Metabolism, nutrition, and nutritional disorders

1. Metabolism, nutrition, and nutritional disorders Lecture 32 Friday, March 16, 2007 Refs. Medical Physiology Chapter 57 and Basic Pathology Chapter 8 p. 290-292, Ross Chapter 9

2. Metabolism terms • Metabolism refers to all chemical processes involved with energy (production, release, growth) • Catabolic- break down • Anabolic- synthesis • Resting metabolic rate • 30 kcal/kg/day • e.g. a 70 kg (154#) person requires 2100 kcal/day • Basal metabolic rate • Conditions: thermal neutral, fasted 12 hr, rested 1hr, after a night of sleep, no stimuli • Units are kcal/hr/m2 body surface • BMR<RMR • BMR is ~ 5% higher in males; decreases with age

3. Energy balance • Obeys laws of thermodynamics: • 1. Total energy is constant. energy input = energy output + storage • Positive energy balance. input>output, weight gain • Negative energy balance. output>input, weight loss • 2. All chemical transformations result in loss of free energy (E = G + TS and TS >0). • Chemical reactions are never 100% efficient. • Energy from transformations is conserved in high energy bonds. • Conversion of ADP to ATP requires 11.5 kcal/mole • 1 mole of glucose in bomb calorimeter yields 686 kcal • 1 mole of glucose in cell ~400 kcal + 286 kcal as heat

4. Energy storage • Energy from foods is stored in 2 ways: • Glycogen- a branched polymer of glucose • Liver • Skeletal muscle • Insulin-dependent uptake of glucose • Glycogenolysis releases glucose to be used in muscle • Triglycerides- major storage form of lipids • Adipose tissue • Muscle • Hepatocytes • Human cannot convert fatty acids to glycogen or protein. • Lipoprotein lipase (LPL) of endothelial cells that hydrolyzes triglycerides of chylomicrons is different from hormone-sensitive lipase in adipocytes (HSL).

5. Energy release • Skeletal muscle • Epinephrine stimulates glycogenolysis via beta receptor • Resulting G6P is used in glycolysis in muscle fiber • Liver • Glucagon triggers glycogenolysis. • Glucose can be released into blood. • Nerve cells depend almost entirely on blood glucose • Liver can also produce glucose by gluconeogenesis from amino acids, lactate, glycerol, and pyruvate. • Adipocytes • Hormone-sensitive lipase (HSL) releases FFA • Epinephrine and growth hormone stimulate lipolysis • Insulin inhibits HSL.

6. Nutritional requirements • No absolute daily requirement for carbohydrates or fat • Essential fatty acids are linoleate (18:2) and linolenate (18:3) • Daily requirement for protein is typically 0.8 g/kg • Requirements are higher for pregnant women, athletes, postsurgical patients, and children • In children, requirement for first 6 months is 2g/kg. • The diet must contain the 9 essential amino acids (T, K, I, L, H, M, F, V, W) • Proteins are scored by the amount of the essential amino acid present in the lowest amount.

7. Malnutrition • Primary malnutrition • Inadequate intake of calories for energy, essential amino acids, essential fatty acids, vitamins and/or minerals • Secondary or conditional malnutrition • Intake is adequate. • Problems with absorbing or using nutrients

8. Factors causing malnutrition • World -wide • Regional shortages due to environmental and/or political problems • In US • Ignorance • Poverty • Chronic alcoholism • Illness e.g. burns • Self-imposed restrictions

9. Protein-energy malnutrition (PEM) • Inadequate intake of calories and protein • Range of clinical syndromes • 2 functional protein compartments • Regulated differently • Somatic • Skeletal muscle mass • Visceral • Primarily liver

10. Clinical assessment of malnutrition • Weight:height ratios • comparison to normals for age/sex etc. • Measurement of upper arm • Muscle mass • Measures somatic compartment not visceral • Skin fold thickness • Subcutaneous fat • Serum proteins • Visceral compartment

11. Malnutrition syndromes in children • Malnutrition • Weight <80% normal • Marasmus • Weight <60% normal • Severe loss of skeletal muscle and body fat result in emaciated limbs. • Preservation of visceral protein • ~normal serum albumin • Kwashiorkor • Weight 60-80% normal, but part of weight is edema • Severe loss of protein from the visceral compartment • Relative sparing of subcutaneous fat and muscle mass

