Theme 11 L6: Nutritional support in trauma

Question 1

What is trauma?

Answer 1

an injury or wound to living tissue caused by an extrinsic agent

Question 2

Following trauma, what is the first phase of injury?

Answer 2

Clinical shock

onset: immediate to 2-4 hours)

Question 3

What are the clinical features of shock?

Answer 3

1. decreased circulating volume
2. decreased red cells –> cellular hypoxia
3. anaerobic metabolism –> lactate accumulation
4. decreased white cells
5. decreased cardiac output / BP / organ perfusion
6. decreased energy substrate delivery to cells and tissues
7. toxic and inflammatory products in circulation + infection barrier penetration (sepsis)

Question 4

What are the primary aims of phase 1 (shock) ?

Answer 4

1. stop haemorrhage

2. prevent infection

Question 5

What is the second phase response after trauma?

Answer 5

hypercatabolic state

24-48 hours

Question 6

Following phase 1 response to trauma (clinical shock), what two things could occur?

Answer 6

1. Spontaneous recovery (physiological adaptation)

2. Resuscitation (intervention) leading to phase 2 –> hypercatabolic state

Question 7

What is the pathogenesis of the hypercatabolic state (phase 2)?

Answer 7

• catecholamines secretion –> increased glucagon, ACTH
• increase in oxygen consumption and metabolic rate
• increase in glycolysis –> glucose
• increase in lipolysis –> free fatty acids
• increase in proteolysis –> amino acids
• negative nitrogen balance develops
• stress / pain, inflammatory cascade activation

Question 8

What are the primary aims of phase 2, the hypercatabolic state?

Answer 8

1. avoid sepsis
2. provide adequate nutrition
3. immune modulation

Question 9

What is the phase 3 response following trauma?

Answer 9

Anabolic state (recovery)
occurs approx 3-8 days after uncomplicated surgery

Question 10

During recovery (phase 3: anabolic state), there is gradual restoration of?

Answer 10

• body protein synthesis
• normal nitrogen balance
• fat stores
• muscle strength

Question 11

What is critical during the anabolic state?

Answer 11

adequate nutrition supply

Question 12

What is the main risk during phase 3, the anabolic state?

Answer 12

refeeding syndrome

Question 13

What is the obesity paradox

Answer 13

more obese patients with more reserves might have better outcomes during phase 3, the recovery phase

Question 14

Explain the inflammatory response at a trauma site (6 steps)

Answer 14

1. Bacteria and pathogens enter wound
2. Platelets release clotting factors
3. Mast cells secrete factors that mediate vasodilation to increase blood delivery to the injured areas
4. Neutrophils + macrophages recruited to phagocytose pathogens
5. Macrophages secrete cytokines to attract immune cells + proliferative inflammatory response
6. Inflammatory response continues until wound is healed

Question 15

What are the two main pro inflammatory cytokines?

Answer 15

IL-1, TNF-a

Question 16

What are the endocrine effects of pro inflammatory cytokines (IL-1, TNF-a)?

Answer 16

• increase catabolic hormones
• increase ACTH –> increase cortisol
• increase catecholamines –> increase glucagon
• decrease anabolic hormones (growth hormone and insulin)
• decrease appetite

Question 17

What are the catabolic hormones?

Answer 17

adrenaline, cortisol and glucagon

Question 18

Which inflammatory modulators can be given?

Answer 18

glutamine and omega-3-FA

Question 19

What is catabolism?

Answer 19

• ‘break down’ state
• starvation
• stored nutrients put to use - glycogen broken down via adrenaline in muscle or glucagon in liver
• viscious cycle - decreased appetite, increased inflammation

Question 20

In catabolic response to trauma, what is phase 1?

Answer 20

Glycogenolysis:

• in muscle, adrenaline stimulates breakdown of glycogen to glucose
• in liver, glucagon stimulates break down of glycogen to glucose

Question 21

What receptor does adrenaline act on?

Answer 21

B-adrenergic receptor on cell surface

Question 22

In catabolic response to trauma, what is phase 2?

Answer 22

Gluconeogenesis:

• skeletal + secreted protein breakdown
• amino acid break down to glucose + lactate production
• nitrogen loss

Question 23

In catabolic response to trauma, what is phase 3?

Answer 23

Lipolysis and Ketogenesis:

FFA (free fatty acids) –> acetyl coA –> acetoacetate & hydroxybutyrate

Question 24

In health, how long can glycogen stores maintain glucose?

Answer 24

24hrs

Question 25

As the brain has no glycogen store, what does it use as an energy substrate for adaptation during the catabolic state

Answer 25

ketones

Question 26

Why can the kidneys and liver survive hours of interruption of blood supply?

Answer 26

capable of gluconeogenesis

Question 27

Which substrates do the liver and kidney use for gluconeogenesis?

Answer 27

fatty acids/ amino acids

Question 28

Which substrates do skeletal muscle use for gluconeogenesis?

Answer 28

glycogen stores/ fatty acids

Question 29

How does lipolysis occur (the 3rd phase to the catabolic response to trauma)?

