Protein energy malnutrition

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

Protein energy malnutrition is defined by measurements that fall below 2 standard deviations under the normal weight for age (underweight), height for age (stunting) and weight for height (wasting). Protein energy malnutrition is a nutritional deficiency resulting from either inadequate energy (caloric) or protein intake and manifesting as either marasmus or kwashiorkor. Marasmus is characterized by wasting of body tissues, particularly muscles and subcutaneous fat, and is usually a result of severe restrictions in energy intake. Kwashiorkor affects mainly children, is characterized by edema (particularly ascites), and is usually the result of severe restrictions in protein intake. However, both types can be present simultaneously (marasmic-kwashiokor) and mask malnutrition due to the presence of edema. Treatment involves prompt resuscitation, identification of co-morbidities like dehydration and infections. The presence of severe of hypoproteinemia, hypoalbuminemia, electrolyte imbalance or an underlying HIV infection is associated with poorer prognosis among patients with protein energy malnutrition.

The first clinical description of protein-energy malnutrition was made in 1865 in Spanish language which led to little dissemination of the information. In 1932, kwashiorkor was first described by Dr. Cicely Williams, working with African children on the Gold Coast. The word kwashiorkor comes from the Ga language of Accra, Ghana meaning the ‘diseaseof the deposed baby when the next one is born’. The term marasmus is derived from the Greek word ‘marasmos‘, which means withering or wasting.

Protein energy malnutrition may be classified according to the ‘Gomez classification’ based on weight for age, or the ‘Waterlow classification’ based on stunting and wasting, or the ‘Welcome classification’ based on the presence or absence of edema.

Protein-energy malnutrition represents a shift of the body from fed to fasting/starvation state. Starvation leads to a decreased basal plasma insulin concentration and in decrease of glucose-stimulated insulin secretion. Prolonged fasting results in a deficiency in amino acids used for gluconeogenesis. It is thought that kwashiorkor is produced by a deficiency in the adequate consumption of protein-rich foods during the weaning process. However, the associated edema is not fully understood. Several theories have been put forward to explain this finding. Marasmus on the other hand is thought to be due to the total caloric deficiency leading to wastingin a child. Marasmus always results from a negative energy balance.

Protein energy malnutrition may be caused by reduced breast feeding, poor weaning practices, limited availability of food and inadequate child care in cases of extreme poverty. This classically affects several poor people in regions of poor social and economic background. Other environmental causes such as infections, drought and earthquakes leading to decreased availability of food have also been identified.

Protein-energy malnutrition must be differentiated from other diseases that cause failure to thrive, edema, wasting recurrent infections, skin and hair changes. It is important to also differentiate kwashiorkor from marasmus as the two diseases are casued by protein- energy malnutrition and share similar features such as, weight loss, muscle wasting, low blood glucose levels and growth retardation.

The prevalence of protein-energy malnutrition in children under 5 is estimated to be 150 million cases annually. In Nigeria, the prevalence is as high as 41,600 per 100,000 children. Protein-energy malnutrition is majorly a disease of the developing countries. There is no racial or sexual predisposition.

Common risk factors in the development of protein-energy malnutrition may be classified as maternal and environmental.

There is insufficient evidence to recommend routine screening for protein-energy malnutrition.

If left untreated, all children with protein energy malnutrition will progress to develop permanent stunting (height for age), poorly developed immune system which causes overwhelming bacteremia and sepsis which is the cause of death in most malnourished individuals.

The history of protein-energy malnutrition includes a failure to thrive in children under 1 year of age especially after they have just been weaned of breast milk. Some common signs and symptoms include failure to thrive, fatigue, irritability, changes in skin and hair pigment, decreased muscle mass, diarrhea, increased occurrence of severe infectionsdue to damaged immune system, edema and hepatomegaly.

