(22) Trauma and Nutrition Flashcards
1
Q
What is the medical definition of trauma?
A
An injury or wound to living tissue caused by an extrinsic agent
2
Q
Give some examples of trauma
A
- road traffic accident
- stabbing
- gunshot wound
- burns
- aneurysm repair
- tumour excision
- caesarean section
- amputation of diabetic foot
3
Q
What was the mortality rate of the wounded reaching hospital in the Vietnam War (1973) compared to World War I (1918)?
A
World War I = 40%
Vietnam War = 13%
4
Q
Give 4 possible immediate features of physical trauma
A
- intravascular fluid loss
- extravascular volume
- tissue destruction
- obstructed/impaired breathing
all can lead to potential mortality
5
Q
In addition to the immediate features, give 3 possible later features of physical trauma
A
- starvation
- infection
- inflammation
all can lead to potential mortality
6
Q
Describe an example of how fractures and internal injuries due to RTA can lead to organ dysfunction and infection
A
Blood loss + impaired breathing + infection barrier penetration
- reduced circulating volume
- reduced red cells so reduced O2
- reduced white cells so reduced immune response
- reduced cardiac output and blood pressure
- reduced organ perfusion
- reduced energy substrate delivery to cells and tissues
7
Q
Blood loss + impaired breathing + infection barrier penetration leads to a reduction in many things eg. organ perfusion and O2 levels. What are the 2 ultimate consequences?
A
Major organ dysfunction (GI/heart/brain/renal etc)
Infection barrier penetration (sepsis)
8
Q
What are the 2 components of shock?
A
- interruption to the supply of substrates to the cell
- interruption to the removal of metabolites from the cell
9
Q
Give examples of substrates required by a cell
A
- oxygen
- glucose
- water
- lipids
- amino acids
- micronutrients
10
Q
Give examples of metabolites that need to be removed from cells
A
- CO2
- water
- free radicals
- toxic metabolites
11
Q
What are the 3 phases after injury/surgery/burns/infection?
A
Phase 1 = clinical shock
Phase 2 = hypercatabolic state
Phase 3 = recovery (anabolic state)
12
Q
Spontaneous recovery can occur after phase 1. What is this called?
A
Physiological adaptation
13
Q
What intervention can occur after phase 1?
A
Resuscitation
14
Q
When does phase 1 (clinical shock) occur?
A
Develops within 2-6 hours after injury
15
Q
How long does phase 1 (clinical shock) last for?
A
24-48 hours
16
Q
What is secreted during phase 1 (clinical shock)?
A
- cytokines
- catecholamines
- cortisol
17
Q
Cytokines, catecholamines and cortisol are secreted during phase 1 (clinical shock). What does this lead to?
A
- increased heart rate (tachycardia)
- increased respiratory rate
- peripheral vasoconstriction (selective peripheral shut-down to preserve vital organs)
- hypovolaemia
18
Q
What are the primary aims of phase 1 (clinical shock) after injury?
A
- stop bleeding
2. prevent infection
19
Q
When does phase 2 (catabolic state) occur?
A
Approx 2 days after injury
20
Q
Is phase 2 (catabolic state) necessary?
A
Necessary for survival but if it persists or if it is severe, it can increased chance of mortality
21
Q
What is released in phase 2 (catabolic state)?
A
- catecholamines
- glucagon
- ACTH causing increased cortisol
22
Q
What happens in phase 2 (catabolic state)?
A
- increased oxygen consumption
- increased metabolic rate
- increased negative nitrogen balance (skeletal muscle breakdown to release amino acids)
- increased glycolysis (skeletal energy reserve depleted)
- increased lipolysis (adipose tissue breakdown to release fatty acids)
23
Q
What are the primary aims of phase 2 (catabolic state) after injury?
A
- avoid sepsis
2. provide adequate nutrition
24
Q
When does phase 3 (anabolic state) occur?
A
Approx 3-8 days after uncomplicated surgery
May not occur for weeks after severe trauma and sepsis
25
Phase 3 (anabolic state) coincides with what?
The beginning of diuresis and request for oral intake
26
In phase 3 (anabolic state) there is gradual restoration of what?
