(See also Overview of Undernutrition Overview of Undernutrition Undernutrition is a form of malnutrition. (Malnutrition also includes overnutrition.) Undernutrition can result from inadequate ingestion of nutrients, malabsorption, impaired metabolism, loss... read more .)
In countries with sufficient food resources, PEU is common among institutionalized older patients (although often not suspected) and among patients with disorders that decrease appetite or impair nutrient digestion, absorption, or metabolism. In countries with high rates of food insecurity, PEU affects children who do not consume enough calories or protein.
Classification and Etiology of PEU
PEU is graded as mild, moderate, or severe. Grade is determined by calculating weight as a percentage of expected weight for length or height using international standards (normal, 90 to 110%; mild PEU, 85 to 90%; moderate, 75 to 85%; severe, < 75%).
PEU may be
Primary: Caused by inadequate nutrient intake
Secondary: Results from disorders or drugs that interfere with nutrient use
Worldwide, primary PEU occurs mostly in children and older people who lack access to nutrients, although a common cause in older people is depression. PEU can also result from fasting or anorexia nervosa Anorexia Nervosa Anorexia nervosa is characterized by a relentless pursuit of thinness, a morbid fear of obesity, a distorted body image, and restriction of intake relative to requirements, leading to a significantly... read more . Child or elder abuse may be a cause.
In children, chronic primary PEU has 2 common forms:
The form depends on the balance of nonprotein and protein sources of energy. Starvation is an acute severe form of primary PEU.
Marasmus (also called the dry form of PEU) causes weight loss and depletion of fat and muscle. In countries with high rates of food insecurity, marasmus is the most common form of PEU in children.
Kwashiorkor (also called the wet, swollen, or edematous form) is a risk after premature abandonment of breastfeeding, which typically occurs when a younger sibling is born, displacing the older child from the breast. So children with kwashiorkor tend to be older than those with marasmus. Kwashiorkor may also result from an acute illness, often gastroenteritis Overview of Gastroenteritis Gastroenteritis is inflammation of the lining of the stomach and small and large intestines. Most cases are infectious, although gastroenteritis may occur after ingestion of drugs and chemical... read more or another infection (probably secondary to cytokine release), in a child who already has PEU. A diet that is more deficient in protein than energy may be more likely to cause kwashiorkor than marasmus. Less common than marasmus, kwashiorkor tends to be confined to specific parts of the world, such as rural Africa, the Caribbean, and the Pacific islands. In these areas, staple foods (eg, yams, cassavas, sweet potatoes, green bananas) are low in protein and high in carbohydrates. In kwashiorkor, cell membranes leak, causing extravasation of intravascular fluid and protein, resulting in peripheral edema.
In both marasmus and kwashiorkor, cell-mediated immunity is impaired, increasing susceptibility to infections. Bacterial infections (eg, pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more , gastroenteritis Overview of Gastroenteritis Gastroenteritis is inflammation of the lining of the stomach and small and large intestines. Most cases are infectious, although gastroenteritis may occur after ingestion of drugs and chemical... read more , otitis media Otitis Media (Acute) Acute otitis media is a bacterial or viral infection of the middle ear, usually accompanying an upper respiratory infection. Symptoms include otalgia, often with systemic symptoms (eg, fever... read more , urinary tract infections Bacterial Urinary Tract Infections Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more , sepsis Sepsis and Septic Shock Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection. In septic shock, there is critical reduction in tissue perfusion; acute failure... read more ) are common. Infections result in release of cytokines, which cause anorexia, worsen muscle wasting, and cause a marked decrease in serum albumin levels.
Starvation is a complete lack of nutrients. It occasionally occurs when food is available (as in fasting or anorexia nervosa) but usually occurs because food is unavailable (eg, during famine or wilderness exposure).
This type most commonly results from the following:
Disorders that affect gastrointestinal function: These disorders can interfere with digestion (eg, pancreatic insufficiency), absorption (eg, enteritis, enteropathy), or lymphatic transport of nutrients (eg, retroperitoneal fibrosis, Milroy disease).
