Nutritional Support in Trauma Flashcards
Definition of trauma?
An injury or wound to living tissue caused by an extrinsic agent.
Immediate potential causes of mortality following physical trauma?
- Intravascular fluid loss
- Extravascular volume increase
- Tissue destruction
- Obstructed/Impaired breathing
Later potential causes of mortality following physical trauma?
- Starvation
- Infection
- Inflammation
- Psychological
What year was penicillin discovered?
1928
Major causes of mortality following trauma;
Clinical Case:
Joe suffered multiple fractures and severe internal injuries in a motorcycle accident.
- As he could not eat or drink he was given iv fluids (3L 5% dextrose / day)
- He lost weight rapidly and died 15 days later
- The death certificate cited “Pneumonia” as the cause of death
What happened to Joe’s energy metabolism? What was the cause of death?
- Haemorrhage
- Brain injury
- Muscle wasting –> respiratory –> pneumonia
- Infection
Phases of trauma;
- Phase 1 –> clinical shock
- Phase 2 –> hypercatabolic state
- Phase 3 –> recovery (anabolic state)
What is a hypercatabolic state?
A biochemical state characterised by;
- increased circulating catabolic hormones (eg, cortisol, catecholamines)
- Increased inflammatory cytokines (eg, tumor necrosis factors, interleukin-1beta)
- Decreased anabolic insulin effects** with consequent **insulin resistance
During phase 1 (clinical shock) describe the;
- Circulating volume
- RBCs
- WBCs
- Cardiac output
- Organ perfusion
- Energy substrate delivery
ALL DECREASED –> can lead to major organ dysfunction AND infection barrier penetration leading to sepsis
Signs and symptoms of shock?
- Tachycardia
- Tachypnoea
- Peripheral vasoconstriction (cold, pale): selective peripheral shut-down to preserve vital organs
- Hypovolaemia
What can a decrease in RBCs in shock lead to?
- Cellular hypoxia
- Anaerobic metabolism
- Lactate accumulation
What are your primary aims in phase 1 (clinical shock)?
- Stop haemorrhage
- Prevent infection
Why are patients in shock following trauma susceptible to infection?
- Decreased WBCs
- Infection barrier penetration from trauma
There is an increased secretion of catecholamines in phase 2 (catabolic state). What is the purpose of this?
Body is in catabolic state –> trying to release energy!
- Catecholamines activate glucagon secretion
- There is also activated ACTH secretion which increases cortisol secretion
These both have insulin resistant effects.
How does this increase in catecholamines/cortisol/glucagon increase glucose levels?
- Increased oxygen consumption
- Increased metabolic rate
- Increased negative nitrogen balance
- Increase glycolysis –> glucose
- Increased lipolysis –> free fatty acids
- Increased proteolysis –> amino acids
What triggers this catabolic state?
- Stress/pain (adrenaline)
- Inflammatory cascade activated
What are your primary aims in phase 2 (catabolic)?
- Avoid sepsis
- Provide adequate nutrition
When does the anabolic state/recovery state occur?
- Occurs approx 3-8 days after uncomplicated surgery
- May not occur for several weeks after severe trauma and sepsis
What does the anabolic state typically coincide with?
Beginning of diuresis and request for oral intake
The anabolic state invovles the gradual restoration of what?
- body protein synthesis
- Normal nitrogen balance
- Fat stores
- Muscle strength
What is there a risk of during the anabolic state?
Refeeding syndrome risk
What is the obesity paradox during the anabolic state?
Those who are a little overweight tend to recover better
Describe the inflammatory response at a trauma site
- Bacteria and pathogens enter wound
- Platelets release clotting factors
- Mast cells secrete factors that mediate vasodilation to increase blood delivery to the injured area
- Neutrophils + macrophages recruited to phagocytose pathogens
- Macrophages secrete cytokines to attract immune cells + proliferate the inflammatory response
- Inflammatory response continues until wound is healed
What are the major proinflammatory cytokines?
IL-1, TNF-a
What is IL-1 and TNF-a produced mainly by?
Activated macrophages
Effect of IL-1 and TNF-a on;
a) catabolic hormones
b) anabolic hormones
c) appetite
d) acute phase proteins
a) increases catabolic hormomones (ACTH –> cortisol, catecholamines –> glucagon)
b) decreases anabolic hormones (GH, insulin)
c) decreased appetite
d) increased acute phase proteins
what are the catabolic hormones?
Adrenaline, cortisol, and glucagon are catabolic hormones
What is the catabolic state?
A breakdown state where stored nutrients are put to use;
- Glycogen [via Adrenaline (muscle) / Glucagon (liver)] –> glucose
- Fat –> free fatty acids
- Protein –> amino acids
Catabolism is necessary for survival but if persists / is severe can cause mortality. How?
Decreased appetite and increased inflammation
What are the 3 phases of the catabolic response to trauma?
- Phase 1. Glycogenolysis (24 hours max)
- Phase 2. Gluconeogenesis
- Phase 3. Lipolysis + Ketogenesis
What is occurring during the glycogenolsysis phase of the catabolic response?
