Term
| know this -> what is cachexia? |
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Definition
| a wasting syndrome that involves altered metabolism of proteins/carbs/lipids; resulting in anorexia, weight loss (unintentional >5% in 6 mos), loss of lean body and fat mass (disporportionate muscle wasting), decreased albumin (from altered protein metabolism), and increased C-reactive protein (marker of inflammation) |
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Term
| know this -> what are the clinical manifestations of cachexia? |
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Definition
| nonvoluntary weight loss, anorexia, early satiety (delayed stomach emptying), hypermetabolism (high resting energy expenditure), loss of lean body and total body mass (significant proteolysis and lack of protein synthesis particularly in skeletal muscle), loss of body fat (significant lipolysis), anemia (mediated by anemia inducing substance), weakness, and poor physical performance |
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Term
| what are cachexia-related diseases? what is the link between these diseases and cachexia? |
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Definition
| CA, RA, end-stage renal disease, CHF, HIV/AIDS, chronic obstructive pulmonary disease, and chronic liver disease (20-40% risk with each of these, pro-inflammatory cytokines are the link between these diseases and cachexia) |
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Term
| what is the definition of cancer cachexia? |
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Definition
| a wasting syndrome involving the loss of muscle and fat directly caused by an aberrant host response to the tumor presence |
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Term
| what % of cancer pts have syptoms of cachexia? what % die from it? |
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Definition
| 50-80% have symptoms, 20% die |
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Term
| which cancers cause the worst cachexia? |
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Definition
| lung, pancreatic and gastrointestinal |
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Term
| what is the general definition of starvation? |
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Definition
| the body enters an energy conserving state, it tries to prevent lean body mass loss and weight loss |
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Term
| what kind of metabolism is cachexia? |
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Definition
| an energy wasting metabolism |
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Term
| what happens to resting energy expenditure between starvation and cachexia? |
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Definition
| in starvation, resting energy expenditure goes down, but in cachexia, it goes up (due to a constantly high level of epinephrine in the blood increasing the energy metabolism) |
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Term
| why do people with cachexia have high blood glucose? |
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Definition
| a constant level of cortisol is released that leads to insulin resistance |
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Term
| what is the metabolic trend in terms of energy source in starvation? |
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Definition
| at first, AAs are released from skeletal muscle, but this is shifted to ketone bodies as starvation progresses (lose more fat, less protein/muscle - gluconeogenesis is decreased) |
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Term
| what is the metabolic trend in terms of energy source in cachexia? |
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Definition
| tumors need a lot of glucose, which they convert to lactate, which is very inefficient. muscles are targeted for breakdown b/c they have glucogenic amino acids (ketone production is suppressed) |
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Term
| do people in cachexia also lose fat as well as muscle? |
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Definition
| yes; excess fat oxidation leads to depletion of fat mass w/elevated triglycerides and decreased lipoprotein lipase activity |
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Term
| what is the primary source of weight loss in starvation? |
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Definition
| primary weight loss is fat, with secondary loss of skeletal muscle and visceral protein mass |
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Term
| what is the primary source of weight loss in cachexia?? |
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Definition
| there is equal loss of fat and lean body mass. skeletal muscle comprises the bulk of protein loss w/preservation of visceral protein mass |
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Term
| is there a desire to eat in starvation and cachexia? |
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Definition
| yes, w/starvation there is a increasing desire to eat, where with cachexia neuropeptide Y (responsible for food-seeking behavior) is suppressed, and hunger is decreased |
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Term
| how does starvation respond to increased caloric intake? |
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Definition
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Term
| how does cachexia respond to increased caloric intake? |
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Definition
| there is an inability to gain or maintain weight despite adequate caloric intake; proteolysis and lipolysis not diminished with increase intake of substrates |
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Term
| what does neuropeptide Y do? |
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Definition
| when a person is hungry, neuropeptide Y increases in the hypothalamus thus increasing the person’s food seeking behavior |
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Term
| what cytokines are most prominent in cancer related cachexia? where are they released from? what is their significance? |
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Definition
| IL-1 alpha and beta, IL-6, TNF-alpha, and IFN gamma. these are released from white blood cells, skeletal muscle, and the tumor itself - these cytokines are the regulators and mediators of cachexia. they suppress neuropeptide Y, promote altered energy metabolism where anerobic processes are predominant, they promote cortisol and epinephrine release from the adrenal glands (insulin resistance/boost in energy metabolism), they directly stimulate proteolysis and lipolysis as well as promoting PIF/LMF in tumor cells |
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Term
| are there other substances beyond cytokines that are released and play a part in cachexia? |
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Definition
| yes, prostaglandin E-2 (PGE2), 15-hydroxyeicosatetraenoic acid (HETE), and reactive oxygen species (ROS) are also released. |
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Term
| what special role do the ROSs released in cachexia play? |
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Definition
| these ROS damage DNA and cells membranes, but also *activate enzymes. |
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Term
| are there proteins that tumors secrete that promote cachexia? |
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Definition
| yes, proteolysis inducing factor (PIF - mediates skeletal muscle breakdown through ubiquitin-proteasome pathway) and lipid mobilizing factor (LMF - inhibits lipoprotein lipase and stimulates hormone sensitive lipase) are released |
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Term
| how are ROS, arachidonic acid and cachexia related? |
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Definition