Wasting disorders: In wasting disorders (eg, AIDS AIDS Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more , cancer Cachexia in Cancer Cachexia is wasting of both adipose tissue and skeletal muscle. It occurs in many conditions and is common with many cancers when their control fails. Some cancers, especially pancreatic and... read more , COPD Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease (COPD) is airflow limitation caused by an inflammatory response to inhaled toxins, often cigarette smoke. Alpha-1 antitrypsin deficiency and various occupational... read more ) and renal failure Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more , catabolism causes cytokine excess, resulting in undernutrition via anorexia and cachexia (wasting of muscle and fat). End-stage heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular failure causes shortness of breath and fatigue, and right ventricular failure causes peripheral and abdominal fluid... read more can cause cardiac cachexia, a severe form of undernutrition; mortality rate is particularly high. Factors contributing to cardiac cachexia may include passive hepatic congestion (causing anorexia), edema of the intestinal tract (impairing absorption), and, in advanced disease, increased oxygen requirement due to anaerobic metabolism. Wasting disorders can decrease appetite or impair metabolism of nutrients.
Conditions that increase metabolic demands: These conditions include infections Manifestations of Infection Manifestations of infection may be local (eg, cellulitis, abscess) or systemic (most often fever). Manifestations may develop in multiple organ systems. Severe, generalized infections may have... read more , hyperthyroidism Hyperthyroidism Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms are many and include tachycardia, fatigue, weight loss, nervousness, and tremor... read more , pheochromocytoma Pheochromocytoma A pheochromocytoma is a catecholamine-secreting tumor of chromaffin cells typically located in the adrenals. It causes persistent or paroxysmal hypertension. Diagnosis is by measuring catecholamine... read more , other endocrine disorders, burns Burns Burns are injuries of skin or other tissue caused by thermal, radiation, chemical, or electrical contact. Burns are classified by depth (superficial and deep partial-thickness, and full-thickness)... read more , trauma, surgery Nutritional disorders Before elective surgical procedures, whether done in an outpatient or inpatient setting, the surgical team may consult an internist for a formal preoperative evaluation to minimize risk by identifying... read more , and other critical illnesses.
Pathophysiology of PEU
The initial metabolic response of PEU is decreased metabolic rate. To supply energy, the body first breaks down adipose tissue. However, later, when these tissues are depleted, the body may use protein for energy, resulting in a negative nitrogen balance. Visceral organs and muscle are broken down and decrease in weight. Loss of organ weight is greatest in the liver and intestine, intermediate in the heart and kidneys, and least in the nervous system.
Symptoms and Signs of PEU
Symptoms of moderate PEU can be constitutional or involve specific organ systems. Apathy and irritability are common. The patient is weak, and work capacity decreases. Cognition and sometimes consciousness are impaired. Temporary lactose deficiency and achlorhydria develop. Diarrhea is common and can be aggravated by deficiency of intestinal disaccharidases, especially lactase Etiology . Gonadal tissues atrophy. PEU can cause amenorrhea in women and loss of libido in men and women.
Wasting of fat and muscle is common in all forms of PEU. In adult volunteers who fasted for 30 to 40 days, weight loss was marked (25% of initial weight). If starvation is more prolonged, weight loss may reach 50% in adults and possibly more in children.
In adults, cachexia is most obvious in areas where prominent fat depots normally exist. Muscles shrink and bones protrude. The skin becomes thin, dry, inelastic, pale, and cold. The hair is dry and falls out easily, becoming sparse. Wound healing is impaired. In older patients, risk of hip fractures and pressure (decubitus) ulcers increases.
With acute or chronic severe PEU, heart size and cardiac output decrease; pulse slows and blood pressure falls. Respiratory rate and vital capacity decrease. Body temperature falls, sometimes contributing to death. Edema, anemia, jaundice, and petechiae can develop. Liver, kidney, or heart failure may occur.
Marasmus in infants causes hunger, weight loss, growth retardation, and wasting of subcutaneous fat and muscle. Ribs and facial bones appear prominent. Loose, thin skin hangs in folds.
