Malnutrition 
                                                                                                                                 Topic 5 
                     
                     
                    Module 5.1  
                     
                    Undernutrition – Simple and Stress Starvation                                                               
                                                                                                                            Lubos Sobotka 
                                                                                                                             Peter Soeters 
                                                                                                                                Remy Meier 
                                                                                                                            Yitshal Berner 
                                                                                                                                               
                              
                    Learning Objectives 
                     
                    •    To know how the body reacts to short-term and long-term starvation during non-stress 
                         conditions; 
                    •    To understand the difference between simple and stress starvation; 
                    •    To know the consequences of stress on metabolic pathways related to starvation. 
                     
                    Contents 
                     
                    1.     Definition and classification of malnutrition 
                    2.     Undernutrition 
                    3.     Aetiology of undernutrition  
                    4.     Adaptation to undernutrition – non stress starvation  
                    5.     Stress starvation  
                    6.     Summary  
                     
                    Key Messages 
                     
                    •    Humans adapt well to short or a longer-term starvation, using their reserve stores of 
                         carbohydrates, fat and protein;  
                    •    Reduction of energy expenditure and conservation of body protein are further reaction to 
                         starvation. Energy stores are replenished during feeding period; 
                    •    Long-term partial or total cessation of energy intake leads to marasmic wasting; 
                    •    With the addition of the stress response, catabolism and wasting are accelerated and the 
                         normal adaptive responses to simple starvation are overridden; 
                    •    Weight loss in either situation results in impaired mental and physical function, as well as 
                         poorer clinical outcome.  
                                                            Copyright © 2006 by ESPEN
                1. Definition and classification of malnutrition 
                 
                Malnutrition can be defined as a state of nutrition in which a deficiency or excess (or imbalance) of 
                energy, protein and other nutrients causes measurable adverse effects on tissue/body form (body 
                shape, size, composition), body function and clinical outcome.  
                In broad term, malnutrition 
                includes not only protein-energy 
                malnutrition (both over- and under-      Classification of energy and protein malnutrition
                nutrition) but also malnutrition of 
                other nutrients, such as 
                micronutrients.                                            Malnutrition
                Malnutrition of micronutrients can 
                cause deficiency states or toxic 
                symptoms - these are discussed in           Overnutrition             Undernutrition
                particular modules related to 
                vitamins and trace elements.  
                                   
                                                              Obesity      Marasmus         Kwashiorkor
                                                                                            or kwashiorkor-like 
                                                                                            malnutrition    
                                   
                            Fig. 1 Classification of 
                            energy and protein 
                            malnutrition  
                 
                The most widely used classification of malnutrition is based on calculation of body mass index (BMI) 
                – see Table 1. 
                 
                Table 1  Classification of malnutrition according to body mass index 
                (Body mass index (BMI) = weight (kg) / body height2 (m2)) 
                                         2
                 Body mass index (kg/m ) Classification 
                 Less than 18.5                Severely underweight 
                 Less than 20                  Underweight 
                 20 to 25                      Desirable or healthy range 
                 Over 25 to 30                 Overweight 
                 Over 30 to 35                 Obese (Class I) 
                 Over 35 to 40                 Obese (Class II) 
                 Over 40                       Morbidly or severely obese (Class III) 
                 
                2. Undernutrition 
                 
                Undernutrition can be defined as a state of nutrition deficiency, which is connected with adverse 
                consequences on physical functions or clinical outcome. Usually BMI < 20 kg/m2 identifies high 
                probability of undernutrition. However, individuals with BMI > 20 kg/m2  may be at risk of 
                undernutrition when losing unintentionally more than 10% weight loss over 3-6 months. In opposite 
                weight stable healthy individuals with a BMI < 20 kg/m2 can be without any functional changes 
                related to malnutrition.  
                Risk of undernutrition related clinical and functional problems can be predicted using nutrition 
                screening tool (see module 3.1).  
                 
                3. Aetiology of undernutrition  
                 
                Undernutrition results from an imbalance among nutrient intake and nutrient needs. The rapidity, 
                severity and clinical outcome of undernutrition are dependent on: 
                •   difference between energy intake and energy expenditure;  
                                                 Copyright © 2006 by ESPEN
                    •    nutritional status and energy reserves at the onset of the undernutrition - theoretical energy 
                         reserves are shown in Table 2; 
                    •    extend of adaptive processes to the undernutrition; 
                    •    potential incidence of stress response (e.g. inflammation, bleeding, surgery) during a period of 
                         undernutrition. 
                     
                    Table 2  The theoretical reserves of a 74 kg man although survival is unusual 
                    when fat content is reduced below 3 kg and protein is depleted by more than 
                    50% (Hill 1992) 
                    Body substrate                            Substrate weight                    Energy content 
                                                                     ( kg )                           ( kcal ) 
                                                                                                            
                    Fat                                               15                               141.000 
                    Protein 12 48.000 
                    Glycogen (muscle)                                 0.5 2000 
                     
                     
                    Glycogen (liver)                                  0.2                                800 
                    Glucose (extracellular fluid)                    0.02                                 80 
                                                                                                            
                                                                         
                    Total                                                                              191.880 
                     
                     
                    The main factors that lead to undernutrition are:  
                    •    disease;  
                    •    social and psychosocial factors.  
           