- Glucagon triggers glycogen –> glucose
- Adrenaline triggers glycogen –> glucose
What drives the breakdown of glycogen in muscle?
Adrenaline
What drives the breakdown of glycogen in liver?
Glucagon
Can adrenaline directly stimulate glycogen breakdown?
Yes; markedly stimulates glycogen breakdown in muscle and, to a lesser extent, in the liver.
What occurs during the gluconeogenesis phase of catabolism?
Run out of glycogen, body switches to breaking down protein (skeletal musle and secreted protein breakdown)
Is the gluconeogenesis phase of catabolism effective?
Not really;
- 1Kg muscle = 200g protein = 120g glucose
- Amino-acids → Glucose + Lactate production (lactate poisonous if builds up)
- Nitrogen loss ~ 60-70 g/day but may be up to 300 g (body enters negative nitrogen balance)
What occurs during phase 3 (lipolysis and ketogenesis) of catabolism?
- Lipids broken down –> free fatty acids
- FFAs metabolised –> acetyl CoA
- Acetyl CoA causes release of –> acetoacetate and hydroxybutyrate (ketones that can be used energy substrate)
Glucose pathway;
Catabolic response to trauma - Glycogenolysis;
In health, glycogen stores can maintain [Glucose] for how long?
Up to 24 hours
Does the brain have a glycogen store?
No
What are the O2 and glucose requirements of the brain?
- Requirement of 120g / day
- WILL NOT SURVIVE MORE THAN 2 MINUTES OF CIRCULATORY FAILURE
- Adapts to using ketones as an energy substrate (when glucose runs out)
Are the kidneys and liver capable of gluconeogenesis?
Yes - can survive hours of interruption of blood supply
Different tissues use different substrates to make glucose.
a) what can the liver/kidney use?
b) what can skeletal muscle use?
a) fatty acids / amino acids
b) glycogen stores / fatty acids
Catabolic response to trauma - Lipolysis
Catabolic response to trauma - Proteolysis
Describe the protein turnover during catabolic state
- Amount of new protein synthesised reduces and profile of proteins synthesised changes
- Skeletal muscle proteolysis increases
What is the purpose of skeletal muscle proteolysis increasing following trauma?
Amino acids transported to liver for gluconeogenesis + protein synthesis.
How are albumin levels affected during protein turnover in trauma?
Decreased albumin
How are inflammatory modulators and scavengers (CRP, haptoglobin, clotting factors, modulators of clotting e.g. protease inhibitors) affected during protein turnover in trauma?
Increased
What is the primary stimulation for protein breakdown in trauma/sepsis?
Cytokine secretion from activated macrophages
How can prolonged proteolysis dring trauma be life threatening?
Further proteolysis results in life-threatening damage to essential structural and secreted protein;
- Stuctural; Respiratory muscle weakness results in poor cough, retention of secretions –> pneumonia
Which of the following are features of a hypercatabolic state that follows traumatic shock?
- Negative nitrogen balance
- Insulin resistance
- Fluid retention
- Increased energy requirements
ALL OF THEM
When is lactate produced?
Anaerobic metabolism and hypoxia
How does anaerobic metabolism lead to lactate production? How can lactate affect tissues?
- 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 = tissue hypoxia
What does the failure of blood lactate to return to normal following trauma resuscitation indicate?
Poor prognosis
Blood lactate prognostic values;
How can anaerobic respiration lead to a viscious cycle?
- Mitochondrial failure due to hypoxia
- Decreased Oxidative Phosphorylation
- NADH accumulates instead of NAD+ (so no energy drive in cell)
- Anaerobic glycolysis continues
What is a good prognostic marker following trauma?
Lactate levels
Can adequate nutrition reverse a hypercatabolic state?
No - but can help prognosis
What is primary malnutrition?
- Protein/calorie undernutrition (starvation)
- Dietary deficiency of specific nutrients (e.g. trace elements, water soluble vitamins / fat soluble vitamins)
What is secondary malnutrition?
Secondary malnutrition arises when an individual’s dietary intake is sufficient, but energy is not adequately absorbed by the body;
- Appetite is suppressed
- Absorption and utilisation are inadequate
OR increased demand for specific nutrients to meet physiological needs
When dealing with nutrition during trauma, what needs to be considered?
- demands of hypermetabolic phase
- pre-trauma nutritional state
Why does trauma lead to nitrogen loss?
- Stress produces nitrogen losses, driven by the catabolic actions of cortisol and adrenaline
- Skeletal muscle breakdown provides substrate for gluconeogenesis and also releases nonessential amino acids that are excreted in the urine as urea.
Immobilisation increases the loss of which electrolytes?
Calcium, Phosphate, Magnesium etc
How can trauma affect the protective cell barriers in the gut?
Trauma-induced breakdown of protective cell barriers in the gut
What are the consequences of malnutrition?
