Why Kwashiorkor Is Critical In Sick Patients?

Lecturer : Dr. Ongko Susetia Totoprajogo MNs, Sp.GK

Group 7 Group Coordinator : Dwi Auliya Tyas P. Group Member : 1. Ilmi Dewi Astuti 2. Indah Nur Qurani 3. Intan Rakhma K. 4. Farikha Alfi Fairuza 5. Geryna Puspitasari 6. Putri Mamluatun N. 7. Masyrotut Taqwiyah 8. Sharira Ramadhani (125070300111013) (125070300111044) (125070300111052) (125070301111007) (125070301111016) (125070305111001) (125070307111014) (125070307111020) (125070300111001)

Nutrition Biomolekuler 2013

TABLE OF CONTENT

COVER..i TABLE OF CONTENTii INTRODUCTION 1.1 Background of the Study..1 1.2 Objectives.1 DISCUSSION 2.1 Definition of Malnutrition3 2.2 Kwashiorkor.3 2.3 Pathophysiology of Severe Acute Malnutrition (Kwashiorkor)...3 2.4 Sources of Malnutrition and Nutrient Deficiencies..5 2.5 Immune-modulating Enteral Nutrients : Arginine6 2.6 Increased Oxidative Damage...7 2.7 Nutrient Synergy in Patients with Risk of Infectious Disease.7 SUMMARY.9 REFERENCES..10

CHAPTER I INTRODUCTION

1.1 Background of the Study Malnutrition is an important public health issue particularly for children under five years old which have higher risk of mortality and morbidity than well nourished one. Deficiencis of macronutrients and micronutrients are one of the major cause of the childhood death every years in low and middle income countries. The first major cause of malnutrition is immediate causes, which is inadequate food intake and disease. Immediate causes is factor that directly affect malnutrition. Inadequate food intake and disease create a vicious cycle in which disease and malnutrition exacerbate each other, which known as the MalnutritionInfection Complex. Kwashiorkor is a form of severe acute protein-energy malnutrition caused by inadequate intake of protein with reasonable caloric intake. The characteristics of kwashiorkor are pitting edema and fluid accumulation, loss of appetite, brittle thinning hair, hair colour change, apathetic and irritable, and swollen face. Patients diagnosed with kwashiorkor are extremely malnourished and at a great risk of death. Since disease is an immediate causes of malnutrition, especially kwashiorkor, need a further discussion to explain why kwashiorkor are critical to ill patients. Patients with chronic disease susceptible to kwashiorkor because there are so many factors that affect their food intake such as appetite, immune system etc. Meanwhile patients that diagnosed with kwashiorkor have a high risk of infection, decreased immune and inflammation leading to an acute disease. For example, people with kwashiorkor have free iron in their blood that can lead to bacteria that are not normally invasive, such as Staphylococcus epidermidis, and another bacteria to translocate and causing systemic infection or septicaemia. Therefore, a treatment that can recover an ill patient is not only one that is able to heal the disease but also give adequate intake of macronutrients and micronutrients that the body required to support the recovery patients. A screening and early assessment of nutritional status of hospitalized in-patient also very important to diagnose whether he or she has the characteristic of kwashiorkor and to control the nutritional status in normal condition persistently.

1.2 Objectives The objectives of this presentation is to understand : 1. What is Kwashiorkor ? a. Definition of Kwashiorkor b. Pathophisiology of Kwashiorkor

2. Sources of Malnutrition and Nutrient Deficiencies 3. Immune-modulating Enteral Nutrients: Arginine 4. Increased Oxidative Damage 5. Nutrient Synergy in Patient with Risk of Infectious Disease

CHAPTER II DISCUSSION

2.1 Definition of Malnutrition Malnutrition is defined as a state in which the physical function of an individual is impaired to the point where he/she can no longer maintain adequate bodily performance processes such as growth, pregnancy, lactation, physical work, and resisting and recovering from disease.