Physical examination of patients with kwashiorkor is usually remarkable for rounded prominence of the cheeks known as the moon face, and distended abdomen due to an enlarged liver, hyperkeratosis and hyperpigmentation of the skin, generalized edema especially on the dependent areas of the body like the feet. On the other hand, patients with marasmus usually look listless, emaciated with monkey-like faces due to absence of subcutaneous fat pad in the cheeks. The skin looks atrophic and dry.

There are no specific laboratory tests, group of tests, or indices that are satisfactory for the assessment of protein-energy malnutrition. However, laboratory findings that may aid in the diagnosis of protein-energy malnutrition include abnormally low blood glucose, hypoalbuminemia (10-25 g/L), hypoproteinemia (transferrin, essential amino acids, lipoprotein) and hypoglycemia.

There are no chest X ray findings associated with protein energy malnutrition.

There are no CT scan findings associated with protein energy malnutrition.

There are no MRI findings associated with protein energy malnutrition. However, a MRI may be helpful in the diagnosis of complications of protein-energy malnutrition which include cerebral atrophy and ventricular dilation.

Echocardiography findings may be helpful in the diagnosis of protein-energy malnutrition. Findings on an echocardiography suggestive of protein-energy malnutrition include decrease of R wave and QTc interval, decreased cardiac index which improved significantly after rehabilitation.

There are no other imaging findings associated with protein-energy malnutrition.

There are several parameters that can be used in the assessment of a child with protein-energy malnutrition. Malnutrition can be assessed according to the WHO based on mid upper arm circumference into moderate and severe malnutrition. Other parameters include the Z-score which assesses linear growth and weight for length.

In some cases, protein-energy malnutrition may be complicated by dehydration and specific infections, such as pneumonia and septicemia. In such cases, protein-energy malnutrition is a is a medical emergency and requires prompt treatment with antibiotics.

Surgical intervention is not recommended for the management of protein-energy malnutrition.

To prevent kwashiorkor, make sure the diet has enough carbohydrates, fat (at least 10% of total calories), and protein (12% of total calories).

The secondary prevention of protein-energy malnutrition is the same as primary prevention.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

The first clinical description of protein-energy malnutrition was made in 1865 in Spanish language which led to little dissemination of the information. In 1932, kwashiorkor was first described by Dr. Cicely Williams, working with African children on the Gold Coast. The word kwashiorkor comes from the Ga language of Accra, Ghana meaning the ‘disease of the deposed baby when the next one is born’. The term marasmus is derived from the Greek word ‘marasmos‘, which means withering or wasting.

• Prior to 1959, the term protein-energy malnutrition (PEM), or protein-calorie malnutrition was attributed principally to dietary deficiency and therefore it could be prevented or treated by dietary measures alone.^[1]
• The disease called kwashiorkor in the “Ga” language of Accra, Ghana means ‘the disease of the deposed baby’. The term signifies sickness an elder child may suffer from when a younger one is born.^[2]
• In 1932, kwashiorkor was first described by Dr. Cicely Williams, while working with African children on the Gold Coast.^[3]
• Williams identified a relationship between the low-protein maize diet of the children and the occurrence of the protein-energy malnutrition.^[3]
• In 1933, kwashiorkor was first described in the classic way as a ‘well-marked syndrome of the deposed infant’ in the literature.^[4]
• In the 1950s kwashiorkor became a major topic of debate in medicine, in South Africa and also in the international arena.
• In 1970s, nutritionists were the first to focus on the development of high protein foods for weaning the disease.
• The term marasmus is a derivative of the ‘marasmos‘, a Greek word. This ancient word means withering or wasting, that is thought to be used for the same conditions in ancient Greek.^[5]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2], Syed Hassan A. Kazmi BSc, MD [3]

Protein energy malnutrition may be classified according to the ‘Gomez classification’ based on weight for age, or the ‘Waterlow’s classification’ based on stunting and wasting, or the ‘Welcome classification’ based on the presence or absence of edema.

