Chapter 8. Chapter 8: Protein-energy Malnutrition

Transcription

1 Chapter 8 Introduction to Nutrition and Metabolism, 3 rd edition David A Bender Taylor & Francis Ltd, London 2002 Chapter 8: Protein-energy Malnutrition Press the space bar or click the mouse to build each slide; when each slide is complete a hand will appear in the lower right corner to indicate that the next click will take you to the next slide. You are welcome to use or adapt this presentation for use in teaching, with due acknowledgement, but you may not publish it in any form without written permission.

2 Asia near East USA Ireland France Israel New Zealand UK Europe Australia Canada South Africa Japan Central America South America east and SE Asia India Africa Caribbean sub-saharan Africa Papua New Guinea Bangladesh MJ / day available Food available per head of population, MJ /d Food available per head of population, MJ /d

3 population, billions 12 World population growth, World population growth,

4 population, billions World population growth, World population growth, developed countries developing countries

5 rate /1000 World population growth birth and death rates World population growth birth and death rates developed developing least developed 0 birth death

6 Life expectancy in developed and developing countries Life expectancy developed developing least developed

7 Specific nutrient deficiencies: vitamin A 14 million children deficient 190 million people at risk Vitamin A deficiency Eastern Mediterranean 13m at risk, 1m deficient Americas 2m at risk, 0.1m deficient Africa 18m at risk, 1.3m deficient south-east Asia 138m at risk, 10m deficient western Pacific 19m at risk, 1.4m deficient WHO 1995

8 Specific nutrient deficiencies: iodine deficiency affects many millions of people Iodine deficiency Goitre was known as Derbyshire neck in Britain because of its (former) prevalence in Derbyshire inland upland areas over limestone Himalayas more than 90% of the population may have iodine deficiency goitre in these areas Brazil central Africa

9 Iron deficiency anaemia affects many millions of women in developed and developing countries Iron deficiency anaemia normal blood iron deficiency anaemia

10 Protein-energy malnutrition Protein-energy malnutrition Generally inadequate food intake as opposed to specific nutrient deficiency Not specifically a deficiency of protein lack of metabolic fuels dietary protein is used as an energy source tissue protein synthesis is reduced protein synthesis is energy expensive Protein synthesis can be increased by feeding just additional carbohydrate as an energy source.

11 Classification of protein-energy malnutrition in adults Body Mass Index = weight (kg) / height Classification of protein-energy 2 (m) malnutrition in adults BMI < 16 BMI severe protein-energy malnutrition moderately severe protein-energy malnutrition BMI moderate protein-energy malnutrition BMI desirable range

12 Starvation prolonged inadequate food intake Starvation prolonged inadequate food intake muscle and liver glycogen exhausted in < 24h increased ketogenesis from adipose tissue triacylglycerol increased catabolism of muscle protein for gluconeogenesis after 2 3 weeks: plasma ketone bodies high enough for significant utilization by cns now less need for muscle protein catabolism for gluconeogenesis when adipose tissue reserves are exhausted: much increased catabolism of muscle and other tissue protein as metabolic fuel death results from loss of essential tissue protein

13 glucose and ketone bodies, mmol /L fatty acids, mmol /L Plasma metabolic fuels in fed and fasting states Plasma metabolic fuels in fed and fasting states glucose ketone bodies fatty acids fed 40h fasting 7d starving

14 relative weight Weight changes with negative energy balance 1.1 Weight changes with negative energy balance as less food is eaten: decreased cost of digestion decreased cost of absorption decreased cost of synthesis of: triacylglycerol reserves glycogen reserves decreased protein turnover 0.6 theoretical as body weight decreases decreased BMR decreased cost of physical activity 0.5 time

15 Marasmus the predictable response to starvation Marasmus the predictable response to starvation - 1 very low adipose tissue reserves hence emaciation and wasting impaired protein synthesis high energy cost of protein synthesis protein catabolism is normal replacement is impaired decreasing muscle mass hence emaciation and wasting death follows from loss of essential tissue proteins

16 Marasmus the predictable response to starvation Marasmus the predictable response to starvation - 2 Impaired protein synthesis low synthesis of retinol binding protein functional vitamin A deficiency despite adequate reserves impaired synthesis of immunoglobulins greater susceptibility to infection mild infections may be ultimate cause of death loss of intestinal mucosa and flattening of villi impaired absorption of such food as is available diarrhoea

17 loss of intestinal mucosa and flattening of villi Loss of intestinal mucosa and flattening of villi Normal mucosa villi / mm 2 each mm long total absorptive surface of small intestine ~ 300 m 2

18 Marasmus causes of marasmus in developed countries Causes of marasmus in developed countries disorders of appetite anorexia nervosa and bulimia malabsorption food intolerance and allergy