2.2 Kwashiorkor The word "kwashiorkor" comes from the Ga language of West Africa and can be translated as "disease of the displaced child" because it was commonly seen after weaning. The presence of peripheral edema distinguishes children with kwashiorkor from those with marasmus and nutritional dwarfism. Kwashiorkor is the commonest and most widespread nutritional disorders in developing countries. It occurs in areas of famine or areas of limited food supply, and particularly in those countries where the diet consists mainly of corn, rice and beans. It is more common in children than in adults. The onset in infancy is during the weaning or post-weaning period where protein intake has not been sufficiently replaced. Kwashiorkor occurs when there is physiologic stress, such as an infection, in an already malnourished child. This explains why kwashiorkor is an acute illness compared with the chronicity of undernutrition alone and why there is overlap between marasmus and kwashiorkor. Kwashiorkor is characterized by leaky cell membranes, which permit the movement of potassium and other intracellular ions into the extracellular space. The increased osmotic load in the interstitium causes water movement and edema. Severe acute malnutrition is often a life-threatening condition. These patients are very fragile, often with a serious electrolyte imbalance. They do not always present with the typical symptoms of an illness (e.g. fever, rapid pulse or rapid respirations). Also, it can be very difficult to diagnose dehydration or anaemia however it is extremely important to do so accurately. A misdiagnosis can lead to a high risk of mortality.

2.3 Pathophysiology of Severe Acute Malnutrition (Kwashiorkor) Severe acute malnutrition can result in profound metabolic, physiological and anatomical changes. Virtually all physiological processes are altered due to severe acute malnutrition. Every organs and systems are involved in reductive adaptation. Reductive adaptation is the physiological response of the body to under nutrition i.e. systems slowing down to survive on limited macro and micro-nutrients intake.

Cardiovascular system: Cardiac muscle mass decreases and is accompanied myofibrils. Bradycardia (heart rate can decrease to less than 40 beats/min) Cardiac output and stroke volume are reduced. Infusion of saline may cause an increase in venous pressure. Any increase in blood volume can easily produce acute heart failure.47 Any decrease will further compromise tissue perfusion. Blood pressure is low. Renal perfusion and circulation time are reduced. Plasma volume is usually normal and red cell volume is reduced. Gastro-intestinal system Production of gastric acid is reduced. Intestinal motility is reduced. Pancreas is atrophied and production of digestive enzymes is reduced. Small intestinal mucosa is atrophied; secretion of digestive enzymes is reduced. Absorption of nutrients is reduced. The abdomen may become protuberant because distension. Liver function Synthesis of all proteins is reduced. Abnormal metabolites of amino acids are produced. Capacity of liver to take up, metabolize and excrete toxins are severely reduced. of hypomotility and gas by fragmentation of

Energy production from substrates such as galactose and fructose is much slower than normal. Gluconeogenesis is reduced, which increases the risk of hypoglycemia during infection. Bile secretion is reduced. Lungs Function Respiratory muscle function is altered by malnutrition, as evidenced by a decrease in vital capacity, tidal

volume, and minute ventilation. Kidney Function There is a decrease in kidney weight, glomerular filtration rate, the ability to excrete acid, the ability to excrete sodium, and to concentrate urine. Mild proteinuria may also occur. Genitourinary system Glomerular filtration is reduced. Capacity of kidney to excrete excess acid or a water load is greatly reduced. Urinary phosphate output is low. Sodium excretion is reduced. Urinary tract infection is common. Immune system All aspects of immunity are diminished. Lymph glands, tonsils and the thymus are atrophied Cell-mediated (T-cell)

immunity is severely depressed. IgA levels in secretions are reduced. Complement components are low. Phagocytes do not kill ingested bacteria efficiently. Tissue damage does not result in inflammation or migration of white cells to the affected area.

 Acute phase immune response is diminished. Typical signs of infection, such as an increased white cell count and fever, are frequently absent. Hypoglycaemia and hypothermia are both signs of severe infection and are usually associated with septic shock. Endocrine system Insulin levels are reduced and the child has glucose intolerance. Insulin growth factor 1 (IGF-1) levels are reduced.