The three different classification schemes of protein-energy malnutrition are described below:^[1][2]

Definitions of general terms that are used in the classification of protein-energy malnutrition include the following:

Terminology	Meaning
Undrweight	Underweight for one’s age (Weight for age )
Stunted	Too short for one’s age (Height for age )
Wasted	Dangerously thin (Weight for height )
Micronutrient malnutrition	Deficient in vitamins and minerals (Hidden Hunger )

Grade of PEM	Weight for age (%)	General considerations and formula
Normal	90-100	Normal reference child is the 50th centile of the Boston standard Weight for age (%) = (Weight of the child / Weight of the normal child of same age ) X100
Mild malnutrition, Grade I	75-89
Moderate malnutrition, Grade II	60-74
Severe malnutrition, Grade III	Less than 60

General scheme

Feature	Basic definition
Stunting	Drop in height for age (< 90%)
Wasting	Drop in weight for height (<80%)
Under weight	Drop in Weight for Age (<80%)

Grading

Grade of PEM	Stunting (low height for age)	Wasting (low weight for height)
Normal	95	90
Mild malnutrition	87.5-95	80-90
Moderate malnutrition	80-87.5	70-80
Severe malnutrition	Less than 80	Less than 70

Weight for age	With edema	Without edema	General considerations
60-80%	Kwashiorkor	Undernutrition	Weight for age +/- oedema Reference standard (50th percentile)
<60%	Marasmic kwashiorkor	Marasmus

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2], Syed Hassan A. Kazmi BSc, MD [3]

Protein-energy malnutrition represents a shift of the body from fed to fasting/starvation state. Starvation leads to a decreased basal plasma insulin concentration and in decrease of glucose-stimulated insulin secretion. Prolonged fasting results in a deficiency in amino acids used for gluconeogenesis. It is thought that kwashiorkor is produced by a deficiency in the adequate consumption of protein-rich foods during the weaning process. However, the associated edema is not fully understood. Several theories have been put forward to explain this finding. Marasmus on the other hand is thought to be due to the total caloric deficiency leading to wastingin a child. Marasmus always results from a negative energy balance.

Several studies have shown that a deficiency in the consumption of protein, carbohydrates and fat is responsible for the development of protein-energy malnutrition. However, other studies have proposed that chronic infections such as helminthic infections are mainly responsible for the development of protein-energy malnutrition.^[1] The underlying mechanisms include the following:

• Decreased food intake because of anorexia
• Decreased nutrient absorption
• Increased metabolic requirements
• Direct nutrient losses

The pathologic changes involved in protein-energy malnutrition include:^[2]

• Immunologic deficiency in the humoral and cellular subsystem as a result of protein deficiency.
• Metabolic disturbances cause impaired intercellular degradation of fatty acids as a result of carbohydrate deficiency.
• Poor synthesis of pigments in the hair and skin is observed, with more frequency among children with low levels of zinc.

• Protein-energy malnutrition represents a shift of the body from fed to fasting/starvation state.
• The post-fed state may be considered as a useful reference point, as it denotes the period of metabolic transition from the fed to the fasted condition.
• Physiologically, the decrease in circulating insulin to postabsorptive levels results in a marked reduction of glucose uptake by peripheral insulin-dependent tissues (muscle and adipose tissues) and a shift toward utilization of fatty acids as energy currency.
• Glucose consumption continues by non-insulin dependent tissues (brain, renal medulla, and formed elements of the blood) and the splanchnic bed.
• The major site of glucose utilization is the brain, which depends completely upon a continuous supply of glucose for oxidative metabolism during pot-absorptive state.
• Maintenance of blood glucose balance is achieved by the hepatic production of glucose at rates equal to those of tissue utilization.

