Protein-energy deficiency

Protein-energy malnutrition, or protein-calorie malnutrition, is an energy deficit due to chronic deficiency of all macronutrients. It usually includes deficiencies of many micronutrients as well. Protein-energy malnutrition may be sudden and total (starvation) or gradual. Severity ranges from subclinical manifestations to overt cachexia (with edema, hair loss, and skin atrophy), and multiorgan and multisystem failure is observed. Diagnosis usually involves laboratory tests, including serum albumin. Treatment involves correction of fluid and electrolyte deficits with intravenous fluids, followed by gradual replacement of nutrients orally if possible.

In developed countries, protein-energy malnutrition is a condition common among institutionalized elderly people (though often unaware of it) and among patients with disorders that reduce appetite or impair the digestion, absorption, and metabolism of nutrients. In developing countries, protein-energy malnutrition is common among children who do not consume enough calories or protein.

[ 1 ], [ 2 ], [ 3 ]

Classification and causes of protein-energy malnutrition

Protein-energy malnutrition can be mild, moderate or severe. The stage is determined by determining the difference in percentage between the patient's actual and estimated (ideal) weight corresponding to his height, using international standards (normal, 90-110%; mild protein-energy malnutrition, 85-90%; moderate, 75-85%; severe, less than 75%).

Protein-energy malnutrition can be primary or secondary. Primary protein-energy malnutrition is caused by inadequate nutrient intake, while secondary protein-energy malnutrition is a consequence of various disorders or medications that interfere with the utilization of nutrients.

[ 4 ], [ 5 ], [ 6 ], [ 7 ], [ 8 ]

Symptoms of protein-energy malnutrition

Symptoms of moderate protein-energy malnutrition may be general (systemic) or affect specific organs and systems. Apathy and irritability are characteristic. The patient is weakened, performance is reduced. Cognitive abilities and sometimes consciousness are impaired. Temporary lactose deficiency and achlorhydria develop. Diarrhea is frequent and is aggravated by a deficiency of intestinal disaccharidases, especially lactase. Gonadal tissues are atrophic. PEM can cause amenorrhea in women and loss of libido in men and women.

Loss of fat and muscle mass is a common feature of all forms of PEM. In adult volunteers who fasted for 30-40 days, weight loss was significant (25% of initial weight). If the fast is longer, weight loss can reach 50% in adults and perhaps more in children.

Cachexia in adults is most evident in areas where visible fat deposits would normally be present. Muscles are reduced in volume and bones are prominent. The skin becomes thin, dry, inelastic, pale and cold. Hair is dry and falls out easily, becoming sparse. Wound healing is impaired. In older patients, the risk of hip fractures, bedsores, and trophic ulcers increases.

In acute or chronic severe protein-energy malnutrition, heart size and cardiac output decrease; pulse rate slows; arterial pressure decreases. Respiratory rate and vital capacity decrease. Body temperature falls, sometimes resulting in death. Edema, anemia, jaundice, and petechiae may develop. Liver, kidney, or heart failure may occur.

Cellular immunity is weakened, susceptibility to infections increases. Bacterial infections (e.g. pneumonia, gastroenteritis, otitis media, urogenital tract infections, sepsis) are characteristic of all forms of protein-energy malnutrition. Infections lead to activation of cytokine production, which aggravate anorexia, resulting in even greater loss of muscle mass and a significant decrease in serum albumin levels.

In infants, marasmus causes hunger, weight loss, growth retardation, loss of subcutaneous fat and muscle mass. Ribs and facial bones protrude. Loose, thin, "dangling" skin hangs in folds.

Kwashiorkor is characterized by peripheral edema. The abdomen is protruding, but there is no ascites. The skin is dry, thin, and wrinkled; it becomes hyperpigmented, cracked, and then hypopigmented, lax, and atrophic. The skin of different areas of the body may be affected at different times. The hair becomes thin, brown, or gray. The scalp hair falls out easily, eventually becoming sparse, but the eyelash hair may even grow excessively. Alternating undernutrition and adequate nutrition results in a "striped flag" appearance to the hair. Affected children may be apathetic, but become irritable if stirred.

Complete starvation is fatal if it lasts more than 8-12 weeks. Thus, the symptoms characteristic of protein-energy deficiency do not have time to develop.