| in inflammatory processes, macrophages release ROS which activate PLA2 (phospholipase A2) which causes arachidonic acid from the phospholipid bilayer of cell membranes. arachidonic acid is then cleaved by COX 1+2 into series 2 prostaglandins, series 4 leukotrienes and *PGE2 |
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Term
| what is PGE2's significant role in cachexia? |
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Definition
| PGE2 leads to the activation of transcription and translation of cytokines |
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Term
| what else does arachidonic acid get cleaved into besides series 2 prostaglandins and series 4 leukotrienes and PGE? |
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Definition
| HPETE which is the result of lipoxygenase cleavage. HPETE induces tumor cells to produce PIF and LMF |
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Term
| if which 2 enzymes were arrested, would cachexia stop? |
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Definition
| cyclooxygenase and lipooxygenase |
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Term
| what is the key to treating cachexia via nutritional care? |
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Definition
| cytokine antagonism, with the cornerstone being medications/nutriceuticals to counteract the pathophysiology |
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Term
| what do progestagens megesterol and medroxyprogesterone acetate do? |
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Definition
| these inhibit cytokine production and counteract neuropeptide Y down regulation |
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Term
| what does thalidomide do? |
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Definition
| profoundly blocks the production of cytokines |
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Term
| what does testosterone do? |
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Definition
| inhibits the effects of cytokines in proteolysis and promtes protein synthesis in muscle |
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Term
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Definition
| inhibit COX, therefore inhibiting PGE2 and cytokine production (ibuprofen, indomethacin, celecoxib) |
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Term
| what does eicosapentaenoic acid (EPA) do? |
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Definition
| this nutriceutical has proven to be the most effective in managing cytokines of cachexia. it competes with arachidonic acid for COX/LOX; decreasing series 2 and 4 eiconasoids and increasing series 3 and 5 eiconasoids |
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Term
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Definition
| foods or food-derived substances that can have pharmalogical effects |
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Term
| what are dronabinol and reglan? |
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Definition
| these both increase neuropeptide Y. dronabinol is a chemical relative of marijuana. |
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Term
| where does arachidonic acid come from? |
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Definition
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Term
| where does EPA (eicosapentanoic acid) come from? |
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Definition
| linolenic acid (from which DHA - docosahexaenoic acid, another omega fatty acid also comes) |
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Term
| what is the difference in eicosaniod production between consumption of predominately omega 6 and 3? |
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Definition
| omega 6:linoleic acid -> arachiconic acid -> COX -> series 2 prostaglandins and series 4 leucotrienes (more inflammatory cytokines). omega 3: linolenic acid -> competitive for COX -> EPA ->DHA -> series 3 prostaglandins, series 5 leucotrienes (less inflammtory cytokines) |
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Term
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Definition
| release of arachidonic by phospholipase A from plasma membranes, competes with COX/LOX in a matter that inhibits prostaglandin 2 and leuctriene 4 production, and NFkappaB (nuclear transcription factor) for the production of cytokines |
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Term
| what is an effective dose of EPA/day? |
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Definition
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Term
| can EPA depress muscle proteolysis? |
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Definition
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Term
| what do polyphenols do? what are some examples? |
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Definition
| polyphenols such as catechin (green tea) and resveratol (grapes) inhibit PIF, (and therefore proteolysis), COX and cytokine production are inhibited |
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Term
| how can antioxidants like vitamins A, C, E, alpha-lipoic acid help with cachexia? |
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Definition
| these quench ROSs (reduced stimulus for phospholipase A to release arachionic acid) |
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Term
| what will leucine (a branched chain AA) do in 3g per day quantities? |
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Definition
| enhance protein synthesis |
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Term
| how can HMB (beta hydroxy beta methylbutyrate - metabolite of leucine) + arginine + glutamine help reverse cachexia? |
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Definition
| HMB+arginine+glutamine together counteract PIF. individually, arg and glut (14g/day) enhance protein synthesis and HMB (3g/day) minimizes proteolysis |
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Term
| once the cytokine (inflammatory) problem has been addressed in cachexia, what is the next step? |
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Definition
| hypercaloric feeding, with enteral emphasis. there are commercial formulas that have included in them many of the necessary nutriceuticals already. extra (catch-up) feedings may be necessary between chemo bouts (this may include paraenteral/enteral feeding depending on appetite). |
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Term
| why is using cold liquid food useful in cachexia? |
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Definition
| it leaves the stomach faster than hot/solid food |
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Term
| what is the key to treating pts with anorexia (after inflammation of cachexia has subsided)? |
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Definition
| let them eat whatever they want (might have food jags) |
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Term
| how can nutrient density be increased in food? |
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Definition
| adding (flax) oil, milk powder, egg whites |
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Term
| after addressing inflammation and nutrient deficit, what is the next step in recovery from cachexia? |
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Definition
| resistance training, promotion of physical activity to stimulate muscles toward protein anabolism. 3 days/wk, 12 large muscle groups with 3 sets of weight that the pt can't life more than x |
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Term
| what needs to be treated before aggressive nutrition therapy can work? |
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Definition
| the chronic inflammatory state |
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Term
| what can be done early to prevent substantial weight loss before tx? |
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Definition
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