Insulin and glucagon in starvation

• Starvation leads to a decreased basal plasma insulin concentration and in decrease of glucose-stimulated insulin secretion. There is also an increase in counter-regulatory hormone concentration, for example, glucagon, cortisol and catecholamines in order to replete the glucose levels in the blood plasma.^[3][4]
• In case of starvation, there is regulated and controlled production of ketone bodies causes a harmless physiological state known as dietary ketosis. In ketosis, the blood pH remains within normal limits.^[5]

• The rate of lipolysis and ketogenesis depends upon the action of three enzymes:^[5]
  • Hormone-sensitive lipase (or triglyceride lipase), which is found in peripheral adipocytes
  • Acetyl CoA carboxylase, which is found in the liver
  • Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS), which is also found in the liver

• Insulin and glucagon play the key roles in regulating lipolysis and ketogenesis by acting in opposition to each other.
• Insulin inhibits ketogenesis by causing the dephosphorylation of hormone-sensitive lipase (HSL) and leads to lipogenesis by stimulating acetyl CoA carboxylase.^[6]
• In the adipose tissue, dephosphorylation of hormone-sensitive lipase (HSL) decreases the degradation of triglycerides into fatty acids and glycerol, the rate-limiting step in the release of free fatty acids from the adipocyte. This subsequently reduces the amount of substrate that is available for ketogenesis.^[7]
• Insulin also dephosphorylates the inhibitory sites on acetyl CoA carboxylase leading to enzyme activation and increased production of malonyl CoA. Malonyl CoA inhibitsbeta oxidation of fatty acids thereby decreasing ketogenesis.^[7]
• Glucagon stimulates ketogenesis by causing the phosphorylation of both hormone-sensitive lipase (HSL) and acetyl CoA carboxylase via cyclic AMP-dependent protein kinase. In the adipocytes, phosphorylation of lipase by cyclic AMP-dependent protein kinase causes degradation of triglycerides into fatty acids.^[8][9]
• In hepatocytes, phosphorylation of acetyl CoA carboxylase by cyclic AMP-dependent protein kinase decreases the production of malonyl CoA which subsequently stimulates fatty acid uptake by the mitochondria of the cells for oxidation, and thus increases the amount of substrate available for ketogenesis.
• The activity of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS) is increased by starvation and a high-fat diet, and it is decreased by insulin.^[10]

Eventual decreased gluconeogenesis in protein-energy malnutrition

• Prolonged fasting results in a deficiency in amino acids used for gluconeogenesis.
• Glucagon concentrations have been found to be lower in children with kwashiorkor compared with marasmus but similar to normal controls.^[6]

Malnutrition, Leptin, and Immunity

• Leptin is a central mediator connecting nutrition and immunity.^[7]
• Protein-energy malnutrition reduces leptin concentrations and increases serum levels of stress hormones, i.e., glucocorticoids.^[8]
• Leptin concentrations are related to body adipose tissue and are rapidly reduced by fasting.
• Low leptin concentrations and glucocorticoids impair macrophage functions by decreasing NF-kB translocation into the nucleus.^[9]

• Marasmus results when subcutaneous fat and muscle are lost because of endogenous mobilization of all available energy and nutrients.
• The overall metabolic adaptations that occur during marasmus are similar to those in starvation.
• Initially, gluconeogenesis is triggered and aims at maintaining the energy requirements of the body leading to a perceived increase in metabolic rate.
• As fasting progresses, gluconeogenesis is suppressed to minimize muscle protein breakdown, and ketones derived from fat become the main fuel for the brain.
• One of the main adaptations to long-standing energy deficiency is a decreased rate of linear growth, leading to permanent stunting.

Several theories have been postulated to explain the mechanism of edema seen in children with kwashiorkor. Some of them include:

1. Protein deficiency / hypoalbuminemia

It was initially believed that a deficiency in the consumption of protein was responsible for the development of kwashiorkor in children.

• Albumin concentrations were also noted to increase steadily within two weeks after refeeding.
• Presence of features similar to congenital nephrotic syndrome, in which the primary pathology is renal loss of albumin.^[10]

Multiple evidences have now shown that inadequate intake of dietary protein is not the primary trigger for edematous malnutrition.