Kwashiorkor is characterized by peripheral and periorbital edema due to the decrease in serum albumin. The abdomen protrudes because abdominal muscles are weakened, the intestine is distended, the liver enlarges, and ascites is present. The skin is dry, thin, and wrinkled; it can become hyperpigmented and fissured and later hypopigmented, friable, and atrophic. Skin in different areas of the body may be affected at different times. The hair can become thin, reddish brown, or gray. Scalp hair falls out easily, eventually becoming sparse, but eyelash hair may grow excessively. Alternating episodes of undernutrition and adequate nutrition may cause the hair to have a dramatic “striped flag” appearance. Affected children may be apathetic but become irritable when held.
Total starvation is fatal in 8 to 12 weeks. Thus, certain symptoms of PEU do not have time to develop.
Diagnosis of PEU
Diagnosis usually based on history
To determine severity: Body mass index (BMI), serum albumin, total lymphocyte count, CD4+ count, serum transferrin
To diagnose complications and consequences: Complete blood count, electrolytes, blood urea nitrogen, glucose, calcium, magnesium, phosphate
Diagnosis of PEU can be based on history when dietary intake is markedly inadequate. The cause of inadequate intake, particularly in children, needs to be identified. In children and adolescents, child abuse Overview of Child Maltreatment Child maltreatment is behavior toward a child that is outside the norms of conduct and entails substantial risk of causing physical or emotional harm. Four types of maltreatment are generally... read more and anorexia nervosa Anorexia Nervosa Anorexia nervosa is characterized by a relentless pursuit of thinness, a morbid fear of obesity, a distorted body image, and restriction of intake relative to requirements, leading to a significantly... read more should be considered.
Physical examination may include measurement of height and weight, inspection of body fat distribution, and anthropometric measurements of lean body mass. Body mass index (BMI = weight[kg]/height[m]2) is calculated to determine severity. Findings can usually confirm the diagnosis.
Laboratory tests are required if dietary history does not clearly indicate inadequate caloric intake. Measurement of serum albumin, total lymphocyte count, CD4+ T lymphocytes, transferrin, and response to skin antigens may help determine the severity of PEU (see table Values Commonly Used to Grade the Severity of Protein-Energy Undernutrition Values Commonly Used to Grade the Severity of Protein-Energy Undernutrition ) or confirm the diagnosis in borderline cases. Many other test results may be abnormal: eg, decreased levels of hormones, vitamins, lipids, cholesterol, prealbumin, insulin-like growth factor-1, fibronectin, and retinol-binding protein. Urinary creatine and methylhistidine levels can be used to gauge the degree of muscle wasting. Because protein catabolism slows, urinary urea level also decreases. These findings rarely affect treatment.
Laboratory tests are required to identify causes of suspected secondary PEU. C-reactive protein or soluble interleukin-2 receptor should be measured when the cause of undernutrition is unclear; these measurements can help determine whether there is cytokine excess. Thyroid function tests may also be done.
Other laboratory tests can detect associated abnormalities that may require treatment. Serum electrolytes, blood urea nitrogen, glucose, and possibly levels of calcium, magnesium, and phosphate should be measured. Levels of blood glucose, electrolytes (especially potassium, occasionally sodium), phosphate, calcium, and magnesium are usually low. Blood urea nitrogen is often low unless renal failure is present. Metabolic acidosis may be present. Complete blood count is usually obtained; normocytic anemia (usually due to protein deficiency) or microcytic anemia (due to simultaneous iron deficiency) is usually present.
Stool cultures should be obtained and checked for ova and parasites Diagnosis Human parasites are organisms that live on or in a person and derive nutrients from that person (its host). There are 3 types of parasites: Single-cell organisms (protozoa, microsporidia) Multicellular... read more if diarrhea is severe or does not resolve with treatment. Sometimes urinalysis, urine culture, blood cultures, tuberculin testing, and a chest x-ray are used to diagnose occult infections because people with PEU may have a muted response to infections.
Prognosis for PEU
In children, mortality varies from 5 to 40%. Mortality rates are lower in children with mild PEU and those given intensive care. Death in the first days of treatment is usually due to electrolyte deficits, sepsis, hypothermia, or heart failure. Impaired consciousness, jaundice, petechiae, hyponatremia, and persistent diarrhea are ominous signs. Resolution of apathy, edema, and anorexia is a favorable sign. Recovery is more rapid in kwashiorkor than in marasmus.
