TBL-Obesity and Nutrition

Question 1

Primary malnutrition

Answer 1

Carbs, fats, proteins, vitamins and/or minerals are missing from the diet

Question 2

Secondary malnutrition

Answer 2

Nutrient supply is adequate, but malnutrition is due to insufficient intake, malabsorption, impaired utilization/storage, excess loss or increased need for nutrients

Question 3

6 common causes for malnutrition

Answer 3

1) Poverty 2) Infection 3) Illness 4) Alcoholism 5) Ignorance 6) Self-imposed dietary restriction

Question 4

Definition of a malnourished child. What could this definition possibly be masked by?

Answer 4

< 80% normal weight. May be masked by generalized edema. Fat stores, muscle mass and serum proteins can provide a better picture in this setting.

Question 5

A child presents with recurrent infections, emaciated extremities and his head appears too large for his body. He below 60% normal weight for his age group. What nutritional deficiency is causing his condition? What would you expect to see on labs of serum albumin, leptin, cortisol and CBC?

Answer 5

Marasmus. This is caused by depletion of the somatic protein compartment and fat stores. Serum albumin will be normal, leptin will be low, cortisol high and CBC will show anemia and leukopenia, particularly T-cells.

Question 6

A child presents with a recurrent infections, swollen abdomen, apathy, listlessness and loss of appetite. On physical exam you note the skin has a flaky paint appearance, alternating bands of pale and darker hair and spared subcutaneous fat and muscle mass. What is likely causing this child’s condition?

Answer 6

Kwashiorkor. Protein depravation associated with a strictly carbohydrate-only diet causes severe loss of the visceral protein compartment, hypoalbuminemia and generalized edema. This can also be caused by chronic diarrhea, nephrotic syndrome and extensive burns.

Question 7

You visit an 89 year old bedridden patient complaining of recurrent infections and impaired wound healing. On physical exam you note depletion of subcutaneous fat in the arms, chest, shoulders and metacarpal regions. Muscle is wasted in the quadriceps and deltoid muscles. She has ankle edema. What is likely causing her symptoms and how do you assess her nutritional status?

Answer 7

She has secondary protein-energy malnutrition (PEM). You can assess her nutritional status with the Mininutritional assessment (MNA).

Question 8

Kwashiorkor liver

Answer 8

Enlarged and fatty

Question 9

Why infants with kwashiorkor initially do not respond well to milk-based diets

Answer 9

Small bowel loss of villi and intestinal enzymes due to decreased mitotic activity.

Question 10

Why is the bone marrow hypoplastic in kwashiorkor and marasmus?

Answer 10

Decreased red cell precursors from iron, folate and/or protein deficiency. It could also be due to anemia of chronic disease from chronic parasitic or worm infection.

Question 11

CNS effects of kwashiorkor

Answer 11

Cerebral atrophy, reduced neurons, impaired myelinization

Question 12

Conditions that present with cachexia

Answer 12

AIDS, GI, pancreatic and lung cancers

Question 13

A patient with a history of HIV presents with 20 pound weight loss in the past 2 months and fatigue. Physical exam shows muscle atrophy, anorexia and edema. Labs reveal anemia. What is likely causing his condition? What is a common cause of mortality associated with this condition?

Answer 13

Cachexia is common w/AIDS. Proteolysis-inducing factor (PIF found in urine) and pro-inflammatory cytokines (TNF, IL-2 & IL-6) produced by tumors activate NF-kB signaling to activate the muscle-specific ubiquitin ligases that degrade the myosin heavy chain.

Question 14

A patient presents with amenorrhea, cold intolerance, bradycardia, constipation, changes in skin/hair, dry/scaly skin, decreased bone density, anemia, lymphopenia and hypoalbuminemia. What is causing her condition? What is a common cause of mortality associated with this condition?

Answer 14

Anorexia: decreased gonadotropin-releaseing hormone -> decreased LH -> decreased FSH, which causes amenorrhea and is diagnostic for anorexia. Thyroid hormone decrease -> cold intolerance, bradycardia, constipation and changes in skin/hair. Electrolyte abnormalities -> dry/scaly skin. Low estrogen levels -> decreased bone density. Cardiac arrhythmia is common cause of sudden death due to hypokalemia electrolyte imbalance.

Question 15

A patient presents with cardiac arrhythmias, aspiration pneumonia and gastric cardiac rupture. What is likely causing this patient’s condition?

Answer 15

Bulimia.

Question 16

What are the components of the peripheral afferent systems in regulation of satiety, energy expenditure and hunger?

Answer 16

Leptin/adiponectin from fat cells. Ghrelin from stomach, peptide YY from ileum/colon and insulin from pancreas.

Question 17

What efferent neurohormonal signals are generated by the arcuate nucleus in the hypothalamus?

