Metabolic Reaction to Illness and Stress

Normal metabolism – protein

In a healthy person, protein is used for cell repair, growth, normal tissue turnover, and creation of new glucose through deamination.

Protein deamination

Removal of the amino group from an amino acid so the remaining carbon skeleton can be used for energy or glucose production.

Insulin and protein metabolism

Insulin signals the body that it is in the fed/anabolic state and promotes storage and building of nutrients, including protein.

Counterregulatory hormones

Hormones such as glucagon, epinephrine, and cortisol that increase blood glucose and promote a catabolic state.

Glucagon

Counterregulatory hormone that raises blood glucose and promotes gluconeogenesis and protein breakdown during fasting or stress.

Epinephrine

Counterregulatory hormone released during stress that increases blood glucose and promotes fuel mobilization.

Cortisol

Counterregulatory hormone that promotes protein breakdown and gluconeogenesis, helping provide fuel during stress.

Normal metabolism – carbohydrate

Carbohydrates are the body's main source of energy in healthy individuals.

Blood glucose regulation

Keeping blood glucose within normal limits provides a consistent supply of energy, especially for tissues that depend heavily on glucose.

Glucose-dependent tissues

Tissues that require or strongly depend on glucose for energy, especially the central nervous system and red blood cells.

Protein-sparing effect of carbohydrate

Adequate carbohydrate reduces the need to break down protein because non-carbohydrate sources do not have to be used as extensively to make glucose.

Normal metabolism – fat

Fat is used for energy and is an important component of cell membranes and hormones.

Fat metabolism and glucose

Fat generally cannot be converted into glucose; only the glycerol backbone can contribute to glucose production.

Fat and protein sparing

Fat does not directly have a protein-sparing effect because fatty acids cannot be converted into glucose.

Overnight fast

During a short fast, blood glucose is primarily maintained by glucose released from liver glycogen.

Liver glycogen

Stored carbohydrate in the liver that can be broken down to maintain blood glucose during the early stages of fasting.

Glycogen depletion

Liver glycogen stores are generally depleted after about 24 hours of fasting.

Longer-term fasting

After liver glycogen is depleted, the body increasingly relies on gluconeogenesis, fat metabolism, and ketone bodies for energy.

Gluconeogenesis during starvation

Production of glucose from non-carbohydrate sources, especially amino acids and glycerol, when glycogen stores are depleted.

Alanine and glutamine

Amino acids preferentially used during fasting to support gluconeogenesis.

Skeletal muscle protein during starvation

Skeletal muscle protein is used as an amino acid source for gluconeogenesis, with skeletal proteins generally being used before visceral proteins.

Lipolysis

Breakdown of stored fat into fatty acids and glycerol for energy and fuel production.

Ketone bodies

Compounds produced from fatty acids by the liver during prolonged fasting that can be used as an alternative energy source.

Adapted starvation

A prolonged fasting state in which the body increasingly uses ketone bodies for energy, including by the central nervous system, reducing the need to break down body protein.

Calorie needs during starvation

Energy needs decrease as the body adapts to prolonged fasting and lowers energy expenditure.

Muscle preservation during starvation

Muscle loss slows during prolonged starvation because the body increasingly uses fat stores and ketone bodies for energy, reducing the need for gluconeogenesis from protein.

Decreased glucose during starvation

Blood glucose decreases during prolonged fasting, and the body adapts to function at lower glucose levels.

Lipolytic activity

Increased breakdown of stored fat that occurs during fasting to provide fatty acids for energy.

Ketosis

Metabolic state in which ketone body production increases because the body is relying heavily on fat for fuel.

Ketosis during starvation

Ketosis develops during prolonged food deprivation, with ketone bodies eventually supplying much of the body's energy and reducing the need for gluconeogenesis from protein.

Metabolic stress

A physiological response to conditions such as sepsis, trauma, burns, or surgery that activates systemic metabolic and hormonal changes.