                    Disease-related factors which lead to undernutrition 
                    •    insufficient food/nutrient intake (anorexia, taste disturbances, nausea, vomiting, treatment-
                         induced side effects, eating and swallowing difficulties); 
                    •    impaired nutrient digestion and absorption (especially in gastrointestinal diseases); 
                    •    increased requirements for nutrients (sepsis, trauma, endocrine disease);  
                    •    increased losses (e.g. from wounds, malabsorption and intestinal losses); 
                    •    catabolism.  
                     
                    Social and psychological factors which lead to undernutrition 
                    •    problems with shopping or preparing meals; 
                    •    anxiety; 
                    •    depression; 
                    •    poverty; 
                    •    lack of suitable or enjoyable food; 
                    •    environmental factors (nursing homes etc.);  
                    •    inadequate catering practices; 
                    •    anorexia nervosa; 
                    •    hunger strikers. 
                     
                    Metabolic consequences of undernutrition are dependent on clinical conditions (adaptive changes of 
                    presence of stress, sepsis or critical illness).  
                     
                    4. Adaptation to undernutrition – non-stress starvation 
                     
                    Development of adaptive mechanisms to food shortage was necessary for survival of famine periods. 
                    These adaptive changes allow to healthy subjects of normal initial body composition to survive more 
                    than two months of total starvation.  
                     
                     
                                                            Copyright © 2006 by ESPEN
                         Short starvation (< 72 hours)  
                         Short period of starvation is connected with:  
                         •     diminished insulin and increased glucagon and catecholamine secretions; 
                         •     increased glycogenolysis and lipolysis;  
                         •     hydrolysis of triglycerides in adipose tissue releases fatty acids (FFAs) and glycerol into the 
                               circulation; 
                         •     increased gluconeogenesis from amino acids after depletion of glycogen stores. 
                                                                                                                                      
                                                                                                                                      
                                          Uncomplicatedfasting (12-24 hours)                                                          
                                                                                                                                      
                                                                                                                                      
                                                                                                                                      
                                                                                             periphery                                
                                                                                                                                      
                                                                                                                                      
                                                                                 glucose                                              
                                                               glucose            glucose              
                                                               glucose                                                                
                                                               140 g            100-200 g
                                                               140 g            100-200 g                     FA + 
                                                                                                              FA +                    
                                                                                                              glycerol
                                                                                                              glycerol                
                                                    AA 75 g             gluconeo-   glycogen
                                                    AA 75 g             genesis                                                       
                                                                   liver                                                              
                                                                                     FA 40 g +           fat                          
                                                                                     FA 40 g +                                       Fig. 2 Metabolic fluxes during 
                                                                                     glycerol
                                                                                     glycerol                                        short term simple starvation 
                                                                                                                                     (non stress conditions). 
                          
                          
                         Prolonged starvation (> 72 hours) 
                         Beyond 72 hours starvation is connected with:  
                               •     further decrease in insulin level; 
                               •     glycogen stores depletion; 
                               •     reduction of energy expenditure related to physical activity;   
                               •     decline in resting metabolic rate by 10-15%; 
                               •     increased β-oxidation of fatty acids;  
                               •     increased production of ketone bodies in the liver;  
                               •     adaptation of the brain to using ketones as energy fuel;   
                               •     reduction in net tissue protein catabolism. 
                          
                         During simple starvation albumin concentration is unchanged, although plasma proteins with a 
                         shorter half-life may be decreased. 
                                                                                                                                  
                                                                                                                                  
                                             Uncomplicatedfasting (7 days)                                                        
                                                                                                                                  
                                                                                                                                  
                                                                                                                                  
                                                                                         periphery                                
                                                                                                                                  
                                                                                          ketone                                  
                                                                        ketone            ketone 
                                                            glucose     ketone                                                    
                                                            glucose                       bodies + 
                                                                        bodies            bodies + 
                                                              60 g      bodies
                                                              60 g                        glucose
                                                                         66 g             glucose                                 
                                                                         66 g                            FA + 
                                                                                                         FA +                     
                                                                                                         glycerol
                                                                                                         glycerol                 
                                                 AA 20 g               ketogenesis
                                                 AA 20 g      gluconeo-                                                           
                                                              genesis                                                             
                                                              liver             100 g FA + 
                                                                                100 g FA +            fat                        Fig. 3 Metabolic fluxes during 
                                                                                 glycerol
                                                                                 glycerol                                        long term simple starvation (non 
                                                                                                                                 stress conditions). 
                                                                             Copyright © 2006 by ESPEN