Part 8.2

Question 1

Acute phase response

Answer 1

Coordinated adaptations of the body to limit and clear tissue damage caused by hydrolase breakdown
- due to inflammatory, injured or malignant cells

Hepatic synthesis of of acute-phase proteins
- ↑ plasma proteins is positive response (↑ during infection)
- ↓ plasma proteins is negative response (↓ during infection)

Question 2

Positive acute phase response proteins

Answer 2

Proteins which ↑ during an infection

• Complement system
• Coagulation and fibrinolytic system
• Antiproteases
• Participants in inflammatory response
• C-reactive protein
• fibronectin - tissue repair
• ferritin
• ceruloplasmin - copper transport
• haptoglobin - attaches to hemoglobin

Question 3

Negative acute phase response proteins

Albumin response in acute phase

Answer 3

Decrease during an infection

• Albumin
• Transferrin
• Transthyretin - binds thyroid hormone
• Thyroxin-binding globulin
• IGF-1
• Factor XII

Albumin synthesis increases yet albumin decreases during infection/inflammatory response (catabolism?)

Albumin concentration is maintained in simple malnutrition (not indicative of PEM) - more representative of acute phase response

Question 4

Modulation of acute phase response

Answer 4

Cytokines produced by tumor and host modulate acute phase response
- lymphocytes and macrophages secrete them

They can act locally (para/autocrine) or systemically (endocrine)

Question 5

Proinflammatory cytokines found in some cancers

Answer 5

Common:
Tumor necrosis factor alpha (TNF-a)
Interleukin 1 and 6 (IL-1/IL-6)

Less common:
Interferon gamma (IFN-y)
Leukemia inhibitory factor (LIF)

Question 6

Effects of cytokines

Answer 6

Resistance to food intake and hypermetabolism:
↓ appetite (central and peripheral)

↓ GI function, ↓ gastric emptying and intestinal motility

↓ blood flow

Inhibition of LPL, growth hormone, IGF-1 signaling (↓ anabolism)

Induced insulin resistance (↑ catabolic response)

Question 7

Cachexia and hypermetabolism

Metabolic effect compared to starvation

Answer 7

Cachexia often accompanied by hyper metabolism and reduced total energy expenditure

Resting energy expenditure increases while active and thermic food energy expenditure decreases

In starvation metabolism is hypometabolic and there is a decreased energy expenditure

Question 8

Metabolic alterations in response to cachexia

Answer 8

↓ concentration of/responsiveness to anabolic factors: Insulin, IGF-1, Growth hormone, Thyroid hormone, Testosterone

↑ concentration of catabolic factors: glucagon, cortisol, pro-inflammatory cytokines, tumor derived factors

↑ mobilization of lipids and turnover of FA: ↑ lipolysis, ↓ LPL activity, hypertriglyceridemia

Altered glucose metabolism: glucose fuels tumors, tumor lactate production and Cori cycle (ATP consuming), ↑ gluconeogenesis, ↑ proteolysis of muscle, insulin resistance

Altered protein metabolism: negative N balance, ↑ basal protein turnover, ↑ hepatic protein synthesis