• Some patients have edematous malnutrition without hypoalbuminemia.
• Others develop edematous malnutrition (kwashiorkor) despite adequate proportion of protein in the diet (e.g, in exclusively breastfed infants).
• Some recover from edematous malnutrition with supportive care even without enhancing the protein content of the diet.^[11][12][13]

2. Oxidant stress

• Excessive oxidant stress was also proposed as a mechanism of development of kwashiorkor, however, it was discovered that that the administration of antioxidant was not successful in the prevention of the development of this malnutrition in a series of trials.
• Antioxidant depletion is a consequence rather than cause of kwashiorkor.^[14]

3. Microbiome

• Changes in intestinal microbiome have also been suggested as a cause of the development of kwashiorkor.
• This has not been fully supported because evidence shows that neither the fecal microbiota transfer nor the local diet alone was sufficient to cause the malnutrition leading to the conclusion that changes in fecal microbiota are only effects rather than causes of kwashiorkor.^[15][16][17]

Protein-energy malnutrition is frequently reported in Cri du chat syndrome(CDS), a genetic disease that causes developmental delay and global growth retardation.

Some of the conditions that are associated with kwashiorkor include:

• Vitamin A deficiency
• Vitamin D deficiency
• Thiamine deficiency
• Zinc deficiency
• Iodine deficiency
• Iron deficiency
• Dehydration
• Sepsis
• Shigella and Campylobacter infections

Post mortem examination of the liver shows the presence of fatty infiltration and necrosis which disappears with adequate treatment.^[18]

Both in kwashiorkor and marasmus hair analysis is therefore advocated as a useful diagnostic procedure for both conditions. In both cases, there is a decrease in the amount of melanin present in the scalp hair.

• In kwashiorkor, microscopic studies reveal a decreased proportion of hairs in anagen follicles

• In marasmic patients, no hairs were in the anagen phase, with a shift to the telogen phase
• Marasmic patients have many more broken hairs when compared with patients with kwashiorkor

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

Protein energy malnutrition may be caused by reduced breast feeding, poor weaning practices, limited availability of food and inadequate child care in cases of extreme poverty. This classically affects several poor people in regions of poor social and economic background. Other environmental causes such as infections, drought and earthquakes leading to decreased availability of food have also been identified.

Protein energy malnutrition may be caused by:^{[1][2][3][4][5][6][7][8][9][10]}

• Economic and social factors:
  • Extreme poverty prevents parents from buying healthy and nutritious meals for their children
  • Limited availability of food due to floods and earthquake
  • Reduced breast feeding and poor weaning practices
  • Poor distribution of food to reach people in the remote areas
• Environmental factors:
  • Infections such as diarrhea.
  • Scarcity of food due to floods, earthquakes and poor agricultural practices
• Age:
  • Increased nutritional requirements for growth
• Biological factors:
  • Maternal undernutrition
  • Infectious diseases such as measles and diarrhea
• Level of education and sanitation
• Season and climate conditions
• Cultural and religious food customs

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

Protein energy malnutrition must be differentiated from other diseases that cause failure to thrive, edema, wasting recurrent infections, skin and hair changes. It is important to also differentiate kwashiorkor from marasmus as the two diseases are caused by protein-energy malnutrition and share similar features such as, weight loss, muscle wasting, low blood glucose levels and growth retardation.

Differentiating kwashiorkor from marasmus

Kwashiorkor must be differentiated from marasmus as the two diseases are caused by protein-energy malnutrition and share similar features such as, weight loss, muscle wasting, low blood glucose levels and growth retardation. The followwing table differentiates between the two:^{[1][2][3][4][5][6][7][8][9][10][11][12]}