Sepsis

A severe systemic response to infection that can cause major metabolic changes and potentially lead to septic shock.

Trauma

Physical injury, including burns, that can trigger a systemic stress response and increased metabolism.

Systemic stress response

A widespread physiological response to severe illness or injury involving hormonal, metabolic, and inflammatory changes.

Metabolic response to stress

A response involving most metabolic pathways, characterized by increased energy expenditure, gluconeogenesis, protein breakdown, ureagenesis, and muscle wasting.

Lean body mass (LBM)

The body's non-fat mass, including muscle and organs, that is rapidly broken down during severe metabolic stress.

Hypermetabolism

A state of increased energy expenditure that occurs during acute illness, trauma, or severe stress.

Negative nitrogen balance

A state in which nitrogen losses exceed nitrogen intake, indicating net protein breakdown and muscle wasting.

Muscle wasting

Loss of skeletal muscle caused by increased protein breakdown, particularly during metabolic stress.

Ureagenesis

Production of urea from nitrogen released during amino acid breakdown; increases during protein catabolism.

Energy expenditure during starvation

Generally decreases, with an approximate stress factor of 0.85.

Energy expenditure during elective surgery

Generally increases, with an approximate stress factor of 1.1–1.2.

Energy expenditure during sepsis

Can increase substantially, with an approximate stress factor of 1.2–1.8.

Energy expenditure during multiple trauma

Increases due to the stress response, with an approximate stress factor of 1.2–1.4.

Ebb phase

The immediate survival phase after severe injury or illness characterized by hypovolemia, shock, tissue hypoxia, decreased cardiac output, decreased oxygen consumption, and lowered body temperature.

Hypovolemia

Abnormally low blood volume, which can occur immediately after severe trauma or illness.

Tissue hypoxia

Inadequate oxygen delivery to body tissues.

Ebb phase and insulin

Insulin levels decrease during the ebb phase while glucagon levels increase.

Flow phase

The healing phase that follows fluid resuscitation and restoration of oxygen transport, characterized by increased cardiac output, temperature, energy expenditure, and protein catabolism.

Flow phase hormones

The flow phase involves increased circulating insulin, catecholamines, glucagon, and cortisol.

Catecholamines

Stress hormones, primarily epinephrine and norepinephrine, that help mobilize energy during illness and stress.

Ebb vs. flow phase

The ebb phase is the immediate survival response with reduced metabolic activity, while the flow phase is the subsequent healing response with increased metabolism and energy expenditure.

Hormonal response to stress

Stress hormones promote protein catabolism, lipolysis, gluconeogenesis, and increased blood glucose.

Acute-phase proteins

Proteins produced by the liver in response to inflammation; their production changes during illness and can contribute to changes in protein metabolism.

Protein catabolism during stress

Increased breakdown of body protein to provide amino acids for energy production, gluconeogenesis, and acute-phase protein synthesis.

Acute-phase protein mobilization

During severe stress, body protein is mobilized to support production of proteins needed for the inflammatory response, contributing to rapid loss of lean body mass.

Free fatty acids (FFAs)

Fatty acids released into the bloodstream through increased lipolysis and used as an energy source.

Hyperglycemia

Abnormally high blood glucose, commonly occurring during metabolic stress because of increased glucose production and hormonal changes.

Sodium and water retention

Retention of sodium and fluid that can occur during the stress response.

Cytokines

Signaling proteins released in response to tissue damage and inflammation that help regulate the immune and metabolic stress response.

Protein metabolism during stress

During severe stress, protein is heavily catabolized because the body has poor ability to rely exclusively on carbohydrate and fat for all metabolic needs.

Glucagon during stress

Promotes gluconeogenesis, amino acid uptake, ureagenesis, and protein catabolism.

Protein-dependent energy production

Increased reliance on amino acids from protein breakdown to provide energy or substrates for glucose production during stress.

Glucogenic amino acids

Amino acids that can be converted into glucose through gluconeogenesis and are preferentially used during metabolic stress.