- body protein synthesis
- normal nitrogen balance
- fat stores
- muscle strength
27
What is critical during phase 3 (anabolic state)?
Adequate nutrition supply
28
What syndrome are patients in phase 3 (anabolic state) at risk of?
Refeeding syndrome
May last a few weeks/months
- obesity paradox
29
What is the 1st stage of inflammatory response at a trauma site
Bacteria and pathogens enter wound
30
What is the 2nd stage of inflammatory response at a trauma site?
Platelets release clotting factors
31
What is the 3rd stage of inflammatory response at a trauma site?
Mast cells secrete factors that mediate vasodilation to increase blood delivery to the injured area
32
What is the 4th stage of inflammatory response at a trauma site?
Neutrophils and macrophages recruited to phagocytose pathogens
33
What is the 5th state of inflammatory response at a trauma site?
Macrophages secrete cytokines to attract immune cells and proliferate the inflammatory response
34
What is the 6th stage of inflammatory response at a trauma site?
Inflammatory response continues until wound is healed
35
What happens in systemic capillary leak?
An injury causes inflammatory mediator release which causes H2O, NaCl, albumin and energy substrates to leak from the capillaries causing dangerous hypotension
36
What is involved in an inflammatory response mediated by cytokines IL-1, IL-6 and TNF?
- fibroblast proliferation (repair)
- local effects eg. chemotaxis, vasodilatation, cell adhesion proteins
- metabolic effects (catabolic)
- acute phase proteins
- T cell activation and B cell proliferation
- anorexia
- endocrine effects (catabolic, anabolic)
- fever
37
What are the 5 cardinal signs of inflammation?
- heat
- redness
- swelling
- pain
- loss of function
38
What are the effects of cytokine-mediated secretion of catabolic hormones (endocrine effects of cytokines)?
eg. IL-1 and TNF-a
- increased ACTH leading to increased cortisol
- increased glucagon
- increased catecholamines
39
What are the effects of cytokine-mediated inhibition of anabolic hormones (endocrine effects of cytokines)?
- decreased growth hormone
| - decreased insulin
40
What happens in normal metabolism?
Oxidation of dietary carbohydrate, lipid and protein
41
How long can glycogen stores maintain glucose for in health?
Up to 24 hours
42
Does the brain have a glycogen store?
No
Requires continuous supply of glucose and O2
43
What is the obligate substrate of the brain?
Glucose
44
How much glucose does the brain need?
120g per day per 1kg of muscle
45
How long will the brain survive in circulatory failure?
No more than 2 minutes
46
What happens when the brain is in circulatory failure?
Adapts to using ketones as an energy substrate
47
Which organs can survive hours of interruption of blood supply and why?
- kidney
- liver
They are capable of gluconeogenesis
48
Different tissues use different substrates. What do the liver and kidney use?
Fatty acids/amino acids
49
Different tissues use different substrates. What does skeletal muscle use?
Glycogen stores/fatty acids
50
What 3 things happen when the supply of glucose and oxygen is interrupted? (metabolic response to trauma)
1. glycogenolysis
2. gluconeogenesis
3. lipolysis and ketogenesis
51
What if glycogenolysis and how long can it last for?
Break down of glycogen to glucose
24 hours max
52
What happens in gluoneogenesis?
Skeletal + secreted protein breakdown
amino acids to glucose and lactate production
53
How much glucose can be made from muscle?
1kg muscle = 200g protein = 120g glucose
54
How much nitrogen loss occurs in gluconeogenesis?
60-70g per day but may be up to 300g
55
Name 2 common ketones in humans
- actetoacetic acid
| - B-hydroxybutyrate
56
State the pathway of lipolysis and ketongeneis
FFA (free fatty acids) converted to acetyl CoA converted to acetoacetate and hydroxybutyrate
57
What happens to the metabolism when there is increased ketones due to ketogenesis?
There is a gradual change to ketone metabolism by CNS which spares protein stores and muscles (metabolic response to trauma)
58
Ketones are acids. Therefore what does increased levels cause?
A diuresis with loss of H2O and electrolytes
59
What is the key adaptation to hypoxia?
