Metabolic Response To Starvation, Sepsis, Injury

Question 1

Cardinal features of inflammation

Answer 1

• heat
• redness
• swelling
• pain
• loss of function

Question 2

Sickness behaviours

Answer 2

• the concept that illness or injury will give rise to a stereotyped response
• symptoms: feeling sick, loss of energy and fatigue, loss of interest in usual activities, poor appetite and significant weight loss, sleep changes, fever
• physiological elements: shift in liver metabolism, reduced albumin, reduced carrier protein, increased acute phase proteins, alterations in plasma copper/Fe/Zn, leukocytosis, increased sleep (slow wave)
• muscle wasting is a well known consequence of injury (possibly due to extended bed rest), urinary nitrogen increases (this is typically during the fever phase)

Question 3

Immune defenses

Answer 3

• first line: intact skin, mucous membranes and secretions
• second line: phagocytes, inflammation and fever, antimicrobial substances, natural killer cells
• third line: specialised lymphocytes, antibodies

Question 4

The inflammatory response: macrophages

Answer 4

• macrophages: either specialised residents in tissues or used in surveillance in fluid
• M1 classically activated by TH1/NK cell via IFNy or by PAMPs. These increase inflammation and kills pathogens with NO
• M2 alternatively activated by TH2/neutrophil via IL4 and IL13 (just TH). These decrease inflammation and are used for healing and repair
• deactivated macrophages are caused by release of IL10 and TGFb by Treg and glucocorticoids and prostaglandins. These inhibit inflammatory cytokines and lower IFNy and cell killing
• all macrophages have PRR to recognise PAMPs
• high fat diet can stimulate inflammation, fasting can mitigate

Question 5

Behaviours to reduce inflammation

Answer 5

• use of probiotics, as may prevent pathogens binding to peyers patches in the gut and prevent pro-inflammatory cytokines being released from bacteria
• lower fat diets
• fasting: anti-inflammatory effect on the neuro-immune system

Question 6

Cytokines and reducing inflammation (use of fatty acids)

Answer 6

• IL10 and IL1ra reduce inflammation
• eicosanoids (produced from PUFAs) can bind to NFkB TF therefore cannot upregulate pro-inflammatory cytokines
• resolvin (which is product of omega 3 metabolism) generates healing at the end of inflammatory response

Question 7

Summary of the coordinated response to infection and injury

Answer 7

• in response to inflammatory stimuli, there is the release of IL1, IL6, TNFa
• this activates and modulates the immune system: IL2-IL4, IL8. IL2 activates T cell proliferation. IL3 for haematopoeisis. IL4 causes Ig class switching. IL8 activates chemotaxis.
• the inflammatory response causes: NO and free radical production, fever, altered Cu/Zn/Fe metabolism, gluconeogenesis, anorexia, enhanced antioxidant defences, muscle proteolysis, acute phase proteins
• stress hormones increase causing greater utilisation of glucose by issues
• O2 consumption increases: EE increases

Question 8

The acute phase response

Answer 8

• CRP increases in the first 7 days
• albumin decreases in the first 7 days (more is escaping into the ISF): and albumin levels are a good predictor for mortality

Question 9

Involvement of NO in inflammation

Answer 9

NO produced from arginine released from muscle. Increases in beginning infection and reduces with proliferation of endothelial cells (scar tissue)

Question 10

How is critical illness a failure of adaptation?

Answer 10

• glycogen and protein mobilised for glucose and acute-phase reactants
• less or no ketogenesis or ketosis, gluconeogenesis from protein remains high
• metabolic rate rises
• energy needs increase
• accelerated protein and energy depletion

Question 11

Stages in critical illness

Answer 11

• surgery, trauma, burns, acute pancreatitis, IBD
• hyper-metabolism, anorexia, catabolism, neuroendocrine/cytokine mediated
• can lead to sepsis-> recovery or death

Question 12

The hypermetabolic inflammatory catabolic state

Answer 12

• insult
• SIRS (2 or more of: temperature, heart rate, respiratory rate, leukocytes)
• sepsis (SIRS with assumed or certain infection)
• MOF, severe sepsis
• septic shock (metabolic acidosis, refractory hypotension) leads to 40-80% mortality risk

Question 13

Lipid metabolism during acute phase response

Answer 13

• looking at EE expenditure and seen that those in deficit were financing from fat oxidation

Question 14

Protein metabolism and the inflammatory response

Answer 14

• loss of body protein during the inflammatory response
• total urinary N persists, mild acidosis and ammonium increases
• inflammatory cytokines stimulate muscle protein loss, suppresses albumin synthesis, immobility leads to loss of muscle mass
• resistance to anabolic hormones stimulates muscle protein loss (e.g insulin resistance)
• metabolic acidosis stimulates muscle protein loss and suppresses albumin synthesis