Proteolysis

Breakdown of proteins into amino acids; greatly increased during metabolic stress.

Lipid metabolism during stress

Stress increases lipolysis, causing more free fatty acids to circulate in the blood.

Free fatty acid oxidation

Breakdown of free fatty acids to generate energy.

Ketone production during stress

Fatty acids can be converted into ketones, which provide energy to tissues that do not depend entirely on glucose.

Nonglucose-dependent tissues

Tissues that can use alternative fuels such as fatty acids and ketones instead of relying primarily on glucose.

Glucose metabolism during stress

Stress causes increased glucose production and utilization, contributing to elevated blood glucose.

Increased gluconeogenesis during stress

The liver increases glucose production from non-carbohydrate sources to meet increased energy demands.

Insulin resistance during stress

Stress hormones reduce insulin effectiveness, contributing to increased blood glucose.

Glucagon and stress-induced glucose production

Increased glucagon during stress promotes gluconeogenesis and raises blood glucose.

Hallmark of catabolism

Negative nitrogen balance, indicating that protein breakdown exceeds protein synthesis.

Preferential amino acid use during stress

Certain glucogenic amino acids are preferentially used to support gluconeogenesis.

Preferential tissue catabolism

During severe stress, muscle and fat tissues are preferentially broken down to provide fuel and metabolic substrates.

Patients at risk for metabolic stress

Patients experiencing surgery, infection, sepsis, burns, or multiple trauma.

Starvation metabolism

Characterized by decreased energy expenditure, decreased gluconeogenesis, increased ketone production, and decreased ureagenesis.

Stress metabolism

Characterized by increased energy expenditure, increased gluconeogenesis, increased proteolysis, and increased ureagenesis.

Starvation vs. stress – energy expenditure

Energy expenditure decreases during starvation but increases during metabolic stress.

Starvation vs. stress – gluconeogenesis

Gluconeogenesis decreases during adapted starvation but increases significantly during stress.

Starvation vs. stress – ketones

Ketone production is very high during starvation but relatively lower during metabolic stress.

Starvation vs. stress – proteolysis

Protein breakdown is increased during both, but it is much greater during metabolic stress.

Starvation vs. stress – ureagenesis

Ureagenesis decreases during starvation but increases significantly during metabolic stress.

Cachexia

Involuntary weight loss occurring over approximately 6 months, typically involving loss of both fat and skeletal muscle.

Starvation – resting energy expenditure

Decreased REE as the body adapts to conserve energy.

Cachexia – resting energy expenditure

Normal or increased REE.

Acute critical illness – resting energy expenditure

Increased REE due to the hypermetabolic stress response.

Starvation – primary fuel

Fat is the primary fuel, with increased fatty acid oxidation and ketosis.

Cachexia – protein breakdown

Increased protein breakdown with relatively equal mobilization of fat and skeletal muscle.

Acute critical illness – protein breakdown

Marked skeletal muscle and protein breakdown.

Starvation – glucose turnover

Decreased glucose turnover as the body adapts to use more fat and ketones.

Acute critical illness – glucose metabolism

Increased gluconeogenesis, insulin resistance, and hyperglycemia.

Starvation – acute-phase proteins

Transport protein levels are generally maintained during starvation.

Acute illness – acute-phase proteins

Negative acute-phase proteins decrease while positive acute-phase proteins increase.

Positive acute-phase proteins

Proteins whose production increases during inflammation, such as proteins involved in the acute inflammatory response.

Negative acute-phase proteins

Proteins whose production decreases during inflammation, including some transport proteins.

Resting energy expenditure (REE)

Energy required by the body at rest; it decreases during starvation but increases during stress hypermetabolism.

Respiratory quotient (RQ)

Ratio of carbon dioxide produced to oxygen consumed that reflects which fuel is primarily being metabolized.

RQ during starvation

Approximately 0.6–0.7, reflecting predominant fat metabolism.