Malnutrition and Inflammation

What is malnutrition?

Nutrition imbalance that causes change in body composition and diminished function.

Note: in acute care, “malnutrition” and “undernutrition” are used synonymously.

What are the causes of malnutrition?

• Inadequate intake

• Increased requirements

• Impaired absorption

• Altered transport

• Altered nutrient utilization

Individuals may present with inflammatory, hypermetabolic, and/or hypercatabolic conditions.

What is the relevance of inflammation to malnutrition?

Inflammation increases malnutrition risk; may contribute to suboptimal response to nutrition interventions; increased mortality.

Why do we care about malnutrition? What does it contribute to?

• Increased morbidity and mortality

• Increased frequency and length of hospital stay

• Decreased function

• Decreased quality of life

• Higher healthcare costs

How did malnutrition show up historically?

This was based on visible manifestations of nutrient deficiency, i.e., scurvy, rickets, beriberi, pellagra.

When kwashiorkor emerged, it was a severe nutritional disease of children thought to be associated with weaning process from breastmilk to grains.

How was malnutrition historically classified and what were its limitations?

Classified by weight-for-age percentage and presence or absence of edema.

However, this focused on phenotype rather than cause and did not account for inflammation, disease burden, metabolic alterations.

What is marasmus vs. kwashiorkor?

1. Insufficient calories and protein

   • Clinical characteristics: emaciated & weak, bradycardic, hypotensive, hypothermic, thin dry skin, ravenously hungry, mental status normal with stimulation

2. Sufficient calories, insufficient protein

   • Clinical characteristics: loss of appetite, moon-face, massive peri-orbital and pitting edema of lower extremities & hands, protuberant bellies, hepatomegaly, dull dry skin, hair easily plucked, irritable, susceptible to infection (e.g. gastroenteritis, pneumonia)

What are Etiology-based (cause-based) definitions of malnutrition?

• Starvation-related: chronic starvation without inflammation, related to social or environmental circumstances

• Chronic disease-related: chronic diseases or conditions that impose sustained inflammation of a mild to moderate degree

• Acute disease or injury-related: acute disease or injury states with marked inflammatory response

What is inflammation and when should we be concerned?

Normal, injury and disease related response that functions locally and systemically for immunity and healing.

However, this becomes problematic because _________ mechanisms affect metabolism subtly and frankly from short to long term duration. Systemic infection and chronic disease cause responses that can change substrate metabolism. _________ induced changes in substrate metabolism are generally not responsive to nutrient intake.

What are hepatic proteins? What is the AA pool?

These are proteins made in the liver, synthesized in hepatocytes, then released into circulation.

• 40% in muscle

• 10% in organs

• 30% in skin and blood

• 20% in other tissues

Body protein is constantly in anabolism and catabolism, this turnover contributes to the AA pool. AA flux from catabolism and dietary intake supply pool for structural muscle and functional protein synthesis. When body’s needs exceed availability, muscle proteins are catabolized to maintain functional proteins.

What are low albumin levels an indicator of?

This is a marker of inflammation, not malnutrition as we historically thought.

What is an acute phase response?

This is a nonspecific response to inflammation—acute injury, infection, or neoplasm—that leads to marked changes in metabolism.

During this response, the synthesis of specific plasma proteins are either increased or decreased signaled by pro-inflammatory cytokines.

• Positive = increase

• Negative = decrease

What is the systemic response to acute or chronic inflammation?

This response promotes cytokine release. The liver reprioritizes synthesis of protein to those most essential.

What are the negative (and one positive) acute phase proteins?

Negative acute phase proteins will decrease: albumin, prealbumin, transferrin, retinol binding protein.

Positive acute phase proteins increase: CRP, etc.

What are inflammatory biomarkers?

These are serum proteins (albumin, prealbumin, transferrin) that are indicators of inflammation and reflects severity of inflammatory response.

What is the relationship between inflammatory biomarkers and nutrition status?

These serum proteins (negative acute phase proteins) do not change with feeding interventions in setting of inflammation. It reflects degree of injury which can impact appetite, GI, and hemodynamic stability which can negatively impact nutritional status as it can reduce likelihood for adequate nutrient intake.

How to diagnose malnutrition?

Identification of ≥ 2 out of 6 criteria

• Insufficient energy intake

• Weight loss

• Loss of muscle mass

• Loss of subcutaneous fat

• Localized or generalized fluid accumulation

• Diminished functional status

How is handgrip strength used and what are its limitations in malnutrition assessment?

This is validated as a proxy for LBM. Assessed using a handgrip dynamometer as a functional parameter for assessing malnutrition.

However, it’s not always feasible as malnutrition assessment so rarely used: rheumatoid arthritis, CVA, neuromuscular disease, unresponsive, etc.

What are some key things to remember when writing a PES statement for malnutrition?

Always identify severity of malnutrition, specify the context (chronic disease, acute, etc.), need ≥ 2 specific criteria to diagnose.

Example:

Severe malnutrition related to chronic disease as evidenced by unintentional loss of 12% BW in 3 months, intake <75% EER for > 1 month.

What are some factors that should be considered in relation to true weight loss?

• Scale error (MD vs hospital vs home; bed scale vs standing scale)

• Recall and reporting error

• Medical conditions with fluid shifts (CKD, CHF, cirrhosis)

• Fluid loss from procedures or medications (LVP, diuretics)

• Could also be edema or ascites masking weight loss

• Recent pregnancy

• Amputation

What are some factors that should be considered in relation to wasting vs atrophy weight loss?

• Age-related sarcopenia

• Neurodegenerative disorders (AD, PD, Huntington’s, etc.)

• Muscle disorders

• Spinal cord injury, paralysis.

• Muscular dystrophy secondary to de-innervation and disuse