Distinguishing Features	Kwashiorkor	Marasmus
Cause	Deficiency of protein in the diet of child	Deficiency of protein as well as energy nutrients (that is carbohydrates and fats) in the diet
Age	Occurs in children in the age group 1-5 years	Typically occurs in children below the age of 1 year
Association	More common in villages where there is small gap period between successive pregnancies	More common in towns and cities where breast-feeding in discontinued quite early
Edema	Presence of edema	Absence of edema
Muscles	Wasting of muscles	Wasting of muscles is quite evident. The child is reduced to skin and bones
Skin changes	Dermatitis and hyperpigmentation noticed	Dry and atrophic skin but no changes in color
Serum cortisol	Decreased/Normal	Increased
Fasting blood glucose	Decreased	Decreased
Growth retardation	Mildly retarded in growth	Severely retarded in growth
Facial appearance	Moon-like face	Sunken eyes, maxillary prominence, loss of buccal fat pad
Abdomen	Protuded	Shrunken
Vitamin deficiency	Present	Present
Weight	60-80% of normal weight for age	<60% of normal weight for age

Disease	Cause	Age(years)	Presentation	Prevention	Workup	Prognosis	Treatment
Kwashiorkor	Deficiency of protein-rich foods like meat and poultry in diet Early weaning	< 1	Apathy Lethargy Irritability Cachexia Flag sign of hair Hyperkeratosis / dermatitis of skin Anemia Congestive heart failure Hypoalbuminemia Chronic fatty liver Hepatomegaly Edema	Balanced diet of carbohydrates, protein and fat	Complete blood count (CBC) Arterial blood gas (ABG) Blood urea nitrogen to creatnine ratio Serum potassium Total protein Urinalysis	Prognosis is good if treated early Lipiduria and ketonuria portend a poorer prognosis	Caloric replacement Protein replacement Vitamin and mineral supplementation Antibiotics if infections are present Plasma expanders and oral rehydration solution (ORS), if shock is present Lactase if lactose intolerant
Marasmus	Protein energy malnutrition (PEM) Hospitalized patients with malignancy Cystic fibrosis Neurologic diseases Genetic diseases End stage renal diseases	< 5	Hypo / hyperthermia Dehydration Skin pallor Anemia Corneal lesions (due to vitamin A deficiency) Decreased peripheral pulses Confusion	Balanced diet Prophylactic antibiotics	Blood glucose Peripheral blood smear Hemoglobin Urinalysis and culture Stool exam Albumin tests Electrolyte level	: Prognosis is good if underlying medical illness is treated Bacterial infection and renal failure may portend a poorer prognosis	: Blood glucose control Prevent hypothermia Prompt correction of dehydration Early detection and correction of electrolyte imbalance Active control of infections Screening and stabilization of micronutrient deficiencies Feeding for initial stabilization Nutritional support to support normal growth Psychological support, care and stimulation Careful follow-up of cases upon discharge
Protein losing enteropathy	Infectious agents Immune related diseases Neoplasms affecting the GI tract	All age groups	Generalized peripheral edema Gastrointestinal disorders Abdominal pain Diarrhea Malnutrition Weight loss	Avoidance of infections and other diseases associated with protein losing enteropathy	Measurement of albumin/globulin levels Presence of α1-antitrypsin in stool samples Measuremnent of vitamins A, D, E and K	Prognosis largely depends on the underlying disease If it is potentially curable, prognosis improves considerably	Antiparasitic agents ACE inhibitors and diuretics Surgical interventions may be required to resect neoplasms Low-fat diets supplemented with medium-chain triglycerides
