Overview, Causes and Manifestations of Marasmus (Severe Malnutrition 1)

Introduction

To maintain the physiological requirements of the body, it is essential to take a sufficient amount of micro and macronutrients; however, the overconsumption of micronutrients and macronutrients can also be harmful. As defined by the World Health Organization (WHO), malnutrition is an ‘inadequate or excess intake of protein, energy, and micronutrients such as vitamins, and the frequent infections and disorders that result’. The excess intake would be known as overnutrition, whereas an insufficient intake would be known as undernutrition.

Undernutrition can be further classified according to the cause and presentation. The term ‘protein-energy malnutrition’ refers to acute malnutrition as a result of an insufficient intake of protein and calories. This includes the conditions of kwashiorkor and marasmus. Acute malnutrition is an inadequate weight relative to vertical height. Severe acute malnutrition is further divided into two main categories: marasmus and kwashiorkor. Chronic malnutrition, otherwise known as growth stunting, is characterized by linear growth (length/height) below the average for age.

BioTalk on Overview, Causes and Manifestations of Marasmus.

A micronutrient deficiency refers to a deficiency of the essential vitamins and minerals which are needed for physiological function and development. The main micronutrient deficiencies in developing countries are iodine, vitamin A, iron, and zinc.

Kwashiorkor is a severe manifestation of protein-energy malnutrition. It is associated with a poor-quality diet high in carbohydrates but low in protein content such that the child may have a sufficient total energy intake. Severe protein insufficiency leads to characteristic bilateral pitting pedal edema and ascites.

Marasmus is a severe manifestation of protein-energy malnutrition. It occurs as a result of total calorie insufficiency. This leads to overt loss of adipose tissue and muscle. The child may have a weight-for-height value that is more than 3 standard deviations below the average for age or sex. A child with marasmus may develop pitting edema due to protein insufficiency, this is known as marasmic-kwashiorkor.

Etiology (Causes and Factors Responsible)

The underlying cause of marasmus is insufficient total calorie intake. However, it is important to understand what precipitates a reduced calorie intake in a person suffering from marasmus. Furthermore, the precipitating cause of a reduced-calorie intake may vary between adults and children. However, the causes of marasmus in both adults and children can be broadly divided into social and biological causes.

Precipitating Factors in Children

The underlying social cause of marasmus in children is poverty. Poverty may occur as a result of low status and insufficient education of mothers along with war, natural disasters, and civil instability. Poverty directly influences the ability of a household to secure a reliable source of food for children leading to an insufficient calorie supply. Unstable and unreliable childcare may occur in mothers that are unable to care for their children as a result of displacement, along with an unhygienic environment; this contributes to a higher frequency of infections such as diarrhea. In particular, the HIV/AIDS epidemic has been shown to create a significant burden of disease in South African households leading to reduced viability of agrarian livelihoods.

Maternal education is another key factor in the likelihood of childhood malnutrition occurring. Nairobi mothers with a primary level of education have been shown to have a 94% lower chance of growth stunting compared to mothers with no education.

Biological causes of malnutrition in children include HIV/AIDS and other infectious diseases, as mentioned earlier. Children who have been infected with HIV have poor nutritional outcomes compared to those who do not. Breastfeeding mothers who are infected with HIV also tend to have poor protein and micronutrient stores compared to those who are not infected with HIV.

Malaria is associated with poor growth and stunting in children below the age of 2 years but is not associated with protein-energy deficiency.

Precipitating Factors in Adults

Marasmus typically affects children; however, there are circumstances in which adults may also be affected.

There is a pattern of reduced intake of food with age, typically declining by 30% in males and 20% in females, otherwise known as physiological anorexia of aging. It is thought that physiological anorexia of aging occurs as a result of reduced satisfaction associated with food, which occurs due to a decrease in taste and olfaction abilities. Furthermore, with age, the rate at which ingested food reaches the antrum is increased along with decreased gastric emptying. The combination of reduced transit time to the antrum and decreased gastric emptying leads to early satiety. Depression is a common cause of anorexia in the elderly, especially those living in care homes.