Primary protein-energy malnutrition

Throughout the world, primary protein-energy malnutrition occurs mainly in children and the elderly, i.e., those with limited opportunities to obtain food, although the most common cause in old age is depression. It can also be a consequence of fasting, therapeutic starvation, or anorexia. It can also be caused by poor (cruel) treatment of children or the elderly.

In children, chronic primary protein-energy malnutrition has three forms: marasmus, kwashiorkor, and a form that has characteristics of both (marasmic kwashiorkor). The form of protein-energy malnutrition depends on the ratio of non-protein and protein energy sources in the diet. Starvation is an acute severe form of primary protein-energy malnutrition.

Marasmus (also called dry protein-energy malnutrition) causes weight loss and wasting of muscle and fat stores. In developing countries, marasmus is the most common form of protein-energy malnutrition in children.

Kwashiorkor (also called the wet, puffy, or edematous form) is associated with premature weaning of an older child, which typically occurs when a younger child is born, "pushing" the older child away from the breast. Thus, children with kwashiorkor are usually older than those with marasmus. Kwashiorkor may also result from an acute illness, often gastroenteritis or another infection (probably secondary, due to cytokine production) in children who already have protein-energy malnutrition. A diet that is more deficient in protein than in energy may be more likely to cause kwashiorkor than marasmus. Less common than marasmus, kwashiorkor tends to be limited to certain regions of the world, such as rural Africa, the Caribbean, and the Pacific islands. In these areas, staple foods (eg, cassava, sweet potatoes, green bananas) are low in protein and high in carbohydrates. In kwashiorkor, the permeability of cell membranes increases, causing transudation of intravascular fluid and protein, leading to peripheral edema.

Marasmatic kwashiorkor is characterized by the combined features of marasmus and kwashiorkor. Affected children are edematous and have more fat in their body composition than those with marasmus.

Fasting is a complete lack of nutrients. Sometimes fasting is voluntary (as during religious fasting or neurogenic anorexia), but usually it is caused by external factors (for example, natural disasters, being in the desert).

Secondary protein-energy malnutrition

This type usually results from disorders that affect GI function, cachectic disorders, and conditions that increase metabolic demands (eg, infections, hyperthyroidism, Addison's disease, pheochromocytoma, other endocrine disorders, burns, trauma, surgery). In cachectic disorders (eg, AIDS, cancer) and renal failure, catabolic processes lead to the formation of excess cytokines, which in turn leads to malnutrition. End-stage heart failure can cause cardiac cachexia, a severe form of malnutrition that has a particularly high mortality rate. Cachectic disorders may decrease appetite or impair nutrient metabolism. Disorders that affect GI function may impair digestion (eg, pancreatic insufficiency), absorption (eg, enteritis, enteropathy), or lymphatic transport of nutrients (eg, retroperitoneal fibrosis, Milroy disease).

Pathophysiology

The initial metabolic reaction is a decrease in the intensity of metabolism. To provide energy, the body first "breaks down" fatty tissue. However, then the internal organs and muscles also begin to break down, and their mass decreases. The liver and intestines "lose" the most weight, the heart and kidneys are in an intermediate position, and the nervous system loses the least weight.

Diagnosis of protein-energy malnutrition

The diagnosis is based on the clinical history, where clearly inadequate food intake is established. The cause of inadequate food intake must be identified, especially in children. In children and adolescents, the possibility of abuse and anorexia nervosa must be considered.

Physical examination findings can usually confirm the diagnosis. Laboratory tests are needed to identify the cause of secondary protein-energy malnutrition. Measurement of plasma albumin, total lymphocyte count, CD4 ⁺ T-lymphocyte count, and skin antigen response can help to determine the severity of protein-energy malnutrition or to confirm the diagnosis in borderline conditions. Measurement of C-reactive protein or soluble interleukin-2 receptor levels can help to identify the cause of malnutrition when it is unclear and to confirm abnormal cytokine production. Many additional parameters may deviate from normal values: for example, decreased levels of hormones, vitamins, lipids, cholesterol, prealbumin, insulin-like growth factor-1, fibronectin, and retinol-binding protein are common. Urinary creatinine and methylhistidine levels can be used as criteria for assessing the degree of muscle wasting. As protein catabolism slows, urinary urea levels also decrease. These data are rarely taken into account when choosing a treatment strategy.

