191. Starvation + Metabolic Adaptation

Question 1

Define the following:

• starvation
• starvation-assoc malnutrition
• disease-assoc malnutrition
• caloric restriction
• sarcopenia
• determinants of BMR

Answer 1

Starvation: state of negative energy or protein balance
SAM: prolonged deficit of energy/protein causing CM
DAM: occurs with illness (cachexia), high protein catabolism due to inflammatory cytokines
CR: volitional reduction in energy intake (below needs) with adequate intake of protein/micronutrients (for more health/longevity)
Sarcopenia: loss of muscle mass assoc with aging (hormonal/metabolic factors - normal)

BMR: Body comp (high FFM = high BMR), Age, Gender, Nutritional/Health Status

Question 2

How long can the average man survive with his body’s energy stores?

What are the fuel types used during starvation? When?

What are the origins of new blood glucose?

What are the substrates for gluconeogenesis?

What are other fuel sources used in starvation? What parts of the body can use them?

Answer 2

Survive 2-3 months (majority FAs, some protein, small glycogen)

1. Exogenous food (after meal)
2. Glycogen stores (4-12 hours)
3. Gluconeogenesis (2-3 days): after 3 days, inhibit gluconeogenesis and switch to other source: ketones and FFA (spare lean body mass to survive longer)

Origins of New BG: Liver, Kidney (gluconeogenesis)

Substrates for GNG: RBCs (Lactate, pyruvate), muscle (Alanine, glutamine), adipose (glycerol)

Other sources: FFA, ketone bodies
Brain: uses ketone bodies, glucose
Muscle: FFA, ketone bodies
Liver: FFA
RBCs, renal medulla: glucose only (need some GNG)
FFA released from adipose via HSL (lipolysis) in low insulin states (starvation, T1DM)

Question 3

How do the following change in starvation: TEE, BMR, EEPA, TEF

What hormones change in starvation?

Answer 3

TEE low, BMR very low and EEPA very low (due to muscle becoming more efficient), low TEF

Increase in ghrelin, glucagon
Decrease in leptin, ins, T3/T4, LH/FSH, E/T

Question 4

Metabolic Adaptation to Weight Loss in Obesity

• what metabolic/hormone changes occur?
• how can you reverse this metabolic adaptation? why don’t we?
• how long do adaptations persist?

Answer 4

Similar to starvation
Decrease in: leptin, EE, T3/T4, satiety hormones (CCK, GLP1, PYY)
Increase in: ghrelin, muscular efficiency (burn fewer calories doing same work)
Hyperactive neural response to visual food cues

Leptin administration reverses metabolic adaptation (restore leptin to pre-weight-loss levels)
NOT used b/c leads to leptin Ab development and resistance = obesity + hyperphagia

Adaptations persist for even 6 years after weight loss!

Question 5

How do energy and protein metabolism change in illness? Why?

What illness have the highest energy metabolism changes?

Answer 5

Energy: INCREASE BMR: via increase catecholamines/SNS, high body temp/fever, inflammation/cytokines

Protein: INCREASE CATABOLISM: via inflammation/cytokines, high cortisol, higher insulin resistance
(Catabolism decreases in starvation)

Burn pts - highest BMR
Skeletal trauma - higher BMR
Sepsis/Infection - high BMR

Question 6

Marasmus vs. Kwashiorkor

- CM, labs, features

Answer 6

MARASMUS

• primary CALORIE deficit = LOW body weight
• wasted appearance = loss of fat + muscle
• normal liver fx
• +/- hypoalbuminemia
• dry, inelastic skin
• seen in anorexia nervosa; cachexia in AIDS

Kwashiorkor

• primary PROTEIN deficit = LOW/NORMAL body weight due to EDEMA masking weight loss
• distended abdomen
• fatty liver and LIVER DYSFX
• MARKED HYPOalbuminemia
• skin + hair changes: depigmentation (flag sign), flaky paint rash, deaquamative rash

PGen:

1. Primary Protein Deficiency: carb intake = ins release = protein anabolism = less AA available for albumin synthesis (hypoalbuminemia) and apoprotein synthesis (less VLDL) = liver lipogenesis = fatty liver and dysfx
2. Inadequate Antioxidant Capacity: ROS damage to cells
3. Gut Microbiome: disordered microbiota metabolism

Question 7

Malnutrition

• manifestations
• tx

Answer 7

stunted growth in children
low body temp = hypothermia
CV: hypotension, bradycardia, low CO (low SNS)
Pulm: low resp muscle mass/fx, low resp drive
Endo: hypogonadotropic hypogonadism, osteoporasis
GI: delayed gastric emptying
Heme: anemia, leukopenia (low WBC)
Neuro: low volume grey matter, low SNS

Anorexia Nervosa: reduction of myocardial mass
Behavior changes: preoccupied with food, hoarding/stealing, abnormal taste preferences, binge eating, depression/apathy/irritability

1. ORAL NUTRITION: whole foods/supplements
2. ENTERAL NUTRITION: via gut (tube through nose/mouth, thru abd wall, into stomach/intestine)
3. PARENTERAL NUTRITION: IV Nutrition
   - formula with water, macronutrients (dextrose, AA, emulsified lipids), electrolytes/minerals, vitamins
   - TPN: HIGH OSM - needs central line
   - Peripheral PN: LOW OSM - infused peripherally, cannot meet energy/protein needs (supplemental only)

Question 8

Refeeding Syndrome

• pathophys
• prevention

Answer 8

Refeeding = glu availability causes shift of electrolytes into cell
Low blood electrolytes = arrhythmias, decreased contractility
Reduced heart size in malnutrition + increased circulatory blood volume from TPN + arrhythmias = HEART FAILURE (weakness, SoB, fluid overload)

Prevention: ID high risk patients (weight loss w/o trying, less appetite causing less intake), replete all electrolytes BEFORE nutritional support, frequent monitoring
REPLETE THIAMINE (high glu metabolism from refeeding will deplete this = causing wet beriberi/deficiency)