1. Luigi Greco - Faculty of Medicine of the University of Gulu Physiopathology of Malnutrition CALORIC EQUILIBRIUM : Meal energy stored into High Energy Phosphates, Fat and Glycogen Stores are mobilized daily during : –fasting –Increased energy expenditure (cold, activity, disease) –NO STORES = reduction of nutrients demand, no chances to meet extra demands and reduction of activities down to MAX ADAPTATION

2. Luigi Greco - Faculty of Medicine of the University of Gulu Schwartz, M. W. et al. N Engl J Med 1997;336:1802-1811 Hypothetical Model for the Coupling of Starvation to the Compensatory Response That Serves to Restore Lost Weight

3. Luigi Greco - Faculty of Medicine of the University of Gulu Schwartz, M. W. et al. N Engl J Med 1997;336:1802-1811 Hypothetical Model for the Interaction of Insulin and Leptin with Hypothalamic Neuropeptide Y and Corticotropin-Releasing Hormone (CRH), Neuropeptides That Can Stimulate the Hypothalamic-Pituitary-Adrenal Axis

4. Luigi Greco - Faculty of Medicine of the University of Gulu Schwartz, M. W. et al. N Engl J Med 1997;336:1802-1811 Model to Explain the Differences between Neuroendocrine Responses during Active Weight Loss and Those during the Maintenance of Stable, Reduced Weight in an Obese Person

5. Luigi Greco - Faculty of Medicine of the University of Gulu Adaptation to Restriction of Calories and/or Proteins Adaptation to the lowest metabolic equilibrium : –Susceptibility to infections, overall fragility to offenses –Functional alterations correlate with protein depletion –Hormonal-mediated adaptation –Fat mobilization from adipose tissue

6. Hormonal Adaptive Mechanism HormoneStimulusResultsCalorie depriv Protein depriv Insulin Glucose Amino acids Protein synthesis (muscle) Growth Decreased Growth Hormone Glucose Amino acids Lipogenesis Protein synthesis (body) Glucocortucoids Glucose Amino acids Growth Lipolysis Urea synthesis Protein turnover (viscera) Variable, generally normal Increased Variable, generally normal Thyroid Hormones Energy metabolism Neoglucogenesis Lipolysis Energy homeostasis Protein turnover Decreased

7. Luigi Greco - Faculty of Medicine of the University of Gulu Nucleo arcuato PY Y GHrelin a PY Y

8. Luigi Greco - Faculty of Medicine of the University of Gulu Initial Phase of PCM Decreased physical activity Lower basale energy expenditure Decreased fat body mass and then lean body mass Muscle catabolism  release amino acids Progression of PCM Decreased lean body mass (non fatty mass) Energy expenditure adequate to the lean body mass Faster decrease of lean body mass (no feed back)

9. Luigi Greco - Faculty of Medicine of the University of Gulu Protein Deficit Decrease in the protein Synthesis (altered amino acid proportions) Catabolism (altered Free Amino Acid Pool) Catabolism >>> Synthesis (Anabolism) Stop to any growth process No renewal of tissue (skin, intestinal mucosa, hairs ) Decreased protein turnover Altered distribution of proteins Albumin lower in tissue = oedema

10. Luigi Greco - Faculty of Medicine of the University of Gulu COMMON COMPLICATIONS INFECTIONS –Less Immunoglobulins –Impaired Cell-mediated immunity –Impaired tissues barrier protection –EFFECTS : –Increased energy demand –Anorexia –Tissue catabolism and destruction

11. Luigi Greco - Faculty of Medicine of the University of Gulu ADAPTATION TO PCM Sparing of body proteins Decreased body protein mass Decreased oxygen consumption Decreased demand of energy Reduction of total body K Decreased Hemoglobin : less O2 Slower cardiac activity : hypotension

12. Luigi Greco - Faculty of Medicine of the University of Gulu Physiological Consequences KIDNEY : decreased filtration, low urea Increased Na retention and total body water MUSCLE : wasting, reduced strenght, reduced capacity to purchase and eat food INTESTINE : impaired absorption Diarrhoea and malabsorption (fat, CH, proteins) CNS : Depression

13. Luigi Greco - Faculty of Medicine of the University of Gulu Severe Calorie Deficiency Hypoglicemia Hypotermia Impaired Circulatory function Impaired Renal function Acidosis Tissue breakdown and complication Coma and death

14. Luigi Greco - Faculty of Medicine of the University of Gulu Progressive Fatal Malnutrition LIVER : inability to synthetize –Albumin –Clotting factors –Transport Proteins –Haemorragic diathesis –Fatty Liver –Stress proteins and Cortisol –Jaundice

15. Luigi Greco - Faculty of Medicine of the University of Gulu