesis and muscle repair 2. inhibits macrophage release of TNF-alpha Low testosterone levels in hypogonadal pts--> -muscle wasting - testosterone --> potential therapeutic for cachexia |
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Diagnosis of Cachexia
A progressive and unexplained loss of weight |
1. Presence of a chronic disease, PLUS
2. loss of body weight > 5% within the previous 12 months, PLUS 3. Presense of at least 3: - reduce muscle strength - fatigue -anorexia -low fat-free mass index - abnormal biochemistry: inflammation of anemia or low albumin |
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Diagnosis of Cachexia
2. lost of body weight |
- weight loss of 5% of body weight w/in 4-6 months associated with inc risk of mortality
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BMI and type of weight loss
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- BMI --> no info on body composition, interpreted with caution
- bod composition analysis --> cachectic state--> morbidity and mortality is directly associated with depletion of lean body mass (LBM) not fat - measure involuntary weight loss is a decline in body cell mass (BCM) |
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1. BCM- Body cell mass
2. LBM- leadn body mass |
1. cells that metabolize glucose, utilize oxygen and produce carbon dioxide
- loss of 40% of BCM is fatal 2. Includes extracellular compartment which may expand due to edema |
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1. Cachexia
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general physical wasting usually associated with chronic disease
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2. Anorexia
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loss of appetite especially when prolonged
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3. Malnutrition
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faulty nutrition due to inadequate or unbalanced intake of nutrients or their impaired assimilation or utilization
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4. Asthenia
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lack or loss of strength
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5. Sarcopenia
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degenerative loss of skeletal muscle mass and strength
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1. Full energy expenditures
2. Resting energy expenditure |
1. using energy but not accomplishing work or storage of energy
2. Amt of energy used during a non active period |