Long-term effects of PEU in children are not fully documented. Some children develop chronic malabsorption and pancreatic insufficiency. In very young children, mild intellectual disability may develop and persist until at least school age. Permanent cognitive impairment may occur, depending on the duration, severity, and age at onset of PEU.
In adults, PEU can result in morbidity and mortality (eg, progressive weight loss increases mortality rate for older patients in nursing homes). In older patients, PEU increases the risk of morbidity and mortality due to surgery, infections, or other disorders.
Except when organ failure occurs, treatment is uniformly successful.
Treatment of PEU
Usually oral feeding
Possibly avoidance of lactose (eg, if persistent diarrhea suggests lactose intolerance)
Supportive care (eg, environmental changes, assistance with feeding, orexigenic drugs)
For children, feeding delayed 24 to 48 hours
Worldwide, the most important PEU preventive strategy is to reduce poverty and improve nutritional education and public health measures.
Mild or moderate PEU, including brief starvation, can be treated by providing a balanced diet, preferably orally. Liquid oral food supplements (usually lactose-free) can be used when solid food cannot be adequately ingested. Diarrhea often complicates oral feeding because starvation makes the gastrointestinal tract more likely to move bacteria into Peyer patches, facilitating infectious diarrhea. If diarrhea persists (suggesting lactose intolerance), yogurt-based rather than milk-based formulas are given because people with lactose intolerance can tolerate yogurt. Patients should also be given a multivitamin supplement.
Severe PEU or prolonged starvation requires treatment in a hospital with a controlled diet. The first priority is to correct fluid and electrolyte abnormalities Water and Sodium Balance Body fluid volume and electrolyte concentration are normally maintained within very narrow limits despite wide variations in dietary intake, metabolic activity, and environmental stresses. Homeostasis... read more and treat infections. A recent study suggested that children may benefit from antibiotic prophylaxis. The next priority is to supply macronutrients orally or, if necessary (eg, when swallowing is difficult), through a feeding tube, a nasogastric tube (usually), or a gastrostomy tube (enteral nutrition Enteral Tube Nutrition Enteral tube nutrition is indicated for patients who have a functioning gastrointestinal (GI) tract but cannot ingest enough nutrients orally because they are unable or unwilling to take oral... read more ). Parenteral nutrition Total Parenteral Nutrition (TPN) Parenteral nutrition is by definition given IV. Partial parenteral nutrition supplies only part of daily nutritional requirements, supplementing oral intake. Many hospitalized patients are given... read more is indicated if malabsorption is severe.
Other treatments may be needed to correct specific deficiencies, which may become evident as weight increases. To avoid deficiencies, patients should take micronutrients at about twice the recommended daily allowance until recovery is complete.
Underlying disorders in children with PEU should be treated.
For children with diarrhea, feeding may be delayed 24 to 48 hours to avoid making the diarrhea worse; during this interval, children require oral or IV rehydration. Feedings are given often (6 to 12 times/day) but, to avoid overwhelming the limited intestinal absorptive capacity, are limited to small amounts (< 100 mL). During the first week, milk-based formulas with supplements added are usually given in progressively increasing amounts; after a week, the full amounts of 175 kcal/kg and 4 g of protein/kg can be given. Twice the recommended daily allowance of micronutrients should be given, using commercial multivitamin supplements. After 4 weeks, the formula can be replaced with whole milk plus cod liver oil and solid foods, including eggs, fruit, meats, and yeast.
Energy distribution among macronutrients should be about 16% protein, 50% fat, and 34% carbohydrate. An example is a combination of powdered cow’s skimmed milk (110 g), sucrose (100 g), vegetable oil (70 g), and water (900 mL). Many other formulas (eg, whole [full-fat] fresh milk plus corn oil and maltodextrin) can be used. Milk powders used in formulas are diluted with water.
Usually, supplements should be given with the formulas:
Magnesium 0.4 mEq/kg/day IM is given for 7 days.
B-complex vitamins at twice the recommended daily allowance are given parenterally for the first 3 days, usually with vitamin A, phosphorus, zinc, manganese, copper, iodine, fluoride, molybdenum, and selenium.