Malabsorption may occur in adults. Typical causes of malabsorption in adults include coeliac disease and pancreatic insufficiency.

Epidemiology and Spread

Malnutrition is a particular public health problem throughout many countries in the developing world, especially those in Southern Asia and sub-Saharan Africa. Malnutrition is a direct cause of 300,000 deaths per year and contributes to fifty percent of deaths in young children. It is estimated that there are 852 million undernourished people worldwide, with the majority (815 million) in undeveloped countries. In particular, it is thought that there are 18 million children living in low-income or middle-income countries that are suffering from marasmus with the majority in Asia.

Pediatric malnutrition is frequently associated with pediatric hospitalization in the developing world and is associated with mortality rates up to 20%.

Malnutrition-associated mortality tends to have a seasonal fluctuation such that it is highest during the pre-harvest rainy season as a result of food scarcity and increased burden of infectious diseases.

It is estimated that 155 million children below the age of 5 suffered from growth stunting in 2016, 52 million suffered from wasting, and of these, 17 million children suffered from severe wasting.

Gender

Marasmus is equally distributed between the genders, however, as a result of cultural differences in some parts of the world women may be at an increased risk of marasmus.

Pathophysiology (Body’s Physiological Response)

To understand the pathophysiology of marasmus, it is important to understand the body’s physiological response to a deficiency in calorie intake.

Physiological Response to Starvation

There are multiple stages of starvation that occur in a stepwise manner.

  1. Gastrointestinal absorption of a substrate (1 to 6 hours)
  2. Glycogenolysis (1 to 2 days)
  3. Gluconeogenesis (1 week)
  4. Ketosis (3 to 4 days+)
  5. Increased cerebral ketone use (2 weeks+)

The physiological response during the gastrointestinal stage of starvation is dependent on what was eaten. A high carbohydrate meal will lead to increased blood levels of insulin and reduced levels of glucagon. This leads to increased glycogenesis and reduced gluconeogenesis and glycogenolysis. However, if the meal is deficient in carbohydrates, this leads to insulin release greater than the basal rate but lower than if a high carbohydrate meal was consumed along with a higher level of glucagon secretion, which causes higher levels of hepatic glycogenolysis and gluconeogenesis.

The body only has enough free glucose to supply one hours’ worth of metabolism. Reduced carbohydrate absorption from the gastrointestinal tract leads to reduced levels of insulin secretion. Between approximately 4 to 5 hours, glucose, which is stored in the liver as glycogen, begins to break down to provide the body with glucose. There are certain organs that are dependent on glucose for their metabolism, such as the central nervous system. The tissues which are not dependent on glucose for metabolism are muscle and adipose tissue and by 8 to 10 hours, half of the muscle energy requirements are met by free fatty acids.

The stores of glycogen in the liver are only capable of sustaining the energy demands of the body for 12-16 hours. Following this, gluconeogenesis must occur to maintain blood glucose levels. This is mediated by increased activity of glucokinase and reduced activity of glucose-6-phosphatase.[19] Over 2 to 3 days, muscle and adipose tissue become less dependent on glucose for metabolism through the blocking of glucose uptake. Furthermore, the liver reduces its use of glucose as a source of energy and becomes dependent on partially oxidized fatty acids.

Ketoacid production reaches a maximum by the third day of starvation. Ketoacid production provides a sufficient gradient of the substrate to fuel the central nervous system as free fatty acids are unable to cross the blood-brain barrier. The transition to lipid-dependent metabolism allows the early preservation of muscle protein. It is thought that hyperleptinemia leading to activation of the hypothalamic-pituitary-adrenal axis contributes to the breakdown of adipose tissue.

