Chapter 8 Chapter 8: Protein-Energy Malnutrition

computing Chapter 8

Introduction to Nutrition and Metabolism, 3rd edition David A Bender Taylor & Francis Ltd, London 2002

Chapter 8: Protein-energy Malnutrition

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Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Food available per head of population, MJ /d 16 computing 1998 Food available per head of population, MJ /d 14 1961

Ireland MJ / day / MJ available

6 France

USA

Europe

Australia

Israel

Canada

NewZealand

Japan South Africa South

4 India

Africa

nearEast

Asia

Caribbean

South America South

CentralAmerica

Bangladesh sub-Saharan Africa sub-Saharan

2 eastAsia SE and Papua New Papua Guinea

population, billions population, 4

0 1800 1850 1900 1950 2000 2050 2100

7 developed countries developing countries 6

4 population, billions population, 3

0 1950 1975 2000 2025

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  World population growth – birth and death rates computing World population growth – birth and death rates

40 developed 35 developing 30 least developed 25

rate /1000 15

0 birth death

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  computing Life expectancy in developed and Life expectancy developing countriesdeveloped developing 80 least developed 70 74.5 60 62.4 50

40 50.6

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Specific nutrient deficiencies: computing  vitamin A  14 million children deficient Vitamin A deficiency  190 million people at risk

Eastern Mediterranean 13m at risk, 1m deficient

south-east Asia 138m at risk, 10m deficient

Africa western Pacific 18m at risk, 19m at risk, Americas 1.3m deficient 1.4m deficient 2m at risk, 0.1m deficient

WHO 1995

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Specific nutrient deficiencies: computing  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 more than 90% of the population may have iodine deficiency goitre in these areas

Himalayas

central Africa

Brazil

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  computing Iron deficiency anaemia affects many millions of women in developed and developing Iron deficiency countries anaemia

normal blood iron deficiency anaemia

http://pathy.med.nagoya-u.ac.jp/atlas http://pathy.med.nagoya-u.ac.jp/atlas

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Protein-energy malnutrition computing Generally inadequate food intake as opposed to specific nutrient deficiency Protein-energy malnutrition

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.

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Classification of protein-energy malnutrition in adults computing Body Mass Index = weight (kg) / height2 (m) Classification of protein-energy malnutrition in adults

BMI < 16 severe protein-energy malnutrition

BMI 16 - 17 moderately severe protein-energy malnutrition

BMI 17 - 18.4 moderate protein-energy malnutrition

BMI 20 - 25 desirable range

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Starvation – prolonged inadequate food intake computing 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

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Plasma metabolic fuels in fed and fasting states computing Plasma metabolic fuels in fed and fasting states

6 1.2

5 1

4 0.8

3 0.6

2 0.4 fatty acids, mmol /L mmol acids, fatty glucose 1 ketone bodies 0.2

glucose and ketone bodies, mmol /L mmol bodies, ketoneandglucose fatty acids 0 0 fed 40h fasting 7d starving

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Weight changes with negative energy balance computing 1.1 Weight changes with negative energy balance

0.9 as less food is eaten:  decreased cost of digestion  decreased cost of absorption 0.8  decreased cost of synthesis of:  triacylglycerol reserves

relativeweight  glycogen reserves 0.7  decreased protein turnover

as body weight decreases  decreased BMR 0.6  decreased cost of physical activity theoretical

0.5 time

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Marasmus – the predictable response to starvation computing 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

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

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  loss of intestinal mucosa and flattening of villi computing Loss of intestinal mucosa and flattening of villi

Normal mucosa 20 – 40 villi / mm2 each 0.5 – 1.5 mm long total absorptive surface of small intestine ~ 300 m2

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Marasmus – causes of marasmus in developed countries computing Causes of marasmus in developed countries  disorders of appetite – anorexia nervosa and bulimia  malabsorption  food intolerance and allergy

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

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Cancer cachexia and patients with AIDS computing  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

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Hypermetabolism – increased Cori cycle activity computing 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 2 GTP 4 ATP 4 ATP

CH3 CH3 NADH NADH C O C O + NAD + COOH NAD COOH CH pyruvate 2 pyruvate CH3 3 per glucose CHOH lactate CHOH lactate lactate COOH dehydrogenaseCOOH dehydrogenase lactate lactate

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Hypermetabolism – increased Cori cycle activity computing Hypermetabolism – increased Cori cycle activity - 2 1000 glucose 900 oxidation 800 700 Cori cycle 600 500 400 300 200 100 0 stable weight weight loss hypermetabolic

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Hypermetabolism – futile cycling of lipids computing  Stimulation ofHypermetabolism adipose tissue hormone – futile-sensitive cycling lipaseof lipids (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

CH3 (CH2)n COOH fatty acid

CoASH ATP AMP + pyrophosphate O A cost of 6 x ATP CH3 (CH2)n C SCoA for each mol of triacylglycerol formed fatty acyl CoA

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Cancer cachexia – increased nett protein breakdown Decreased synthesis and increased catabolism computing 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)

Cancer cachexia – increased nett protein breakdown Decreased synthesis and increased catabolism computing 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

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Protein-energy malnutrition in children computing weight for age Protein-energyno malnutrition oedema in children oedema- 1 % of expected 60 - 80 undernutrition kwashiorkor < 60 marasmus marasmic kwashiorkor

marasmus kwashiorkor

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Kwashiorkor – in addition to emaciation and wasting: computing oedema, especially of arms and legs  masks emaciation Kwashiorkor and wasting - oedema  easy tissue damage can lead to gangrene

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Kwashiorkor – in addition to emaciation and wasting: fatty infiltration of the liver computing  pot-bellied Kwashiorkor appearance – fatty liver

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Kwashiorkor – in addition to emaciation and wasting: sunburn-like sooty dermatitis computing Kwashiorkor - dermatitis

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Kwashiorkor – in addition to emaciation and wasting: loss of hair colour and texture computing characteristically miserable Kwashiorkor appearance - hair

100

86 84.5 92 length for age, % age, expected of for length 70 marasmus marasmic kwashiorkor kwashiorkor

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd  Kwashiorkor is not due to protein deficiency alone but to a lack of metabolic fuel (general food shortage) computing Examination of dietsKwashiorkor of children with - rehabilitation 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

 frequently triggeredIs 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

Introduction to Nutrition and Metabolism, 3rd edition David A Bender Taylor & Francis Ltd, London 2002

Chapter 8: Protein-energy Malnutrition End of presentation