Because absorption of oral iron is poor in children with PEU, oral or IM iron supplementation may be necessary.
Parents are taught about nutritional requirements.
Underlying disorders should be treated. For example, if AIDS or cancer results in excess cytokine production, megestrol acetate or medroxyprogesterone may improve food intake. However, because these drugs dramatically decrease testosterone in men (possibly causing muscle loss), testosterone should be replaced. Because these drugs can cause adrenal insufficiency, they should be used only short-term (< 3 months).
An orexigenic drug, such as the cannabis extract dronabinol, should be given to patients with anorexia when no cause is obvious or to patients at the end of life when anorexia impairs quality of life. An anabolic steroid (eg, testosterone enanthate, nandrolone) or growth hormone can benefit patients with cachexia due to renal failure and possibly older patients (eg, by increasing lean body mass or possibly by improving function).
Correction of PEU in adults generally resembles that in children; feedings are often limited to small amounts. However, for most adults, feeding does not need to be delayed. A commercial formula for oral feeding can be used. Daily nutrient supply should be given at a rate of 60 kcal/kg and 1.2 to 2 g of protein/kg. If liquid oral supplements are used with solid food, they should be given at least 1 hour before meals so that the amount of food eaten at the meal is not reduced.
Treatment of institutionalized older patients with PEU requires multiple interventions:
Environmental measures (eg, making the dining area more attractive)
Changes in diet (eg, use of food enhancers and caloric supplements between meals)
Treatment of depression and other underlying disorders
Use of orexigenic drugs, anabolic steroids, or both
The long-term use of gastrostomy tube feeding is essential for patients with severe dysphagia; its use in patients with dementia is controversial. Increasing evidence supports the avoidance of unpalatable therapeutic diets (eg, low salt, diabetic, low cholesterol) in institutionalized patients because these diets decrease food intake and may cause severe PEU.
In patients with functional limitations, home delivery of meals and feeding assistance are key.
Complications of treatment
Treatment of PEU can cause complications (refeeding syndrome), including fluid overload, electrolyte deficits, hyperglycemia, cardiac arrhythmias, and diarrhea. Diarrhea is usually mild and resolves; however, diarrhea in patients with severe PEU occasionally causes severe dehydration or death. Causes of diarrhea (eg, sorbitol used in elixir tube feedings, Clostridium difficile if the patient has received an antibiotic) may be correctable. Osmotic diarrhea due to excess calories is rare in adults and should be considered only when other causes have been excluded.
Because PEU can impair cardiac and renal function, overhydration can cause intravascular volume overload. Treatment decreases extracellular potassium and magnesium. Depletion of potassium or magnesium may cause arrhythmias. Carbohydrate metabolism that occurs during treatment stimulates insulin release, which drives phosphate into cells. Hypophosphatemia can cause muscle weakness, paresthesias, seizures, coma, and arrhythmias. Because phosphate levels can change rapidly during parenteral feeding, levels should be measured regularly.
During treatment, endogenous insulin may become ineffective, leading to hyperglycemia. Dehydration and hyperosmolarity can result. Fatal ventricular arrhythmias can develop, possibly caused by a prolonged QT interval.
PEU can be primary (ie, caused by decreased intake of nutrients) or secondary to gastrointestinal disorders, wasting disorders, or conditions that increase metabolic demand.
In severe forms of PEU, body fat and eventually visceral tissue are lost, immunity is impaired, and organ function slows, sometimes resulting in multiple organ failure.
To determine severity, measure body mass index (BMI), serum albumin, total lymphocyte count, CD4 count, and serum transferrin.
To diagnose complications and consequences, measure complete blood count, electrolytes, blood urea nitrogen, glucose, calcium, magnesium, and phosphate.
For mild PEU, recommend a balanced diet, sometimes avoiding foods that contain lactose.
For severe PEU, hospitalize patients, give them a controlled diet, correct fluid and electrolyte abnormalities, and treat infections; common complications of treatment (refeeding syndrome) include fluid overload, electrolyte deficits, hyperglycemia, cardiac arrhythmias, and diarrhea.