19 Cancer cachexia and patients with AIDS Cancer cachexia and patients with AIDS Superficially similar to marasmus emaciation and wasting reduced food intake impairment of appetite distortion of sense of taste, nausea caused by drugs malabsorption chemotherapy and radiotherapy inhibit cell division loss of intestinal mucosa and villi

20 Cancer cachexia and patients with AIDS Hypermetabolism Hypermetabolism (increased metabolic rate) increased stimulation of mitochondrial uncoupling proteins (increased non-shivering thermogenesis) increased Cori cycle activity (anaerobic glycolysis in tumour, gluconeogenesis in liver) futile cycling of lipids

21 Hypermetabolism increased Cori cycle activity Hypermetabolism increased Cori cycle activity - 1 anaerobic glycolysis gluconeogenesis in liver glucose glucose glucose 2 ATP 2 ADP 2 NAD + 2 NAD + 2 NADH 2 NADH 4 ADP 4 ADP 2 GDP 4 ATP 4 ATP 2 GTP CH 3 C O COOH NADH NAD + 2 pyruvate CH 3 per glucose CHOH lactate dehydrogenasecooh lactate lactate NADH NAD + CH 3 CHOH COOH lactate CH 3 C O COOH pyruvate lactate dehydrogenase

22 Hypermetabolism increased Cori cycle activity Hypermetabolism increased Cori cycle activity - 2 stable weight weight loss hypermetabolic glucose oxidation Cori cycle

23 Hypermetabolism futile cycling of lipids Hypermetabolism futile cycling of lipids Stimulation of adipose tissue hormone-sensitive lipase (by small proteoglycan secreted by tumours that cause cachexia) Release of non-esterified fatty acids into circulation Re-esterification of fatty acids in liver and export in VLDL the reaction of acyl CoA synthase CH 3 (CH 2 )n COOH fatty acid CoASH ATP O CH 3 (CH 2 )n C SCoA fatty acyl CoA AMP + pyrophosphate A cost of 6 x ATP for each mol of triacylglycerol formed

24 Cancer cachexia increased nett protein breakdown Decreased synthesis and increased catabolism Cancer cachexia increased nett protein breakdown - 1 Decreased protein synthesis low energy availability and high ATP cost of protein synthesis (as in marasmus) depletion of tissue pools of amino acids: many tumours have high requirement for Glu and Leu increased gluconeogenesis from alanine (response to tumour necrosis factor a) depletion of Trp by increased indoleamine dioxygenase (induced by interferon-g) insulin resistance (tumour necrosis factor a impairs function of insulin receptor)

25 Cancer cachexia increased nett protein breakdown Decreased synthesis and increased catabolism Cancer cachexia increased nett protein breakdown - 2 Increased protein catabolism tumour necrosis factor a induces ubiquitin gene expression in muscle increases ubiquitin-dependent proteolysis proteoglycan secreted by tumours that cause cachexia increases protein catabolism mechanism unknown

26 Protein-energy malnutrition in children Protein-energy malnutrition in children - 1

27 Protein-energy malnutrition in children weight for age Protein-energy no malnutrition oedema in children oedema - 1 % of expected undernutrition kwashiorkor < 60 marasmus marasmic kwashiorkor kwashiorkor marasmus

28 Kwashiorkor in addition to emaciation and wasting: oedema, especially of arms and legs masks emaciation and wasting easy tissue damage can lead to gangrene Kwashiorkor - oedema

29 Kwashiorkor in addition to emaciation and wasting: fatty infiltration of the liver pot-bellied appearance Kwashiorkor fatty liver

30 Kwashiorkor in addition to emaciation and wasting: sunburn-like sooty dermatitis Kwashiorkor - dermatitis

31 Kwashiorkor in addition to emaciation and wasting: loss of hair colour and texture characteristically miserable appearance Kwashiorkor - hair

32 length for age, % of expected Kwashiorkor is not due to protein deficiency alone but to a lack of metabolic fuel (general food shortage) Protein deficiency Kwashiorkor leads is to not stunting due to protein of growth deficiency alone marasmus marasmic kwashiorkor kwashiorkor

33 Kwashiorkor is not due to protein deficiency alone but to a lack of metabolic fuel (general food shortage) Kwashiorkor - rehabilitation Examination of diets of children with kwashiorkor shows: protein as % energy intake is (just) adequate for maintenance total food intake is inadequate Rehabilitation with energy alone leads to resolution of oedema

34 Is kwashiorkor due to radical damage? frequently triggered Is kwashiorkor by infection due to radical damage? increased oxygen radical burden from macrophage action superimposed on deficiency of radical scavenging nutrients: carotene, vitamins C and E, selenium, zinc, copper

35 End Introduction to Nutrition and Metabolism, 3 rd edition David A Bender Taylor & Francis Ltd, London 2002 Chapter 8: Protein-energy Malnutrition End of presentation