THE ENDOCRINE SYSTEM and METABOLISM

STARVATION

A 26-year-old male prisoner begins a hunger strike to protest what he considers unfair prison
policies. He drinks only tap water, and his only exercise is two daily half-hour walks at
approximately 2.5 miles/hr. The temperature in his cell is maintained at 72 oF. His starting
weight is 70 kg (154 lbs), of which 14% is body fat. At the end of 4 weeks, he is urged by the
prison physician, family, friends, and his attorney to stop his fast because of his deteriorating
condition.

1. What would you estimate his daily energy expenditure to be?

2. Approximately how much weight would he have lost in 4 weeks? What would be the
approximate distribution of this lost weight in carbohydrate, protein, and fat? In lean body
mass and adipose tissue? What would his respiratory quotient be at that time?
3. What changes in plasma levels of energy substrates would occur in the first 3 days of his
fast? What changes in urinary constituents would be expected?
4. On what immediate and on what ultimate sources of energy would brain metabolism
depend?
5. What early changes in plasma levels of hormones would occur? How would this regulate
his energy metabolism?
6. What other hormonal compensatory mechanisms would be called into play to conserve
energy and prolong life?

7. What physiologic events would occur when he stopped his fast by drinking a large
quantity of orange juice? What is the cause of this patient’s very high plasma glucose
level?

[ANSWER]

1. A typical, healthy adult man in the resting basal state expends approximately 20 kcal/kg,
which equals 1400 kcal/day in this person. Ordinary spontaneous movements would
account for another 300 to 400 kcal/day. His 1 hour of exercise would require
approximately 250 kcal. Thus his total daily energy expenditure might be approximately
2000 kcal initially. As fasting continued, his basal metabolic rate would diminish about
15% to approximately 1200 kcal/day and lethargy might also reduce both spontaneous
and voluntary physical movement. Thus, for the 4 weeks, his overall energy expenditure
could average 1800 kcal/day.

2. His total caloric needs for 28 days would be 56,000 endogenous kcal (1800 per day x 28
days). Ninety percent of this would be supplied by fat at 9 kcal/g. Thus, 0.9 x 56,000 ¡Â 9
equals 5600 g or 5.6 kg of fat. Adipose tissue is composed of 15% water. Hence, 5.6 ¡Â
0.85 or 6.6 kg of adipose tissue would be lost. Ten percent of the caloric needs would be
supplied by protein at 4 kcal/g. Thus, 0.1 x 56,000 ¡Â 4 equals 1400 g or 1.4 kg of protein
that would be lost. The source of this protein is lean body mass, which is composed of 72%
water. Thus, 1.4 ¡Â 0.28, or 5 kg, of lean body mass would be lost. Carbohydrate stores of
energy are very low and contribute no more than 0.3 to 0.4 kg, all in the first 2 days. Thus
the estimated total weight loss would be 6.6 plus 5, plus 0.4, or 12 kg. His respiratory
quotient would be slightly greater than 0.7 because of the predominance of fat as a
substrate for oxidation.

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3. Plasma glucose would decrease to a lower, but stable level after glycogen stores were
depleted. Plasma free fatty acids and glycerol would increase because of accelerated
lipolysis, and keto acids (beta-hydroxybutyrate and acetoacetate) would increase as a
result of increased free fatty acid delivery to the liver. Plasma branch chain amino acids
would increase because of increased proteolysis in muscle. Urinary nitrogen would
increase, indicating degradation of endogenous protein. Excretion of sodium in the urine
would promptly cease in the absence of sodium intake after a small fall in extracellular
fluid volume. Excretion of the predominantly intracellular electrolytes (potassium and
phosphate) would continue, indicating the loss of protoplasm.

4. Initially, the brain would be almost entirely dependent on glucose generated by

gluconeogenesis, mostly from amino acid substrates liberated by muscle proteolysis.
Gradually, however, keto acids generated by oxidation of free fatty acids would become
brain substrates and would eventually supply two thirds of the brain's energy needs. This
would help to conserve lean body mass during fasting.

5. Plasma insulin would decrease and plasma glucagon would increase. The lower ratio of
insulin to glucagon facilitates mobilization of liver glycogen, adipose tissue triglycerides,
and muscle protein.

6. Serum thyroid-stimulating hormone (TSH) and its response to thyrotropin-releasing

hormone (TRH) would decrease. In addition, serum triiodothyronine (T3) would decrease
because of reduced 5' monodeiodination of thyroxine (T4). The net result is a lower level
of the active T3 molecule, which contributes to the decrease in resting energy
expenditure. Cortisol secretion would increase modestly, facilitating muscle proteolysis
and gluconeogenesis. Growth hormone levels increase, facilitating lipolysis. However,
conversion of growth hormone to somatomedin would be greatly diminished. The loss of
somatomedin's stimulation of protein synthesis shunts amino acids away from anabolic
storage toward conversion to needed glucose. Maintenance of cortisol and elevated
growth hormone levels diminishes the sensitivity of muscle to insulin and further
preserves the glucose supply to the brain.

7. Ingestion of any source of carbohydrate would raise plasma glucose and thereby rapidly
stimulate insulin release and inhibit glucagon and growth hormone release. Glucose
oxidation would increase and thus raise the respiratory quotient. Storage of glucose as
glycogen in liver and muscle would be stimulated by insulin. At the same time, uptake of
potassium and phosphate by these tissues would be stimulated, causing a decrease in
their plasma levels. A sharp decrease in plasma free fatty acids, keto acids, and branch
chain amino acids would be expected as the high insulin levels reduced lipolysis,
ketogenesis, and proteolysis.