[endoc. & Metab.] Starvation

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.

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