Answer 29

Catecholamines trigger c-AMP cascade that results in free fatty acid and glycerol release. Glucocorticoids also fuel this response

Question 30

In the fed state, how does insulin have a negative role in proteolysis?

Answer 30

if insulin is around, proteolysis doesnt occur

Question 31

Why does proteolysis increase in the fasting state/ diabetes?

Answer 31

insulin is not available so there is protein degradation which results in atrophy of muscles and high protein turnover in the cells

Question 32

What occurs in a state of high protein turnover?

Answer 32

- amount of protein synthesis reduces and profile of proteins synthesised changes - inflammatory modulates e.g CRP, clotting factors increase - albumin decreases - skeletal muscle proteolysis increases

Question 33

In trauma and sepsis, what is the primary stimulation for protein breakdown?

Answer 33

cytokine secretion from activated macrophages

Question 34

What is the main prognostic marker in trauma?

Answer 34

lactate - failure of blood lactate to return to normal following trauma resuscitation carries a poor prognosis

Question 35

What are the effects of a raised lactate?

Answer 35

- - anaerobic metabolism - tissue hypoxia - pyruvate does not undergo oxidative phosphorylation via the TCA cycle but is reduced to lactate - mitochondrial failure due to hypoxia - decreased oxidative phosphorlyation - NADH accumulates rather than NAD+ - anaerobic metabolism can only continue until lactate becomes toxic

Question 36

Can adequate nutrition reverse the catabolic state?

Answer 36

no - prognosis is better with nutrition but provision of adequate nutrition cannot reverse the catabolic state - cytokine driven pro inflammatory state

Question 37

What is primary malnutrition?

Answer 37

- protein / calorie undernutrition (starvation) | - dietary deficiency of specific nutrients

Question 38

What is secondary malnutrition?

Answer 38

-nutrients present in adequate amounts but appetite is suppressed OR absorption / utilization are inadequate

Question 39

What are the consequences of malnutrition?

Answer 39

- negative nitrogen balance - muscle wasting - widespread cellular dysfunction - infection, poor would healing, changes in drug metabolism, prolonged hospitalisation, increased mortality

Question 40

Explain the pathogenesis of refeeding syndrome

Answer 40

-increased insulin secretion --> glucose uptake -increased proteins and glycogen synthesis -uptake of magnesium, phosphorus, potassium leads to hypophosphataemia, hypokalaemia, hypomagnesaemia -thiamine use leads to thiamine deficiency = refeeding syndrome

Question 41

What are the signs and symptoms of RFS?

Answer 41

- convulsions - delirium - ataxia - wernicke's encephalopathy - hypotension - arrhythmias - heart failure - renal failure - paralytic ileus - anaemia - hyperglycaemia - peripheral oedema - paraesthesia - rhabdomyolysis - fasciculation

Question 42

Which autosomal recessive condition is associated with malnutrition?

Answer 42

cystic fibrosis

Question 43

How does CFTR dysfunction cause malnutrition?

Answer 43

- failure to maintain hydration of macromolecules in the lumen of the ducts of the pancreas and intestine - secretions precipitate - obstruction - digestive enzyme deficiencies --> malnutrition

Question 44

In bacterial colonisations of lungs, neutrophils accumulate and secrete what to cause structural lung damage?

Answer 44

elastase

Question 45

Which nutritional deficits are seen in CF?

Answer 45

- meconium ileus at birth - cannot produce insulin - diabetes - cannot produce lipase - lipid malabsorption, steatorrhoea, fat volume vitamin deficiency - proteases - protein malnutrition - poor appetite, failure to thrive, low weight

Question 46

What treatments can you give for the respiratory disease associated with CF?

Answer 46

-exercise -bronchodilators -anti biotics (oral/ nebuliser / iv) -steroids -mucolytics (DNase) reduce infection and inflammation

Question 47

What treatments can you give for the GI disease associated with CF?

Answer 47

- pancreatic enzyme replacement (creon capsules contain lipase, protease and amylase) - nutritional supplements - fat-soluble vitamins - high calorie diet - ursodeoxycholic acid

Question 48

Which syndrome is associated with a thiamine (B1) deficiency?

Answer 48

Wernicke-Korsakoff syndrome

Question 49

What is thiamine a co-factor for?

Answer 49

transketolase, PDH, a-KGDH

Question 50

What is thiamine important for?

Answer 50

glycolysis, citric acid cycle, synthesis of nucleic acid, neurotransmitter glutathione, steroids

Question 51

What occurs cellularly during a thiamine deficiency?

Answer 51

mitochondrial damage, cellular necrosis, oxidative stress, purkinje cells in cerebellum

Question 52

What are the signs of Wernickes encephalopathy?

Answer 52

confusion ataxia (unsteady gait) neural oculomotor disturbances

Question 53

Who is at risk of Wernicke Korsakoff syndrome?

Answer 53

1. Alcoholics - decreased thiamine absorption and stores in the liver 2. Cancer chemotherapy - appetite decreased - demand for nucleic acid synthesis 3. Anorexia nervosa 4. Refeeding syndrome