Growth hormone levels are increased. Cortisol levels are usually increased. Circulatory system Basic metabolic rate is reduced by about 30%. Energy expenditure due to activity is very low. Both heat generation and heat loss are impaired; the child becomes hypothermic in a cold environment and hyperthermic in a hot environment.

2.4 Sources of Malnutrition and Nutrient Deficiencies Malnutrition is not always synonymous with the state of starvation seen in many places in the world. Most often, malnutrition is caused by an inadequate or imbalanced diet and unhealthy lifestyle common in the developing world, as well as among apparently wellnourished people living in western economies. Another face of malnutrition is evidenced in people who suffer from diseases, such as cancer, and by patients who undergo various medical treatments or surgeries. In many cases, they develop micro-malnutrition related particularly to vitamins and other specific micronutrients. These deficiencies are asymptomatic and can go unnoticed for a long period of time. Unfortunately, disease therapies focus on pharmacology and proper nutrient supplementation is rarely addressed. Such malnutrition relating to micronutrients further weakens the functions of the body, making patients susceptible to various opportunistic infections and impairing their recovery. In this situation, ignoring or not recognizing nutrient deficiencies as the source of the impairment of immune function has detrimental consequences and further facilitates immune deficiency problems. Malnutrition, unhealthy diets deficient in micronutrients, and micronutrient imbalances can disrupt the function of various immune system components. This weakens immune defense, decreasing its effectiveness in the elimination of pathogens and making patients vulnerable to various diseases.

2.5 Immune-modulating Enteral Nutrients : Arginine There are a number of conditionally essential pharmaconutrients, which become depleted during stress associated with surgery, trauma, and critical illness. These nutrients, are vital to maintenance of immune homeostasis as immune dysfunction is common in patients with nutritional deficits, particularly in patients following physical injury, such as trauma or surgical injury. A key example of this nutrient-induced immune dysfunction is the arginine deficiency known to develop in patients who have experienced surgery or trauma, as well as in malignancy settings. Results of recent investigations have helped elucidate how the function of the immune system is intimately linked to arginine metabolism. Arginine has long been known as a biosynthetic substrate for nitric oxide (a signaling molecule for immune and other cells). However, the improved understanding of the pathophysiology following physical injury indicated that immature cells of myeloid origin appear in circulation and in lymph tissues. These cells express arginase-1, a key enzyme in the degradation of arginine. Coupled with poor arginine intake and with an inadequate endogenous synthesis of arginine, arginase1 expression leads to a state of conditional arginine deficiency. The latter is associated with suppression of T-lymphocyte function; the cells synthesising arginase-1 are thus called myeloid-derived suppressor cells (MDSC). Dysfunction of T-lymphocytes after surgery or trauma is characterized by a decrease in the number of circulating CD4 cells; blunted T-cell

proliferation; production of IL-2 and interferon gamma; and loss of the zeta () chain, a peptide essential in the T-cell receptor complex. Results of several clinical studies showed that repletion of arginine, along with Omega-3 (-3) fatty acids, helps restore T-lymphocyte numbers and function, i.e. CD4 cell counts and IL-2 production. It also appears that dietary -3 fatty acids blunt the expression of arginase-1. Thus, substantial, but variable, evidence supports the concept that immunemodulating diets may exert their beneficial effects by restoring T-cell function that was impaired by MDSC-mediated arginine depletion. Arginine are easily found in every protein containing food with various ammount. High levels of arginine can be found in wheat, the material for flour. Appropriate medical care isnt just healing the infection and disease but also giving adequate nutrients the patients needed for metabolism and recovery.