Answer 17

1st order neurons: pro-opiomelanocortin/ cocaine and amphetamine-regulated transcripts (POMC/CART) and neuropeptide Y/Agouti-related peptide (NPY/AgRP). 2nd order neurons that communicate w/POMC and CART carry signals to control food intake and regulate energy expenditure from the hypothalamus.

Question 18

How do POMC/CART neurons enhance energy expenditure and weight loss?

Answer 18

The induce production of alpha-melanocyte-stimulating hormone (MSH) and activate melanocortin receptors (MC3/4) in second order neurons

Question 19

How do POMC/CART neurons promote food intake and weight gain?

Answer 19

Activation of Y1/5 receptors on secondary neurons.

Question 20

What genetic conditions can cause disorders of leptin?

Answer 20

Ob gene (leptin) or db gene (leptin receptor)

Question 21

What stimulates leptin secretion? What effect does leptin have on the body?

Answer 21

Abundant fat stores. Leptin stimulates physical activity, heat production and energy expenditure. It also mediates thermogenesis, hematopoiesis and lymphopoiesis.

Question 22

How does leptin increase energy expenditure and inhibit hunger?

Answer 22

Stimulation of POMC/CART neurons to produce MSH. Inhibit NPY/AgRP neurons.

Question 23

Mutations responsible for 5% of obese patients

Answer 23

MC4R. This results in no signaling of satiety. Note that leptin mutations are rare.

Question 24

Mutation that causes obesity associated with Wilm’s tumor, anuria, genitourinary defects and mental retardation (WAGR syndrome)

Answer 24

Brain-derived neurotrophic factor (BDNF)

Question 25

What does adiponectin do?

Answer 25

Binding to AdipoR1/R2 stimulates fatty acid oxidation in muscle, decreases influx of fatty acids to liver, decreases glucose production in liver (increasing insulin sensitivity) and inactivates acetyl CoA carboxylase (inactivating fatty acid synthesis). Note that decreased levels of adiponectin in obese people contributes to hyperinsulinemia and insulin insensitivity.

Question 26

Why do obese people struggle with sub-clinical inflammatory states?

Answer 26

Adipose tissue secretes cytokines (TNF, IL-6, IL-1, IL-18), chemokines and steroid hormones.

Question 27

Why might genetics make it difficult to maintain healthy weight after losing weight?

Answer 27

of adipocytes remains the same.

Question 28

Where does ghrelin come from and what does it do?

Answer 28

Produced in stomach and hypothalamus. Binds to growth hormone secretagogue receptor in hypothalamus and pituitary. Stimulates NPY/AgRP neurons to increase food intake. Note that these levels rise before meals and fail to fall after meals in obese patients.

Question 29

Where does PYY come from and what does it do? What syndrome is it associated with?

Answer 29

Produced in ileum and colon. It reduces energy intake by stimulating POMC/CART neurons and is associated with hyperphagia and obesity in patients with Prader-Willi syndrome (has low levels of PYY)

Question 30

Where does amylin come from and what does it due?

Answer 30

Comes from pancreas. Reduces food intake and weight gain by stimulating POMC/CART neurons.

Question 31

Metabolic syndrome

Answer 31

Adiposity, insulin resistance, hyperinsulinemia, glucose intolerance, HTN, hypertriglyceridemia and low HDL.

Question 32

What causes hypertension in obese patients?

Answer 32

Insulin resistance/hyperinsulinemia

Question 33

Why are obese patients at risk for coronary artery disease?

Answer 33

Hypertriglyceridemia and low HDL levels

Question 34

Liver disease w/obesity

Answer 34

Non-alcoholic fatty liver disease

Question 35

Why are obese patients at risk for cholelithiasis?

Answer 35

Increased total body cholesterol

Question 36

Why are obese patients at risk for right-sided heart failure?

Answer 36

Hypoventilation (pickwickian) syndrome. Apnea -> polycythemia -> right-sided heart failure.

Question 37

Obese male cancer associations

Answer 37

Esophageal adenocarcinoma, thyroid, colon and kidney cancers.

Question 38

Obese female cancer associations

Answer 38

Esophageal adenocarcinoma, endometrial, gallbladder and kidney cancers.

Question 39

Why can obesity be a significant risk factor for cancer?

Answer 39

Hyperinsulinemia can activate cell growth pathways. It also increases insulin-like growth factor-1 (IGF-1) and inhibits IGF-binding proteins (IGFBP-1 and IGFBP-2). IGF-1 is mitogenic and anti-apoptotic and is expressed in many tumors. In addition to activating many insulin receptors that stimulate cell growth, it also increases production of VEGF.

Question 40

How does obesity specifically increase risk for breast and uterine cancers?

Answer 40

Increases synthesis of estrogen from androgen precursors in adipose tissue. Insulin increases androgen synthesis and enhances estrogen availability by inhibiting the production of sex-hormone-binding globulin (SHBG) in the liver.