Anaerobic metabolism
60
What are the main pathways in AEROBIC metabolism
glycolysis + TCA cycle + oxidative phosphorylation
61
How many moles of ATP can be made from 1 mole of glucose in AEROBIC metabolism?
36 moles of ATP
62
How many moles of ATP can be made from 1 mole of glucose in ANAEROBIC metabolism?
2 moles of ATP
63
Anaerobic metabolism leads to loss of ATP. What effect does this have on the cell?
- loss of membrane Na/K pump = cellular swelling
| - loss of membrane integrity = lysosomal enzyme release
64
Lactic acidosis may occur in anaerobic metabolism. What defines lactic acidosis?
pH 60nmol/L
[lactate] > 5.0 mmol/L
65
Describe the pathways in which inadequate oxygen can lead to cell death via anaerobic metabolism
- inadequate oxygen
- anaerobic metabolism
- inadequate energy production
- metabolic failure
- cell death
- inadequate oxygen
- anaerobic metabolism
- lactic acid production
- metabolic acidosis
- cell death
66
What two components make up normal protein turnover (to maintain muscle mass and maintain plasma protein)?
- synthesis of new protein
| - skeletal muscle proteolysis
67
There can be an imbalance in protein turnover (trauma protein turnover). What two components create this?
- decreased synthesis of new protein
| - increased skeletal muscle proteolysis
68
In trauma protein turnover, what causes decreased synthesis of new protein?
- increased inflammatory mediators and scavengers (CRP, haptoglobin, clotting factors, modulators of clotting eg. protease inhibitors)
- decreased albumin
69
In trauma protein turnover, what causes increased skeletal muscle proteolysis?
- increase in free amino acids (transported to liver for gluconeogenesis and protein synthesis)
- increase in plasma ammonia
- increased N2 loss (via urinary excretion of urea)
70
What proportion of the body's protein is readily available as a source of energy?
Around 30%
71
What stops muscle wasting in starvation?
Administration of adequate calories as carbohydrate/lipid
72
In starvation, administration of adequate calories as carbohydrate/lipid would normally stop muscle wasting. Why is this not true for trauma/sepsis patients?
Because the primary stimulation for protein breakdown is cytokine secretion from activated macrophages
73
What does further proteolysis result in?
Life-threatening damage to essential structural and secreted protein
74
What does respiratory muscle weakness (due to proteolysis) result in?
Poor cough, retention of secretions ultimately pneumonia
75
Why is lactate produced from pyruvate in hypoxia?
Pyruvate cannot undergo oxidative phosphorylation via the TCA cycle but is reduced to lactate
76
Anaerobic metabolism can only continue until when?
Until lactate becomes toxic and the H+ inhibits enzymes
Increased lactate = tissue hypoxia
77
What can lactate be used as in trauma?
A prognostic marker
78
Lactate can be used as a prognostic marker in trauma. What would indicate a poor prognosis?
Failure of blood lactate to return to normal following a trauma resuscitation
79
What is the % mortality with blood lactate
18%
80
What is the % mortality with blood lactate 2-4mmol/L?
74%
81
What is the % mortality with blood lactate >5mmol/L?
Around 100%
82
Describe the viscous cycle in hypoxia and lactate production
- mitochondrial failure due to hypoxia
- reduced oxidative phosphorylation
- NADH converted to NAD+
- anaerobic glycolysis continues
83
In nutrition and recovery, nutritional support should consider..
- demands of hyper metabolic state
| - pre-trauma nutritional state
84
When does nitrogen loss peak?
4-8 days
#long bone: 60-70g muscle protein
severe burns: 300g muscle protein
85
What does immobilisation increase loss of?
- calcium
- phosphate
- magnesium
etc
86
Nutrition is crucial in helping patients through hyper-metabolic phase and preparing for anabolic recovery. State 3 important things you should remember
- ambient temperature
- use the gut if possible (nasogastric tubes)
- TPN (trace elements, fat-soluble vitamins)
87
What is primary malnutrition?
- protein-calorie undernutrition (starvation)
| - dietary deficiency of specific nutrients (eg. trace elements, water-soluble vitamins, fat-soluble vitamins)
88
What is secondary malnutrition?