- Negative Nitrogen balance
- Muscle wasting
- Widespread cellular dysfunction
- infection
- poor wound healing
- changes in drug metabolism
- prolonged hospitalisation
- increased mortality
What is the overall incidence of malnutrition in hospitalised patients?
Approx 50%
How should nutrition be delivered in a trauma patient?
- Use the gut if possible (nasogastric tubes)
- If gut not working, need TPN (total parenteral nutrition)
What is refeeding syndrome?
Refeeding syndrome involves metabolic abnormalities when a malnourished person begins feeding, after a period of starvation or limited intake.
Pathogenesis of refeeding syndrome?
- Refeeding causes insulin release
- Insulin causes;
- rapid uptake of glucose, phosphorus, magneium and potasssium (cause hypo- of these)
- increased thiamine use –> thiamine deficiency
What are the consequences of refeeding syndrome?
- Cardiovascular arrhythmias – cardiogenic shock
- Gastrointestinal disturbance – D+V, maldigestion
- Musculoskeletal – weakness, rhabdomyolysis
- Respiratory – respiratory failure
- Neurologic – Wernicke encephalopathy, tetany
- Renal – acute tubular nephrosis
- Hepatological – acute liver failure
- Increased mortality
CF involves a mutation in the CFTR protein (a cAMP dependent chloride channel). Where is this located?
Localises to the apical membrane of secretory and absorptive epithelial cells within;
- airways,
- pancreas,
- liver,
- intestine,
- sweat glands,
- vas deferens
What does the CFTR protein facilitate?
- CFTR facilitates production of thin, watery, free-flowing mucus
- Lubricating airways and secretory ducts
- Protecting the lining of the airways, digestive system, reproductive system
- So that macromolecules (e.g. digestive enzymes) can be secreted smoothly out of secretory ducts
The failure to maintain hydration of macromolecules in the lumen of the ducts of the pancreas and intestine in CF leads to what?
- Secretions precipitate –> obstruction
- Digestive enzyme deficiencies –> malnutrition
How can CF lead to
a) structural lung damage?
b) infection in lung?
a) ↑ bacterial colonisation –> neutrophils accumulate + secrete elastase —> structural lung damage
b) Dead neutrophils release DNA ↑ viscocity of sputum –> Infection + Persistent inflammatory state
What can babies with CF present with at birth?
Meconium ileus (around 15%) –> may require surgical resection (risk of intestinal failure)
How can CF lead to nutrional deficiencies?
- Surgical resection of bowel at birth if born with meconium ileus
- Pancreatic damage –> exocrine insufficieny
What exocrine insufficiencies are often present in CF? What can each lead to?
- Decreased insulin –> diabetes
- Decreased lipase –> lipid malabsorption, steatorrhoea, fat soluble vitamin deficiency
- Decreased protease –> protein malnutrition
How can nutritional deficiencies present in infants with CF?
Poor appetite, failure to thrive, low weight
Treatment for respiratory disease in CF?
To decrease infection and inflammation:
- Physiotherapy
- Exercise
- Bronchodilators
- Antibiotics (oral / nebuliser / iv)
- Steroids
- Mucolytics (DNase)
Treatment for GI disease in CF?
To maintain body weight and avoid catabolic state;
- Pancreatic enzyme replacement (Creon)
- Nutritional supplements
- Fat-soluble vitamins
- High calorie diet
- Ursodeoxycholic acid
What are creon delayed release capsules? Used to treat?
Capsules containing lipases, proteases, and amylases for the treatment of exocrine pancreatic insufficiency (EPI) due to cystic fibrosis, chronic pancreatitis, pancreatectomy, or other conditions.
CF treatment?
- Prompt use of appropriate Antibiotics
- Lifelong nutritional supplements
- Early use of nutritional support in acute illness
- CFTR modulators – Ivakaftor, Tezacaftor, Elaxacaftor
What is Wernicke-Korsakoff Syndrome?
A type of brain disorder caused by a vitamin B-1/thiamine deficiency
What is thiamine a cofactor for?
Several enzymes; transketolase, PDH, α-KGDH
These are important enzymes for;
- Glycolysis
- Citric acid cycle (TCA)
- Synthesis of Nucleic acid, neurotransmitter, glutathione, steroids
What can thiamine deficiency lead to?
Mitochondrial damage, cellular necrosis, oxidative stress, Purkinje cells in cerebellum.
Clinical presentation of Wernicke Encephalopathy?
- Confusion
- Ataxia (unsteady gait)
- Neural Oculomotor disturbances
- Korsakoff psychosis
What is Korsakoff psychosis?
Korsakoff psychosis is a late complication of persistent Wernicke encephalopathy and results in memory deficits, confusion, and behavioral changes.
What is the major risk factor for B1/thiamine deficiency?
Alcohol dependency;
- decreased thiamine absorption
- decreased thiamine stores in liver
- poor diet
- ?Genetic predisposition
What are other risk factors for B1/thiamine deficiency?
- Cancer chemo; decreased appetite, increased demand for nucleic acid synthesis
- Anorexia nervosa
- Refeeding syndrome