2.6 Increased Oxidative Damage Edema is one of the symptoms of kwashiorkor patient. Potassium deficiency, dietary protein deficiency, hypoalbuminemia and renal electrolyte wasting are implicated with the pathogenesis of edema. Oxidative damage to cell membranes may also play a role in causing edema. Erythrocite membranes from people with kwashiorkor show increased susceptibility to oxidative stress and ion-pump dysfunction. Also, disruption in pathogens trigger oxidant production by white blood cells is one of the kwashiorkors clinical symptoms. People with serious systemic infection, for example cerebral malaria, are in high risk of kwashiorkor. The body cannot manage or even cannot absorb adequate calories and protein from the food. It makes the body dont have any storaged food inside and force it to use available protein and energy from muscle, adipose and another unappropriate resources. When the bodys protein are deficiency, which is it function is to maintain intracellular fluid stay in its place, the fluid start to move to the extracellular or interstitial and causing edema. The edema of kwashiorkor might result from increased cation permeability across cell membranes damaged by oxidant stress. The mortality in kwashiorkor patient with infection is higher than in other forms of malnutrition. Developing therapeutic strategies to improve the oxidant status of patients at risk for kwashiorkor may lower the number of death related with kwashiorkor cases.

2.7 Nutrient Synergy in Patients with Risk of Infectious Disease 1. Improves the synthesis and function of immune cells essential in preventing and eliminating infections. Nutrients used in the right combinations and proportions support optimum blood cell production in the bone marrow and lymphoid tissues. In addition,

they can modulate immune system mediators critical for eliminating pathological agents and controlling tissue damage. 2. Stops infectious agents from spreading. This new understanding of the power of micronutrients was initiated by the work of Matthias Rath, M.D. more than 10 years ago, who defined therapeutic targets common in various pathological conditions, including cancer and infectious diseases. Similar to cancer cells, all infectious agents destroy connective tissue to spread in the body. Nutrients support two critical mechanisms involved in infections : Building strong collagen and connective tissue, which helps create a natural barrier that is difficult to penetrate by the invader. Critical nutrients in this process include vitamin C, lysine, proline, vitamin B6, copper and manganese. Stopping the activity of enzymes that all infectious agents use to destroy connective tissue and facilitate their spread. Nutrients essential for controlling this enzymatic activity include vitamin C, lysine, N-acetyl cysteine (NAC) and Epigallocatechin Gallate (EGCG).

CHAPTER III SUMMARY

3. Summary Malnutrition is a state in which the physical function of an individual is impaired to the point where he/she can no longer maintain adequate bodily performance processes acute malnutrition and chronic malnutrition. Kwashiorkor is a form of severe acute protein-energy malnutrition caused by inadequate intake of protein with reasonable caloric intake. The characteristics of kwashiorkor are pitting edema and fluid accumulation, loss of appetite, brittle thinning hair, hair color change, apathetic and irritable, and swollen face. Malnutrition, unhealthy diets deficient in micronutrients, and micronutrient imbalances can disrupt the function of various immune system components. This weakens immune defense, decreasing its effectiveness in the elimination of pathogens and making us vulnerable to various diseases. Potassium deficiency, dietary protein deficiency, hypoalbuminemia and renal electrolyte wasting are implicated with the pathogenesis of edema. Improves the synthesis and function of immune cells essential in preventing and eliminating infections. Nutrients essential for controlling this enzymatic activity include vitamin C, lysine, Nacetyl cysteine (NAC) and EpigallocatechinGallate (EGCG).

REFERENCES Firani NK, 2012, The Lymphocites Number in The Blood of Kwashiorkor Rat Model Induced by Oral Immunization with 38-kDa Mycobacterium Tuberculosis Protein, World Academy of Science Engineering and Technology, page 165-166. Downloaded on September 29th 2013, at 20.30 WIB. Dr. Kimani F , 2009, National Guideline for Integrated Management of Acute Malnutrition, Ministry of Medical Services, page 4, 46-48 . Manary MJ, 2000, Increased Oxidative Stress in Kwashiorkor, Department of Pediatrics St. Louis Children Hospital and Department of Medicine Washington University School of Medicine, page 421-423. Downloaded on September 27th 2013, at 19.00 WIB. Niedzwiecki A, 2010, Malnutrition : The Leading Cause of Immune Deficiency Diseases Worldwide, Dr. Rath Research Institute, page 6; 10;13; 15. Wischmeyer PE, 2011, Malnutrition in The Acutely Ill Patient : Is It More Than Just Protein and Energy ?, SAJ Clinical Nutrition, page 54-55.