- nutrients suppressed in adequate amounts but appetite is suppressed
- nutrients present in adequate amounts but absorption and utilisation are inadequate
- increased demand for specific nutrients to meet physiological needs
89
What are the consequences of malnutrition?
- negative nitrogen balance
- muscle wasting
- widespread cellular dysfunction
- other complications
90
What is malnutrition associated with?
- infection
- poor wound healing
- changes in drug metabolism
- prolonged hospitalisation
- increased mortality
91
What is the overall incidence of malnutrition in hospitalised patients?
Approximately 50%
92
State the stages in the pathway where starvation and malnutrition can lead to referring syndrome
- starvation/malnutrition
- glycogenolysis, gluconeogenesis, and protein catabolism
- protein, fat, mineral, electrolyte and vitamin depletion (salt and water intolerance)
- refeeding (switch to anabolism)
- fluid, salt, nutrients (CHO major energy source)
- insulin secretion
- increased protein and glycogen synthesis (increased glucose uptake, utilisation of thiamine, uptake of K+, Mg2+, PO42- )
- hypokalaemia, hypomagnesaemia, hypophosphataemia, thiamine deficiency, salt and water retention-odema
- refeeding syndrome
93
Why does refeeding syndrome cause depletion of electrolytes?
During refeeding, insulin secretion resumes in response to increased blood sugar; resulting in increased glycogen, fat and protein synthesis. This process requires phosphates, magnesium and potassium which are already depleted and the stores rapidly become used up.
94
How many newborn infants are affected by CF in the UK?
1 in 2,500
95
What does CFTR protein stand for?
Cystic fibrosis transmembrane regulator protein
96
Where are the cAMP dependent chloride channels found? (affected by CF)
The apical membrane of secretory and absorptive epithelial cells within the
- airways
- pancreas
- liver
- intestine
- sweat glands
- vas deferens
97
What is the function of the CFTR protein?
Facilitates production of thin, watery, free-flowing mucus
- lubricating airways and secretory ducts
- protecting the lining of the airways, digestive system and reproductive system
So that macromolecules (eg. digestive enzymes) can be secreted smoothly out of secretory ducts
98
What does CFTR dysfunction lead to?
Failure to maintain hydration of macromolecules in the lumen of the ducts of the lungs, pancreas, intestine, liver and vas deference - causing secretions to precipitate and cause obstruction
99
CFTR dysfunction leads to digestive enzyme deficiencies. What does this lead to?
Malnutrition
100
Why does CFTR dysfunction lead to lung disease and persistent infection and inflammatory state?
- mucous plugging
- bacterial colonisation
- neutrophils accumulate
- elastase is secreted which digests lung proteins causing tissue damage
- dead neutrophils release DNA which increased viscosity of CF sputum
- this leads to more mucous plugging and therefore more infection
101
Give 4 main aspects of gastrointestinal disease in cystic fibrosis
- meconium ileus at birth (15%)
- severe hepatobiliary disease
- pancreatic cysts = exocrine insufficiency
- poor appetite, failure to thrive, low weight
102
What does meconium ileus have an associated risk of?
Intestinal failure
103
What does severe hepatobiliary disease in CF lead to?
Compromised hepatic metabolism of lipids, steroid hormones, drugs and toxins
104
What does exocrine insufficiency due to pancreatic cysts in CF lead to?
Insulin - diabetes
Lipase - lipid malabsorption, steatorrhoea, fat soluble vitamin deficiency
Proteases - protein malnutrition
105
What treatments are used in CF for respiratory disease ?
- physiotherapy
- exercise
- bronchodilators
- antibiotics (oral/nebuliser/IV)
- steroids
- mucolytics (DNase)
106
What treatment is used in CF for GI disease?
- pancreatic enzyme replacement (Creon)
- lifelong nutritional supplements
- fat-soluble vitamins
- high calorie diet
- ursodeoxycholic acid
107
What are the aims of CF treatment for GI disease?
- maintain body weight
- avoid catabolic state
- introduce artificial feed early if sick
108
What are the aims of CF treatment for respiratory disease?
- reduce infection
| - reduce inflammation
109
What is Creon?
Drug for CF - pancreatic enzyme replacement
Contains lipase, protease and amylase
Made from pig pancreas