Susceptibility to Infection

Severe prolonged calorie restriction causes an increased susceptibility to infection, which occurs due to secondary immunodeficiency.

A breakdown of mucosal barrier integrity in the respiratory and gastrointestinal systems is associated with prolonged calorie restriction. Increased levels of inflammatory cytokines such as IL1, IL6, and IL12, alter the function of growth hormone, contributing to short stature. There is an increased susceptibility to infection as a result of T-cell dysfunction and reduced neutrophil microbicidal activity.

In particular, infection with Gram-negative organisms is associated with marasmus. Infections of the urinary, gastrointestinal, and respiratory tracts are associated with marasmus; however, patients suffering from marasmus may not present with the typical features of an infection such as fever.

There is also an impaired response to bacterial and viral vaccines. Atrophy of the thymus gland, tonsils, and lymph nodes contributes to an impairment in cellular immunity.

Total Body Water

Marasmus is associated with an increase in total body water compared to body weight; furthermore, there is a direct correlation between weight loss in marasmus and total body water such that children with the greatest degree of wasting have the highest total body water.

Electrolyte Changes

Total body potassium decreases of 10-33% may be seen in marasmus.[26] Potassium is lost in diarrhea, causing an intracellular deficit. There is also further depletion of other minerals such as sodium, phosphorus, and calcium.

Oxidative Stress

Severe malnutrition and calorie restriction are associated with increased levels of oxidative stress. It is thought that this occurs due to a reduced intake of antioxidants such as glutathione and vitamin E, which is further compounded with reduced glutathione synthesis.

Gastrointestinal System

Severe malnutrition is associated with villous atrophy and the subsequent loss of brush border enzymes such as disaccharidases, crypt hypoplasia, and impaired absorption across the gastric mucosa. Reduced gastric acid secretion contributes to bacterial overgrowth.

Central Nervous System

Severe malnutrition can contribute to altered brain function and changes in behavior. Furthermore, developmental impairment is associated with severe malnutrition.

Endocrine Function

Severe malnutrition can lead to atrophy of the adrenal and pituitary glands without a significant reduction in endocrinological function. Plasma cortisol levels may be raised due to reduced cortisol binding to albumin secondary to hypoalbuminemia. Insulin secretion in response to glucose loads returns to normal function following 3-6 weeks of treatment. This leads to impaired glucose clearance rates in children suffering from marasmus.

Cardiovascular System

Severe malnutrition is associated with thinning of the cardiac myofibrils and impairment in contractile ability. This leads to a reduction in cardiac output, which is proportional to weight loss. Along with electrolyte abnormalities, impaired cardiac output and bradycardia predispose children suffering from severe malnutrition to arrhythmias.

Refeeding Syndrome

An unfortunate consequence of uncoordinated initiation of therapy may be the development of refeeding syndrome. In children suffering from marasmus, there are physiological changes that occur, and this includes reduced insulin secretion and increased secretion of glucagon. Furthermore, there is a shift of phosphate, potassium, and magnesium from intracellular spaces to extracellular spaces to maintain serum electrolyte levels. The child may have normal serum electrolyte levels whilst the total electrolyte levels in the body are low.

During the initiation of refeeding, there is hyperglycemia. There is an impairment in insulin secretion in response to raised blood glucose levels. This leads to fluid shifts and the development of dehydration. To facilitate cellular processes, there is a shift of electrolytes into intracellular spaces leading to depletion of serum electrolyte levels. As there is a general shift from the utilization of fatty acids as an energy source to glucose, there is an increased production of adenosine triphosphate. This results in hypophosphatemia from glucose phosphorylation.

Thiamine deficiency occurs as the shift from fatty acid metabolism to carbohydrate metabolism increases thiamine requirements. Furthermore, thiamine is needed in the synthesis of glycogen, proteins, and fats.

Source

Titi-Lartey OA, Gupta V. Marasmus. [Updated 2022 Jul 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559224/

Facebook Comments

Leave a Reply