12. Comparison of marasmus and kwashiorkor • Kwashiorkor is a more severe form of malnutrition than marasmus. • They represent opposite ends of a spectrum with considerable overlap. • Both are associated with • Multiple vitamin deficiencies • Anemia • Immune deficiency especially T cell • Secondary infections add to catabolic state • Growth retardation/failure

13. Pathogenesis of kwashiorkor • Protein deprivation is relatively greater than reduction of total calories. This occurs when children are weaned to total carbohydrate diet. • Severe loss of protein in visceral compartment. • Decreased serum albumin causes edema. • Enlarged, fatty liver due to lack of carrier proteins. • Skin lesions- alternating zones of hyper/hypopigmentation, desquamation. • Small intestine atrophies- decreased mitotic index, loss of villi and microvilli

14. Signs in kwashiorkor • Children become listless and apathetic. • Loss of appetite. • Do not respond well at first to feeding. • Often fatal.

15. Secondary PEM • Common in chronically ill and hospitalized patients (Table 8-12) • Marasmus-like syndrome • Chronic lung disease, advanced cancer etc. • Muscle wasting, loss of fat • Kwashiorkor-like syndrome • Burns, severe trauma, sepsis • Low serum albumin, normal fat and muscle • Less severe form in patients with protein-losing enteropathy and nephrotic syndrome

16. Cachexia versus starvation • Cachexia- severe PEM in chronically ill or cancer patients • Mediated by cytokines- TNFa, IL-1, IL-6, IFN-g and other factors • May occur before anorexia • In cachexia, basal metabolic rate is increased • In starvation, basal metabolic rate is decreased.

17. Starvation • Depletion of glycogen occurs first • Liver and muscle can store up to 700 g or 3000 kcal • Depletion of fat follows glycogen • Body stores are much larger about 131,000 kcal • Depletion of protein is rapid at first • about 1/2 is easily mobilized ~ 20,000 kcal • gluconeogenesis • Theoretical survival time is over 2 months • Survival time shorter than predicted due to vitamin deficiencies • Ketone bodies produced by b-oxidation of fatty acids can be used as fuel by CNS. • Acetone, acetoacetic acid, and b-hydroxybutyric acid

18. Anorexia nervosa and bulimia • Anorexia nervosa = self-induced starvation • Usually young women with obsession with thinness • Signs of severe PEM and endocrine effects: • Amenorrhea due to lack of GnRH • Decreased thyroid hormone • Decreased bone density (low estrogen) • Anemia and lymphopenia • Susceptible to cardiac arrhythmias and sudden death • Bulimia- Patient binges on food then induces vomiting • Usually weight and hormone levels are near normal. • May develop electrolyte disturbances (hypokalemia). • Cardiac arrhythmias, aspiration, gastric/esophageal rupture

19. Essential Minerals • Ca 800-1200 mg bone • Cr 50-200 µg ? cofactor • Cu 1.5-3 mg enzyme cofactor • Fe 10 mg (15) Hb and cytochromes • I 150 µg thyroid hormones • Mg 350 mg (280) complexes with ATP • Mn 2-5 mg antioxidant • Mo 75-250 µg cofactor • P 800-1000 mg bone • Se 70 µg (55) antioxidant • Zn 15 mg (12) antioxidant, cofactor

20. RDA for minerals and vitamins • Scientific evidence is not available for levels of many minerals and vitamins. • Problems in determining RDA: • Natural deficiencies are often multiple. • Physiologic functions not completely known. • Assays to determine deficiency are not available. • Interactions between different minerals and vitamins. • Redundancy of some minerals and vitamins. • Recommendations are based on a combination of balance studies and usual dietary intake. • Absorption may vary with intake, e.g. copper. • Revisions are frequent.

21. Vitamins • 13 vitamins are required by humans (Table 57-6) • Deficiencies of a single vitamin are uncommon • Primary deficiency- lack in diet • Secondary deficiency- inability to absorb, transport, or convert • Fat-soluble vitamins • Four: A, D, E, and K • Readily stored in body- have reserves • Ability to absorb depends on fat digestion and absorption. • Excess quantities can be toxic. • Water-soluble vitamins • Nine: Thiamine (B1), riboflavin (B2), niacin (B3), pyridoxine (B6), B12, C, folate, pantothenic acid, and biotin. • Excess water soluble vitamins are excreted in the urine.