Anasarca	Protein energy malnutrition Increased hydrostatic pressure Reduced oncotic pressure Lymphatic obstruction Some cancers	1-4	Generalized edema of body tissues with profound subcutaneous swelling	Healthy balanced diet in children Treatment of underlying heart problems Treatment of cancers	CBC ABG Brain natriuretic peptide (BNP) BUN:Cr Serum potassium Total protein Urinalysis	Good prognosis if the underlying cause is identified and treated early	Treatment is targeted at the underlying cause Diuretics if due to fluid overload Albumin infusion to correct hypoproteinemia
HIV wasting syndrome	HIV infection	All age groups	>10% total body weight loss Severe diarrhea Chronic weakness Fever lasting for more than three to four weeks HIV infection	Use of HAART	Nutritional assessment Serial measurements of weight Body mass index (BMI) Total body water and fat Sequential anthropometry (mid arm circumference, triceps, skinfold thickness) to predict prognosis	Prognosis is good with the use of highly active anti-retroviral therapy (HAART)	HAART Megestrol acetate Marijuana (in some states) Dronabinol Somatropin
Chronic pancreatitis	Tumors or stones Toxic metabolites Necrosis Fibrosis Oxidative stress Ischemia Alcohol consumption Autoimmune disorders	30 to 40 years	Epigastric abdominal pain Nausea Vomiting Decreased appetite Exocrine and endocrine dysfunction Weight loss Protein deficiency Diarrhea and steatorrhoea Secondary diabetes mellitus	Avoiding alcohol can reduce the risk for the development of chronic pancreatitis	Pancreatic enzymes Blood sugar Stool analysis for presence of enzymes and fat Computerized tomography X-rays Magnetic resonance cholangiopancreatography Transabdominal ultrasound	Patients who get medical care early have a good prognosis Increased risk of pancreatic cancer	Ibuprofen and acetaminophen along with antioxidants Surgical options are considered if medical options fail
Pediatric nephrotic syndrome	Glomerular lesions such as minimal change nephrotic syndrome Secondary nephrotic syndromes Genetic abnormalities such as infantile nephrotic syndromes Infections Drugs	<16years	Nephrotic-range proteinuria Edema Hyperlipidemia Hypoalbuminemia	Avoid infections and drugs that may predispose to nephrotic syndrome	Urinalysis Urine protein quantification (by first-morning urine protein / creatinine or 24-hour urine protein) Serum albumin Lipid panel	Prognosis depends on whether the nephrotic syndrome is steroid responsive or steroid resistant	Corticosteroids Diuretics Antihypertensive agents Alkylating agents Calcineurin inhibitors Home monitoring of urine protein and fluid status
Portal cirrhosis	Hepatitis C (26%) Alcoholic liver disease (21%) Hepatitis C plus alcoholic liver disease (15%) Cryptogenic causes (18%) – Many cases actually are due to NAFLD Hepatitis B – May be coincident with hepatitis D (15%) Miscellaneous (5%)	5th – 6th decade of life	Hepatomegaly Abdominal pain Ascites Abdominal distension Bulging flanks Shifting dullness Puddle sign	Avoid alcohol Treatment and vaccination against hepatitis Good diet and exercise	CBC Albumin Culture Total protein Serum ascites albumin gradient Ammonia level	Prognosis is poor	Prednisone and azathioprine – For autoimmune hepatitis Interferon and other antiviral agents – For hepatitis B and C Phlebotomy – For hemochromatosis Ursodeoxycholic acid – For primary biliary cirrhosis Trientine and zinc – For Wilson disease Liver transplantation