Other laboratory tests may reveal associated abnormalities that require treatment. Serum electrolytes, blood urea and creatinine, BUN, glucose, and possibly Ca, Mg, phosphate, and Na should be measured. Blood glucose and electrolyte levels (especially K, Ca, Mg, phosphate, and sometimes Na) are usually low. BUN, blood urea, and creatinine remain low in most cases until renal failure develops. Metabolic acidosis may be detected. A complete blood count is obtained; normocytic anemia (primarily due to protein deficiency) or microcytic anemia (due to concomitant iron deficiency) is usually present.

Indicators used to assess the severity of protein-energy malnutrition

Indicator	Norm	Easy	Moderate	Heavy
Normal weight (%)	90-110	85-90	75-85	<75
Body Mass Index (BMI)	19-24	18-18.9	16-17.9	<16
Whey protein (g/dL)	3.5-5.0	3.1-3.4	2.4-3.0	<2.4
Serum transferrin (mg/dL)	220-400	201-219	150-200	< 150
Total lymphocyte count (in mm3 )	2000-3500	1501-1999	800-1500	<800
Delayed-type hypersensitivity index	2	2	1	0

In the elderly, BMI <21 may increase the risk of mortality.

The index of delayed-type hypersensitivity shows the magnitude of induration revealed by a skin test using a common antigen obtained from Candida sp. or Trichophyton sp. The degree of induration is 0 - < 0.5 cm, 1 - 0.5-0.9 cm, 2 - > 1.0 cm.

A stool culture is also taken for worm eggs and parasites if the diarrhea is severe and does not respond to treatment. Sometimes a urine test is performed, urine culture, blood culture, tuberculin test, and chest X-ray are performed to diagnose latent infections, because people with protein-energy malnutrition may have a delayed response to infections.

[ 9 ], [ 10 ], [ 11 ]

Prevention and treatment of protein-energy malnutrition

Globally, the most important strategy for preventing protein-energy malnutrition is to reduce poverty, improve nutritional knowledge and improve health care.

Mild to moderate protein-energy malnutrition, including short-term starvation, is treated by feeding a balanced diet, preferably orally. Liquid oral nutritional supplements (usually lactose-free) may be used if solid foods cannot be adequately digested. Diarrhea often complicates oral feeding because starvation increases gastrointestinal sensitivity and allows bacteria to enter the Peyer's patches, promoting infectious diarrhea. If diarrhea persists (presumably due to lactose intolerance), yogurt-based rather than milk-based formulas are given because lactose-intolerant individuals can tolerate yogurt and other fermented milk products. Patients also require multivitamin supplements.

Severe protein-energy malnutrition or prolonged starvation require inpatient treatment with a controlled diet. The main priorities are correction of water and electrolyte imbalances and treatment of infections. The next step is replenishment of macronutrients orally or, if necessary, through a tube: nasogastric (usually) or gastric. Parenteral nutrition is prescribed in case of severe malabsorption.

Other treatments may be needed to correct specific nutrient deficiencies that may become apparent with weight gain. To avoid micronutrient deficiencies, patients should continue to take micronutrients at doses approximately twice the recommended daily allowance (RDA) until recovery occurs.

In children

Underlying disorders should be treated. In children with diarrhoea, feeding may be delayed for 24 to 48 hours to avoid worsening the diarrhoea. Feedings should be frequent (6 to 12 times/day) but should be small (<100 ml) to avoid damaging the already limited absorptive capacity of the intestine. During the first week, supplemented formula is usually given in progressively increasing amounts; after one week, full amounts of 175 kcal/kg and 4 g protein/kg can be given. Double the RDA for micronutrients is essential, and commercial multivitamin supplements are recommended. After 4 weeks, formula can be replaced by whole milk, fish oil, and solid foods including eggs, fruits, meat, and yeast.

The energy distribution of macronutrients should be approximately 16% protein, 50% fat and 34% carbohydrate. As an example, we use a combination of skimmed cow's milk powder (110 g), sucrose (100 g), vegetable oil (70 g) and water (900 ml). Many other milk mixtures can be used (e.g. whole fat fresh milk plus corn oil and maltodextrin). The dry milk used in milk mixtures is diluted with water.

Supplements are usually added to milk formulas: Md 0.4 meq/kg/day intramuscularly for 7 days; B vitamins in double the RDA, given parenterally for the first 3 days, usually with vitamin A, phosphorus, zinc, manganese, copper, iodine, fluorine, molybdenum and selenium. Since absorption of dietary iron in children with B-protein-energy deficiency is difficult, it is prescribed in supplements orally or intramuscularly. Parents are instructed on nutritional requirements.

