Nutritional Support in Trauma

Question 1

What is the medical definition of trauma?

Answer 1

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

Question 2

What are examples of trauma?

Answer 2

• road traffic accident
• stabbing
• gunshot wound
• burns
• aneurysm repair
• tumour excision
• caesarean section
• amputation of diabetic foot

Question 3

What are the immediate and later features of physical trauma?

Answer 3

immediate:

• intravascular fluid loss
• extravascular volume
• tissue destruction
• obstructed / impaired breathing

later:

• as above as well as:
• starvation
• infection
• inflammation

all of these factors have potential mortality

Question 4

How might someone in a RTA be treated?

What may they die from if they do not recover?

Answer 4

if they cannot eat or drink, they are given IV fluids (3L 5% dextrose / day)

they may then rapidly lose weight

the death certificate cites “pneumonia” as the cause of death

Question 5

What are the stages involved in someone dying from pneumonia after a RTA where they cannot eat or drink?

Answer 5

blood loss + impaired breathing + infection barrier penetration

1. decreased circulating volume
2. decreased red cells + O₂
3. decreased white cells + immune response
4. decreased cardiac output / blood pressure
5. decreased organ perfusion
6. decreased energy substrate delivery to cells and tissues

this leads to major organ dysfunction (GI / heart / brain / renal) and infection barrier penetration (sepsis)

Question 6

What do the following lines represent for causes of mortality after major trauma?

Answer 6

red = haematological shock

pink = head injury

green = acute respiratory distress syndrome

blue = multi-organ failure

Question 7

What can cause shock?

Answer 7

interruption to the supply of substrates to the cell:

• oxygen, glucose, water, lipids, amino acids, micronutrients

interruption to the removal of metabolites from the cell:

• CO2, water, free radicals, toxic metabolites

Question 8

What are the 3 stages involved in mortality from trauma?

Answer 8

phase 1 - clinical shock

someone may make a spontaneous recovery - physiological adaptation

or an intervention may be needed - resuscitation

phase 2 - hypercatabolic state

phase 3 - recovery (anabolic state)

Question 9

When does shock (phase 1) tend to develop?

What is secreted?

Answer 9

• develops within 2-6 hours after injury
• lasts from 24-48 hours
• cytokines, cortisol and catecholamines are secreted

Question 10

What happens to the body during phase 1 (shock)?

What are the primary aims in this phase?

Answer 10

• increased heart rate (tachycardia)
• increased respiratory rate
• peripheral vasoconstriction
  
  • selective peripheral shut-down to preserve vital organs
• hypovolaemia

primary aims:

• stop bleeding
• prevent infection

Question 11

When does phase 2 (catabolic state) develop?

What is secreted during this stage?

Answer 11

• develops around 2 days after injury
• it is necessary for survival but if it persists/is severe it increases mortality
• secretion of catecholamines, glucagon and ACTH leading to cortisol production

Question 12

What are the effects on the body of phase 2 (catabolic state)?

What are the primary aims in this phase?

Answer 12

• increased oxygen consumption
• increased metabolic rate
• increased negative nitrogen balance
• increased glycolysis
• increased lipolysis

primary aims:

• avoid sepsis
• provide adequate nutrition

Question 13

When does phase 3 (anabolic state) occur?

What does it coincide with?

Answer 13

occurs around 3-8 days after uncomplicated surgery

may not occur for several weeks after severe trauma and sepsis

coincides with beginning of diuresis and request for oral intake

Question 14

What happens to the body during phase 3 (anabolic state)

What is most critical during this phase?

Answer 14

gradual restoration of:

• body protein synthesis
• normal nitrogen balance
• fat stores
• muscle strength
• adequate nutrition supply is critical in this phase
• risk of refeeding syndrome
• may last a few weeks / few months
• obesity paradox

Question 15

What are the 6 stages involved in the inflammatory response at a trauma site?

Answer 15

1. bacteria and pathogens enter the wound
2. platelets release clotting factors
3. mast cells secrete factors that mediate vasodilation to increase blood delivery to the injured area
4. neutrophils & macrophages recruited to phagocytose pathogens
5. macrophages secrete cytokines to attract immune cells + proliferate the inflammatory response
6. inflammatory response continues until wound is healed

Question 16

What are the endocrine effects of pro-inflammatory cytokines?

(e.g. IL-1, TNF-a)

Answer 16

increase in catabolic hormones:

• increased ACTH and cortisol
• increased glucagon
• increased catecholamines

decrease in anabolic hormones:

• decreased growth hormone
• decreased insulin

Question 17

What are the effects of cytokines IL-1, IL-6 and TNF on the inflammatory response?

Answer 17

• fibroblast proliferation (repair)
• fever
• endocrine effects - catabolic & anabolic
• anorexia
• T cell activation & B cell proliferation
• acute phase proteins
• metabolic effects (catabolic)
• local effects
  
  • chemotaxis
  • vasodilation
  • cell adhesion proteins

Question 18

What are the 5 cardinal signs of inflammation?

