B5.035 Involuntary Weight Loss Flashcards
what is temporal wasting
atrophy of muscles on the side of a person’s head associated with rapid weight loss
describe the concept of weight homeostasis
the body reacts to changes in weight to return to its usual body weight
primarily mediated by leptin and ghrelin
response of the body to increased weight
increased energy expenditure and/or decreased intake
mediated by: increased leptin from fat cells > hypothalamus > decreased feeding
response of the body to decreased weight
decreased energy expenditure and/or increased intake
mediated by: decreased leptin from fat cells, increased ghrelin and other GI/fat signals > hypothalamus > increased feeding
normal weight fluctuations
day to day weight fluctuates up to 5 lbs
- changes in intake and output
- changes in day of measurement
what amount of weight loss is pathologic
4% weight loss has about a 75% sensitivity and 61% specificity for increased mortality risk
possible mechanisms for involuntary weight loss
inflammatory cytokines (TNF, IL-6) increased energy expenditure decreased appetite social factors psychiatric illness
pathogenesis of involuntary weight loss
stimulus as described previously
muscle and fat breakdown
usual regulatory mechanisms in defense of body fat mass not functioning or not effective
definition of involuntary weight loss
weight loss that is not intended by the patient, and is not a consequence of the expected treatment of a known condition
>5% weight loss within 6-12 months
weight loss measured or by objective clinical criteria
definition of unexplained weight loss
weight loss that is not intended, and of which the cause is not found after a workup
the exact amount of workup and time is not precisely defined
definition of sarcopenia
geriatric syndrome consisting of low muscle mass (2 SDs below reference) and poor physical performance
definition of cachexia
metabolic syndrome: loss of muscle mass caused by an underlying illness
weight loss of 5% or greater over 12 mo or less and:
-decreased muscle strength
-fatigue
-anorexia
-low fat-free mass index
-abnormal laboratory tests (increased inflammatory markers, anemia)
how often is a cause of involuntary weight loss found
33-60% of the time etiology identified
94% of those with initial negative workup found to have a diagnosis
10-25% still without a primary diagnosis after extended follow up
what are the 3 primary etiologies of involuntary weight loss
38% malignancy
23% psychiatric
10% GI diseases
MEALS ON WHEELS
M: medication E: emotional problems A; anorexia nervosa, alcoholism L: late life paranoia S: swallowing disorders O: oral factors N: no money W: wandering and dementia like behaviors H: hyper- hypo- thyroidism E: enteric problems E: eating problems L: low salt, low cholesterol diet S: stones, social problems
what markers might indicate and increased risk of malignancy as an etiology of weight loss
age > 60 WBC > 12,000 alk phos > 300 LDH > 500 hemoglobin < 10 ESR > 29
factors associated with decreased risk of malignancy
smoking < 20 years
no decrease in physical activity
initial testing for involuntary weight loss
CBC liver enzymes albumin creatinine level calcium TSH HIV ESR CRP LDH chest x-ray
symptoms that may be associated with involuntary weight loss
fever, fatigue
dysphagia, oral/gum problems
dyspnea, exertional fatigue
indigestion, abdominal pain, change in stool pattern, early satiety
involuntary weight loss associated with cardiovascular disease
independent marker of increased mortality in context of cardiac disease
mediated
presents with loss of muscle mass and fat
heart failure diagnosis established prior to development of cachexia
involuntary weight loss associated with renal disease
protein energy malnutrition
inflammatory cytokines and neuropeptide signaling to hypothalamus
at times hard to distinguish from medication causes (diuretics)
involuntary weight loss associated with neurological conditions
dementia- cognitive decline causing decreased intake
MS and neuromuscular disorders- physical function of chewing and swallowing
Parkinson’s- reduced swallowing, reduced GI function
involuntary weight loss associated with endocrinopathies
hyperthyroidism- weight loss in 50% affected
adrenal insufficiency
DM - 50% present with weight loss
involuntary weight loss associated with infectious disease
HIV
TB
prescription drugs that can lead to weight loss
topiramate SSRIs buproprion metformin GLP-1 agonists laxatives diuretics
types of substance abuse that can lead to weight loss
cocaine (fat dysregulation, appetite suppression)
EtOH
heroin
meth
what are some adverse effects associated with prescriptions that can lead to weight loss
altered taste or smell anorexia dry mouth dysphagia nausea and vomiting
involuntary weight loss associated with psych/social factors
depression
anxiety
meds used in psychiatric illnesses
poverty = inadequate intake of calories
involuntary weight loss associated with pulmonary disease
advanced COPD, rheumatologic disease, malignancy, TB, interstitials lung disease
low muscle mass = higher mortality
etiology: increased work of breathing, neuro-hormonal changes
involuntary weight loss associated with GI diseases
pancreatic insufficiency celiac diarrheal illnesses IBD peptic ulcer disease mesenteric ischemia protein losing enteropathy dental disease
3rd most common cancer related death
colon cancer
which cancers cause weight loss?
pancreatic cancer
GI cancer
head and neck cancer
lung cancer
direct effect of tumor on cancer cachexia
release cytokines
release proteolysis inducing factor
release lipid mobilizing factor
secondary hormonal effects of tumor on cancer cachexia
acts on adrenal and pancreatic B cells to release insulin, cortisol, and glucagon
effect of tumor cytokines
stimulate hypothalamus to encourage anorexia and increased energy expenditure
stimulate liver to release acute phase proteins
effect of lipid mobilizing factor
fat breakdown
effect of proteolysis inducing factor
protein breakdown
tumor derived catabolic factors
activins myostatin TGFB serotonin parathyroid hormone related protein
important pro-inflammatory mediators arising from tumor immune system crosstalk
IL-1
TNF
IL-6
what is futile cycling?
the browning of adipose to increase energy expenditure
mechanism of tumor induced muscle atrophy
upregulated pathways that produce E3 ubiquitin ligase and autophagy proteins leading to myofibrillar protein breakdown
Ca2+ mishandling leads to contractile dysfunction