Table adapted from CDC Pinkbook.^[21]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2] Mahshid Mir, M.D. [3]

The prevalence of protein-energy malnutrition in children under 5 years is estimated to be 150 million cases annually. In Nigeria, the prevalence is as high as 41,600 per 100,000 children. Protein-energy malnutrition is majorly a disease of the developing countries. There is no racial or sexual predisposition.

The prevalence of protein energy malnutrition in children under 5 years is estimated to be 41,600 per 100,000 children in developing countries like Nigeria.^[1]

The table below show the prevalence of protein energy malnutrition in children under 5 years of age in developing countries in 1995.

Region	Stunting (%)	Underweight (%)	Wasting (%)
Africa	39	28	8
Asia	41	35	10
Latin America and the caribbean	18	10	3
Oceania	31	23	5

The case-fatality rate of protein energy malnutrition is unknown.

Protein energy malnutrition commonly affects children under 5 years of age.

There prevalence and incidence of protein energy malnutrition does not vary by gender.

There is no racial predilection for protein energy malnutrition but it is a disease seen more frequently in Sub-Saharan Africa, Southeast Asia and Central America.

Protein energy malnutrition is almost never seen in developed countries. It is a disease of underdeveloped/developing countries. However, some studies conducted in 2005 – 2007 on children in United States that an estimated 3.5 million children under the age of 5 are at risk of hunger due to an underutilization of existing programs designed to address the issue of proper distribution such as food stamps or school meals.

Protein energy malnutrition is a disease prevalent in the underdeveloped/developing countries of the world. It is widespread in Sub-Saharan Africa and common in Southeast Asia and Central America occurring in young children living in areas with endemic food insecurity or famine. Some of the major countries stricken by kwashiorkor include but are not limited to India, China, Pakistan, Tanzania, North Korea, Nigeria and Kenya.

• Countries are divided approximately by population into ten groups.
• Dependencies of France, United Kingdom, United States of America, The Netherlands and Denmark are grouped with their respective countries.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

Common risk factors in the development of protein energy malnutrition may be classified as maternal and environmental.

Common risk factors in the development of protein energy malnutrition may be classified as maternal and environmental.^[1] The causes of protein energy malnutrition may be distributed unequally and thus, the degree of protein–energy malnutrition disorders including kwashiorkor and marasmus may vary in a given population depending on many factors including:^[2][3][4]

• The political and economical situation of the area
• The level of education amongst the people
• The sanitatary conditions
• The climatic conditions
• Food production and availability
• Cultural food preferences in the area
• Breast-feeding preference among the female population
• Prevalence of infectious diseases
• The existence and effectiveness of governmental nutrition programs
• The quality of health services

Maternal factors:

• Formal education of mother:
  • Children of mothers with little or no formal education have an increased risk of developing protein energy malnutrition when compared with the children of the mothers who have a secondary education or higher
• Number of children under 5 years:
  • Mothers who have three or more children under 5 years have an increased risk of having a child with protein energy malnutrition when compared to mothers who only have one
• Young maternal age
• Occupation of the mother
• Marital status of the mother

Environmental and child factors:

• Area of residence: Rural vs urban dwelling
• Very low economic status of the family
• Unprotected source of water
• Use of firewood as only source of fuel
• Use of charcoal as main source of fuel
• Use of paraffin as main source of fuel
• Poor hygiene/cleanliness
• Poor health status of the child

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

There is insufficient evidence to recommend routine screening for protein energy malnutrition.

There is insufficient evidence to recommend routine screening for protein energy malnutrition.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

If left untreated, all children with protein energy malnutrition will progress to develop a failure to thrive, poorly developed immune system which causes overwhelming bacteremia and sepsis which is the cause of death in most malnourished individuals.

The symptoms of protein energy malnutrition usually develop between the first and fifth year of life, and start with symptoms such as lethargy, irritability, failure to thrive, decreased muscle mass, diarrhea, and recurrent infections due to decreased immunity. Without treatment patients with protein energy malnutrition which comprises of kwashiorkor and marasmus present with changes in their facial appearance with children with kwashiorkor having moon faces while those with marasmus develop monkey-like face due to loss of subcutaneous fat pad in the cheeks. There is generalized edema, hepatomegaly, changes in skin, hair color and texture, recurrent infections like diarrhea with kwashiorkor which will eventually lead to overwhelming shock and sepsis and death.^[1][2][3]

Complications that can develop as a result of protein energy malnutrition are:^{[4][5][6][7][8]}

• Congestive heart failure
• Fatty liver disease
• Renal insufficiency
• Bacteremia and sepsis
• Immune dysfunction
• Disorders of endocrine system
• Permanent mental and physical retardation
• Shock
• Coma

The presence of severe of hypoproteinemia, hypoalbuminemia, electrolyte imbalance or an underlying HIV infection is associated with poorer prognosis among patients with protein energy malnutrition.^[9]

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