Answer 18

1. heat
2. redness
3. swelling
4. pain
5. loss of function

Question 19

In health, how long do glycogen stores maintain glucose concentration?

Answer 19

in health, glycogen stores can maintain [glucose] for up to 24 hours

Question 20

How long does the brain survive after circulatory failure?

How does it store glycogen and what is its requirement?

Answer 20

the brain has NO glycogen store

obligate substrate is glucose and oxygen

(requirement = 120g/day which is equivalent to 1kg muscle)

it will not survive for more than 2 minutes of circulatory failure

it adapts to using ketones as an energy substrate

Question 21

How long can the kidneys and liver survive after interruption of blood supply?

Answer 21

the kidneys and liver are capable of gluconeogenesis

they can survive for hours after interruption of blood supply

Question 22

What substrates are used by the liver/kidney and skeletal muscle?

Answer 22

different tissues use different substrates

the liver & kidneys use fatty acids / amino acids

skeletal muscle uses glycogen stores / fatty acids

Question 23

What are the first 2 phases that occur when the supply of oxygen and glucose is interrupted?

Answer 23

Phase 1 - glycogenolysis:

• glycogen is converted to glucose
• this lasts for 24 hours maximum

Phase 2 - gluconeogenesis:

• involves skeletal + secreted protein breakdown
• amino acids are converted to glucose + lactate production

Question 24

How much glucose can be produced from 1kg of muscle in gluconeogenesis?

What is the nitrogen loss during this phase?

Answer 24

1 kg of muscle contains 200g protein which produces 120g glucose

nitrogen loss is around 60-70 g/day but it can be up to 300g

Question 26

What happens in phase 3 when the supply of oxygen and glucose is interrupted?

Answer 26

**Phase 3 - lipolysis + ketogenesis:** * free fatty acids are converted to acetyl CoA * this is converted to **acetoacetate & hydroxybutyrate** * there is a gradual change to ketone metabolism by the CNS which spares protein stores and muscles

Question 27

What is the main problem associated with ketogenesis?

Answer 27

ketones are acids and cause a diuresis with loss of water and electrolytes

Question 28

What happens to skeletal muscle proteolysis as part of trauma protein turnover? How does this happen?

Answer 28

**skeletal muscle proteolysis *INCREASES*** * increase in [free amino acids] * these are transported to the liver for gluconeogenesis + protein synthesis * increased plasma [ammonia] * increased nitrogen loss * ​via urinary excretion of urea

Question 29

How does the amount of new protein synthesised change in trauma protein turnover? How does this happen?

Answer 29

amount of new protein synthesised ***REDUCES*** and the profile of proteins synthesised changes * increase in inflammatory modulators and scavengers * e.g. CRP, haptoglobin, clotting actors, modulators of clotting such as protease inhibitors * this leads to decreased albumin

Question 30

What will administration of adequate calories do in starvation? In what type of patients is this not true?

Answer 30

in starvation, administration of adequate calories as carbohydrate/lipid will stop muscle wasting this is not true in **trauma/sepsis** patients as the primary stimulation for protein breakdown is **cytokine secretion** from activated macrophages

Question 31

After starvation, what may further proteolysis lead to? How can this lead to pneumonia?

Answer 31

further proteolysis results in life-threatening damage to essential structural and secreted protein structural respiratory muscle weakness results in poor cough, retention of secretions (pneumonia)

Question 32

Why does lactate production happen in hypoxia? What is the result of this?

Answer 32

due to decreased aerobic metabolism and increased anaerobic metabolism * pyruvate does not undergo oxidative phosphorylation via the TCA cycle but is reduced to lactate * anaerobic metabolism can only continue until [lactate] becomes toxic * H⁺ inhibits enzymes * increased [lactate] is equivalent to tissue hypoxia

Question 33

How can blood lactate act as a prognostic marker in trauma?

Answer 33

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

Question 34

What is the vicious cycle involved in lactate metabolism?

Answer 34

* mitochondrial failure due to hypoxia * decreased oxidative phosphorylated * NADH \> NAD⁺ * anaerobic glycolysis continues

Question 35

What should nutritional support consider?

Answer 35

* demands of hypermetabolic phase * pre-trauma nutritional state

Question 36

When does nitrogen loss peak? How much muscle protein is lost in fractures and severe burns?

Answer 36

nitrogen loss peaks at 4-8 days in fracture of long bone - 60-70g muscle protein in severe burns - 300g muscle protein

Question 37

How does immobilisation affect recovery?

Answer 37

immobilisation increases losses calcium, phosphate, magnesium, etc.

Question 38

What techniques are used to help patients through the hypermetabolic phase?

Answer 38

nutrition is crucial in helping patients through the hyper-metabolic phase and preparing for anabolic recovery * ambient temperature * use the gut if possible (nasogastric tubes) * TPN (trace elements, fat soluble vitamins)

Question 39

What is meant by primary malnutrition?

