B5.035 Involuntary Weight Loss

Question 1

what is temporal wasting

Answer 1

atrophy of muscles on the side of a person’s head associated with rapid weight loss

Question 2

describe the concept of weight homeostasis

Answer 2

the body reacts to changes in weight to return to its usual body weight
primarily mediated by leptin and ghrelin

Question 3

response of the body to increased weight

Answer 3

increased energy expenditure and/or decreased intake

mediated by: increased leptin from fat cells > hypothalamus > decreased feeding

Question 4

response of the body to decreased weight

Answer 4

decreased energy expenditure and/or increased intake
mediated by: decreased leptin from fat cells, increased ghrelin and other GI/fat signals > hypothalamus > increased feeding

Question 5

normal weight fluctuations

Answer 5

day to day weight fluctuates up to 5 lbs

• changes in intake and output
• changes in day of measurement

Question 6

what amount of weight loss is pathologic

Answer 6

4% weight loss has about a 75% sensitivity and 61% specificity for increased mortality risk

Question 7

possible mechanisms for involuntary weight loss

Answer 7

inflammatory cytokines (TNF, IL-6)
increased energy expenditure
decreased appetite
social factors
psychiatric illness

Question 8

pathogenesis of involuntary weight loss

Answer 8

stimulus as described previously
muscle and fat breakdown
usual regulatory mechanisms in defense of body fat mass not functioning or not effective

Question 9

definition of involuntary weight loss

Answer 9

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

Question 10

definition of unexplained weight loss

Answer 10

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

Question 11

definition of sarcopenia

Answer 11

geriatric syndrome consisting of low muscle mass (2 SDs below reference) and poor physical performance

Question 12

definition of cachexia

Answer 12

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)

Question 13

how often is a cause of involuntary weight loss found

Answer 13

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

Question 14

what are the 3 primary etiologies of involuntary weight loss

Answer 14

38% malignancy
23% psychiatric
10% GI diseases

Question 15

MEALS ON WHEELS

Answer 15

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

Question 16

what markers might indicate and increased risk of malignancy as an etiology of weight loss

Answer 16

age > 60
WBC > 12,000
alk phos > 300
LDH > 500
hemoglobin < 10
ESR > 29

Question 17

factors associated with decreased risk of malignancy

Answer 17

smoking < 20 years

no decrease in physical activity

Question 18

initial testing for involuntary weight loss

Answer 18

CBC
liver enzymes
albumin
creatinine level
calcium
TSH
HIV
ESR
CRP
LDH
chest x-ray

Question 19

symptoms that may be associated with involuntary weight loss

Answer 19

fever, fatigue
dysphagia, oral/gum problems
dyspnea, exertional fatigue
indigestion, abdominal pain, change in stool pattern, early satiety

Question 20

involuntary weight loss associated with cardiovascular disease

Answer 20

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

Question 21

involuntary weight loss associated with renal disease

Answer 21

protein energy malnutrition
inflammatory cytokines and neuropeptide signaling to hypothalamus
at times hard to distinguish from medication causes (diuretics)

Question 22

involuntary weight loss associated with neurological conditions

Answer 22

dementia- cognitive decline causing decreased intake
MS and neuromuscular disorders- physical function of chewing and swallowing
Parkinson’s- reduced swallowing, reduced GI function

Question 23

involuntary weight loss associated with endocrinopathies

Answer 23

hyperthyroidism- weight loss in 50% affected
adrenal insufficiency
DM - 50% present with weight loss

Question 24

involuntary weight loss associated with infectious disease

Answer 24

HIV

TB

Question 25

prescription drugs that can lead to weight loss

Answer 25

``` topiramate SSRIs buproprion metformin GLP-1 agonists laxatives diuretics ```

Question 26

types of substance abuse that can lead to weight loss

Answer 26

cocaine (fat dysregulation, appetite suppression) EtOH heroin meth

Question 27

what are some adverse effects associated with prescriptions that can lead to weight loss

Answer 27

``` altered taste or smell anorexia dry mouth dysphagia nausea and vomiting ```

Question 28

involuntary weight loss associated with psych/social factors

Answer 28

depression anxiety meds used in psychiatric illnesses poverty = inadequate intake of calories

Question 29

involuntary weight loss associated with pulmonary disease

Answer 29

advanced COPD, rheumatologic disease, malignancy, TB, interstitials lung disease low muscle mass = higher mortality etiology: increased work of breathing, neuro-hormonal changes

Question 30

involuntary weight loss associated with GI diseases

Answer 30

``` pancreatic insufficiency celiac diarrheal illnesses IBD peptic ulcer disease mesenteric ischemia protein losing enteropathy dental disease ```

Question 31

3rd most common cancer related death

Answer 31

colon cancer

Question 32

which cancers cause weight loss?

Answer 32

pancreatic cancer GI cancer head and neck cancer lung cancer

Question 33

direct effect of tumor on cancer cachexia

Answer 33

release cytokines release proteolysis inducing factor release lipid mobilizing factor

Question 34

secondary hormonal effects of tumor on cancer cachexia

Answer 34

acts on adrenal and pancreatic B cells to release insulin, cortisol, and glucagon

Question 35

effect of tumor cytokines

Answer 35

stimulate hypothalamus to encourage anorexia and increased energy expenditure stimulate liver to release acute phase proteins

Question 36

effect of lipid mobilizing factor

Answer 36

fat breakdown

Question 37

effect of proteolysis inducing factor

Answer 37

protein breakdown

Question 38

tumor derived catabolic factors

Answer 38

``` activins myostatin TGFB serotonin parathyroid hormone related protein ```

Question 39

important pro-inflammatory mediators arising from tumor immune system crosstalk

Answer 39

IL-1 TNF IL-6

Question 40

what is futile cycling?

Answer 40

the browning of adipose to increase energy expenditure

Question 41

mechanism of tumor induced muscle atrophy

Answer 41

upregulated pathways that produce E3 ubiquitin ligase and autophagy proteins leading to myofibrillar protein breakdown Ca2+ mishandling leads to contractile dysfunction