In adults

Disorders associated with protein-energy malnutrition should be addressed. For example, if AIDS or cancer results in excess cytokine production, megestrol acetate or hydroxyprogesterone may improve food intake. However, because these drugs dramatically reduce testosterone production in men (possibly causing muscle loss), testosterone should be used concomitantly. Because these drugs may cause adrenal hypofunction, they should be used only for short periods (<3 months). In patients with functional limitations, home-delivered meals and feeding assistance are key to treatment.

Appetite stimulants (hashish extract - dronabinol) should be given to patients with anorexia when no cause for their illness is clear, or to patients in the last years of life when anorexia impairs their quality of life. Anabolic steroids have some beneficial effects (e.g., increased lean body mass, possibly functional improvement) in patients with cachexia due to renal failure and possibly in elderly patients.

The principles of correction of protein-energy malnutrition in adults are generally similar to those in children. For most adults, feeding should not be delayed; small amounts of food fed frequently are recommended. Commercial oral formula may be used. Nutrients are given at a rate of 60 kcal/kg and 1.2-2 g protein/kg. If liquid oral supplements are used with solid food, they should be taken at least 1 hour before solid food intake so that the amount of solid food eaten is not reduced.

Treatment of patients with protein-energy malnutrition admitted to a nursing home requires many measures, including environmental modifications (eg, making the dining area more attractive); assistance with feeding; dietary modifications (eg, increased food intake and caloric supplementation between meals); treatment of depression or other underlying disorders; and use of appetite stimulants, anabolic steroids, or a combination of both. For patients with severe dysphagia, long-term use of a gastrostomy tube for feeding is essential; although its use in patients with dementia is controversial. Avoidance of unpalatable therapeutic diets (eg, low-salt, diabetic, low-cholesterol) is also beneficial, as these diets reduce food intake and may cause severe protein-energy malnutrition.

Complications of protein-energy malnutrition treatment

Treatment of protein-energy malnutrition may cause complications (refeeding syndrome), including fluid overload, electrolyte deficits, hyperglycemia, cardiac arrhythmias, and diarrhea. Diarrhea is usually mild and self-limited; however, diarrhea in patients with severe PEM occasionally causes severe dehydration or death. Causes of diarrhea, such as sorbitol used in tube feeding or Clostridium difficile if the patient has received antibiotic therapy, may be treated with specific interventions. Osmotic diarrhea due to excess calories is rare in adults and should be considered only when other causes of PEM have been excluded.

Since protein-energy malnutrition can impair cardiac and renal function, hydration can cause an increase in intravascular fluid volume. Treatment also reduces the concentration of extracellular K and Mg. A decrease in K or Mg can cause arrhythmias. Activation of carbohydrate metabolism during treatment stimulates the release of insulin, which leads to the entry of phosphate into cells. Hypophosphatemia can cause muscle weakness, paresthesia, paralysis, arrhythmias, and comatose states. Blood phosphate levels during parenteral nutrition should be measured regularly.

During treatment, endogenous insulin may become ineffective, leading to hyperglycemia. This may result in dehydration and hyperosmolarity. Fatal ventricular arrhythmias may develop, characterized by an increase in the QT interval.

[ 12 ], [ 13 ]

Prognosis of protein-energy malnutrition

In children, case fatality rates range from 5 to 40%. Case fatality rates are lower in children with mild protein-energy malnutrition and in those who have received intensive care. Death in the first days of treatment is usually due to electrolyte deficiency, sepsis, hypothermia, or heart failure. Impaired consciousness, jaundice, petechiae, hyponatremia, and persistent diarrhea are ominous prognostic signs. Resolution of apathy, edema, and anorexia are favorable signs. Recovery is more rapid in kwashiorkor than in marasmus.

To date, it has not been fully established what long-term protein-energy malnutrition leads to in children. Some children develop chronic malabsorption syndrome and pancreatic insufficiency. Young children may develop moderate mental retardation, which may persist until school age. Permanent cognitive impairment may be observed, depending on the duration, severity, and age at which protein-energy malnutrition began.

In adults, protein-energy malnutrition can lead to morbidity and mortality (for example, progressive weight loss increases mortality by 10% in elderly people in nursing homes). Unless organ or system failure develops, treatment of protein-energy malnutrition is almost always successful. In elderly patients, protein-energy malnutrition increases the risk of complications and mortality from surgery, infections, or other disorders.