Answer 39

* protein-calorie undernutrition (starvation) * dietary deficiency of specific nutrients (e.g. trace elements, water soluble vitamins / fat soluble vitamins)

Question 40

What is meant by secondary malnutrition?

Answer 40

* nutrients present in adequate amounts but appetite is suppressed * nutrients present in adequate amounts but absorption and utilization are inadequate * increased demand for specific nutrients to meet physiological needs

Question 41

What are the consequences of malnutrition? What is it associated with and what is the incidence in hospitalised patients?

Answer 41

* negative nitrogen balance * muscle wasting * widespread cellular dysfunction * associated with: * infection * poor wound healing * changes in drug metabolism * prolonged hospitalisation * increased mortality the overall incidence of malnutrition in hospitalised patients is approximately 50%

Question 42

What are the stages that can lead to refeeding syndrome?

Answer 42

1. starvation / malnutrition 2. glycogenolysis, gluconeogenesis and protein catabolism 3. protein, fat, mineral and electrolyte/vitamin depletion - salt and water intolerance 4. refeeding (switch to anabolism) 5. fluid, salt, nutrients (CHO major energy source) 6. insulin secretion 7. increased protein and glycogen sysnthesis 8. hypokalaemia, hypomagnesaemia, hypophophataemia, thiamine deficiency, salt/water retention (oedema) lead to refeeding syndrome

Question 43

What actually is refeeding syndrome?

Answer 43

a metabolic disturbance that occurs as a result of reinstitution of nutrition to people who are starved, severely malnourished or metabolically stressed due to severe illness

Question 44

What is a common disease associated with malnutrition that affects 1 in 2,500 newborn infants in the UK?

Answer 44

cystic fibrosis

Question 45

What is the cystic fibrosis transmembrane regulator (CFTR) protein? What is its function and where is it found?

Answer 45

a cAMP dependent chloride channel localises to the apical membrane of secretory and absorptive epithelial cells within the: * airways * pancreas * liver * intestine * sweat glands and the vas deferens

Question 46

What is the role of the CFTR protein?

Answer 46

CFTR faciliates the production of thin, watery, free-flowing mucus this lubricates airways and secretory ducts and protects the lining of the airways, digestive system and reproductive system so that macromolecules (e.g. digestive enzymes) can be secreted smoothly out of secretory ducts

Question 47

What is the main cause of CFTR dysfunction?

Answer 47

failure to maintain hydration of macromolecules in the lumen of the ducts of the lungs, pancreas, intestine, liver and vas deferens causes secretions to precipitate and cause obstruction

Question 48

What do digestive enzyme deficiencies lead to in CFTR dysfunction?

Answer 48

malnutrition

Question 49

What happens in lung disease where there is CFTR dysfunction?

Answer 49

* increased bacterial colonisation * neutrophils accumulate * elastase is secreted which digests lung proteins causing tissue damage * dead neutrophils release DNA which increases the viscosity of the CF sputum **infection + persistent inflammatory state**

Question 50

What are the 3 main gastrointestinal diseases in cystic fibrosis? What do they result in?

Answer 50

* meconium ileus at birth * severe hepatobiliary disease * pancreatic cysts , exocrine insuffiency leads to poor appetite, failure to thrive and low weight

Question 51

What is the treatment for meconium ileus?

Answer 51

occurs in around 15% of births with CF may require surgical resection as there is an associated risk of intestinal failure

Question 52

What are the consequences of severe hepatobiliary disease in CF?

Answer 52

hepatic metabolism of lipids, steroid hormones, drugs and toxins is compromised

Question 53

What is the result of pancreatic cysts and exocrine insufficiency in CF?

Answer 53

* decreased insulin - diabetes * decreased lipase - lipid malabsorption, steatorrhoea, fat soluble vitamin deficiency * decreased proteases - protein malnutrition

Question 54

What is the treatment for respiratory disease due to cystic fibrosis?

Answer 54

* physiotherapy * exercise * bronchodilators * antibiotics (oral / nebuliser / IV) * steroids * mucolytics (DNase) the aim is to reduce infection and inflammationn

Question 55

What is the treatment for GI disease caused by cystic fibrosis?

Answer 55

* pancreatic enzyme replacement (Creon) * nutritional supplements * fat-soluble vitamins * high calorie diet * ursodeoxycholic acid * maintain body weight * avoid catabolic state * introduce artifical feed early if sick

Question 56

What is contained within Creon delayed release capsules?

Answer 56

lipase, protease and amylase they are made from pig pancreas

Question 57

What is a nebuliser used for in cystic fibrosis treatment?

Answer 57

drug delivery into the lungs

Question 58

What are the 3 main stages in cystic fibrosis treatment?

Answer 58

1. prompt use of appropriate antibiotics 2. lifelong nutritional supplements 3. early use of nutritional support in acute illness