FORM & FUNCTION (Cachexia & Pregnancy Toxemia) Flashcards
Cachexia:
-metabolic wasting disorder accompanied primarily by loss of lean body mass (muscle)
Cachexia symptoms:
-decrease skeletal muscle mass
-with or without weight loss
-loss of appetite
-increase metabolic rate
Cachexia is commonly observed in:
-cancer
-congestive heart failure
-chronic kidney disease
-COPD (chronic obstructive pulmonary disease)
Cachexia vs. starvation:
Starvation:
-no nutrient intake
-adaptive response to conserve muscle mass (CHO to lipids to proteins)
Cachexia:
-nutrient intake
-no adaptive response: proteins are targeted as first source of nutrient (proteins to lipids to
CHO)
Both:
-progressive loss of muscle mass
*non-muscle proteins are preserved in cachexia, but NOT in starvation
TNF-a
-an inflammatory cytokine (small signalling protein)
-highly elevated in many disease states
*triggers another enzyme which leads to inhibition of growth and maintenance of muscle mass
*metabolic effects
TNF-a triggers another enzyme
-promotes ubiquitin-proteasome system
-promotes inflammation
-inhibits myogenesis (muscle build up)
*increase catabolism of muscle
Metabolic effects of TNF-a
- Increase muscle loss
- Decrease food intake: anorexia
- Impaired glucose control: insulin resistance (inhibits IRS-1: so don’t get GLUT4)
- Increase lipid metabolism/lipolysis (elevated serum triglycerides
>inhibition of PP1
Muscle wasting:
-primary feature of cachexia
*elevated inflammation is the underlying mechanism
-can be followed by subsequent weight loss (anorexia)
Congestive heart failure:
-inadequate blood pumping to the body
>hypoxemia: impaired oxygen to tissues
*50% of dogs with CHG display cachexia
-loss of lean muscle mass is greater than total weight loss
-elevated levels of TNF-a
Cardiac cachexia: multifactorial cause of muscle and fat loss (lesser extent)
-lack of appetite
-decrease perfusion to GI system: malabsorption and maldigestion
-increase in inflammatory factors: enhances muscle protein degradation
-increased resting energy requirement
Cyclical relationship of cardiac cachexia:
- Heart failure leads to increased TNF-a
- Muscle loss
- Contributes more to heart failure
REPEAT
Cachexia: edema and ascites
-have reduced levels of serum albumin
-increase in metabolism of AA for energy reduces the protein synthesis in liver
>loss fluid to interstitial space or abdominal cavity
Body weight vs. muscle mass:
-increase in fluid retention can mask loss of muscle and fat in terms of total body weight
-assessing total body weight can underestimate the development of cachexia
-need to use direct assessment of muscle mass
Cachexia and morbidity:
-increases morbidity of animals with CHF
Obesity paradox:
-obese animals have increased survival rate in CHF, cancer and chronic kidney disease
-excess fat may be protective against cachexia by reducing starvation-related complications
