1. Acute phase proteins and other systemic responses to inflammation
Dr Donald C McMillan,
University Department of Surgery,
Royal Infirmary, Glasgow, UK.

2. Non-infective diseases
Infection
Shock/
hypoxia
SYSTEMIC
INFLAMMATION
MODS
Pancreatitis
Trauma
Burn
Infective diseases
Non-infective diseases

3. Ebb and flow phases of Cuthbertson
Ebb Flow Phase
Pre-resuscitation phase Recovery phase
Poor tissue perfusion Normal tissue perfusion
Hypometabolic Hypermetabolic
Decreased energy expenditure Increased energy expenditure
Increased glucocorticoids Normal glucocorticoids
Increased catecholamines Normal catecholamines
Low insulin Increased insulin
Normal glucose production Increased glucose production
Mild protein breakdown Profound protein breakdown

4. The metabolic response to injury
Cuthbertson et al. 1930

5. Pathophysiological changes of the systemic inflammatory response
Neuroendocrine changes
Fever, somnolence, fatigue and anorexia
Increased adrenal secretion of cortisol, adrenaline and glucagon
Haematopoietic changes
Anaemia
Leucocytosis
Thrombocytosis
Metabolic changes
Loss of muscle and negative nitrogen balance
Increased Lipolysis
Trace metal sequestration
Diuresis
Hepatic changes
Increased blood flow
Increased acute phase protein production
Gabay and Kushner, NEJM, 1999

6. Mediators of the metabolic response to injury
Cuthberston (1930) Increased protein breakdown and REE
Selye (1940’s) Corticosteroids proposed as mediator
Allison (1960’s) Insulin resistance proposed as mediator
Cytokines (1980’s) TNF, Il-1, Il-6 proposed as mediators
Adipokines (1990’s) Leptin, adiponectin, ghrelin?

7. Mediators of the metabolic response
to injury

8. SIRS (Systemic Inflammatory Response Syndrome)
The systemic response to a wide range of stresses.
Temperature >38°C (100.4°) or <36°C (96.8°F).
Heart rate >90 beats/min.
Respiratory rate >20 breaths/min or PaCO2 <32 mmHg.
White blood cells > 12,000 cells/ml or < 4,000 cells/ml or >10% immature (band) forms.
Note
Two or more of the following must be present.
These changes should be represent acute alterations from baseline in the absence of other known cause for the abnormalities.
American College of Chest Physicians/Society of Critical Care Medicine Consensus.
Crit Care Med. 1992;20:

9. Acute phase proteins and the systemic inflammatory response
Gabay and Kushner, 1999

10. C-reactive protein in patients undergoing
curative surgery for colorectal cancer
Crozier et al., 2004

12. Resting energy expenditure in injury
Skeletal Trauma
Major Burn
Multitrauma
Closed Head Injury
Sepsis
Elective Surgery
Starvation
-20 20 40 60 80
% Above Usual Requirement

13. Resting energy expenditure in disease
% Above Usual Requirement

14. Energy Requirements Following Surgery
Resting energy expenditure increased by 10-50%
to support increased metabolic workload
An additional allowance is added for activity
20 % if confined to bed
30 % if ambulatory

15. Surgery: Protein & Amino Acid Metabolism
If there are insufficient protein reserves there is:
decreased wound healing
decreased immune response
defective gut-mucosal barrier
decreased mobility/ respiratory effort

16. Loss of Lean Body Mass Lean body mass= body cell mass
metabolically active compartment
Irreversible at some point
critical mass

17. Protein requirements are increased to accommodate:
Immune response
Increased metabolic activity
Replacement of damaged cells
Replacement of protein losses
perspiration, blood, exudates, renal, intestinal
 if anorexia accompanies fever/infection
 by muscle proteolysis

18. Operative measures to reduce protein loss in surgical injury
Minimise the inflammatory stimulus
Surgical techniques
Anaesthesia
Control of sepsis
Environmental temperature
Control of pain and anxiety
Nutritional intervention
If oral intake less than 60% of energy and protein
requirements by 10 days

19. Release of Il-6, Il-1, TNF, Interferons, growth factors
Injury and the systemic inflammatory response
Activation of white blood cells, fibroblasts, endothelial cells
Release of Il-6, Il-1, TNF, Interferons, growth factors
CIRCULATION
C-reactive protein Zinc Retinol
Albumin Iron Alpha-tocopherol
Haemoglobin Copper Carotenoids
INFLAMMATORY PROCESS
WHOLE BODY
Resting energy expenditure Weight loss Body cell Mass
QUALITY OF LIFE
Fatigue Performance status
HEALING

20. Conclusions The systemic inflammatory response plays an important role
in determining protein loss in acute and chronic disease.
Conclusions
Acute phase proteins in particular C-reactive protein and
albumin are useful in quantifying the magnitude of this response
and both are associated with poor outcome