Metabolic Adaptation and Initial Response
When the body experiences a deficiency in protein and energy, it initiates a series of adaptive metabolic responses to conserve energy and maintain vital functions. The basal metabolic rate decreases to minimize energy expenditure. The body first mobilizes its adipose tissue to meet energy demands. However, as malnutrition progresses, these fat reserves are depleted, forcing the body to break down lean body mass, particularly muscle and visceral protein. This is an attempt to supply amino acids necessary for the synthesis of critical proteins and to provide a source of energy.
Impact on Protein and Amino Acid Metabolism
In PEM, the body prioritizes the synthesis of essential proteins over non-essential ones. The liver's production of plasma proteins is significantly reduced, leading to several key biochemical markers of the condition.
Hypoalbuminemia and Edema
Serum albumin, the most abundant plasma protein, has a relatively long half-life of 14–20 days and is a common indicator of prolonged protein depletion. A significant reduction in albumin concentration (hypoalbuminemia) decreases the plasma oncotic pressure. This drop in pressure causes fluid to move from the intravascular space into the interstitial tissues, resulting in the characteristic edema seen in Kwashiorkor.
Amino Acid Profile Changes
Protein breakdown also alters the circulating amino acid profile. Levels of essential amino acids in the blood decrease, while non-essential amino acids may remain stable or even increase. The ratio of essential to non-essential amino acids often increases, which is a sensitive marker for PEM. The urinary excretion of creatinine and 3-methylhistidine, which are indicators of muscle mass breakdown, also decreases in PEM, reflecting muscle wasting.
Carbohydrate and Fat Metabolism Alterations
- Carbohydrate Metabolism: Due to insufficient energy intake, the body's glycogen stores in the liver and muscles are rapidly depleted. This can lead to hypoglycemia, a dangerously low blood glucose level, especially in severe PEM.
- Fat Metabolism: Early on, fat reserves are mobilized to provide energy. However, the liver is severely affected in Kwashiorkor. Impaired synthesis of apolipoproteins, which are necessary for triglyceride transport, causes fat to accumulate in the liver, leading to hepatomegaly and a fatty liver. In Marasmus, fat reserves are severely depleted due to a more pronounced overall energy deficit.
Electrolyte and Mineral Imbalances
PEM is often accompanied by significant electrolyte and mineral disturbances that can lead to severe clinical complications.
- Sodium and Potassium: Hyponatremia (low sodium) and hypokalemia (low potassium) are common due to gastrointestinal fluid loss, hormonal changes, and altered renal function.
- Magnesium and Zinc: Deficiency in magnesium, zinc, and other trace minerals is widespread, further impairing cellular function and immune response. Low serum zinc levels, in particular, are implicated in the skin lesions and impaired growth seen in Kwashiorkor.
- Phosphate: During refeeding, a rapid shift of electrolytes into cells can cause severe hypophosphatemia, a condition known as refeeding syndrome.
Hormonal Dysregulation
Endocrine changes play a pivotal role in mediating the catabolic state of PEM.
- Insulin and Glucagon: There is an impaired serum insulin level and an increase in glucagon. The resulting low insulin-to-glucagon ratio drives catabolism and contributes to low glucose uptake in tissues.
- Cortisol and Growth Hormone: Cortisol and growth hormone levels are elevated. While growth hormone normally promotes growth, its effects are counteracted by low insulin-like growth factor-1 (IGF-1) levels, which are also suppressed in PEM. Elevated cortisol further promotes protein breakdown and suppresses the immune system.
Distinct Biochemical Profiles: Marasmus vs. Kwashiorkor
While both forms of PEM share a common endpoint, their specific biochemical profiles differ significantly, reflecting the relative severity of energy versus protein deficiency.
| Feature | Marasmus | Kwashiorkor |
|---|---|---|
| Energy Deficit | Severe | Moderate to Severe |
| Protein Deficit | Severe | Pronounced |
| Primary Feature | Severe wasting, depletion of fat and muscle | Edema, often with fatty liver |
| Serum Albumin | Usually near normal initially, but drops later | Markedly reduced, leading to edema |
| Cortisol | Elevated | Elevated |
| Insulin | Reduced or near normal | Markedly reduced |
| Liver Enzymes | Often normal | Often elevated, indicating liver damage |
| Fatty Liver | Not typical | Very common due to impaired lipoprotein synthesis |
Conclusion
The biochemical changes in protein-energy malnutrition represent a complex, multisystemic metabolic crisis. The body's initial survival mechanisms, including slowing metabolism and mobilizing fat, eventually give way to widespread catabolism of muscle and visceral protein. This leads to characteristic features like hypoalbuminemia, fluid imbalance, electrolyte disturbances, and hormonal dysregulation. The specific manifestation, whether Marasmus or Kwashiorkor, is determined by the relative balance of protein versus total calorie deficiency. A comprehensive understanding of these biochemical shifts is critical for accurate diagnosis and for guiding the careful process of nutritional rehabilitation to avoid complications like refeeding syndrome.
For a deeper review of metabolic changes in PEM, consult the article A review of some metabolic changes in protein-energy malnutrition.
